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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-te...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    of complex diseases, it may be useful to look at combinations of genotypes. Genes related to signal transmission, e.g., ion channel genes, may be of interest in this respect in the context of bipolar disorder. In the present study, we analysed 803 SNPs in 55 genes related to aspects of signal transmission...... and calculated all combinations of three genotypes from the 3×803 SNP genotypes for 1355 controls and 607 patients with bipolar disorder. Four clusters of patient-specific combinations were identified. Permutation tests indicated that some of these combinations might be related to bipolar disorder. The WTCCC...... in the clusters in the two datasets. The present analyses of the combinations of SNP genotypes support a role for both genetic heterogeneity and interactions in the genetic architecture of bipolar disorder....

  3. Signal transduction and chemotaxis in mast cells

    Czech Academy of Sciences Publication Activity Database

    Dráber, Petr; Hálová, Ivana; Polakovičová, Iva; Kawakami, T.

    2016-01-01

    Roč. 778, jaro (2016), s. 11-23 ISSN 0014-2999 R&D Projects: GA ČR(CZ) GA14-09807S; GA ČR(CZ) GBP302/12/G101; GA ČR(CZ) GA14-00703S Institutional support: RVO:68378050 Keywords : Mast cell * IgE receptor * KIT receptor * Signal transduction * Chemotaxis * Plasma membrane Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.896, year: 2016

  4. Endothelial cell oxidative stress and signal transduction

    Directory of Open Access Journals (Sweden)

    ROCIO FONCEA

    2000-01-01

    Full Text Available Endothelial dysfunction (ED is an early event in atherosclerotic disease, preceding clinical manifestations and complications. Increased reactive oxygen species (ROS have been implicated as important mechanisms that contribute to ED, and ROS’s may function as intracellular messengers that modulate signaling pathways. Several intracellular signal events stimulated by ROS have been defined, including the identification of two members of the mitogen activated protein kinase family (ERK1/2 and big MAP kinase, BMK1, tyrosine kinases (Src and Syk and different isoenzymes of PKC as redox-sensitive kinases. ROS regulation of signal transduction components include the modification in the activity of transcriptional factors such as NFkB and others that result in changes in gene expression and modifications in cellular responses. In order to understand the intracellular mechanisms induced by ROS in endothelial cells (EC, we are studying the response of human umbilical cord vein endothelial cells to increased ROS generation by different pro-atherogenic stimuli. Our results show that Homocysteine (Hcy and oxidized LDL (oxLDL enhance the activity and expression of oxidative stress markers, such as NFkB and heme oxygenase 1. These results suggest that these pro-atherogenic stimuli increase oxidative stress in EC, and thus explain the loss of endothelial function associated with the atherogenic process

  5. TMC function in hair cell transduction

    Science.gov (United States)

    Holt, Jeffrey R.; Pan, Bifeng; Koussa, Mounir A.; Asai, Yukako

    2014-01-01

    Transmembrane channel-like (TMC) proteins 1 and 2 are necessary for hair cell mechanotransduction but their precise function is controversial. A growing body of evidence supports a direct role for TMC1 and TMC2 as components of the transduction complex. However, a number of important questions remain and alternate hypotheses have been proposed. Here we present an historical overview of the identification and cloning of Tmc genes, a discussion of mutations in TMC1 that cause deafness in mice and humans and a brief review of other members of the Tmc gene superfamily. We also examine expression of Tmc mRNAs and localization of the protein products. The review focuses on potential functions of TMC proteins and the evidence from Beethoven mice that suggests a direct role for TMC1 in hair cell mechanotransduction. Data that support alternate interpretations are also considered. The article concludes with a discussion of outstanding questions and future directions for TMC research. This article is part of a Special Issue entitled “Annual Reviews 2014”. PMID:24423408

  6. NO signaling in retinal bipolar cells.

    Science.gov (United States)

    Agurto, A; Vielma, A H; Cadiz, B; Couve, E; Schmachtenberg, O

    2017-08-01

    Nitric oxide (NO) is a neuromodulator involved in physiological and pathological processes in the retina. In the inner retina, a subgroup of amacrine cells have been shown to synthesize NO, but bipolar cells remain controversial as NO sources. This study correlates NO synthesis in dark-adapted retinas, through labeling with the NO marker DAF-FM, with neuronal nitric oxide synthase (nNOS) and inducible NOS expression, and presence of the NO receptor soluble guanylate cyclase in bipolar cells. NO containing bipolar cells were morphologically identified by dialysis of DAF fluorescent cells with intracellular dyes, or by DAF labeling followed by immunohistochemistry for nNOS and other cellular markers. DAF fluorescence was observed in all types of bipolar cells that could be identified, but the most intense DAF fluorescence was observed in bipolar cells with severed processes, supporting pathological NO signaling. Among nNOS expressing bipolar cells, type 9 was confirmed unequivocally, while types 2, 3a, 3b, 4, 5, 7, 8 and the rod bipolar cell were devoid of this enzyme. These results establish specific bipolar cell types as NO sources in the inner retina, and support the involvement of NO signaling in physiological and pathological processes in the inner retina. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Diffusion wave and signal transduction in biological live cells

    OpenAIRE

    Fan, Tian You; Fan, Lei

    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.

  8. Cell biology symposium: Membrane trafficking and signal transduction

    Science.gov (United States)

    In general, membrane trafficking is a broad group of processes where proteins and other large molecules are distributed throughout the cell as well as adjacent extracellular spaces. Whereas signal transduction is a process where signals are transmitted through a series of chemical or molecular event...

  9. Novel Vectors for Dendritic Cell Transduction

    National Research Council Canada - National Science Library

    Strong, Teresa

    2003-01-01

    .... Polynucleotide vaccines have several advantages compared to traditional vaccines including the ability to elicit antigen-specific T cells, inherent immunogenicity, ability to modify the encoded...

  10. 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

    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...

  11. 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

    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...

  12. 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...... will be discussed. In contrast to the simple pathway of osmosensing in yeast, cells from vertebrate organisms appear to exhibit multiple volume sensing systems, the specific mechanism(s) activated being cell type- and stimulus-dependent. Candidate sensors include integrins and growth factor receptors, while other...

  13. 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

  14. 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...

  15. Single-cell analysis of G-protein signal transduction.

    Science.gov (United States)

    Clister, Terri; Mehta, Sohum; Zhang, Jin

    2015-03-13

    The growing use of fluorescent biosensors to directly probe the spatiotemporal dynamics of biochemical processes in living cells has revolutionized the study of intracellular signaling. In this review, we summarize recent developments in the use of biosensors to illuminate the molecular details of G-protein-coupled receptor (GPCR) signaling pathways, which have long served as the model for our understanding of signal transduction, while also offering our perspectives on the future of this exciting field. Specifically, we highlight several ways in which biosensor-based single-cell analyses are being used to unravel many of the enduring mysteries that surround these diverse signaling pathways. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. A microfluidic platform for regulating signal transduction in single cells

    Science.gov (United States)

    Wong, Pak Kin; Yu, Fuqu; Sun, Ren; Ho, Chih-Ming

    2004-11-01

    Recent progress in micro cell culture systems has lead to new approaches in cell biology studies. Using micro devices for cell culturing possesses distinctive advantages over traditional methods. Length scale matching facilitates manipulation and detection at the single cell level. Previously, we have demonstrated generation of various stimulations such as spatial chemical gradient, electric field, and shear stress to study the dynamic responses of individual cells. Dynamic stimulations and continuous monitoring in a microfluidic system can be useful in studying different aspects of cellular process. In this work, we present a microfluidic platform for regulating nuclear factor kappa B (NF-kB) signal transduction in human embryonic kidney 293T cells. Time-varying bio-chemical stimulants, such as interleukin 1 and tumor necrosis factor, are introduced into the microchannel to activate the NF-kB signaling pathway. The dynamic responses of individual cells are monitored with the expression of reporter gene, green fluorescent protein. Regulation of the NF-kB activity is successfully demonstrated. This work is supported by CMISE through NASA URETI program.

  17. Exploring transduction mechanisms of protein transduction domains (PTDs) in living cells utilizing single-quantum dot tracking (SQT) technology.

    Science.gov (United States)

    Suzuki, Yasuhiro

    2012-01-01

    Specific protein domains known as protein transduction domains (PTDs) can permeate cell membranes and deliver proteins or bioactive materials into living cells. Various approaches have been applied for improving their transduction efficacy. It is, therefore, crucial to clarify the entry mechanisms and to identify the rate-limiting steps. Because of technical limitations for imaging PTD behavior on cells with conventional fluorescent-dyes, how PTDs enter the cells has been a topic of much debate. Utilizing quantum dots (QDs), we recently tracked the behavior of PTD that was derived from HIV-1 Tat (TatP) in living cells at the single-molecule level with 7-nm special precision. In this review article, we initially summarize the controversy on TatP entry mechanisms; thereafter, we will focus on our recent findings on single-TatP-QD tracking (SQT), to identify the major sequential steps of intracellular delivery in living cells and to discuss how SQT can easily provide direct information on TatP entry mechanisms. As a primer for SQT study, we also discuss the latest findings on single particle tracking of various molecules on the plasma membrane. Finally, we discuss the problems of QDs and the challenges for the future in utilizing currently available QD probes for SQT. In conclusion, direct identification of the rate-limiting steps of PTD entry with SQT should dramatically improve the methods for enhancing transduction efficiency.

  18. Exploring Transduction Mechanisms of Protein Transduction Domains (PTDs in Living Cells Utilizing Single-Quantum Dot Tracking (SQT Technology

    Directory of Open Access Journals (Sweden)

    Yasuhiro Suzuki

    2012-01-01

    Full Text Available Specific protein domains known as protein transduction domains (PTDs can permeate cell membranes and deliver proteins or bioactive materials into living cells. Various approaches have been applied for improving their transduction efficacy. It is, therefore, crucial to clarify the entry mechanisms and to identify the rate-limiting steps. Because of technical limitations for imaging PTD behavior on cells with conventional fluorescent-dyes, how PTDs enter the cells has been a topic of much debate. Utilizing quantum dots (QDs, we recently tracked the behavior of PTD that was derived from HIV-1 Tat (TatP in living cells at the single-molecule level with 7-nm special precision. In this review article, we initially summarize the controversy on TatP entry mechanisms; thereafter, we will focus on our recent findings on single-TatP-QD tracking (SQT, to identify the major sequential steps of intracellular delivery in living cells and to discuss how SQT can easily provide direct information on TatP entry mechanisms. As a primer for SQT study, we also discuss the latest findings on single particle tracking of various molecules on the plasma membrane. Finally, we discuss the problems of QDs and the challenges for the future in utilizing currently available QD probes for SQT. In conclusion, direct identification of the rate-limiting steps of PTD entry with SQT should dramatically improve the methods for enhancing transduction efficiency.

  19. 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.

  20. 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.

  1. 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. © 2015 AlphaMed Press.

  2. Oxidative Stress, Signal Transduction, Cell-Cell Communication

    National Research Council Canada - National Science Library

    Trosko, James

    1999-01-01

    .... The integration of intercellular communication through gap junctions and intracellular pathways plays a role in maintaining the homeostasis by controlling the expression of genes that control cell...

  3. 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.

  4. 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.

  5. 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.

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

    NARCIS (Netherlands)

    vanNetten, Sietse M.

    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

  7. [Cellular adhesion signal transduction network of tumor necrosis factor-alpha induced hepatocellular carcinoma cells].

    Science.gov (United States)

    Zheng, Yongchang; Du, Shunda; Xu, Haifeng; Xu, Yiyao; Zhao, Haitao; Chi, Tianyi; Lu, Xin; Sang, Xinting; Mao, Yilei

    2014-11-18

    To systemically explore the cellular adhesion signal transduction network of tumor necrosis factor-alpha (TNF-α)-induced hepatocellular carcinoma cells with bioinformatics tools. Published microarray dataset of TNF-α-induced HepG2, human transcription factor database HTRI and human protein-protein interaction database HPRD were used to construct and analyze the signal transduction network. In the signal transduction network, MYC and SP1 were the key nodes of signaling transduction. Several genes from the network were closely related with cellular adhesion.Epidermal growth factor receptor (EGFR) is a possible key gene of effectively regulating cellular adhesion during the induction of TNF-α. EGFR is a possible key gene for TNF-α-induced metastasis of hepatocellular carcinoma.

  8. A Computational Study on the Structure, Dynamics and Mechanoelectric Transduction of Vestibular Hair cell

    OpenAIRE

    Nam, Jong-Hoon

    2005-01-01

    The hair cell, a specialized cell in the inner ear, is responsible for hearing and balance. The hair cell is an exquisite sensor that captures mechanical stimuli and generates neurosensory signals. A theory called gating theory has been developed and widely used to analyze the experimental data of hair cell transduction. Despite increasing knowledge about molecular structures of hair cells, the mechanical model in the gating theory remained simple. Efforts to make the most of the recent f...

  9. Design of metallic bipolar plates for PEM fuel cells.

    Science.gov (United States)

    2012-01-01

    This project focused on the design and production of metallic bipolar plates for use in PEM fuel cells. Different metals were explored : and stainless steel was found out to be best suited to our purpose. Following the selection of metal, it was calc...

  10. Characterization of adenoviral transduction profile in prostate cancer cells and normal prostate tissue.

    Science.gov (United States)

    Ai, Jianzhong; Tai, Phillip W L; Lu, Yi; Li, Jia; Ma, Hong; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

    2017-09-01

    Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector. The aims of this study are to explore transduction efficiency of Ad in prostate cancer cells and normal prostate tissue, thus further providing guidance for future prostate pathophysiological studies and therapeutic development of prostate diseases. We produced Ad expressing enhanced green fluorescence protein (EGFP), and characterized the transduction efficiency of Ad in both human and mouse prostate cancer cell lines in vitro, as well as prostate tumor xenograft, and wild-type mouse prostate tissue in vivo. Ad transduction efficiency was determined by EGFP fluorescence using microscopy and flow cytometry. Cell type-specific transduction was examined by immunofluorescence staining of cell markers. Our data showed that Ad efficiently transduced human and mouse prostate cancer cells in vitro in a dose dependent manner. Following intratumoral and intraprostate injection, Ad could efficiently transduce prostate tumor xenograft and the major prostatic cell types in vivo, respectively. Our findings suggest that Ad can efficiently transduce prostate tumor cells in vitro as well as xenograft and normal prostate tissue in vivo, and further indicate that Ad could be a potentially powerful toolbox for future gene therapy of prostate diseases. © 2017 Wiley Periodicals, Inc.

  11. Alternative bipolar plates design and manufacturing for PEM fuel cell

    International Nuclear Information System (INIS)

    Lee Chang Chuan; Norhamidi Muhamad; Jaafar Sahari

    2006-01-01

    Bipolar plates is one of the important components in fuel cell stack, it comprise up to 80% of the stack volume. Traditionally, these plates have been fabricated from graphite, owing to its chemical nobility, and high electrical and thermal conductivity; but these plates are brittle and relatively thick. Therefore increasing the stack volume and size. Alternatives to graphite are carbon-carbon composite, carbon-polymer composite and metal (aluminum, stainless steel, titanium and nickel based alloy). The use of coated and uncoated metal bipolar plates has received attention recently due to the simplicity of plate manufacturing. The thin nature of the metal substrate allows for smaller stack design with reduced weight. Lightweight coated metals as alternative to graphite plate is being developed. Beside the traditional method of machining and slurry molding, metal foam for bipolar plates fabrication seems to be a good alternative. The plates will be produced with titanium powder by Powder Metallurgy method using space holders technique to produce the meal foam flow-field. This work intends to facilitate the materials and manufacturing process requirements to produce cost effective foamed bipolar plates for fuel cell

  12. Targeted Lymphoma Cell Death by Novel Signal Transduction Modifications

    Science.gov (United States)

    2011-07-01

    killing potential in a malignant T cell line, Jurkat , figure 4. While the peptides did demonstrate some cytotoxicty in T cells it was not of the same...assessed as described in figure 2 A ssessm ent of C ytotoxic P otentail of C D 22 B inding P eptides in Jurkat T cells, Figure 4 0 20 40 60 80...60 80 100 120 Jurkat R am os R aji M C 116 D O H H 2 W S U -W M W S U -C LL K arpas 519 C ell Lines A s C o n tr o l ( % ) Figure 6

  13. Generation of pluripotent stem cells via protein transduction.

    Science.gov (United States)

    Li, Xia; Zhang, Pengfei; Wei, Chao; Zhang, Yunhai

    2014-01-01

    The development of techniques for reprogramming somatic cells led to the birth of the cloned sheep “Dolly” and the generation of induced pluripotent stem cells (iPSCs). iPSCs hold great promise for in vitro disease modeling, new drug screening, regenerative medicine and agricultural production. These cells can differentiate into almost any tissue types and they can be used to produce autografts that will not be rejected by the patient. However, practical application has been limited by the potential for insertion mutagenesis and by the complexity of the associated procedures. A protein-based approach to generation of iPSCs could offer better prospects by avoiding these problems. This review provides an overview of the key processes and mechanism involved in protein-based somatic cell reprogramming, discusses some promising methods for increasing its efficiency and future challenges.

  14. Adeno-associated virus vector transduction of vascular smooth muscle cells in vivo.

    Science.gov (United States)

    Richter, M; Iwata, A; Nyhuis, J; Nitta, Y; Miller, A D; Halbert, C L; Allen, M D

    2000-04-27

    Adeno-associated virus (AAV) vectors might offer solutions for restenosis and angiogenesis by transducing nondividing cells and providing long-term gene expression. We investigated the feasibility of vascular cell transduction by AAV vectors in an in vivo rabbit carotid artery model. Time course of gene expression, inflammatory reaction to the vector, and effects of varying viral titer, exposure time, and intraluminal pressures on gene expression were examined. Recombinant AAV vectors with an Rous sarcoma virus promoter and alkaline phosphatase reporter gene were injected intraluminally into transiently isolated carotid segments. Following transduction, gene expression increased significantly over 14 days and then remained stable to 28 days, the last time point examined. Medial vascular smooth muscle cells were the main cell type transduced even with an intact endothelial layer. Increasing the viral titer and intraluminal pressure both enhanced transduction efficiency to achieve a mean of 34 +/- 7% of the subintimal layer of smooth muscle cells expressing gene product. A mild inflammatory reaction, composed of T cells with only rare macrophages, with minimal intimal thickening was demonstrated in 40% of transduced vessels; inflammatory cells were not detected in sham-operated control arteries. These findings demonstrate that AAV is a promising vector for intravascular applications in coronary and peripheral vascular diseases.

  15. ON Cone Bipolar Cell Axonal Synapses in the OFF Inner Plexiform Layer of the Rabbit Retina

    Science.gov (United States)

    Lauritzen, J. Scott; Anderson, James R.; Jones, Bryan W.; Watt, Carl B.; Mohammed, Shoeb; Hoang, John V.; Marc, Robert E.

    2012-01-01

    Analysis of the rabbit retinal connectome RC1 reveals that the division between the ON and OFF inner plexiform layer (IPL) is not structurally absolute. ON cone bipolar cells make non-canonical axonal synapses onto specific targets and receive amacrine cell synapses in the nominal OFF layer, creating novel motifs, including inhibitory crossover networks. Automated transmission electron microscope (ATEM) imaging, molecular tagging, tracing, and rendering of ≈ 400 bipolar cells reveals axonal ribbons in 36% of ON cone bipolar cells, throughout the OFF IPL. The targets include GABA-positive amacrine cells (γACs), glycine-positive amacrine cells (GACs) and ganglion cells. Most ON cone bipolar cell axonal contacts target GACs driven by OFF cone bipolar cells, forming new architectures for generating ON-OFF amacrine cells. Many of these ON-OFF GACs target ON cone bipolar cell axons, ON γACs and/or ON-OFF ganglion cells, representing widespread mechanisms for OFF to ON crossover inhibition. Other targets include OFF γACs presynaptic to OFF bipolar cells, forming γAC-mediated crossover motifs. ON cone bipolar cell axonal ribbons drive bistratified ON-OFF ganglion cells in the OFF layer and provide ON drive to polarity-appropriate targets such as bistratified diving ganglion cells (bsdGCs). The targeting precision of ON cone bipolar cell axonal synapses shows that this drive incidence is necessarily a joint distribution of cone bipolar cell axonal frequency and target cell trajectories through a given volume of the OFF layer. Such joint distribution sampling is likely common when targets are sparser than sources and when sources are coupled, as are ON cone bipolar cells. PMID:23042441

  16. 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

  17. Bipolar Cell-Photoreceptor Connectivity in the Zebrafish (Danio rerio) Retina

    Science.gov (United States)

    Li, Yong N.; Tsujimura, Taro; Kawamura, Shoji; Dowling, John E.

    2013-01-01

    Bipolar cells convey luminance, spatial and color information from photoreceptors to amacrine and ganglion cells. We studied the photoreceptor connectivity of 321 bipolar cells in the adult zebrafish retina. 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was inserted into whole-mounted transgenic zebrafish retinas to label bipolar cells. The photoreceptors that connect to these DiI-labeled cells were identified by transgenic fluorescence or their positions relative to the fluorescent cones, as cones are arranged in a highly-ordered mosaic: rows of alternating blue- (B) and ultraviolet-sensitive (UV) single cones alternate with rows of red- (R) and green-sensitive (G) double cones. Rod terminals intersperse among cone terminals. As many as 18 connectivity subtypes were observed, 9 of which – G, GBUV, RG, RGB, RGBUV, RGRod, RGBRod, RGBUVRod and RRod bipolar cells – accounted for 96% of the population. Based on their axon terminal stratification, these bipolar cells could be further sub-divided into ON, OFF, and ON-OFF cells. The dendritic spread size, soma depth and size, and photoreceptor connections of the 308 bipolar cells within the 9 common connectivity subtypes were determined, and their dendritic tree morphologies and axonal stratification patterns compared. We found that bipolar cells with the same axonal stratification patterns could have heterogeneous photoreceptor connectivity whereas bipolar cells with the same dendritic tree morphology usually had the same photoreceptor connectivity, although their axons might stratify on different levels. PMID:22907678

  18. Preclinical validation: LV/IL-12 transduction of patient leukemia cells for immunotherapy of AML

    Directory of Open Access Journals (Sweden)

    Ju Huang

    2016-01-01

    Full Text Available Interleukin-12 (IL-12 is a potent cytokine that may be harnessed to treat cancer. To date, nearly 100 IL-12-based clinical trials have been initiated worldwide. Yet systemic administration of IL-12 is toxic. Different strategies are being developed to reduce such toxicities by restricting IL-12 distribution. Our previous studies employed lentivector-mediated expression of murine IL-12 in tumor cells and demonstrated effective protection in both mouse leukemia and solid tumor challenge models. In this study, we carried out preclinical validation studies using a novel lentivector to engineer expression of human IL-12 in acute myeloid leukemia blast cells isolated from 21 patients. Acute myeloid leukemia cells were transduced with a bicistronic lentivector that encodes the human IL-12 cDNA as a fusion, as well as a LNGFR (ΔLNGFR/mutant thymidylate kinase cassette as a marking and cell-fate control element. A range of 20–70% functional transduction efficiencies was achieved. Transduced acute myeloid leukemia cells produced bioactive IL-12 protein and displayed dose-dependent sensitivity to the prodrug 3′-azido-3′-deoxythymidine. In vitro immortalization assays using transduced mouse hematopoietic stem cells demonstrated minimal genotoxic risk from our IL-12 vector. Scale-up transduction and cell processing was subsequently validated in a GMP facility to support our (now approved Clinical Trial Application (CTA.

  19. Cell loss during pseudoislet formation hampers profound improvements in islet lentiviral transduction efficacy for transplantation purposes.

    Science.gov (United States)

    Callewaert, H; Gysemans, C; Cardozo, A K; Elsner, M; Tiedge, M; Eizirik, D L; Mathieu, C

    2007-01-01

    Islet transplantation is a promising treatment in type 1 diabetes, but the need for chronic immunosuppression is a major hurdle to broad applicability. Ex vivo introduction of agents by lentiviral vectors-improving beta-cell resistance against immune attack-is an attractive path to pursue. The aim of this study was to investigate whether dissociation of islets to single cells prior to viral infection and reaggregation before transplantation would improve viral transduction efficacy without cytotoxicity. This procedure improved transduction efficacy with a LV-pWPT-CMV-EGFP construct from 11.2 +/- 4.1% at MOI 50 in whole islets to 80.0 +/- 2.8% at MOI 5. Viability (as measured by Hoechst/PI) and functionality (as measured by glucose challenge) remained high. After transplantation, the transfected pseudoislet aggregates remained EGFP positive for more than 90 days and the expression of EGFP colocalized primarily with the insulin-positive beta-cells. No increased vulnerability to immune attack was observed in vitro or in vivo. These data demonstrate that dispersion of islets prior to lentiviral transfection and reaggregation prior to transplantation is a highly efficient way to introduce genes of interest into islets for transplantation purposes in vitro and in vivo, but the amount of beta-cells needed for normalization of glycemia was more than eightfold higher when using dispersed cell aggregates versus unmanipulated islets. The high price to pay to reach stable and strong transgene expression in islet cells is certainly an important cell loss.

  20. A competitive cell growth assay for the detection of subtle effects of gene transduction on cell proliferation

    NARCIS (Netherlands)

    Eekels, J. J. M.; Pasternak, A. O.; Schut, A. M.; Geerts, D.; Jeeninga, R. E.; Berkhout, B.

    2012-01-01

    RNA interference (RNAi) is a sequence-specific gene silencing mechanism with therapeutic potential against many human pathogens. To obtain a durable therapeutic effect, stable transduction of target cells with for instance a lentiviral vector that expresses a short hairpin (shRNA) inducer of the

  1. Cell type specificity of signaling: view from membrane receptors distribution and their downstream transduction networks.

    Science.gov (United States)

    He, Ying; Yu, Zhonghao; Ge, Dongya; Wang-Sattler, Rui; Thiesen, Hans-Jürgen; Xie, Lu; Li, Yixue

    2012-09-01

    Studies on cell signaling pay more attention to spatial dynamics and how such diverse organization can relate to high order of cellular capabilities. To overview the specificity of cell signaling, we integrated human receptome data with proteome spatial expression profiles to systematically investigate the specificity of receptors and receptor-triggered transduction networks across 62 normal cell types and 14 cancer types. Six percent receptors showed cell-type-specific expression, and 4% signaling networks presented enriched cell-specific proteins induced by the receptors. We introduced a concept of "response context" to annotate the cell-type dependent signaling networks. We found that most cells respond similarly to the same stimulus, as the "response contexts" presented high functional similarity. Despite this, the subtle spatial diversity can be observed from the difference in network architectures. The architecture of the signaling networks in nerve cells displayed less completeness than that in glandular cells, which indicated cellular-context dependent signaling patterns are elaborately spatially organized. Likewise, in cancer cells most signaling networks were generally dysfunctional and less complete than that in normal cells. However, glioma emerged hyper-activated transduction mechanism in malignant state. Receptor ATP6AP2 and TNFRSF21 induced rennin-angiotensin and apoptosis signaling were found likely to explain the glioma-specific mechanism. This work represents an effort to decipher context-specific signaling network from spatial dimension. Our results indicated that although a majority of cells engage general signaling response with subtle differences, the spatial dynamics of cell signaling can not only deepen our insights into different signaling mechanisms, but also help understand cell signaling in disease.

  2. Generation of Functional Human Cardiac Progenitor Cells by High-Efficiency Protein Transduction.

    Science.gov (United States)

    Li, Xiao-Hong; Li, Qianqian; Jiang, Lin; Deng, Chunyu; Liu, Zaiyi; Fu, Yongheng; Zhang, Mengzhen; Tan, Honghong; Feng, Yuliang; Shan, Zhixin; Wang, Jianjun; Yu, Xi-Yong

    2015-12-01

    The reprogramming of fibroblasts to induced pluripotent stem cells raises the possibility that somatic cells could be directly reprogrammed to cardiac progenitor cells (CPCs). The present study aimed to assess highly efficient protein-based approaches to reduce or eliminate the genetic manipulations to generate CPCs for cardiac regeneration therapy. A combination of QQ-reagent-modified Gata4, Hand2, Mef2c, and Tbx5 and three cytokines rapidly and efficiently reprogrammed human dermal fibroblasts (HDFs) into CPCs. This reprogramming process enriched trimethylated histone H3 lysine 4, monoacetylated histone H3 lysine 9, and Baf60c at the Nkx2.5 cardiac enhancer region by the chromatin immunoprecipitation quantitative polymerase chain reaction assay. Protein-induced CPCs transplanted into rat hearts after myocardial infarction improved cardiac function, and this was related to differentiation into cardiomyocyte-like cells. These findings demonstrate that the highly efficient protein-transduction method can directly reprogram HDFs into CPCs. This protein reprogramming strategy lays the foundation for future refinements both in vitro and in vivo and might provide a source of CPCs for regenerative approaches. The findings from the present study have demonstrated an efficient protein-transduction method of directly reprogramming fibroblasts into cardiac progenitor cells. These results have great potential in cell-based therapy for cardiovascular diseases. ©AlphaMed Press.

  3. Towards a clinically relevant lentiviral transduction protocol for primary human CD34 hematopoietic stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Michelle Millington

    2009-07-01

    Full Text Available Hematopoietic stem cells (HSC, in particular mobilized peripheral blood stem cells, represent an attractive target for cell and gene therapy. Efficient gene delivery into these target cells without compromising self-renewal and multi-potency is crucial for the success of gene therapy. We investigated factors involved in the ex vivo transduction of CD34(+ HSCs in order to develop a clinically relevant transduction protocol for gene delivery. Specifically sought was a protocol that allows for efficient transduction with minimal ex vivo manipulation without serum or other reagents of animal origin.Using commercially available G-CSF mobilized peripheral blood (PB CD34(+ cells as the most clinically relevant target, we systematically examined factors including the use of serum, cytokine combinations, pre-stimulation time, multiplicity of infection (MOI, transduction duration and the use of spinoculation and/or retronectin. A self-inactivating lentiviral vector (SIN-LV carrying enhanced green fluorescent protein (GFP was used as the gene delivery vehicle. HSCs were monitored for transduction efficiency, surface marker expression and cellular function. We were able to demonstrate that efficient gene transduction can be achieved with minimal ex vivo manipulation while maintaining the cellular function of transduced HSCs without serum or other reagents of animal origin.This study helps to better define factors relevant towards developing a standard clinical protocol for the delivery of SIN-LV into CD34(+ cells.

  4. Expression of cDNAs in human Natural Killer cell lines by retroviral transduction.

    Science.gov (United States)

    Miah, S M Shahjahan; Campbell, Kerry S

    2010-01-01

    Human NK-like cell lines are difficult to transfect using standard mammalian expression vectors and conventional transfection protocols, but they are susceptible to retroviral transduction as a means to introduce cDNAs. Our laboratory has exploited this technique to study a number of receptors in human NK cell lines. The method utilizes a bicistronic retroviral vector that co-expresses either drug resistance or enhanced green fluorescent protein (EGFP) in parallel with the gene of interest. After a single infection with recombinant retrovirus, transduced NK cells can be sorted for expression of EGFP or the transduced cell surface marker. Alternatively, cells expressing the transduced cDNAs can be selected for by treatment with neomycin, puromycin, or hygromycin. Using this method, the sorted/selected cells uniformly express the gene of interest and the expression is stable for many weeks of culture.

  5. Retroviral transduction of murine and human hematopoietic progenitors and stem cells.

    Science.gov (United States)

    Ciuculescu, Marioara F; Brendel, Christian; Harris, Chad E; Williams, David A

    2014-01-01

    Genetic modification of cells using retroviral vectors is the method of choice when the cell population is difficult to transfect and/or requires persistent transgene expression in progeny cells. There are innumerable potential applications for these procedures in laboratory research and clinical therapeutic interventions. One paradigmatic example is the genetic modification of hematopoietic stem and progenitor cells (HSPCs). These are rare nucleated cells which reside in a specialized microenvironment within the bone marrow, and have the potential to self-renew and/or differentiate into all hematopoietic lineages. Due to their enormous regenerative capacity in steady state or under stress conditions these cells are routinely used in allogeneic bone marrow transplantation to reconstitute the hematopoietic system in patients with metabolic, inflammatory, malignant, and other hematologic disorders. For patients lacking a matched bone marrow donor, gene therapy of autologous hematopoietic stem cells has proven to be an alternative as highlighted recently by several successful gene therapy trials. Genetic modification of HSPCs using retrovirus vectors requires ex vivo manipulation to efficiently introduce the new genetic material into cells (transduction). Optimal culture conditions are essential to facilitate this process while preserving the stemness of the cells. The most frequently used retroviral vector systems for the genetic modifications of HSPCs are derived either from Moloney murine leukemia-virus (Mo-MLV) or the human immunodeficiency virus-1 (HIV-1) and are generally termed according to their genus gamma-retroviral (γ-RV) or lentiviral vectors (LV), respectively. This chapter describes in a step-by-step fashion some techniques used to produce research grade vector supernatants and to obtain purified murine or human hematopoietic stem cells for transduction, as well as follow-up methods for analysis of transduced cell populations.

  6. 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.

  7. Transduction with the antioxidant enzyme catalase protects human T cells against oxidative stress.

    Science.gov (United States)

    Ando, Takashi; Mimura, Kousaku; Johansson, C Christian; Hanson, Mikael G; Mougiakakos, Dimitrios; Larsson, Charlotte; Martins da Palma, Telma; Sakurai, Daiju; Norell, Håkan; Li, Mingli; Nishimura, Michael I; Kiessling, Rolf

    2008-12-15

    Patients with diseases characterized by chronic inflammation, caused by infection or cancer, have T cells and NK cells with impaired function. The underlying molecular mechanisms are diverse, but one of the major mediators in this immune suppression is oxidative stress caused by activated monocytes, granulocytes, or myeloid-derived suppressor cells. Reactive oxygen species can seriously hamper the efficacy of active immunotherapy and adoptive transfer of T and NK cells into patients. In this study, we have evaluated whether enhanced expression of the antioxidant enzyme catalase in human T cells can protect them against reactive oxygen species. Human CD4(+) and CD8(+) T cells retrovirally transduced with the catalase gene had increased intracellular expression and activity of catalase. Catalase transduction made CD4(+) T cells less sensitive to H(2)O(2)-induced loss-of-function, measured by their cytokine production and ability to expand in vitro following anti-CD3 stimulation. It also enhanced the resistance to oxidative stress-induced cell death after coculture with activated granulocytes, exposure to the oxidized lipid 4-hydroxynonenal, or H(2)O(2). Expression of catalase by CMV-specific CD8(+) T cells saved cells from cell death and improved their capacity to recognize CMV peptide-loaded target cells when exposed to H(2)O(2). These findings indicate that catalase-transduced T cells potentially are more efficacious for the immunotherapy of patients with advanced cancer or chronic viral infections.

  8. Self-Complementary Adeno-Associated Virus Vectors Improve Transduction Efficiency of Corneal Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Anja K Gruenert

    Full Text Available Transplantation of a donor cornea to restore vision is the most frequently performed transplantation in the world. Corneal endothelial cells (CEC are crucial for the outcome of a graft as they maintain corneal transparency and avoid graft failure due to corneal opaqueness. Given the characteristic of being a monolayer and in direct contact with culture medium during cultivation in eye banks, CEC are specifically suitable for gene therapeutic approaches prior to transplantation. Recombinant adeno-associated virus 2 (rAAV2 vectors represent a promising tool for gene therapy of CEC. However, high vector titers are needed to achieve sufficient gene expression. One of the rate-limiting steps for transgene expression is the conversion of single-stranded (ss- DNA vector genome into double-stranded (ds- DNA. This step can be bypassed by using self-complementary (sc- AAV2 vectors. Aim of this study was to compare for the first time transduction efficiencies of ss- and scAAV2 vectors in CEC. For this purpose AAV2 vectors containing enhanced green fluorescent protein (GFP as transgene were used. Both in CEC and in donor corneas, transduction with scAAV2 resulted in significantly higher transgene expression compared to ssAAV2. The difference in transduction efficiency decreased with increasing vector titer. In most cases, only half the vector titer of scAAV2 was required for equal or higher gene expression rates than those of ssAAV2. In human donor corneas, GFP expression was 64.7±11.3% (scAAV and 38.0±8.6% (ssAAV (p<0.001, respectively. Furthermore, transduced cells maintained their viability and showed regular morphology. Working together with regulatory authorities, a translation of AAV2 vector-mediated gene therapy to achieve a temporary protection of corneal allografts during cultivation and transplantation could therefore become more realistic.

  9. A graphite-coated carbon fiber epoxy composite bipolar plate for polymer electrolyte membrane fuel cell

    Science.gov (United States)

    Yu, Ha Na; Lim, Jun Woo; Suh, Jung Do; Lee, Dai Gil

    A PEMFC (polymer electrolyte membrane fuel cell or proton exchange membrane fuel cell) stack is composed of GDLs (gas diffusion layers), MEAs (membrane electrode assemblies), and bipolar plates. One of the important functions of bipolar plates is to collect and conduct the current from cell to cell, which requires low electrical bulk and interfacial resistances. For a carbon fiber epoxy composite bipolar plate, the interfacial resistance is usually much larger than the bulk resistance due to the resin-rich layer on the composite surface. In this study, a thin graphite layer is coated on the carbon/epoxy composite bipolar plate to decrease the interfacial contact resistance between the bipolar plate and the GDL. The total electrical resistance in the through-thickness direction of the bipolar plate is measured with respect to the thickness of the graphite coating layer, and the ratio of the bulk resistance to the interfacial contact resistance is estimated using the measured data. From the experiment, it is found that the graphite coating on the carbon/epoxy composite bipolar plate has 10% and 4% of the total electrical and interfacial contact resistances of the conventional carbon/epoxy composite bipolar plate, respectively, when the graphite coating thickness is 50 μm.

  10. Enhanced transduction and replication of RGD-fiber modified adenovirus in primary T cells.

    Directory of Open Access Journals (Sweden)

    Sadhak Sengupta

    2011-03-01

    Full Text Available Adenoviruses are often used as vehicles to mediate gene delivery for therapeutic purposes, but their research scope in hematological cells remains limited due to a narrow choice of host cells that express the adenoviral receptor (CAR. T cells, which are attractive targets for gene therapy of numerous diseases, remain resistant to adenoviral infection because of the absence of CAR expression. Here, we demonstrate that this resistance can be overcome when murine or human T cells are transduced with an adenovirus incorporating the RGD-fiber modification (Ad-RGD.A luciferase-expressing replication-deficient Ad-RGD infected 3-fold higher number of activated primary T cells than an adenovirus lacking the RGD-fiber modification in vitro. Infection with replication-competent Ad-RGD virus also caused increased cell cycling, higher E1A copy number and enriched hexon antigen expression in both human and murine T cells. Transduction with oncolytic Ad-RGD also resulted in higher titers of progeny virus and enhanced the killing of T cells. In vivo, 35-45% of splenic T cells were transduced by Ad-RGD.Collectively, our results prove that a fiber modified Ad-RGD successfully transduces and replicates in primary T cells of both murine and human origin.

  11. 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.

  12. Coating with spermine-pullulan polymer enhances adenoviral transduction of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Wan L

    2016-12-01

    coating could enhance adenoviral transduction of MSCs without detectable cytotoxicity or effects on differentiation. Our results argue in favor of the potentiality of the SP-coated Adv as a prototype vector for efficient and safe transduction of MSCs. Keywords: mesenchymal stem cells, adenovirus vectors, spermine-pullulan, polymer, gene transduction

  13. Advanced Composite Bipolar Plate for Unitized Regenerative Fuel Cell/Electrolyzer Systems, Phase II

    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...

  14. Advanced Composite Bipolar Plate for Unitized Regenerative Fuel Cell/Electrolyzer Systems, Phase I

    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. Isolation, culture and adenoviral transduction of parietal cells from mouse gastric mucosa

    Energy Technology Data Exchange (ETDEWEB)

    Gliddon, Briony L; Nguyen, Nhung V; Gunn, Priscilla A; Gleeson, Paul A; Driel, Ian R van [The Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, 30 Flemington Road, Parkville, Melbourne, Victoria 3010 (Australia)], E-mail: i.vandriel@unimelb.edu.au

    2008-09-01

    Here we describe a method for the isolation of intact gastric glands from mice and primary culture and transfection of mouse gastric epithelial cells. Collagenase digestion of PBS-perfused mouse stomachs released large intact gastric glands that were plated on a basement membrane matrix. The heterogeneous gland cell cultures typically contain {approx}60% parietal cells. Isolated mouse parietal cells remain viable in culture for up to 5 days and react strongly with an antibody specific to the gastric H{sup +}/K{sup +} ATPase. Isolated intact mouse gastric glands and primary cultures of mouse parietal cells respond to the secretagogue, histamine. Typical morphological changes from a resting to an acid-secreting active parietal cell were observed. In resting cultures of mouse parietal cells, the H{sup +}/K{sup +} ATPase displayed a cytoplasmic punctate staining pattern consistent with tubulovesicle element structures. Following histamine stimulation, an expansion of internal apical vacuole structures was observed together with a pronounced redistribution of the H{sup +}/K{sup +} ATPase from the cytoplasm to the apical vacuoles. A reproducible procedure to express genes of interest exogenously in these cultures of mouse parietal cells was also established. This method combines recombinant adenoviral transduction with magnetic field-assisted transfection resulting in {approx}30% transduced parietal cells. Adenoviral-transduced parietal cells maintain their ability to undergo agonist-induced activation. This protocol will be useful for the isolation, culture and expression of genes in parietal cells from genetically modified mice and as such will be an invaluable tool for studying the complex exocytic and endocytic trafficking events of the H{sup +}/K{sup +} ATPase which underpin the regulation of acid secretion.

  16. Isolation, culture and adenoviral transduction of parietal cells from mouse gastric mucosa

    International Nuclear Information System (INIS)

    Gliddon, Briony L; Nguyen, Nhung V; Gunn, Priscilla A; Gleeson, Paul A; Driel, Ian R van

    2008-01-01

    Here we describe a method for the isolation of intact gastric glands from mice and primary culture and transfection of mouse gastric epithelial cells. Collagenase digestion of PBS-perfused mouse stomachs released large intact gastric glands that were plated on a basement membrane matrix. The heterogeneous gland cell cultures typically contain ∼60% parietal cells. Isolated mouse parietal cells remain viable in culture for up to 5 days and react strongly with an antibody specific to the gastric H + /K + ATPase. Isolated intact mouse gastric glands and primary cultures of mouse parietal cells respond to the secretagogue, histamine. Typical morphological changes from a resting to an acid-secreting active parietal cell were observed. In resting cultures of mouse parietal cells, the H + /K + ATPase displayed a cytoplasmic punctate staining pattern consistent with tubulovesicle element structures. Following histamine stimulation, an expansion of internal apical vacuole structures was observed together with a pronounced redistribution of the H + /K + ATPase from the cytoplasm to the apical vacuoles. A reproducible procedure to express genes of interest exogenously in these cultures of mouse parietal cells was also established. This method combines recombinant adenoviral transduction with magnetic field-assisted transfection resulting in ∼30% transduced parietal cells. Adenoviral-transduced parietal cells maintain their ability to undergo agonist-induced activation. This protocol will be useful for the isolation, culture and expression of genes in parietal cells from genetically modified mice and as such will be an invaluable tool for studying the complex exocytic and endocytic trafficking events of the H + /K + ATPase which underpin the regulation of acid secretion

  17. Phage Transduction.

    Science.gov (United States)

    Goh, Shan

    2016-01-01

    Bacteriophages mediate horizontal gene transfer through a mechanism known as transduction. Phage transduction carried out in the laboratory involves a bacterial donor and a recipient, both of which are susceptible to infection by the phage of interest. Phage is propagated in the donor, concentrated, and exposed transiently to recipient at different multiplicity of infection ratios. Transductants are selected for the desired phenotype by culture on selective medium. Here we describe transduction of ermB conferring resistance to erythromycin by the C. difficile phage ϕC2.

  18. Targeting specific cell signaling transduction pathways by dietary and medicinal phytochemicals in cancer chemoprevention

    International Nuclear Information System (INIS)

    Neergheen, Vidushi S.; Bahorun, Theeshan; Taylor, Ethan Will; Jen, Ling-Sun; Aruoma, Okezie I.

    2010-01-01

    Natural phytochemicals derived from dietary sources or medicinal plants have gained significant recognition in the potential management of several human clinical conditions. Much research has also been geared towards the evaluation of plant extracts as effective prophylactic agents since they can act on specific and/or multiple molecular and cellular targets. Plants have been an abundant source of highly effective phytochemicals which offer great potential in the fight against cancer by inhibiting the process of carcinogenesis through the upregulation of cytoprotective genes that encode for carcinogen detoxifying enzymes and antioxidant enzymes. The mechanistic insight into chemoprevention further includes induction of cell cycle arrest and apoptosis or inhibition of signal transduction pathways mainly the mitogen-activated protein kinases (MAPK), protein kinases C (PKC), phosphoinositide 3-kinase (PI3K), glycogen synthase kinase (GSK) which lead to abnormal cyclooxygenase-2 (COX-2), activator protein-1 (AP-1), nuclear factor-kappaB (NF-κB) and c-myc expression. Effectiveness of chemopreventive agents reflects their ability to counteract certain upstream signals that leads to genotoxic damage, redox imbalances and other forms of cellular stress. Targeting malfunctioning molecules along the disrupted signal transduction pathway in cancer represent a rational strategy in chemoprevention. NF-κB and AP-1 provide mechanistic links between inflammation and cancer, and moreover regulate tumor angiogenesis and invasiveness, indicating that signaling pathways that mediate their activation provide attractive targets for new chemotherapeutic approaches. Thus cell signaling cascades and their interacting factors have become important targets of chemoprevention and phenolic phytochemicals and plant extracts seem to be promising in this endeavor.

  19. The transduction channel TRPM5 is gated by intracellular calcium in taste cells.

    Science.gov (United States)

    Zhang, Zheng; Zhao, Zhen; Margolskee, Robert; Liman, Emily

    2007-05-23

    Bitter, sweet, and umami tastants are detected by G-protein-coupled receptors that signal through a common second-messenger cascade involving gustducin, phospholipase C beta2, and the transient receptor potential M5 (TRPM5) ion channel. The mechanism by which phosphoinositide signaling activates TRPM5 has been studied in heterologous cell types with contradictory results. To resolve this issue and understand the role of TRPM5 in taste signaling, we took advantage of mice in which the TRPM5 promoter drives expression of green fluorescent protein and mice that carry a targeted deletion of the TRPM5 gene to unequivocally identify TRPM5-dependent currents in taste receptor cells. Our results show that brief elevation of intracellular inositol trisphosphate or Ca2+ is sufficient to gate TRPM5-dependent currents in intact taste cells, but only intracellular Ca2+ is able to activate TRPM5-dependent currents in excised patches. Detailed study in excised patches showed that TRPM5 forms a nonselective cation channel that is half-activated by 8 microM Ca2+ and that desensitizes in response to prolonged exposure to intracellular Ca2+. In addition to channels encoded by the TRPM5 gene, we found that taste cells have a second type of Ca2+-activated nonselective cation channel that is less sensitive to intracellular Ca2+. These data constrain proposed models for taste transduction and suggest a link between receptor signaling and membrane potential in taste cells.

  20. Homologous desensitization of histamine-mediated signal transduction system in C6 glioma cells.

    Science.gov (United States)

    Tseng, Chin-Lu; Wei, Jiann-Wu

    2013-04-30

    Molecular events involved in the homologous desensitization of histamine-mediated signal transduction system in glioma cells are not well understood. The aim of this study was designed to gain further insight into possible events in the process using the C6 glioma cells. Incubation of histamine caused increases in inositol phosphate (IP1) formation and intracellular free-calcium concentration [Ca2+]i in C6 glioma cells via the activation of a G-protein-coupled phospholipase C (PI-PLC). Histamine also caused an increase in extracellular release of arachidonic acid (AA) and formation of glycerophosphoinositol (GPI). These effects are likely to be mediated through the activation of receptor-coupled phospholipase A2 (PLA2). Pretreatment of C6 cells with histamine, from 0.1 microM to 1 mM concentrations, for 10 to 60 min significantly reduced the histamine-induced IP1 production, [Ca2+]i accumulation, AA release and GPI formation, despite repeated wash of the cells with buffer solution. Staurosporine (10 nM), a protein kinase C (PKC) inhibitor, reversed almost completely IP1 production, or partially for [Ca2+]i, GPI formation and AA release of this homologous desensitization effect of histamine. Pretreatment of C6 cells with phorbol 12-myristate 13-acetate (PMA), a PKC activator, at 0.1 nM to 0.1 microM for 2 to 15 min caused a reduction of histamine-induced IP1 formation and [Ca2+] accumulation, but enhanced histamine-induced AA release and GPI formation. Ten nM staurosporine completely reversed the effect of PMA on histamine-induced IP1 formation and partially on [Ca2+]i accumulation. However, staurosporine potentiated the effect of PMA on histamine-induced AA release and GPI formation, but the effect could be blocked by H7, a calcium-dependent PKC inhibitor. Our results indicate that activation of PKC by histamine in the signal transduction system is involved in the histamine-induced homologous desensitization event. Since PMA pretreatment could not mimic histamine

  1. 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.

  2. 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.

  3. 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…

  4. Efficient Transduction of Vascular Endothelial Cells with Recombinant Adeno-Associated Virus Serotype 1 and 5 Vectors

    Science.gov (United States)

    CHEN, SIFENG; KAPTURCZAK, MATTHIAS; LOILER, SCOTT A.; ZOLOTUKHIN, SERGEI; GLUSHAKOVA, OLENA Y.; MADSEN, KIRSTEN M.; SAMULSKI, RICHARD J.; HAUSWIRTH, WILLIAM W.; CAMPBELL-THOMPSON, MARTHA; BERNS, KENNETH I.; FLOTTE, TERENCE R.; ATKINSON, MARK A.; TISHER, C. CRAIG

    2006-01-01

    Recombinant adeno-associated virus (rAAV) has become an attractive tool for gene therapy because of its ability to transduce both dividing and nondividing cells, elicit a limited immune response, and the capacity for imparting long-term transgene expression. Previous studies have utilized rAAV serotype 2 predominantly and found that transduction of vascular cells is relatively inefficient. The purpose of the present study was to evaluate the transduction efficiency of rAAV serotypes 1 through 5 in human and rat aortic endothelial cells (HAEC and RAEC). rAAV vectors with AAV2 inverted terminal repeats containing the human α1-antitrypsin (hAAT) gene were transcapsidated using helper plasmids to provide viral capsids for the AAV1 through 5 serotypes. True type rAAV2 and 5 vectors encoding β-galactosidase or green fluorescence protein were also studied. Infection with rAAV1 resulted in the most efficient transduction in both HAEC and RAEC compared to other serotypes (p < 0.001) at 7 days posttransduction. Interestingly, expression was increased in cells transduced with rAAV5 to levels surpassing rAAV1 by day 14 and 21. Transduction with rAAV1 was completely inhibited by removal of sialic acid with sialidase, while heparin had no effect. These studies are the first demonstration that sialic acid residues are required for rAAV1 transduction in endothelial cells. Transduction of rat aortic segments ex vivo and in vivo demonstrated significant transgene expression in endothelial and smooth muscle cells with rAAV1 and 5 serotype vectors, in comparison to rAAV2. These results suggest the unique potential of rAAV1 and rAAV5-based vectors for vascular-targeted gene-based therapeutic strategies. OVERVIEW SUMMARY Gene delivery to the vasculature has significant potential as a therapeutic strategy for several cardiovascular disorders including atherosclerosis, hypertension, angiogenesis, and chronic vascular rejection of transplanted organs. However, limited advances have been

  5. 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.

  6. Signal transduction mechanisms and nitric oxide in hypoxic and ischemic human cardiac ventricular cell.

    Science.gov (United States)

    Corbucci, G C; Ricchi, A; Lettieri, B; Mastronardi, P

    2001-11-01

    Nitric oxide (NO) plays a well-known role in regulating endocellular adaptive changes to acute hypoxia and ischemia. The reversible inhibition of complex IV of the mitochondrial respiratory chain fulfils a cytoprotective function, whereas the progressive inhibition of complex I and II reveals the onset of irreversible oxidative damage due to persistent NO production in response to prolonged hypoxia and/or ischemia. In hypoxic or ischemic human myocardial cells, death may be caused by apoptosis or necrosis following the activation of the biomolecular signal transduction mechanisms. The activation of MAPK (mitogen-activated protein kinase) followed by ERK (extracellular regulated kinase) and p21waf is necessary in this respect. The myocardial cell is well known for its postmitotic nature and through their activation these kinases aim to repair DNA damaged by oxidative stress in order to guarantee the survival of the cell itself. A direct correlation has been found between the activation of these kinases and NO production. It was decided to carry out this study in hypoxic and ischemic human heart ventricular tissue in order to confirm this connection. In 10 patients undergoing cardiac valvular replacement, ventricular samples were collected before aortic clamping, after 15 min of ischemia and after 60 minutes during which the patients received doses of hematic cardioplegic solution at regular intervals. The results show a rapid increase in NO production in response to ischemia followed by a tendency for levels of this element to fall. MAPK, ERK and p21waf activation was parallel to No production, irrespective of the repeated administration of hematic cardioplegic solution. The heart tissue examined 60 minutes after aortic clamping came from a ventricular area subject to preconditioning mechanisms. In view of this, the data obtained must be seen in terms of the close correlation between the mitochondrial action played by NO and the contemporary and consequent

  7. 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.

  8. Electroretinographic assessment of rod- and cone-mediated bipolar cell pathways using flicker stimuli in mice

    Science.gov (United States)

    Tanimoto, Naoyuki; Sothilingam, Vithiyanjali; Kondo, Mineo; Biel, Martin; Humphries, Peter; Seeliger, Mathias W.

    2015-01-01

    Mouse full-field electroretinograms (ERGs) are dominated by responses of photoreceptors and depolarizing (ON-) bipolar cells, but not much of hyperpolarizing (OFF-) bipolar cells under conventional recording conditions. Here we investigate a novel ERG protocol in mice for functional assessment of the major ON- and OFF-bipolar cell pathways using flicker stimuli for a high luminance with varying frequency up to 30 Hz. Wild-type (WT) and functionally specific transgenic mice (Cnga3-/-, no cone photoreceptor function; rho-/-, no rod photoreceptor function; mGluR6-/-, no ON-bipolar cell function) were examined. The Cnga3-/- flicker ERG was similar to the WT flicker ERG at very low stimulus frequencies, whereas ERGs were comparable between WT and rho-/- mice at 5 Hz and above. Between 5 and 15 Hz, ERGs in mGluR6-/- mice differed in configuration and amplitude from those in WT and rho-/- mice; in contrast, response amplitudes above 15 Hz were comparable among WT, rho-/- and mGluR6-/- mice. In summary, we found three frequency ranges with these conditions that are dominated by activity in the rod pathways (below 5 Hz), cone ON-pathway (between 5 and 15 Hz), and cone OFF-pathway (above 15 Hz) that enables a quick overview of the functionality of the major bipolar cell pathways. PMID:26029863

  9. Transduction of hematopoietic stem cells to stimulate RNA interference against feline infectious peritonitis.

    Science.gov (United States)

    Anis, Eman A; Dhar, Madhu; Legendre, Alfred M; Wilkes, Rebecca P

    2017-06-01

    Objectives The goals of the study were: (1) to develop and evaluate non-replicating lentivirus vectors coding for feline coronavirus (FCoV)-specific micro (mi)RNA as a potential antiviral therapy for feline infectious peritonitis (FIP); (2) to assess the feasibility of transducing hematopoietic stem cells (HSCs) with ex vivo introduction of the miRNA-expressing lentivirus vector; and (3) to assess the ability of the expressed miRNA to inhibit FCoV replication in HSCs in vitro. Methods HSCs were obtained from feline bone marrow and replicated in vitro. Three lentiviruses were constructed, each expressing a different anti-FCoV miRNA. HSCs were stably transduced with the miRNA-expressing lentivirus vector that produced the most effective viral inhibition in a feline cell line. The effectiveness of the transduction and the expression of anti-FCoV miRNA were tested by infecting the HSCs with two different strains of FCoV. The inhibition of coronavirus replication was determined by relative quantification of the inhibition of intracellular viral genomic RNA synthesis using real-time, reverse-transcription PCR. The assessment of virus replication inhibition was determined via titration of extracellular virus using the TCID 50 assay. Results Inhibition of FCoV was most significant in feline cells expressing miRNA-L2 that targeted the viral leader sequence, 48 h postinfection. miRNA-L2 expression in stably transduced HSCs resulted in 90% and 92% reductions in FIPV WSU 79-1146 genomic RNA synthesis and extracellular virus production, respectively, as well as 74% and 80% reduction in FECV WSU 79-1683 genomic RNA synthesis and extracellular virus production, respectively, as compared with an infected negative control sample producing non-targeting miRNA. Conclusions and relevance These preliminary results show that genetic modification of HSCs for constitutive production of anti-coronavirus miRNA will reduce FCoV replication.

  10. Signal transduction of p53-independent apoptotic pathway induced by hexavalent chromium in U937 cells

    International Nuclear Information System (INIS)

    Hayashi, Yoko; Kondo, Takashi; Zhao Qingli; Ogawa Ryohei; Cui Zhengguo; Feril, Loreto B.; Teranishi, Hidetoyo; Kasuya, Minoru

    2004-01-01

    It has been reported that the hexavalent chromium compound (Cr(VI)) can induce both p53-dependent and p53-independent apoptosis. While a considerable amount of information is available on the p53-dependent pathway, only little is known about the p53-independent pathway. To elucidate the p53-independent mechanism, the roles of the Ca 2+ -calpain- and mitochondria-caspase-dependent pathways in apoptosis induced by Cr(VI) were investigated. When human lymphoma U937 cells, p53 mutated cells, were treated with 20 μM Cr(VI) for 24 h, nuclear morphological changes and DNA fragmentation were observed. Production of hydroxyl radicals revealed by electron paramagnetic resonance (EPR)-spin trapping, and increase of intracellular calcium ion concentration monitored by digital imaging were also observed in Cr(VI)-treated cells. An intracellular Ca 2+ chelator, BAPTA-AM, and calpain inhibitors suppressed the Cr(VI)-induced DNA fragmentation. The number of cells showing low mitochondrial membrane potential (MMP), high level of superoxide anion radicals (O 2 - ), and high activity of caspase-3, which are indicators of mitochondria-caspase-dependent pathway, increased significantly in Cr(VI)-treated cells. An antioxidant, N-acetyl-L-cysteine (NAC), decreased DNA fragmentation and inhibited the changes in MMP, O 2 - formation, and activation of caspase-3 induced by Cr(VI). No increase of the expressions of Fas and phosphorylated JNK was observed after Cr(VI) treatment. Cell cycle analysis revealed that the fraction of G2/M phase tended to increase after 24 h of treatment, suggesting that Cr(VI)-induced apoptosis is related to the G2 block. These results indicate that Ca 2+ -calpain- and mitochondria-caspase-dependent pathways play significant roles in the Cr(VI)-induced apoptosis via the G2 block, which are independent of JNK and Fas activation. The inhibition of apoptosis and all its signal transductions by NAC suggests that intracellular reactive oxygen species (ROS) are

  11. Properties of graphite-composite bipolar plate prepared by compression molding technique for PEM fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Dhakate, S.R.; Mathur, R.B.; Dhami, T.L. [National Physical Laboratory, New Delhi (India). Engineering Material Division, Carbon Technology Unit; Kakati, B.K. [Tezpur University, Assam (India). Department of Energy

    2007-12-15

    Bipolar plate is an important key component of fuel cell on the basis of its manifold function. In this direction a lot of effort is going on worldwide to make light-weight and cost-effective bipolar plate for fuel cell application. In the present investigation effort was made to develop graphite-composites bipolar plate by compression molding technique to achieve the requisite goal. The composites plates were prepared by using different reinforcing fillers such as natural graphite, synthetic graphite, carbon black, carbon fibers with phenolic resin as polymer matrix precursor in its liquid and powder form. The composition of different filler constituent adjusted in between 5 and 40 vol%. The composite plates prepared with appropriate proportion of filler components were characterized for physical and mechanical properties. It is found that no single reinforcing filler constituent composites plate gives the requisite properties for being used as bipolar plate in the PEM fuel cell. The judicious combination of reinforcing constituents gives the properties which are required for bipolar plate to use in fuel cell. By controlling the ratio of reinforcing constituents, one can able to achieve properties such as bulk density {proportional_to}1.85gcm{sup -3}, electrical conductivity >150Scm{sup -1}, shore hardness >65, bending strength >60MPa, modulus >10GPa and compressive >70MPa by applying the pressure (100kgcm{sup -2}) during compression molding. I-V characteristic of the composite bipolar plate, with optimum combination of reinforcing constituent, is found to be adequate as per the US-DOE target for composite bipolar plate. (author)

  12. 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.

  13. Estrogen Stimulates Proliferation and Differentiation of Neural Stem/Progenitor Cells through Different Signal Transduction Pathways

    Directory of Open Access Journals (Sweden)

    Makiko Okada

    2010-10-01

    Full Text Available Our previous study indicated that both 17β-estradiol (E2, known to be an endogenous estrogen, and bisphenol A (BPA, known to be a xenoestrogen, could positively influence the proliferation or differentiation of neural stem/progenitor cells (NS/PCs. The aim of the present study was to identify the signal transduction pathways for estrogenic activities promoting proliferation and differentiation of NS/PCs via well known nuclear estrogen receptors (ERs or putative membrane-associated ERs. NS/PCs were cultured from the telencephalon of 15-day-old rat embryos. In order to confirm the involvement of nuclear ERs for estrogenic activities, their specific antagonist, ICI-182,780, was used. The presence of putative membrane-associated ER was functionally examined as to whether E2 can activate rapid intracellular signaling mechanism. In order to confirm the involvement of membrane-associated ERs for estrogenic activities, a cell-impermeable E2, bovine serum albumin-conjugated E2 (E2-BSA was used. We showed that E2 could rapidly activate extracellular signal-regulated kinases 1/2 (ERK 1/2, which was not inhibited by ICI-182,780. ICI-182,780 abrogated the stimulatory effect of these estrogens (E2 and BPA on the proliferation of NS/PCs, but not their effect on the differentiation of the NS/PCs into oligodendroglia. Furthermore, E2-BSA mimicked the activity of differentiation from NS/PCs into oligodendroglia, but not the activity of proliferation. Our study suggests that (1 the estrogen induced proliferation of NS/PCs is mediated via nuclear ERs; (2 the oligodendroglial generation from NS/PCs is likely to be stimulated via putative membrane‑associated ERs.

  14. 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.

  15. 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...... in a higher percentage of cells than the EGFP gene, but there seemed to be a positive correlation between expression of the two genes. The effect of cytokine prestimulation was therefore monitored using EGFP as marker for transduction. When SCF was compared to SCF in combination with more potent cytokines...

  16. Corrosion of metal bipolar plates for PEM fuel cells: A review

    Energy Technology Data Exchange (ETDEWEB)

    Antunes, Renato A. [Engenharia de Materiais, Universidade Federal do ABC (UFABC), 09210-170 Santo Andre, SP (Brazil); Oliveira, Mara Cristina L.; Ett, Gerhard; Ett, Volkmar [Electrocell Ind. Com. Equip. Elet. LTDA, Centro de Inovacao, Empreendedorismo e Tecnologia (CIETEC), 05508-000 Sao Paulo, SP (Brazil)

    2010-04-15

    PEM fuel cells are of prime interest in transportation applications due to their relatively high efficiency and low pollutant emissions. Bipolar plates are the key components of these devices as they account for significant fractions of their weight and cost. Metallic materials have advantages over graphite-based ones because of their higher mechanical strength and better electrical conductivity. However, corrosion resistance is a major concern that remains to be solved as metals may develop oxide layers that increase electrical resistivity, thus lowering the fuel cell efficiency. This paper aims to present the main results found in recent literature about the corrosion performance of metallic bipolar plates. (author)

  17. 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

    Purpose. Propofol (2,6-diisopropyl phenol), a widely used systemic anesthetic, is known to potentiate GABA(A) receptor activity in a number of CNS neurons and to produce changes in electroretinographically recorded responses of the retina. However, little is known about propofol's effects...... on 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...

  18. Induced Pluripotent Stem Cell Clones Reprogrammed via Recombinant Adeno-Associated Virus-Mediated Transduction Contain Integrated Vector Sequences

    OpenAIRE

    Weltner, J.; Anisimov, A.; Alitalo, K.; Otonkoski, T.; Trokovic, R.

    2012-01-01

    Fibroblasts can be reprogrammed into induced pluripotent stem cells (iPSC) by ectopic expression of key transcription factors. Current methods for the generation of integration-free iPSC are limited by the low efficiency of iPSC generation and by challenges in reprogramming methodology. Recombinant adeno-associated virus (rAAV) is a potent gene delivery vehicle capable of efficient transduction of transgenic DNA into cells. rAAV stays mainly as an episome in nondividing cells, and the extent ...

  19. Direct Measurement of Bipolar Cell Responses to Electrical Stimulation in Wholemount Mouse Retina.

    Science.gov (United States)

    Walston, Steven T; Chow, Robert H; Weiland, James D

    2018-03-07

    This in vitro investigation examines the response of retinal bipolar cells to extracellular electrical stimulation. Approach: In vitro investigations characterizing the response of retinal neurons to electrical stimulation have primarily focused on retinal ganglion cells because they are the output neurons of the retina and their superficial position in the retina makes them readily accessible to in vitro recording techniques. Thus, the majority of information regarding the response of inner retinal neurons has been inferred from ganglion cell activity. Here we use patch clamp electrophysiology to directly record electrically-evoked activity in bipolar cells within the inner retina of normal Tg(Gng13-EGFP)GI206Gsat and degenerate rd10 Tg(Gng13-EGFP)GI206Gsat mice using a wholemount preparation. Main Results: Bipolar cells respond to electrical stimulation with time-locked depolarizing voltage transients. The latency of the response declines with increases in stimulation amplitude. A desensitizing response is observed during repeated stimulation with 25-ms biphasic current pulses delivered at pulse rates greater than 6 pps. A burst of long-latency (200-1000 ms) inhibitory postsynaptic potentials are evoked by the stimulus and the burst exhibits evidence of a lower and upper stimulation threshold. Significance: These results provide insights into the various types of bipolar cell activity elicited by electrical stimulation and may be useful for future retinal prosthesis stimulation protocols. . © 2018 IOP Publishing Ltd.

  20. Kinome profiling for studying lipopolysaccharide signal transduction in human peripheral blood mononuclear cells

    NARCIS (Netherlands)

    Diks, SH; Kok, K; O'Toole, T; Hommes, DW; van Dijken, P; Joore, J; Peppelenbosch, MP

    2004-01-01

    The DNA array technique allows comprehensive analysis of the genome and transcriptome, but the high throughput array-based assessment of intracellular signal transduction remains troublesome. The goal of this study was to test a new peptide array technology for studying the activity of all kinases

  1. Age-related decrease in rod bipolar cell density of the human retina ...

    Indian Academy of Sciences (India)

    PRAKASH

    Rod bipolar cells in ageing human retina. 293. J. Biosci. ... During normal ageing, the rods (and other neurones) undergo a significant decrease in density in the human retina ..... Brain Res. 84 293–300. Figure 3. Immunohistochemical demonstration of protein kinase C-α labelling in the macula of the 91-year-old donor. The.

  2. Age-related decrease in rod bipolar cell density of the human retina ...

    Indian Academy of Sciences (India)

    PRAKASH

    Age-related decrease in rod bipolar cell density of the human retina: an immunohistochemical study. P AGGARWAL, T C NAG and S WADHWA*. Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India. *Corresponding author (Fax, 91-11-26588663; Email, shashiwadhwa@hotmail.com).

  3. Vpx rescues HIV-1 transduction of dendritic cells from the antiviral state established by type 1 interferon

    Directory of Open Access Journals (Sweden)

    Reinhard Christian

    2011-06-01

    Full Text Available Abstract Background Vpx is a virion-associated protein encoded by SIVSM, a lentivirus endemic to the West African sooty mangabey (Cercocebus atys. HIV-2 and SIVMAC, zoonoses resulting from SIVSM transmission to humans or Asian rhesus macaques (Macaca mulatta, also encode Vpx. In myeloid cells, Vpx promotes reverse transcription and transduction by these viruses. This activity correlates with Vpx binding to DCAF1 (VPRBP and association with the DDB1/RBX1/CUL4A E3 ubiquitin ligase complex. When delivered experimentally to myeloid cells using VSV G-pseudotyped virus-like particles (VLPs, Vpx promotes reverse transcription of retroviruses that do not normally encode Vpx. Results Here we show that Vpx has the extraordinary ability to completely rescue HIV-1 transduction of human monocyte-derived dendritic cells (MDDCs from the potent antiviral state established by prior treatment with exogenous type 1 interferon (IFN. The magnitude of rescue was up to 1,000-fold, depending on the blood donor, and was also observed after induction of endogenous IFN and IFN-stimulated genes (ISGs by LPS, poly(I:C, or poly(dA:dT. The effect was relatively specific in that Vpx-associated suppression of soluble IFN-β production, of mRNA levels for ISGs, or of cell surface markers for MDDC differentiation, was not detected. Vpx did not rescue HIV-2 or SIVMAC transduction from the antiviral state, even in the presence of SIVMAC or HIV-2 VLPs bearing additional Vpx, or in the presence of HIV-1 VLPs bearing all accessory genes. In contrast to the effect of Vpx on transduction of untreated MDDCs, HIV-1 rescue from the antiviral state was not dependent upon Vpx interaction with DCAF1 or on the presence of DCAF1 within the MDDC target cells. Additionally, although Vpx increased the level of HIV-1 reverse transcripts in MDDCs to the same extent whether or not MDDCs were treated with IFN or LPS, Vpx rescued a block specific to the antiviral state that occurred after HIV-1 c

  4. Signal transduction of Helicobacter pylori during interaction with host cell protein receptors of epithelial and immune cells

    Science.gov (United States)

    Pachathundikandi, Suneesh Kumar; Tegtmeyer, Nicole; Backert, Steffen

    2013-01-01

    Helicobacter pylori infections can induce pathologies ranging from chronic gastritis, peptic ulceration to gastric cancer. Bacterial isolates harbor numerous well-known adhesins, vacuolating cytotoxin VacA, protease HtrA, urease, peptidoglycan, and type IV secretion systems (T4SS). It appears that H. pylori targets more than 40 known host protein receptors on epithelial or immune cells. A series of T4SS components such as CagL, CagI, CagY, and CagA can bind to the integrin α5β1 receptor. Other targeted membrane-based receptors include the integrins αvβ3, αvβ5, and β2 (CD18), RPTP-α/β, GP130, E-cadherin, fibronectin, laminin, CD46, CD74, ICAM1/LFA1, T-cell receptor, Toll-like receptors, and receptor tyrosine kinases EGFR, ErbB2, ErbB3, and c-Met. In addition, H. pylori is able to activate the intracellular receptors NOD1, NOD2, and NLRP3 with important roles in innate immunity. Here we review the interplay of various bacterial factors with host protein receptors. The contribution of these interactions to signal transduction and pathogenesis is discussed. PMID:24280762

  5. 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.

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

    International Nuclear Information System (INIS)

    Krauss, Robert S.

    2010-01-01

    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.

  7. Process for production of electrical energy from the neutralization of acid and base in a bipolar membrane cell

    International Nuclear Information System (INIS)

    Walther, J.F.

    1982-01-01

    Electrical energy is generated from acid-base neutralization reactions in electrodialytic cells. Permselective bipolar membranes in these cells are contacted on their cation selective faces by aqueous acid streams and on their anion-selective faces by aqueous base streams. Spontaneous neutralization reactions between the basic anions and acidic cations through the bipolar membranes produce electrical potential differences between the acid and base streams. These potential differences are transmitted to electrodes to produce electrical energy which is withdrawn from the cell

  8. ON Bipolar Cells in Macaque Retina: Type-Specific Synaptic Connectivity with Special Reference to OFF Counterparts

    Science.gov (United States)

    Tsukamoto, Yoshihiko; Omi, Naoko

    2016-01-01

    To date, 12 macaque bipolar cell types have been described. This list includes all morphology types first outlined by Polyak (1941) using the Golgi method in the primate retina and subsequently identified by other researchers using electron microscopy (EM) combined with the Golgi method, serial section transmission EM (SSTEM), and immunohistochemical imaging. We used SSTEM for the rod-dense perifoveal area of macaque retina, reconfirmed ON (cone) bipolar cells to be classified as invaginating midget bipolar (IMB), diffuse bipolar (DB)4, DB5, DB6, giant bipolar (GB), and blue bipolar (BB) types, and clarified their type-specific connectivity. DB4 cells made reciprocal synapses with a kind of ON-OFF lateral amacrine cell, similar to OFF DB2 cells. GB cells contacted rods and cones, similar to OFF DB3b cells. Retinal circuits formed by GB and DB3b cells are thought to substantiate the psychophysical finding of fast rod signals in mesopic vision. DB6 cell output synapses were directed to ON midget ganglion (MG) cells at 70% of ribbon contacts, similar to OFF DB1 cells that directed 60% of ribbon contacts to OFF MG cells. IMB cells contacted medium- or long-wavelength sensitive (M/L-) cones but not short-wavelength sensitive (S-) cones, while BB cells contacted S-cones but not M/L-cones. However, IMB and BB dendrites had similar morphological architectures, and a BB cell contacting a single S-cone resembled an IMB cell. Thus, both IMB and BB may be the ON bipolar counterparts of the OFF flat midget bipolar (FMB) type, likewise DB4 of DB2, DB5 of DB3a, DB6 of DB1, and GB of DB3b OFF bipolar type. The ON DB plus GB, and OFF DB cells predominantly contacted M/L-cones and their outputs were directed mainly to parasol ganglion (PG) cells but also moderately to MG cells. BB cells directed S-cone-driven outputs almost exclusively to small bistratified ganglion (SBG) cells. Some FMB cells predominantly contacted S-cones and their outputs were directed to OFF MG cells. Thus, two

  9. Efficient myogenic differentiation of human adipose-derived stem cells by the transduction of engineered MyoD protein

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Min Sun [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Biosystems and Bioengineering Program, University of Science and Technology (UST), Daejeon 305-350 (Korea, Republic of); Mun, Ji-Young [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Kwon, Ohsuk [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Biosystems and Bioengineering Program, University of Science and Technology (UST), Daejeon 305-350 (Korea, Republic of); Kwon, Ki-Sun [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Oh, Doo-Byoung, E-mail: dboh@kribb.re.kr [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Biosystems and Bioengineering Program, University of Science and Technology (UST), Daejeon 305-350 (Korea, Republic of)

    2013-07-19

    Highlights: •MyoD was engineered to contain protein transduction domain and endosome-disruptive INF7 peptide. •The engineered MyoD-IT showed efficient nuclear targeting through an endosomal escape by INF7 peptide. •By applying MyoD-IT, human adipose-derived stem cells (hASCs) were differentiated into myogenic cells. •hASCs differentiated by applying MyoD-IT fused to myotubes through co-culturing with mouse myoblasts. •Myogenic differentiation using MyoD-IT is a safe method without the concern of altering the genome. -- Abstract: Human adipose-derived stem cells (hASCs) have great potential as cell sources for the treatment of muscle disorders. To provide a safe method for the myogenic differentiation of hASCs, we engineered the MyoD protein, a key transcription factor for myogenesis. The engineered MyoD (MyoD-IT) was designed to contain the TAT protein transduction domain for cell penetration and the membrane-disrupting INF7 peptide, which is an improved version of the HA2 peptide derived from influenza. MyoD-IT showed greatly improved nuclear targeting ability through an efficient endosomal escape induced by the pH-sensitive membrane disruption of the INF7 peptide. By applying MyoD-IT to a culture, hASCs were efficiently differentiated into long spindle-shaped myogenic cells expressing myosin heavy chains. Moreover, these cells differentiated by an application of MyoD-IT fused to myotubes with high efficiency through co-culturing with mouse C2C12 myoblasts. Because internalized proteins can be degraded in cells without altering the genome, the myogenic differentiation of hASCs using MyoD-IT would be a safe and clinically applicable method.

  10. Differential Effects of Strategies to Improve the Transduction Efficiency of Lentiviral Vector that Conveys an Anti-HIV Protein, Nullbasic, in Human T Cells.

    Science.gov (United States)

    Rustanti, Lina; Jin, Hongping; Li, Dongsheng; Lor, Mary; Sivakumaran, Haran; Harrich, David

    2018-03-14

    Nullbasic is a mutant form of HIV-1 Tat that has strong ability to protect cells from HIV-1 replication by inhibiting three different steps of viral replication: reverse transcription, Rev export of viral mRNA from the nucleus to the cytoplasm and transcription of viral mRNA by RNA polymerase II. We previously showed that Nullbasic inhibits transduction of human cells including T cells by HIV-1-based lentiviral vectors. Here we investigated whether the Nullbasic antagonists huTat2 (a Tat targeting intrabody), HIV-1 Tat or Rev proteins or cellular DDX1 protein could improve transduction by a HIV-1 lentiviral vector conveying Nullbasic-ZsGreen1 to human T cells. We show that overexpression of huTat2, Tat-FLAG and DDX1-HA in virus-like particle (VLP) producer cells significantly improved transduction efficiency of VLPs that convey Nullbasic in Jurkat cells. Specifically, co-expression of Tat-FLAG and DDX1-HA in the VLP producer cell improved transduction efficiency better than if used individually. Transduction efficiencies could be further improved by including a spinoculation step. However, the same optimised protocol and using the same VLPs failed to transduce primary human CD4 + T cells. The results imply that the effects of Nullbasic on VLPs on early HIV-1 replication are robust in human CD4 + T cells. Given this significant block to lentiviral vector transduction by Nullbasic in primary CD4 + T cells, our data indicate that gammaretroviral, but not lentiviral, vectors are suitable for delivering Nullbasic to primary human T cells.

  11. Hoxa9 transduction induces hematopoietic stem and progenitor cell activity through direct down-regulation of geminin protein.

    Science.gov (United States)

    Ohno, Yoshinori; Yasunaga, Shin'ichiro; Janmohamed, Salima; Ohtsubo, Motoaki; Saeki, Keita; Kurogi, Toshiaki; Mihara, Keichiro; Iscove, Norman N; Takihara, Yoshihiro

    2013-01-01

    Hoxb4, a 3'-located Hox gene, enhances hematopoietic stem cell (HSC) activity, while a subset of 5'-located Hox genes is involved in hematopoiesis and leukemogenesis, and some of them are common translocation partners for Nucleoporin 98 (Nup98) in patients with leukemia. Although these Hox gene derivatives are believed to act as transcription regulators, the molecular involvement of the Hox gene derivatives in hematopoiesis and leukemogenesis remains largely elusive. Since we previously showed that Hoxb4 forms a complex with a Roc1-Ddb1-Cul4a ubiquitin ligase core component and functions as an E3 ubiquitin ligase activator for Geminin, we here examined the E3 ubiquitin ligase activities of the 5'-located Hox genes, Hoxa9 and Hoxc13, and Nup98-Hoxa9. Hoxa9 formed a similar complex with the Roc1-Ddb1-Cul4a component to induce ubiquitination of Geminin, but the others did not. Retroviral transduction-mediated overexpression or siRNA-mediated knock-down of Hoxa9 respectively down-regulated or up-regulated Geminin in hematopoietic cells. And Hoxa9 transduction-induced repopulating and clonogenic activities were suppressed by Geminin supertransduction. These findings suggest that Hoxa9 and Hoxb4 differ from Hoxc13 and Nup98-Hoxa9 in their molecular role in hematopoiesis, and that Hoxa9 induces the activity of HSCs and hematopoietic progenitors at least in part through direct down-regulation of Geminin.

  12. Hoxa9 transduction induces hematopoietic stem and progenitor cell activity through direct down-regulation of geminin protein.

    Directory of Open Access Journals (Sweden)

    Yoshinori Ohno

    Full Text Available Hoxb4, a 3'-located Hox gene, enhances hematopoietic stem cell (HSC activity, while a subset of 5'-located Hox genes is involved in hematopoiesis and leukemogenesis, and some of them are common translocation partners for Nucleoporin 98 (Nup98 in patients with leukemia. Although these Hox gene derivatives are believed to act as transcription regulators, the molecular involvement of the Hox gene derivatives in hematopoiesis and leukemogenesis remains largely elusive. Since we previously showed that Hoxb4 forms a complex with a Roc1-Ddb1-Cul4a ubiquitin ligase core component and functions as an E3 ubiquitin ligase activator for Geminin, we here examined the E3 ubiquitin ligase activities of the 5'-located Hox genes, Hoxa9 and Hoxc13, and Nup98-Hoxa9. Hoxa9 formed a similar complex with the Roc1-Ddb1-Cul4a component to induce ubiquitination of Geminin, but the others did not. Retroviral transduction-mediated overexpression or siRNA-mediated knock-down of Hoxa9 respectively down-regulated or up-regulated Geminin in hematopoietic cells. And Hoxa9 transduction-induced repopulating and clonogenic activities were suppressed by Geminin supertransduction. These findings suggest that Hoxa9 and Hoxb4 differ from Hoxc13 and Nup98-Hoxa9 in their molecular role in hematopoiesis, and that Hoxa9 induces the activity of HSCs and hematopoietic progenitors at least in part through direct down-regulation of Geminin.

  13. Hoxa9 Transduction Induces Hematopoietic Stem and Progenitor Cell Activity through Direct Down-Regulation of Geminin Protein

    Science.gov (United States)

    Ohno, Yoshinori; Yasunaga, Shin'ichiro; Janmohamed, Salima; Ohtsubo, Motoaki; Saeki, Keita; Kurogi, Toshiaki; Mihara, Keichiro; Iscove, Norman N.; Takihara, Yoshihiro

    2013-01-01

    Hoxb4, a 3′-located Hox gene, enhances hematopoietic stem cell (HSC) activity, while a subset of 5′-located Hox genes is involved in hematopoiesis and leukemogenesis, and some of them are common translocation partners for Nucleoporin 98 (Nup98) in patients with leukemia. Although these Hox gene derivatives are believed to act as transcription regulators, the molecular involvement of the Hox gene derivatives in hematopoiesis and leukemogenesis remains largely elusive. Since we previously showed that Hoxb4 forms a complex with a Roc1-Ddb1-Cul4a ubiquitin ligase core component and functions as an E3 ubiquitin ligase activator for Geminin, we here examined the E3 ubiquitin ligase activities of the 5′-located Hox genes, Hoxa9 and Hoxc13, and Nup98-Hoxa9. Hoxa9 formed a similar complex with the Roc1-Ddb1-Cul4a component to induce ubiquitination of Geminin, but the others did not. Retroviral transduction-mediated overexpression or siRNA-mediated knock-down of Hoxa9 respectively down-regulated or up-regulated Geminin in hematopoietic cells. And Hoxa9 transduction-induced repopulating and clonogenic activities were suppressed by Geminin supertransduction. These findings suggest that Hoxa9 and Hoxb4 differ from Hoxc13 and Nup98-Hoxa9 in their molecular role in hematopoiesis, and that Hoxa9 induces the activity of HSCs and hematopoietic progenitors at least in part through direct down-regulation of Geminin. PMID:23326393

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

    International Nuclear Information System (INIS)

    Shimada, Hidenori; Hashimoto, Yoshiya; Nakada, Akira; Shigeno, Keiji; Nakamura, Tatsuo

    2012-01-01

    Highlights: ► Very rapid generation of human iPS cells under optimized conditions. ► Five chemical inhibitors under hypoxia boosted reprogramming. ► 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 generating bona fide human iPS cells and facilitates the application of i

  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. Stem cell-derived neurons in the development of targeted treatment for schizophrenia and bipolar disorder.

    Science.gov (United States)

    Watmuff, Bradley; Liu, Bangyan; Karmacharya, Rakesh

    2017-04-01

    The recent advent of induced pluripotent stem cells has enabled the study of patient-specific and disease-related neurons in vitro and has facilitated new directions of inquiry into disease mechanisms. With these approaches, we now have the possibility of correlating ex vivo cellular phenotypes with individual patient response to treatment and/or side effects, which makes targeted treatments for schizophrenia and bipolar disorder a distinct prospect in the coming years. Here, we briefly review the current state of stem cell-based models and explore studies that are providing new insights into the disease biology of schizophrenia and bipolar disorder, which are laying the foundations for the development of novel targeted therapies.

  17. Evaluation of silver-coated stainless steel bipolar plates for fuel cell applications

    Science.gov (United States)

    Huang, Ing-Bang

    In this study, computer-aided design and manufacturing (CAD/CAM) technology were applied to develop and produce stainless steel bipolar plates for DMFC (direct methanol fuel cell). Effect of surface modification on the cell performance of DMFC was investigated. Surface modifications of the stainless steel bipolar plates were made by the electroless plating method. A DMFC consisting of silver coated stainless steel as anode and uncoated stainless steel as cathode was assembled and evaluated. The methanol crossover rate (R c) of the proton exchange membrane (PEM) was decreased by about 52.8%, the efficiency (E f) of DMFC increased about 7.1% and amounts of methanol electro-oxidation at the cathode side (M co) were decreased by about 28.6%, as compared to uncoated anode polar plates. These measurements were determined by the transient current and mathematical analysis.

  18. Astragalus mongholicus regulate the Toll-like-receptor 4 meditated signal transduction of dendritic cells to restrain stomach cancer cells.

    Science.gov (United States)

    Tian, Ye; Li, Xueliang; Li, Hongxia; Lu, Qing; Sun, Guoping; Chen, Hongjing

    2014-01-01

    -preritoneal injection with MKN45 have been divided into two groups: the treatment group challenged with AMs injection and the control group with saline injection. We took the average of the diameter of each group as the y axis and the days after administered with AMs as x axis. After 40 days, all animals were killed by detruncation, and the tumor were removed and measured. We compare the diameter (40 days) of the tumor as well as the survival days between different groups to investigate the effect of inhibition of cancer. All results show that AMs is effective in treating human stomach cancer and the mechanism might be regulated by TLR4 mediated signal transduction of DCs. The results are briefly introduced as follows: First, we succeed in culturing the DCs induced by IL-4 and GM-CSF and find the positive rate of CD11c expression, the mark of DCs, is beyond 90% (Fig-1). We detect AMs can precipitate DCs maturation by upregulating TLR4 in SYBR-Green I Real-time PCR (Fig-2) and suppressing I.B-aby Western-Blot (Fig-3). Second, after the MKN45 co-cultured with DCs, T cells and AMs injection, the result show that AMs can great reduce the amount of cell lines by MTT assay (Fig-4) and induce apoptosis with Immunofluorescence (Fig-5). Finally, we have conducted animal studies beside the experiment in vitro, and the result in vivo show that AMs can delay tumor development from the diameter and weight of the tumor (Fig-6, Fig-7), prolong life-span and improve life-quality. Figure 1the morphology and phenotypic identification of DCs.The form of DCs observed by microscope with field 20*.The isotype antibody control using FCM.The positive rate of CD11c expression.Figure 2the melting curve and the chart of TLR4 expressiona) the melting curve of beta-actin; b)the melting curve of TLR4;c)the TLR4 expression of DCs stimulated with AM at different dose. There is significant statistic difference between the 60ng/mL and 80ng/mL group and other group (Pstomach cancers as a good Chinese herbal medicine by

  19. 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.

  20. 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.

  1. Oscillation and noise determine signal transduction in shark multimodal sensory cells.

    Science.gov (United States)

    Braun, H A; Wissing, H; Schäfer, K; Hirsch, M C

    1994-01-20

    Oscillating membrane potentials that generate rhythmic impulse patterns are considered to be of particular significance for neuronal information processing. In contrast, noise is usually seen as a disturbance which limits the accuracy of information transfer. We show here, however, that noise in combination with intrinsic oscillations can provide neurons with particular encoding properties, a discovery we made when recording from single electro-sensory afferents of a fish. The temporal sequence of the impulse trains indicates oscillations that operate near the spike-triggering threshold. The oscillation frequency determines the basic rhythm of impulse generation, but whether or not an impulse is actually triggered essentially depends on superimposed noise. The probability of impulse generation can be altered considerably by minor modifications of oscillation baseline and amplitude, which may underlie the exquisite sensitivity of these receptors to thermal and electrical stimuli. Additionally, thermal, but not electrical, stimuli alter the oscillation frequency, allowing dual sensory messages to be conveyed in a single spike train. These findings demonstrate novel properties of sensory transduction which may be relevant for neuronal signalling in general.

  2. Cell-penetrating peptides (CPPs): From delivery of nucleic acids and antigens to transduction of engineered nucleases for application in transgenesis.

    Science.gov (United States)

    Rádis-Baptista, Gandhi; Campelo, Iana S; Morlighem, Jean-Étienne R L; Melo, Luciana M; Freitas, Vicente J F

    2017-06-20

    Cell-penetrating peptides (CPPs) have been studied for their capacity to translocate across the lipid membrane of several cell types. In membrane translocation, these peptides can remarkably transport biologically active hydrophilic molecules, such as pharmaceuticals, nucleic acids (DNA and RNA) and even high-molecular-weight proteins, Fig. 3 into the cell cytoplasm and organelles. The development of CPPs as transduction agents includes the modification of gene and protein expression, the reprogramming and differentiation of induced pluripotent stem cells and the preparation of cellular vaccines. A relatively recent field of CPP application is the transduction of plasmid DNA vectors and CPP-fusion proteins to modify genomes and introduce new traits in cells and organisms. CPP-mediated transduction of components for genome editing is an advantageous alternative to viral DNA vectors. Engineered site-specific nucleases, such as Cre recombinase, ZFN, TALENs and CRISPR associated protein (Cas), have been coupled to CPPs, and the fused proteins have been used to permeate targeted cells and tissues. The functionally active fusion CPP-nucleases subsequently home to the nucleus, incise genomic DNA at specific sites and induce repair and recombination. This review has the objective of discussing CPPs and elucidating the prospective use of CPP-mediated transduction technology, particularly in genome modification and transgenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. 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.

  4. 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.

  5. Development of a bipolar cell for lithium production

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, J.F.; Ebbinghaus, B.B.; Peterman, K.; Weinland, S. [Lawrence Livermore National Lab., CA (United States); McKenzie, P. [Martin Marietta Energy Systems, Inc., Oak Ridge, TN (United States)

    1995-07-01

    The authors report development and bench-scale testing of an electrolytic process for reduction of LiOH to lithium metal through an amalgam intermediate. The amalgam is formed in an aqueous-electrolyte cell and stripped in a molten salt cell using a LiI-CsI eutectic at 225 C. Total energy efficiency is >70%. The process obviates high temperature materials problems, chlorine evolution and anhydrous feedstocks. While the principle is proven, sustained operation of the cell is now needed to obtain statistical data on reliability and maintainability.

  6. Efficient treatment of aniline containing wastewater in bipolar membrane microbial electrolysis cell-Fenton system.

    Science.gov (United States)

    Li, Xiaohu; Jin, Xiangdan; Zhao, Nannan; Angelidaki, Irini; Zhang, Yifeng

    2017-08-01

    Aniline-containing wastewater can cause significant environmental problems and threaten the humans's life. However, rapid degradation of aniline with cost-efficient methods remains a challenge. In this work, a novel microbial electrolysis cell with bipolar membrane was integrated with Fenton reaction (MEC-Fenton) for efficient treatment of real wastewater containing a high concentration (4460 ± 52 mg L -1 ) of aniline. In this system, H 2 O 2 was in situ electro-synthesized from O 2 reduction on the graphite cathode and was simultaneously used as source of OH for the oxidation of aniline wastewater under an acidic condition maintained by the bipolar membrane. The aniline was effectively degraded following first-order kinetics at a rate constant of 0.0166 h -1 under an applied voltage of 0.5 V. Meanwhile, a total organic carbon (TOC) removal efficiency of 93.1 ± 1.2% was obtained, revealing efficient mineralization of aniline. The applicability of bipolar membrane MEC-Fenton system was successfully demonstrated with actual aniline wastewater. Moreover, energy balance showed that the system could be a promising technology for removal of biorefractory organic pollutants from wastewaters. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Konduktifitas Listrik Komposit Polimer Polipropilena/Karbon Untuk Aplikasi Pelat Bipolar Fuel Cell

    Directory of Open Access Journals (Sweden)

    Agus Pramono

    2016-02-01

    Full Text Available Proton exchange membrane fuel cell (PEMFC merupakan salah satu sumber energi alternatif yang saat ini sedang dikembangkan untuk mengatasi permasahan krisis energi dan lingkungan. Salah satu komponen yang mempunyai peran  signifikan dalam efisiensi biaya dan proses PEMFC adalah pelat bipolar. Untuk itu diperlukan pelat bipolar yang ringan, murah, dan mudah diproduksi secara masal. Dalam penelitian ini dikembangkan komposit pelat bipolar menggunakan matriks polipropilena (PP, penguat karbon hitam dan grafit elektroda dengan variasi komposisi wt% PP/grafit/CB sebesar 85:10:5; 75:20:5; 65:30:5;dan 55:40:5, sehingga mendapatkan sifat daya hantar listrik yang baik. Sifat-sifat dari komposit yang dihasilkan diuji dengan pengujian konduktivitas, Dari keempat formula, didapatkan bahwa sifat listrik yang paling baik terdapat pada formula empat dengan penambahan grafit sebesar 40 wt%. Formulasi empat memiliki konduktivitas listrik sebesar 2,523E-03 S/cm. sifat listrik juga belum optimal dikarenakan masih terdapatnya banyak rongga atau pori dalam komposit PP/grafit/CB yang disebabkan oleh udara yang terjebak selama proses penekanan.

  8. Silencing of CEMIP suppresses Wnt/β-catenin/Snail signaling transduction and inhibits EMT program of colorectal cancer cells.

    Science.gov (United States)

    Liang, Guodong; Fang, Xuedong; Yang, Yubo; Song, Yan

    2018-01-01

    Cell migration inducing hyaluronan binding protein (CEMIP) is a hyaluronic acid binding protein, the abnormal elevation of which is suggested as a contributor in the carcinogenesis of colorectal cancer (CRC). Cancer cells lose their adhesive properties and acquire an enhanced mobility by undergoing epithelial-mesenchymal transition (EMT). This study is performed to investigate whether and how CEMIP orchestrates the EMT process of CRC cells. To avoid the unexpected off-target effects possibly caused by one single shRNA, two shRNAs targeting different mRNA regions of CEMIP gene were used to knock down the mRNA and protein expression of CEMIP. Our data showed that the proliferation, migration and invasion of two CRC cell lines, HCT116 and SW480 cells, were inhibited by CEMIP shRNA. We here defined EMT as the complete or partial loss of E-cadherin and zona occludens protein 1 (ZO-1) (epithelial markers) and the gain of Vimentin and N-cadherin (mesenchymal markers), and found that the EMT process was attenuated in CEMIP-silenced SW480 cells. Snail, a direct target of β-catenin/T cell factor complex, is known to activate the EMT program during cancer metastasis. CEMIP shRNA was further found to suppress the Wnt/β-catenin/Snail signaling transduction in CRC cells as manifested by the decreased nuclear β-catenin and Snail. Collectively, our work demonstrates that CEMIP contributes to metastatic phenotype of CRC cells in vitro. Copyright © 2017 Elsevier GmbH. All rights reserved.

  9. Participation of intercellular communication and intracellular signal transduction in the radio-adaptive response of human fibroblastic cells

    International Nuclear Information System (INIS)

    Ishii, Keiichiro; Hoshi, Yuko; Iwasaki, Toshiyasu; Watanabe, Masami

    1997-01-01

    To investigate the radio-adaptive response of normal cells to low-dose radiation, we irradiated human embryonic cells with low-dose X-rays and examined the changes in sensitivity to subsequent high-dose X-irradiation. When the cells were irradiated by 200 cGy, the growth ratio of the viable cells five days after the irradiation decreased to 37% of that of the cells which received no X-irradiation. When the cells received a conditioning irradiation of 10 to 20 cGy four hours before the irradiation of 200 cGy, the growth ratio increased significantly to 45-53%, and a peak was reached at a conditioning dose of 13 cGy. Cells blocked off intercellular communication either in Ca 2+ ion-free medium or in TPA added medium during the conditioning irradiation of 13 cGy did not show the improvement of growth ratio. Addition of H-7, as an inhibitor of PKC, to the medium during the conditioning irradiation inhibited the induction of the radio-adaptive response. However, addition of either inhibitor of A kinase, H-89, or inhibitor of G kinase, H-8, failed to inhibit the induction of the radio-adaptive response. These results suggest that: (1) normal cells show an adaptive response to low-dose radiation, (2) intercellular communication may play a role in radio-adaptive responses, (3) the transduction of the signal induced in cells by low-dose X-irradiation via protein kinase C was involved in radio-adaptive responses, not via A kinase nor G kinase. (author)

  10. The importance of valency in enhancing the import and cell routing potential of protein transduction domain-containing molecules.

    Science.gov (United States)

    Sung, Michael; Poon, Gregory M K; Gariépy, Jean

    2006-03-01

    Protein transduction domains (PTDs) are peptides that afford the internalization of cargo macromolecules (including plasmid DNA, proteins, liposomes, and nanoparticles). In the case of polycationic peptides, the efficiency of PTDs to promote cellular uptake is directly related to their molecular mass or their polyvalent presentation. Similarly, the efficiency of routing to the nucleus increases with the number of nuclear localization signals (NLS) associated with a cargo. The quantitative enhancement, however, depends on the identity of the PTD sequence as well as the targeted cell type. Thus the choice and multivalent presentation of PTD and NLS sequences are important criteria guiding the design of macromolecules intended for specific intracellular localization. This review outlines synthetic and recombinant strategies whereby PTDs and signal sequences can be assembled into multivalent peptide dendrimers and promote the uptake and routing of their cargoes. In particular, the tetramerization domain of the tumour suppressor p53 (p53tet) is emerging as a useful scaffold to present multiple routing and targeting moieties. Short cationic peptides fused to the 31-residue long p53tet sequence resulted in tetramers displaying a significant enhancement (up to 1000 fold) in terms of their ability to be imported into cells and delivered to the cell nucleus in relation to their monomeric analogues. The design of future polycationic peptide dendrimers as effective delivering vehicles will need to incorporate selective cell targeting functions and provide solutions to the issue of endosomal entrapment.

  11. Endogenous protection derived from activin A/Smads transduction loop stimulated via ischemic injury in PC12 cells.

    Science.gov (United States)

    Mang, Jing; Mei, Chun-Li; Wang, Jiao-Qi; Li, Zong-Shu; Chu, Ting-Ting; He, Jin-Ting; Xu, Zhong-Xin

    2013-10-17

    Activin A (ActA), a member of transforming growth factor-beta (TGF-b) super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD) injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate ischemic injury on neurons in vitro. Cells were pre-treated by monoclonal antibody against activin receptor type IIA (ActRII-Ab). We found that ActRII-Ab augments ischemic injury in PC12 cells. Further, the extracellular secretion of ActA as well as phosphorylation of smad3 in PC12 cells was also up-regulated by OGD, but suppressed by ActRII-Ab. Taken together, our results show that ActRII-Ab may augment ischemic injury via blocking of transmembrane signal transduction of ActA, which confirmed the existence of endogenous neuroprotective effects derived from the ActA/Smads pathway. ActRIIA plays an important role in transferring neuronal protective signals inside. It is highly possible that ActA transmembrance signaling is a part of the positive feed-back loop for extracellular ActA secretion.

  12. Endogenous Protection Derived from Activin A/Smads Transduction Loop Stimulated via Ischemic Injury in PC12 Cells

    Directory of Open Access Journals (Sweden)

    Zhong-Xin Xu

    2013-10-01

    Full Text Available Activin A (ActA, a member of transforming growth factor-beta (TGF-b super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate ischemic injury on neurons in vitro. Cells were pre-treated by monoclonal antibody against activin receptor type IIA (ActRII-Ab. We found that ActRII-Ab augments ischemic injury in PC12 cells. Further, the extracellular secretion of ActA as well as phosphorylation of smad3 in PC12 cells was also up-regulated by OGD, but suppressed by ActRII-Ab. Taken together, our results show that ActRII-Ab may augment ischemic injury via blocking of transmembrane signal transduction of ActA, which confirmed the existence of endogenous neuroprotective effects derived from the ActA/Smads pathway. ActRIIA plays an important role in transferring neuronal protective signals inside. It is highly possible that ActA transmembrance signaling is a part of the positive feed-back loop for extracellular ActA secretion.

  13. Mesenchymal stem cells from osteoporotic patients feature impaired signal transduction but sustained osteoinduction in response to BMP-2 stimulation.

    Science.gov (United States)

    Prall, Wolf Christian; Haasters, Florian; Heggebö, Jostein; Polzer, Hans; Schwarz, Christina; Gassner, Christoph; Grote, Stefan; Anz, David; Jäger, Marcus; Mutschler, Wolf; Schieker, Matthias

    2013-11-01

    Osteoporotic fractures show reduced callus formation and delayed bone healing. Cellular sources of fracture healing are mesenchymal stem cells (MSC) that differentiate into osteoblasts by stimulation with osteoinductive cytokines, such as BMP-2. We hypothesized that impaired signal transduction and reduced osteogenic differentiation capacity in response to BMP-2 may underlie the delayed fracture healing. Therefore, MSC were isolated from femoral heads of healthy and osteoporotic patients. Grouping was carried out by bone mineral densitometry in an age-matched manner. MSC were stimulated with BMP-2. Signal transduction was assessed by western blotting of pSMAD1/5/8 and pERK1/2 as well as by quantitative RT-PCR of Runx-2, Dlx5, and Osteocalcin. Osteogenic differentiation was assessed by quantifying Alizarin Red staining. Osteoporotic MSC featured an accurate phosphorylation pattern of SMAD1/5/8 but a significantly reduced activation of ERK1/2 by BMP-2 stimulation. Furthermore, osteoporotic MSC showed significantly reduced basal expression levels of Runx-2 and Dlx5. However, Runx-2, Dlx5, and Osteocalcin expression showed adequate up-regulation due to BMP-2 stimulation. The global osteogenic differentiation in standard osteogenic differentiation media was reduced in osteoporotic MSC. Nevertheless, osteoporotic MSC were shown to feature an adequate induction of osteogenic differentiation due to BMP-2 stimulation. Taken together, we here demonstrate osteoporosis associated alterations in BMP-2 signaling but sustained specific osteogenic differentiation capacity in response to BMP-2. Therefore, BMP-2 may represent a promising therapeutic agent for the treatment of fractures in osteoporotic patients. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. 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...

  15. 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...

  16. The transduction of Coxsackie and Adenovirus Receptor-negative cells and protection against neutralizing antibodies by HPMA-co-oligolysine copolymer-coated adenovirus.

    Science.gov (United States)

    Wang, Chung-Huei K; Chan, Leslie W; Johnson, Russell N; Chu, David S H; Shi, Julie; Schellinger, Joan G; Lieber, André; Pun, Suzie H

    2011-12-01

    Adenoviral (AdV) gene vectors offer efficient nucleic acid transfer into both dividing and non-dividing cells. However issues such as vector immunogenicity, toxicity and restricted transduction to receptor-expressing cells have prevented broad clinical translation of these constructs. To address this issue, engineered AdV have been prepared by both genetic and chemical manipulation. In this work, a polymer-coated Ad5 formulation is optimized by evaluating a series of N-(2-hydroxypropyl) methacrylamide (HPMA)-co-oligolysine copolymers synthesized by living polymerization techniques. This synthesis approach was used to generate highly controlled and well-defined polymers with varying peptide length (K(5), K(10) and K(15)), polymer molecular weight, and degradability to coat the viral capsid. The optimal formulation was not affected by the presence of serum during transduction and significantly increased Ad5 transduction of several cell types that lack the Coxsackie and Adenovirus Receptor (CAR) by up to 6-fold compared to unmodified AdV. Polymer-coated Ad5 also retained high transduction capability in the presence of Ad5 neutralizing antibodies. The critical role of heparan sulfate proteoglycans (HSPGs) in mediating cell binding and internalization of polymer-coated AdV was also demonstrated by evaluating transduction in HSPG-defective recombinant CHO cells. The formulations developed here are attractive vectors for ex vivo gene transfer in applications such as cell therapy. In addition, this platform for adenoviral modification allows for facile introduction of alternative targeting ligands. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. 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.

  18. Differences in radiosensitivity of the respiratory burst generated in HL-60 cells via different signal transduction pathways

    International Nuclear Information System (INIS)

    Kaffenberger, W.; Beuningen, D. van

    1994-01-01

    Induced differentiation of the promyelocytic leukaemia cell line, HL-60, is associated with the acquisition of functional properties, like the expression of specific receptors and the competence to exert the respiratory burst (RB). In this system we evaluated the effects of ionizing radiation on the signal transduction processes involved in the activation of the respiratory burst/NADPH oxidase. HL-60 cells were X-irradiated with up to 1 Gy and induced towards granulocytic differentiation by treatment with 1.25% DMSO on day 0. The expression of the formyl peptide receptor (FPR), the development of responsiveness of the cells to its ligand (f-MLP) and to 4 β-phorbol 12-myristate 13-acetate (PMA) were measured up to day 7 postinduction/irradiation. Using flow cytometry, fluorescinated formyl-hexapeptide or unlabelled f-MLP as ligands and dihydrorhodamine 123 (DHR 123) as an indicator of RB activity, respectively, the acquisition of functional responsiveness to both stimuli was determined. (author)

  19. Signal transduction events induced by extracellular guanosine 5?triphosphate in excitable cells

    OpenAIRE

    Pietrangelo, T.; Guarnieri, S.; Fulle, S.; Fan?, G.; Mariggi?, M. A.

    2006-01-01

    A better understanding of the physiological effects of guanosine-based purines should help clarify the complex subject of purinergic signalling. We studied the effect of extracellular guanosine 5?triphosphate (GTP) on the differentiation of two excitable cell lines that both have specific binding sites for GTP: PC12 rat pheochromocytoma cells and C2C12 mouse skeletal muscle cells. PC12 cells can be differentiated into fully functional sympathetic-like neurons with 50?00 ng ml?1 of nerve growt...

  20. Targeting of the Hedgehog signal transduction pathway suppresses survival of malignant pleural mesothelioma cells in vitro.

    Science.gov (United States)

    You, Min; Varona-Santos, Javier; Singh, Samer; Robbins, David J; Savaraj, Niramol; Nguyen, Dao M

    2014-01-01

    The present study sought to determine whether the Hedgehog (Hh) pathway is active and regulates the cell growth of cultured malignant pleural mesothelioma (MPM) cells and to evaluate the efficacy of pathway blockade using smoothened (SMO) antagonists (SMO inhibitor GDC-0449 or the antifungal drug itraconazole [ITRA]) or Gli inhibitors (GANT61 or the antileukemia drug arsenic trioxide [ATO]) in suppressing MPM viability. Selective knockdown of SMO to inhibit Hh signaling was achieved by small interfering RNA in 3 representative MPM cells. The growth inhibitory effect of GDC-0449, ITRA, GANT61, and ATO was evaluated in 8 MPM lines, with cell viability quantified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell death was determined by annexinV/propidium iodide staining and flow cytometry. SMO small interfering RNA mediated a two- to more than fivefold reduction of SMO and Gli1 gene expression as determined by real-time quantitative reverse-transcriptase polymerase chain reaction, indicating significant Hh pathway blockade. This was associated with significantly reduced cell viability (34% ± 7% to 61% ± 14% of nontarget small interfering RNA controls; P = .0024 to P = .043). Treating MPM cells with Hh inhibitors resulted in a 1.5- to 4-fold reduction of Gli1 expression. These 4 Hh antagonists strongly suppressed MPM cell viability. More importantly, ITRA, ATO, GANT61 induced significant apoptosis in the representative MPM cells. Hh signaling is active in MPM and regulates cell viability. ATO and ITRA were as effective as the prototypic SMO inhibitor GDC-0449 and the Gli inhibitor GANT61 in suppressing Hh signaling in MPM cells. Pharmaceutical agents Food and Drug Administration-approved for other indications but recently found to have anti-Hh activity, such as ATO or ITRA, could be repurposed to treat MPM. Copyright © 2014 The American Association for Thoracic Surgery. All rights reserved.

  1. 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...

  2. 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,

  3. 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.

  4. Disease signatures for schizophrenia and bipolar disorder using patient-derived induced pluripotent stem cells.

    Science.gov (United States)

    Watmuff, Bradley; Berkovitch, Shaunna S; Huang, Joanne H; Iaconelli, Jonathan; Toffel, Steven; Karmacharya, Rakesh

    2016-06-01

    Schizophrenia and bipolar disorder are complex psychiatric disorders that present unique challenges in the study of disease biology. There are no objective biological phenotypes for these disorders, which are characterized by complex genetics and prominent roles for gene-environment interactions. The study of the neurobiology underlying these severe psychiatric disorders has been hindered by the lack of access to the tissue of interest - neurons from patients. The advent of reprogramming methods that enable generation of induced pluripotent stem cells (iPSCs) from patient fibroblasts and peripheral blood mononuclear cells has opened possibilities for new approaches to study relevant disease biology using iPSC-derived neurons. While early studies with patient iPSCs have led to promising and intriguing leads, significant hurdles remain in our attempts to capture the complexity of these disorders in vitro. We present here an overview of studies to date of schizophrenia and bipolar disorder using iPSC-derived neuronal cells and discuss potential future directions that can result in the identification of robust and valid cellular phenotypes that in turn can lay the groundwork for meaningful clinical advances. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    OpenAIRE

    Cavalieri, Duccio; Rivero, Damariz; Beltrame, Luca; Buschow, Sonja I.; Calura, Enrica; Rizzetto, Lisa; Gessani, Sandra; Gauzzi, Maria C.; Reith, Walter; Baur, Andreas; Bonaiuti, Roberto; Brandizi, Marco; De Filippo, Carlotta; D'Oro, Ugo; Draghici, Sorin

    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, and capturing this specificity is of paramount importance when using pathway-based analyses to decipher complex immunological datasets. Here, we present DC-ATLAS, a novel and versatile resource fo...

  6. Guard Cell Signal Transduction Network: Advances in Understanding Abscisic Acid, CO2, and Ca2+ Signaling

    KAUST Repository

    Kim, Tae-Houn

    2010-05-04

    Stomatal pores are formed by pairs of specialized epidermal guard cells and serve as major gateways for both CO2 influx into plants from the atmosphere and transpirational water loss of plants. Because they regulate stomatal pore apertures via integration of both endogenous hormonal stimuli and environmental signals, guard cells have been highly developed as a model system to dissect the dynamics and mechanisms of plant-cell signaling. The stress hormone ABA and elevated levels of CO2 activate complex signaling pathways in guard cells that are mediated by kinases/phosphatases, secondary messengers, and ion channel regulation. Recent research in guard cells has led to a new hypothesis for how plants achieve specificity in intracellular calcium signaling: CO2 and ABA enhance (prime) the calcium sensitivity of downstream calcium-signaling mechanisms. Recent progress in identification of early stomatal signaling components are reviewed here, including ABA receptors and CO2-binding response proteins, as well as systems approaches that advance our understanding of guard cell-signaling mechanisms.

  7. Functional properties of a metabotropic glutamate receptor at dendritic synapses of ON bipolar cells in the amphibian retina.

    Science.gov (United States)

    Tian, N; Slaughter, M M

    1995-01-01

    Perforated patch-voltage and current-clamp recordings were obtained from ON bipolar cells in the amphibian retinal slice preparation. The currents produced by the photoreceptor transmitter were compared to the currents produced by selective metabotropic glutamate agonists: L-2-amino-4-phosphonobutyrate (L-AP4, APB) and IS,3R 1-amino-1,3 cyclopentanedicarboxylic acid (1S, 3R ACPD). Both agonists produced currents that were very similar to that produced by the photoreceptor transmitter in terms of conductance and reversal potential. The similarities suggest that the metabotropic glutamate receptors are functionally localized to the synaptic region of ON bipolar dendrites. The synaptic conductance rarely exceeded the non-synaptic conductance. The mean input resistance of ON bipolar neurons was 770 M omega in the light and 1.2 G omega in the dark. The average light-regulated synaptic conductance was 57% of the non-synaptic conductance. The L-AP4 regulated conductance averaged 77% of the non-synaptic conductance, while the 1S, 3R ACPD regulated conductance averaged 95% of the non-synaptic conductance. This balance between synaptic and non-synaptic conductance indicates that the synapse will not shunt the cell and the conductance ratio serves to maximize incremental gain at the photoreceptor to ON bipolar synapse. This conductance mechanism makes the ON bipolar cell well equipped to relay rod signals.

  8. Signal transduction of MCP-1 expression induced by pancreatitis-associated ascitic fluid in pancreatic acinar cells

    Science.gov (United States)

    Ramudo, Laura; Yubero, Sara; Manso, Manuel A; Vicente, Secundino; De Dios, Isabel

    2009-01-01

    Pancreatitis-associated ascitic fluid (PAAF) is known to contribute to the progression of acute pancreatitis (AP). We have investigated the capability of PAAF to activate the expression of MCP-1 in pancreatic acinar cells and the involvement of MAPK, NF-κB and STAT3 as downstream signalling transduction pathways. The actions of dexamethasone (Dx) and N-acetylcysteine (NAC) on the PAAF’s acinar effects have also been evaluated. Acinar cells were incubated for 1 hr with PAAF collected from rats with severe AP induced by sodium taurocholate in the absence or presence of Dx (10−7 M) or NAC (30 mM). MCP-1 mRNA expression, phospho-p38-MAPK, IκBα, nuclear p65 levels and nuclear translocation of STAT3 were analysed. In response to PAAF, overexpression of MCP-1, phosphorylation of p38-MAPK, degradation of IκBα and increases in p65 nuclear levels and STAT3 activity were found in acinar cells. PAAF-mediated MCP-1 up-regulation was completely suppressed by Dx and NAC. MAPK activation was only inhibited by NAC, NF-κB activation was repressed by Dx and NAC, and STAT3 pathway was strongly blocked by Dx and significantly reduced by NAC. In conclusion, acinar cells were activated by PAAF to produce MCP-1, mainly via NF-κB and STAT3 pathways. Both downstream pathways were targeted by Dx and NAC to repress the PAAF-mediated acinar MCP-1 up-regulation. PMID:19604316

  9. Neurospora crassa female development requires the PACC and other signal transduction pathways, transcription factors, chromatin remodeling, cell-to-cell fusion, and autophagy.

    Directory of Open Access Journals (Sweden)

    Jennifer L Chinnici

    Full Text Available Using a screening protocol we have identified 68 genes that are required for female development in the filamentous fungus Neurospora crassa. We find that we can divide these genes into five general groups: 1 Genes encoding components of the PACC signal transduction pathway, 2 Other signal transduction pathway genes, including genes from the three N. crassa MAP kinase pathways, 3 Transcriptional factor genes, 4 Autophagy genes, and 5 Other miscellaneous genes. Complementation and RIP studies verified that these genes are needed for the formation of the female mating structure, the protoperithecium, and for the maturation of a fertilized protoperithecium into a perithecium. Perithecia grafting experiments demonstrate that the autophagy genes and the cell-to-cell fusion genes (the MAK-1 and MAK-2 pathway genes are needed for the mobilization and movement of nutrients from an established vegetative hyphal network into the developing protoperithecium. Deletion mutants for the PACC pathway genes palA, palB, palC, palF, palH, and pacC were found to be defective in two aspects of female development. First, they were unable to initiate female development on synthetic crossing medium. However, they could form protoperithecia when grown on cellophane, on corn meal agar, or in response to the presence of nearby perithecia. Second, fertilized perithecia from PACC pathway mutants were unable to produce asci and complete female development. Protein localization experiments with a GFP-tagged PALA construct showed that PALA was localized in a peripheral punctate pattern, consistent with a signaling center associated with the ESCRT complex. The N. crassa PACC signal transduction pathway appears to be similar to the PacC/Rim101 pathway previously characterized in Aspergillus nidulans and Saccharomyces cerevisiae. In N. crassa the pathway plays a key role in regulating female development.

  10. Sensory transduction at the frog semicircular canal: how hair cell membrane potential controls junctional transmission

    Science.gov (United States)

    Martini, Marta; Canella, Rita; Rubbini, Gemma; Fesce, Riccardo; Rossi, Maria Lisa

    2015-01-01

    At the frog semicircular canals, the afferent fibers display high spontaneous activity (mEPSPs), due to transmitter release from hair cells. mEPSP and spike frequencies are modulated by stimulation that activates the hair cell receptor conductance. The relation between receptor current and transmitter release cannot be studied at the intact semicircular canal. To circumvent the problem, we combined patch-clamp recordings at the isolated hair cell and electrophysiological recordings at the cytoneural junction in the intact preparation. At isolated hair cells, the K channel blocker tetraethylammonium (TEA) is shown to block a fraction of total voltage-dependent K-conductance (IKD) that depends on TEA concentration but not on membrane potential (Vm). Considering the bioelectric properties of the hair cell, as previously characterized by this lab, a fixed fractional block of IKD is shown to induce a relatively fixed shift in Vm, provided it lies in the range −30 to −10 mV. The same concentrations of TEA were applied to the intact labyrinth while recording from single afferent fibers of the posterior canal, at rest and during mechanical stimulation. At the peak of stimulation, TEA produced increases in mEPSP rate that were linearly related to the shifts produced by the same TEA concentrations (0.1–3 mM) in hair cell Vm (0.7–5 mV), with a slope of 29.8 Hz/mV. The membrane potential of the hair cell is not linearly related to receptor conductance, so that the slope of quantal release vs. receptor conductance depends on the prevailing Vm (19.8 Hz/nS at −20 mV; 11 Hz/nS at −10 mV). Changes in mEPSP peak size were negligible at rest as well as during stimulation. Since ample spatial summation of mEPSPs occurs at the afferent terminal and threshold-governed spike firing is intrinsically nonlinear, the observed increases in mEPSP frequency, though not very large, may suffice to trigger afferent spike discharge. PMID:26157360

  11. Evaluation of materials for bipolar plates in simulated PEM fuel-cell cathodic environments

    Energy Technology Data Exchange (ETDEWEB)

    Rivas, S.V.; Belmonte, M.R.; Moron, L.E.; Torres, J.; Orozco, G. [Centro de Investigacion y Desarrollo Technologico en Electroquimica S.C. Parcque Sanfandila, Queretaro (Mexico); Perez-Quiroz, J.T. [Mexican Transport Inst., Queretaro (Mexico); Cortes, M. A. [Mexican Petroleum Inst., Mexico City (Mexico)

    2008-04-15

    The bipolar plates in proton exchange membrane fuel cells (PEMFC) are exposed to an oxidizing environment on the cathodic side, and therefore are susceptible to corrosion. Corrosion resistant materials are needed for the bipolar plates in order to improve the lifespan of fuel cells. This article described a study in which a molybdenum (Mo) coating was deposited over austenitic stainless steel 316 and carbon steel as substrates in order to evaluate the resulting surfaces with respect to their corrosion resistance in simulated anodic and cathodic PEMFC environments. The molybdenum oxide films were characterized by scanning electron microscopy (SEM) and Raman spectroscopy. The article presented the experiment and discussed the results of the corrosion behaviour of coated stainless steel. In general, the electrochemical characterization of bare materials and coated steel consisted of slow potentiodynamic polarization curves followed by a constant potential polarization test. The test medium was 0.5M sulfuric acid with additional introduction of oxygen to simulate the cathodic environment. All tests were performed at ambient temperature and at 50 degrees Celsius. The potentiostat used was a Gamry instrument. It was concluded that it is possible to deposit Mo-oxides on steel without using another alloying metal. The preferred substrate for corrosion prevention was found to be an alloy with high chromium content. 24 refs., 4 figs.

  12. Glia and immune cell signaling in bipolar disorder: insights from neuropharmacology and molecular imaging to clinical application.

    Science.gov (United States)

    Watkins, C C; Sawa, A; Pomper, M G

    2014-01-21

    Bipolar disorder (BD) is a debilitating mental illness characterized by severe fluctuations in mood, sleep, energy and executive functioning. Pharmacological studies of selective serotonin reuptake inhibitors and the monoamine system have helped us to clinically understand bipolar depression. Mood stabilizers such as lithium and valproic acid, the first-line treatments for bipolar mania and depression, inhibit glycogen synthase kinase-3 beta (GSK-3β) and regulate the Wnt pathway. Recent investigations suggest that microglia, the resident immune cells of the brain, provide a physiological link between the serotonin system and the GSK-3β/Wnt pathway through neuroinflammation. We review the pharmacological, translational and brain imaging studies that support a role for microglia in regulating neurotransmitter synthesis and immune cell activation. These investigations provide a model for microglia involvement in the pathophysiology and phenotype of BD that may translate into improved therapies.

  13. Requirements and testing methods for surfaces of metallic bipolar plates for low-temperature PEM fuel cells

    Science.gov (United States)

    Jendras, P.; Lötsch, K.; von Unwerth, T.

    2017-03-01

    To reduce emissions and to substitute combustion engines automotive manufacturers, legislature and first users aspire hydrogen fuel cell vehicles. Up to now the focus of research was set on ensuring functionality and increasing durability of fuel cell components. Therefore, expensive materials were used. Contemporary research and development try to substitute these substances by more cost-effective material combinations. The bipolar plate is a key component with the greatest influence on volume and mass of a fuel cell stack and they have to meet complex requirements. They support bending sensitive components of stack, spread reactants over active cell area and form the electrical contact to another cell. Furthermore, bipolar plates dissipate heat of reaction and separate one cell gastight from the other. Consequently, they need a low interfacial contact resistance (ICR) to the gas diffusion layer, high flexural strength, good thermal conductivity and a high durability. To reduce costs stainless steel is a favoured material for bipolar plates in automotive applications. Steel is characterized by good electrical and thermal conductivity but the acid environment requires a high chemical durability against corrosion as well. On the one hand formation of a passivating oxide layer increasing ICR should be inhibited. On the other hand pitting corrosion leading to increased permeation rate may not occur. Therefore, a suitable substrate lamination combination is wanted. In this study material testing methods for bipolar plates are considered.

  14. Participation of IAA in transduction of gravistimulus in apical cells of moss protonema

    Science.gov (United States)

    Oksyniuk, U. A.; Khorkavtsiv, O. Y.; Lesniak, Y. I.

    Growth movements of vascular plant axis organs -- photo-, gravi- and other tropisms -- are tightly connected with IAA transport (Hertel, 1983; Medvedev, 1996; Kiss, 2000). Moss protonema synthesizes IAA (indole-3-acetic acid) and transports it basipetally favouring growth and differentiation of caulonema (Bopp, 1979; Rose, Bopp, 1983; Rose et al., 1983). We aimed at studying the role of IAA in moss protonema gravitropism using exogenous IAA, 1-NAA (1-naphthaleneacetic acid), 2,4D (2,4-dichlorophenoxyacetic acid) and inhibitors of polar IAA transport -- phytotropins NPA (N-1-naphthylphthalamic acid) and TIBA (2,3,5-triiodobenzoic acid). Six-day gravitropic protonema of Ceratodon purpureus and Pohlia nutans were taken for experiments. Auxin and phytotropins solutions were laid on protonema mats the latters being kept in solutions for 30 min. Then the surplus of solutions were poured off and Petri dishes were placed vertically for 6 h. 20 μ M of IAA and of other synthetic auxins did not significantly influence the angle of protonema gravity bending, 40 μ M of the agents, howewer, reduced the per cent of apical cells bendings and their angles. The most expressed influence on the angles of bending had the inhibitors of polar IAA transport -- NPA. 0,1 -- 3,0 μ M of this phytotropin did not change the form of apical cell, did not disturb the general distribution of amyloplasts and did not significantly lower the per cent and the value of gravity bending angle, though 10 μ M of the phytotropin - inhibited gravity bending. The mixture of 1-NAA and NPA having been added into the medium the influence of NPA was lowered and gravitropic growth renewed in course of time. 10 μ M of other phytopropin TIBA also inhibited gravitropism of Ceratodon purpureus and Pohlia nutans protonema. The analysis of basipetal transport of IAA in moss rhizoids and protonema may indicate the availability of special IAA transport in these structures (Bopp, Cerier, 1988). On the basis of the

  15. Predictive and prognostic factors in non small cell lung cancer: identification of new genes and signal transduction pathways in the study of genomic and oncoproteomic

    International Nuclear Information System (INIS)

    Crino, L.; Martelli, M.

    2009-01-01

    The aim of the project is the comprehension of resistance and survival mechanisms of the neoplastic cell in Non-Small Cell Lung Cancer (NSCLC) in both patients subjected to surgery or with advanced disease. In order to identify new genes, proteins and signal transduction pathways, involved in the establishment of the treatment resistance of neoplastic cells, cellular cohort derived from lung cancers will be compared, by gene expression profiling, to normal cells and cells derived from cancer relapse. Twenty patients with NSCLC surgically resected and one patient with advanced NSCLC have been enrolled in this study

  16. A comprehensive, multi-scale dynamical model of ErbB receptor signal transduction in human mammary epithelial cells.

    Directory of Open Access Journals (Sweden)

    Tomáš Helikar

    Full Text Available The non-receptor tyrosine kinase Src and receptor tyrosine kinase epidermal growth factor receptor (EGFR/ErbB1 have been established as collaborators in cellular signaling and their combined dysregulation plays key roles in human cancers, including breast cancer. In part due to the complexity of the biochemical network associated with the regulation of these proteins as well as their cellular functions, the role of Src in EGFR regulation remains unclear. Herein we present a new comprehensive, multi-scale dynamical model of ErbB receptor signal transduction in human mammary epithelial cells. This model, constructed manually from published biochemical literature, consists of 245 nodes representing proteins and their post-translational modifications sites, and over 1,000 biochemical interactions. Using computer simulations of the model, we find it is able to reproduce a number of cellular phenomena. Furthermore, the model predicts that overexpression of Src results in increased endocytosis of EGFR in the absence/low amount of the epidermal growth factor (EGF. Our subsequent laboratory experiments also suggest increased internalization of EGFR upon Src overexpression under EGF-deprived conditions, further supporting this model-generated hypothesis.

  17. Transduction proteins of olfactory receptor cells: identification of guanine nucleotide binding proteins and protein kinase C

    International Nuclear Information System (INIS)

    Anholt, R.R.H.; Mumby, S.M.; Stoffers, D.A.; Girard, P.R.; Kuo, J.F.; Snyder, S.H.

    1987-01-01

    The authors have analyzed guanine nucleotide binding proteins (G-proteins) in the olfactory epithelium of Rana catesbeiana using subunit-specific antisera. The olfactory epithelium contained the α subunits of three G-proteins, migrating on polyacrylamide gels in SDS with apparent molecular weights of 45,000, 42,000, and 40,000, corresponding to G/sub s/, G/sub i/, and G/sub o/, respectively. A single β subunit with an apparent molecular weight of 36,000 was detected. An antiserum against the α subunit of retinal transducin failed to detect immunoreactive proteins in olfactory cilia detached from the epithelium. The olfactory cilia appeared to be enriched in immunoreactive G/sub sα/ relative to G/sub ichemical bond/ and G/sub ochemical bond/ when compared to membranes prepared from the olfactory epithelium after detachment of the cilia. Bound antibody was detected by autoradiography after incubation with [ 125 I]protein. Immunohistochemical studies using an antiserum against the β subunit of G-proteins revealed intense staining of the ciliary surface of the olfactory epithelium and of the axon bundles in the lamina propria. In contrast, an antiserum against a common sequence of the α subunits preferentially stained the cell membranes of the olfactory receptor cells and the acinar cells of Bowman's glands and the deep submucosal glands. In addition to G-proteins, they have identified protein kinase C in olfactory cilia via a protein kinase C specific antiserum and via phorbol ester binding. However, in contrast to the G-proteins, protein kinase C occurred also in cilia isolated from respiratory epithelium

  18. 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)

    Neves, Bruno Miguel; Goncalo, Margarida; Figueiredo, Americo; Duarte, Carlos B.; Lopes, Maria Celeste; Cruz, Maria Teresa

    2011-01-01

    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.

  19. Glial cells as key elements in the pathophysiology and treatment of bipolar disorder.

    Science.gov (United States)

    Keshavarz, Mojtaba

    2017-06-01

    The exact pathophysiology of bipolar disorder (BD) is not yet fully understood, and there are many questions in this area which should be answered. This review aims to discuss the roles of glial cells in the pathophysiology of BD and their contribution to the mechanism of action of mood-stabilising drugs. We critically reviewed the most recent advances regarding glial cell roles in the pathophysiology and treatment of BD and the neuroprotective and neurotrophic effects of these cells. Postmortem studies revealed a decrease in the glial cell number or density in the specific layers of prefrontal and anterior cingulate cortex in the patients with BD, whereas there was no difference in other brain regions, such as entorhinal cortex, amygdala and hippocampus. Astrocytes and oligodendrocytes were the most important glial types that were responsible for the glial reduction, but microglia activation rather than loss may be implicated in BD. The decreased number or density of glial cells may contribute to the pathological changes observed in neurons in the patients with BD. Alteration of specific neurotrophic factors such as glial cell line-derived neurotrophic factor and S100B may be an important feature of BD. Glial cells mediate the therapeutic effects of mood-stabilising agents in the treatment of BD. Recent studies provide important evidence on the impairment of glial cells in the pathophysiology and treatment of BD. However, future controlled studies are necessary to elucidate different aspects of glial cells contribution to BD, and the mechanism of action of mood-stabilising drugs.

  20. 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.

  1. A self-pumping and self-breathing micro direct methanol fuel cell with polymer bipolar plates

    Science.gov (United States)

    Sun, Lingjun; Liu, Chong; Liang, Junsheng; Zhu, Xuelin; Cui, Tianhong

    A passive micro direct methanol fuel cell (DMFC) for reducing volume and parasitic power is designed and fabricated using several integrated technologies. New bipolar plates with tapered channels at the anode and a pillar array at the cathode are first applied to a passive micro-DMFC. The substrate of the bipolar plates made of acrylonitrile butadiene styrene (ABS) is hot embossed with two molds, fabricated by UV-LIGA and micro machining. To make the bipolar plates conductive and hydrophilic, a nickel layer is electroplated on the ABS plates, and three PDDA/PSS bi-layers are self-assembled onto the nickel layer. The bipolar plates are produced using hot embossing, a low cost, highly accurate batch process. A single cell is assembled to verify the self-pumping function, and it can generate a peak power density of 7.4 mW cm -2 with a 3 M methanol solution. The fuel cell is verified to work in three different orientations. When the fuel cell is placed horizontally, the self-pumping rate is about 0.1-0.15 mL h -1. And the fuel cell can work through self-pumping for 5 h under this condition.

  2. 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

  3. Electrical and thermal conductivities of novel metal mesh hybrid polymer composite bipolar plates for proton exchange membrane fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Hsiao, Min-Chien; Liao, Shu-Hang; Yen, Ming-Yu.; Ma, Chen-Chi M. [Department of Chemical Engineering, National Tsing Hua University, 101, Section 2 Kuang Fu Road, Hsin-Chu 30043 (China); Lee, Shuo-Jen; Chen, Yung-Hung [Fuel Cell Center, Yuan Ze University, Tao-Yuan 32003 (China); Hung, Chih-Hung [Plastics Industry Development Center, Tai-Chung 40768 (China); Lin, Yu-Feng [Chemicals and Chemical Engineering, Chung Shan Institute of Science and Technology, Taoyuan 325 (China); Xie, Xiao-Feng [Institute of Nuclear and New Energy technology, Tsinghua University, Beijing 100084 (China)

    2010-01-15

    This study prepares novel metal mesh hybrid polymer composite bipolar plates for proton exchange membrane fuel cells (PEMFCs) via inserting a copper or aluminum mesh in polymer composites. The composition of polymer composites consists of 70 wt% graphite powder and 0-2 wt% modified multi-walled carbon nanotubes (m-MWCNTs). Results indicate that the in-plane electrical conductivity of m-MWCNTs/polymer composite bipolar plates increased from 156 S cm{sup -1} (0 wt% MWCNT) to 643 S cm{sup -1} (with 1 wt% MWCNT) (D.O.E. target >100 S cm{sup -1}). The bulk thermal conductivities of the copper and aluminum mesh hybrid polymer composite bipolar plates (abbreviated to Cu-HPBP and Al-HPBP) increase from 27.2 W m{sup -1} K{sup -1} to 30.0 W m{sup -1} K{sup -1} and 30.4 W m{sup -1} K{sup -1}, respectively. The through-plane conductivities decrease from 37.8 S cm{sup -1} to 36.7 S cm{sup -1} for Cu-HPBP and 22.9 S cm{sup -1} for Al-HPBP. Furthermore, the current and power densities of a single fuel cell using copper or aluminum mesh hybrid polymer composite bipolar plates are more stable than that of using neat polymer composite bipolar plates, especially in the ohmic overpotential region of the polarization curves of single fuel cell tests. The overall performance confirms that the metal mesh hybrid polymer composite bipolar plates prepared in this study are promising for PEMFC application. (author)

  4. Niobized AISI 304 stainless steel bipolar plate for proton exchange membrane fuel cell

    Science.gov (United States)

    Wang, Lixia; Sun, Juncai; Li, Pengbin; Jing, Bo; Li, Song; Wen, Zhongsheng; Ji, Shijun

    2012-06-01

    AISI 304 stainless steel (SS) has been niobized by a plasma surface diffusion alloying method. A 3 μm niobized layer with dominant niobium elements has been formed on the 304 SS surface and the performances of the niobized 304 SS has been examined and evaluated as bipolar plate for proton exchange membrane fuel cell (PEMFC). Results show that the average contact angle with water for the niobized 304 SS is about 90.4°, demonstrating better hydrophobicity as compared with the untreated 304 SS (68.1°). The corrosion resistance of the 304 SS is considerably improved by the niobized layer with the corrosion current densities decreased at 0.2 and 0.4 μA cm-2 in simulated PEMFC anode purged with hydrogen and the cathode purged with air condition (0.05 M H2SO4 + 2 ppm F- solution at 70 °C), respectively. The interfacial contact resistance (ICR) for the as-prepared niobized 304 SS is 10.53 mΩ cm2 at the compaction of 140 N cm-2. Furthermore, after 4 h potentiostatic tests, the niobizied specimens exhibit much lower ICR than that for the untreated ones. Thus, the niobized layer can act as a conductively protective layer of the 304 SS bipolar plate for PEMFC.

  5. 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

    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...... mobilization of intracellular free calcium compared with MHC-I crosslinking of wild-type DT40 cells. Thus, expression of BCR at the cell surface is likely to be important for the signal cascade initiated by MHC-I crosslinking. Our data suggest that signal transduction initiated through ligation of the MHC...

  6. 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.

  7. 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.

  8. Bipolar stacked quasi-all-solid-state lithium secondary batteries with output cell potentials of over 6 V.

    Science.gov (United States)

    Matsuo, Takahiro; Gambe, Yoshiyuki; Sun, Yan; Honma, Itaru

    2014-08-15

    Designing a lithium ion battery (LIB) with a three-dimensional device structure is crucial for increasing the practical energy storage density by avoiding unnecessary supporting parts of the cell modules. Here, we describe the superior secondary battery performance of the bulk all-solid-state LIB cell and a multilayered stacked bipolar cell with doubled cell potential of 6.5 V, for the first time. The bipolar-type solid LIB cell runs its charge/discharge cycle over 200 times in a range of 0.1-1.0 C with negligible capacity decrease despite their doubled output cell potentials. This extremely high performance of the bipolar cell is a result of the superior battery performance of the single cell; the bulk all-solid-state cell has a charge/discharge cycle capability of over 1500 although metallic lithium and LiFePO₄ are employed as anodes and cathodes, respectively. The use of a quasi-solid electrolyte consisting of ionic liquid and Al₂O₃ nanoparticles is considered to be responsible for the high ionic conductivity and electrochemical stability at the interface between the electrodes and the electrolyte. This paper presents the effective applications of SiO₂, Al₂O₃, and CeO₂ nanoparticles and various Li(+) conducting ionic liquids for the quasi-solid electrolytes and reports the best ever known cycle performances. Moreover, the results of this study show that the bipolar stacked three-dimensional device structure would be a smart choice for future LIBs with higher cell energy density and output potential. In addition, our report presents the advantages of adopting a three-dimensional cell design based on the solid-state electrolytes, which is of particular interest in energy-device engineering for mobile applications.

  9. Bipolar stacked quasi-all-solid-state lithium secondary batteries with output cell potentials of over 6 V

    Science.gov (United States)

    Matsuo, Takahiro; Gambe, Yoshiyuki; Sun, Yan; Honma, Itaru

    2014-01-01

    Designing a lithium ion battery (LIB) with a three-dimensional device structure is crucial for increasing the practical energy storage density by avoiding unnecessary supporting parts of the cell modules. Here, we describe the superior secondary battery performance of the bulk all-solid-state LIB cell and a multilayered stacked bipolar cell with doubled cell potential of 6.5 V, for the first time. The bipolar-type solid LIB cell runs its charge/discharge cycle over 200 times in a range of 0.1–1.0 C with negligible capacity decrease despite their doubled output cell potentials. This extremely high performance of the bipolar cell is a result of the superior battery performance of the single cell; the bulk all-solid-state cell has a charge/discharge cycle capability of over 1500 although metallic lithium and LiFePO4 are employed as anodes and cathodes, respectively. The use of a quasi-solid electrolyte consisting of ionic liquid and Al2O3 nanoparticles is considered to be responsible for the high ionic conductivity and electrochemical stability at the interface between the electrodes and the electrolyte. This paper presents the effective applications of SiO2, Al2O3, and CeO2 nanoparticles and various Li+ conducting ionic liquids for the quasi-solid electrolytes and reports the best ever known cycle performances. Moreover, the results of this study show that the bipolar stacked three-dimensional device structure would be a smart choice for future LIBs with higher cell energy density and output potential. In addition, our report presents the advantages of adopting a three-dimensional cell design based on the solid-state electrolytes, which is of particular interest in energy-device engineering for mobile applications. PMID:25124398

  10. hHO-1 combined with GATA-4 transduction promotes myocardial transdifferentiation and anti- apoptosis of rat mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Ning-bo DENG

    2017-06-01

    Full Text Available Objectives To explore if the rat bone marrow mesenchymal stem cells (BMSCs modified by human heme oxygenase 1 (hHO-1 gene combined with GATA-4 gene may promote the ability of anti-apoptosis and myocardial transdifferentiation in vitro in hypoxia ischemic environment. Methods The rat BMSCs were isolated and cultured by whole bone marrow adherence and identified in vitro, and then were transfected with recombinant adenovirus; Western blotting was used to determinate the optimal time of gene expression; the genetically modified BMSCs were taken to hypoxia serum-free conditions simulating ischemia hypoxia microenvironment in vivo; CCK-8 kit and trypan blue staining were performed to detect the 12, 24, 48 and 72h survival rates in hypoxia ischemia respectively; flow cytometry was used to detect the apoptosis of BMSCs in hypoxia ischemia for 24h. The cardiomyocyte-specific cardiac troponin I (cTnI was detected by Western blotting and cellular immunofluorescence. Results The 12, 24, 48 and 72h survival rates were higher in hHO-1+GATA-4 group cultured in ischemia and hypoxia condition than in hHO-1 group (P<0.05 and GATA-4 group (P<0.05. After 24h cultivation in ischemia hypoxia condition, the apoptotic rates were lower in hHO-1+GATA-4 group than in hHO-1 group (P<0.05 and GATA-4 group (P<0.05. No significant difference existed in cTnI expressions between GATA-4 group and hHO-1+GATA-4 group. Conclusion Compared with transfection of hHO-1 or GATA-4 single gene, hHO-1 combined with GATA-4 transduction can significantly increase the survival rate of BMSCs in hypoxia ischemic condition, but myocardial transdifferentiation does not increase significantly. DOI: 10.11855/j.issn.0577-7402.2017.04.08

  11. 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.

  12. Adenovirus serotype 5 vectors with Tat-PTD modified hexon and serotype 35 fiber show greatly enhanced transduction capacity of primary cell cultures.

    Directory of Open Access Journals (Sweden)

    Di Yu

    Full Text Available Recombinant adenovirus serotype 5 (Ad5 vectors represent one of the most efficient gene delivery vectors in life sciences. However, Ad5 is dependent on expression of the coxsackievirus-adenovirus-receptor (CAR on the surface of target cell for efficient transduction, which limits it's utility for certain cell types. Herein we present a new vector, Ad5PTDf35, which is an Ad5 vector having serotype 35 fiber-specificity and Tat-PTD hexon-modification. This vector shows dramatically increased transduction capacity of primary human cell cultures including T cells, monocytes, macrophages, dendritic cells, pancreatic islets and exocrine cells, mesenchymal stem cells and tumor initiating cells. Biodistribution in mice following systemic administration (tail-vein injection show significantly reduced uptake in the liver and spleen of Ad5PTDf35 compared to unmodified Ad5. Therefore, replication-competent viruses with these modifications may be further developed as oncolytic agents for cancer therapy. User-friendly backbone plasmids containing these modifications were developed for compatibility to the AdEasy-system to facilitate the development of surface-modified adenoviruses for gene delivery to difficult-to-transduce cells in basic, pre-clinical and clinical research.

  13. Localised corrosion processes of austenitic stainless steel bipolar plates for polymer electrolyte membrane fuel cells

    Science.gov (United States)

    Mele, Claudio; Bozzini, Benedetto

    This research addresses the problem of localised corrosion of stainless steel PEMFC bipolar plates. The susceptibility to pitting and crevice corrosion of austenitic AISI 304 stainless steel has been investigated both by post-mortem microscopic analysis of the end-plates of a laboratory single-cell and by studies of electrochemically corroded stainless steels, in the presence of specially-designed crevice-formers simulating the operating conditions of a PEMFC. This work is based on optical and scanning-electron microscopies as well as potentiostatic and potentiodynamic measurements. The crevice-formers we considered were: Teflon, graphite and AISI 304. The samples, coupled to the crevice-formers have been tested in aqueous solutions containing Cl -, SO 4 2- and F -. From the E-log i plot, the values of corrosion, pitting, crevice and protection potential have been obtained and perfect and imperfect passivity conditions have been identified.

  14. Bipolar Switching Characteristics of RRAM Cells with CaBi4Ti4O15 Film

    Directory of Open Access Journals (Sweden)

    Jian-Yang Lin

    2014-01-01

    Full Text Available The electrical conduction and bipolar switching properties of resistive random access memory (RRAM cells with transparent calcium bismuth titanate (CaBi4Ti4O15—CBTi144 thin films were investigated. Experimentally, the (119-oriented CBTi144 thin films were deposited onto the ITO/glass substrates by RF magnetron sputtering followed by rapid thermal annealing (RTA at a temperature range of 450–550°C. The surface morphologies and crystal structures of the CBTi144 thin films were examined by using field-emission scanning electron microscopy and X-ray diffraction measurements. The on/off ratio and switching behaviors of the transparent Al/CBTi144/ITO/glass RRAM devices were further discussed in this work.

  15. Flow field bipolar plates in a proton exchange membrane fuel cell: Analysis & modeling

    International Nuclear Information System (INIS)

    Kahraman, Huseyin; Orhan, Mehmet F.

    2017-01-01

    Highlights: • Covers a comprehensive review of available flow field channel configurations. • Examines the main design considerations and limitations for a flow field network. • Explores the common materials and material properties used for flow field plates. • Presents a case study of step-by-step modeling for an optimum flow field design. - Abstract: This study investigates flow fields and flow field plates (bipolar plates) in proton exchange membrane fuel cells. In this regard, the main design considerations and limitations for a flow field network have been examined, along with a comprehensive review of currently available flow field channel configurations. Also, the common materials and material properties used for flow field plates have been explored. Furthermore, a case study of step-by-step modeling for an optimum flow field design has been presented in-details. Finally, a parametric study has been conducted with respect to many design and performance parameters in a flow field plate.

  16. Nitric Oxide Mediates Activity-Dependent Plasticity of Retinal Bipolar Cell Output via S-Nitrosylation

    Science.gov (United States)

    Tooker, Ryan E.; Lipin, Mikhail Y.; Leuranguer, Valerie; Rozsa, Eva; Bramley, Jayne R.; Harding, Jacqueline L.; Reynolds, Melissa M.

    2013-01-01

    Coding a wide range of light intensities in natural scenes poses a challenge for the retina: adaptation to bright light should not compromise sensitivity to dim light. Here we report a novel form of activity-dependent synaptic plasticity, specifically, a “weighted potentiation” that selectively increases output of Mb-type bipolar cells in the goldfish retina in response to weak inputs but leaves the input–output ratio for strong stimuli unaffected. In retinal slice preparation, strong depolarization of bipolar terminals significantly lowered the threshold for calcium spike initiation, which originated from a shift in activation of voltage-gated calcium currents (ICa) to more negative potentials. The process depended upon glutamate-evoked retrograde nitric oxide (NO) signaling as it was eliminated by pretreatment with an NO synthase blocker, TRIM. The NO-dependent ICa modulation was cGMP independent but could be blocked by N-ethylmaleimide (NEM), indicating that NO acted via an S-nitrosylation mechanism. Importantly, the NO action resulted in a weighted potentiation of Mb output in response to small (≤−30 mV) depolarizations. Coincidentally, light flashes with intensity ≥2.4 × 108 photons/cm2/s lowered the latency of scotopic (≤2.4 × 108 photons/cm2/s) light-evoked calcium spikes in Mb axon terminals in an NEM-sensitive manner, but light responses above cone threshold (≥3.5 × 109 photons/cm2/s) were unaltered. Under bright scotopic/mesopic conditions, this novel form of Mb output potentiation selectively amplifies dim retinal inputs at Mb → ganglion cell synapses. We propose that this process might counteract decreases in retinal sensitivity during light adaptation by preventing the loss of visual information carried by dim scotopic signals. PMID:24305814

  17. Generation of retroviral particles for the spleen necrosis virus (SNV)-based vector system and their use in transduction of various cell types.

    Science.gov (United States)

    Parveen, Zahida; Mukhtar, Muhammad; Pomerantz, Roger J

    2010-06-01

    Genetically engineered retroviruses are widely used for gene delivery into human cells. A number of investigators have studied spleen necrosis virus (SNV) as a vehicle for gene delivery. Vectors developed from SNV and its closely associated avian reticuloendotheliosis virus strain A (REV-A) can be used for gene transfer into a variety of cells, including primary hematopoietic cells and human brain and post-mitotic neuronal cells that are difficult to transduce with other vector systems. SNV-based vector systems have the advantage of being quite safe, because wild-type SNV is unable to infect human cells and has less preference for integration into transcriptionally active sites or genes. However, the generation of retroviral vectors requires cotransfection of more than one plasmid into a packaging cell line, which is a tedious process. The development of stable packaging cell lines expressing envelope (Env) proteins and the structural proteins Gag-Pol will enhance mass production of retroviral vectors for future gene therapy experiments both in vitro and in vivo. This protocol describes the generation of retroviral particles for the SNV-based vector system. These particles can then be used for transduction of various cell types; as an example, a technique for transduction of post-mitotic neurons is also presented.

  18. Distinct UV-B and UV-A/blue light signal transduction pathways induce chalcone synthase gene expression in Arabidopsis cells

    International Nuclear Information System (INIS)

    Christie, J.M.; Jenkins, G.I.

    1996-01-01

    UV and blue light control the expression of flavonoid biosynthesis genes in a range of higher plants. To investigate the signal transduction processes involved in the induction of chalcone synthase (CHS) gene expression by UV-B and UV-A/blue light, we examined the, effects of specific agonists and inhibitors of known signaling components in mammalian systems in a photomixotrophic Arabidopsis cell suspension culture. CHS expression is induced specifically by these wavelengths in the cell culture, in a manner similar to that in mature Arabidopsis leaf tissue. Both the UV-B and UV-A/blue phototransduction processes involve calcium, although the elevation of cytosolic calcium is insufficient on its own to stimulate CHS expression. The UV-A/blue light induction of CHS expression does not appear to involve calmodulin, whereas the UV-B response does; this difference indicates that the signal transduction pathways are, at least in part, distinct. We provide evidence that both pathways involve reversible protein phosphorylation and require protein synthesis. The UV-B and UV-A/blue light signaling pathways are therefore different from the phytochrome signal transduction pathway regulating CHS expression in other species

  19. 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

  20. 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,…

  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. Portulaca oleracea extract can inhibit nodule formation of colon cancer stem cells by regulating gene expression of the Notch signal transduction pathway.

    Science.gov (United States)

    Jin, Heiying; Chen, Li; Wang, Shuiming; Chao, Deng

    2017-07-01

    To investigate whether Portulaca oleracea extract affects tumor formation in colon cancer stem cells and its chemotherapy sensitivity. In addition, to analyze associated genetic changes within the Notch signal transduction pathway. Serum-free cultures of colon cancer cells (HT-29) and HT-29 cancer stem cells were treated with the chemotherapeutic drug 5-fluorouracil to assess sensitivity. Injections of the stem cells were also given to BALB/c mice to confirm tumor growth and note its characteristics. In addition, the effect of different concentrations of P. oleracea extract was tested on the growth of HT-29 colon cancer cells and HT-29 cancer stem cells, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The effects of P. oleracea extract on the expression of β-catenin, Notch1, and Notch2 in the HT-29 cells were studied using reverse transcription polymerase chain reaction and Western blotting. The tumor volume of the HT29 cells was two times larger than that of HT29 cancer stem cells. Treatment with P. oleracea extract inhibited the proliferation of both HT-29 cancer cells and HT-29 cancer stem cells at doses from 0.07 to 2.25 µg/mL. Apoptosis of HT-29 cancer cells and HT-29 cancer stem cells was assessed by flow cytometry; it was enhanced by the addition of P. oleracea extract. Finally, treatment with P. oleracea extract significantly downregulated the expression of the Notch1 and β-catenin genes in both cell types. The results of this study show that P. oleracea extract inhibits the growth of colon cancer stem cells in a dose-dependent manner. Furthermore, it inhibits the expression of the Notch1 and β-catenin genes. Taken together, this suggests that it may elicit its effects through regulatory and target genes that mediate the Notch signal transduction pathway.

  3. 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

    and acidification, include hypoxia and mechanical stimuli, such as cell stretch. It has recently become apparent that NHE1-mediated modulation of, e.g., cell migration, morphology, proliferation, and death results not only from NHE1-mediated changes in pHi, cell volume, and/or [Na+]i, but also from direct protein...... signaling event activated by stress conditions and modulating cell proliferation and death. The pathophysiological importance of NHE1 in modulating the balance between cell proliferation and cell death in cancer and in ischemia/severe hypoxia will also be briefly addressed.......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 function...

  4. Bipolar Disorder

    Science.gov (United States)

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

  5. Porous Composite for Bipolar Plate in Low Emission Hydrogen Fuel Cells

    Directory of Open Access Journals (Sweden)

    Renata Katarzyna Włodarczyk

    2018-01-01

    Full Text Available The paper presents the results of graphite-stainless steel composites for the bipolar plates in low-temperature fuel cells. The sinters were performed by powder metallurgy technology. The influenceof technological parameters, especially molding pressure were examined. Following the requirements formulated by the DOE concerning the parameters of the materials, it indicated by the value of the parameters. The density, flowabilit, particle size of graphite and stainless steel powders have been evaluated. Composites have been tested by microstructure and phase analysis, properties of strength, functional properties: wettability, porosity, roughness. The special attention was paid to the analysis of corrosion resistance obtained sinters and influenceof technological parameters on the corrosion. Corrosion tests were carried out under conditions simulating the environment of the fuel cell under anode and cathode conditions. The effectof pH solution during working of the cell on corrosion resistance of composites have been evaluated. Contact resistance depends on roughness of sinters. Low ICR determined high contact area GDL-BP and high electrical conductivity on the contact surface. The ICR in anode conditions after corrosion tests are not change significantly; composite materials can be used for materials for B in terms of H 2 .

  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. Serum TRPM1 autoantibodies from melanoma associated retinopathy patients enter retinal on-bipolar cells and attenuate the electroretinogram in mice.

    Directory of Open Access Journals (Sweden)

    Wei-Hong Xiong

    Full Text Available Melanoma-associated retinopathy (MAR is a paraneoplastic syndrome associated with cutaneous malignant melanoma and the presence of autoantibodies that label neurons in the inner retina. The visual symptoms and electroretinogram (ERG phenotype characteristic of MAR resemble the congenital visual disease caused by mutations in TRPM1, a cation channel expressed by both melanocytes and retinal bipolar cells. Four serum samples from MAR patients were identified as TRPM1 immunoreactive by 1. Labeling of ON-bipolar cells in TRPM1+/+ but not TRPM1-/- mouse retina, 2. Labeling of TRPM1-transfected CHO cells; and 3. Attenuation of the ERG b-wave following intravitreal injection of TRPM1-positive MAR IgG into wild-type mouse eyes, and the appearance of the IgG in the retinal bipolar cells at the conclusion of the experiment. Furthermore, the epitope targeted by the MAR autoantibodies was localized within the amino-terminal cytoplasmic domain of TRPM1. Incubation of live retinal neurons with TRPM1-positive MAR serum resulted in the selective accumulation of IgG in ON-bipolar cells from TRPM1+/+ mice, but not TRPM1-/- mice, suggesting that the visual deficits in MAR are caused by the uptake of TRPM1 autoantibodies into ON-bipolar cells, where they bind to an intracellular epitope of the channel and reduce the ON-bipolar cell response to light.

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

    Directory of Open Access Journals (Sweden)

    Claudio eElgueta

    2015-02-01

    Full Text Available Abstract 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 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 acetyl-cholinesterase 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, 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.

  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. Human conjunctival epithelial cell responses to platelet-activating factor (PAF): signal transduction and release of proinflammatory cytokines.

    Science.gov (United States)

    Sharif, Najam A; Xu, Shouxi; Hellberg, Peggy E; Pang, Iok-Hou; Gamache, Daniel A; Yanni, John M

    2009-06-06

    The aims of the study were to characterize the signal transduction responses to platelet-activating factor (PAF) and to monitor the downstream effects of PAF on the production of proinflammatory cytokines in human conjunctival epithelial cells (HCECs). The generation of inositol phosphates ([(3)H]IPs) from [(3)H]phosphoinositide (PI) hydrolysis and the mobilization of intracellular calcium ([Ca(2+)](i)) were evaluated using ion exchange chromatography and Fura-2 fluorescence techniques, respectively. The production of the cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], and granulocyte macrophage colony-stimulating factor [GM-CSF]) from PAF-stimulated HCECs was quantified using specific ELISA assays. Specific PAF antagonists were used to study the pharmacological aspects of PAF actions in HCECs. PAF (100 nM) maximally stimulated PI turnover in HCECs by 2.3+/-0.02 fold (n=21) above basal levels and with a potency (EC(50)) of 5.9+/-1.7 nM (n=4). PAF or its stabilized analog, methyl carbamyl (mc)PAF (EC(50)=0.8 nM), rapidly mobilized [Ca(2+)](i), which peaked within 30-60 s and remained elevated for 3 min. PAF (10 nM-1 microM) stimulated the release of the proinflammatory cytokines, IL-6, IL-8, and GM-CSF, 1.4-3.5 fold above basal levels. The effects of PAF (100 nM) on PI turnover and [Ca(2+)](i) were potently antagonized by the PAF antagonists, 1-o-hexadecyl-2-o-acetyl-sn-glycero-3-phospho (N,N,N-trimethyl) hexanolamine (IC(50)=0.69 microM; K(i)=38 nM), methyl 2-(phenylthio)ethyl-1,4-dihydro-2,4,6-trimethyl-pyridine-3,5-dicsrboxylate (PCA-42481; IC(50)=0.89 microM; K(i)=50 nM), rac-3-(N-octadecylcarbomoyl)-2-methoxy) propyl-(2-thiazolioethyl) phosphate (CV-3988; IC(50)=13 microM; K(i)=771 nM), and (+/-)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl (SM-10661; IC(50)=14 microM; K(i)=789 nM [n=3 for each antagonist]). PAF-induced production of IL-6, IL-8, and GM-CSF from HCECs was also blocked by these PAF antagonists (IC(50)=4.6- 8.6 microM). HCECs respond

  11. A rapid and efficient polyethylenimine-based transfection method to prepare lentiviral or retroviral vectors: useful for making iPS cells and transduction of primary cells.

    Science.gov (United States)

    Yang, Shaozhe; Shi, Haijun; Chu, Xinran; Zhou, Xiaoling; Sun, Pingnan

    2016-09-01

    To improve the efficiency, reproducibility and consistency of the PEI-based transfection method that is often used in preparation of recombinant lentiviral or retroviral vectors. The contributions to transfection efficiency of multi-factors including concentration of PEI or DNA, dilution buffer for PEI/DNA, manner to prepare PEI/DNA complexes, influence of serum, incubation time for PEI/DNA complexes, and transfection time were studied. Gentle mixing during the preparation of PEI/DNA transfection complexes is critical for a high transfection efficiency. PEI could be stored at room temperature or 4 °C, and most importantly, multigelation should be avoided. The transfection efficiency of the PEI-based new method in different types of cells, such as 293T, Cos-7, HeLa, HepG2, Hep3B, Huh7 and L02, was also higher than that of the previous method. After optimization, the titer of our lentiviral system or retroviral system produced by PEI-based new method was about 10- or 3-times greater than that produced by PEI-based previous method, respectively. We provide a rapid and efficient PEI-based method for preparation of recombinant lentiviral or retroviral vectors which is useful for making iPS cells as well as transduction of primary cell cultures.

  12. Controlling Cell Functions and Fate with Surfaces and Hydrogels: The Role of Material Features in Cell Adhesion and Signal Transduction

    Directory of Open Access Journals (Sweden)

    Maurizio Ventre

    2016-03-01

    Full Text Available In their natural environment, cells are constantly exposed to a cohort of biochemical and biophysical signals that govern their functions and fate. Therefore, materials for biomedical applications, either in vivo or in vitro, should provide a replica of the complex patterns of biological signals. Thus, the development of a novel class of biomaterials requires, on the one side, the understanding of the dynamic interactions occurring at the interface of cells and materials; on the other, it requires the development of technologies able to integrate multiple signals precisely organized in time and space. A large body of studies aimed at investigating the mechanisms underpinning cell-material interactions is mostly based on 2D systems. While these have been instrumental in shaping our understanding of the recognition of and reaction to material stimuli, they lack the ability to capture central features of the natural cellular environment, such as dimensionality, remodelling and degradability. In this work, we review the fundamental traits of material signal sensing and cell response. We then present relevant technologies and materials that enable fabricating systems able to control various aspects of cell behavior, and we highlight potential differences that arise from 2D and 3D settings.

  13. Influences of bipolar plate channel blockages on PEM fuel cell performances

    International Nuclear Information System (INIS)

    Heidary, Hadi; Kermani, Mohammad J.; Dabir, Bahram

    2016-01-01

    Highlights: • Effect of partial- or full-blockage of PEMFC flow channels is numerically studied. • The anode blockage does not show any positive effects on cell performance. • Full blockages, despite higher pressure drop, better enhance net electrical power. • Additions of blocks more than five do not improve the cell performance. • Full blockage of cathode channels with five blocks enhances the net power by 30%. - Abstract: In this paper, the effect of partial- or full-block placement along the flow channels of PEM fuel cells is numerically studied. Blockage in the channel of flow-field diverts the flow into the gas diffusion layer (GDL) and enhances the mass transport from the channel core part to the catalyst layer, which in turn improves the cell performance. By partial blockage, only a part of the channel flow is shut off. While in full blockage, in which the flow channel cross sections are fully blocked, the only avenue left for the continuation of the gas is to travel over the blocks via the porous zone (GDL). In this study, a 3D numerical model consisting of a 9-layer PEM fuel cell is performed. A wide spectrum of numerical studies is performed to study the influences of the number of blocks, blocks height, and anode/cathode-side flow channel blockage. The results show that the case of full blockage enhances the net electrical power more than that of the partial blockage, in spite of higher pressure drop. Performed studies show that full blockage of the cathode-side flow channels with five blocks along the 5 cm channel enhances the net power by 30%. The present work provides helpful guidelines to bipolar plate manufacturers.

  14. Nerve growth factor inhibits osmotic swelling of rat retinal glial (Müller) and bipolar cells by inducing glial cytokine release.

    Science.gov (United States)

    Garcia, Tarcyane Barata; Pannicke, Thomas; Vogler, Stefanie; Berk, Benjamin-Andreas; Grosche, Antje; Wiedemann, Peter; Seeger, Johannes; Reichenbach, Andreas; Herculano, Anderson Manoel; Bringmann, Andreas

    2014-11-01

    Osmotic swelling of neurons and glial cells contributes to the development of retinal edema and neurodegeneration. We show that nerve growth factor (NGF) inhibits the swelling of glial (Müller) and bipolar cells in rat retinal slices induced by barium-containing hypoosmotic solution. NGF also reduced Müller and bipolar cell swelling in the post-ischemic retina. On the other hand, NGF prevented the swelling of freshly isolated Müller cells, but not of isolated bipolar cells, suggesting that NGF induces a release of factors from Müller cells that inhibit bipolar cell swelling in retinal slices. The inhibitory effect of NGF on Müller cell swelling was mediated by activation of TrkA (the receptor tyrosine kinase A), but not p75(NTR) , and was prevented by blockers of metabotropic glutamate, P2Y1 , adenosine A1 , and fibroblast growth factor receptors. Basic fibroblast growth factor fully inhibited the swelling of freshly isolated Müller cells, but only partially the swelling of isolated bipolar cells. In addition, glial cell line-derived neurotrophic factor and transforming growth factor-β1, but not epidermal growth factor and platelet-derived growth factor, reduced the swelling of bipolar cells. Both Müller and bipolar cells displayed TrkA immunoreactivity, while Müller cells were also immunostained for p75(NTR) and NGF. The data suggest that the neuroprotective effect of NGF in the retina is in part mediated by prevention of the cytotoxic glial and bipolar cell swelling. Cytotoxic cell swelling contributes to retinal neurodegeneration. Nerve growth factor (NGF) inhibits the osmotic swelling of glial cells by acting at TrkA, release of bFGF, and opening of K(+) and Cl(-) channels. The NGF-induced glial release of cytokines like bFGF inhibits the osmotic swelling of bipolar cells, suggesting that the neuroprotective effect of NGF is in part mediated by prevention of cytotoxic cell swelling. © 2014 International Society for Neurochemistry.

  15. PrPc capping in T cells promotes its association with the lipid raft proteins reggie-1 and reggie-2 and leads to signal transduction : [Langfassung

    OpenAIRE

    Stürmer, Claudia; Langhorst, Matthias F.; Wiechers, Marianne F.; Legler, Daniel F.; Hannbeck von Hanwehr, Sylvia; Guse, Andreas H.; Plattner, Helmut

    2004-01-01

    The cellular prion protein (PrPc) resides in lipid rafts, yet the type of raft and the physiological function of PrPc are unclear. We show here that cross-linking of PrPc with specific antibodies leads to 1) PrPc capping in Jurkat and human peripheral blood T cells; 2) to cocapping with the intracellular lipid raft proteins reggie-1 and reggie-2; 3) to signal transduction as seen by MAP kinase phosphorylation and an elevation of the intracellular Ca2+ concentration; 4) to the recruitment of T...

  16. The underlying neurobiology of bipolar disorder

    Science.gov (United States)

    MANJI, HUSSEINI K; QUIROZ, JORGE A; PAYNE, JENNIFER L; SINGH, JASKARAN; LOPES, BARBARA P; VIEGAS, JENILEE S; ZARATE, CARLOS A

    2003-01-01

    Clinical studies over the past decades have attempted to uncover the biological factors mediating the pathophysiology of bipolar disorder (BD) utilizing a variety of biochemical and neuroendocrine strategies. Indeed, assessments of cerebrospinal fluid chemistry, neuroendocrine responses to pharmacological challenge, and neuroreceptor and transporter binding have demonstrated a number of abnormalities in the amine neurotransmitter systems in this disorder. However, recent studies have also implicated critical signal transduction pathways as being integral to the pathophysiology and treatment of BD, in addition to a growing body of data suggesting that impairments of neuroplasticity and cellular resilience may also underlie the pathophysiology of the disorder. It is thus noteworthy that mood stabilizers and antidepressants indirectly regulate a number of factors involved in cell survival pathways - including MAP kinases, CREB, BDNF and bcl-2 protein - and may thus bring about some of their delayed long-term beneficial effects via underappreciated neurotrophic effects. PMID:16946919

  17. Neogenesis and proliferation of β-cells induced by human betacellulin gene transduction via retrograde pancreatic duct injection of an adenovirus vector

    International Nuclear Information System (INIS)

    Tokui, Yae; Kozawa, Junji; Yamagata, Kazuya; Zhang, Jun; Ohmoto, Hiroshi; Tochino, Yoshihiro; Okita, Kohei; Iwahashi, Hiromi; Namba, Mitsuyoshi; Shimomura, Iichiro; Miyagawa, Jun-ichiro

    2006-01-01

    Betacellulin (BTC) has been shown to have a role in the differentiation and proliferation of β-cells both in vitro and in vivo. We administered a human betacellulin (hBTC) adenovirus vector to male ICR mice via retrograde pancreatic duct injection. As a control, we administered a β-galactosidase adenovirus vector. In the mice, hBTC protein was mainly overexpressed by pancreatic duct cells. On immunohistochemical analysis, we observed features of β-cell neogenesis as newly formed insulin-positive cells in the duct cell lining or islet-like cell clusters (ICCs) closely associated with the ducts. The BrdU labeling index of β-cells was also increased by the betacellulin vector compared with that of control mice. These results indicate that hBTC gene transduction into adult pancreatic duct cells promoted β-cell differentiation (mainly from duct cells) and proliferation of pre-existing β-cells, resulting in an increase of the β-cell mass that improved glucose tolerance in diabetic mice

  18. PrPc capping in T cells promotes its association with the lipid raft proteins reggie-1 and reggie-2 and leads to signal transduction.

    Science.gov (United States)

    Stuermer, Claudia A O; Langhorst, Matthias F; Wiechers, Marianne F; Legler, Daniel F; Von Hanwehr, Sylvia Hannbeck; Guse, Andreas H; Plattner, Helmut

    2004-11-01

    The cellular prion protein (PrPc) resides in lipid rafts, yet the type of raft and the physiological function of PrPc are unclear. We show here that cross-linking of PrPc with specific antibodies leads to 1) PrPc capping in Jurkat and human peripheral blood T cells; 2) to cocapping with the intracellular lipid raft proteins reggie-1 and reggie-2; 3) to signal transduction as seen by MAP kinase phosphorylation and an elevation of the intracellular Ca2+ concentration; 4) to the recruitment of Thy-1, TCR/CD3, fyn, lck and LAT into the cap along with local tyrosine phosphorylation and F-actin polymerization, and later, internalization of PrPc together with the reggies into limp-2 positive lysosomes. Thus, PrPc association with reggie rafts triggers distinct transmembrane signal transduction events in T cells that promote the focal concentration of PrPc itself by guiding activated PrPc into preformed reggie caps and then to the recruitment of important interacting signaling molecules.

  19. 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.

  20. Distinct lithium-induced gene expression effects in lymphoblastoid cell lines from patients with bipolar disorder.

    Science.gov (United States)

    Fries, Gabriel R; Colpo, Gabriela D; Monroy-Jaramillo, Nancy; Zhao, Junfei; Zhao, Zhongming; Arnold, Jodi G; Bowden, Charles L; Walss-Bass, Consuelo

    2017-11-01

    Lithium is the most commonly prescribed medication for the treatment of bipolar disorder (BD), yet the mechanisms underlying its beneficial effects are still unclear. We aimed to compare the effects of lithium treatment in lymphoblastoid cell lines (LCLs) from BD patients and controls. LCLs were generated from sixty-two BD patients (based on DSM-IV) and seventeen healthy controls matched for age, sex, and ethnicity. Patients were recruited from outpatient clinics from February 2012 to October 2014. LCLs were treated with 1mM lithium for 7 days followed by microarray gene expression assay and validation by real-time quantitative PCR. Baseline differences between groups, as well as differences between vehicle- and lithium-treated cells within each group were analyzed. The biological significance of differentially expressed genes was examined by pathway enrichment analysis. No significant differences in baseline gene expression (adjusted p-value < 0.05) were detected between groups. Lithium treatment of LCLs from controls did not lead to any significant differences. However, lithium altered the expression of 236 genes in LCLs from patients; those genes were enriched for signaling pathways related to apoptosis. Among those genes, the alterations in the expression of PIK3CG, SERP1 and UPP1 were validated by real-time PCR. A significant correlation was also found between circadian functioning and CEBPG and FGF2 expression levels. In summary, our results suggest that lithium treatment induces expression changes in genes associated with the apoptosis pathway in BD LCLs. The more pronounced effects of lithium in patients compared to controls suggest a disease-specific effect of this drug. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

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

    International Nuclear Information System (INIS)

    Chen, Chien-Liang; Chou, Kang-Ju; Lee, Po-Tsang; Chen, Ying-Shou; Chang, Tsu-Yuan; Hsu, Chih-Yang; Huang, Wei-Chieh; Chung, Hsiao-Min; Fang, Hua-Chang

    2010-01-01

    Purpose: Tumor growth factor-β1 (TGF-β1) 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-β1-mediated EMT and fibrosis in kidney injury. Methods: We examined apoptosis and EMT in TGF-β1-treated LLC-PK1 cells in the presence or absence of EPO. We examined the effect of EPO on TGF-β1-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-β1 signal pathway proteins and EMT markers. Results: We demonstrated that ZVAD-FMK (a caspase inhibitor) inhibited TGF-β1-induced apoptosis but did not inhibit EMT. In contrast, EPO reversed TGF-β1-mediated apoptosis and also partially inhibited TGF-β1-mediated EMT. We showed that EPO treatment suppressed TGF-β1-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-β1-treated cells. Conclusions: EPO inhibited apoptosis and EMT in TGF-β1-treated LLC-PK1 cells. This effect of EPO was partially mediated by a mitogen-activated protein kinase-dependent inhibition of Smad signal transduction.

  2. Dielectric Transduction of NEMS

    OpenAIRE

    Howell, Kaitlin

    2017-01-01

    We report on a four-mask process flow for creating resonant NanoElectroMechanical Systems (NEMS) based on dielectric transduction. Current transduction mechanisms for NEMS include piezoelectricity, flexoelectricity and dielectric force. While piezoelectricity gives the highest electromechanical efficiency in, NEMS using flexoelectricity and dielectric force are interesting alternatives with a larger range of possible active materials and potentially simpler fabrication. In this four-mask proc...

  3. Transduction of an immortalized olfactory ensheathing glia cell line with the green fluorescent protein (GFP) gene: Evaluation of its neuroregenerative capacity as a proof of concept.

    Science.gov (United States)

    Plaza, N; Simón, D; Sierra, J; Moreno-Flores, M T

    2016-01-26

    Olfactory ensheathing glia (OEG) cells are known to foster axonal regeneration of central nervous system (CNS) neurons. Several lines of reversibly immortalized human OEG (ihOEG) have been previously established that enabled to develop models for their validation in vitro and in vivo. In this work, a constitutively GFP-expressing ihOEG cell line was obtained, and named Ts14-GFP. Ts14-GFP neuroregenerative ability was similar to that found for the parental line Ts14 and it can be assayed using in vivo transplantation experimental paradigms, after spinal cord or optic nerve damage. Additionally, we have engineered a low-regenerative ihOEG line, hTL2, using lentiviral transduction of the large T antigen from SV40 virus, denominated from now on Ts12. Ts12 can be used as a low regeneration control in these experiments. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Effect of Lipoglycans from Mycobacterium Chelonae on the expression of inflammatory factors IL-8 and IL-6 in human corneal epithelial cells and its possible signal transduction pathway

    Directory of Open Access Journals (Sweden)

    Chun-Zhou Tang

    2015-06-01

    Full Text Available AIM: To study the influence of Lipoglycans from Mycobacterium Chelonae(Cheon the expression of IL-6 and IL-8 in human corneal epithelia cells and its possible signal transduction pathway.METHODS: Lipoglycans was extracted by the Triton X-114 phase partitioning. Lipoglycans from Che were purified, by successive detergent and phenol extractions. Lipoglycans were separated by gel filtration on a Sephacryl 200 column and Sephacryl 100 column in series, followed by extensive dialisis. Purified Lipoglycans(50μg/mLwere added into culture medium to stimulate primary human corneal epithelial(HCEcells. Cells and supernatant were collected at 0, 6, 12, 24h after the stimulation. The IL-6 and IL-8 expression at mRNA level was assayed by using real time RT-PCR and the secreted IL-6 and IL-8 in the supernatants was measured by ELISA. Immunochemistry was used to detect the expression and location of NF-κB in HCE cells.RESULTS: After the treatment of Lipoglycans, the expression of IL-8 and IL-6 at mRNA level obviouly increased within 12h, and reached peak level at 6h(IL-8 was 36.8 times that of the blank control, and IL-6 was 32.7 times. Compared with the blank control group, the expression of IL-8 at protein level in the supernatant increased 2.8 folds at 6h(P>0.05, 13.4 folds at 12h(PPPPPCONCLUSION: Lipoglycans from Che can induce HCE cells to produce inflammatory factors(IL-6 and IL-8, and its signal transduction pathway probably is mediated by NF-κB.

  5. 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.

  6. 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.

  7. 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...... 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...

  8. Effect of filler content on the properties of expanded- graphite-based composite bipolar plates for application in polymer electrolyte membrane fuel cells

    Science.gov (United States)

    Masand, Aakash; Borah, Munu; Pathak, Abhishek K.; Dhakate, Sanjay R.

    2017-09-01

    Minimization of the weight and volume of a hydrogen-based PEM fuel cell stack is an essential area of research for the development and commercialization of PEMFCs for various applications. Graphite-based composite bipolar plates have significant advantages over conventional metallic bipolar plates due to their corrosion resistivity and low cost. On the other hand, expanded graphite is seen to be a potential candidate for facilitating the required electrical, thermal and mechanical properties of bipolar plates with a low density. Therefore, in the present study, the focus is on minimization of the high loading of graphite and optimizes its composition to meet the target properties of bipolar plates as per the USDOE target. Three types of expanded graphite (EG)-phenolic-resin-based composite bipolar plates were developed by partially replacing the expanded graphite content with natural graphite (NG) and carbon black as an additional filler. The three types of composite plate with the reinforcing constituent ratio EG:NG:R (25:25:50) give a bending strength of 49 MPa, a modulus of ~6 GPa, electrical conductivity  >100 S cm-1, a shore hardness of 55 and a bulk density of 1.55 g/cc. The 50 wt% loading of resin is sufficient to wet the 50 wt% filler content in the composite plate. This study gives an insight into using hybrid reinforcements in order to achieve the desired properties of bipolar plates.

  9. Transduction of the SkBr3 breast carcinoma cell line with the HOXB7 gene induces bFGF expression, increases cell proliferation and reduces growth factor dependence.

    Science.gov (United States)

    Caré, A; Silvani, A; Meccia, E; Mattia, G; Peschle, C; Colombo, M P

    1998-06-25

    Several melanomas, carcinomas, glioblastomas and leukemias showed coordinated expression of HOXB7 and bFGF with exception of the SkBr3 mammary carcinoma that was negative for both. Transduction of HOXB7 gene into SkBr3 cells, induced bFGF expression, increased growth rate, independence from serum withdrawal and ability to form colonies in semisolid medium. ELISA assay showed that most of bFGF was associated to cell lysate when cells were cultured at 1% serum whereas in cells kept to 10% serum bFGF was detected both within cell lysate or secreted into cell supernatants. Antisense oligos to bFGF inhibited the growth of cells cultured in 1%, indicating that beside the possible activation of additional genes other than bFGF by HOXB7 transduction, only bFGF induction accounts for the observed results. Moreover, since inhibition of cell proliferation occurred in cells kept in 1% but not 10% serum, a bFGF intracrine loop appears operative in serum starved SkBr3/HOXB7 cells. Also, these results further indicate bFGF as target of HOXB7.

  10. Developmental changes in NMDA receptor subunit composition at ON and OFF bipolar cell synapses onto direction-selective retinal ganglion cells.

    Science.gov (United States)

    Stafford, Benjamin K; Park, Silvia J H; Wong, Kwoon Y; Demb, Jonathan B

    2014-01-29

    In the developing mouse retina, spontaneous and light-driven activity shapes bipolar→ganglion cell glutamatergic synapse formation, beginning around the time of eye-opening (P12-P14) and extending through the first postnatal month. During this time, glutamate release can spill outside the synaptic cleft and possibly stimulate extrasynaptic NMDA-type glutamate receptors (NMDARs) on ganglion cells. Furthermore, the role of NMDARs during development may differ between ON and OFF bipolar synapses as in mature retina, where ON synapses reportedly include extrasynaptic NMDARs with GluN2B subunits. To better understand the function of glutamatergic synapses during development, we made whole-cell recordings of NMDAR-mediated responses, in vitro, from two types of genetically identified direction-selective ganglion cells (dsGCs): TRHR (thyrotropin-releasing hormone receptor) and Drd4 (dopamine receptor 4). Both dsGC types responded to puffed NMDA between P7 and P28; and both types exhibited robust light-evoked NMDAR-mediated responses at P14 and P28 that were quantified by conductance analysis during nicotinic and GABA(A) receptor blockade. For a given cell type and at a given age, ON and OFF bipolar cell inputs evoked similar NMDAR-mediated responses, suggesting that ON-versus-OFF differences in mature retina do not apply to the cell types or ages studied here. At P14, puff- and light-evoked NMDAR-mediated responses in both dsGCs were partially blocked by the GluN2B antagonist ifenprodil, whereas at P28 only TRHR cells remained ifenprodil-sensitive. NMDARs contribute at both ON and OFF bipolar cell synapses during a period of robust activity-dependent synaptic development, with declining GluN2B involvement over time in specific ganglion cell types.

  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. 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. FEMS Microbiology Letters © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. No claim to original US government works.

  13. Bipolar disorder

    Science.gov (United States)

    ... of pleasure in activities once enjoyed Loss of self-esteem Thoughts of death or suicide Trouble getting to ... other. This is called rapid cycling. Exams and Tests To diagnose bipolar disorder, the provider may do ...

  14. Bipolar disorder

    Directory of Open Access Journals (Sweden)

    F Colin

    2013-08-01

    Full Text Available Bipolar disorder (BD presents in different phases over time and is oftencomplicated by comorbid conditions such as substance-use disordersand anxiety disorders. Treatment usually involves pharmacotherapywith combinations of different classes of medications and frequentmedication revisions.

  15. 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.

  16. Differences in physico-mechanical behaviors of resol(e) and novolac type phenolic resin based composite bipolar plate for proton exchange membrane (PEM) fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Kakati, Biraj Kumar [Department of Chemical Engineering, Indian Institute of Technology Guwahati, North Guwahati, PIN 781 039, Dist. Kamrup (Assam) (India); Deka, Dhanapati [Department of Energy, Tezpur University, Tezpur 784 028, Dist. Sonitpur (Assam) (India)

    2007-09-15

    Composite bipolar plates for Proton Exchange Membrane Fuel Cell (PEMFC) are prepared by compression molding technique using polymer as binder and graphite as electric filler material with some other reinforcements. Study on the effect of resole and novolac type phenolic resin on the properties of composite bipolar plate, such as bulk density, porosity, bulk conductivity, hardness, flexural strength, etc. shows that both of the resin shows different physico-mechanical properties. Moreover, single cell performance analysis also shows variation for resole and novolac based composites. A novel concept of triple continuous structure to provide graphite polymer blends with high electrical conductivity, high shore hardness, high flexural strength, less porosity and low density has been proposed and study on the effect of different types of phenolic resin on the properties and performance of bipolar plate reveals that novolac type powdered phenolic resin gives better mechanical properties than resole type phenolic resin. However, resole type phenolic resin compound has slightly higher electrical conductivity due to more number of polar -OH group presents on its cured form. But due to the less porosity and higher mechanical strength, bipolar plates with novolac type phenolic resin gives better performance in I-V analysis than bipolar plates with resole type phenolic resin. (author)

  17. Losses of immunoreactive parvalbumin amacrine and immunoreactive alphaprotein kinase C bipolar cells caused by methylmercury chloride intoxication in the retina of the tropical fish Hoplias malabaricus

    Directory of Open Access Journals (Sweden)

    Bonci D.M.O.

    2006-01-01

    Full Text Available To quantify the effects of methylmercury (MeHg on amacrine and on ON-bipolar cells in the retina, experiments were performed in MeHg-exposed groups of adult trahiras (Hoplias malabaricus at two dose levels (2 and 6 µg/g, ip. The retinas of test and control groups were processed by mouse anti-parvalbumin and rabbit anti-alphaprotein kinase C (alphaPKC immunocytochemistry. Morphology and soma location in the inner nuclear layer were used to identify immunoreactive parvalbumin (PV-IR and alphaPKC (alphaPKC-IR in wholemount preparations. Cell density, topography and isodensity maps were estimated using confocal images. PV-IR was detected in amacrine cells in the inner nuclear layer and in displaced amacrine cells from the ganglion cell layer, and alphaPKC-IR was detected in ON-bipolar cells. The MeHg-treated group (6 µg/g showed significant reduction of the ON-bipolar alphaPKC-IR cell density (mean density = 1306 ± 393 cells/mm² compared to control (1886 ± 892 cells/mm²; P < 0.001. The mean densities found for amacrine PV-IR cells in MeHg-treated retinas were 1040 ± 56 cells/mm² (2 µg/g and 845 ± 82 cells/mm² (6 µg/g, also lower than control (1312 ± 31 cells/mm²; P < 0.05, differently from the data observed in displaced PV-IR amacrine cells. These results show that MeHg changed the PV-IR amacrine cell density in a dose-dependent way, and reduced the density of alphaKC-IR bipolar cells at the dose of 6 µg/g. Further studies are needed to identify the physiological impact of these findings on visual function.

  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

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    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. 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

  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. Modulation of both activator protein-1 and nuclear factor-kappa B signal transduction of human T cells by amiodarone.

    Science.gov (United States)

    Cheng, Shu-Meng; Lin, Wei-Hsiang; Lin, Chin-Sheng; Ho, Ling-Jun; Tsai, Tsung-Neng; Wu, Chun-Hsien; Lai, Jenn-Haung; Yang, Shih-Ping

    2015-01-01

    Amiodarone, a common and effective antiarrhythmic drug, has been reported to have anti-inflammatory effects such as reducing the activation and movement of neutrophils. However, its effects on human T cells remain unclear. The aim of this study was to elucidate the effects and possible underlying mechanisms of amiodarone on human T cells. We isolated human primary T cells from the peripheral blood of healthy volunteers and performed enzyme-linked immunosorbent assay (ELISA), flow cytometry, electrophoretic mobility shift assay, luciferase assay, and Western blotting to evaluate the modulatory effects of amiodarone on human T cells. We found that amiodarone dose dependently inhibited the production of cytokines, including interleukin-2 (IL-2), IL-4, tumor necrosis factor-alpha, and interferon-gamma in activated human T cells. By flow cytometry, we demonstrated that amiodarone suppressed the expression of IL-2 receptor-alpha (CD25) and CD69, the cell surface markers of activated T cells. Moreover, molecular investigations revealed that amiodarone down-regulated activator protein-1 (AP-1) and nuclear factor kappa-B (NF-κB) DNA-binding activities in activated human T cells and also inhibited DNA binding and transcriptional activities of both AP-1 and NF-κB in Jurkat cells. Finally, by Western blotting, we showed that amiodarone reduced the activation of c-Jun NH(2)-terminal protein kinase and P38 mitogen-activated protein kinase, and suppressed stimuli-induced I-kappa B-alpha degradation in activated human T cells. Through regulation of AP-1 and NF-κB signaling, amiodarone inhibits cytokine production and T cell activation. These results show the pleiotropic effects of amiodarone on human T cells and suggest its therapeutic potential in inflammation-related cardiovascular disorders. © 2014 by the Society for Experimental Biology and Medicine.

  2. 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

  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. 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.

  5. 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)

  6. 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.

  7. 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

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

    International Nuclear Information System (INIS)

    Plante, Ianik; Cucinotta, Francis A.

    2011-01-01

    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.

  9. 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

    class II. Here we address the question of whether SEA can directly activate psoriatic T cells in the absence of professional antigen-presenting cells. We show that SEA induces i) tyrosine phosphorylation of several proteins, ii) downregulation of the T-cell receptor (TCR), and iii) production...... of SEA. Mutations in only one of the two MHC class II binding sites of SEA has different effects on T-cell activation. Thus, SEA molecules with a mutation in the MHC class II beta-binding site induce protein tyrosine phosphorylation, but not IFN-gamma production or co-stimulation of cytokine......-mediated proliferation. In contrast, SEA with a mutation in the MHC class II alpha-binding site induces IFN-gamma and a qualitatively changed tyrosine phosphorylation profile. Both mutations delete the co-stimulatory effect on cytokine-mediated proliferation. This suggests that both MHC class II binding sites...

  10. 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.

  11. Protection of the Crayfish Mechanoreceptor Neuron and Glial Cells from Photooxidative Injury by Modulators of Diverse Signal Transduction Pathways.

    Science.gov (United States)

    Uzdensky, Anatoly; Berezhnaya, Elena; Khaitin, Andrej; Kovaleva, Vera; Komandirov, Maxim; Neginskaya, Maria; Rudkovskii, Mikhail; Sharifulina, Svetlana

    2015-10-01

    Oxidative stress is the reason of diverse neuropathological processes. Photodynamic therapy (PDT), an effective inducer of oxidative stress, is used for cancer treatment, including brain tumors. We studied the role of various signaling pathways in photodynamic injury and protection of single neurons and satellite glial cells in the isolated crayfish mechanoreceptor. It was photosensitized with alumophthalocyanine Photosens in the presence of inhibitors or activators of various signaling proteins. PDT eliminated neuronal activity and killed neurons and glial cells. Inhibitory analysis showed the involvement of protein kinases Akt, glycogen synthase kinase-3β (GSK-3β), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinases 1 and 2 (MEK1/2), calmodulin, calmodulin-dependent kinase II (CaMKII), adenylate cyclase, and nuclear factor NF-κB in PDT-induced necrosis of neurons. Nitric oxide (NO) and glial cell-derived neurotrophic factor (GDNF) reduced neuronal necrosis. In glial cells, protein kinases Akt, calmodulin, and CaMKII; protein kinases C and G, adenylate cyclase, and p38; and nuclear transcription factor NF-κB also mediated PDT-induced necrosis. In contrast, NO and neurotrophic factors nerve growth factor (NGF) and GDNF demonstrated anti-necrotic activity. Phospholipase Cγ, protein kinase C, GSK-3β, mTOR, NF-κB, mitochondrial permeability transition pores, and NO synthase mediated PDT-induced apoptosis of glial cells, whereas protein kinase A, tyrosine phosphatases, and neurotrophic factors NGF, GDNF, and neurturin were involved in protecting glial cells from photoinduced apoptosis. Signaling pathways that control cell survival and death differed in neurons and glia. Inhibitors or activators of some signaling pathways may be used as potential protectors of neurons and glia from photooxidative stress and following death.

  12. NADPH oxidase 1 supports proliferation of colon cancer cells by modulating reactive oxygen species-dependent signal transduction.

    Science.gov (United States)

    Juhasz, Agnes; Markel, Susan; Gaur, Shikha; Liu, Han; Lu, Jiamo; Jiang, Guojian; Wu, Xiwei; Antony, Smitha; Wu, Yongzhong; Melillo, Giovanni; Meitzler, Jennifer L; Haines, Diana C; Butcher, Donna; Roy, Krishnendu; Doroshow, James H

    2017-05-12

    Reactive oxygen species (ROS) play a critical role in cell signaling and proliferation. NADPH oxidase 1 (NOX1), a membrane-bound flavin dehydrogenase that generates O 2 ̇̄ , is highly expressed in colon cancer. To investigate the role that NOX1 plays in colon cancer growth, we used shRNA to decrease NOX1 expression stably in HT-29 human colon cancer cells. The 80-90% decrease in NOX1 expression achieved by RNAi produced a significant decline in ROS production and a G 1 /S block that translated into a 2-3-fold increase in tumor cell doubling time without increased apoptosis. The block at the G 1 /S checkpoint was associated with a significant decrease in cyclin D 1 expression and profound inhibition of mitogen-activated protein kinase (MAPK) signaling. Decreased steady-state MAPK phosphorylation occurred concomitant with a significant increase in protein phosphatase activity for two colon cancer cell lines in which NOX1 expression was knocked down by RNAi. Diminished NOX1 expression also contributed to decreased growth, blood vessel density, and VEGF and hypoxia-inducible factor 1α (HIF-1α) expression in HT-29 xenografts initiated from NOX1 knockdown cells. Microarray analysis, supplemented by real-time PCR and Western blotting, revealed that the expression of critical regulators of cell proliferation and angiogenesis, including c-MYC, c-MYB, and VEGF, were down-regulated in association with a decline in hypoxic HIF-1α protein expression downstream of silenced NOX1 in both colon cancer cell lines and xenografts. These studies suggest a role for NOX1 in maintaining the proliferative phenotype of some colon cancers and the potential of NOX1 as a therapeutic target in this disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Characterization and processing of bipolar semiconductor electrodes in a dual electrolyte cell

    Energy Technology Data Exchange (ETDEWEB)

    Cattarin, S.; Musiani, M.M. [Istituto di Polarografia ed Elettrochimica Preparativa del C.N.R., Padova (Italy)

    1995-11-01

    Photoelectrochemical (PEC) processes may be induced at both faces of a bipolar semiconductor electrode without application of metal contacts by using the dual electrolyte arrangement -- metal/electrolyte 1/semiconductor/electrolyte 2/metal -- and by applying a voltage to the end metal electrodes. The possibilities of semiconductor characterization (determination of action spectra and doping level) and processing (photoetching and metal electrodeposition) are discussed on the basis of model experiments, performed with n-InP wafers. The advantages of this approach over traditional PEC and electroless techniques are discussed with particular emphasis on etching.

  14. 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

  15. Regulation of ERK-mediated signal transduction by p38 MAP kinase in human monocytic THP-1 cells.

    Science.gov (United States)

    Numazawa, Satoshi; Watabe, Masahiko; Nishimura, Satoshi; Kurosawa, Masahiro; Izuno, Makoto; Yoshida, Takemi

    2003-05-01

    SB 203580 has been widely used to specifically shut down the p38 MAP kinase-dependent pathway, although it is capable of inducing c-Raf kinase activity in cells. The present study demonstrates that SB 203580 activates members of the ERK cascade, c-Raf, MEK, and ERK, in human monocytic THP-1 cells. The activation of these kinases was sustained for at least 24 h after SB 203580 treatment and was also observed in U937 cells, suggesting that c-Raf efficiently transduces the signal even in the presence of the inhibitor in these cells. However, the expression of ERK cascade-dependent genes, such as c-fos and IL-1beta, was extremely limited. Analysis of the cellular distribution of ERK in SB 203580-treated cells indicated that nuclear translocation of phosphorylated ERK was impaired. Also, nuclear translocation of ERK induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was inhibited by SB 239063, which does not associate with c-Raf and is highly selective for p38 MAP kinase. In addition, the forced expression of the dominant negative mutant of p38 MAP kinase suppressed serum responsive element-dependent transactivation induced by TPA. These results suggest that the steady-state level of p38 MAP kinase activity modulates ERK signaling.

  16. 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.

  17. Signal transduction in artichoke [Cynara cardunculus L. subsp. scolymus (L.) Hayek] callus and cell suspension cultures under nutritional stress.

    Science.gov (United States)

    Lattanzio, Vincenzo; Caretto, Sofia; Linsalata, Vito; Colella, Giovanni; Mita, Giovanni

    2018-03-16

    Stimulated production of secondary phenolic metabolites and proline was studied by using cell cultures of artichoke [Cynara cardunculus L. subsp. scolymus (L.) Hayek] submitted to nutritional stress. Artichoke cell cultures accumulated phenolic secondary metabolites in a pattern similar to that seen in artichoke leaves and heads (capitula). This paper shows that both callus and cell suspension cultures under nutritional stress accumulated phenolic compounds and proline, at the same time their biomass production was negatively affected by nutrient deficiency. The results obtained strongly suggest that plant tissues respond to nutrient deprivation by a defensive costly mechanism, which determines the establishment of a mechanism of trade-off between growth and adaptive response. Furthermore, the results of this research suggest that perception of abiotic stress and increased phenolic metabolites are linked by a sequence of biochemical processes that also involves the intracellular free proline and the oxidative pentose phosphate pathway. The main conclusion of this paper is that, once calli and cell suspension cultures respond to nutrient deficiency, in acclimated cells the establishment of a negative correlation between primary metabolism (growth) and secondary metabolism (defence compounds) is observed. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  18. Isolation, Characterization, and Transduction of Endometrial Decidual Tissue Multipotent Mesenchymal Stromal/Stem Cells from Menstrual Blood

    Directory of Open Access Journals (Sweden)

    Filippo Rossignoli

    2013-01-01

    Full Text Available Mesenchymal stromal/stem cells (MSCs reveal progenitor cells-like features including proliferation and differentiation capacities. One of the most historically recognized sources of MSC has been the bone marrow, while other sources recently include adipose tissue, teeth, bone, muscle, placenta, liver, pancreas, umbilical cord, and cord blood. Frequently, progenitor isolation requires traumatic procedures that are poorly feasible and associated with patient discomfort. In the attempt to identify a more approachable MSC source, we focused on endometrial decidual tissue (EDT found within menstrual blood. Based also on recent literature findings, we hypothesized that EDT may contain heterogeneous populations including some having MSC-like features. Thus, we here sought to isolate EDT-MSC processing menstrual samples from multiple donors. Cytofluorimetric analyses revealed that resulting adherent cells were expressing mesenchymal surface markers, including CD56, CD73, CD90, CD105 and CD146, and pluripotency markers such as SSEA-4. Moreover, EDT-MSC showed a robust clonogenic potential and could be largely expanded in vitro as fibroblastoid elements. In addition, differentiation assays drove these cells towards osteogenic, adipogenic, and chondrogenic lineages. Finally, for the first time, we were able to gene modify these progenitors by a retroviral vector carrying the green fluorescent protein. From these data, we suggest that EDT-MSC could represent a new promising tool having potential within cell and gene therapy applications.

  19. GLP-1 secretion is stimulated by 1,10-phenanthroline via colocalized T2R5 signal transduction in human enteroendocrine L cell

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jiyoung; Kim, Ki-Suk; Kim, Kang-Hoon; Lee, In-Seung; Jeong, Hyeon-soo; Kim, Yumi; Jang, Hyeung-Jin, E-mail: hjjang@khu.ac.kr

    2015-12-04

    Glucagon-like peptide-1 (GLP-1) hormone is known to regulate blood glucose by an insulinotropic effect and increases proliferation as and also prevents apoptosis of pancreatic β cells. We know that GLP-1 is secreted by nutrients such as fatty acids and sweet compounds but also bitter compounds via stimulation of G-protein coupled receptors (GPCRs) in the gut. Among these, bitter compounds are multiply-contained in phytochemicals or artificial materials and perceived as ligands of various bitter taste receptors. We hypothesized that GLP-1 hormone is secreted through stimulation of a single bitter taste receptor by 1,10-phenanthroline which is known agonist of taste receptor type 2 member 5 (T2R5). To prove this hypothesis, we used the representatively well-known 1,10-phenanthroline as ligand of single receptor and evaluated the existence of T2R5 by double-labeling immunofluorescence and then 1,10-phenanthroline is able to secrete GLP-1 hormone through stimulation of T2R5 in human enteroendocrine cells. Consequently, we verify that GLP-1 hormone is colocalized with T2R5 in the human duodenum and ileum tissue and is secreted by 1,10-phenanthroline via T2R5 signal transduction in differentiated human enteroendocrine L cells. - Highlights: • Taste receptor type 2 member 5 (T2R5) is colocalized with GLP-1 hormone in human enteroendocrine cells. • GLP-1 secretion is stimulated by 1,10-phenanthroline via stimulation of T2R5. • Inhibition of the bitter taste pathway reduce GLP-1 secretion.

  20. The Regulation of Lactogenic Differentiation in Mammary Epithelial Cells by Ras-Dependent and -Independent Signal Transduction

    Science.gov (United States)

    2006-01-06

    Risk factor identification provides clues for elucidating physiological and molecular pathogenetic mechanisms. For example, physiological...Dumitrescu, 2005). Epidemiology provides only clues, however. A thorough appreciation for the physiological and molecular pathogenetic mechanisms...the viruses described above and incubated for a period of 24 h in media without EGF. The cells were then either stimulated with DIP for 24 h or

  1. Double transduction of a Cre/LoxP lentiviral vector: a simple method to generate kidney cell-specific knockdown mice.

    Science.gov (United States)

    Nam, Bo Young; Kim, Dong Ki; Park, Jung Tak; Kang, Hye-Young; Paeng, Jisun; Kim, Seonghun; Park, Jimin; Um, Jae Eun; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2015-12-15

    In a lentivirus-based gene delivery system, the incorporated gene is continuously expressed for a long time. In this study, we devised a simple way to knock down a specific gene in a kidney cell-specific pattern in adult mice by lentivirus-assisted transfer of short hairpin RNA (shRNA). Kidney collecting duct (CD)-specific aquaporin-3 (AQP3)-knockdown mice were generated by consecutive injection of Hoxb7-Cre-expressing lentivirus (LV-Hoxb7 Cre) and loxP-AQP3 shRNA-expressing lentivirus (LV-loxP shAQP3) in adult C57BL6/J mice. LV-Hoxb7 Cre was designed to express mCherry, while LV-loxP shAQP3 was designed with a floxed enhanced green fluorescent protein (EGFP)-tagged stop sequence, and thus EGFP would be expressed only in the absence of Cre recombination. In mice treated with LV-Hoxb7 Cre alone, mCherry protein expression, which indicates the presence of Cre recombinase, occurred only in CD cells. However, LV-loxP shAQP3 injection alone resulted in an increase in EGFP expression in all kidney cells, indicating the transcription of the floxed region. When LV-Hoxb7 Cre and LV-loxP shAQP3 were sequentially transduced, EGFP expression was attenuated while mCherry expression was sustained in CD cells, demonstrating a CD cell-specific recombination of the floxed region. AQP3 expression in mice injected with LV-Hoxb7 Cre or LV-loxP shAQP3 alone did not differ, but consecutive injection of LV-Hoxb7 Cre and LV-loxP shAQP3 significantly reduced AQP3 expression in CD cells. However, the expression levels of AQP3 were not altered in other cell types. Double transduction of Cre- and loxP-based lentivirus can easily generate kidney cell-specific knockdown mice, and this method might be applicable to other species. Copyright © 2015 the American Physiological Society.

  2. Membrane guanylate cyclase, a multimodal transduction machine: history, present, and future directions.

    Science.gov (United States)

    Sharma, Rameshwar K; Duda, Teresa

    2014-01-01

    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 sections. 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. Sections ROS-GC, a Ca(2+)-Modulated Two Component Transduction System to Migration Patterns and Translations of the GCAP Signals Into Production of Cyclic GMP are Different cover its biochemistry and physiology. The noteworthy events are that augmented by GCAPs, ROS-GC proves to be a transducer of the free Ca(2+) 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. Section ROS-GC1 Gene Linked Retinal Dystrophies demonstrates how this knowledge begins to be translated into the diagnosis and providing the molecular definition of retinal dystrophies. Section Controlled By Low and High Levels of [Ca(2+)]i, ROS-GC1 is a Bimodal Transduction Switch discusses a striking property of ROS-GC where it becomes a "[Ca(2+)]i bimodal switch" and transcends its signaling role in other neural processes. In this course, discovery of the first CD-GCAP (Ca(2+)-dependent guanylate cyclase activator), the S100B protein, is made. It extends the role of the ROS-GC transduction system beyond the phototransduction to the signaling processes in the synapse region between photoreceptor and cone ON-bipolar cells; in section Ca(2

  3. 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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Endogenous Protection Derived from Activin A/Smads Transduction Loop Stimulated via Ischemic Injury in PC12 Cells

    OpenAIRE

    Mang, Jing; Mei, Chun-Li; Wang, Jiao-Qi; Li, Zong-Shu; Chu, Ting-Ting; He, Jin-Ting; Xu, Zhong-Xin

    2013-01-01

    Activin A (ActA), a member of transforming growth factor-beta (TGF-b) super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD) injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate isch...

  5. Effective suppression of Dengue fever virus in mosquito cell cultures using retroviral transduction of hammerhead ribozymes targeting the viral genome

    Directory of Open Access Journals (Sweden)

    Mohammed Ahmed

    2009-06-01

    Full Text Available Abstract Outbreaks of Dengue impose a heavy economic burden on developing countries in terms of vector control and human morbidity. Effective vaccines against all four serotypes of Dengue are in development, but population replacement with transgenic vectors unable to transmit the virus might ultimately prove to be an effective approach to disease suppression, or even eradication. A key element of the refractory transgenic vector approach is the development of transgenes that effectively prohibit viral transmission. In this report we test the effectiveness of several hammerhead ribozymes for suppressing DENV in lentivirus-transduced mosquito cells in an attempt to mimic the transgenic use of these effector molecules in mosquitoes. A lentivirus vector that expresses these ribozymes as a fusion RNA molecule using an Ae. aegypti tRNAval promoter and terminating with a 60A tail insures optimal expression, localization, and activity of the hammerhead ribozyme against the DENV genome. Among the 14 hammerhead ribozymes we designed to attack the DENV-2 NGC genome, several appear to be relatively effective in reducing virus production from transduced cells by as much as 2 logs. Among the sequences targeted are 10 that are conserved among all DENV serotype 2 strains. Our results confirm that hammerhead ribozymes can be effective in suppressing DENV in a transgenic approach, and provide an alternative or supplementary approach to proposed siRNA strategies for DENV suppression in transgenic mosquitoes.

  6. Effect of surface treatment on the interfacial contact resistance and corrosion resistance of Fe–Ni–Cr alloy as a bipolar plate for polymer electrolyte membrane fuel cells

    International Nuclear Information System (INIS)

    Yang, Meijun; Zhang, Dongming

    2014-01-01

    The bipolar plate is an important component of the PEMFC (polymer electrolyte membrane fuel cell) because it supplies the pathway of electron flow between each unit cell. Fe–Ni–Cr alloy is considered as a good candidate material for bipolar plate, but it is limited to use as a bipolar plate due to its high ICR (interfacial contact resistance) and corrosion problem. In order to explore a cost-effective method on surface modification, various chemical and electrochemical treatments are performed on Fe–Ni–Cr alloy to acquire the effect of the surface modification on the ICR and corrosion behavior. The ICR and corrosion resistance of Fe–Ni–Cr alloy can be effectively controlled by the chemical treatment of immersion in the mixed acid solution with 10 vol% HNO 3 , 2 vol% HCl and 1 vol% HF for 10 min at 65 °C and then was placed in 30 vol% HNO 3 solution for 5 min. The chemical treatment is more effective on reducing ICR and improving corrosion resistance than that of electrochemical methods (be carried out in the 2 mol/L H 2 SO 4 solution with the electrical potential from −0.4 V to 0.6 V) for Fe–Ni–Cr alloy as a bipolar plate for polymer electrolyte membrane fuel cells. - Highlights: • The procedure of the surface treatments on Fe–Ni–Cr alloy as bipolar plate was described in detail. • Effects of various surface treatments on the interfacial contact resistivity and corrosion behavior were discussed. • The mechanism of the surface modification was particularly analyzed

  7. Bipolar Disorder (For Teens)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Bipolar Disorder KidsHealth / For Teens / Bipolar Disorder What's in this ... Disorder Print en español Trastorno bipolar What Is Bipolar Disorder? Bipolar disorders are one of several medical conditions ...

  8. 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...... approach offers a systematic explanation of how such bipolar structures appear and can be identified....

  9. [Inhibitory effect of taurine in hypoxia-induced rat pulmonary artery smooth muscle cell proliferation and signal transduction mechanism].

    Science.gov (United States)

    Zhang, Xiao-Dan; Sun, Peng; Zhu, Da-Ling; Xie, Nan

    2014-05-01

    To discuss the effect of taurine (Tau) on the proliferation of hypoxia-induced pulmonary artery smooth muscle cells (PASMCs), and study whether the extracellular signal-regulated kinase 1/2 (ERK1/2) signal pathway participated in the Tau-inhibited PASMC proliferation process and the possible molecular mechanism. The primary culture was performed for PASMCs in rats. The second to fifth generations were adopted for the experiment. The Tau concentration was 80 mmol x L(-1). The concentration of ERK1/2 blocker (PD98059) was 50 micromol x L(-1). The drug administration time was 24 h. The effect of Tau on the PASMC proliferation was detected by MTT assay, immunofluorescence staining method and western blot under different conditions. The PASMCs were growing were divided into four groups: the normoxia group, the normoxia + Tau group, the hypoxia group and the hypoxia + Tau group. The Western blot was adopted to detect whether the ERK1/2 signal pathway participated in the Tau-inhibited PASMC proliferation process. Subsequently, the PASMCs were divided into five groups: the normoxia group, the hypoxia group, the hypoxia + Tau group, the hypoxia + Tau + PD98059 group and the hypoxia + PD98059 group. Hypoxia could induce the PASMC proliferation. Under the conditions of normoxia, Tau had no effect on the PASMC proliferation. Under the conditions of normoxia and hypoxia, Tau had no effect on the expression of the tumor necrosis factor-alpha (TNF-alpha) among PASMCs. Tau could reverse the expression up-regulation of hypoxia-induced proliferative cell nuclear antigen (PCNA) (P effect on the expression of phosphoryl extracellular signal-regulated kinase 1/2 (p-ERK1/2). Hypoxia could up-regulate the p-ERK1/2 expression (P < 0.01). Tau could reverse the up-regulation of the hypoxia-induced p-ERK1/2 expression(P < 0.01). Both PD98059 and Tau could inhibit the up-regulated expressions of PCNA, Cyclin A and p-ERK1/2. According to the comparison between the single addition of Tau and PD

  10. Signal transductions induced by bone morphogenetic protein-2 and transforming growth factor-beta in normal human osteoblastic cells.

    Science.gov (United States)

    Lai, Chung-Fang; Cheng, Su-Li

    2002-05-03

    Transforming growth factor beta (TGF-beta) activates Ras/MAPK signaling in many cell types. Because TGF-beta and BMP-2 exert similar effects, we examined if this signaling is stimulated by both factors and analyzed the relationship between this signaling and the Smads in osteoblasts. BMP-2 and TGF-beta stimulated Ras, MAPK, and AP-1 activities. The DNA binding activities of c-Fos, FosB/Delta FosB, Fra-1, Fra-2, and JunB were up-regulated whereas JunD activity was decreased. c-Fos, FosB/Delta FosB, and JunB were associated with Smad4. The stimulation of AP-1 by BMP-2 and TGF-beta was dependent on Smad signaling, and anti-Smad4 antibody interfered with AP-1 activity. Thus, BMP-2 and TGF-beta activate both Ras/MAPK/AP-1 and Smad signaling in osteoblasts with Smads modulating AP-1 activity. To determine the roles of MAPK in BMP-2 and TGF-beta function, we analyzed the effect of ERK and p38 inhibitors on the regulation of bone matrix protein expression and JunB and JunD levels by these two factors. ERK and p38 mediated TGF-beta suppression of osteocalcin and JunD as well as stimulation of JunB. p38 was essential in BMP-2 up-regulation of type I collagen, fibronectin, osteopontin, osteocalcin, and alkaline phosphatase activity whereas ERK mediated BMP-2 stimulation of fibronectin and osteopontin. Thus, ERK and p38 differentially mediate TGF-beta and BMP-2 function in osteoblasts.

  11. 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.

  12. The combined transduction of copper, zinc-superoxide dismutase and catalase mediated by cell-penetrating peptide, PEP-1, to protect myocardium from ischemia-reperfusion injury.

    Science.gov (United States)

    Huang, Guang-Qing; Wang, Jia-Ning; Tang, Jun-Ming; Zhang, Lei; Zheng, Fei; Yang, Jian-Ye; Guo, Ling-Yun; Kong, Xia; Huang, Yong-Zhang; Liu, Yong; Chen, Shi-You

    2011-05-21

    Our previous studies indicate that either PEP-1-superoxide dismutase 1 (SOD1) or PEP-1-catalase (CAT) fusion proteins protects myocardium from ischemia-reperfusion-induced injury in rats. The aim of this study is to explore whether combined use of PEP-1-SOD1 and PEP-1-CAT enhances their protective effects. SOD1, PEP-1-SOD1, CAT or PEP-1-CAT fusion proteins were prepared and purified by genetic engineering. In vitro and in vivo effects of these proteins on cell apoptosis and the protection of myocardium after ischemia-reperfusion injury were measured. Embryo cardiac myocyte H9c2 cells were used for the in vitro studies. In vitro cellular injury was determined by the expression of lactate dehydrogenase (LDH). Cell apoptosis was quantitatively assessed with Annexin V and PI double staining by Flow cytometry. In vivo, rat left anterior descending coronary artery (LAD) was ligated for one hour followed by two hours of reperfusion. Hemodynamics was then measured. Myocardial infarct size was evaluated by TTC staining. Serum levels of myocardial markers, creatine kinase-MB (CK-MB) and cTnT were quantified by ELISA. Bcl-2 and Bax expression in left ventricle myocardium were analyzed by western blot. In vitro, PEP-1-SOD1 or PEP-1-CAT inhibited LDH release and apoptosis rate of H9c2 cells. Combined transduction of PEP-1-SOD1 and PEP-1-CAT, however, further reduced the LDH level and apoptosis rate. In vivo, combined usage of PEP-1-SOD1 and PEP-1-CAT produced a greater effect than individual proteins on the reduction of CK-MB, cTnT, apoptosis rate, lipoxidation end product malondialdehyde, and the infarct size of myocardium. Functionally, the combination of these two proteins further increased left ventricle systolic pressure, but decreased left ventricle end-diastolic pressure. This study provided a basis for the treatment or prevention of myocardial ischemia-reperfusion injury with the combined usage of PEP-1-SOD1 and PEP-1-CAT fusion proteins.

  13. What is Bipolar Disorder?

    Science.gov (United States)

    ... affect friends and family? For More Information Share Bipolar Disorder Download PDF Download ePub Order a free hardcopy ... brochure will give you more information. What is bipolar disorder? Bipolar disorder is a serious brain illness. It ...

  14. 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.

  15. Naringenin induces mitochondria-mediated apoptosis and endoplasmic reticulum stress by regulating MAPK and AKT signal transduction pathways in endometriosis cells.

    Science.gov (United States)

    Park, Sunwoo; Lim, Whasun; Bazer, Fuller W; Song, Gwonhwa

    2017-12-01

    Does the flavonoid naringenin inhibit proliferation of human endometriosis cells? Naringenin suppresses proliferation and increases apoptosis via depolarization of mitochondrial membrane potential and generation of reactive oxygen species (ROS) in human endometriosis cells. For management of endometriosis, hormonal therapy is commonly used to decrease production of estrogens by the ovaries, but that has limitations including undesirable side effects with long-term therapies. To overcome these limitations, it is important to discover novel compounds which have no adverse effects, but inhibit expression of target molecules involved in the pathogenesis of endometriosis. Well-established endometriosis cell lines (VK2/E6E7 and End1/E6E7) were purchased from the American Type Culture Collection. Effects of naringenin on VK2/E6E7 and End1/E6E7 cells were assessed in diverse assays in a dose- and time-dependent manner. Effects of naringenin on viability, apoptosis (Annexin V expression, propidium iodide staining, TUNEL and invasion assays), mitochondria-mediated apoptosis, production of ROS and endoplasmic reticulum (ER) stress proteins of VK2/E6E7 and End1/E6E7 cells were determined. Signal transduction pathways in VK2/E6E7 and End1/E6E7 cells in response to naringenin were determined by western blot analyses. In the present study, we demonstrated that naringenin suppressed proliferation and increased apoptosis through depolarization of mitochondrial membrane potential and inducing pro-apoptotic proteins, Bax and Bak, in both endometriosis cell lines. In addition, naringenin increased ROS, ER stress, through activation of eIF2α and IRE1α, GADD153 and GRP78 proteins in a dose-dependent manner. Furthermore, the induction of apoptosis by naringenin involved activation of MAPK and inactivation of PI3K pathways in VK2/E6E7 and End1/E6E7 cells. Lack of in vivo animal studies is a major limitation of this research. Effectiveness of naringenin to induce apoptosis of human

  16. Effect of Chaiqin Chengqi Decoction on cholecystokinin receptor 1-mediated signal transduction of pancreatic acinar cells in acute necrotizing pancreatitis rats.

    Science.gov (United States)

    Guo, Jia; Jin, Tao; Lin, Zi-Qi; Wang, Xiao-Xiang; Yang, Xiao-Nan; Xia, Qing; Xue, Ping

    2015-01-01

    To investigate the effect of Chaiqin Chengqi Decoction (,CQCQD) on cholecystokinin receptor 1 (CCKR1)-mediated signal transduction of pancreatic acinar cell in rats with acute necrotic pancreatitis (ANP). Twenty-seven Sprague-Dawley rats were randomized into three groups: the control group, the ANP group, and the CQCQD group (9 in each group). ANP rats were induced by two intraperitoneal injections of 8% L-arginine (pH=7.0, 4.4 g/kg) over a 2-h period. Rats were treated with 1.5 mL/100 g body weight of CQCQD (CQCQD group) or physiological saline (control and ANP groups) at 2 h interval. And 6 h after induction, pancreatic tissues were collected for histopathological examination. Pancreatic acinar cells were isolated for determination of CCKR1 mRNA and protein expression, phospholipase C (PLC) and inositol-1,4,5-triphosphate (IP3), and determination of fluorescence intensity (FI) as a measure of intracellular calcium ion concentration [Ca(2+)]i. The pancreatic histopathological score (6.2 ± 1.1) and the levels of PLC (1,187.2 ± 228.2 μg/mL) and IP3 (872.2 ± 88.4 μg/mL) of acinar cells in the ANP group were higher than those in the control (2.8 ± 0.4, 682.5 ± 121.8 μg/mL, 518.4 ± 115.8 μg/mL) and the CQCQD (3.8 ± 0.8, 905.3 ± 78.5 μg/mL, 611.0 ± 42.5 μg/mL) groups (Ppancreatic acinar cell CCKR1 mRNA in the ANP group was up-regulated (expression ratio=1.761; P=0.024) compared with the control group. The expression of pancreatic acinar cell CCKR1 mRNA in the CQCQD group was down-regulated (expression ratio=0.311; P=0.035) compared with the ANP group. The ratio of gray values of the CCKR1 and β-actin in the ANP group (1.43 ± 0.17) was higher than those in the control (0.70 ± 0.15) and CQCQD (0.79 ± 0.11) groups (PPancreatic acinar cell calcium overload of ANP induced by L-arginine was related to the up-regulated expressions of pancreatic acinar cell CCKR1 mRNA and protein. CQCQD can down-regulate expressions of pancreatic acinar cell CCKR1 mRNA and

  17. Thermal and electrochemical durability of carbonaceous composites used as a bipolar plate of proton exchange membrane fuel cell

    Science.gov (United States)

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

    Thermal and electrochemical durability of carbonaceous composite plates, which are made from graphite powders and a resin for use as bipolar plates of PEMFC (proton exchange membrane fuel cell), were investigated. The thermal durability was investigated by TG (thermal gravimetry) coupled with DTA (differential thermal analysis) technique under air up to 600 °C. A weight loss was significant over 300 °C, but the hydrophobicity was decreased after heated at 80 °C for 192 h. The electrochemical durability was investigated in 10 μmol dm -3 of hydrochloric acid solution under nitrogen or oxygen atmosphere by means of potential holding test from 0.8 to 1.5 V against RHE (reversible hydrogen electrode) at 80 °C. During the potential holding tests, CO 2 production due to the corrosion was quantified by a GC (gas-chromatography) and the production was detectable above 1.3 V irrespective with atmosphere; on the other hand, it was clarified from the contact angle measurements that the hydrophobicity was changed below 1.3 V. The results of this study showed that the carbonaceous composite plates were electrochemically degraded under PEMFC condition and were seriously degraded in URFC (unitized regenerative fuel cell) condition.

  18. Piracy of decay-accelerating factor (CD55) signal transduction by the diffusely adhering strain Escherichia coli C1845 promotes cytoskeletal F-actin rearrangements in cultured human intestinal INT407 cells.

    Science.gov (United States)

    Peiffer, I; Servin, A L; Bernet-Camard, M F

    1998-09-01

    Diffusely adhering Escherichia coli (DAEC) C1845 (clinical isolate) harboring the fimbrial adhesin F1845 can infect cultured human differentiated intestinal epithelial cells; this process is followed by the disassembly of the actin network in the apical domain. The aim of this study was to examine the mechanism by which DAEC C1845 promotes F-actin rearrangements. For this purpose, we used a human embryonic intestinal cell line (INT407) expressing the membrane-associated glycosylphosphatidylinositol (GPI) protein-anchored decay-accelerating factor (DAF), the receptor of the F1845 adhesin. We show here that infection of INT407 cells by DAEC C1845 can provoke dramatic F-actin rearrangements without cell entry. Clustering of phosphotyrosines was observed, revealing that the DAEC C1845-DAF interaction involves the recruitment of signal transduction molecules. A pharmacological approach with a subset of inhibitors of signal transduction molecules was used to identify the cascade of signal transduction molecules that are coupled to the DAF, that are activated upon infection, and that promote the F-actin rearrangements. DAEC C1845-induced F-actin rearrangements can be blocked dose dependently by protein tyrosine kinase, phospholipase Cgamma, phosphatidylinositol 3-kinase, protein kinase C, and Ca2+ inhibitors. F-actin rearrangements and blocking by inhibitors were observed after infection of the cells with two E. coli recombinants carrying the plasmids containing the fimbrial adhesin F1845 or the fimbrial hemagglutinin Dr, belonging to the same family of adhesins. These findings show that the DAEC Dr family of pathogens promotes alterations in the intestinal cell cytoskeleton by piracy of the DAF-GPI signal cascade without bacterial cell entry.

  19. Molecular electroporation and the transduction of oligoarginines

    Science.gov (United States)

    Cahill, Kevin

    2010-03-01

    Certain short polycations, such as TAT and polyarginine, rapidly pass through the plasma membranes of mammalian cells by an unknown mechanism called transduction as well as by endocytosis and macropinocytosis. These cell-penetrating peptides (CPPs) promise to be medically useful when fused to biologically active peptides. I offer a simple model in which one or more CPPs and the phosphatidylserines of the inner leaflet form a kind of capacitor with a voltage in excess of about 200 mV, high enough to create a molecular electropore. The model is consistent with an empirical upper limit on the cargo peptide of 40-60 amino acids and with experimental data on how the transduction of a polyarginine-fluorophore into mouse C2C12 myoblasts depends on the number of arginines in the CPP and on the CPP concentration. The model makes three testable predictions.

  20. Fabrication of gas impervious edge seal for a bipolar gas distribution assembly for use in a fuel cell

    Science.gov (United States)

    Kaufman, Arthur; Werth, John

    1986-01-01

    A bipolar gas reactant distribution assembly for use in a fuel cell is disclosed, the assembly having a solid edge seal to prevent leakage of gaseous reactants wherein a pair of porous plates are provided with peripheral slits generally parallel to, and spaced apart from two edges of the plate, the slit being filled with a solid, fusible, gas impervious edge sealing compound. The plates are assembled with opposite faces adjacent one another with a layer of a fusible sealant material therebetween the slits in the individual plates being approximately perpendicular to one another. The plates are bonded to each other by the simultaneous application of heat and pressure to cause a redistribution of the sealant into the pores of the adjacent plate surfaces and to cause the edge sealing compound to flow and impregnate the region of the plates adjacent the slits and comingle with the sealant layer material to form a continuous layer of sealant along the edges of the assembled plates.

  1. Renal cell carcinoma metastasis involving vertebral hemangioma: dual percutaneous treatment by navigational bipolar radiofrequency ablation and high viscosity cement vertebroplasty.

    Science.gov (United States)

    Zerlauth, Jean-Baptiste; Meuli, Reto; Dunet, Vincent

    2017-09-01

    The case of a 70-year-old woman with progressive renal cell carcinoma (RCC) metastatic invasion of a L3 vertebral hemangioma treated by dual percutaneous radiofrequency ablation (RFA) and vertebroplasty is reported. The patient was surgically treated for RCC in 2001. Chemotherapy and immunotherapy were introduced in 2013 for ovarian, bladder and cerebral metastatic disease. An asymptomatic L3 benign hemangioma was noticed at this time. One-year CT and MRI follow-up studies demonstrated a nodular isolated soft tissue lesion involving the anterior edge of the hemangioma. Percutaneous treatment consisted of a L3 vertebral body unipedicular approach to perform a biopsy, RFA with a navigational bipolar RFA device and vertebroplasty using high viscosity cement. Histopathological examination confirmed metastasis of RCC. The 5-month spinal MRI and CT examinations demonstrated complete disappearance of the tumor. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  2. Bipolar disorder: an overview

    African Journals Online (AJOL)

    which is the reason that up to 69% of patients with BD are misdiagnosed.1 Bipolar ... Cyclothymic disorder. • Substance/medication induced bipolar and related disorder. • Bipolar and related disorder due to another medical condition ... patients. Keywords: bipolar disorder, mania, depression, pharmacological management.

  3. C-reactive protein and white blood cell levels in schizophrenia, bipolar disorders and depression - associations with mortality and psychiatric outcomes

    DEFF Research Database (Denmark)

    Horsdal, H T; Köhler-Forsberg, O; Benros, Michael E

    2017-01-01

    BACKGROUND: Mental disorders have been associated with increased levels of inflammatory markers, which can affect disease trajectories. We aimed to assess levels of C-reactive protein (CRP) and white blood cells (WBC) across individuals with schizophrenia, bipolar disorder, and depression......, and to investigate associations with subsequent psychiatric admission and mortality. METHODS: We identified all adults in the Central Denmark Region during 2000-2012 with a first diagnosis of schizophrenia, bipolar disorder, or depression and a baseline measurement of CRP and/or WBC count. We followed.......5mg/L) (particularly during manic states, 3.9mg/L), followed by schizophrenia (3.1mg/L), and depression (2.8mg/L), while baseline WBC count did not differ (median 7.1×10(9)/L). Elevated CRP levels were associated with increased all-cause mortality by adjusted HRs of 1.56 (95% CI: 1.02-2.38) for levels...

  4. 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.

  5. Loss of tumorigenicity of murine colon carcinoma MC38/0 cell line after transduction with a retroviral vector carrying murine IL-12 genes

    Czech Academy of Sciences Publication Activity Database

    Pajtasz-Piasecka, E.; Szyda, A.; Rossowska, J.; Krawczenko, A.; Indrová, Marie; Grabarczyk, P.; Wysocki, P.; Mackiewicz, A.; DuĽ, D.

    2004-01-01

    Roč. 50, č. 1 (2004), s. 7-14 ISSN 0015-5500 Grant - others:State Committee for Scientific Research of the Republic of Poland (KBN)(PL) PBZ-KBN 004/PO4/98/5f Institutional research plan: CEZ:AV0Z5052915 Keywords : MC38 murine colon carcinoma * IL-12 transduction * tumorigenicity Subject RIV: EC - Immunology Impact factor: 0.507, year: 2004

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

    Science.gov (United States)

    Martí, A; Luque, A

    2015-04-22

    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 that are required to match the limiting efficiency of dual-junction solar cells without using tunnel junctions. The device naturally emerges as a three-terminal solar cell and can also be used as building block of multijunction solar cells with an increased number of junctions.

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

    Science.gov (United States)

    Martí, A.; Luque, A.

    2015-04-01

    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 that are required to match the limiting efficiency of dual-junction solar cells without using tunnel junctions. The device naturally emerges as a three-terminal solar cell and can also be used as building block of multijunction solar cells with an increased number of junctions.

  8. Bipolar Items

    Directory of Open Access Journals (Sweden)

    Nishiguchi Sumiyo

    2016-12-01

    Full Text Available This article asserts that the Japanese wide-scope mo ‘even’ in simple sentences are bipolar items (BPIs antilicensed or forbidden by negation and licensed in a non-monotonic (NM environment. BPIs share the features of negative polarity items (NPIs as well as positive polarity items (PPIs. The Dutch ooit ‘ever’, the Serbo-Croatian i-series ‘and/even’, and the Hungarian is-series ‘and/even’ are antilicensed by clausemate negation and licensed by extraclausal negation (van der Wouden, 1997; Progovac, 1994; Szabolcsi, 2002 or non-monotonic negative (and positive, for Serbo-Croatian emotive predicates. Adding an NPI rescues BPIs in uncomfortable clausemate negation.

  9. 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.

  10. The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells

    International Nuclear Information System (INIS)

    Cherukuri, Durga Prasad; Chen, Xiao B.O.; Goulet, Anne-Christine; Young, Robert N.; Han, Yongxin; Heimark, Ronald L.; Regan, John W.; Meuillet, Emmanuelle; Nelson, Mark A.

    2007-01-01

    Accumulating evidence indicates that elevated levels of prostaglandin E 2 (PGE 2 ) can increase intestinal epithelial cell proliferation, and thus play a role in colorectal tumorigenesis. PGE 2 exerts its effects through four G-protein-coupled PGE receptor (EP) subtypes, named the EP1, EP2, EP3, and EP4. Increased phosphorylation of extracellular regulated kinases (ERK1/2) is required for PGE 2 to stimulate cell proliferation of human colon cancer cells. However, the EP receptor(s) that are involved in this process remain unknown. We provide evidence that L-161,982, a selective EP4 receptor antagonist, completely blocks PGE 2 -induced ERK phosphorylation and cell proliferation of HCA-7 cells. In order to identify downstream target genes of ERK1/2 signaling, we found that PGE 2 induces expression of early growth response gene-1 (EGR-1) downstream of ERK1/2 and regulates its expression at the level of transcription. PGE 2 treatment induces phosphorylation of cyclic AMP response element binding protein (CREB) at Ser133 residue and CRE-mediated luciferase activity in HCA-7 cells. Studies with dominant-negative CREB mutant (ACREB) provide clear evidence for the involvement of CREB in PGE 2 driven egr-1 transcription in HCA-7 cells. In conclusion, this study reveals that egr-1 is a target gene of PGE 2 in HCA-7 cells and is regulated via the newly identified EP4/ERK/CREB pathway. Finally our results support the notion that antagonizing EP4 receptors may provide a novel therapeutic approach to the treatment of colon cancer

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    . However, in organic devices the nature of the dominant spin-dependent processes is still subject to considerable debate. Using multi-frequency pulsed electrically detected magnetic resonance (pEDMR), we show that the spin-dependent response of P3HT/PCBM solar cells at low temperatures is governed...... 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...

  12. 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...

  13. Surface composition effect of nitriding Ni-free stainless steel as bipolar plate of polymer electrolyte fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Yang; Shironita, Sayoko [Nagaoka University of Technology, 1603-1, Kamitomioka, Nagaoka, Niigata 940-2188 (Japan); Nakatsuyama, Kunio [Nakatsuyama Heat Treatment Co., Ltd., 1-1089-10, Nanyou, Nagaoka, Niigata 940-1164 (Japan); Souma, Kenichi [Nagaoka University of Technology, 1603-1, Kamitomioka, Nagaoka, Niigata 940-2188 (Japan); Hitachi Industrial Equipment Systems Co., Ltd., 3 Kanda Neribei, Chiyoda, Tokyo 101-0022 (Japan); Umeda, Minoru, E-mail: mumeda@vos.nagaokaut.ac.jp [Nagaoka University of Technology, 1603-1, Kamitomioka, Nagaoka, Niigata 940-2188 (Japan)

    2016-12-01

    Graphical abstract: The anodic current densities in the passive region of nitrided SUS445-N stainless steel are lower than those of a non heat-treated SUS445 stainless steel and heat-treated SUS445-Ar stainless steel under an Ar atmosphere. It shows a better corrosion resistance for the SUS445 stainless steel after the nitriding heat treatment. - Highlights: • The nitriding heat treatment was carried out using Ni-free SUS445 stainless steel. • The corrosion resistance of the nitrided SUS445-N stainless steel was improved. • The structure of the nitrided SUS445-N stainless steel changed from α-Fe to γ-Fe. • The surface elemental components present in the steels affect the corrosion resistance. - Abstract: In order to increase the corrosion resistance of low cost Ni-free SUS445 stainless steel as the bipolar plate of a polymer electrolyte fuel cell, a nitriding surface treatment experiment was carried out in a nitrogen atmosphere under vacuum conditions, while an Ar atmosphere was used for comparison. The electrochemical performance, microstructure, surface chemical composition and morphology of the sample before and after the electrochemical measurements were investigated using linear sweep voltammetry (LSV), X-ray diffraction (XRD), glow discharge optical emission spectroscopy (GDS) and laser scanning microscopy (LSM) measurements. The results confirmed that the nitriding heat treatment not only increased the corrosion resistance, but also improved the surface conductivity of the Ni-free SUS445 stainless steel. In contrast, the corrosion resistance of the SUS445 stainless steel decreased after heat treatment in an Ar atmosphere. These results could be explained by the different surface compositions between these samples.

  14. 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

  15. Arsenic interferes with the signaling transduction pathway of T cell receptor activation by increasing basal and induced phosphorylation of Lck and Fyn in spleen cells

    International Nuclear Information System (INIS)

    Soto-Pena, Gerson A.; Vega, Libia

    2008-01-01

    Arsenic is known to produce inhibition as well as induction of immune cells proliferative responses depending on the doses as one of its mechanisms of immunotoxicity. Here we evaluate the effect of arsenic exposure on the activation of splenic mononuclear cells (SMC) in male CD57BL6N mice. Intra-gastric exposure to arsenic (as sodium arsenite) for 30 days (1, 0.1, or 0.01 mg/kg/day), reduced the proportion of CD4+ cells and the CD4+/CD8+ ratio in the spleen, increasing the proportion of CD11b+ cells. Arsenic exposure did not modify the proportion of B cells. SMC showed an increased level of phosphorylation of lck and fyn kinases (first kinases associated to TCR complex when activated). Although normal levels of apoptosis were observed on freshly isolated SMC, an increase in apoptotic cells related with the increase in phosphorylation of lck and fyn was observed when SMC were activated with Concanavalin-A (Con-A). Arsenic exposure reduced the proliferative response of SMC to Con-A, and also reduced secretion of IL-2, IL-6, IL-12 and IFNγ. No effect was observed on IL-4, and IL-10 secretion. The same effects were observed when SMC of exposed animals were activated with anti-CD3/CD28 antibodies for 24 h, but these effects were transitory since a recovery, up to control levels or even higher, were observed after 72 h of stimulation. This study demonstrates that repeated and prolonged exposure to arsenic alters cell populations and produces functional changes depending on the specific activation pathway, and could be related with the phosphorylation status of lck and fyn kinases

  16. 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...

  17. Analysis of diverse signal transduction pathways using the genetic model system Caenorhabditis elegans

    NARCIS (Netherlands)

    Moorman, Celine

    2003-01-01

    Signal transduction allows cells to respond to signals from their environment and is therefore important for most biological processes. The binding of an extracellular signalling molecule to a cell-surface receptor is the first step in most signal transduction pathways. Cell-surface receptors

  18. High rate lithium/thionyl chloride bipolar battery development

    Science.gov (United States)

    Russell, P. G.; Goebel, F.

    The lithium/thionyl chloride ( {Li}/{SOCl2}) electrochemistry is capable of providing high power and high specific power, especially under pulse discharge conditions, when cells containing thin components are arranged in a bipolar configuration. This paper describes recent work concerned with bipolar cell design, cathode evaluation, component manufacturing methods, and the assembly and testing of bipolar modules containing up to 150 cells for Sonobuoy application.

  19. High rate lithium-thionyl chloride bipolar battery development

    Energy Technology Data Exchange (ETDEWEB)

    Russell, P.G.; Goebel, F. [Yardney Technical Products, Inc., Pawcatuck, CT (United States)

    1994-12-31

    The lithium/thionyl chloride system is capable of providing both high power and high energy density when cells containing thin components are arranged in a bipolar configuration. Electrode current densities in excess of 300mA/cm{sup 2} are achieved during pulse discharge. The present work is concerned with bipolar cell design, cathode evaluation, component manufacturing methods, and the assembly and testing of bipolar modules containing up to 150 cells.

  20. High rate lithium/thionyl chloride bipolar battery development

    Energy Technology Data Exchange (ETDEWEB)

    Russell, P.G. [Yardney Technical Products, Inc., Pawcatuck, CT (United States); Goebel, F. [Yardney Technical Products, Inc., Pawcatuck, CT (United States)

    1995-04-01

    The lithium/thionyl chloride (Li/SOCl{sub 2}) electrochemistry is capable of providing high power and high specific power, especially under pulse discharge conditions, when cells containing thin components are arranged in a bipolar configuration. This paper describes recent work concerned with bipolar cell design, cathode evaluation, component manufacturing methods, and the assembly and testing of bipolar modules containing up to 150 cells for Sonobuoy application. (orig.)

  1. 2017 Bipolar Plate Workshop Summary Report

    Energy Technology Data Exchange (ETDEWEB)

    Kopasz, John P. [Argonne National Lab. (ANL), Argonne, IL (United States); Benjamin, Thomas G. [Argonne National Lab. (ANL), Argonne, IL (United States); Schenck, Deanna [Argonne National Lab. (ANL), Argonne, IL (United States)

    2017-08-17

    The Bipolar Plate (BP) Workshop was held at USCAR1 in Southfield, Michigan on February 14, 2017 and included 63 participants from industry, government agencies, universities, and national laboratories with expertise in the relevant fields. The objective of the workshop was to identify research and development (R&D) needs, in particular early-stage R&D, for bipolar plates for polymer electrolyte membrane (PEM) fuel cells for transportation applications. The focus of the workshop was on materials, manufacturing, and design aspects of bipolar plates with the goal of meeting DOE’s 2020 bipolar plate targets. Of special interest was the cost target of ≤$3/kW for the bipolar plate.

  2. Unidirectional threshold switching in Ag/Si-based electrochemical metallization cells for high-density bipolar RRAM applications

    Science.gov (United States)

    Wang, Chao; Song, Bing; Li, Qingjiang; Zeng, Zhongming

    2018-03-01

    We herein present a novel unidirectional threshold selector for cross-point bipolar RRAM array. The proposed Ag/amorphous Si based threshold selector showed excellent threshold characteristics in positive field, such as high selectivity ( 105), steep slope (experiments showed that the undesired sneak was significantly suppressed, indicating its potentiality for high-density integrated nonvolatile memory applications.

  3. Adenovirus transduction: More complicated than receptor expression.

    Science.gov (United States)

    Sharma, Priyanka; Martis, Prithy C; Excoffon, Katherine J D A

    2017-02-01

    The abundance and accessibility of a primary virus receptor are critical factors that impact the susceptibility of a host cell to virus infection. The Coxsackievirus and adenovirus receptor (CAR) has two transmembrane isoforms that occur due to alternative splicing and differ in localization and function in polarized epithelia. To determine the relevance of isoform-specific expression across cell types, the abundance and localization of both isoforms were determined in ten common cell lines, and correlated with susceptibility to adenovirus transduction relative to polarized primary human airway epithelia. Data show that the gene and protein expression for each isoform of CAR varies significantly between cell lines and polarization, as indicated by high transepithelial resistance, is inversely related to adenovirus transduction. In summary, the variability of polarity and isoform-specific expression among model cells are critical parameters that must be considered when evaluating the clinical relevance of potential adenovirus-mediated gene therapy and anti-adenovirus strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Types of Bipolar Disorder

    Science.gov (United States)

    ... many people have bipolar disorder along with another illness such as anxiety disorder, substance abuse, or an eating disorder. People with ... are sometimes misdiagnosed with schizophrenia. Anxiety and ADHD: ... such as bipolar disorder. Risk Factors Scientists are ...

  5. 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.

  6. Cytokines in bipolar disorder

    DEFF Research Database (Denmark)

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

    2012-01-01

    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......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...

  7. Nyctalopin expression in retinal bipolar cells restores visual function in a mouse model of complete X-linked congenital stationary night blindness.

    Science.gov (United States)

    Gregg, Ronald G; Kamermans, Maarten; Klooster, Jan; Lukasiewicz, Peter D; Peachey, Neal S; Vessey, Kirstan A; McCall, Maureen A

    2007-11-01

    Mutations in the NYX gene that encodes the protein nyctalopin cause congenital stationary night blindness type 1. In no b-wave (nob) mice, a mutation in Nyx results in a functional phenotype that includes the absence of the electroretinogram b-wave and abnormal spontaneous and light-evoked activity in retinal ganglion cells (RGCs). In contrast, there is no morphological abnormality in the retina at either the light or electron microscopic levels. These functional deficits suggest that nyctalopin is required for normal synaptic transmission between retinal photoreceptors and depolarizing bipolar cells (DBCs). However, the synaptic etiology and, specifically, the exact location and function of nyctalopin, remain uncertain. We show that nob DBCs fail to respond to exogenous application of the photoreceptor neurotransmitter, glutamate, thus demonstrating a postsynaptic deficit in photoreceptor to bipolar cell communication. To determine if postsynaptic expression of nyctalopin is necessary and sufficient to rescue the nob phenotype, we constructed transgenic mice that expressed an EYFP-nyctalopin fusion protein on the dendritic tips of the DBCs. Immunohistochemical and ultrastructural studies verified that fusion protein expression was limited to the DBC dendritic tips. Fusion gene expression in nob mice restored normal outer and inner visual function as determined by the electroretinogram and RGC spontaneous and evoked responses. Together, our data show that nyctalopin expression on DBC dendrites is required for normal function of the murine retina.

  8. Psychotic and Bipolar Disorders: Bipolar Disorder.

    Science.gov (United States)

    Holder, Sarah D

    2017-04-01

    Bipolar disorder is a severe chronic mental illness that affects a large number of individuals. This disorder is separated into two major types, bipolar I disorder, with mania and typically recurrent depression, and bipolar II disorder, with recurrent major depression and hypomania. Patients with bipolar disorder spend the majority of time experiencing depression, and this typically is the presenting symptom. Because outcomes are improved with earlier diagnosis and treatment, physicians should maintain a high index of suspicion for bipolar disorder. The most effective long-term treatments are lithium and valproic acid, although other drugs also are used. In addition to referral to a mental health subspecialist for initiation and management of drug treatment, patients with bipolar disorder should be provided with resources for psychotherapy. Several comorbidities commonly associated with bipolar disorder include other mental disorders, substance use disorders, migraine headaches, chronic pain, stroke, metabolic syndrome, and cardiovascular disease. Family physicians who care for patients with bipolar disorder should focus their efforts on prevention and management of comorbidities. These patients should be assessed continually for risk of suicide because they are at high risk and their suicide attempts tend to be successful. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  9. Cellular semiotics and signal transduction

    DEFF Research Database (Denmark)

    Bruni, Luis Emilio

    2007-01-01

    (s)" in signal transduction; i.e.: how specificity is determined, how ubiquitous signals or messengers convey specific information, how undesired cross-talk is avoided, how redundancy integrates the system. This chapter proposes a basic conceptual toolbox for interpreting empirical data that deals...

  10. Nutrition and Bipolar Depression.

    Science.gov (United States)

    Beyer, John L; Payne, Martha E

    2016-03-01

    As with physical conditions, bipolar disorder is likely to be impacted by diet and nutrition. Patients with bipolar disorder have been noted to have relatively unhealthy diets, which may in part be the reason they also have an elevated risk of metabolic syndrome and obesity. An improvement in the quality of the diet should improve a bipolar patient's overall health risk profile, but it may also improve their psychiatric outcomes. New insights into biological dysfunctions that may be present in bipolar disorder have presented new theoretic frameworks for understanding the relationship between diet and bipolar disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Controlling Signal Transduction with Synthetic Ligands

    Science.gov (United States)

    Spencer, David M.; Wandless, Thomas J.; Schreiber, Stuart L.; Crabtree, Gerald R.

    1993-11-01

    Dimerization and oligomerization are general biological control mechanisms contributing to the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and other classes of intra- and extracellular proteins. Cell permeable, synthetic ligands were devised that can be used to control the intracellular oligomerization of specific proteins. To demonstrate their utility, these ligands were used to reduce intracellular oligomerization of cell surface receptors that lacked their transmembrane and extracellular regions but contained intracellular signaling domains. Addition of these ligands to cells in culture resulted in signal transmission and specific target gene activation. Monomeric forms of the ligands blocked the pathway. This method of ligandregulated activation and termination of signaling pathways has the potential to be applied wherever precise control of a signal transduction pathway is desired.

  12. Bipolar Treatment: Are Bipolar I and Bipolar II Treated Differently?

    Science.gov (United States)

    ... management strategies. In addition to medications and other types of treatment, successful management of your bipolar disorder includes living a healthy lifestyle, such as getting enough sleep, eating a healthy diet and being physically active. ...

  13. Gene environment interactions in bipolar disorder.

    Science.gov (United States)

    Pregelj, Peter

    2011-09-01

    It has been estimated that the heritable component of bipolar disorder ranges between 80 and 90%. However, even genome-wide association studies explain only a fraction of phenotypic variability not resolving the problem of "lost heritability". Although direct evidence for epigenetic dysfunction in bipolar disorder is still limited, methodological technologies in epigenomic profiling have advanced, offering even single cell analysing and resolving the problem of cell heterogeneity in epigenetics research. Gene overlapping with other mental disorders represents another problem in identifying potential susceptibility genes in bipolar disorder. Better understanding of the interplay between multiple environmental and genetic factors involved in the patogenesis of bipolar disorder could provide relevant information for treatment of patients with this complex disorder. Future studies on the role of these factors in psychopathological conditions, subphenotypes and endophenotypes may greatly benefit by using more precise clinical data and a combined approach with multiple research tools incorporated into a single study.

  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. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Simulated evolution of signal transduction networks.

    Directory of Open Access Journals (Sweden)

    Mohammad Mobashir

    Full Text Available Signal transduction is the process of routing information inside cells when receiving stimuli from their environment that modulate the behavior and function. In such biological processes, the receptors, after receiving the corresponding signals, activate a number of biomolecules which eventually transduce the signal to the nucleus. The main objective of our work is to develop a theoretical approach which will help to better understand the behavior of signal transduction networks due to changes in kinetic parameters and network topology. By using an evolutionary algorithm, we designed a mathematical model which performs basic signaling tasks similar to the signaling process of living cells. We use a simple dynamical model of signaling networks of interacting proteins and their complexes. We study the evolution of signaling networks described by mass-action kinetics. The fitness of the networks is determined by the number of signals detected out of a series of signals with varying strength. The mutations include changes in the reaction rate and network topology. We found that stronger interactions and addition of new nodes lead to improved evolved responses. The strength of the signal does not play any role in determining the response type. This model will help to understand the dynamic behavior of the proteins involved in signaling pathways. It will also help to understand the robustness of the kinetics of the output response upon changes in the rate of reactions and the topology of the network.

  16. Electronic monitoring in bipolar disorder.

    Science.gov (United States)

    Faurholt-Jepsen, Maria

    2018-03-01

    Major reasons for the insufficient effects of current treatment options in bipolar disorder include delayed intervention for prodromal depressive and manic symptoms and decreased adherence to psychopharmacological treatment. The reliance on subjective information and clinical evaluations when diagnosing and assessing the severity of depressive and manic symptoms calls for less biased and more objective markers. By using electronic devices, fine-grained data on complex psychopathological aspects of bipolar disorder can be evaluated unobtrusively over the long term. Moreover, electronic data could possibly represent candidate markers of diagnosis and illness activity in bipolar disorder and allow for early and individualized intervention for prodromal symptoms outside clinical settings. 
The present dissertation concerns the use of electronic monitoring as a marker and treatment intervention in bipolar disorder and investigated the scientific literature and body of evidence within the area, which includes ten original study reports and two systematic reviews, one of which included a meta-analysis, conducted by the author of the dissertation. 
Taken together, the literature presented in this dissertation illustrates that 1) smartphone-based electronic self-monitoring of mood seems to reflect clinically assessed depressive and manic symptoms and enables the long-term characterization of mood

instability in bipolar disorder; 2) preliminary results suggest that smartphone-based automatically generated data (e.g. the number of text messages sent/day; the number of incoming and outgoing calls/day; the number of changes in cell tower IDs/day; and voice features) seem to reflect clinically assessed depressive and manic symptoms in bipolar disorder; 3) smartphone-based electronic self-monitoring had no effects on the severity of depressive and manic symptoms in bipolar disorder, according to a randomized controlled trial; and 4) electronic monitoring of psychomotor

  17. Bipolar soft connected, bipolar soft disconnected and bipolar soft compact spaces

    Directory of Open Access Journals (Sweden)

    Muhammad Shabir

    2017-06-01

    Full Text Available Bipolar soft topological spaces are mathematical expressions to estimate interpretation of data frameworks. Bipolar soft theory considers the core features of data granules. Bipolarity is important to distinguish between positive information which is guaranteed to be possible and negative information which is forbidden or surely false. Connectedness and compactness are the most important fundamental topological properties. These properties highlight the main features of topological spaces and distinguish one topology from another. Taking this into account, we explore the bipolar soft connectedness, bipolar soft disconnectedness and bipolar soft compactness properties for bipolar soft topological spaces. Moreover, we introduce the notion of bipolar soft disjoint sets, bipolar soft separation, and bipolar soft hereditary property and study on bipolar soft connected and disconnected spaces. By giving the detailed picture of bipolar soft connected and disconnected spaces we investigate bipolar soft compact spaces and derive some results related to this concept.

  18. Ion bipolar junction transistors.

    Science.gov (United States)

    Tybrandt, Klas; Larsson, Karin C; Richter-Dahlfors, Agneta; Berggren, Magnus

    2010-06-01

    Dynamic control of chemical microenvironments is essential for continued development in numerous fields of life sciences. Such control could be achieved with active chemical circuits for delivery of ions and biomolecules. As the basis for such circuitry, we report a solid-state ion bipolar junction transistor (IBJT) based on conducting polymers and thin films of anion- and cation-selective membranes. The IBJT is the ionic analogue to the conventional semiconductor BJT and is manufactured using standard microfabrication techniques. Transistor characteristics along with a model describing the principle of operation, in which an anionic base current amplifies a cationic collector current, are presented. By employing the IBJT as a bioelectronic circuit element for delivery of the neurotransmitter acetylcholine, its efficacy in modulating neuronal cell signaling is demonstrated.

  19. Energy metabolism and transduction in smooth muscle.

    Science.gov (United States)

    Lynch, R M; Paul, R J

    1985-08-15

    Early investigations into the nature of the coupling between energy transduction and metabolism in smooth muscle, particularly from the laboratories of Bülbring and Lundholm, suggested that specific metabolic pathways could independently supply energy for ion transport and actin-myosin interactions. Subsequent work has solidified the concept that oxidative phosphorylation is specifically coupled to tension generation and maintenance, whereas, aerobic glycolysis is not only a vital characteristic of smooth muscle metabolism, but also is likely to be independently coupled to Na-K transport at the plasmalemma. The independence of oxidative and glycolytic metabolism is reflected as a compartmentation of carbohydrate metabolism in the porcine carotid artery. The coupling of these independent metabolic pathways with specific energy utilizing processes, indicates a means by which energy production and transduction can be closely and efficiently regulated. The coupling of glycogenolysis to mitochondrial respiration may have evolved as a direct response to the energetic needs of VSM. That is, the large glycogenolytic response in the initial minutes of stimulation may be necessary to maximize the cellular production of ATP during the presteady state. Likewise, the coupling between aerobic glycolysis and Na-K transport indicates a sensitive and efficient means of coordinating energy metabolism with ion transport at the membrane level. Additionally, the regulation of substrate supply, i.e. glucose transport, also may be closely coordinated with changes in ion transport. One may speculate that alterations in the microenvironment of each compartment can independently regulate intermediary metabolism and therefore allow the cell to quickly and efficiently respond to localized stimuli. Thus, stimulation of Na-K transport could effectively regulate energy production at the membrane level without mobilizing or competing with the energy transduction of other cellular processes. This

  20. 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

    BACKGROUND: Disturbances related to the arachidonic acid cascade and prostaglandin metabolism may be involved in the pathophysiology of bipolar disorder, as supported by a recent genome-wide association study meta-analysis; however, evidence from clinical studies on a transcriptional level...... 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...

  1. Effect of Momordica charantia protein on proliferation, apoptosis and the AKT signal transduction pathway in the human endometrial carcinoma Ishikawa H cell line in vitro

    Science.gov (United States)

    Gu, Hang-Zhi; Lin, Rong-Rong; Wang, Han-Chu; Zhu, Xue-Jie; Hu, Yan; Zheng, Fei-Yun

    2017-01-01

    Endometrial carcinoma (EC) is one of the most common female malignancies, and there is an urgent requirement to explore new therapeutic strategies. In the present study, Ishikawa H cells were treated with Momordica charantia protein (MCP30). The cell morphology, growth inhibition rate, cell cycle distribution, and expression of phosphate and tensin homolog, P-AKT and AKT were measured. DNA fragmentation analysis and Annexin V-fluorescein isothiocyanate/propidium iodide double staining assay were used to analyze cell apoptosis. MCP30 decreased the viability of Ishikawa H cells in a dose- and time-dependent manner. The early apoptotic rates of Ishikawa H cells treated with MCP30 at 666.67 pM reached to 16.07±0.15%, following 72 h of treatment. DNA ladder was observed in cells treated with 333.33 and 666.67 pM MCP30 following 72 h of treatment. MCP30 blocks Ishikawa H cells from progressing between the S-phase and the G2/M-phase in a time- and concentration-dependent manner. Western blotting revealed that MCP30 treatment decreased the levels of P-AKT in a dose-dependent manner. It was revealed that MCP30 decreases cell proliferation, and induces apoptosis and S-phase cell cycle arrest through the AKT signaling pathway in Ishikawa H cells. PMID:28521410

  2. The characteristics and performance of electroless nickel and immersion Au plated aluminum alloy bipolar plates in polymer electrolyte membrane fuel cells

    Science.gov (United States)

    Tsai, Sung-Ying; Bai, Ching-Yuan; Lin, Chien-Hung; Shi, Gia-Nan; Hou, Kung-Hsu; Liu, Yih-Ming; Ger, Ming-Der

    2012-09-01

    Cheap, lightweight, and malleable Al-alloy 5052 is suggested as alternative materials of graphite bipolar plates (BPPs) in proton exchange membrane fuel cells (PEMFCs). This work presents the first research in producing Au/Ni-P multilayer coatings on Al-alloy BPPs using an electroless Ni-P along with immersion gold techniques. The modified Al-alloy BPPs are investigated to evaluate the coating structure, corrosion resistance, interfacial contact resistance, electrochemical impedance of single cells, and single cell performance. The results indicate that the Al-alloy BPPs with Au/Ni-P coatings, in which Ni-P is prepared at pH 4.5, reveal the lowest contact resistance and the best corrosion resistance (Icorr = 8.43 × 10-6 A cm-2) in a 0.5 M H2SO4 + 2 ppm HF solution among all of the modified specimens. The electrochemical impedance of the Au/Ni-P coating after long-term operation is 9.1 mΩ. In addition, the power density of the single cells assembled with the Au/Ni-P/Al-alloy BPPs is 0.84 W cm-2 measured at a cell voltage of 0.7 V, comparable to that with graphite BPPs (0.80 W cm-2), in the test conditions of this study. We find that the Au/Ni-P multilayer coating is very appropriate for modifying Al-ally BPPs in PEMFC systems.

  3. Closed Bipolar Electrodes for Spatial Separation of H2and O2Evolution during Water Electrolysis and the Development of High-Voltage Fuel Cells.

    Science.gov (United States)

    Goodwin, Sean; Walsh, Darren A

    2017-07-19

    Electrolytic water splitting could potentially provide clean H 2 for a future "hydrogen economy". However, as H 2 and O 2 are produced in close proximity to each other in water electrolyzers, mixing of the gases can occur during electrolysis, with potentially dangerous consequences. Herein, we describe an electrochemical water-splitting cell, in which mixing of the electrogenerated gases is impossible. In our cell, separate H 2 - and O 2 -evolving cells are connected electrically by a bipolar electrode in contact with an inexpensive dissolved redox couple (K 3 Fe(CN) 6 /K 4 Fe(CN) 6 ). Electrolytic water splitting occurs in tandem with oxidation/reduction of the K 3 Fe(CN) 6 /K 4 Fe(CN) redox couples in the separate compartments, affording completely spatially separated H 2 and O 2 evolution. We demonstrate operation of our prototype cell using conventional Pt electrodes for each gas-evolving reaction, as well as using earth-abundant Ni 2 P electrocatalysts for H 2 evolution. Furthermore, we show that our cell can be run in reverse and operate as a H 2 fuel cell, releasing the energy stored in the electrogenerated H 2 and O 2 . We also describe how the absence of an ionically conducting electrolyte bridging the H 2 - and O 2 -electrode compartments makes it possible to develop H 2 fuel cells in which the anode and cathode are at different pH values, thereby increasing the voltage above that of conventional fuel cells. The use of our cell design in electrolyzers could result in dramatically improved safety during operation and the generation of higher-purity H 2 than available from conventional electrolysis systems. Our cell could also be readily modified for the electrosynthesis of other chemicals, where mixing of the electrochemical products is undesirable.

  4. Bipolar Disorder - Multiple Languages

    Science.gov (United States)

    ... MP3 Bipolar Disorder (An Introduction) - English MP4 Bipolar Disorder (An Introduction) - español (Spanish) MP4 Healthy Roads Media Characters not displaying correctly on this page? See language display issues . Return to the MedlinePlus Health Information ...

  5. Magnetic bipolar transistor

    OpenAIRE

    Fabian, Jaroslav; Zutic, Igor; Sarma, S. Das

    2003-01-01

    A magnetic bipolar transistor is a bipolar junction transistor with one or more magnetic regions, and/or with an externally injected nonequilibrium (source) spin. It is shown that electrical spin injection through the transistor is possible in the forward active regime. It is predicted that the current amplification of the transistor can be tuned by spin.

  6. 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

  7. Charge transport and bipolar switching mechanism in a Cu/HfO2/Pt resistive switching cell

    International Nuclear Information System (INIS)

    Tan Tingting; Guo Tingting; Wu Zhihui; Liu Zhengtang

    2016-01-01

    Bipolar resistance switching characteristics are investigated in Cu/sputtered-HfO 2 /Pt structure in the application of resistive random access memory (RRAM). The conduction mechanism of the structure is characterized to be SCLC conduction. The dependence of resistances in both high resistance state (HRS) and low resistance state (LRS) on the temperature and device area are studied. Then, the composition and chemical bonding state of Cu and Hf at Cu/HfO 2 interface region are analyzed by x-ray photoelectron spectroscopy (XPS). Combining the electrical characteristics and the chemical structure at the interface, a model for the resistive switching effect in Cu/HfO 2 /Pt stack is proposed. According to this model, the generation and recovery of oxygen vacancies in the HfO 2 film are responsible for the resistance change. (paper)

  8. 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.

  9. 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.

  10. 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

    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, circulates the gases that participate in the electrochemical reaction within the fuel cell and allows for removal of the excess heat from the system. The materials fabricated in this work were tested to determine their mechanical and thermal properties. These materials were produced by adding varying amounts of single carbon fillers to a polypropylene matrix (2.5 to 15 wt.% Ketjenblack EC-600 JD carbon black, 10 to 80 wt.% Asbury Carbons' Thermocarb TC-300 synthetic graphite, and 2.5 to 15 wt.% of Hyperion Catalysis International's FIBRIL(TM) multi-walled carbon nanotubes) In addition, composite materials containing combinations of these three fillers were produced. The thermal conductivity results showed an increase in both through-plane and in-plane thermal conductivities, with the largest increase observed for synthetic graphite. The Department of Energy (DOE) had previously set a thermal conductivity goal of 20 W/m·K, which was surpassed by formulations containing 75 wt.% and 80 wt.% SG, yielding in-plane thermal conductivity values of 24.4 W/m·K and 33.6 W/m·K, respectively. In addition, composites containing 2.5 wt.% CB, 65 wt.% SG, and 6 wt.% CNT in PP had an in-plane thermal conductivity of 37 W/m·K. Flexural and tensile tests were conducted. All composite formulations exceeded the flexural strength target of 25 MPa set by DOE. The tensile and flexural modulus of the composites increased with higher concentration of carbon fillers. Carbon black and synthetic graphite caused a decrease in the tensile and flexural strengths of the composites. However, carbon nanotubes increased the composite tensile and flexural

  11. Coronin 1B regulates S1P-induced human lung endothelial cell chemotaxis: role of PLD2, protein kinase C and Rac1 signal transduction.

    Directory of Open Access Journals (Sweden)

    Peter V Usatyuk

    Full Text Available Coronins are a highly conserved family of actin binding proteins that regulate actin-dependent processes such as cell motility and endocytosis. We found that treatment of human pulmonary artery endothelial cells (HPAECs with the bioactive lipid, sphingosine-1-phosphate (S1P rapidly stimulates coronin 1B translocation to lamellipodia at the cell leading edge, which is required for S1P-induced chemotaxis. Further, S1P-induced chemotaxis of HPAECs was attenuated by pretreatment with small interfering RNA (siRNA targeting coronin 1B (∼36%, PLD2 (∼45% or Rac1 (∼50% compared to scrambled siRNA controls. Down regulation PLD2 expression by siRNA also attenuated S1P-induced coronin 1B translocation to the leading edge of the cell periphery while PLD1 silencing had no effect. Also, S1P-induced coronin 1B redistribution to cell periphery and chemotaxis was attenuated by inhibition of Rac1 and over-expression of dominant negative PKC δ, ε and ζ isoforms in HPAECs. These results demonstrate that S1P activation of PLD2, PKC and Rac1 is part of the signaling cascade that regulates coronin 1B translocation to the cell periphery and the ensuing cell chemotaxis.

  12. 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)

    Feng, Kai; Li, Zhuguo

    2013-01-01

    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 (Ti 0.9 Si 0.1 N) 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 Ti 0.9 Si 0.1 N films exhibit a dense (111) plane preferred growth, denser structure and smoother surface topography. The potentiodynamic test results indicate that the TiN and Ti 0.9 Si 0.1 N 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 Ti 0.9 Si 0.1 N films reaches minimum when the deposition bias voltage is − 20 V. - Highlights: • Dense TiN and Ti 0.9 Si 0.1 N films are deposited by magnetron sputtering. • Preferred growth orientation of TiN depends on the bias voltage and Si doping. • TiN and Ti 0.9 Si 0.1 N films have excellent corrosion resistance. • Surface conductivity of TiN and Ti 0.9 Si 0.1 N films evolves with bias voltage

  13. 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.

  14. 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...

  15. Properties of Bipolar Fuzzy Hypergraphs

    OpenAIRE

    Akram, M.; Dudek, W. A.; Sarwar, S.

    2013-01-01

    In this article, we apply the concept of bipolar fuzzy sets to hypergraphs and investigate some properties of bipolar fuzzy hypergraphs. We introduce the notion of $A-$ tempered bipolar fuzzy hypergraphs and present some of their properties. We also present application examples of bipolar fuzzy hypergraphs.

  16. Analysis of bipolar and amacrine populations in marmoset retina.

    Science.gov (United States)

    Weltzien, Felix; Percival, Kumiko A; Martin, Paul R; Grünert, Ulrike

    2015-02-01

    About 15 parallel ganglion cell pathways transmit visual signals to the brain, but the interneuron (bipolar and amacrine) populations providing input to ganglion cells remain poorly understood in primate retina. We carried out a quantitative analysis of the inner nuclear layer in the retina of the marmoset (Callithrix jacchus). Vertical Vibratome sections along the horizontal meridian were processed with immunohistochemical markers. Image stacks were taken with a confocal microscope, and densities of cell populations were determined. The density of flat midget bipolar cells fell from 15,746 cells/mm(2) at 1 mm (8 deg) to 7,827 cells/mm(2) at 3 mm (25 deg). The rod bipolar cell density fell from 8,640 cells/mm(2) at 1 mm to 4,278 cells/mm(2) at 3 mm, but the ratio of the two bipolar cell types did not change with eccentricity. The amacrine cell density ranged from 30,000 cells/mm(2) at 8 deg to less than 15,000 cells/mm(2) at 25 deg, but throughout the retina, the ratio of glycinergic to γ-aminobutyric acid (GABA)ergic to amacrine cells remained relatively constant. The fractions of rod bipolar, cone bipolar, amacrine, Müller, and horizontal cells of all cells in the inner nuclear layer were comparable in central and peripheral retina. Marmosets had lower proportions of midget bipolar and rod bipolar in comparison with macaque. These differences were correlated with differences in rod and cone densities between the two species and did not reflect fundamental differences in the wiring between the two species. © 2014 Wiley Periodicals, Inc.

  17. 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.

  18. 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.

  19. Fluid shear stress primes mouse embryonic stem cells for differentiation in a self-renewing environment via heparan sulfate proteoglycans transduction.

    Science.gov (United States)

    Toh, Yi-Chin; Voldman, Joel

    2011-04-01

    Shear stress is a ubiquitous environmental cue experienced by stem cells when they are being differentiated or expanded in perfusion cultures. However, its role in modulating self-renewing stem cell phenotypes is unclear, since shear is usually only studied in the context of cardiovascular differentiation. We used a multiplex microfluidic array, which overcomes the limitations of macroperfusion systems in shear application throughput and precision, to initiate a comprehensive, quantitative study of shear effects on self-renewing mouse embryonic stem cells (mESCs), where shear stresses varying by >1000 times (0.016-16 dyn/cm(2)) are applied simultaneously. When compared with static controls in the presence or absence of a saturated soluble environment (i.e., mESC-conditioned medium), we ascertained that flow-induced shear stress specifically up-regulates the epiblast marker Fgf5. Epiblast-state transition in mESCs involves heparan sulfate proteoglycans (HSPGs), which have also been shown to transduce shear stress in endothelial cells. By disrupting (with sulfation inhibitors and heparinase) and partially reconstituting (with heparin) HSPG function, we show that mESCs also mechanically sense shear stress via HSPGs to modulate Fgf5 expression. This study demonstrates that self-renewing mESCs possess the molecular machinery to sense shear stress and provides quantitative shear application benchmarks for future scalable stem cell culture systems.

  20. Bipolar Disorder in Children

    Science.gov (United States)

    2014-01-01

    Although bipolar disorder historically was thought to only occur rarely in children and adolescents, there has been a significant increase in children and adolescents who are receiving this diagnosis more recently (Carlson, 2005). Nonetheless, the applicability of the current bipolar disorder diagnostic criteria for children, particularly preschool children, remains unclear, even though much work has been focused on this area. As a result, more work needs to be done to further the understanding of bipolar symptoms in children. It is hoped that this paper can assist psychologists and other health service providers in gleaning a snapshot of the literature in this area so that they can gain an understanding of the diagnostic criteria and other behaviors that may be relevant and be informed about potential approaches for assessment and treatment with children who meet bipolar disorder criteria. First, the history of bipolar symptoms and current diagnostic criteria will be discussed. Next, assessment strategies that may prove helpful for identifying bipolar disorder will be discussed. Then, treatments that may have relevance to children and their families will be discussed. Finally, conclusions regarding work with children who may have a bipolar disorder diagnosis will be offered. PMID:24800202

  1. Bipolar Disorder in Children

    Directory of Open Access Journals (Sweden)

    Kimberly Renk

    2014-01-01

    Full Text Available Although bipolar disorder historically was thought to only occur rarely in children and adolescents, there has been a significant increase in children and adolescents who are receiving this diagnosis more recently (Carlson, 2005. Nonetheless, the applicability of the current bipolar disorder diagnostic criteria for children, particularly preschool children, remains unclear, even though much work has been focused on this area. As a result, more work needs to be done to further the understanding of bipolar symptoms in children. It is hoped that this paper can assist psychologists and other health service providers in gleaning a snapshot of the literature in this area so that they can gain an understanding of the diagnostic criteria and other behaviors that may be relevant and be informed about potential approaches for assessment and treatment with children who meet bipolar disorder criteria. First, the history of bipolar symptoms and current diagnostic criteria will be discussed. Next, assessment strategies that may prove helpful for identifying bipolar disorder will be discussed. Then, treatments that may have relevance to children and their families will be discussed. Finally, conclusions regarding work with children who may have a bipolar disorder diagnosis will be offered.

  2. Quantum Transduction with Adaptive Control.

    Science.gov (United States)

    Zhang, Mengzhen; Zou, Chang-Ling; Jiang, Liang

    2018-01-12

    Quantum transducers play a crucial role in hybrid quantum networks. A good quantum transducer can faithfully convert quantum signals from one mode to another with minimum decoherence. Most investigations of quantum transduction are based on the protocol of direct mode conversion. However, the direct protocol requires the matching condition, which in practice is not always feasible. Here we propose an adaptive protocol for quantum transducers, which can convert quantum signals without requiring the matching condition. The adaptive protocol only consists of Gaussian operations, feasible in various physical platforms. Moreover, we show that the adaptive protocol can be robust against imperfections associated with finite squeezing, thermal noise, and homodyne detection, and it can be implemented to realize quantum state transfer between microwave and optical modes.

  3. [Progress on Hedgehog signaling transduction].

    Science.gov (United States)

    Tang, Ying; Cheng, Steven

    2014-08-25

    Hedgehog (Hh) signaling pathway plays an important role during embryonic development and pattern formation. Disruption of Hh pathway results in various developmental disorders and increasing cancer incidence. Here we provide a comprehensive review of the pathway members, focusing on how mammalian Hh regulates the Gli family of transcription factors through its downstream members, the so-called "canonical signaling pathway". Hh signaling pathway is highly conserved among species, and primary cilia plays an important role as a "signaling center" during vertebrate signal transduction. Further, in the past few years, numerous studies have shown that Hh signal can also be transduced through Gli-independent ways collectively referred to as "non-canonical signaling pathways", which can be subdivided into two modules: (i) those not requiring Smo and (ii) those downstream of Smo that do not require Gli transcription factors. Thus, we review the rapid progress on canonical and non-canonical Hh pathways.

  4. Cross-talk between Smad and p38 MAPK signalling in transforming growth factor β signal transduction in human glioblastoma cells

    International Nuclear Information System (INIS)

    Dziembowska, Magdalena; Danilkiewicz, Malgorzata; Wesolowska, Aleksandra; Zupanska, Agata; Chouaib, Salem; Kaminska, Bozena

    2007-01-01

    Transforming growth factor-beta (TGF-β) is a multifunctional cytokine involved in the regulation of cell proliferation, differentiation, and survival. Malignant tumour cells often do not respond to TGF-β by growth inhibition, but retain responsiveness to cytokine in regulating extracellular matrix deposition, cell adhesion, and migration. We demonstrated that TGF-β1 does not affect viability or proliferation of human glioblastoma T98G, but increases transcriptional responses exemplified by induction of MMP-9 expression. TGF-β receptors were functional in T98G glioblastoma cells leading to SMAD3/SMAD4 nuclear translocation and activation of SMAD-dependent promoter. In parallel, a selective activation of p38 MAPK, and phosphorylation of its substrates: ATF2 and c-Jun proteins were followed by a transient activation of AP-1 transcription factor. Surprisingly, an inhibition of p38 MAPK with a specific inhibitor, SB202190, abolished TGF-inducible activation of Smad-dependent promoter and decreased Smad2 phosphorylation. It suggests an unexpected interaction between Smad and p38 MAPK pathways in TGF-β1-induced signalling

  5. TRPM5 and taste transduction.

    Science.gov (United States)

    Liman, E R

    2007-01-01

    TRPM5 is a cation channel that it is essential for transduction of bitter, sweet and umami tastes. Signaling of these tastes involves the activation of G protein-coupled receptors that stimulate phospholipase C (PLC) beta2, leading to the breakdown of phosphatidylinositol bisphosphate (PIP2) into diacylglycerol (DAG) and inositol trisphosphate (IP3), and release of Ca2+ from intracellular stores. TRPM5 forms a nonselective cation channel that is directly activated by Ca2+ and it is likely to be the downstream target of this signaling cascade. Therefore, study of TRPM5 promises to provide insight into fundamental mechanisms of taste transduction. This review highlights recent work on the mechanisms of activation of the TRPM5 channel. The mouse TRPM5 gene encodes a protein of 1,158 amino acids that is proposed to have six transmembrane domains and to function as a tetramer. TRPM5 is structurally most closely related to the Ca(2+)-activated channel TRPM4 and it is more distantly related to the cold-activated channel TRPM8. In patch clamp recordings, TRPM5 channels are activated by micromolar concentrations of Ca2+ and are permeable to monovalent but not divalent cations. TRPM5 channel activity is strongly regulated by voltage, phosphoinositides and temperature, and is blocked by acid pH. Study of TRPM4 and TRPM8, which show similar modes of regulation, has yielded insights into possible structural domains of TRPM5. Understanding the structural basis for TRPM5 function will ultimately allow the design of pharmaceuticals to enhance or interfere with taste sensations.

  6. Investigations on the corrosion resistance of metallic bipolar plates (BPP) in proton exchange membrane fuel cells (PEMFC) - understanding the effects of material, coating and manufacturing

    Science.gov (United States)

    Dur, Ender

    Polymer Electrolyte Membrane Fuel Cell (PEMFC) systems are promising technology for contributing to meet the deficiency of world`s clean and sustainable energy requirements in the near future. Metallic bipolar plate (BPP) as one of the most significant components of PEMFC device accounts for the largest part of the fuel cell`s stack. Corrosion for metallic bipolar plates is a critical issue, which influences the performance and durability of PEMFC. Corrosion causes adverse impacts on the PEMFC`s performance jeopardizing commercialization. This research is aimed at determining the corrosion resistance of metallic BPPs, particularly stainless steels, used in PEMFC from different aspects. Material selection, coating selection, manufacturing process development and cost considerations need to be addressed in terms of the corrosion behavior to justify the use of stainless steels as a BPP material in PEMFC and to make them commercially feasible in industrial applications. In this study, Ti, Ni, SS304, SS316L, and SS 430 blanks, and BPPs comprised of SS304 and SS316L were examined in terms of the corrosion behavior. SS316L plates were coated to investigate the effect of coatings on the corrosion resistance performance. Stamping and hydroforming as manufacturing processes, and three different coatings (TiN, CrN, ZrN) applied via the Physical Vapor Deposition (PVD) method in three different thicknesses were selected to observe the effects of manufacturing processes, coating types and coating thicknesses on the corrosion resistance of BPP, respectively. Uncoated-coated blank and formed BPP were subjected to two different corrosion tests: potentiostatic and potentiodynamic. Some of the substantial results: 1- Manufacturing processes have an adverse impact on the corrosion resistance. 2- Hydroformed plates have slightly higher corrosion resistance than stamped samples. 3- BPPs with higher channel size showed better corrosion resistance. 4- Since none of the uncoated samples

  7. The Impact of GFP Reporter Gene Transduction and Expression on Metabolomics of Placental Mesenchymal Stem Cells Determined by UHPLC-Q/TOF-MS

    Directory of Open Access Journals (Sweden)

    Jinfeng Yang

    2017-01-01

    Full Text Available Introduction. Green fluorescent protein (GFP is widely used as a reporter gene in regenerative medicine research to label and track stem cells. Here, we examined whether expressing GFP gene may impact the metabolism of human placental mesenchymal stem cells (hPMSCs. Methods. The GFP gene was transduced into hPMSCs using lentiviral-based infection to establish GFP+hPMSCs. A sensitive 13C/12C-dansyl labeling LC-MS method targeting the amine/phenol submetabolome was used for in-depth cell metabolome profiling. Results. A total of 1151 peak pairs or metabolites were detected from 12 LC-MS runs. Principal component analysis and partial least squares discriminant analysis showed poor separation, and the volcano plots demonstrated that most of the metabolites were not significantly changed when hPMSCs were tagged with GFP. Overall, 739 metabolites were positively or putatively identified. Only 11 metabolites showed significant changes. Metabolic pathway analyses indicated that three of the identified metabolites were involved in nine pathways. However, these metabolites are unlikely to have a large impact on the metabolic pathways due to their nonessential roles and limited hits in pathway analysis. Conclusion. This study indicated that the expression of ectopic GFP reporter gene did not significantly alter the metabolomics pathways covered by the amine/phenol submetabolome.

  8. The J-Domain of Heat Shock Protein 40 Can Enhance the Transduction Efficiency of Arginine-Rich Cell-Penetrating Peptides

    Directory of Open Access Journals (Sweden)

    Tzu-Yin Lin

    2015-01-01

    Full Text Available Sense and antisense oligonucleotide pairs encoding cell-penetrating peptides PTD (Tat47–57, DPV3A, E162, pVEC, R11, and TP13 were used to construct two sets of pET22b-CPP-DsRed and pET22b-CPP-J-DsRed vectors for CPP-DsRed and CPP-J-DsRed recombinant proteins expression. PTD-DsRed, DPV3A-DsRed, PTD-J-DsRed, and DPV3A-J-DsRed recombinant proteins were expressed in a soluble form. PTD-J-DsRed and DPV3A-J-DsRed recombinant proteins were able to escape from E. coli host cells into the culture medium. The membrane-penetrating activity of PTD-J-DsRed and DPV3A-J-DsRed recombinant proteins to mammalian cells was more effective than that of PTD-DsRed and DPV3A-DsRed. The route of the cellular membrane translocation of these recombinant proteins is suggested via macropinocytosis followed by an endosomal escape pathway.

  9. E2/ER β Enhances Calcineurin Protein Degradation and PI3K/Akt/MDM2 Signal Transduction to Inhibit ISO-Induced Myocardial Cell Apoptosis

    Directory of Open Access Journals (Sweden)

    Kuan-Ho Lin

    2017-04-01

    Full Text Available Secretion of multifunctional estrogen and its receptor has been widely considered as the reason for markedly higher frequency of heart disease in men than in women. 17β-Estradiol (E2, for instance, has been reported to prevent development of cardiac apoptosis via activation of estrogen receptors (ERs. In addition, protein phosphatase such as protein phosphatase 1 (PP1 and calcineurin (PP2B are also involved in cardiac hypertrophy and cell apoptosis signaling. However, the mechanism by which E2/ERβ suppresses apoptosis is not fully understood, and the role of protein phosphatase in E2/ERβ action also needs further investigation. In this study, we observed that E2/ERβ inhibited isoproterenol (ISO-induced myocardial cell apoptosis, cytochrome c release and downstream apoptotic markers. Moreover, we found that E2/ERβ blocks ISO-induced apoptosis in H9c2 cells through the enhancement of calcineurin protein degradation through PI3K/Akt/MDM2 signaling pathway. Our results suggest that supplementation with estrogen and/or overexpression of estrogen receptor β gene may prove to be effective means to treat stress-induced myocardial damage.

  10. 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.

  11. Architectures and representations for string transduction

    NARCIS (Netherlands)

    Chrupala, Grzegorz

    2015-01-01

    String transduction problems are ubiquitous in natural language processing: they include transliteration, grapheme-to-phoneme conversion, text normalization and translation. String transduction can be reduced to the simpler problems of sequence labeling by expressing the target string as a sequence

  12. Glycosphingolipid–Protein Interaction in Signal Transduction

    Directory of Open Access Journals (Sweden)

    Domenico Russo

    2016-10-01

    Full Text Available Glycosphingolipids (GSLs are a class of ceramide-based glycolipids essential for embryo development in mammals. The synthesis of specific GSLs depends on the expression of distinctive sets of GSL synthesizing enzymes that is tightly regulated during development. Several reports have described how cell surface receptors can be kept in a resting state or activate alternative signalling events as a consequence of their interaction with GSLs. Specific GSLs, indeed, interface with specific protein domains that are found in signalling molecules and which act as GSL sensors to modify signalling responses. The regulation exerted by GSLs on signal transduction is orthogonal to the ligand–receptor axis, as it usually does not directly interfere with the ligand binding to receptors. Due to their properties of adjustable production and orthogonal action on receptors, GSLs add a new dimension to the control of the signalling in development. GSLs can, indeed, dynamically influence progenitor cell response to morphogenetic stimuli, resulting in alternative differentiation fates. Here, we review the available literature on GSL–protein interactions and their effects on cell signalling and development.

  13. 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.

  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. The role of the PI3K-Akt signal transduction pathway in Autographa californica multiple nucleopolyhedrovirus infection of Spodoptera frugiperda cells

    International Nuclear Information System (INIS)

    Xiao Wei; Yang Yi; Weng Qingbei; Lin Tiehao; Yuan Meijin; Yang Kai; Pang Yi

    2009-01-01

    Many viruses activate the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, thereby modulating diverse downstream signaling pathways associated with antiapoptosis, proliferation, cell cycling, protein synthesis and glucose metabolism, in order to augment their replication. To date, the role of the PI3K-Akt pathway in Baculovirus replication has not been defined. In the present study, we demonstrate that infection of Sf9 cells with Autographa californica multiple nucleopolyhedrovirus (AcMNPV) elevated cellular Akt phosphorylation at 1 h post-infection. The maximum Akt phosphorylation occurred at 6 h post-infection and remained unchanged until 18 h post-infection. The PI3K-specific inhibitor, LY294002, suppressed Akt phosphorylation in a dose-dependent manner, suggesting that AcMNPV-induced Akt phosphorylation is PI3K-dependent. The inhibition of PI3K-Akt activation by LY294002 significantly reduced the viral yield, including a reduction in budded viruses and occlusion bodies. The virus production was reduced only when the inhibitor was added within 24 h of infection, implying that activation of PI3K occurred early in infection. Correspondingly, both viral DNA replication and late (VP39) and very late (POLH) viral protein expression were impaired by LY294002 treatment; LY294002 had no effect on immediate-early (IE1) and early-late (GP64) protein expression. These results demonstrate that the PI3K-Akt pathway is required for efficient Baculovirus replication.

  17. Genetics of bipolar disorder

    OpenAIRE

    Kerner, Berit

    2014-01-01

    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 ...

  18. [Antidepressants in bipolar disorder].

    Science.gov (United States)

    Courtet, P; Samalin, L; Olié, E

    2011-12-01

    Whereas mania defines the bipolar disorder, depression is the major challenge of treatment. In general, depressions are more frequent, longer, with a major prognostic impact in terms of disability and suicide. How should we treat a patient with bipolar depression? Antidepressants are the treatment of choice for depression, but not in the bipolar disorder. In this context, we have traditionally accepted that antidepressants are effective but they were inducing a significant risk of destabilization of the bipolar disorder, because of the transitions to mania and rapid cycling. Current data reconsider both the two aspects of this risk-benefit ratio. The effectiveness of antidepressants finally seems very limited, especially after the more recent studies with a robust methodology. Manic switches and rapid cycling may not be increased, particularly with new antidepressants and mood stabilizer combinations. The current literature reminds us that these course's modalities are inherent to the disease, with numerous risk factors, and among them, exposure to antidepressants. Who are the bipolar patients who only get the benefits of antidepressant treatment? Research will tell. They are in any case limited. How to navigate in our treatment strategies ? By choosing first drugs that demonstrated efficacy in bipolar depression. When the situation is more complex, "primum non nocere" should lead to support the prescription of the antidepressant in association with mood stabilizer. Copyright © 2011 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

  19. Selection-free gene repair after adenoviral vector transduction of designer nucleases: rescue of dystrophin synthesis in DMD muscle cell populations.

    Science.gov (United States)

    Maggio, Ignazio; Stefanucci, Luca; Janssen, Josephine M; Liu, Jin; Chen, Xiaoyu; Mouly, Vincent; Gonçalves, Manuel A F V

    2016-02-18

    Duchenne muscular dystrophy (DMD) is a fatal X-linked muscle-wasting disorder caused by mutations in the 2.4 Mb dystrophin-encoding DMD gene. The integration of gene delivery and gene editing technologies based on viral vectors and sequence-specific designer nucleases, respectively, constitutes a potential therapeutic modality for permanently repairing defective DMD alleles in patient-derived myogenic cells. Therefore, we sought to investigate the feasibility of combining adenoviral vectors (AdVs) with CRISPR/Cas9 RNA-guided nucleases (RGNs) alone or together with transcriptional activator-like effector nucleases (TALENs), for endogenous DMD repair through non-homologous end-joining (NHEJ). The strategies tested involved; incorporating small insertions or deletions at out-of-frame sequences for reading frame resetting, splice acceptor knockout for DNA-level exon skipping, and RGN-RGN or RGN-TALEN multiplexing for targeted exon(s) removal. We demonstrate that genome editing based on the activation and recruitment of the NHEJ DNA repair pathway after AdV delivery of designer nuclease genes, is a versatile and robust approach for repairing DMD mutations in bulk populations of patient-derived muscle progenitor cells (up to 37% of corrected DMD templates). These results open up a DNA-level genetic medicine strategy in which viral vector-mediated transient designer nuclease expression leads to permanent and regulated dystrophin synthesis from corrected native DMD alleles. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Plasma membrane events associated with the meiotic divisions in the amphibian oocyte: insights into the evolution of insulin transduction systems and cell signaling

    Directory of Open Access Journals (Sweden)

    Morrill Gene A

    2013-01-01

    Full Text Available Abstract Background Insulin and its plasma membrane receptor constitute an ancient response system critical to cell growth and differentiation. Studies using intact Rana pipiens oocytes have shown that insulin can act at receptors on the oocyte surface to initiate resumption of the first meiotic division. We have reexamined the insulin-induced cascade of electrical and ion transport-related plasma membrane events using both oocytes and intact plasma membranes in order to characterize the insulin receptor-steroid response system associated with the meiotic divisions. Results [125I]Insulin binding (Kd = 54 ± 6 nM at the oocyte plasma membrane activates membrane serine protease(s, followed by the loss of low affinity ouabain binding sites, with a concomitant 3–4 fold increase in high affinity ouabain binding sites. The changes in protease activity and ouabain binding are associated with increased Na+/Ca2+ exchange, increased endocytosis, decreased Na+ conductance resulting in membrane hyperpolarization, increased 2-deoxy-D-glucose uptake and a sustained elevation of intracellular pH (pHi. Hyperpolarization is largely due to Na+-channel inactivation and is the main driving force for glucose uptake by the oocyte via Na+/glucose cotransport. The Na+ sym- and antiporter systems are driven by the Na+ free energy gradient generated by Na+/K+-ATPase. Shifts in α and/or β Na+-pump subunits to caveolar (lipid raft membrane regions may activate Na/K-ATPase and contribute to the Na+ free energy gradient and the increase in both Na+/glucose co-transport and pHi. Conclusions Under physiological conditions, resumption of meiosis results from the concerted action of insulin and progesterone at the cell membrane. Insulin inactivates Na+ channels and mobilizes fully functional Na+-pumps, generating a Na+ free energy gradient which serves as the energy source for several membrane anti- and symporter systems.

  1. Transduction of normal and malignant oral epithelium by particle bombardment.

    Science.gov (United States)

    Shillitoe, E J; Noonan, S; Hinkle, C C; Marini, F C; Kellman, R M

    1998-01-01

    Although genetic approaches to the treatment and prevention of oral cancer are being developed, there are no suitable methods of transduction of the oral mucosa or early cancers. We therefore tested the technique of particle bombardment for its ability to transduce oral cancer cells in vitro and normal epithelium of the hamster cheek pouch in vivo. A gene gun was used to transfer a plasmid that encoded a marker/suicide fusion gene, beta-galactosidase-thymidine kinase (GAL-TEK), under control of a CMV promoter. For comparison we used the method of lipofection and an adenovirus vector. Particle bombardment transduced up to 13% of cells in culture, resulting in a 24.3% reduction in growth in the presence of ganciclovir. The efficiency of transduction was similar to that of lipofection but was much less than that of the adenovirus vector, which transduced 54% of cells and completely inhibited their growth in the presence of ganciclovir. Transduction of the hamster cheek pouch by particle bombardment produced expression of beta-galactosidase as judged by macroscopic staining, for up to 5 days. However, histological examination showed that the transduced cells were rare and superficial, and that administration of systemic ganciclovir did not lead to any changes in the tissue. Improvements in efficiency are necessary before the gene gun can be used in the management of oral cancer.

  2. 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.

  3. Depression and Bipolar Support Alliance

    Science.gov (United States)

    Depression and Bipolar Support Alliance Crisis Hotline Information Coping with a Crisis Suicide Prevention Information Psychiatric Hospitalization ... sign-up Education info, training, events Mood Disorders Depression Bipolar Disorder Anxiety Screening Center Co-occurring Illnesses/ ...

  4. 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.

  5. Signal transduction by the major histocompatibility complex class I molecule

    DEFF Research Database (Denmark)

    Pedersen, A E; Skov, Svend; 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...... and functioning, MHC-I molecules might be of importance for the maintenance of cellular homeostasis not only within the immune system, but also in the interplay between the immune system and other organ systems....

  6. Protein Transduction Based Therapies for Breast Cancer

    National Research Council Canada - National Science Library

    Robbins, Paul D

    2006-01-01

    We have demonstrated that certain transduction peptides such as 12 lysines and 12 arginines can facilitateinternalization into breast tumor lines with higher efficiency than smaller polymers of cationic amino acids...

  7. Capacitive axial position and speed transduction system

    International Nuclear Information System (INIS)

    Jimenez D, H.; Flores Ll, H.; Cabral P, A.; Ramirez J, F.J.; Galindo, S.

    1984-01-01

    A new and inexpensive circuit arrangement of a capacitive axial position and speed transduction system is described. Design details and the theory of operation of the device are briefly outlined together with performance results. (author)

  8. Protein Transduction Based Therapies for Breast Cancer

    National Research Council Canada - National Science Library

    Robbins, Paul D

    2004-01-01

    We have demonstrated that certain transduction peptides such as 12 lysines and 12 arginines can facilitate internalization into breast tumor lines with higher efficiency than smaller polymers of cationic amino acids...

  9. Protein Transduction Based Therapies for Breast Cancer

    National Research Council Canada - National Science Library

    Robbins, Paul D

    2005-01-01

    We have demonstrated that certain transduction peptides such as 12 lysines and 12 arginines can facilitate internalization into breast tumor lines with higher efficiency than smaller polymers of cationic amino acids...

  10. Bipolar Plasma Membrane Distribution of Phosphoinositides and Their Requirement for Auxin-Mediated Cell Polarity and Patterning in Arabidopsis

    NARCIS (Netherlands)

    Tejos, R.; Sauer, M.; Vanneste, S.; Palacios-Gomez, M.; Li, H.; Heilmann, M.; van Wijk, R.; Vermeer, J.E.M.; Heilmann, I.; Munnik, T.; Friml, J.

    2014-01-01

    Cell polarity manifested by asymmetric distribution of cargoes, such as receptors and transporters, within the plasma membrane (PM) is crucial for essential functions in multicellular organisms. In plants, cell polarity (re)establishment is intimately linked to patterning processes. Despite the

  11. 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. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Increased mRNA expression of peripheral glial cell markers in bipolar disorder: The effect of long-term lithium treatment.

    Science.gov (United States)

    Ferensztajn-Rochowiak, Ewa; Tarnowski, Maciej; Samochowiec, Jerzy; Michalak, Michal; Ratajczak, Mariusz Z; Rybakowski, Janusz K

    2016-09-01

    Neuroinflammation, with microglial activation as an important element, plays a role in the pathogenesis of bipolar disorder (BD). Also, in mood disorders, pathological changes have been demonstrated in macroglial cells, such as astrocyctes and oligodendrocytes. Postmortem brain studies of BD patients to assess glial cells, such as astrocytes and oligodendrocytes and their markers such as glial fibrillary acidic protein (GFAP), Olig1 and Olig2, produced controversial results. On the other hand, investigation of these markers in the peripheral blood of such patients has not been performed so far. In this study, we examined the mRNA levels of GFAP, Olig1 and Olig2, in the peripheral blood of three groups: 15 BD subjects with a duration of illness at least 10 years (mean 20±9 years) but never treated with lithium, 15 subjects with BD treated continuously with lithium for 8-40 years (mean 16±8 years), and 15 control subjects. The groups were age-and sex-matched. Expression of mRNA markers was measured by real-time quantitative reverse transcription PCR (RQ-PCR). We observed increased mRNA levels of the Olig1 and Olig 2 glial markers studied in the BD patients not taking lithium, compared with the control subjects and increased mRNA level of GFAP, compared with lithium-treated patients. In the lithium-treated BD patients GFAP and Olig1 expression was at similar levels to that in the control group. However, Olig 2 expression was even higher than in the BD patients not taking lithium. The possible mechanisms concerning the higher expression of peripheral mRNA markers in BD patients may involve ongoing inflammatory process, compensatory mechanisms and regenerative responses. The beneficial effect of lithium may be related to its anti-inflammatory properties. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  13. Depressive and bipolar disorders

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Hansen, Hanne Vibe; Demyttenaere, Koen

    2005-01-01

    BACKGROUND: There is increasing evidence that attitudes and beliefs are important in predicting adherence to treatment and medication in depressive and bipolar disorders. However, these attitudes have received little study in patients whose disorders were sufficiently severe to require...... hospitalization. METHOD: The Antidepressant Compliance Questionnaire (ADCQ) was mailed to a large population of patients with depressive or bipolar disorder, representative of patients treated in hospital settings in Denmark. RESULTS: Of the 1005 recipients, 49.9% responded to the letter. A large proportion....... Moreover, their partners agreed on these negative views. Women had a more negative view of the doctor-patient relationship than men, and patients with a depressive disorder had a more negative view of antidepressants than patients with bipolar disorder. The number of psychiatric hospitalizations...

  14. Finite-State Channel Models for Signal Transduction in Neural Systems

    OpenAIRE

    Eckford, Andrew W.; Loparo, Kenneth A.; Thomas, Peter J.

    2016-01-01

    Information theory provides powerful tools for understanding communication systems. This analysis can be applied to intercellular signal transduction, which is a means of chemical communication among cells and microbes. We discuss how to apply information-theoretic analysis to ligand-receptor systems, which form the signal carrier and receiver in intercellular signal transduction channels. We also discuss the applications of these results to neuroscience.

  15. Disruption of Microtubules Post-Virus Entry Enhances Adeno-Associated Virus Vector Transduction

    Science.gov (United States)

    Xiao, Ping-Jie; Mitchell, Angela M.; Huang, Lu; Li, Chengwen; Samulski, R. Jude

    2016-01-01

    Perinuclear retention of viral particles is a poorly understood phenomenon observed during many virus infections. In this study, we investigated whether perinuclear accumulation acts as a barrier to limit recombinant adeno-associated virus (rAAV) transduction. After nocodazole treatment to disrupt microtubules at microtubule-organization center (MT-MTOC) after virus entry, we observed higher rAAV transduction. To elucidate the role of MT-MTOC in rAAV infection and study its underlying mechanisms, we demonstrated that rAAV's perinuclear localization was retained by MT-MTOC with fluorescent analysis, and enhanced rAAV transduction from MT-MTOC disruption was dependent on the rAAV capsid's nuclear import signals. Interestingly, after knocking down RhoA or inhibiting its downstream effectors (ROCK and Actin), MT-MTOC disruption failed to increase rAAV transduction or nuclear entry. These data suggest that enhancement of rAAV transduction is the result of increased trafficking to the nucleus via the RhoA-ROCK-Actin pathway. Ten-fold higher rAAV transduction was also observed by disrupting MT-MTOC in brain, liver, and tumor in vivo. In summary, this study indicates that virus perinuclear accumulation at MT-MTOC is a barrier-limiting parameter for effective rAAV transduction and defines a novel defense mechanism by which host cells restrain viral invasion. PMID:26942476

  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. CesRK, a two-component signal transduction system in Listeria monocytogenes, responds to the presence of cell wall-acting antibiotics and affects beta-lactam resistance

    DEFF Research Database (Denmark)

    Kallipolitis, Birgitte H; Ingmer, Hanne; Gahan, Cormac G

    2003-01-01

    of a putative two-component signal transduction system that plays a role in the virulence and ethanol tolerance of L. monocytogenes. Here we present evidence that the response regulator, CesR, and a histidine protein kinase, CesK, which is encoded by the gene downstream from cesR, are involved in the ability...

  18. MRP-1/CD9 gene transduction regulates the actin cytoskeleton through the downregulation of WAVE2.

    Science.gov (United States)

    Huang, C-L; Ueno, M; Liu, D; Masuya, D; Nakano, J; Yokomise, H; Nakagawa, T; Miyake, M

    2006-10-19

    Motility-related protein-1 (MRP-1/CD9) is involved in cell motility. We studied the change in the actin cytoskeleton, and the expression of actin-related protein (Arp) 2 and Arp3 and the Wiskott-Aldrich syndrome protein (WASP) family according to MRP-1/CD9 gene transduction into HT1080 cells. The frequency of cells with lamellipodia was significantly lower in MRP-1/CD9-transfected HT1080 cells than in control HT1080 cells (PMRP-1/CD9 gene transduction affected the subcellular localization of Arp2 and Arp3 proteins. Furthermore, MRP-1/CD9 gene transduction induced a downregulation of WAVE2 expression (PMRP-1/CD9 monoclonal antibody inhibited downregulation of WAVE2 in MRP-1/CD9-transfected HT1080 cells (PMRP-1/CD9 gene transduction. Furthermore, downregulation of WAVE2 by transfection of WAVE2-specific small interfering RNA (siRNA) mimicked the morphological effects of MRP-1/CD9 gene transduction and suppressed cell motility. However, transfection of each siRNA for Wnt1, Wnt2b1 or Wnt5a did not affect WAVE2 expression. Transfection of WAVE2-specific siRNA also did not affect expressions of these Wnts. These results indicate that MRP-1/CD9 regulates the actin cytoskeleton by downregulating of the WAVE2, through the Wnt-independent signal pathway.

  19. Defective neuronal migration and inhibition of bipolar to multipolar transition of migrating neural cells by Mesoderm-Specific Transcript, Mest, in the developing mouse neocortex.

    Science.gov (United States)

    Ji, Liting; Bishayee, Kausik; Sadra, Ali; Choi, Seunghyuk; Choi, Wooyul; Moon, Sungho; Jho, Eek-Hoon; Huh, Sung-Oh

    2017-07-04

    Brain developmental disorders such as lissencephaly can result from faulty neuronal migration and differentiation during the formation of the mammalian neocortex. The cerebral cortex is a modular structure, where developmentally, newborn neurons are generated as a neuro-epithelial sheet and subsequently differentiate, migrate and organize into their final positions in the cerebral cortical plate via a process involving both tangential and radial migration. The specific role of Mest, an imprinted gene, in neuronal migration has not been previously studied. In this work, we reduced expression of Mest with in utero electroporation of neuronal progenitors in the developing embryonic mouse neocortex. Reduction of Mest levels by shRNA significantly reduced the number of neurons migrating to the cortical plate. Also, Mest-knockdown disrupted the transition of bipolar neurons into multipolar neurons migrating out of the sub-ventricular zone region. The migrating neurons also adopted a more tangential migration pattern upon knockdown of the Mest message, losing their potential to attach to radial glia cells, required for radial migration. The differentiation and migration properties of neurons via Wnt-Akt signaling were affected by Mest changes. In addition, miR-335, encoded in a Mest gene intron, was identified as being responsible for blocking the default tangential migration of the neurons. Our results suggest that Mest and its intron product, miR-335, play important roles in neuronal migration with Mest regulating the morphological transition of primary neurons required in the formation of the mammalian neocortex. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Novel multiple criteria decision making methods based on bipolar neu trosophic sets and bipolar neutrosophic graphs

    OpenAIRE

    Muhammad Akram; Musavarah Sarwar

    2017-01-01

    In this research article, we present certain notions of bipolar neutrosophic graphs. We study the dominating and independent sets of bipolar neutrosophic graphs. We describe novel multiple criteria decision making methods based on bipolar neutrosophic sets and bipolar neutrosophic graphs.

  1. Discrete bipolar universal integrals

    Czech Academy of Sciences Publication Activity Database

    Greco, S.; Mesiar, Radko; Rindone, F.

    2014-01-01

    Roč. 252, č. 1 (2014), s. 55-65 ISSN 0165-0114 R&D Projects: GA ČR GAP402/11/0378 Institutional support: RVO:67985556 Keywords : bipolar integral * universal integral * Choquet integral Subject RIV: BA - General Mathematics Impact factor: 1.986, year: 2014 http://library.utia.cas.cz/separaty/2014/E/mesiar-0432224.pdf

  2. Does bipolar pacemaker current activate blood platelets?

    DEFF Research Database (Denmark)

    Gjesdal, Grunde; Hansen, Annebirthe Bo; Brandes, Axel

    2009-01-01

    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......OBJECTIVE: The aim of this study was to investigate whether bipolar pacemaker current lead can activate blood platelets. The null hypothesis was that 1 minute of electrical stimulation of platelets would not influence their subsequent reactivity to adenosine diphosphate (ADP). BACKGROUND: Both...... 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...

  3. Bipolar Plasma Membrane Distribution of Phosphoinositides and Their Requirement for Auxin-Mediated Cell Polarity and Patterning in Arabidopsis.

    Science.gov (United States)

    Tejos, Ricardo; Sauer, Michael; Vanneste, Steffen; Palacios-Gomez, Miriam; Li, Hongjiang; Heilmann, Mareike; van Wijk, Ringo; Vermeer, Joop E M; Heilmann, Ingo; Munnik, Teun; Friml, Jiří

    2014-05-01

    Cell polarity manifested by asymmetric distribution of cargoes, such as receptors and transporters, within the plasma membrane (PM) is crucial for essential functions in multicellular organisms. In plants, cell polarity (re)establishment is intimately linked to patterning processes. Despite the importance of cell polarity, its underlying mechanisms are still largely unknown, including the definition and distinctiveness of the polar domains within the PM. Here, we show in Arabidopsis thaliana that the signaling membrane components, the phosphoinositides phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P 2 ] as well as PtdIns4P 5-kinases mediating their interconversion, are specifically enriched at apical and basal polar plasma membrane domains. The PtdIns4P 5-kinases PIP5K1 and PIP5K2 are redundantly required for polar localization of specifically apical and basal cargoes, such as PIN-FORMED transporters for the plant hormone auxin. As a consequence of the polarity defects, instructive auxin gradients as well as embryonic and postembryonic patterning are severely compromised. Furthermore, auxin itself regulates PIP5K transcription and PtdIns4P and PtdIns(4,5)P 2 levels, in particular their association with polar PM domains. Our results provide insight into the polar domain-delineating mechanisms in plant cells that depend on apical and basal distribution of membrane lipids and are essential for embryonic and postembryonic patterning. © 2014 American Society of Plant Biologists. All rights reserved.

  4. [Spouses and bipolar disorder].

    Science.gov (United States)

    Ellouze, F; Ayedi, S; Cherif, W; Ben Abla, T; M'rad, M F

    2011-02-01

    To assess the quality of life of a population of spouses of bipolar patients compared with a control population. We conducted a cross-sectional study which included two groups: a group of 30 spouses of patients followed for bipolar I disorder according to DSM IV criteria and a second group of 30 subjects from the general population. Both groups were matched by age, sex, marital status and socioeconomic level. This device was designed to limit the differences between the two groups solely those of the bipolar illness. Evaluating the quality of life was achieved using the quality of life scale: SF-36. This is a scale that has already been translated and validated in dialect Arabic. Regarding sociodemographic variables, the two study groups differed only for: recreation, friendly relations and the couple relationship that included more and better skills among the control group. In the categorical approach, the quality of life was impaired in 60% of spouses and 40% of controls with a statistically significant difference. The following standardized dimensions: mental health (D4), limitation due to mental health (D5), life and relationship with others (D6) and perceived health (D8) and mental component (CM) were significantly altered in patients' spouses compared to controls. We found significant differences between the two groups for: overall average score (51.1 vs. 68.2), mental health (D4), limitation due to mental health (D5), life and relationship with others (D6), perceived health (D8) and perceived health (D8) standards. The impairment of quality of life of bipolar patients' spouses is related to the extra responsibility, stress, financial problems and health problems, stigma, and loss of security of the person loved. Considering the consequences that the appearance of bipolar disorder on the patient's spouse may have, certain measures must be proposed to improve their quality of life. Copyright © 2010 L'Encéphale, Paris. Published by Elsevier Masson SAS. All

  5. ON BIPOLAR SINGLE VALUED NEUTROSOPHIC GRAPHS

    OpenAIRE

    Broumi, Said; Talea, Mohamed; Bakali, Assia; Smarandache, Florentin

    2016-01-01

    In this article, we combine the concept of bipolar neutrosophic set and graph theory. We introduce the notions of bipolar single valued neutrosophic graphs, strong bipolar single valued neutrosophic graphs, complete bipolar single valued neutrosophic graphs, regular bipolar single valued neutrosophic graphs and investigate some of their related properties.

  6. 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.

  7. Early Intervention in Bipolar Disorder.

    Science.gov (United States)

    Vieta, Eduard; Salagre, Estela; Grande, Iria; Carvalho, André F; Fernandes, Brisa S; Berk, Michael; Birmaher, Boris; Tohen, Mauricio; Suppes, Trisha

    2018-01-24

    Bipolar disorder is a recurrent disorder that affects more than 1% of the world population and usually has its onset during youth. Its chronic course is associated with high rates of morbidity and mortality, making bipolar disorder one of the main causes of disability among young and working-age people. The implementation of early intervention strategies may help to change the outcome of the illness and avert potentially irreversible harm to patients with bipolar disorder, as early phases may be more responsive to treatment and may need less aggressive therapies. Early intervention in bipolar disorder is gaining momentum. Current evidence emerging from longitudinal studies indicates that parental early-onset bipolar disorder is the most consistent risk factor for bipolar disorder. Longitudinal studies also indicate that a full-blown manic episode is often preceded by a variety of prodromal symptoms, particularly subsyndromal manic symptoms, therefore supporting the existence of an at-risk state in bipolar disorder that could be targeted through early intervention. There are also identifiable risk factors that influence the course of bipolar disorder, some of them potentially modifiable. Valid biomarkers or diagnosis tools to help clinicians identify individuals at high risk of conversion to bipolar disorder are still lacking, although there are some promising early results. Pending more solid evidence on the best treatment strategy in early phases of bipolar disorder, physicians should carefully weigh the risks and benefits of each intervention. Further studies will provide the evidence needed to finish shaping the concept of early intervention.

  8. Purinergic mechanosensory transduction and visceral pain

    Directory of Open Access Journals (Sweden)

    Burnstock Geoffrey

    2009-11-01

    Full Text Available Abstract In this review, evidence is presented to support the hypothesis that mechanosensory transduction occurs in tubes and sacs and can initiate visceral pain. Experimental evidence for this mechanism in urinary bladder, ureter, gut, lung, uterus, tooth-pulp and tongue is reviewed. Potential therapeutic strategies are considered for the treatment of visceral pain in such conditions as renal colic, interstitial cystitis and inflammatory bowel disease by agents that interfere with mechanosensory transduction in the organs considered, including P2X3 and P2X2/3 receptor antagonists that are orally bioavailable and stable in vivo and agents that inhibit or enhance ATP release and breakdown.

  9. Molecular mechanisms of root gravity sensing and signal transduction.

    Science.gov (United States)

    Strohm, Allison K; Baldwin, Katherine L; Masson, Patrick H

    2012-01-01

    Plants use gravity as a guide to direct their roots down into the soil to anchor themselves and to find resources needed for growth and development. In higher plants, the columella cells of the root tip form the primary site of gravity sensing, and in these cells the sedimentation of dense, starch-filled plastids (amyloplasts) triggers gravity signal transduction. This generates an auxin gradient across the root cap that is transmitted to the elongation zone where it promotes differential cell elongation, allowing the root to direct itself downward. It is still not well understood how amyloplast sedimentation leads to auxin redistribution. Models have been proposed to explain how mechanosensitive ion channels or ligand-receptor interactions could connect these events. Although their roles are still unclear, possible second messengers in this process include protons, Ca(2+), and inositol 1,4,5-triphosphate. Upon gravistimulation, the auxin efflux facilitators PIN3 and PIN7 relocalize to the lower side of the columella cells and mediate auxin redistribution. However, evidence for an auxin-independent secondary mechanism of gravity sensing and signal transduction suggests that this physiological process is quite complex. Furthermore, plants must integrate a variety of environmental cues, resulting in multifaceted relationships between gravitropism and other directional growth responses such as hydro-, photo-, and thigmotropism. Copyright © 2011 Wiley Periodicals, Inc.

  10. 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.

  11. 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...

  12. Lysophosphatidylcholine-induced taurine release in HeLa cells involves kinases activity

    DEFF Research Database (Denmark)

    Lambert, Ian H.; Falktoft, Birgitte

    2000-01-01

    Cell biology, Signal transduction, Lysophospholipids, regulatory volume decrease, Organic osmolytes......Cell biology, Signal transduction, Lysophospholipids, regulatory volume decrease, Organic osmolytes...

  13. Swelling induced taurine efflux from HeLa cells. In: Taurine 4: Taurine and Excitable Tissues

    DEFF Research Database (Denmark)

    Lambert, Ian H.; Sepúlveda, Francisco V.

    2000-01-01

    Cell biology, Signal transduction, Lysophospholipids, Regulatory volume decrease, Organic osmolytes......Cell biology, Signal transduction, Lysophospholipids, Regulatory volume decrease, Organic osmolytes...

  14. Bipolar Disorder and Alcoholism: Are They Related?

    Science.gov (United States)

    ... Is there a connection between bipolar disorder and alcoholism? Answers from Daniel K. Hall-Flavin, M.D. Bipolar disorder and alcoholism often occur together. Although the association between bipolar ...

  15. Modeling evolution of crosstalk in noisy signal transduction networks

    Science.gov (United States)

    Tareen, Ammar; Wingreen, Ned S.; Mukhopadhyay, Ranjan

    2018-02-01

    Signal transduction networks can form highly interconnected systems within cells due to crosstalk between constituent pathways. To better understand the evolutionary design principles underlying such networks, we study the evolution of crosstalk for two parallel signaling pathways that arise via gene duplication. We use a sequence-based evolutionary algorithm and evolve the network based on two physically motivated fitness functions related to information transmission. We find that one fitness function leads to a high degree of crosstalk while the other leads to pathway specificity. Our results offer insights on the relationship between network architecture and information transmission for noisy biomolecular networks.

  16. [Creativity and bipolar disorder].

    Science.gov (United States)

    Maçkalı, Zeynep; Gülöksüz, Sinan; Oral, Timuçin

    2014-01-01

    The relationship between creativity and bipolar disorder has been an intriguing topic since ancient times. Early studies focused on describing characteristics of creative people. From the last quarter of the twentieth century, researchers began to focus on the relationship between mood disorders and creativity. Initially, the studies were based on biographical texts and the obtained results indicated a relationship between these two concepts. The limitations of the retrospective studies led the researchers to develop systematic investigations into this area. The systematic studies that have focused on artistic creativity have examined both the prevalence of mood disorders and the creative process. In addition, a group of researchers addressed the relationship in terms of affective temperaments. Through the end of the 90's, the scope of creativity was widened and the notion of everyday creativity was proposed. The emergence of this notion led researchers to investigate the associations of the creative process in ordinary (non-artist) individuals. In this review, the descriptions of creativity and creative process are mentioned. Also, the creative process is addressed with regards to bipolar disorder. Then, the relationship between creativity and bipolar disorder are evaluated in terms of aforementioned studies (biographical, systematic, psychobiographical, affective temperaments). In addition, a new model, the "Shared Vulnerability Model" which was developed to explain the relationship between creativity and psychopathology is introduced. Finally, the methodological limitations and the suggestions for resolving these limitations are included.

  17. 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.

  18. Energy transduction in lactic acid bacteria

    NARCIS (Netherlands)

    Poolman, Bert

    In the discovery of some general principles of energy transduction, lactic acid bacteria have played an important role. In this review, the energy transducing processes of lactic acid bacteria are discussed with the emphasis on the major developments of the past 5 years. This work not only includes

  19. Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity.

    Science.gov (United States)

    Elosegui-Artola, Alberto; Oria, Roger; Chen, Yunfeng; Kosmalska, Anita; Pérez-González, Carlos; Castro, Natalia; Zhu, Cheng; Trepat, Xavier; Roca-Cusachs, Pere

    2016-05-01

    Cell function depends on tissue rigidity, which cells probe by applying and transmitting forces to their extracellular matrix, and then transducing them into biochemical signals. Here we show that in response to matrix rigidity and density, force transmission and transduction are explained by the mechanical properties of the actin-talin-integrin-fibronectin clutch. We demonstrate that force transmission is regulated by a dynamic clutch mechanism, which unveils its fundamental biphasic force/rigidity relationship on talin depletion. Force transduction is triggered by talin unfolding above a stiffness threshold. Below this threshold, integrins unbind and release force before talin can unfold. Above the threshold, talin unfolds and binds to vinculin, leading to adhesion growth and YAP nuclear translocation. Matrix density, myosin contractility, integrin ligation and talin mechanical stability differently and nonlinearly regulate both force transmission and the transduction threshold. In all cases, coupling of talin unfolding dynamics to a theoretical clutch model quantitatively predicts cell response.

  20. The effect of antimicrobials on verocytotoxin bacteriophage transduction under bovine rumen fluid and broth conditions

    Directory of Open Access Journals (Sweden)

    Nyambe S.

    2017-11-01

    Full Text Available The verocytotoxin genes in verocytotoxigenic Escherichia coli (VTEC are carried by bacteriophages, incorporated into the bacterial genome (prophage. Antibiotics may promote phage replication and release to infect other cells (transduction, thus leading to the emergence of new VTEC strains. This study investigated transduction of a verocytotoxin2-encoding bacteriophage (3538(vtx2::cat under laboratory conditions, including the effect of antibiotic treatments. Luria-Bertani Miller broth and rumen fluid (raw and sterilised by irradiation were inoculated with the donor (C600φ3538(Δvtx2::cat and recipient (E. coli C600::kanamycinR strains (4 log10 cfu/mL and incubated at 38°C. Antibiotic treatments (minimal inhibitory and sub-inhibitory concentrations of ampicillin, cefquinome, oxytetracycline and sodium sulfamethazine were applied after 3 h. Samples were tested for donor, recipient, cell-free phage and transductants at times t = 0, 3, 4, 6, 27 (24 h post-antibiotic treatment and 51 h. Free phage was detected in the untreated broth and rumen samples, as were the transductants confirmed by polymerase chain reaction. The antibiotic treatments did not significantly (P > 0.01 increase the concentrations of free phage or transductants detected. It was therefore concluded that, under laboratory conditions, the antibiotics tested did not induce bacteriophage lysis, release and infection of new bacterial cells beyond that constitutively found in the phage population.

  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)

    De Asis, Edward D Jr; Wood, Sally; Leung, Joseph; Nguyen, Cattien V

    2010-01-01

    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. Tyrosine phosphorylation in signal transduction

    International Nuclear Information System (INIS)

    Roberts, T.M.; Kaplan, D.; Morgan, W.; Keller, T.; Mamon, H.; Piwnica-Worms, H.; Druker, B.; Whitman, M.; Morrison, D.; Cohen, B.; Schaffhausen, B.; Cantley, L.; Rapp, U.

    1988-01-01

    Recent work has focused on the elucidation of the mechanisms by which membrane-bound tyrosine kinases transmit signals within the cell. To examine the role of tyrosine phosphorylation the authors have employed the following strategy. First, they have utilized antibodies to phosphotyrosine (anti-P.Tyr) to identify candidate substrates of various tyrosine kinases, such as pp60 c-src , the CSF- receptor, or the platelet-derived growth factor (PDGF) receptor. Second, they have attempted to characterize the biochemical properties of the putative substrates and to determine in what manner these properties are modified by phosphorylation on tyrosine residues. In this endeavor, they are recapitulating the classic biochemical analysis used to study the effect of kinases on metabolism. The final portion of our work consists of using modern molecular biological strategies to clone the genes or cDNAs for the substrates and overproduce the relevant proteins for studies in vitro in defined systems. This paper describes the first and second aspects of this strategy, the identification and characterization of novel substrate molecules

  3. Rod Outer Segment Development Influences AAV-Mediated Photoreceptor Transduction After Subretinal Injection.

    Science.gov (United States)

    Petit, Lolita; Ma, Shan; Cheng, Shun-Yun; Gao, Guangping; Punzo, Claudio

    2017-06-01

    Vectors based on the adeno-associated virus (AAV) are currently the preferred tools for delivering genes to photoreceptors (PR) in small and large animals. AAVs have been applied successfully in various models of PR dystrophies. However, unknown barriers still limit AAV's efficient application in several forms of severe PR degenerations due to insufficient transgene expression and/or treated cells at the time of injection. Optimizations of PR gene therapy strategies will likely benefit from the identification of the cellular factors that influence PR transduction. Interestingly, recent studies have shown that the AAV transduction profile of PRs differs significantly between neonatal and adult mouse retinas after subretinal injection. This phenomenon may provide clues to identify host factors that influence the efficiency of AAV-mediated PR transduction. This study demonstrates that rod outer segments are critical modulators of efficient AAV-mediated rod transduction. During retinal development, rod transduction correlated temporally and spatially with the differentiation order of PRs when vectors were introduced subretinally but not when introduced intravitreally. All subretinally injected vectors had an initial preference to transduce cones in the absence of formed rod outer segments and then displayed a preference for rods as the cells matured, independently of the expression cassette or AAV serotype. Consistent with this observation, altered development of rod outer segments was associated with a strong reduction of rod transduction and an increase in the percentage of transduced cones by 2- to 2.8-fold. A similar increase of cone transduction was observed in the adult retinal degeneration 1 (rd1) retina compared to wild-type mice. These results suggest that the loss of rod outer segments in diseased retinas could markedly affect gene transfer efficiency of AAV vectors by limiting the ability of AAVs to infect dying rods efficiently. This information could be

  4. The impact of bipolar depression.

    Science.gov (United States)

    Post, Robert M

    2005-01-01

    Bipolar disorder is a chronic, intermittent illness that is associated with high morbidity and mortality. In addition, patients with bipolar disorder often have comorbid psychiatric conditions (such as anxiety disorders, alcohol or substance abuse, and eating disorders) or medical disorders (such as obesity), which result in increased burden of illness for the patients, family members, and treating clinicians. Although bipolar disorder consists of recurring episodes of mania and depression, patients spend more time depressed than manic. Bipolar depression is associated with a greater risk of suicide and of impairment in work, social, or family life than mania. This health burden also results in direct and indirect economic costs to the individual and society at large. Bipolar depression is often undiagnosed or misdiagnosed as unipolar depression, resulting in incorrect or inadequate treatment. Available treatments for bipolar depression include medications such as lithium, selected anticonvulsants, and the atypical antipsychotics. Traditional antidepressants are not recommended as monotherapy for bipolar depression as they can induce switching to mania. Early and accurate diagnosis, aggressive management, and earlier prophylactic treatment regimens are needed to overcome the impact of depressive episodes in patients with bipolar disorder.

  5. 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

  6. 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

  7. The SUMOylation Pathway Restricts Gene Transduction by Adeno-Associated Viruses.

    Directory of Open Access Journals (Sweden)

    Christina Hölscher

    2015-12-01

    Full Text Available Adeno-associated viruses are members of the genus dependoviruses of the parvoviridae family. AAV vectors are considered promising vectors for gene therapy and genetic vaccination as they can be easily produced, are highly stable and non-pathogenic. Nevertheless, transduction of cells in vitro and in vivo by AAV in the absence of a helper virus is comparatively inefficient requiring high multiplicity of infection. Several bottlenecks for AAV transduction have previously been described, including release from endosomes, nuclear transport and conversion of the single stranded DNA into a double stranded molecule. We hypothesized that the bottlenecks in AAV transduction are, in part, due to the presence of host cell restriction factors acting directly or indirectly on the AAV-mediated gene transduction. In order to identify such factors we performed a whole genome siRNA screen which identified a number of putative genes interfering with AAV gene transduction. A number of factors, yielding the highest scores, were identified as members of the SUMOylation pathway. We identified Ubc9, the E2 conjugating enzyme as well as Sae1 and Sae2, enzymes responsible for activating E1, as factors involved in restricting AAV. The restriction effect, mediated by these factors, was validated and reproduced independently. Our data indicate that SUMOylation targets entry of AAV capsids and not downstream processes of uncoating, including DNA single strand conversion or DNA damage signaling. We suggest that transiently targeting SUMOylation will enhance application of AAV in vitro and in vivo.

  8. Analysis of the gravitaxis signal transduction chain in Euglena gracilis

    Science.gov (United States)

    Nasir, Adeel

    Abstract Euglena gracilis is a photosynthetic, eukaryotic flagellate. It can adapt autotrophic and heterotrophic mode of growth and respond to different stimuli, this makes it an organism of choice for different research disciplines. It swims to reach a suitable niche by employing different stimuli such as oxygen, light, gravity and different chemicals. Among these stimuli light and gravity are the most important. Phototaxis (locomotion under light stimulus) and gravitaxis (locomotion under gravity stimulus) synergistically help cells to attain an optimal niche in the environment. However, in the complete absence of light or under scarcity of detectable light, cells can totally depend on gravity to find its swimming path. Therefore gravity has certain advantages over other stimuli.Unlike phototatic signal transduction chain of Euglena gracilis no clear primary gravity receptor has been identified in Euglena cells so far. However, there are some convincing evidence that TRP like channels act as a primary gravity receptor in Euglena gracilis.Use of different inhibitors gave rise to the involvement of protein kinase and calmodulin proteins in signal transduction chain of Euglena gracilis. Recently, specific calmodulin (Calmodulin 2) and protein kinase (PKA) have been identified as potential candidates of gravitactic signal transduction chain. Further characterization and investigation of these candidates was required. Therefore a combination of biochemical and genetic techniques was employed to localize proteins in cells and also to find interacting partners. For localization studies, specific antibodies were raised and characterized. Specificity of antibodies was validated by knockdown mutants, Invitro-translated proteins and heterologously expressed proteins. Cell fractionation studies, involving separation of the cell body and flagella for western blot analysis and confocal immunofluorescence studies were performed for subcellular localization. In order to find

  9. Novel multiple criteria decision making methods based on bipolar neutrosophic sets and bipolar neutrosophic graphs

    OpenAIRE

    Muhammad, Akram; Musavarah, Sarwar

    2016-01-01

    In this research study, we introduce the concept of bipolar neutrosophic graphs. We present the dominating and independent sets of bipolar neutrosophic graphs. We describe novel multiple criteria decision making methods based on bipolar neutrosophic sets and bipolar neutrosophic graphs. We also develop an algorithm for computing domination in bipolar neutrosophic graphs.

  10. Effects of pergolide mesylate on transduction efficiency of PEP-1-catalase protein

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Eun Jeong; Kim, Dae Won; Kim, Young Nam; Kim, So Mi [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Lim, Soon Sung [Department of Food Science and Nutrition and RIC Center, Hallym University, Chunchon 200-702 (Korea, Republic of); Kang, Tae-Cheon [Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Kwon, Hyeok Yil [Department of Physiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Kim, Duk-Soo [Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 330-090 (Korea, Republic of); Cho, Sung-Woo [Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Hwang, Hyun Sook, E-mail: wazzup@hallym.ac.kr [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)

    2011-03-18

    Research highlights: {yields} We studied effects of pergolide mesylate (PM) on in vitro and in vivo transduction of PEP-1-catalase. {yields} PEP-1-catatase inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation. {yields} PM enhanced the transduction of PEP-1-catalase into HaCaT cells and skin tissue. {yields} PM increased anti-inflammatory activity of PEP-1-catalase. {yields} PM stimulated therapeutic action of anti-oxidant enzyme catalase in oxidative-related diseases. -- Abstract: The low transduction efficiency of various proteins is an obstacle to their therapeutic application. However, protein transduction domains (PTDs) are well-known for a highly effective tool for exogenous protein delivery to cells. We examined the effects of pergolide mesylate (PM) on the transduction of PEP-1-catalase into HaCaT human keratinocytes and mice skin and on the anti-inflammatory activity of PEP-1-catatase against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation using Western blot and histological analysis. PM enhanced the time- and dose-dependent transduction of PEP-1-catalase into HaCaT cells without affecting the cellular toxicity. In a mouse edema model, PEP-1-catalase inhibited the increased expressions of inflammatory mediators and cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1{beta}, and tumor necrosis factor-{alpha} induced by TPA. On the other hand, PM alone failed to exert any significant anti-inflammatory effects. However, the anti-inflammatory effect of co-treatment with PEP-1-catalase and PM was more potent than that of PEP-1-catalase alone. Our results indicate that PM may enhance the delivery of PTDs fusion therapeutic proteins to target cells and tissues and has potential to increase their therapeutic effects of such drugs against various diseases.

  11. Effects of pergolide mesylate on transduction efficiency of PEP-1-catalase protein

    International Nuclear Information System (INIS)

    Sohn, Eun Jeong; Kim, Dae Won; Kim, Young Nam; Kim, So Mi; Lim, Soon Sung; Kang, Tae-Cheon; Kwon, Hyeok Yil; Kim, Duk-Soo; Cho, Sung-Woo; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Hwang, Hyun Sook; Choi, Soo Young

    2011-01-01

    Research highlights: → We studied effects of pergolide mesylate (PM) on in vitro and in vivo transduction of PEP-1-catalase. → PEP-1-catatase inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation. → PM enhanced the transduction of PEP-1-catalase into HaCaT cells and skin tissue. → PM increased anti-inflammatory activity of PEP-1-catalase. → PM stimulated therapeutic action of anti-oxidant enzyme catalase in oxidative-related diseases. -- Abstract: The low transduction efficiency of various proteins is an obstacle to their therapeutic application. However, protein transduction domains (PTDs) are well-known for a highly effective tool for exogenous protein delivery to cells. We examined the effects of pergolide mesylate (PM) on the transduction of PEP-1-catalase into HaCaT human keratinocytes and mice skin and on the anti-inflammatory activity of PEP-1-catatase against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation using Western blot and histological analysis. PM enhanced the time- and dose-dependent transduction of PEP-1-catalase into HaCaT cells without affecting the cellular toxicity. In a mouse edema model, PEP-1-catalase inhibited the increased expressions of inflammatory mediators and cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1β, and tumor necrosis factor-α induced by TPA. On the other hand, PM alone failed to exert any significant anti-inflammatory effects. However, the anti-inflammatory effect of co-treatment with PEP-1-catalase and PM was more potent than that of PEP-1-catalase alone. Our results indicate that PM may enhance the delivery of PTDs fusion therapeutic proteins to target cells and tissues and has potential to increase their therapeutic effects of such drugs against various diseases.

  12. Polarization Vision and the Development of Retinal Network Models. Neuronal Information Transfer Functions From Cones and Horizontal Cells to Bipolar Cells

    National Research Council Canada - National Science Library

    Kamermans, Maarten; Hawryshyn, Craig

    2008-01-01

    ... with. Furthermore, the study demonstrated how horizontal cells, that store global stimulus parameters such as spectral composition and e-vector orientation of the global stimulus, adjust the gains...

  13. Prolactin receptor and signal transduction to milk protein genes

    Energy Technology Data Exchange (ETDEWEB)

    Djiane, J.; Daniel, N.; Bignon, C. [Unite d`Endocrinologie Moleculaire, Jouy en Josas (France)] [and others

    1994-06-01

    After cloning of the mammary gland prolactin (PRL) receptor cDNA, a functional assay was established using co-transfection of PRL receptor cDNA together with a milk protein promoter/chloramphenicol acetyl transferase (CAT) construct in Chinese hamster ovary (CHO) cells. Different mutants of the PRL receptor were tested in this CAT assay to delimit the domains in the receptor necessary for signal transduction to milk protein genes. In CHO cells stably transfected with PRL receptor cDNA, high numbers of PRL receptor are expressed. By metabolic labeling and immunoprecipitation, expressed PRL receptor was identified as a single species of 100 kDa. Using these cells, we analyzed the effects of PRL on intracellular free Ca{sup ++} concentration. PRL stimulates Ca{sup ++} entry and induces secondary Ca{sup ++} mobilization. The entry of Ca{sup ++} is a result of an increase in K{sup +} conductance that hyperpolarizes the membranes. We have also analyzed tyrosine phosphorylation induced by PRL. In CHO cells stably transfected with PRL receptor cDNA, PRL induced a very rapid and transient tyrosine phosphorylation of a 100-kDa protein which is most probably the PRL receptor. The same finding was obtained in mammary membranes after PRL injection to lactating rabbits. Whereas tyrosine kinase inhibitors genistein and lavendustin were without effect, PRL stimulation of milk protein gene promoters was partially inhibited by 2 {mu}M herbimycin in CHO cells co-transfected with PRL receptor cDNA and the {Beta} lactoglobulin CAT construct. Taken together these observations indicate that the cytoplasmic domain of the PRL receptor interacts with one or several tyrosine kinases, which may represent early postreceptor events necessary for PRL signal transduction to milk protein genes. 14 refs., 4 figs.

  14. Bipolar pulse forming line

    Science.gov (United States)

    Rhodes, Mark A.

    2008-10-21

    A bipolar pulse forming transmission line module for linear induction accelerators having first, second, third, fourth, and fifth planar conductors which form an interleaved stack with dielectric layers between the conductors. Each conductor has a first end, and a second end adjacent an acceleration axis. The first and second planar conductors are connected to each other at the second ends, the fourth and fifth planar conductors are connected to each other at the second ends, and the first and fifth planar conductors are connected to each other at the first ends via a shorting plate adjacent the first ends. The third planar conductor is electrically connectable to a high voltage source, and an internal switch functions to short a high voltage from the first end of the third planar conductor to the first end of the fourth planar conductor to produce a bipolar pulse at the acceleration axis with a zero net time integral. Improved access to the switch is enabled by an aperture through the shorting plate and the proximity of the aperture to the switch.

  15. Signal transduction by growth factor receptors: signaling in an instant

    DEFF Research Database (Denmark)

    Dengjel, Joern; Akimov, Vyacheslav; Blagoev, Blagoy

    2007-01-01

    -out by mass spectrometry-based proteomics has allowed exciting views on the very early events in signal transduction. Activation profiles of regulated phosphorylation sites on epidermal growth factor receptor and downstream signal transducers showed different kinetics within the first ten seconds......Phosphorylation-based signaling events happening within the first minute of receptor stimulation have so far only been analyzed by classical cell biological approaches like live-cell microscopy. The development of a quench flow system with a time resolution of one second coupled to a read...... of stimulation. This new technique opens the perspectives for accurate analysis of rapid cellular processes and will help to establish models describing signal initiation at the plasma membrane....

  16. Signal transduction by interferon-α through arachidonic acid metabolism

    International Nuclear Information System (INIS)

    Hannigan, G.E.; Williams, B.R.G.

    1991-01-01

    Molecular mechanisms that mediate signal transduction by growth inhibitory cytokines are poorly understood. Type 1 (α and β) interferons (IFNs) are potent growth inhibitory cytokines whose biological activities depend on induced changes in gene expression. IFN-α induced the transient activation of phospholipase A 2 in 3T3 fibroblasts and rapid hydrolysis of [ 3 H]arachidonic acid (AA) from prelabeled phospholipid pools. The phospholipase inhibitor, bromophenacyl bromide (BPB), specifically blocked IFN-induced binding of nuclear factors to a conserved, IFN-regulated enhancer element, the interferon-stimulated response element (ISRE). BPB also caused a dose-dependent inhibition of IFN-α-induced ISRE-dependent transcription in transient transfection assays. Specific inhibition of AA oxygenation by eicosatetraynoic acid prevented IFN-α induction of factor binding to the ISRE. Treatment of intact cells with inhibitors of fatty acid cyclooxygenase or lipoxygenase enzymes resulted in amplification of IFN-α-induced ISRE binding and gene expression. Thus, IFN-α receptor-coupled AA hydrolysis may function in activation of latent transcription factors by IFN-α and provides a system for studying the role of AA metabolism in transduction of growth inhibitory signals

  17. Efficient transduction of neurons using Ross River glycoprotein-pseudotyped lentiviral vectors

    DEFF Research Database (Denmark)

    Jakobsson, J; Nielsen, T Tolstrup; Staflin, K

    2006-01-01

    Lentiviral vectors are promising tools for CNS gene transfer since they efficiently transduce the cells of the nervous system in vivo. In this study, we have investigated the transduction efficiency of lentiviral vectors pseudotyped with Ross River virus glycoprotein (RRV-G) (RRV-G-pseudotyped le......Lentiviral vectors are promising tools for CNS gene transfer since they efficiently transduce the cells of the nervous system in vivo. In this study, we have investigated the transduction efficiency of lentiviral vectors pseudotyped with Ross River virus glycoprotein (RRV-G) (RRV...... and human glial fibrillary acidic protein, we demonstrated cell-specific transgene expression in the desired cell type. Ross River virus glycoprotein-pseudotyped lentiviral vectors also transduced human neural progenitor cells in vitro, showing that receptors for the RRV-G are present on human neural cells....

  18. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis

    Directory of Open Access Journals (Sweden)

    Gareth W. Fearnley

    2016-05-01

    Full Text Available Vascular endothelial growth factor A (VEGF-A binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A–VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor–ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145 promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes.

  19. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis.

    Science.gov (United States)

    Fearnley, Gareth W; Smith, Gina A; Abdul-Zani, Izma; Yuldasheva, Nadira; Mughal, Nadeem A; Homer-Vanniasinkam, Shervanthi; Kearney, Mark T; Zachary, Ian C; Tomlinson, Darren C; Harrison, Michael A; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

    2016-05-15

    Vascular endothelial growth factor A (VEGF-A) binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A-VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor-ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145) promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes. © 2016. Published by The Company of Biologists Ltd.

  20. Sensory cilia and integration of signal transduction in human health and disease

    DEFF Research Database (Denmark)

    Christensen, Søren T; Pedersen, Lotte B; Schneider, Linda

    2007-01-01

    The primary cilium is a hallmark of mammalian tissue cells. Recent research has shown that these organelles display unique sets of selected signal transduction modules including receptors, ion channels, effector proteins and transcription factors that relay chemical and physical stimuli from the ...

  1. Molecular insights into the mechanism of sensing and signal transduction of the thermosensor DesK

    NARCIS (Netherlands)

    Ballering, J.

    2016-01-01

    The ability to sense and respond to environmental signals is essential for cell survival. Unraveling the molecular mechanisms underlying signaling processes remains a challenge, however. This thesis provides molecular insights into the mechanism of sensing and signal transduction of the thermosensor

  2. NA+ AS COUPLING ION IN ENERGY TRANSDUCTION IN EXTREMOPHILIC BACTERIA AND ARCHAEA

    NARCIS (Netherlands)

    Speelmans, G.; Poolman, B.; Konings, W.N

    For microoganisms to live under extreme physical conditions requires important adaptations of the cells. In many organisms the use of Na+ instead of protons as coupling ion in energy transduction is associated with such adaptation. This review focuses on the enzymes that are responsible for the

  3. 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

  4. Signal transduction around thymic stromal lymphopoietin (TSLP in atopic asthma

    Directory of Open Access Journals (Sweden)

    Kuepper Michael

    2008-08-01

    Full Text Available Abstract Thymic stromal lymphopoietin (TSLP, a novel interleukin-7-like cytokine, triggers dendritic cell-mediated inflammatory responses ultimately executed by T helper cells of the Th2 subtype. TSLP emerged as a central player in the development of allergic symptoms, especially in the airways, and is a prime regulatory cytokine at the interface of virus- or antigen-exposed epithelial cells and dendritic cells (DCs. DCs activated by epithelium-derived TSLP can promote naïve CD4+ T cells to adopt a Th2 phenotype, which in turn recruite eosinophilic and basophilic granulocytes as well as mast cells into the airway mucosa. These different cells secrete inflammatory cytokines and chemokines operative in inducing an allergic inflammation and atopic asthma. TSLP is, thus, involved in the control of both an innate and an adaptive immune response. Since TSLP links contact of allergen with the airway epithelium to the onset and maintainance of the asthmatic syndrome, defining the signal transduction underlying TSLP expression and function is of profound interest for a better understandimg of the disease and for the development of new therapeutics.

  5. Indirect bipolar electrodeposition.

    Science.gov (United States)

    Loget, Gabriel; Roche, Jérome; Gianessi, Eugenio; Bouffier, Laurent; Kuhn, Alexander

    2012-12-12

    Based on the principles of bipolar electrochemistry, localized pH gradients are generated at the surface of conducting particles in solution. This allows the toposelective deposition of inorganic and organic polymer layers via a pH-triggered precipitation mechanism. Due to the intrinsic symmetry breaking of the process, the concept can be used to generate in a straightforward way Janus particles, with one section consisting of deposits obtained from non-electroactive precursors. These indirect electrodeposits, such as SiO(2), TiO(2), or electrophoretic paints, can be further used as an immobilization matrix for other species like dyes or nanoparticles, thus opening promising perspectives for the synthesis of a variety of bifunctional objects with a controlled shape.

  6. Genetics of bipolar disorder.

    Science.gov (United States)

    Kerner, Berit

    2014-01-01

    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 currently not fulfilled for common genomic variants in psychiatric disorders. Further work is clearly needed before genetic testing for common variants in

  7. Modeling suicide in bipolar disorders.

    Science.gov (United States)

    Malhi, Gin S; Outhred, Tim; Das, Pritha; Morris, Grace; Hamilton, Amber; Mannie, Zola

    2018-02-19

    Suicide is a multicausal human behavior, with devastating and immensely distressing consequences. Its prevalence is estimated to be 20-30 times greater in patients with bipolar disorders than in the general population. The burden of suicide and its high prevalence in bipolar disorders make it imperative that our current understanding be improved to facilitate prediction of suicide and its prevention. In this review, we provide a new perspective on the process of suicide in bipolar disorder, in the form of a novel integrated model that is derived from extant knowledge and recent evidence. A literature search of articles on suicide in bipolar disorder was conducted in recognized databases such as Scopus, PubMed, and PsycINFO using the keywords "suicide", "suicide in bipolar disorders", "suicide process", "suicide risk", "neurobiology of suicide" and "suicide models". Bibliographies of identified articles were further scrutinized for papers and book chapters of relevance. Risk factors for suicide in bipolar disorders are well described, and provide a basis for a framework of epigenetic mechanisms, moderated by neurobiological substrates, neurocognitive functioning, and social inferences within the environment. Relevant models and theories include the diathesis-stress model, the bipolar model of suicide and the ideation-to-action models, the interpersonal theory of suicide, the integrated motivational-volitional model, and the three-step theory. Together, these models provide a basis for the generation of an integrated model that illuminates the suicidal process, from ideation to action. Suicide is complex, and it is evident that a multidimensional and integrated approach is required to reduce its prevalence. The proposed model exposes and provides access to components of the suicide process that are potentially measurable and may serve as novel and specific therapeutic targets for interventions in the context of bipolar disorder. Thus, this model is useful not only

  8. Accumulation of (3H)glycine by cone bipolar neurons in the cat retina

    International Nuclear Information System (INIS)

    Cohen, E.; Sterling, P.

    1986-01-01

    Cone bipolar neurons in the cat retina were studied in serial sections prepared as electron microscope autoradiograms following intravitreal injection of ( 3 H)glycine. The goal was to learn whether the cone bipolar types that accumulate glycine correspond to the types thought on other grounds to be inhibitory. About half of the cone bipolars in a given patch of retina showed specific accumulation of silver grains. The specificity of accumulation was similar to that shown by glycine-accumulating amacrines. All of the cone bipolars arborizing in sublamina b accumulated glycine but none of the cone bipolars arborizing in sublamina a did so. The types of cone bipolars accumulating glycine did not match the types thought to be inhibitory. Cone bipolar types CBb1 and CBb2 both form gap junctions with the glycine-accumulating AII amacrine, thus raising the possibility that glycine might accumulate in these cone bipolars by diffusion from the AII cell or vice versa. Thus it is logically impossible to tell which of these three cells contains a high-affinity uptake mechanism for glycine and consequently which of the three might actually use glycine as a neurotransmitter

  9. Quetiapine monotherapy for bipolar depression

    Directory of Open Access Journals (Sweden)

    Michael E Thase

    2008-03-01

    Full Text Available Michael E ThaseDepartments of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; the Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA; and the University of Pittsburgh Medical Center, Pittsburgh, PA, USAAbstract: Bipolar depression is more common, disabling, and difficult-to-treat than the manic and hypomanic phases that define bipolar disorder. Unlike the treatment of so-called “unipolar” depressions, antidepressants generally are not indicated as monotherapies for bipolar depressions and recent studies suggest that - even when used in combination with traditional mood stabilizers – antidepressants may have questionable value for bipolar depression. The current practice is that mood stabilizers are initiated first as monotherapies; however, the antidepressant efficacy of lithium and valproate is modest at best. Within this context the role of atypical antipsychotics is being evaluated. The combination of olanzapine and the antidepressant fluoxetine was the first treatment to receive regulatory approval in the US specifically for bipolar I depression. Quetiapine was the second medication to be approved for this indication, largely as the result of two pivotal trials known by the acronyms of BOLDER (BipOLar DEpRession I and II. Both studies demonstrated that two doses of quetiapine (300 mg and 600 mg given once daily at bedtime were significantly more effective than placebo, with no increased risk of patients switching into mania. Pooling the two studies, quetiapine was effective for both bipolar I and bipolar II depressions and for patients with (and without a history of rapid cycling. The two doses were comparably effective in both studies. Although the efficacy of quetiapine monotherapy has been established, much additional research is necessary. Further studies are needed to more fully investigate dose-response relationships and comparing quetiapine monotherapy to other mood stabilizers

  10. 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

  11. Improved migration of tumor ascites lymphocytes to ovarian cancer microenvironment by CXCR2 transduction

    DEFF Research Database (Denmark)

    Idorn, Manja; Olsen, Maria; Halldórsdóttir, Hólmfrídur Rósa

    2018-01-01

    analyzed by flow cytometry. We found that FoxP3+ regulatory T cells accumulation in patients with OC associates with CCR4 expression. We characterized a chemokine profile of ascites chemokines, and expression of corresponding receptors on circulating T cells and tumor ascites lymphocytes (TALs). CCL22......, CXCL9, CXCL10 and CXCL12 associated with enrichment of CCR4+, CCR5+, CXCR3+ and CXCR4+ T cells in ascites. Circulating T cells and TALs however did not express CXCR2, identifying CXCR2 as candidate for chemokine receptor transduction. TALs readily expressed IFNγ and TNFα upon stimulation despite...... the frequency decreasing with in vitro expansion. Lentiviral transduction of TALs (n = 4) with chemokine receptor CXCR2 significantly increased transwell migration of TALs towards rhIL8 and autologous ascites. The majority of expanded and transduced TALs were of a T effector memory subtype. This proof...

  12. Electric modelling and image analysis of channel flow in bipolar plates

    Energy Technology Data Exchange (ETDEWEB)

    Martin, D.; Gonzalez, L.; Garcia-Alegre, M.C.; Guinea, D. [Instituto de Automatica Industrial, Consejo Superior de Investigaciones Cientificas, 28500 Arganda, Madrid (Spain); Guinea, D.M.; Moreno, B. [Instituto de Ceramica y Vidrio, Consejo Superior de Investigaciones Cientificas, Kelsen 5, 28049 Madrid (Spain)

    2007-07-15

    Bipolar plates are an essential part of Polymer Electrolyte Membrane Fuel Cells (PEMFC) and are related to fluid conduction. The topology of a bipolar plate is critical to the homogeneous distribution of the feeding gases over the accessible zone of the electrode. An electric model that simulates flow in bipolar plates and permits the optimisation of gas feeding in PEMFCs is proposed. As a first approach, an analogy is made between the gas pressure P and an electric voltage U in a circuit and a gas flow F and an electric current I. The fluidic resistance in a bipolar plate channel is thus R=P/F and is equivalent to the electric resistance R=U/I in a branch of a circuit. Computer image processing techniques allow the validation of the present flow estimation approach based on electrical variables. Separate plates were developed to experimentally implement a complete parallel bipolar topology. (author)

  13. Prenatal Alcohol Exposure Damages Brain Signal Transduction Systems

    National Research Council Canada - National Science Library

    Caldwell, Kevin

    2001-01-01

    .... One and twenty-four hours following fear conditioning this learning deficit is associated with altered brain signal transduction mechanisms that are dependent on an enzyme termed phosphatidylinositol...

  14. Transductive Ridge Regression in Structure-activity Modeling.

    Science.gov (United States)

    Marcou, Gilles; Delouis, Grace; Mokshyna, Olena; Horvath, Dragos; Lachiche, Nicolas; Varnek, Alexandre

    2018-01-01

    In this article we consider the application of the Transductive Ridge Regression (TRR) approach to structure-activity modeling. An original procedure of the TRR parameters optimization is suggested. Calculations performed on 3 different datasets involving two types of descriptors demonstrated that TRR outperforms its non-transductive analogue (Ridge Regression) in more than 90 % of cases. The most significant transductive effect was observed for small datasets. This suggests that transduction may be particularly useful when the data are expensive or difficult to collect. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. 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

  16. An Efficient Large-Scale Retroviral Transduction Method Involving Preloading the Vector into a RetroNectin-Coated Bag with Low-Temperature Shaking

    Science.gov (United States)

    Dodo, Katsuyuki; Chono, Hideto; Saito, Naoki; Tanaka, Yoshinori; Tahara, Kenichi; Nukaya, Ikuei; Mineno, Junichi

    2014-01-01

    In retroviral vector-mediated gene transfer, transduction efficiency can be hampered by inhibitory molecules derived from the culture fluid of virus producer cell lines. To remove these inhibitory molecules to enable better gene transduction, we had previously developed a transduction method using a fibronectin fragment-coated vessel (i.e., the RetroNectin-bound virus transduction method). In the present study, we developed a method that combined RetroNectin-bound virus transduction with low-temperature shaking and applied this method in manufacturing autologous retroviral-engineered T cells for adoptive transfer gene therapy in a large-scale closed system. Retroviral vector was preloaded into a RetroNectin-coated bag and incubated at 4°C for 16 h on a reciprocating shaker at 50 rounds per minute. After the supernatant was removed, activated T cells were added to the bag. The bag transduction method has the advantage of increasing transduction efficiency, as simply flipping over the bag during gene transduction facilitates more efficient utilization of the retroviral vector adsorbed on the top and bottom surfaces of the bag. Finally, we performed validation runs of endoribonuclease MazF-modified CD4+ T cell manufacturing for HIV-1 gene therapy and T cell receptor-modified T cell manufacturing for MAGE-A4 antigen-expressing cancer gene therapy and achieved over 200-fold (≥1010) and 100-fold (≥5×109) expansion, respectively. In conclusion, we demonstrated that the large-scale closed transduction system is highly efficient for retroviral vector-based T cell manufacturing for adoptive transfer gene therapy, and this technology is expected to be amenable to automation and improve current clinical gene therapy protocols. PMID:24454964

  17. [Genetics of bipolar disorder].

    Science.gov (United States)

    Budde, M; Forstner, A J; Adorjan, K; Schaupp, S K; Nöthen, M M; Schulze, T G

    2017-07-01

    Bipolar disorder (BD) has a multifactorial etiology. Its development is influenced by genetic as well as environmental factors. Large genome-wide association studies (GWAS), in which genetic risk allelic variants for the disorder could be replicated for the first time, marked the breakthrough in the identification of the responsible risk genes. In addition to these common genetic variants with moderate effects identified by GWAS, rare variants with a higher penetrance are expected to play a role in disease development. The results of recent studies suggest that copy number variants might contribute to BD development, although to a lesser extent than in other psychiatric disorders, such as schizophrenia or autism. Results from the initial next generation sequencing studies indicate an enrichment of rare variants in pathways and genes that were previously found to be associated with BD. In the field of pharmacogenetics, a risk gene that influences the individual variance in the response to lithium treatment was identified for the first time in a recent large international GWAS. Currently the reported risk alleles do not sufficiently explain the phenotypic variance to be used for individual prediction of disease risk, disease course or response to medication. Future genetic research will provide important insights into the biological basis of BD by the identification of additional genes associated with BD. This knowledge of genetics will help identify potential etiological subgroups as well as cross-diagnostic disease mechanisms.

  18. Towards the systematic discovery of signal transduction networks using phosphorylation dynamics data

    Directory of Open Access Journals (Sweden)

    Yachie Nozomu

    2010-05-01

    Full Text Available Abstract Background Phosphorylation is a ubiquitous and fundamental regulatory mechanism that controls signal transduction in living cells. The number of identified phosphoproteins and their phosphosites is rapidly increasing as a result of recent mass spectrometry-based approaches. Results We analyzed time-course phosphoproteome data obtained previously by liquid chromatography mass spectrometry with the stable isotope labeling using amino acids in cell culture (SILAC method. This provides the relative phosphorylation activities of digested peptides at each of five time points after stimulating HeLa cells with epidermal growth factor (EGF. We initially calculated the correlations between the phosphorylation dynamics patterns of every pair of peptides and connected the strongly correlated pairs to construct a network. We found that peptides extracted from the same intracellular fraction (nucleus vs. cytoplasm tended to be close together within this phosphorylation dynamics-based network. The network was then analyzed using graph theory and compared with five known signal-transduction pathways. The dynamics-based network was correlated with known signaling pathways in the NetPath and Phospho.ELM databases, and especially with the EGF receptor (EGFR signaling pathway. Although the phosphorylation patterns of many proteins were drastically changed by the EGF stimulation, our results suggest that only EGFR signaling transduction was both strongly activated and precisely controlled. Conclusions The construction of a phosphorylation dynamics-based network provides a useful overview of condition-specific intracellular signal transduction using quantitative time-course phosphoproteome data under specific experimental conditions. Detailed prediction of signal transduction based on phosphoproteome dynamics remains challenging. However, since the phosphorylation profiles of kinase-substrate pairs on the specific pathway were localized in the dynamics

  19. Bipolar Disorder in Children and Teens

    Science.gov (United States)

    ... I do? Share Bipolar Disorder in Children and Teens Download PDF Download ePub Order a free hardcopy ... Think about death or suicide Can children and teens with bipolar disorder have other problems? Young people ...

  20. Mutations of TMC1 cause deafness by disrupting mechanoelectrical transduction

    Science.gov (United States)

    Nakanishi, Hiroshi; Kurima, Kiyoto; Kawashima, Yoshiyuki; Griffith, Andrew J.

    2014-01-01

    Objective Mutations of transmembrane channel-like 1 gene (TMC1) can cause dominant (DFNA36) or recessive (DFNB7/B11) deafness. In this article, we describe the characteristics of DFNA36 and DFNB7/B11 deafness, the features of the Tmc1 mutant mouse strains, and recent advances in our understanding of TMC1 function. Methods Publications related to TMC1, DFNA36 or DFNB7/B11 were identified through PubMed. Results All affected DFNA36 subjects showed post-lingual, progressive, sensorineural hearing loss (HL), initially affecting high frequencies. In contrast, almost all affected DFNB7/B11 subjects demonstrated congenital or prelingual severe to profound sensorineural HL. The mouse Tmc1 gene also has dominant and recessive mutant alleles that cause HL in mutant strains, including Beethoven, deafness and Tmc1 knockout mice. These mutant mice have been instrumental for revealing that Tmc1 and its closely related paralog Tmc2 are expressed in cochlear and vestibular hair cells, and are required for hair cell mechanoelectrical transduction (MET). Recent studies suggest that TMC1 and TMC2 may be components of the long-sought hair cell MET channel. Conclusion TMC1 mutations disrupt hair cell MET. PMID:24933710

  1. Mutations of TMC1 cause deafness by disrupting mechanoelectrical transduction.

    Science.gov (United States)

    Nakanishi, Hiroshi; Kurima, Kiyoto; Kawashima, Yoshiyuki; Griffith, Andrew J

    2014-10-01

    Mutations of transmembrane channel-like 1 gene (TMC1) can cause dominant (DFNA36) or recessive (DFNB7/B11) deafness. In this article, we describe the characteristics of DFNA36 and DFNB7/B11 deafness, the features of the Tmc1 mutant mouse strains, and recent advances in our understanding of TMC1 function. Publications related to TMC1, DFNA36, or DFNB7/B11 were identified through PubMed. All affected DFNA36 subjects showed post-lingual, progressive, sensorineural hearing loss (HL), initially affecting high frequencies. In contrast, almost all affected DFNB7/B11 subjects demonstrated congenital or prelingual severe to profound sensorineural HL. The mouse Tmc1 gene also has dominant and recessive mutant alleles that cause HL in mutant strains, including Beethoven, deafness, and Tmc1 knockout mice. These mutant mice have been instrumental for revealing that Tmc1 and its closely related paralog Tmc2 are expressed in cochlear and vestibular hair cells, and are required for hair cell mechanoelectrical transduction (MET). Recent studies suggest that TMC1 and TMC2 may be components of the long-sought hair cell MET channel. TMC1 mutations disrupt hair cell MET. Published by Elsevier Ireland Ltd.

  2. Micropatterning of a Bipolar Plate Using Direct Laser Melting Process

    Science.gov (United States)

    Jang, Jeong-hwan; Joo, Byeong-don; Mun, Sung-min; Moona, Young-hoon

    2010-06-01

    Direct laser melting (DLM) technology has been used to fabricate the micro-pattern of the bipolar plate in a direct methanol fuel cell (DMFC). A suitable approach to enhance the performance of the bipolar plate has been performed to optimize the DLM process. To fabricate the micro pattern, a DLM process with 316L stainless steel powder has been used. For the melted height of 1 mm, the DLM process conditions were optimized such as; laser power of 200 W, scan rate of 36.62 mm/s and the 8-layer structures. To characterize the effect of material type, the bipolar plates of various types were analyzed. In case of the 316L stainless steel DLM patterning, a current density of 297 mA/cm2 was achieved but the case of the 316L stainless steel plate, 248 mA/cm2 current density that is lower than that of other materials was achieved. The overall cell performance of 316L stainless steel DLM patterning bipolar plate was better than that of the 316L stainless steel plate. This has significant advantages for the micropatterning using DLM process. The use of 316L stainless steel powder material as micro pattern material will reduce the machining cost as well as volume of the fuel cell stack.

  3. Exercising control over bipolar disorder.

    Science.gov (United States)

    Malhi, Gin S; Byrow, Yulisha

    2016-11-01

    Following extensive research exercise has emerged as an effective treatment for major depressive disorder, and it is now a recognised therapy alongside other interventions. In contrast, there is a paucity of research examining the therapeutic effects of exercise for those with bipolar disorder. Given that dysfunctional reward processing is central to bipolar disorder, research suggests that exercise can perhaps be framed as a reward-related event that may have the potential to precipitate a manic episode. The behavioural activation system (BAS) is a neurobehavioural system that is associated with responding to reward and provides an appropriate framework to theoretically examine and better understand the effects of exercise treatment on bipolar disorder. This article discusses recent research findings and provides an overview of the extant literature related to the neurobiological underpinnings of BAS and exercise as they relate to bipolar disorder. This is important clinically because depending on mood state in bipolar disorder, we postulate that exercise could be either beneficial or deleterious with positive or negative effects on the illness. Clearly, this complicates the evaluation of exercise as a potential treatment in terms of identifying its optimal characteristics in this population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Imunologia do transtorno bipolar Immunology of bipolar disorder

    Directory of Open Access Journals (Sweden)

    Izabela Guimarães Barbosa

    2009-01-01

    Full Text Available 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. As bases de dados avaliadas foram MedLine e Scopus, entre os anos de 1980 e 2008. RESULTADOS: Foram identificados 28 trabalhos que estudaram alterações imunes em pacientes com transtorno bipolar. Seis artigos investigaram genes relacionados à resposta imune; cinco, autoanticorpos; quatro, populações leucocitárias; 13, citocinas e/ou moléculas relacionadas à resposta imune e seis, leucócitos de pacientes in vitro. CONCLUSÕES: Embora haja evidências na literatura correlacionando o transtorno bipolar a alterações imunes, os dados não são conclusivos. O transtorno bipolar parece estar associado a níveis mais elevados de autoanticorpos circulantes, assim como à tendência à ativação imune com produção de citocinas pró-inflamatórias e redução de parâmetros anti-inflamatórios.OBJECTIVE: Emerging research has implicated immune factors in the pathogenesis of a variety of neuropsychiatric disorders. The objective of the present paper is to review the studies that investigated the association between bipolar disorder and immune parameters. METHODS: Papers that included the keywords "bipolar to disorder", "mania", "immunology", "cytokines", "chemokines", "interleukins", "interferon" and "tumor necrosis factor" were selected in a systematic review of the literature. The evaluated databases were MedLine and Scopus in the period between 1980 and 2008. RESULTS: Twenty eight works were found. Six studies investigated immune response

  5. 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.

  6. Tritium isotope separation from light and heavy water by bipolar electrolysis

    International Nuclear Information System (INIS)

    Petek, M.; Ramey, D.W.; Taylor, R.D.; Kobisk, E.H.

    1980-01-01

    A process for separating tritium from light and heavy water is described. Hydrogen is transferred at and through bipolar electrodes at rates H > D > T. In a cell containing several bipolar electrodes placed in series between two terminal electrodes, a flow of hydrogen is established from the terminal anode compartment toward the terminal cathode. An electrolyte feed containing tritium is continuously added to the system and is subsequently transported countercurrent to the hydrogen mass transfer. A cascaded system is established, in which effluent streams enriched and depleted in tritium can be withdrawn. The voltage drop is smaller at any bipolar electrode as compared to the voltage for normal electrolysis. Cell design is compact because isotope separation occurs at bipolar electrodes without evolution of gas. Isotope separation was demonstrated in laboratory cells where a steady-state tritium concentration gradient was attained. This gradient was in agreement with concentrations calculated from a derived mathematical model

  7. Metformin selectively targets redox control of complex I energy transduction

    Directory of Open Access Journals (Sweden)

    Amy R. Cameron

    2018-04-01

    Full Text Available Many guanide-containing drugs are antihyperglycaemic but most exhibit toxicity, to the extent that only the biguanide metformin has enjoyed sustained clinical use. Here, we have isolated unique mitochondrial redox control properties of metformin that are likely to account for this difference. In primary hepatocytes and H4IIE hepatoma cells we found that antihyperglycaemic diguanides DG5-DG10 and the biguanide phenformin were up to 1000-fold more potent than metformin on cell signalling responses, gluconeogenic promoter expression and hepatocyte glucose production. Each drug inhibited cellular oxygen consumption similarly but there were marked differences in other respects. All diguanides and phenformin but not metformin inhibited NADH oxidation in submitochondrial particles, indicative of complex I inhibition, which also corresponded closely with dehydrogenase activity in living cells measured by WST-1. Consistent with these findings, in isolated mitochondria, DG8 but not metformin caused the NADH/NAD+ couple to become more reduced over time and mitochondrial deterioration ensued, suggesting direct inhibition of complex I and mitochondrial toxicity of DG8. In contrast, metformin exerted a selective oxidation of the mitochondrial NADH/NAD+ couple, without triggering mitochondrial deterioration. Together, our results suggest that metformin suppresses energy transduction by selectively inducing a state in complex I where redox and proton transfer domains are no longer efficiently coupled. Keywords: Diabetes, Metformin, Mitochondria, NADH, NAD+

  8. Modulation of signal transduction by tea catechins and related phytochemicals

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Masahito [Herbert Irving Comprehensive Cancer Center and Department of Medicine, Columbia University Medical Center, HHSC-1509, 701 West 168 Street, NY 10032-2704 (United States); Weinstein, I. Bernard [Herbert Irving Comprehensive Cancer Center and Department of Medicine, Columbia University Medical Center, HHSC-1509, 701 West 168 Street, NY 10032-2704 (United States)]. E-mail: ibw1@columbia.edu

    2005-12-11

    Epidemiologic studies in human populations and experimental studies in rodents provide evidence that green tea and its constituents can inhibit both the development and growth of tumors at a variety of tissue sites. In addition, EGCG, a major biologically active component of green tea, inhibits growth and induces apoptosis in a variety of cancer cell lines. The purpose of this paper is to review evidence that these effects are mediated, at least in part, through inhibition of the activity of specific receptor tyrosine kinases (RTKs) and related downstream pathways of signal transduction. We also review evidence indicating that the antitumor effects of the related polyphenolic phytochemicals resveratrol, genistein, curcumin, and capsaicin are exerted via similar mechanisms. Some of these agents (EGCG, genistein, and curcumin) appear to directly target specific RTKs, and all of these compounds cause inhibition of the activity of the transcription factors AP-1 and NF-{kappa}B, thus inhibiting cell proliferation and enhancing apoptosis. Critical areas of future investigation include: (1) identification of the direct molecular target(s) of EGCG and related polyphenolic compounds in cells; (2) the in vivo metabolism and bioavailability of these compounds; (3) the ancillary effects of these compounds on tumor-stromal interactions; (4) the development of synergistic combinations with other antitumor agents to enhance efficacy in cancer prevention and therapy, and also minimize potential toxicities.

  9. FCJ-124 Interactive Environments as Fields of Transduction

    Directory of Open Access Journals (Sweden)

    Cristoph Brunner

    2011-10-01

    Full Text Available This article proposes a critical inquiry of interactive environments as fields of transduction. It is argued that Gilbert Simondon’s concepts of individuation, transduction, in-formation, the preindividual, and the associated milieu enable a processual thinking of the analysis and design of interactive technologies as technogenetic emergence. These concepts offer a way for interaction design to understand interactive environments through the dynamics between fields of transduction and fields of experience in relational and affective terms. The article analyses the way in which two technological assemblages, Voz Alta and the Impossible Room, provide different experiential fields experimenting with the transductive power of digital and interactive media. We emphasise the potential for creating new modes of experience. Our aim is to underline the necessary convergences between practices of design and thought; to enable affectively engaging fields of transduction.

  10. Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors

    Directory of Open Access Journals (Sweden)

    Mayumi Oakland

    2013-01-01

    Full Text Available Persistent viral vector-mediated transgene expression in the airways requires delivery to cells with progenitor capacity and avoidance of immune responses. Previously, we observed that GP64-pseudotyped feline immunodeficiency virus (FIV-mediated gene transfer was more efficient in the nasal airways than the large airways of the murine lung. We hypothesized that in vivo gene transfer was limited by immunological and physiological barriers in the murine intrapulmonary airways. Here, we systematically investigate multiple potential barriers to lentiviral gene transfer in the airways of mice. We show that GP64-FIV vector transduced primary cultures of well-differentiated murine nasal epithelia with greater efficiency than primary cultures of murine tracheal epithelia. We further demonstrate that neutrophils, type I interferon (IFN responses, as well as T and B lymphocytes are not the major factors limiting the transduction of murine conducting airways. In addition, we observed better transduction of GP64-pseudotyped vesicular stomatitis virus (VSV in the nasal epithelia compared with the intrapulmonary airways in mice. VSVG glycoprotein pseudotyped VSV transduced intrapulmonary epithelia with similar efficiency as nasal epithelia. Our results suggest that the differential transduction efficiency of nasal versus intrapulmonary airways by FIV vector is not a result of immunological barriers or surface area, but rather differential expression of cellular factors specific for FIV vector transduction.

  11. Transcultural aspects of bipolar disorder

    OpenAIRE

    Sanches, Marsal; Jorge, Miguel Roberto

    2004-01-01

    Considerando-se que existem diferenças importantes na maneira como as emoções são vivenciadas e expressas em diferentes culturas, a apresentação e o manejo do transtorno afetivo bipolar sofrem influência de fatores culturais. O presente artigo realiza uma breve revisão da evidência referente aos aspectos transculturais do transtorno bipolar.Cultural variations in the expression of emotions have been described. Consequently, there are cross-cultural influences on the diagnosis and management o...

  12. Application of bipolar electrodialysis to E.coli fermentation for simultaneous acetate removal and pH control

    DEFF Research Database (Denmark)

    Wong, M.; Woodley, John; Lye, G.J.

    2010-01-01

    The application of bipolar electrodialysis (BPED) for the simultaneous removal of inhibitory acetate and pH control during E. coli fermentation was investigated. A two cell pair electrodialysis module, consisting of cation exchange, anion exchange and bipolar membranes with working area of 100 cm...

  13. Epidemiologia do transtorno bipolar Epidemiology of bipolar disorders

    Directory of Open Access Journals (Sweden)

    Maurício Silva de Lima

    2005-01-01

    Full Text Available A formulação de políticas em saúde mental depende essencialmente de informações a respeito da freqüência e distribuição dos transtornos mentais. Nas últimas duas décadas, pesquisas de base populacional em epidemiologia psiquiátrica têm sido conduzidas, gerando informações detalhadas sobre freqüência, fatores de risco, incapacidade social e utilização de serviços de saúde. Neste artigo, dados sobre a epidemiologia do transtorno bipolar (TB são discutidos, a partir de resultados de recentes pesquisas populacionais: o estudo da Área de Captação Epidemiológica do Instituto Nacional de Saúde Mental dos Estados Unidos (ECA-NIMH, a Pesquisa Nacional de Comorbidade (NCS, a Pesquisa de Morbidade Psiquiátrica na Grã-Bretanha (OPCS, o Estudo Brasileiro Multicêntrico de Morbidade Psiquiátrica e os estudos longitudinais conduzidos por Angst, em Zurique. As estimativas de prevalências de transtorno bipolar são relativamente baixas, independentemente do lugar onde a pesquisa foi conduzida, do tipo de instrumento diagnóstico usado e dos períodos de tempo para os quais a prevalência se aplica. A partir da introdução do conceito de espectro bipolar, ampliando as fronteiras diagnósticas do TB, as estimativas de prevalências encontradas são substancialmente mais altas. Tais estimativas, entretanto, ainda carecem de validação em estudos populacionais. O transtorno afetivo bipolar é igualmente prevalente entre homens e mulheres, sendo mais freqüente entre solteiros ou separados. Indivíduos acometidos têm maiores taxas de desemprego e estão mais sujeitos a utilizarem serviços médicos e serem hospitalizados. O custo e a eficácia dos tratamentos do TB devem ser balanceados com o alto custo individual e social associados à enfermidade.Information about the epidemiology of bipolar disorders is essential for providing a framework for the formulation of effective mental health policy. In the last two decades, population

  14. Mixed features in bipolar disorder.

    Science.gov (United States)

    Solé, Eva; Garriga, Marina; Valentí, Marc; Vieta, Eduard

    2017-04-01

    Mixed affective states, defined as the coexistence of depressive and manic symptoms, are complex presentations of manic-depressive illness that represent a challenge for clinicians at the levels of diagnosis, classification, and pharmacological treatment. The evidence shows that patients with bipolar disorder who have manic/hypomanic or depressive episodes with mixed features tend to have a more severe form of bipolar disorder along with a worse course of illness and higher rates of comorbid conditions than those with non-mixed presentations. In the updated Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5), the definition of "mixed episode" has been removed, and subthreshold nonoverlapping symptoms of the opposite pole are captured using a "with mixed features" specifier applied to manic, hypomanic, and major depressive episodes. However, the list of symptoms proposed in the DSM-5 specifier has been widely criticized, because it includes typical manic symptoms (such as elevated mood and grandiosity) that are rare among patients with mixed depression, while excluding symptoms (such as irritability, psychomotor agitation, and distractibility) that are frequently reported in these patients. With the new classification, mixed depressive episodes are three times more common in bipolar II compared with unipolar depression, which partly contributes to the increased risk of suicide observed in bipolar depression compared to unipolar depression. Therefore, a specific diagnostic category would imply an increased diagnostic sensitivity, would help to foster early identification of symptoms and ensure specific treatment, as well as play a role in suicide prevention in this population.

  15. Self-organization of signal transduction.

    Science.gov (United States)

    Scheler, Gabriele

    2013-01-01

    We propose a model of parameter learning for signal transduction, where the objective function is defined by signal transmission efficiency. We apply this to learn kinetic rates as a form of evolutionary learning, and look for parameters which satisfy the objective. This is a novel approach compared to the usual technique of adjusting parameters only on the basis of experimental data. The resulting model is self-organizing, i.e. perturbations in protein concentrations or changes in extracellular signaling will automatically lead to adaptation. We systematically perturb protein concentrations and observe the response of the system. We find compensatory or co-regulation of protein expression levels. In a novel experiment, we alter the distribution of extracellular signaling, and observe adaptation based on optimizing signal transmission. We also discuss the relationship between signaling with and without transients. Signaling by transients may involve maximization of signal transmission efficiency for the peak response, but a minimization in steady-state responses. With an appropriate objective function, this can also be achieved by concentration adjustment. Self-organizing systems may be predictive of unwanted drug interference effects, since they aim to mimic complex cellular adaptation in a unified way.

  16. Integrated Neurobiology of Bipolar Disorder

    Science.gov (United States)

    Maletic, Vladimir; Raison, Charles

    2014-01-01

    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 hypothalamic–pituitary–adrenal 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

  17. An intimate link: two-component signal transduction systems and metal transport systems in bacteria

    OpenAIRE

    Singh, Kamna; Senadheera, Dilani B; Cvitkovitch, Dennis G

    2014-01-01

    Bacteria have evolved various strategies to contend with high concentrations of environmental heavy metal ions for rapid, adaptive responses to maintain cell viability. Evidence gathered in the past two decades suggests that bacterial two-component signal transduction systems (TCSTSs) are intimately involved in monitoring cation accumulation, and can regulate the expression of related metabolic and virulence genes to elicit adaptive responses to changes in the concentration of these ions. Usi...

  18. Role of Glycolytic Intermediates in Global Regulation and Signal Transduction. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Liao, J.C.

    2000-05-08

    The goal of this project is to determine the role of glycolytic intermediates in regulation of cell physiology. It is known that many glycolytic intermediates are involved in regulation of enzyme activities at the kinetic level. However, little is known regarding the role of these metabolites in global regulation and signal transduction. This project aims to investigate the role of glycolytic intermediates in the regulation of gene expression.

  19. Transduction-like gene transfer in the methanogen Methanococcus voltae

    Science.gov (United States)

    Bertani, G.

    1999-01-01

    Strain PS of Methanococcus voltae (a methanogenic, anaerobic archaebacterium) was shown to generate spontaneously 4.4-kbp chromosomal DNA fragments that are fully protected from DNase and that, upon contact with a cell, transform it genetically. This activity, here called VTA (voltae transfer agent), affects all markers tested: three different auxotrophies (histidine, purine, and cobalamin) and resistance to BES (2-bromoethanesulfonate, an inhibitor of methanogenesis). VTA was most effectively prepared by culture filtration. This process disrupted a fraction of the M. voltae cells (which have only an S-layer covering their cytoplasmic membrane). VTA was rapidly inactivated upon storage. VTA particles were present in cultures at concentrations of approximately two per cell. Gene transfer activity varied from a minimum of 2 x 10(-5) (BES resistance) to a maximum of 10(-3) (histidine independence) per donor cell. Very little VTA was found free in culture supernatants. The phenomenon is functionally similar to generalized transduction, but there is no evidence, for the time being, of intrinsically viral (i.e., containing a complete viral genome) particles. Consideration of VTA DNA size makes the existence of such viral particles unlikely. If they exist, they must be relatively few in number;perhaps they differ from VTA particles in size and other properties and thus escaped detection. Digestion of VTA DNA with the AluI restriction enzyme suggests that it is a random sample of the bacterial DNA, except for a 0.9-kbp sequence which is amplified relative to the rest of the bacterial chromosome. A VTA-sized DNA fraction was demonstrated in a few other isolates of M. voltae.

  20. DMFC bipolar material and new processing for μDMFC microchannel

    Science.gov (United States)

    Yin, Bifeng; Guan, Tao; Wang, Yun

    2010-10-01

    DMFC (Direct Methanol Fuel Cell) is attractive as green energy with the characteristics of high energy conversion rate, lower carbon and emission, eco-friendly alternative energy. In DMFC, bipolar plate is one key component because of its high performance requirements, the bipolar plate nearly always makes about 60% contribution to the cost of all fuel cell, seriously affected the commercialization progress of DMFC. Furthermore, the flow channel design and arrangement in bipolar plate has a great influence on water and heat management, distribution of reactants and smooth resultant discharge. So the DMFC bipolar plate material and flow channel processing technique obtains more concerns. After introducing the bipolar plate structure and its functions, it points out that the bipolar plate material nowadays mainly involves the graphite materials, metals and composite. Then the corresponding preparation method, advantages and disadvantages of these three kinds of bipolar plate materials are analyzed. With the rapid development of Micro and Nano-technology and the demand for electricity supply of MEMS (Micro Electro Mechanical systems, micro-energy sources have been the focus, resulting in the miniaturization DMFC (μ DMFC). As the micro-bipolar plates has to survive the severe rugged working environment, such as high temperature, deep-etching, multi-field and alternating pressure), which challenges the material selection, flow channel configuration, processing method and precision. Therefore, hard-to-deform material such as titanium alloy is the preferred material for micro-bipolar plate. However, the new processing method has to be initialized for hard-to-deform material. This paper introduces the traditional and advanced processing methods of μDMFC bipolar plate. The existing problems of the DMFC bipolar plate material selection and processing are analyzed. We initialized one new technique that combines the laser-assisted heating method and micro die-pressing. The

  1. Evaluation of the impact of two flow field designs with bipolar plate flow on the performance of a PEM fuel cell; Evaluacion del impacto de dos disenos de campo de flujo de placa bipolar en el desempeno de una celda de combustible tipo PEM

    Energy Technology Data Exchange (ETDEWEB)

    Loyola-Morales, F.; Cano-Castillo, U. [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico)]. E-mail: feloyola@yahoo.com.mx

    2009-09-15

    The flow field (FF) designs of bipolar plates play a fundamental role in the performance of a set of PEM fuel cells. The FF is directly related with diverse processes that occur inside the cells, such as: feeding and uniform distribution of reactant gases and the handling of water produced by the overall electrochemical reaction. Therefore, a FF design that promotes each one of those processes in an optimal manner is of utmost importance to attain the best performance of a set of fuel cells. The present work evaluated the impact of two different FF on the performance of a fuel cell. The FF designs evaluated were 4 serpentine and parallels (4SP) and 2 serpentine counter flow (SC). The stability tests for the operation of the cell applied to each of the flow fields were: flood tolerance, dehydration tolerance conditions and stoichiometry performance of 1.1, 1.3, 1.5 and 2.5. The 4SP design showed high performance stability during operation with a gradual process of flooding the system and operating at different stoichiometries. Only for the test with dehydration conditions was there a gradual decrease in its performance, of up to 27%. Compared to these results, the SC design showed a rapid fall of 45% in its performance when operating under gradual flooding of the system, a constant fall in its performance (also around 45%) with stoichiometries of 1.1, 1.3 and 1.5 due to accumulation of water, and only with a stoichiometry of 2.5 did it have highly stable performance as a result of good water handling. In the test of operations under dehydration conditions, the performance of the SC design dropped to 40% and remained at this value during the rest of the test. According to these results, the performance of the 4SP design was more stable than the SC design for all of the tests implemented. [Spanish] Los disenos de campo de flujo (CF) de las placas bipolares tienen un papel fundamental en el desempeno de un conjunto de celdas de combustible tipo PEM. Los CF tienen una

  2. Transduction mechanisms and their applications in micromechanical devices

    NARCIS (Netherlands)

    Elwenspoek, Michael Curt; Blom, F.R.; Bouwstra, S.; Lammerink, Theodorus S.J.; van de Pol, F.C.M.; Tilmans, H.A.C.; Popma, T.J.A.; Fluitman, J.H.J.

    1989-01-01

    Transduction mechanisms and their applications in micromechanical actuators and resonating sensors are presented. They include piezoelectric, dielectric, electro-thermo-mechanic, opto-thermo-mechanic, and thermo-pneumatic mechanisms. Advantages and disadvantages with respect to technology and

  3. Bipolar polygenic loading and bipolar spectrum features in major depressive disorder

    NARCIS (Netherlands)

    Wiste, Anna; Robinson, Elise B.; Milaneschi, Yuri; Meier, Sandra; Ripke, Stephan; Clements, Caitlin C.; Fitzmaurice, Garrett M.; Rietschel, Marcella; Penninx, Brenda W.; Smoller, Jordan W.; Perlis, Roy H.

    Objectives Family and genetic studies indicate overlapping liability for major depressive disorder and bipolar disorder. The purpose of the present study was to determine whether this shared genetic liability influences clinical presentation. Methods A polygenic risk score for bipolar disorder,

  4. Bipolar disorder and diabetes mellitus: evidence for disease-modifying effects and treatment implications.

    Science.gov (United States)

    Charles, Ellen F; Lambert, Christophe G; Kerner, Berit

    2016-12-01

    Bipolar disorder refers to a group of chronic psychiatric disorders of mood and energy levels. While dramatic psychiatric symptoms dominate the acute phase of the diseases, the chronic course is often determined by an increasing burden of co-occurring medical conditions. High rates of diabetes mellitus in patients with bipolar disorder are particularly striking, yet unexplained. Treatment and lifestyle factors could play a significant role, and some studies also suggest shared pathophysiology and risk factors. In this systematic literature review, we explored data around the relationship between bipolar disorder and diabetes mellitus in recently published population-based cohort studies with special focus on the elderly. A systematic search in the PubMed database for the combined terms "bipolar disorder" AND "elderly" AND "diabetes" in papers published between January 2009 and December 2015 revealed 117 publications; 7 studies were large cohort studies, and therefore, were included in our review. We found that age- and gender- adjusted risk for diabetes mellitus was increased in patients with bipolar disorder and vice versa (odds ratio range between 1.7 and 3.2). Our results in large population-based cohort studies are consistent with the results of smaller studies and chart reviews. Even though it is likely that heterogeneous risk factors may play a role in diabetes mellitus and in bipolar disorder, growing evidence from cell culture experiments and animal studies suggests shared disease mechanisms. Furthermore, disease-modifying effects of bipolar disorder and diabetes mellitus on each other appear to be substantial, impacting both treatment response and outcomes. The risk of diabetes mellitus in patients with bipolar disorder is increased. Our findings add to the growing literature on this topic. Increasing evidence for shared disease mechanisms suggests new disease models that could explain the results of our study. A better understanding of the complex

  5. Glucagon-like peptide 1 receptor agonist ameliorates the insulin resistance function of islet β cells via the activation of PDX-1/JAK signaling transduction in C57/BL6 mice with high-fat diet-induced diabetes.

    Science.gov (United States)

    Hao, Tao; Zhang, Hongtao; Li, Sheyu; Tian, Haoming

    2017-04-01

    Long-term exposure to a high-fat diet (HFD) causes glucotoxicity and lipotoxicity in islet β cells and leads to the development of metabolic dysfunctions. Reductions in pancreatic and duodenal homeobox-1 (PDX-1) expression have been shown to induce type 2 diabetes mellitus by causing impairments to islet β cells. Glucagon-like peptide 1 (GLP-1) treatment reduces endogenous insulin resistance in HFD-induced type 2 diabetes mellitus. In the present study, the underlying mechanism by which GLP-1 exerts its function in type 2 diabetes mellitus was investigated. The effect of liraglutide (GLP-1 receptor agonist) administration on glucose tolerance, insulin release, and glucose-dependent insulinotropic polypeptide level was detected in a HFD-induced diabetes C57/BL6 mouse model. Moreover, the role of liraglutide administration on the activity of PDX-1 was quantified to demonstrate the association between the two indicators. The results showed that administration of liraglutide could ameliorate the impairments to β cells due to HFD consumption. Liraglutide restored the insulin capacity and stimulated glucose disposal by improving the function and increasing the number of islet β cells. Furthermore, the hyperplasia and redundant function of islet α cells were inhibited by liraglutide treatment as well. At the molecular level, administration of liraglutide induced the expression of PDX-1, MafA, p-JAK2 and p-Stat3 in HFD model to relatively normal levels. It was suggested that the effect of liraglutide-induced activation of GLP-1 was exerted via activation of PDX-1 rather than its function in decreasing body weight. The study demonstrated that GLP-1 played an essential role in type 2 diabetes mellitus.

  6. Phosphoproteomics-based systems analysis of signal transduction networks

    Directory of Open Access Journals (Sweden)

    Hiroko eKozuka-Hata

    2012-01-01

    Full Text Available Signal transduction systems coordinate complex cellular information to regulate biological events such as cell proliferation and differentiation. Although the accumulating evidence on widespread association of signaling molecules has revealed essential contribution of phosphorylation-dependent interaction networks to cellular regulation, their dynamic behavior is mostly yet to be analyzed. Recent technological advances regarding mass spectrometry-based quantitative proteomics have enabled us to describe the comprehensive status of phosphorylated molecules in a time-resolved manner. Computational analyses based on the phosphoproteome dynamics accelerate generation of novel methodologies for mathematical analysis of cellular signaling. Phosphoproteomics-based numerical modeling can be used to evaluate regulatory network elements from a statistical point of view. Integration with transcriptome dynamics also uncovers regulatory hubs at the transcriptional level. These omics-based computational methodologies, which have firstly been applied to representative signaling systems such as the epidermal growth factor receptor pathway, have now opened up a gate for systems analysis of signaling networks involved in immune response and cancer.

  7. Oxygen sensing and signal transduction in hypoxic pulmonary vasoconstriction.

    Science.gov (United States)

    Sommer, Natascha; Strielkov, Ievgen; Pak, Oleg; Weissmann, Norbert

    2016-01-01

    Hypoxic pulmonary vasoconstriction (HPV), also known as the von Euler-Liljestrand mechanism, is an essential response of the pulmonary vasculature to acute and sustained alveolar hypoxia. During local alveolar hypoxia, HPV matches perfusion to ventilation to maintain optimal arterial oxygenation. In contrast, during global alveolar hypoxia, HPV leads to pulmonary hypertension. The oxygen sensing and signal transduction machinery is located in the pulmonary arterial smooth muscle cells (PASMCs) of the pre-capillary vessels, albeit the physiological response may be modulated in vivo by the endothelium. While factors such as nitric oxide modulate HPV, reactive oxygen species (ROS) have been suggested to act as essential mediators in HPV. ROS may originate from mitochondria and/or NADPH oxidases but the exact oxygen sensing mechanisms, as well as the question of whether increased or decreased ROS cause HPV, are under debate. ROS may induce intracellular calcium increase and subsequent contraction of PASMCs via direct or indirect interactions with protein kinases, phospholipases, sarcoplasmic calcium channels, transient receptor potential channels, voltage-dependent potassium channels and L-type calcium channels, whose relevance may vary under different experimental conditions. Successful identification of factors regulating HPV may allow development of novel therapeutic approaches for conditions of disturbed HPV. Copyright ©ERS 2016.

  8. Signal transduction by the platelet-derived growth factor receptor

    International Nuclear Information System (INIS)

    Williams, L.T.; Escobedo, J.A.; Keating, M.T.; Coughlin, S.R.

    1988-01-01

    The mitogenic effects of platelet-derived growth factor (PDGF) are mediated by the PDGF receptor. The mouse PDGF receptor was recently purified on the basis of its ability to become tyrosine phosphorylated in response to the A-B human platelet form of PDGF, and the receptor amino acid sequence was determined from a full-length cDNA clone. Both the human and mouse receptor cDNA sequences have been expressed in Chinese hamster ovary fibroblast (CHO) cells that normally lack PDGF receptors. This paper summarizes recent results using this system to study signal transduction by the PDGF receptor. Some of the findings show that the KI domain of the PDGF receptor plays an important role in the stimulation of DNA synthesis by PDGF. Surprisingly, the kinase insert region is not essential for PDGF stimulation of PtdIns turnover, pH change, increase in cellular calcium, and receptor autophosphorylation. In addition, PDGF stimulates a conformational change in the receptor

  9. Nox family NADPH oxidases in mechano-transduction: mechanisms and consequences.

    Science.gov (United States)

    Brandes, Ralf P; Weissmann, Norbert; Schröder, Katrin

    2014-02-20

    The majority of cells in a multi-cellular organism are continuously exposed to ever-changing physical forces. Mechano-transduction links these events to appropriate reactions of the cells involving stimulation of signaling cascades, reorganization of the cytoskeleton and alteration of gene expression. Mechano-transduction alters the cellular redox balance and the formation of reactive oxygen species (ROS). Nicotine amide adenine dinucleotide reduced form (NADPH) oxidases of the Nox family are prominent ROS generators and thus, contribute to this stress-induced ROS formation. Different types and patterns of mechano-stress lead to Nox-dependent ROS formation and Nox-mediated ROS formation contributes to cellular responses and adaptation to physical forces. Thereby, Nox enzymes can mediate vascular protection during physiological mechano-stress. Despite this, over-activation and induction of Nox enzymes and a subsequent substantial increase in ROS formation also promotes oxidative stress in pathological situations like disturbed blood flow or extensive stretch. Individual protein targets of Nox-mediated redox-signaling will be identified to better understand the specificity of Nox-dependent ROS signaling in mechano-transduction. Nox-inhibitors will be tested to reduce cellular activation in response to mechano-stimuli.

  10. A Prize-Collecting Steiner Tree Approach for Transduction Network Inference

    Science.gov (United States)

    Bailly-Bechet, Marc; Braunstein, Alfredo; Zecchina, Riccardo

    Into the cell, information from the environment is mainly propagated via signaling pathways which form a transduction network. Here we propose a new algorithm to infer transduction networks from heterogeneous data, using both the protein interaction network and expression datasets. We formulate the inference problem as an optimization task, and develop a message-passing, probabilistic and distributed formalism to solve it. We apply our algorithm to the pheromone response in the baker’s yeast S. cerevisiae. We are able to find the backbone of the known structure of the MAPK cascade of pheromone response, validating our algorithm. More importantly, we make biological predictions about some proteins whose role could be at the interface between pheromone response and other cellular functions.

  11. Unsplit bipolar pulse forming line

    Science.gov (United States)

    Rhodes, Mark A [Pleasanton, CA

    2011-05-24

    A bipolar pulse forming transmission line module and system for linear induction accelerators having first, second, third, and fourth planar conductors which form a sequentially arranged interleaved stack having opposing first and second ends, with dielectric layers between the conductors. The first and second planar conductors are connected to each other at the first end, and the first and fourth planar conductors are connected to each other at the second end via a shorting plate. The third planar conductor is electrically connectable to a high voltage source, and an internal switch functions to short at the first end a high voltage from the third planar conductor to the fourth planar conductor to produce a bipolar pulse at the acceleration axis with a zero net time integral. Improved access to the switch is enabled by an aperture through the shorting plate and the proximity of the aperture to the switch.

  12. The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part II: signal transduction.

    Science.gov (United States)

    Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

    2015-02-01

    The unique mechanoelectrochemical environment of cartilage has motivated researchers to investigate the effect of multiple biophysical cues, including mechanical, magnetic, and electrical stimulation, on chondrocyte biology. It is well established that biophysical stimuli promote chondrocyte proliferation, differentiation, and maturation within "biological windows" of defined dose parameters, including mode, frequency, magnitude, and duration of stimuli (see companion review Part I: Cellular Response). However, the underlying molecular mechanisms and signal transduction pathways activated in response to multiple biophysical stimuli remain to be elucidated. Understanding the mechanisms of biophysical signal transduction will deepen knowledge of tissue organogenesis, remodeling, and regeneration and aiding in the treatment of pathologies such as osteoarthritis. Further, this knowledge will provide the tissue engineer with a potent toolset to manipulate and control cell fate and subsequently develop functional replacement cartilage. The aim of this article is to review chondrocyte signal transduction pathways in response to mechanical, magnetic, and electrical cues. Signal transduction does not occur along a single pathway; rather a number of parallel pathways appear to be activated, with calcium signaling apparently common to all three types of stimuli, though there are different modes of activation. Current tissue engineering strategies, such as the development of "smart" functionalized biomaterials that enable the delivery of growth factors or integration of conjugated nanoparticles, may further benefit from targeting known signal transduction pathways in combination with external biophysical cues.

  13. Single Quantum Dot Tracking Reveals that an Individual Multivalent HIV-1 Tat Protein Transduction Domain Can Activate Machinery for Lateral Transport and Endocytosis

    OpenAIRE

    Suzuki, Yasuhiro; Roy, Chandra Nath; Promjunyakul, Warunya; Hatakeyama, Hiroyasu; Gonda, Kohsuke; Imamura, Junji; Vasudevanpillai, Biju; Ohuchi, Noriaki; Kanzaki, Makoto; Higuchi, Hideo; Kaku, Mitsuo

    2013-01-01

    The mechanisms underlying the cellular entry of the HIV-1 Tat protein transduction domain (TatP) and the molecular information necessary to improve the transduction efficiency of TatP remain unclear due to the technical limitations for direct visualization of TatP's behavior in cells. Using confocal microscopy, total internal reflection fluorescence microscopy, and four-dimensional microscopy, we developed a single-molecule tracking assay for TatP labeled with quantum dots (QDs) to examine th...

  14. COMP-angiopoietin 1 increases proliferation, differentiation, and migration of stem-like cells through Tie-2-mediated activation of p38 MAPK and PI3K/Akt signal transduction pathways

    Energy Technology Data Exchange (ETDEWEB)

    Kook, Sung-Ho [Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Lim, Shin-Saeng [School of Dentistry and Dental Research Institute, Seoul National University, Seoul (Korea, Republic of); Cho, Eui-Sic; Lee, Young-Hoon; Han, Seong-Kyu; Lee, Kyung-Yeol [Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Kwon, Jungkee [College of Veterinary Medicine, Chonbuk National University, Jeonju (Korea, Republic of); Hwang, Jae-Won; Bae, Cheol-Hyeon [Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Seo, Young-Kwon [Research Institute of Biotechnology, Dongguk University, Seoul (Korea, Republic of); Lee, Jeong-Chae, E-mail: leejc88@jbnu.ac.kr [Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of)

    2014-12-12

    Highlights: • COMP-Ang1 induces Tie-2 activation in BMMSCs, but not in primary osteoblasts. • Tie-2 knockdown inhibits COMP-Ang1-stimulated proliferation and osteoblastogenesis. • Tie-2 knockdown prevents COMP-Ang1-induced activation of PI3K/Akt and p38 MAPK. • COMP-Ang1 induces migration of cells via activation of PI3K/Akt and CXCR4 pathways. • COMP-Ang1 stimulates in vivo migration of PDLSCs into a calvarial defect site of rats. - Abstract: Recombinant COMP-Ang1, a chimera of angiopoietin-1 (Ang1) and a short coiled-coil domain of cartilage oligomeric matrix protein (COMP), is under consideration as a therapeutic agent capable of inducing the homing of cells with increased angiogenesis. However, the potentials of COMP-Ang1 to stimulate migration of mesenchymal stem cells (MSCs) and the associated mechanisms are not completely understood. We examined the potential of COMP-Ang1 on bone marrow (BM)-MSCs, human periodontal ligament stem cells (PDLSCs), and calvarial osteoblasts. COMP-Ang1 augmented Tie-2 induction at protein and mRNA levels and increased proliferation and expression of runt-related transcription factor 2 (Runx2), osterix, and CXCR4 in BMMSCs, but not in osteoblasts. The COMP-Ang1-mediated increases were inhibited by Tie-2 knockdown and by treating inhibitors of phosphoinositide 3-kinase (PI3K), LY294002, or p38 mitogen-activated protein kinase (MAPK), SB203580. Phosphorylation of p38 MAPK and Akt was prevented by siRNA-mediated silencing of Tie-2. COMP-Ang1 also induced in vitro migration of BMMSCs and PDLSCs. The induced migration was suppressed by Tie-2 knockdown and by CXCR4-specific peptide antagonist or LY294002, but not by SB203580. Furthermore, COMP-Ang1 stimulated the migration of PDLSCs into calvarial defect site of rats. Collectively, our results demonstrate that COMP-Ang1-stimulated proliferation, differentiation, and migration of progenitor cells may involve the Tie-2-mediated activation of p38 MAPK and PI3K/Akt pathways.

  15. COMP-angiopoietin 1 increases proliferation, differentiation, and migration of stem-like cells through Tie-2-mediated activation of p38 MAPK and PI3K/Akt signal transduction pathways

    International Nuclear Information System (INIS)

    Kook, Sung-Ho; Lim, Shin-Saeng; Cho, Eui-Sic; Lee, Young-Hoon; Han, Seong-Kyu; Lee, Kyung-Yeol; Kwon, Jungkee; Hwang, Jae-Won; Bae, Cheol-Hyeon; Seo, Young-Kwon; Lee, Jeong-Chae

    2014-01-01

    Highlights: • COMP-Ang1 induces Tie-2 activation in BMMSCs, but not in primary osteoblasts. • Tie-2 knockdown inhibits COMP-Ang1-stimulated proliferation and osteoblastogenesis. • Tie-2 knockdown prevents COMP-Ang1-induced activation of PI3K/Akt and p38 MAPK. • COMP-Ang1 induces migration of cells via activation of PI3K/Akt and CXCR4 pathways. • COMP-Ang1 stimulates in vivo migration of PDLSCs into a calvarial defect site of rats. - Abstract: Recombinant COMP-Ang1, a chimera of angiopoietin-1 (Ang1) and a short coiled-coil domain of cartilage oligomeric matrix protein (COMP), is under consideration as a therapeutic agent capable of inducing the homing of cells with increased angiogenesis. However, the potentials of COMP-Ang1 to stimulate migration of mesenchymal stem cells (MSCs) and the associated mechanisms are not completely understood. We examined the potential of COMP-Ang1 on bone marrow (BM)-MSCs, human periodontal ligament stem cells (PDLSCs), and calvarial osteoblasts. COMP-Ang1 augmented Tie-2 induction at protein and mRNA levels and increased proliferation and expression of runt-related transcription factor 2 (Runx2), osterix, and CXCR4 in BMMSCs, but not in osteoblasts. The COMP-Ang1-mediated increases were inhibited by Tie-2 knockdown and by treating inhibitors of phosphoinositide 3-kinase (PI3K), LY294002, or p38 mitogen-activated protein kinase (MAPK), SB203580. Phosphorylation of p38 MAPK and Akt was prevented by siRNA-mediated silencing of Tie-2. COMP-Ang1 also induced in vitro migration of BMMSCs and PDLSCs. The induced migration was suppressed by Tie-2 knockdown and by CXCR4-specific peptide antagonist or LY294002, but not by SB203580. Furthermore, COMP-Ang1 stimulated the migration of PDLSCs into calvarial defect site of rats. Collectively, our results demonstrate that COMP-Ang1-stimulated proliferation, differentiation, and migration of progenitor cells may involve the Tie-2-mediated activation of p38 MAPK and PI3K/Akt pathways

  16. Course of Subthreshold Bipolar Disorder in Youth: Diagnostic Progression from Bipolar Disorder Not Otherwise Specified

    Science.gov (United States)

    Axelson, David A.; Birmaher, Boris; Strober, Michael A.; Goldstein, Benjamin I.; Ha, Wonho; Gill, Mary Kay; Goldstein, Tina R.; Yen, Shirley; Hower, Heather; Hunt, Jeffrey I.; Liao, Fangzi; Iyengar, Satish; Dickstein, Daniel; Kim, Eunice; Ryan, Neal D.; Frankel, Erica; Keller, Martin B.

    2011-01-01

    Objective: To determine the rate of diagnostic conversion from an operationalized diagnosis of bipolar disorder not otherwise specified (BP-NOS) to bipolar I disorder (BP-I) or bipolar II disorder (BP-II) in youth over prospective follow-up and to identify factors associated with conversion. Method: Subjects were 140 children and adolescents…

  17. Bipolar one diode-one resistor integration for high-density resistive memory applications.

    Science.gov (United States)

    Li, Yingtao; Lv, Hangbing; Liu, Qi; Long, Shibing; Wang, Ming; Xie, Hongwei; Zhang, Kangwei; Huo, Zongliang; Liu, Ming

    2013-06-07

    Different from conventional unipolar-type 1D-1R RRAM devices, a bipolar-type 1D-1R memory device concept is proposed and successfully demonstrated by the integration of Ni/TiOx/Ti diode and Pt/HfO2/Cu bipolar RRAM cell to suppress the undesired sneak current in a cross-point array. The bipolar 1D-1R memory device not only achieves self-compliance resistive switching characteristics by the reverse bias current of the Ni/TiOx/Ti diode, but also exhibits excellent bipolar resistive switching characteristics such as uniform switching, satisfactory data retention, and excellent scalability, which give it high potentiality for high-density integrated nonvolatile memory applications.

  18. A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Peijs, L; Vinberg, M

    2015-01-01

    as a diagnostic and state biomarker in bipolar disorder. First, messenger RNA levels of 19 candidate genes were assessed in peripheral blood mononuclear cells of 37 rapid cycling bipolar disorder patients in different affective states (depression, mania and euthymia) during a 6-12-month period and in 40 age......- and gender-matched healthy control subjects. Second, a composite gene expression measure was constructed in the first half study sample and independently validated in the second half of the sample. We found downregulation of POLG and OGG1 expression in bipolar disorder patients compared with healthy control...... subjects. In patients with bipolar disorder, upregulation of NDUFV2 was observed in a depressed state compared with a euthymic state. The composite gene expression measure for discrimination between patients and healthy control subjects on the basis of 19 genes generated an area under the receiver...

  19. Bipolar (spectrum) disorder and mood stabilization: standing at the crossroads?

    OpenAIRE

    De Fruyt, Jurgen; Demyttenaere, Koen

    2007-01-01

    Diagnosis and treatment of bipolar disorder has long been a neglected discipline. Recent years have shown an upsurge in bipolar research. When compared to major depressive disorder, bipolar research still remains limited and more expert based than evidence based. In bipolar diagnosis the focus is shifting from classic mania to bipolar depression and hypomania. There is a search for bipolar signatures in symptoms and course of major depressive episodes. The criteria for hypomania are softened,...

  20. Elementary signaling modes predict the essentiality of signal transduction network components.

    Science.gov (United States)

    Wang, Rui-Sheng; Albert, Réka

    2011-03-22

    Understanding how signals propagate through signaling pathways and networks is a central goal in systems biology. Quantitative dynamic models help to achieve this understanding, but are difficult to construct and validate because of the scarcity of known mechanistic details and kinetic parameters. Structural and qualitative analysis is emerging as a feasible and useful alternative for interpreting signal transduction. In this work, we present an integrative computational method for evaluating the essentiality of components in signaling networks. This approach expands an existing signaling network to a richer representation that incorporates the positive or negative nature of interactions and the synergistic behaviors among multiple components. Our method simulates both knockout and constitutive activation of components as node disruptions, and takes into account the possible cascading effects of a node's disruption. We introduce the concept of elementary signaling mode (ESM), as the minimal set of nodes that can perform signal transduction independently. Our method ranks the importance of signaling components by the effects of their perturbation on the ESMs of the network. Validation on several signaling networks describing the immune response of mammals to bacteria, guard cell abscisic acid signaling in plants, and T cell receptor signaling shows that this method can effectively uncover the essentiality of components mediating a signal transduction process and results in strong agreement with the results of Boolean (logical) dynamic models and experimental observations. This integrative method is an efficient procedure for exploratory analysis of large signaling and regulatory networks where dynamic modeling or experimental tests are impractical. Its results serve as testable predictions, provide insights into signal transduction and regulatory mechanisms and can guide targeted computational or experimental follow-up studies. The source codes for the algorithms

  1. [Bipolar disorders in DSM-5].

    Science.gov (United States)

    Severus, E; Bauer, M

    2014-05-01

    In spring 2013 the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) edited by the American Psychiatric Association was published. The DSM-5 has also brought some important changes regarding bipolar disorders. The goal of this manuscript is to review the novelties in DSM-5 and to evaluate the implications of these changes. The diagnostic criteria as well as the additional remarks provided in the running text of DSM-5 were carefully appraised. For the first time diagnostic criteria are provided for disorders which up to now have been considered as subthreshold bipolar disorders. Furthermore, mixed episodes were eliminated and instead a mixed specifier was introduced. An increase in goal-directed activity/energy is now one of the obligatory symptoms for a (hypo)manic episode. Diagnostic guidance is provided as to when a (hypo)manic episode that has developed during treatment with an antidepressant has to be judged to be causally related to antidepressants and when this episode has only occurred coincidentally with antidepressant use. While some of the novelties are clearly useful, e.g. addition of increased goal-directed activity/energy as obligatory symptom for (hypo)manic episodes, this remains to be demonstrated for others, such as the definition of various subthreshold bipolar disorders.

  2. Bipolar Disorder and Obsessive Compulsive Disorder Comorbidity

    Directory of Open Access Journals (Sweden)

    Necla Keskin

    2014-08-01

    Full Text Available The comorbidity of bipolar disorder and anxiety disorders is a well known concept. Obsessive-compulsive disorder is the most commonly seen comorbid anxiety disorder in bipolar patients. Some genetic variants, neurotransmitters especially serotonergic systems and second-messenger systems are thought to be responsible for its etiology. Bipolar disorder alters the clinical aspects of obsessive compulsive disorder and is associated with poorer outcome. The determination of comorbidity between bipolar disorder and obsessive compulsive disorder is quite important for appropriate clinical management and treatment. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(4.000: 429-437

  3. Homer1a protein expression in schizophrenia, bipolar disorder, and major depression.

    Science.gov (United States)

    Leber, Stefan L; Llenos, Ida C; Miller, Christine L; Dulay, Jeannette R; Haybaeck, Johannes; Weis, Serge

    2017-10-01

    In recent years, there was growing interest in postsynaptic density proteins in the central nervous system. Of the most important candidates of this specialized region are proteins belonging to the Homer protein family. This family of scaffolding proteins is suspected to participate in the pathogenesis of a variety of diseases. The present study aims to compare Homer1a expression in the hippocampus and cingulate gyrus of patients with major psychiatric disorders including schizophrenia, bipolar disorder and major depression. Immunohistochemistry was used to analyze changes of Homer1a protein expression in the hippocampal formation and the cingulate gyrus from the respective disease groups. Glial cells of the cingulate gyrus gray matter showed decreased Homer1a levels in bipolar disorder when compared to controls. The same results were seen when comparing cingulate gyrus gray matter glial cells in bipolar disorder with major depression. Stratum oriens glial cells of the hippocampus showed decreased Homer1a levels in bipolar disorder when compared to controls and major depression. Stratum lacunosum glial cells showed decreased Homer1a levels in bipolar disorder when compared to major depression. In stratum oriens interneurons Homer1a levels were increased in all disease groups when compared to controls. Stratum lucidum axons showed decreased Homer1a levels in bipolar disorder when compared to controls. Our data demonstrate altered Homer1a levels in specific brain regions and cell types of patients suffering from schizophrenia, bipolar disorder and major depression. These findings support the role of Homer proteins as interesting candidates in neuropsychiatric pathophysiology and treatment.

  4. Localization of Cacna1s to ON Bipolar Dendritic Tips Requires mGluR6-Related Cascade Elements

    OpenAIRE

    Tummala, Shanti R.; Neinstein, Adam; Fina, Marie E.; Dhingra, Anuradha; Vardi, Noga

    2014-01-01

    The pore forming subunit of a L-type voltage gated calcium channel colocalizes with the components of the ON bipolar cell signaling cascade and its localization is dependent on the normal expression of these components.

  5. Bipolar mixed features - Results from the comparative effectiveness for bipolar disorder (Bipolar CHOICE) study.

    Science.gov (United States)

    Tohen, Mauricio; Gold, Alexandra K; Sylvia, Louisa G; Montana, Rebecca E; McElroy, Susan L; Thase, Michael E; Rabideau, Dustin J; Nierenberg, Andrew A; Reilly-Harrington, Noreen A; Friedman, Edward S; Shelton, Richard C; Bowden, Charles L; Singh, Vivek; Deckersbach, Thilo; Ketter, Terence A; Calabrese, Joseph R; Bobo, William V; McInnis, Melvin G

    2017-08-01

    DSM-5 changed the criteria from DSM-IV for mixed features in mood disorder episodes to include non-overlapping symptoms of depression and hypomania/mania. It is unknown if, by changing these criteria, the same group would qualify for mixed features. We assessed how those meeting DSM-5 criteria for mixed features compare to those meeting DSM-IV criteria. We analyzed data from 482 adult bipolar patients in Bipolar CHOICE, a randomized comparative effectiveness trial. Bipolar diagnoses were confirmed through the MINI International Neuropsychiatric Interview (MINI). Presence and severity of mood symptoms were collected with the Bipolar Inventory of Symptoms Scale (BISS) and linked to DSM-5 and DSM-IV mixed features criteria. Baseline demographics and clinical variables were compared between mood episode groups using ANOVA for continuous variables and chi-square tests for categorical variables. At baseline, the frequency of DSM-IV mixed episodes diagnoses obtained with the MINI was 17% and with the BISS was 20%. Using DSM-5 criteria, 9% of participants met criteria for hypomania/mania with mixed features and 12% met criteria for a depressive episode with mixed features. Symptom severity was also associated with increased mixed features with a high rate of mixed features in patients with mania/hypomania (63.8%) relative to those with depression (8.0%). Data on mixed features were collected at baseline only and thus do not reflect potential patterns in mixed features within this sample across the study duration. The DSM-5 narrower, non-overlapping definition of mixed episodes resulted in fewer patients who met mixed criteria compared to DSM-IV. Copyright © 2017. Published by Elsevier B.V.

  6. Signal transduction through the IL-4 and insulin receptor families.

    Science.gov (United States)

    Wang, L M; Keegan, A; Frankel, M; Paul, W E; Pierce, J H

    1995-07-01

    Activation of tyrosine kinase-containing receptors and intracellular tyrosine kinases by ligand stimulation is known to be crucial for mediating initial and subsequent events involved in mitogenic signal transduction. Receptors for insulin and insulin-like growth factor 1 (IGF-1) contain cytoplasmic tyrosine kinase domains that undergo autophosphorylation upon ligand stimulation. Activation of these receptors also leads to pronounced and rapid tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in cells of connective tissue origin. A related substrate, designated 4PS, is similarly phosphorylated by insulin and IGF-1 stimulation in many hematopoietic cell types. IRS-1 and 4PS possess a number of tyrosine phosphorylation sites that are within motifs that bind specific SH2-containing molecules known to be involved in mitogenic signaling such as PI-3 kinase, SHPTP-2 (Syp) and Grb-2. Thus, they appear to act as docking substrates for a variety of signaling molecules. The majority of hematopoietic cytokines bind to receptors that do not possess intrinsic kinase activity, and these receptors have been collectively termed as members of the hematopoietin receptor superfamily. Despite their lack of tyrosine kinase domains, stimulation of these receptors has been demonstrated to activate intracellular kinases leading to tyrosine phosphorylation of multiple substrates. Recent evidence has demonstrated that activation of different members of the Janus family of tyrosine kinases is involved in mediating tyrosine phosphorylation events by specific cytokines. Stimulation of the interleukin 4 (IL-4) receptor, a member of the hematopoietin receptor superfamily, is thought to result in activation of Jak1, Jak3, and/or Fes tyrosine kinases.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. New insights into transduction pathways that regulate boar sperm function.

    Science.gov (United States)

    Hurtado de Llera, A; Martin-Hidalgo, D; Gil, M C; Garcia-Marin, L J; Bragado, M J

    2016-01-01

    Detailed molecular mechanisms mediating signal transduction cascades that regulate boar sperm function involving Ser/Thr and tyrosine phosphorylation of proteins have been reviewed previously. Therefore, this review will focus in those kinase pathways identified recently (functional spermatozoa processes. AMP-activated protein kinase (AMPK) is a cell energy sensor kinase that was first identified in mammalian spermatozoa in 2012, and since then it has emerged as an essential regulator of boar sperm function. Signaling pathways leading to AMPK activation in boar sperm are highlighted in this review (PKA, CaMKKα/β, and PKC as well as Ca(2+) and cAMP messengers as upstream regulators). Interestingly, stimuli considered as cell stress (hyperosmotic stress, inhibition of mitochondrial activity, absence of intracellular Ca(2+)) markedly activate AMPK in boar spermatozoa. Moreover, AMPK plays a remarkable and necessary regulatory role in mammalian sperm function, controlling essential boar sperm functional processes such as motility, viability, mitochondrial membrane potential, organization and fluidity of plasma membrane, and outer acrosome membrane integrity. These mentioned processes are all required under fluctuating environment of spermatozoa when transiting through the female reproductive tract to achieve fertilization. An applied role of AMPK in artificial insemination techniques is also suggested as during boar seminal doses preservation at 17 °C, physiological levels of AMPK activity markedly increase (maximum on Day 7) and result essential to maintain the aforementioned fundamental sperm processes. Moreover, regulation of sperm function exerted by the glycogen synthase kinase 3 and Src family kinase pathways is summarized. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Resting lymphocyte transduction with measles virus glycoprotein pseudotyped lentiviral vectors relies on CD46 and SLAM

    International Nuclear Information System (INIS)

    Zhou Qi; Schneider, Irene C.; Gallet, Manuela; Kneissl, Sabrina; Buchholz, Christian J.

    2011-01-01

    The measles virus (MV) glycoproteins hemagglutinin (H) and fusion (F) were recently shown to mediate transduction of resting lymphocytes by lentiviral vectors. MV vaccine strains use CD46 or signaling lymphocyte activation molecule (SLAM) as receptor for cell entry. A panel of H protein mutants derived from vaccine strain or wild-type MVs that lost or gained CD46 or SLAM receptor usage were investigated for their ability to mediate gene transfer into unstimulated T lymphocytes. The results demonstrate that CD46 is sufficient for efficient vector particle association with unstimulated lymphocytes. For stable gene transfer into these cells, however, both MV receptors were found to be essential.

  9. [Thinking organization and defense mechanisms in bipolar disorders. Clinical and psychopathological study on bipolar I and bipolar II].

    Science.gov (United States)

    Lo Baido, Rosa; Di Blasi, Marie; Alfano, Pietro; Audino, Palma; Bellavia, Carmela; Blando, Anna Antonia; Merendino, Adelaide; Messina, Rossana; Poma, Maria Luisa; La Grutta, Sabina

    2013-01-01

    The aim of this research is to explore the psychical functioning in bipolar I or bipolar II disorder people through the analysis and comparison of their thought styles and defense patterns. 29 bipolar I and bipolar II people afferent to Palermo University Policlinical Psychriatic Hospital Department were selected during the whole 2009-2010 year. The following tests were administred: Wechsler Adult Intelligent Scale-R (WAIS-R) in order to measure the general cognitive function; Defense Mechanisms Inventory (DMI) in order to measure defense patterns. Afterwards, the results of the two tests were analysed and compared. Bipolar disorder people use cognitive mechanisms and defense strategies that are very different from standard population. Bipolar I subjects show both wider and more serious cognitive deterioration and stricter defense mechanisms than bipolar II subjects. Generally bipolar patients show an immature personality based on archaic mechanisms that can be found in all the spheres of their personality: emotions, cognition, Ego-strength, adaptability to reality. The peculiar achieved cognitive and defense profile leads to important considerations about how psychological strategies can contribute to use "bespoke" treatments for these patients.

  10. Recent Advances in the Study of Bipolar/Rod-Shaped Microglia and their Roles in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Ngan Pan Bennett Au

    2017-05-01

    Full Text Available Microglia are the resident immune cells of the central nervous system (CNS and they contribute to primary inflammatory responses following CNS injuries. The morphology of microglia is closely associated with their functional activities. Most previous research efforts have attempted to delineate the role of ramified and amoeboid microglia in the pathogenesis of neurodegenerative diseases. In addition to ramified and amoeboid microglia, bipolar/rod-shaped microglia were first described by Franz Nissl in 1899 and their presence in the brain was closely associated with the pathology of infectious diseases and sleeping disorders. However, studies relating to bipolar/rod-shaped microglia are very limited, largely due to the lack of appropriate in vitro and in vivo experimental models. Recent studies have reported the formation of bipolar/rod-shaped microglia trains in in vivo models of CNS injury, including diffuse brain injury, focal transient ischemia, optic nerve transection and laser-induced ocular hypertension (OHT. These bipolar/rod-shaped microglia formed end-to-end alignments in close proximity to the adjacent injured axons, but they showed no interactions with blood vessels or other types of glial cell. Recent studies have also reported on a highly reproducible in vitro culture model system to enrich bipolar/rod-shaped microglia that acts as a powerful tool with which to characterize this form of microglia. The molecular aspects of bipolar/rod-shaped microglia are of great interest in the field of CNS repair. This review article focuses on studies relating to the morphology and transformation of microglia into the bipolar/rod-shaped form, along with the differential gene expression and spatial distribution of bipolar/rod-shaped microglia in normal and pathological CNSs. The spatial arrangement of bipolar/rod-shaped microglia is crucial in the reorganization and remodeling of neuronal and synaptic circuitry following CNS injuries. Finally, we

  11. Bipolar Plasma Membrane Distribution of Phosphoinositides and Their Requirement for Auxin-Mediated Cell Polarity and Patterning in Arabidopsis[W

    Science.gov (United States)

    Tejos, Ricardo; Sauer, Michael; Vanneste, Steffen; Palacios-Gomez, Miriam; Li, Hongjiang; Heilmann, Mareike; van Wijk, Ringo; Vermeer, Joop E.M.; Heilmann, Ingo; Munnik, Teun; Friml, Jiří

    2014-01-01

    Cell polarity manifested by asymmetric distribution of cargoes, such as receptors and transporters, within the plasma membrane (PM) is crucial for essential functions in multicellular organisms. In plants, cell polarity (re)establishment is intimately linked to patterning processes. Despite the importance of cell polarity, its underlying mechanisms are still largely unknown, including the definition and distinctiveness of the polar domains within the PM. Here, we show in Arabidopsis thaliana that the signaling membrane components, the phosphoinositides phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] as well as PtdIns4P 5-kinases mediating their interconversion, are specifically enriched at apical and basal polar plasma membrane domains. The PtdIns4P 5-kinases PIP5K1 and PIP5K2 are redundantly required for polar localization of specifically apical and basal cargoes, such as PIN-FORMED transporters for the plant hormone auxin. As a consequence of the polarity defects, instructive auxin gradients as well as embryonic and postembryonic patterning are severely compromised. Furthermore, auxin itself regulates PIP5K transcription and PtdIns4P and PtdIns(4,5)P2 levels, in particular their association with polar PM domains. Our results provide insight into the polar domain–delineating mechanisms in plant cells that depend on apical and basal distribution of membrane lipids and are essential for embryonic and postembryonic patterning. PMID:24876254

  12. Regulation of TGF-β Signal Transduction.

    Science.gov (United States)

    Zhao, Bing; Chen, Ye-Guang

    2014-01-01

    Transforming growth factor-β (TGF-β) signaling regulates diverse cellular processes, including cell proliferation, differentiation, apoptosis, cell plasticity, and migration. TGF-β signaling can be mediated by Smad proteins or other signaling proteins such as MAP kinases and Akt. TGF-β signaling is tightly regulated at different levels along the pathways to ensure its proper physiological functions in different cells and tissues. Deregulation of TGF-β signaling has been associated with various kinds of diseases, such as cancer and tissue fibrosis. This paper focuses on our recent work on regulation of TGF-β signaling.

  13. Poorer sustained attention in bipolar I than bipolar II disorder

    Directory of Open Access Journals (Sweden)

    Chen Shih-Heng

    2010-02-01

    Full Text Available Abstract Background Nearly all information processing during cognitive processing takes place during periods of sustained attention. Sustained attention deficit is among the most commonly reported impairments in bipolar disorder (BP. The majority of previous studies have only focused on bipolar I disorder (BP I, owing to underdiagnosis or misdiagnosis of bipolar II disorder (BP II. With the refinement of the bipolar spectrum paradigm, the goal of this study was to compare the sustained attention of interepisode patients with BP I to those with BP II. Methods In all, 51 interepisode BP patients (22 with BP I and 29 with BP II and 20 healthy controls participated in this study. The severity of psychiatric symptoms was assessed by the 17-item Hamilton Depression Rating Scale and the Young Mania Rating Scale. All participants undertook Conners' Continuous Performance Test II (CPT-II to evaluate sustained attention. Results After controlling for the severity of symptoms, age and years of education, BP I patients had a significantly longer reaction times (F(2,68 = 7.648, P = 0.001, worse detectability (d' values (F(2,68 = 6.313, P = 0.003 and more commission errors (F(2,68 = 6.182, P = 0.004 than BP II patients and healthy controls. BP II patients and controls scored significantly higher than BP I patients for d' (F = 6.313, P = 0.003. No significant difference was found among the three groups in omission errors and no significant correlations were observed between CPT-II performance and clinical characteristics in the three groups. Conclusions These findings suggested that impairments in sustained attention might be more representative of BP I than BP II after controlling for the severity of symptoms, age, years of education and reaction time on the attentional test. A longitudinal follow-up study design with a larger sample size might be needed to provide more information on chronological sustained attention deficit in BP patients, and to illustrate

  14. Adenovirus coxsackie adenovirus receptor-mediated binding to human erythrocytes does not preclude systemic transduction.

    Science.gov (United States)

    Rojas, L A; Moreno, R; Calderón, H; Alemany, R

    2016-12-01

    There is great skepticism in the capability of adenovirus vectors and oncolytic adenoviruses to reach specific organs or tumors upon systemic administration. Besides antibodies, the presence of CAR (coxsackie and adenovirus receptor) in human erythrocytes has been postulated to sequester CAR-binding adenoviruses, commonly used in gene therapy and oncolytic applications. The use of non-CAR-binding fibers or serotypes has been postulated to solve this limitation. Given the lack of integrins in erythrocytes and therefore of internalization of the CAR-bound virus, we hypothesized that the interaction of adenovirus type 5 (Ad5) with CAR in human erythrocytes could be reversible. In this work, we have studied the effects of Ad5 interaction with human erythrocytes via CAR. Although erythrocyte binding was observed, it did not reduce viral transduction of tumor cells in vitro after long-term incubations. Transplantation of human erythrocytes into nude mice did not reduce Ad5 extravasation and transduction of liver and human xenograft tumors after systemic administration. These findings indicate that despite human erythrocytes are able to bind to Ad5, this binding is reversible and does not prevent extravasation and organ transduction after systemic delivery. Thus, the poor bioavailability of systemically delivered CAR-binding adenoviruses in humans is likely due to other factors such as liver sequestration or neutralizing antibodies.

  15. Efficient Transduction of Electricity by Bacteria

    National Research Council Canada - National Science Library

    Ellington, Andrew

    2004-01-01

    .... Further optimization of this fuel cell system should allow us to practically implement electric power production from the carbohydrate energy sources that are available in a variety of settings...

  16. Ca2+-sensors and ROS-GC: Interlocked sensory transduction elements: A review

    Directory of Open Access Journals (Sweden)

    Rameshwar K Sharma

    2012-04-01

    Full Text Available From its initial discovery that ROS-GC membrane guanylate cyclase is a mono-modal Ca2+-transduction system linked exclusively with the phototransduction machinery to the successive finding that it embodies a remarkable bimodal Ca2+signaling device, its widened transduction role in the general signaling mechanisms of the sensory neuron cells was envisioned. A theoretical concept was proposed where Ca2+-modulates ROS-GC through its generated cyclic GMP via a nearby cyclic nucleotide gated channel and creates a hyper- or depolarized sate in the neuron membrane (Ca2+ Binding Proteins 1:1, 7-11, 2006. The generated electric potential then becomes a mode of transmission of the parent [Ca2+]i signal. Ca2+ and ROS-GC are interlocked messengers in multiple sensory transduction mechanisms.This comprehensive review discusses the developmental stages to the present status of this concept and demonstrates how neuronal Ca2+-sensor proteins are the interconnected elements of this elegant ROS-GC transduction system. The focus is on the dynamism of the structural composition of this system, and how it accommodates selectivity and elasticity for the Ca2+ signals to perform multiple tasks linked with the SENSES of vision, smell and possibly of taste and the pineal gland. An intriguing illustration is provided for the Ca2+ sensor GCAP1 which displays its remarkable ability for its flexibility in function from being a photoreceptor sensor to an odorant receptor sensor. In doing so it reverses its function from an inhibitor of ROS-GC to the stimulator of ONE-GC membrane guanylate cyclase.

  17. Integrated Electromechanical Transduction Schemes for Polymer MEMS Sensors

    Directory of Open Access Journals (Sweden)

    Damien Thuau

    2018-04-01

    Full Text Available Polymer Micro ElectroMechanical Systems (MEMS have the potential to constitute a powerful alternative to silicon-based MEMS devices for sensing applications. Although the use of commercial photoresists as structural material in polymer MEMS has been widely reported, the integration of functional polymer materials as electromechanical transducers has not yet received the same amount of interest. In this context, we report on the design and fabrication of different electromechanical schemes based on polymeric materials ensuring different transduction functions. Piezoresistive transduction made of carbon nanotube-based nanocomposites with a gauge factor of 200 was embedded within U-shaped polymeric cantilevers operating either in static or dynamic modes. Flexible resonators with integrated piezoelectric transduction were also realized and used as efficient viscosity sensors. Finally, piezoelectric-based organic field effect transistor (OFET electromechanical transduction exhibiting a record sensitivity of over 600 was integrated into polymer cantilevers and used as highly sensitive strain and humidity sensors. Such advances in integrated electromechanical transduction schemes should favor the development of novel all-polymer MEMS devices for flexible and wearable applications in the future.

  18. Theory and modeling of cylindrical thermo-acoustic transduction

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Lihong, E-mail: lhtong@ecjtu.edu.cn [School of Civil Engineering and Architecture, East China Jiaotong University, Nanchang, Jiangxi (China); Lim, C.W. [Department of Architecture and Civil Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR (China); Zhao, Xiushao; Geng, Daxing [School of Civil Engineering and Architecture, East China Jiaotong University, Nanchang, Jiangxi (China)

    2016-06-03

    Models both for solid and thinfilm-solid cylindrical thermo-acoustic transductions are proposed and the corresponding acoustic pressure solutions are obtained. The acoustic pressure for an individual carbon nanotube (CNT) as a function of input power is investigated analytically and it is verified by comparing with the published experimental data. Further numerical analysis on the acoustic pressure response and characteristics for varying input frequency and distance are also examined both for solid and thinfilm-solid cylindrical thermo-acoustic transductions. Through detailed theoretical and numerical studies on the acoustic pressure solution for thinfilm-solid cylindrical transduction, it is concluded that a solid with smaller thermal conductivity favors to improve the acoustic performance. In general, the proposed models are applicable to a variety of cylindrical thermo-acoustic devices performing in different gaseous media. - Highlights: • Theory and modeling both for solid and thinfilm-solid cylindrical thermo-acoustic transductions are proposed. • The modeling is verified by comparing with the published experimental data. • Acoustic response characteristics of cylindrical thermo-acoustic transductions are predicted by the proposed model.

  19. Swimming in Deep Water: Childhood Bipolar Disorder

    Science.gov (United States)

    Senokossoff, Gwyn W.; Stoddard, Kim

    2009-01-01

    The authors focused on one parent's struggles in finding a diagnosis and intervention for a child who had bipolar disorder. The authors explain the process of identification, diagnosis, and intervention of a child who had bipolar disorder. In addition to the personal story, the authors provide information on the disorder and outline strategies…

  20. Bipolar disorder diagnosis: challenges and future directions

    Science.gov (United States)

    Phillips, Mary L; Kupfer, David J

    2018-01-01

    Bipolar disorder refers to a group of affective disorders, which together are characterised by depressive and manic or hypomanic episodes. These disorders include: bipolar disorder type I (depressive and manic episodes: this disorder can be diagnosed on the basis of one manic episode); bipolar disorder type II (depressive and hypomanic episodes); cyclothymic disorder (hypomanic and depressive symptoms that do not meet criteria for depressive episodes); and bipolar disorder not otherwise specified (depressive and hypomanic-like symptoms that do not meet the diagnostic criteria for any of the aforementioned disorders). Bipolar disorder type II is especially difficult to diagnose accurately because of the difficulty in differentiation of this disorder from recurrent unipolar depression (recurrent depressive episodes) in depressed patients. The identification of objective biomarkers that represent pathophysiologic processes that differ between bipolar disorder and unipolar depression can both inform bipolar disorder diagnosis and provide biological targets for the development of new and personalised treatments. Neuroimaging studies could help the identification of biomarkers that differentiate bipolar disorder from unipolar depression, but the problem in detection of a clear boundary between these disorders suggests that they might be better represented as a continuum of affective disorders. Innovative combinations of neuroimaging and pattern recognition approaches can identify individual patterns of neural structure and function that accurately ascertain where a patient might lie on a behavioural scale. Ultimately, an integrative approach, with several biological measurements using different scales, could yield patterns of biomarkers (biosignatures) to help identify biological targets for personalised and new treatments for all affective disorders. PMID:23663952

  1. Transient Stuttering in Catatonic Bipolar Patients

    Directory of Open Access Journals (Sweden)

    Anthony B. Joseph

    1991-01-01

    Full Text Available Two cases of transient stuttering occurring in association with catatonia and bipolar disorder are described. Affective decompensation has been associated with lateralized cerebral dysfunction, and it is hypothesized that in some bipolar catatonic patients a concomitant disorder of the lateralization of language function may lead to a variety of clinical presentations including aphasia, mutism, and stuttering.

  2. Cognitive behavioral therapy for bipolar disorders

    OpenAIRE

    Lotufo Neto, Francisco

    2004-01-01

    Descrição dos objetivos e principais técnicas da terapia comportamental cognitiva usadas para a psicoterapia das pessoas com transtorno bipolar.Objectives and main techniques of cognitive behavior therapy for the treatment of bipolar disorder patients are described.

  3. AAV8 capsid variable regions at the two-fold symmetry axis contribute to high liver transduction by mediating nuclear entry and capsid uncoating

    Energy Technology Data Exchange (ETDEWEB)

    Tenney, Rebeca M.; Bell, Christie L.; Wilson, James M., E-mail: wilsonjm@mail.med.upenn.edu

    2014-04-15

    Adeno-associated virus serotype 8 (AAV8) is a promising vector for liver-directed gene therapy. Although efficient uncoating of viral capsids has been implicated in AAV8's robust liver transduction, much about the biology of AAV8 hepatotropism remains unclear. Our study investigated the structural basis of AAV8 liver transduction efficiency by constructing chimeric vector capsids containing sequences derived from AAV8 and AAV2 – a highly homologous yet poorly hepatotropic serotype. Engineered vectors containing capsid variable regions (VR) VII and IX from AAV8 in an AAV2 backbone mediated near AAV8-like transduction in mouse liver, with higher numbers of chimeric genomes detected in whole liver cells and isolated nuclei. Interestingly, chimeric capsids within liver nuclei also uncoated similarly to AAV8 by 6 weeks after administration, in contrast with AAV2, of which a significantly smaller proportion were uncoated. This study links specific AAV capsid regions to the transduction ability of a clinically relevant AAV serotype. - Highlights: • We construct chimeric vectors to identify determinants of AAV8 liver transduction. • An AAV2-based vector with 17 AAV8 residues exhibited high liver transduction in mice. • This vector also surpassed AAV2 in cell entry, nuclear entry and onset of expression. • Most chimeric vector particles were uncoated at 6 weeks, like AAV8 and unlike AAV2. • Chimera retained heparin binding and was antigenically distinct from AAV2 and AAV8.

  4. Ubiquitination of basal VEGFR2 regulates signal transduction and endothelial function.

    Science.gov (United States)

    Smith, Gina A; Fearnley, Gareth W; Abdul-Zani, Izma; Wheatcroft, Stephen B; Tomlinson, Darren C; Harrison, Michael A; Ponnambalam, Sreenivasan

    2017-10-15

    Cell surface receptors can undergo recycling or proteolysis but the cellular decision-making events that sort between these pathways remain poorly defined. Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) regulate signal transduction and angiogenesis, but how signaling and proteolysis is regulated is not well understood. Here, we provide evidence that a pathway requiring the E1 ubiquitin-activating enzyme UBA1 controls basal VEGFR2 levels, hence metering plasma membrane receptor availability for the VEGF-A-regulated endothelial cell response. VEGFR2 undergoes VEGF-A-independent constitutive degradation via a UBA1-dependent ubiquitin-linked pathway. Depletion of UBA1 increased VEGFR2 recycling from endosome-to-plasma membrane and decreased proteolysis. Increased membrane receptor availability after UBA1 depletion elevated VEGF-A-stimulated activation of key signaling enzymes such as PLCγ1 and ERK1/2. Although UBA1 depletion caused an overall decrease in endothelial cell proliferation, surviving cells showed greater VEGF-A-stimulated responses such as cell migration and tubulogenesis. Our study now suggests that a ubiquitin-linked pathway regulates the balance between receptor recycling and degradation which in turn impacts on the intensity and duration of VEGF-A-stimulated signal transduction and the endothelial response. © 2017. Published by The Company of Biologists Ltd.

  5. Dynamic receptor team formation can explain the high signal transduction gain in Escherichia coli.

    Science.gov (United States)

    Albert, Réka; Chiu, Yu-Wen; Othmer, Hans G

    2004-05-01

    Evolution has provided many organisms with sophisticated sensory systems that enable them to respond to signals in their environment. The response frequently involves alteration in the pattern of movement, either by directed movement, a process called taxis, or by altering the speed or frequency of turning, which is called kinesis. Chemokinesis has been most thoroughly studied in the peritrichous bacterium Escherichia coli, which has four helical flagella distributed over the cell surface, and swims by rotating them. When rotated counterclockwise the flagella coalesce into a propulsive bundle, producing a relatively straight "run," and when rotated clockwise they fly apart, resulting in a "tumble" which reorients the cell with little translocation. A stochastic process generates the runs and tumbles, and in a chemoeffector gradient, runs that carry the cell in a favorable direction are extended. The cell senses spatial gradients as temporal changes in receptor occupancy and changes the probability of counterclockwise rotation (the bias) on a fast timescale, but adaptation returns the bias to baseline on a slow timescale, enabling the cell to detect and respond to further concentration changes. The overall structure of the signal transduction pathways is well characterized in E. coli, but important details are still not understood. Only recently has a source of gain in the signal transduction network been identified experimentally, and here we present a mathematical model based on dynamic assembly of receptor teams that can explain this observation.

  6. Ubiquitination of basal VEGFR2 regulates signal transduction and endothelial function

    Directory of Open Access Journals (Sweden)

    Gina A. Smith

    2017-10-01

    Full Text Available Cell surface receptors can undergo recycling or proteolysis but the cellular decision-making events that sort between these pathways remain poorly defined. Vascular endothelial growth factor A (VEGF-A and vascular endothelial growth factor receptor 2 (VEGFR2 regulate signal transduction and angiogenesis, but how signaling and proteolysis is regulated is not well understood. Here, we provide evidence that a pathway requiring the E1 ubiquitin-activating enzyme UBA1 controls basal VEGFR2 levels, hence metering plasma membrane receptor availability for the VEGF-A-regulated endothelial cell response. VEGFR2 undergoes VEGF-A-independent constitutive degradation via a UBA1-dependent ubiquitin-linked pathway. Depletion of UBA1 increased VEGFR2 recycling from endosome-to-plasma membrane and decreased proteolysis. Increased membrane receptor availability after UBA1 depletion elevated VEGF-A-stimulated activation of key signaling enzymes such as PLCγ1 and ERK1/2. Although UBA1 depletion caused an overall decrease in endothelial cell proliferation, surviving cells showed greater VEGF-A-stimulated responses such as cell migration and tubulogenesis. Our study now suggests that a ubiquitin-linked pathway regulates the balance between receptor recycling and degradation which in turn impacts on the intensity and duration of VEGF-A-stimulated signal transduction and the endothelial response.

  7. Mechanical transduction by ion channels: A cautionary tale.

    Science.gov (United States)

    Sachs, Frederick

    2015-09-28

    Mechanical transduction by ion channels occurs in all cells. The physiological functions of these channels have just begun to be elaborated, but if we focus on the upper animal kingdom, these channels serve the common sensory services such as hearing and touch, provide the central nervous system with information on the force and position of muscles and joints, and they provide the autonomic system with information about the filling of hollow organs such as blood vessels. However, all cells of the body have mechanosensitive channels (MSCs), including red cells. Most of these channels are cation selective and are activated by bilayer tension. There are also K + selective MSCs found commonly in neurons where they may be responsible for both general anesthesia and knockout punches in the boxing ring by hyperpolarizing neurons to reduce excitability. The cationic MSCs are typically inactive under normal mechanical stress, but open under pathologic stress. The channels are normally inactive because they are shielded from stress by the cytoskeleton. The cationic MSCs are specifically blocked by the externally applied peptide GsMtx4 (aka, AT-300). This is the first drug of its class and provides a new approach to many pathologies since it is nontoxic, non-immunogenic, stable in a biological environment and has a long pharmacokinetic lifetime. Pathologies involving excessive stress are common. They produce cardiac arrhythmias, contraction in stretched dystrophic muscle, xerocytotic and sickled red cells, etc . The channels seem to function primarily as "fire alarms", providing feedback to the cytoskeleton that a region of the bilayer is under excessive tension and needs reinforcing. The eukaryotic forms of MSCs have only been cloned in recent years and few people have experience working with them. "Newbies" need to become aware of the technology, potential artifacts, and the fundamentals of mechanics. The most difficult problem in studying MSCs is that the actual stimulus

  8. Thyroid Functions and Bipolar Affective Disorder

    Directory of Open Access Journals (Sweden)

    Subho Chakrabarti

    2011-01-01

    Full Text Available Accumulating evidence suggests that hypothalamo-pituitary-thyroid (HPT axis dysfunction is relevant to the pathophysiology and clinical course of bipolar affective disorder. Hypothyroidism, either overt or more commonly subclinical, appears to the commonest abnormality found in bipolar disorder. The prevalence of thyroid dysfunction is also likely to be greater among patients with rapid cycling and other refractory forms of the disorder. Lithium-treatment has potent antithyroid effects and can induce hypothyroidism or exacerbate a preexisting hypothyroid state. Even minor perturbations of the HPT axis may affect the outcome of bipolar disorder, necessitating careful monitoring of thyroid functions of patients on treatment. Supplementation with high dose thyroxine can be considered in some patients with treatment-refractory bipolar disorder. Neurotransmitter, neuroimaging, and genetic studies have begun to provide clues, which could lead to an improved understanding of the thyroid-bipolar disorder connection, and more optimal ways of managing this potentially disabling condition.

  9. Diagnostic stability in pediatric bipolar disorder

    DEFF Research Database (Denmark)

    Vedel Kessing, Lars; Vradi, Eleni; Andersen, Per Kragh

    2015-01-01

    BACKGROUND: The diagnostic stability of pediatric bipolar disorder has not been investigated previously. The aim was to investigate the diagnostic stability of the ICD-10 diagnosis of pediatric mania/bipolar disorder.METHODS: All patients below 19 years of age who got a diagnosis of mania/bipolar...... disorder at least once in a period from 1994 to 2012 at psychiatric inpatient or outpatient contact in Denmark were identified in a nationwide register.RESULTS: Totally, 354 children and adolescents got a diagnosis of mania/bipolar disorder at least once; a minority, 144 patients (40.7%) got the diagnosis...... at the first contact whereas the remaining patients (210; 59.3%) got the diagnosis at later contacts before age 19. For the latter patients, the median time elapsed from first treatment contact with the psychiatric service system to the first diagnosis with a manic episode/bipolar disorder was nearly 1 year...

  10. Nanofluidic diode and bipolar transistor.

    Science.gov (United States)

    Daiguji, Hirofumi; Oka, Yukiko; Shirono, Katsuhiro

    2005-11-01

    Theoretical modeling of ionic distribution and transport in a nanochannel containing a surface charge on its wall, 30 nm high and 5 microm long, suggests that ionic current can be controlled by locally modifying the surface charge density through a gate electrode, even if the electrical double layers are not overlapped. When the surface charge densities at the right and left halves of a channel are the same absolute value but of different signs, this could form the basis of a nanofluidic diode. When the surface charge density at the middle part of a channel is modified, this could form the basis of a nanofluidic bipolar transistor.

  11. Effect of different surface treatments on the stability of stainless steels for use as bipolar plates in low and high temperature proton exchange membrane fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Richards, J.; Schmidt, K. [Fraunhofer-Institut fuer Chemische Technologie (ICT), Wolfsburg (Germany); Tuebke, J.; Cremers, C. [Fraunhofer-Institut fuer Chemische Technologie (ICT), Pfinztal (Germany)

    2010-07-01

    The stability of different stainless steels against corrosion under simulated low and high temperature proton exchange membrane fuel cell (PEMFC) operating conditions was studied. These investigations showed a moderate corrosion resistance for a couple of steels under LT-PEMFC conditions. However, for the HT-PEMFC conditions all specimens except one exhibit visible corrosion traces. With regards to their corrosion resistance after different surface treatments results show a minor improvement in corrosion resistance after the electro polishing process for most of the tested stainless steel samples. (orig.)

  12. Signal Transduction in Histidine Kinases: Insights from New Structures

    Science.gov (United States)

    Bhate, Manasi P.; Molnar, Kathleen S.; Goulian, Mark; DeGrado, William F.

    2015-01-01

    Histidine kinases (HKs) are major players in bacterial signaling. There has been an explosion of new HK crystal structures in the last five years. We globally analyze the structures of HKs to yield insights into the mechanisms by which signals are transmitted to and across protein structures in this family. We interpret known enzymological data in the context of new structural data to show how asymmetry across the dimer interface is a key feature of signal transduction in HKs, and discuss how different HK domains undergo asymmetric-to-symmetric transitions during signal transduction and catalysis. A thermodynamic framework for signaling that encompasses these various properties is presented and the consequences of weak thermodynamic coupling are discussed. The synthesis of observations from enzymology, structural biology, protein engineering and thermodynamics paves the way for a deeper molecular understanding of histidine kinase signal transduction. PMID:25982528

  13. Comparative genomics and transduction potential of Enterococcus faecalis temperate bacteriophages.

    Science.gov (United States)

    Yasmin, Azra; Kenny, John G; Shankar, Jayendra; Darby, Alistair C; Hall, Neil; Edwards, Clive; Horsburgh, Malcolm J

    2010-02-01

    To determine the relative importance of temperate bacteriophage in the horizontal gene transfer of fitness and virulence determinants of Enterococcus faecalis, a panel of 47 bacteremia isolates were treated with the inducing agents mitomycin C, norfloxacin, and UV radiation. Thirty-four phages were purified from culture supernatants and discriminated using pulsed-field gel electrophoresis (PFGE) and restriction mapping. From these analyses the genomes of eight representative phages were pyrosequenced, revealing four distinct groups of phages. Three groups of phages, PhiFL1 to 3, were found to be sequence related, with PhiFL1A to C and PhiFL2A and B sharing the greatest identity (87 to 88%), while PhiFL3A and B share 37 to 41% identity with PhiFL1 and 2. PhiFL4A shares 3 to 12% identity with the phages PhiFL1 to 3. The PhiFL3A and B phages possess a high DNA sequence identity with the morphogenesis and lysis modules of Lactococcus lactis subsp. cremoris prophages. Homologs of the Streptococcus mitis platelet binding phage tail proteins, PblA and PblB, are encoded on each sequenced E. faecalis phage. Few other phage genes encoding potential virulence functions were identified, and there was little evidence of carriage of lysogenic conversion genes distal to endolysin, as has been observed with genomes of many temperate phages from the opportunist pathogens Staphylococcus aureus and Streptococcus pyogenes. E. faecalis JH2-2 lysogens were generated using the eight phages, and these were examined for their relative fitness in Galleria mellonella. Several lysogens exhibited different effects upon survival of G. mellonella compared to their isogenic parent. The eight phages were tested for their ability to package host DNA, and three were shown to be very effective for generalized transduction of naive host cells of the laboratory strains OG1RF and JH2-2.

  14. Scale-up of Carbon/Carbon Bipolar Plates

    Energy Technology Data Exchange (ETDEWEB)

    David P. Haack

    2009-04-08

    This project was focused upon developing a unique material technology for use in PEM fuel cell bipolar plates. The carbon/carbon composite material developed in this program is uniquely suited for use in fuel cell systems, as it is lightweight, highly conductive and corrosion resistant. The project further focused upon developing the manufacturing methodology to cost-effectively produce this material for use in commercial fuel cell systems. United Technology Fuel Cells Corp., a leading fuel cell developer was a subcontractor to the project was interested in the performance and low-cost potential of the material. The accomplishments of the program included the development and testing of a low-cost, fully molded, net-shape carbon-carbon bipolar plate. The process to cost-effectively manufacture these carbon-carbon bipolar plates was focused on extensively in this program. Key areas for cost-reduction that received attention in this program was net-shape molding of the detailed flow structures according to end-user design. Correlations between feature detail and process parameters were formed so that mold tooling could be accurately designed to meet a variety of flow field dimensions. A cost model was developed that predicted the cost of manufacture for the product in near-term volumes and long-term volumes (10+ million units per year). Because the roduct uses lowcost raw materials in quantities that are less than competitive tech, it was found that the cost of the product in high volume can be less than with other plate echnologies, and can meet the DOE goal of $4/kW for transportation applications. The excellent performance of the all-carbon plate in net shape was verified in fuel cell testing. Performance equivalent to much higher cost, fully machined graphite plates was found.

  15. DeepBipolar: Identifying genomic mutations for bipolar disorder via deep learning.

    Science.gov (United States)

    Laksshman, Sundaram; Bhat, Rajendra Rana; Viswanath, Vivek; Li, Xiaolin

    2017-09-01

    Bipolar disorder, also known as manic depression, is a brain disorder that affects the brain structure of a patient. It results in extreme mood swings, severe states of depression, and overexcitement simultaneously. It is estimated that roughly 3% of the population of the United States (about 5.3 million adults) suffers from bipolar disorder. Recent research efforts like the Twin studies have demonstrated a high heritability factor for the disorder, making genomics a viable alternative for detecting and treating bipolar disorder, in addition to the conventional lengthy and costly postsymptom clinical diagnosis. Motivated by this study, leveraging several emerging deep learning algorithms, we design an end-to-end deep learning architecture (called DeepBipolar) to predict bipolar disorder based on limited genomic data. DeepBipolar adopts the Deep Convolutional Neural Network (DCNN) architecture that automatically extracts features from genotype information to predict the bipolar phenotype. We participated in the Critical Assessment of Genome Interpretation (CAGI) bipolar disorder challenge and DeepBipolar was considered the most successful by the independent assessor. In this work, we thoroughly evaluate the performance of DeepBipolar and analyze the type of signals we believe could have affected the classifier in distinguishing the case samples from the control set. © 2017 Wiley Periodicals, Inc.

  16. Comparison of depressive episodes in bipolar disorder and in major depressive disorder within bipolar disorder pedigrees.

    Science.gov (United States)

    Mitchell, Philip B; Frankland, Andrew; Hadzi-Pavlovic, Dusan; Roberts, Gloria; Corry, Justine; Wright, Adam; Loo, Colleen K; Breakspear, Michael

    2011-10-01

    Although genetic epidemiological studies have confirmed increased rates of major depressive disorder among the relatives of people with bipolar affective disorder, no report has compared the clinical characteristics of depression between these two groups. To compare clinical features of depressive episodes across participants with major depressive disorder and bipolar disorder from within bipolar disorder pedigrees, and assess the utility of a recently proposed probabilistic approach to distinguishing bipolar from unipolar depression. A secondary aim was to identify subgroups within the relatives with major depression potentially indicative of 'genetic' and 'sporadic' subgroups. Patients with bipolar disorder types 1 and 2 (n = 246) and patients with major depressive disorder from bipolar pedigrees (n = 120) were assessed using the Diagnostic Interview for Genetic Studies. Logistic regression was used to identify distinguishing clinical features and assess the utility of the probabilistic approach. Hierarchical cluster analysis was used to identify subgroups within the major depressive disorder sample. Bipolar depression was characterised by significantly higher rates of psychomotor retardation, difficulty thinking, early morning awakening, morning worsening and psychotic features. Depending on the threshold employed, the probabilistic approach yielded a positive predictive value ranging from 74% to 82%. Two clusters within the major depressive disorder sample were found, one of which demonstrated features characteristic of bipolar depression, suggesting a possible 'genetic' subgroup. A number of previously identified clinical differences between unipolar and bipolar depression were confirmed among participants from within bipolar disorder pedigrees. Preliminary validation of the probabilistic approach in differentiating between unipolar and bipolar depression is consistent with dimensional distinctions between the two disorders and offers clinical utility in

  17. A YinYang bipolar fuzzy cognitive TOPSIS method to bipolar disorder diagnosis.

    Science.gov (United States)

    Han, Ying; Lu, Zhenyu; Du, Zhenguang; Luo, Qi; Chen, Sheng

    2018-05-01

    Bipolar disorder is often mis-diagnosed as unipolar depression in the clinical diagnosis. The main reason is that, different from other diseases, bipolarity is the norm rather than exception in bipolar disorder diagnosis. YinYang bipolar fuzzy set captures bipolarity and has been successfully used to construct a unified inference mathematical modeling method to bipolar disorder clinical diagnosis. Nevertheless, symptoms and their interrelationships are not considered in the existing method, circumventing its ability to describe complexity of bipolar disorder. Thus, in this paper, a YinYang bipolar fuzzy multi-criteria group decision making method to bipolar disorder clinical diagnosis is developed. Comparing with the existing method, the new one is more comprehensive. The merits of the new method are listed as follows: First of all, multi-criteria group decision making method is introduced into bipolar disorder diagnosis for considering different symptoms and multiple doctors' opinions. Secondly, the discreet diagnosis principle is adopted by the revised TOPSIS method. Last but not the least, YinYang bipolar fuzzy cognitive map is provided for the understanding of interrelations among symptoms. The illustrated case demonstrates the feasibility, validity, and necessity of the theoretical results obtained. Moreover, the comparison analysis demonstrates that the diagnosis result is more accurate, when interrelations about symptoms are considered in the proposed method. In a conclusion, the main contribution of this paper is to provide a comprehensive mathematical approach to improve the accuracy of bipolar disorder clinical diagnosis, in which both bipolarity and complexity are considered. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. PEMFC Performance with Metal Bipolar Plates Depending on the Channel Dimension

    Directory of Open Access Journals (Sweden)

    Kwon Kuikam

    2016-01-01

    Full Text Available Bipolar plates of a proton exchange membrane fuel cell (PEMFC play an important role in removing liquid phase water as a by-product in order to facilitate the reaction between fuel and oxygen. A great amount of effort has been made to improve the performance of a fuel cell such as maximum current density or maximum power, by improving water removability of a bipolar plate. Most of the studies, however, are conducted numerically because of the complexity of analysing gas and liquid and the poor manufacturability of graphite bipolar plates. In this proceeding, we demonstrate that the performance of a PEMFC with metal bipolar plates can be enhanced by reducing the dimension of the channel. Bipolar plates were machined with stainless steel (type 316L to have three different channel size (1000 μm, 500 μm and 300 μm and the performance of each assembled cells were tested. As a result, the maximum power density and the maximum current density increased by 25%.

  19. Displacement and hybridization reactions in aptamer-functionalized hydrogels for biomimetic protein release and signal transduction.

    Science.gov (United States)

    Lai, Jinping; Li, Shihui; Shi, Xuechen; Coyne, James; Zhao, Nan; Dong, Fengping; Mao, Yingwei; Wang, Yong

    2017-11-01

    A variety of hydrogels have been synthesized for controlling the release of signaling molecules in applications such as drug delivery and regenerative medicine. However, it remains challenging to synthesize hydrogels with the ability to control the release of signaling molecules sequentially or periodically under physiological conditions as living cells do in response to the variation of metabolism. The purpose of this work was to study a novel biomimetic hydrogel system with the ability of recapitulating the procedure of cellular signal transduction and controlling the sequential release of signaling molecules under physiological conditions. In the presence of a small chemical, the signaling molecule is regulated to change from a DNA-bound state to a free state and the freed signaling molecule is able to regulate intracellular signal transduction and cell migration. Moreover, periodic exposure of the hydrogel system to the small chemical leads to sequential protein release. Since signaling molecules are important for every activity of the cell, this hydrogel system holds potential as a metabolism-responsive platform for controlled release of signaling molecules and cell regulation in various applications.

  20. Can neuroimaging disentangle bipolar disorder?

    Science.gov (United States)

    Hozer, Franz; Houenou, Josselin

    2016-05-01

    Bipolar disorder heterogeneity is large, leading to difficulties in identifying neuropathophysiological and etiological mechanisms and hindering the formation of clinically homogeneous patient groups in clinical trials. Identifying markers of clinically more homogeneous groups would help disentangle BD heterogeneity. Neuroimaging may aid in identifying such groups by highlighting specific biomarkers of BD subtypes or clinical dimensions. We performed a systematic literature search of the neuroimaging literature assessing biomarkers of relevant BD phenotypes (type-I vs. II, presence vs. absence of psychotic features, suicidal behavior and impulsivity, rapid cycling, good vs. poor medication response, age at onset, cognitive performance and circadian abnormalities). Consistent biomarkers were associated with suicidal behavior, i.e. frontal/anterior alterations (prefrontal and cingulate grey matter, prefrontal white matter) in patients with a history of suicide attempts; and with cognitive performance, i.e. involvement of frontal and temporal regions, superior and inferior longitudinal fasciculus, right thalamic radiation, and corpus callosum in executive dysfunctions. For the other dimensions and sub-types studied, no consistent biomarkers were identified. Studies were heterogeneous both in methodology and outcome. Though theoretically promising, neuroimaging has not yet proven capable of disentangling subtypes and dimensions of bipolar disorder, due to high between-study heterogeneity. We issue recommendations for future studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Vascular endothelium receptors and transduction mechanisms

    CERN Document Server

    Gillis, C; Ryan, Una; Proceedings of the Advanced Studies Institute on "Vascular Endothelium: Receptors and Transduction Mechanisms"

    1989-01-01

    Beyond their obvious role of a barrier between blood and tissue, vascular endothelial