WorldWideScience

Sample records for bipolar cell transduction

  1. Human hematopoietic cell culture, transduction, and analyses

    DEFF Research Database (Denmark)

    Bonde, Jesper; Wirthlin, Louisa; Kohn, Donald B;

    2008-01-01

    This unit provides methods for introducing genes into human hematopoietic progenitor cells. The Basic Protocol describes isolation of CD34(+) cells, transduction of these cells with a retroviral vector on fibronectin-coated plates, assaying the efficiency of transduction, and establishing long......-term cultures. Support protocols describe methods for maintenance of vector-producing fibroblasts (VPF) and supernatant collection from these cells, screening medium components for the ability to support hematopoietic cell growth, and establishing colonies from long-term cultures. Other protocols provide PCR...

  2. Cell cycle and cell signal transduction in marine phytoplankton

    Institute of Scientific and Technical Information of China (English)

    LIU Jingwen; JIAO Nianzhi; CAI Huinong

    2006-01-01

    As unicellular phytoplankton, the growth of a marine phytoplankton population results directly from the completion of a cell cycle, therefore, cell-environment communication is an important way which involves signal transduction pathways to regulate cell cycle progression and contribute to growth, metabolism and primary production and respond to their surrounding environment in marine phytoplankton. Cyclin-CDK and CaM/Ca2+ are essentially key regulators in control of cell cycle and signal transduction pathway, which has important values on both basic research and applied biotechnology. This paper reviews progress made in this research field, which involves the identification and characterization of cyclins and cell signal transduction system, cell cycle control mechanisms in marine phytoplankton cells, cell cycle proteins as a marker of a terminal event to estimate the growth rate of phytoplankton at the species level, cell cycle-dependent toxin production of toxic algae and cell cycle progression regulated by environmental factors.

  3. Corrosion test cell for bipolar plates

    Science.gov (United States)

    Weisbrod, Kirk R.

    2002-01-01

    A corrosion test cell for evaluating corrosion resistance in fuel cell bipolar plates is described. The cell has a transparent or translucent cell body having a pair of identical cell body members that seal against opposite sides of a bipolar plate. The cell includes an anode chamber and an cathode chamber, each on opposite sides of the plate. Each chamber contains a pair of mesh platinum current collectors and a catalyst layer pressed between current collectors and the plate. Each chamber is filled with an electrolyte solution that is replenished with fluid from a much larger electrolyte reservoir. The cell includes gas inlets to each chamber for hydrogen gas and air. As the gases flow into a chamber, they pass along the platinum mesh, through the catalyst layer, and to the bipolar plate. The gas exits the chamber through passageways that provide fluid communication between the anode and cathode chambers and the reservoir, and exits the test cell through an exit port in the reservoir. The flow of gas into the cell produces a constant flow of fresh electrolyte into each chamber. Openings in each cell body is member allow electrodes to enter the cell body and contact the electrolyte in the reservoir therein. During operation, while hydrogen gas is passed into one chamber and air into the other chamber, the cell resistance is measured, which is used to evaluate the corrosion properties of the bipolar plate.

  4. Temporal order of bipolar cell genesis in the neural retina

    Directory of Open Access Journals (Sweden)

    Chen C-M Amy

    2008-01-01

    Full Text Available Abstract Background Retinal bipolar cells comprise a diverse group of neurons. Cone bipolar cells and rod bipolar cells are so named for their connections with cone and rod photoreceptors, respectively. Morphological criteria have been established that distinguish nine types of cone bipolar cells and one type of rod bipolar cell in mouse and rat. While anatomical and physiological aspects of bipolar types have been actively studied, little is known about the sequence of events that leads to bipolar cell type specification and the potential relationship this process may have with synapse formation in the outer plexiform layer. In this study, we have examined the birth order of rod and cone bipolar cells in the developing mouse and rat in vivo. Results Using retroviral lineage analysis with the histochemical marker alkaline phosphatase, the percentage of cone and rod bipolar cells born on postnatal day 0 (P0, P4, and P6 were determined, based upon the well characterized morphology of these cells in the adult rat retina. In this in vivo experiment, we have demonstrated that cone bipolar genesis clearly precedes rod bipolar genesis. In addition, in the postnatal mouse retina, using a combination of tritiated-thymidine birthdating and immunohistochemistry to distinguish bipolar types, we have similarly found that cone bipolar genesis precedes rod bipolar genesis. The tritiated-thymidine birthdating studies also included quantification of the birth of all postnatally generated retinal cell types in the mouse. Conclusion Using two independent in vivo methodologies in rat and mouse retina, we have demonstrated that there are distinct waves of genesis of the two major bipolar cell types, with cone bipolar genesis preceding rod bipolar genesis. These waves of bipolar genesis correspond to the order of genesis of the presynaptic photoreceptor cell types.

  5. Immunocytochemical Evidence that Monkey Rod Bipolar Cells Use GABA

    OpenAIRE

    Lassová, Luisa; Fina, Marie; Sulaiman, Pyroja; Vard, Noga

    2010-01-01

    Certain bipolar cells in most species immunostain for GABA or its synthesizing enzyme, GAD. However it is unknown whether they actually release GABA, and if so, from which cellular compartment, and by what release mechanism. We investigated these questions in monkey retina where rod bipolar cells immunostain for GABA. We found that rod bipolar cells immunostain for one isoform of GAD, GAD65, in their somas, dendrites, and axon terminals. Near the fovea, the somatic stain of rod bipolar cells ...

  6. Feedforward lateral inhibition in retinal bipolar cells: input-output relation of the horizontal cell-depolarizing bipolar cell synapse.

    OpenAIRE

    Yang, X. L.; S. M. Wu

    1991-01-01

    Lateral inhibition is the ubiquitous strategy used by visual neurons for spatial resolution throughout the animal kingdom. It has been a puzzle whether lateral inputs in retinal bipolar cells are mediated by the horizontal cell (HC)-cone feedback synapse, by the HC-bipolar cell feedforward synapse, or by both. By blocking the central inputs of the depolarizing bipolar cells (DBCs) with L-2-amino-4-phosphonobutyrate, we were able to eliminate the contribution of the feedback synapse and to dem...

  7. Birth of cone bipolar cells, but not rod bipolar cells, is associated with existing RGCs.

    Directory of Open Access Journals (Sweden)

    Ling Bai

    Full Text Available Retinal ganglion cells (RGCs play important roles in retinogenesis. They are required for normal retinal histogenesis and retinal cell number balance. Developmental RGC loss is typically characterized by initial retinal neuronal number imbalance and subsequent loss of retinal neurons. However, it is not clear whether loss of a specific non-RGC cell type in the RGC-depleted retina is due to reduced cell production or subsequent degeneration. Taking advantage of three knockout mice with varying degrees of RGC depletion, we re-examined bipolar cell production in these retinas from various aspects. Results show that generation of the cone bipolar cells is correlated with the existing number of RGCs. However, generation of the rod bipolar cells is unaffected by RGC shortage. Results report the first observation that RGCs selectively influence the genesis of subsequent retinal cell types.

  8. Birth of cone bipolar cells, but not rod bipolar cells, is associated with existing RGCs.

    Science.gov (United States)

    Bai, Ling; Kiyama, Takae; Li, Hongyan; Wang, Steven W

    2014-01-01

    Retinal ganglion cells (RGCs) play important roles in retinogenesis. They are required for normal retinal histogenesis and retinal cell number balance. Developmental RGC loss is typically characterized by initial retinal neuronal number imbalance and subsequent loss of retinal neurons. However, it is not clear whether loss of a specific non-RGC cell type in the RGC-depleted retina is due to reduced cell production or subsequent degeneration. Taking advantage of three knockout mice with varying degrees of RGC depletion, we re-examined bipolar cell production in these retinas from various aspects. Results show that generation of the cone bipolar cells is correlated with the existing number of RGCs. However, generation of the rod bipolar cells is unaffected by RGC shortage. Results report the first observation that RGCs selectively influence the genesis of subsequent retinal cell types.

  9. Modeling Signal Transduction and Lipid Rafts in Immune Cells

    Science.gov (United States)

    Prasad, Ashok

    2011-03-01

    Experimental evidence increasingly suggests that lipid rafts are nanometer sized cholesterol dependent dynamic assemblies enriched in sphingolipids and associated proteins. Lipid rafts are dynamic structures that break-up and reform on a relatively short time-scale, and are believed to facilitate the interactions of raft-associated proteins. The role of these rafts in signaling has been controversial, partly due to controversies regarding the existence and nature of the rafts themselves. Experimental evidence has indicated that in several cell types, especially T cells, rafts do influence signal transduction and T cell activation. Given the emerging consensus on the biophysical character of lipid rafts, the question can be asked as to what roles they possibly play in signal transduction. Here we carry out simulations of minimal models of the signal transduction network that regulates Src-family kinase dynamics in T cells and other cell types. By separately treating raft-based biochemical interactions, we find that rafts can indeed putatively play an important role in signal transduction, and in particular may affect the sensitivity of signal transduction. This illuminates possible functional consequences of membrane heterogeneities on signal transduction and points towards mechanisms for spatial control of signaling by cells.

  10. Commercialization of Fuel Cell Bipolar Plate Manufacturing by Electromagnetic Forming

    OpenAIRE

    Daehn, G. S.; Hatkevich, S.; Shang, J.; Wilkerson, L.

    2010-01-01

    The cost of manufacturing bipolar plates is a major component to the overall cost structure of a Proton Exchange Membrane (PEM) fuel cell stack. To achieve the commercialization of PEM fuel cells, a high volume and low cost manufacturing process for the bipolar plate must be developed. American Trim has identified high velocity electromagnetic forming as a suitable technology to manufacture metallic fuel cell bipolar plates, because of its low capital cost, flexible tooling and rapid prototyp...

  11. Diffusion wave and signal transduction in biological live cells

    CERN Document Server

    Fan, Tian You

    2012-01-01

    Transduction of mechanical stimuli into biochemical signals is a fundamental subject for cell physics. In the experiments of FRET signal in cells a wave propagation in nanoscope was observed. We here develop a diffusion wave concept and try to give an explanation to the experimental observation. The theoretical prediction is in good agreement to result of the experiment.

  12. Hypergravity signal transduction and gene expression in cultured mammalian cells

    Science.gov (United States)

    Kumei, Y.; Whitson, P. A.

    1994-01-01

    A number of studies have been conducted during space flight and with clinostats and centrifuges, suggesting that gravity effects the proliferation and differentiation of mammalian cells in vitro. However, little is known about the mechanisms by which mammalian cells respond to changes in gravitational stress. This paper summarizes studies designed to clarify the effects of hypergravity on the cultured human HeLa cells and to investigate the mechanism of hypergravity signal transduction in these cells.

  13. Cell type-specific bipolar cell input to ganglion cells in the mouse retina.

    Science.gov (United States)

    Neumann, S; Hüser, L; Ondreka, K; Auler, N; Haverkamp, S

    2016-03-01

    Many distinct ganglion cell types, which are the output elements of the retina, were found to encode for specific features of a visual scene such as contrast, color information or movement. The detailed composition of retinal circuits leading to this tuning of retinal ganglion cells, however, is apart from some prominent examples, largely unknown. Here we aimed to investigate if ganglion cell types in the mouse retina receive selective input from specific bipolar cell types or if they sample their synaptic input non-selectively from all bipolar cell types stratifying within their dendritic tree. To address this question we took an anatomical approach and immunolabeled retinae of two transgenic mouse lines (GFP-O and JAM-B) with markers for ribbon synapses and type 2 bipolar cells. We morphologically identified all green fluorescent protein (GFP)-expressing ganglion cell types, which co-stratified with type 2 bipolar cells and assessed the total number of bipolar input synapses and the proportion of synapses deriving from type 2 bipolar cells. Only JAM-B ganglion cells received synaptic input preferentially from bipolar cell types other than type 2 bipolar cells whereas the other analyzed ganglion cell types sampled their bipolar input most likely from all bipolar cell terminals within their dendritic arbor.

  14. Molecular signal transduction in vascular cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Apoptosis is a form of genetically programmed cell death, which plays a key role in regulation of cellularity in a variety of tissue and cell types including the cardiovascular tissues. Under both physiological and pathophysiological conditions, various biophysiological and biochemical factors, including mechanical forces, reactive oxygen and nitrogen species, cytokines, growth factors, oxidized lipoproteins, etc., may influence apoptosis of vascular cells. The Fas/Fas ligand/caspase death-signaling pathway, Bcl-2 protein family/mitochondria, the tumor suppressive gene p53, and the proto-oncogene c-myc may be activated in atherosclerotic lesions, and mediates vascular apoptosis during the development of atherosclerosis. Abnormal expression and dysfunction of these apoptosis-regulating genes may attenuate or accelerate vascular cell apoptosis and affect the integrity and stability of atherosclerotic plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of atherosclerosis and its major complication, the acute vascular syndromes.

  15. Key cancer cell signal transduction pathways as therapeutic targets.

    Science.gov (United States)

    Bianco, Roberto; Melisi, Davide; Ciardiello, Fortunato; Tortora, Giampaolo

    2006-02-01

    Growth factor signals are propagated from the cell surface, through the action of transmembrane receptors, to intracellular effectors that control critical functions in human cancer cells, such as differentiation, growth, angiogenesis, and inhibition of cell death and apoptosis. Several kinases are involved in transduction pathways via sequential signalling activation. These kinases include transmembrane receptor kinases (e.g., epidermal growth factor receptor EGFR); or cytoplasmic kinases (e.g., PI3 kinase). In cancer cells, these signalling pathways are often altered and results in a phenotype characterized by uncontrolled growth and increased capability to invade surrounding tissue. Therefore, these crucial transduction molecules represent attractive targets for cancer therapy. This review will summarize current knowledge of key signal transduction pathways, that are altered in cancer cells, as therapeutic targets for novel selective inhibitors. The most advanced targeted agents currently under development interfere with function and expression of several signalling molecules, including the EGFR family; the vascular endothelial growth factor and its receptors; and cytoplasmic kinases such as Ras, PI3K and mTOR.

  16. MAPK Cascades in Guard Cell Signal Transduction

    Science.gov (United States)

    Lee, Yuree; Kim, Yun Ju; Kim, Myung-Hee; Kwak, June M.

    2016-01-01

    Guard cells form stomata on the epidermis and continuously respond to endogenous and environmental stimuli to fine-tune the gas exchange and transpirational water loss, processes which involve mitogen-activated protein kinase (MAPK) cascades. MAPKs form three-tiered kinase cascades with MAPK kinases and MAPK kinase kinases, by which signals are transduced to the target proteins. MAPK cascade genes are highly conserved in all eukaryotes, and they play crucial roles in myriad developmental and physiological processes. MAPK cascades function during biotic and abiotic stress responses by linking extracellular signals received by receptors to cytosolic events and gene expression. In this review, we highlight recent findings and insights into MAPK-mediated guard cell signaling, including the specificity of MAPK cascades and the remaining questions. PMID:26904052

  17. MAPK cascades in guard cell signal transduction

    Directory of Open Access Journals (Sweden)

    Yuree eLee

    2016-02-01

    Full Text Available Guard cells form stomata on the epidermis and continuously respond to endogenous and environmental stimuli to fine-tune the gas exchange and transpirational water loss, processes which involve mitogen-activated protein kinase (MAPK cascades. MAPKs form three-tiered kinase cascades with MAPK kinases and MAPK kinase kinases, by which signals are transduced to the target proteins. MAPK cascade genes are highly conserved in all eukaryotes, and they play crucial roles in myriad developmental and physiological processes. MAPK cascades function during biotic and abiotic stress responses by linking extracellular signals received by receptors to cytosolic events and gene expression. In this review, we highlight recent findings and insights into MAPK-mediated guard cell signaling, including the specificity of MAPK cascades and the remaining questions.

  18. Composite Bipolar Plate for Unitized Fuel Cell/Electrolyzer Systems

    Science.gov (United States)

    Mittelsteadt, Cortney K.; Braff, William

    2009-01-01

    In a substantial improvement over present alkaline systems, an advanced hybrid bipolar plate for a unitized fuel cell/electrolyzer has been developed. This design, which operates on pure feed streams (H2/O2 and water, respectively) consists of a porous metallic foil filled with a polymer that has very high water transport properties. Combined with a second metallic plate, the pore-filled metallic plates form a bipolar plate with an empty cavity in the center.

  19. Sensory Transduction of the CO2 Response of Guard Cells

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Eduardo Zeiger

    2003-06-30

    Stomata have a key role in the regulation of gas exchange and intercellular CO2 concentrations of leaves. Guard cells sense internal and external signals in the leaf environment and transduce these signals into osmoregulatory processes that control stomatal apertures. This research proposal addresses the characterization of the sensory transduction of the CO2 signal in guard cells. Recent studies have shown that in Vicia leaves kept at constant light and temperature in a growth chamber, changes in ambient CO2 concentrations cause large changes in guard cell zeaxanthin that are linear with CO2-dependent changes in stomatal apertures. Research proposed here will test the hypothesis that zeaxanthin function as a transducer of CO2 signals in guard cells. Three central aspects of this hypothesis will be investigated: CO2 sensing by the carboxylation reaction of Rubisco in the guard cell chloroplast, which would modulate zeaxanthin concentrations via changes in lumen pH; transduction of the CO2 signal by zeaxanthin via a transducing cascade that controls guard cell osmoregulation; and blue light dependence of the CO2 signal transduction by zeaxanthin, required for the formation of an isomeric form of zeaxanthin that is physiologically active as a transducer. The role of Rubisco in CO2 sensing will be investigated in experiments characterizing the stomatal response to CO2 in the Arabidopsis mutants R100 and rca-, which have reduced rates of Rubisco-dependent carboxylation. The role of zeaxanthin as a CO2 transducer will be studied in npq1, a zeaxanthin-less mutant. The blue light-dependence of CO2 sensing will be studied in experiments characterizing the stomatal response to CO2 under red light. Arabidopsis mutants will also be used in further studies of an acclimation of the stomatal response to CO2, and a possible role of the xanthophyll cycle of the guard cell chloroplast in acclimations of the stomatal response to CO2. Studies on the osmoregulatory role of sucrose in

  20. Multidrug resistance and retroviral transduction potential in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Theilade, M D; Gram, G J; Jensen, P B;

    1999-01-01

    blue colonies after X-Gal staining of the cells grown in soft agar. All examined SCLC cell lines were transducible with either vector. Transduction efficiencies varied from 5.7% to 33.5% independent of the presence of MDR. These results indicate that MDR does not severely impair transduction of SCLC......Multidrug resistance (MDR) remains a major problem in the successful treatment of small cell lung cancer (SCLC). New treatment strategies are needed, such as gene therapy specifically targeting the MDR cells in the tumor. Retroviral LacZ gene-containing vectors that were either pseudotyped for the...... gibbon ape leukemia virus (GALV-1) receptor or had specificity for the amphotropic murine leukemia virus (MLV-A) receptor were used for transduction of five SCLC cell lines differing by a range of MDR mechanisms. Transduction efficiencies in these cell lines were compared by calculating the percentage of...

  1. Multidrug resistance and retroviral transduction potential in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Theilade, M D; Gram, G J; Jensen, P B;

    1999-01-01

    Multidrug resistance (MDR) remains a major problem in the successful treatment of small cell lung cancer (SCLC). New treatment strategies are needed, such as gene therapy specifically targeting the MDR cells in the tumor. Retroviral LacZ gene-containing vectors that were either pseudotyped...... for the gibbon ape leukemia virus (GALV-1) receptor or had specificity for the amphotropic murine leukemia virus (MLV-A) receptor were used for transduction of five SCLC cell lines differing by a range of MDR mechanisms. Transduction efficiencies in these cell lines were compared by calculating the percentage...... of blue colonies after X-Gal staining of the cells grown in soft agar. All examined SCLC cell lines were transducible with either vector. Transduction efficiencies varied from 5.7% to 33.5% independent of the presence of MDR. These results indicate that MDR does not severely impair transduction of SCLC...

  2. Gravity perception and signal transduction in single cells

    Science.gov (United States)

    Block, I.; Wolke, A.; Briegleb, W.; Ivanova, K.

    Cellular signal processing in multi-, as well as in unicellular organisms, has to rely on fundamentally similar mechanisms. Free-living single cells often use the gravity vector for their spatial orientation (gravitaxis) and show distinct gravisensitivities. In this investigation the gravisensitive giant ameboid cell Physarum polycephalum (Myxomycetes, acellular slime molds) is used. Its gravitaxis and the modulation of its intrinsic rhythmic contraction activity by gravity was demonstrated in 180 °turn experiments and in simulated, as well as in actual, near-weightlessness studies (fast-rotating clinostat; Spacelab D1, IML-1). The stimulus perception was addressed in an IML-2 experiment, which provided information on the gravireceptor itself by the determination of the cell's acceleration-sensitivity threshold. Ground-based experiments designed to elucidate the subsequent steps in signal transduction leading to a motor response, suggest that an acceleration stimulus induces changes in the level of second messenger, adenosine 3',5'-cyclic monophosphate (cAMP), indicating also that the acceleration-stimulus signal transduction chain of Physarum uses an ubiquitous second messenger pathway.

  3. PEM fuel cell bipolar plate material requirements for transportation applications

    Energy Technology Data Exchange (ETDEWEB)

    Borup, R.L.; Stroh, K.R.; Vanderborgh, N.E. [Los Alamos National Lab., NM (United States)] [and others

    1996-04-01

    Cost effective bipolar plates are currently under development to help make proton exchange membrane (PEM) fuel cells commercially viable. Bipolar plates separate individual cells of the fuel cell stack, and thus must supply strength, be electrically conductive, provide for thermal control of the fuel stack, be a non-porous materials separating hydrogen and oxygen feed streams, be corrosion resistant, provide gas distribution for the feed streams and meet fuel stack cost targets. Candidate materials include conductive polymers and metal plates with corrosion resistant coatings. Possible metals include aluminium, titanium, iron/stainless steel and nickel.

  4. Alterations in Kainate Receptor and TRPM1 Localization in Bipolar Cells after Retinal Photoreceptor Degeneration

    OpenAIRE

    Gayet-Primo, Jacqueline; Puthussery, Theresa

    2015-01-01

    Photoreceptor degeneration differentially impacts glutamatergic signaling in downstream On and Off bipolar cells. In rodent models, photoreceptor degeneration leads to loss of glutamatergic signaling in On bipolar cells, whereas Off bipolar cells appear to retain glutamate sensitivity, even after extensive photoreceptor loss. The localization and identity of the receptors that mediate these residual glutamate responses in Off bipolar cells have not been determined. Recent studies show that ma...

  5. Alterations in kainate receptor and TRPM1 localization in bipolar cells after retinal photoreceptor degeneration

    OpenAIRE

    Jacqueline eGayet-Primo; Theresa ePuthussery

    2015-01-01

    Photoreceptor degeneration differentially impacts glutamatergic signaling in downstream On and Off bipolar cells. In rodent models, photoreceptor degeneration leads to loss of glutamatergic signaling in On bipolar cells, whereas Off bipolar cells appear to retain glutamate sensitivity, even after extensive photoreceptor loss. The localization and identity of the receptors that mediate these residual glutamate responses in Off bipolar cells have not been determined. Recent studies show that ma...

  6. Signal transduction events in aluminum-induced cell death in tomato suspension cells

    NARCIS (Netherlands)

    Iakimova, E.T.; Kapchina-Toteva, V.M.; Woltering, E.J.

    2007-01-01

    In this study, some of the signal transduction events involved in AlCl3-induced cell death in tomato (Lycopersicon esculentum Mill.) suspension cells were elucidated. Cells treated with 100 ¿M AlCl3 showed typical features of programmed cell death (PCD) such as nuclear and cytoplasmic condensation.

  7. Solar ultraviolet radiation as a trigger of cell signal transduction

    International Nuclear Information System (INIS)

    Ultraviolet light radiation in sunlight is known to cause major alterations in growth and differentiation patterns of exposed human tissues. The specific effects depend on the wavelengths and doses of the light, and the nature of the exposed tissue. Both growth inhibition and proliferation are observed, as well as inflammation and immune suppression. Whereas in the clinical setting, these responses may be beneficial, for example, in the treatment of psoriasis and atopic dermatitis, as an environmental toxicant, ultraviolet light can induce significant tissue damage. Thus, in the eye, ultraviolet light causes cataracts, while in the skin, it induces premature aging and the development of cancer. Although ultraviolet light can damage many tissue components including membrane phospholipids, proteins, and nucleic acids, it is now recognized that many of its cellular effects are due to alterations in growth factor- and cytokine-mediated signal transduction pathways leading to aberrant gene expression. It is generally thought that reactive oxygen intermediates are mediators of some of the damage induced by ultraviolet light. Generated when ultraviolet light is absorbed by endogenous photosensitizers in the presence of molecular oxygen, reactive oxygen intermediates and their metabolites induce damage by reacting with cellular electrophiles, some of which can directly initiate cell signaling processes. In an additional layer of complexity, ultraviolet light-damaged nucleic acids initiate signaling during the activation of repair processes. Thus, mechanisms by which solar ultraviolet radiation triggers cell signal transduction are multifactorial. The present review summarizes some of the mechanisms by which ultraviolet light alters signaling pathways as well as the genes important in the beneficial and toxic effects of ultraviolet light

  8. Enrichment of human hematopoietic stem/progenitor cells facilitates transduction for stem cell gene therapy.

    Science.gov (United States)

    Baldwin, Kismet; Urbinati, Fabrizia; Romero, Zulema; Campo-Fernandez, Beatriz; Kaufman, Michael L; Cooper, Aaron R; Masiuk, Katelyn; Hollis, Roger P; Kohn, Donald B

    2015-05-01

    Autologous hematopoietic stem cell (HSC) gene therapy for sickle cell disease has the potential to treat this illness without the major immunological complications associated with allogeneic transplantation. However, transduction efficiency by β-globin lentiviral vectors using CD34-enriched cell populations is suboptimal and large vector production batches may be needed for clinical trials. Transducing a cell population more enriched for HSC could greatly reduce vector needs and, potentially, increase transduction efficiency. CD34(+) /CD38(-) cells, comprising ∼1%-3% of all CD34(+) cells, were isolated from healthy cord blood CD34(+) cells by fluorescence-activated cell sorting and transduced with a lentiviral vector expressing an antisickling form of beta-globin (CCL-β(AS3) -FB). Isolated CD34(+) /CD38(-) cells were able to generate progeny over an extended period of long-term culture (LTC) compared to the CD34(+) cells and required up to 40-fold less vector for transduction compared to bulk CD34(+) preparations containing an equivalent number of CD34(+) /CD38(-) cells. Transduction of isolated CD34(+) /CD38(-) cells was comparable to CD34(+) cells measured by quantitative PCR at day 14 with reduced vector needs, and average vector copy/cell remained higher over time for LTC initiated from CD34(+) /38(-) cells. Following in vitro erythroid differentiation, HBBAS3 mRNA expression was similar in cultures derived from CD34(+) /CD38(-) cells or unfractionated CD34(+) cells. In vivo studies showed equivalent engraftment of transduced CD34(+) /CD38(-) cells when transplanted in competition with 100-fold more CD34(+) /CD38(+) cells. This work provides initial evidence for the beneficial effects from isolating human CD34(+) /CD38(-) cells to use significantly less vector and potentially improve transduction for HSC gene therapy.

  9. Signal transduction in cells of the immune system in microgravity

    Directory of Open Access Journals (Sweden)

    Huber Kathrin

    2008-10-01

    Full Text Available Abstract Life on Earth developed in the presence and under the constant influence of gravity. Gravity has been present during the entire evolution, from the first organic molecule to mammals and humans. Modern research revealed clearly that gravity is important, probably indispensable for the function of living systems, from unicellular organisms to men. Thus, gravity research is no more or less a fundamental question about the conditions of life on Earth. Since the first space missions and supported thereafter by a multitude of space and ground-based experiments, it is well known that immune cell function is severely suppressed in microgravity, which renders the cells of the immune system an ideal model organism to investigate the influence of gravity on the cellular and molecular level. Here we review the current knowledge about the question, if and how cellular signal transduction depends on the existence of gravity, with special focus on cells of the immune system. Since immune cell function is fundamental to keep the organism under imnological surveillance during the defence against pathogens, to investigate the effects and possible molecular mechanisms of altered gravity is indispensable for long-term space flights to Earth Moon or Mars. Thus, understanding the impact of gravity on cellular functions on Earth will provide not only important informations about the development of life on Earth, but also for therapeutic and preventive strategies to cope successfully with medical problems during space exploration.

  10. Bipolar membranes in forward bias region for fuel cell reactors

    International Nuclear Information System (INIS)

    Three bipolar membranes, two home-made composed of commercial cation (DuPont) and anion (FuMA-Tech) exchange membranes (called Nafion/FT-FAA and Nafion/FT-FAS) and a commercial one, BP-1 from FuMA-Tech, were investigated in order to characterize their suitability to use in a H2/O2 fuel cell intended to produce hydrogen peroxide on the cathode instead of water. The Nafion/FT-FAA and Nafion/FT-FAS membranes were prepared using a hot-pressing method. The optimal hot-pressing conditions were determined by measuring the ionic conductivity of the membranes. The latter was observed to depend on the relative humidity of the bipolar membrane. Of the studied bipolar membranes, Nafion/FT-FAA showed the best performance. The transport number of protons measured in a concentration cell was observed to depend on the direction of the proton diffusion flux through these membranes so that transport numbers of ca. unity were obtained when the cation exchange side faced the solution with higher proton concentration. In the opposite case, when the higher concentration faced anion exchange side, the transport number of proton was clearly lower, indicating the usefulness of the bipolar membranes for hydrogen peroxide production in the fuel cell

  11. Compact bipolar plate-free direct methanol fuel cell stacks.

    Science.gov (United States)

    Dong, Xue; Takahashi, Motohiro; Nagao, Masahiro; Hibino, Takashi

    2011-05-14

    Fuel cells with a PtAu/C anode and a Pr-doped Mn(2)O(3)/C cathode were stacked without using a bipolar plate, and their discharge properties were investigated in a methanol aqueous solution bubbled with air. A three-cell stack exhibited a stack voltage of 2330 mV and a power output of 21 mW. PMID:21451850

  12. Low Cost PEM Fuel Cell Metal Bipolar Plates

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Conghua [TreadStone Technologies, Inc.

    2013-05-30

    Bipolar plate is an important component in fuel cell stacks and accounts for more than 75% of stack weight and volume. The technology development of metal bipolar plates can effectively reduce the fuel cells stack weight and volume over 50%. The challenge is the metal plate corrosion protection at low cost for the broad commercial applications. This project is aimed to develop innovative technological solutions to overcome the corrosion barrier of low cost metal plates. The feasibility of has been demonstrated and patented (US Patent 7,309,540). The plan is to further reduce the cost, and scale up the technology. The project is built on three pillars: 1) robust experimental evidence demonstrating the feasibility of our technology, 2) a team that consists of industrial leaders in fuel cell stack application, design, and manufactures; 3) a low-risk, significant-milestone driven program that proves the feasibility of meeting program objectives The implementation of this project will reduce the fuel cell stack metal bipolar separator plate cost which accounts 15-21% of the overall stack cost. It will contribute to the market adoption of fuel cell technologies. In addition, this corrosion protection technology can be used similar energy devices, such as batteries and electrolyzers. Therefore, the success of the project will be benefit in broad markets.

  13. Alterations in kainate receptor and TRPM1 localization in bipolar cells after retinal photoreceptor degeneration

    Directory of Open Access Journals (Sweden)

    Jacqueline eGayet-Primo

    2015-12-01

    Full Text Available Photoreceptor degeneration differentially impacts glutamatergic signaling in downstream On and Off bipolar cells. In rodent models, photoreceptor degeneration leads to loss of glutamatergic signaling in On bipolar cells, whereas Off bipolar cells appear to retain glutamate sensitivity, even after extensive photoreceptor loss. The localization and identity of the receptors that mediate these residual glutamate responses in Off bipolar cells have not been determined. Recent studies show that macaque and mouse Off bipolar cells receive glutamatergic input primarily through kainate-type glutamate receptors. Here, we studied the impact of photoreceptor degeneration on glutamate receptor associated proteins in Off and On bipolar cells. We show that the kainate receptor subunit, GluK1, persists in remodeled Off bipolar cell dendrites of the rd10 mouse retina. However, the pattern of expression is altered and the intensity of staining is reduced compared to wild-type retina. The kainate receptor auxiliary subunit, Neto1, also remains in Off bipolar cell dendrites after complete photoreceptor degeneration. Similar preservation of kainate receptor subunits was evident in human retina in which photoreceptors had degenerated due to serous retinal detachment. In contrast, photoreceptor degeneration leads to loss of synaptic expression of TRPM1 in mouse and human On bipolar cells, but strong somatic expression remains. These findings demonstrate that Off bipolar cells retain dendritic glutamate receptors during retinal degeneration and could thus serve as a conduit for signal transmission from transplanted or optogenetically-restored photoreceptors.

  14. Cohesin is needed for bipolar mitosis in human cells.

    Science.gov (United States)

    Díaz-Martínez, Laura A; Beauchene, Nicole A; Furniss, Katherine; Esponda, Pedro; Giménez-Abián, Juan F; Clarke, Duncan J

    2010-05-01

    Multi-polar mitosis is strongly linked with aggressive cancers and it is a histological diagnostic of tumor-grade. However, factors that cause chromosomes to segregate to more than two spindle poles are not well understood. Here we show that cohesins Rad21, Smc1 and Smc3 are required for bipolar mitosis in human cells. After Rad21 depletion, chromosomes align at the metaphase plate and bipolar spindles assemble in most cases, but in anaphase the separated chromatids segregate to multiple poles. Time-lapse microscopy revealed that the spindle poles often become split in Rad21-depleted metaphase cells. Interestingly, exogenous expression of non-cleavable Rad21 results in multi-polar anaphase. Since cohesins are present at the spindle poles in mitosis, these data are consistent with a non-chromosomal function of cohesin. PMID:20436271

  15. Next Generation Bipolar Plates for Automotive PEM Fuel Cells

    Energy Technology Data Exchange (ETDEWEB)

    Adrianowycz, Orest; Norley, Julian; Stuart, David J; Flaherty, David; Wayne, Ryan; ; Williams, Warren; Tietze, Roger; Nguyen, Yen-Loan H; Zawodzinski, Tom; Pietrasz, Patrick

    2010-04-15

    The results of a successful U.S. Department of Energy (DoE) funded two-year $2.9 MM program lead by GrafTech International Inc. (GrafTech) are reported and summarized. The program goal was to develop the next generation of high temperature proton exchange membrane (PEM) fuel cell bipolar plates for use in transportation fuel cell applications operating at temperatures up to 120 °C. The bipolar plate composite developed during the program is based on GrafTech’s GRAFCELL resin impregnated flexible graphite technology and makes use of a high temperature Huntsman Advanced Materials resin system which extends the upper use temperature of the composite to the DoE target. High temperature performance of the new composite is achieved with the added benefit of improvements in strength, modulus, and dimensional stability over the incumbent resin systems. Other physical properties, including thermal and electrical conductivity of the new composite are identical to or not adversely affected by the new resin system. Using the new bipolar plate composite system, machined plates were fabricated and tested in high temperature single-cell fuel cells operating at 120 °C for over 1100 hours by Case Western Reserve University. Final verification of performance was done on embossed full-size plates which were fabricated and glued into bipolar plates by GrafTech. Stack testing was done on a 10-cell full-sized stack under a simulated drive cycle protocol by Ballard Power Systems. Freeze-thaw performance was conducted by Ballard on a separate 5-cell stack and shown to be within specification. A third stack was assembled and shipped to Argonne National Laboratory for independent performance verification. Manufacturing cost estimate for the production of the new bipolar plate composite at current and high volume production scenarios was performed by Directed Technologies Inc. (DTI). The production cost estimates were consistent with previous DoE cost estimates performed by DTI for the

  16. Carrier injection dynamics in heterojunction solar cells with bipolar molecule

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Yosuke; Yonezawa, Kouhei [Graduate School of Pure and Applied Science, University of Tsukuba, Tsukuba 305-8571 (Japan); Yasuda, Takeshi, E-mail: YASUDA.Takeshi@nims.go.jp, E-mail: moritomo.yutaka.gf@u.tsukuba.ac.jp [Photovoltaic Materials Unit, National Institute for Materials Science (NIMS), Tsukuba 305-0047 (Japan); Moritomo, Yutaka, E-mail: YASUDA.Takeshi@nims.go.jp, E-mail: moritomo.yutaka.gf@u.tsukuba.ac.jp [Graduate School of Pure and Applied Science, University of Tsukuba, Tsukuba 305-8571 (Japan); Center for Integrated Research in Fundamental Science and Engineering (CiRfSE), University of Tsukuba, Tsukuba 305-8571 (Japan)

    2015-03-23

    A boron subphthalocyanine chloride (SubPc) is a bipolar molecule and is used in hetero-junction organic solar cells. Here, we investigated the carrier injection dynamics from the donor α-sexithiophene (6T) or acceptor C{sub 60} layers to the bipolar SubPc layer by means of the femtosecond time-resolved spectroscopy. We observed gradual increase of the SubPc{sup –} (SubPc{sup +}) species within ≈300 ps. The increases are interpreted in terms of the exciton diffusion within the 6T (C{sub 60}) layer and subsequent electron (hole) injection at the interface. In 6T/SubPc heterojunction, the electron injection is observed even at 80 K. The robust electron injection is ascribed to the efficient charge separation within the 6T layer under photo exciation at 400 nm.

  17. Sensors and signal transduction pathways in vertebrate cell volume regulation

    DEFF Research Database (Denmark)

    Hoffmann, Else K; Pedersen, Stine F

    2006-01-01

    to the identification of transporter binding partners such as protein kinases and phosphatases, cytoskeletal elements and lipids. Considerable progress has also been made recently in understanding the upstream elements in volume sensing and volume-sensitive signal transduction, and salient features of these systems...

  18. Retinal Physiology: Non-Bipolar-Cell Excitatory Drive in the Inner Retina.

    Science.gov (United States)

    Baden, Tom; Euler, Thomas

    2016-08-01

    The long-held view that bipolar cells provide the exclusive excitatory drive to the mammalian inner retina has been challenged: new studies indicate that, instead, at least two cells that lack the dendrites characteristic for bipolar cells, and therefore resemble amacrine cells, excite inner retinal circuits using glutamate.

  19. Adeno-associated viral vector transduction of human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Stender, Stefan; Murphy, Mary; O'Brien, Tim;

    2007-01-01

    Mesenchymal stem cells (MSCs) have received considerable attention in the emerging field of regenerative medicine. One aspect of MSC research focuses on genetically modifying the cells with the aim of enhancing their regenerative potential. Adeno-associated virus (AAV) holds promise as a vector...... for human gene therapy, primarily due to its lack of pathogenicity and low risk of insertional mutagenesis. However, the existing data pertaining to AAV transduction of MSCs is limited. The objective of this work was to examine the efficiency and kinetics of in vitro transduction using AAV serotype 2...... in human MSCs and to assess whether AAV transduction affects MSC multipotentiality. The results indicated that human MSCs could indeed be transiently transduced in vitro by the AAV2 vector with efficiencies of up to 65%. The percentage of GFP-positive cells peaked at 4 days post-transduction and declined...

  20. Suppression of tumorigenicity and metastatic potential of melanoma cells by transduction of interferon gene

    Directory of Open Access Journals (Sweden)

    Lykhova A. A.

    2014-01-01

    Full Text Available The aim of this study was to investigate an inhibitory effect of baculovirus-mediated transduction of the murine interferon-beta gene on mouse melanoma in vitro and in vivo. Methods. Studies were performed on B16 mouse melanoma (MM-4 cell line. Transduction, immunocytochemical and tumor cell biology approaches have been used in this study. Results. Transduction of MM-4 cells by the recombinant baculovirus with IFN-beta gene is accompanied by morphological changes of tumor cells, suppression of cell proliferation, significant inhibition of platting efficiency of cells and their colonies formation in semisolid agar. Moreover, transduction of melanoma MM-4 cells by the baculovirus IFN-transgene leads to inhibition of tumorigenicity and metastatic ability of the cells in vivo. The intravenous administration of recombinant baculovirus vector with IFN gene inhibits growth of metastases induced in the lungs of mice by intravenously injected tumor cells. Conclusions. Transduction of mouse melanoma cells by the recombinant baculovirus with murine IFN-beta gene inhibits their proliferative potential, tumorigenicity and metastatic activity.

  1. Analysis of 4070A envelope levels in retroviral preparations and effect on target cell transduction efficiency.

    Science.gov (United States)

    Slingsby, J H; Baban, D; Sutton, J; Esapa, M; Price, T; Kingsman, S M; Kingsman, A J; Slade, A

    2000-07-01

    A number of stable producer cell lines for high-titer Mo-MuLV vectors have been constructed. Development has previously centered on increasing end-point titers by producing maximal levels of Mo-MuLV Gag/Pol, envelope glycoproteins, and retroviral RNA genomes. We describe the production yields and transduction efficiency characteristics of two Mo-MuLV packaging cell lines, FLYA13 and TEFLYA. Although they both produce 4070A-pseudotyped retroviral vectors reproducibly at >1 x 10(6) LFU ml(-1), the transduction efficiency of unconcentrated and concentrated virus from FLYA13 lines is poor compared with vector preparations from TEFLYA lines. A powerful inhibitor of retroviral transduction is secreted by FLYA13 packaging cells. We show that the inhibitory factor does not affect transduction of target cells by RD114-pseudotyped vectors. This suggests that the inhibitory factor functions at the level of envelope-receptor interactions. Phosphate starvation of target cells shows a two-fold increase in Pit2 receptor mRNA and causes some improvement in FLYA13 virus transduction efficiency. Western blots show that FLYA13 viral samples contain an eight-fold higher ratio of 4070A envelope to p30gag than that of virus produced by TEFLYA producer cell lines. This study correlates overexpression of 4070A envelope glycoprotein in retroviral preparations with a reduction of transduction efficiency at high multiplicities of infection. We suggest that TEFLYA packaging cells express preferable levels of 4070A compared with FLYA13, which not only enables high-titer stocks to be generated, but also facilitates a high efficiency of transduction of target cells. PMID:10910141

  2. Hair cell mechano-transduction : Its influence on the gross mechanical characteristics of a hair cell sense organ

    NARCIS (Netherlands)

    vanNetten, SM

    1997-01-01

    The complex mechanical behaviour of a hair cell bundle appears to be a direct consequence of the gating forces on the individual transduction channels. The mechanical molecular interactions involved in transduction channel gating, therefore, also bear a reciprocal influence, via the hair bundles; on

  3. Decitabine suspends human CD34+ cell differentiation and proliferation during lentiviral transduction.

    Science.gov (United States)

    Uchida, Naoya; Hsieh, Matthew M; Platner, Charlotte; Saunthararajah, Yogen; Tisdale, John F

    2014-01-01

    Efficient ex vivo transduction of hematopoietic stem cells (HSCs) is encumbered by differentiation which reduces engraftment. We hypothesized that inhibiting DNA methyltransferase with decitabine would block differentiation of transduced CD34+ cells under cytokine stimulation and thus improve transduction efficiency for engrafting HSCs. Human CD34+ cells in cytokine-containing media were treated with or without decitabine for 24 or 48 hours, and then these cells were transduced with a GFP-expressing lentiviral vector. Utilizing decitabine pre-treatment for 48 hours, we observed an equivalent percentage of successfully transduced cells (GFP-positivity) and a higher percentage of cells that retained CD34 positivity, compared to no decitabine exposure. Cell proliferation was inhibited after decitabine exposure. Similar results were observed among CD34+ cells from six different donors. Repopulating activity was evaluated by transplantation into NOD/SCID/IL2Rγnull mice and demonstrated an equivalent percentage of GFP-positivity in human cells from decitabine-treated samples and a trend for higher human cell engraftment (measured 20-24 weeks after transplantation), compared to no decitabine exposure. In conclusion, ex vivo decitabine exposure inhibits both differentiation and proliferation in transduced human CD34+ cells and modestly increases the engraftment ability in xenograft mice, while the transduction efficiency is equivalent in decitabine exposure, suggesting improvement of lentiviral transduction for HSCs.

  4. Decitabine suspends human CD34+ cell differentiation and proliferation during lentiviral transduction.

    Directory of Open Access Journals (Sweden)

    Naoya Uchida

    Full Text Available Efficient ex vivo transduction of hematopoietic stem cells (HSCs is encumbered by differentiation which reduces engraftment. We hypothesized that inhibiting DNA methyltransferase with decitabine would block differentiation of transduced CD34+ cells under cytokine stimulation and thus improve transduction efficiency for engrafting HSCs. Human CD34+ cells in cytokine-containing media were treated with or without decitabine for 24 or 48 hours, and then these cells were transduced with a GFP-expressing lentiviral vector. Utilizing decitabine pre-treatment for 48 hours, we observed an equivalent percentage of successfully transduced cells (GFP-positivity and a higher percentage of cells that retained CD34 positivity, compared to no decitabine exposure. Cell proliferation was inhibited after decitabine exposure. Similar results were observed among CD34+ cells from six different donors. Repopulating activity was evaluated by transplantation into NOD/SCID/IL2Rγnull mice and demonstrated an equivalent percentage of GFP-positivity in human cells from decitabine-treated samples and a trend for higher human cell engraftment (measured 20-24 weeks after transplantation, compared to no decitabine exposure. In conclusion, ex vivo decitabine exposure inhibits both differentiation and proliferation in transduced human CD34+ cells and modestly increases the engraftment ability in xenograft mice, while the transduction efficiency is equivalent in decitabine exposure, suggesting improvement of lentiviral transduction for HSCs.

  5. Potentiating action of propofol at GABAA receptors of retinal bipolar cells

    DEFF Research Database (Denmark)

    Yue, Lan; Xie, An; Bruzik, Karol S;

    2011-01-01

    specific retinal neurons. The authors investigated the action of propofol on GABA-elicited membrane current responses of retinal bipolar cells, which have both GABA(A) and GABA(C) receptors. Methods. Single, enzymatically dissociated bipolar cells obtained from rat retina were treated with propofol...

  6. CarbonNanoTubes (CNT) in bipolar plates for PEM fuel cell applications

    Energy Technology Data Exchange (ETDEWEB)

    Grundler, M.; Derieth, T.; Beckhaus, P.; Heinzel, A. [centre for fuel cell technology ZBT GmbH (Germany)

    2010-07-01

    Using standard mass production techniques for the fabrication of fuel cell components, such as bipolar plates, is a main issue for the commercialisation of PEM fuel cell systems. Bipolar plates contribute significantly to the cost structure of PEM stacks. In an upcoming fuel cell market a large number of bipolar plates with specific high-quality standards will be needed. At the Centre for Fuel Cell Technology (ZBT) together with the University of Duisburg-Essen fuel cell stacks based on injection moulded bipolar plates have been developed and demonstrated successfully [1]. This paper focuses on the interactions between carbon filling materials (graphite, carbon black and carbon nanotubes (CNT)) in compound based bipolar plates and especially the potential of CNTs, which were used in bipolar plates for the first time. The entire value added chain based on the feedstock, the compounding and injection moulding process, the component bipolar plate, up to the operation of a PEM single fuel cell stack with CNT-based bipolar plates is disclosed. (orig.)

  7. Comparative Transduction Mechanisms of Vestibular Otolith Hair Cells

    Science.gov (United States)

    Baird, Richard A.

    1994-01-01

    Hair cells in the bullfrog vestibular otolith organs regenerate following aminoglycoside ototoxicity. Hair cells in these organs are differentially sensitive to gentamicin, with saccular hair cells and hair cells in the utricular striola being damaged at lower gentamicin concentrations than hair cells in the utricular extrastriola. Regenerating hair cells in these organs have short hair bundles and can be classified into a number of phenotypes using the same morphological criteria used to identify their mature counterparts. Our studies suggest that some supporting cells can convert, or transdifferentiate,into hair cells without an intervening cell division. By stimulating these processes in humans, clinicians may be able to alleviate human deafness and peripheral vestibular disorders by regenerating and replacing lost hair cells. In vivo and in vitro studies were done on cell proliferation and hair cell regeneration.

  8. Vectofusin-1, a new viral entry enhancer, strongly promotes lentiviral transduction of human hematopoietic stem cells.

    Science.gov (United States)

    Fenard, David; Ingrao, Dina; Seye, Ababacar; Buisset, Julien; Genries, Sandrine; Martin, Samia; Kichler, Antoine; Galy, Anne

    2013-05-07

    Gene transfer into hCD34(+) hematopoietic stem/progenitor cells (HSCs) using human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors (LVs) has several promising therapeutic applications. Yet, efficiency, safety, and cost of LV gene therapy could be ameliorated by enhancing target cell transduction levels and reducing the amount of LV used on the cells. Several transduction enhancers already exist such as fibronectin fragments and cationic compounds, but all present limitations. In this study, we describe a new transduction enhancer called Vectofusin-1, which is a short cationic peptide, active on several LV pseudotypes. Vectofusin-1 is used as a soluble additive to safely increase the frequency of transduced HSCs and to augment the level of transduction to one or two copies of vector per cell in a vector dose-dependent manner. Vectofusin-1 acts at the entry step by promoting the adhesion and the fusion between viral and cellular membranes. Vectofusin-1 is therefore a promising additive that could significantly ameliorate hCD34(+) cell-based gene therapy.Molecular Therapy-Nucleic Acids (2013) 2, e90; doi:10.1038/mtna.2013.17; published online 7 May 2013.

  9. Ex Vivo and In Vivo Lentivirus-Mediated Transduction of Airway Epithelial Progenitor Cells.

    Science.gov (United States)

    Leoni, Giulia; Wasowicz, Marguerite Y; Chan, Mario; Meng, Cuixiang; Farley, Raymond; Brody, Steven L; Inoue, Makoto; Hasegawa, Mamoru; Alton, Eric W F W; Griesenbach, Uta

    2015-01-01

    A key challenge in pulmonary gene therapy for cystic fibrosis is to provide long-term correction of the genetic defect. This may be achievable by targeting airway epithelial stem/progenitor cells with an integrating vector. Here, we evaluated the ability of a lentiviral vector, derived from the simian immunodeficiency virus and pseudotyped with F and HN envelope proteins from Sendai virus, to transduce progenitor basal cells of the mouse nasal airways. We first transduced basal cell-enriched cultures ex vivo and confirmed efficient transduction of cytokeratin-5 positive cells. We next asked whether progenitor cells could be transduced in vivo. We evaluated the transduction efficiency in mice pretreated by intranasal administration of polidocanol to expose the progenitor cell layer. Compared to control mice, polidocanol treated mice demonstrated a significant increase in the number of transduced basal cells at 3 and 14 days post vector administration. At 14 days, the epithelium of treated mice contained clusters (4 to 8 adjacent cells) of well differentiated ciliated, as well as basal cells suggesting a clonal expansion. These results indicate that our lentiviral vector can transduce progenitor basal cells in vivo, although transduction required denudation of the surface epithelium prior to vector administration. PMID:26471068

  10. The efficiency of expressing human neprilysin by using lentiviral vector transduction in neural stem cells

    Institute of Scientific and Technical Information of China (English)

    黄文

    2013-01-01

    Objective To study the transduction efficiency of expressing human neprilysin by using lentiviral(Lenti-NEP) in mouse embryonic neural stem cells(NSC) in vitro. Methods Primary NSC were harvested from C57BL/6J pregnant mouse at embryonic day

  11. Enhancement of gene transduction efficiency in cancer cells using cationic liposome with hyperthermia.

    Directory of Open Access Journals (Sweden)

    Mushiake H

    2002-02-01

    Full Text Available We evaluated the effects of hyperthermia on the efficiency of gene transduction by using a cationic liposome to develop an efficient method for lipofection. We used Lewis lung carcinoma (LLC, NIH3T3, and A549 cell lines, with Lipofectamine reagent as the cationic liposome and the LacZ gene as the reporter gene. In LLC, co-incubation of the cationic liposome and plasmid DNA complex (lipoplex with the cells for 2 h at 41 degrees C enhanced the efficiency of gene transduction approximately 1.4-fold compared to incubation for 2 h at 37 degrees C, as measured by X-gal staining and beta-galactosidase activity. In cell lines NIH3T3 and A549, the efficiency of gene transduction showed a tendency toward enhancement after 2 h co-incubation with lipoplex at 41 degrees C compared to that at 37 degrees C, as measured by X-gal staining. This is the first study to demonstrate the enhancement of gene transduction efficiency achieved by using a cationic liposome under conditions of hyperthermia. This method should prove useful for lipofection in other cancer cells.

  12. Synaptic plasticity in GNGA3-/- mice: Cone bipolar cells react up0onthe missing cone input and form ectopic synapses with rods

    OpenAIRE

    Humphries, Peter

    2006-01-01

    PUBLISHED In the mammalian retina, rods and cones connect to distinct sets of bipolar cells. Rods are presynaptic to a single type of rod bipolar cell, whereas cones connect to different types of cone bipolar cells. Synaptic rewiring between cone photoreceptor terminals and rod bipolar cell dendrites has been described as a general result of photoreceptor degeneration. To investigate whether cone bipolar cells also show synaptic plasticity in the absence of cone input, we studied the conne...

  13. Osmotin, a plant antifungal protein, subverts signal transduction to enhance fungal cell susceptibility.

    Science.gov (United States)

    Yun, D J; Ibeas, J I; Lee, H; Coca, M A; Narasimhan, M L; Uesono, Y; Hasegawa, P M; Pardo, J M; Bressan, R A

    1998-05-01

    The plant pathogenesis-related protein osmotin is an antifungal cytotoxic agent that causes rapid cell death in the yeast S. cerevisiae. We show here that osmotin uses a signal transduction pathway to weaken defensive cell wall barriers and increase its cytotoxic efficacy. The pathway activated by osmotin includes the regulatory elements of the mating pheromone response STE4, STE18, STE20, STE5, STE11, STE7, FUS3, KSS1, and STE12. Neither the pheromone receptor nor its associated G protein alpha subunit GPA1 are required for osmotin action. However, mutation of SST2, a negative regulator of G alpha proteins, resulted in supersensitivity to osmotin. Phosphorylation of STE7 was rapidly stimulated by osmotin preceding any changes in cell vitality or morphology. These results demonstrate that osmotin subverts target cell signal transduction as part of its mechanism of action. PMID:9660964

  14. Advanced Composite Bipolar Plate for Unitized Regenerative Fuel Cell/Electrolyzer Systems Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Development of an advanced composite bipolar plate is proposed for a unitized regenerative fuel cell and electrolyzer system that operates on pure feed streams...

  15. Transduction of the MPG-tagged fusion protein into mammalian cells and oocytes depends on amiloride-sensitive endocytic pathway

    Directory of Open Access Journals (Sweden)

    Cheon Yong-Pil

    2009-08-01

    Full Text Available Abstract Background MPG is a cell-permeable peptide with proven efficiency to deliver macromolecular cargoes into cells. In this work, we examined the efficacy of MPG as an N-terminal tag in a fusion protein to deliver a protein cargo and its mechanism of transduction. Results We examined transduction of MPG-EGFP fusion protein by live imaging, flow cytometry, along with combination of cell biological and pharmacological methods. We show that MPG-EGFP fusion proteins efficiently enter various mammalian cells within a few minutes and are co-localized with FM4-64, a general marker of endosomes. The transduction of MPG-EGFP occurs rapidly and is inhibited at a low temperature. The entry of MPG-EGFP is inhibited by amiloride, but cytochalasin D and methyl-β-cyclodextrin did not inhibit the entry, suggesting that macropinocytosis is not involved in the transduction. Overexpression of a mutant form of dynamin partially reduced the transduction of MPG-EGFP. The partial blockade of MPG-EGFP transduction by a dynamin mutant is abolished by the treatment of amiloride. MPG-EGFP transduction is also observed in the mammalian oocytes. Conclusion The results show that the transduction of MPG fusion protein utilizes endocytic pathway(s which is amiloride-sensitive and partially dynamin-dependent. Collectively, the MPG fusion protein could be further developed as a novel tool of "protein therapeutics", with potentials to be used in various cell systems including mammalian oocytes.

  16. The Development of Compression Moldable Polymer Composite Bipolar Plates for Fuel Cells

    OpenAIRE

    Cunningham, Brent David

    2007-01-01

    The development, design, and modeling of a rapid continuous processing scheme is developed to economically manufacture conductive polymer composite bipolar plates for fuel cells. Bipolar plates are required to possess several important properties for fuel cell operation, with the most sought after being electrical conductivity and mechanical strength. The polymer composite material generated at Virginia Tech is based on material generated by a wet-lay process and uses polyethylene terepthal...

  17. The use of additive manufacture for metallic bipolar plates in polymer electrolyte fuel cell stacks

    OpenAIRE

    Dawson, Richard; Patel, Anant; Rennie, Allan; White, Simon

    2014-01-01

    The bipolar plate is of critical importance to the efficient and long lasting operation of a polymer electrolyte fuel cell (PEMFC) stack. With advances in membrane electrode assembly (MEA) design greater attention has been focused on the bipolar plate and the important role it plays in performance and durability. Although carbon composite plates are a likely candidate for the mass introduction of fuel cells, it is metallic plates made from thin strip materials (typically 0.2 mm thick stainles...

  18. Image informatics for studying signal transduction in cells interacting with 3D matrices

    Science.gov (United States)

    Tzeranis, Dimitrios S.; Guo, Jin; Chen, Chengpin; Yannas, Ioannis V.; Wei, Xunbin; So, Peter T. C.

    2014-03-01

    Cells sense and respond to chemical stimuli on their environment via signal transduction pathways, complex networks of proteins whose interactions transmit chemical information. This work describes an implementation of image informatics, imaging-based methodologies for studying signal transduction networks. The methodology developed focuses on studying signal transduction networks in cells that interact with 3D matrices. It utilizes shRNA-based knock down of network components, 3D high-content imaging of cells inside the matrix by spectral multi-photon microscopy, and single-cell quantification using features that describe both cell morphology and cell-matrix adhesion pattern. The methodology is applied in a pilot study of TGFβ signaling via the SMAD pathway in fibroblasts cultured inside porous collagen-GAG scaffolds, biomaterials similar to the ones used clinically to induce skin regeneration. Preliminary results suggest that knocking down all rSMAD components affects fibroblast response to TGFβ1 and TGFβ3 isoforms in different ways, and suggest a potential role for SMAD1 and SMAD5 in regulating TGFβ isoform response. These preliminary results need to be verified with proteomic results that can provide solid evidence about the particular role of individual components of the SMAD pathway.

  19. Signal Transduction at the Single-Cell Level: Approaches to Study the Dynamic Nature of Signaling Networks.

    Science.gov (United States)

    Handly, L Naomi; Yao, Jason; Wollman, Roy

    2016-09-25

    Signal transduction, or how cells interpret and react to external events, is a fundamental aspect of cellular function. Traditional study of signal transduction pathways involves mapping cellular signaling pathways at the population level. However, population-averaged readouts do not adequately illuminate the complex dynamics and heterogeneous responses found at the single-cell level. Recent technological advances that observe cellular response, computationally model signaling pathways, and experimentally manipulate cells now enable studying signal transduction at the single-cell level. These studies will enable deeper insights into the dynamic nature of signaling networks.

  20. Method for Efficient Transduction of Cancer Stem Cells

    Science.gov (United States)

    Walker, Kiera; Hjelmeland, Anita

    2016-01-01

    Ectopic gene expression through introduction of cDNA and gene silencing by RNA interference each facilitate the elucidation of molecular pathways in both normal and pathologic states. As transfection efficiency in some primary and established cells is low, lentivirus based expression systems with high infection rates can improve experimental design. For example, glioblastoma cells and particularly the cancer stem cell (CSC) fraction can be difficult to transfect but are amenable to viral infection. Greater utilization of lentivirus for expression of cDNA and shRNA in CSCs may be limited due to technical challenges, including elimination of pro-differentiating fetal bovine serum (FBS). We therefore generated a subline of 293Ts that can proliferate and efficiently produce virus in CSC media, designated CSC293Ts. We provide detailed protocols for the generation of CSC293Ts and for the production of lentivirus for CSC infection using glioblastoma as a model. Our data demonstrate that serum free media from CSC293Ts consistently produces greater than 80% infection rates without virus concentration. We believe that the detailed protocols provided here can be adapted for multiple cell types for broad utility.

  1. Age-related decrease in rod bipolar cell density of the human retina: an immunohistochemical study

    Indian Academy of Sciences (India)

    P Aggarwal; T C Nag; S Wadhwa

    2007-03-01

    During normal ageing, the rods (and other neurones) undergo a significant decrease in density in the human retina from the fourth decade of life onward. Since the rods synapse with the rod bipolar cells in the outer plexiform layer, a decline in rod density (mainly due to death) may ultimately cause an associated decline of the neurones which, like the rod bipolar cells, are connected to them. The rod bipolar cells are selectively stained with antibodies to protein kinase C-. This study examined if rod bipolar cell density changes with ageing of the retina, utilizing donor human eyes (age: 6–91 years). The retinas were fixed and their temporal parts from the macula to the mid-periphery sectioned and processed for protein kinase C- immunohistochemistry. The density of the immunopositive rod bipolar cells was estimated in the mid-peripheral retina (eccentricity: 3–5 mm) along the horizontal temporal axis. The results show that while there is little change in the density of the rod bipolar cells from 6 to 35 years (2.2%), the decline during the period from 35 to 62 years is about 21% and between seventh and tenth decades, it is approximately 27%.

  2. Performance evaluation and characterization of metallic bipolar plates in a proton exchange membrane (PEM) fuel cell

    Science.gov (United States)

    Hung, Yue

    Bipolar plate and membrane electrode assembly (MEA) are the two most repeated components of a proton exchange membrane (PEM) fuel cell stack. Bipolar plates comprise more than 60% of the weight and account for 30% of the total cost of a fuel cell stack. The bipolar plates perform as current conductors between cells, provide conduits for reactant gases, facilitate water and thermal management through the cell, and constitute the backbone of a power stack. In addition, bipolar plates must have excellent corrosion resistance to withstand the highly corrosive environment inside the fuel cell, and they must maintain low interfacial contact resistance throughout the operation to achieve optimum power density output. Currently, commercial bipolar plates are made of graphite composites because of their relatively low interfacial contact resistance (ICR) and high corrosion resistance. However, graphite composite's manufacturability, permeability, and durability for shock and vibration are unfavorable in comparison to metals. Therefore, metals have been considered as a replacement material for graphite composite bipolar plates. Since bipolar plates must possess the combined advantages of both metals and graphite composites in the fuel cell technology, various methods and techniques are being developed to combat metallic corrosion and eliminate the passive layer formed on the metal surface that causes unacceptable power reduction and possible fouling of the catalyst and the electrolyte. The main objective of this study was to explore the possibility of producing efficient, cost-effective and durable metallic bipolar plates that were capable of functioning in the highly corrosive fuel cell environment. Bulk materials such as Poco graphite, graphite composite, SS310, SS316, incoloy 800, titanium carbide and zirconium carbide were investigated as potential bipolar plate materials. In this work, different alloys and compositions of chromium carbide coatings on aluminum and SS316

  3. Carbon composite bipolar plate for high-temperature proton exchange membrane fuel cells (HT-PEMFCs)

    Science.gov (United States)

    Lee, Dongyoung; Lee, Dai Gil

    2016-09-01

    A carbon/epoxy composite bipolar plate is an ideal substitute for the brittle graphite bipolar plate for lightweight proton exchange membrane fuel cells (PEMFCs) because of its high specific strength and stiffness. However, conventional carbon/epoxy composite bipolar plates are not applicable for high-temperature PEMFCs (HT-PEMFCs) because these systems are operated at higher temperatures than the glass transition temperatures of conventional epoxies. Therefore, in this study, a cyanate ester-modified epoxy is adopted for the development of a carbon composite bipolar plate for HT-PEMFCs. The composite bipolar plate with exposed surface carbon fibers is produced without any surface treatments or coatings to increase the productivity and is integrated with a silicone gasket to reduce the assembly cost. The developed carbon composite bipolar plate exhibits not only superior electrical properties but also high thermo-mechanical properties. In addition, a unit cell test is performed, and the results are compared with those of the conventional graphite bipolar plate.

  4. Highly conductive thermoplastic composites for rapid production of fuel cell bipolar plates

    Science.gov (United States)

    Huang, Jianhua [Blacksburg, VA; Baird, Donald G [Blacksburg, VA; McGrath, James E [Blacksburg, VA

    2008-04-29

    A low cost method of fabricating bipolar plates for use in fuel cells utilizes a wet lay process for combining graphite particles, thermoplastic fibers, and reinforcing fibers to produce a plurality of formable sheets. The formable sheets are then molded into a bipolar plates with features impressed therein via the molding process. The bipolar plates formed by the process have conductivity in excess of 150 S/cm and have sufficient mechanical strength to be used in fuel cells. The bipolar plates can be formed as a skin/core laminate where a second polymer material is used on the skin surface which provides for enhanced conductivity, chemical resistance, and resistance to gas permeation.

  5. CD28 and T cell antigen receptor signal transduction coordinately regulate interleukin 2 gene expression in response to superantigen stimulation

    OpenAIRE

    1992-01-01

    Activation of an immune response requires intercellular contact between T lymphocytes and antigen-presenting cells (APC). Interaction of the T cell antigen receptor (TCR) with antigen in the context of major histocompatibility molecules mediates signal transduction, but T cell activation appears to require the induction of a second costimulatory signal transduction pathway. Recent studies suggest that interaction of CD28 with B7 on APC might deliver such a costimulatory signal. To investigate...

  6. STAT1 is involved in signal transduction in the EPO induced HEL cells

    Institute of Scientific and Technical Information of China (English)

    JIANGCHU; CHANGYUNGUI; 等

    1998-01-01

    Erythropoietin(EPO) is the major regulator of mamalian erythropoisis,which stimulates the growth and differentiation of hematopoietic cells through interaction with its receptor(EPO-R),Here we use HEL cells (a human erythro-leukemia cell line) as a model to elucidate the pathway of signal transduction in the EPO-induced HEL cells.Our data show that the EPOR (EPO receptor) on the surface of HEL cells interacts with the Janus tyrosine protein kinase(Jak2) to transduce intracellular signals through phosphorylation of cytoplasmic proteins in EPO-treated HEL cells.Both STAT1 and STAT5 in this cell line are tyrosine-phosphorylated and translocated to nucleus following the dinding of EPO to HEL cells.Furthermore,the dinding of both STAT1 and STAT5 proteins to specific DNA elements(SIE and PIE elements) is revealed in an EPO-dependent manner,Our data demonstrate that the pathway of signal transduction following the binding of EPO to HEL cells is similar to immature eryhroid cell from the spleen of mice infected with anemia strain of Friend virus.

  7. Mitochondria-derived hydrogen peroxide selectively enhances T cell receptor-initiated signal transduction.

    Science.gov (United States)

    Gill, Tejpal; Levine, Alan D

    2013-09-01

    T cell receptor (TCR)-initiated signal transduction is reported to increase production of intracellular reactive oxygen species, such as superoxide (O2˙(-)) and hydrogen peroxide (H2O2), as second messengers. Although H2O2 can modulate signal transduction by inactivating protein phosphatases, the mechanism and the subcellular localization of intracellular H2O2 as a second messenger of the TCR are not known. The antioxidant enzyme superoxide dismutase (SOD) catalyzes the dismutation of highly reactive O2˙(-) into H2O2 and thus acts as an intracellular generator of H2O2. As charged O2˙(-) is unable to diffuse through intracellular membranes, cells express distinct SOD isoforms in the cytosol (Cu,Zn-SOD) and mitochondria (Mn-SOD), where they locally scavenge O2˙(-) leading to production of H2O2. A 2-fold organelle-specific overexpression of either SOD in Jurkat T cell lines increases intracellular production of H2O2 but does not alter the levels of intracellular H2O2 scavenging enzymes such as catalase, membrane-bound peroxiredoxin1 (Prx1), and cytosolic Prx2. We report that overexpression of Mn-SOD enhances tyrosine phosphorylation of TCR-associated membrane proximal signal transduction molecules Lck, LAT, ZAP70, PLCγ1, and SLP76 within 1 min of TCR cross-linking. This increase in mitochondrial H2O2 specifically modulates MAPK signaling through the JNK/cJun pathway, whereas overexpressing Cu,Zn-SOD had no effect on any of these TCR-mediated signaling molecules. As mitochondria translocate to the immunological synapse during TCR activation, we hypothesize this translocation provides the effective concentration of H2O2 required to selectively modulate downstream signal transduction pathways.

  8. Nitric Oxide Modulates the Temporal Properties of the Glutamate Response in Type 4 OFF Bipolar Cells

    Science.gov (United States)

    Vielma, Alex H.; Agurto, Adolfo; Valdés, Joaquín; Palacios, Adrián G.; Schmachtenberg, Oliver

    2014-01-01

    Nitric oxide (NO) is involved in retinal signal processing, but its cellular actions are only partly understood. An established source of retinal NO are NOACs, a group of nNOS-expressing amacrine cells which signal onto bipolar, other amacrine and ganglion cells in the inner plexiform layer. Here, we report that NO regulates glutamate responses in morphologically and electrophysiologically identified type 4 OFF cone bipolar cells through activation of the soluble guanylyl cyclase-cGMP-PKG pathway. The glutamate response of these cells consists of two components, a fast phasic current sensitive to kainate receptor agonists, and a secondary component with slow kinetics, inhibited by AMPA receptor antagonists. NO shortened the duration of the AMPA receptor-dependent component of the glutamate response, while the kainate receptor-dependent component remained unchanged. Application of 8-Br-cGMP mimicked this effect, while inhibition of soluble guanylate cyclase or protein kinase G prevented it, supporting a mechanism involving a cGMP signaling pathway. Notably, perfusion with a NOS-inhibitor prolonged the duration of the glutamate response, while the NO precursor L-arginine shortened it, in agreement with a modulation by endogenous NO. Furthermore, NO accelerated the response recovery during repeated stimulation of type 4 cone bipolar cells, suggesting that the temporal response properties of this OFF bipolar cell type are regulated by NO. These results reveal a novel cellular mechanism of NO signaling in the retina, and represent the first functional evidence of NO modulating OFF cone bipolar cells. PMID:25463389

  9. THE ENHANCED GREEN FLUORESCENT PROTEIN AS A MARKER FOR HUMAN TUMOR CELLS LABELLED BY RETROVIRAL TRANSDUCTION

    Institute of Scientific and Technical Information of China (English)

    傅建新; 王玮; 白霞; 卢大儒; 阮长耿; 陈子兴

    2002-01-01

    Objective: To investigate the feasibility of marking the human tumor cells with enhanced green fluorescent protein (EGFP) in vitro. Methods: The retroviral vector LGSN encoding EGFP was constructed and three human tumor cell lines were infected with LGSN amphotropic virus. Tumor cell lines that stably express EGFP were selected with G418. The integration and expression of EGFP gene were analyzed by polymerase chain reaction, and flow cytometry (FCM). Results: After gene transfection and ping-pong transduction, amphotropic producer line Am12/LGSN was generated with a stable green fluorescence signal readily detectable by FCM in up to 97% of examined cells. The viral titer in the supernatants was up to 8.2×105CFU/ml. After transduction and selection, G418-resistant leukemia K562, mammary carcinoma MCF-7, and bladder cancer 5637 cells were developed, in which the integration of both EGFP and neomycin resistance gene was confirmed by DNA amplification. In comparison with uninfected cells, FCM analysis revealed EGFP expression in up to 90% (range 85.5%~90.0%) of tumor cells containing LGSN provirus. Conclusion: The retroviral vector LGSN can effectively mark the human tumor cells with a stably EGFP expression which may be in studying tumor growth, metastasis and angiogenesis.

  10. AUDITORY HAIR CELL EXPLANT CO-CULTURES PROMOTE THE DIFFERENTIATION OF STEM CELLS INTO BIPOLAR NEURONS

    OpenAIRE

    Coleman, B.; Fallon, J. B.; Gillespie, L.N.; Silva, M.G.; Shepherd, R.K.

    2006-01-01

    Auditory neurons, the target neurons of the cochlear implant, degenerate following a sensorineural hearing loss. The goal of this research is to direct the differentiation of embryonic stem cells (SCs) into bipolar auditory neurons that can be used to replace degenerating neurons in the deafened mammalian cochlea. Successful replacement of auditory neurons is likely to result in improved clinical outcomes for cochlear implant recipients. We examined two post-natal auditory co-culture models w...

  11. Comparative transduction mechanisms of hair cells in the bullfrog utriculus. 1: Responses to intracellular current

    Science.gov (United States)

    Baird, Richard A.

    1994-01-01

    Hair cells in the bullfrog sacculus are specifically adapted to sense small-amplitude, high-frequency linear accelerations. These hair cells display many properties that are undesirable or inappropriate for hair cells that must provide static gravity sensitivity. This study resulted in part due to an interest in seeing how the transduction mechanisms of hair cells in a gravity-sensing otolith endorgan would differ from those in the bullfrog sacculus. The bullfrog utriculus is an appropriate model for these studies, because its structure is representative of higher vertebrates in general and its function as a sensor of static gravity and dynamic linear acceleration is well known. Hair cells in the bullfrog utriculus, classifiable as Type 2 by cell body and synapse morphology, differ markedly in hair bundle morphology from those in the bullfrog sacculus. Moreover, the hair bundle morphologies of utricular hair cells, unlike those in the sacculus, differ in different membrane regions.

  12. Kainate receptors mediate signaling in both transient and sustained OFF bipolar cell pathways in mouse retina.

    Science.gov (United States)

    Borghuis, Bart G; Looger, Loren L; Tomita, Susumu; Demb, Jonathan B

    2014-04-30

    A fundamental question in sensory neuroscience is how parallel processing is implemented at the level of molecular and circuit mechanisms. In the retina, it has been proposed that distinct OFF cone bipolar cell types generate fast/transient and slow/sustained pathways by the differential expression of AMPA- and kainate-type glutamate receptors, respectively. However, the functional significance of these receptors in the intact circuit during light stimulation remains unclear. Here, we measured glutamate release from mouse bipolar cells by two-photon imaging of a glutamate sensor (iGluSnFR) expressed on postsynaptic amacrine and ganglion cell dendrites. In both transient and sustained OFF layers, cone-driven glutamate release from bipolar cells was blocked by antagonists to kainate receptors but not AMPA receptors. Electrophysiological recordings from bipolar and ganglion cells confirmed the essential role of kainate receptors for signaling in both transient and sustained OFF pathways. Kainate receptors mediated responses to contrast modulation up to 20 Hz. Light-evoked responses in all mouse OFF bipolar pathways depend on kainate, not AMPA, receptors.

  13. The signal transduction pathway in the proliferation of airway smooth muscle cells induced by urotensin Ⅱ

    Institute of Scientific and Technical Information of China (English)

    陈亚红; 赵鸣武; 姚婉贞; 庞永政; 唐朝枢

    2004-01-01

    Background Human urotensin Ⅱ (UⅡ) is the most potent mammalian vasoconstrictor identified so far. Our previous study showed that UⅡ is a potent mitogen of airway smooth muscle cells (ASMC) inducing ASMC proliferation in a dose-dependent manner. The signal transduction pathway of UⅡ mitogenic effect remains to be clarified. This study was conducted to investigate the signal transduction pathway in the proliferation of ASMC induced by UⅡ.Methods In primary cultures of rat ASMCs, activities of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and calcineurin (CaN) induced by UⅡ were measured. The effect of CaN on PKC and MAPK was studied by adding cyclosporin A (CsA), a specific inhibitor of CaN. Using H7 and PD98059, inhibitors of PKC and MAPK, respectively, to study the effect of PKC and MAPK on CaN. The cytosolic free calcium concentration induced by UⅡ was measured using Fura-2/AM. Results UⅡ 10-7 mol/L stimulated ASMC PKC and MAPK activities by 44% and 24% (P0.05). CsA 10-6 mol/L inhibited UⅡ-stimulated PKC activity by 14% (P0.05).Conclusions UⅡ increases cytosolic free calcium concentration and activates PKC, MAPK and CaN. The signal transduction pathway between PKC and CaN has cross-talk.

  14. Transduction of Murine Hematopoietic Stem Cells with Tetracycline-regulated Lentiviral Vectors.

    Science.gov (United States)

    Stahlhut, Maike; Schambach, Axel; Kustikova, Olga S

    2016-01-01

    Tetracycline-regulated integrating vectors allow pharmacologically controlled genetic modification of murine and human hematopoietic stem cells (HSCs). This approach combines the stable transgene insertion into a host genome with the opportunity for time- and dose-controlled reversible transgene expression in HSCs. Here, we describe the step-by-step protocol for transduction of murine stem-cell enriched populations of bone marrow cells, such as lineage negative cells (Lin(-)), with a lentiviral vector expressing the enhanced green fluorescent protein (EGFP) under the control of the tetracycline-regulated promoter. This chapter explains how to establish in vitro and in vivo systems to study transgene dose-dependent mechanisms affecting cell fate decisions of genetically modified hematopoietic cells. PMID:27317173

  15. Signal transduction pathway of nitric oxide inducing PC12 cell death

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To study signal transduction pathway of nitric oxideinducing death of PC12 cells.Methods: Cell survival rate was measured with MTT assay, and caspase-3 activity with caspase-3 assay kits after PC12 cells were incubated with sodium nitroprusside (SNP), caspase-3 inhibitor Ⅱ plus SNP or p38 inhibitor-SB203580 plus SNP.Results: SNP induced death of PC12 cells in dose- and time-dependent manner and enhanced caspase-3 activity gradually. Both caspase-3 inhibitor Ⅱ and SB203580 reduced cell death, but SB203580 reduced caspase-3 activity significantly.Conclusions: NO may induce death of PC12 cells through activation of p38 and caspase-3.

  16. Adaptation to background light enables contrast coding at rod bipolar cell synapses

    OpenAIRE

    Ke, Jiang-Bin; Wang, Yanbin V.; Borghuis, Bart G.; Cembrowski, Mark S.; Riecke, Hermann; Kath, William L.; Demb, Jonathan B; Joshua H Singer

    2013-01-01

    Rod photoreceptors contribute to vision over a ~6 log-unit range of light intensities. The wide dynamic range of rod vision is thought to depend upon light intensity-dependent switching between two parallel pathways linking rods to ganglion cells: a rod→rod bipolar (RB) cell pathway that operates at dim backgrounds and a rod→cone→cone bipolar cell pathway that operates at brighter backgrounds. We evaluated this conventional model of rod vision by recording rod-mediated light responses from ga...

  17. Gene transfer and genome-wide insertional mutagenesis by retroviral transduction in fish stem cells.

    Directory of Open Access Journals (Sweden)

    Qizhi Liu

    Full Text Available Retrovirus (RV is efficient for gene transfer and integration in dividing cells of diverse organisms. RV provides a powerful tool for insertional mutagenesis (IM to identify and functionally analyze genes essential for normal and pathological processes. Here we report RV-mediated gene transfer and genome-wide IM in fish stem cells from medaka and zebrafish. Three RVs were produced for fish cell transduction: rvLegfp and rvLcherry produce green fluorescent protein (GFP and mCherry fluorescent protein respectively under control of human cytomegalovirus immediate early promoter upon any chromosomal integration, whereas rvGTgfp contains a splicing acceptor and expresses GFP only upon gene trapping (GT via intronic in-frame integration and spliced to endogenous active genes. We show that rvLegfp and rvLcherry produce a transduction efficiency of 11~23% in medaka and zebrafish stem cell lines, which is as 30~67% efficient as the positive control in NIH/3T3. Upon co-infection with rvGTgfp and rvLcherry, GFP-positive cells were much fewer than Cherry-positive cells, consistent with rareness of productive gene trapping events versus random integration. Importantly, rvGTgfp infection in the medaka haploid embryonic stem (ES cell line HX1 generated GTgfp insertion on all 24 chromosomes of the haploid genome. Similar to the mammalian haploid cells, these insertion events were presented predominantly in intergenic regions and introns but rarely in exons. RV-transduced HX1 retained the ES cell properties such as stable growth, embryoid body formation and pluripotency gene expression. Therefore, RV is proficient for gene transfer and IM in fish stem cells. Our results open new avenue for genome-wide IM in medaka haploid ES cells in culture.

  18. A Review of Metallic Bipolar Plates for Proton Exchange Membrane Fuel Cells: Materials and Fabrication Methods

    Directory of Open Access Journals (Sweden)

    Shahram Karimi

    2012-01-01

    Full Text Available The proton exchange membrane fuel cell offers an exceptional potential for a clean, efficient, and reliable power source. The bipolar plate is a key component in this device, as it connects each cell electrically, supplies reactant gases to both anode and cathode, and removes reaction products from the cell. Bipolar plates have been fabricated primarily from high-density graphite, but in recent years, much attention has been paid to developing cost-effective and feasible alternative materials. Two different classes of materials have attracted attention: metals and composites. This paper offers a comprehensive review of the current research being carried out on metallic bipolar plates, covering materials and fabrication methods.

  19. A CRISPR-Based Toolbox for Studying T Cell Signal Transduction

    Science.gov (United States)

    Chi, Shen; Weiss, Arthur; Wang, Haopeng

    2016-01-01

    CRISPR/Cas9 system is a powerful technology to perform genome editing in a variety of cell types. To facilitate the application of Cas9 in mapping T cell signaling pathways, we generated a toolbox for large-scale genetic screens in human Jurkat T cells. The toolbox has three different Jurkat cell lines expressing distinct Cas9 variants, including wild-type Cas9, dCas9-KRAB, and sunCas9. We demonstrated that the toolbox allows us to rapidly disrupt endogenous gene expression at the DNA level and to efficiently repress or activate gene expression at the transcriptional level. The toolbox, in combination with multiple currently existing genome-wide sgRNA libraries, will be useful to systematically investigate T cell signal transduction using both loss-of-function and gain-of-function genetic screens. PMID:27057542

  20. Comprehensive analysis of signal transduction in three-dimensional ECM-based tumor cell cultures

    Directory of Open Access Journals (Sweden)

    Iris Eke

    2015-11-01

    Full Text Available Analysis of signal transduction and protein phosphorylation is fundamental to understand physiological and pathological cell behavior as well as identification of novel therapeutic targets. Despite the fact that more physiological three-dimensional cell culture assays are increasingly used, particularly proteomics and phosphoproteomics remain challenging due to easy, robust and reproducible sample preparation. Here, we present an easy-to-perform, reliable and time-efficient method for the production of 3D cell lysates without compromising cell adhesion before cell lysis. The samples can be used for Western blotting as well as phosphoproteome array technology. This technique would be of interest for researchers working in all fields of biology and drug development.

  1. A CRISPR-Based Toolbox for Studying T Cell Signal Transduction

    Directory of Open Access Journals (Sweden)

    Shen Chi

    2016-01-01

    Full Text Available CRISPR/Cas9 system is a powerful technology to perform genome editing in a variety of cell types. To facilitate the application of Cas9 in mapping T cell signaling pathways, we generated a toolbox for large-scale genetic screens in human Jurkat T cells. The toolbox has three different Jurkat cell lines expressing distinct Cas9 variants, including wild-type Cas9, dCas9-KRAB, and sunCas9. We demonstrated that the toolbox allows us to rapidly disrupt endogenous gene expression at the DNA level and to efficiently repress or activate gene expression at the transcriptional level. The toolbox, in combination with multiple currently existing genome-wide sgRNA libraries, will be useful to systematically investigate T cell signal transduction using both loss-of-function and gain-of-function genetic screens.

  2. MAPKs and Signal Transduction in the Control of Gastrointestinal Epithelial Cell Proliferation and Differentiation

    Directory of Open Access Journals (Sweden)

    Luciana H. Osaki

    2013-05-01

    Full Text Available Mitogen-activated protein kinase (MAPK pathways are activated by several stimuli and transduce the signal inside cells, generating diverse responses including cell proliferation, differentiation, migration and apoptosis. Each MAPK cascade comprises a series of molecules, and regulation takes place at different levels. They communicate with each other and with additional pathways, creating a signaling network that is important for cell fate determination. In this review, we focus on ERK, JNK, p38 and ERK5, the major MAPKs, and their interactions with PI3K-Akt, TGFβ/Smad and Wnt/β-catenin pathways. More importantly, we describe how MAPKs regulate cell proliferation and differentiation in the rapidly renewing epithelia that lines the gastrointestinal tract and, finally, we highlight the recent findings on nutritional aspects that affect MAPK transduction cascades.

  3. Novel optical methodologies in studying mechanical signal transduction in mammalian cells

    Science.gov (United States)

    Stamatas, G. N.; McIntire, L. V.

    1999-01-01

    For the last 3 decades evidence has been accumulating that some types of mammalian cells respond to their mechanically active environment by altering their morphology, growth rate, and metabolism. The study of such responses is very important in understanding, physiological and pathological conditions ranging from bone formation to atherosclerosis. Obtaining this knowledge has been the goal for an active research area in bioengineering termed cell mechanotransduction. The advancement of optical methodologies used in cell biology research has given the tools to elucidate cellular mechanisms that would otherwise be impossible to visualize. Combined with molecular biology techniques, they give engineers invaluable tools in understanding the chemical pathways involved in mechanotransduction. Herein we briefly review the current knowledge on mechanical signal transduction in mammalian cells, focusing on the application of novel optical techniques in the ongoing research.

  4. THE TRANSMEMBRANE SIGNAL TRANSDUCTION IN HEp-2 CELLS INDUCED BY BACTERIAL ADHERENCE

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ In order to understand the role of transmembrane signal transduction of host cells in the early steps of infection,the adherence of E. coli to HEp-2 cells and the change of activity of phospholipase C-γ (PLC-γ) induced by the adherence were investigated.The adherence of enteropathogenic E.coli (EPEC), strain E.7, induced a significant increase of inositol-triphosphat (IP-3) level in HEp-2 cells. The adherence of the bacteria and the increase of IP-3 was kinetically correlated. Whereas the increase of IP3 level induced by the adherence of the control strain EPEC (H511), a non-piliated strain, was much meager than that by E7, a piliated strain. The results highlighted an important role of transmembrane signals like IP-3 in the pathogenesis of EPEC.

  5. Dimensional metrology of bipolar fuel cell plates using laser spot triangulation probes

    Science.gov (United States)

    Muralikrishnan, Bala; Ren, Wei; Everett, Dennis; Stanfield, Eric; Doiron, Ted

    2011-07-01

    As in any engineering component, manufacturing a bipolar fuel cell plate for a polymer electrolyte membrane (PEM) hydrogen fuel cell power stack to within its stated design tolerances is critical in achieving the intended function. In a bipolar fuel cell plate, the dimensional features of interest include channel width, channel height, channel parallelism, side wall taper, straightness of the bottom or side walls, plate parallelism, etc. Such measurements can be performed on coordinate measuring machines (CMMs) with micro-probes that can access the narrow channels. While CMM measurements provide high accuracy (less than 1 µm), they are often very slow (taking several hours to measure a single plate) and unsuitable for the manufacturing environment. In this context, we describe a system for rapid dimensional measurement of bipolar fuel cell plates using two laser spot triangulation probes that can achieve comparable accuracies to those of a touch probe CMM, while offering manufacturers the possibility for 100% part inspection. We discuss the design of the system, present our approach to calibrating system parameters, present validation data, compare bipolar fuel cell plate measurement results with those obtained using a Mitutoyo UMAP (see footnote 1) fiber probe CMM, and finally describe the uncertainty in channel height and width measurements.

  6. Materials and design development for bipolar/end plates in fuel cells

    Science.gov (United States)

    Kumar, Atul; Reddy, Ramana G.

    Bipolar/end plate is one of the most important and costliest components of the fuel cell stack and accounts to more than 80% of the total weight of the stack. In the present work, we focus on the development of alternative materials and design concepts for these plates. A prototype one-cell polymer electrolyte membrane (PEM) fuel cell stack made out of SS-316 bipolar/end plate was fabricated and assembled. The use of porous material in the gas flow-field of bipolar/end plates was proposed, and the performance of these was compared to the conventional channel type of design. Three different porous materials were investigated, viz. Ni-Cr metal foam (50 PPI), SS-316 metal foam (20 PPI), and the carbon cloth. It was seen that the performance of fuel cell with Ni-Cr metal foam was highest, and decreased in the order SS-316 metal foam, conventional multi-parallel flow-field channel design and carbon cloth. This trend was explained based on the effective permeability of the gas flow-field in the bipolar/end plates. The use of metal foams with low permeability values resulted in an increased pressure drop across the flow-field which enhanced the cell performance.

  7. Performance evaluation and characterization of metallic bipolar plates in a proton exchange membrane (PEM) fuel cell

    Science.gov (United States)

    Hung, Yue

    Bipolar plate and membrane electrode assembly (MEA) are the two most repeated components of a proton exchange membrane (PEM) fuel cell stack. Bipolar plates comprise more than 60% of the weight and account for 30% of the total cost of a fuel cell stack. The bipolar plates perform as current conductors between cells, provide conduits for reactant gases, facilitate water and thermal management through the cell, and constitute the backbone of a power stack. In addition, bipolar plates must have excellent corrosion resistance to withstand the highly corrosive environment inside the fuel cell, and they must maintain low interfacial contact resistance throughout the operation to achieve optimum power density output. Currently, commercial bipolar plates are made of graphite composites because of their relatively low interfacial contact resistance (ICR) and high corrosion resistance. However, graphite composite's manufacturability, permeability, and durability for shock and vibration are unfavorable in comparison to metals. Therefore, metals have been considered as a replacement material for graphite composite bipolar plates. Since bipolar plates must possess the combined advantages of both metals and graphite composites in the fuel cell technology, various methods and techniques are being developed to combat metallic corrosion and eliminate the passive layer formed on the metal surface that causes unacceptable power reduction and possible fouling of the catalyst and the electrolyte. The main objective of this study was to explore the possibility of producing efficient, cost-effective and durable metallic bipolar plates that were capable of functioning in the highly corrosive fuel cell environment. Bulk materials such as Poco graphite, graphite composite, SS310, SS316, incoloy 800, titanium carbide and zirconium carbide were investigated as potential bipolar plate materials. In this work, different alloys and compositions of chromium carbide coatings on aluminum and SS316

  8. Anticorrosion properties of tin oxide coatings for carbonaceous bipolar plates of proton exchange membrane fuel cells

    Science.gov (United States)

    Kinumoto, Taro; Nagano, Keita; Yamamoto, Yuji; Tsumura, Tomoki; Toyoda, Masahiro

    2014-03-01

    An anticorrosive surface treatment of a carbonaceous bipolar plate used in proton exchange membrane fuel cells (PEMFCs) was demonstrated by addition of a tin oxide surface coating by liquid phase deposition (LPD), and its effectiveness toward corrosion prevention was determined. The tin oxide coating was deposited by immersion in tin fluoride and boric acid solutions, without any observable decrease in the bipolar plate electrical conductivity. Anticorrosion properties of a flat carbonaceous bipolar plate were investigated in an aqueous HClO4 electrolyte solution (10 μmol dm-3) at 80 °C. CO2 release due to corrosion was significant for the bare specimen above 1.3 V, whereas no CO2 release was noted for the tin-oxide-coated specimen, even approaching 1.5 V. Moreover, minimal changes in contact angle against a water droplet before and after treatment indicated suppressed corrosion of the surface-coated specimen. Anticorrosion properties were also confirmed for a model bipolar plate having four gas flow channels. The tin oxide layer remained on the channel surfaces (inner walls, corners and intersections) after durability tests. Based on these results, tin-oxide-based surface coatings fabricated by LPD show promise as an anticorrosion technique for carbonaceous bipolar plates for PEMFCs.

  9. Real-time monitoring of intracellular signal transduction in PC12 cells by non-adiabatic tapered optical fiber biosensor

    Science.gov (United States)

    Zibaii, M. I.; Latifi, H.; Asadollahi, A.; Noraeipoor, Z.; Dargahi, L.

    2014-05-01

    Real-time observation of intracellular process of signal transduction is very useful for biomedical and pharmaceutical applications as well as for basic research work of cell biology. For feasible and reagentless observation of intracellular alterations in real time, we examined the use of a nonadiabatic tapered optical fiber (NATOF) biosensor for monitoring of intracellular signal transduction that was mainly translocation of protein kinase C via refractive index change in PC12 cells adhered on tapered fiber sensor without any indicator reagent. PC12 cells were stimulated with KCl . Our results suggest that complex intracellular reactions could be real-time monitored and characterized by NATOF biosensor.

  10. Highly conductive composites for fuel cell flow field plates and bipolar plates

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Bor Z; Zhamu, Aruna; Song, Lulu

    2014-10-21

    This invention provides a fuel cell flow field plate or bipolar plate having flow channels on faces of the plate, comprising an electrically conductive polymer composite. The composite is composed of (A) at least 50% by weight of a conductive filler, comprising at least 5% by weight reinforcement fibers, expanded graphite platelets, graphitic nano-fibers, and/or carbon nano-tubes; (B) polymer matrix material at 1 to 49.9% by weight; and (C) a polymer binder at 0.1 to 10% by weight; wherein the sum of the conductive filler weight %, polymer matrix weight % and polymer binder weight % equals 100% and the bulk electrical conductivity of the flow field or bipolar plate is at least 100 S/cm. The invention also provides a continuous process for cost-effective mass production of the conductive composite-based flow field or bipolar plate.

  11. Connexin 36 and rod bipolar cell independent rod pathways drive retinal ganglion cells and optokinetic reflexes.

    Science.gov (United States)

    Cowan, Cameron S; Abd-El-Barr, Muhammad; van der Heijden, Meike; Lo, Eric M; Paul, David; Bramblett, Debra E; Lem, Janis; Simons, David L; Wu, Samuel M

    2016-02-01

    Rod pathways are a parallel set of synaptic connections which enable night vision by relaying and processing rod photoreceptor light responses. We use dim light stimuli to isolate rod pathway contributions to downstream light responses then characterize these contributions in knockout mice lacking rod transducin-α (Trα), or certain pathway components associated with subsets of rod pathways. These comparisons reveal that rod pathway driven light sensitivity in retinal ganglion cells (RGCs) is entirely dependent on Trα, but partially independent of connexin 36 (Cx36) and rod bipolar cells. Pharmacological experiments show that rod pathway-driven and Cx36-independent RGC ON responses are also metabotropic glutamate receptor 6-dependent. To validate the RGC findings in awake, behaving animals we measured optokinetic reflexes (OKRs), which are sensitive to changes in ON pathways. Scotopic OKR contrast sensitivity was lost in Trα(-/-) mice, but indistinguishable from controls in Cx36(-/-) and rod bipolar cell knockout mice. Mesopic OKRs were also altered in mutant mice: Trα(-/-) mice had decreased spatial acuity, rod BC knockouts had decreased sensitivity, and Cx36(-/-) mice had increased sensitivity. These results provide compelling evidence against the complete Cx36 or rod BC dependence of night vision's ON component. Further, the findings suggest the parallel nature of rod pathways provides considerable redundancy to scotopic light sensitivity but distinct contributions to mesopic responses through complicated interactions with cone pathways. PMID:26718442

  12. Optimum design of bipolar plates for separate air flow cooling system of PEM fuel cells stacks

    Science.gov (United States)

    Franco, Alessandro

    2015-12-01

    The paper discusses about thermal management of PEM fuel cells. The objective is to define criteria and guidelines for the design of the air flow cooling system of fuel cells stacks for different combination of power density, bipolar plates material, air flow rate, operating temperature It is shown that the optimization of the geometry of the channel permits interesting margins for maintaining the use of separate air flow cooling systems for high power density PEM fuel cells.

  13. Adenoviral transduction of mesenchymal stem cells: in vitro responses and in vivo immune responses after cell transplantation.

    Directory of Open Access Journals (Sweden)

    Oliver Treacy

    Full Text Available Adult mesenchymal stem cells (MSCs are non-hematopoietic cells with multi-lineage potential which makes them attractive targets for regenerative medicine applications. However, to date, therapeutic success of MSC-therapy is limited and the genetic modification of MSCs using viral vectors is one option to improve their therapeutic potential. Ex-vivo genetic modification of MSCs using recombinant adenovirus (Ad could be promising to reduce undesired immune responses as Ad will be removed before cell/tissue transplantation. In this regard, we investigated whether Ad-modification of MSCs alters their immunological properties in vitro and in vivo. We found that Ad-transduction of MSCs does not lead to up-regulation of major histocompatibility complex class I and II and co-stimulatory molecules CD80 and CD86. Moreover, Ad-transduction caused no significant changes in terms of pro-inflammatory cytokine expression, chemokine and chemokine receptor and Toll-like receptor expression. In addition, Ad-modification of MSCs had no affect on their ability to suppress T cell proliferation in vitro. In vivo injection of Ad-transduced MSCs did not change the frequency of various immune cell populations (antigen presenting cells, T helper and cytotoxic T cells, natural killer and natural killer T cells neither in the blood nor in tissues. Our results indicate that Ad-modification has no major influence on the immunological properties of MSCs and therefore can be considered as a suitable gene vector for therapeutic applications of MSCs.

  14. The signal transduction pathways and molecules for ES cells self-renewal

    Institute of Scientific and Technical Information of China (English)

    LIU Na; LU Min

    2005-01-01

    Embryonic stem cells (ES cells) are derived from the inner cell mass (ICM) of blastocysts. ES cells can divide and produce identical copies of them over and over again (self-renewal) in vitro for a long time, and retain the capability of differentiating into all cell types when induced by appropriate signals. Their capability of multilineage differentiation might be exploited for cell-based therapies. Therefore, ES cells have a broad prospect in many clinical applications. To achieve success in the clinical applications, we have to understand how ES cells propagate and differentiate into specific cell types. The cytokine LIF can sustain the self-renewal of certain mouse ES cells (mES cells) through activation of the signal transduction pathway LIF/gp130/ STAT3. In this pathway the transcription factor STAT3 is a crucial factor. Furthermore, Oct-3/4 plays a very important role in maintaining the ES cell pluripotency. Oct-3/4 regulates embryo development through its co-factor Sox2 and Rox-1. Recently nanog, a new homeodomain gene, was found and it has been shown to be crucial for the renewal and pluripotency of ES cells. Three other signals BMP, Wnt and ERK also can influence differentiation and propagation of ES cells. This review article summarizes recent progress in this area, mainly focusing on the LIF signaling pathway and the transcription factors Oct-3/4 and Nanog. Although it is still unclear how these components cooperate, a model is presented here to provide a design for solving this problem.

  15. SEU-hardened silicon bipolar and GaAs MESFET SRAM cells using local redundancy techniques

    International Nuclear Information System (INIS)

    Silicon bipolar and GaAs FET SRAM's have proven to be more difficult to harden with respect to single-event upset mechanisms than have silicon CMOS SRAM's. This is a fundamental property of bipolar and JFET or MESFET device technologies which do not have a high-impedance, nonactive isolation between the control electrode and the current or voltage being controlled. All SEU circuit level hardening techniques applied at the local level must use some type of information storage redundancy so that information loss on one node due to an SEU event can be recovered from information stored elsewhere in the cell. In CMOS technologies, this can be achieved by the use of simple cross-coupling resistors, whereas in bipolar and FET technologies, no such simple approach is possible. Several approaches to the use of local redundancy in bipolar and FET technologies are discussed in this paper. At the expense of increased cell complexity and increased power consumption and write time, several approaches are capable of providing complete SEU hardness at the local cell level

  16. Reduced Neurite Density in Neuronal Cell Cultures Exposed to Serum of Patients with Bipolar Disorder

    Science.gov (United States)

    Wollenhaupt-Aguiar, Bianca; Pfaffenseller, Bianca; Chagas, Vinicius de Saraiva; Castro, Mauro A A; Passos, Ives Cavalcante; Kauer-Sant’Anna, Márcia; Kapczinski, Flavio

    2016-01-01

    Background: Increased inflammatory markers and oxidative stress have been reported in serum among patients with bipolar disorder (BD). The aim of this study is to assess whether biochemical changes in the serum of patients induces neurotoxicity in neuronal cell cultures. Methods: We challenged the retinoic acid-differentiated human neuroblastoma SH-SY5Y cells with the serum of BD patients at early and late stages of illness and assessed neurite density and cell viability as neurotoxic endpoints. Results: Decreased neurite density was found in neurons treated with the serum of patients, mostly patients at late stages of illness. Also, neurons challenged with the serum of late-stage patients showed a significant decrease in cell viability. Conclusions: Our findings showed that the serum of patients with bipolar disorder induced a decrease in neurite density and cell viability in neuronal cultures. PMID:27207915

  17. Effect of fragile histidine triad gene transduction on proliferation and apoptosis of human hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Rong-Hua Xu; Ji-Lin Yi; Liang-Yan Zheng; Dong-Lei He; Jian Tong; Li-Ping Zheng; Wu-Ping Zheng; Jin Meng; Li-Ping Xia; Cong-Jun Wang

    2008-01-01

    AIM: To evaluate the inhibitory effects of human fragile histidine triad (FHIT) gene on cell proliferation and apoptosis in human hepatocellular carcinoma line Hep3B in vitro.METHODS: A recombinant pcDNA3.1 (+)/FHIT including the functional region of FHIT gene was constructed and transferred into human hepatocellular carcinoma cells in vitro, mRNA and protein expression of the FHIT gene in the transfected cells was detected by RT-PCR and Western blot, respectively. The effect of FHIT on proliferation was detected by MTT assay. Changes in cell cycle and apoptosis were assayed by flow cytometry. Five mice received subcutaneous transplantation of Hep3B-FHIT; 5 mice received subcutaneous transplantation of normal Hep3B and Hep3B-C as controls. The body weight of nude mice and tumor growth were measured.RESULTS: RT-PCR and Western blot analysis showed that the expression level of FHIT-mRNA and FHIT protein was higher in Hep3B cells alter infection with pcDNA3.1 (+)/FHIT. The growth of Hep3B cells treated with pcDNA3.1 (+)/FHIT was significantly inhibited. The pcDNA3.1 (+)/FHIT-transfected Hep3B cells showed a significantly higher cell rate at G>0-G1 phase and increased apoptosis in comparison with controls (P<0.05). The growth of transplanted tumor was inhibited markedly by FHIT. Tumors arising from the Hep3B-FHIT cells occurred much later than those arising from the Hep3B and Hep3B-C cells. The growth of Hep3B-FHIT cells was slow and the tumor volume was low.CONCLUSION: Transduction of FHIT gene inhibits the growth of human hepatocellular carcinoma cells and induces cell apoptosis in vivo and in vitro.

  18. Microgravity-induced alterations in signal transduction in cells of the immune system

    Science.gov (United States)

    Paulsen, Katrin; Thiel, Cora; Timm, Johanna; Schmidt, Peter M.; Huber, Kathrin; Tauber, Svantje; Hemmersbach, Ruth; Seibt, Dieter; Kroll, Hartmut; Grote, Karl-Heinrich; Zipp, Frauke; Schneider-Stock, Regine; Cogoli, Augusto; Hilliger, Andre; Engelmann, Frank; Ullrich, Oliver

    2010-11-01

    Since decades it is known that the activity of cells of the immune system is severely dysregulated in microgravity, however, the underlying molecular aspects have not been elucidated yet. The identification of gravity-sensitive molecular mechanisms in cells of the immune system is an important and indispensable prerequisite for the development of counteractive measures to prevent or treat disturbed immune cell function of astronauts during long-term space missions. Moreover, their sensitivity to altered gravity renders immune cells an ideal model system to understand if and how gravity on Earth is required for normal mammalian cell function and signal transduction. We investigated the effect of simulated weightlessness (2D clinostat) and of real microgravity (parabolic flights) on key signal pathways in a human monocytic and a T lymphocyte cell line. We found that cellular responses to microgravity strongly depend on the cell-type and the conditions in which the cells are subjected to microgravity. In Jurkat T cells, enhanced phosphorylation of the MAP kinases ERK-1/2, MEK and p38 and inhibition of nuclear translocation of NF-kB were the predominant responses to simulated weightlessness, in either stimulated or non-stimulated cells. In contrast, non-stimulated monocytic U937 cells responded to simulated weightlessness with enhanced overall tyrosine-phosphorylation and activation of c-jun, whereas PMA-stimulated U937 cells responded the opposite way with reduced tyrosine-phosphorylation and reduced activation of c-jun, compared with PMA-stimulated 1 g controls. P53 protein was phosphorylated rapidly in microgravity. The identification of gravi-sensitive mechanisms in cells of the immune system will not only enable us to understand and prevent the negative effects of long time exposure to microgravity on Astronauts, but could also lead to novel therapeutic targets in general.

  19. The merged basins of signal transduction pathways in spatiotemporal cell biology.

    Science.gov (United States)

    Hou, Yingchun; Hou, Yang; He, Siyu; Ma, Caixia; Sun, Mengyao; He, Huimin; Gao, Ning

    2014-03-01

    Numerous evidences have indicated that a signal system is composed by signal pathways, each pathway is composed by sub-pathways, and the sub-pathway is composed by the original signal terminals initiated with a protein/gene. We infer the terminal signals merged signal transduction system as "signal basin". In this article, we discussed the composition and regulation of signal basins, and the relationship between the signal basin control and triple W of spatiotemporal cell biology. Finally, we evaluated the importance of the systemic regulation to gene expression by signal basins under triple W. We hope our discussion will be the beginning to cause the attention for this area from the scientists of life science.

  20. Differential loss and preservation of glutamate receptor function in bipolar cells in the rd10 mouse model of retinitis pigmentosa

    OpenAIRE

    Puthussery, Theresa; Gayet-Primo, Jacqueline; Pandey, Shilpi; Duvoisin, Robert M; Taylor, W. Rowland

    2009-01-01

    Photoreceptor degenerations can trigger morphological alterations in second-order neurons, however, the functional implications of such changes are not well known. We conducted a longitudinal study, using whole-cell patch-clamp, immunohistochemistry and electron microscopy to correlate physiological with anatomical changes in bipolar cells of the rd10 mouse - a model of autosomal recessive retinitis pigmentosa. Rod bipolar cells (RBCs) showed progressive changes in mGluR6-induced currents wit...

  1. Comparative mechanisms of protein transduction mediated by cell-penetrating peptides in prokaryotes.

    Science.gov (United States)

    Liu, Betty Revon; Huang, Yue-Wern; Aronstam, Robert S; Lee, Han-Jung

    2015-04-01

    Bacterial and archaeal cell envelopes are complex multilayered barriers that serve to protect these microorganisms from their extremely harsh and often hostile environments. Import of exogenous proteins and nanoparticles into cells is important for biotechnological applications in prokaryotes. In this report, we demonstrate that cell-penetrating peptides (CPPs), both bacteria-expressed nona-arginine peptide (R9) and synthetic R9 (SR9), are able to deliver noncovalently associated proteins or quantum dots into four representative species of prokaryotes: cyanobacteria (Synechocystis sp. PCC 6803), bacteria (Escherichia coli DH5α and Arthrobacter ilicis D-50), and archaea (Thermus aquaticus). Although energy-dependent endocytosis is generally accepted as a hallmark that distinguishes eukaryotes from prokaryotes, cellular uptake of uncomplexed green fluorescent protein (GFP) by cyanobacteria was mediated by classical endocytosis. Mechanistic studies revealed that macropinocytosis plays a critical and major role in CPP-mediated protein transduction in all four prokaryotes. Membrane damage was not observed when cyanobacterial cells were treated with R9/GFP complexes, nor was cytotoxicity detected when bacteria or archaea were treated with SR9/QD complexes in the presence of macropinocytic inhibitors. These results indicate that the uptake of protein is not due to a compromise of membrane integrity in cyanobacteria, and that CPP can be an effective and safe carrier for membrane trafficking in prokaryotic cells. Our investigation provides important new insights into the transport of exogenous proteins and nanoparticles across the complex membrane systems of prokaryotes.

  2. A self-humidifying acidic-alkaline bipolar membrane fuel cell

    Science.gov (United States)

    Peng, Sikan; Xu, Xin; Lu, Shanfu; Sui, Pang-Chieh; Djilali, Ned; Xiang, Yan

    2015-12-01

    To maintain membrane hydration and operate effectively, polymer electrolyte membrane fuel cells (PEMFCs) require elaborate water management, which significantly increases the complexity and cost of the fuel cell system. Here we propose a novel and entirely different approach to membrane hydration by exploiting the concept of bipolar membranes. Bipolar membrane (BPM) fuel cells utilize a composite membrane consisting of an acidic polymer electrolyte membrane on the anode side and an alkaline electrolyte membrane on the cathode side. We present a novel membrane electrode assembly (MEA) fabrication method and demonstrate experimentally and theoretically that BPM fuel cells can (a) self-humidify to ensure high ionic conductivity; and (b) allow use of non-platinum catalysts due to inherently faster oxygen reduction kinetics on an alkaline cathode. Our Pt-based BPM fuel cell achieves a two orders of magnitude gain in power density of 327 mW cm-2 at 323 K under dry gas feed, the highest power output achieved under anhydrous operation conditions. A theoretical analysis and in situ measurements are presented to characterize the unique interfacial water generation and transport behavior that make self-humidification possible during operation. Further optimization of these features and advances in fabricating bipolar MEAs would open the way for a new generation of self-humidifying and water-management-free PEMFCs.

  3. Signal transduction induced in Trypanosoma cruzi metacyclic trypomastigotes during the invasion of mammalian cells

    Directory of Open Access Journals (Sweden)

    N. Yoshida

    2000-03-01

    Full Text Available Penetration of Trypanosoma cruzi into mammalian cells depends on the activation of the parasite's protein tyrosine kinase and on the increase in cytosolic Ca2+ concentration. We used metacyclic trypomastigotes, the T. cruzi developmental forms that initiate infection in mammalian hosts, to investigate the association of these two events and to identify the various components of the parasite signal transduction pathway involved in host cell invasion. We have found that i both the protein tyrosine kinase activation, as measured by phosphorylation of a 175-kDa protein (p175, and Ca2+ mobilization were induced in the metacyclic forms by the HeLa cell extract but not by the extract of T. cruzi-resistant K562 cells; ii treatment of parasites with the tyrosine kinase inhibitor genistein blocked both p175 phosphorylation and the increase in cytosolic Ca2+ concentration; iii the recombinant protein J18, which contains the full-length sequence of gp82, a metacyclic stage surface glycoprotein involved in target cell invasion, interfered with tyrosine kinase and Ca2+ responses, whereas the monoclonal antibody 3F6 directed at gp82 induced parasite p175 phosphorylation and Ca2+ mobilization; iv treatment of metacyclic forms with phospholipase C inhibitor U73122 blocked Ca2+ signaling and impaired the ability of the parasites to enter HeLa cells, and v drugs such as heparin, a competitive IP3-receptor blocker, caffeine, which affects Ca2+ release from IP3-sensitive stores, in addition to thapsigargin, which depletes intracellular Ca2+ compartments and lithium ion, reduced the parasite infectivity. Taken together, these data suggest that protein tyrosine kinase, phospholipase C and IP3 are involved in the signaling cascade that is initiated on the parasite cell surface by gp82 and leads to Ca2+ mobilization required for target cell invasion.

  4. Inquiry into Chemotherapy-Induced P53 Activation in Cancer Cells as a Model for Teaching Signal Transduction

    Science.gov (United States)

    Srougi, Melissa C.; Carson, Susan

    2013-01-01

    Intracellular and extracellular communication is conducted through an intricate and interwoven network of signal transduction pathways. The mechanisms for how cells speak with one another are of significant biological importance to both basic and industrial scientists from a number of different disciplines. We have therefore developed and…

  5. HLA-DR molecules enhance signal transduction through the CD3/Ti complex in activated T cells

    DEFF Research Database (Denmark)

    Odum, Niels; Martin, P J; Schieven, G L;

    1991-01-01

    Crosslinking HLA-DR molecules by monoclonal antibodies (mAb) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic Ca2+ concentration ([Ca2+]i) in activated human T cells. Here we have studied the effect of DR on CD3-induced signal transduction...

  6. MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hong-hua Peng

    2012-01-01

    Full Text Available The matrix metalloprotease-1 (MMP-1/protease-activated receptor-1 (PAR-1 signal transduction axis plays an important role in tumorigenesis. To explore the expression and prognostic value of MMP-1 and PAR-1 in esophageal squamous cell carcinoma (ESCC, we evaluated the expression of two proteins in resected specimens from 85 patients with ESCC by immunohistochemistry. Sixty-two (72.9% and 58 (68.2% tumors were MMP-1- and PAR-1-positive, respectively, while no significant staining was observed in normal esophageal squamous epithelium. MMP-1 and PAR-1 overexpression was significantly associated with tumor node metastasis (TNM stage and regional lymph node involvement. Patients with MMP-1- and PAR-1-positive tumors, respectively, had poorer disease-free survival (DFS than those with negative ESCC (P = 0.002 and 0.003, respectively. Univariate analysis showed a significant relationship between TNM stage [hazard ratio (HR = 2.836, 95% confidence interval (CI = 1.866-4.308], regional lymph node involvement (HR = 2.955, 95%CI = 1.713-5.068, MMP-1 expression (HR = 2.669, 95%CI = 1.229-6.127, and PAR-1 expression (HR = 1.762, 95%CI = 1.156-2.883 and DFS. Multivariate analysis including the above four parameters identified TNM stage (HR = 2.035, 95%CI = 1.167-3.681, MMP-1 expression (HR = 2.109, 95%CI = 1.293-3.279, and PAR-1 expression (HR = 1.967, 95%CI = 1.256-2.881 as independent and significant prognostic factors for DFS. Our data suggest for the first time that MMP-1 and PAR-1 were both overexpressed in ESCC and are novel predictors of poor patient prognosis after curative resection. The MMP-1/PAR-1 signal transduction axis might be a new therapeutic target for future therapies tailored against ESCC.

  7. MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Hong-hua; Zhang, Xi; Cao, Pei-guo [Department of Oncology, the Third Xiangya Hospital, Central South University, Changsha, Hunan Province (China)

    2011-11-18

    The matrix metalloprotease-1 (MMP-1)/protease-activated receptor-1 (PAR-1) signal transduction axis plays an important role in tumorigenesis. To explore the expression and prognostic value of MMP-1 and PAR-1 in esophageal squamous cell carcinoma (ESCC), we evaluated the expression of two proteins in resected specimens from 85 patients with ESCC by immunohistochemistry. Sixty-two (72.9%) and 58 (68.2%) tumors were MMP-1- and PAR-1-positive, respectively, while no significant staining was observed in normal esophageal squamous epithelium. MMP-1 and PAR-1 overexpression was significantly associated with tumor node metastasis (TNM) stage and regional lymph node involvement. Patients with MMP-1- and PAR-1-positive tumors, respectively, had poorer disease-free survival (DFS) than those with negative ESCC (P = 0.002 and 0.003, respectively). Univariate analysis showed a significant relationship between TNM stage [hazard ratio (HR) = 2.836, 95% confidence interval (CI) = 1.866-4.308], regional lymph node involvement (HR = 2.955, 95%CI = 1.713-5.068), MMP-1 expression (HR = 2.669, 95%CI = 1.229-6.127), and PAR-1 expression (HR = 1.762, 95%CI = 1.156-2.883) and DFS. Multivariate analysis including the above four parameters identified TNM stage (HR = 2.035, 95%CI = 1.167-3.681), MMP-1 expression (HR = 2.109, 95%CI = 1.293-3.279), and PAR-1 expression (HR = 1.967, 95%CI = 1.256-2.881) as independent and significant prognostic factors for DFS. Our data suggest for the first time that MMP-1 and PAR-1 were both overexpressed in ESCC and are novel predictors of poor patient prognosis after curative resection. The MMP-1/PAR-1 signal transduction axis might be a new therapeutic target for future therapies tailored against ESCC.

  8. Lipid Rafts and Signal Transduction of Cell%脂筏与细胞信号转导

    Institute of Scientific and Technical Information of China (English)

    范玉贞

    2011-01-01

    论述了脂筏的组成、结构与功能,脂筏在细胞信号转导正负调控、T细胞的信号转导、精子膜的信号转导过程中的作用及其机制.小窝蛋白及其参与的信号转导过程与葡萄糖运输、糖尿病及其并发症有密切关系.%This article discusses the composition,structure and function of lipid rafts and the mechanism of lipid rafts in signal transduction plus or minus regulation,T cell signal transduction,signal transduction process of sperm membrane.Caveolins and its partic

  9. Multilayer graphene for long-term corrosion protection of stainless steel bipolar plates for polymer electrolyte membrane fuel cell

    DEFF Research Database (Denmark)

    Stoot, Adam Carsten; Camilli, Luca; Spiegelhauer, Susie Ann;

    2015-01-01

    Abstract Motivated by similar investigations recently published (Pu et al., 2015), we report a comparative corrosion study of three sets of samples relevant as bipolar plates for polymer electrolyte fuel cells: stainless steel, stainless steel with a nickel seed layer (Ni/SS) and stainless steel...... graphene film is still intact with unchanged defect density. Our results show that even non-perfect multilayer graphene films can considerably increase the lifetime of future-generation bipolar plates for fuel cells....

  10. Development and degeneration of cone bipolar cells are independent of cone photoreceptors in a mouse model of retinitis pigmentosa

    OpenAIRE

    Miao Chen; Ke Wang; Bin Lin

    2012-01-01

    Retinal photoreceptors die during retinal synaptogenesis in a portion of retinal degeneration. Whether cone bipolar cells establish regular retinal mosaics and mature morphologies, and resist degeneration are not completely understood. To explore these issues, we backcrossed a transgenic mouse expressing enhanced green fluorescent protein (EGFP) in one subset of cone bipolar cells (type 7) into rd1 mice, a classic mouse model of retinal degeneration, to examine the development and survival of...

  11. ISL1 protein transduction promotes cardiomyocyte differentiation from human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Hananeh Fonoudi

    Full Text Available BACKGROUND: Human embryonic stem cells (hESCs have the potential to provide an unlimited source of cardiomyocytes, which are invaluable resources for drug or toxicology screening, medical research, and cell therapy. Currently a number of obstacles exist such as the insufficient efficiency of differentiation protocols, which should be overcome before hESC-derived cardiomyocytes can be used for clinical applications. Although the differentiation efficiency can be improved by the genetic manipulation of hESCs to over-express cardiac-specific transcription factors, these differentiated cells are not safe enough to be applied in cell therapy. Protein transduction has been demonstrated as an alternative approach for increasing the efficiency of hESCs differentiation toward cardiomyocytes. METHODS: We present an efficient protocol for the differentiation of hESCs in suspension by direct introduction of a LIM homeodomain transcription factor, Islet1 (ISL1 recombinant protein into the cells. RESULTS: We found that the highest beating clusters were derived by continuous treatment of hESCs with 40 µg/ml recombinant ISL1 protein during days 1-8 after the initiation of differentiation. The treatment resulted in up to a 3-fold increase in the number of beating areas. In addition, the number of cells that expressed cardiac specific markers (cTnT, CONNEXIN 43, ACTININ, and GATA4 doubled. This protocol was also reproducible for another hESC line. CONCLUSIONS: This study has presented a new, efficient, and reproducible procedure for cardiomyocytes differentiation. Our results will pave the way for scaled up and controlled differentiation of hESCs to be used for biomedical applications in a bioreactor culture system.

  12. Optimization of lentiviral vector transduction into peripheral blood mononuclear cells in combination with the fibronectin fragment CH-296 stimulation.

    Science.gov (United States)

    Chono, Hideto; Goto, Yumi; Yamakawa, Satoko; Tanaka, Shinya; Tosaka, Yasuhiro; Nukaya, Ikuei; Mineno, Junichi

    2011-03-01

    Large scale T-cell expansion and efficient gene transduction are required for adoptive T-cell gene therapy. Based on our previous observations, human peripheral blood mononuclear cells (PBMCs) can be expanded efficiently while conserving a naïve phenotype by stimulating with both recombinant human fibronectin fragment (CH-296) and anti-CD3 monoclonal antibodies. In this article, we explored the possibility of using this co-stimulation method to generate engineered T cells using lentiviral vector. Human PBMCs were stimulated with anti-CD3 together with immobilized CH-296 or anti-CD28 antibody as well as anti-CD3/anti-CD28 conjugated beads and transduced with lentiviral vector simultaneously. Co-stimulation with CH-296 gave superior transduction efficiency than with anti-CD28. Next, PBMCs were stimulated and transduced with anti-CD3/CH-296 or with anti-CD3/CD28 beads. T-cell expansion, gene transfer efficiencies and immunophenotypes were analysed. Stimulation with anti-CD3/CH-296 resulted in more than 10-times higher cell expansion and higher gene transfer efficiency with conservation of the naïve phenotype compared with anti-CD3/CD28 stimulation method. Thus, lentiviral transduction with anti-CD3/CH-296 co-stimulation is an efficient way to generate large numbers of genetically modified T cells and may be suitable for many gene therapy protocols that use adoptive T-cell transfer therapy.

  13. Development and degeneration of cone bipolar cells are independent of cone photoreceptors in a mouse model of retinitis pigmentosa.

    Directory of Open Access Journals (Sweden)

    Miao Chen

    Full Text Available Retinal photoreceptors die during retinal synaptogenesis in a portion of retinal degeneration. Whether cone bipolar cells establish regular retinal mosaics and mature morphologies, and resist degeneration are not completely understood. To explore these issues, we backcrossed a transgenic mouse expressing enhanced green fluorescent protein (EGFP in one subset of cone bipolar cells (type 7 into rd1 mice, a classic mouse model of retinal degeneration, to examine the development and survival of cone bipolar cells in a background of retinal degeneration. Our data revealed that both the development and degeneration of cone bipolar cells are independent of the normal activity of cone photoreceptors. We found that type 7 cone bipolar cells achieved a uniform tiling of the retinal surface and developed normal dendritic and axonal arbors without the influence of cone photoreceptor innervation. On the other hand, degeneration of type 7 cone bipolar cells, contrary to our belief of central-to-peripheral progression, was spatially uniform across the retina independent of the spatiotemporal pattern of cone degeneration. The results have important implications for the design of more effective therapies to restore vision in retinal degeneration.

  14. Signal transduction in Plasmodium-Red Blood Cells interactions and in cytoadherence

    Directory of Open Access Journals (Sweden)

    Laura N. Cruz

    2012-06-01

    Full Text Available Malaria is responsible for more than 1.5 million deaths each year, especially among children (Snow et al. 2005. Despite of the severity of malaria situation and great effort to the development of new drug targets (Yuan et al. 2011 there is still a relative low investment toward antimalarial drugs. Briefly there are targets classes of antimalarial drugs currently being tested including: kinases, proteases, ion channel of GPCR, nuclear receptor, among others (Gamo et al. 2010. Here we review malaria signal transduction pathways in Red Blood Cells (RBC as well as infected RBCs and endothelial cells interactions, namely cytoadherence. The last process is thought to play an important role in the pathogenesis of severe malaria. The molecules displayed on the surface of both infected erythrocytes (IE and vascular endothelial cells (EC exert themselves as important mediators in cytoadherence, in that they not only induce structural and metabolic changes on both sides, but also trigger multiple signal transduction processes, leading to alteration of gene expression, with the balance between positive and negative regulation determining endothelial pathology during a malaria infection.A Malária é responsavel por mais de 1.5 milhões de mortes anualmente, especialmente entre crianças (Snow et al. 2005. Apesar da gravidade da situação e grande esforço para o desenvolvimento de novas drogas (Yuan et al. 2011, os investimentos em drogas antimaláricas ainda é relativamente baixo. Brevemente, os alvos antimaláricos atualmente testados incluem: quinases, proteases, canais iônicos para GPCR, receptores nucleares entre outros (Gamo et al. 2010. No presente trabalho nós revisamos as vias de transdução de sinal em eritrócitos assim como eritrócitos infectados e interações com células endoteliais, denominada citoaderência. Este processo é conhecido por sua importante função na patogenicidade da malária severa. As moléculas expressas na superf

  15. Cost and performance prospects for composite bipolar plates in fuel cells and redox flow batteries

    Science.gov (United States)

    Minke, Christine; Hickmann, Thorsten; dos Santos, Antonio R.; Kunz, Ulrich; Turek, Thomas

    2016-02-01

    Carbon-polymer-composite bipolar plates (BPP) are suitable for fuel cell and flow battery applications. The advantages of both components are combined in a product with high electrical conductivity and good processability in convenient polymer forming processes. In a comprehensive techno-economic analysis of materials and production processes cost factors are quantified. For the first time a technical cost model for BPP is set up with tight integration of material characterization measurements.

  16. Development of novel proton exchange membrane fuel cells using stamped metallic bipolar plates

    Science.gov (United States)

    Jung, Shiauh-Ping; Lee, Chun-I.; Chen, Chi-Chang; Chang, Wen-Sheng; Yang, Chang-Chung

    2015-06-01

    This study presents the development of novel proton exchange membrane fuel cells using stamped metallic bipolar plates. To achieve uniformly distributed and low pressure-drop flow fields within fuel cells, a novel bipolar plate with straight channels is designed and verification of a fuel-cell short stack using this bipolar plate is performed. In the experiments, low-temperature and low-humidity operations and high-temperature and high-humidity operations are adopted to evaluate effects of stack temperature and inlet relative humidity on performance at various outlet pressures. Experimental results show that under low-temperature and low-humidity operations, increasing the outlet pressure enhances stack performance and reduces performance differences between various stack temperatures. Under high-temperature and high-humidity operations, stack performance increases with increasing outlet pressures, while the extent of their increase becomes smaller. Compared to low-temperature and low-humidity operations, high-temperature and high-humidity operations have better electrochemical reactions and membrane hydration and, thus, better stack performance. In this study, the operation with a stack temperature of 80 °C and outlet pressure of 4 atm produces the best performance of 1100 mA cm-2 at 0.646 V.

  17. Cell cycle requirements for transduction by foamy virus vectors compared to those of oncovirus and lentivirus vectors.

    Science.gov (United States)

    Trobridge, Grant; Russell, David W

    2004-03-01

    Retroviral vectors based on foamy viruses (FV) are efficient gene delivery vehicles for therapeutic and research applications. While previous studies have shown that FV vectors transduce quiescent cell cultures more efficiently than oncoviral vectors, their specific cell cycle requirements have not been determined. Here we compare the transduction frequencies of FV vectors with those of onco- and lentiviral vectors in nondividing and dividing normal human fibroblasts by several methods. FV vectors transduced serum-deprived fibroblast cultures more efficiently than oncoretroviral vectors and at rates comparable to those of lentiviral vectors. However, in these cultures FV vectors only transduced a subpopulation of proliferating cells, as determined by bromodeoxyuridine staining for DNA synthesis. In contrast to lentiviral vectors, FV vectors were unable to transduce human fibroblasts arrested by aphidicolin (G(1)/S phase) or gamma-irradiation (G(2) phase), and a partial cell cycle that included mitosis but not DNA synthesis was required. We could not determine if mitosis facilitated nuclear entry of FV vectors, since cell-free vector preparations contained long terminal repeat circles, precluding their use as nuclear markers. In contrast to oncoviral vectors, both FV and lentiviral vectors efficiently transduced G(0) fibroblasts that were later stimulated to divide. In the case of FV vectors, this was due to the persistence of a stable transduction intermediate in quiescent cells. Our findings support the use of FV vectors as a safe and effective alternative to lentiviral vectors for ex vivo transduction of stem cells that are quiescent during culture but divide following transplantation.

  18. Vpx-Independent Lentiviral Transduction and shRNA-Mediated Protein Knock-Down in Monocyte-Derived Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Wojciech Witkowski

    Full Text Available The function of dendritic cells (DCs in the immune system is based on their ability to sense and present foreign antigens. Powerful tools to research DC function and to apply in cell-based immunotherapy are either silencing or overexpression of genes achieved by lentiviral transduction. To date, efficient lentiviral transduction of DCs or their monocyte derived counterparts (MDDCs required high multiplicity of infection (MOI or the exposure to the HIV-2/SIV protein Vpx to degrade viral restriction factor SAM domain and HD domain-containing protein 1 (SAMHD1. Here we present a Vpx-independent method for efficient (>95% transduction of MDDCs at lower MOI. The protocol can be used both for ectopic gene expression and knock-down. Introducing shRNA targeting viral entry receptor CD4 and restriction factor SAMHD1 into MDDCs resulted in down-regulation of targeted proteins and, consequently, expected impact on HIV infection. This protocol for MDDCs transduction is robust and free of the potential risk arising from the use of Vpx which creates a virus infection-prone environment, potentially dangerous in clinical setting.

  19. Effect of proline rich domain of an RNA-binding protein Sam68 in cell growth process, death and B cell signal transduction

    Institute of Scientific and Technical Information of China (English)

    LI Qing-hua; FAN Tian-xue; PANG Tian-xiang; YUAN Wen-su; HAN Zhong-chao

    2006-01-01

    Background Sam68 plays an important role as a multiple functional RNA binding nuclear protein in cell cycle progress, RNA usage, signal transduction, and tyrosine phosphorylation by Src during mitosis. However, its precise impact on these essential cellular functions remains unclear. The purpose of this study is to further elucidate Sam68 functions in RNA metabolism, signal transduction regulation of cell growth and cell proliferation in DT40 cell line.Methods By using gene targeting method, we isolated a mutation form of Sam68 in DT40 cells and described its effect on cell growth process and signal transduction. Southern, Northern, and Western blot, phosphorylation and flow-cytometfic analyses were performed to investigate the Sam68 functions.Results A slower growth rate (2.1 hours growth elongation) and longer S phase (1.7 hours elongation) was observed in the Sam68 mutant cells. Serum depletion resulted in increased amounts of dead cells, and expansion of S phase in mutant cells. Upon B cell cross-linking, the maximal level of tyrosine phosphorylation on BLNK was observed to be significantly lower in mutant cells.Conclusions The proline rich domain of Sam68 is involved in cell growth control by modulating the function of mRNAs in S phase or earlier and the functions as an adaptor molecule in B cell signal transduction pathways.

  20. Surface roughness effect on the metallic bipolar plates of a proton exchange membrane fuel cell

    International Nuclear Information System (INIS)

    Highlights: ► Various degrees of roughness are caused by the sandblasting method. ► An improper surface modification depletes the PEMFC performance severely. ► The AC impedance are used to assess the fuel gas transfer effect. ► The Warburg resistance form in the coarse flow channel surface. - Abstract: Proton exchange membrane fuel cells (PEMFCs) is a promising candidate as energy systems. However, the stability and lifetime of cells are still important issues. The effect of surface roughness on metallic bipolar plate is discussed in this paper. Various roughness on the bulk surface are obtained by the sandblasting method. The grain sizes of sand are selected as 50, 100 and 200 μm. The Ac impedance experiment results show that the bipolar plate roughness and carbon paper porosity are well matched when the surface roughness is within 1–2 μm. Superior condition decreases the contact resistance loss in the fuel cell. The high frequency resistance of the coarse surface was larger than that of the substrate by around 5 mΩ. Furthermore, a new arc was formed at the low frequency region. Hence, the unmatch roughness condition of the bipolar plate significantly increases the contact resistance and mass transfer resistance. This paper develops a sequential approach to study an optimum surface roughness by combining the whole performance (I–V) curve and AC impedance result. It benefits us to quantify the contact and mass transfer resistance exists in the PEMFC. The proposed surface treatment improves the surface effect and promotes the implement of potential metallic bipolar plate in near future

  1. Materials, design, and modeling for bipolar/end plates in polymer electrolyte membrane fuel cells

    Science.gov (United States)

    Kumar, Atul

    New vehicle technologies are required to improve upon conventional internal combustion engine technologies. In this regard, the development of fuel cell (polymer electrolyte membrane type) vehicles with improved efficiency and reliability seems promising. However, some technical issues exist that hinder the commercialization of this technology. One such issue is the high cost, volume, and mass of the bipolar/end plates in the polymer electrolyte membrane fuel cell (PEMFC) stack. This research, therefore, focuses on materials, design, and modeling for bipolar/end plates in PEMFC stack. Alternative materials were tested that can replace the conventionally used graphite in the PEMFC stack. With regards to these, a two-cell PEMFC stack was fabricated with SS-316 multi-parallel flow-field (MPFF) designed bipolar/end plates. The stack was run for over 1000 hours and showed no appreciable drop in performance. To enhance the understanding and for determining the effect of operating parameters in PEMFC, a single cell model was developed. The model results agree well with the experimental data. The gas flow-field in bipolar/end plates of the PEMFC was optimized with respect to channel dimensions, channel shape, flow-field design, and flow-field permeability. It was seen that lower the flow-field permeability better is the fuel cell performance. Based on this, the concept of use of metal foams in the gas flow-field was proposed. Experiments were carried out to test the feasibility of metal foams in the gas flow-field of bipolar/end plates in PEMFC stack. Three different porous materials, viz. Ni-Cr metal foam (50 P PI, pores per inch), S S-316 metal foam (20 PPI), and carbon cloth were tested, and the results were compared to the conventional MPFF channel design concept. It was seen that the performance with Ni-Cr metal foam was highest, and decreased in the order of SS-316 metal foam, conventional MPFF design, and carbon cloth. This trend was explained based on the effective

  2. Creation and validation of a ligation-independent cloning (LIC retroviral vector for stable gene transduction in mammalian cells

    Directory of Open Access Journals (Sweden)

    Patel Asmita

    2012-01-01

    Full Text Available Abstract Background Cloning vectors capable of retroviral transduction have enabled stable gene overexpression in numerous mitotic cell lines. However, the relatively small number of feasible restriction enzyme sequences in their cloning sites can hinder successful generation of overexpression constructs if these sequences are also present in the target cDNA insert. Results Utilizing ligation-independent cloning (LIC technology, we have modified the highly efficient retroviral transduction vector, pBABE, to eliminate reliance on restriction enzymes for cloning. Instead, the modified plasmid, pBLIC, utilizes random 12/13-base overhangs generated by T4 DNA polymerase 3' exonuclease activity. PCR-based introduction of the complementary sequence into any cDNA of interest enables universal cloning into pBLIC. Here we describe creation of the pBLIC plasmid, and demonstrate successful cloning and protein overexpression from three different cDNAs, Bax, catalase, and p53 through transduction into the human prostate cancer cell line, LNCaP or the human lung cancer line, H358. Conclusions Our results show that pBLIC vector retains the high transduction efficiency of the original pBABE while eliminating the requirement for checking individual cDNA inserts for internal restriction sites. Thus it comprises an effective retroviral cloning system for laboratory-scale stable gene overexpression or for high-throughput applications such as creation of retroviral cDNA libraries. To our knowledge, pBLIC is the first LIC vector for retroviral transduction-mediated stable gene expression in mammalian cells.

  3. Predicting essential components of signal transduction networks: a dynamic model of guard cell abscisic acid signaling.

    Directory of Open Access Journals (Sweden)

    Song Li

    2006-10-01

    Full Text Available Plants both lose water and take in carbon dioxide through microscopic stomatal pores, each of which is regulated by a surrounding pair of guard cells. During drought, the plant hormone abscisic acid (ABA inhibits stomatal opening and promotes stomatal closure, thereby promoting water conservation. Dozens of cellular components have been identified to function in ABA regulation of guard cell volume and thus of stomatal aperture, but a dynamic description is still not available for this complex process. Here we synthesize experimental results into a consistent guard cell signal transduction network for ABA-induced stomatal closure, and develop a dynamic model of this process. Our model captures the regulation of more than 40 identified network components, and accords well with previous experimental results at both the pathway and whole-cell physiological level. By simulating gene disruptions and pharmacological interventions we find that the network is robust against a significant fraction of possible perturbations. Our analysis reveals the novel predictions that the disruption of membrane depolarizability, anion efflux, actin cytoskeleton reorganization, cytosolic pH increase, the phosphatidic acid pathway, or K(+ efflux through slowly activating K(+ channels at the plasma membrane lead to the strongest reduction in ABA responsiveness. Initial experimental analysis assessing ABA-induced stomatal closure in the presence of cytosolic pH clamp imposed by the weak acid butyrate is consistent with model prediction. Simulations of stomatal response as derived from our model provide an efficient tool for the identification of candidate manipulations that have the best chance of conferring increased drought stress tolerance and for the prioritization of future wet bench analyses. Our method can be readily applied to other biological signaling networks to identify key regulatory components in systems where quantitative information is limited.

  4. Signal transduction factors on the modulation of radiosusceptibility in K562 cells

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Kwang Mo; Jeong, Soo Jin [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Youn, Seon Min [College of Medicine, Eulji Univ., Daejeon (Korea, Republic of)

    2003-09-01

    The human chronic myelogenous leukemia cell line, K562, expresses the chimeric bcr-abl oncoprotein, whose deregulated protein tyrosine kinase activity antagonizes the induction of apoptosis via DNA damaging agents. Previous experiments have shown that nanomolar concentrations of herbimycin A [HMA] coupled with X-irradiation have a synergistic effect in inducing apoptosis in the Ph-positive K562 leukemia cell line, but genistein, a PTK inhibitor, is non selective for the radiation-induced apoptosis of p210{sup bcr}/{sup abl} protected K562 cells. In these experiments, the cytoplasmic signal transduction pathways, the induction of a number of transcription factors and the differential gene expression in this model were investigated. K562 cells in the exponential growth phase were used in this study. The cells were irradiated with 0.5-12 Gy, using a 6 MeV Linac (Clinac 1800, Varian, USA). Immediately after irradiation, the cells were treated with 0.25{mu}M of HMA and 25{mu}M of genistein, and the expressions and the activities of ablkinase, MAPK family, NF-KB, c-fos, c-myc, and thymidine kinase1 (TK1) were examined. The differential gene expressions induced by PTK inhibitors were also investigated. The modulating effects of herbimycin A and genistein on the radiosensitivity of K562 cells were not related to the bcr-abl kinase activity. The signaling responses through the MAPK family of proteins, were not involved either. In association with the radiation-induced apoptosis, which is accelerated by HMA, the expression of c-myc was increased. The combined treatment of genistein, with irradiation, enhanced NF-KB activity and the TK 1 expression and activity. The effects of HMA and genistein on the radiosensitivity of the K562 cells were not related to the bcr-abl kinase activity. In this study, another signaling pathway, besides the MAPK family responses to radiation to K562 cells, was found. Further evaluation using this model will provide valuable information for the

  5. Development of preform moulding technique using expanded graphite for proton exchange membrane fuel cell bipolar plates

    Energy Technology Data Exchange (ETDEWEB)

    Heo, S.I.; Oh, K.S.; Yun, J.C.; Han, K.S. [Department of Mechanical Engineering, Pohang University of Science and Technology, San 31 Hyoja-dong, Nam-gu, Pohang, 790-784 (Korea); Jung, S.H.; Yang, Y.C. [Fuel Cell Vehicle Team, Advanced Technology Center, Research and Development Division for Hyundai Motor Company and Kia Motors Corporation, 104, Mabuk-dong, Giheung-Gu, Yongin, 446-912 (Korea)

    2007-09-27

    A preform moulding technique using expanded graphite is developed to manufacture composite bipolar plates for proton exchange membrane fuel cells (PEMFCs). The preform is composed of expanded graphite, graphite flake and phenol resin. Preforms utilizing the tangled structure of expanded graphite are easily fabricated at a low pressure of 0.07-0.28 MPa. A pre-curing temperature (100 C) slightly above the melting point of phenol powders (90 C) induces moderate curing, but also prevents excessive curing. After the preform is placed in a steel mould, compression moulding is carried out at high pressure (10 MPa) and temperature (150 C). The fabrication conditions are optimized by checking the electrical conductivity, flexural strength and microstructure of the composite. The optimized electrical conductivity and flexural strength, 250 S cm{sup -1} and 50 MPa, respectively, met the requirements for PEMFC bipolar plates. (author)

  6. Effect of hydroxyurea and etoposide on transduction of human bone marrow mesenchymal stem and progenitor cell by adeno-associated virus vectors

    Institute of Scientific and Technical Information of China (English)

    Xiao-dong JU; Si-quan LOU; Wei-guo WANG; Jian-qiang PENG; Hua TIAN

    2004-01-01

    AIM: To study the effect of hydroxyurea and etoposide on transduction of human marrow mesenchymal and progenitor stem cells by adeno-associated virus (AAV). METHODS: Isolated human bone marrow mesenchymal stem and progenitor cells (hMSCs) were cultured in DMEM containing 10 % FBS or 5 % FBS and dexamethasone 1 μmol/L respectively. After being treated with hydroxyurea and etoposide, hMSCs were transduced by AAV-LUC.After two days luciferase activity (relative light unites per second or RLU/s) were tested, which indirectly reflected the relative transduction efficiency of different groups, and virus DNA was isolated by Hirt extraction for Southern hybridization. RESULTS: Transduction luciferase activity and transduction efficiency in cultures treated with hydroxyurea and etoposide were significantly higher than that in control cultures. Dividing cells had about 20-fold higher transduction efficiency compared with control cells. Transduction efficiency in stationary cells was about 50 times higher than that in control cells. Southern analysis showed that hydroxyurea and etoposide enhanced second-strand DNA synthesis by rAAV. CONCLUSION: Hydroxyurea and etoposide could increase transduction efficiency of hMSCs by AAV vectors, and stationary cells were more sensitive to these drugs than dividing cells.

  7. Syntrophin proteins as Santa Claus: role(s) in cell signal transduction.

    Science.gov (United States)

    Bhat, Hina F; Adams, Marvin E; Khanday, Firdous A

    2013-07-01

    Syntrophins are a family of cytoplasmic membrane-associated adaptor proteins, characterized by the presence of a unique domain organization comprised of a C-terminal syntrophin unique (SU) domain and an N-terminal pleckstrin homology (PH) domain that is split by insertion of a PDZ domain. Syntrophins have been recognized as an important component of many signaling events, and they seem to function more like the cell's own personal 'Santa Claus' that serves to 'gift' various signaling complexes with precise proteins that they 'wish for', and at the same time care enough for the spatial, temporal control of these signaling events, maintaining overall smooth functioning and general happiness of the cell. Syntrophins not only associate various ion channels and signaling proteins to the dystrophin-associated protein complex (DAPC), via a direct interaction with dystrophin protein but also serve as a link between the extracellular matrix and the intracellular downstream targets and cell cytoskeleton by interacting with F-actin. They play an important role in regulating the postsynaptic signal transduction, sarcolemmal localization of nNOS, EphA4 signaling at the neuromuscular junction, and G-protein mediated signaling. In our previous work, we reported a differential expression pattern of alpha-1-syntrophin (SNTA1) protein in esophageal and breast carcinomas. Implicated in several other pathologies, like cardiac dys-functioning, muscular dystrophies, diabetes, etc., these proteins provide a lot of scope for further studies. The present review focuses on the role of syntrophins in membrane targeting and regulation of cellular proteins, while highlighting their relevance in possible development and/or progression of pathologies including cancer which we have recently demonstrated. PMID:23263165

  8. Degeneration of retinal on bipolar cells induced by serum including autoantibody against TRPM1 in mouse model of paraneoplastic retinopathy.

    Directory of Open Access Journals (Sweden)

    Shinji Ueno

    Full Text Available The paraneoplastic retinopathies (PRs are a group of eye diseases characterized by a sudden and progressive dysfunction of the retina caused by an antibody against a protein in a neoplasm. Evidence has been obtained that the transient receptor potential melastatin 1 (TRPM1 protein was one of the antigens for the autoantibody against the ON bipolar cells in PR patients. However, it has not been determined how the autoantibody causes the dysfunction of the ON bipolar cells. We hypothesized that the antibody against TRPM1 in the serum of patients with PR causes a degeneration of retinal ON bipolar cells. To test this hypothesis, we injected the serum from the PR patient, previously shown to contain anti-TRPM1 antibodies by westerblot, intravitreally into mice and examined the effects on the retina. We found that the electroretinograms (ERGs of the mice were altered acutely after the injection, and the shape of the ERGs resembled that of the patient with PR. Immunohistochemical analysis of the eyes injected with the serum showed immunoreactivity against bipolar cells only in wild-type animals and not in TRPM1 knockout mice,consistent with the serum containing anti-TRPM1 antibodies. Histology also showed that some of the bipolar cells were apoptotic by 5 hours after the injection in wild type mice, but no bipolar cell death was found in TRPM1 knockout mice, . At 3 months, the inner nuclear layer was thinner and the amplitudes of the ERGs were still reduced. These results indicate that the serum of a patient with PR contained an antibody against TRPM1 caused an acute death of retinal ON bipolar cells of mice.

  9. Forward Programming of Cardiac Stem Cells by Homogeneous Transduction with MYOCD plus TBX5.

    Directory of Open Access Journals (Sweden)

    Elisa Belian

    Full Text Available Adult cardiac stem cells (CSCs express many endogenous cardiogenic transcription factors including members of the Gata, Hand, Mef2, and T-box family. Unlike its DNA-binding targets, Myocardin (Myocd-a co-activator not only for serum response factor, but also for Gata4 and Tbx5-is not expressed in CSCs. We hypothesised that its absence was a limiting factor for reprogramming. Here, we sought to investigate the susceptibility of adult mouse Sca1+ side population CSCs to reprogramming by supplementing the triad of GATA4, MEF2C, and TBX5 (GMT, and more specifically by testing the effect of the missing co-activator, Myocd. Exogenous factors were expressed via doxycycline-inducible lentiviral vectors in various combinations. High throughput quantitative RT-PCR was used to test expression of 29 cardiac lineage markers two weeks post-induction. GMT induced more than half the analysed cardiac transcripts. However, no protein was detected for the induced sarcomeric genes Actc1, Myh6, and Myl2. Adding MYOCD to GMT affected only slightly the breadth and level of gene induction, but, importantly, triggered expression of all three proteins examined (α-cardiac actin, atrial natriuretic peptide, sarcomeric myosin heavy chains. MYOCD + TBX was the most effective pairwise combination in this system. In clonal derivatives homogenously expressing MYOCD + TBX at high levels, 93% of cardiac transcripts were up-regulated and all five proteins tested were visualized.(1 GMT induced cardiac genes in CSCs, but not cardiac proteins under the conditions used. (2 Complementing GMT with MYOCD induced cardiac protein expression, indicating a more complete cardiac differentiation program. (3 Homogeneous transduction with MYOCD + TBX5 facilitated the identification of differentiating cells and the validation of this combinatorial reprogramming strategy. Together, these results highlight the pivotal importance of MYOCD in driving CSCs toward a cardiac muscle fate.

  10. Cell surface receptors for signal transduction and ligand transport: a design principles study.

    Directory of Open Access Journals (Sweden)

    Harish Shankaran

    2007-06-01

    Full Text Available Receptors constitute the interface of cells to their external environment. These molecules bind specific ligands involved in multiple processes, such as signal transduction and nutrient transport. Although a variety of cell surface receptors undergo endocytosis, the systems-level design principles that govern the evolution of receptor trafficking dynamics are far from fully understood. We have constructed a generalized mathematical model of receptor-ligand binding and internalization to understand how receptor internalization dynamics encodes receptor function and regulation. A given signaling or transport receptor system represents a particular implementation of this module with a specific set of kinetic parameters. Parametric analysis of the response of receptor systems to ligand inputs reveals that receptor systems can be characterized as being: i avidity-controlled where the response control depends primarily on the extracellular ligand capture efficiency, ii consumption-controlled where the ability to internalize surface-bound ligand is the primary control parameter, and iii dual-sensitivity where both the avidity and consumption parameters are important. We show that the transferrin and low-density lipoprotein receptors are avidity-controlled, the vitellogenin receptor is consumption-controlled, and the epidermal growth factor receptor is a dual-sensitivity receptor. Significantly, we show that ligand-induced endocytosis is a mechanism to enhance the accuracy of signaling receptors rather than merely serving to attenuate signaling. Our analysis reveals that the location of a receptor system in the avidity-consumption parameter space can be used to understand both its function and its regulation.

  11. The biological networks in studying cell signal transduction complexity: The examples of sperm capacitation and of endocannabinoid system

    OpenAIRE

    Nicola Bernabò; Barbara Barboni; Mauro Maccarrone

    2014-01-01

    Cellular signal transduction is a complex phenomenon, which plays a central role in cell surviving and adaptation. The great amount of molecular data to date present in literature, together with the adoption of high throughput technologies, on the one hand, made available to scientists an enormous quantity of information, on the other hand, failed to provide a parallel increase in the understanding of biological events. In this context, a new discipline arose, the systems biology, aimed to ma...

  12. Bipolar polaron pair recombination in polymer/fullerene solar cells

    DEFF Research Database (Denmark)

    Kupijai, Alexander J.; Behringer, Konstantin M.; Schaeble, Florian G.;

    2015-01-01

    We present a study of the rate-limiting spin-dependent charge-transfer processes in different polymer/fullerene bulk-heterojunction solar cells at 10 K. Observing central spin-locking signals in pulsed electrically detected magnetic resonance and an inversion of Rabi oscillations in multifrequency...

  13. Signal transduction pathways in mast cell granule-mediated endothelial cell activation

    Directory of Open Access Journals (Sweden)

    Luqi Chi

    2003-01-01

    Full Text Available Background: We have previously shown that incubation of human endothelial cells with mast cell granules results in potentiation of lipopolysaccharide-induced production of interleukin-6 and interleukin-8.

  14. Nanosized TiN-SBR hybrid coating of stainless steel as bipolar plates for polymer electrolyte membrane fuel cells

    International Nuclear Information System (INIS)

    In attempt to improve interfacial electrical conductivity of stainless steel for bipolar plates of polymer electrolyte membrane fuel cells, TiN nanoparticles were electrophoretically deposited on the surface of stainless steel with elastic styrene butadiene rubber (SBR) particles. From transmission electron microscopic observation, it was found that the TiN nanoparticles (ca. 50 nm) surrounded the spherical SBR particles (ca. 300-600 nm), forming agglomerates. They were well adhered on the surface of the type 310S stainless steel. With help of elasticity of SBR, the agglomerates were well fitted into the interfacial gap between gas diffusion layer (GDL) and stainless steel bipolar plate, and the interfacial contact resistance (ICR), simultaneously, was successfully reduced. A single cell using the TiN nanoparticles-coated bipolar plates, consequently, showed comparable cell performance with the graphite employing cell at a current density of 0.5 A cm-2 (12.5 A). Inexpensive TiN nanoparticle-coated type 310S stainless steel bipolar plates would become a possible alternate for the expensive graphite bipolar plates as use in fuel cell applications

  15. Molecular purging of multiple myeloma cells by ex-vivo culture and retroviral transduction of mobilized-blood CD34+ cells

    Directory of Open Access Journals (Sweden)

    Corneo Gianmarco

    2007-07-01

    Full Text Available Abstract Background Tumor cell contamination of the apheresis in multiple myeloma is likely to affect disease-free and overall survival after autografting. Objective To purge myeloma aphereses from tumor contaminants with a novel culture-based purging method. Methods We cultured myeloma-positive CD34+ PB samples in conditions that retained multipotency of hematopoietic stem cells, but were unfavourable to survival of plasma cells. Moreover, we exploited the resistance of myeloma plasma cells to retroviral transduction by targeting the hematopoietic CD34+ cell population with a retroviral vector carrying a selectable marker (the truncated form of the human receptor for nerve growth factor, ΔNGFR. We performed therefore a further myeloma purging step by selecting the transduced cells at the end of the culture. Results Overall recovery of CD34+ cells after culture was 128.5%; ΔNGFR transduction rate was 28.8% for CD34+ cells and 0% for CD138-selected primary myeloma cells, respectively. Recovery of CD34+ cells after ΔNGFR selection was 22.3%. By patient-specific Ig-gene rearrangements, we assessed a decrease of 0.7–1.4 logs in tumor load after the CD34+ cell selection, and up to 2.3 logs after culture and ΔNGFR selection. Conclusion We conclude that ex-vivo culture and retroviral-mediated transduction of myeloma leukaphereses provide an efficient tumor cell purging.

  16. Pdx-1 or Pdx-1-VP16 protein transduction induces β-cell gene expression in liver-stem WB cells

    Directory of Open Access Journals (Sweden)

    Dubreil Laurence

    2009-01-01

    Full Text Available Abstract Background Pancreatic duodenal homeobox-1 (Pdx-1 or Pdx-1-VP16 gene transfer has been shown to induce in vitro rat liver-stem WB cell conversion into pancreatic endocrine precursor cells. High glucose conditions were necessary for further differentiation into functional insulin-producing cells. Pdx-1 has the ability to permeate different cell types due to an inherent protein transduction domain (PTD. In this study, we evaluated liver-to-pancreas conversion of WB cells following Pdx-1 or Pdx-1-VP16 protein transduction. Findings WB cells were grown in high glucose medium containing Pdx-1 or Pdx-1-VP16 recombinant proteins for two weeks. β-like cell commitment was analysed by RT-PCR of pancreatic endocrine genes. We found that WB cells in high glucose culture spontaneously express pancreatic endocrine genes (Pdx-1, Ngn3, Nkx2.2, Kir6.2. Their further differentiation into β-like cells expressing genes related to endocrine pancreas development (Ngn3, NeuroD, Pax4, Nkx2.2, Nkx6.1, Pdx-1 and β-cell function (Glut-2, Kir6.2, insulin was achieved only in the presence of Pdx-1(-VP16 protein. Conclusion These results demonstrate that Pdx-1(-VP16 protein transduction is instrumental for in vitro liver-to-pancreas conversion and is an alternative to gene therapy for β-cell engineering for diabetes cell therapy.

  17. Bipolar Disorder.

    Science.gov (United States)

    Miller, Thomas H

    2016-06-01

    Bipolar disorder is a chronic mental health disorder that is frequently encountered in primary care. Many patients with depression may actually have bipolar disorder. The management of bipolar disorder requires proper diagnosis and awareness or referral for appropriate pharmacologic therapy. Patients with bipolar disorder require primary care management for comorbidities such as cardiovascular and metabolic disorders. PMID:27262007

  18. Live cell imaging of primary rat neonatal cardiomyocytes following adenoviral and lentiviral transduction using confocal spinning disk microscopy.

    Science.gov (United States)

    Sakurai, Takashi; Lanahan, Anthony; Woolls, Melissa J; Li, Na; Tirziu, Daniela; Murakami, Masahiro

    2014-01-01

    Primary rat neonatal cardiomyocytes are useful in basic in vitro cardiovascular research because they can be easily isolated in large numbers in a single procedure. Due to advances in microscope technology it is relatively easy to capture live cell images for the purpose of investigating cellular events in real time with minimal concern regarding phototoxicity to the cells. This protocol describes how to take live cell timelapse images of primary rat neonatal cardiomyocytes using a confocal spinning disk microscope following lentiviral and adenoviral transduction to modulate properties of the cell. The application of two different types of viruses makes it easier to achieve an appropriate transduction rate and expression levels for two different genes. Well focused live cell images can be obtained using the microscope's autofocus system, which maintains stable focus for long time periods. Applying this method, the functions of exogenously engineered proteins expressed in cultured primary cells can be analyzed. Additionally, this system can be used to examine the functions of genes through the use of siRNAs as well as of chemical modulators. PMID:24998400

  19. Theoretical design strategies of bipolar membrane fuel cell with enhanced self-humidification behavior

    Science.gov (United States)

    Li, Qiushi; Gong, Jian; Peng, Sikan; Lu, Shanfu; Sui, Pang-Chieh; Djilali, Ned; Xiang, Yan

    2016-03-01

    The bipolar membrane fuel cells (BPMFCs), which have a unique acid-alkaline jointed membrane electrode assembly (MEA) structure, have demonstrated their great potential for self-humidification during operation. Although the self-humidification ability of such bipolar membranes (BPMs) has recently been validated by a one-dimensional BPM model, the transport mechanism and the formation of self-humidification in the MEAs are not well understood. In the present study, a two-dimensional cross-channel MEA model is developed to elucidate the mechanisms and enhancement of water transport on self-humidification with comprehensive consideration of the three electrochemical reaction zones. The water-formation interface model has been successfully investigated by theoretical and experimental interface reaction kinetics, streamlines of water flux present the formation process and mechanism of self-humidification. A critical current (voltage) value, beyond which self-humidification is initiated, is identified. It is also found that such critical current (voltage) can be adjusted by changing the membrane thickness and the water uptake property of the ionomer. It is concluded that fabricating BPMs with proper membrane thickness and water uptake property are effective strategies to enhance the water management and cell performance in BPMFCs.

  20. Polyaniline and polypyrrole coatings on aluminum for PEM fuel cell bipolar plates

    Energy Technology Data Exchange (ETDEWEB)

    Joseph, Shine; McClure, J.C. [Metallurgical and Materials Department, University of Texas El Paso, El Paso, TX (United States); Sebastian, P.J. [Centro de Investigation en Energia, UNAM, Temixco, Morelos (Mexico); CAES, UP Chiapas, Tuxtla Gutierrez, Chiapas (Mexico); Moreira, J.; Valenzuela, Edgar [CAES, UP Chiapas, Tuxtla Gutierrez, Chiapas (Mexico)

    2008-02-15

    The conducting polymers polypyrrole and polyaniline were deposited on 6061 aluminum using cyclic voltammetry and painting, respectively. These samples are intended for proton exchange membrane fuel cell applications where surface contact resistance as well as bulk corrosion resistance are requirements for the bipolar plates that separate the cells. Corrosion current and voltage were measured on the samples as well as contact resistance between coated samples as a function of contact pressure. The polypyrrole samples showed neither improved corrosion resistance nor acceptable contact resistance. The painted polyaniline samples, however, showed about an order of magnitude reduction in corrosion current with only a minor increase in contact resistance. It is believed that in the more acidic environment of a fuel cell, the polyaniline will become even more conductive and that further reduction in contact resistance should be possible. (author)

  1. Transduction of interleukin-10 through renal artery attenuates vascular neointimal proliferation and infiltration of immune cells in rat renal allograft.

    Science.gov (United States)

    Xie, Jingxin; Li, Xueyi; Meng, Dan; Liang, Qiujuan; Wang, Xinhong; Wang, Li; Wang, Rui; Xiang, Meng; Chen, Sifeng

    2016-08-01

    Renal transplantation is the treatment of choice for end-stage renal failure. Although acute rejection is not a major issue anymore, chronic rejection, especially vascular rejection, is still a major factor that might lead to allograft dysfunction on the long term. The role of the local immune-regulating cytokine interleukin-10 (IL-10) in chronic renal allograft is unclear. Many clinical observations showed that local IL-10 level was negatively related to kidney allograft function. It is unknown this negative relationship was the result of immunostimulatory property or insufficient immunosuppression property of local IL-10. We performed ex vivo transduction before transplantation through artery of the renal allograft using adeno-associated viral vectors carrying IL-10 gene. Twelve weeks after transplantation, we found intrarenal IL-10 gene transduction significantly inhibited arterial neointimal proliferation, the number of occluded intrarenal artery, interstitial fibrosis, peritubular capillary congestion and glomerular inflammation in renal allografts compared to control allografts receiving PBS or vectors carrying YFP. IL-10 transduction increased serum IL-10 level at 4 weeks but not at 8 and 12 weeks. Renal IL-10 level increased while serum creatinine decreased significantly in IL-10 group at 12 weeks compared to PBS or YFP controls. Immunohistochemical staining showed unchanged total T cells (CD3) and B cells (CD45R/B220), decreased cytotoxic T cells (CD8), macrophages (CD68) and increased CD4+ and FoxP3+ cells in IL-10 group. In summary, intrarenal IL-10 inhibited the allograft rejection while modulated immune response.

  2. Single molecule narrowfield microscopy of protein-DNA binding dynamics in glucose signal transduction of live yeast cells

    CERN Document Server

    Wollman, Adam J M

    2016-01-01

    Single-molecule narrowfield microscopy is a versatile tool to investigate a diverse range of protein dynamics in live cells and has been extensively used in bacteria. Here, we describe how these methods can be extended to larger eukaryotic, yeast cells, which contain sub-cellular compartments. We describe how to obtain single-molecule microscopy data but also how to analyse these data to track and obtain the stoichiometry of molecular complexes diffusing in the cell. We chose glucose mediated signal transduction of live yeast cells as the system to demonstrate these single-molecule techniques as transcriptional regulation is fundamentally a single molecule problem - a single repressor protein binding a single binding site in the genome can dramatically alter behaviour at the whole cell and population level.

  3. Regulation of promyogenic signal transduction by cell-cell contact and adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, Robert S., E-mail: Robert.Krauss@mssm.edu [Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029 (United States)

    2010-11-01

    Skeletal myoblast differentiation involves acquisition of the muscle-specific transcriptional program and morphological changes, including fusion into multinucleated myofibers. Differentiation is regulated by extracellular signaling cues, including cell-cell contact and adhesion. Cadherin and Ig adhesion receptors have been implicated in distinct but overlapping stages of myogenesis. N-cadherin signals through the Ig receptor Cdo to activate p38 MAP kinase, while the Ig receptor neogenin signals to activate FAK; both processes promote muscle-specific gene expression and myoblast fusion. M-cadherin activates Rac1 to enhance fusion. Specific Ig receptors (Kirre and Sns) are essential for myoblast fusion in Drosophila, also signaling through Rac, and vertebrate orthologs of Kirre and Sns have partially conserved function. Mice lacking specific cytoplasmic signaling factors activated by multiple receptors (e.g., Rac1) have strong muscle phenotypes in vivo. In contrast, mice lacking individual adhesion receptors that lie upstream of these factors have modest phenotypes. Redundancy among receptors may account for this. Many of the mammalian Ig receptors and cadherins associate with each other, and multivalent interactions within these complexes may require removal of multiple components to reveal dramatic defects in vivo. Nevertheless, it is possible that the murine adhesion receptors rate-limiting in vivo have not yet been identified or fully assessed.

  4. Small-Molecule Inhibitors of Cytokine-Mediated STAT1 Signal Transduction In ß-Cells With Improved Aqueous Solubility

    DEFF Research Database (Denmark)

    Scully, Stephen Shane; Tang, Alicia J; Lundh, Morten;

    2013-01-01

    We previously reported the discovery of BRD0476 (1), a small molecule generated by diversity-oriented synthesis that suppresses cytokine-induced ß-cell apoptosis. Herein, we report the synthesis and biological evaluation of 1 and analogs with improved aqueous solubility. By replacing naphthyl wit...... with quinoline moieties, we prepared active analogs with up to a 1400-fold increase in solubility from 1. In addition, we demonstrated that compound 1 and analogs inhibit STAT1 signal transduction induced by IFN-¿....

  5. FLT3 ligand preserves the uncommitted CD34+CD38- progenitor cells during cytokine prestimulation for retroviral transduction

    DEFF Research Database (Denmark)

    Nielsen, S D; Husemoen, L L; Sørensen, T U;

    2000-01-01

    Before stem cell gene therapy can be considered for clinical applications, problems regarding cytokine prestimulation remain to be solved. In this study, a retroviral vector carrying the genes for the enhanced version of green fluorescent protein (EGFP) and neomycin resistance (neo(r)) was used...... (SCF), FLT3 ligand, interleukin-3 (IL-3), IL-6, and IL-7 prior to transduction. Expression of the two genes was assessed by flow cytometry and determination of neomycin-resistant colonies in a selective colony-forming unit (CFU) assay, respectively. The neomycin resistance gene was expressed...

  6. Stereotyped initiation of retinal waves by bipolar cells via presynaptic NMDA autoreceptors.

    Science.gov (United States)

    Zhang, Rong-Wei; Li, Xiao-Quan; Kawakami, Koichi; Du, Jiu-Lin

    2016-01-01

    Glutamatergic retinal waves, the spontaneous patterned neural activities propagating among developing retinal ganglion cells (RGCs), instruct the activity-dependent refinement of visuotopic maps. However, its initiation and underlying mechanism remain largely elusive. Here using larval zebrafish and multiple in vivo approaches, we discover that bipolar cells (BCs) are responsible for the generation of glutamatergic retinal waves. The wave originates from BC axon terminals (ATs) and propagates laterally to nearby BCs and vertically to downstream RGCs and the optic tectum. Its initiation is triggered by the activation of and consequent glutamate release from BC ATs, and is mediated by the N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) expressed at these ATs. Intercellular asymmetry of NMDAR expression at BC ATs enables the preferential initiation of waves at the temporal retina, where BC ATs express more NMDARs. Thus, our findings indicate that glutamatergic retinal waves are initiated by BCs through a presynaptic NMDA autoreceptor-dependent process. PMID:27586999

  7. Photothermally induced bromination of carbon/polymer bipolar plate materials for fuel cell applications

    Energy Technology Data Exchange (ETDEWEB)

    Schade, Martin; Franzka, Steffen [Fakultät für Chemie, Universität Duisburg-Essen, 45117 Essen (Germany); Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Carl-Benz-Straße 199, 47057 Duisburg (Germany); Cappuccio, Franco; Peinecke, Volker; Heinzel, Angelika [Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Carl-Benz-Straße 199, 47057 Duisburg (Germany); Zentrum für BrennstoffzellenTechnik (ZBT), Carl-Benz-Straße 201, 47057 Duisburg (Germany); Hartmann, Nils, E-mail: nils.hartmann@uni-due.de [Fakultät für Chemie, Universität Duisburg-Essen, 45117 Essen (Germany); Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Carl-Benz-Straße 199, 47057 Duisburg (Germany)

    2015-05-01

    Graphical abstract: - Highlights: • Photothermal laser bromination of carbon/polymer materials is demonstrated. • Using a microfocused laser functionalized domains with diameters of 5 μm and 100 μm and more can be fabricated. • Bromine groups can be transformed in a variety of other chemical functionalities, i.e. amine groups. • Depending on the chemical functionality, the local chemical affinity and wettability is changed. • The routine can be applied to standard bipolar plate materials used for fuel cell applications. - Abstract: A facile photothermal procedure for direct functionalization of carbon/polymer bipolar plate materials is demonstrated. Through irradiation with a microfocused beam of an Ar{sup +}-laser at λ = 514 nm in gaseous bromine and distinct laser powers and pulse lengths local bromination of the carbon/polymer material takes place. At a 1/e spot diameter of 2.1 μm, functionalized surface areas with diameters down to 5 μm are fabricated. In complementary experiments large-area bromination is investigated using an ordinary tungsten lamp. For characterization contact angle goniometry, X-ray photoelectron spectroscopy and electron microscopy in conjunction with labeling techniques are employed. After irradiation bromine groups can easily be substituted by other chemical functionalities, e.g. azide and amine groups. This provides a facile approach in order to fabricate surface patterns and gradient structures with varying wetting characteristics. Mechanistic aspects and prospects of photothermal routines in micropatterning of carbon/polymer materials are discussed.

  8. Surface modification and performance of inexpensive Fe-based bipolar plates for proton exchange membrane fuel cells

    Science.gov (United States)

    Bai, Ching-Yuan; Wen, Tse-Min; Huang, Mao-Suan; Hou, Kung-Hsu; Ger, Ming-Der; Lee, Shuo-Jen

    A reforming pack chromization with rolling pretreatment process is utilized to develop inexpensive and high-performance Fe-based metal bipolar plates (SS 420, SS 430, and SS 316 stainless steels) for PEMFC systems. Rolling process is previously performed to reduce the chromizing temperature and generate a coating possessing excellent conductivity and corrosion resistance on the steels during chromization. The power efficiencies of rolled-chromized and simple chromized bipolar plates are compared with graphite bipolar plates employed in PEMFCs. The results show that the rolled-chromized bipolar plates have a corrosion current (I corr) of 7.87 × 10 -8 A cm -2 and an interfacial contact resistance of 9.7 mΩ cm 2. Moreover, the power density of the single cell assembled with rolled-chromized bipolar plates is 0.46 W cm -2, which is very close to that of graphite (0.50 W cm -2), in the tested conditions of this study.

  9. Improvements of electrical properties containing carbon nanotube in epoxy/graphite bipolar plate for polymer electrolyte membrane fuel cells.

    Science.gov (United States)

    Lee, HongKi; Rim, HyungRyul; Lee, JaeYoung; Lee, Jongmin; Yoon, JeongMo; Bae, WooJung; Yang, SeungWeon

    2008-10-01

    The epoxy based graphite bipolar plate containing carbon nanotube (CNT) for polymer electrolyte membrane fuel cells (PEMFC) has been prepared and the electrical properties were compared. The density of graphite composite bipolar plate showed from 1.85 to 0.94 as expanded graphite content is increased from 10 to 50 w/o. The improvement of electrical properties was accomplished by addition of CNT. Rapid increase of conductivity was found due to the compensation between increases of the electrical pathway by addition of CNT and sufficient electrical contact among isolated large graphite particle. The polarisation curves of bipolar plate were measured at 1 M H2SO4 solution with 1 mV/sec of scan rate and the value of 1.903 uA/cm2 of corrosion rate was obtained. PMID:19198477

  10. A bipolar membrane combined with ferric iron reduction as an efficient cathode system in microbial fuel cells

    NARCIS (Netherlands)

    Heijne, ter A.; Hamelers, H.V.M.; Wilde, de V.; Rozendal, R.A.; Buisman, C.J.N.

    2006-01-01

    There is a need for alternative catalysts for oxygen reduction in the cathodic compartment of a microbial fuel cell (MFC). In this study, we show that a bipolar membrane combined with ferric iron reduction on a graphite electrode is an efficient cathode system in MFCs. A flat plate MFC with graphite

  11. Signal transduction in cells induced by endotoxin%内毒素诱导的细胞内信息转导

    Institute of Scientific and Technical Information of China (English)

    单于; 陆大祥

    2001-01-01

    Depending on LBP/CD14 systems, LPS activates a series ofsignal-transducing systems in cells. Protein tyrosin kinase(PTK)system,ceramide activated kinase(CAK)system might play an important role in cells signal-transducing.This article give a summary about signal transduction in cells induced by endotoxin.

  12. Bipolar Disorder

    Science.gov (United States)

    Bipolar disorder is a serious mental illness. People who have it go through unusual mood changes. They go from ... down feeling is depression. The causes of bipolar disorder aren't always clear. It runs in families. ...

  13. Bipolar Disorder

    Science.gov (United States)

    ... types of psychotherapies. Other Treatment Options Electroconvulsive Therapy (ECT) : ECT can provide relief for people with severe bipolar ... been able to recover with other treatments. Sometimes ECT is used for bipolar symptoms when other medical ...

  14. Preparation and characterization of mono-sheet bipolar membranes by pre-irradiation grafting method for fuel cell applications

    Science.gov (United States)

    Guan, Yingjie; Fang, Jun; Fu, Tao; Zhou, Huili; Wang, Xin; Deng, Zixiang; Zhao, Jinbao

    2016-09-01

    A new method for the preparation of the mono-sheet bipolar membrane applied to fuel cells was developed based on the pre-irradiation grafting technology. A series of bipolar membranes were successfully prepared by simultaneously grafting of styrene onto one side of the poly(ethylene-co-tetrafluoroethylene) base film and 1-vinylimidazole onto the opposite side, followed by the sulfonation and alkylation, respectively. The chemical structures and microstructures of the prepared membranes were investigated by ATR-FTIR and SEM-EDS. The TGA measurements demonstrated the prepared bipolar membranes have reasonable thermal stability. The ion exchange capacity, water uptake and ionic conductivity of the membranes were also characterized. The H2/O2 single fuel cells using these membranes were evaluated and revealed a maximum power density of 107 mW cm-2 at 35 °C with unhumidified hydrogen and oxygen. The preliminary performances suggested the great prospect of these membranes in application of bipolar membrane fuel cells.

  15. Accelerated generation of human induced pluripotent stem cells with retroviral transduction and chemical inhibitors under physiological hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Hidenori [Department of Bioartificial Organs, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507 (Japan); Hashimoto, Yoshiya [Department of Biomaterials, Osaka Dental University, 8-1, Hanazonocho, Kuzuha, Hirakatashi, Osaka 573-1121 (Japan); Nakada, Akira; Shigeno, Keiji [Department of Bioartificial Organs, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507 (Japan); Nakamura, Tatsuo, E-mail: nakamura@frontier.kyoto-u.ac.jp [Department of Bioartificial Organs, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507 (Japan)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Very rapid generation of human iPS cells under optimized conditions. Black-Right-Pointing-Pointer Five chemical inhibitors under hypoxia boosted reprogramming. Black-Right-Pointing-Pointer We performed genome-wide DNA methylation analysis. -- Abstract: Induced pluripotent stem (iPS) cells are generated from somatic cells by the forced expression of a defined set of pluripotency-associated transcription factors. Human iPS cells can be propagated indefinitely, while maintaining the capacity to differentiate into all cell types in the body except for extra-embryonic tissues. This technology not only represents a new way to use individual-specific stem cells for regenerative medicine but also constitutes a novel method to obtain large amounts of disease-specific cells for biomedical research. Despite their great potential, the long reprogramming process (up to 1 month) remains one of the most significant challenges facing standard virus-mediated methodology. In this study, we report the accelerated generation of human iPS cells from adipose-derived stem (ADS) cells, using a new combination of chemical inhibitors under a setting of physiological hypoxia in conjunction with retroviral transduction of Oct4, Sox2, Klf4, and L-Myc. Under optimized conditions, we observed human embryonic stem (ES)-like cells as early as 6 days after the initial retroviral transduction. This was followed by the emergence of fully reprogrammed cells bearing Tra-1-81-positive and DsRed transgene-silencing properties on day 10. The resulting cell lines resembled human ES cells in many respects including proliferation rate, morphology, pluripotency-associated markers, global gene expression patterns, genome-wide DNA methylation states, and the ability to differentiate into all three of the germ layers, both in vitro and in vivo. Our method, when combined with chemical inhibitors under conditions of physiological hypoxia, offers a powerful tool for rapidly

  16. Reduced number of peripheral natural killer cells in schizophrenia but not in bipolar disorder.

    Science.gov (United States)

    Karpiński, Paweł; Frydecka, Dorota; Sąsiadek, Maria M; Misiak, Błażej

    2016-05-01

    Overwhelming evidence indicates that subthreshold inflammatory state might be implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BPD). It has been reported that both groups of patients might be characterized by abnormal lymphocyte counts. However, little is known about alterations in lymphocyte proportions that may differentiate SCZ and BPD patients. Therefore, in this study we investigated blood cell proportions quantified by means of microarray expression deconvolution using publicly available data from SCZ and BPD patients. We found significantly lower counts of natural killer (NK) cells in drug-naïve and medicated SCZ patients compared to healthy controls across all datasets. In one dataset from SCZ patients, there were no significant differences in the number of NK cells between acutely relapsed and remitted SCZ patients. No significant difference in the number of NK cells between BPD patients and healthy controls was observed in all datasets. Our results indicate that SCZ patients, but not BPD patients, might be characterized by reduced counts of NK cells. Future studies looking at lymphocyte counts in SCZ should combine the analysis of data obtained using computational deconvolution and flow cytometry techniques.

  17. Bipolar plate materials in molten carbonate fuel cells. Final CRADA report.

    Energy Technology Data Exchange (ETDEWEB)

    Krumpelt, M.

    2004-06-01

    Advantages of implementation of power plants based on electrochemical reactions are successfully demonstrated in the USA and Japan. One of the msot promising types of fuel cells (FC) is a type of high temperature fuel cells. At present, thanks to the efforts of the leading countries that develop fuel cell technologies power plants on the basis of molten carbonate fuel cells (MCFC) and solid oxide fuel cells (SOFC) are really close to commercialization. One of the problems that are to be solved for practical implementation of MCFC and SOFC is a problem of corrosion of metal components of stacks that are assembled of a number of fuel cells. One of the major components of MCFC and SOFC stacks is a bipolar separator plate (BSP) that performs several functions - it is separation of reactant gas flows sealing of the joints between fuel cells, and current collection from the surface of electrodes. The goal of Task 1 of the project is to develop new cost-effective nickel coatings for the Russian 20X23H18 steel for an MCFC bipolar separator plate using technological processes usually implemented to apply corrosion stable coatings onto the metal parts for products in the defense. There was planned the research on production of nickel coatings using different methods, first of all the galvanic one and the explosion cladding one. As a result of the works, 0.4 x 712 x 1296 mm plates coated with nickel on one side were to be made and passed to ANL. A line of 4 galvanic baths 600 liters was to be built for the galvanic coating applications. The goal of Task 2 of the project is the development of a new material of an MCFC bipolar separator plate with an upgraded corrosion stability, and development of a technology to produce cold roll sheets of this material the sizes of which will be 0.8 x 712x 1296 mm. As a result of these works, a pilot batch of the rolled material in sheets 0.8 x 712 x 1296 mm in size is to be made (in accordance with the norms and standards of the Russian

  18. Receptive field properties of bipolar cell axon terminals in direction-selective sublaminas of the mouse retina

    OpenAIRE

    Chen, Minggang; Lee, Seunghoon; Park, Silvia J.H.; Loren L Looger; Zhou, Z. Jimmy

    2014-01-01

    Retinal bipolar cells (BCs) transmit visual signals in parallel channels from the outer to the inner retina, where they provide glutamatergic inputs to specific networks of amacrine and ganglion cells. Intricate network computation at BC axon terminals has been proposed as a mechanism for complex network computation, such as direction selectivity, but direct knowledge of the receptive field property and the synaptic connectivity of the axon terminals of various BC types is required in order t...

  19. A Simulation Tool for Geometrical Analysis and Optimization of Fuel Cell Bipolar Plates: Development, Validation and Results

    OpenAIRE

    Javier Pino; Felipe Rosa; Alfredo Iranzo

    2009-01-01

    Bipolar plates (BPs) are one of the most important components in Proton Exchange Membrane Fuel Cells (PEMFC) due to the numerous functions they perform. The objective of the research work described in this paper was to develop a simplified and validated method based on Computational Fluid Dynamics (CFD), aimed at the analysis and study of the influence of geometrical parameters of BPs on the operation of a cell. A complete sensibility analysis of the influence of dimensions and shape of the B...

  20. Prolonged maturation and enhanced transduction of dendritic cells migrated from human skin explants after in situ delivery of CD40-targeted adenoviral vectors

    NARCIS (Netherlands)

    de Gruijl, TD; Luykx-de Bakker, SA; Tillman, BW; van den Eertwegh, AJM; Buter, J; Lougheed, SM; van der Bij, GJ; Safer, AM; Haisma, HJ; Curiel, DT; Scheper, RJ; Pinedo, HM; Gerritsen, WR

    2002-01-01

    Therapeutic tumor vaccination with viral vectors or naked DNA, carrying the genetic code for tumor-associated Ags, critically depends on the in vivo transduction of dendritic cells (DC). Transfection of predominantly nonprofessional APC and only small numbers of DC may hamper proper T cell activatio

  1. Comparative transduction mechanisms of hair cells in the bullfrog uticulus. 2: Sensitivity and response dynamics to hair bundle displacement

    Science.gov (United States)

    Baird, Richard A.

    1994-01-01

    The present study was motivated by an interest in seeing whether hair cell types in the bullfrog utriculus might differ in their voltage responses to hair bundle displacement. Particular interest was in assessing the contributions of two factors to the responses of utricular hair cells. First, interest in examining the effect of hair bundle morphology on the sensitivity of hair cells to natural stimulation was motivated by the observation that vestibular hair cells, unlike many auditory hair cells, are not free-standing but rather linked to an accessory cupular or otolithic membrane via the tip of their kinocilium. Interest also laid in examining the contribution, if any, of adaptation to the response properties of utricular hair cells. Hair cells in auditory and vibratory inner ear endorgans adapt to maintained displacements of their hair bundles, sharply limiting their low frequency sensitivity. This adaptation is mediated by a shift in the displacement-response curve (DRC) of the hair cell along the displacement axis. Observations suggest that the adaptation process occurs within the hair bundle and precedes mechanoelectric transduction. Recent observations of time-dependent changes in hair bundle stiffness are consistent with this conclusion. Adaptation would be expected to be most useful in inner ear endorgans in which hair cells are subject to large static displacements that could potentially saturate their instantaneous response and compromise their sensitivity to high frequency stimulation. The adaptation process also permits hair cells to maintain their sensory hair bundle in the most sensitive portion of their DRC. In vestibular otolith organs in which static sensitivity is desirable, any adaptation process in the hair cells may be undesirable. The rate and extent of the decline of the voltage responses was measured of utricular hair cells to step and sinusoidal hair bundle displacements. Then for similar resting potentials and response amplitudes, the

  2. Autoantibody against transient receptor potential M1 cation channels of retinal ON bipolar cells in paraneoplastic vitelliform retinopathy

    Directory of Open Access Journals (Sweden)

    Wang Yujuan

    2012-11-01

    Full Text Available Abstract Background Paraneoplastic retinopathy is caused by the cross-reaction of neoplasm-directed autoantibodies against retinal antigens and results in retinal damage. Paraneoplastic vitelliform retinopathy, a presumed paraneoplastic retinopathy with features of atypical melanoma-associated retinopathy, has recently been reported in patients with metastatic melanoma. Ocular ultrastructure and its autoantibody localization of paraneoplastic vitelliform retinopathy are still indefinable. This is the first report of anti-transient receptor potential M1 antibody directly against human retinal bipolar dendritic tips in a melanoma patient with paraneoplastic vitelliform retinopathy. Case presentation We present a pair of postmortem eyes of an 80-year-old male with metastatic cutaneous melanoma, who developed paraneoplastic vitelliform retinopathy. The autopsied eyes were examined with light microscopy, immunohistochemistry, and transmission electron microscopy. Microscopically, the inner nuclear layer and outer plexiform layer were the most affected retinal structures, with local thinning. The lesions extended to the outer nuclear layer, resulting in focal retinal degeneration, edema, and atrophy. No active inflammation or melanoma cells were observed. Immunohistochemistry showed tightly compact bipolar cell nuclei (protein kinase C alpha/calbindin positive with blur/loss of ON bipolar cell dendritic tips (transient receptor potential M1 positive in diffusely condensed outer plexiform layer. The metastatic melanoma cells in his lung also showed immunoreactivity against transient receptor potential M1 antibody. Transmission electron microscopy illustrated degenerated inner nuclear layer with disintegration of cells and loss of cytoplasmic organelles. These cells contained many lysosomal and autophagous bodies and damaged mitochondria. Their nuclei appeared pyknotic and fragmentary. The synapses in the outer plexiform layer were extensively

  3. Characterization of Thermal and Mechanical Properties of Polypropylene-Based Composites for Fuel Cell Bipolar Plates and Development of Educational Tools in Hydrogen and Fuel Cell Technologies

    Science.gov (United States)

    Lopez Gaxiola, Daniel

    2011-01-01

    In this project we developed conductive thermoplastic resins by adding varying amounts of three different carbon fillers: carbon black (CB), synthetic graphite (SG) and multi-walled carbon nanotubes (CNT) to a polypropylene matrix for application as fuel cell bipolar plates. This component of fuel cells provides mechanical support to the stack,…

  4. The targeted transduction of MMP-overexpressing tumor cells by ACPP-HPMA copolymer-coated adenovirus conjugates.

    Directory of Open Access Journals (Sweden)

    Shuhua Li

    Full Text Available We have designed and tested a new way to selectively deliver HPMA polymer-coated adenovirus type 5 (Ad5 particles into matrix metalloproteinase (MMP-overexpressing tumor cells. An activatable cell penetrating peptide (ACPP was designed and attached to the reactive 4-nitrophenoxy groups of HPMA polymers by the C-terminal amino acid (asparagine, N. ACPPs are activatable cell penetrating peptides (CPPs with a linker between polycationic and polyanionic domains, and MMP-mediated cleavage releases the CPP portion and its attached cargo to enable cell entry. Our data indicate that the transport of these HPMA polymer conjugates by a single ACPP molecule to the cytoplasm occurs via a nonendocytotic and concentration-independent process. The uptake was observed to finish within 20 minutes by inverted fluorescence microscopy. In contrast, HPMA polymer-coated Ad5 without ACPPs was internalized solely by endocytosis. The optimal formulation was not affected by the presence of Ad5 neutralizing antibodies during transduction, and ACPP/polymer-coated Ad5 also retained high targeting capability to several MMP-overexpressing tumor cell types. For the first time, ACPP-mediated cytoplasmic delivery of polymer-bound Ad5 to MMP-overexpressing tumor cells was demonstrated. These findings are significant, as they demonstrate the use of a polymer-based system for the targeted delivery into MMP-overexpressing solid tumors and highlight how to overcome major cellular obstacles to achieve intracellular macromolecular delivery.

  5. Integrins mediating bone signal transduction

    Institute of Scientific and Technical Information of China (English)

    HE Chuanglong; WANG Yuanliang; YANG Lihua; ZHANG Jun

    2004-01-01

    Integrin-mediated adhesions play critical roles in diverse cell functions. Integrins offers a platform on which mechanical stimuli, cytoskeletal organization, biochemical signals can concentrate. Mechanical stimuli transmitted by integrins influence the cytoskeleton, in turn, the cytoskeleton influences cell adhesion via integrins, then cell adhesion results in a series of signal transduction cascades. In skeleton, integrins also have a key role for bone resoption by osteoclasts and reformation by osteoblasts. In present review, the proteins involved in integrin signal transduction and integrin signal transduction pathways were discussed, mainly on the basic mechanisms of integrin signaling and the roles of integrins in bone signal transduction, which may give insight into new therapeutic agents to all kinds of skeletal diseases and new strategies for bone tissue engineering.

  6. Preparation and properties of functionalized multiwalled carbon nanotubes/polypropylene nanocomposite bipolar plates for polymer electrolyte membrane fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Shu-Hang; Weng, Cheng-Chih; Yen, Chuan-Yu.; Hsiao, Min-Chien; Ma, Chen-Chi M.; Yen, Ming-Yu.; Liu, Po-Lan [Department of Chemical Engineering, National Tsing Hua University, Hsin-Chu 30043 (China); Tsai, Ming-Chi [Department of Engineering and System Science, National Tsing Hua University, Hsin-Chu 30043 (China); Su, Ay [Fuel Cell Center, Yuan Ze University, Tao-Yuan 32003 (China); Lin, Yu-Feng [Plastics Industry Development Center, Tai-Chung 40768 (China)

    2010-01-01

    Multiwalled carbon nanotubes (MWCNTs) are covalently modified with different molecular weights 400 and 2000 poly(oxyalkylene)-amine bearing the diglycidyl ether of bisphenol A (DGEBA) epoxy (POA400-DGEBA and POA2000-DGEBA) oligomers. The oxidized MWCNTs (MWCNTs-COOH) are converted to the acid chloride-functionalized MWCNTs, followed by the reaction with POA-DGEBAs to prepare the MWCNTs/POA400-DGEBA and MWCNTs/POA2000-DGEBA. FTIR, thermogravimetric analysis (TGA) and high resolution X-ray photoelectron spectra (XPS) reveal that the POA-DGEBAs are covalently attached to the surface of MWCNTs. The morphology of MWCNTs/POA-DGEBA is observed by TEM. The POA400-DGEBA coated on the MWCNTs is thicker and more uniform. However, the coating of POA2000-DGEBA on the MWCNTs shows a worm-like bulk substance and the MWCNT surface is bare. In addition, the flexural strength and the bulk electrical conductivity of the MWCNTs/polypropylene nanocomposite bipolar plates are measured 59% and 505% higher than those of the original composite bipolar plates by adding 8 phr of MWCNTs/POA400-DGEBA. The maximum current density and power density of the single cell test for the nanocomposite bipolar plate with 4 phr MWCNTs/POA400-DGEBA are 1.32 A cm{sup -2} and 0.533 W cm{sup -2}, respectively. The overall performance confirms the functionalized MWCNTs/polypropylene nanocomposite bipolar plates prepared in this study are suitable for PEMFC application. (author)

  7. Lipid rafts are required for signal transduction by angiotensin II receptor type 1 in neonatal glomerular mesangial cells

    Energy Technology Data Exchange (ETDEWEB)

    Adebiyi, Adebowale, E-mail: aadebiyi@uthsc.edu; Soni, Hitesh; John, Theresa A.; Yang, Fen

    2014-05-15

    Angiotensin II (ANG-II) receptors (AGTRs) contribute to renal physiology and pathophysiology, but the underlying mechanisms that regulate AGTR function in glomerular mesangium are poorly understood. Here, we show that AGTR1 is the functional AGTR subtype expressed in neonatal pig glomerular mesangial cells (GMCs). Cyclodextrin (CDX)-mediated cholesterol depletion attenuated cell surface AGTR1 protein expression and ANG-II-induced intracellular Ca{sup 2+} ([Ca{sup 2+}]{sub i}) elevation in the cells. The COOH-terminus of porcine AGTR1 contains a caveolin (CAV)-binding motif. However, neonatal GMCs express CAV-1, but not CAV-2 and CAV-3. Colocalization and in situ proximity ligation assay detected an association between endogenous AGTR1 and CAV-1 in the cells. A synthetic peptide corresponding to the CAV-1 scaffolding domain (CSD) sequence also reduced ANG-II-induced [Ca{sup 2+}]{sub i} elevation in the cells. Real-time imaging of cell growth revealed that ANG-II stimulates neonatal GMC proliferation. ANG-II-induced GMC growth was attenuated by EMD 66684, an AGTR1 antagonist; BAPTA, a [Ca{sup 2+}]{sub i} chelator; KN-93, a Ca{sup 2+}/calmodulin-dependent protein kinase II inhibitor; CDX; and a CSD peptide, but not PD 123319, a selective AGTR2 antagonist. Collectively, our data demonstrate [Ca{sup 2+}]{sub i}-dependent proliferative effect of ANG-II and highlight a critical role for lipid raft microdomains in AGTR1-mediated signal transduction in neonatal GMCs. - Highlights: • AGTR1 is the functional AGTR subtype expressed in neonatal mesangial cells. • Endogenous AGTR1 associates with CAV-1 in neonatal mesangial cells. • Lipid raft disruption attenuates cell surface AGTR1 protein expression. • Lipid raft disruption reduces ANG-II-induced [Ca{sup 2+}]{sub i} elevation in neonatal mesangial cells. • Lipid raft disruption inhibits ANG-II-induced neonatal mesangial cell growth.

  8. MAPK Signal Transduction Pathway Regulation: A Novel Mechanism of Rat HSC-T6 Cell Apoptosis Induced by FUZHENGHUAYU Tablet

    Directory of Open Access Journals (Sweden)

    Qi Wang

    2013-01-01

    Full Text Available FUZHENGHUAYU Tablets have been widely used in the treatment of liver fibrosis in China. Here, we investigate the apoptotic effect of FUZHENGHUAYU Tablet in rat liver stellate cell line HSC-T6. HSC-T6 cells were incubated with control serum or drug serum from rats fed with 0.9% NaCl or FUZHENGHUAYU Tablet, respectively. Cells exposed to drug serum showed higher proportions of early and late apoptotic cells than controls. The mRNA levels of collagens I and III, TGF-β1 and α-SMA were reduced by drug serum compared to control serum. Differentially expressed mRNAs and miRNAs were analyzed by microarray and sequencing, respectively. We identified 334 differentially expressed mRNAs and also 60 GOs and two pathways related to the mRNAs. Seventy-five differentially expressed miRNAs were down-regulated by drug serum and 1963 target genes were predicted. 134 GOs up-regulated in drug serum group were linked to miRNA targets, and drug serum also regulated 43 miRNA signal transduction pathways. Protein levels were evaluated by Western blot. Drug serum down-regulated (phospho-SAPK/JNK/(SAPK/JNK and up-regulated phospho-p38/p38 ratios. The study showed that FUZHENGHUAYU Tablet induced apoptosis in rat HSC-T6 cells possibly in part by activating p38 and inhibiting SAPK/JNK.

  9. PEM fuel cells with injection moulded bipolar plates of highly filled graphite compounds; PEM-Brennstoffzellen mit spritzgegossenen Bipolarplatten aus hochgefuelltem Graphit-Compound

    Energy Technology Data Exchange (ETDEWEB)

    Kreuz, Can

    2008-04-11

    This work concerns with the injection moulding of highly filled graphite compounds to bipolar plates for PEM fuel cells in a power output range between 100 - 500 Watts. A particular focus is laid on the combination of the three multidisciplinary scopes like material development, production technology and component development / design. The results of the work are specified by the process-oriented characterisation of the developed and manufactured bipolar plates as well as their application in a functioning fuel cell. (orig.)

  10. An investigation into the use of additive manufacture for the production of metallic bipolar plates for polymer electrolyte fuel cell stacks

    OpenAIRE

    Dawson, Richard; Patel, Anant; Rennie, Allan; White, Simon

    2015-01-01

    The bipolar plate is of critical importance to the efficient and long lasting operation of a polymer electrolyte fuel cell (PEMFC) stack. With advances in membrane electrode assembly design, greater attention has been focused on the bipolar plate and the important role it plays. Although carbon composite plates are a likely candidate for the mass introduction of fuel cells, it is metallic plates made from thin strip materials which could deliver significant advantages in terms of part cost, e...

  11. Properties of graphite-stainless steel composite in bipolar plates in simulated anode and cathode environments of PEM fuel cells

    Science.gov (United States)

    Włodarczyk, Renata

    2014-09-01

    The use of a graphite-stainless steel composite as bipolar plates (BP) in polymer electrolyte membrane fuel cells (PEMFCs) has been evaluated. The study covers measurements of mechanical properties, microstructural examination, analysis of surface profile, wettability, porosity and corrosion resistance of the composite. The corrosion properties of the composite were examined in 0.1 mol·dm-3 H2SO4 + 2 ppm F- saturated with H2 or with O2 and in solutions with different pH: in Na2SO4+ 2 ppm F- (pH = 1.00, 3.00, 5.00) at 80 °C. The performed tests indicate that the graphite modified with stainless steel can be a good choice to be used as a bipolar plate in PEM fuel cells.

  12. Differences in kinetics between GABAC and GABAA receptors on carp retinal bipolar cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The present work was undertaken to characterize kinetics, including activation, desensitization and deactivation, of responses mediated by GABAA and GABAC receptors on carp retinal bipolar cells, using the whole-cell patch-clamp technique. It was revealed that the GABAC response was generally slower in kinetics than the GABAA response. Activation kinetics of both the receptors could be well fit by monoexponential functions with time constants τ, being 44.57 ms (GABAC) and 10.86 ms (GABAA) respectively. Desensitization of the GABAA response was characterized by a fast and a slow exponential component with time constants of τfast = 2.16 s and τslow = 19.78 s respectively, whereas desensitization of the GABAC response was fit by a monoexponential function of the time constant τ = 6.98 s. Deactivation at both the receptors was adequately described by biexponential functions with time constants being much higher for the GABAC response (τfast = 674.8 ms; τslow = 2 090 ms) than those for the GABAA response (τfast = 42.07 ms; τslow = 275.1 ms). These differences in kinetics suggest that GABAC and GABAA receptors may be involved in processing signals in different frequency domains.

  13. Acetylcholine induces GABA release onto rod bipolar cells through heteromeric nicotinic receptors expressed in A17 amacrine cells

    Science.gov (United States)

    Elgueta, Claudio; Vielma, Alex H.; Palacios, Adrian G.; Schmachtenberg, Oliver

    2015-01-01

    Acetylcholine (ACh) is a major retinal neurotransmitter that modulates visual processing through a large repertoire of cholinergic receptors expressed on different retinal cell types. ACh is released from starburst amacrine cells (SACs) under scotopic conditions, but its effects on cells of the rod pathway have not been investigated. Using whole-cell patch clamp recordings in slices of rat retina, we found that ACh application triggers GABA release onto rod bipolar (RB) cells. GABA was released from A17 amacrine cells and activated postsynaptic GABAA and GABAC receptors in RB cells. The sensitivity of ACh-induced currents to nicotinic ACh receptor (nAChR) antagonists (TMPH ~ mecamylamine > erysodine > DhβE > MLA) together with the differential potency of specific agonists to mimic ACh responses (cytisine >> RJR2403 ~ choline), suggest that A17 cells express heteromeric nAChRs containing the β4 subunit. Activation of nAChRs induced GABA release after Ca2+ accumulation in A17 cell dendrites and varicosities mediated by L-type voltage-gated calcium channels (VGCCs) and intracellular Ca2+ stores. Inhibition of acetylcholinesterase depolarized A17 cells and increased spontaneous inhibitory postsynaptic currents in RB cells, indicating that endogenous ACh enhances GABAergic inhibition of RB cells. Moreover, injection of neostigmine or cytisine reduced the b-wave of the scotopic flash electroretinogram (ERG), suggesting that cholinergic modulation of GABA release controls RB cell activity in vivo. These results describe a novel regulatory mechanism of RB cell inhibition and complement our understanding of the neuromodulatory control of retinal signal processing. PMID:25709566

  14. Paired pulse plasticity in the strength and latency of light-evoked lateral inhibition to retinal bipolar cell terminals

    OpenAIRE

    Vickers, Evan; Kim, Mean-Hwan; Vigh, Jozsef; von Gersdorff, Henrique

    2012-01-01

    Synapses in the inner plexiform layer of the retina undergo short-term plasticity that may mediate different forms of adaptation to regularities in light stimuli. Using patch-clamp recordings from axotomized goldfish Mb bipolar cell (BC) terminals with paired-pulse light stimulation, we isolated and quantified the short-term plasticity of GABAergic lateral inhibitory postsynaptic currents (L-IPSCs). Bright light stimulation evoked ON and OFF L-IPSCs in axotomized BCs, which had distinct onset...

  15. Opposing effects of bile acids deoxycholic acid and ursodeoxycholic acid on signal transduction pathways in oesophageal cancer cells.

    Science.gov (United States)

    Abdel-Latif, Mohamed M; Inoue, Hiroyasu; Reynolds, John V

    2016-09-01

    Ursodeoxycholic acid (UDCA) was reported to reduce bile acid toxicity, but the mechanisms underlying its cytoprotective effects are not fully understood. The aim of the present study was to examine the effects of UDCA on the modulation of deoxycholic acid (DCA)-induced signal transduction in oesophageal cancer cells. Nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) activity was assessed using a gel shift assay. NF-κB activation and translocation was performed using an ELISA-based assay and immunofluorescence analysis. COX-2 expression was analysed by western blotting and COX-2 promoter activity was assessed by luciferase assay. DCA induced NF-κB and AP-1 DNA-binding activities in SKGT-4 and OE33 cells. UDCA pretreatment inhibited DCA-induced NF-κB and AP-1 activation and NF-κB translocation. This inhibitory effect was coupled with a blockade of IκB-α degradation and inhibition of phosphorylation of IKK-α/β and ERK1/2. Moreover, UDCA pretreatment inhibited COX-2 upregulation. Using transient transfection of the COX-2 promoter, UDCA pretreatment abrogated DCA-induced COX-2 promoter activation. In addition, UDCA protected oesophageal cells from the apoptotic effects of deoxycholate. Our findings indicate that UDCA inhibits DCA-induced signalling pathways in oesophageal cancer cells. These data indicate a possible mechanistic role for the chemopreventive actions of UDCA in oesophageal carcinogenesis.

  16. Ca2+ is involved in muscarine-acetylcholine-receptor-mediated acetylcholine signal transduction in guard cells of Vicia faba L.

    Institute of Scientific and Technical Information of China (English)

    MENG Fanxia; MIAO Long; ZHANG Shuqiu; LOU Chenghou

    2004-01-01

    Acetylcholine (ACh) is an important neurochemical transmitter in animals; it also exists in plants and plays a significant role in various kinds of physiological functions in plants. ACh has been known to induce the stomatal opening. By monitoring the changes of cytosolic Ca2+ with fluorescent probe Fluo-3 AM under the confocal microscopy,we found that exogenous ACh increased cytosolic Ca2+ concentration of guard cells of Vicia faba L. Muscarine, an agonist of muscarine acetylcholine receptor (mAChR), could do so as well. In contrast, atropine, the antagonist of mAChR abolished the ability of ACh to increase Ca2+ in guard cells.This mechanism is similar to mAChR in animals. When EGTA was used to chelate Ca2+ or ruthenium red to block Ca2+ released from vacuole respectively, the results showed that the increased cytosolic Ca2+ mainly come from intracellular Ca2+ store. The evidence supports that Ca2+ is involved in guard-cell response to ACh and that Ca2+ signal is coupled to mAChRs in ACh signal transduction in guard cells.

  17. Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: a system-level analysis.

    Directory of Open Access Journals (Sweden)

    Jeffrey M Skerker

    2005-10-01

    Full Text Available Two-component signal transduction systems, comprised of histidine kinases and their response regulator substrates, are the predominant means by which bacteria sense and respond to extracellular signals. These systems allow cells to adapt to prevailing conditions by modifying cellular physiology, including initiating programs of gene expression, catalyzing reactions, or modifying protein-protein interactions. These signaling pathways have also been demonstrated to play a role in coordinating bacterial cell cycle progression and development. Here we report a system-level investigation of two-component pathways in the model organism Caulobacter crescentus. First, by a comprehensive deletion analysis we show that at least 39 of the 106 two-component genes are required for cell cycle progression, growth, or morphogenesis. These include nine genes essential for growth or viability of the organism. We then use a systematic biochemical approach, called phosphotransfer profiling, to map the connectivity of histidine kinases and response regulators. Combining these genetic and biochemical approaches, we identify a new, highly conserved essential signaling pathway from the histidine kinase CenK to the response regulator CenR, which plays a critical role in controlling cell envelope biogenesis and structure. Depletion of either cenK or cenR leads to an unusual, severe blebbing of cell envelope material, whereas constitutive activation of the pathway compromises cell envelope integrity, resulting in cell lysis and death. We propose that the CenK-CenR pathway may be a suitable target for new antibiotic development, given previous successes in targeting the bacterial cell wall. Finally, the ability of our in vitro phosphotransfer profiling method to identify signaling pathways that operate in vivo takes advantage of an observation that histidine kinases are endowed with a global kinetic preference for their cognate response regulators. We propose that this

  18. STANDARDIZATION AND VALIDATION OF ADENOVIRAL TRANSDUCTION OF AN ANDROGEN RECEPTOR POSITIVE CELL LINE WITH AN MMTV-LUC REPORTER FOR ENDOCRINE SCREENING

    Science.gov (United States)

    Standardization and Validation of Adenoviral Transduction of an Androgen Receptor Positive Cell Line with an MMTV-Luc Reporter for Endocrine Screening P. Hartig, K . Bobseine, M. Cardon, C. Lambright and L. E. Gray, Jr. USEPA, Reproductive Toxicology Division, NHEERL, RTP, NC...

  19. Signal transduction and metabolic changes during tumor cell apoptosis following phthalocyanine-sensitized photodynamic therapy

    Science.gov (United States)

    Oleinick, Nancy L.; Agarwal, Munna L.; Berger, Nathan A.; Cheng, Ming-Feng; Chatterjee, Satadel; He, Jin; Kenney, Malcolm E.; Larkin, Hedy E.; Mukhter, Hasan; Rihter, Boris D.; Zaidi, Syed I. A.

    1993-06-01

    Mechanisms of cell death have been explored in cells and tumors treated with photodynamic therapy (PDT). Photosensitizers used for these studies were Photofrin, tetrasulfonated and nonsulfonated aluminum phthalocyanine, and a new silicon phthalocyanine [SiPc(OH)OSi(CH3)2(CH2)3N(CH3)2], referred to as PcIV. In mouse lymphoma L5178Y cells, a dose of PDT sensitized by PcIV which causes a 90% loss of cell survival induces apoptosis (programmed cell death) over a several-hour time course, beginning within 10 minutes of irradiation. Apoptosis is a metabolic process initiated by PDT-induced damage to membranes and triggered by the activation of phospholipases A2 and C and the release of Ca++ from intracellular stores. An endogenous endonuclease is activated and cleaves nuclear DNA in the internucleosomal region of chromatin. Subsequent metabolic events now appear to cause the loss of cellular NAD and ATP, the former a result of the activation of a second nuclear enzyme, poly(ADP-ribose) polymerase, by the endonucleolytically generated DNA strand breaks. Loss of ATP follows upon the loss of NAD needed for energy metabolism. Although the induction of apoptosis is efficiently produced by direct PDT damage to L5178Y cells, we now find that apoptosis is also produced by treatment of certain other lymphoid-derived cells and cells of epithelial origin. Under the limited set of conditions tested, there was no evidence for PDT-induced apoptosis in a fibroblast cell line, in mouse fibrosarcoma RIF-1 and L929 cells, in human adenocarcinoma A549 cells, or in human squamous cell carcinoma cells in culture. The evidence suggests that apoptosis, a form of metabolic cell death, is an important mechanism of tumor ablation in PDT-treated tumors, and that the induction of apoptosis may involve the interaction of direct PDT damage to malignant cells with factors produced by PDT action on vascular and other host cells.

  20. Signal transduction by HLA class II antigens expressed on activated T cells

    DEFF Research Database (Denmark)

    Ødum, Niels; Martin, P J; Schieven, G L;

    1991-01-01

    Human T cells express HLA class II antigens upon activation. Although activated, class II+ T cells can present alloantigens under certain circumstances, the functional role of class II antigens on activated T cells remains largely unknown. Here, we report that cross-linking of HLA-DR molecules ex...

  1. Pancreatic acinar cells: molecular insight from studies of signal-transduction using transgenic animals.

    Science.gov (United States)

    Yule, David I

    2010-11-01

    Pancreatic acinar cells are classical exocrine gland cells. The apical regions of clusters of coupled acinar cells collectively form a lumen which constitutes the blind end of a tube created by ductal cells - a structure reminiscent of a "bunch of grapes". When activated by neural or hormonal secretagogues, pancreatic acinar cells are stimulated to secrete a variety of proteins. These proteins are predominately inactive digestive enzyme precursors called "zymogens". Acinar cell secretion is absolutely dependent on secretagogue-induced increases in intracellular free Ca(2+). The increase in [Ca(2+)](i) has precise temporal and spatial characteristics as a result of the exquisite regulation of the proteins responsible for Ca(2+) release, Ca(2+) influx and Ca(2+) clearance in the acinar cell. This brief review discusses recent studies in which transgenic animal models have been utilized to define in molecular detail the components of the Ca(2+) signaling machinery which contribute to these characteristics.

  2. Pluripotency transcription factor Sox2 is strongly adsorbed by heparin but requires a protein transduction domain for cell internalization

    Energy Technology Data Exchange (ETDEWEB)

    Albayrak, Cem [Department of Chemical Engineering, Stanford University, 381 North-South Mall, Stanford, CA 94305 (United States); Yang, William C. [Department of Bioengineering, Stanford University, 318 Campus Drive, Stanford, CA 94305 (United States); Swartz, James R., E-mail: jswartz@stanford.edu [Department of Chemical Engineering, Stanford University, 381 North-South Mall, Stanford, CA 94305 (United States); Department of Bioengineering, Stanford University, 318 Campus Drive, Stanford, CA 94305 (United States)

    2013-02-15

    Highlights: ► Both R9Sox2 and Sox2 bind heparin with comparable affinity. ► Both R9Sox2 and Sox2 bind to fibroblasts, but only R9Sox2 is internalized. ► Internalization efficiency of R9Sox2 is 0.3% of the administered protein. ► Heparan sulfate adsorption may be part of a mechanism for managing cell death. -- Abstract: The binding of protein transduction domain (PTD)-conjugated proteins to heparan sulfate is an important step in cellular internalization of macromolecules. Here, we studied the pluripotency transcription factor Sox2, with or without the nonaarginine (R9) PTD. Unexpectedly, we observed that Sox2 is strongly adsorbed by heparin and by the fibroblasts without the R9 PTD. However, only the R9Sox2 fusion protein is internalized by the cells. These results collectively show that binding to heparan sulfate is not sufficient for cellular uptake, thereby supporting a recent hypothesis that other proteins play a role in cell internalization of PTD-conjugated proteins.

  3. The biological networks in studying cell signal transduction complexity: The examples of sperm capacitation and of endocannabinoid system

    Science.gov (United States)

    Bernabò, Nicola; Barboni, Barbara; Maccarrone, Mauro

    2014-01-01

    Cellular signal transduction is a complex phenomenon, which plays a central role in cell surviving and adaptation. The great amount of molecular data to date present in literature, together with the adoption of high throughput technologies, on the one hand, made available to scientists an enormous quantity of information, on the other hand, failed to provide a parallel increase in the understanding of biological events. In this context, a new discipline arose, the systems biology, aimed to manage the information with a computational modeling-based approach. In particular, the use of biological networks has allowed the making of huge progress in this field. Here we discuss two possible application of the use of biological networks to explore cell signaling: the study of the architecture of signaling systems that cooperate in determining the acquisition of a complex cellular function (as it is the case of the process of activation of spermatozoa) and the organization of a single specific signaling systems expressed by different cells in different tissues (i.e. the endocannabinoid system). In both the cases we have found that the networks follow a scale free and small world topology, likely due to the evolutionary advantage of robustness against random damages, fastness and specific of information processing, and easy navigability. PMID:25379139

  4. A new model for thermal contact resistance between fuel cell gas diffusion layers and bipolar plates

    Science.gov (United States)

    Sadeghifar, Hamidreza; Djilali, Ned; Bahrami, Majid

    2014-11-01

    A new analytical model is developed to predict the thermal contact resistance (TCR) between fibrous porous media such as gas diffusion layers (GDLs) of polymer electrolyte membrane fuel cells (PEMFCs) and flat surfaces (bipolar plates). This robust model accounts for the salient geometrical parameters of GDLs, mechanical deformation, and thermophysical properties of the contacting bodies. The model is successfully validated against experimental data, and is used to perform in a comprehensive parametric study to investigate the effects of fiber parameters such as waviness and GDL properties on the TCR. Fiber waviness, diameter and surface curvature, as well as GDL porosity, are found to have a strong influence on TCR whereas fiber length does not affect the TCR when the porosity is kept constant. Such findings provide useful guidance for design and manufacturing of more effective GDLs for PEMFC heat management. The analytic model can be readily implemented in simulation and modeling of PEMFCs, and can be extended with minor modifications to other fibrous porous media such as fibrous catalysts, insulating media and sintered metals.

  5. Simulated bipolar cells in fovea of human retina. V. Use of Fourier analysis to determine resolution.

    Science.gov (United States)

    Siminoff, R

    1991-01-01

    Fourier analysis is used to study resolution of images processed by the matrix of simulated red-center (BCR) and green-center (BCG) bipolar cells (BC) of the human central fovea. Simulated achromatic and chromatic sine and square waves, and a two-bar stimulus are used to activate the BCs. Due to the "honeycomb" packing of the cones and BC matrices Fourier transforms are computed row by row using a one-dimensional FFT. Resolution computed by the Fourier transform is compared with the resolution index (RI), which is a method for determining resolution based on two-point discrimination in the space domain. In general the harmonic with the maximum amplitude gives the best correlation with RI for the three stimuli. Amplitudes at all spatial frequencies are enhanced by increasing the number of cycles in the sine and square wave gratings. Results with simulated BCs compare favorably with human and macaque psychophysics measuring contrast sensitivity. Square wave gratings are better than sine wave greetings for studying resolution.

  6. Molecular basis of mechanosensory transduction

    Science.gov (United States)

    Gillespie, Peter G.; Walker, Richard G.

    2001-09-01

    Mechanotransduction - a cell's conversion of a mechanical stimulus into an electrical signal - reveals vital features of an organism's environment. From hair cells and skin mechanoreceptors in vertebrates, to bristle receptors in flies and touch receptors in worms, mechanically sensitive cells are essential in the life of an organism. The scarcity of these cells and the uniqueness of their transduction mechanisms have conspired to slow molecular characterization of the ensembles that carry out mechanotransduction. But recent progress in both invertebrates and vertebrates is beginning to reveal the identities of proteins essential for transduction.

  7. Visualization of the gas flow in fuel cell bipolar plates using molecular flow seeding and micro-particle image velocimetry

    Energy Technology Data Exchange (ETDEWEB)

    Hecht, Christian; Wlokas, Irenaeus; Schulz, Christof [University of Duisburg-Essen, IVG and CeNIDE, Duisburg (Germany); Schoot, Nadine van der; Lindken, Ralph [Center for Fuel Cell Technology ZBT GmbH, Duisburg (Germany); Kronemayer, Helmut [University of Duisburg-Essen, IVG and CeNIDE, Duisburg (Germany); BASF SE, Ludwigshafen (Germany)

    2012-03-15

    Main components of proton exchange membrane fuel cells are bipolar plates that electrically connect the electrodes and provide a gas flow to the membrane. We investigate the flow in the channel structures of bipolar plates. Flow seeding is used to visualize the propagating and mixing gas stream. It is shown that a part of the gas is transported perpendicularly to the channel structure. An analysis of the diffusion compared with the convection shows different transport behavior for both flow directions. Additionally, the convective flow field is investigated in detail near the channel wall using Micro-PIV in a Reynolds-number-scaled liquid fluid system. For a more exact comparison of the experimental setups, flow seeding in both gas and liquid systems is performed. (orig.)

  8. MICROTUBULE-ASSOCIATED PROTEIN65 is essential for maintenance of phragmoplast bipolarity and formation of the cell plate in Physcomitrella patens.

    Science.gov (United States)

    Kosetsu, Ken; de Keijzer, Jeroen; Janson, Marcel E; Goshima, Gohta

    2013-11-01

    The phragmoplast, a plant-specific apparatus that mediates cytokinesis, mainly consists of microtubules (MTs) arranged in a bipolar fashion, such that their plus ends interdigitate at the equator. Membrane vesicles are thought to move along the MTs toward the equator and fuse to form the cell plate. Although several genes required for phragmoplast MT organization have been identified, the mechanisms that maintain the bipolarity of phragmoplasts remain poorly understood. Here, we show that engaging phragmoplast MTs in a bipolar fashion in protonemal cells of the moss Physcomitrella patens requires the conserved MT cross-linking protein MICROTUBULE-ASSOCIATED PROTEIN65 (MAP65). Simultaneous knockdown of the three MAP65s expressed in those cells severely compromised MT interdigitation at the phragmoplast equator after anaphase onset, resulting in the collapse of the phragmoplast in telophase. Cytokinetic vesicles initially localized to the anaphase midzone as normal but failed to further accumulate in the next several minutes, although the bipolarity of the MT array was preserved. Our data indicate that the presence of bipolar MT arrays is insufficient for vesicle accumulation at the equator and further suggest that MAP65-mediated MT interdigitation is a prerequisite for maintenance of bipolarity of the phragmoplast and accumulation and/or fusion of cell plate-destined vesicles at the equatorial plane. PMID:24272487

  9. Methoxychlor enhances degranulation of murine mast cells by regulating FcεRI-mediated signal transduction.

    Science.gov (United States)

    Yasunaga, Sho; Nishi, Kosuke; Nishimoto, Sogo; Sugahara, Takuya

    2015-01-01

    Methoxychlor, an organochlorine insecticide developed to replace DDT (dichlorodiphenyltrichloroethane), has been reported to induce mast cell degranulation and to enhance IgE-mediated allergic responses. However, the mechanisms underlying these effects are not clear. To clarify potential mechanisms, the effects of methoxychlor on degranulation of mast cells were examined. Degranulation responses were evaluated using RBL-2H3 cells and mouse bone marrow-derived mast cells with either the antigen-induced or calcium ionophore-induced stimulation. Phosphorylation of enzymes related to signaling events associated with mast cell degranulation was analyzed by immunoblotting. Effects on vascular permeability in the passive cutaneous anaphylaxis reaction were evaluated following oral administration of methoxychlor to BALB/c mice. The results indicated that methoxychlor caused increased mast cell degranulation in the presence of antigen, whereas it had no effect on calcium ionophore-induced degranulation of RBL-2H3 cells. Immunoblot analyses demonstrated that the phosphorylation level of phosphoinositide 3-kinase (which plays a central role in mast cell signaling) was increased by methoxychlor during antigen-induced degranulation. In addition, methoxychlor activated the signaling pathway via the high-affinity IgE receptor by inducing phosphorylation of Syk and PLCγ1/2, which transfer the signal for degranulation downstream. Lastly, oral administration of methoxychlor exhibited a tendency to promote vascular permeability in passive cutaneous anaphylaxis model mice. Taken together, the results here suggested that methoxychlor enhanced degranulation through FcεRI-mediated signaling and promoted allergenic symptoms involved in mast cell degranulation.

  10. Efficient Transduction of Feline Neural Progenitor Cells for Delivery of Glial Cell Line-Derived Neurotrophic Factor Using a Feline Immunodeficiency Virus-Based Lentiviral Construct

    Directory of Open Access Journals (Sweden)

    X. Joann You

    2011-01-01

    Full Text Available Work has shown that stem cell transplantation can rescue or replace neurons in models of retinal degenerative disease. Neural progenitor cells (NPCs modified to overexpress neurotrophic factors are one means of providing sustained delivery of therapeutic gene products in vivo. To develop a nonrodent animal model of this therapeutic strategy, we previously derived NPCs from the fetal cat brain (cNPCs. Here we use bicistronic feline lentiviral vectors to transduce cNPCs with glial cell-derived neurotrophic factor (GDNF together with a GFP reporter gene. Transduction efficacy is assessed, together with transgene expression level and stability during induction of cellular differentiation, together with the influence of GDNF transduction on growth and gene expression profile. We show that GDNF overexpressing cNPCs expand in vitro, coexpress GFP, and secrete high levels of GDNF protein—before and after differentiation—all qualities advantageous for use as a cell-based approach in feline models of neural degenerative disease.

  11. Bipolar disorder.

    Science.gov (United States)

    Grande, Iria; Berk, Michael; Birmaher, Boris; Vieta, Eduard

    2016-04-01

    Bipolar disorder is a recurrent chronic disorder characterised by fluctuations in mood state and energy. It affects more than 1% of the world's population irrespective of nationality, ethnic origin, or socioeconomic status. Bipolar disorder is one of the main causes of disability among young people, leading to cognitive and functional impairment and raised mortality, particularly death by suicide. A high prevalence of psychiatric and medical comorbidities is typical in affected individuals. Accurate diagnosis of bipolar disorder is difficult in clinical practice because onset is most commonly a depressive episode and looks similar to unipolar depression. Moreover, there are currently no valid biomarkers for the disorder. Therefore, the role of clinical assessment remains key. Detection of hypomanic periods and longitudinal assessment are crucial to differentiate bipolar disorder from other conditions. Current knowledge of the evolving pharmacological and psychological strategies in bipolar disorder is of utmost importance. PMID:26388529

  12. Sensory transduction in eukaryotes : A comparison between Dictyosteliurn and vertebrate cells

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Janssens, Pim M.W.; Erneux, Christophe

    1991-01-01

    The organization of multicellular organisms depends on cell-cell communication. The signal molecules are often soluble components in the extracellular fluid, but also include odors and light. A large array of surface receptors is involved in the detection of these signals. Signals are then transduce

  13. DC-ATLAS : a systems biology resource to dissect receptor specific signal transduction in dendritic cells

    NARCIS (Netherlands)

    Cavalieri, D.; Rivero, D.; Beltrame, L.; Buschow, S.I.; Calura, E.; Rizzetto, L.; Gessani, S.; Gauzzi, M.C.; Reith, W.; Baur, A.; Bonaiuti, R.; Brandizi, M.; Filippo, C. De; D'Oro, U.; Draghici, S.; Dunand-Sauthier, I.; Gatti, E.; Granucci, F.; Gundel, M.; Kramer, M.; Kuka, M.; Lanyi, A.; Melief, C.J.; Montfoort, N. van; Ostuni, R.; Pierre, P.; Popovici, R.; Rajnavolgyi, E.; Schierer, S.; Schuler, G.; Soumelis, V.; Splendiani, A.; Stefanini, I.; Torcia, M.G.; Zanoni, I.; Zollinger, R.; Figdor, C.G.; Austyn, J.M.

    2010-01-01

    BACKGROUND: The advent of Systems Biology has been accompanied by the blooming of pathway databases. Currently pathways are defined generically with respect to the organ or cell type where a reaction takes place. The cell type specificity of the reactions is the foundation of immunological research,

  14. A TRPV2–PKA Signaling Module for Transduction of Physical Stimuli in Mast Cells

    Science.gov (United States)

    Stokes, Alexander J.; Shimoda, Lori M.N.; Koblan-Huberson, Murielle; Adra, Chaker N.; Turner, Helen

    2004-01-01

    Cutaneous mast cell responses to physical (thermal, mechanical, or osmotic) stimuli underlie the pathology of physical urticarias. In vitro experiments suggest that mast cells respond directly to these stimuli, implying that a signaling mechanism couples functional responses to physical inputs in mast cells. We asked whether transient receptor potential (vanilloid) (TRPV) cation channels were present and functionally coupled to signaling pathways in mast cells, since expression of this channel subfamily confers sensitivity to thermal, osmotic, and pressure inputs. Transcripts for a range of TRPVs were detected in mast cells, and we report the expression, surface localization, and oligomerization of TRPV2 protein subunits in these cells. We describe the functional coupling of TRPV2 protein to calcium fluxes and proinflammatory degranulation events in mast cells. In addition, we describe a novel protein kinase A (PKA)–dependent signaling module, containing PKA and a putative A kinase adapter protein, Acyl CoA binding domain protein (ACBD)3, that interacts with TRPV2 in mast cells. We propose that regulated phosphorylation by PKA may be a common pathway for TRPV modulation. PMID:15249591

  15. Anticorrosion Coating of Carbon Nanotube/Polytetrafluoroethylene Composite Film on the Stainless Steel Bipolar Plate for Proton Exchange Membrane Fuel Cells

    OpenAIRE

    Yoshiyuki Show; Toshimitsu Nakashima; Yuta Fukami

    2013-01-01

    Composite film of carbon nanotube (CNT) and polytetrafluoroethylene (PTFE) was formed from dispersion fluids of CNT and PTFE. The composite film showed high electrical conductivity in the range of 0.1–13 S/cm and hydrophobic nature. This composite film was applied to stainless steel (SS) bipolar plates of the proton exchange membrane fuel cell (PEMFC) as anticorrosion film. This coating decreased the contact resistance between the surface of the bipolar plate and the membrane electrode assemb...

  16. Lentiviral transduction of Tar Decoy and CCR5 ribozyme into CD34+ progenitor cells and derivation of HIV-1 resistant T cells and macrophages

    Directory of Open Access Journals (Sweden)

    Rossi John

    2004-12-01

    Full Text Available Abstract Background RNA based antiviral approaches against HIV-1 are among the most promising for long-term gene therapy. These include ribozymes, aptamers (decoys, and small interfering RNAs (siRNAs. Lentiviral vectors are ideal for transduction of such inhibitory RNAs into hematopoietic stem cells due to their ability to transduce non-dividing cells and their relative refractiveness to gene silencing. The objective of this study is to introduce an HIV-1 Tar aptamer either alone or in combination with an anti-CCR5 ribozyme into CD34+ hematopoietic progenitor cells via an HIV-based lentiviral vector to derive viral resistant progeny T cells and macrophages. Results High efficiency and sustained gene transfer into CD34+ cells were achieved with lentiviral vector constructs harboring either Tar decoy or Tar decoy in combination with CCR5 ribozyme. Cells transduced with these constructs differentiated normally into T-lymphocytes in vivo in thy/liv grafts of SCID-hu mice, and into macrophages in vitro in the presence of appropriate growth factors. When challenged in vitro, the differentiated T lymphocytes and macrophages showed marked resistance against HIV-1 infection. Conclusions Viral resistant transgenic T cells and macrophages that express HIV-1 Tar aptamer either alone or in combination with an anti-CCR5 ribozyme could be obtained by lentiviral gene transduction of CD34+ progenitor cells. These results showed for the first time that expression of these anti-HIV-1 transgenes in combination do not interfere with normal thymopoiesis and thus have set the stage for their application in stem cell based gene therapy for HIV/AIDS.

  17. The Role of Intrinsic Flexibility in Signal Transduction Mediated by the Cell Cycle Regulator, p27Kip1

    Energy Technology Data Exchange (ETDEWEB)

    Galea, Charles A. [St. Jude Children' s Research Hospital; Nourse, Amanda [St. Jude Children' s Research Hospital; Wang, Yuefeng [St. Jude Children' s Research Hospital; Sivakolundu, Sivashankar G. [St. Jude Children' s Research Hospital; Heller, William T [ORNL; Kriwacki, Richard W [University of Tennessee (UT) Health Science Center, Memphis

    2008-02-01

    p27{sup Kip1} (p27), which controls eukaryotic cell division through interactions with cyclin-dependent kinases (Cdks), integrates and transduces promitogenic signals from various nonreceptor tyrosine kinases by orchestrating its own phosphorylation, ubiquitination and degradation. Intrinsic flexibility allows p27 to act as a 'conduit' for sequential signaling mediated by tyrosine and threonine phosphorylation and ubiquitination. While the structural features of the Cdk/cyclin-binding domain of p27 are understood, how the C-terminal regulatory domain coordinates multistep signaling leading to p27 degradation is poorly understood. We show that the 100-residue p27 C-terminal domain is extended and flexible when p27 is bound to Cdk2/cyclin A. We propose that the intrinsic flexibility of p27 provides a molecular basis for the sequential signal transduction conduit that regulates p27 degradation and cell division. Other intrinsically unstructured proteins possessing multiple sites of posttranslational modification may participate in similar signaling conduits.

  18. Quantitative phosphoproteomics of murine Fmr1-KO cell lines provides new insights into FMRP-dependent signal transduction mechanisms.

    Science.gov (United States)

    Matic, Katarina; Eninger, Timo; Bardoni, Barbara; Davidovic, Laetitia; Macek, Boris

    2014-10-01

    Fragile X mental retardation protein (FMRP) is an RNA-binding protein that has a major effect on neuronal protein synthesis. Transcriptional silencing of the FMR1 gene leads to loss of FMRP and development of Fragile X syndrome (FXS), the most common known hereditary cause of intellectual impairment and autism. Here we utilize SILAC-based quantitative phosphoproteomics to analyze murine FMR1(-) and FMR1(+) fibroblastic cell lines derived from FMR1-KO embryos to identify proteins and phosphorylation sites dysregulated as a consequence of FMRP loss. We quantify FMRP-related changes in the levels of 5,023 proteins and 6,133 phosphorylation events and map them onto major signal transduction pathways. Our study confirms global downregulation of the MAPK/ERK pathway and decrease in phosphorylation level of ERK1/2 in the absence of FMRP, which is connected to attenuation of long-term potentiation. We detect differential expression of several key proteins from the p53 pathway, pointing to the involvement of p53 signaling in dysregulated cell cycle control in FXS. Finally, we detect differential expression and phosphorylation of proteins involved in pre-mRNA processing and nuclear transport, as well as Wnt and calcium signaling, such as PLC, PKC, NFAT, and cPLA2. We postulate that calcium homeostasis is likely affected in molecular pathogenesis of FXS.

  19. Quantitative phosphoproteomics of murine Fmr1-KO cell lines provides new insights into FMRP-dependent signal transduction mechanisms.

    Science.gov (United States)

    Matic, Katarina; Eninger, Timo; Bardoni, Barbara; Davidovic, Laetitia; Macek, Boris

    2014-10-01

    Fragile X mental retardation protein (FMRP) is an RNA-binding protein that has a major effect on neuronal protein synthesis. Transcriptional silencing of the FMR1 gene leads to loss of FMRP and development of Fragile X syndrome (FXS), the most common known hereditary cause of intellectual impairment and autism. Here we utilize SILAC-based quantitative phosphoproteomics to analyze murine FMR1(-) and FMR1(+) fibroblastic cell lines derived from FMR1-KO embryos to identify proteins and phosphorylation sites dysregulated as a consequence of FMRP loss. We quantify FMRP-related changes in the levels of 5,023 proteins and 6,133 phosphorylation events and map them onto major signal transduction pathways. Our study confirms global downregulation of the MAPK/ERK pathway and decrease in phosphorylation level of ERK1/2 in the absence of FMRP, which is connected to attenuation of long-term potentiation. We detect differential expression of several key proteins from the p53 pathway, pointing to the involvement of p53 signaling in dysregulated cell cycle control in FXS. Finally, we detect differential expression and phosphorylation of proteins involved in pre-mRNA processing and nuclear transport, as well as Wnt and calcium signaling, such as PLC, PKC, NFAT, and cPLA2. We postulate that calcium homeostasis is likely affected in molecular pathogenesis of FXS. PMID:25168779

  20. In situ transduction of stromal cells and thymocytes upon intrathymic injection of lentiviral vectors

    Directory of Open Access Journals (Sweden)

    Klatzmann David

    2004-08-01

    Full Text Available Abstract Background The thymus is the primary site for T-cell development and induction of self-tolerance. Previous approaches towards manipulation of T-cell differentiation have used intrathymic injection of antigens, as proteins, cells or adenoviruses, leading to transient expression of the foreign protein. Lentiviral vectors, due to their unique ability to integrate into the genome of quiescent cells, may be best suited for long-term expression of a transgene in the thymus. Results Young adult mice were injected in the thymus with lentiviral vectors expressing eGFP or the hemaglutinin of the Influenza virus under the control of the ubiquitous phospho glycerate kinase promoter. Thymi were examined 5 to 90 days thereafter directly under a UV-light microscope and by flow cytometry. Intrathymic injection of lentiviral vectors predominantly results in infection of stromal cells that could be detected for at least 3 months. Importantly, hemaglutinin expression by thymic stromal cells mediated negative selection of thymocytes expressing the cognate T-cell receptor. In addition and despite the low multiplicity of infection, transduced thymocytes were also detected, even 30 days after injection. Conclusions Our results demonstrate that intrathymic delivery of a lentiviral vector is an efficient means for stable expression of a foreign gene in the thymus. This new method of gene delivery may prove useful for induction of tolerance to a specific antigen and for gene therapy of severe combined immunodeficiencies.

  1. 3D-dynamic visualization of complex molecular cell biology processes : 1-year university students' understanding of visualizations of signal transduction

    OpenAIRE

    Jacobsson, Johan Lars Henrik

    2008-01-01

    This study deals with the use of 3D-dynamic visualizations for teaching complex molecular cell biology concepts. The focus is on signal transduction, which is a concept that constitutes an important part of biological systems. 3D-dynamic visualizations (animations) were produced and shown for a total of 24 students attending a course in molecular cell biology at Karlstad University, Sweden. Data were collected by questionnaires and interviews which were structured around the understandability...

  2. Comparative transduction mechanisms of hair cells in the bullfrog utriculus. II. Sensitivity and response dynamics to hair bundle displacement

    Science.gov (United States)

    Baird, R. A.

    1994-01-01

    1. Hair cells in whole-mount in vitro preparations of the utricular macula of the bullfrog (Rana catesbeiana) were selected according to their macular location and hair bundle morphology. The sensitivity and response dynamics of selected hair cells to natural stimulation were examined by recording their voltage responses to step and sinusoidal hair bundle displacements applied to their longest stereocilia. 2. The voltage responses of 31 hair cells to sinusoidal hair bundle displacements were characterized by their gains and phases, taken with respect to peak hair bundle displacement. The gains of Type B and Type C cells at both 0.5 and 5.0 Hz were markedly lower than those of Type F and Type E cells. Phases, with the exception of Type C cells, lagged hair bundle displacement at 0.5 Hz. Type C cells had phase leads of 25-40 degrees. At 5.0 Hz, response phases in all cells were phase lagged with respect to those at 0.5 Hz. Type C cells had larger gains and smaller phase leads at 5.0 Hz than at 0.5 Hz, suggesting the presence of low-frequency adaptation. 3. Displacement-response curves, derived from the voltage responses to 5.0-Hz sinusoids, were sigmoidal in shape and asymmetrical, with the depolarizing response having a greater magnitude and saturating less abruptly than the hyperpolarizing response. When normalized to their largest displacement the linear ranges of these curves varied from hair bundle to linear range and sensitivity were predicted from realistic models of utricular hair bundles created using morphological data obtained from light and electron microscopy. Three factors, including 1) the inverse ratio of the lengths of the kinocilium and longest stereocilia, representing the lever arm between kinociliary and stereociliary displacement; 2) tip link extension/linear displacement, largely a function of stereociliary height and separation; and 3) stereociliary number, an estimate of the number of transduction channels, were considered in this analysis

  3. THE INFLUENCE OF HUMAN SINGLE CHAIN INTELEUKIN-12 GENE TRANSDUCTION ON THE BIOLOGICAL BEHAVIOR OF HEPATOMA 7721 CELLS

    Institute of Scientific and Technical Information of China (English)

    金莉; 来保长; 耿宜萍; 王一理; 司履生

    2001-01-01

    Objective. To investigate the anti-tumor effects of human single chain interleukin-12 (hscIL-12). Method. pcDNA/hscIL-12 recombinant was transfected into human hepatic carcinoma cells (7721 cells) by lipofectin method. The 7721/hscIL-12 cells which secrete hscIL-12 stably, were obtained via G418 selection, and in vitro the influence of hscIL-12 gene transduction on the growth of tumor cells was evaluated by cellcycle analysis. In vivo, genetically engineered 7721 cells (7721/hscIL-12, 7721/pcDNA) and parental cells were implanted into BALB/c nude mice, respectively. 7721/pcDNA and 7721/hscIL-12 groups were divided into two sub-groups on day 8: one was administered with hPBL twice, 6 days at interval; the other was given equalvolume of PBS. Mice were sacrificed on day 26, and spleens and tumors were taken out for histologic assay. Results. hscIL-12 produced stably by 7721/hscIL-12 cells had bioactivity, and it was proved by Western blot, immunocytochemistry, and in situ hybridization. In vitro, compared with 7721 and 7721/pcDNA, the7721/hscIL-12 grew much more slowly. FACS assay showed apparent G1 arrest of 7721/hscIL-12 cells. In ani-mal experiment, on day 8 after inoculation, the tumors of 7721 and 7721/pcDNA group were up to 5 -7mm,while those of 7721/hscIL-12 group were 2 -4mm. When treated with hPBL, the tumor of 7721/hscIL-12 groupdisappeared completely. Histologically, the tumors from 7721/hscIL-12 without hPBL treatment had numerouslymphocyte infiltration, the tumor cells displayed depression looking, atrophy, focal necrosis and apoptosis, whereas the tumors of 7721 and 772l/pcDNA groups grew thrivingly.Conclusion. hsclL-12 transduced 7721 cells could induced significant antitumor immune response which resulted in tumor regression totally when the hPBL was inoculated, and also hscIL-12 has certain effects on mice immune system. These findings suggest that hscIL-12 and hscIL-12 gene therapy might have promising prospects in clinical application.

  4. Low concentration of ethanol induce apoptosis in HepG2 cells: role of various signal transduction pathways

    Directory of Open Access Journals (Sweden)

    Francisco Castaneda, Sigrid Rosin-Steiner

    2006-01-01

    Full Text Available As we previously demonstrated in human hepatocellular carcinoma (HepG2 cells, ethanol at low concentration triggers the Fas apoptotic pathway. However, its role in other intracellular signaling pathways remains unknown. Therefore, the aim of the present study was to evaluate the role of low concentration of ethanol on different intracellular signaling pathways. For this purpose, HepG2 cells were treated with 1 mM ethanol for 10 min and the phosphorylation state of protein kinases was determined. In addition, the mRNA levels of transcription factors and genes associated with the Fas apoptotic pathway were determined. Our data demonstrated that ethanol-induced phosphorylation of protein kinases modulates both anti-apoptotic and pro-apoptotic mechanisms in HepG2 cells. Pro-apoptosis resulted mainly from the strong inhibition of the G-protein couple receptor signaling pathway. Moreover, the signal transduction initiated by ethanol-induced protein kinases phosphorylation lead to increased expression of the transcription factors with subsequent expression of genes associated with the Fas apoptotic pathway (Fas receptor, Fas ligand, FADD and caspase 8. These results indicate that low concentration of ethanol exert their effect by predominant activation of pro-apoptotic events that can be divided in two phases. An early phase characterized by a rapid transient effect on protein kinases phosphorylation, after 10 min exposure, with subsequent increased expression of transcription factors for up to 6 hr. This early phase is followed by a second phase associated with increased gene expression that began after 6 hr and persisted for more than 24 hr. This information provided a novel insight into the mechanisms of action of ethanol (1mM in human hepatocellular carcinoma cells.

  5. Development Of PIXE Measurement Of Ca Changes Resulting From Viral Transduction In Cells

    Science.gov (United States)

    Whitlow, Harry J.; Chienthavorn, Orapin; Eronen, Hannele; Sajavaara, Timo; Laitinen, Mikko; Norarat, Rattanaporn; Gilbert, Leona K.

    2011-06-01

    Ca is a life-element of particular interest because it is both bound to proteins, and as Ca2+ which functions as a signal molecule in apoptosis. Here we report development of chemical-matrix blind assaying the Ca fluxes from transduced HepG2 cells using particle induced X-ray emission. The cells were transduced with recombinant baculoviruses hosting the DNA for non-structural protein 1 (NS1) of the human pavovirus B19. Different recombinant baculoviruses were used that carried different DNA payloads of this NS1. Two different approaches have been developed to assay Ca in cells. The first is where the cells were directly cultured using a self-supporting pioloform as a substrate. In the second approach the cells are permeabilized, and bound-Ca content in the debris, and unbound-Ca in the wash solutions were measured using an internal V reference standard. The results support a difference in the Ca contents depending on the payload of the infecting virus, however the PIXE signals were too close to the minimum detection limit to draw reliable conclusions.

  6. A therapeutic anti-CD4 monoclonal antibody inhibits T cell receptor signal transduction in mouse autoimmune cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    WANG Zhao-hui; LIAO Yu-hua; YUAN Jing; ZHANG Li; WANG Min; ZHANG Jing-hui; LIU Zhong-ping; DONG Ji-hua

    2007-01-01

    Background T cell immune abnormalities in patients with dilated cardiomyopathy (DCM) has been intensively studied over the past 10 years. Our previous study has suggested that immunization of mice with the peptides derived from human adenine nucleotide translocator (ANT) result in the production of autoantibodies against the ANT and histopathological changes similar to those in human DCM. The ANT peptides can induce autoimmune cardiomyopathy like DCM in Balb/c mice. In this study we aimed to focus on the molecular mechanism of T cells in the autoimmune cardiomyopathy mouse model by detecting the expression of the two T cell signaling molecules.Methods The ANT peptides were used to cause autoimmune cardiomyopathy in Balb/c mice. Anti-L3T4 or rat anti-mouse IgG was administered to the mice (n=6 in each group) simultaneously immunized with ANT. ELISA analysis was used to detect autoantibodies against the ANT peptides and the percentages of interferon-Y and interleukin-4 producing cells among splenic CD4+ lymphocytes was determined by using flow cytometry analysis. The expression of CD45 in spleen T cells was determined by immunohistochemistry and the mRNAs of T cell signaling molecules were detected by real-time PCR.Results Treatment of ANT immunized Balb/c mice with anti-CD4 mAb caused a reduction in the gene expression of P56lck and Zap-70 and a lower level of CD45 expression by spleen T cells. Aiso, a reverse of the Th1/Th2 ratio that results in the reduced production of antibodies against ANT was found in the anti-CD4 monoclonal antibodies (mAb)group. Whereas irrelevant antibody (rat anti-mouse IgG) did not suppress T cell signaling molecules nor inhibit CD45 expression, and control-antibody mice did not show any significant differences compared with the DCM group.Conclusion The results show that anti-CD4 mAb is a powerful inhibitor of the early initiating events of T cell receptor(TCR) signal transduction in mouse autoimmune dilated cardiomyopathy.

  7. Signal transduction of the physical environment in the neural differentiation of stem cells

    Science.gov (United States)

    Thompson, Ryan; Chan, Christina

    2016-01-01

    Neural differentiation is largely dependent on extracellular signals within the cell microenvironment. These extracellular signals are mainly in the form of soluble factors that activate intracellular signaling cascades that drive changes in the cell nucleus. However, it is becoming increasingly apparent that the physical microenvironment provides signals that can also influence lineage commitment and very low modulus surfaces has been repeatedly demonstrated to promote neurogenesis. The molecular mechanisms governing mechano-induced neural differentiation are still largely uncharacterized; however, a growing body of evidence indicates that physical stimuli can regulate known signaling cascades and transcription factors involved in neural differentiation. Understanding how the physical environment affects neural differentiation at the molecular level will enable research and design of materials that will eventually enhance neural stem cell (NSC) differentiation, homogeneity and specificity.

  8. The Mammary Epithelial Cell Secretome and its Regulation by Signal Transduction Pathways

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, Jon M.; Waters, Katrina M.; Kathmann, Loel E.; Camp, David G.; Wiley, H. S.; Smith, Richard D.; Thrall, Brian D.

    2008-02-01

    Extracellular proteins released by mammary epithelial cells are critical mediators of cell communication, proliferation and organization, yet the actual spectrum of proteins released by any given cell (the secretome) is poorly characterized. To define the set of proteins secreted by human mammary epithelial cells (HMEC), we combined analytical and computational approaches to define a secretome protein set based upon probable biological significance. Analysis of HMEC-conditioned medium by liquid chromatography-mass spectrometry resulted in identification of 889 unique proteins, of which 151 were found to be specifically enriched in the extracellular compartment when compared with a database of proteins expressed in whole HMEC lysates. Additional high mass accuracy analysis revealed 36 proteins whose extracellular abundance increased after treatment with phorbol ester (PMA), a protein kinase C agonist and general secretagogue. Many of the PMA stimulated proteins have been reported to be aberrantly expressed in human cancers and appear to be co-regulated as multigene clusters. By inhibiting PMA-mediated transactivation of the epidermal growth factor receptor (EGFR), a pathway critically required for normal HMEC function, we found that the secretion of specific matrix metalloproteases were also coordinately regulated through EGFR transactivation. This study demonstrates a tiered strategy by which extracellular proteins can be identified and progressively assigned to classes of increasing confidence and regulatory importance.

  9. A Case Study of Representing Signal Transduction in Liver Cells as a Feedback Control Problem

    Science.gov (United States)

    Singh, Abhay; Jayaraman, Arul; Hahn, Juergen

    2007-01-01

    Cell signaling pathways often contain feedback loops where proteins are produced that regulate signaling. While feedback regulatory mechanisms are commonly found in signaling pathways, there is no example available in the literature that is simple enough to be presented in an undergraduate control class. This paper presents a simulation study of…

  10. Endoglin promotes endothelial cell proliferation and TGF-beta/ALK1 signal transduction

    NARCIS (Netherlands)

    Lebrin, F; Goumans, MJ; Jonker, L; Carvalho, RLC; Valdimarsdottir, G; Thorikay, M; Mummery, C; Arthur, HM; ten Dijke, P

    2004-01-01

    Endoglin is a transmembrane accessory receptor for transforming growth factor-beta (TGF-beta) that is predominantly expressed on proliferating endothelial cells in culture and on angiogenic blood vessels in vivo. Endoglin, as well as other TGF-beta signalling components, is essential during angiogen

  11. Current density and catalyst-coated membrane resistance distribution of hydro-formed metallic bipolar plate fuel cell short stack with 250 cm2 active area

    Science.gov (United States)

    Haase, S.; Moser, M.; Hirschfeld, J. A.; Jozwiak, K.

    2016-01-01

    An automotive fuel cell with an active area of 250 cm2 is investigated in a 4-cell short stack with a current and temperature distribution device next to the bipolar plate with 560 current and 140 temperature segments. The electrical conductivities of the bipolar plate and gas diffusion layer assembly are determined ex-situ with this current scan shunt module. The applied fuel cell consists of bipolar plates constructed of 75-μm-thick, welded stainless-steel foils and a graphitic coating. The electrical conductivities of the bipolar plate and gas diffusion layer assembly are determined ex-situ with this module with a 6% deviation in in-plane conductivity. The current density distribution is evaluated up to 2.4 A cm-2. The entire cell's investigated volumetric power density is 4.7 kW l-1, and its gravimetric power density is 4.3 kW kg-1 at an average cell voltage of 0.5 V. The current density distribution is determined without influencing the operating cell. In addition, the current density distribution in the catalyst-coated membrane and its effective resistivity distribution with a finite volume discretisation of Ohm's law are evaluated. The deviation between the current density distributions in the catalyst-coated membrane and the bipolar plate is determined.

  12. Evaluation of CoBlast Coated Titanium Alloy as Proton Exchange Membrane Fuel Cell Bipolar Plates

    Directory of Open Access Journals (Sweden)

    Atinuke M. Oladoye

    2014-01-01

    Full Text Available We investigated the potential of graphite based coatings deposited on titanium V alloy by a low-cost powder based process for bipolar plate application. The coatings which were deposited from a mixture of graphite and alumina powders at ambient temperature, pressure of 90 psi, and speed of 20 mm were characterised and electrochemically polarised in 0.5 M H2SO4 + 2 ppm HF bubbled with air and hydrogen gas to depict the cathode and anode PEM fuel cell environment, respectively. Surface conductivity and water contact angles were also evaluated. Corrosion current in the 1 μA/cm2 range in both cathodic and anodic environment at room temperature and showed negligible influence on the electrochemical behaviour of the bare alloy. Similar performance, which was attributed to the discontinuities in the coatings, was also observed when polarised at 0.6 V and −0.1 V with air and hydrogen bubbling at 70∘C respectively. At 140 N/cm2, the coated alloy exhibited contact resistance of 45.70 mΩ·cm2 which was lower than that of the bare alloy (66.50 mΩ·cm2 but twice that of graphite (21.29 mΩ·cm2. Similarly, the wettability test indicated that the coated layer exhibited higher contact angle of 99.63° than that of the bare alloy (66.32°. Over all, these results indicated need for improvement in the coating process to achieve a continuous layer.

  13. Signal transduction profile of chemical sensitisers in dendritic cells: An endpoint to be included in a cell-based in vitro alternative approach to hazard identification?

    International Nuclear Information System (INIS)

    The development of non-animal testing methods for the assessment of skin sensitisation potential is an urgent challenge within the framework of existing and forthcoming legislation. Efforts have been made to replace current animal tests, but so far no alternative methods have been developed. It is widely recognised that alternatives to animal testing cannot be accomplished with a single approach, but rather will require the integration of results obtained from different in vitro and in silico assays. The argument subjacent to the development of in vitro dendritic cell (DC)-based assays is that sensitiser-induced changes in the DC phenotype can be differentiated from those induced by irritants. This assumption is derived from the unique capacity of DC to convert environmental signals encountered at the skin into a receptor expression pattern (MHC class II molecules, co-stimulatory molecules, chemokine receptors) and a soluble mediator release profile that will stimulate T lymphocytes. Since signal transduction cascades precede changes in surface marker expression and cytokine/chemokine secretion, these phenotypic modifications are a consequence of a signal transduction profile that is specifically triggered by sensitisers and not by irritants. A limited number of studies have addressed this subject and the present review attempts to summarise and highlight all of the signalling pathways modulated by skin sensitisers and irritants. Furthermore, we conclude this review by focusing on the most promising strategies suitable for inclusion into a cell-based in vitro alternative approach to hazard identification.

  14. Chronic Hyperinsulinism Induced Down-regulation of Insulin Post-Recentor Signaling Transduction in Hep G2 Cells

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Summary: To study the regulatory effect of acute and chronic insulin treatment on insulin post-re-ceptor signaling transduction pathway in a human hepatoma cell line (Hep G2), Hep G2 cells wereincubated in the presence or absence of insulin with different concentrations in serum free mediafor 16 h and then stimulated with 100 nmol/L insulin for 1 min. Protein levels of insulin receptorβ-subunit (IRβ), insulin receptor substrate-1 (IRS-1) and p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) were determined in total cell lysates by Western-immunoblot. Phosphorylat-ed proteins IRβ, IRS-1 and interaction of PI 3-kinase with IRS-1 were determined by immunopre-cipitation. Results showed that 1-min insulin stimulation rapidly induced tyrosine phosphorylationof IRβ and IRS-l, which in turn, resulting in association of PI 3-kinase with IRS-1. 1-100 nmol/L chronic insulin treatment induced a dose-dependent decrease in the protein level of IRβ and aslight decrease in the protein level of IRS-1. There wass more marked reduction in the phospho-rylation of IRβ, IRS-1, reaching a nadir of 22 % (P<0. 01) and 15 % (P<0. 01) of control lev-els, respectively, after 16 h treatment with 100 nmol/L insulin. The association between IRS-1and PI 3-kinase was decreased by 66 % (P<0. 01). There was no significant change in PI 3-ki-nase protein levels. These data suggest that chronic insulin treatment can induce alterations ofIRβ, IRS-1 and PI 3-kinase three early steps in insulin action, which contributes significantly toinsulin resistance, and may account for desensitization of insulin action.

  15. Action of luteinizing hormone-releasing hormone in rat ovarian cells: Hormone production and signal transduction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jian.

    1989-01-01

    The present study was conducted to investigate the hypothesis that the breakdown of membrane phosphoinositides may participate in the actions of luteinizing hormone-releasing hormone (LHRH) on hormone production in rat granulosa cells. In cells prelabeled with ({sup 3}H)inositol or ({sup 3}H)arachidonic acid (AA), treatment with LHRH increased the formation of radiolabeled inositol 1,4,5-trisphosphate (IP{sub 3}) and diacylglycerol (DG), and the release of radiolabeled AA. Since IP{sub 3} induces intracellular Ca{sup 2+} mobilization, changes in the cytosolic free calcium ion concentrations ((Ca{sup 2+})i) induced by LHRH were studied in individual cells using fura-2 microspectrofluorimetry. Alterations in (Ca{sup 2+})i induced by LHRH were rapid and transient, and could be completely blocked by a LHRH antagonist. Sustained perifusion of LHRH resulted in a desensitization of the (Ca{sup 2+})i response to LHRH. LHRH treatment accelerated (Ca{sup 2+})i depletion in the cells perifused with Ca{sup 2+} free medium, indicating the involvement of intracellular Ca{sup 2+} pool(s) in (Ca{sup 2+})i changes. The actions of LHRH on the regulation of progesterone (P{sub 4}) and prostaglandin E{sub 2} (PGE{sub 2}) production were also examined. LHRH increased basal P{sub 4} production and attenuated FSH induced P{sub 4} production. Both basal and FSH stimulated PGE{sub 2} formation were increased by LHRH. Since LHRH also increased the formation of DG that stimulates the activity of protein kinase C, an activator of protein kinase C (12-0-tetradecanolyphorbol-13-acetate: TPA) was used with the Ca{sup 2+} ionophore A23187 and melittin (an activator of phospholipase A{sub 2}) to examine the roles of protein kinase C, Ca{sup 2+} and free AA, respectively, in LHRH action.

  16. Sorbitol induces apoptosis of human colorectal cancer cells via p38 MAPK signal transduction.

    Science.gov (United States)

    Lu, Xue; Li, Chun; Wang, Yong-Kun; Jiang, Kun; Gai, Xiao-Dong

    2014-06-01

    Sorbitol has been reported to have anticancer effects in several tumor models, however its effects on colorectal cancer remain elusive. In the present study, the effects of sorbitol on growth inhibition and apoptosis in the colorectal cancer HCT116 cell line were evaluated and its mechanism of action was examined. An MTT assay was utilized to determine the effect of sorbitol on HCT116 cell proliferation at different time points and variable doses. Western blot analysis was used to examine the effect of sorbitol on apoptosis-related protein expression and the p38 MAPK signaling pathway. The results revealed that sorbitol may inhibit the growth of HCT116 cells in a time- and dose-dependent manner. Following treatment with sorbitol for 3 h, western blotting demonstrated cleavage of the caspase-3 zymogen protein and a cleavage product of poly (ADP-ribose) polymerase (PARP), a known substrate of caspase-3, was also evident. During sorbitol-induced apoptosis, the mitochondrial pathway was activated by a dose-dependent increase in Bax expression and cytochrome c release, while the expression of anti-apoptotic protein Bcl-2 was significantly decreased in a dose-dependent manner. The investigation for the downstream signal pathway revealed that sorbitol-induced apoptosis was mediated by an increase in phosphorylated p38 MAPK expression. Overall, the observations from the present study imply that sorbitol causes increased levels of Bax in response to p38 MAPK signaling, which results in the initiation of the mitochondrial death cascade. Therefore, sorbitol is a promising candidate as a potential chemotherapeutic agent for the treatment of colorectal cancer HCT116 cells.

  17. Whole Cell Biosensor Using Anabaena torulosa with Optical Transduction for Environmental Toxicity Evaluation

    OpenAIRE

    Ling Shing Wong; Yook Heng Lee; Salmijah Surif

    2013-01-01

    A whole cell-based biosensor using Anabaena torulosa for the detection of heavy metals (Cu, Pb, and Cd), 2,4-dichlorophenoxyacetate (2,4-D), and chlorpyrifos was constructed. The cyanobacteria were entrapped on a cellulose membrane through filtration. Then, the membrane was dried and fixed into a cylindrical well, which was designed to be attached to an optical probe. The probe was connected to fluorescence spectrometer with optical fibre. The presence of the toxicants was indicated by the ch...

  18. Leptin differentially regulates NPY secretion in hypothalamic cell lines through distinct intracellular signal transduction pathways.

    Science.gov (United States)

    Dhillon, Sandeep S; Belsham, Denise D

    2011-04-11

    Leptin acts as a key peripheral hormone in distinct neurons in the hypothalamus to modulate both reproductive function and energy homeostasis. The control of neuropeptide Y (NPY) secretion is an example of a process that can be differentially regulated by leptin. In order to further understand these distinct modulatory effects, we have used immortalized, neuronal hypothalamic cell lines expressing NPY, mHypoE-38 and mHypoE-46. We found that these cell lines express the endogenous leptin receptor, ObRb, and secrete detectable levels of NPY. We exposed the neurons to 100nM leptin for 1h and determined that the basal levels of NPY in the cell lines were differentially regulated: NPY secretion was inhibited in mHypoE-46 neurons, whereas NPY secretion was induced in the mHypoE-38 neurons. In order to determine the mechanisms involved in the divergent regulation of NPY release, we analyzed the activity of a number of signaling components using phospho-specific antibodies directed towards specific proteins in the MAP kinase, PI3K, and AMPK pathways, among others. We found that leptin activated a different combination of second messengers in each cell line. Importantly, we could link the regulation of NPY secretion to different signaling pathways, AMPK in the mHypoE-46 and both MAPK and PI3K in the mHypoE-38 neurons. This is the first demonstration that leptin can specifically regulate individual NPY neuron secretory responses through distinct signaling pathways.

  19. Transduction of PEP-1-heme oxygenase-1 into insulin-producing INS-1 cells protects them against cytokine-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Su Jin; Kang, Hyung Kyung [Department of Physiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Song, Dong Keun [Department of Pharmacology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Eum, Won Sik; Park, Jinseu [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Kwon, Hyeok Yil, E-mail: hykwon@hallym.ac.kr [Department of Physiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of)

    2015-06-05

    Pro-inflammatory cytokines play a crucial role in the destruction of pancreatic β-cells, thereby triggering the development of autoimmune diabetes mellitus. We recently developed a cell-permeable fusion protein, PEP-1-heme oxygenase-1 (PEP-1-HO-1) and investigated the anti-inflammatory effects in macrophage cells. In this study, we transduced PEP-1-HO-1 into INS-1 insulinoma cells and examined its protective effect against cytokine-induced cell death. PEP-1-HO-1 was successfully delivered into INS-1 cells in time- and dose-dependent manner and was maintained within the cells for at least 48 h. Pre-treatment with PEP-1-HO-1 increased the survival of INS-1 cells exposed to cytokine mixture (IL-1β, IFN-γ, and TNF-α) in a dose-dependent manner. PEP-1-HO-1 markedly decreased cytokine-induced production of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA). These protective effects of PEP-1-HO-1 against cytokines were correlated with the changes in the levels of signaling mediators of inflammation (iNOS and COX-2) and cell apoptosis/survival (Bcl-2, Bax, caspase-3, PARP, JNK, and Akt). These results showed that the transduced PEP-1-HO-1 efficiently prevented cytokine-induced cell death of INS-1 cells by alleviating oxidative/nitrosative stresses and inflammation. Further, these results suggested that PEP-1-mediated HO-1 transduction may be a potential therapeutic strategy to prevent β-cell destruction in patients with autoimmune diabetes mellitus. - Highlights: • We showed that PEP-1-HO-1 was efficiently delivered into INS-1 cells. • Transduced PEP-1-HO-1 exerted a protective effect against cytokine-induced cell death. • Transduced PEP-1-HO-1 inhibited cytokine-induced ROS and NO accumulation. • PEP-1-HO-1 suppressed cytokine-induced expression of iNOS, COX-2, and Bax. • PEP-1-HO-1 transduction may be an efficient tool to prevent β-cell destruction.

  20. Signal transduction in red blood cells of the lizards Ameiva ameiva and Tupinambis merianae (Squamata, Teiidae).

    Science.gov (United States)

    Beraldo, F H; Sartorello, R; Lanari, R D; Garcia, C R

    2001-06-01

    The fluorescent calcium probe, Fluo-3, AM was used to measure the intracellular calcium concentration in red blood cells (RBCs) of the teiid lizards Ameiva ameiva and Tupinambis merianae. The cytosolic [Ca2+] is maintained around 20 nM and the cells contain membrane-bound Ca2+ pools. One pool appears to be identifiable with the endoplasmic reticulum (ER) inasmuch as addition of the sarco-endoplasmic reticulum Ca2+ ATPase, SERCA, inhibitor thapsigargin induces an increase in cytosolic [Ca2+ both in the presence and in the absence of extracellular Ca2+. In addition to the ER, an acidic compartment appears to be involved in Ca2+ storage, as collapse of intracellular pHgradients by monensin, a Na+ -H+ exchanger, and nigericin, a K+ -H+ exchanger, induce the release of Ca2+ from internal pools. A vacuolar H+ pump, sensitive to NBD-Cl and bafilomycin appears to be necessary to load the acidic Ca2+ pools. Finally, the purinergic agonist ATP triggers a rapid and transient increase of [Ca2+]c in the cells from both lizard species, mostly by mobilization of the cation from internal stores. PMID:11352509

  1. Automated Enrichment, Transduction, and Expansion of Clinical-Scale CD62L+ T Cells for Manufacturing of Gene Therapy Medicinal Products

    Science.gov (United States)

    Priesner, Christoph; Aleksandrova, Krasimira; Esser, Ruth; Mockel-Tenbrinck, Nadine; Leise, Jana; Drechsel, Katharina; Marburger, Michael; Quaiser, Andrea; Goudeva, Lilia; Arseniev, Lubomir; Kaiser, Andrew D.; Glienke, Wolfgang; Koehl, Ulrike

    2016-01-01

    Multiple clinical studies have demonstrated that adaptive immunotherapy using redirected T cells against advanced cancer has led to promising results with improved patient survival. The continuously increasing interest in those advanced gene therapy medicinal products (GTMPs) leads to a manufacturing challenge regarding automation, process robustness, and cell storage. Therefore, this study addresses the proof of principle in clinical-scale selection, stimulation, transduction, and expansion of T cells using the automated closed CliniMACS® Prodigy system. Naïve and central memory T cells from apheresis products were first immunomagnetically enriched using anti-CD62L magnetic beads and further processed freshly (n = 3) or split for cryopreservation and processed after thawing (n = 1). Starting with 0.5 × 108 purified CD3+ T cells, three mock runs and one run including transduction with green fluorescent protein (GFP)-containing vector resulted in a median final cell product of 16 × 108 T cells (32-fold expansion) up to harvesting after 2 weeks. Expression of CD62L was downregulated on T cells after thawing, which led to the decision to purify CD62L+CD3+ T cells freshly with cryopreservation thereafter. Most important in the split product, a very similar expansion curve was reached comparing the overall freshly CD62L selected cells with those after thawing, which could be demonstrated in the T cell subpopulations as well by showing a nearly identical conversion of the CD4/CD8 ratio. In the GFP run, the transduction efficacy was 83%. In-process control also demonstrated sufficient glucose levels during automated feeding and medium removal. The robustness of the process and the constant quality of the final product in a closed and automated system give rise to improve harmonized manufacturing protocols for engineered T cells in future gene therapy studies. PMID:27562135

  2. Bipolar Disorder

    Science.gov (United States)

    ... lows). These aren't the normal periods of happiness and sadness that everyone experiences from time to ... with long-lasting medical conditions (such as asthma , diabetes , or epilepsy ), teens with bipolar disorder need to ...

  3. Molecular Basis of Mechano-Signal Transduction in Vascular Endothelial Cells

    Science.gov (United States)

    Jo, Hanjoong

    2004-01-01

    Simulated microgravity studies using a random positioning machine (RPM). One RPM machine has been built for us by Fokker Science in Netherland. Using the device, we have developed an in vitro system to examine the effect of simulated microgravity on osteoblastic bone cells. Using this system, we have carried out gene chip studies to determine the gene expression profiles of osteoblasts cultured under simulated microgravity conditions in comparison to static controls. From this study, we have identified numerous genes, some of which are expected ones inducing bone loss, but many of which are unexpected and unknown. These findings are being prepared for publications.

  4. Corrective transduction of human epidermal stem cells in laminin-5-dependent junctional epidermolysis bullosa.

    Science.gov (United States)

    Dellambra, E; Vailly, J; Pellegrini, G; Bondanza, S; Golisano, O; Macchia, C; Zambruno, G; Meneguzzi, G; De Luca, M

    1998-06-10

    Laminin-5 is composed of three distinct polypeptides, alpha3, beta3, and gamma2, which are encoded by three different genes, LAMA3, LAMB3, and LAMC2, respectively. We have isolated epidermal keratinocytes from a patient presenting with a lethal form of junctional epidermolysis bullosa characterized by a homozygous mutation of the LAMB3 gene, which led to complete absence of the beta3 polypeptide. In vitro, beta3-null keratinocytes were unable to synthesize laminin-5 and to assemble hemidesmosomes, maintained the impairment of their adhesive properties, and displayed a decrease of their colony-forming ability. A retroviral construct expressing a human beta3 cDNA was used to transduce primary beta3-null keratinocytes. Clonogenic beta3-null keratinocytes were transduced with an efficiency of 100%. Beta3-transduced keratinocytes were able to synthesize and secrete mature heterotrimeric laminin-5. Gene correction fully restored the keratinocyte adhesion machinery, including the capacity of proper hemidesmosomal assembly, and prevented the loss of the colony-forming ability, suggesting a direct link between adhesion to laminin-5 and keratinocyte proliferative capacity. Clonal analysis demonstrated that holoclones expressed the transgene permanently, suggesting stable correction of epidermal stem cells. Because cultured keratinocytes are used routinely to make autologous grafts for patients suffering from large skin or mucosal defects, the full phenotypic reversion of primary human epidermal stem cells defective for a structural protein opens new perspectives in the long-term treatment of genodermatoses. PMID:9650620

  5. Bipolar disorder

    OpenAIRE

    Goodwin, Frederick K; Ghaemi, S Nassir

    1999-01-01

    Bipolar disorder's unique combination of three characteristics - clear genetic diathesis, distinctive clinical features, early availability of an effective treatment (lithium) - explains its special place in the history of psychiatry and its contribution to the current explosive growth of neuroscience. This article looks at the state of the art in bipolar disorder from the vantage point of: (i) genetics (possible linkages on chromosomes 18 and 21q, polygenic hypothesis, research into genetic ...

  6. Thyroxine signal transduction in liver cells involves phospholipase C and phospholipase D activation. Genomic independent action of thyroid hormone

    Directory of Open Access Journals (Sweden)

    Krasilnikova Oksana A

    2001-04-01

    Full Text Available Abstract Background Numerous investigations demonstrate a novel role of thyroid hormone as a modulator of signal transduction. Protein kinase C (PKC is critical to the mechanism by which thyroid hormones potentiate both the antiviral and immunomodulatory actions of IFNγ in different cells and regulate the exchange of signalling phospholipids in hepatocytes. Because nothing is known about accumulation of PKC modulator - diacylglycerol in cells treated with T4, we examined the nongenomic effect of thyroid hormones on DAG formation and phospholipase activation in liver cells. Results The results obtained provide the first demonstration of phospholipase C, phospholipase D and protein kinase C nongenomic activation and diacylglycerol (DAG accumulation by L-T4 in liver cells. The experiments were performed in either the [14C]CH3COOH-labeled rat liver slices or isolated hepatocytes pre-labeled by [14C]oleic acid. L-T4 activates the DAG production in a concentration- and time-dependent manner. DAG formation in stimulated cells is biphasic and short-lived event: there is an initial, rapid rise in DAG concentration and then a slower accumulation that can be sustained for a few minutes. The early phase of L-T4 generated DAG only is accompanied by phosphatidylinositol 4,5-bisphosphate level decrease and inositol 1,4,5-trisphosphate formation while the second phase is abolished by PKC inhibitor l,(5-isoquinolinesulphonyl2methylpiperasine dihydrochloride (H7 and propranolol. The second phase of DAG production is accompanied by free choline release, phosphatidylcholine content drop and phosphatidylethanol (Peth formation. Inhibitor of phospholipase-C-dependent phosphoinositide hydrolysis, neomycin sulfate, reduced the Peth as well as the DAG response to L-T4. Conclusions The present data have indicated the DAG signaling in thyroid hormone-stimulated liver cells. L-thyroxine activates a dual phospholipase pathway in a sequential and synchronized manner

  7. Ex situ evaluation of nanometer range gold coating on stainless steel substrate for automotive polymer electrolyte membrane fuel cell bipolar plate

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, A.; Ricketts, M.; Hirano, S. [Ford Motor Company, 2101 Village Road, Dearborn, MI 48121 (United States)

    2010-03-01

    The bipolar plate in polymer electrolyte membrane (PEM) fuel cell helps to feed reactant gases to the membrane electrode assembly (MEA) and collect current from the MEA. To facilitate these functions, the bipolar plate material should exhibit excellent electrical conductivity and corrosion resistance under fuel cell operating conditions, and simultaneously be of low-cost to meet commercialization enabling targets for automotive fuel cells. In the present work, we focus on the benchmarking of 10 nm gold coated SS316L (a.k.a. Au Nanoclad {sup registered}) bipolar plate material through ex situ tests, which is provided by Daido Steel (Japan). The use of nanometer range Au coatings help to retain the noble properties of gold while significantly reducing the cost of the bipolar plate. The area specific resistance of the flat sample is 0.9 m{omega} cm{sup 2} while that for the formed bipolar plate is 6.3 m{omega} cm{sup 2} at compaction force of 60 N cm{sup -2}. The corrosion current density was less than 1 {mu}A cm{sup -2} at 0.8 V/NHE with air sparge simulating cathodic conditions. Additionally, gold coated SS316L showed anodic passivation of SS316L, thereby exhibiting robustness towards coating defects including surface scratches that may originate during the manufacturing of the bipolar plate. These series of ex situ tests indicate that 10 nm gold coated SS316L has good potential to be considered for commercial bipolar plates in automotive fuel cell stack. (author)

  8. Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility.

    LENUS (Irish Health Repository)

    O'Dushlaine, C

    2011-03-01

    Susceptibility to schizophrenia and bipolar disorder may involve a substantial, shared contribution from thousands of common genetic variants, each of small effect. Identifying whether risk variants map to specific molecular pathways is potentially biologically informative. We report a molecular pathway analysis using the single-nucleotide polymorphism (SNP) ratio test, which compares the ratio of nominally significant (P<0.05) to nonsignificant SNPs in a given pathway to identify the \\'enrichment\\' for association signals. We applied this approach to the discovery (the International Schizophrenia Consortium (n=6909)) and validation (Genetic Association Information Network (n=2729)) of schizophrenia genome-wide association study (GWAS) data sets. We investigated each of the 212 experimentally validated pathways described in the Kyoto Encyclopaedia of Genes and Genomes in the discovery sample. Nominally significant pathways were tested in the validation sample, and five pathways were found to be significant (P=0.03-0.001); only the cell adhesion molecule (CAM) pathway withstood conservative correction for multiple testing. Interestingly, this pathway was also significantly associated with bipolar disorder (Wellcome Trust Case Control Consortium (n=4847)) (P=0.01). At a gene level, CAM genes associated in all three samples (NRXN1 and CNTNAP2), which were previously implicated in specific language disorder, autism and schizophrenia. The CAM pathway functions in neuronal cell adhesion, which is critical for synaptic formation and normal cell signaling. Similar pathways have also emerged from a pathway analysis of autism, suggesting that mechanisms involved in neuronal cell adhesion may contribute broadly to neurodevelopmental psychiatric phenotypes.

  9. CT-guided Bipolar and Multipolar Radiofrequency Ablation (RF Ablation) of Renal Cell Carcinoma: Specific Technical Aspects and Clinical Results

    Energy Technology Data Exchange (ETDEWEB)

    Sommer, C. M., E-mail: christof.sommer@med.uni-heidelberg.de [University Hospital Heidelberg, INF 110, Department of Diagnostic and Interventional Radiology (Germany); Lemm, G.; Hohenstein, E. [Minimally Invasive Therapies and Nuclear Medicine, SLK Kliniken Heilbronn GmbH, Clinic for Radiology (Germany); Bellemann, N.; Stampfl, U. [University Hospital Heidelberg, INF 110, Department of Diagnostic and Interventional Radiology (Germany); Goezen, A. S.; Rassweiler, J. [Clinic for Urology, SLK Kliniken Heilbronn GmbH (Germany); Kauczor, H. U.; Radeleff, B. A. [University Hospital Heidelberg, INF 110, Department of Diagnostic and Interventional Radiology (Germany); Pereira, P. L. [Minimally Invasive Therapies and Nuclear Medicine, SLK Kliniken Heilbronn GmbH, Clinic for Radiology (Germany)

    2013-06-15

    Purpose. This study was designed to evaluate the clinical efficacy of CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma (RCC) and to analyze specific technical aspects between both technologies. Methods. We included 22 consecutive patients (3 women; age 74.2 {+-} 8.6 years) after 28 CT-guided bipolar or multipolar RF ablations of 28 RCCs (diameter 2.5 {+-} 0.8 cm). Procedures were performed with a commercially available RF system (Celon AG Olympus, Berlin, Germany). Technical aspects of RF ablation procedures (ablation mode [bipolar or multipolar], number of applicators and ablation cycles, overall ablation time and deployed energy, and technical success rate) were analyzed. Clinical results (local recurrence-free survival and local tumor control rate, renal function [glomerular filtration rate (GFR)]) and complication rates were evaluated. Results. Bipolar RF ablation was performed in 12 procedures and multipolar RF ablation in 16 procedures (2 applicators in 14 procedures and 3 applicators in 2 procedures). One ablation cycle was performed in 15 procedures and two ablation cycles in 13 procedures. Overall ablation time and deployed energy were 35.0 {+-} 13.6 min and 43.7 {+-} 17.9 kJ. Technical success rate was 100 %. Major and minor complication rates were 4 and 14 %. At an imaging follow-up of 15.2 {+-} 8.8 months, local recurrence-free survival was 14.4 {+-} 8.8 months and local tumor control rate was 93 %. GFR did not deteriorate after RF ablation (50.8 {+-} 16.6 ml/min/1.73 m{sup 2} before RF ablation vs. 47.2 {+-} 11.9 ml/min/1.73 m{sup 2} after RF ablation; not significant). Conclusions. CT-guided bipolar and multipolar RF ablation of RCC has a high rate of clinical success and low complication rates. At short-term follow-up, clinical efficacy is high without deterioration of the renal function.

  10. An electrochemical treatment to improve corrosion and contact resistance of stainless steel bipolar plates used in polymer electrolyte fuel cells

    Science.gov (United States)

    Gabreab, Ebrahim M.; Hinds, Gareth; Fearn, Sarah; Hodgson, David; Millichamp, Jason; Shearing, Paul R.; Brett, Daniel J. L.

    2014-01-01

    An electrochemical surface treatment is presented that improves the properties of stainless steel (316SS) used as bipolar plates for polymer electrolyte fuel cells (PEFCs). The process is an anodic treatment, whereby the material is polarised beyond the transpassive region. Potentiodynamic corrosion testing, chemical and morphological surface characterisation and interfacial contact resistance measurements indicate that the improved properties of 316SS are primarily a consequence of an enrichment of Cr at the near-surface of the material. The surface treatment increases the corrosion resistance and significantly reduces interfacial contact resistance.

  11. Pharmacological Analysis of the Activation and Receptor Properties of the Tonic GABACR Current in Retinal Bipolar Cell Terminals

    OpenAIRE

    Jones, Stefanie M.; Palmer, Mary J

    2011-01-01

    GABAergic inhibition in the central nervous system (CNS) can occur via rapid, transient postsynaptic currents and via a tonic increase in membrane conductance, mediated by synaptic and extrasynaptic GABA(A) receptors (GABA(A)Rs) respectively. Retinal bipolar cells (BCs) exhibit a tonic current mediated by GABA(C)Rs in their axon terminal, in addition to synaptic GABA(A)R and GABA(C)R currents, which strongly regulate BC output. The tonic GABA(C)R current in BC terminals (BCTs) is not dependen...

  12. Hypergravity signal transduction in HeLa cells with concomitant phosphorylation of proteins immunoprecipitated with anti-microtubule-associated protein antibodies

    Science.gov (United States)

    Kumei, Yasuhiro; Whitson, Peggy A.; Sato, Atsushige; Cintron, Nitza M.

    1991-01-01

    It is shown that hypergravity (35g) stimulates the production of inositol 1,4,5-trisphosphate (IP3) and decreases adenosine 3-prime,5-prime-cyclic monophosphate (cAMP) levels in HeLa cells. It is proposed that IP3 and cAMP may act as second messengers in hypergravity signal transduction. Phosphorylation of microtubule-associated proteins in both the detergent-soluble and -insoluble fractions suggests that cytoskeletal structures may be influenced by gravity.

  13. Whole Cell Biosensor Using Anabaena torulosa with Optical Transduction for Environmental Toxicity Evaluation

    Directory of Open Access Journals (Sweden)

    Ling Shing Wong

    2013-01-01

    Full Text Available A whole cell-based biosensor using Anabaena torulosa for the detection of heavy metals (Cu, Pb, and Cd, 2,4-dichlorophenoxyacetate (2,4-D, and chlorpyrifos was constructed. The cyanobacteria were entrapped on a cellulose membrane through filtration. Then, the membrane was dried and fixed into a cylindrical well, which was designed to be attached to an optical probe. The probe was connected to fluorescence spectrometer with optical fibre. The presence of the toxicants was indicated by the change of fluorescence emission, before and after the exposure. The linear detection ranges for Cu, Pb, and Cd were 2.5–10.0 µg/L, 0.5–5.0 µg/L, and 0.5–10.0 µg/L, respectively, while 2,4-D and chlorpyrifos shared similar linear ranges of 0.05–0.75 µg/L. The biosensor showed good sensitivity with the lowest limits of detection (LLD for Cu, Pb, Cd, 2,4-D and chlorpyrifos determined at 1.195 µg/L, 0.100 µg/L, 0.027 µg/L, 0.025 µg/L, and 0.025 µg/L, respectively. The overall reproducibility of the biosensor (n=3 was <±6.35%. The biosensor had been tested with different combinations of toxicants, with the results showing predominantly antagonistic responses. The results confirmed that the biosensor constructed in this report is suitable to be used in quantitative and qualitative detections of heavy metals and pesticides.

  14. HIV-TAT mediated protein transduction of Cu/Zn-superoxide dismutase-1 (SOD1) protects skin cells from ionizing radiation

    International Nuclear Information System (INIS)

    Radiation-induced skin injury remains a serious concern during radiotherapy. Cu/Zn-superoxide dismutase (Cu/Zn-SOD, SOD1) is a conserved enzyme for scavenging superoxide radical in cells. Because of the integrity of cell membranes, exogenous molecule is not able to be incorporated into cells, which limited the application of natural SOD1. The aim of this study was to evaluate the protective role of HIV-TAT protein transduction domain mediated protein transduction of SOD1 (TAT-SOD1) against ionizing radiation. The recombinant TAT-SOD1 and SOD1 were obtained by prokaryotic–based protein expression system. The transduction effect and biological activity of TAT-SOD1 was measured by immunofluorescence and antioxidant capability assays in human keratinocyte HaCaT cells. Mito-Tracker staining, reactive oxygen species (ROS) generation assay, cell apoptosis analysis and malondialdehyde (MDA) assay were used to access the protective effect of TAT- SOD1. Uptake of TAT-SOD1 by HaCaT cells retained its biological activity. Compared with natural SOD1, the application of TAT-SOD1 significantly enhanced the viability and decreased the apoptosis induced by X-ray irradiation. Moreover, TAT-SOD1 reduced ROS and preserved mitochondrial integrity after radiation exposure in HaCaT cells. Radiation-induced γH2AX foci, which are representative of DNA double strand breaks, were decreased by pretreatment with TAT-SOD1. Furthermore, subcutaneous application of TAT-SOD1 resulted in a significant decrease in 45 Gy electron beam-induced ROS and MDA concentration in the skins of rats. This study provides evidences for the protective role of TAT-SOD1 in alleviating radiation-induced damage in HaCaT cells and rat skins, which suggests a new therapeutic strategy for radiation-induced skin injury

  15. LRIT3 is essential to localize TRPM1 to the dendritic tips of depolarizing bipolar cells and may play a role in cone synapse formation.

    Science.gov (United States)

    Neuillé, Marion; Morgans, Catherine W; Cao, Yan; Orhan, Elise; Michiels, Christelle; Sahel, José-Alain; Audo, Isabelle; Duvoisin, Robert M; Martemyanov, Kirill A; Zeitz, Christina

    2015-08-01

    Mutations in LRIT3 lead to complete congenital stationary night blindness (cCSNB). The exact role of LRIT3 in ON-bipolar cell signaling cascade remains to be elucidated. Recently, we have characterized a novel mouse model lacking Lrit3 [no b-wave 6, (Lrit3(nob6/nob6) )], which displays similar abnormalities to patients with cCSNB with LRIT3 mutations. Here we compare the localization of components of the ON-bipolar cell signaling cascade in wild-type and Lrit3(nob6/nob6) retinal sections by immunofluorescence confocal microscopy. An anti-LRIT3 antibody was generated. Immunofluorescent staining of LRIT3 in wild-type mice revealed a specific punctate labeling in the outer plexiform layer (OPL), which was absent in Lrit3(nob6/nob6) mice. LRIT3 did not co-localize with ribeye or calbindin but co-localized with mGluR6. TRPM1 staining was severely decreased at the dendritic tips of all depolarizing bipolar cells in Lrit3(nob6/nob6) mice. mGluR6, GPR179, RGS7, RGS11 and Gβ5 immunofluorescence was absent at the dendritic tips of cone ON-bipolar cells in Lrit3(nob6/nob6) mice, while it was present at the dendritic tips of rod bipolar cells. Furthermore, peanut agglutinin (PNA) labeling was severely reduced in the OPL in Lrit3(nob6/nob6) mice. This study confirmed the localization of LRIT3 at the dendritic tips of depolarizing bipolar cells in mouse retina and demonstrated the dependence of TRPM1 localization on the presence of LRIT3. As tested components of the ON-bipolar cell signaling cascade and PNA revealed disrupted localization, an additional function of LRIT3 in cone synapse formation is suggested. These results point to a possibly different regulation of the mGluR6 signaling cascade between rod and cone ON-bipolar cells. PMID:25997951

  16. LRIT3 is essential to localize TRPM1 to the dendritic tips of depolarizing bipolar cells and may play a role in cone synapse formation

    OpenAIRE

    Neuillé, Marion; Morgans, Catherine W.; Cao, Yan; Orhan, Elise; Michiels, Christelle; Sahel, José-Alain; Audo, Isabelle; Duvoisin, Robert M; Martemyanov, Kirill A.; Zeitz, Christina

    2015-01-01

    International audience Mutations in LRIT3 lead to complete congenital stationary night blindness (cCSNB). The exact role of LRIT3 in ON-bipolar cell signaling cascade remains to be elucidated. Recently, we have characterized a novel mouse model lacking Lrit3 [no b-wave 6, (Lrit3nob6/nob6)], which displays similar abnormalities to patients with cCSNB with LRIT3 mutations. Here we compare the localization of components of the ON-bipolar cell signaling cascade in wild-type and Lrit3nob6/nob6 ...

  17. Information flow during gene activation by signaling molecules: ethylene transduction in Arabidopsis cells as a study system

    Directory of Open Access Journals (Sweden)

    Díaz José

    2009-05-01

    Full Text Available Abstract Background We study root cells from the model plant Arabidopsis thaliana and the communication channel conformed by the ethylene signal transduction pathway. A basic equation taken from our previous work relates the probability of expression of the gene ERF1 to the concentration of ethylene. Results The above equation is used to compute the Shannon entropy (H or degree of uncertainty that the genetic machinery has during the decoding of the message encoded by the ethylene specific receptors embedded in the endoplasmic reticulum membrane and transmitted into the nucleus by the ethylene signaling pathway. We show that the amount of information associated with the expression of the master gene ERF1 (Ethylene Response Factor 1 can be computed. Then we examine the system response to sinusoidal input signals with varying frequencies to determine if the cell can distinguish between different regimes of information flow from the environment. Our results demonstrate that the amount of information managed by the root cell can be correlated with the frequency of the input signal. Conclusion The ethylene signaling pathway cuts off very low and very high frequencies, allowing a window of frequency response in which the nucleus reads the incoming message as a sinusoidal input. Out of this window the nucleus reads the input message as an approximately non-varying one. From this frequency response analysis we estimate: a the gain of the system during the synthesis of the protein ERF1 (~-5.6 dB; b the rate of information transfer (0.003 bits during the transport of each new ERF1 molecule into the nucleus and c the time of synthesis of each new ERF1 molecule (~21.3 s. Finally, we demonstrate that in the case of the system of a single master gene (ERF1 and a single slave gene (HLS1, the total Shannon entropy is completely determined by the uncertainty associated with the expression of the master gene. A second proposition shows that the Shannon entropy

  18. Multilayer graphene for long-term corrosion protection of stainless steel bipolar plates for polymer electrolyte membrane fuel cell

    Science.gov (United States)

    Stoot, Adam C.; Camilli, Luca; Spiegelhauer, Susie-Ann; Yu, Feng; Bøggild, Peter

    2015-10-01

    Motivated by similar investigations recently published (Pu et al., 2015), we report a comparative corrosion study of three sets of samples relevant as bipolar plates for polymer electrolyte fuel cells: stainless steel, stainless steel with a nickel seed layer (Ni/SS) and stainless steel with Ni seed layer coated by a multi-layered graphene thin film (G/Ni/SS). The graphene film, synthesized by chemical vapour deposition (CVD), has a moderate amount of defects according to Raman spectroscopy. Short/medium-term corrosion test shows no significant advantage of using G/Ni/SS rather than Ni/SS, both samples exhibiting a similar trend, thus questioning the short-term positive effect of graphene coatings. However, partial immersion in boiling seawater for three weeks reveals a clear superiority of the graphene coating with respect to steel just protected by Ni. After the test, the graphene film is still intact with unchanged defect density. Our results show that even non-perfect multilayer graphene films can considerably increase the lifetime of future-generation bipolar plates for fuel cells.

  19. Thermoplastic composite bipolar plates for polymer electrolyte membrane fuel cells (PEMFC). Paper no. IGEC-1-089

    International Nuclear Information System (INIS)

    Polymer electrolyte membrane fuel cells (PEMFC) are one significant component of the Hydrogen Economy. In order to make fuel cells economically feasible, processing and material cost need to be reduced. This reduction extends to the cost associated with bipolar plates. In an effort to produce functional bipolar plates at a competitive cost thermoplastic composite materials were extruded and injection molded, combining commercial materials such as polypropylene, carbon fiber, Vulcan carbon black, and acetylene carbon black. Two trials were executed. Trial 1 is a twenty sample experimental design and Trial 2 consists of different filler loadings with filler ratio 1:1:1. Thermal gravimetric analysis (TGA) was used to determine the actual filler loading following processing. Two methods of measuring electrical conductivity were investigated for Trial 1. Using method 1 a filler loading of 35 wt% and filler ratio of 1:1:1 reveals the best conductivity of 155 S/m. Method 2 has a maximum conductivity of 38 S/m and is achieved with a 32 wt% of only Vulcan carbon black. In Trial 2 a significant portion of the percolation curve for the filler ratio 1:1:1 is obtained. (author)

  20. Anticorrosion Coating of Carbon Nanotube/Polytetrafluoroethylene Composite Film on the Stainless Steel Bipolar Plate for Proton Exchange Membrane Fuel Cells

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Show

    2013-01-01

    Full Text Available Composite film of carbon nanotube (CNT and polytetrafluoroethylene (PTFE was formed from dispersion fluids of CNT and PTFE. The composite film showed high electrical conductivity in the range of 0.1–13 S/cm and hydrophobic nature. This composite film was applied to stainless steel (SS bipolar plates of the proton exchange membrane fuel cell (PEMFC as anticorrosion film. This coating decreased the contact resistance between the surface of the bipolar plate and the membrane electrode assembly (MEA of the PEMFC. The output power of the fuel cell is increased by 1.6 times because the decrease in the contact resistance decreases the series resistance of the PEMFC. Moreover, the coating of this composite film protects the bipolar plate from the surface corrosion.

  1. [6]-Gingerol Prevents Disassembly of Cell Junctions and Activities of MMPs in Invasive Human Pancreas Cancer Cells through ERK/NF-κB/Snail Signal Transduction Pathway

    Directory of Open Access Journals (Sweden)

    Sung Ok Kim

    2013-01-01

    Full Text Available To study the effects of [6]-gingerol, a ginger phytochemical, on tight junction (TJ molecules, we investigated TJ tightening and signal transduction pathways in human pancreatic duct cell-derived cancer cell line PANC-1. The following methods were utilized: MTT assay to determine cytotoxicity; zymography to examine matrix metalloproteinase (MMP activities; transepithelial electrical resistance (TER and paracellular flux for TJ measurement; RT-PCR and immunoblotting for proteins related to TJ and invasion; and EMSA for NF-κB activity in PANC-1 cells. Results revealed that TER significantly increased and claudin 4 and MMP-9 decreased compared to those of the control. TJ protein levels, including zonula occludens (ZO- 1, occludin, and E-cadherin, increased in [6]-gingerol-treated cells, which correlated with a decrease in paracellular flux and MMP activity. Furthermore, NF-κB/Snail nuclear translocation was suppressed via downregulation of the extracellular signal-regulated kinase (ERK pathway in response to [6]-gingerol treatment. Moreover, treatment with U0126, an ERK inhibitor, completely blocked NF-κB activity. In conclusion, these findings demonstrate that [6]-gingerol regulates TJ-related proteins and suppresses invasion and metastasis through NF-κB/Snail inhibition via inhibition of the ERK pathway. Therefore, [6]-gingerol may suppress the invasive activity of PANC-1 cells.

  2. The role of a cell surface inhibitor in early signal transduction associated with the regulation of cell division and differentiation

    Science.gov (United States)

    Johnson, T. C.; Enebo, D. J.; Moos, P. J.; Fattaey, H. K.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    Serum stimulation of quiescent human fibroblast cultures resulted in a hyperphosphorylation of the nuclear retinoblastoma gene susceptibility product (RB). However, serum stimulation in the presence of 9 x 10(-8) M of a purified bovine sialoglycopeptide (SGP) cell surface inhibitor abrogated the hyperphosphorylation of the RB protein and the subsequent progression of cells through the mitotic cycle. The experimental results suggest that the SGP mediated its cell cycle arrest at a site in the cell cycle that was at the time of RB phosphorylation or somewhat upstream of the modification of this regulatory protein of cell division. Both cells serum-deprived and serum stimulated in the presence of the SGP displayed only a hypophosphorylated RB protein, consistent with the SGP-mediated cell cycle arrest point being near the G1/S interface.

  3. Fabrication of CNT Dispersion Fluid by Wet-Jet Milling Method for Coating on Bipolar Plate of Fuel Cell

    Directory of Open Access Journals (Sweden)

    Anas Almowarai

    2015-01-01

    Full Text Available Water based carbon nanotube (CNT dispersion was produced by wet-jet milling method. Commercial CNT was originally agglomerated at the particle size of less than 1 mm. The wet-jet milling process exfoliated CNTs from the agglomerates and dispersed them into water. Sedimentation of the CNTs in the dispersion fluid was not observed for more than a month. The produced CNT dispersion was characterized by the SEM and the viscometer. CNT/PTFE composite film was formed with the CNT dispersion in this study. The electrical conductivity of the composite film increased to 10 times when the CNT dispersion, which was produced by the wet-jet milling method, was used as a constituent of the film. Moreover, the composite film was applied to bipolar plate of fuel cell and increased the output power of the fuel cell to 1.3 times.

  4. Alumina-carbon nanofibers nanocomposites obtained by spark plasma sintering for proton exchange membrane fuel cell bipolar plates

    Energy Technology Data Exchange (ETDEWEB)

    Borrell, A.; Torrecillas, R. [Centro de Investigacion en Nanomateriales y Nanotecnologia (CINN) Consejo Superior de Investigaciones Cientificas, Universidad de Oviedo, Principado de Asturias, Parque Tecnologico de Asturias, Llanera Asturias (Spain); Rocha, V.G.; Fernandez, A. [ITMA Materials Technology, Parque Tecnologico de Asturias, Llanera Asturias (Spain)

    2012-08-15

    There is an increasing demand of multifunctional materials for a wide variety of technological developments. Bipolar plates for proton exchange membrane fuel cells are an example of complex functionality components that must show among other properties high mechanical strength, electrical, and thermal conductivity. The present research explored the possibility of using alumina-carbon nanofibers (CNFs) nanocomposites for this purpose. In this study, it was studied for the first time the whole range of powder compositions in this system. Homogeneous powders mixtures were prepared and subsequently sintered by spark plasma sintering. The materials obtained were thoroughly characterized and compared in terms of properties required to be used as bipolar plates. The control on material microstructure and composition allows designing materials where mechanical or electrical performances are enhanced. A 50/50 vol.% alumina-CNFs composite appears to be a very promising material for this kind of application. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  5. Laminated exfoliated graphite composite-metal compositions for fuel cell flow field plate or bipolar plate applications

    Science.gov (United States)

    Zhamu, Aruna; Shi, Jinjun; Guo, Jiusheng; Jang, Bor Z

    2014-05-20

    An electrically conductive laminate composition for fuel cell flow field plate or bipolar plate applications. The laminate composition comprises at least a thin metal sheet having two opposed exterior surfaces and a first exfoliated graphite composite sheet bonded to the first of the two exterior surfaces of the metal sheet wherein the exfoliated graphite composite sheet comprises: (a) expanded or exfoliated graphite and (b) a binder or matrix material to bond the expanded graphite for forming a cohered sheet, wherein the binder or matrix material is between 3% and 60% by weight based on the total weight of the first exfoliated graphite composite sheet. Preferably, the first exfoliated graphite composite sheet further comprises particles of non-expandable graphite or carbon in the amount of between 3% and 60% by weight based on the total weight of the non-expandable particles and the expanded graphite. Further preferably, the laminate comprises a second exfoliated graphite composite sheet bonded to the second surface of the metal sheet to form a three-layer laminate. Surface flow channels and other desired geometric features can be built onto the exterior surfaces of the laminate to form a flow field plate or bipolar plate. The resulting laminate has an exceptionally high thickness-direction conductivity and excellent resistance to gas permeation.

  6. Transduction and oncolytic profile of a potent replication-competent adenovirus 11p vector (RCAd11pGFP in colon carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Jim Silver

    Full Text Available Replication-competent adenovirus type 5 (Ad5 vectors promise to be more efficient gene delivery vehicles than their replication-deficient counterparts, and chimeric Ad5 vectors that are capable of targeting CD46 are more effective than Ad5 vectors with native fibers. Although several strategies have been used to improve gene transduction and oncolysis, either by modifying their tropism or enhancing their replication capacity, some tumor cells are still relatively refractory to infection by chimeric Ad5. The oncolytic effects of the vectors are apparent in certain tumors but not in others. Here, we report the biological and oncolytic profiles of a replication-competent adenovirus 11p vector (RCAd11pGFP in colon carcinoma cells. CD46 was abundantly expressed in all cells studied; however, the transduction efficiency of RCAd11pGFP varied. RCAd11pGFP efficiently transduced HT-29, HCT-8, and LS174T cells, but it transduced T84 cells, derived from a colon cancer metastasis in the lung, less efficiently. Interestingly, RCAd11p replicated more rapidly in the T84 cells than in HCT-8 and LS174T cells and as rapidly as in HT-29 cells. Cell toxicity and proliferation assays indicated that RCAd11pGFP had the highest cell-killing activities in HT29 and T84 cells, the latter of which also expressed the highest levels of glycoproteins of the carcinoma embryonic antigen (CEA family. In vivo experiments showed significant growth inhibition of T84 and HT-29 tumors in xenograft mice treated with either RCAd11pGFP or Ad11pwt compared to untreated controls. Thus, RCAd11pGFP has a potent cytotoxic effect on colon carcinoma cells.

  7. Enhancement of cytotoxic T lymphocyte activity by dendritic cells loaded with Tat-protein transduction domain-fused hepatitis B virus core antigen

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The protein transduction domain (PTD) of human immuno-deficiency virus-1-Tat protein has a unique potency to pen-etrate the cellular membranes. To synthesize the sequence of Tat-PTD and hepatitis B virus core antigen (HBcAg), we spliced these sequences and linked a fusion gene into the pMAL-c2x vector. The fusion proteins were purified by affin-ity chromatography and pulsed with bone marrow -derived den-dritic cells (DCs), and the transduction of recombinant pro-tein was detected by immunofluorescence antibody assay.Results showed that recombinant PTD-HBcAg could pen-etrate into DC cytoplasm while recombinant HBcAg was de-tected on the surface of cells. The percentage of DC surface molecules, such as CD80, CD86 and major histocompatibii-ity complex Ⅱ, and production of cytokine (IL-12pT0) induced by recombinant PTD-HBcAg were significantly higher than those induced by recombinant HBcAg or tumor necrosis fac-tor-α. DCs treated with PTD-HBcAg induced T cells to dif-ferentiate into specific cytotoxic T lymphocytes (CTLs) and enhanced the CTL killing response. In conclusion, the ex-pressed and purified PTD-HBcAg fusion protein could pen-etrate into cells through the plasma membrane, promote DC maturation, and enhance T cells response to generate HBcAg-specific CTLs efficiently.

  8. Effects of potassium channel on shear stress - induced signal transduction in vascular endothelial cells%K离子通道在剪切力诱导血管内皮细胞信号转导中的作用

    Institute of Scientific and Technical Information of China (English)

    胡金麟

    1999-01-01

    Fluid shear stress play an important role in many physiological and pathophysiological processes of cardiovascular system. Shear stress - induced signal transduction throughout the vascular endothelial cell includes ion channels,G- protein linked receptors, tyrosine kinase receptors and integrins. The one impossible pathway of shear stress - induced signal transduction was biochemical reaction through second messenger, activating protein kinases and cytosolic transcription factors, and then regulating gene transcription . The other pathway was cytoskeletal system. This article reviewed the cellular and molecular mechanism of potassium channel signal transduction resulting from shear stress.

  9. As bases neurobiológicas do transtorno bipolar Neurobiological basis of bipolar disorder

    Directory of Open Access Journals (Sweden)

    Rodrigo Machado-Vieira

    2005-01-01

    Full Text Available Neste artigo, os autores revisam importantes aspectos associados às bases biológicas do transtorno de humor bipolar (THB. O THB está relacionado com o surgimento de diversas alterações bioquímicas e moleculares em sistemas de neurotransmissão e vias de segundos-mensageiros geradores de sinais intracelulares. Essas modificações em neurônios e glia parecem estar associadas com o surgimento de sintomas maníacos e depressivos. Ainda neste contexto, disfunções na homeostasia e no metabolismo energético cerebral tem sido associado com alterações comportamentais, na modulação do humor e ritmo circadiano em humanos e em modelos animais da doença. Assim, alterações metabólicas em neurônios e células gliais têm sido associadas com quadros depressivos e maníacos. Nos últimos anos, avanços nas técnicas de neuroimagem, genéticos e de biologia moleculares têm gerado novos conhecimentos acerca das bases biológicas da bipolaridade. Os autores destacam que a doença parece estar relacionada diretamente com disfunções em diferentes mecanismos adaptativos a estresse em células neurais, gerando perda na capacidade celular de induzir neuroplasticidade e neurotrofismo, facilitando assim o surgimento da doença.In this article, the authors review relevant aspects related to the neurobiological basis of bipolar disorder. This illness has been associated with complex biochemical and molecular changes in brain circuits linked to neurotransmission and intracellular signal transduction pathways, and changes on neurons and glia have been proposed to be directly associated with clinical presentation of mania and depression. In the same context, dysfunctions on brain homeostasis and energy metabolism have been associated with alterations on circadian rythms, behavior and mood in human and animal models of bipolarity. In the recent years, advances on techniques of neuroimaging, molecular biology and genetics has provided new insights about

  10. Microtubule-associated protein65 is essential for maintenance of Phragmoplast bipolarity and formation of the cell plate in Physcomitrella patens

    NARCIS (Netherlands)

    Kosetsu, K.; Keijzer, de J.; Janson, M.E.; Goshima, G.

    2013-01-01

    The phragmoplast, a plant-specific apparatus that mediates cytokinesis, mainly consists of microtubules (MTs) arranged in a bipolar fashion, such that their plus ends interdigitate at the equator. Membrane vesicles are thought to move along the MTs toward the equator and fuse to form the cell plate.

  11. Effect of cigarette smoke extract on lipopolysaccha-ride-activated mitogen-activated protein kinase signal transduction pathway in cultured cells

    Institute of Scientific and Technical Information of China (English)

    LI Wen; XU Yong-jian; SHEN Hua-hao

    2007-01-01

    Background Lipopolysaccharide (LPS) forms outer membrane of the wall of Gram-negative cells. LPS can directly cause damage to epithelia of respiratory tract and is the major factor responsible for the chronic inflammation of respiratory passage. The mitogen-activated protein kinase (MAPK) signal transduction pathway of the airway epithelia is intimately associated with the action of LPS. The chronic inflammation of respiratory tract and smoking are interrelated and entwined in the development and progression of chronic lung diseases. This study was designed to examine the effects of cigarette smoke extract (CSE) and LPS on MAPK signal transduction pathway in order to further understand the roles CSE and LPS play in chronic lung inflammation.Methods Cultured primary human epithelial cells of airway were divided into four groups according to the stimulants used: blank control group, LPS-stimulation group, CSE-stimulation group and CSE plus LPS group. Western blotting was employed for the detection of phosphorylation level of extracellular-signal-regulated-kinase (ERK1/2), p38 MAPK and c-Jun N-terminal kinase (JNK). The expression of cytokines of MAPK transduction pathway (granulocyte-macrophage colony stimulating factor (GM-CSF) and mRNA of IL-8) in the primary epithelial cells of respiratory tract was also determined.Results Western blotting revealed that the phosphorylation levels of ERK1/2, p38 MAPK and JNK were low and 2 hours after the LPS stimulation, the phosphorylation of ERK1/2, p38 MAPK and JNK were all increased. There was a significant difference in the phosphorylation between the LPS-stimulation group and blank control group (P<0.05); no significant difference was found between CSE-stimulation group and blank control group (P>0.05); there was a significant difference between CSE + LPS group and blank control group and between CSE + LPS group and LPS group (P<0.05). The phosphorylation of CSE-LPS group was higher than that of blank control group but

  12. Methylmercury, an environmental electrophile capable of activation and disruption of the Akt/CREB/Bcl-2 signal transduction pathway in SH-SY5Y cells

    Science.gov (United States)

    Unoki, Takamitsu; Abiko, Yumi; Toyama, Takashi; Uehara, Takashi; Tsuboi, Koji; Nishida, Motohiro; Kaji, Toshiyuki; Kumagai, Yoshito

    2016-01-01

    Methylmercury (MeHg) modifies cellular proteins via their thiol groups in a process referred to as “S-mercuration”, potentially resulting in modulation of the cellular signal transduction pathway. We examined whether low-dose MeHg could affect Akt signaling involved in cell survival. Exposure of human neuroblastoma SH-SY5Y cells of up to 2 μM MeHg phosphorylated Akt and its downstream signal molecule CREB, presumably due to inactivation of PTEN through S-mercuration. As a result, the anti-apoptotic protein Bcl-2 was up-regulated by MeHg. The activation of Akt/CREB/Bcl-2 signaling mediated by MeHg was, at least in part, linked to cellular defence because either pretreatment with wortmannin to block PI3K/Akt signaling or knockdown of Bcl-2 enhanced MeHg-mediated cytotoxicity. In contrast, increasing concentrations of MeHg disrupted Akt/CREB/Bcl-2 signaling. This phenomenon was attributed to S-mercuration of CREB through Cys286 rather than Akt. These results suggest that although MeHg is an apoptosis-inducing toxicant, this environmental electrophile is able to activate the cell survival signal transduction pathway at lower concentrations prior to apoptotic cell death. PMID:27357941

  13. Effect of NK4 Transduction in Bone Marrow-Derived Mesenchymal Stem Cells on Biological Characteristics of Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yun-Peng Sun

    2014-03-01

    Full Text Available Pancreatic cancer usually has a poor prognosis, and no gene therapy has yet been developed that is effective to treat it. Since a unique characteristic of bone marrow-derived mesenchymal stem cells (MSCs is that they migrate to tumor tissues, we wanted to determine whether MSCs could serve as a vehicle of gene therapy for targeting pancreatic cancer. First, we successfully extracted MSCs from SD rats. Next, MSCs were efficiently transduced with NK4, an antagonist of hepatocyte growth factor (HGF which comprising the N-terminal and the subsequent four kringle domains of HGF, by an adenoviral vector. Then, we confirmed that rat MSCs preferentially migrate to pancreatic cancer cells. Last, MSCs expressing NK4 (NK4-MSCs strongly inhibited proliferation and migration of the pancreatic cancer cell line SW1990 after co-culture. These results indicate that MSCs can serve as a vehicle of gene therapy for targeting pancreatic cancer.

  14. Harmonin-b, an actin-binding scaffold protein, is involved in the adaptation of mechanoelectrical transduction by sensory hair cells

    OpenAIRE

    Michalski, Nicolas; Michel, Vincent; Caberlotto, Elisa; Lefèvre, Gaelle M.; Van Aken, Alexander F J; Tinevez, Jean-Yves; Bizard, Emilie; Houbron, Christophe; Weil, Dominique; Hardelin, Jean-Pierre; Richardson, Guy P.; Kros, Corné J.; Martin, Pascal; Petit, Christine

    2009-01-01

    We assessed the involvement of harmonin-b, a submembranous protein containing PDZ domains, in the mechanoelectrical transduction machinery of inner ear hair cells. Harmonin-b is located in the region of the upper insertion point of the tip link that joins adjacent stereocilia from different rows and that is believed to gate transducer channel(s) located in the region of the tip link's lower insertion point. In Ush1c dfcr-2J/dfcr-2J mutant mice defective for harmonin-b, step deflections of the...

  15. The Na+/H+ exchanger NHE1 in stress-induced signal transduction: implications for cell proliferation and cell death

    DEFF Research Database (Denmark)

    Pedersen, Stine Falsig

    2006-01-01

    The ubiquitous plasma membrane Na+/H+ exchanger NHE1 is highly conserved across vertebrate species and is extensively characterized as a major membrane transport mechanism in the regulation of cellular pH and volume. In recent years, the understanding of the role of NHE1 in regulating cell functi...

  16. Involvement of phospholipase D-related signal transduction in chemical-induced programmed cell death in tomato cell cultures

    NARCIS (Netherlands)

    Iakimova, E.T.; Michaeli, R.; Woltering, E.J.

    2013-01-01

    Phospholipase D (PLD) and its product phosphatidic acid (PA) are incorporated in a complex metabolic network in which the individual PLD isoforms are suggested to regulate specific developmental and stress responses, including plant programmed cell death (PCD). Despite the accumulating knowledge, th

  17. Effect of mitogen-activated protein kinase signal transduction pathway on multidrug resistance induced by vincristine in gastric cancer cell line MGC803

    Institute of Scientific and Technical Information of China (English)

    Bo Chen; Feng Jin; Ping Lu; Xiang-Lan Lu; Ping-Ping Wang; Yun-Peng Liu; Fan Yao; Shu-Bao Wang

    2004-01-01

    AIM: To investigate the correlation between mitogenactivated protein kinase (MAPK) signal transduction pathway and multidrug resistance (MDR) in MGC803 cells. METHODS: Western blot was used to analyze the expression of MDR associated gene in transient vincristine (VCR) induced MGC803 cells, which were treated with or without the specific inhibitor of MAPK, PD098059. Morphologic analysis of the cells treated by VCR with or without PD098059 was determined by Wright-Giemsa staining. The cell cycle analysis was performed by using flow cytometric assay and the drug sensitivity of MGC803 cells which were exposed to VCR with or without PD098059 was tested by using MTT assay. RESULTS: Transient exposure to VCR induced P-gp but not MRP1 or GST-π expression in MGC803 cells and the expression of P-gp was inhibited by PD098059. Apoptotic bodies were found in the cells treated with VCR or VCR+PD098059. FCM results indicated that more MGC803 cells showed apoptotic phenotype when treated by VCR and PD098059 (rate: 3L.23%) than treated by VCR only (rate:18.42%) (P<0.05). The ICs0 (284±13.2 μg/L) of MGC803 cells pretreated with VCR was 2.24-fold as that of negative control group (127±17.6 μg/L) and 1.48-fold as that of the group treated with PD098059 (191±27.9 μg/L). CONCLUSION: This study shows that the expression of P-gp can be induced by transient exposure to VCR and this induction can be prevented by PD098059, which can block the activity of MAPK. MAPK signal transduction pathway may play some roles in modulating MDR1 expression in gastric cancer.

  18. Transtorno bipolar

    OpenAIRE

    Alda Martin

    1999-01-01

    Os resultados de estudos de famílias sugerem que o transtorno bipolar tenha uma base genética. Essa hipótese foi reforçada em estudos de adoção e de gêmeos. A herança do transtorno bipolar é complexa, envolve vários genes, além de apresentar heterogeneidade e interação entre fatores genéticos e não-genéticos. Achados, que já foram replicados, já implicaram os cromossomos 4, 12, 18 e 21, entre outros, na busca por genes de suscetibilidade. Os resultados mais promissores foram obtidos através d...

  19. Participation of intracellular signal transduction in the radio-adaptive response induced by low-dose X-irradiation in human embryonic cells

    Energy Technology Data Exchange (ETDEWEB)

    Ishii, Keiichiro; Hoshi, Yuko; Iwasaki, Toshiyasu [Central Research Inst. of Electric Power Industry, Komae, Tokyo (Japan). Komae Research Lab.; Watanabe, Masami

    1996-11-01

    To elucidate the induction mechanism of radio-adaptive response in normal cells, we searched the literatures of the intracellular signal transduction. Furthermore, we examined the induction of radio-adaptive response with or without inhibitors of several kinds of protein kinase. The major results obtained were as follows; (1) According to the literature survey it is revealed that there are 4 intracellular signal transduction pathways which are possibly involved in the induction of radio-adaptive response: pathways depending on cAMP, calcium, cGMP, or protein-tyrosine kinase. (2) Addition of either inhibitor of protein-tyrosine kinase or protein kinase C to the cell culture medium during the low-dose X-irradiation inhibited the induction of radio-adaptive response. However, the addition of inhibitor of cAMP-dependent protein kinase, cGMP-dependent protein kinase, or Ca{sup 2+}-calmodulin kinase II failed to inhibit the induction of radio-adaptive response. (3) These results suggest that the signal induced in cells by low-dose X-irradiation was transduced from protein-tyrosine kinase to protein kinase C via either pathway of phosphatidylinositol 3-kinase or splitting of profilin binding phosphatidylinositol 4,5-bisphosphate. (author)

  20. Transtorno bipolar

    Directory of Open Access Journals (Sweden)

    Alda Martin

    1999-01-01

    Full Text Available Os resultados de estudos de famílias sugerem que o transtorno bipolar tenha uma base genética. Essa hipótese foi reforçada em estudos de adoção e de gêmeos. A herança do transtorno bipolar é complexa, envolve vários genes, além de apresentar heterogeneidade e interação entre fatores genéticos e não-genéticos. Achados, que já foram replicados, já implicaram os cromossomos 4, 12, 18 e 21, entre outros, na busca por genes de suscetibilidade. Os resultados mais promissores foram obtidos através de estudos de ligação. Por outro lado, os estudos de associação geraram dados interessantes, mas ainda vagos. Os estudos de populações de pacientes homogêneos e a melhor definição do fenótipo deverão contribuir para avanços futuros. A identificação dos genes relacionados ao transtorno bipolar irá permitir o melhor entendimento e tratamento dessa doença.

  1. A review of composite and metallic bipolar plates in proton exchange membrane fuel cell: Materials, fabrication, and material selection

    Science.gov (United States)

    Taherian, Reza

    2014-11-01

    Proton exchange membrane (PEM) fuel cells offer exceptional potential for a clean, efficient, and reliable power source. The bipolar plate (BP) is a key component in this device, as it connects each cell electrically, supplies reactant gases to both anode and cathode, and removes reaction products from the cell. BPs have primarily been fabricated from high-density graphite, but in recent years, much attention has been paid to develop the cost-effective and feasible alternative materials. Recently, two different classes of materials have been attracted attention: metals and composite materials. This paper offers a comprehensive review of the current researches being carried out on the metallic and composite BPs, covering materials and fabrication methods. In this research, the phenomenon of ionic contamination due to the release of the corrosion products of metallic BP and relative impact on the durability as well as performance of PEM fuel cells is extensively investigated. Furthermore, in this paper, upon several effective parameters on commercialization of PEM fuel cells, such as stack cost, weight, volume, durability, strength, ohmic resistance, and ionic contamination, a material selection is performed among the most common BPs currently being used. This material selection is conducted by using Simple Additive Weighting Method (SAWM).

  2. Isotropic Versus Bipolar Functionalized Biomimetic Artificial Basement Membranes and Their Evaluation in Long-Term Human Cell Co-Culture.

    Science.gov (United States)

    Rossi, Angela; Wistlich, Laura; Heffels, Karl-Heinz; Walles, Heike; Groll, Jürgen

    2016-08-01

    In addition to dividing tissues into compartments, basement membranes are crucial as cell substrates and to regulate cellular behavior. The development of artificial basement membranes is indispensable for the ultimate formation of functional engineered tissues; however, pose a challenge due to their complex structure. Herein, biodegradable electrospun polyester meshes are presented, exhibiting isotropic or bipolar bioactivation as a biomimetic and biofunctional model of the natural basement membrane. In a one-step preparation process, reactive star-shaped prepolymer additives, which generate a hydrophilic fiber surface, are electrospun with cell-adhesion-mediating peptides, derived from major components of the basement membrane. Human skin cells adhere to the functionalized meshes, and long-term co-culture experiments confirm that the artificial basement membranes recapitulate and preserve tissue specific functions. Several layers of immortalized human keratinocytes grow on the membranes, differentiating toward the surface and expressing typical epithelial markers. Fibroblasts migrate into the reticular lamina mimicking part of the mesh. Both cells types begin to produce extracellular matrix proteins and to remodel the initial membrane. It is shown at the example of skin that the artificial basement membrane design provokes biomimetic responses of different cell types and can thus be used as basis for the future development of basement membrane containing tissues. PMID:27283510

  3. Deposition of gold-titanium and gold-nickel coatings on electropolished 316L stainless steel bipolar plates for proton exchange membrane fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Young-Hoon [Department of Hydrogen and Fuel Cell Tech., Dongshin University, Daeho-dong 253, Jeonnam, Naju 520-714 (Korea)

    2010-02-15

    The effects of electropolishing and coating deposition on electrical resistance and chemical stability were studied for the stainless steel bipolar plates in proton exchange membrane fuel cell (PEMFC). A series of 316L stainless steel plates, selected as the substrate for a proton exchange membrane fuel cell (PEMFC) bipolar plate, were electropolished with a solution of H{sub 2}SO{sub 4} and H{sub 3}PO{sub 4} at temperatures ranging from 70 to 110 C. The surface regions of the two electropolished stainless steel plates were coated with gold and either a titanium or nickel layer using electron beam evaporation. The electropolished stainless steel plates coated in 2-{mu}m thick gold with a 0.1-{mu}m titanium or nickel interlayer showed remarkably smooth and uniform surface morphologies in AFM and FE-SEM images compared to the surfaces of the plates that were coated after mechanical polishing only. The electrical resistance and water contact angle of the deposited stainless steel bipolar plates are strongly dependent on the surface modification treatments (i.e., mechanical polishing versus electropolishing). ICP-MS and XPS results indicate that after electropolishing, the coating layers show excellent chemical stability after exposure to an H{sub 2}SO{sub 4} solution of pH 3. Finally, it was concluded that before coating deposition, the surface modification using electropolishing was very suitable for enhancing the electrical property and chemical stability of the stainless steel bipolar plate. (author)

  4. Cellular Prion Protein and Caveolin-1 Interaction in a Neuronal Cell Line Precedes Fyn/Erk 1/2 Signal Transduction

    Directory of Open Access Journals (Sweden)

    Mattia Toni

    2006-01-01

    Full Text Available It has been reported that cellular prion protein (PrPc is enriched in caveolae or caveolae-like domains with caveolin-1 (Cav-1 participating to signal transduction events by Fyn kinase recruitment. By using the Glutathione-S-transferase (GST-fusion proteins assay, we observed that PrPc strongly interacts in vitro with Cav-1. Thus, we ascertained the PrPc caveolar localization in a hypothalamic neuronal cell line (GN11, by confocal microscopy analysis, flotation on density gradient, and coimmunoprecipitation experiments. Following the anti-PrPc antibody-mediated stimulation of live GN11 cells, we observed that PrPc clustered on plasma membrane domains rich in Cav-1 in which Fyn kinase converged to be activated. After these events, a signaling cascade through p42/44 MAP kinase (Erk 1/2 was triggered, suggesting that following translocations from rafts to caveolae or caveolae-like domains PrPc could interact with Cav-1 and induce signal transduction events.

  5. Effects of TNF-α on the expression of monocyte chemoattractant protein-1 and the corresponding signal transduction pathway in dental follicle cells

    Directory of Open Access Journals (Sweden)

    Ying-chun BI

    2011-02-01

    Full Text Available Objective To study the effect of different concentration of tumor necrosis factor-α(TNF-α on the expression of monocyte chemoattractant protein-1(MCP-1 and the corresponding signal transduction pathway in human dental follicle cells.Methods The 5th passage of human dental follicle cells were co-incubated with 0(control group,5,10,25,50 and 100 ng/ml TNF-α,respectively,for 6 hours.The contents of MCP-1 in the supernatant were measured by using sandwich ELISA,and the expression of MCP-1 mRNA was determined by reverses transcription polymerase chain reaction(RT-PCR.Furthermore,to determine the corresponding signal transduction pathway,the 5th passage of human dental follicle cells were incubated with 25 μmol/L SB203580 to inhibit p38 mitogen-activated protein kinase(p38MARK,with 50 μmol/L PD98059 to inhibit extracellular signal-regulated kinases(ERK,and with 15 μmol/L SP600125 to inhibit c-Jun N-terminal kinases(JNK for 30min,then incubated with TNF-α(10ng/ml for 6h.MCP-1 mRNA was detected by RT-PCR.Results The results of ELISA revealed that 10-100 ng/ml of TNF-α enhanced MCP-1 secretion(P < 0.05 compared to that in human dental follicle cells without TNF-α treatment.Cells treated with 10-50 ng/ml of TNF-α showed a significant increase of MCP-1 mRNA expression(P < 0.05,and the action was inhibited by SP600125,which was the special inhibitor of c-Jun N-terminal kinase(JNK.Conclusion TNF-α may enhance MCP-1 gene expression and secretion in human dental follicle cells,and the activation of JNK signal transduction pathway is required in this process.

  6. Erythropoietin suppresses epithelial to mesenchymal transition and intercepts Smad signal transduction through a MEK-dependent mechanism in pig kidney (LLC-PK1) cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chien-Liang; Chou, Kang-Ju; Lee, Po-Tsang [Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Chen, Ying-Shou; Chang, Tsu-Yuan; Hsu, Chih-Yang; Huang, Wei-Chieh [Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Chung, Hsiao-Min [Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Fang, Hua-Chang, E-mail: hcfang@isca.vghks.gov.tw [Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (China)

    2010-04-15

    Purpose: Tumor growth factor-{beta}1 (TGF-{beta}1) plays a pivotal role in processes like kidney epithelial-mesenchymal transition (EMT) and interstitial fibrosis, which correlate well with progression of renal disease. Little is known about underlying mechanisms that regulate EMT. Based on the anatomical relationship between erythropoietin (EPO)-producing interstitial fibroblasts and adjacent tubular cells, we investigated the role of EPO in TGF-{beta}1-mediated EMT and fibrosis in kidney injury. Methods: We examined apoptosis and EMT in TGF-{beta}1-treated LLC-PK1 cells in the presence or absence of EPO. We examined the effect of EPO on TGF-{beta}1-mediated Smad signaling. Apoptosis and cell proliferation were assessed with flow cytometry and hemocytometry. We used Western blotting and indirect immunofluorescence to evaluate expression levels of TGF-{beta}1 signal pathway proteins and EMT markers. Results: We demonstrated that ZVAD-FMK (a caspase inhibitor) inhibited TGF-{beta}1-induced apoptosis but did not inhibit EMT. In contrast, EPO reversed TGF-{beta}1-mediated apoptosis and also partially inhibited TGF-{beta}1-mediated EMT. We showed that EPO treatment suppressed TGF-{beta}1-mediated signaling by inhibiting the phosphorylation and nuclear translocation of Smad 3. Inhibition of mitogen-activated protein kinase kinase 1 (MEK 1) either directly with PD98059 or with MEK 1 siRNA resulted in inhibition of EPO-mediated suppression of EMT and Smad signal transduction in TGF-{beta}1-treated cells. Conclusions: EPO inhibited apoptosis and EMT in TGF-{beta}1-treated LLC-PK1 cells. This effect of EPO was partially mediated by a mitogen-activated protein kinase-dependent inhibition of Smad signal transduction.

  7. Involvement of M3 Cholinergic Receptor Signal Transduction Pathway in Regulation of the Expression of Chemokine MOB-1, MCP-1 Genes in Pancreatic Acinar Cells

    Institute of Scientific and Technical Information of China (English)

    郑海; 陈道达; 张景輝; 田原

    2004-01-01

    Whether M3 cholinergic receptor signal transduction pathway is involved in regulation of the activation of NF-κB and the expression of chemokine MOB-1, MCP-1genes in pancreatic acinar cells was investigated. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, atropine and PDTC in vitro. The MOB-1 and MCP-1 mRNA expression was detected by using RT-PCR. The activation of NF-κB was monitored by using electrophoretic mobility shift assay.The results showed that as compared with control group, M3 cholinergic receptor agonist (103mol/L, 104-4ol/L carbachol) could induce a concentration-dependent and time-dependent increase in the expression of MOB-1, MCP-1 mRNA in pancreatic acinar cells. After treatment with 10 -3mol/L carbachol for 2 h, the expression of MOB-1, MCP-1 mRNA was strongest. The activity of NF-κB in pancreatic acinar cells was significantly increased (P<0.01) after treated with M3 cholinergic receptor agonist (10-3 mol/L carbachol) in vitro for 30 min. Either M3 cholinergic receptor antagonist (10-5 mol/L atropine) or NF-κB inhibitor (10-2 mol/L PDTC) could obviously inhibit the activation of NF-κB and the chemokine MOB-1, MCP-1 mRNA expression induced by carbachol (P <0.05). This inhibitory effect was significantly increased by atropine plus PDTC (P<0.01). The results of these studies indicated that M3 cholinergic receptor signal transduction pathway was likely involved in regulation of the expression of chemokine MOB-1 and MCP-1genes in pancreatic acinar cells in vitro through the activation of NF-κB.

  8. A Simulation Tool for Geometrical Analysis and Optimization of Fuel Cell Bipolar Plates: Development, Validation and Results

    Directory of Open Access Journals (Sweden)

    Javier Pino

    2009-07-01

    Full Text Available Bipolar plates (BPs are one of the most important components in Proton Exchange Membrane Fuel Cells (PEMFC due to the numerous functions they perform. The objective of the research work described in this paper was to develop a simplified and validated method based on Computational Fluid Dynamics (CFD, aimed at the analysis and study of the influence of geometrical parameters of BPs on the operation of a cell. A complete sensibility analysis of the influence of dimensions and shape of the BP can be obtained through a simplified CFD model without including the complexity of other components of the PEMFC. This model is compared with the PEM Fuel Cell Module of the FLUENT software, which includes the physical and chemical phenomena relevant in PEMFCs. Results with both models regarding the flow field inside the channels and local current densities are obtained and compared. The results show that it is possible to use the simple model as a standard tool for geometrical analysis of BPs, and results of a sensitivity analysis using the simplified model are presented and discussed.

  9. Elastomer based composite materials for bipolar plates in polymer electrolyte membrane fuel cells

    Science.gov (United States)

    Petrach, Elaine M.

    2011-07-01

    In most investigations, polymer conductive composite bipolar plates have failed to achieve the low resistivity required for PEMFCs. The goal of this dissertation is to investigate whether a composite of conductive fillers and a two-phase polymeric matrix will achieve low resistivity through preferred distribution of the fillers at the interface of the two phases. The use of an elastomer as one component of the blend will impart fracture resistance. Three types of matrices were investigated, a single phase polyvinyl ester plastic matrix, a compatible one-phase blend of polyvinyl ester (VER) and polyurethane (PU) elastomer, and a two-phase system of polyvinyl ester and ethylene propylene diene monomer (EPDM) elastomer. The different phases were determined by the theory of mixing. When solubility parameters are closer together it is likely that the system will be one phase. The one and two-phase systems were analyzed within the composition containing natural Cytec DKD graphite fibers, Asbury synthetic graphite 4012 flakes and ultra high surface area synthetic graphite TC 307. Phase systems affect the mechanical, electrical, and thermal properties. The percolation theory analysis was applied to determine the optimal percentage of conductive fillers and polymer blends. The optimal composition for composite materials consisted of 35vo1% of conductive fillers and 65vo1% of a two-phase blend matrix. The conductive filler included 3vol% of synthetic graphite TC307, 25.5vol% of Cytec DKD graphite fibers and 6.5vol% of Asbury synthetic graphite 4012 flakes. The two-phase blend matrix included 40vol% of EPDM to 60vol% of VER. This resulted in an electrical resistivity of 0.009O-cm and a thermal conductivity of 11.6W/m-K. The two-phase blend matrix added more ductility to the composition with the ability to withstand a stress of 10MPa with over 1% strain applied to the overall composite bipolar plates. The composition also absorbed 60% more mechanical energy than that

  10. 质子交换膜燃料电池双极板的研究进展%Progress of bipolar plate of proton exchange membrane fuel cell

    Institute of Scientific and Technical Information of China (English)

    张园园; 王匀; 戴亚春; 丁盛; 尹必峰

    2012-01-01

    质子交换膜燃料电池具有低温快速启动、比能量高、零排放、高效率等特点,应用前景广阔.低成本高效双极板成形方法成为制约质子交换膜燃料电池商业化的瓶颈之一.主要从材料选择和制备、流场结构布置以及双极板制造方法等方面,详细阐述了双极板的国内外研究现状及发展趋势,提出了微累积成形新方法,最后展望了双极板的研究方向.%Proton exchange membrane fuel cell (PEMFC) has the characteristics of easy-start up at low temperature,high energy density,zero discharge and high efficiency with broad application.The low cost and efficient forming methods of bipolar plates become the bottleneck of the commercialization of PEMFC.The state of arts of bipolar plate was introduced in this paper,mainly focusing on material selection and preparation,flow structure layout and bipolar plate manufacturing methods etc.A new forming method,micro accumulation was presented.Finally,the future research development of the bipolar plate was proposed.

  11. SnO2:F Coated Duplex Stainless Steel for PEM Fuel Cell Bipolar Plates

    Energy Technology Data Exchange (ETDEWEB)

    Wang, H.; Turner, J. A.

    2008-01-01

    Duplex 2205 stainless steel was deposited with 0.6 {micro}m thick SnO2:F coating; coated steel was characterized for PEMFC bipolar plate application. Compared with bare alloy, interfacial contact resistance (ICR) values of the coated 2205 steel are higher. SnO2:F coating adds its own resistance to the air-formed film on the steel. In a PEMFC anode environment, a current peak of ca. 25 {micro}A/cm2 registered at ca. 30 min for coated 2205 steel. It stabilized at ca. 2.0 {approx} -1.0 {micro}A/cm2. This peak is related to the complicated process of coating dissolution and oxide-layer formation. Anodic-cathodic current transfer occurred at ca. 200 min polarization. In a PEMFC cathode environment, current was stable immediately after polarization. The stable current was ca. 0.5 {approx} 2.0 {micro}A/cm2 during the entire polarization period. AES depth profiles with tested samples and ICP analysis with the tested solutions confirmed the excellent corrosion resistance of the SnO2:F coated 2205 alloy in simulated PEMFC environments.

  12. Photothermally induced bromination of carbon/polymer bipolar plate materials for fuel cell applications

    Science.gov (United States)

    Schade, Martin; Franzka, Steffen; Cappuccio, Franco; Peinecke, Volker; Heinzel, Angelika; Hartmann, Nils

    2015-05-01

    A facile photothermal procedure for direct functionalization of carbon/polymer bipolar plate materials is demonstrated. Through irradiation with a microfocused beam of an Ar+-laser at λ = 514 nm in gaseous bromine and distinct laser powers and pulse lengths local bromination of the carbon/polymer material takes place. At a 1/e spot diameter of 2.1 μm, functionalized surface areas with diameters down to 5 μm are fabricated. In complementary experiments large-area bromination is investigated using an ordinary tungsten lamp. For characterization contact angle goniometry, X-ray photoelectron spectroscopy and electron microscopy in conjunction with labeling techniques are employed. After irradiation bromine groups can easily be substituted by other chemical functionalities, e.g. azide and amine groups. This provides a facile approach in order to fabricate surface patterns and gradient structures with varying wetting characteristics. Mechanistic aspects and prospects of photothermal routines in micropatterning of carbon/polymer materials are discussed.

  13. Receptive field properties of bipolar cell axon terminals in direction-selective sublaminas of the mouse retina.

    Science.gov (United States)

    Chen, Minggang; Lee, Seunghoon; Park, Silvia J H; Looger, Loren L; Zhou, Z Jimmy

    2014-10-15

    Retinal bipolar cells (BCs) transmit visual signals in parallel channels from the outer to the inner retina, where they provide glutamatergic inputs to specific networks of amacrine and ganglion cells. Intricate network computation at BC axon terminals has been proposed as a mechanism for complex network computation, such as direction selectivity, but direct knowledge of the receptive field property and the synaptic connectivity of the axon terminals of various BC types is required in order to understand the role of axonal computation by BCs. The present study tested the essential assumptions of the presynaptic model of direction selectivity at axon terminals of three functionally distinct BC types that ramify in the direction-selective strata of the mouse retina. Results from two-photon Ca(2+) imaging, optogenetic stimulation, and dual patch-clamp recording demonstrated that 1) CB5 cells do not receive fast GABAergic synaptic feedback from starburst amacrine cells (SACs); 2) light-evoked and spontaneous Ca(2+) responses are well coordinated among various local regions of CB5 axon terminals; 3) CB5 axon terminals are not directionally selective; 4) CB5 cells consist of two novel functional subtypes with distinct receptive field structures; 5) CB7 cells provide direct excitatory synaptic inputs to, but receive no direct GABAergic synaptic feedback from, SACs; and 6) CB7 axon terminals are not directionally selective, either. These findings help to simplify models of direction selectivity by ruling out complex computation at BC terminals. They also show that CB5 comprises two functional subclasses of BCs. PMID:25031256

  14. Cell separator for use in bipolar-stack energy storage devices

    Science.gov (United States)

    Mayer, Steven T.; Feikert, John H.; Kachmitter, James L.; Pekala, Richard W.

    1995-01-01

    An improved multi-cell electrochemical energy storage device, such as a battery, fuel cell, or double layer capacitor using a cell separator which allows cells to be stacked and interconnected with low electrical resistance and high reliability while maximizing packaging efficiency. By adding repeating cells, higher voltages can be obtained. The cell separator is formed by applying an organic adhesive on opposing surfaces of adjacent carbon electrodes or surfaces of aerogel electrodes of a pair of adjacent cells prior to or after pyrolysis thereof to form carbon aerogel electrodes. The cell separator is electronically conductive, but ionically isolating, preventing an electrolytic conduction path between adjacent cells in the stack.

  15. Neutrality in bipolar structures

    DEFF Research Database (Denmark)

    Montero, Javier; Rodríguez, J. Tinguaro; Franco, Camilo;

    2014-01-01

    In this paper, we want to stress that bipolar knowledge representation naturally allows a family of middle states which define as a consequence different kinds of bipolar structures. These bipolar structures are deeply related to the three types of bipolarity introduced by Dubois and Prade, but our...

  16. Single residue AAV capsid mutation improves transduction of photoreceptors in the Abca4-/- mouse and bipolar cells in the rd1 mouse and human retina ex-vivo

    OpenAIRE

    Silva, SR; Charbel Issa, P; Singh, MS; Lipinski, DM; Barnea-Cramer, AO; Walker, NJ; Barnard, AR; Hankins, MW; MacLaren, RE

    2016-01-01

    Gene therapy using adeno-associated viral vectors (AAV) for the treatment of retinal degenerations has shown safety and efficacy in clinical trials. However, very high levels of vector expression may be necessary for the treatment of conditions such as Stargardt disease where a dual vector approach is potentially needed, or in optogenetic strategies for end-stage degeneration in order to achieve maximal light sensitivity. In this study, we assessed two vectors with single ca...

  17. Optimization of electrical conduction and passivity properties of stainless steels used for PEM fuel cell bipolar plates

    International Nuclear Information System (INIS)

    Among the new technologies for energy for sustainable development, PEMFC (proton exchange membrane fuel cells) offer seducing aspects. However, in order to make this technology fit large scale application requirements, it has to comply with stringent cost, performance, and durability criteria. In such a frame, the goal of this work was to optimize electrical conduction properties and passivity of stainless steels for the conception of PEMFC bipolar plates, used instead of graphite, the reference material. This work presents the possible ways of performance loss when using stainless steels and some methods to solve this problem. Passive film properties were studied, as well as their modifications by low cost industrial surface treatments, without deposition. Ex situ characterizations of corrosion resistance and electrical conduction were performed. Electrochemical impedance spectroscopy, water analysis, surface analysis by microscopy and photoelectron spectroscopy allowed to study the impact of ageing on two alloys in different states, and several conditions representative of an exposure to PEMFC media. Correlations between semi-conductivity properties, composition, and structure of passive layers were considered, but not leading to clear identification of all parameters responsible for electrical conduction and passivity. The plate industrial state is not convenient for direct use in fuel cell to comply with durability and performance requirements. A surface modification studied improves widely electrical conduction at initial state. The performance is degraded with ageing, but maintaining a level higher than the initial industrial state. This treatment increases also corrosion resistance, particularly on the anode side. (author)

  18. Differences in kinetics between GABA_C and GABA_A receptors on carp retinal bipolar cells

    Institute of Scientific and Technical Information of China (English)

    韩明虎; 沈颖; 杨雄里

    2000-01-01

    The present work was undertaken to characterize kinetics, including activation, desensitization and deactivation, of responses mediated by GABAA and GABAc receptors on carp retinal bipolar cells, using the whole-cell patch-clamp technique. It was revealed that the GABAC response was generally slower in kinetics than the GABAA response. Activation kinetics of both the receptors could be well fit by monoexponential functions with time constants r, being 44.57 ms (GABAC) and 10.86 ms (GABAA) respectively. Desensitization of the GABAA response was characterized by a fast and a slow exponential component with time constants of τfast = 2.16 s and τslow = 19.78 s respectively, whereas desensitization of the GABAc response was fit by a monoexponential function of the time constant T = 6.98 s. Deactivation at both the receptors was adequately described by biexponential functions with time constants being much higher for the GABAC response (τfast = 674.8 ms; τslow = 2 090 ms) than those for the GABAA response

  19. 熔融碳酸盐燃料电池双极板数值模拟%Numerical Simulation on the Bipolar Plate of Molten Carbonate Fuel Cell

    Institute of Scientific and Technical Information of China (English)

    程健; 郭烈锦; 许世森; 张瑞云; 李晨

    2011-01-01

    Aiming to study effect of the temperature stress and assembly of stress on molten carbonate fuel cell (MCFC) bipolar plate flatness, a three-dimensional finite element model was built on the basic theory of thermal elasticity. Some calculation was carried out to simulate the bipolar plate thermal strain generated in the temperature and stress fields in the course of MCFC stack sintering. The simulation results show that deformation are some concentric circles with the bipolar plate as the center and becomes concave surface in the bipolar plate, and the maximum deformation occurs in the bipolar plates of the four vertices. The deformation of bipolar plate is in the range of 0.5~2.9 mm, and the flatness is 1.5%, and the maximum deformation is within the design scope of bipolar plate flatness.%为研究熔融碳酸盐电池双极板因温度应力和组装压力对其平整度产生的影响,以热弹性力学为基本理论建立三维有限元模型,模拟计算双极板由电池启动到稳定运行期间,由于温度场和应力场产生的热应变,并对模拟结果进行分析讨论.模拟计算结果表明:电池启动至稳定运行期间的变形是以双极板为中心的同心圆并在整个双极板表面成凹面,最大变形量发生在双极板的4个项角.双极板变形量范围为0.5~2.9 mm,平整度为1.5%,最大变形量在双极板的平整度设计要求范围之内.

  20. Intrinsic oscillatory activity arising within the electrically coupled AII amacrine-ON cone bipolar cell network is driven by voltage-gated Na + channels

    OpenAIRE

    Trenholm, S; Borowska, J; Zhang, J; Hoggarth, A; Johnson, K.; Barnes, S.; Lewis, TJ; Awatramani, GB

    2012-01-01

    In the rd1 mouse model for retinal degeneration, the loss of photoreceptors results in oscillatory activity (∼10-20 Hz) within the remnant electrically coupled network of retinal ON cone bipolar and AII amacrine cells. We tested the role of hyperpolarization-activated currents (I h), voltage-gated Na + channels and gap junctions in mediating such oscillatory activity. Blocking I h (1 mm Cs +) hyperpolarized the network and augmented activity, while antagonizing voltage-dependent Na + channels...

  1. Selective in vitro expansion and efficient retroviral transduction of human CD34(+) CD38(-) haematopoietic stem cells

    NARCIS (Netherlands)

    Ng, YY; Bloem, AC; van Kessel, B; Lokhorst, H; Logtenberg, T; Staal, FJT

    2002-01-01

    Ex vivo expansion of primitive human haematopoietic stem cells (HSC) is clinically relevant for stem cell transplantation and gene therapy. Here, we demonstrate the selective expansion of CD34(+) CD38(-) cells from purified CD34(+) cells upon stimulation with Flt3-ligand, stem cell factor and thromb

  2. Retinoschisin, a photoreceptor-secreted protein, and its interaction with bipolar and muller cells

    OpenAIRE

    Reid, SNM; Yamashita, C; Farber, D B

    2003-01-01

    Usually, photoreceptors interact with other retinal cells through the neurotransmitter glutamate. Here we describe a nonsynaptic interaction via a secreted protein, retinoschisin. Using in situ hybridization, we found that from early postnatal life retinoschisin mRNA is present only in the outer retina of the mouse, and with single-cell RT-PCR we demonstrated its localization in rod and cone photoreceptor cells but not in Muller cells. Western blot analyses of proteins from cultured ocular ti...

  3. New process for fuel cell fabrication. 3D screen printing of metal bipolar plates; Neues Verfahren zur Brennstoffzellenfertigung. 3D-Siebdruck von metallischen Bipolarplatten

    Energy Technology Data Exchange (ETDEWEB)

    Studnitzky, Thomas [Fraunhofer-Institut fuer Fertigungstechnik und Angewandte Materialforschung (IFAM), Dresden (Germany); Helm, Peter; Heinzel, Angelika [Zentrum fuer BrennstoffzellenTechnik GmbH (ZBT), Duisburg (Germany)

    2011-01-15

    Minimization of space requirements, weight, and production cost is one of the key preconditions for successful launching of the polymer electrolyte membrane fuel cell (PEM). In the stacks constructed from single PEM cells, the bipolar plate is a central component. It determines the weight and volume of the stack and accounts for more than 30 percent of the overall cost, depending on the fabrication process. It is therefore important for producers of fuel cells to develop a process that combines free design, high functionality and low cost in serial production.

  4. Inhibition of Grb2-mediated activation of MAPK signal transduction suppresses NOR1/CB1954-induced cytotoxicity in the HepG2 cell line.

    Science.gov (United States)

    Gui, Rong; Li, Dengqing; Qi, Guannan; Suhad, Ali; Nie, Xinmin

    2012-09-01

    The nitroreductase oxidored-nitro domain containing protein 1 (NOR1) gene may be involved in the chemical carcinogenesis of hepatic cancer and nasopharyngeal carcinoma (NPC). We have previously demonstrated that NOR1 overexpression is capable of converting the monofunctional alkylating agent 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) into a toxic form by reducing the 4-nitro group of CB1954. Toxic CB1954 is able to enhance cell killing in the NPC cell line CNE1; however, the underlying mechanisms remain unknown. Using cDNA microarrays and quantitative real-time PCR, we previously discovered that NOR1 increases the expression of growth factor receptor-bound protein 2 (Grb2) mRNA by 4.8-fold in the human hepatocellular carcinoma cell line HepG2. In the present study, we revealed that NOR1 increased Grb2 protein expression by 3-fold in HepG2 cells. Additionally, we demonstrated that NOR1 enhanced CB1954-induced cell killing in HepG2 cells, and cell cytotoxicity was inhibited with the tyrosine kinase inhibitor genistein, or by stable transfection of Grb2 small hairpin RNA (shRNA) pU6(+27)-shGrb2 to silence the expression of Grb2. Western blot analysis revealed that Grb2 downregulation may reduce the activity of the mitogen-activated protein kinase (MAPK). Inhibiting the activation of MAPK using the methyl ethyl ketone (MEK) inhibtor PD98059 suppressed CB1954-induced cell killing. These results suggested that the NOR1 gene enhances CB1954-mediated cell cytotoxicity through the upregulation of Grb2 expression and the activation of MAPK signal transduction in the HepG2 cell line. PMID:23741254

  5. Mitochondrial activity and oxidative stress markers in peripheral blood mononuclear cells of patients with bipolar disorder, schizophrenia, and healthy subjects.

    Science.gov (United States)

    Gubert, Carolina; Stertz, Laura; Pfaffenseller, Bianca; Panizzutti, Bruna Schilling; Rezin, Gislaine Tezza; Massuda, Raffael; Streck, Emilio Luiz; Gama, Clarissa Severino; Kapczinski, Flávio; Kunz, Maurício

    2013-10-01

    Evidence suggests that mitochondrial dysfunction is involved in the pathophysiology of psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD). However, the exact mechanisms underlying this dysfunction are not well understood. Impaired activity of electron transport chain (ETC) complexes has been described in these disorders and may reflect changes in mitochondrial metabolism and oxidative stress markers. The objective of this study was to compare ETC complex activity and protein and lipid oxidation markers in 12 euthymic patients with BD type I, in 18 patients with stable chronic SZ, and in 30 matched healthy volunteers. Activity of complexes I, II, and III was determined by enzyme kinetics of mitochondria isolated from peripheral blood mononuclear cells (PBMCs). Protein oxidation was evaluated using the protein carbonyl content (PCC) method, and lipid peroxidation, the thiobarbituric acid reactive substances (TBARS) assay kit. A significant decrease in complex I activity was observed (p = 0.02), as well as an increase in plasma levels of TBARS (p = 0.00617) in patients with SZ when compared to matched controls. Conversely, no significant differences were found in complex I activity (p = 0.17) or in plasma TBARS levels (p = 0.26) in patients with BD vs. matched controls. Our results suggest that mitochondrial complex I dysfunction and oxidative stress play important roles in the pathophysiology of SZ and may be used in potential novel adjunctive therapy for SZ, focusing primarily on cognitive impairment and disorder progression. PMID:23870796

  6. A high voltage silicon-on-insulator lateral insulated gate bipolar transistor with a reduced cell-pitch

    Institute of Scientific and Technical Information of China (English)

    Luo Xiao-Rong; Wang Qi; Yao Guo-Liang; Wang Yuan-Gang; Lei Tian-Fei; Wang Pei; Jiang Yong-Heng

    2013-01-01

    A high voltage (> 600 V) integrable silicon-on-insulator (SOI) trench-type lateral insulated gate bipolar transistor (LIGBT) with a reduced cell-pitch is proposed.The LIGBT features multiple trenches (MTs):two oxide trenches in the drift region and a trench gate extended to the buried oxide (BOX).Firstly,the oxide trenches enhance electric field strength because of the lower permittivity of oxide than that of Si.Secondly,oxide trenches bring in multi-directional depletion,leading to a reshaped electric field distribution and an enhanced reduced-surface electric-field (RESURF) effect.Both increase the breakdown voltage (BV).Thirdly,oxide trenches fold the drift region around the oxide trenches,leading to a reduced cell-pitch.Finally,the oxide trenches enhance the conductivity modulation,resulting in a high electron/hole concentration in the drift region as well as a low forward voltage drop (Von).The oxide trenches cause a low anode-cathode capacitance,which increases the switching speed and reduces the turn-off energy loss (Eoff).The MT SOI LIGBT exhibits a BV of 603 V at a small cell-pitch of 24 μtm,a Von of 1.03 V at 100 A/cm-2,a turn-off time of 250 ns and Eoff of 4.1 × 10 3 mJ.The trench gate extended to BOX synchronously acts as dielectric isolation between high voltage LIGBT and low voltage circuits,simplifying the fabrication processes.

  7. Development of a brazing process for the production of water- cooled bipolar plates made of chromium-coated metal foils for PEM fuel cells

    Science.gov (United States)

    Mueller, M.; Hoehlich, D.; Scharf, I.; Lampke, T.; Hollaender, U.; Maier, H. J.

    2016-03-01

    Beside lithium batteries, PEM fuel cells are the most promising strategy as a power source to achieve the targets for introducing and increasing the usage of electric vehicles. Due to limited space and weight problems, water cooled, metallic bipolar plates in a fuel cell metal stack are preferred in motor vehicles. These plates are stamped metal sheets with a complex structure, interconnected media-tight. To meet the multiple tasks and requirements in use, complex and expensive combinations of materials are currently in use (carbon fiber composites, graphite, gold-plated nickel, stainless and acid resistant steel). The production of such plates is expensive as it is connected with considerable effort or the usage of precious metals. As an alternative, metalloid nitrides (CrN, VN, W2N, etc.) show a high chemical resistance, hardness and a good conductivity. So this material category meets the basic requirements of a top layer. However, the standard methods for their production (PVD, CVD) are expensive and have a slow deposition rate and a lower layer thicknesses. Because of these limitations, a full functionality over the life cycle of a bipolar plate is not guaranteed. The contribution shows the development and quantification of an alternative production process for bipolar plates. The expectation is to get significant advantages from the combination of chromium electrodeposition and thermochemical treatment to form chromium nitrides. Both processes are well researched and suitable for series production. The thermochemical treatment of the chromium layer also enables a process-integrated brazing.

  8. Mitotic rounding alters cell geometry to ensure efficient bipolar spindle formation.

    Science.gov (United States)

    Lancaster, Oscar M; Le Berre, Maël; Dimitracopoulos, Andrea; Bonazzi, Daria; Zlotek-Zlotkiewicz, Ewa; Picone, Remigio; Duke, Thomas; Piel, Matthieu; Baum, Buzz

    2013-05-13

    Accurate animal cell division requires precise coordination of changes in the structure of the microtubule-based spindle and the actin-based cell cortex. Here, we use a series of perturbation experiments to dissect the relative roles of actin, cortical mechanics, and cell shape in spindle formation. We find that, whereas the actin cortex is largely dispensable for rounding and timely mitotic progression in isolated cells, it is needed to drive rounding to enable unperturbed spindle morphogenesis under conditions of confinement. Using different methods to limit mitotic cell height, we show that a failure to round up causes defects in spindle assembly, pole splitting, and a delay in mitotic progression. These defects can be rescued by increasing microtubule lengths and therefore appear to be a direct consequence of the limited reach of mitotic centrosome-nucleated microtubules. These findings help to explain why most animal cells round up as they enter mitosis.

  9. Membrane Guanylate Cyclase, A Multimodal Transduction Machine: History, Present and Future Directions

    Directory of Open Access Journals (Sweden)

    Rameshwar K Sharma

    2014-07-01

    Full Text Available A sequel to these authors’ earlier comprehensive reviews which covered the field of mammalian membrane guanylate cyclase (MGC from its origin to the year 2010, this article contains 13 parts. The first is HISTORICAL and covers MGC from the year 1963-1987, summarizing its colorful developmental stages from its passionate pursuit to its consolidation. The second deals with the establishment of its BIOCHEMICAL IDENTITY. MGC becomes the transducer of a hormonal signal and founder of the peptide hormone receptor family, and creates the notion that hormone signal transduction is its sole physiological function. The third defines its EXPANSION. The discovery of ROS-GC subfamily is made and it links ROS-GC with the physiology of PHOTOTRANSDUCTION. Parts 4 to 7 cover its BIOCHEMISTRY and PHYSIOLOGY. The noteworthy events are that augmented by GCAPs, ROS-GC proves to be a transducer of the free Ca2+ signals generated within neurons; ROS-GC becomes a two-component transduction system and establishes itself as a source of cyclic GMP, the second messenger of phototransduction. Part 8 demonstrates how this knowledge begins to be TRANSLATED into the diagnosis and providing the molecular definition of retinal dystrophies. Part 9 discusses a striking property of ROS-GC where it becomes a [Ca2+]i bimodal switch and transcends its signaling role in other neural transduction processes. In this course, discovery of the first CD-GCAP (Ca2+-dependent guanylate cycles activator, the S100B protein, is made. It extends the role of ROS-GC transduction system beyond the photoreceptor cells to the signaling processes in the synapse region between photoreceptor and cone ON-bipolar cells; in Part 10, discovery of ANOTHER CD-GCAP, NC, is made and its linkage with signaling of the inner plexiform layer neurons is established. Part 11 discusses linkage of the ROS-GC transduction system with other sensory transduction processes: Pineal gland, Olfaction and Gustation. In the

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

    Science.gov (United States)

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

    2011-01-01

    To compete in complex microbial communities, bacteria must sense environmental changes and adjust cellular functions for optimal growth. Chemotaxis-like signal transduction pathways are implicated in the regulation of multiple behaviors in response to changes in the environment, including motility patterns, exopolysaccharide production, and cell-to-cell interactions. In Azospirillum brasilense, cell surface properties, including exopolysaccharide production, are thought to play a direct role in promoting flocculation. Recently, the Che1 chemotaxis-like pathway from A. brasilense was shown to modulate flocculation, suggesting an associated modulation of cell surface properties. Using atomic force microscopy, distinct changes in the surface morphology of flocculating A. brasilense Che1 mutant strains were detected. Whereas the wild-type strain produces a smooth mucosal extracellular matrix after 24 h, the flocculating Che1 mutant strains produce distinctive extracellular fibril structures. Further analyses using flocculation inhibition, lectin-binding assays, and comparison of lipopolysaccharides profiles suggest that the extracellular matrix differs between the cheA1 and the cheY1 mutants, despite an apparent similarity in the macroscopic floc structures. Collectively, these data indicate that disruption of the Che1 pathway is correlated with distinctive changes in the extracellular matrix, which likely result from changes in surface polysaccharides structure and/or composition.

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

    Energy Technology Data Exchange (ETDEWEB)

    Doktycz, Mitchel John [ORNL; Morrell-Falvey, Jennifer L [ORNL

    2011-01-01

    To compete in complex microbial communities, bacteria must sense environmental changes and adjust cellular functions for optimal growth. Chemotaxis-like signal transduction pathways are implicated in the regulation of multiple behaviors in response to changes in the environment, including motility patterns, exopolysaccharide production, and cell-to-cell interactions. In Azospirillum brasilense, cell surface properties, including exopolysaccharide production, are thought to play a direct role in promoting flocculation. Recently, the Che1 chemotaxis-like pathway from A. brasilense was shown to modulate flocculation, suggesting an associated modulation of cell surface properties. Using atomic force microscopy, distinct changes in the surface morphology of flocculating A. brasilense Che1 mutant strains were detected. Whereas the wild-type strain produces a smooth mucosal extracellular matrix after 24 h, the flocculating Che1 mutant strains produce distinctive extracellular fibril structures. Further analyses using flocculation inhibition, lectin-binding assays, and comparison of lipopolysaccharides profiles suggest that the extracellular matrix differs between the cheA1 and the cheY1 mutants, despite an apparent similarity in the macroscopic floc structures. Collectively, these data indicate that disruption of the Che1 pathway is correlated with distinctive changes in the extracellular matrix, which likely result from changes in surface polysaccharides structure and/or composition.

  12. Combinations of SNPs Related to Signal Transduction in Bipolar Disorder

    DEFF Research Database (Denmark)

    Koefoed, Pernille; Andreassen, Ole A; Bennike, Bente;

    2011-01-01

    Any given single nucleotide polymorphism (SNP) in a genome may have little or no functional impact. A biologically significant effect may possibly emerge only when a number of key SNP-related genotypes occur together in a single organism. Thus, in analysis of many SNPs in association studies of c...

  13. Quantifying efficient information transduction of biochemical signaling cascades

    CERN Document Server

    Tsuruyama, Tatsuaki

    2016-01-01

    Cells can be considered as systems that utilize changes in thermodynamic entropy as information. Therefore, they serve as useful models for investigating the relationships between entropy production and information transmission, i.e., signal transduction. Based on the hypothesis that cells apply a chemical reaction cascade for the most efficient transduction of information, we adopted a coding design that minimizes the number of bits per concentration of molecules that are employed for information transduction. As a result, the average rate of entropy production is uniform across all cycles in a cascade reaction. Thus, the entropy production rate can be a valuable measure for the quantification of intracellular signal transduction.

  14. Stable EGFP Gene Expression in C6 Glioma Cell Line after Transduction with HIV-1-based Lentiviral Vector

    Institute of Scientific and Technical Information of China (English)

    JIN Gui-shan; LIU Fu-sheng; CHAI Qi; WANG Jian-jao; LI Jun-hua

    2008-01-01

    Objective:To establish a stable C6/EGFP glioma cell line for studies on glioma. Methods:The C6 glioma cell line was transfected with the human immunodeficiency virus type Ⅰ(HIV-1)based lentivirus vector containing two enhancer-promoters CMV and EF1α.Enhanced green fluorescent protein(EGFP)-positive C6 cells were sorted out by fluorescence-activated cell sort.Expression of EGFP was observed by fluorescent microscopy.EGFP gene in C6 genome was assessed by Polymerase chain reaction(PCR)and DNA sequencing.Original and transfected cells were compared biologically and cytomorphologically. Results:Lentivirus vector transfection produced up to 40% EGFP-positive cells.After fluorescence-activated cell sort selection,a pure cell line C6/EGFP was established.PCR and DNA sequencing revealed integration of EGFP gene in C6 cell genome.Analysis of cell characteristics revealed no difference between transfected and original cells. Conclusion:A C6/EGFP cell line expressing EGFP as a marker is established,in which the EGFP gene is integrated into the genome.This cell line can be served as a promising tool for further basic research and gene therapy studies.

  15. Pharmacological analysis of the activation and receptor properties of the tonic GABA(CR current in retinal bipolar cell terminals.

    Directory of Open Access Journals (Sweden)

    Stefanie M Jones

    Full Text Available GABAergic inhibition in the central nervous system (CNS can occur via rapid, transient postsynaptic currents and via a tonic increase in membrane conductance, mediated by synaptic and extrasynaptic GABA(A receptors (GABA(ARs respectively. Retinal bipolar cells (BCs exhibit a tonic current mediated by GABA(CRs in their axon terminal, in addition to synaptic GABA(AR and GABA(CR currents, which strongly regulate BC output. The tonic GABA(CR current in BC terminals (BCTs is not dependent on vesicular GABA release, but properties such as the alternative source of GABA and the identity of the GABA(CRs remain unknown. Following a recent report that tonic GABA release from cerebellar glial cells is mediated by Bestrophin 1 anion channels, we have investigated their role in non-vesicular GABA release in the retina. Using patch-clamp recordings from BCTs in goldfish retinal slices, we find that the tonic GABA(CR current is not reduced by the anion channel inhibitors NPPB or flufenamic acid but is reduced by DIDS, which decreases the tonic current without directly affecting GABA(CRs. All three drugs also exhibit non-specific effects including inhibition of GABA transporters. GABA(CR ρ subunits can form homomeric and heteromeric receptors that differ in their properties, but BC GABA(CRs are thought to be ρ1-ρ2 heteromers. To investigate whether GABA(CRs mediating tonic and synaptic currents may differ in their subunit composition, as is the case for GABA(ARs, we have examined the effects of two antagonists that show partial ρ subunit selectivity: picrotoxin and cyclothiazide. Tonic and synaptic GABA(CR currents were differentially affected by both drugs, suggesting that a population of homomeric ρ1 receptors contributes to the tonic current. These results extend our understanding of the multiple forms of GABAergic inhibition that exist in the CNS and contribute to visual signal processing in the retina.

  16. Dopamine modulation of rod pathway signaling by suppression of GABAC feedback to rod-driven depolarizing bipolar cells.

    Science.gov (United States)

    Smith, Benjamin J; Côté, Patrice D; Tremblay, François

    2015-09-01

    Reducing signal gain in the highly sensitive rod pathway prevents saturation as background light levels increase, allowing the dark-adapted retina to encode stimuli over a range of background luminances. Dopamine release is increased during light adaptation and is generally accepted to suppress rod signaling in light-adapted retinas. However, recent research has suggested that dopamine, acting through D1 receptors, could additionally produce a sensitization of the rod pathway in dim light conditions via gamma-aminobutyric acid (GABA) type C receptors. Here, we evaluated the overall activity of the depolarizing bipolar cell (DBC) population in vivo to ensure the integrity of long-distance network interactions by quantifying the b-wave of the electroretinogram in mice. We showed that dopamine, acting through D1 receptors, reduced the amplitude and sensitivity of rod-driven DBCs during light adaptation by suppressing GABA type A receptor-mediated serial inhibition onto rod DBC GABA type C receptors. Block of D1 receptors did not suppress rod-driven DBC sensitivity when GABAA -mediated serial inhibition was blocked by gabazine, suggesting that the reduction in rod-driven DBC sensitivity in the absence of D1 receptors was due to disinhibition of serial inhibitory GABAergic circuitry rather than a direct facilitatory effect on GABA release onto rod-driven DBC GABA type C receptors. Finally, the large population of GABAergic A17 wide-field amacrine cells known to maintain reciprocal inhibition with rod DBCs could be excluded from the proposed disinhibitory circuit after treatment with 5,7-dihydroxytryptamine. PMID:26080286

  17. Physalis peruviana extract induces apoptosis in human Hep G2 cells through CD95/CD95L system and the mitochondrial signaling transduction pathway.

    Science.gov (United States)

    Wu, Shu-Jing; Ng, Lean-Teik; Lin, Doung-Liang; Huang, Shan-Ney; Wang, Shyh-Shyan; Lin, Chun-Ching

    2004-11-25

    Physalis species is a popular folk medicine used for treating cancer, leukemia, hepatitis and other diseases. Studies have shown that the ethanol extract of Physalis peruviana (EEPP) inhibits growth and induces apoptotic death of human Hep G2 cells in culture, whereas proliferation of the mouse BALB/C normal liver cells was not affected. In this study, we performed detailed studies to define the molecular mechanism of EEPP-induced apoptosis in Hep G2 cells. The results further confirmed that EEPP inhibited cell proliferation in a dose- and time-dependent manner. At 50 microg/ml, EEPP significantly increased the accumulation of the sub-G1 peak (hypoploid) and the portion of apoptotic annexin V positive cells. EEPP was found to trigger apoptosis through the release of cytochrome c, Smac/DIABLO and Omi/HtrA2 from mitochondria to cytosol and consequently resulted in caspase-3 activation. Pre-treatment with a general caspase inhibitor (z-VAD-fmk) prevented cytochrome c release. After 48 h of EEPP treatment, the apoptosis of Hep G2 cells was found to associate with an elevated p53, and CD95 and CD95L proteins expression. Furthermore, a marked down-regulation of the expression of the Bcl-2, Bcl-XL and XIAP, and up-regulation of the Bax and Bad proteins were noted. Taken together, the present results suggest that EEPP-induced Hep G2 cell apoptosis was possibly mediated through the CD95/CD95L system and the mitochondrial signaling transduction pathway. PMID:15488639

  18. Involvement of formyl peptide receptors in receptor for advanced glycation end products (RAGE - and amyloid beta 1-42-induced signal transduction in glial cells

    Directory of Open Access Journals (Sweden)

    Slowik Alexander

    2012-11-01

    Full Text Available Abstract Background Recent studies suggest that the chemotactic G-protein-coupled-receptor (GPCR formyl-peptide-receptor-like-1 (FPRL1 and the receptor-for-advanced-glycation-end-products (RAGE play an important role in the inflammatory response involved in neurodegenerative disorders such as Alzheimer’s disease (AD. Therefore, the expression and co-localisation of mouse formyl peptide receptor (mFPR 1 and 2 as well as RAGE in an APP/PS1 transgenic mouse model using immunofluorescence and real-time RT-PCR were analysed. The involvement of rat or human FPR1/FPRL1 (corresponds to mFPR1/2 and RAGE in amyloid-β 1–42 (Aβ1-42-induced signalling were investigated by extracellular signal regulated kinase 1/2 (ERK1/2 phosphorylation. Furthermore, the cAMP level in primary rat glial cells (microglia and astrocytes and transfected HEK 293 cells was measured. Formyl peptide receptors and RAGE were inhibited by a small synthetic antagonist WRW4 and an inactive receptor variant delta-RAGE, lacking the intracytoplasmatic domains. Results We demonstrated a strong increase of mFPR1/2 and RAGE expression in the cortex and hippocampus of APP/PS1 transgenic mice co-localised to the glial cells. In addition, the Aβ1-42-induced signal transduction is dependant on FPRL1, but also on FPR1. For the first time, we have shown a functional interaction between FPRL1/FPR1 and RAGE in RAGE ligands S100B- or AGE-mediated signalling by ERK1/2 phosphorylation and cAMP level measurement. In addition a possible physical interaction between FPRL1 as well as FPR1 and RAGE was shown with co-immunoprecipitation and fluorescence microscopy. Conclusions The results suggest that both formyl peptide receptors play an essential role in Aβ1-42-induced signal transduction in glial cells. The interaction with RAGE could explain the broad ligand spectrum of formyl peptide receptors and their important role for inflammation and the host defence against infections.

  19. Targeting astrocytes in bipolar disorder.

    Science.gov (United States)

    Peng, Liang; Li, Baoman; Verkhratsky, Alexei

    2016-06-01

    Astrocytes are homeostatic cells of the central nervous system, which are critical for development and maintenance of synaptic transmission and hence of synaptically connected neuronal ensembles. Astrocytic densities are reduced in bipolar disorder, and therefore deficient astroglial function may contribute to overall disbalance in neurotransmission and to pathological evolution. Classical anti-bipolar drugs (lithium salts, valproic acid and carbamazepine) affect expression of astroglial genes and modify astroglial signalling and homeostatic cascades. Many effects of both antidepressant and anti-bipolar drugs are exerted through regulation of glutamate homeostasis and glutamatergic transmission, through K(+) buffering, through regulation of calcium-dependent phospholipase A2 (that controls metabolism of arachidonic acid) or through Ca(2+) homeostatic and signalling pathways. Sometimes anti-depressant and anti-bipolar drugs exert opposite effects, and some effects on gene expression in drug treated animals are opposite in neurones vs. astrocytes. Changes in the intracellular pH induced by anti-bipolar drugs affect uptake of myo-inositol and thereby signalling via inositoltrisphosphate (InsP3), this being in accord with one of the main theories of mechanism of action for these drugs. PMID:27015045

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

    Energy Technology Data Exchange (ETDEWEB)

    Billings, Amanda N [ORNL; Siuti, Piro [ORNL; Bible, Amber [University of Tennessee, Knoxville (UTK); Alexandre, Gladys [University of Tennessee, Knoxville (UTK); Retterer, Scott T [ORNL; Doktycz, Mitchel John [ORNL; Morrell-Falvey, Jennifer L [ORNL

    2011-01-01

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

  1. Growth inhibition and apoptosis in cancer cells induced by polyphenolic compounds of Acacia hydaspica: Involvement of multiple signal transduction pathways

    Science.gov (United States)

    Afsar, Tayyaba; Trembley, Janeen H.; Salomon, Christine E.; Razak, Suhail; Khan, Muhammad Rashid; Ahmed, Khalil

    2016-01-01

    Acacia hydaspica R. Parker is known for its medicinal uses in multiple ailments. In this study, we performed bioassay-guided fractionation of cytotoxic compounds from A. hydaspica and investigated their effects on growth and signaling activity in prostate and breast cancer cell lines. Four active polyphenolic compounds were identified as 7-O-galloyl catechin (GC), catechin (C), methyl gallate (MG), and catechin-3-O-gallate (CG). The four compounds inhibited prostate cancer PC-3 cell growth in a dose-dependent manner, whereas CG and MG inhibited breast cancer MDA-MB-231 cell growth. All tested compounds inhibited cell survival and colony growth in both cell lines, and there was evidence of chromatin condensation, cell shrinkage and apoptotic bodies. Further, acridine orange, ethidium bromide, propidium iodide and DAPI staining demonstrated that cell death occurred partly via apoptosis in both PC-3 and MDA-MB-231 cells. In PC-3 cells treatment repressed the expression of anti-apoptotic molecules Bcl-2, Bcl-xL and survivin, coupled with down-regulation of signaling pathways AKT, NFκB, ERK1/2 and JAK/STAT. In MDA-MB-231 cells, treatment induced reduction of CK2α, Bcl-xL, survivin and xIAP protein expression along with suppression of NFκB, JAK/STAT and PI3K pathways. Our findings suggest that certain polyphenolic compounds derived from A. hydaspica may be promising chemopreventive/therapeutic candidates against cancer. PMID:26975752

  2. Efficient induction of cross-presentating human B cell by transduction with human adenovirus type 7 vector.

    Science.gov (United States)

    Peng, Ying; Lai, Meimei; Lou, Yunyan; Liu, Yanqing; Wang, Huiyan; Zheng, Xiaoqun

    2016-01-01

    Although human autologous B cells represent a promising alternative to dendritic cells (DCs) for easy large-scale preparation, the naive human B cells are always poor at antigen presentation. The safe and effective usage record of human adenovirus type 7 (HAdV7) live vaccines makes it attractive as a promising vaccine vector candidate. To investigate whether HAdV7 vector could be used to induce the human B cells cross-presentation, in the present study, we constructed the E3-defective recombinant HAdV7 vector encoding green fluorescent protein (GFP) and carcinoembryonic antigen (CEA). We demonstrated that naive human B cells can efficiently be transduced, and that the MAPKs/NF-κB pathway can be activated by recombinant HAdV7. We proved that cytokine TNF-α, IL-6 and IL-10, surface molecule MHC class I and the CD86, antigen-processing machinery (APM) compounds ERp57, TAP-1, and TAP-2. were upregulated in HAdV7 transduced human B cells. We also found that CEA-specific IFNγ expression, degranulation, and in vitro and ex vivo cytotoxicities are induced in autologous CD8(+) T cells presensitized by HAd7CEA modified human B cells. Meanwhile, our evidences clearly show that Toll-like receptors 9 (TLR9) antagonist IRS 869 significantly eliminated most of the HAdV7 initiated B cell activation and CD8(+) T cells response, supporting the role and contribution of TLR9 signaling in HAdV7 induced human B cell cross-presentation. Besides a better understanding of the interactions between recombinant HAdV7 and human naive B cells, to our knowledge, the present study provides the first evidence to support the use of HAdV7-modified B cells as a vehicle for vaccines and immunotherapy.

  3. Corrosion resistant metallic bipolar plate

    Science.gov (United States)

    Brady, Michael P.; Schneibel, Joachim H.; Pint, Bruce A.; Maziasz, Philip J.

    2007-05-01

    A corrosion resistant, electrically conductive component such as a bipolar plate for a PEM fuel cell includes 20 55% Cr, balance base metal such as Ni, Fe, or Co, the component having thereon a substantially external, continuous layer of chromium nitride.

  4. Quantitative analysis of signal transduction in motile and phototactic cells by computerized light stimulation and model based tracking

    Science.gov (United States)

    Streif, Stefan; Staudinger, Wilfried Franz; Oesterhelt, Dieter; Marwan, Wolfgang

    2009-02-01

    To investigate the responses of Halobacterium salinarum to stimulation with light (phototaxis and photokinesis), we designed an experimental setup consisting of optical devices for automatic video image acquisition and computer-controlled light stimulation, and developed algorithms to analyze physiological responses of the cells. Cells are categorized as motile and nonmotile by a classification scheme based on the square displacement of cell positions. Computerized tracking based on a dynamic model of the stochastic cell movement and a Kalman filter-based algorithm allows smoothed estimates of the cell tracks and the detection of physiological responses to complex stimulus patterns. The setup and algorithms were calibrated which allows quantitative measurements and systematic analysis of cellular sensing and response. Overall, the setup is flexible, extensible, and consists mainly of commercially available products. This facilitates modifications of the setup and algorithms for physiological studies of the motility of cells or microorganisms.

  5. Transduction of proteins into leishmania tarentolae by formation of non-covalent complexes with cell-penetrating peptides.

    Science.gov (United States)

    Keller, Andrea-Anneliese; Breitling, Reinhard; Hemmerich, Peter; Kappe, Katarina; Braun, Maria; Wittig, Berith; Schaefer, Buerk; Lorkowski, Stefan; Reissmann, Siegmund

    2014-02-01

    Cell-penetrating peptides (CPPs) are used to transport peptides, proteins, different types of ribonucleic acids (or mimics of these molecules), and DNA into live cells, both plant and mammalian. Leishmania belongs to the class of protozoa having, in comparison to mammalian cells, a different lipid composition of the membrane, proteoglycans on the surface, and signal pathways. We investigated the uptake of two different and easily detectable proteins into the non-pathogenic strain Leishmania tarentolae. From the large number of CPPs available, six and a histone were chosen specifically for their ability to form non-covalent complexes. For Leishmania we used the enzyme β-galactosidase and fluorescent labeled bovine serum albumin as cargoes. The results are compared to similar internalization studies using mammalian cells [Mussbach et al., ]. Leishmania cells can degrade CPPs by a secreted and membrane-bound chymotrypsin-like protease. Both cargo proteins were internalized with sufficient efficiency and achieved intramolecular concentrations similar to mammalian cells. The transport efficiencies of the CPPs differed from each other, and showed a different rank order for both cargoes. The intracellular distribution of fluorescent-labeled bovine serum albumin showed highest concentrations in the nucleus and kinetoplast. Leishmania are susceptible to high concentrations of some CPPs, although comparably dissimilar to mammalian cells. MPG-peptides are more cytotoxic in Leishmania than in mammalian cells, acting as antimicrobial peptides. Our results contribute to a better understanding of molecular interactions in Leishmania cells and possibly to new treatments of leishmaniasis.

  6. Miniaturized polymer electrolyte fuel cell (PEFC) stack using micro structured bipolar plate

    Energy Technology Data Exchange (ETDEWEB)

    Veziridis, Z.; Scherer, G.G.; Marmy, Ch.; Glaus, F. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1999-08-01

    In Polymer Electrolyte Fuel Cell (PEFC) technology the reducing of volume and mass of the fuel cell stack and the improvement of catalyst utilization are of great interest. These parameters affect applicability and system cost. In this work we present an alternative way for reducing the stack volume by combining gas distribution and catalytic active area in one plate. Micro machined glassy carbon electrodes serve as support material for the platinum catalyst, as well as gas distributor at the same time. A comparison of these electrodes with conventional platinum-black gas diffusion electrodes under fuel cell conditions shows that the new system is a promising electrode type for enhanced power density and catalyst utilization. (author) 3 figs., 5 refs.

  7. Three-terminal heterojunction bipolar transistor solar cell for high-efficiency photovoltaic conversion

    OpenAIRE

    Martí, A.; De Luque, A.

    2015-01-01

    Here we propose, for the first time, a solar cell characterized by a semiconductor transistor structure (n/p/n or p/n/p) where the base–emitter junction is made of a high-bandgap semiconductor and the collector is made of a low-bandgap semiconductor. We calculate its detailed-balance efficiency limit and prove that it is the same one than that of a double-junction solar cell. The practical importance of this result relies on the simplicity of the structure that reduces the number of layers th...

  8. Three-terminal heterojunction bipolar transistor solar cell for high-efficiency photovoltaic conversion

    OpenAIRE

    Martí Vega, Antonio; Luque López, Antonio

    2015-01-01

    Here we propose, for the first time, a solar cell characterized by a semiconductor transistor structure (n/p/n or p/n/p) where the base-emitter junction is made of a high-bandgap semiconductor and the collector is made of a low-bandgap semiconductor. We calculate its detailed-balance efficiency limit and prove that it is the same one than that of a double-junction solar cell. The practical importance of this result relies on the simplicity of the structure that reduces the number of layers th...

  9. Cytokines in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Vinberg, Maj; Vedel Kessing, Lars

    2012-01-01

    BACKGROUND: Current research and hypothesis regarding the pathophysiology of bipolar disorder suggests the involvement of immune system dysfunction that is possibly related to disease activity. Our objective was to systematically review evidence of cytokine alterations in bipolar disorder according...... to affective state. METHODS: We conducted a systemtic review of studies measuring endogenous cytokine concentrations in patients with bipolar disorder and a meta-analysis, reporting results according to the PRISMA statement. RESULTS: Thirteen studies were included, comprising 556 bipolar disorder patients...

  10. Staging Bipolar Disorder.

    OpenAIRE

    Vieta i Pascual, Eduard, 1963-; Reinares, M.; Rosa, A. R.

    2011-01-01

    The purpose of this study was to analyze the evidence supporting a staging model for bipolar disorder. The authors conducted an extensive Medline and Pubmed search of the published literature using a variety of search terms (staging, bipolar disorder, early intervention) to find relevant articles, which were reviewed in detail. Only recently specific proposals have been made to apply clinical staging to bipolar disorder. The staging model in bipolar disorder suggests a progression from prodro...

  11. Bipolar Role for Myelo-Monocytic Cells in Autoimmune Diseases and Psychiatric Disorders

    NARCIS (Netherlands)

    W. Beumer (Wouter)

    2013-01-01

    markdownabstract__Abstract__ The immune system is a complex system of tissue with cells and messenger molecules interacting to protect an organism against pathogens. Autoimmunity is the failure of the immune system to recognize its own constituent parts as harmless self and therefore it leads to an

  12. Bipolar polaron pair recombination in P3HT/PCBM solar cells

    DEFF Research Database (Denmark)

    Kupijai, Alexander J.; Behringer, Konstantin M.; Corazza, Michael;

    2015-01-01

    of the electron spin on charge transport which can be exploited in spintronic devices or to improve solar cell eciencies. Magnetic resonance techniques are particularly helpful to elucidate the microscopic structure of paramagnetic states in semiconductors as well as the transport processes they are involved in...

  13. Signal transduction by HLA class II molecules in human T cells: induction of LFA-1-dependent and independent adhesion

    DEFF Research Database (Denmark)

    Odum, Niels; Yoshizumi, H; Okamoto, Y;

    1992-01-01

    Crosslinking HLA-DR molecules by monoclonal antibodies (moAbs) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic calcium concentrations in activated human T cells. Binding of bacterial superantigens or moAbs to DR molecules on activated T cells was ...

  14. Calcium-mediated transductive systems and functionally active gap junctions in astrocyte-like GL15 cells

    Directory of Open Access Journals (Sweden)

    Steimberg Nathalie

    2001-05-01

    Full Text Available Abstract Background It has been proposed that GL15, a human cell line derived from glioblastoma multiforme, is a possible astroglial-like cell model, based on the presence of cytoplasmic glial fibrillary acidic protein. Results The aim of this work was to delineate the functional characteristics of GL15 cells using various experimental approaches, including the study of morphology, mechanism of induction of intracellular Ca2+ increase by different physiological agonists, and the presence and permeability of the gap-junction system during cell differentiation. Immunostaining experiments showed the presence and localization of specific glial markers, such as glial fibrillary acidic protein and S100B, and the lack of the neuronal marker S100A. Notably, all the Ca2+ pathways present in astrocytes were detected in GL15 cells. In particular, oscillations in intracellular Ca2+ levels were recorded either spontaneously, or in the presence of ATP or glutamate (but not KCl. Immunolabelling assays and confocal microscopy, substantiated by Western blot analyses, revealed the presence of connexin43, a subunit of astrocyte gap-junction channels. The protein is organised in characteristic spots on the plasma membrane at cell-cell contact regions, and its presence and distribution depends on the differentiative status of the cell. Finally, a microinjection/dye-transfer assay, employed to determine gap-junction functionality, clearly demonstrated that the cells were functionally coupled, albeit to varying degrees, in differentiated and undifferentiated phenotypes. Conclusions In conclusion, results from this study support the use of the GL15 cell line as a suitable in vitro astrocyte model, which provides a valuable guide for studying glial physiological features at various differentiation phases.

  15. Model of the initiation of signal transduction by ligands in a cell culture: Simulation of molecules near a plane membrane comprising receptors

    Science.gov (United States)

    Plante, Ianik; Cucinotta, Francis A.

    2011-11-01

    Cell communication is a key mechanism in tissue responses to radiation. Several molecules are implicated in radiation-induced signaling between cells, but their contributions to radiation risk are poorly understood. Meanwhile, Green's functions for diffusion-influenced reactions have appeared in the literature, which are applied to describe the diffusion of molecules near a plane membrane comprising bound receptors with the possibility of reversible binding of a ligand and activation of signal transduction proteins by the ligand-receptor complex. We have developed Brownian dynamics algorithms to simulate particle histories in this system which can accurately reproduce the theoretical distribution of distances of a ligand from the membrane, the number of reversibly bound particles, and the number of receptor complexes activating signaling proteins as a function of time, regardless of the number of time steps used for the simulation. These simulations will be of great importance to model interactions at low doses where stochastic effects induced by a small number of molecules or interactions come into play.

  16. Yeast Ca(2+)-signal transduction inhibitors isolated from Dominican amber prevent the degranulation of RBL-2H3 cells through the inhibition of Ca(2+)-influx.

    Science.gov (United States)

    Abe, Tomomi; Kobayashi, Miki; Okawa, Yusuke; Inui, Tomoki; Yoshida, Jun; Higashio, Hironori; Shinden, Hisao; Uesugi, Shota; Koshino, Hiroyuki; Kimura, Ken-Ichi

    2016-09-01

    A new norlabdane compound, named kujigamberol has previously been isolated from Kuji amber (but not from Baltic amber) by activity guided fractionation. However, there has been no study of biological compounds in Dominican amber. Biological activities were examined using the hypersensitive mutant yeast (zds1Δ erg3Δ pdr1Δ pdr3Δ) with respect to Ca(2+)-signal transduction, enzymes and rat basophilic leukemia (RBL)-2H3 cells. The structures were elucidated on the basis of spectral analysis including high resolution (HR)-EI-MS, 1D NMR and 2D NMR. Three diterpenoid compounds, 5(10)-halimen-15-oic acid (1), 3-cleroden-15-oic acid (2) and 8-labden-15-oic acid (3), which are different from the bioactive compounds in Kuji and Baltic ambers, were isolated from Dominican amber. They inhibited both calcineurin (CN) (IC50=40.0, 21.2 and 34.2μM) and glycogen synthase kinase-3β (GSK-3β) (IC50=48.9, 43.8 and 41.1μM) which are involved in the growth restored activity against the mutant yeast. The most abundant compound 2 showed inhibitory activity against both degranulation and Ca(2+)-influx in RBL-2H3 cells. The compounds having the growth restoring activity against the mutant yeast have potential as anti-allergic compounds.

  17. Yeast Ca(2+)-signal transduction inhibitors isolated from Dominican amber prevent the degranulation of RBL-2H3 cells through the inhibition of Ca(2+)-influx.

    Science.gov (United States)

    Abe, Tomomi; Kobayashi, Miki; Okawa, Yusuke; Inui, Tomoki; Yoshida, Jun; Higashio, Hironori; Shinden, Hisao; Uesugi, Shota; Koshino, Hiroyuki; Kimura, Ken-Ichi

    2016-09-01

    A new norlabdane compound, named kujigamberol has previously been isolated from Kuji amber (but not from Baltic amber) by activity guided fractionation. However, there has been no study of biological compounds in Dominican amber. Biological activities were examined using the hypersensitive mutant yeast (zds1Δ erg3Δ pdr1Δ pdr3Δ) with respect to Ca(2+)-signal transduction, enzymes and rat basophilic leukemia (RBL)-2H3 cells. The structures were elucidated on the basis of spectral analysis including high resolution (HR)-EI-MS, 1D NMR and 2D NMR. Three diterpenoid compounds, 5(10)-halimen-15-oic acid (1), 3-cleroden-15-oic acid (2) and 8-labden-15-oic acid (3), which are different from the bioactive compounds in Kuji and Baltic ambers, were isolated from Dominican amber. They inhibited both calcineurin (CN) (IC50=40.0, 21.2 and 34.2μM) and glycogen synthase kinase-3β (GSK-3β) (IC50=48.9, 43.8 and 41.1μM) which are involved in the growth restored activity against the mutant yeast. The most abundant compound 2 showed inhibitory activity against both degranulation and Ca(2+)-influx in RBL-2H3 cells. The compounds having the growth restoring activity against the mutant yeast have potential as anti-allergic compounds. PMID:27491756

  18. Importin β1 mediates nuclear factor-κB signal transduction into the nuclei of myeloma cells and affects their proliferation and apoptosis.

    Science.gov (United States)

    Yan, Wenqing; Li, Rong; He, Jie; Du, Juan; Hou, Jian

    2015-04-01

    Multiple myeloma (MM) is a plasma cell neoplasm that is currently incurable. The activation of nuclear factor-κB (NF-κB) signalling plays a crucial role in the immortalisation of MM cells. As the most important transcription factor of the canonical NF-κB pathway, the p50/p65 heterodimer requires transportation into the nucleus for its successful signal transduction. Importin β1 is the key transport receptor that mediates p50/p65 nuclear import. Currently, it remains unclear whether the regulation of importin β1 function affects the biological behaviour of MM cells. In the present study, we investigated the changes in p65 translocation and the proliferation and apoptosis of MM cells after treatment with small interfering RNA (siRNA) or an importin β1 inhibitor. The underlying mechanisms were also investigated. We found importin β1 over-expression and the excessive nuclear transport of p65 in myeloma cells. Confocal laser scanning microscopy and Western blot analysis results indicated that p65 nuclear transport was blocked after inhibiting importin β1 expression with siRNA and the importin β1-specific inhibitor importazole (IPZ). Importantly, electronic mobility shift assay results also verified that p65 nuclear transport was dramatically reduced. Moreover, the expression of the NF-κB signalling target genes involved in MM cell apoptosis, such as BCL-2, c-IAP1 and XIAP, were markedly reduced, as demonstrated by the RT-PCR results. Furthermore, the proliferation of MM cells was inhibited, as demonstrated by MTT assay results, and the MM cell apoptosis rate was higher, as demonstrated by the annexin V/propidium iodide (PI) double-staining assay results. Additionally, the percentage of S phase cells in the myeloma cell lines treated with IPZ was dramatically reduced. In conclusion, our results clearly show that importin β1 mediates the translocation of NF-κB into the nuclei of myeloma cells, thereby regulating proliferation and blocking apoptosis, which

  19. Sensitive Tumorigenic Potential Evaluation of Adult Human Multipotent Neural Cells Immortalized by hTERT Gene Transduction

    Science.gov (United States)

    Jeong, Da Eun; Kim, Sung Soo; Song, Hye Jin; Pyeon, Hee Jang; Kang, Kyeongjin; Hong, Seung-Cheol; Nam, Do-Hyun; Joo, Kyeung Min

    2016-01-01

    Stem cells and therapeutic genes are emerging as a new therapeutic approach to treat various neurodegenerative diseases with few effective treatment options. However, potential formation of tumors by stem cells has hampered their clinical application. Moreover, adequate preclinical platforms to precisely test tumorigenic potential of stem cells are controversial. In this study, we compared the sensitivity of various animal models for in vivo stem cell tumorigenicity testing to identify the most sensitive platform. Then, tumorigenic potential of adult human multipotent neural cells (ahMNCs) immortalized by the human telomerase reverse transcriptase (hTERT) gene was examined as a stem cell model with therapeutic genes. When human glioblastoma (GBM) cells were injected into adult (4–6-week-old) Balb/c-nu, adult NOD/SCID, adult NOG, or neonate (1–2-week-old) NOG mice, the neonate NOG mice showed significantly faster tumorigenesis than that of the other groups regardless of intracranial or subcutaneous injection route. Two kinds of ahMNCs (682TL and 779TL) were primary cultured from surgical samples of patients with temporal lobe epilepsy. Although the ahMNCs were immortalized by lentiviral hTERT gene delivery (hTERT-682TL and hTERT-779TL), they did not form any detectable masses, even in the most sensitive neonate NOG mouse platform. Moreover, the hTERT-ahMNCs had no gross chromosomal abnormalities on a karyotype analysis. Taken together, our data suggest that neonate NOG mice could be a sensitive animal platform to test tumorigenic potential of stem cell therapeutics and that ahMNCs could be a genetically stable stem cell source with little tumorigenic activity to develop regenerative treatments for neurodegenerative diseases. PMID:27391353

  20. Sensitive Tumorigenic Potential Evaluation of Adult Human Multipotent Neural Cells Immortalized by hTERT Gene Transduction.

    Directory of Open Access Journals (Sweden)

    Kee Hang Lee

    Full Text Available Stem cells and therapeutic genes are emerging as a new therapeutic approach to treat various neurodegenerative diseases with few effective treatment options. However, potential formation of tumors by stem cells has hampered their clinical application. Moreover, adequate preclinical platforms to precisely test tumorigenic potential of stem cells are controversial. In this study, we compared the sensitivity of various animal models for in vivo stem cell tumorigenicity testing to identify the most sensitive platform. Then, tumorigenic potential of adult human multipotent neural cells (ahMNCs immortalized by the human telomerase reverse transcriptase (hTERT gene was examined as a stem cell model with therapeutic genes. When human glioblastoma (GBM cells were injected into adult (4-6-week-old Balb/c-nu, adult NOD/SCID, adult NOG, or neonate (1-2-week-old NOG mice, the neonate NOG mice showed significantly faster tumorigenesis than that of the other groups regardless of intracranial or subcutaneous injection route. Two kinds of ahMNCs (682TL and 779TL were primary cultured from surgical samples of patients with temporal lobe epilepsy. Although the ahMNCs were immortalized by lentiviral hTERT gene delivery (hTERT-682TL and hTERT-779TL, they did not form any detectable masses, even in the most sensitive neonate NOG mouse platform. Moreover, the hTERT-ahMNCs had no gross chromosomal abnormalities on a karyotype analysis. Taken together, our data suggest that neonate NOG mice could be a sensitive animal platform to test tumorigenic potential of stem cell therapeutics and that ahMNCs could be a genetically stable stem cell source with little tumorigenic activity to develop regenerative treatments for neurodegenerative diseases.

  1. Signal transduction and downregulation of C-MET in HGF stimulated low and highly metastatic human osteosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Husmann, Knut, E-mail: khusmann@research.balgrist.ch [Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich (Switzerland); Ducommun, Pascal [Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich (Switzerland); Division of Plastic Surgery and Hand Surgery, Department of Surgery, University Hospital Zurich, Zurich (Switzerland); Sabile, Adam A.; Pedersen, Else-Marie; Born, Walter; Fuchs, Bruno [Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich (Switzerland)

    2015-09-04

    The poor outcome of osteosarcoma (OS), particularly in patients with metastatic disease and a five-year survival rate of only 20%, asks for more effective therapeutic strategies targeting malignancy-promoting mechanisms. Dysregulation of C-MET, its ligand hepatocyte growth factor (HGF) and the fusion oncogene product TPR-MET, first identified in human MNNG-HOS OS cells, have been described as cancer-causing factors in human cancers. Here, the expression of these molecules at the mRNA and the protein level and of HGF-stimulated signaling and downregulation of C-MET was compared in the parental low metastatic HOS and MG63 cell lines and the respective highly metastatic MNNG-HOS and 143B and the MG63-M6 and MG63-M8 sublines. Interestingly, expression of TPR-MET was only observed in MNNG-HOS cells. HGF stimulated the phosphorylation of Akt and Erk1/2 in all cell lines investigated, but phospho-Stat3 remained at basal levels. Downregulation of HGF-stimulated Akt and Erk1/2 phosphorylation was much faster in the HGF expressing MG63-M8 cells than in HOS cells. Degradation of HGF-activated C-MET occurred predominantly through the proteasomal and to a lesser extent the lysosomal pathway in the cell lines investigated. Thus, HGF-stimulated Akt and Erk1/2 signaling as well as proteasomal degradation of HGF activated C-MET are potential therapeutic targets in OS. - Highlights: • Expression of TPR-MET was only observed in MNNG-HOS cells. • HGF stimulated the phosphorylation of Akt and Erk1/2 but not of Stat3 in osteosarcoma cell lines. • Degradation of HGF-activated C-MET occurred predominantly through the proteasomal pathway.

  2. Staphylococcal enterotoxin-A directly stimulates signal transduction and interferon-gamma production in psoriatic T-cell lines

    DEFF Research Database (Denmark)

    Nielsen, M B; Odum, N; Gerwien, J;

    1998-01-01

    Bacterial superantigens such as staphylococcal enterotoxin-A (SEA) have been implicated in the pathogenesis of psoriasis vulgaris. Major histocompatibility complex (MHC) class II molecules are high affinity receptors for SEA, and T cells found in psoriatic skin lesions express high levels of MHC...... are involved in the autopresentation of SEA by psoriatic T cells. In conclusion, we provide evidence that SEA directly activates MVHC class H-positive psoriatic T-cell lines to produce IFN-gamma, a key cytokine in the pathogenesis of psoriasis vulgaris....... of interferon-gamma (IFN-gamma), but not autocrine mitogenesis in CD8-positive T clones obtained from skin lesions of a patient with psoriasis vulgaris. Psoriatic T cells do not respond to SEA molecules if mutations are introduced in the TCRbeta- or in both the two MHC class II alpha- and beta-binding sites...

  3. Association of reactive oxygen species-mediated signal transduction with in vitro apoptosis sensitivity in chronic lymphocytic leukemia B cells.

    Directory of Open Access Journals (Sweden)

    Adam L Palazzo

    Full Text Available BACKGROUND: Chronic lymphocytic leukemia (CLL is a B cell malignancy with a variable clinical course and unpredictable response to therapeutic agents. Single cell network profiling (SCNP utilizing flow cytometry measures alterations in signaling biology in the context of molecular changes occurring in malignancies. In this study SCNP was used to identify proteomic profiles associated with in vitro apoptotic responsiveness of CLL B cells to fludarabine, as a basis for ultimately linking these with clinical outcome. METHODOLOGY/PRINCIPAL FINDING: SCNP was used to quantify modulated-signaling of B cell receptor (BCR network proteins and in vitro F-ara-A mediated apoptosis in 23 CLL samples. Of the modulators studied the reactive oxygen species, hydrogen peroxide (H₂O₂, a known intracellular second messenger and a general tyrosine phosphatase inhibitor stratified CLL samples into two sub-groups based on the percentage of B cells in a CLL sample with increased phosphorylation of BCR network proteins. Separately, in the same patient samples, in vitro exposure to F-ara-A also identified two sub-groups with B cells showing competence or refractoriness to apoptotic induction. Statistical analysis showed that in vitro F-ara-A apoptotic proficiency was highly associated with the proficiency of CLL B cells to undergo H₂O₂-augmented signaling. CONCLUSIONS/SIGNIFICANCE: This linkage in CLL B cells among the mechanisms governing chemotherapy-induced apoptosis increased signaling of BCR network proteins and a likely role of phosphatase activity suggests a means of stratifying patients for their response to F-ara-A based regimens. Future studies will examine the clinical applicability of these findings and also the utility of this approach in relating mechanism to function of therapeutic agents.

  4. Signal transduction in T lymphocytes in microgravity

    Science.gov (United States)

    Cogoli, A.

    1997-01-01

    More than 120 experiments conducted in space in the last 15 years have shown that dramatic changes are occurring in several types of single cells during their exposure to microgravity. One focus of today's research on cells in space is on signal transduction, especially those steps involving the cytoskeleton and cell-cell interactions. Signal transduction is often altered in microgravity as well as in hypergravity. This leads to changes in cell proliferation, genetic expression and differentiation. Interesting examples are leukocytes, HeLa cells, epidermoid cells and osteoblastic cells. Signalling pathways were studied in T lymphocytes in microgravity by several investigators after the discovery that mitogenic activation in vitro is virtually nil at 0g. T cells are a good model to study signal transduction because three extracellular signals (mitogen, IL-1 and IL-2) are required for full activation, and two classical pathways (via proteins G and PKC) are activated within the cell. In addition, low molecular weight GTP-binding proteins (Ras and Rap) are interacting with the cytoskeleton. The data at 0g support the notion that the expression of IL-2 receptor is inhibited at 0g, while mitogen binding and the transmission of IL-1 by accessory cells occur normally. In addition, alterations of the cytoskeleton suggest that the interaction with Rap proteins is disturbed. Data obtained with phorbol esters indicate that the function of PKC is changed in microgravity. Similar conclusions are drawn from the results with epidermoid cells A431.

  5. Resistance of SKW6 cell to apoptosis induction with anti-Fas antibody upon transduction of a reverse fragment to a cDNA encoding human 6A8 α-mannosidase

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The effect of transduction with a reverse fragment to a cDNA encoding human 6A8 a-mannosidase on apoptosis induction of human B cell line SKW6 by anti-Fas antibody was tested. Apoptosis-inducer of anti-Fas monoclonal antibody was used to induce apoptosis in SKW6 cells. Giemsa's staining, Annexin-V-FLUOS staining and DNA ladder test were used to determine the events of apoptosis. Indirect immunofluorescent staining with anti-Fas antibody was performed to detect the surface Fas expression. In a time-course test of 12, 24 and 36 h for apoptosis induction by anti-Fas antibody, DNA ladder was observed in the wild-type SKW6 cells in a time-dependent fashion. Mock transduction had no effect on DNA ladder production. However, no DNA ladder was detected in the rAAV-antisense 6A8 cDNA-transduced SKW6. Results from Annexin-V-FLUOS staining on anti-Fas antibody-treated cells revealed that the staining-positive rate in the rAAV-antisense 6A8 cDNA-transduced SKW6 cells was decreased in comparison to that in the wild-type and the mock-transduced cells. Giemsa's staining observation showed that the number of dying (with apoptotic bodies) and dead cells was reduced in the rAAV-antisense 6A8 cDNA-transduced SKW6 cells in comparison with that in the wild-type and the mock-transduced cells upon anti-Fas antibody induction. The transduction did not affect the expression of Fas molecular on cell surface. 100% cells in all the groups showed Fas expression. The SKW6 cells became resistant to apoptosis induction by anti-Fas antibody upon transduction with a reverse fragment to a cDNA encoding human 6A8 a-mannosidase. The transduction did not affect the expression of Fas molecule on cells.

  6. Tamarind Seed Xyloglucans Promote Proliferation and Migration of Human Skin Cells through Internalization via Stimulation of Proproliferative Signal Transduction Pathways

    Directory of Open Access Journals (Sweden)

    W. Nie

    2013-01-01

    Full Text Available Xyloglucans (XGs of Tamarindus indica L. Fabaceae are used as drug vehicles or as ingredients of cosmetics. Two xyloglucans were extracted from T. indica seed with cold water (TSw and copper complex precipitation (TSc. Both were analyzed in regard to composition and influence on cell viability, proliferation, cell cycle progression, migration, MAPK phosphorylation, and gene expression of human skin keratinocytes (NHEK and HaCaT and fibroblasts (NHDF in vitro. TSw and TSc differed in molecular weight, rhamnose content, and ratios of xylose, arabinose, galactose, and glucose. Both XGs improved keratinocytes and fibroblast proliferation, promoted the cell cycle, and stimulated migration and intracellular enzyme activity of NHDF after endosomal uptake. Only TSw significantly enhanced HaCaT migration and extracellular enzyme activity of NHDF and HaCaT. TSw and TSc predominantly enhanced the phosphorylation of molecules that referred to Erk signaling in NHEK. In NHDF parts of the integrin signaling and SAPK/JNK pathway were affected. Independent of cell type TSw marginally regulated the expression of genes, which referred to membrane proteins, cytoskeleton, cytokine signaling, and ECM as well as to processes of metabolism and transcription. Results show that T. indica xyloglucans promote skin regeneration by a direct influence on cell proliferation and migration.

  7. Tamarind Seed Xyloglucans Promote Proliferation and Migration of Human Skin Cells through Internalization via Stimulation of Proproliferative Signal Transduction Pathways.

    Science.gov (United States)

    Nie, W; Deters, A M

    2013-01-01

    Xyloglucans (XGs) of Tamarindus indica L. Fabaceae are used as drug vehicles or as ingredients of cosmetics. Two xyloglucans were extracted from T. indica seed with cold water (TSw) and copper complex precipitation (TSc). Both were analyzed in regard to composition and influence on cell viability, proliferation, cell cycle progression, migration, MAPK phosphorylation, and gene expression of human skin keratinocytes (NHEK and HaCaT) and fibroblasts (NHDF) in vitro. TSw and TSc differed in molecular weight, rhamnose content, and ratios of xylose, arabinose, galactose, and glucose. Both XGs improved keratinocytes and fibroblast proliferation, promoted the cell cycle, and stimulated migration and intracellular enzyme activity of NHDF after endosomal uptake. Only TSw significantly enhanced HaCaT migration and extracellular enzyme activity of NHDF and HaCaT. TSw and TSc predominantly enhanced the phosphorylation of molecules that referred to Erk signaling in NHEK. In NHDF parts of the integrin signaling and SAPK/JNK pathway were affected. Independent of cell type TSw marginally regulated the expression of genes, which referred to membrane proteins, cytoskeleton, cytokine signaling, and ECM as well as to processes of metabolism and transcription. Results show that T. indica xyloglucans promote skin regeneration by a direct influence on cell proliferation and migration.

  8. Tamarind Seed Xyloglucans Promote Proliferation and Migration of Human Skin Cells through Internalization via Stimulation of Proproliferative Signal Transduction Pathways.

    Science.gov (United States)

    Nie, W; Deters, A M

    2013-01-01

    Xyloglucans (XGs) of Tamarindus indica L. Fabaceae are used as drug vehicles or as ingredients of cosmetics. Two xyloglucans were extracted from T. indica seed with cold water (TSw) and copper complex precipitation (TSc). Both were analyzed in regard to composition and influence on cell viability, proliferation, cell cycle progression, migration, MAPK phosphorylation, and gene expression of human skin keratinocytes (NHEK and HaCaT) and fibroblasts (NHDF) in vitro. TSw and TSc differed in molecular weight, rhamnose content, and ratios of xylose, arabinose, galactose, and glucose. Both XGs improved keratinocytes and fibroblast proliferation, promoted the cell cycle, and stimulated migration and intracellular enzyme activity of NHDF after endosomal uptake. Only TSw significantly enhanced HaCaT migration and extracellular enzyme activity of NHDF and HaCaT. TSw and TSc predominantly enhanced the phosphorylation of molecules that referred to Erk signaling in NHEK. In NHDF parts of the integrin signaling and SAPK/JNK pathway were affected. Independent of cell type TSw marginally regulated the expression of genes, which referred to membrane proteins, cytoskeleton, cytokine signaling, and ECM as well as to processes of metabolism and transcription. Results show that T. indica xyloglucans promote skin regeneration by a direct influence on cell proliferation and migration. PMID:24106497

  9. Corrosive characteristics of surface-modified stainless steel bipolar plate in solid polymer fuel cell

    Science.gov (United States)

    Zhang, Xiaowen; Wang, Lixia; Sun, Juncai

    2015-03-01

    In this paper, corrosion behavior of an AISI 304 stainless steel modified by niobium or niobium nitride (denoted as niobized 304 SS and Nb-N 304 SS, respectively) is investigated in simulated solid polymer fuel cell (SPFC) operating conditions. Potentiodynamic polarizations show that the corrosion potentials of surface modified 304 SS shift to positive direction while the corrosion current densities decrease greatly comparing with the bare 304 SS in simulated anodic SPFC environments. The order of corrosive resistance in corrosive potential, corrosive current density and pitting potential is: Nb-N 304 SS > niobized 304 SS > bare 304 SS. In the methanol-fueled SPFC operating conditions, the results show that the corrosion resistance of bare and niobized 304 SS increases with the methanol concentration increasing in the test solutions.

  10. Epidermal growth factor and ras regulate gene expression in GH4 pituitary cells by separate, antagonistic signal transduction pathways

    Energy Technology Data Exchange (ETDEWEB)

    Pickett, C.A.; Gutierrez-Hartmann, A. [Univ. of Colorado Health Sciences Center, Denver, CO (United States)

    1995-12-01

    This report discusses the role of the epidermal growth factor (EGF) in promoting activation of the rat prolactin promoter in neuroendocrine cells via a Ras-independent mechanism. It also discusses the role of phosphotransferases in mediating EGF response. 32 refs., 8 figs., 1 tab.

  11. Arginine, leucine, and glutamine stimulate proliferation of porcine trophectoderm cells through the MTOR-RPS6K-RPS6-EIF4EBP1 signal transduction pathway.

    Science.gov (United States)

    Kim, Jinyoung; Song, Gwonhwa; Wu, Guoyao; Gao, Haijun; Johnson, Gregory A; Bazer, Fuller W

    2013-05-01

    During the peri-implantation and early placentation periods in pigs, conceptuses (embryo and its extra-embryonic membranes) undergo dramatic morphological changes and differentiation that require the exchange of nutrients (histotroph) and gasses across the trophectoderm and a true epitheliochorial placenta. Of these nutrients, arginine (Arg), leucine (Leu), and glutamine (Gln) are essential components of histotroph; however, little is known about changes in their total amounts in the uterine lumen of cyclic and pregnant gilts and their effects on cell signaling cascades. Therefore, we determined quantities of Arg, Leu, and Gln in uterine luminal fluids and found that total recoverable amounts of these amino acids increased in pregnant but not cyclic gilts between Days 12 and 15 after onset of estrus. We hypothesized that Arg, Leu, and Gln have differential effects on hypertrophy, hyperplasia, and differentiated functions of trophectoderm cells that are critical to conceptus development. Primary porcine trophectoderm (pTr) cells treated with either Arg, Leu, or Gln had increased abundance of phosphorylated RPS6K, RPS6, and EIF4EBP1 compared to basal levels, and this effect was maintained for up to 120 min. When pTr cells were treated with Arg, Leu, and Gln, low levels of pRPS6K and pEIF4EBP1 were detected in the cytosol, but the abundance of nuclear pRPS6K increased. Immunofluorescence analyses revealed abundant amounts of pRPS6 protein in the cytoplasm of pTr cells treated with Arg, Leu, and Gln. These amino acids also increased proliferation of pTr cells. Furthermore, when Arg, Leu, and Gln were combined with siRNAs for either MTOR, RPTOR, or RICTOR, effects of those amino acids on proliferation of pTr cells were significantly inhibited. Collectively, these results indicate that Arg, Leu, and Gln act coordinately to stimulate proliferation of pTr cells through activation of the MTOR-RPS6K-RPS6-EIF4EBP1 signal transduction pathway.

  12. The cornucopia of intestinal chemosensory transduction

    Directory of Open Access Journals (Sweden)

    Paul P Bertrand

    2009-12-01

    Full Text Available The chemosensory transduction mechanisms that the gastrointestinal (GI tract uses to detect chemical and nutrient stimuli are poorly understood. The GI tract is presented with a wide variety of stimuli including potentially harmful chemicals or toxins as well as 'normal' stimuli including nutrients, bacteria and mechanical forces. Sensory transduction is at its simplest the conversion of these stimuli into a neural code in afferent nerves. Much of the information encoded is used by the enteric nervous system (ENS to generate local reflexes while complementary information is sent to the central nervous system (CNS via afferents or by release of hormones to affect behaviour. This review focuses on the chemosensory transduction mechanisms present in the GI tract. It examines the expression and localisation of the machinery for chemosensory transduction. It summarises the types of cells which might be involved in detecting stimuli and releasing neuroactive transmitters. Finally, it highlights the idea that chemosensory transduction mechanisms in the GI tract utilise many overlapping and complementary mechanisms for detecting and transducing stimuli into reflex action.

  13. Kv7 potassium channels in airway smooth muscle cells: signal transduction intermediates and pharmacological targets for bronchodilator therapy

    OpenAIRE

    Brueggemann, Lioubov I.; Kakad, Priyanka P.; Robert B Love; Solway, Julian; Dowell, Maria L.; Cribbs, Leanne L.; Byron, Kenneth L.

    2011-01-01

    Expression and function of Kv7 (KCNQ) voltage-activated potassium channels in guinea pig and human airway smooth muscle cells (ASMCs) were investigated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), patch-clamp electrophysiology, and precision-cut lung slices. qRT-PCR revealed expression of multiple KCNQ genes in both guinea pig and human ASMCs. Currents with electrophysiological and pharmacological characteristics of Kv7 currents were measured in freshly isolated ...

  14. Gravitational Effects on Signal Transduction

    Science.gov (United States)

    Sytkowski, Arthur J.

    1999-01-01

    An understanding of the mechanisms by which individual cells perceive gravity and how these cells transduce and respond to gravitational stimuli is critical for the development of long-term manned space flight experiments. We now propose to use a well-characterized model erythroid cell system and to investigate gravitational perturbations of its erythropoietin (Epo) signaling pathway and gene regulation. Cells will be grown at 1-G and in simulated microgravity in the NASA Rotating Wall Vessel bioreactor (RWV). Cell growth and differentiation, the Epo-receptor, the protein kinase C pathway to the c-myc gene, and the protein phosphatase pathway to the c-myb gene will be studied and evaluated as reporters of gravitational stimuli. The results of these experiments will have impact on the problems of 1) gravitational sensing by individual cells, and 2) the anemia of space flight. This ground-based study also will serve as a Space Station Development Study in gravitational effects on intracellular signal transduction.

  15. Electrochemical behavior of nanocrystalline Ta/TaN multilayer on 316L stainless steel: Novel bipolar plates for proton exchange membrane fuel-cells

    Science.gov (United States)

    Alishahi, M.; Mahboubi, F.; Mousavi Khoie, S. M.; Aparicio, M.; Hübner, R.; Soldera, F.; Gago, R.

    2016-08-01

    Insufficient corrosion resistance and surface conductivity are two main issues that plague large-scale application of stainless steel (SS) bipolar plates in proton exchange membrane fuel cells (PEMFCs). This study explores the use of nanocrystalline Ta/TaN multilayer coatings to improve the electrical and electrochemical performance of polished 316L SS bipolar plates. The multilayer coatings have been deposited by (reactive) magnetron sputtering and characterized by X-ray diffraction, field-emission scanning electron microscopy and transmission electron microscopy. The electrochemical behavior of bare and coated substrates has been evaluated in simulated PEMFC working environments by potentiodynamic and potentiostatic polarization tests at ambient temperature and 80 °C. The results show that the Ta/TaN multilayer coating increases the polarization resistance of 316L SS by about 30 and 104 times at ambient and elevated temperatures, respectively. The interfacial contact resistance (ICR) shows a low value of 12 mΩ × cm2 before the potentiostatic test. This ICR is significantly lower than for the bare substrate and remains mostly unchanged after potentiostatic polarization for 14 h. In addition, the high contact angle (92°) with water for coated substrates indicates a hydrophobic character, which can improve the water management within the cell in PEMFC stacks.

  16. Cellular semiotics and signal transduction

    DEFF Research Database (Denmark)

    Bruni, Luis Emilio

    2007-01-01

    to the processes of sign interpretation and transmission between organisms of the same or different species). In Biosemiotics it is customary to recognise the cell as the most elementary integration unit for semiosis. Therefore intra and intercellular communication constitute the departure point for the study......Semiosis, the processes of production, communication and interpretation of signs - coding and de-coding - takes place within and between organisms. The term "endosemiosis" refers to the processes of interpretation and sign transmission inside an organism (as opposed to "exosemiosis", which refers...... considering semiotic logic in order to construct our understanding of living phenomena. Given the central integrating role of signal transduction in physiological and ecological studies, this chapter outlines its semiotic implications. The multi-modality and modularity of signal molecules and relative...

  17. Kv7 potassium channels in airway smooth muscle cells: signal transduction intermediates and pharmacological targets for bronchodilator therapy.

    Science.gov (United States)

    Brueggemann, Lioubov I; Kakad, Priyanka P; Love, Robert B; Solway, Julian; Dowell, Maria L; Cribbs, Leanne L; Byron, Kenneth L

    2012-01-01

    Expression and function of Kv7 (KCNQ) voltage-activated potassium channels in guinea pig and human airway smooth muscle cells (ASMCs) were investigated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), patch-clamp electrophysiology, and precision-cut lung slices. qRT-PCR revealed expression of multiple KCNQ genes in both guinea pig and human ASMCs. Currents with electrophysiological and pharmacological characteristics of Kv7 currents were measured in freshly isolated guinea pig and human ASMCs. In guinea pig ASMCs, Kv7 currents were significantly suppressed by application of the bronchoconstrictor agonists methacholine (100 nM) or histamine (30 μM), but current amplitudes were restored by addition of a Kv7 channel activator, flupirtine (10 μM). Kv7 currents in guinea pig ASMCs were also significantly enhanced by another Kv7.2-7.5 channel activator, retigabine, and by celecoxib and 2,5-dimethyl celecoxib. In precision-cut human lung slices, constriction of airways by histamine was significantly reduced in the presence of flupirtine. Kv7 currents in both guinea pig and human ASMCs were inhibited by the Kv7 channel blocker XE991. In human lung slices, XE991 induced robust airway constriction, which was completely reversed by addition of the calcium channel blocker verapamil. These findings suggest that Kv7 channels in ASMCs play an essential role in the regulation of airway diameter and may be targeted pharmacologically to relieve airway hyperconstriction induced by elevated concentrations of bronchoconstrictor agonists. PMID:21964407

  18. Investigation of the Mechanoelectrical Transduction at Single Stereocilia by Afm

    Science.gov (United States)

    Langer, M. G.; Fink, S.; Löffler, K.; Koitschev, A.; Zenner, H.-P.

    2003-02-01

    The transduction of sound into an electrical signal in the inner ear is closely related to the mechanical properties of the hair bundles cytoskeleton and cross-linkage. In this study the effect of lateral cross-links on hair bundle mechanics and the transduction current response is demonstrated on the level of individual stereocilia. For experiments stereocilia of outer hair cells of postnatal rats (P3 - P8) were scanned with a sharp AFM tip at nanometerscale. Transduction currents were simultaneously recorded in the whole-cell-recording mode with patch clamp. AFM was used as a nanotool for local mechanical stimulation and force measurement at stereocilia whereas patch clamp serves as a detector for the electrical response of the cell. In a first experiment force transmission between adjacent stereocilia of the V- and W- shaped hair bundles of outer hair cells was investigated. Results showed that a force exerted to a single stereocilium declined to 36 % at the nearest adjacent stereocilium of the same row. This result supposes AFM to be convenient for local displacement of single stereocilia. For control, the local response of transduction channels was measured at single stereocilia of the same hair bundle. Measured transduction current amplitudes ranged from 9 to 49 pA supposing an opening of one to five transduction channels. Both, weak force transmission by lateral cross-links and small transduction current amplitudes indicate a weak mechanical interaction between individual stereocilia of the tallest row of stereocilia of outer hair cells from postnatal rats.

  19. Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells.

    Science.gov (United States)

    Gaub, Benjamin M; Berry, Michael H; Holt, Amy E; Reiner, Andreas; Kienzler, Michael A; Dolgova, Natalia; Nikonov, Sergei; Aguirre, Gustavo D; Beltran, William A; Flannery, John G; Isacoff, Ehud Y

    2014-12-23

    Most inherited forms of blindness are caused by mutations that lead to photoreceptor cell death but spare second- and third-order retinal neurons. Expression of the light-gated excitatory mammalian ion channel light-gated ionotropic glutamate receptor (LiGluR) in retinal ganglion cells (RGCs) of the retina degeneration (rd1) mouse model of blindness was previously shown to restore some visual functions when stimulated by UV light. Here, we report restored retinal function in visible light in rodent and canine models of blindness through the use of a second-generation photoswitch for LiGluR, maleimide-azobenzene-glutamate 0 with peak efficiency at 460 nm (MAG0(460)). In the blind rd1 mouse, multielectrode array recordings of retinal explants revealed robust and uniform light-evoked firing when LiGluR-MAG0(460) was targeted to RGCs and robust but diverse activity patterns in RGCs when LiGluR-MAG0(460) was targeted to ON-bipolar cells (ON-BCs). LiGluR-MAG0(460) in either RGCs or ON-BCs of the rd1 mouse reinstated innate light-avoidance behavior and enabled mice to distinguish between different temporal patterns of light in an associative learning task. In the rod-cone dystrophy dog model of blindness, LiGluR-MAG0(460) in RGCs restored robust light responses to retinal explants and intravitreal delivery of LiGluR and MAG0(460) was well tolerated in vivo. The results in both large and small animal models of photoreceptor degeneration provide a path to clinical translation. PMID:25489083

  20. The Role of Matrine and Mitogen-Ativated Protein Kinase/Extracellular Signal-Regulated Kinase Signal Transduction in the Inhibition of the Proliferation and Migration of Human Umbilical Veins Endothelial Cells Induced by Lung Cancer cells

    Directory of Open Access Journals (Sweden)

    Ming BAI

    2009-07-01

    Full Text Available Background and objective Matrine, one of the major alkaloid components of the traditional Chinese medicine Sophora roots, has a wide range of pharmacological effects including anti-inflammatory activities, growth inhibition and induction of cell differentiation and apoptosis. Motigen-activated protein kinase (MAPK/extracellular signal-regulated kinase (ERK has found to be a crucial signaling pathway in endothelial cells. The aim of this study is to investigate the role of Matrine and MAPK/ERK signal transduction in the inhibition of the proliferation and migration of human umbilical veins endothelial cells (HUVECs induced by lung cancer cells. Methods HUVECs were cultured with A549CM. Mat or PD98059 (i.e PD, specific inhibitor of MAPK/ERK, was added into the A549CM. The proliferation of the HUVECs was measured by cell counting. The migration of the HUVECs was observed by wound healing assay. The expression levels of ERK and p-ERK protein were detected by Western Blot analysis. Results On 24 hours after intervention, the A549CM significantly stimulated the proliferation, migration and expression of p-ERK of HUVECs. Compared with the A549CM group, Mat significantly inhibited the proliferation, migration and p-ERK expression of HUVECs induced by A549CM. While PD only decreased the proliferation and p-ERK expression of HUVECs induced by A549CM. PD had no effect in the migration of HUVECs. Conclusion The results demonstrated that Mat and PD98059 can effectively decrease proliferation and expression of p-ERK of HUVECs induced by A549CM. Furthermore Mat can also inhibit migration of HUVECs induced by A549CM that did not changed by PD98059. These data implied that suppressing MAPK/ERK signal transduction may play the crucial role in resisting lung cacinoma angiogenesis with Mat.

  1. Fabrication and performance research on bipolar plates of fuel cells%燃料电池双极板的制备与工作性能研究

    Institute of Scientific and Technical Information of China (English)

    吴懋亮; 曹寿峰; 顾竹筠

    2013-01-01

    质子交换膜燃料电池是直接将化学能转换为电能的装置,双极板是燃料电池的关键部件.研究了用来加工双极板的混合石墨材料的制备方法,通过对比,45%天然石墨、10%合成石墨、8%石墨纤维、2%炭黑和35%粘结剂的混合物作为加工材料,通过选择性激光烧结加工,并经过800℃高温焙烧和渗透树脂处理获得燃料电池双极板,具有120 S/cm电导率和40 MPa抗弯强度.实验证明混合石墨材质的双极板符合燃料电池的使用要求,但是不同流道结构影响燃料电池的输出电流-电压特性,尤其是平行流道燃料电池表现出较差的性能.不同流道形式受温度变化的影响不同,单希尔伯特流道表现最为敏感,60℃至80℃时燃料电池表现出良好的工作性能.%Proton exchange membrane fuel cell converts directly electrochemical energy into electricity,and bipolar plate is a critical component.The selection and mixture method of mixed graphite were studied,and 45% nature graphite,10% synthetic graphite,8% graphite fiber,2% carbon black and 35% binder were adopted to mix as material.The bipolar plates were fabricated with the mixed graphite by the selective laser sintering apparatus,which had pretty electrical conductivity of 120 S/cm and enough flexural strength of 40 MPa after carbonization at 800 ℃ and infiltration with liquid conductive resin.The experiments testity that mixed graphite is suitable to fabricate PEM fuel cell bipolar plates.Channel pattems influence fuel cell performance,parallel pattern especially express poor performance.Polarization curves of a fuel cell vary with different temperatures,and the single Hilbert channel type is more sensitive.A fuel cell obtains good performance under the temperature of 60-80 ℃.

  2. Modeling of single-event upset in bipolar integrated circuits

    Science.gov (United States)

    Zoutendyk, J. A.

    1983-01-01

    The results of work done on the quantitative characterization of single-event upset (SEU) in bipolar random-access memories (RAMs) have been obtained through computer simulation of SEU in RAM cells that contain circuit models for bipolar transistors. The models include current generators that emulate the charge collected from ion tracks. The computer simulation results are compared with test data obtained from a RAM in a bipolar microprocessor chip. This methodology is applicable to other bipolar integrated circuit constructions in addition to RAM cells.

  3. Neuroimaging in Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Kemal Kara

    2013-03-01

    Full Text Available Bipolar disorder is characterized by recurrent attacks, significantly disrupts the functionality of a chronic mental disorder. Although there is growing number of studies on the neurobiological basis of the disorder, the pathophysiology has not yet been clearly understood. Structural and functional imaging techniques present a better understanding of the etiology of bipolar disorder and has contributed significantly to the development of the diagnostic approach. Recent developments in brain imaging modalities have let us learn more about the underlying abnormalities in neural systems of bipolar patients. Identification of objective biomarkers would help to determine the pathophysiology of bipolar disorder, a disorder which causes significant deterioration in neurocognitive and emotional areas.

  4. Removal of inhibitory substances with recombinant fibronectin-CH-296 plates enhances the retroviral transduction efficiency of CD34(+)CD38(-) bone marrow cells.

    Science.gov (United States)

    Chono, H; Yoshioka, H; Ueno, M; Kato, I

    2001-09-01

    In retroviral gene transduction, the efficiency of viral infection was reduced by the proteoglycans and some other materials secreted by the producer lines. In order to remove these inhibitors we have developed the rFN-CH-296-facilitated protocol. Because the rFN-CH-296 molecule has strong ability to bind a retroviral vector, rFN-CH-296 bound plates are utilized to wash out the unbound putative inhibitors present in a virus supernatant. The gene transduction efficiencies of human CD34(+)CD38(-) BMCs with a GALV-pseudotyped vector and the rFN-CH-296-facilitated protocol were compared with the protocol without a coating plate with CH-296, the mean gene transduction efficiencies being found to be 95.5 and 71.1%, respectively.

  5. Separate TRP channels mediate amplification and transduction in drosophila

    Science.gov (United States)

    Lehnert, Brendan P.; Baker, Allison E.; Wilson, Rachel I.

    2015-12-01

    Auditory receptor cells rely on mechanically-gated channels to transform sound stimuli into neural activity. Several TRP channels have been implicated in Drosophila auditory transduction, but mechanistic studies have been hampered by the inability to record subthreshold signals from receptor neurons. We developed a non-invasive method for measuring these signals by recording from a central neuron that is electrically coupled to a genetically-defined population of auditory receptors. We find that the TRPN family member NompC, which is necessary for the active amplification of motion by the auditory organ, is not required for transduction. Instead, NompC sensitizes the transduction complex to movement and precisely regulates the static forces on the complex. In contrast, the TRPV channels Nanchung and Inactive are required for responses to sound, suggesting they are components of the transduction complex. Thus, transduction and active amplification are genetically separable processes in Drosophila hearing.

  6. Preparation of corrosion-resistant and conductive trivalent Cr-C coatings on 304 stainless steel for use as bipolar plates in proton exchange membrane fuel cells by electrodeposition

    Science.gov (United States)

    Wang, Hsiang-Cheng; Sheu, Hung-Hua; Lu, Chen-En; Hou, Kung-Hsu; Ger, Ming-Der

    2015-10-01

    In this study, Cr-C-coated bipolar plates are produced by electroplating on the SS304 plates with a machined flow channel. The resulting plates were tested using potentiodynamic and potentiostatic measurements in simulated PEMFC environments, which show that the bipolar plate coated with Cr-C exhibited good anticorrosion performance. The corrosive current density of the Cr-C coating formed for a plating time of 10 min for 10 h exhibits a low stable value of 1.51 × 10-10 A/cm2 during the potentiostatic test in a 0.5 M H2SO4 + 2 ppm HF solution at 70 °C with an air purge, indicating that the Cr-C coating plated for 10 min is stable in a cathode environment. The interfacial contact resistance (ICR) of the bipolar plate with the Cr-C coating clearly improved, presenting an ICR of 19.52 mΩ cm2 at a pressure of 138 N/cm2. The results from scanning electron microscopy (SEM) and ICR before and after the corrosion tests indicate that the bipolar plate with the Cr-C coating is electrochemically stable. In this study, the maximum power density (212.41 mW/cm2) is obtained at a cell temperature of 80 °C and a gas flow rate of 300 standard cubic centimeters per minute (sccm) when Cr-C coated SS304 bipolar plates were used.

  7. Signal transduction by HLA-DR is mediated by tyrosine kinase(s) and regulated by CD45 in activated T cells

    DEFF Research Database (Denmark)

    Odum, Niels; Martin, P J; Schieven, G L;

    1991-01-01

    , but the inhibitory effect of CD45 dominated over the enhancing effect of CD4. These data indicate that PTK activation is obligatory for DR-induced (Ca2+)i responses, suggesting a linkage between these pathways in class II signal transduction. This conclusion is consistent with our observation that in activated human...

  8. Management of bipolar depression

    Directory of Open Access Journals (Sweden)

    Jae Seung Chang

    2011-01-01

    Full Text Available Patients with bipolar disorder spend more time in a depressed than manic state, even with individualized treatment. To date, bipolar depression is often misdiagnosed and ineffectively managed both for acute episodes and residual symptoms. This review attempts to summarize the current status of available treatment strategies in the treatment of bipolar depression. For acute and prophylactic treatment, a substantial body of evidence supports the antidepressive efficacy of lithium for bipolar disorders and its antisuicidal effects. Among numerous anticonvulsants with mood-stabilizing properties, valproate and lamotrigine could be first-line options for bipolar depression. Due to receptor profile, mood-stabilizing properties of second-generation antipsychotics have been explored, and up to date, quetiapine and olanzapine appear to be a reasonable option for bipolar depression. The usefulness of antidepressants in bipolar depression is still controversial. Current guidelines generally recommend the cautious antidepressant use in combination with mood stabilizers to reduce the risk of mood elevation or cycle acceleration. Results from clinical trials on psychosocial intervention are promising, especially when integrated with pharmacotherapy. Most patients with bipolar depression need individualized and combined treatment, although the published evidence on this type of treatment strategy is limited. Future studies on the utility of currently available agents and modalities including psychosocial intervention are required.

  9. Study on mould pressing composite bipolar plates made of expanded graphite/resin for fuel cells%燃料电池模压膨胀石墨/树脂复合双极板研究

    Institute of Scientific and Technical Information of China (English)

    史惟澄; 杨代军; 刘金玲; 钱铮; 马建新

    2013-01-01

    The resin and expanded graphite used to prepare the mould pressing composite bipolar plates of fuel cells were discussed: the influence of ratio of resin on bipolar plates, the resin would not only ensure the high mechanical strength and gas permeability of bipolar plates, but also would be beneficial to reduce the manufacture. It could help to develop the fuel cells and marketization. In order to make up the decline of electrical conductivity when adding resin to bipolar plates, some auxiliary conductive filler should be added, such as carbon fiber, carbon nano tube to bipolar plates. Furthermore, the technological parameter of mould pressing would influence on the property of bipolar plates.%综述了用于质子交换膜燃料电池的模压膨胀石墨/树脂复合双极板的树脂选型以及膨胀石墨:树脂的配比对双极板性能的影响,所选树脂除了要能保证双极板的较高机械强度和气密性外,还要有利于低成本化的模压生产,才能有效地促进燃料电池的发展,推动其商业化.为了弥补双极板加入树脂后带来的电导率下降的问题,还需加入碳纤维、碳纳米管等辅助导电填料.此外,模压工艺及参数的选择与确定对双极板的性能也有直接影响.

  10. Signal transduction pathways in liver and the influence of hepatitis C virus infection on their activities

    Institute of Scientific and Technical Information of China (English)

    Magdalena M Dabrowska; Anatol Panasiuk; Robert Flisiak

    2009-01-01

    In liver, the most intensively studied transmembrane and intracellular signal transduction pathways are the Janus kinase signal transduction pathway, the mitogen-activated protein kinases signal transduction pathway, the transforming growth factor b signal transduction pathway, the tumor necrosis factor a signal transduction pathway and the recently discovered sphingolipid signal transduction pathway. All of them are activated by many different cytokines and growth factors. They regulate specific cell mechanisms such as hepatocytes proliferation, growth, differentiation, adhesion, apoptosis, and synthesis and degradation of the extracellular matrix. The replication cycle of hepatitis C virus (HCV) is intracellular and requires signal transduction to the nucleus to regulate transcription of its genes. Moreover, HCV itself, by its structural and nonstructural proteins, could influence the activity of the second signal messengers. Thus, the inhibition of the transmembrane and intracellular signal transduction pathways could be a new therapeutic target in chronic hepatitis C treatment.

  11. Comparison of corrosion behaviors between SS304 and Ti substrate coated with (Ti,Zr)N thin films as Metal bipolar plate for unitized regenerative fuel cell

    International Nuclear Information System (INIS)

    In this study, a (Ti,Zr)N coating consisting of nano-composite structure of the TiN and ZrN phases is deposited on SS304 and titanium substrates as the metal bipolar plate through the cathodic arc evaporation techniques. This improves the corrosion resistance of SS304 and Ti metal when used in a unitized regenerative fuel cell (URFC). The corrosion behaviors of these two substrates are compared. Scanning electron microscope, energy dispersive spectrometer, and X-ray diffractometer are used to characterize the microstructure, thickness, chemical composition, as well as crystalline and phase states of the deposited thin films. The potentiodynamic polarization of the (Ti,Zr)N coating is tested in a simulated URFC H2 environment, i.e., 0.50 M H2SO4 with 3 ppm NaF solution purging with H2 gas at 60 °C. Experimental results demonstrate that the (Ti,Zr)N coating improves the corrosion resistance of SS304 (about 215 times that of uncoated SS304) better than that of the Ti substrate (about 200 times that of uncoated Ti). The enhanced corrosion resistance is attributed to the nano-composite structure of TiN and ZrN, which has a dense and columnar microstructure that is impermeable to a corrosive medium. The coating of the (Ti,Zr)N layer has better corrosion resistance than the increased sheet resistance for both substrates. Therefore, the (Ti,Zr)N–SS304 and (Ti,Zr)N–Ti samples, specifically the (Ti,Zr)N–SS304 sample, are good candidates as the material for URFC H2 side metal bipolar plate. - Highlights: • A (Ti,Zr)N coating is deposited on SS304 and titanium substrates. • This coating contains a nano-composite structure of TiN and ZrN phases. • Effective improvement of corrosion resistance on substrates has been obtained. • Coating on SS304 has better enhancement of corrosion resistance than that on Ti. • It can be used for bipolar-plate material of the unitized regenerative fuel cell

  12. 中药对肝癌细胞信号转导通路影响的研究进展%Advances in research on Chinese medicines that can induce apoptosis of hepatocellular carcinoma cells by the signal transduction pathway

    Institute of Scientific and Technical Information of China (English)

    濮忠建; 华海清

    2011-01-01

    As the research on the signal transduction pathway of tumor is developing, people has become more aware of the confusion of the signal transduction mechanisms on the tumor cells and their effects on tumor growth, apoptosis, and metastasis. Currently, the research that Chinese medicine and its extract inducing apoptosis and angiogenesis of hepatocellular carcinoma by acting on the signal transduction pathway has made gratifying progress. In this article, we will provide an overview of recent literature about this.%随着对肿瘤信号转导通路研究的不断深入,人们对肿瘤细胞内部复杂的信号转导机制以及它们对肿瘤生长、凋亡和转移等的影响越来越了解.目前,中药及其提取物通过作用于信号转导通路诱导肝癌细胞凋亡、影响肝癌血管生成的研究已取得可喜进步.现对近年来有关文献进行回顾,就此进展作一综述.

  13. Corrosion protection of aluminum bipolar plates with polyaniline coating containing carbon nanotubes in acidic medium inside the polymer electrolyte membrane fuel cell

    Science.gov (United States)

    Deyab, M. A.

    2014-12-01

    The effect of addition of carbon nanotubes (CNTs) on the corrosion resistance of conductive polymer coating (polyaniline) that coated aluminum bipolar plates in acidic environment inside the PEM fuel cell (0.1 M H2SO4) was investigated using electrical conductivity, polarization and electrochemical impedance spectroscopy (EIS) measurements. Scanning electron microscopy (SEM) was used to characterize the coating morphology. The results show that the addition of CNTs to polyaniline coating enhanced the electrical conductivity and the corrosion resistance of polyaniline polymer. The inhibition efficiency of polyaniline polymer increased with increasing CNTs concentration. The best inhibition was generally obtained at 0.8% CNTs concentration in the acidic medium. This was further confirmed by decreasing the oxygen and water permeability and increasing coating adhesion in the presence of CNTs. EIS measurements indicated that the incorporation of CNTs in coating increased both the charge transfer and pore resistances while reducing the double layer capacitance.

  14. Signal transduction by the Fat cytoplasmic domain

    OpenAIRE

    Pan, Guohui; Feng, Yongqiang; Ambegaonkar, Abhijit A.; Sun, Gongping; Huff, Matthew; Rauskolb, Cordelia; Irvine, Kenneth D.

    2013-01-01

    The large atypical cadherin Fat is a receptor for both Hippo and planar cell polarity (PCP) pathways. Here we investigate the molecular basis for signal transduction downstream of Fat by creating targeted alterations within a genomic construct that contains the entire fat locus, and by monitoring and manipulating the membrane localization of the Fat pathway component Dachs. We establish that the human Fat homolog FAT4 lacks the ability to transduce Hippo signaling in Drosophila, but can trans...

  15. Heme oxygenase-1 in cholecystokinin-octapeptipe attenuated injury of pulmonary artery smooth muscle cells induced by lipopolysaccharide and its signal transduction mechanism

    Institute of Scientific and Technical Information of China (English)

    Xin-Li Huang; Yi-Ling Ling; Yi-Qun Ling; Jun-Lin Zhou; Yah Liu; Qiu-Hong Wang

    2004-01-01

    AIM: To study the effect of cholecystokinin-octapeptide (CCK-8) on lipopolysaccharide (LPS) -induced pulmonary artery smooth muscle cell (PASMCs) injury and the role of heme oxygenase-1 (HO-1), and to explore the regulation mechanism of c-Jun N-terminal kinase (JNK) and activator protein-L (AP-1) signal transduction pathway in inducing HO-1 expression further.METHODS: Cultured PASMCs were randomly divided into 4 or 6 groups: normal culture group, LPS (10 mg/L), CCK-8(10-6 mol/L) plus LPS (10 mg/L) group, CCK-8 (10-6 mol/L)group, zinc protoporphyrin 9 (ZnPPIX) (10-6 mol/L) plus LPS (10 mg/L) group, CCK-8 (10-6 mol/L) plus ZnPPIX and LPS (10 mg/L) group. Seven hours after LPS administration,ulterstructrual changes and content of malondialdehyde (MDA) of PASMCs in each group were investigated by electron microscopy and biochemical assay respectively.HO-1 mRNA and protein of PASMCs in the former4 groups were examined by reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry staining.Changes of c-fos expression and activation of JNK of PASMCs in the former 4 groups were detected with immunocytochemistry staining and Western blot 30 min after LPS administration.RESULTS: The injuries of PASMCs and the increases of MDA content induced by LPS were alleviated and significantly reduced by CCK-8 (P<0.05). The specific HO-1 inhibitorZnPPIX could worsen LPS-induced injuries and weaken the protective effect of CCK-8. The expressions of c-fos,p-JNK protein and HO-1 mRNA and protein were all slightly increased in LPS group, and significantly enhanced by CCK-8 further (P<0.05).CONCLUSION: HO-1 may be a key factor in CCK-8attenuated injuries of PASMCs induced by LPS, and HO-1expression may be related to the activation of JNK and activator protein (AP-1).

  16. 结肠癌干细胞表面标志的研究和信号传导%Colon cancer stem cell surface markers and signal transduction research

    Institute of Scientific and Technical Information of China (English)

    陈远崇

    2011-01-01

    背景:近年来研究表明,结肠癌干细胞参与肿瘤的复发和转移,为恶性肿瘤靶向治疗带来新的希望.目的:探讨结肠癌干细胞特异表面标志的分离和鉴定方法,以及与结肠癌干细胞研究紧密相关的信号通路.方法:以"结肠癌干细胞,肿瘤干细胞,细胞表面标志,信号传导"为中文关键词,以"colon cancer stem cell,cancer stem cell,cell surface sign,signal transduction"为英文关键词,采用计算机检索Medline和CNKI数据库2000-01/2011-06有关结肠癌干细胞表面标志和信号传导的相关文章,排除重复研究或Meta分析类文章,筛选纳入40篇文献进行评价.结果与结论:CD133+与CD44+可作结肠癌干细胞的表面标志.与结肠癌干细胞紧密相关的信号通路有Wnt和Notch等,Wnt信号通路在干细胞内环境稳定中起重要作用,Notch信号通路是干细胞信号网络的重要通路.通过研究结肠癌干细胞的表面标志,可以及早地检测出肿瘤的存在;掌握结肠癌干细胞的生物学特性和信号转导路径,可减少肿瘤的复发,为结肠癌的诊断和治疗降低难度.%BACKGROUND: In recent years, studies have shown that colon cancer stem cells are involved in tumor recurrence andmetastasis, which have brought a new hope for cancer targeted therapy.OBJECTIVE: To investigate the isolation and identification method of colon cancer stem cell surface markers as well as relevantsignal transduction pathways.METHODS: A computer-based search of Medline and CNKI databases (2000-01/2011-06) was performed to retrieve coloncancer stem cell surface markers and signal transduction using the keywords of "colon cancer stem cell, cancer stem cell, cellsurface sign, signal transduction" in English and Chinese, respectively. Repetitive articles or Meta analyses were excluded, andfinally 40 articles were included in result analysis.RESULTS AND CONCLUSION: CD133+ and CD44+ are used as colon cancer stem cell surface markers. Closely related

  17. Molecular purging of multiple myeloma cells by ex-vivo culture and retroviral transduction of mobilized-blood CD34+ cells

    OpenAIRE

    Corneo Gianmarco; Pogliani Enrico; Monari Marta; Vai Sergio; Voena Claudia; Dando Jonathan; Ficara Francesca; Cergnul Massimiliano; Birolo Roberto; Scaramuzza Samantha; Deola Sara; Peccatori Jacopo; Selleri Silvia; Bordignon Claudio; Roncarolo Maria

    2007-01-01

    Abstract Background Tumor cell contamination of the apheresis in multiple myeloma is likely to affect disease-free and overall survival after autografting. Objective To purge myeloma aphereses from tumor contaminants with a novel culture-based purging method. Methods We cultured myeloma-positive CD34+ PB samples in conditions that retained multipotency of hematopoietic stem cells, but were unfavourable to survival of plasma cells. Moreover, we exploited the resistance of myeloma plasma cells ...

  18. Neuroinflammation in bipolar disorders

    Directory of Open Access Journals (Sweden)

    Georgios D Kotzalidis

    2015-01-01

    Full Text Available Recent literature based on peripheral immunity findings speculated that neuroinflammation, with its connection to microglial activation, is linked to bipolar disorder. The endorsement of the neuroinflammatory hypotheses of bipolar disorder requires the demonstration of causality, which requires longitudinal studies. We aimed to review the evidence for neuroinflammation as a pathogenic mechanism of the bipolar disorder. We carried out a hyper inclusive PubMed search using all appropriate neuroinflammation-related terms and crossed them with bipolar disorder-related terms. The search produced 310 articles and the number rose to 350 after adding articles from other search engines and reference lists. Twenty papers were included that appropriately tackled the issue of the presence (but not of its pathophysiological role of neuroinflammation in bipolar disorder. Of these, 15 were postmortem and 5 were carried out in living humans. Most articles were consistent with the presence of neuroinflammation in bipolar disorder, but factors such as treatment may mask it. All studies were cross-sectional, preventing causality to be inferred. Thus, no inference can be currently made about the role of neuroinflammation in bipolar disorder, but a link is likely. The issue remains little investigated, despite an excess of reviews on this topic.

  19. Mechanisms of Centrosome Separation and Bipolar Spindle Assembly

    NARCIS (Netherlands)

    Tanenbaum, Marvin E.; Medema, Rene H.

    2010-01-01

    Accurate segregation of chromosomes during cell division is accomplished through the assembly of a bipolar microtubule-based structure called the mitotic spindle. Work over the past two decades has identified a core regulator of spindle bipolarity, the microtubule motor protein kinesin-5. However, a

  20. An investigation of the typical corrosion parameters used to test polymer electrolyte fuel cell bipolar plate coatings, with titanium nitride coated stainless steel as a case study

    Science.gov (United States)

    Orsi, A.; Kongstein, O. E.; Hamilton, P. J.; Oedegaard, A.; Svenum, I. H.; Cooke, K.

    2015-07-01

    Stainless steel bipolar plates (BPP) for polymer electrolyte membrane fuel cells (PEMFCs) have good manufacturability, durability and low costs, but inadequate corrosion resistance and elevated interfacial contact resistance (ICR) in the fuel cell environment. Thin film coatings of titanium nitride (TiN) of 1 μm in thickness, were deposited by means of physical vapour deposition (PVD) process on to stainless steel (SS) 316L substrates and were evaluated, in a series of tests, for their level of corrosion protection and ICR. In the ex-situ corrosion tests, variables such as applied potential, experimental duration and pH of the sulphate electrolyte at 80 °C were altered. The ICR values were found to increase after exposure to greater applied potentials and electrolytes of a higher pH. In terms of experimental duration, the ICR increased most rapidly at the beginning of each experiment. It was also found that the oxidation of TiN was accelerated after exposure to electrolytes of a higher pH. When coated BPPs were incorporated into an accelerated fuel cell test, the degradation of the fuel cell cathode resembled the plates that were tested at the highest anodic potential (1.4 VSHE).

  1. Pheromone transduction in moths

    Directory of Open Access Journals (Sweden)

    Monika Stengl

    2010-12-01

    Full Text Available Calling female moths attract their mates late at night with intermittent release of a species-specific sex-pheromone blend. Mean frequency of pheromone filaments encodes distance to the calling female. In their zig-zagging upwind search male moths encounter turbulent pheromone blend filaments at highly variable concentrations and frequencies. The male moth antennae are delicately designed to detect and distinguish even traces of these sex pheromones amongst the abundance of other odors. Its olfactory receptor neurons sense even single pheromone molecules and track intermittent pheromone filaments of highly variable frequencies up to about 30 Hz over a wide concentration range. In the hawkmoth Manduca sexta brief, weak pheromone stimuli as encountered during flight are detected via a metabotropic PLCβ-dependent signal transduction cascade which leads to transient changes in intracellular Ca2+ concentrations. Strong or long pheromone stimuli, which are possibly perceived in direct contact with the female, activate receptor-guanylyl cyclases causing long-term adaptation. In addition, depending on endogenous rhythms of the moth´s physiological state, hormones such as the stress hormone octopamine modulate second messenger levels in sensory neurons. High octopamine levels during the activity phase maximize temporal resolution cAMP-dependently as a prerequisite to mate location. Thus, I suggest that sliding adjustment of odor response threshold and kinetics is based upon relative concentration ratios of intracellular Ca2+ and cyclic nucleotide levels which gate different ion channels synergistically. In addition, I propose a new hypothesis for the cyclic nucleotide-dependent ion channel formed by insect olfactory receptor/coreceptor complexes. Instead of being employed for an ionotropic mechanism of odor detection it is proposed to control subthreshold membrane potential oscillation of sensory neurons, as a basis for temporal encoding of odors.

  2. Effect of microstructure of TiN film on properties as bipolar plate coatings in polymer electrolyte membrane fuel cell prepared by inductively coupled plasma assisted magnetron sputtering

    International Nuclear Information System (INIS)

    As potential application in bipolar plate of polymer electrolyte membrane fuel cell, the microstructure, corrosion resistance and the electrical conductivity of titanium nitride (TiN) and Si doped titanium nitride (Ti0.9Si0.1N) films deposited by magnetron sputtering with different bias voltages are investigated by X-ray diffraction (XRD), scanning electron microscope (SEM), atomic force microscope (AFM), electrochemical test and four-point probe method, respectively. XRD, SEM and AFM results reveal that the texture and topography of TiN film depend on the bias voltage and incorporation of Si. When the bias voltage is − 20 V and − 30 V, the TiN and Ti0.9Si0.1N films exhibit a dense (111) plane preferred growth, denser structure and smoother surface topography. The potentiodynamic test results indicate that the TiN and Ti0.9Si0.1N films have higher chemical inertness and better corrosion resistance. The films can satisfy the requirement of current density for bipolar plate materials. Incorporation of Si element into TiN film makes the passive current density more stable. Four-point probe measurement results show that the resistivity of both TiN and Ti0.9Si0.1N films reaches minimum when the deposition bias voltage is − 20 V. - Highlights: • Dense TiN and Ti0.9Si0.1N films are deposited by magnetron sputtering. • Preferred growth orientation of TiN depends on the bias voltage and Si doping. • TiN and Ti0.9Si0.1N films have excellent corrosion resistance. • Surface conductivity of TiN and Ti0.9Si0.1N films evolves with bias voltage

  3. The study of electroplating trivalent CrC alloy coatings with different current densities on stainless steel 304 as bipolar plate of proton exchange membrane fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hsiang-Cheng [Graduate School of Defense Science, Chung Cheng Institute of Technology, National Defense University, Taoyuan, Taiwan (China); Hou, Kung-Hsu, E-mail: khou@ndu.edu.tw [Department of Power Vehicle and Systems Engineering, Chung Cheng Institute of Technology, National Defense University, Taoyuan, Taiwan (China); Lu, Chen-En [Graduate School of Defense Science, Chung Cheng Institute of Technology, National Defense University, Taoyuan, Taiwan (China); Ger, Ming-Der [Department of Applied Chemistry and Materials Engineering, Chung Cheng Institute of Technology, National Defense University, Taoyuan, Taiwan (China)

    2014-11-03

    In this study, the trivalent Cr–C coatings were electroplated on stainless steel 304 (SS304) substrates for an application in bipolar plates (BPPs) that was because of coating's excellent electric conductivity and corrosion resistance. The images of scanning electron microscope showed that the thickness of the coatings was between 1.4 and 11.4 μm, which increased with increase of coating current density. The surface morphology of Cr–C plated at coating current density of 10 A/dm{sup 2} was smooth, crack- and pinhole-free, while cracks and pinholes appearing in networks were observed apparently in the deposits plated at a higher coating current density. Additionally, the C content in the coating decreased with increasing the coating current density. Moreover, the polarization curve with different coating current densities (10, 30, 50 A/dm{sup 2}) exhibited the coating prepared at 10 A/dm{sup 2} and 10 min possessing the best corrosion resistance (I{sub corr} = 9.360 × 10{sup −8} A/cm{sup 2}). The contact resistance of Cr–C plated at coating current density of 10 A/dm{sup 2} was the lowest (16.54 mΩ cm{sup 2} at 150 N cm{sup −2}), which showed great potential of application. The single cell test with Cr–C coated SS304 prepared at coating current density of 10 A/dm{sup 2} as BPPs showed the highest current density (about 791.532 mA/cm{sup 2}) and power density (about 270.150 mW/cm{sup 2}). - Highlights: • The Cr–C coatings on steel are electroplated for utilization as bipolar plate. • The electrical conductivity and corrosion resistance increase with carbon content. • The power density of Cr–C coated steel is superior to the bare steel.

  4. Multilayered Zr-C/a-C film on stainless steel 316L as bipolar plates for proton exchange membrane fuel cells

    Science.gov (United States)

    Bi, Feifei; Peng, Linfa; Yi, Peiyun; Lai, Xinmin

    2016-05-01

    A multilayered zirconium-carbon/amorphous carbon (Zr-C/a-C) coating is synthesized by magnetron sputtering in order to improve the corrosion resistance and interfacial conductivity of stainless steel 316L (SS316L) as bipolar plates for proton exchange membrane fuel cells (PEMFCs). Zr-C/a-C film contains an outmost pure amorphous carbon layer and a sub zirconium containing carbon layer. Interfacial contact resistance (ICR) between carbon paper and coated SS316L decreases to 3.63 mΩ cm2 at 1.4 MPa. Potentiodynamic polarization results reveal that the corrosion potential of Zr-C/a-C coated sample is more positive than pure a-C coated sample and the current density is only 0.49 μA cm-2 at the cathode applied potential 0.6 V. Electrochemical impendence spectroscopy also indicates that multilayered Zr-C/a-C film coated SS316L has much higher charge transfer resistance than the bare sample. After potentiostatic polarization, ICR values are 3.92 mΩ cm2 and 3.82 mΩ cm2 in the simulated PEMFCs cathode and anode environment, respectively. Moreover, XPS analysis of the coated samples before and after potential holding tests shows little difference, which disclose the chemical stability of multilayered Zr-C/a-C film. Therefore, the multilayered Zr-C/a-C coating exhibits excellent performance in various aspects and is preferred for the application of stainless steel bipolar plates.

  5. Serotonin released from amacrine neurons is scavenged and degraded in bipolar neurons in the retina

    OpenAIRE

    Ghai, Kanika; Zelinka, Christopher; Fischer, Andy J.

    2009-01-01

    The neurotransmitter serotonin is synthesized in the retina by one type of amacrine neuron but accumulates in bipolar neurons in many vertebrates. The mechanisms, functions and purpose underlying of serotonin in bipolar cells remain unknown. Here, we demonstrate that exogenous serotonin transiently accumulates in a distinct type of bipolar neuron. KCl-mediated depolarization causes the depletion of serotonin from amacrine neurons and, subsequently, serotonin is taken-up by bipolar neurons. Th...

  6. The ethylene signal transduction pathway in Arabidopsis

    Science.gov (United States)

    Kieber, J. J.; Evans, M. L. (Principal Investigator)

    1997-01-01

    The gaseous hormone ethylene is an important regulator of plant growth and development. Using a simple response of etiolated seedlings to ethylene as a genetic screen, genes involved in ethylene signal transduction have been identified in Arabidopsis. Analysis of two of these genes that have been cloned reveals that ethylene signalling involves a combination of a protein (ETR1) with similarity to bacterial histidine kinases and a protein (CTR1) with similarity to Raf-1, a protein kinase involved in multiple signalling cascades in eukaryotic cells. Several lines of investigation provide compelling evidence that ETR1 encodes an ethylene receptor. For the first time there is a glimpse of the molecular circuitry underlying the signal transduction pathway for a plant hormone.

  7. Types of Bipolar Disorder

    Science.gov (United States)

    ... improve the lives of people who have mood disorders. The Power of Peers DBSA envisions wellness for people who live with depression and bipolar disorder. Because DBSA was created for and is led ...

  8. 孕期酒精暴露对子鼠视网膜双极细胞和水平细胞发育的影响%Prenatal alcohol exposure affects development of retinal bipolar and horizontal cells in mice

    Institute of Scientific and Technical Information of China (English)

    刘曦; 王永毅; 姚焕玲; 赵博; 于亚东; 胡馨; 邓锦波

    2012-01-01

    Objective To investigate effects of alcohol exposure during pregnancy on retinal bipolar and horizontal cells in filial mice. Methods The animal model of prenatal alcohol exposure was made. The development of bipolar cells and horizontal cells at prenatal days 7, 14 and 30 was investigated with immunofluorescent labeling and Dil scattering techniques. Results In all age groups, the density of the bipolar cells was significantly lower in the experiment groups than in the control groups. The dendritic field and the number of branches of horizontal cells were significantly lower in the experimental group than in the control group (P < 0. 01). Conclusion Alcohol exposure during pregnancy affects development of retinal bipolar and horizontal cells in mice.%目的 探讨孕期酒精暴露对子鼠视网膜双极细胞和水平细胞发育的影响.方法 建立孕期酒精暴露小鼠模型;采用免疫荧光染色和DiI散射技术,观察酒精对日龄7d(P7)、P14和P30子鼠视网膜双极细胞和水平细胞的影响.结果 各年龄组中,酒精组视网膜双极细胞的密度明显低于对照组,且呈剂量依赖性和长时程效应;水平细胞的树突野及树突数也明显低于对照组,呈剂量依赖性和长时程效应(P<0.01).结论 孕期酒精暴露影响子鼠视网膜双极细胞和水平细胞的发育.

  9. Bipolar nickel-hydrogen battery development - A program review

    Science.gov (United States)

    Manzo, Michelle; Lenhart, Stephen; Hall, Arnold

    1989-01-01

    An overview of spacecraft power system design trends, focusing on higher power bus voltages and improved energy storage systems, is followed by a discussion of bipolar Ni/H2 battery development efforts. Several 10-cell batteries and one 50-cell battery are described, and performance results are presented. A comparison of individual-pressure-vessel and bipolar Ni/H2 technologies is used to suggest a new direction for bipolar Ni/H2 battery development efforts, toward a large number of passively cooled cells in parallel.

  10. Signal transduction by the major histocompatibility complex class I molecule

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Skov, S; Bregenholt, S;

    1999-01-01

    Ligation of cell surface major histocompatibility class I (MHC-I) proteins by antibodies, or by their native counter receptor, the CD8 molecule, mediates transduction of signals into the cells. MHC-I-mediated signaling can lead to both increased and decreased activity of the MHC-I-expressing cell...

  11. Analysis of signal transduction in brain cells using molecular signal microscope; Bunshi jiho kenbikyo wo mochiita nousaibou no joho henkan kiko no kaiseki

    Energy Technology Data Exchange (ETDEWEB)

    Kawato, Suguru [The University of Tokyo, Tokyo (Japan). Dept. of Biophysics and Life Sciences

    1999-12-16

    We analyzed the signal transduction in brain neurons by real-time imaging of Ca/NO signals using the Molecular Signal Microscope. We also analyzed synthesis and action of neurosteroids in the hippocampus. We discovered steroid synthesis machinery containing cytochrome P 450 scc in hippocampal neurons. We found that pregnenolone sulfate acutely potentiated NMDA receptor-mediated Ca conductivity in hippocampal neurons. We also found that stress steroid corticosterone acutely prolonged NMDA receptor-mediated Ca{sup 2+} influx, resulting in Ca-induced neuro-toxicity. (author)

  12. One-way calcium spill-over during signal transduction in Paramecium cells: from the cell cortex into cilia, but not in the reverse direction.

    Science.gov (United States)

    Husser, Marc R; Hardt, Martin; Blanchard, Marie-Pierre; Hentschel, Joachim; Klauke, Norbert; Plattner, Helmut

    2004-11-01

    We asked to what extent Ca(2+) signals in two different domains of Paramecium cells remain separated during different stimulations. Wild-type (7S) and pawn cells (strain d4-500r, without ciliary voltage-dependent Ca(2+)-channels) were stimulated for trichocyst exocytosis within 80 ms by quenched-flow preparation and analysed by energy-dispersive X-ray microanalysis (EDX), paralleled by fast confocal fluorochrome analysis. We also analysed depolarisation-dependent calcium signalling during ciliary beat rerversal, also by EDX, after 80-ms stimulation in the quenched-flow mode. EDX and fluorochrome analysis enable to register total and free intracellular calcium concentrations, [Ca] and [Ca(2+)], respectively. After exocytosis stimulation we find by both methods that the calcium signal sweeps into the basis of cilia, not only in 7S but also in pawn cells which then also perform ciliary reversal. After depolarisation we see an increase of [Ca] along cilia selectively in 7S, but not in pawn cells. Opposite to exocytosis stimulation, during depolarisation no calcium spill-over into the nearby cytosol and no exocytosis occurs. In sum, we conclude that cilia must contain a very potent Ca(2+) buffering system and that ciliary reversal induction, much more than exocytosis stimulation, involves strict microdomain regulation of Ca(2+) signals.

  13. Development of a portable PEM fuel cell system with bipolar plates consisting an electronically conductive thermoplastic Compound material; Entwicklung eines portablen PEM-Brennstoffzellensystems mit Bipolarplatten aus einem elektronisch leitfaehigen thermoplastischen Compound-Material

    Energy Technology Data Exchange (ETDEWEB)

    Niemzig, O.C.

    2005-07-18

    In order to meet the cost targets of PEM fuel cells for commercialization significant cost reductions of cell stack components like membrane/electrode assemblies and bipolar plates have become key aspects of research and development. Central topics of his work are the bipolar plates and humidification for portable applications. Best results concerning conductivity of an extensive screening of a variety of carbon polymer compounds with polypropylene as matrix could be achieved with the carbon black/graphite/polypropylene-base system. Successful tests of this material in a fuel cell stack could be performed as well as the proof of suitability concerning material- and manufacturing costs. Dependent on application a decrease of material cost to 2 Euro/kg to 1,8 Euro/kW seems to be possible. Finally bipolar plates consisting of a selected carbon polymer compound were successfully integrated and tested in a 20-cell stack which was implemented in a portable PEFC-demonstrator unit with a power output between 50 and 150 W. (orig.)

  14. Bipolar batteries based on Ebonex ® technology

    Science.gov (United States)

    Loyns, A. C.; Hill, A.; Ellis, K. G.; Partington, T. J.; Hill, J. M.

    Continuing work by Atraverda on the production of a composite-laminate form of the Ebonex ® material, that can be cheaply formulated and manufactured to form substrate plates for bipolar lead-acid batteries, is described. Ebonex ® is the registered trade name of a range of titanium suboxide ceramic materials, typically Ti 4O 7 and Ti 5O 9, which combine electrical conductivity with high corrosion and oxidation resistance. Details of the structure of the composite, battery construction techniques and methods for filling and forming of batteries are discussed. In addition, lifetime and performance data obtained by Atraverda from laboratory bipolar lead-acid batteries and cells are presented. Battery production techniques for both conventional monopolar and bipolar batteries are reviewed. The findings indicate that substantial time and cost savings may be realised in the manufacture of bipolar batteries in comparison to conventional designs. This is due to the fewer processing steps required and more efficient formation. The results indicate that the use of Ebonex ® composite material as a bipolar substrate will provide lightweight and durable high-voltage lead-acid batteries suitable for a wide range of applications including advanced automotive, stationary power and portable equipment.

  15. The development of taste transduction and taste chip technology

    Institute of Scientific and Technical Information of China (English)

    LI Yan; LIU Qingjun; XU Ying; CAI Hua; QIN Lifeng; WANG Lijiang; WANG Ping

    2005-01-01

    The intrinsic perception process of taste is obviously far less known than those of vision, audition, touch and olfaction. Despite that taste cells utilize a variety of sensory mechanisms to translate plenty of gustatory sensations such as sour, sweet, bitter, salty and umami into cellular signals, gustatory perception mechanisms are still under exploration due to the lack of effective methods on cellular and molecular level. Recently the development of molecular biological and electrophysiological studies has promoted exploration of olfactory and gustatory transduction and coding mechanisms dramatically. Based on the studies of artificial olfaction, artificial taste and cell-based biosensor in our laboratory, this paper reviews the current research on taste transduction mechanism. We introduce the recent advances in cell chip that combined biology with microelectronics, discuss taste cell chip as well as its potential of prospective application in taste transduction mechanism in detail and propose the research trends of taste chip in future.

  16. The herpes virus Fc receptor gE-gI mediates antibody bipolar bridging to clear viral antigens from the cell surface.

    Directory of Open Access Journals (Sweden)

    Blaise Ndjamen

    2014-03-01

    Full Text Available The Herpes Simplex Virus 1 (HSV-1 glycoprotein gE-gI is a transmembrane Fc receptor found on the surface of infected cells and virions that binds human immunoglobulin G (hIgG. gE-gI can also participate in antibody bipolar bridging (ABB, a process by which the antigen-binding fragments (Fabs of the IgG bind a viral antigen while the Fc binds to gE-gI. IgG Fc binds gE-gI at basic, but not acidic, pH, suggesting that IgG bound at extracellular pH by cell surface gE-gI would dissociate and be degraded in acidic endosomes/lysosomes if endocytosed. The fate of viral antigens associated with gE-gI-bound IgG had been unknown: they could remain at the cell surface or be endocytosed with IgG. Here, we developed an in vitro model system for ABB and investigated the trafficking of ABB complexes using 4-D confocal fluorescence imaging of ABB complexes with transferrin or epidermal growth factor, well-characterized intracellular trafficking markers. Our data showed that cells expressing gE-gI and the viral antigen HSV-1 gD endocytosed anti-gD IgG and gD in a gE-gI-dependent process, resulting in lysosomal localization. These results suggest that gE-gI can mediate clearance of infected cell surfaces of anti-viral host IgG and viral antigens to evade IgG-mediated responses, representing a general mechanism for viral Fc receptors in immune evasion and viral pathogenesis.

  17. Bipolar Affective Disorder and Migraine

    Directory of Open Access Journals (Sweden)

    Birk Engmann

    2012-01-01

    Full Text Available This paper consists of a case history and an overview of the relationship, aetiology, and treatment of comorbid bipolar disorder migraine patients. A MEDLINE literature search was used. Terms for the search were bipolar disorder bipolar depression, mania, migraine, mood stabilizer. Bipolar disorder and migraine cooccur at a relatively high rate. Bipolar II patients seem to have a higher risk of comorbid migraine than bipolar I patients have. The literature on the common roots of migraine and bipolar disorder, including both genetic and neuropathological approaches, is broadly discussed. Moreover, bipolar disorder and migraine are often combined with a variety of other affective disorders, and, furthermore, behavioural factors also play a role in the origin and course of the diseases. Approach to treatment options is also difficult. Several papers point out possible remedies, for example, valproate, topiramate, which acts on both diseases, but no first-choice treatments have been agreed upon yet.

  18. Brassinosteroid signal transduction: An emerging picture

    Institute of Scientific and Technical Information of China (English)

    WANG Qiaomei; MA Ligeng

    2003-01-01

    Steroid hormones play essential roles in animal growth and development. Steroid signaling in animal system is focused on the direct gene regulation response mediated by its nuclear receptors. Recently, steroid hormones are also found in plants. Identification of BRI1 - a critical component of the plasma-membrane steroid receptor complex, and the related signal transduction pathway mediated by the membrane receptor have revealed an elementary picture of BR signaling from the cell surface perception to the activation of BR-responsive nuclear genes.

  19. Bipolar battery construction

    Science.gov (United States)

    Rippel, Wally E. (Inventor); Edwards, Dean B. (Inventor)

    1981-01-01

    A lightweight, bipolar battery construction for lead acid batteries in which a plurality of thin, rigid, biplates each comprise a graphite fiber thermoplastic composition in conductive relation to lead stripes plated on opposite flat surfaces of the plates, and wherein a plurality of nonconductive thermoplastic separator plates support resilient yieldable porous glass mats in which active material is carried, the biplates and separator plates with active material being contained and maintained in stacked assembly by axial compression of the stacked assembly. A method of assembling such a bipolar battery construction.

  20. Conductive materials for proton exchange membrane fuel cell bipolar plates made from PVDF, PET and co-continuous PVDF/PET filled with carbon additives

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, L.; Mighri, F.; Deyrail, Y. [CREPEC, Center for Applied Research on Polymers and Composites, QC (Canada); Department of Chemical Engineering, Laval University, QC (Canada); Elkoun, S. [CREPEC, Center for Applied Research on Polymers and Composites, QC (Canada); Department of Mechanical Engineering, Sherbrooke University, QC (Canada)

    2010-12-15

    The aim of this work was to develop and characterise electrically conductive materials for proton exchange membrane fuel cells and bipolar plates (BPPs). These BPPs were made from highly conductive blends of polyethylene terephthalate (PET) and polyvinylidene fluoride (PVDF), as matrix phase. The conductive materials were developed from carefully formulated blends composed of conductive carbon black (CB) powder and, in some cases, graphite synthetic flakes mixed with pure PET, PVDF or with PVDF/PET systems. They were first developed by twin-screw extrusion process then compression-molded to give BPP final shape. As the developed blends have to meet properties suitable for BPP applications, they were characterised for their rheological properties, electrical through-plane resistivity (the inverse of conductivity), oxygen permeability, flexural and impact properties. Results showed that lower resistivity was obtained with PVDF/CB blends due to the higher interfacial energy between the PVDF matrix and CB and also the higher density and crystallinity of PVDF, compared to those of PET. It was also observed that the lowest resistivity values were obtained with mixing PVDF and PET at controlled compositions to ensure PVDF/PET co-continuous morphology. Also, slow cooling rates helped to attain the lowest values of through-plane resistivity for all studied blends. This behaviour was related to the higher crystallinity obtained with low cooling rates leading to smaller amorphous regions in which carbon particles are much more concentrated. (Copyright copyright 2010 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  1. Corrosion and electrical properties of CrN- and TiN-coated 316L stainless steel used as bipolar plates for polymer electrolyte membrane fuel cells

    International Nuclear Information System (INIS)

    Cathode arc ion plating was applied to deposit CrN and TiN coating layers on stainless steel 316L (SS316L) to produce metallic bipolar plates for polymer electrolyte membrane fuel cells (PEMFCs). The interfacial contact resistance between samples and carbon paper was measured and found to be 10 and 23 mΩ ∗ cm2 for TiN and CrN coating layer respectively under 150 N cm−2 compaction forces. The corrosion properties were investigated in the operating environments of PEMFC. While TiN coating layer was dissolved in the operating environments of PEMFC, the corrosion current density of 0.1 μA cm−2 was obtained for CrN coating layer at anodic condition and its protective efficiency was revealed as 99%. This analysis indicates that the improvement may be attributed to the extremely dense coating and the synergistic function of the CrN layered structure. - Highlights: ► CrN and TiN are deposited on the surface of SS316L by cathode arc ion plating. ► Coating layers of CrN and TiN lead to high electrical conductivity. ► CrN coating layer provides higher corrosion resistance than TiN coating layer

  2. New architecture for modulization of membraneless and single-chambered microbial fuel cell using a bipolar plate-electrode assembly (BEA).

    Science.gov (United States)

    An, Junyeong; Kim, Bongkyu; Jang, Jae Kyung; Lee, Hyung-Sool; Chang, In Seop

    2014-09-15

    A new architecture for a membraneless and single-chambered microbial fuel cell (MFC) which has a unique bipolar plate-electrode assembly (BEA) design was demonstrated. The maximum power of MFC units connected in series (denoted as a stacked MFC) was up to 22.8±0.13 mW/m(2) for 0.946±0.003 V working voltage, which is 2.5 times higher than the averaged maximum power density of the non-stacked MFC units. The power density in the stacked MFC using BEA was comparable to the stacked MFC using electric wire. These results demonstrate that BEAs having air-exposed cathodes can potentially be used in the stacking of membraneless single-chambered MFCs. In addition, we confirmed that the current in the stacked mode flowed faster than the non-stacked mode due to voltage increase by series connection, and the poorest of the stacked units quickly faced current depletion at higher external resistance than the non-stacked mode, leading to voltage reversal. These results imply that stacked MFC units require a relatively large current capacity in order to prevent high voltage reversal at high current region. To increase total current capacity and prevent voltage reversal of stacked MFC units, we suggested series/parallel-integrated MFC module system for scaling-up. This new concept could likely allow the application of MFC technology to be extended to various wastewater treatment processes or plants. PMID:24690558

  3. An investigation on corrosion protection of chromium nitride coated Fe-Cr alloy as a bipolar plate material for proton exchange membrane fuel cells

    Science.gov (United States)

    Pan, T. J.; Zhang, B.; Li, J.; He, Y. X.; Lin, F.

    2014-12-01

    The corrosion properties of chromium nitride (CrN) coating are investigated to assess the potential use of this material as a bipolar plate for proton exchange membrane fuel cells (PEMFCs). Conductive metallic ceramic CrN layers are firstly deposited onto Fe-Cr alloy using a multi-arc ion plating technique to increase the corrosion resistance of the base alloy. Electrochemical measurements indicate that the corrosion resistance of the substrate alloy is greatly enhanced by the CrN coating. The free corrosion potential of the substrate is increased by more than 50 mV. Furthermore, a decrease in three orders of magnitude of corrosive current density for the CrN-coated alloy is observed compared to the as-received Fe-Cr alloy. Long-term immersion tests show that the CrN layer is highly stable and effectively acts as a barrier to inhibit permeation of corrosive species. On the contrary, corrosion of the Fe-Cr alloy is rather severe without the protection of CrN coating due to the active dissolution. Finally, the corresponding electrochemical impedance models are proposed to elucidate the corrosion process of the CrN/Fe-Cr alloy submerged in a simulated PEMFCs environment.

  4. Investigation of the effects of process sequence on the contact resistance characteristics of coated metallic bipolar plates for polymer electrolyte membrane fuel cells

    Science.gov (United States)

    Turan, Cabir; Cora, Ömer Necati; Koç, Muammer

    2013-12-01

    In this study, results of an investigation on the effects of manufacturing and coating process sequence on the contact resistance (ICR) of metallic bipolar plates (BPP) for polymer electrolyte membrane fuel cells (PEMFCs) are presented. Firstly, uncoated stainless steel 316L blanks were formed into BPP through hydroforming and stamping processes. Then, these formed BPP samples were coated with three different PVD coatings (CrN, TiN and ZrN) at three different thicknesses (0.1, 0.5 and 1 μm). Secondly, blanks of the same alloy were coated first with the same coatings, thickness and technique; then, they were formed into BPPs of the same shape and dimensions using the manufacturing methods as in the first group. Finally, these two groups of BPP samples were tested for their ICR to reveal the effect of process sequence. ICR tests were also conducted on the BPP plates both before and after exposure to corrosion to disclose the effect of corrosion on ICR. Coated-then-formed BPP samples exhibited similar or even better ICR performance than formed-then-coated BPP samples. Thus, manufacturing of coated blanks can be concluded to be more favorable and worth further investigation in quest of making cost effective BPPs for mass production of PEMFC.

  5. Surface characteristic of chemically converted graphene coated low carbon steel by electro spray coating method for polymer electrolyte membrane fuel cell bipolar plate.

    Science.gov (United States)

    Kim, Jungsoo; Kim, Yang Do; Nam, Dae Geun

    2013-05-01

    Graphene was coated on low carbon steel (SS400) by electro spray coating method to improve its properties of corrosion resistance and contact resistance. Exfoliated graphite was made of the graphite by chemical treatment (Chemically Converted Graphene, CCG). CCG is distributed using dispersing agent, and low carbon steel was coated with diffuse graphene solution by electro spray coating method. The structure of the CCG was analyzed using XRD and the coating layer of surface was analyzed using SEM. Analysis showed that multi-layered graphite structure was destroyed and it was transformed in to fine layers graphene structure. And the result of SEM analysis on the surface and the cross section, graphene layer was uniformly formed with 3-5 microm thickness on the surface of substrate. Corrosion resistance test was applied in the corrosive solution which is similar to the polymer electrolyte membrane fuel cell (PEMFC) stack inside. And interfacial contact resistance (ICR) test was measured to simulate the internal operating conditions of PEMFC stack. As a result of measuring corrosion resistance and contact resistance, it could be confirmed that low carbon steel coated with CCG was revealed to be more effective in terms of its applicability as PEMFC bipolar plate. PMID:23858864

  6. Graphene grown on stainless steel as a high-performance and ecofriendly anti-corrosion coating for polymer electrolyte membrane fuel cell bipolar plates

    Science.gov (United States)

    Pu, Nen-Wen; Shi, Gia-Nan; Liu, Yih-Ming; Sun, Xueliang; Chang, Jeng-Kuei; Sun, Chia-Liang; Ger, Ming-Der; Chen, Chun-Yu; Wang, Po-Chiang; Peng, You-Yu; Wu, Chia-Hung; Lawes, Stephen

    2015-05-01

    In this study, the growth of graphene by chemical vapor deposition (CVD) on SUS304 stainless steel and on a catalyzing Ni/SUS304 double-layered structure was investigated. The results indicated that a thin and multilayered graphene film can be continuously grown across the metal grain boundaries of the Ni/SUS304 stainless steel and significantly enhance its corrosion resistance. A 3.5 wt% saline polarization test demonstrated that the corrosion currents in graphene-covered SUS304 were improved fivefold relative to the corrosion currents in non-graphene-covered SUS304. In addition to enhancing the corrosion resistance of stainless steel, a graphene coating also ameliorates another shortcoming of stainless steel in a corrosive environment: the formation of a passive oxidation layer on the stainless steel surface that decreases conductivity. After a corrosion test, the graphene-covered stainless steel continued to exhibit not only an excellent low interfacial contact resistance (ICR) of 36 mΩ cm2 but also outstanding drainage characteristics. The above results suggest that an extremely thin, lightweight protective coating of graphene on stainless steel can act as the next-generation bipolar plates of fuel cells.

  7. Reduced mRNA expression of PTGDS in peripheral blood mononuclear cells of rapid-cycling bipolar disorder patients compared with healthy control subjects

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Peijs, Lone; Kessing, Lars Vedel;

    2015-01-01

    is lacking. Two enzymes in the arachidonic acid cascade are the prostaglandin D synthase (PTGDS), which catalyzes the conversion of prostaglandin H2 to prostaglandin D2 (PGD2), and the aldo-keto reductase family 1 member C3 (AKR1C3), which catalyzes the reduction of PGD2. We aimed to test the hypothesis...... that mRNA expression of PTGDS and AKR1C3 is deregulated in rapid-cycling disorder patients in a euthymic or current affective state compared with healthy control subjects, and that expression alters with affective states. METHODS: PTGDS and AKR1C3 mRNA expression in peripheral blood mononuclear cells...... was measured in 37 rapid-cycling bipolar disorder patients and 40 age- and gender-matched healthy control subjects using reverse transcription quantitative real-time polymerase chain reaction. Repeated measurements of PTGDS and AKR1C3 mRNA expression were obtained in various affective states during 6-12 months...

  8. Thermally Nitrided Stainless Steels for Polymer Electrolyte Membrane Fuel Cell Bipolar Plates: Part 2: Beneficial Modification of Passive Layer on AISI446

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Heli [National Renewable Energy Laboratory (NREL); Brady, Michael P [ORNL; More, Karren Leslie [ORNL; Meyer III, Harry M [ORNL; Turner, John [National Renewable Energy Laboratory (NREL)

    2004-01-01

    Thermal nitridation of AISI446 mod-1 superferritic stainless steel for 24 h at 1100 C resulted in an adherent, inward growing surface layer based on (Cr, Fe){sub 2}N{sub 1-x} (x = 0--0.5). The layer was not continuous, and although it resulted in low interfacial contact resistance (ICR) and good corrosion resistance under simulated polymer electrolyte membrane fuel cell (PEMFC) cathodic conditions; poor corrosion resistance was observed under simulated anodic conditions. Nitridation for 2 h at 1100 C resulted in little nitrogen uptake and a tinted surface. Analysis by SEM, XPS, and AES suggested a complex heterogeneous modification of the native passive oxide film by nitrogen rather than the desired microns-thick exclusive Cr-rich nitride layer. Surprisingly, this modification resulted in both good corrosion resistance under simulated cathodic and anodic conditions and low ICR, well over an order of magnitude lower than the untreated alloy. Further, little increase in ICR was observed under passivating polarization conditions. The potential of this phenomenon for PEMFC bipolar plates is discussed.

  9. Reliable Signal Transduction

    Science.gov (United States)

    Wollman, Roy

    Stochasticity inherent to biochemical reactions (intrinsic noise) and variability in cellular states (extrinsic noise) degrade information transmitted through signaling networks. We analyzed the ability of temporal signal modulation - that is dynamics - to reduce noise-induced information loss. In the extracellular signal-regulated kinase (ERK), calcium (Ca(2 +)) , and nuclear factor kappa-B (NF- κB) pathways, response dynamics resulted in significantly greater information transmission capacities compared to nondynamic responses. Theoretical analysis demonstrated that signaling dynamics has a key role in overcoming extrinsic noise. Experimental measurements of information transmission in the ERK network under varying signal-to-noise levels confirmed our predictions and showed that signaling dynamics mitigate, and can potentially eliminate, extrinsic noise-induced information loss. By curbing the information-degrading effects of cell-to-cell variability, dynamic responses substantially increase the accuracy of biochemical signaling networks.

  10. Role of tantalum nitride as active top electrode in electroforming-free bipolar resistive switching behavior of cerium oxide-based memory cells

    Energy Technology Data Exchange (ETDEWEB)

    Ismail, Muhammad, E-mail: ismailmalikbzu10@gmail.com [Department of Physics, Bahauddin Zakariya University, Multan 60800 (Pakistan); Ahmed, Ejaz; Rana, Anwar Manzoor; Talib, Ijaz; Khan, Tahira [Department of Physics, Bahauddin Zakariya University, Multan 60800 (Pakistan); Iqbal, Khalid [Department of Radiation Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore (Pakistan); Nadeem, Muhammad Younus [Department of Physics, Bahauddin Zakariya University, Multan 60800 (Pakistan)

    2015-05-29

    Electroforming-free cerium oxide-based bipolar resistive switching memory devices have been deposited using radio frequency magnetron sputtering technique. These devices demonstrate two types of forming-free cells: some in the low-resistance state and the others in high-resistance state. The transmission electron microscopy and X-ray diffraction analyses illustrate the formation of tantalum oxynitride layer between tantalum nitride (TaN) and cerium oxide (CeO{sub x}), which looks to be responsible for the two types of cells as well as their memory performance. Ohmic and Poole-Frenkel conduction mechanisms are found to be responsible for charge transport in the low- and high-resistance states. The current-voltage characteristics and temperature dependence of resistance suggest that resistive switching mechanism in our TaN/CeO{sub x}/Pt devices may be explained by the model of connection and disconnection of filamentary paths made of oxygen vacancies. The reliability characteristics of TaN/CeO{sub x}/Pt devices indicate better endurance and stable retention performance at relatively lower programming voltages and larger memory window (OFF/ON resistance ratio ~ 10{sup 3}) at room temperature and at 100 °C. - Highlights: • Electroforming-free TaN/CeO{sub x}/Pt memory cells have been fabricated by sputtering. • Device exhibits good endurance, long data retention and high-resistance window (~ 10{sup 3}). • Voltages for SET and RESET transitions of our device exhibit narrow distribution. • The device is forming-free due to pre-existence of abundant oxygen vacancies. • TaN top electrode play major role in uniformity of resistive switching characteristics.

  11. Role of tantalum nitride as active top electrode in electroforming-free bipolar resistive switching behavior of cerium oxide-based memory cells

    International Nuclear Information System (INIS)

    Electroforming-free cerium oxide-based bipolar resistive switching memory devices have been deposited using radio frequency magnetron sputtering technique. These devices demonstrate two types of forming-free cells: some in the low-resistance state and the others in high-resistance state. The transmission electron microscopy and X-ray diffraction analyses illustrate the formation of tantalum oxynitride layer between tantalum nitride (TaN) and cerium oxide (CeOx), which looks to be responsible for the two types of cells as well as their memory performance. Ohmic and Poole-Frenkel conduction mechanisms are found to be responsible for charge transport in the low- and high-resistance states. The current-voltage characteristics and temperature dependence of resistance suggest that resistive switching mechanism in our TaN/CeOx/Pt devices may be explained by the model of connection and disconnection of filamentary paths made of oxygen vacancies. The reliability characteristics of TaN/CeOx/Pt devices indicate better endurance and stable retention performance at relatively lower programming voltages and larger memory window (OFF/ON resistance ratio ~ 103) at room temperature and at 100 °C. - Highlights: • Electroforming-free TaN/CeOx/Pt memory cells have been fabricated by sputtering. • Device exhibits good endurance, long data retention and high-resistance window (~ 103). • Voltages for SET and RESET transitions of our device exhibit narrow distribution. • The device is forming-free due to pre-existence of abundant oxygen vacancies. • TaN top electrode play major role in uniformity of resistive switching characteristics

  12. Meeting Report: Teaching Signal Transduction

    Science.gov (United States)

    Kramer, IJsbrand; Thomas, Geraint

    2006-01-01

    In July, 2005, the European Institute of Chemistry and Biology at the campus of the University of Bordeaux, France, hosted a focused week of seminars, workshops, and discussions around the theme of "teaching signal transduction." The purpose of the summer school was to offer both junior and senior university instructors a chance to reflect on the…

  13. SPP1-mediated plasmid transduction.

    OpenAIRE

    Canosi, U; Lüder, G; Trautner, T A

    1982-01-01

    The virulent Bacillus subtilis phage SPP1 transduces plasmid DNA. Plasmid-transducing phages contain only plasmid DNA. Such DNA represents a concatemer of monomeric plasmid molecules with the molecular weight of mature SPP1 DNA. Biological parameters of plasmid transduction are described.

  14. On the nanotoxicity of PAMAM dendrimers: Superfect® stimulates the EGFR-ERK1/2 signal transduction pathway via an oxidative stress-dependent mechanism in HEK 293 cells.

    Science.gov (United States)

    Akhtar, Saghir; Chandrasekhar, Bindu; Attur, Sreeja; Yousif, Mariam H M; Benter, Ibrahim F

    2013-05-01

    Polyamidoamine (PAMAM) dendrimers are cationic branch-like macromolecules that may serve as drug delivery systems for gene-based therapies such as RNA interference. For their safe use in the clinic, they should ideally only enhance drug delivery to target tissues and exhibit no adverse effects. However, little is known about their toxicological profiles in terms of their interactions with cellular signal transduction pathways such as the epidermal growth factor receptor (EGFR). The EGFR is an important signaling cascade that regulates cell growth, differentiation, migration, survival and apoptosis. Here, we investigated the impact of naked, unmodified Superfect (SF), a commercially available generation 6 PAMAM dendrimer, on the epidermal growth factor receptor (EGFR) tyrosine kinase-extracellular-regulated kinase 1/2 (ERK1/2) signaling pathway in human embryonic kidney (HEK 293) cells. At concentrations routinely used for transfection, SF exhibited time and dose-dependent stimulation of EGFR and ERK1/2 phosphorylation whereas AG1478, a selective EGFR tyrosine kinase antagonist, inhibited EGFR-ERK1/2 signaling. SF-induced phosphorylation of EGFR for 1h was partly reversible upon removal of the dendrimer and examination of cells 24 later. Co-treatment of SF with epidermal growth factor (EGF) ligand resulted in greater EGFR stimulation than either agent alone implying that the stimulatory effects of SF and the ligand are synergistic. Dendrimer-induced stimulation of EGFR-ERK1/2 signaling could be attenuated by the antioxidants apocynin, catalase and tempol implying that an oxidative stress dependent mechanism was involved. These results show for the first time that PAMAM dendrimers, aside from their ability to improve drug delivery, can modulate the important EGFR-ERK1/2 cellular signal transduction pathway - a novel finding that may have a bearing on their safe application as drug delivery systems.

  15. IL-2基因转导CD3AK细胞免疫学功能的研究%Research on Immunologic Functions of Interleukin-2 Gene Transducted CD3AK Cells by Retroviral Vector PLIL-2SN

    Institute of Scientific and Technical Information of China (English)

    王立新; 夏圣; 许靖霞; 蔡仙德

    2000-01-01

    目的:观察白细胞介素-2(IL-2)基因转导后CD3AK细胞免疫学功能的变化。方法:应用逆转录病毒载体将IL2基因转导入CD3AK细胞。检测转导细胞中特异性NeoR基因、培养上清IL2的表达水平及转导CD3AK细胞的体外增殖活性、细胞毒活性和细胞表型。结果:从转导细胞mRNA中扩增出长度为347bp的特异性NeoR基因片段,转导细胞培养上清的IL2表达水平显著增高,体外增殖活性和细胞毒活性均强于未转导组细胞,CD4+/CD2+值升高。结论:PLIL2SN逆转录病毒转导CD3AK细胞后,IL-2基因得到表达并增强CD3AK细胞的免疫学功能。%Objective This experiment was designed to observe the immunologic functions of CD3AK cells into which interleukin-2(IL-2) gene had been transducted. Methods The post-transfer CD3AK cells' special NeoR gene and cell immunologic functions including IL-2 expression, proliferation, cytotoxicity and cell phonetype were detected. R~ults The specific 347 bp NeoR gene was amplfiied in post-transfer cells. The post-transfer cells expressed higher IL-2, proliferation and cytotoxicity ability. It was also found that the ratio of CD4 + T cell to CDa + T cell increased in post-transfer group. Conclusion Transducting IL-2 gene into CD3AK cells could enhance their immunologic functions.

  16. Bipolar zinc/oxygen battery development

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, S. [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Schlatter, C. [Swiss Federal Inst. of Technology, Lausanne (Switzerland)

    1997-06-01

    A bipolar electrically rechargeable Zn/O{sub 2} battery has been developed. Reticulated copper foam served as substrate for the zinc deposit on the anodic side, and La{sub 0.6}Ca{sub 0.4}CoO{sub 3}-catalyzed bifunctional oxygen electrodes were used on the cathodic side of the cells. The 100 cm{sup 2} unit cell had an open circuit voltage of 1,4 V(O{sub 2}) in moderately alkaline electrolyte. The open circuit voltage and the peak power measured for a stack containing seven cells were ca. 10V and 90W, respectively. The current-potential behaviour was determined as a function of the number of bipolar cells, and the maximum discharge capacity was determined at different discharge rates. (author) 4 figs., 1 ref.

  17. Bipolar Disorder in Turkey

    Directory of Open Access Journals (Sweden)

    Bulent Kadri Gultekin

    2014-06-01

    Full Text Available Assessment of studies related with bipolar disorder in Turkey did not reveal an epidemiologically qualified field study. Most of the studies are hospital based or clinical studies which did not include a systematical scanning and did not aim to collect any epidemiological data and transfer information to health authorities. The generalizability of these studies to our community is far from being valid and reliable. On the other hand, a profile which will be created by reviewing the findings of these studies performed in various regions of Turkey will have a contribution to knowing the and ldquo;unique to us and rdquo; features of bipolar disorder and determining cultural risk factors. All this information can constitute a basis for formation and development of public mental health services related with bipolar disorder. In Turkey, the need for epidemiologically significant, polycentric, public sampled studies with broad participation is indispensable. Although our psychiatric epidemiology and clinical studies include necessary scientific basis, they are not powerful enough to evaluate the authentic and progressional relations such as rapid urbanization and immigration. The aim of this review is to evaluate and discuss prominent epidemiological findings, deficiencies and possibile future activities related with studies conducted in Turkey about bipolar disorder.. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(2.000: 199-209

  18. Intravitreal delivery of a novel AAV vector targets ON bipolar cells and restores visual function in a mouse model of complete congenital stationary night blindness.

    Science.gov (United States)

    Scalabrino, Miranda L; Boye, Sanford L; Fransen, Kathryn M H; Noel, Jennifer M; Dyka, Frank M; Min, Seok Hong; Ruan, Qing; De Leeuw, Charles N; Simpson, Elizabeth M; Gregg, Ronald G; McCall, Maureen A; Peachey, Neal S; Boye, Shannon E

    2015-11-01

    Adeno-associated virus (AAV) effectively targets therapeutic genes to photoreceptors, pigment epithelia, Müller glia and ganglion cells of the retina. To date, no one has shown the ability to correct, with gene replacement, an inherent defect in bipolar cells (BCs), the excitatory interneurons of the retina. Targeting BCs with gene replacement has been difficult primarily due to the relative inaccessibility of BCs to standard AAV vectors. This approach would be useful for restoration of vision in patients with complete congenital stationary night blindness (CSNB1), where signaling through the ON BCs is eliminated due to mutations in their G-protein-coupled cascade genes. For example, the majority of CSNB1 patients carry a mutation in nyctalopin (NYX), which encodes a protein essential for proper localization of the TRPM1 cation channel required for ON BC light-evoked depolarization. As a group, CSNB1 patients have a normal electroretinogram (ERG) a-wave, indicative of photoreceptor function, but lack a b-wave due to defects in ON BC signaling. Despite retinal dysfunction, the retinas of CSNB1 patients do not degenerate. The Nyx(nob) mouse model of CSNB1 faithfully mimics this phenotype. Here, we show that intravitreally injected, rationally designed AAV2(quadY-F+T-V) containing a novel 'Ple155' promoter drives either GFP or YFP_Nyx in postnatal Nyx(nob) mice. In treated Nyx(nob) retina, robust and targeted Nyx transgene expression in ON BCs partially restored the ERG b-wave and, at the cellular level, signaling in ON BCs. Our results support the potential for gene delivery to BCs and gene replacement therapy in human CSNB1. PMID:26310623

  19. Rapid Prototyping Bipolar Plate of PEMFC by Gelcasting

    Institute of Scientific and Technical Information of China (English)

    LUO Bing; CHEN Shang-wei; HUANG Ming-yu; WANG Lian-jun

    2006-01-01

    Bipolar plate is one key component of proton exchange membrane fuel cell (PEMFC). According to this paper, mesocarbon microbeads were used as raw materials for forming the green bodies of bipolar plates with complex flow channels by gelcasting technique. Then, the final bipolar plates would be gained after the green parts were died, burned out and sintered. Meanwhile, its properties are researched and evaluated by the test of flexible strength and electric resistivity. The resultant flexural strength of sintered sample is 67 Mpa and the electric resistivity is 52 μΩ·m.

  20. Bacteriorhodopsin-based bipolar photosensor for biomimetic sensing

    Science.gov (United States)

    Kasai, Katsuyuki; Haruyama, Yoshihiro; Yamada, Toshiki; Akiba, Makoto; Tominari, Yukihiro; Kaji, Takahiro; Terui, Toshifumi; Peper, Ferdinand; Tanaka, Shukichi; Katagiri, Yoshitada; Kikuchi, Hiroshi; Okada-Shudo, Yoshiko; Otomo, Akira

    2013-10-01

    Bacteriorhodopsin (bR) is a promising biomaterial for several applications. Optical excitation of bR at an electrode-electrolyte interface generates differential photocurrents while an incident light is turned on and off. This unique functional response is similar to that seen in retinal neurons. The bR-based bipolar photosensor consists of the bR dip-coated thin films patterned on two ITO plates and the electrolyte solution. This bipolar photocell will function as a biomimetic photoreceptor cell. The bipolar structure, due to the photocurrent being generated in alignment with the cathodic direction, makes the excitatory and inhibitory regions possible. This scheme shows our bipolar cell can act as a basic unit of edge detection and forms the artificial visual receptive field.

  1. Gibberellin Signal Transduction in Rice

    Institute of Scientific and Technical Information of China (English)

    Liu-Min Fan; Xiaoyan Feng; Yu Wang; Xing Wang Deng

    2007-01-01

    In the past decade, significant knowledge has accumulated regarding gibberellin (GA) signal transduction in rice as a result of studies using multiple approaches, particularly molecular genetics. The present review highlights the recent developments in the identification of GA signaling pathway components, the discovery of GA-induced destruction of GA signaling represser (DELLA protein), and the possible mechanism underlying the regulation of GA-responsive gene expression in rice.

  2. Oxide bipolar electronics: materials, devices and circuits

    Science.gov (United States)

    Grundmann, Marius; Klüpfel, Fabian; Karsthof, Robert; Schlupp, Peter; Schein, Friedrich-Leonhard; Splith, Daniel; Yang, Chang; Bitter, Sofie; von Wenckstern, Holger

    2016-06-01

    We present the history of, and the latest progress in, the field of bipolar oxide thin film devices. As such we consider primarily pn-junctions in which at least one of the materials is a metal oxide semiconductor. A wide range of n-type and p-type oxides has been explored for the formation of such bipolar diodes. Since most oxide semiconductors are unipolar, challenges and opportunities exist with regard to the formation of heterojunction diodes and band lineups. Recently, various approaches have led to devices with high rectification, namely p-type ZnCo2O4 and NiO on n-type ZnO and amorphous zinc-tin-oxide. Subsequent bipolar devices and applications such as photodetectors, solar cells, junction field-effect transistors and integrated circuits like inverters and ring oscillators are discussed. The tremendous progress shows that bipolar oxide electronics has evolved from the exploration of various materials and heterostructures to the demonstration of functioning integrated circuits. Therefore a viable, facile and high performance technology is ready for further exploitation and performance optimization.

  3. BIPOLAR DISORDER IN ADULTS

    Directory of Open Access Journals (Sweden)

    Yadav Jaya

    2013-06-01

    Full Text Available Bipolar disorder is a chronic illness, which may require life-long treatment. Patients will spend 3-5 times more days in the depressed episode then in the manic phase. Due to this variability in episodes, polypharmacy is used quite frequently in practice, though the evidence to do this remains quite limited. Many positive and negative outcomes can occur from this practice. Bipolar disorder is the 6th leading cause of disability in the developed world among those between the ages 15 and 44 years age groups. Serotonin is one of the neurotransmitter in the brain, and one of that strongly affects the person mood. Clozapine (clozaril, olanzapine (zyperexa, risperidone (Risperdal, and ziprasidone (zeldox and the clozapine may be helpful as mood stabilizer for people who do not respond to lithium and anticonvulsant.

  4. Epilepsy and bipolar disorder.

    Science.gov (United States)

    Knott, Sarah; Forty, Liz; Craddock, Nick; Thomas, Rhys H

    2015-11-01

    It is well recognized that mood disorders and epilepsy commonly co-occur. Despite this, our knowledge regarding the relationship between epilepsy and bipolar disorder is limited. Several shared features between the two disorders, such as their episodic nature and potential to run a chronic course, and the efficacy of some antiepileptic medications in the prophylaxis of both disorders, are often cited as evidence of possible shared underlying pathophysiology. The present paper aims to review the bidirectional associations between epilepsy and bipolar disorder, with a focus on epidemiological links, evidence for shared etiology, and the impact of these disorders on both the individual and wider society. Better recognition and understanding of these two complex disorders, along with an integrated clinical approach, are crucial for improved evaluation and management of comorbid epilepsy and mood disorders.

  5. Expression of SMAD signal transduction molecules in the pancreas

    DEFF Research Database (Denmark)

    Brorson, Michael; Hougaard, D.; Nielsen, Jens Høiriis;

    2001-01-01

    Members of the TGF-beta superfamily of cytokines have been implicated in pancreatic cancer, pancreatitis and in regulation and differentiation of pancreatic endocrine and exocrine cells. Different TGF-beta members signal through phosphorylation of different signal transduction proteins, which...

  6. Life expectancy in bipolar disorder

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Vradi, Eleni; Andersen, Per Kragh

    2015-01-01

    OBJECTIVE: Life expectancy in patients with bipolar disorder has been reported to be decreased by 11 to 20 years. These calculations are based on data for individuals at the age of 15 years. However, this may be misleading for patients with bipolar disorder in general as most patients have a later...... onset of illness. The aim of the present study was to calculate the remaining life expectancy for patients of different ages with a diagnosis of bipolar disorder. METHODS: Using nationwide registers of all inpatient and outpatient contacts to all psychiatric hospitals in Denmark from 1970 to 2012 we...... remaining life expectancy in bipolar disorder and that of the general population decreased with age, indicating that patients with bipolar disorder start losing life-years during early and mid-adulthood. CONCLUSIONS: Life expectancy in bipolar disorder is decreased substantially, but less so than previously...

  7. Activity Dependent Signal Transduction in Skeletal Muscle

    Science.gov (United States)

    Hamilton, Susan L.

    1999-01-01

    The overall goals of this project are: 1) to define the initial signal transduction events whereby the removal of gravitational load from antigravity muscles, such as the soleus, triggers muscle atrophy, and 2) to develop countermeasures to prevent this from happening. Our rationale for this approach is that, if countermeasures can be developed to regulate these early events, we could avoid having to deal with the multiple cascades of events that occur downstream from the initial event. One of our major findings is that hind limb suspension causes an early and sustained increase in intracellular Ca(2+) concentration ([Ca (2+)](sub i)). In most cells the consequences of changes in ([Ca (2+)](sub i))depend on the amplitude, frequency and duration of the Ca(2+) signal and on other factors in the intracellular environment. We propose that muscle remodeling in microgravity represents a change in the balance among several CA(2+) regulated signal transduction pathways, in particular those involving the transcription factors NFAT and NFkB and the pro-apoptotic protein BAD. Other Ca(2+) sensitive pathways involving PKC, ras, rac, and CaM kinase II may also contribute to muscle remodeling.

  8. Bipolar Disorder and Cancer

    OpenAIRE

    Sermin Kesebir; Arzu Bayrak

    2012-01-01

    Prevalence studies and studies on causation relations have shown that the relation between psychiatric disorders and chronic physical diseases is neglected. For heterogeneous diseases an increasing number of susceptibility variants are being defined. Alzheimer disease, bipolar disorder, breast and prostate cancer, coronary artery disease, Chron's disease, systemic lupus eritematosus, type 1 and type 2 diabetes mellitus are mentioned together with epigenetic concept. In acrocentric zone of chr...

  9. Treatment of bipolar disorder

    OpenAIRE

    Geddes, John R.; Miklowitz, David J.

    2013-01-01

    We review recent developments in the acute and long-term treatment of bipolar disorder and identify promising future routes to therapeutic innovation. Overall, advances in drug treatment remain quite modest. Antipsychotic drugs are effective in the acute treatment of mania; their efficacy in the treatment of depression is variable with the clearest evidence for quetiapine. Despite their widespread use, considerable uncertainty and controversy remains about the use of antidepressant drugs in t...

  10. Prophylactic treatment in bipolar disorder

    OpenAIRE

    Eroğlu, Meliha Zengin; Özpoyraz, Nurgül; Tamam, Lut

    2014-01-01

    Objective: The aim of this study was to determine the prophylactic treatment response and its relationship between clinical variables among the bipolar disorder patient group followed up in the Bipolar Disorder Unit of Psychiatry Department of Cukurova University Faculty of Medicine. Methods: One hundred patients, in euthymic period, diagnosed as bipolar disorder, were included in this study. “Affective Disorders Patient Registry Form” developed by our unit, SCID-I, Young Mani Rating Scale...

  11. Mathematical models of bipolar disorder

    OpenAIRE

    Daugherty, D; Roque-Urrea, T; Urrea-Roque, J; DE TROYER, J; Wirkus, S; Porter, M. A.

    2009-01-01

    We use limit cycle oscillators to model bipolar II disorder, which is characterized by alternating hypomanic and depressive episodes and afflicts about 1% of the United States adult population. We consider two non-linear oscillator models of a single bipolar patient. In both frameworks, we begin with an untreated individual and examine the mathematical effects and resulting biological consequences of treatment. We also briefly consider the dynamics of interacting bipolar II individuals using ...

  12. The Genetics of Bipolar Disorder

    OpenAIRE

    Jennifer H Barnett; Smoller, Jordan W.

    2009-01-01

    Bipolar disorder is a mood disorder characterized by impairing episodes of mania and depression. Twin studies have established that bipolar disorder is among the most heritable of medical disorders and efforts to identify specific susceptibility genes have intensified over the past two decades. The search for genes influencing bipolar disorder has been complicated by a paucity of animal models, limited understanding of pathogenesis, and the genetic and phenotypic complexity of the syndrome. L...

  13. Mathematical Models of Bipolar Disorder

    OpenAIRE

    Daugherty, Darryl; Roque-Urrea, Tairi; Urrea-Roque, John; Snyder, Jessica; Wirkus, Stephen; Mason A. Porter

    2003-01-01

    We use limit cycle oscillators to model Bipolar II disorder, which is characterized by alternating hypomanic and depressive episodes and afflicts about one percent of the United States adult population. We consider two nonlinear oscillator models of a single bipolar patient. In both frameworks, we begin with an untreated individual and examine the mathematical effects and resulting biological consequences of treatment. We also briefly consider the dynamics of interacting bipolar II individual...

  14. Childhood trauma in bipolar disorder

    OpenAIRE

    Watson, S; Gallagher, P.; Dougall, D.; R Porter; Moncrieff, J.; Ferrier, I. N.; Young, A. H.

    2014-01-01

    Objective: There has been little investigation of early trauma in bipolar disorder despite evidence that stress impacts on the course of this illness. We aimed to compare the rates of childhood trauma in adults with bipolar disorder to a healthy control group, and to investigate the impact of childhood trauma on the clinical course of bipolar disorder. Methods: Retrospective assessment of childhood trauma was conducted using the Childhood Trauma Questionnaire (CTQ) in 60 outpatients with bipo...

  15. Bipolar Disorder in Children and Teens

    Science.gov (United States)

    ... is in crisis. What do I do? Share Bipolar Disorder in Children and Teens Download PDF Download ePub ... brochure will give you more information. What is bipolar disorder? Bipolar disorder is a serious brain illness. It ...

  16. Bipolar Disorder and Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Sermin Kesebir

    2010-04-01

    Full Text Available Comorbid endocrine and cardiovascular situations with bipolar disorder usually result from the bipolar disorder itself or as a consequence of its treatment. With habits and lifestyle, genetic tendency and side effects, this situation is becoming more striking. Subpopulations of bipolar disorders patients should be considered at high risk for diabetes mellitus. The prevalence of diabetes mellitus in bipolar disorder may be three times greater than in the general population. Comorbidity of diabetes causes a pathophysiological overlapping in the neurobiological webs of bipolar cases. Signal mechanisms of glycocorticoid/insulin and immunoinflammatory effector systems are junction points that point out the pathophysiology between bipolar disorder and general medical cases susceptible to stress. Glycogen synthetase kinase (GSK-3 is a serine/treonine kinase and inhibits the transport of glucose stimulated by insulin. It is affected in diabetes, cancer, inflammation, Alzheimer disease and bipolar disorder. Hypoglycemic effect of lithium occurs via inhibiting glycogen synthetase kinase. When comorbid with diabetes, the other disease -for example bipolar disorder, especially during its acute manic episodes-, causes a serious situation that presents its influences for a lifetime. Choosing pharmacological treatment and treatment adherence are another important interrelated areas. The aim of this article is to discuss and review the etiological, clinical and therapeutic properties of diabetes mellitus and bipolar disorder comorbidity.

  17. 质子交换膜燃料电池双极板的研究进展%Research progress on bipolar plates for proton exchange membrane fuel cells

    Institute of Scientific and Technical Information of China (English)

    王海鹏; 王海人; 屈钧娥; 曹志勇

    2014-01-01

    质子交换膜燃料电池(PEM FC )具有使用寿命长,比功率和比能量高,室温下启动速度快等优点,已经成为燃料电池行业研究的热点。如何制得低成本高效率且使用寿命长的双极板是质子交换膜燃料电池商业化的关键。本文归纳了国内外有关质子交换膜燃料电池双极板材料的研究进展,并重点综述了金属双极板的优缺点和表面改性技术。%Research on proton exchange membrane fuel cells (PEMFC) is a hot issue in the field of fuel cell . PEM FC possess normal characteristics (high efficiency in energy transformation ,environmental friendli‐ness ,broad application ,and so on) of fuel cells ,as well as many prominent properties such as easy start‐up at room temperature ,longevity ,high specific power and energy .Development of low‐cost and high‐ef‐ficient long‐life bipolar plates is crucial to the realization of commercial value of PEMFC .This paper is the conclusion of worldwide research on bipolar plate materials .It has mainly reviewed studies on the surface modification methods as well as the merits and defects of metallic bipolar plates .

  18. Highly active microbial phosphoantigen induces rapid yet sustained MEK/Erk- and PI-3K/Akt-mediated signal transduction in anti-tumor human gammadelta T-cells.

    Directory of Open Access Journals (Sweden)

    Daniel V Correia

    Full Text Available BACKGROUND: The unique responsiveness of Vgamma9Vdelta2 T-cells, the major gammadelta subset of human peripheral blood, to non-peptidic prenyl pyrophosphate antigens constitutes the basis of current gammadelta T-cell-based cancer immunotherapy strategies. However, the molecular mechanisms responsible for phosphoantigen-mediated activation of human gammadelta T-cells remain unclear. In particular, previous reports have described a very slow kinetics of activation of T-cell receptor (TCR-associated signal transduction pathways by isopentenyl pyrophosphate and bromohydrin pyrophosphate, seemingly incompatible with direct binding of these antigens to the Vgamma9Vdelta2 TCR. Here we have studied the most potent natural phosphoantigen yet identified, (E-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP, produced by Eubacteria and Protozoa, and examined its gammadelta T-cell activation and anti-tumor properties. METHODOLOGY/PRINCIPAL FINDINGS: We have performed a comparative study between HMB-PP and the anti-CD3epsilon monoclonal antibody OKT3, used as a reference inducer of bona fide TCR signaling, and followed multiple cellular and molecular gammadelta T-cell activation events. We show that HMB-PP activates MEK/Erk and PI-3K/Akt pathways as rapidly as OKT3, and induces an almost identical transcriptional profile in Vgamma9(+ T-cells. Moreover, MEK/Erk and PI-3K/Akt activities are indispensable for the cellular effects of HMB-PP, including gammadelta T-cell activation, proliferation and anti-tumor cytotoxicity, which are also abolished upon antibody blockade of the Vgamma9(+ TCR Surprisingly, HMB-PP treatment does not induce down-modulation of surface TCR levels, and thereby sustains gammadelta T-cell activation upon re-stimulation. This ultimately translates in potent human gammadelta T-cell anti-tumor function both in vitro and in vivo upon transplantation of human leukemia cells into lymphopenic mice, CONCLUSIONS/SIGNIFICANCE: The development of

  19. The Role of Cgrp-Receptor Component Protein (Rcp in Cgrp-Mediated Signal Transduction

    Directory of Open Access Journals (Sweden)

    M. A. Prado

    2001-01-01

    Full Text Available The calcitonin gene-related peptide (CGRP-receptor component protein (RCP is a 17-kDa intracellular peripheral membrane protein required for signal transduction at CGRP receptors. To determine the role of RCP in CGRP-mediated signal transduction, RCP was depleted from NIH3T3 cells using antisense strategy. Loss of RCP protein correlated with loss of cAMP production by CGRP in the antisense cells. In contrast, loss of RCP had no effect on CGRP-mediated binding; therefore RCP is not acting as a chaperone for the CGRP receptor. Instead, RCP is a novel signal transduction molecule that couples the CGRP receptor to the cellular signal transduction machinery. RCP thus represents a prototype for a new class of signal transduction proteins that are required for regulation of G protein-coupled receptors.

  20. Resveratrol inhibits phosphorylation within the signal transduction and activator of transcription 3 signaling pathway by activating sirtuin 1 in SW1353 chondrosarcoma cells.

    Science.gov (United States)

    Jin, Haidong; Chen, Hui; Yu, Kehe; Zhang, Jingdong; Li, Bin; Cai, Ningyu; Pan, Jun

    2016-09-01

    The present study assessed the mechanism by which resveratrol (Res) inhibits the growth of SW1353 chondrosarcoma cells and examined whether sirtuin 1 (Sirt1) activation affects phosphorylation within the signal transduction and activator of transcription 3 (STAT3) signaling pathway. The present study used SW1353 chondrosarcoma cells in the logarithmic phase of growth (control and treatment groups). The latter group was treated with Res at 25 and 50 µmol/l for 24 h, and cell viability, proliferation and apoptosis were analyzed using the cell counting kit‑8 assay, colony counting and Hoechst staining, respectively. The expression levels of caspase‑3, cleaved caspase‑3, B‑cell lymphoma‑2 (BCL‑2), BCL-2 associated X protein (Bax), STAT3 and phosphorylated (p‑)STAT3) were measured by Western blotting. SW1353 cells were transfected with small interfering (si)RNA targeting Sirt1 and the expression levels of Sirt1, STAT3 and p-STAT3 were assessed. Exposure of SW1353 cells to Res reduced cell viability in a dose‑dependent manner (P<0.01). Additionally, cell proliferation was significantly inhibited and the cell nuclei exhibited apoptotic characteristics. Cleaved caspase‑3, Sirt1 and Bax levels were upregulated. The expression levels of BCL‑2 and p‑STAT3 were downregulated. Additionally, the BCL‑2/Bax ratio was reduced compared with the control group. The total STAT3 level was unaffected. Res treatment activated Sirt1, however, in cells transfected with Sirt1‑siRNA, the ability of resveratrol to suppress p‑STAT3 expression was compromised. Overall, it was revealed that Res treatment induced apoptosis, inhibited proliferation and affected phosphorylation within the STAT3 signaling pathway by activating Sirt1 in SW1353 chondrosarcoma cells.

  1. Effects of adenoviral-mediated gene transduction of NK4 on proliferation, movement, and invasion of human colonic LS174T cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Jian-Zheng Jie; Jian-Wei Wang; Jian-Guo Qu; Wei Wang; Tao Hung

    2006-01-01

    AIM: To investigate the inhibitory effects of a recombinant adenovirus vector that expresses NK4,a truncated form of human hepatocyte growth factor (HGF), on human colonic adenocarcinoma cells in vitro to establish a basis for future NK4 gene cancer therapy.METHODS: Cells from the LS174T human colonic adenocarcinoma cell line were infected with recombinant adenovirus rvAdCMV/NK4 and the effects of the manipulation on tumor cell proliferation, scatter,migration, and basement membrane invasion were assessed. Cells infected with a recombinant adenovirus vector (Ad-LacZ) expressing β-galactosidase served as the controls.RESULTS: We found that rvAdCMV/NK4 expression attenuated HGF-induced tumor cell scatter, migration,and basement membrane invasion (P < 0.05), but did not inhibit tumor cell proliferation.CONCLUSION: HGF-induced LS174T tumor cell scatter,migration, and invasion can be antagonized by the recombinant NK4-expressing adenovirus.

  2. Corrosion behaviour of austenitic stainless steel as a function of methanol concentration for direct methanol fuel cell bipolar plate

    Science.gov (United States)

    Wang, Lixia; Kang, Bin; Gao, Na; Du, Xiao; Jia, Linan; Sun, Juncai

    2014-05-01

    The corrosion behaviour of an AISI 304 stainless steel (304 SS) is investigated in aqueous acid methanol solutions (0.5 M H2SO4 + 2 ppm HF + x M CH3OH, x = 0, 1, 5, 10 and 20) at 50 °C to simulate the varied anodic operating conditions of direct methanol fuel cells. Electrochemical measurements including potentiodynamic polarisation, potentiostatic polarisation and electrochemical impedance spectroscopy tests, are employed to analyse the corrosion behaviour. The results reveal that the corrosion resistance of 304 SS is enhanced in solutions with higher methanol content. Scanning electron microscopy and inductively coupled plasma atomic emission spectrometry data indicate that the surface corrosion on 304 SS is alleviated when the methanol concentration is increased. According to the X-ray photoelectron spectroscopy and Mott-Schottky analyses, the passive films formed on the 304 SS after potentiostatic tests in all the test solutions are composed of a duplex electronic structure with an external n-type semiconductor layer and an internal p-type semiconductor layer. Further analyses of the surface conductivity conducted by measuring the interfacial contact resistance between the 304 SS and carbon paper reveal that the passive film formed in the solution with higher methanol content exhibits lower conductivity.

  3. 燃料电池双极板材料趋肤效应的模拟研究%Simulation of skin effect in bipolar plate material of fuel cell

    Institute of Scientific and Technical Information of China (English)

    姚聪; 罗马吉; 罗志平

    2011-01-01

    燃料电池在动态负载输出时,电池内有趋肤效应现象产生.对不锈钢圆柱导体中的趋肤效应现象进行了模拟研究,并将模拟计算结果与理论计算结果进行比较,两者有很好的一致性.在此基础上,模拟研究了燃料电池双极板采用不同材料和不同形状时其趋肤效应现象.计算结果表明:由于趋肤效应作用,双极板边缘电流密度远大于中心电流密度,并且金属材料的趋肤效应比石墨材料更明显;增加双极板横截面长宽比可以减小电流密度的趋肤效应作用.%The skin effect phenomenon generates in fuel cell when it works at an instable condition. In this article, the modeling study of the skin effect in a cylindrical stainless steel conductor was carried out. The simulation results are agreed well with the theory results. Then the skin effects in fuel cell bipolar plates which were in different materials and shapes were numerically investigated. The simulation results show that the edge current density is greater than the center current density in the bipolar plate because of the skin effect, and the skin effect of the metal material is more obvious than that of the graphite material. With the increase of the ratio between the length and the width of the bipolar plate cross section, the skin effect of current density reduces.

  4. Physical aspects of sensory transduction on seeing, hearing and smelling

    Science.gov (United States)

    Yoshioka, Tohru; Sakakibara, Manabu

    2013-01-01

    What is the general principle of sensory transduction? Sensory transduction is defined as energy transformation from the external world to the internal world. The energy of the external world, such as thermal energy (heat), electro-magnetic energy (light), mechanical energy (sound) and the energy from molecules (chemicals), is converted into electrochemical events in the animal nervous system. The following five classes of special sense receptors are utilized for energy conversion: vision (photo); audition (sound); taste and smell (chemo); and tactile (mechano). There are also other special sense receptors, including thermo and noxious receptors. The focus of this study is on photoreceptors, sound-receptors and odorant-receptors because the transduction mechanisms of these receptors are explained biochemically and understood by a common physical principle; these biochemical models are well known in neuroscience. The following notable problems are inherent in these biochemical models: the cGMP ionophore model of the vertebrate photoreceptor cannot explain the fast photo-response (∼msec); the tip links connection model of stereocilia in the basilar membrane for opening the K+ channel on the tip of a hair has difficulty explaining the high frequency vibration of hair cells without a damping of the oscillation, and the odorant shape-specific receptor model for olfactory transduction has difficulty in discriminating the minute differences among similar fragrant smells of essential oils with different molecular shapes. These difficulties might arise from a lack of the physical sense when the transduction models were proposed. This article will reconsider these problems and propose rational models for visual, olfactory and auditory transduction. PMID:27493557

  5. An Electrochromic Bipolar Membrane Diode.

    Science.gov (United States)

    Malti, Abdellah; Gabrielsson, Erik O; Crispin, Xavier; Berggren, Magnus

    2015-07-01

    Conducting polymers with bipolar membranes (a complementary stack of selective membranes) may be used to rectify current. Integrating a bipolar membrane into a polymer electrochromic display obviates the need for an addressing backplane while increasing the device's bistability. Such devices can be made from solution-processable materials.

  6. Sensory Transduction in Caenorhabditis elegans

    Science.gov (United States)

    Brown, Austin L.; Ramot, Daniel; Goodman, Miriam B.

    The roundworm Caenorhabditis elegans has a well-defined and comparatively simple repertoire of sensory-guided behaviors, all of which rely on its ability to detect chemical, mechanical or thermal stimuli. In this chapter, we review what is known about the ion channels that mediate sensation in this remarkable model organism. Genetic screens for mutants defective in sensory-guided behaviors have identified genes encoding channel proteins, which are likely transducers of chemical, thermal, and mechanical stimuli. Such classical genetic approaches are now being coupled with molecular genetics and in vivo cellular physiology to elucidate how these channels are activated in specific sensory neurons. The ion channel superfamilies implicated in sensory transduction in C. elegans - CNG, TRP, and DEG/ENaC - are conserved across phyla and also appear to contribute to sensory transduction in other organisms, including vertebrates. What we learn about the role of these ion channels in C. elegans sensation is likely to illuminate analogous processes in other animals, including humans.

  7. Protein tyrosine kinases p53/56lyn and p72syk in MHC class I-mediated signal transduction in B lymphoma cells

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Bregenholt, S; Skov, S;

    1998-01-01

    Crosslinking of major histocompatibility complex class I (MHC-I) molecules on the surface of human B lymphoma cells was shown to induce protein tyrosine phosphorylation and mobilization of intracellular free calcium. Immunoprecipitations indicated that the protein tyrosine kinases p53/56lyn and p72......syk are among the tyrosine-phosphorylated proteins. The kinetics of phosphorylation of these kinases after MHC-I crosslinking differ from the kinetics observed after crosslinking of the B cell antigen receptor (BCR). Additional experiments were performed with chicken lyn- and syk-negative DT40 B cells...... and the results indicate that these two kinases have different substrate specificity and regulate intracellular free calcium differently in response to MHC-I crosslinking. In addition MHC-I crosslinking of a sIgM-negative DT40 chicken B cell variant results in less activity of tyrosine kinases and less...

  8. Genetics of bipolar disorder

    Directory of Open Access Journals (Sweden)

    Kerner B

    2014-02-01

    Full Text Available Berit Kerner Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA Abstract: Bipolar disorder is a common, complex genetic disorder, but the mode of transmission remains to be discovered. Many researchers assume that common genomic variants carry some risk for manifesting the disease. The research community has celebrated the first genome-wide significant associations between common single nucleotide polymorphisms (SNPs and bipolar disorder. Currently, attempts are under way to translate these findings into clinical practice, genetic counseling, and predictive testing. However, some experts remain cautious. After all, common variants explain only a very small percentage of the genetic risk, and functional consequences of the discovered SNPs are inconclusive. Furthermore, the associated SNPs are not disease specific, and the majority of individuals with a “risk” allele are healthy. On the other hand, population-based genome-wide studies in psychiatric disorders have rediscovered rare structural variants and mutations in genes, which were previously known to cause genetic syndromes and monogenic Mendelian disorders. In many Mendelian syndromes, psychiatric symptoms are prevalent. Although these conditions do not fit the classic description of any specific psychiatric disorder, they often show nonspecific psychiatric symptoms that cross diagnostic boundaries, including intellectual disability, behavioral abnormalities, mood disorders, anxiety disorders, attention deficit, impulse control deficit, and psychosis. Although testing for chromosomal disorders and monogenic Mendelian disorders is well established, testing for common variants is still controversial. The standard concept of genetic testing includes at least three broad criteria that need to be fulfilled before new genetic tests should be introduced: analytical validity, clinical validity, and clinical utility. These criteria are

  9. Scientific attitudes towards bipolar disorders

    Directory of Open Access Journals (Sweden)

    Mohammad-Hossein Biglu

    2014-02-01

    Full Text Available Introduction: Bipolar disorder is a psychiatric condition that is also called manic-depressive disease. It causes unusual changes in mood, energy, activity levels, and the ability to carry out day-to-day tasks. In the present study, 3 sets of data were considered and analyzed: first, all papers categorized under Bipolar Disorders in Science Citation Index Expanded (SCI-E database through 2001-2011; second, papers published by the international journal of Bipolar Disorders indexed in SCI-E during a period of 11 years; and third, all papers distributed by the international journal of Bipolar Disorders indexed in MEDLINE during the period of study. Methods: The SCI-E database was used to extract all papers indexed with the topic of Bipolar Disorders as well as all papers published by The International Journal of Bipolar Disorders. Extraction of data from MEDLINE was restricted to the journals name from setting menu. The Science of Science Tool was used to map the co-authorship network of papers published by The International Journal of Bipolar Disorders through 2009-2011. Results: Analysis of data showed that the majority of publications in the subject area of bipolar disorders indexed in SCI-E were published by The International Journal of Bipolar Disorders. Although journal articles consisted of 59% of the total publication type in SCI-E, 65% of publications distributed by The Journal of Bipolar Disorders were in the form of meetingabstracts. Journal articles consisted of only 23% of the total publications. USA was the leading country regarding sharing data in the field of bipolar disorders followed by England, Canada, and Germany. Conclusion: The editorial policy of The International Journal of Bipolar Disorders has been focused on new themes and new ways of researching in the subject area of bipolar disorder. Regarding the selection of papers for indexing, the SCI-E database selects data more comprehensively than MEDLINE. The number of papers

  10. Host Signal Transduction and Protein Kinases Implicated in Legionella Infection

    OpenAIRE

    Hempstead, Andrew D.; Isberg, Ralph R.

    2013-01-01

    Modulation of the phosphorylation status of proteins by both kinases and phosphatases plays an important role in cellular signal transduction. Challenge of host cells by Legionella pneumophila manipulates the phosphorylation state of multiple host factors. These changes play roles in bacterial uptake, vacuole modification, cellular survival, and the immune response. In addition to modification by host cell kinases in response to the bacterium, L. pneumophila translocates bacterial kinases int...

  11. Tobacco Use in Bipolar Disorder

    Science.gov (United States)

    Thomson, Daniel; Berk, Michael; Dodd, Seetal; Rapado-Castro, Marta; Quirk, Shae E.; Ellegaard, Pernille K.; Berk, Lesley; Dean, Olivia M.

    2015-01-01

    Tobacco use in mental health in general and bipolar disorder in particular remains disproportionally common, despite declining smoking rates in the community. Furthermore, interactions between tobacco use and mental health have been shown, indicating the outcomes for those with mental health disorders are impacted by tobacco use. Factors need to be explored and addressed to improve outcomes for those with these disorders and target specific interventions for people with psychiatric illness to cease tobacco smoking. In the context of bipolar disorder, this review explores; the effects of tobacco smoking on symptoms, quality of life, suicidal behaviour, the biological interactions between tobacco use and bipolar disorder, the interactions between tobacco smoking and psychiatric medications, rates and factors surrounding tobacco smoking cessation in bipolar disorder and suggests potential directions for research and clinical translation. The importance of this review is to bring together the current understanding of tobacco use in bipolar disorder to highlight the need for specific intervention. PMID:25912533

  12. Bipolar Disorder and Childhood Trauma

    Directory of Open Access Journals (Sweden)

    Evrim Erten

    2015-06-01

    Full Text Available Bipolar disorder is a chronic disorder in which irregular course of depressive, mania or mixed episodes or a complete recovery between episodes can be observed. The studies about the effects of traumatic events on bipolar disorder showed that they had significant and long-term effects on the symptoms of the disorder. Psychosocial stress might change the neurobiology of bipolar disorder over time. The studies revealed that the traumatic events could influence not only the onset of the disorder but also the course of the disorder and in these patients the rate of suicide attempt and comorbid substance abuse might increase. Bipolar patients who had childhood trauma had an earlier onset, higher number of episodes and comorbid disorders. In this review, the relationship between childhood trauma and bipolar disorder is reviewed. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(2: 157-165

  13. Secretory TAT-peptide-mediated protein transduction of LIF receptor α-chain distal cytoplasmic motifs into human myeloid HL-60 cells

    Directory of Open Access Journals (Sweden)

    Q. Sun

    2012-10-01

    Full Text Available The distal cytoplasmic motifs of leukemia inhibitory factor receptor α-chain (LIFRα-CT3 can independently induce intracellular myeloid differentiation in acute myeloid leukemia (AML cells by gene transfection; however, there are significant limitations in the potential clinical use of these motifs due to liposome-derived genetic modifications. To produce a potentially therapeutic LIFRα-CT3 with cell-permeable activity, we constructed a eukaryotic expression pcDNA3.0-TAT-CT3-cMyc plasmid with a signal peptide (ss inserted into the N-terminal that codes for an ss-TAT-CT3-cMyc fusion protein. The stable transfection of Chinese hamster ovary (CHO cells via this vector and subsequent selection by Geneticin resulted in cell lines that express and secrete TAT-CT3-cMyc. The spent medium of pcDNA3.0-TAT-CT3-cMyc-transfected CHO cells could be purified using a cMyc-epitope-tag agarose affinity chromatography column and could be detected via SDS-PAGE, with antibodies against cMyc-tag. The direct administration of TAT-CT3-cMyc to HL-60 cell culture media caused the enrichment of CT3-cMyc in the cytoplasm and nucleus within 30 min and led to a significant reduction of viable cells (P < 0.05 8 h after exposure. The advantages of using this mammalian expression system include the ease of generating TAT fusion proteins that are adequately transcripted and the potential for a sustained production of such proteins in vitro for future AML therapy.

  14. Secretory TAT-peptide-mediated protein transduction of LIF receptor α-chain distal cytoplasmic motifs into human myeloid HL-60 cells

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Q. [Department of Hyperbaric Medicine, No. 401 Hospital of PLA, Qingdao (China); Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China); Xiong, J. [Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China); Lu, J. [Office of Medical Education, Training Department, Second Military Medical University, Shanghai (China); Xu, S. [Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China); Li, Y. [State Food and Drug Administration of China,Huangdao Branch, Qingdao (China); Zhong, X.P.; Gao, G.K. [Department of Hyperbaric Medicine, No. 401 Hospital of PLA, Qingdao (China); Liu, H.Q. [2Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China)

    2012-06-22

    The distal cytoplasmic motifs of leukemia inhibitory factor receptor α-chain (LIFRα-CT3) can independently induce intracellular myeloid differentiation in acute myeloid leukemia (AML) cells by gene transfection; however, there are significant limitations in the potential clinical use of these motifs due to liposome-derived genetic modifications. To produce a potentially therapeutic LIFRα-CT3 with cell-permeable activity, we constructed a eukaryotic expression pcDNA3.0-TAT-CT3-cMyc plasmid with a signal peptide (ss) inserted into the N-terminal that codes for an ss-TAT-CT3-cMyc fusion protein. The stable transfection of Chinese hamster ovary (CHO) cells via this vector and subsequent selection by Geneticin resulted in cell lines that express and secrete TAT-CT3-cMyc. The spent medium of pcDNA3.0-TAT-CT3-cMyc-transfected CHO cells could be purified using a cMyc-epitope-tag agarose affinity chromatography column and could be detected via SDS-PAGE, with antibodies against cMyc-tag. The direct administration of TAT-CT3-cMyc to HL-60 cell culture media caused the enrichment of CT3-cMyc in the cytoplasm and nucleus within 30 min and led to a significant reduction of viable cells (P < 0.05) 8 h after exposure. The advantages of using this mammalian expression system include the ease of generating TAT fusion proteins that are adequately transcripted and the potential for a sustained production of such proteins in vitro for future AML therapy.

  15. IN VITRO STUDY ON THE CLONING AND TRANSDUCTION OF HUMAN O6-METHYLGUANINE-DNA-METHYLTRANSFERASE CDNA INTO HUMAN UMBILICAL CORD BLOOD CD34+ CELLS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To explore whether human umbilical cord blood hematopoietic progenitor cells transduced with human O6-methylguanine-DNA-methyltransferase (MGMT) gene could increase resistance to 1,3-Bis(2-Chloroethyl)-1-Nitrosourea (BCNU). Methods: The cDNA encoding the MGMT was isolated by using RT-PCR method from total RNA of fresh human liver, the fragment was cloned into pGEM-T vector and further subcloned into G1Na retrovirus vector. Then the G1Na-MGMT was transduced into the packaging cell lines GP+E86 and PA317 by LipofectAMINE. By using the medium containing BCNU for cloning selection and ping-ponging supernatant infection between ecotropic producer clone and amphotropic producer clone, high titer amphotropic PA317 producer clone with the highest titer up to 5.8′ 105 CFU/ml was obtained. Cord blood CD34+ cells were transfected repeatedly with supernatant of retrovirus containing human MGMT-cDNA under stimulation of hemopoietic growth factors. Results: The retrovirus vector construction was verified by restriction endonuclease analysis and DNA sequencing. PCR, RT-PCR, Southern Blot, Western Blot and MTT analyses showed that MGMT drug resistance gene has been integrated into the genomic DNA of cord blood CD34+ cells and expressed efficiently. The transgene cord blood CD34+ cells conferred 4-folds stronger resistance to BCNU than untransduced cells. Conclusion: The retrovirus vector-mediated transfer of MGMT drug resistance gene into human cord blood CD34+ cells and its expression provided an experimental foundation for gene therapy in clinical trial.

  16. Girdin/GIV is upregulated by cyclic tension, propagates mechanical signal transduction, and is required for the cellular proliferation and migration of MG-63 cells

    International Nuclear Information System (INIS)

    To explore how Girdin/GIV is regulated by cyclic tension and propagates downstream signals to affect cell proliferation and migration. Human osteoblast-like MG-63 cells were exposed to cyclic tension force at 4000 μstrain and 0.5 Hz for 6 h, produced by a four-point bending system. Cyclic tension force upregulated Girdin and Akt expression and phosphorylation in cultured MG-63 cells. Girdin and Akt each promoted the phosphorylation of the other under stimulated tension. In vitro MTT and transwell assays showed that Girdin and Akt are required for cell proliferation and migration during cellular quiescence. Moreover, STAT3 was determined to be essential for Girdin expression under stimulated tension force in the physiological condition, as well as for osteoblast proliferation and migration during quiescence. These findings suggest that the STAT3/Girdin/Akt pathway activates in osteoblasts in response to mechanical stimulation and may play a significant role in triggering osteoblast proliferation and migration during orthodontic treatment. - Highlights: • Tension force upregulates Girdin and Akt expression and phosphorylation. • Girdin and Akt promotes the phosphorylation of each other under tension stimulation. • Girdin and Akt are required for MG-63 cell proliferation and migration. • STAT3 is essential for Girdin expression after application of the tension forces

  17. An increase in galectin-3 causes cellular unresponsiveness to IFN-γ-induced signal transduction and growth inhibition in gastric cancer cells

    Science.gov (United States)

    Tseng, Po-Chun; Chen, Chia-Ling; Shan, Yan-Shen; Lin, Chiou-Feng

    2016-01-01

    Glycogen synthase kinase (GSK)-3β facilitates interferon (IFN)-γ signaling by inhibiting Src homology-2 domain-containing phosphatase (SHP) 2. Mutated phosphoinositide 3-kinase (PI3K) and phosphatase and tensin homolog (PTEN) cause AKT activation and GSK-3β inactivation to induce SHP2-activated cellular unresponsiveness to IFN-γ in human gastric cancer AGS cells. This study investigated the potential role of galectin-3, which acts upstream of AKT/GSK-3β/SHP2, in gastric cancer cells. Increasing or decreasing galectin-3 altered IFN-γ signaling. Following cisplatin-induced galectin-3 upregulation, surviving cells showed cellular unresponsiveness to IFN-γ. Galectin-3 induced IFN-γ resistance independent of its extracellular β-galactoside-binding activity. Galectin-3 expression was not regulated by PI3K activation or by a decrease in PTEN. Increased galectin-3 may cause GSK-3β inactivation and SHP2 activation by promoting PDK1-induced AKT phosphorylation at a threonine residue. Overexpression of AKT, inactive GSK-3βR96A, SHP2, or active SHP2D61A caused cellular unresponsiveness to IFN-γ in IFN-γ-sensitive MKN45 cells. IFN-γ-induced growth inhibition and apoptosis in AGS cells were observed until galectin-3 expression was downregulated. These results demonstrate that an increase in galectin-3 facilitates AKT/GSK-3β/SHP2 signaling, causing cellular unresponsiveness to IFN-γ. PMID:26934444

  18. Girdin/GIV is upregulated by cyclic tension, propagates mechanical signal transduction, and is required for the cellular proliferation and migration of MG-63 cells

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Jiang-Tian; Li, Yan; Yu, Bing; Gao, Guo-Jie; Zhou, Ting; Li, Song, E-mail: song_li59@126.com

    2015-08-21

    To explore how Girdin/GIV is regulated by cyclic tension and propagates downstream signals to affect cell proliferation and migration. Human osteoblast-like MG-63 cells were exposed to cyclic tension force at 4000 μstrain and 0.5 Hz for 6 h, produced by a four-point bending system. Cyclic tension force upregulated Girdin and Akt expression and phosphorylation in cultured MG-63 cells. Girdin and Akt each promoted the phosphorylation of the other under stimulated tension. In vitro MTT and transwell assays showed that Girdin and Akt are required for cell proliferation and migration during cellular quiescence. Moreover, STAT3 was determined to be essential for Girdin expression under stimulated tension force in the physiological condition, as well as for osteoblast proliferation and migration during quiescence. These findings suggest that the STAT3/Girdin/Akt pathway activates in osteoblasts in response to mechanical stimulation and may play a significant role in triggering osteoblast proliferation and migration during orthodontic treatment. - Highlights: • Tension force upregulates Girdin and Akt expression and phosphorylation. • Girdin and Akt promotes the phosphorylation of each other under tension stimulation. • Girdin and Akt are required for MG-63 cell proliferation and migration. • STAT3 is essential for Girdin expression after application of the tension forces.

  19. Structure improvement and electrochemical studies of bipolar nickel metal hydride batteries for hybrid electric vehicles

    Institute of Scientific and Technical Information of China (English)

    DENG Chao; SHI Peng-fei

    2006-01-01

    Nickel metal hydride battery in bipolar design offers some advantages for its application as a power storage system for electric and hybrid vehicles. This paper deals with the structure design and electrochemical studies of bipolar Ni/MH batteries for hybrid vehicles. An improvement is applied in bipolar battery design,and such bipolar Ni/MH batteries with 5 sub-cells have been assembled and investigated. Testing results show that bipolar batteries with improved structure have better compression tolerance and cycle performance than conventional ones. In addition, the improved bipolar batteries display excellent large current discharge ability and high power density. As simulating working conditions for hybrid vehicles, the batteries show good stability during pulse cycles, which verifies the possibility of being used as a power storage device on hybrid vehicles.

  20. Construction Of An Optimized Lentiviral Vector Containing Pdx-1 Gene For Transduction Of Stem Cells Towards Gene Therapy Diabetes Type 1

    Directory of Open Access Journals (Sweden)

    S Rahmati

    2013-02-01

    Full Text Available Abstract Background & aim: Nowadays, most of gene therapy protocols are performed by lentiviral vectors. One of the most important factors which is involved in pancreas development and transcription of insulin gene is pancreatic & duodenal homeobox 1 (PDX-1 transcription factor. The goal of this study was to optimize a lentiviral construct, containing pdx-1 gene, to transfect stem cells towards gene therapy of type-1 diabetes. Methods: In this experimental study, first, the pdx-1 gene was multiplied by PCR from pcDNA3.1-pdx-1 and cloned into pTG19-T vector. Then, pdx-1 was subcloned on upstream of IRES-EGFP gene into IRES2-EGFP vector. At the next step, the cloned parts of IRES-EGFP and pdx-1 were isolated and cloned into the lentiviral expression vector pSINTREM in upstream of TRE-CMV gene. After sequencing, final construct was transfected into HEK 293 cells and gene expression of pdx-1 was evaluated using flow cytometry analysis and reverse fluorescent microscopy. Results: Flow cytometry results and inverted fluorescent microscopy observing showed that pdx-1 and GFP genes are expressed in cells transfected with final recombinant construct. Conclusion: Regarding the design of this construct, to ensure long time expression with higher in vivo and in vitro expression efficiency for stem cells and also use of Tet on induced optimized system, it seems that the current construct can be among the best ones to transfect stem cells. Key words: Gene therapy, Diabetes, Stem cells

  1. Empirical study of unipolar and bipolar configurations using high resolution single multi-walled carbon nanotube electrodes for electrophysiological probing of electrically excitable cells

    International Nuclear Information System (INIS)

    Identifying the neurophysiological basis underlying learning and memory in the mammalian central nervous system requires the development of biocompatible, high resolution, low electrode impedance electrophysiological probes; however, physically, electrode impedance will always be finite and, at times, large. Herein, we demonstrate through experiments performed on frog sartorius muscle that single multi-walled carbon nanotube electrode (sMWNT electrode) geometry and placement are two degrees of freedom that can improve biocompatibility of the probe and counteract the detrimental effects of MWNT/electrolyte interface impedance on the stimulation efficiency and signal-to-noise ratio (SNR). We show that high aspect ratio dependent electric field enhancement at the MWNT tip can boost stimulation efficiency. Derivation of the sMWNT electrode's electrical equivalent indicates that, at low stimulus voltage regimes below 1 V, current conduction is mediated by charge fluctuation in the double layer obviating electrolysis of water, which is potentially toxic to pH sensitive biological tissue. Despite the accompanying increase in electrode impedance, a pair of closely spaced sMWNT electrodes in a two probe (bipolar) configuration maintains biocompatibility and enhances stimulation efficiency and SNR compared to the single probe (unipolar) configuration. For stimulus voltages below 1 V, the electrical equivalent verifies that current conduction in the two probe configuration still proceeds via charge fluctuation in the double layer. As an extracellular stimulation electrode, the two sMWNT electrodes comprise a current dipole that concentrates the electric field and the current density in a smaller region of sartorius; consequently, the bipolar configuration can elicit muscle fiber twitching at low voltages that preclude electrolysis of water. When recording field potentials, the bipolar configuration subtracts the potential between two points allowing for the detection of

  2. Development of Novel Bipolar Nickel/Metal Hydride Batteries for Hybrid Electric Vehicles

    Institute of Scientific and Technical Information of China (English)

    邓超; 史鹏飞; 张森

    2005-01-01

    This paper deals with the design and development of bipolar Ni/MH batteries. After optimizing the parameters of bipolar plates by adjusting electrode thickness and modifying the capacity ratio of two adjacent electrodes of a single cell, some bipolar Ni/MH stacks with a voltage of 6 V were assembled and examined. Electrochemical testing results showed that the bipolar battery has excellent high rate discharge and recharge characteristics, satisfying pulse discharge performance even in a low state of charge (SOC). Moreover, the battery showed good stability during pulse cycles as simulating hybrid electric vehicle working conditions. It would be a promising alternative for power storage system in hybrid electxic vehicles.

  3. Granulosa cells from bovine follicles activate different signal transduction pathways dependent on follicle health status and ability to convert androstenedione to estrogen

    Science.gov (United States)

    Since steroidogenesis is a critical component in the development of competent preovulatory follicles we hypothesized that granulosa cells from follicles of cows treated with normal levels of progesterone (CIDR) or with melengestrol acetate (MGA), which results in the development of persistent follic...

  4. Lentiviral vector-mediated transduction of goat undifferentiated spermatogonia.

    Science.gov (United States)

    Abbasi, Hassan; Hosseini, Sayyed Morteza; Hajian, Mahdi; Nasiri, Zahra; Bahadorani, Mehrnoosh; Tahmoorespur, Mojtaba; Nasiri, Mohammad Reza; Nasr-Esfahani, Mohammad Hossein

    2015-12-01

    Recent studies show that spermatogonial stem cells (SSCs) are able to colonize and form mature spermatozoa following transplantation into germ cell depleted testes of recipient males. Therefore, efficient ways for enrichment and gene transfer into SSCs provides a powerful tool for production of transgenic animals. In order to adapt the technique to goats, three issues were addressed: (i) enrichment of the undifferentiated spermatogonia including SSCs using magnetic activated cell sorting (MACS), (ii) lentiviral vector-mediated transduction of an enhanced green fluorescent protein (EGFP) transgene into enriched cells, and (iii) transplantation of transduced undifferentiated spermatogonia into the germ cell depleted testes of immune-suppressed mice to assess for migration and colony formation ability. Enriched cells were transduced by lentiviral vectors and subsequently analyzed for expression of THY1, PLZF, VASA, UCHL1 and BCL6B genes. Cells were also analyzed for GFP and PLZF by flow cytometry. Enriched transduced cells were transplanted into germ cell depleted mice testis. Quantitative analysis of transcripts revealed that MACS-enrichment significantly increased the expression of SSC-characteristic genes THY1, PLZF, VASA, UCHL1 and BCL6B compared to non-enriched population (P≤0.05). EGFP transduction did not affect the expression levels of SSC-characteristic genes. Flow cytometry revealed that 72% of transduced-enriched cells were positive for EGFP. Finally, transduced-enriched goat SSCs could colonize within the cells into the seminiferous tubules of germ cell depleted recipient mice at higher frequency than non-enriched cells. The results indicated that enrichment of goat undifferentiated spermatogonia by magnetic-activated cell sorting for THY1 antibody combined with lentiviral vector-mediated transduction has the potential to be used for production of transgenic goats. PMID:26481046

  5. FASEB summer research conference on signal transduction in plants. Final report, June 16, 1996--June 21, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Lomax, T.L.; Quatrano, R.S.

    1996-12-31

    This is the program from the second FASEB conference on Signal Transduction in Plants. Topic areas included the following: environmental signaling; perception and transduction of light signals; signaling in plant microbe interactions; signaling in plant pathogen interactions; cell, cell communication; cytoskeleton, plasma membrane, and cellwall continuum; signaling molecules in plant growth and development I and II. A list of participants is included.

  6. Development in research on triggering receptor expressed on myeloid cells-1 signal transduction%髓样细胞表达的触发受体-1与炎症信号转导的研究进展

    Institute of Scientific and Technical Information of China (English)

    苏龙翔; 解立新

    2012-01-01

    The triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently identified molecule involved in the cascade amplification of inflammatory response.Several microbial components can up-regulate the surface expression of TREM-1 and synergizes with the ligand of TREM-1 in activating this receptor.Activation via TREM-1 induces production of pro-inflammatory cytokices and related inflammatory responses because TREM-1 can noticeably amplify the inflammatory response in endotoxemia arisen from lipopolysaccharide (LPS).There are lots of investigations about the TREM-1 activation signal pathway that have been done and have shown some progress.Otherwise,TREM-1 synergizes with the Toll-like receptors signaling pathway in amplifying the inflammatory response mediated by LPS,but the specific mechanism is not clear enough.In this review,we will focus on the mechanism of TREM-1 signal transduction,clarifying the function of some relative signal moleculars such as TLR,DAP-12,MAPKs,NTAL,CARD9,NLRs.TREM-1 signal transduction mechanism in-depth study will further clarify the pathogenesis of sepsis and to find new therapeutic targets.%研究表明髓样细胞表达的触发受体-1(TREM-1)参与了炎性反应的级联放大过程.细菌的某些成分可以上调细胞表面TREM-1的表达,并且能和TREM-1配体协同激活TREM-1受体向下游传递信号.TREM-1被激活后会诱导前炎性因子的产生并引起相关的炎症反应.由于TREM-1是明显放大内毒素脂多糖(LPS)所引起的炎性反应的关键介质,因此对于TREM-1激活炎症信号通路的研究取得了一定的进展.然而,TREM-1在协同Toll样受体激活炎性反应的信号通路的具体机制尚未完全明晰.专注于TREM-1的信号转导,阐明与此通路相关的信号分子,如TLR、DAP-12、MAPKs、NTAL、CARD9、NLRs的作用,为进一步揭示脓毒症的发病机制并寻找新的治疗靶点.

  7. Methionine Regulates mTORC1 via the T1R1/T1R3-PLCβ-Ca2+-ERK1/2 Signal Transduction Process in C2C12 Cells

    Directory of Open Access Journals (Sweden)

    Yuanfei Zhou

    2016-10-01

    Full Text Available The mammalian target of rapamycin complex 1 (mTORC1 integrates amino acid (AA availability to support protein synthesis and cell growth. Taste receptor type 1 member (T1R is a G protein-coupled receptor that functions as a direct sensor of extracellular AA availability to regulate mTORC1 through Ca2+ stimulation and extracellular signal–regulated kinases 1 and 2 (ERK1/2 activation. However, the roles of specific AAs in T1R1/T1R3-regulated mTORC1 are poorly defined. In this study, T1R1 and T1R3 subunits were expressed in C2C12 myotubes, and l-AA sensing was accomplished by T1R1/T1R3 to activate mTORC1. In response to l-AAs, such as serine (Ser, arginine (Arg, threonine (Thr, alanine (Ala, methionine (Met, glutamine (Gln, and glycine (Gly, Met induced mTORC1 activation and promoted protein synthesis. Met also regulated mTORC1 via T1R1/T1R3-PLCβ-Ca2+-ERK1/2 signal transduction. Results revealed a new role for Met-regulated mTORC1 via an AA receptor. Further studies should be performed to determine the role of T1R1/T1R3 in mediating extracellular AA to regulate mTOR signaling and to reveal its mechanism.

  8. Methionine Regulates mTORC1 via the T1R1/T1R3-PLCβ-Ca2+-ERK1/2 Signal Transduction Process in C2C12 Cells

    Science.gov (United States)

    Zhou, Yuanfei; Ren, Jiao; Song, Tongxing; Peng, Jian; Wei, Hongkui

    2016-01-01

    The mammalian target of rapamycin complex 1 (mTORC1) integrates amino acid (AA) availability to support protein synthesis and cell growth. Taste receptor type 1 member (T1R) is a G protein-coupled receptor that functions as a direct sensor of extracellular AA availability to regulate mTORC1 through Ca2+ stimulation and extracellular signal–regulated kinases 1 and 2 (ERK1/2) activation. However, the roles of specific AAs in T1R1/T1R3-regulated mTORC1 are poorly defined. In this study, T1R1 and T1R3 subunits were expressed in C2C12 myotubes, and l-AA sensing was accomplished by T1R1/T1R3 to activate mTORC1. In response to l-AAs, such as serine (Ser), arginine (Arg), threonine (Thr), alanine (Ala), methionine (Met), glutamine (Gln), and glycine (Gly), Met induced mTORC1 activation and promoted protein synthesis. Met also regulated mTORC1 via T1R1/T1R3-PLCβ-Ca2+-ERK1/2 signal transduction. Results revealed a new role for Met-regulated mTORC1 via an AA receptor. Further studies should be performed to determine the role of T1R1/T1R3 in mediating extracellular AA to regulate mTOR signaling and to reveal its mechanism. PMID:27727170

  9. Antibodies against membrane proteins of the cephalopode visual membrane for the investigation of transduction processes of the evertebrate light perceptive cell. Antikoerper gegen Membranproteine der Cephalopoden-Sehzell-Membran als Mittel zur Untersuchung des Transduktionsprozesses der Evertebraten-Lichtsinneszelle

    Energy Technology Data Exchange (ETDEWEB)

    Conen, H.

    1988-01-01

    In invertebrate photoreceptors signal transduction is not as well investigated as in bovine rod outer segments (Stryer, 1989). The initial event in both vertebrate and invertebrate photoreceptors is the photoisomerisation of the chromophor of the photopigment rhodopsin. There is circumstantial evidence for a G-protein being the target enzyme for the active metarhodopsin: There is an intrinsic GTPase activity that is induced by blue and suppressed by red illumination in musca eyes (Blumenfeld et al, 1986) and also a light-dark difference in GTPAase activity in squid photoreceptors (Saibil and Michel-Villaz, 1984). Blumenfeld et al. (1986) showd that the light activated GTPase activity in fly (musca) photoreceptors is assoziated with a long lasting excited state of metarhodopsin. This metarhodopsin seems also to be responsible for a prolonged depolarizing after potential in fly photoreceptors (Hamdorf and Razmjoo, 1977 and 1979/Hamdorf, 1979). Injections of GDP-US -S, a poorly hydrolysable analogues of GDP into the ventral photoreceptor of Limulus depress the sensitivity of the cells to light (Bolsover and Brown, 1982).

  10. Calcium and signal transduction in plants

    Science.gov (United States)

    Poovaiah, B. W.; Reddy, A. S.

    1993-01-01

    Environmental and hormonal signals control diverse physiological processes in plants. The mechanisms by which plant cells perceive and transduce these signals are poorly understood. Understanding biochemical and molecular events involved in signal transduction pathways has become one of the most active areas of plant research. Research during the last 15 years has established that Ca2+ acts as a messenger in transducing external signals. The evidence in support of Ca2+ as a messenger is unequivocal and fulfills all the requirements of a messenger. The role of Ca2+ becomes even more important because it is the only messenger known so far in plants. Since our last review on the Ca2+ messenger system in 1987, there has been tremendous progress in elucidating various aspects of Ca(2+) -signaling pathways in plants. These include demonstration of signal-induced changes in cytosolic Ca2+, calmodulin and calmodulin-like proteins, identification of different Ca2+ channels, characterization of Ca(2+) -dependent protein kinases (CDPKs) both at the biochemical and molecular levels, evidence for the presence of calmodulin-dependent protein kinases, and increased evidence in support of the role of inositol phospholipids in the Ca(2+) -signaling system. Despite the progress in Ca2+ research in plants, it is still in its infancy and much more needs to be done to understand the precise mechanisms by which Ca2+ regulates a wide variety of physiological processes. The purpose of this review is to summarize some of these recent developments in Ca2+ research as it relates to signal transduction in plants.

  11. THOC5, a member of the mRNA export complex: a novel link between mRNA export machinery and signal transduction pathways in cell proliferation and differentiation.

    Science.gov (United States)

    Tran, Doan D H; Koch, Alexandra; Tamura, Teruko

    2014-01-01

    Cell growth, differentiation, and commitment to a restricted lineage are guided by a timely expressed set of growth factor/cytokine receptors and their down-stream transcription factor genes. Transcriptional control mechanisms of gene expression during differentiation have been mainly studied by focusing on the cis- and trans-elements in promoters however, the role of mRNA export machinery during differentiation has not been adequately examined. THO (Suppressors of the transcriptional defects of hpr1 delta by overexpression) complex 5 (THOC5) is a member of THO complex which is a subcomplex of the transcription/export complex (TREX). THOC5 is evolutionarily conserved in higher eukaryotes, however the exact roles of THOC5 in transcription and mRNA export are still unclear. In this review, we focus on recently uncovered aspects of the role of THOC5 in signal transduction induced by extracellular stimuli. THOC5 is phosphorylated by several protein kinases at multiple residues upon extracellular stimuli. These include stimulation with growth factors/cytokines/chemokines, or DNA damage reagents. Furthermore, THOC5 is a substrate for several oncogenic tyrosine kinases, suggesting that THOC5 may be involved in cancer development. Recent THOC5 knockout mouse data reveal that THOC5 is an essential element in the maintenance of stem cells and growth factor/cytokine-mediated differentiation/proliferation. Furthermore, depletion of THOC5 influences less than 1% of total mRNA export in the steady state, however it influences more than 90% of growth factor/cytokine induced genes. THOC5, thereby contributes to the 3' processing and/or export of immediate-early genes induced by extracellular stimuli. These studies bring new insight into the link between the mRNA export complex and immediate-early gene response. The data from these studies also suggest that THOC5 may be a useful tool for studying stem cell biology, for modifying the differentiation processes and for cancer therapy.

  12. Central functions of bicarbonate in S-type anion channel activation and OST1 protein kinase in CO 2 signal transduction in guard cell

    KAUST Repository

    Xue, Shaowu

    2011-03-18

    Plants respond to elevated CO(2) via carbonic anhydrases that mediate stomatal closing, but little is known about the early signalling mechanisms following the initial CO(2) response. It remains unclear whether CO(2), HCO(3)(-) or a combination activates downstream signalling. Here, we demonstrate that bicarbonate functions as a small-molecule activator of SLAC1 anion channels in guard cells. Elevated intracellular [HCO(3)(-)](i) with low [CO(2)] and [H(+)] activated S-type anion currents, whereas low [HCO(3)(-)](i) at high [CO(2)] and [H(+)] did not. Bicarbonate enhanced the intracellular Ca(2+) sensitivity of S-type anion channel activation in wild-type and ht1-2 kinase mutant guard cells. ht1-2 mutant guard cells exhibited enhanced bicarbonate sensitivity of S-type anion channel activation. The OST1 protein kinase has been reported not to affect CO(2) signalling. Unexpectedly, OST1 loss-of-function alleles showed strongly impaired CO(2)-induced stomatal closing and HCO(3)(-) activation of anion channels. Moreover, PYR/RCAR abscisic acid (ABA) receptor mutants slowed but did not abolish CO(2)/HCO(3)(-) signalling, redefining the convergence point of CO(2) and ABA signalling. A new working model of the sequence of CO(2) signalling events in gas exchange regulation is presented.

  13. Protein phosphorylation and its role in archaeal signal transduction.

    Science.gov (United States)

    Esser, Dominik; Hoffmann, Lena; Pham, Trong Khoa; Bräsen, Christopher; Qiu, Wen; Wright, Phillip C; Albers, Sonja-Verena; Siebers, Bettina

    2016-09-01

    Reversible protein phosphorylation is the main mechanism of signal transduction that enables cells to rapidly respond to environmental changes by controlling the functional properties of proteins in response to external stimuli. However, whereas signal transduction is well studied in Eukaryotes and Bacteria, the knowledge in Archaea is still rather scarce. Archaea are special with regard to protein phosphorylation, due to the fact that the two best studied phyla, the Euryarchaeota and Crenarchaeaota, seem to exhibit fundamental differences in regulatory systems. Euryarchaeota (e.g. halophiles, methanogens, thermophiles), like Bacteria and Eukaryotes, rely on bacterial-type two-component signal transduction systems (phosphorylation on His and Asp), as well as on the protein phosphorylation on Ser, Thr and Tyr by Hanks-type protein kinases. Instead, Crenarchaeota (e.g. acidophiles and (hyper)thermophiles) only depend on Hanks-type protein phosphorylation. In this review, the current knowledge of reversible protein phosphorylation in Archaea is presented. It combines results from identified phosphoproteins, biochemical characterization of protein kinases and protein phosphatases as well as target enzymes and first insights into archaeal signal transduction by biochemical, genetic and polyomic studies.

  14. Protein phosphorylation and its role in archaeal signal transduction

    Science.gov (United States)

    Esser, Dominik; Hoffmann, Lena; Pham, Trong Khoa; Bräsen, Christopher; Qiu, Wen; Wright, Phillip C.; Albers, Sonja-Verena; Siebers, Bettina

    2016-01-01

    Reversible protein phosphorylation is the main mechanism of signal transduction that enables cells to rapidly respond to environmental changes by controlling the functional properties of proteins in response to external stimuli. However, whereas signal transduction is well studied in Eukaryotes and Bacteria, the knowledge in Archaea is still rather scarce. Archaea are special with regard to protein phosphorylation, due to the fact that the two best studied phyla, the Euryarchaeota and Crenarchaeaota, seem to exhibit fundamental differences in regulatory systems. Euryarchaeota (e.g. halophiles, methanogens, thermophiles), like Bacteria and Eukaryotes, rely on bacterial-type two-component signal transduction systems (phosphorylation on His and Asp), as well as on the protein phosphorylation on Ser, Thr and Tyr by Hanks-type protein kinases. Instead, Crenarchaeota (e.g. acidophiles and (hyper)thermophiles) only depend on Hanks-type protein phosphorylation. In this review, the current knowledge of reversible protein phosphorylation in Archaea is presented. It combines results from identified phosphoproteins, biochemical characterization of protein kinases and protein phosphatases as well as target enzymes and first insights into archaeal signal transduction by biochemical, genetic and polyomic studies. PMID:27476079

  15. Substance P Activates the Wnt Signal Transduction Pathway and Enhances the Differentiation of Mouse Preosteoblastic MC3T3-E1 Cells

    Directory of Open Access Journals (Sweden)

    Gang Mei

    2014-04-01

    Full Text Available Recent experiments have explored the impact of Wnt/β-catenin signaling and Substance P (SP on the regulation of osteogenesis. However, the molecular regulatory mechanisms of SP on the formation of osteoblasts is still unknown. In this study, we investigated the impact of SP on the differentiation of MC3T3-E1 cells. The osteogenic effect of SP was observed at different SP concentrations (ranging from 10−10 to 10−8 M. To unravel the underlying mechanism, the MC3T3-E1 cells were treated with SP after the pretreatment by neurokinin-1 (NK1 antagonists and Dickkopf-1 (DKK1 and gene expression levels of Wnt/β-catenin signaling pathway components, as well as osteoblast differentiation markers (collagen type I, alkaline phosphatase, osteocalcin, and Runx2, were measured using quantitative polymerase chain reaction (PCR. Furthermore, protein levels of Wnt/β-catenin signaling pathway were detected using Western blotting and the effects of SP, NK1 antagonist, and DKK1 on β-catenin activation were investigated by immunofluorescence staining. Our data indicated that SP (10−9 to 10−8 M significantly up-regulated the expressions of osteoblastic genes. SP (10−8 M also elevated the mRNA level of c-myc, cyclin D1, and lymphocyte enhancer factor-1 (Lef1, as well as c-myc and β-catenin protein levels, but decreased the expression of Tcf7 mRNA. Moreover, SP (10−8 M promoted the transfer of β-catenin into nucleus. The effects of SP treatment were inhibited by the NK1 antagonist and DKK1. These findings suggest that SP may enhance differentiation of MC3T3-E1 cells via regulation of the Wnt/β-catenin signaling pathway.

  16. l-glutamine Improves Skeletal Muscle Cell Differentiation and Prevents Myotube Atrophy After Cytokine (TNF-α) Stress Via Reduced p38 MAPK Signal Transduction.

    Science.gov (United States)

    Girven, Matthew; Dugdale, Hannah F; Owens, Daniel J; Hughes, David C; Stewart, Claire E; Sharples, Adam P

    2016-12-01

    Tumour Necrosis Factor-Alpha (TNF-α) is chronically elevated in conditions where skeletal muscle loss occurs. As l-glutamine can dampen the effects of inflamed environments, we investigated the role of l-glutamine in both differentiating C2C12 myoblasts and existing myotubes in the absence/presence of TNF-α (20 ng · ml(-1) ) ± l-glutamine (20 mM). TNF-α reduced the proportion of cells in G1 phase, as well as biochemical (CK activity) and morphological differentiation (myotube number), with corresponding reductions in transcript expression of: Myogenin, Igf-I, and Igfbp5. Furthermore, when administered to mature myotubes, TNF-α induced myotube loss and atrophy underpinned by reductions in Myogenin, Igf-I, Igfbp2, and glutamine synthetase and parallel increases in Fox03, Cfos, p53, and Bid gene expression. Investigation of signaling activity suggested that Akt and ERK1/2 were unchanged, JNK increased (non-significantly) whereas P38 MAPK substantially and significantly increased in both myoblasts and myotubes in the presence of TNF-α. Importantly, 20 mM l-glutamine reduced p38 MAPK activity in TNF-α conditions back to control levels, with a corresponding rescue of myoblast differentiation and a reversal of atrophy in myotubes. l-glutamine resulted in upregulation of genes associated with growth and survival including; Myogenin, Igf-Ir, Myhc2 & 7, Tnfsfr1b, Adra1d, and restored atrophic gene expression of Fox03 back to baseline in TNF-α conditions. In conclusion, l-glutamine supplementation rescued suppressed muscle cell differentiation and prevented myotube atrophy in an inflamed environment via regulation of p38 MAPK. l-glutamine administration could represent an important therapeutic strategy for reducing muscle loss in catabolic diseases and inflamed ageing. J. Cell. Physiol. 9999: 231: 2720-2732, 2016. © 2016 Wiley Periodicals, Inc.

  17. l-glutamine Improves Skeletal Muscle Cell Differentiation and Prevents Myotube Atrophy After Cytokine (TNF-α) Stress Via Reduced p38 MAPK Signal Transduction.

    Science.gov (United States)

    Girven, Matthew; Dugdale, Hannah F; Owens, Daniel J; Hughes, David C; Stewart, Claire E; Sharples, Adam P

    2016-12-01

    Tumour Necrosis Factor-Alpha (TNF-α) is chronically elevated in conditions where skeletal muscle loss occurs. As l-glutamine can dampen the effects of inflamed environments, we investigated the role of l-glutamine in both differentiating C2C12 myoblasts and existing myotubes in the absence/presence of TNF-α (20 ng · ml(-1) ) ± l-glutamine (20 mM). TNF-α reduced the proportion of cells in G1 phase, as well as biochemical (CK activity) and morphological differentiation (myotube number), with corresponding reductions in transcript expression of: Myogenin, Igf-I, and Igfbp5. Furthermore, when administered to mature myotubes, TNF-α induced myotube loss and atrophy underpinned by reductions in Myogenin, Igf-I, Igfbp2, and glutamine synthetase and parallel increases in Fox03, Cfos, p53, and Bid gene expression. Investigation of signaling activity suggested that Akt and ERK1/2 were unchanged, JNK increased (non-significantly) whereas P38 MAPK substantially and significantly increased in both myoblasts and myotubes in the presence of TNF-α. Importantly, 20 mM l-glutamine reduced p38 MAPK activity in TNF-α conditions back to control levels, with a corresponding rescue of myoblast differentiation and a reversal of atrophy in myotubes. l-glutamine resulted in upregulation of genes associated with growth and survival including; Myogenin, Igf-Ir, Myhc2 & 7, Tnfsfr1b, Adra1d, and restored atrophic gene expression of Fox03 back to baseline in TNF-α conditions. In conclusion, l-glutamine supplementation rescued suppressed muscle cell differentiation and prevented myotube atrophy in an inflamed environment via regulation of p38 MAPK. l-glutamine administration could represent an important therapeutic strategy for reducing muscle loss in catabolic diseases and inflamed ageing. J. Cell. Physiol. 9999: 231: 2720-2732, 2016. © 2016 Wiley Periodicals, Inc. PMID:26991744

  18. EDITORIAL: Special section on signal transduction Special section on signal transduction

    Science.gov (United States)

    Shvartsman, Stanislav

    2012-08-01

    This special section of Physical Biology focuses on multiple aspects of signal transduction, broadly defined as the study of the mechanisms by which cells communicate with their environment. Mechanisms of cell communication involve detection of incoming signals, which can be chemical, mechanical or electromagnetic, relaying these signals to intracellular processes, such as cytoskeletal networks or gene expression systems, and, ultimately, converting these signals to responses such as cell differentiation or death. Given the multiscale nature of signal transduction systems, they must be studied at multiple levels, from the identities and structures of molecules comprising signal detection and interpretation networks, to the systems-level properties of these networks. The 11 papers in this special section illustrate some of the most exciting aspects of signal transduction research. The first two papers, by Marie-Anne Félix [1] and by Efrat Oron and Natalia Ivanova [2], focus on cell-cell interactions in developing tissues, using vulval patterning in worm and cell fate specification in mammalian embryos as prime examples of emergent cell behaviors. Next come two papers from the groups of Julio Saez-Rodriguez [3] and Kevin Janes [4]. These papers discuss how the causal relationships between multiple components of signaling systems can be inferred using multivariable statistical analysis of empirical data. An authoritative review by Zarnitsyna and Zhu [5] presents a detailed discussion of the sequence of signaling events involved in T-cell triggering. Once the structure and components of the signaling systems are determined, they can be modeled using approaches that have been successful in other physical sciences. As two examples of such approaches, reviews by Rubinstein [6] and Kholodenko [7], present reaction-diffusion models of cell polarization and thermodynamics-based models of gene regulation. An important class of models takes the form of enzymatic networks

  19. Effect of calcitonin gene related peptide regulated nuclear factor kappa B signal transduction on c-kit+ cardiac stem cells in hypoxia state

    Directory of Open Access Journals (Sweden)

    Xian-ping LONG

    2015-11-01

    Full Text Available Objective To investigate the effects of calcitonin gene-related peptide (CGRP on the apoptosis of c-kit+ cardiac stem cells in hypoxia. Methods Ischemia and hypoxia models of c-kit+ cardiac stem cells were reproduced in vitro. The models were divided into hypoxia+CGRP group, hypoxia+CGRP8-37 (antagonist of CGRP group, hypoxia control group, normal oxygen group, and hypoxia+BAY11-7082 [antagonist of nuclear factor kappa B (NF-κB] group. NF-κB translocation after hypoxia was detected by immunofluorescence, and NF-κB channel proteins were determined with Western blotting. The NF-κB translocation and the expression of NF-κB channel proteins after CGRP intervention were detected, and the cell apoptosis rate after intervention was determined with flow cytometry in each group. Results Under hypoxia the NF-κB signal pathway was activated, and nuclear translocation occurred in NF-κBP65 (red fluorescence. Compared with hypoxia control group, the expressions of NF-κB related proteins such as P-I-κB, NF-κBP65 and NF-κBP50 decreased obviously (P<0.05. Compared with the hypoxia+CGRP group, the expressions of NF-κB related proteins increased significantly (P<0.05 as mentioned above in hypoxia+CGRP8-37 group. Both the early and late apoptotic rates declined in hypoxia+CGRP group compared with that of hypoxia control group (P<0.05, however, the early apoptotic rate increased markedly in hypoxia+CGRP8-37 group as compared with that of hypoxia+CGRP group (P<0.05. Conclusion Under hypoxia, CGRP may regulate the NF-κB signal pathway, and at the same time suppress the apoptosis of c-kit+ cardiac stem cells. DOI: 10.11855/j.issn.0577-7402.2015.10.03

  20. Asenapine for bipolar disorder

    Directory of Open Access Journals (Sweden)

    Scheidemantel T

    2015-12-01

    Full Text Available Thomas Scheidemantel,1 Irina Korobkova,2 Soham Rej,3,4 Martha Sajatovic1,2 1University Hospitals Case Medical Center, 2Case Western Reserve University School of Medicine, Cleveland, OH, USA; 3Department of Psychiatry, University of Toronto, Toronto, ON, 4Geri PARTy Research Group, Jewish General Hospital, Montreal, QC, Canada Abstract: Asenapine (Saphris® is an atypical antipsychotic drug which has been approved by the US Food and Drug Administration for the treatment of schizophrenia in adults, as well as the treatment of acute manic or mixed episodes of bipolar I in both adult and pediatric populations. Asenapine is a tetracyclic drug with antidopaminergic and antiserotonergic activity with a unique sublingual route of administration. In this review, we examine and summarize the available literature on the safety, efficacy, and tolerability of asenapine in the treatment of bipolar disorder (BD. Data from randomized, double-blind trials comparing asenapine to placebo or olanzapine in the treatment of acute manic or mixed episodes showed asenapine to be an effective monotherapy treatment in clinical settings; asenapine outperformed placebo and showed noninferior performance to olanzapine based on improvement in the Young Mania Rating Scale scores. There are limited data available on the use of asenapine in the treatment of depressive symptoms of BD, or in the maintenance phase of BD. The available data are inconclusive, suggesting the need for more robust data from prospective trials in these clinical domains. The most commonly reported adverse effect associated with use of asenapine is somnolence. However, the somnolence associated with asenapine use did not cause significant rates of discontinuation. While asenapine was associated with weight gain when compared to placebo, it appeared to be modest when compared to other atypical antipsychotics, and its propensity to cause increases in hemoglobin A1c or serum lipid levels appeared to be

  1. Sentra, a database of signal transduction proteins.

    Energy Technology Data Exchange (ETDEWEB)

    Maltsev, N.; Marland, E.; Yu, G. X.; Bhatnagar, S.; Lusk, R.; Mathematics and Computer Science

    2002-01-01

    Sentra (http://www-wit.mcs.anl.gov/sentra) is a database of signal transduction proteins with the emphasis on microbial signal transduction. The database was updated to include classes of signal transduction systems modulated by either phosphorylation or methylation reactions such as PAS proteins and serine/threonine kinases, as well as the classical two-component histidine kinases and methyl-accepting chemotaxis proteins. Currently, Sentra contains signal transduction proteins from 43 completely sequenced prokaryotic genomes as well as sequences from SWISS-PROT and TrEMBL. Signal transduction proteins are annotated with information describing conserved domains, paralogous and orthologous sequences, and conserved chromosomal gene clusters. The newly developed user interface supports flexible search capabilities and extensive visualization of the data.

  2. SENTRA, a database of signal transduction proteins.

    Energy Technology Data Exchange (ETDEWEB)

    D' Souza, M.; Romine, M. F.; Maltsev, N.; Mathematics and Computer Science; PNNL

    2000-01-01

    SENTRA, available via URL http://wit.mcs.anl.gov/WIT2/Sentra/, is a database of proteins associated with microbial signal transduction. The database currently includes the classical two-component signal transduction pathway proteins and methyl-accepting chemotaxis proteins, but will be expanded to also include other classes of signal transduction systems that are modulated by phosphorylation or methylation reactions. Although the majority of database entries are from prokaryotic systems, eukaroytic proteins with bacterial-like signal transduction domains are also included. Currently SENTRA contains signal transduction proteins in 34 complete and almost completely sequenced prokaryotic genomes, as well as sequences from 243 organisms available in public databases (SWISS-PROT and EMBL). The analysis was carried out within the framework of the WIT2 system, which is designed and implemented to support genetic sequence analysis and comparative analysis of sequenced genomes.

  3. p53 amplifies Toll-like receptor 5 response in human primary and cancer cells through interaction with multiple signal transduction pathways

    Science.gov (United States)

    Shatz, Maria; Shats, Igor; Menendez, Daniel; Resnick, Michael A.

    2015-01-01

    The p53 tumor suppressor regulates transcription of genes associated with diverse cellular functions including apoptosis, growth arrest, DNA repair and differentiation. Recently, we established that p53 can modulate expression of Toll-like receptor (TLR) innate immunity genes but the degree of cross-talk between p53 and TLR pathways remained unclear. Here, using gene expression profiling we characterize the global effect of p53 on the TLR5-mediated transcription in MCF7 cells. We found that combined activation of p53 and TLR5 pathways synergistically increases expression of over 200 genes, mostly associated with immunity and inflammation. The synergy was observed in several human cancer cells and primary lymphocytes. The p53-dependent amplification of transcriptional response to TLR5 activation required expression of NFκB subunit p65 and was mediated by several molecular mechanisms including increased phosphorylation of p38 MAP kinase, PI3K and STAT3 signaling. Additionally, p53 induction increased cytokine expression in response to TNFα, another activator of NFκB and MAP kinase pathways, suggesting a broad interaction between p53 and these signaling pathways. The expression of many synergistically induced genes is elevated in breast cancer patients responsive to chemotherapy. We suggest that p53's capacity to enhance immune response could be exploited to increase antitumor immunity and to improve cancer treatment. PMID:26220208

  4. Risk factors for suicide among children and youths with bipolar spectrum and early bipolar disorder.

    Directory of Open Access Journals (Sweden)

    Aleksandra Rajewska-Rager

    2015-06-01

    the overview of recent years literature available in PubMed/MEDLINE database, including the following search criteria: early onset bipolar disorder, bipolar disorder in children and young people, the spectrum of bipolar disorder, and suicidal ideation, suicidal intent, suicide.

  5. Comparison of characteristics of fluorine doped zinc and gallium tin oxide composite thin films deposited on stainless steel 316 bipolar plate by electron cyclotron resonance-metal organic chemical vapor deposition for proton exchange membrane fuel cells.

    Science.gov (United States)

    Park, Jihun; Hudaya, Chairul; Lee, Joong Kee

    2011-09-01

    In order to replace the brittle graphite bipolar plates currently used for the PEMFC stack, coated SUS 316 was employed. As a metallic bipolar plate, coated SUS 316 can provide higher mechanical strength, better durability to shocks and vibration, less permeability, improved thermal and bulk electrical conductivity, as well as being thinner and lighter. To enhance the interfacial contact resistance and corrosion resistance of SUS 316, the deposition of GTO:F and ZTO:F composite films was carried out by ECR-MOCVD. The surface morphology of the films consisted of tiny elliptically shaped grains with a thickness of 1 microm. The corrosion current for GTO:F was 0.13 Acm(-2) which was much lower than that of bare SUS 316 (50.16 Acm(-2)). The GTO:F coated film had the smallest corrosion current due to the formation of a tight surface morphology with very few pin-holes. The GTO:F coated film exhibited the highest cell voltage and power density due to its lower ICR values. PMID:22097519

  6. Research progress of forming process of bipolar plate for micro fuel cell%微型燃料电池双极板成形工艺的研究进展

    Institute of Scientific and Technical Information of China (English)

    许桢英; 张园园; 王匀; 丁盛; 尹必峰

    2015-01-01

    The micro fuel cellis the mainstream of the future mobile power, but the forming process of bipolar plate hinders the application of fuel cell. The forming process of bipolar plates for micro fuel cellwas introduced, including regular plastic deformation means based on micro stamping and so on,micro processing technology based on MEMS and non-traditional machining process. The development trend of forming technology of future micro fuel cellbipolar plate was looked forward.%微型燃料电池是未来可移动电源的主流,但是其双极板成形工艺成为燃料电池推广应用的主要制约之一。介绍了微型燃料电池双极板的成形工艺,包括基于微冲压等常规的塑性变形手段,基于MEMS(Micro-Electro-Mechanical Systems)的微加工技术和非传统加工工艺,展望了未来微型燃料电池双极板成形工艺的发展趋势。

  7. Characterization of the pharmacology, signal transduction and internalization of the fluorescent PACAP ligand, fluor-PACAP, on NIH/3T3 cells expressing PAC1.

    Science.gov (United States)

    Germano, P M; Stalter, J; Le, S V; Wu, M; Yamaguchi, D J; Scott, D; Pisegna, J R

    2001-06-01

    Fluor-PACAP, a fluorescent derivative of PACAP-27, has been confirmed to share a high affinity for PAC1 receptors transfected into NIH/3T3 cells and to have comparable pharmacological characteristics to the unconjugated, native form. Through competitive binding with 125I-PACAP-27, the two ligands exhibited similar dose- dependent inhibition. Additional examination of the efficacy of activating adenylyl cyclase revealed that both ligands analogously stimulated the production of cyclic AMP. Furthermore, PAC1 internalization visualized by our Fluor-PACAP, is compareable to that performed with the radioligand, 125I-PACAP-27, with maximal internalization achieved within thirty minutes. Thus, Fluor-PACAP exhibits intracellular signaling abilities homologous to the native ligand.

  8. 质子交换膜燃料电池双极板的设计与模拟分析%Design and simulation of bipolar plates channels of proton exchange membrane fuel cells

    Institute of Scientific and Technical Information of China (English)

    吴懋亮; 顾竹筠; 曹寿峰

    2012-01-01

    质子交换膜燃料电池是直接将化学能转换为电能的装置,双极板上的流道结构对燃料电池的工作性能具有较大的影响.根据应用要求设计了具有平行流道、蛇形流道及希尔伯特分形流道的双极板结构,模拟计算了氢气在不同类型的流道和气体扩散层中的分布状态,分析了燃料电池的输出电流密度和功率密度随电极间电压的变化特点,比较了不同的流道结构对燃料电池输出电流密度的影响,以及不同的工作温度及气体压强的情况下,燃料电池输出电流密度随温度及压强的变化规律.%Proton exchange membrane (PEM) fuel cell converts directly electrochemical energy into electric enegy, and the performances of fuel cells is affected by channels in bipolar plates . bipolar plates with parallel channels, serpentine channels and Hilbert fractal channels are designed respectively in this paper, and hydrogen flow states in channels and Gas Diffusion Layers (GDLs) is simulated. Relationships of current densities vs. set voltages and power densities vs. voltages between anode and cathode are investigated, anil the influence of channel types on fuel cell output density is compared. At last, the paper analyzes current density variations with different operating temperatures and pressures on fuel cells.

  9. Sleep Disturbances in Bipolar Disorder

    OpenAIRE

    Cátia Alves Moreira; Pedro Afonso

    2015-01-01

    Background: Bipolar disorder, characterized by episodes of mania, hypomania and depression is associated with sleep disturbances and circadian rhythm disruption. These changes have significant impact on quality of life and in the disease prognosis. Aims: Review of the main sleep disturbances observed in the bipolar disorder, their clinical impact and the hypothetical pathophysiological mechanisms involved. Methods: We conducted a non-systematic review of the literature in English through rese...

  10. : Genetic heterogeneity of bipolar disorder

    OpenAIRE

    Mathieu, Flavie; Dizier, Marie-Hélène; Etain, Bruno; Jamain, Stéphane; Rietschel, Marcella; Maier, Wolfgang; Albus, Margot; Mckeon, Patrick; Roche, Siobhan; Blackwood, Douglas; Muir, Walter,; Henry, Chantal; Malafosse, Alain; Preisig, Martin; Ferrero, François

    2010-01-01

    Bipolar disorder has a genetic component, but the mode of inheritance remains unclear. A previous genome scan conducted in 70 European families led to detect eight regions linked to bipolar disease. Here, we present an investigation of whether the phenotypic heterogeneity of the disorder corresponds to genetic heterogeneity in these regions using additional markers and an extended sample of families. The MLS statistic was used for linkage analyses. The predivided sample test and the maximum l...

  11. Bipolar spectrum disorders. New perspectives.

    OpenAIRE

    Piver, Andre; Yatham, Lakshmi N.; Raymond W. Lam

    2002-01-01

    OBJECTIVE: To review new perspectives on diagnosis, clinical features, epidemiology, and treatment of bipolar II and related disorders. QUALITY OF EVIDENCE: Articles were identified by searching MEDLINE and ClinPSYCH from January 1994 to August 2001 using the key words bipolar disorder, type II or 2; hypomania; spectrum; or variants. Reference lists from articles were reviewed. Overall, the quality of evidence was not high; we found no randomized controlled trials that specifically addressed ...

  12. Calcitonin gene-related peptide promotes the expression of osteoblastic genes and activates the WNT signal transduction pathway in bone marrow stromal stem cells

    Science.gov (United States)

    ZHOU, RI; YUAN, ZHI; LIU, JIERONG; LIU, JIAN

    2016-01-01

    Calcitonin gene-related peptide (CGRP) is known to induce osteoblastic differentiation and alkaline phosphatase activity in bone marrow stromal stem cells (BMSCs). However, it has remained elusive whether this effect is mediated by CGRP receptors directly or whether other signaling pathways are involved. The present study assessed the possible involvement of the Wnt/β-catenin signaling pathway in the activation of CGRP signaling during the differentiation of BMSCs. First, the differentiation of BMSCs was induced in vitro and the expression of CGRP receptors was examined by western blot analysis. The effects of exogenous CGRP and LiCl, a stimulator of the Wnt/β-catenin signaling pathway, on the osteoblastic differentiation of BMSCs were assessed; furthermore, the expression of mRNA and proteins involved in the Wnt/β-catenin signaling pathway was assessed using quantitative PCR and western blot analyses. The results revealed that CGRP receptors were expressed throughout the differentiation of BMSCs, at days 7 and 14. Incubation with CGRP and LiCl led to the upregulation of the expression of osteoblastic genes associated with the Wnt/β-catenin pathway, including the mRNA of c-myc, cyclin D1, Lef1, Tcf7 and β-catenin as well as β-catenin protein. However, the upregulation of these genes and β-catenin protein was inhibited by CGRP receptor antagonist or secreted frizzled-related protein, an antagonist of the Wnt/β-catenin pathway. The results of the present study therefore suggested that the Wnt/β-catenin signaling pathway may be involved in CGRP- and LiCl-promoted osteoblastic differentiation of BMSCs. PMID:27082317

  13. Mechanisms of UV-induced signal transduction

    Energy Technology Data Exchange (ETDEWEB)

    Kulms, D.; Schwarz, T. [Univ. Muenster, Muenster (Germany). Ludwing Boltzmann Inst. for Cell Biology and Immunobiology of the Skin

    2002-04-01

    Ultraviolet radiation (UV) causes a variety of biological effects that can be either beneficial or harmful for human health. To exert these effects on a cellular basis, UV uses a variety of signaling pathways. DNA is the major chromophore for UVB. Thus, nuclear DNA damage has been detected to be a major mediator of numerous UVB effects, and experimental reduction of DNA damage is associated with a loss of these effects. On the other hand, UV has been found to utilize molecular components within the cytoplasm or at the cell membrane for signaling. UV can directly activate cell surface receptors, kinases, and transcription factors. The nuclear and extranuclear signaling pathways are generated independently and have been recently recognized to be not mutually exclusive but to contribute to various UV effects in an independent and additive way. Further knowledge of how these signaling pathways relate to each other will certainly increase our understanding of how UV acts as a pathogen. The following review will briefly discuss current aspects of the mechanisms involved in UV-induced signal transduction. (author)

  14. Threat sensitivity in bipolar disorder.

    Science.gov (United States)

    Muhtadie, Luma; Johnson, Sheri L

    2015-02-01

    Life stress is a major predictor of the course of bipolar disorder. Few studies have used laboratory paradigms to examine stress reactivity in bipolar disorder, and none have assessed autonomic reactivity to laboratory stressors. In the present investigation we sought to address this gap in the literature. Participants, 27 diagnosed with bipolar I disorder and 24 controls with no history of mood disorder, were asked to complete a complex working memory task presented as "a test of general intelligence." Self-reported emotions were assessed at baseline and after participants were given task instructions; autonomic physiology was assessed at baseline and continuously during the stressor task. Compared to controls, individuals with bipolar disorder reported greater increases in pretask anxiety from baseline and showed greater cardiovascular threat reactivity during the task. Group differences in cardiovascular threat reactivity were significantly correlated with comorbid anxiety in the bipolar group. Our results suggest that a multimethod approach to assessing stress reactivity-including the use of physiological parameters that differentiate between maladaptive and adaptive profiles of stress responding-can yield valuable information regarding stress sensitivity and its associations with negative affectivity in bipolar disorder. (PsycINFO Database Record (c) 2015 APA, all rights reserved). PMID:25688436

  15. Stacks with TiN/titanium as the bipolar plate for PEMFCs

    International Nuclear Information System (INIS)

    Proton exchange membrane fuel cell (PEMFC) is a potential alternative for the internal combustion engine. But many problems, such as metallic bipolar plate instead of graphite bipolar plate to decrease the cost, should be solved before its application. Based on the previous results that single cell with TiN/Ti as bipolar plates shows high performance and enough long-time durability, the progress on the stacks with TiN/Ti as bipolar plates is reported in this manuscript. Till now seldom report is focused on stacks because of the complicated processing technique, especially for that with TiN/Ti as bipolar plate. The flow field in the plate is punched from titanium deformation, and two plates are welded by laser welding to form one piece of bipolar plate. The adopted processing techniques for stacks with TiN/Ti as bipolar plate exhibit advantage and feasibility in industry. The power density by weight for the stack is as high as 1353 W kg−1, although it still has space to be improved. Next work should be focused on the design of flow channel parameters and flow field type based on plastic deformation of metal materials. -- Highlights: ► The progress on the stacks with TiN/Ti as bipolar plates is reported. ► The adopted processing techniques exhibit feasibility in industry. ► The power density by weight for the stack is as high as 1353 W kg−1.

  16. Thermal conductivity of a graphite bipolar plate (BPP) and its thermal contact resistance with fuel cell gas diffusion layers: Effect of compression, PTFE, micro porous layer (MPL), BPP out-of-flatness and cyclic load

    Science.gov (United States)

    Sadeghifar, Hamidreza; Djilali, Ned; Bahrami, Majid

    2015-01-01

    This paper reports on measurements of thermal conductivity of a graphite bipolar plate (BPP) as a function of temperature and its thermal contact resistance (TCR) with treated and untreated gas diffusion layers (GDLs). The thermal conductivity of the BPP decreases with temperature and its thermal contact resistance with GDLs, which has been overlooked in the literature, is found to be dominant over a relatively wide range of compression. The effects of PTFE loading, micro porous layer (MPL), compression, and BPP out-of-flatness are also investigated experimentally. It is found that high PTFE loadings, MPL and even small BPP out-of-flatness increase the BPP-GDL thermal contact resistance dramatically. The paper also presents the effect of cyclic load on the total resistance of a GDL-BPP assembly, which sheds light on the behavior of these materials under operating conditions in polymer electrolyte membrane fuel cells.

  17. Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells

    OpenAIRE

    Gaub, Benjamin M.; Berry, Michael H.; Holt, Amy E.; Reiner, Andreas; Kienzler, Michael A; Dolgova, Natalia; Nikonov, Sergei; Aguirre, Gustavo D.; Beltran, William A.; Flannery, John G.; Isacoff, Ehud Y.

    2014-01-01

    We restored visual function to animal models of human blindness using a chemical compound that photosensitizes a mammalian ion channel. Virus-mediated expression of this light sensor in surviving retinal cells of blind mice restored light responses in vitro, reanimated innate light avoidance, and enabled learned visually guided behavior. The treatment also restored light responses to the retina of blind dogs. Patients that might benefit from this treatment would need to have intact ganglion c...

  18. Integrated neurobiology of bipolar disorder

    Directory of Open Access Journals (Sweden)

    Vladimir eMaletic

    2014-08-01

    Full Text Available From a neurobiological perspective there is no such thing as bipolar disorder. Rather, it is almost certainly the case that many somewhat similar, but subtly different, pathological conditions produce a disease state that we currently diagnose as bipolarity. This heterogeneity—reflected in the lack of synergy between our current diagnostic schema and our rapidly advancing scientific understanding of the condition—limits attempts to articulate an integrated perspective on bipolar disorder. However, despite these challenges, scientific findings in recent years are beginning to offer a provisional unified field theory of the disease. This theory sees bipolar disorder as a suite of related neurodevelopmental conditions with interconnected functional abnormalities that often appear early in life and worsen over time. In addition to accelerated loss of volume in brain areas known to be essential for mood regulation and cognitive function, consistent findings have emerged at a cellular level, providing evidence that bipolar disorder is reliably associated with dysregulation of glial-neuronal interactions. Among these glial elements are microglia—the brain’s primary immune elements, which appear to be overactive in the context of bipolarity. Multiple studies now indicate that inflammation is also increased in the periphery of the body in both the depressive and manic phases of the illness, with at least some return to normality in the euthymic state. These findings are consistent with changes in the HPA axis, which are known to drive inflammatory activation. In summary, the very fact that no single gene, pathway or brain abnormality is likely to ever account for the condition is itself an extremely important first step in better articulating an integrated perspective on both its ontological status and pathogenesis. Whether this perspective will translate into the discovery of innumerable more homogeneous forms of bipolarity is one of the great

  19. An electrokinetic model of transduction in the semicircular canal.

    Science.gov (United States)

    O'Leary, D P

    1970-09-01

    Transduction in the semicircular canal was studied by focusing an infrared beam on either side of exposed ampullae from the posterior canals of Rana pipiens. The direction of fluid movement resulting from a stimulus was inferred by observing the polarity of the change in afferent impulse mean rate relative to the spontaneous value. On the basis of the accepted functional polarization of this receptor, the results indicate that fluid moved toward the warmer side of the ampulla. Convection and thermal reception were shown to be unlikely explanations for these results. Morover, cupular displacements toward the warmer side would not be expected. Because thermo-osmosis can cause fluid to move toward the warmer side in a gelatin membrane, the results can be interpreted as evidence that thermo-osmosis occurred in the gelatinous cupula and influenced the transduction mechanism. Thermo-osmosis of liquids appears to be due to an electric field that is set up in a charged membrane; hence, the hair cells might have detected an electric field that occurred in the cupula during thermo-osmosis. Electroreception might be an important link in the transduction of physiological stimuli also. Rotational stimuli could result in weak electric fields in the cupula by the mechanoelectric effect. Cupular displacements could be important for large stimuli, but extrapolations to threshold stimuli suggest displacements of angstrom amplitudes. Therefore, electroreception by the hair cells could be an explanation of the great sensitivity that has been observed in the semicircular canal and other labyrinthine receptors. PMID:5496906

  20. Role of the phosphoinositide signal transduction pathway in the endometrium

    Institute of Scientific and Technical Information of China (English)

    Vincenza Rita Lo Vasco

    2012-01-01

    The regulation of calcium concentration triggers physiological events in all cell types. Unregulated elevation in calcium concentrations is often cytotoxic.In fact, uncontrolled calcium levels alter proteins’ function, apoptosis regulation, as well as proliferation, secretion and contraction.Calcium levels are tightly regulated.A great interest was paid to signal transduction pathways for their role in mammalian reproduction.The role of phosphoinositide(PI) signal transduction pathway and related phosphoinositide-specific phospholipaseC(PI-PLC) enzymes in the regulation of calcium levels was actively studied and characterized.However, the role of PI signaling andPI-PLC enzymes in the endometrium is far to be completely highlighted.In the present review the role ofPI, the expression of selectedPI-PLC enzymes and the crosstalk with further signaling systems in the endometrium will be discussed.

  1. 受体的适应性变化及细胞信号转导规律与运动的联系%Association of receptor adaptative change and cell signal transduction with exercise

    Institute of Scientific and Technical Information of China (English)

    李宏伟; 狄朝晖

    2011-01-01

    背景:受体调控和转换信号并启动细胞内信号转导,使靶细胞产生生物学效应.受体调节是机体对运动适应的重要调节方式.目的:总结运动对受体的影响、受体的适应性变化及运动受体细胞信号转导规律.方法:由第一作者用计算机检索中国期刊全文数据库(CNKI:2000/2010)和Medline数据库(2000/2010),检索词分别为"受体,运动,适应"和"receptor regulation,exercise,adaption".共检索到137篇文章,按纳入和排除标准对文献进行筛选,共纳入37篇文章.从受体概念、受体的分类和功能,受体的功能与调节,运动对受体的影响等方面进行总结,对受体在运动中的适应性变化和调节机制等方面进行探讨.结果与结论:运动训练引起瘦素受体和胰岛素受体上调,使瘦素和胰岛素分泌发生适应性改变.适宜运动使雄激素受体结合容量和受体数量提高,长期大运动量训练和力竭使雄激素受体结合容量和受体数量下降,意味着保护细胞免受过量或长期刺激而导致生理功能紊乱.急性应激使机体各组织中糖皮质激素受体含量减少,对于防止物质代谢和能量代谢紊乱,维持机体内环境稳定有重要意义.%BACKGROUND: The receptor regulates and switches signal and starts intracellular signal transduction, which causes target cellsto produce biological effects. Receptor regulation is an important regulation mode for organism to motor adaptation.OBJECTIVE: To summarize the effects of motor on receptor, the adaptati ve change of receptor, and signal transduction rule ofmotor receptor cells.METHODS: A computer-based retrieval was performed by the first author to search manuscripts in the CNKI (2000/2010) andMedline database (2000/2010) with the key word “receptor regulation, exercise, adaption”. A total of 137 manuscripts wereincluded. According to inclusion and exclusion criteria, totally 37 manuscripts were included in the final analysis. The

  2. Molecular mechanisms and dynamic simulations of bipolarization of chemotactic cells%运动细胞初始极化阶段胞内信号分子双向积聚的分子机制及动态数值模拟

    Institute of Scientific and Technical Information of China (English)

    冯世亮; 朱卫平

    2012-01-01

    cells, such as Dictyostelium and Leukocyte, are chemotactic. As a response of the cell to extracellular attractants that spread from the front, a bidirectional material movement occurs in the cell: an enzyme PI3K and its product PI(3,4,5)P3 (Phosphatidylinositol 3,4,5-trisphosphate) in plasma membrane diffuse forward and aggregate in the front edge, while PTEN (A degrading enzyme of PI(3,4,5)P3) and its product PI(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) run in the opposite way, which forms a bipolarization. To interpret this bipolarization phenomenon, a mathematic model was constructed based on the principle of "local excitation and global inhibitation" as well as the mechanism of positive/negative feedback in signal transduction. The activated Rac was employed as a trigger signal, and the evolution of PI(3,4,5)P3 and PI(4,5)P2 along with the activation and inhibitation of enzymes (i.e., PI3K, PTEN) was described by a set of coupled transient diffusion-reaction equations, being simulated by a lattice Boltzmann method. The source terms in the diffusion-reaction equations include the stochastic interactions between the intracellular signalation molecules (i.e., PI3K, PI(3,4,5)P3), being simulated by a Monte-Carlo method according to the Michaelis-Menten catalytic kinetics. The simulation results show that the bipolarization is governed by a short-range positive feedback loop: Rac→PI3K(→)PI(3,4,5)P3, and a long-range negative feedback loop: PI(3,4,5)P3 (→) PTEN→PI(4,5)P2, which is a presentation of "local excitation and global inhabitation". In addition, it is found that the bipolarization rate is dependent on the total average concentration of PI3K or PTEN, and the optimum is 0.07 μmol/L for the rapidest bipolarization.

  3. Molecular neurobiological clues to the pathogenesis of bipolar disorder.

    Science.gov (United States)

    Harrison, Paul J

    2016-02-01

    Bipolar disorder is a serious psychiatric disorder, with a high heritability and unknown pathogenesis. Recent genome-wide association studies have identified the first loci, implicating genes such as CACNA1C and ANK3. The genes highlight several pathways, notably calcium signalling, as being of importance. Molecular studies suggest that the risk variants impact on gene regulation and expression. Preliminary studies using reprogrammed patient-derived cells report alterations in the transcriptome and in cellular adhesion and differentiation. Mouse models show that genes involved in circadian biology, acting via dopaminergic effects, reproduce aspects of the bipolar phenotype. These findings together represent significant advances in identification of the genetic and molecular basis of bipolar disorder, yet we are still far from an integrated, evidence-based understanding of its aetiopathogenesis.

  4. Bipolar budding in yeasts - an electron microscope study

    NARCIS (Netherlands)

    Kreger-van Rij, N.J.W.; Veenhuis, M.

    1971-01-01

    Bud formation in yeasts with bipolar budding was studied by electron microscopy of thin sections. Budding in yeasts of the species Saccharomycodes ludwigii, Hanseniaspora valbyensis and Wickerhamia fluorescens resulted in concentric rings of scar ridges on the wall of the mother cell. The wall betwe

  5. Imunologia do transtorno bipolar Immunology of bipolar disorder

    OpenAIRE

    Izabela Guimarães Barbosa; Rodrigo Barreto Huguet; Fernando Silva Neves; Moisés Evandro Bauer; Antônio Lúcio Teixeira

    2009-01-01

    OBJETIVO: Pesquisas recentes têm implicado fatores imunes na patogênese de diversos transtornos neuropsiquiátricos. O objetivo do presente trabalho é revisar os trabalhos que investigaram a associação entre transtorno bipolar e alterações em parâmetros imunes. MÉTODOS: Artigos que incluíam as palavras-chave: "bipolar disorder", "mania", "immunology", "cytokines", "chemokines", "interleukins", "interferon" e "tumor necrosis factor" foram selecionados em uma revisão sistemática da literatura. A...

  6. Addition of TAT protein transduction domain and GrpE to human p53 provides soluble fusion proteins that can be transduced into dendritic cells and elicit p53-specific T-cell responses in HLA-A*0201 transgenic mice

    DEFF Research Database (Denmark)

    Justesen, S; Buus, S; Claesson, M H;

    2007-01-01

    The protein p53 has been shown to be an efficient tumour antigen in both murine and human cancer vaccine studies and cancer vaccines targeting p53 based on major histocompatibility complex (MHC) class I binding p53-derived peptides that induce cytotoxic T lymphocytes (CTLs) without p53-specific CD4......(+) T-cell help have been tested by several research groups including ours. To obtain such CD4(+) T-cell help and cover a broader repertoire of MHC haplotypes we have previously attempted to produce recombinant human p53 for vaccination purposes. However, attempts to refold a hexahis-tagged p53 protein...... in our laboratory were unsuccessful. Here, we show that fusion of an 11-amino-acid region of the human immunodeficiency virus TAT protein transduction domain (PTD) to human p53 increases the solubility of the otherwise insoluble p53 protein and this rTAT-p53 protein can be transduced into human...

  7. Development and Electrochemical Testing of Novel Bipolar Nickel Metal Hydride Batteries

    Institute of Scientific and Technical Information of China (English)

    DENG Chao; SHI Peng-fei

    2006-01-01

    Some aspects in the design and development of bipolar Ni/MH battery are presented. After optimizing sealing technique and modifying capacity ratio of two adjacent electrodes in one sub-cell, some bipolar Ni/MH stacks with 6 sub-cells have been assembled and investigated. Electrochemical testing results show the bipolar battery has excellent high rate discharge capability and fast recharge ability, and satisfactory charging efficiency in different states of charge. Moreover, the battery also displays good stability under pulse cycles in simulating hybrid vehicle working conditions.

  8. Roles of lipid turnover in transmembrane signal transduction.

    Science.gov (United States)

    Ganong, B R

    1991-11-01

    Cells of higher organisms respond to external stimuli with a cascade of intracellular biochemical events initiated by binding of a hormone, growth factor, or neurotransmitter to a specific cell surface receptor. Previously well-characterized signal transduction pathways involve cyclic nucleotides as intracellular second messengers. Over the past decade, increasing attention has been focused on other signaling pathways in which membrane lipids serve as second messengers or their precursors. This review describes current understanding of these pathways and points to recent discoveries likely to open new frontiers in the coming decade.

  9. Bcl-2 associated with severity of manic symptoms in bipolar patients in a manic phase.

    Science.gov (United States)

    Chen, Wei-Ting; Huang, Tiao-Lai; Tsai, Meng-Chang

    2015-02-28

    B cell lymphoma protein-2 (Bcl-2) may contribute to the pathophysiology of bipolar disorder, and may be involved in the therapeutic action of anti-manic drugs. The aim of this study was to investigate serum levels of Bcl-2 in bipolar patients in a manic phase, and evaluate the Bcl-2 changes after treatment. We consecutively enrolled 23 bipolar inpatients in a manic phase and 40 healthy subjects; 20 bipolar patients were followed up with treatment. Serum Bcl-2 levels were measured with assay kits. All 20 patients were evaluated by examining the correlation between Bcl-2 levels and Young Mania Rating Scale (YMRS) scores, using Spearman׳s correlation coefficients. The serum Bcl-2 levels in bipolar patients in a manic phase were higher than in healthy subjects, but without a significant difference. The YMRS scores were significantly negatively associated with serum Bcl-2 levels (p=0.042). Bcl-2 levels of the 20 bipolar patients were measured at the end of treatment. Using the Wilcoxon Signed Rank test, we found no significant difference in the Bcl-2 levels of bipolar patients after treatment. Our results suggest that Bcl-2 levels might be an indicator of severity of manic symptoms in bipolar patients in a manic phase. PMID:25563670

  10. Mathematical models of bipolar disorder

    Science.gov (United States)

    Daugherty, Darryl; Roque-Urrea, Tairi; Urrea-Roque, John; Troyer, Jessica; Wirkus, Stephen; Porter, Mason A.

    2009-07-01

    We use limit cycle oscillators to model bipolar II disorder, which is characterized by alternating hypomanic and depressive episodes and afflicts about 1% of the United States adult population. We consider two non-linear oscillator models of a single bipolar patient. In both frameworks, we begin with an untreated individual and examine the mathematical effects and resulting biological consequences of treatment. We also briefly consider the dynamics of interacting bipolar II individuals using weakly-coupled, weakly-damped harmonic oscillators. We discuss how the proposed models can be used as a framework for refined models that incorporate additional biological data. We conclude with a discussion of possible generalizations of our work, as there are several biologically-motivated extensions that can be readily incorporated into the series of models presented here.

  11. Transduction of plasmid DNA in Streptomyces spp. and related genera by bacteriophage FP43.

    Science.gov (United States)

    McHenney, M A; Baltz, R H

    1988-05-01

    A segment (hft) of bacteriophage FP43 DNA cloned into plasmid pIJ702 mediated high-frequency transduction of the resulting plasmid (pRHB101) by FP43 in Streptomyces griseofuscus. The transducing particles contained linear concatemers of plasmid DNA. Lysates of FP43 prepared on S. griseofuscus containing pRHB101 also transduced many other Streptomyces species, including several that restrict plaque formation by FP43 and at least two that produce restriction endonucleases that cut pRHB101 DNA. Transduction efficiencies in different species were influenced by the addition of anti-FP43 antiserum to the transduction plates, the temperature for cell growth before transduction, the multiplicity of infection, and the host on which the transducing lysate was prepared. FP43 lysates prepared on S. griseofuscus(pRHB101) also transduced species of Streptoverticillium, Chainia, and Saccharopolyspora.

  12. SELF-ADAPTIVE CONTROLS OF A COMPLEX CELLULAR SIGNALING TRANSDUCTION SYSTEM

    Institute of Scientific and Technical Information of China (English)

    LI Hong; ZHOU Zhiyuan; DAI Rongyang; LUO Bo; ZHENG Xiaoli; YANG Wenli; HE Tao; WU Minglu

    2004-01-01

    In cells, the interactions of distinct signaling transduction pathways originating from cross-talkings between signaling molecules give rise to the formation of signaling transduction networks, which contributes to the changes (emergency) of kinetic behaviors of signaling system compared with single molecule or pathway. Depending on the known experimental data, we have constructed a model for complex cellular signaling transduction system, which is derived from signaling transduction of epidermal growth factor receptor in neuron. By the computational simulating methods, the self-adaptive controls of this system have been investigated. We find that this model exhibits a relatively stable selfadaptive system, especially to over-stimulation of agonist, and the amplitude and duration of signaling intermediates in it could be controlled by multiple self-adaptive effects, such as "signal scattering", "positive feedback", "negative feedback" and "B-Raf shunt". Our results provide an approach to understanding the dynamic behaviors of complex biological systems.

  13. Electrodialytic remediation of copper mine tailings using bipolar electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Rojo, Adrian, E-mail: adrian.rojo@usm.cl [Departamento de Ingenieria Quimica y Ambiental, Universidad Tecnica Federico Santa Maria, Casilla 110-V, Valparaiso (Chile); Cubillos, Luis [Departamento de Ingenieria Quimica y Ambiental, Universidad Tecnica Federico Santa Maria, Casilla 110-V, Valparaiso (Chile)

    2009-09-15

    In this work an electrodialytic remediation (EDR) cell for copper mine tailings with bipolar stainless steel plates was analyzed. The bipolar plates were inserted inside the tailings, dividing it into independent electrochemical cells or sections, in order to increase the copper removal efficiency from mine tailings. The bipolar plates design was tested on acidic copper mine tailings with a fixed: applied electric field, liquid content, initial pH, and remediation time. The laboratory results showed that inserting bipolar plates in EDR cells improves the remediation action, even though the applied electric field is reduced by the electrochemical reactions on the plates. Basically three aspects favor the process: reduction of the ionic migration pathways, increase of the electrode surface, and in-situ generation of protons (H{sup +}) and hydroxyls (OH{sup -}). Furthermore, the laboratory results with citric acid addition significantly improve the remediation actions, reaching copper removal of up to nine times better, compared to conventional EDR experiments without any plates or citric acid addition.

  14. Does bipolar pacemaker current activate blood platelets?

    DEFF Research Database (Denmark)

    Gjesdal, Grunde; Hansen, Annebirthe Bo; Brandes, Axel

    2009-01-01

    platelets and muscle cells contain actin and myosin filaments, and both cells are activated following calcium influx. Muscle cells open their calcium channels and contract when exposed to an electric current. Current through a bipolar pacemaker lead will expose a small volume of blood, including platelets...... to the pacemaker can. METHODS: Platelet-rich plasma was prepared from two healthy subjects. Platelet reactivity to the agonist ADP was tested in paired samples in an aggregometer in a case/control setup. RESULTS: Eighteen of 46 tested pairs of platelet-rich plasma showed increased reactivity in the paced sample......; 26 were unchanged while two showed decreased reactivity in the paced sample. Using a two-sided sign test, the null hypothesis was rejected (P = 0.0004). CONCLUSIONS: The study demonstrates increased reactivity to ADP in platelets exposed in vitro to stimulation by pacemaker current. The clinical...

  15. Hair-bundle friction from transduction channels' gating forces

    Science.gov (United States)

    Bormuth, Volker; Barral, Jérémie; Joanny, Jean-François; Jülicher, Frank; Martin, Pascal

    2015-12-01

    Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. We have shown recently that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle and thus provide a major source of damping [2]. We develop here a physical theory of passive hair-bundle mechanics that explains the origin of channel friction. We show that channel friction can be understood quantitatively by coupling the dynamics of the conformational change associated with channel gating to tip-link tension. As a result, varying channel properties affects friction, with faster channels producing smaller friction. The analysis emphasizes the dual role of transduction channels' gating forces, which affect both hair-bundle stiffness and drag. Friction originating from gating of ion channels is a general concept that is relevant to all mechanosensitive channels.

  16. Woven-grid sealed quasi-bipolar lead-acid battery construction and fabricating method

    Science.gov (United States)

    Rippel, Wally E. (Inventor)

    1989-01-01

    A quasi-bipolar lead-acid battery construction includes a plurality of bipolar cells disposed in side-by-side relation to form a stack, and a pair of monoplanar plates at opposite ends of the stack, the cell stack and monopolar plates being contained within a housing of the battery. Each bipolar cell is loaded with an electrolyte and composed of a bipolar electrode plate and a pair of separator plates disposed on opposite sides of the electrode plate and peripherally sealed thereto. Each bipolar electrode plate is composed of a partition sheet and two bipolar electrode elements folded into a hairpin configuration and applied over opposite edges of the partition sheet so as to cover the opposite surfaces of the opposite halves thereof. Each bipolar electrode element is comprised of a woven grid with a hot-melt strip applied to a central longitudinal region of the grid along which the grid is folded into the hairpin configuration, and layers of negative and positive active material pastes applied to opposite halves of the grid on opposite sides of the central hot-melt strip. The grid is made up of strands of conductive and non-conductive yarns composing the respective transverse and longitudinal weaves of the grid. The conductive yarn has a multi-stranded glass core surrounded and covered by a lead sheath, whereas the non-conductive yarn has a multi-stranded glass core surrounded and covered by a thermally activated sizing.

  17. Social support and bipolar disorder

    OpenAIRE

    Paula Mendonça Studart; Severino Bezerra Filho; Ana Beatriz Didier Studart; Amanda Galvão-de Almeida; Ângela Miranda-Scippa

    2015-01-01

    Background Bipolar disorder is a chronic condition that affects the functioning of its carriers in many different ways, even when treated properly. Therefore, it’s also important to identify the psychosocial aspects that could contribute to an improvement of this population’s quality of life.Objective Carry out a literature review on the role of social support in cases of bipolar disorder.Method A research on the following online databases PubMed, Lilacs and SciELO was conducted by using the ...

  18. Bipolar lead acid battery development

    Science.gov (United States)

    Eskra, Michael; Vidas, Robin; Miles, Ronald; Halpert, Gerald; Attia, Alan; Perrone, David

    1991-01-01

    A modular bipolar battery configuration is under development at Johnson Control, Inc. (JCI) and the Jet Propulsion Laboratory (JPL). The battery design, incorporating proven lead acid electrochemistry, yields a rechargeable, high-power source that is light weight and compact. This configuration offers advantages in power capability, weight, and volume over conventional monopolar batteries and other battery chemistries. The lead acid bipolar battery operates in a sealed, maintenance-free mode allowing for maximum application flexibility. It is ideal for high-voltage and high-power applications.

  19. Bipolar dislocation of the clavicle

    Directory of Open Access Journals (Sweden)

    Wei Jiang

    2012-01-01

    Full Text Available Bipolar dislocation of the clavicle at acromioclavicular and sternoclavicular joint is an uncommon traumatic injury. The conservative treatments adopted in the past is associated with redislocation dysfunction and deformity. A 41 years old lady with bipolar dislocation of right shoulder is treated surgically by open reduction and internal fixation by oblique T-plate at sternoclavicular joint and Kirschner wire stabilization at acromioclavicular joint. The patient showed satisfactory recovery with full range of motion of the right shoulder and normal muscular strength. The case reported in view of rarity and at 2 years followup.

  20. Bipolar dislocation of the clavicle.

    Science.gov (United States)

    Jiang, Wei; Gao, Shu-Guang; Li, Yu-Sheng; Lei, Guang-Hua

    2012-11-01

    Bipolar dislocation of the clavicle at acromioclavicular and sternoclavicular joint is an uncommon traumatic injury. The conservative treatments adopted in the past is associated with redislocation dysfunction and deformity. A 41 years old lady with bipolar dislocation of right shoulder is treated surgically by open reduction and internal fixation by oblique T-plate at sternoclavicular joint and Kirschner wire stabilization at acromioclavicular joint. The patient showed satisfactory recovery with full range of motion of the right shoulder and normal muscular strength. The case reported in view of rarity and at 2 years followup. PMID:23325981