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Sample records for cellular interactions uncouple

  1. Electromagnetic cellular interactions

    Czech Academy of Sciences Publication Activity Database

    Cifra, Michal; Fields, J. S.; Farhadi, A.

    2011-01-01

    Roč. 105, č. 3 (2011), 223-246. ISSN 0079-6107. [36th International Congress of Physiological Sciences (IUPS2009). Kyoto, 27.07.2009-01.08.2009] R&D Projects: GA ČR(CZ) GPP102/10/P454 Institutional research plan: CEZ:AV0Z20670512 Keywords : bioelectric phenomena * cellular biophysics Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 3.203, year: 2011

  2. Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Han Wern; Lim, Hwee Ying [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260 (Singapore); Wong, Kim Ping, E-mail: bchsitkp@nus.edu.sg [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260 (Singapore)

    2009-11-06

    Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5'-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F{sub 0}F{sub 1}-ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50 {mu}M, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F{sub 0}F{sub 1}-ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. The resulting change in ATP:AMP could disrupt the phosphorylation status of the cell; this provides a possible mechanism for its activation of AMPK and its downstream mTOR and STAT-3 signaling.

  3. Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action

    International Nuclear Information System (INIS)

    Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5'-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F0F1-ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50 μM, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F0F1-ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. The resulting change in ATP:AMP could disrupt the phosphorylation status of the cell; this provides a possible mechanism for its activation of AMPK and its downstream mTOR and STAT-3 signaling.

  4. Natural and Semisynthetic Mammea-Type Isoprenlated Dihydroxycoumarins Uncouple Cellular Respiration

    Science.gov (United States)

    Du, Lin; Mahdi, Fakhri; Jekabsons, Mika B.; Nagle, Dale G.; Zhou, Yu-Dong

    2011-01-01

    In an effort to identify natural product-based molecular-targeted antitumor agents, mammea-type coumarins from the tropical/subtropical plant Mammea americana were found to inhibit the activation of HIF-1 (hypoxia-inducible factor-1) in human breast and prostate tumor cells. In addition to the recently reported mammea E/BB (15), bioassay-guided fractionation of the active extract yielded fourteen mammea-type coumarins including three new compounds mammea F/BB 1 (1), mammea F/BA (2), and C/AA (3). The absolute configuration of C-1′ in 1 was determined by the modified Mosher’s method on a methylated derivative. These coumarins were evaluated for their effects on mitochondrial respiration, HIF-1 signaling, and tumor cell proliferation/viability. Acetylation of 1 afforded a triacetoxylated product (A-2) that inhibited HIF-1 activation with increased potency in both T47D (IC50 0.83 μM for hypoxia-induced) and PC3 cells (IC50 0.94 μM for hypoxia-induced). Coumarins possessing a 6-prenyl-8-(3-methyl-oxobutyl)-substituent pattern exhibited enhanced HIF-1 inhibitory effects. The O-methylated derivatives were less active at inhibiting HIF-1 and suppressing cell proliferation/viability. Mechanistic studies indicate that these compounds act as anionic protonophores that potently uncouple mitochondrial electron transport and disrupt hypoxic signaling. PMID:21214226

  5. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

    Directory of Open Access Journals (Sweden)

    O.Popescu

    1999-01-01

    Full Text Available Cellular interactions involve many types of cell surface molecules and operate via homophilic and/or heterophilic protein-protein and protein-carbohydrate binding. Our investigations in different model-systems (marine invertebrates and mammals have provided direct evidence that a novel class of primordial proteoglycans, named by us gliconectins, can mediate cell adhesion via a new alternative molecular mechanism of polyvalent carbohydrate-carbohydrate binding. Biochemical characterization of isolated and purified glyconectins revealed the presence of specific carbohydrate structures, acidic glycans, different from classical glycosaminoglycans. Such acidic glycans of high molecular weight containing fucose, glucuronic or galacturonic acids, and sulfate groups, originally found in sponges and sea urchin embryos, may represent a new class of carbohydrate carcino-embryonal antigens in mice and humans. Such interactions between biological macromolecules are usually investigated by kinetic binding studies, calorimetric methods, X-ray diffraction, nuclear magnetic resonance, and other spectroscopic analyses. However, these methods do not supply a direct estimation of the intermolecular binding forces that are fundamental for the function of the ligand-receptor association. Recently, we have introduced atomic force microscopy to quantify the binding strength between cell adhesion proteoglycans. Measurement of binding forces intrinsic to cell adhesion proteoglycans is necessary to assess their contribution to the maintenance of the anatomical integrity of multicellular organisms. As a model, we selected the glyconectin 1, a cell adhesion proteoglycan isolated from the marine sponge Microciona prolifera. This glyconectin mediates in vivo cell recognition and aggregation via homophilic, species-specific, polyvalent, and calcium ion-dependent carbohydrate-carbohydrate interactions. Under physiological conditions, an adhesive force of up to 400 piconewtons

  6. Interaction of free fatty acids with mitochondria: coupling, uncoupling and permeability transition.

    Science.gov (United States)

    Di Paola, Marco; Lorusso, Michele

    2006-01-01

    Long chain free fatty acids (FFA) exert, according to their actual concentration, different effects on the energy conserving system of mitochondria. Sub-micromolar concentrations of arachidonic acid (AA) rescue DeltapH-dependent depression of the proton pumping activity of the bc1 complex. This effect appears to be due to a direct interaction of AA with the proton-input mouth of the pump. At micromolar concentrations FFA increase the proton conductance of the inner membrane acting as protonophores. FFA can act as natural uncouplers, causing a mild uncoupling, which prevents reactive oxygen species production in the respiratory resting state. When Ca(2+)-loaded mitochondria are exposed to micromolar concentrations of FFA, the permeability of the inner membrane increases, resulting in matrix swelling, rupture of the outer membrane and release of intermembrane pro-apoptotic proteins. The characteristics of AA-induced swelling appear markedly different in mitochondria isolated from heart or liver. While in the latter it presents the canonical features of the classical permeability transition (PT), in heart mitochondria substantial differences are observed concerning CsA sensitivity, DeltaPsi dependence, reversibility by BSA and specificity for the activating divalent cation. In heart mitochondria, the AA-dependent increase of the inner membrane permeability is affected by ANT ligands such as adenine nucleotides and atractyloside. AA apparently causes a Ca2+-mediated conversion of ANT from a translocator to a channel system. Upon diamide treatment of heart mitochondria, the Ca2+/AA-induced CsA insensitive channel is converted into the classical PT pore. The relevance of these observations in terms of tissue-specific components of the putative PTP and heart ischemic and post-ischemic process is discussed. PMID:16697347

  7. Cellular structure in system of interacting particles

    OpenAIRE

    Lev, Bohdan

    2008-01-01

    The general description of formation the cellular structure in the system of interacting particles is proposed. Interactions between particles are presumably well-understood and the phase transition in which can be studied in the scale of particle resolution. We presented analytical results of possible cellular structures for suspension of colloidal particles, in system particles immersed in liquid crystal and gravitational system. We have shown that cellular structure formation can occur in ...

  8. Regulation of Thermogenesis In Plants: The Interaction of Alternative Oxidase and Plant Uncoupling Mitochondrial Protein

    Institute of Scientific and Technical Information of China (English)

    Yan Zhu; Jianfei Lu; Jing Wang; Fu Chen; Feifan Leng; Hongyu Li

    2011-01-01

    Thermogenesis is a process of heat production in living organisms.It is rare in plants,but it does occur in some species of angiosperm.The heat iS generated via plant mitochondrial respiration.As possible Involvement in thermogenesis of mitochondrial factors,alternative oxidases(AOXs)and plant uncoupling mitochondrial proteins(PUMPs)have been well studied.AOXs and PUMPs are ubiquitously present in the inner membrane of plant mitochondria.They serve as two major energy dissipation systems that balance mitochondrial respiration and uncoupled phosphorylation by dissipating the H+ redox energy and proton electrochemical gradient(△μH+)as heat,respectively.AOXs and PUMPs exert similar physiological functions during homeothermic heat production in thermogenic plants.AOXs have five isoforms,while PUMPs have six.Both AOXS and PUMPS are encoded by small nuclear multigene families.Multiple isoforms are expressed in different tissues or organs.Extensive studies have been done in the area of thermogenesis in higher plants.In this review,we focus on the involvement and regulation of AOXs and PUMPs in thermogenesis.

  9. Activity and functional interaction of alternative oxidase and uncoupling protein in mitochondria from tomato fruit

    Directory of Open Access Journals (Sweden)

    F.E. Sluse

    2000-03-01

    Full Text Available Cyanide-resistant alternative oxidase (AOX is not limited to plant mitochondria and is widespread among several types of protists. The uncoupling protein (UCP is much more widespread than previously believed, not only in tissues of higher animals but also in plants and in an amoeboid protozoan. The redox energy-dissipating pathway (AOX and the proton electrochemical gradient energy-dissipating pathway (UCP lead to the same final effect, i.e., a decrease in ATP synthesis and an increase in heat production. Studies with green tomato fruit mitochondria show that both proteins are present simultaneously in the membrane. This raises the question of a specific physiological role for each energy-dissipating system and of a possible functional connection between them (shared regulation. Linoleic acid, an abundant free fatty acid in plants which activates UCP, strongly inhibits cyanide-resistant respiration mediated by AOX. Moreover, studies of the evolution of AOX and UCP protein expression and of their activities during post-harvest ripening of tomato fruit show that AOX and plant UCP work sequentially: AOX activity decreases in early post-growing stages and UCP activity is decreased in late ripening stages. Electron partitioning between the alternative oxidase and the cytochrome pathway as well as H+ gradient partitioning between ATP synthase and UCP can be evaluated by the ADP/O method. This method facilitates description of the kinetics of energy-dissipating pathways and of ATP synthase when state 3 respiration is decreased by limitation of oxidizable substrate.

  10. Towards a continuum theory of movement in interacting cellular systems

    Science.gov (United States)

    Newman, Timothy

    2003-10-01

    Interacting cellular systems form the basis of all higher organisms, and are fundamental to the understanding of embryogenesis, organ function, and neoplasms. I will describe a stochastic model of cell interactions which can be applied to these problems, and present some of our recent results on chemotactic response.

  11. Learning Cellular Sorting Pathways Using Protein Interactions and Sequence Motifs

    OpenAIRE

    Lin, Tien-ho; Bar-Joseph, Ziv; Murphy, Robert F.

    2011-01-01

    Proper subcellular localization is critical for proteins to perform their roles in cellular functions. Proteins are transported by different cellular sorting pathways, some of which take a protein through several intermediate locations until reaching its final destination. The pathway a protein is transported through is determined by carrier proteins that bind to specific sequence motifs. In this article, we present a new method that integrates protein interaction and sequence motif data to m...

  12. Bacterial resistance to uncouplers.

    Science.gov (United States)

    Lewis, K; Naroditskaya, V; Ferrante, A; Fokina, I

    1994-12-01

    Uncoupler resistance presents a potential challenge to the conventional chemiosmotic coupling mechanism. In E. coli, an adaptive response to uncouplers was found in cell growing under conditions requiring oxidative phosphorylation. It is suggested that uncoupler-resistant mutants described in the earlier literature might represent a constitutive state of expression of this "low energy shock" adaptive response. In the environment, bacteria are confronted by nonclassical uncoupling factors such as organic solvents, heat, and extremes of pH. It is suggested that the low energy shock response will aid the cell in coping with the effects of natural uncoupling factors. The genetic analysis of uncoupler resistance has only recently began, and is yielding interesting and largely unexpected results. In Bacillus subtilis, a mutation in fatty acid desaturase causes an increased content of saturated fatty acids in the membrane and increased uncoupler resistance. The protonophoric efficiency of uncouplers remains unchanged in the mutants, inviting nonorthodox interpretations of the mechanism of resistance. In E. coli, two loci conferring resistance to CCCP and TSA were cloned and were found to encode multidrug resistance pumps. Resistance to one of the uncouplers, TTFB, remained unchanged in strains mutated for the MDRs, suggesting a resistance mechanism different from uncoupler extrusion. PMID:7721726

  13. Imaging protein interactions in vivo with sub-cellular resolution

    CERN Document Server

    Raicu, Valerica; Fung, Russell; Melnichuk, Mike; Jansma, David B; Pisterzi, Luca; Fox, Michael; Wells, James W; Saldin, Dilano K

    2008-01-01

    Resonant Energy Transfer (RET) from an optically excited donor molecule (D) to a non-excited acceptor molecule (A) residing nearby is widely used to detect molecular interactions in living cells. Stoichiometric information, such as the number of proteins forming a complex, has been obtained so far for a handful of proteins, but only after exposing the sample sequentially to at least two different excitation wavelengths. During this lengthy process of measurement, the molecular makeup of a cellular region may change, and this has so far limited the applicability of RET to determination of cellular averages. Here we demonstrate a method for imaging protein complex distribution in living cells with sub-cellular spatial resolution, which relies on a spectrally-resolved two-photon microscope, a simple but competent theory, and a keen selection of fluorescent tags. This technology may eventually lead to tracking dynamics of macromolecular complex formation and dissociation with spatial resolution inside living cell...

  14. Development and validation of computational models of cellular interaction

    OpenAIRE

    Smallwood, R H; Holcombe, W.M.L.; Walker, D C

    2004-01-01

    In this paper we take the view that computational models of biological systems should satisfy two conditions – they should be able to predict function at a systems biology level, and robust techniques of validation against biological models must be available. A modelling paradigm for developing a predictive computational model of cellular interaction is described, and methods of providing robust validation against biological models are explored, followed by a consideration of soft...

  15. Cellular mechanisms underlying the interaction between cannabinoid and opioid system.

    Science.gov (United States)

    Parolaro, D; Rubino, T; Viganò, D; Massi, P; Guidali, C; Realini, N

    2010-04-01

    Recently, the presence of functional interaction between the opioid and cannabinoid system has been shown in various pharmacological responses. Although there is an increasing interest for the feasible therapeutic application of a co-administration of cannabinoids and opioids in some disorders (i.e. to manage pain, to modulate immune system and emotions) and the combined use of the two drugs by drug abusers is becoming largely diffuse, only few papers focused on cellular and molecular mechanisms underlying this interaction. This review updates the biochemical and molecular underpinnings of opioid and cannabinoid interaction, both within the central nervous system and periphery. The most convincing theory for the explanation of this reciprocal interaction involves (i) the release of opioid peptides by cannabinoids or endocannabinoids by opioids, (ii) the existence of a direct receptor-receptor interaction when the receptors are co-expressed in the same cells, and (iii) the interaction of their intracellular pathways. Finally, the cannabinoid/opioid interaction might be different in the brain rewarding networks and in those accounting for other pharmacological effects (antinociception, modulation of emotionality and cognitive behavior), as well as between the central nervous system and periphery. Further insights about the cannabinoid/opioid interaction could pave the way for new and promising therapeutic approaches. PMID:20017730

  16. Cellular interactions in the pathogenesis of interstitial lung diseases.

    Science.gov (United States)

    Bagnato, Gianluca; Harari, Sergio

    2015-03-01

    Interstitial lung disease (ILD) encompasses a large and diverse group of pathological conditions that share similar clinical, radiological and pathological manifestations, despite potentially having quite different aetiologies and comorbidities. Idiopathic pulmonary fibrosis (IPF) represents probably the most aggressive form of ILD and systemic sclerosis is a multiorgan fibrotic disease frequently associated with ILD. Although the aetiology of these disorders remains unknown, in this review we analyse the pathogenic mechanisms by cell of interest (fibroblast, fibrocyte, myofibroblast, endothelial and alveolar epithelial cells and immune competent cells). New insights into the complex cellular contributions and interactions will be provided, comparing the role of cell subsets in the pathogenesis of IPF and systemic sclerosis. PMID:25726561

  17. Investigation of cellular responses upon interaction with silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Subbiah R

    2015-08-01

    Full Text Available Ramesh Subbiah,1,2 Seong Beom Jeon,3,4 Kwideok Park,1,2 Sang Jung Ahn,4,5 Kyusik Yun3 1Center for Biomaterials, Korea Institute of Science and Technology, Seoul, 2Department of Biomedical Engineering, Korea University of Science and Technology, Daejon, 3Department of Bionanotechnology, Gachon University, Gyeonggi-do, 4Centre for Advanced Instrumentation, Korea Research Institute of Standard and Science, 5Major of Nano Science, Korea University of Science and Technology, Daejeon, Republic of Korea Abstract: In order for nanoparticles (NPs to be applied in the biomedical field, a thorough investigation of their interactions with biological systems is required. Although this is a growing area of research, there is a paucity of comprehensive data in cell-based studies. To address this, we analyzed the physicomechanical responses of human alveolar epithelial cells (A549, mouse fibroblasts (NIH3T3, and human bone marrow stromal cells (HS-5, following their interaction with silver nanoparticles (AgNPs. When compared with kanamycin, AgNPs exhibited moderate antibacterial activity. Cell viability ranged from ≤80% at a high AgNPs dose (40 µg/mL to >95% at a low dose (10 µg/mL. We also used atomic force microscopy-coupled force spectroscopy to evaluate the biophysical and biomechanical properties of cells. This revealed that AgNPs treatment increased the surface roughness (P<0.001 and stiffness (P<0.001 of cells. Certain cellular changes are likely due to interaction of the AgNPs with the cell surface. The degree to which cellular morphology was altered directly proportional to the level of AgNP-induced cytotoxicity. Together, these data suggest that atomic force microscopy can be used as a potential tool to develop a biomechanics-based biomarker for the evaluation of NP-dependent cytotoxicity and cytopathology. Keywords: AFM, roughness, nanoindentation, biomarker, cytotoxicity, biomechanics

  18. Cellular interactions in the pathogenesis of interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Gianluca Bagnato

    2015-03-01

    Full Text Available Interstitial lung disease (ILD encompasses a large and diverse group of pathological conditions that share similar clinical, radiological and pathological manifestations, despite potentially having quite different aetiologies and comorbidities. Idiopathic pulmonary fibrosis (IPF represents probably the most aggressive form of ILD and systemic sclerosis is a multiorgan fibrotic disease frequently associated with ILD. Although the aetiology of these disorders remains unknown, in this review we analyse the pathogenic mechanisms by cell of interest (fibroblast, fibrocyte, myofibroblast, endothelial and alveolar epithelial cells and immune competent cells. New insights into the complex cellular contributions and interactions will be provided, comparing the role of cell subsets in the pathogenesis of IPF and systemic sclerosis.

  19. Charged group surface accessibility determines micelleplexes formation and cellular interaction

    Science.gov (United States)

    Zhang, Yu; Liu, Yang; Sen, Soumyo; Král, Petr; Gemeinhart, Richard A.

    2015-04-01

    Micelleplexes are a class of nucleic acid carriers that have gained acceptance due to their size, stability, and ability to synergistically carry small molecules. MicroRNAs (miRNAs) are small non-coding RNA gene regulator that is consists of 19-22 nucleotides. Altered expression of miRNAs plays an important role in many human diseases. Using a model 22-nucleotide miRNA sequence, we investigated the interaction between charged groups on the micelle surface and miRNA. The model micelle system was formed from methoxy-poly(ethylene glycol)-b-poly(lactide) (mPEG-PLA) mixed with methoxy-poly(ethylene glycol)-b-poly(lactide)-b-oligoarginine (mPEG-PLA-Rx, x = 8 or 15). Surface properties of the micelles were varied by controlling the oligoarginine block length and conjugation density. Micelles were observed to have a core-shell conformation in the aqueous environment where the PLA block constituted the hydrophobic core, mPEG and oligoarginine formed a hydrophilic corona. Significantly different thermodynamic behaviors were observed during the interaction of single stranded miRNA with micelles of different surface properties, and the resulting micelleplexes mediated substantial cellular association. Depending upon the oligoarginine length and density, micelles exhibited miRNA loading capacity directly related to the presentation of charged groups on the surface. The effect of charged group accessibility of cationic micelle on micelleplex properties provides guidance on future miRNA delivery system design.Micelleplexes are a class of nucleic acid carriers that have gained acceptance due to their size, stability, and ability to synergistically carry small molecules. MicroRNAs (miRNAs) are small non-coding RNA gene regulator that is consists of 19-22 nucleotides. Altered expression of miRNAs plays an important role in many human diseases. Using a model 22-nucleotide miRNA sequence, we investigated the interaction between charged groups on the micelle surface and miRNA. The

  20. Thymocyte migration: an affair of multiple cellular interactions?

    Directory of Open Access Journals (Sweden)

    Savino W.

    2003-01-01

    Full Text Available Cell migration is a crucial event in the general process of thymocyte differentiation. The cellular interactions involved in the control of this migration are beginning to be defined. At least chemokines and extracellular matrix proteins appear to be part of the game. Cells of the thymic microenvironment produce these two groups of molecules, whereas developing thymocytes express the corresponding receptors. Moreover, although chemokines and extracellular matrix can drive thymocyte migration per se, a combined role for these molecules appears to contribute to the resulting migration patterns of thymocytes in their various stages of differentiation. The dynamics of chemokine and extracellular matrix production and degradation is not yet well understood. However, matrix metalloproteinases are likely to play a role in the breakdown of intrathymic extracellular matrix contents. Thus, the physiological migration of thymocytes should be envisioned as a resulting vector of multiple, simultaneous and/or sequential stimuli involving chemokines, adhesive and de-adhesive extracellular matrix proteins, as well as matrix metalloproteinases. Accordingly, it is conceivable that any pathological change in any of these loops may result in the alteration of normal thymocyte migration. This seems to be the case in murine infection by the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas' disease. A better knowledge of the physiological mechanisms governing thymocyte migration will provide new clues for designing therapeutic strategies targeting developing T cells.

  1. Thermoregulatory uncoupling in heart muscle mitochondria: involvement of the ATP/ADP antiporter and uncoupling protein.

    Science.gov (United States)

    Simonyan, R A; Skulachev, V P

    1998-09-25

    Possible involvement of the ATP/ADP antiporter and uncoupling protein (UCP) in thermoregulatory uncoupling of oxidative phosphorylation in heart muscle has been studied. To this end, effects of carboxyatractylate (cAtr) and GDP, specific inhibitors of the antiporter and UCP, on the membrane potential of the oligomycin-treated mitochondria from cold-exposed (6 degrees C, 48 h) and control rats have been measured. It is found that cAtr increases the membrane potential level in both cold-exposed and non-exposed groups, the effect being strongly enhanced by cooling. As for GDP, it is effective only in mitochondria from the cold-exposed rats. In these mitochondria, the coupling effect of GDP is smaller than that of cAtr. CDP, which does not interact with UCP, is without any influence on membrane potential. The cold exposure is found to increase the uncoupling efficiency of added natural (palmitate) or artificial (SF6847) uncouplers, the increase being cAtr- and GDP-sensitive in the case of palmitate. The fatty acid-free bovine serum albumin enhances delta psi in both cold-exposed and control groups, the effect being much larger in the former case. It is concluded that in heart muscle mitochondria the ATP/ADP antiporter is responsible for the 'mild uncoupling' under normal conditions and for major portion of the thermoregulatory uncoupling in the cold whereas the rest of thermoregulatory uncoupling is served by UCP (presumably by UCP2 since the UCP2 mRNA level is shown to strongly increase in rat heart muscle under the cold exposure conditions used). PMID:9771898

  2. Respiratory uncoupling in white fat and high-fat diet interact to decrease plasma triglycerides in the AP2-UCP1 transcenic mice

    Czech Academy of Sciences Publication Activity Database

    Rossmeisl, Martin; Kovář, J.; Flachs, Pavel; Kolář, František; Poledne, R.; Kopecký, Jan

    Elsevier. Roč. 6, č. 1 (2005), s. 44-44. ISSN 1567-5688. [Congress of the European Atherosclerosis Society /75./. 23.04.2005-26.04.2005, Prague] R&D Projects: GA MŠk(CZ) 1M0520; GA ČR GA303/05/2580 Institutional research plan: CEZ:AV0Z50110509 Keywords : obesity * high- fat diet * lipoprotein * lipase * transgenic mice * uncoupling protein Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

  3. Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression

    DEFF Research Database (Denmark)

    Dhamrait, Sukhbir S; Maubaret, Cecilia; Pedersen-Bjergaard, Ulrik;

    2016-01-01

    Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin-angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial...

  4. Thrombospondin-1 Interacts with Trypanosoma cruzi Surface Calreticulin to Enhance Cellular Infection

    OpenAIRE

    Johnson, Candice A.; Kleshchenko, Yulia Y.; Ikejiani, Adaeze O.; Udoko, Aniekanabasi N.; Cardenas, Tatiana C.; Pratap, Siddharth; Duquette, Mark A.; Lima, Maria F.; Lawler, Jack; Villalta, Fernando; Nde, Pius N.

    2012-01-01

    Trypanosoma cruzi causes Chagas disease, which is a neglected tropical disease that produces severe pathology and mortality. The mechanisms by which the parasite invades cells are not well elucidated. We recently reported that T. cruzi up-regulates the expression of thrombospondin-1 (TSP-1) to enhance the process of cellular invasion. Here we characterize a novel TSP-1 interaction with T. cruzi that enhances cellular infection. We show that labeled TSP-1 interacts specifically with the surfac...

  5. Cellular interactions of surface modified nanoporous silicon particles

    Science.gov (United States)

    Bimbo, Luis M.; Sarparanta, Mirkka; Mäkilä, Ermei; Laaksonen, Timo; Laaksonen, Päivi; Salonen, Jarno; Linder, Markus B.; Hirvonen, Jouni; Airaksinen, Anu J.; Santos, Hélder A.

    2012-05-01

    In this study, the self-assembly of hydrophobin class II (HFBII) on the surface of thermally hydrocarbonized porous silicon (THCPSi) nanoparticles was investigated. The HFBII-coating converted the hydrophobic particles into more hydrophilic ones, improved the particles' cell viability in both HT-29 and Caco-2 cell lines compared to uncoated particles, and enhanced the particles' cellular association. The amount of HFBII adsorbed onto the particles was also successfully quantified by both the BCA assay and a HPLC method. Importantly, the permeation of a poorly water-soluble drug, indomethacin, loaded into THCPSi particles across Caco-2 monolayers was not affected by the protein coating. In addition, 125I-radiolabelled HFBII did not extensively permeate the Caco-2 monolayer and was found to be stably adsorbed onto the THCPSi nanoparticles incubated in pH 7.4, which renders the particles the possibility for further track-imaging applications. The results highlight the potential of HFBII coating for improving wettability, increasing biocompatibility and possible intestinal association of PSi nanoparticulates for drug delivery applications.In this study, the self-assembly of hydrophobin class II (HFBII) on the surface of thermally hydrocarbonized porous silicon (THCPSi) nanoparticles was investigated. The HFBII-coating converted the hydrophobic particles into more hydrophilic ones, improved the particles' cell viability in both HT-29 and Caco-2 cell lines compared to uncoated particles, and enhanced the particles' cellular association. The amount of HFBII adsorbed onto the particles was also successfully quantified by both the BCA assay and a HPLC method. Importantly, the permeation of a poorly water-soluble drug, indomethacin, loaded into THCPSi particles across Caco-2 monolayers was not affected by the protein coating. In addition, 125I-radiolabelled HFBII did not extensively permeate the Caco-2 monolayer and was found to be stably adsorbed onto the THCPSi

  6. Achromatic and Uncoupled Medical Gantry

    Science.gov (United States)

    Tsoupas, N.; Kayran, D.; Litvinenko, V.

    One of the functions of a medical gantry is to irradiate a tumor from different angles to reduce the dose received by the healthy tissue which surrounds the tumor. The rotation of the gantry rotates also its quadrupoles that focus the beam, as a result the beam is "coupled" in the sense that the horizontal motion of the beam particles is affected by the vertical motion and vice-versa therefore the beam spot size at the tumor may vary with the angular orientation of the gantry. Although such a beam-coupling is inevitable in a rotated gantry in which the horizontal plane is not the symmetry plane of the quadrupoles, it is possible to find a solution that the optics of the gantry"appears uncoupled" at any angular orientation of the gantry. As we show in the paper, the condition of an uncoupled gantry is equivalent to an uncoupled linear-beam-transport-matrix which is independent of the angular orientation of the gantry, therefore the beam spot size at the location of the tumor is independent of the orientation of the gantry. In this paper we present the theoretical basis to generate the beam optics for a gantry which is constrained to provide uncoupled and also achromatic beamtransport to the location of the tumor. In addition we present the layout of the magnetic elements and the optics of a medical gantrywhich satisfies the achromaticity and uncoupled conditions.

  7. Interactions between X-rays and antimitotic drugs: cellular effects

    International Nuclear Information System (INIS)

    The interactions between three drugs and X-rays were examined in rat hepatoma cells in vitro. Incubation with Daunomycine or 9-hydroxy ellipticine decreases the survival of both exponential and plateau phase cells, whereas cis-Pt (II) decreases the survival of plateau cells, especially irradiated in anoxia. The decrease in the Do was greater when the cells were incubated with the drugs prior to X-irradiation, and was greater in the case of plateau cells than in the case of exponential cells. The repair of potentially lethal damages was inhibited by these three compounds. However, the repair of sublethal damages was inhibited by cis-Pt II, but was modified neither by Daunomycine nor 9-hydroxy ellipticine

  8. Interactions of the HSV-1 UL25 Capsid Protein with Cellular Microtubule-associated Protein

    Institute of Scientific and Technical Information of China (English)

    Lei GUO; Ying ZHANG; Yan-chun CHE; Wen-juan WU; Wei-zhong LI; Li-chun WANG; Yun LIAO; Long-ding LIU; Qi-han LI

    2008-01-01

    An interaction between the HSV-1 UL25 capsid protein and cellular microtubule-associated protein was found using a yeast two-hybrid screen and β-D-galactosidase activity assays. Immunofluorescence microscopy of the UL25 protein demonstrated its co-localization with cellular microtubule-associated protein in the plasma membrane. Further investigations with deletion mutants suggest that UL25 is likely to have a function in the nucleus.

  9. Cellular mechanisms regulating sperm-zona pellucida interaction

    Institute of Scientific and Technical Information of China (English)

    Andrew T Reid; Kate Redgrove; R John Aitken; Brett Nixon

    2011-01-01

    For mammalian spermatozoa to exhibit the ability to bind the zona pellucida(ZP)they must undergo three distinct phases of maturation,namely,spermatogenesis(testis),epididymal maturation(epididymis)and capacitation(female reproductive tract).An impressive array of spermatozoa surface remodeling events accompany these phases of maturation and appear critical for recognition and adhesion of the outer vestments of the oocyte,a structure known as the ZP.It is becoming increasingly apparent that species-specific zona adhesion is not mediated by a single receptor.Instead,compelling evidence now points toward models implicating a multiplicity of receptor-ligand interactions.This notion is in keeping with emerging research that has shown that there is a dynamic aggregation of proteins believed to be important in sperm-ZP recognition to the regions of sperm that mediate this binding event.Such remodeling may in turn facilitate the assembly of a multimeric zona recognition complex(MZRC).Though formation of MZRCs raises questions regarding the nature of the block to polyspermy,formation and assembly of such a structure would no doubt explain the strenuous maturation process that sperm endure on their sojourn to functional maturity.

  10. Uncoupling Mitochondrial Respiration for Diabesity.

    Science.gov (United States)

    Larrick, James W; Larrick, Jasmine W; Mendelsohn, Andrew R

    2016-08-01

    Until recently, the mechanism of adaptive thermogenesis was ascribed to the expression of uncoupling protein 1 (UCP1) in brown and beige adipocytes. UCP1 is known to catalyze a proton leak of the inner mitochondrial membrane, resulting in uncoupled oxidative metabolism with no production of adenosine triphosphate and increased energy expenditure. Thus increasing brown and beige adipose tissue with augmented UCP1 expression is a viable target for obesity-related disorders. Recent work demonstrates an UCP1-independent pathway to uncouple mitochondrial respiration. A secreted enzyme, PM20D1, enriched in UCP1+ adipocytes, exhibits catalytic and hydrolytic activity to reversibly form N-acyl amino acids. N-acyl amino acids act as endogenous uncouplers of mitochondrial respiration at physiological concentrations. Administration of PM20D1 or its products, N-acyl amino acids, to diet-induced obese mice improves glucose tolerance by increasing energy expenditure. In short-term studies, treated animals exhibit no toxicity while experiencing 10% weight loss primarily of adipose tissue. Further study of this metabolic pathway may identify novel therapies for diabesity, the disease state associated with diabetes and obesity. PMID:27378359

  11. Host-Parasite Interaction of Root-Knot Nematodes (Nematoda: Meloidogynidae): Cellular and Molecular Aspect

    OpenAIRE

    Gökhan Aydınlı; Sevilhan Mennan

    2014-01-01

    Root-knot nematodes (Meloidogyne spp.) have specialized and complex relationships with their host plants. A better understanding of interaction between nematode and their host will help to provide new point of view for root-knot nematode management. For this purpose, recently investigations on cellular and molecular basis of root-knot nematode parasitism and host response were reviewed.

  12. A `Clicked' Tetrameric Hydroxamic Acid Glycopeptidomimetic Antagonizes Sugar-Lectin Interactions On The Cellular Level

    Science.gov (United States)

    Zhang, Hai-Lin; Zang, Yi; Xie, Juan; Li, Jia; Chen, Guo-Rong; He, Xiao-Peng; Tian, He

    2014-07-01

    A tetrameric N-acetyl galactosaminyl (GalNAc) peptidomimetic was constructed by N-acetylation of repeating proline-based hydroxamic acid units, followed by a convergent `click chemistry' coupling. This novel glycopeptidomimetic was determined to effectively antagonize the interaction between a transmembrane hepatic lectin and GalNAc on the cellular level.

  13. Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions.

    Directory of Open Access Journals (Sweden)

    Thomas Wallach

    2013-03-01

    Full Text Available Essentially all biological processes depend on protein-protein interactions (PPIs. Timing of such interactions is crucial for regulatory function. Although circadian (~24-hour clocks constitute fundamental cellular timing mechanisms regulating important physiological processes, PPI dynamics on this timescale are largely unknown. Here, we identified 109 novel PPIs among circadian clock proteins via a yeast-two-hybrid approach. Among them, the interaction of protein phosphatase 1 and CLOCK/BMAL1 was found to result in BMAL1 destabilization. We constructed a dynamic circadian PPI network predicting the PPI timing using circadian expression data. Systematic circadian phenotyping (RNAi and overexpression suggests a crucial role for components involved in dynamic interactions. Systems analysis of a global dynamic network in liver revealed that interacting proteins are expressed at similar times likely to restrict regulatory interactions to specific phases. Moreover, we predict that circadian PPIs dynamically connect many important cellular processes (signal transduction, cell cycle, etc. contributing to temporal organization of cellular physiology in an unprecedented manner.

  14. Nanoparticle-cell interactions: molecular structure of the protein corona and cellular outcomes.

    Science.gov (United States)

    Fleischer, Candace C; Payne, Christine K

    2014-08-19

    The use of nanoparticles (NPs) in biology and medicine requires a molecular-level understanding of how NPs interact with cells in a physiological environment. A critical difference between well-controlled in vitro experiments and in vivo applications is the presence of a complex mixture of extracellular proteins. It has been established that extracellular serum proteins present in blood will adsorb onto the surface of NPs, forming a "protein corona". Our goal was to understand how this protein layer affected cellular-level events, including NP binding, internalization, and transport. A combination of microscopy, which provides spatial resolution, and spectroscopy, which provides molecular information, is necessary to probe protein-NP-cell interactions. Initial experiments used a model system composed of polystyrene NPs functionalized with either amine or carboxylate groups to provide a cationic or anionic surface, respectively. Serum proteins adsorb onto the surface of both cationic and anionic NPs, forming a net anionic protein-NP complex. Although these protein-NP complexes have similar diameters and effective surface charges, they show the exact opposite behavior in terms of cellular binding. In the presence of bovine serum albumin (BSA), the cellular binding of BSA-NP complexes formed from cationic NPs is enhanced, whereas the cellular binding of BSA-NP complexes formed from anionic NPs is inhibited. These trends are independent of NP diameter or cell type. Similar results were obtained for anionic quantum dots and colloidal gold nanospheres. Using competition assays, we determined that BSA-NP complexes formed from anionic NPs bind to albumin receptors on the cell surface. BSA-NP complexes formed from cationic NPs are redirected to scavenger receptors. The observation that similar NPs with identical protein corona compositions bind to different cellular receptors suggested that a difference in the structure of the adsorbed protein may be responsible for the

  15. Integrated cellular network of transcription regulations and protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Chen Bor-Sen

    2010-03-01

    Full Text Available Abstract Background With the accumulation of increasing omics data, a key goal of systems biology is to construct networks at different cellular levels to investigate cellular machinery of the cell. However, there is currently no satisfactory method to construct an integrated cellular network that combines the gene regulatory network and the signaling regulatory pathway. Results In this study, we integrated different kinds of omics data and developed a systematic method to construct the integrated cellular network based on coupling dynamic models and statistical assessments. The proposed method was applied to S. cerevisiae stress responses, elucidating the stress response mechanism of the yeast. From the resulting integrated cellular network under hyperosmotic stress, the highly connected hubs which are functionally relevant to the stress response were identified. Beyond hyperosmotic stress, the integrated network under heat shock and oxidative stress were also constructed and the crosstalks of these networks were analyzed, specifying the significance of some transcription factors to serve as the decision-making devices at the center of the bow-tie structure and the crucial role for rapid adaptation scheme to respond to stress. In addition, the predictive power of the proposed method was also demonstrated. Conclusions We successfully construct the integrated cellular network which is validated by literature evidences. The integration of transcription regulations and protein-protein interactions gives more insight into the actual biological network and is more predictive than those without integration. The method is shown to be powerful and flexible and can be used under different conditions and for different species. The coupling dynamic models of the whole integrated cellular network are very useful for theoretical analyses and for further experiments in the fields of network biology and synthetic biology.

  16. Agonistic encounters and cellular angst: social interactions induce heat shock proteins in juvenile salmonid fish

    OpenAIRE

    Currie, Suzanne; LeBlanc, Sacha; Watters, M. Alexandrea; Gilmour, Kathleen M.

    2009-01-01

    Juvenile salmonid fish readily form dominance hierarchies when faced with limited resources. While these social interactions may result in profound behavioural and physiological stress, it is unknown if this social stress is evident at the level of the cellular stress response—specifically, the induction of stress or heat shock proteins (Hsps). Thus, the goal of our study was to determine if Hsps are induced during hierarchy formation in juvenile rainbow trout (Oncorhynchus mykiss). To this e...

  17. ELF (extremely-low-frequency) field interactions at the animal, tissue and cellular levels

    Energy Technology Data Exchange (ETDEWEB)

    Tenforde, T.S.

    1990-10-01

    A description is given of the fundamental physical properties of extremely-low-frequency (ELF) electromagnetic fields, and the mechanisms through which these fields interact with the human body at a macroscopic level. Biological responses to ELF fields at the tissue, cellular and molecular levels are summarized, including new evidence that ELF field exposure produces alterations in gene expression and the cytoplasmic concentrations of specific proteins.

  18. On the photonic cellular interaction and the electric activity of neurons in the human brain

    Czech Academy of Sciences Publication Activity Database

    Salari, V.; Tuszynski, J. A.; Bokkon, I.; Rahnama, M.; Cifra, Michal

    Vol. 329. Bristol: IOP, 2011 - (Cifra, M.; Pokorny, J.; Kučera, O.), 012006 ISSN 1742-6588. [9th International Frohlich's Symposium on Electrodynamic Activity of Living Cells - Including Microtubule Coherent Modes and Cancer Cell Physics. Praha (CZ), 01.07.2011-03.07.2011] Institutional support: RVO:67985882 Keywords : Electric activity * Cellular interaction * Empirical evidence Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

  19. The evolution of early cellular systems viewed through the lens of biological interactions

    Directory of Open Access Journals (Sweden)

    Anthony M Poole

    2015-10-01

    Full Text Available The minimal cell concept represents a pragmatic approach to the question of how few genes are required to run a cell. This is a helpful way to build a parts-list, and has been more successful than attempts to deduce a minimal gene set for life by inferring the gene repertoire of the Last Universal Common Ancestor, as few genes trace back to this hypothetical ancestral state. However, the study of minimal cellular systems is the study of biological outliers where, by practical necessity, coevolutionary interactions are minimised or ignored. In this paper, we consider the biological context from which minimal genomes have been removed. For instance, some of the most reduced genomes are from endosymbionts and are the result of coevolutionary interactions with a host; few such organisms are ‘free-living’. As few, if any, biological systems exist in complete isolation, we expect that, as with modern life, early biological systems were part of an ecosystem, replete with organismal interactions. We favour refocusing discussions of the evolution of cellular systems on processes rather than gene counts. We therefore draw a distinction between a pragmatic minimal cell (an interesting engineering problem, a distributed genome (a system resulting from an evolutionary transition involving more than one cell and the looser coevolutionary interactions that are ubiquitous in ecosystems. Finally, we consider the distributed genome and coevolutionary interactions between genomic entities in the context of early evolution.

  20. Effects of multiple enzyme–substrate interactions in basic units of cellular signal processing

    International Nuclear Information System (INIS)

    Covalent modification cycles are a ubiquitous feature of cellular signalling networks. In these systems, the interaction of an active enzyme with the unmodified form of its substrate is essential for signalling to occur. However, this interaction is not necessarily the only enzyme–substrate interaction possible. In this paper, we analyse the behaviour of a basic model of signalling in which additional, non-essential enzyme–substrate interactions are possible. These interactions include those between the inactive form of an enzyme and its substrate, and between the active form of an enzyme and its product. We find that these additional interactions can result in increased sensitivity and biphasic responses, respectively. The dynamics of the responses are also significantly altered by the presence of additional interactions. Finally, we evaluate the consequences of these interactions in two variations of our basic model, involving double modification of substrate and scaffold-mediated signalling, respectively. We conclude that the molecular details of protein–protein interactions are important in determining the signalling properties of enzymatic signalling pathways. (paper)

  1. Interactions between small viral RNAs of vesicular stomatitis virus and components of cellular gene expression.

    Science.gov (United States)

    Keene, J D

    1985-05-01

    Recent interest in the details of virus-host interactions has come to focus on molecular contacts between cell factors and components of viruses. These generally concern protein-protein and protein-nucleic acid interactions. In this review, protein-nucleic acid interactions involving viral transcription products and cell proteins are considered. Also examined here will be the hypothesis that such interactions have evolved because viruses have adopted cellular processes to favour their own replication and that the consequences of this co-evolution can be the disruption of the macromolecular functions of the cell, and eventual cytopathology. For its own survival in the long term, the host may evolve more refined mechanisms to evade the damage levied by the intruding virus. PMID:2856377

  2. Patterns of HIV-1 protein interaction identify perturbed host-cellular subsystems.

    Directory of Open Access Journals (Sweden)

    Jamie I MacPherson

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 exploits a diverse array of host cell functions in order to replicate. This is mediated through a network of virus-host interactions. A variety of recent studies have catalogued this information. In particular the HIV-1, Human Protein Interaction Database (HHPID has provided a unique depth of protein interaction detail. However, as a map of HIV-1 infection, the HHPID is problematic, as it contains curation error and redundancy; in addition, it is based on a heterogeneous set of experimental methods. Based on identifying shared patterns of HIV-host interaction, we have developed a novel methodology to delimit the core set of host-cellular functions and their associated perturbation from the HHPID. Initially, using biclustering, we identify 279 significant sets of host proteins that undergo the same types of interaction. The functional cohesiveness of these protein sets was validated using a human protein-protein interaction network, gene ontology annotation and sequence similarity. Next, using a distance measure, we group host protein sets and identify 37 distinct higher-level subsystems. We further demonstrate the biological significance of these subsystems by cross-referencing with global siRNA screens that have been used to detect host factors necessary for HIV-1 replication, and investigate the seemingly small intersect between these data sets. Our results highlight significant host-cell subsystems that are perturbed during the course of HIV-1 infection. Moreover, we characterise the patterns of interaction that contribute to these perturbations. Thus, our work disentangles the complex set of HIV-1-host protein interactions in the HHPID, reconciles these with siRNA screens and provides an accessible and interpretable map of infection.

  3. Photonic crystals as templates and active devices for cellular and molecular interactions

    Science.gov (United States)

    Sonek, G. J.

    2005-04-01

    Photonic crystals are emerging as an important class of engineered nanophotonic devices that possess unique optical properties and which can also provide textured surfaces for the study and control of cellular and molecular interactions. From among the many types of photonic crystal structures, two-dimensional (2D) and planar (slab) photonic crystals are the most attractive because of their ability to support guided-wave and active optical devices in semiconductor and polymer materials, serve as templates for device replication, and interface with colloidal and nanoparticle systems. This paper reports on the results of modeling and design efforts that show how 2d and slab silicon photonic crystals, based on their in-plane optical waveguiding and out-of-plane radiation properties, might be used to probe surface-bound cells and molecules or perform localized spectroscopy. The results of a parametric analysis show that photonic crystals comprised of high-index contrast materials (e.g. Si, air) are sensitive to geometric and material factors, potentially making them an effective medium to study molecular and cellular interactions critical to a number of biotechnological applications

  4. Use of specific glycosidases to probe cellular interactions in the sea urchin embryo.

    Science.gov (United States)

    Idoni, Brian; Ghazarian, Haike; Metzenberg, Stan; Hutchins-Carroll, Virginia; Oppenheimer, Steven B; Carroll, Edward J

    2010-08-01

    We present an unusual and novel model for initial investigations of a putative role for specifically conformed glycans in cellular interactions. We have used alpha- and ss-amylase and alpha- and ss-glucosidase in dose-response experiments evaluating their effects on archenteron organization using the NIH designated sea urchin embryo model. In quantitative dose-response experiments, we show that defined activity levels of alpha-glucosidase and ss-amylase inhibited archenteron organization in living Lytechinus pictus gastrula embryos, whereas all concentrations of ss-glucosidase and alpha-amylase were without substantial effects on development. Product inhibition studies suggested that the enzymes were acting by their specific glycosidase activities and polyacrylamide gel electrophoresis suggested that there was no detectable protease contamination in the active enzyme samples. The results provide evidence for a role of glycans in sea urchin embryo cellular interactions with special reference to the possible structural conformation of these glycans based on the differential activities of the alpha- and ss-glycosidases. PMID:20435035

  5. Interacting factors and cellular localization of SR protein-specific kinase Dsk1

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Zhaohua, E-mail: ztang@jsd.claremont.edu [W.M. Keck Science Center, The Claremont Colleges, Claremont, CA 91711 (United States); Luca, Maria; Taggart-Murphy, Laura; Portillio, Jessica; Chang, Cathey; Guven, Ayse [W.M. Keck Science Center, The Claremont Colleges, Claremont, CA 91711 (United States); Lin, Ren-Jang [Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010 (United States); Murray, Johanne; Carr, Antony [Genome Damage and Stability Center, University of Sussex, Falmer, BN1 9RQ (United Kingdom)

    2012-10-01

    Schizosaccharomyces pombe Dsk1 is an SR protein-specific kinase (SRPK), whose homologs have been identified in every eukaryotic organism examined. Although discovered as a mitotic regulator with protein kinase activity toward SR splicing factors, it remains largely unknown about what and how Dsk1 contributes to cell cycle and pre-mRNA splicing. In this study, we investigated the Dsk1 function by determining interacting factors and cellular localization of the kinase. Consistent with its reported functions, we found that pre-mRNA processing and cell cycle factors are prominent among the proteins co-purified with Dsk1. The identification of these factors led us to find Rsd1 as a novel Dsk1 substrate, as well as the involvement of Dsk1 in cellular distribution of poly(A){sup +} RNA. In agreement with its role in nuclear events, we also found that Dsk1 is mainly localized in the nucleus during G{sub 2} phase and at mitosis. Furthermore, we revealed the oscillation of Dsk1 protein in a cell cycle-dependent manner. This paper marks the first comprehensive analysis of in vivo Dsk1-associated proteins in fission yeast. Our results reflect the conserved role of SRPK family in eukaryotic organisms, and provide information about how Dsk1 functions in pre-mRNA processing and cell-division cycle.

  6. Interaction of alpha particles at the cellular level - Implications for the radiation weighting factor

    International Nuclear Information System (INIS)

    Since low dose effects of alpha particles are produced by cellular hits in a relatively small fraction of exposed cells, the present study focuses on alpha particle interactions in bronchial epithelial cells following exposure to inhaled radon progeny. A computer code was developed for the calculation of microdosimetric spectra, dose and hit probabilities for alpha particles emitted from uniform and non-uniform source distributions in cylindrical and Y-shaped bronchial airway geometries. Activity accumulations at the dividing spur of bronchial airway bifurcations produce hot spots of cellular hits, indicating that a small fraction of cells located at such sites may receive substantially higher doses. While presently available data on in vitro transformation frequencies suggest that the relative biological effectiveness for alpha particles ranges from about 3 to 10, the effect of inhomogeneous activity distributions of radon progeny may slightly increase the radiation weighting factor relative to a uniform distribution. Thus a radiation weighting factor of about 10 may be more realistic than the current value of 20, at least for lung cancer risk following inhalation of short-lived radon progeny. (authors)

  7. Interacting factors and cellular localization of SR protein-specific kinase Dsk1

    International Nuclear Information System (INIS)

    Schizosaccharomyces pombe Dsk1 is an SR protein-specific kinase (SRPK), whose homologs have been identified in every eukaryotic organism examined. Although discovered as a mitotic regulator with protein kinase activity toward SR splicing factors, it remains largely unknown about what and how Dsk1 contributes to cell cycle and pre-mRNA splicing. In this study, we investigated the Dsk1 function by determining interacting factors and cellular localization of the kinase. Consistent with its reported functions, we found that pre-mRNA processing and cell cycle factors are prominent among the proteins co-purified with Dsk1. The identification of these factors led us to find Rsd1 as a novel Dsk1 substrate, as well as the involvement of Dsk1 in cellular distribution of poly(A)+ RNA. In agreement with its role in nuclear events, we also found that Dsk1 is mainly localized in the nucleus during G2 phase and at mitosis. Furthermore, we revealed the oscillation of Dsk1 protein in a cell cycle-dependent manner. This paper marks the first comprehensive analysis of in vivo Dsk1-associated proteins in fission yeast. Our results reflect the conserved role of SRPK family in eukaryotic organisms, and provide information about how Dsk1 functions in pre-mRNA processing and cell-division cycle.

  8. The cellular membrane as a mediator for small molecule interaction with membrane proteins.

    Science.gov (United States)

    Mayne, Christopher G; Arcario, Mark J; Mahinthichaichan, Paween; Baylon, Javier L; Vermaas, Josh V; Navidpour, Latifeh; Wen, Po-Chao; Thangapandian, Sundarapandian; Tajkhorshid, Emad

    2016-10-01

    The cellular membrane constitutes the first element that encounters a wide variety of molecular species to which a cell might be exposed. Hosting a large number of structurally and functionally diverse proteins associated with this key metabolic compartment, the membrane not only directly controls the traffic of various molecules in and out of the cell, it also participates in such diverse and important processes as signal transduction and chemical processing of incoming molecular species. In this article, we present a number of cases where details of interaction of small molecular species such as drugs with the membrane, which are often experimentally inaccessible, have been studied using advanced molecular simulation techniques. We have selected systems in which partitioning of the small molecule with the membrane constitutes a key step for its final biological function, often binding to and interacting with a protein associated with the membrane. These examples demonstrate that membrane partitioning is not only important for the overall distribution of drugs and other small molecules into different compartments of the body, it may also play a key role in determining the efficiency and the mode of interaction of the drug with its target protein. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg. PMID:27163493

  9. An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein

    International Nuclear Information System (INIS)

    The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection.

  10. Evolution of altruism in spatial prisoner's dilemma: Intra- and inter-cellular interactions

    Science.gov (United States)

    Yokoi, Hiroki; Uehara, Takashi; Sakata, Tomoyuki; Naito, Hiromi; Morita, Satoru; Tainaka, Kei-ichi

    2014-12-01

    Iterated prisoner's dilemma game is carried out on lattice with “colony” structure. Each cell is regarded as a colony which contains plural players with an identical strategy. Both intra- and inter-cellular interactions are assumed. In the former a player plays with all other players in the same colony, while in the latter he plays with one player each from adjacent colonies. Spatial patterns among four typical strategies exhibit various dynamics and winners. Both theory and simulation reveal that All Cooperation (AC) wins, when the members of colony or the intensity of noise increases. This result explains the evolution of altruism in animal societies, even though errors easily occur in animal communications.

  11. Targeting the molecular and cellular interactions of the bone marrow niche in immunologic disease.

    Science.gov (United States)

    Brozowski, Jaime M; Billard, Matthew J; Tarrant, Teresa K

    2014-02-01

    Recent investigations have expanded our knowledge of the regulatory bone marrow (BM) niche, which is critical in maintaining and directing hematopoietic stem cell (HSC) self-renewal and differentiation. Osteoblasts, mesenchymal stem cells (MSCs), and CXCL12-abundant reticular (CAR) cells are niche components in close association with HSCs and have been more clearly defined in immune cell function and homeostasis. Importantly, cellular inhabitants of the BM niche signal through G protein-coupled surface receptors (GPCRs) for various appropriate immune functions. In this article, recent literature on BM niche inhabitants (HSCs, osteoblasts, MSCs, CAR cells) and their GPCR mechanistic interactions are reviewed for better understanding of the BM cells involved in immune development, immunologic disease, and current immune reconstitution therapies. PMID:24408534

  12. DNA-controlled dynamic colloidal nanoparticle systems for mediating cellular interaction

    Science.gov (United States)

    Ohta, Seiichi; Glancy, Dylan; Chan, Warren C. W.

    2016-02-01

    Precise control of biosystems requires development of materials that can dynamically change physicochemical properties. Inspired by the ability of proteins to alter their conformation to mediate function, we explored the use of DNA as molecular keys to assemble and transform colloidal nanoparticle systems. The systems consist of a core nanoparticle surrounded by small satellites, the conformation of which can be transformed in response to DNA via a toe-hold displacement mechanism. The conformational changes can alter the optical properties and biological interactions of the assembled nanosystem. Photoluminescent signal is altered by changes in fluorophore-modified particle distance, whereas cellular targeting efficiency is increased 2.5 times by changing the surface display of targeting ligands. These concepts provide strategies for engineering dynamic nanotechnology systems for navigating complex biological environments.

  13. Biomaterial design for specific cellular interactions: Role of surface functionalization and geometric features

    Science.gov (United States)

    Kolhar, Poornima

    The areas of drug delivery and tissue engineering have experienced extraordinary growth in recent years with the application of engineering principles and their potential to support and improve the field of medicine. The tremendous progress in nanotechnology and biotechnology has lead to this explosion of research and development in biomedical applications. Biomaterials can now be engineered at a nanoscale and their specific interactions with the biological tissues can be modulated. Various design parameters are being established and researched for design of drug-delivery carriers and scaffolds to be implanted into humans. Nanoparticles made from versatile biomaterial can deliver both small-molecule drugs and various classes of bio-macromolecules, such as proteins and oligonucleotides. Similarly in the field of tissue engineering, current approaches emphasize nanoscale control of cell behavior by mimicking the natural extracellular matrix (ECM) unlike, traditional scaffolds. Drug delivery and tissue engineering are closely connected fields and both of these applications require materials with exceptional physical, chemical, biological, and biomechanical properties to provide superior therapy. In the current study the surface functionalization and the geometric features of the biomaterials has been explored. In particular, a synthetic surface for culture of human embryonic stem cells has been developed, demonstrating the importance of surface functionalization in maintaining the pluripotency of hESCs. In the second study, the geometric features of the drug delivery carriers are investigated and the polymeric nanoneedles mediated cellular permeabilization and direct cytoplasmic delivery is reported. In the third study, the combined effect of surface functionalization and geometric modification of carriers for vascular targeting is enunciated. These studies illustrate how the biomaterials can be designed to achieve various cellular behaviors and control the

  14. Optimal cellular mobility for synchronization arising from the gradual recovery of intercellular interactions

    International Nuclear Information System (INIS)

    Cell movement and intercellular signaling occur simultaneously during the development of tissues, but little is known about how movement affects signaling. Previous theoretical studies have shown that faster moving cells favor synchronization across a population of locally coupled genetic oscillators. An important assumption in these studies is that cells can immediately interact with their new neighbors after arriving at a new location. However, intercellular interactions in cellular systems may need some time to become fully established. How movement affects synchronization in this situation has not been examined. Here, we develop a coupled phase oscillator model in which we consider cell movement and the gradual recovery of intercellular coupling experienced by a cell after movement, characterized by a moving rate and a coupling recovery rate, respectively. We find (1) an optimal moving rate for synchronization and (2) a critical moving rate above which achieving synchronization is not possible. These results indicate that the extent to which movement enhances synchrony is limited by a gradual recovery of coupling. These findings suggest that the ratio of time scales of movement and signaling recovery is critical for information transfer between moving cells. (paper)

  15. Special Issue: Redox Active Natural Products and Their Interaction with Cellular Signalling Pathways

    Directory of Open Access Journals (Sweden)

    Claus Jacob

    2014-11-01

    Full Text Available During the last decade, research into natural products has experienced a certain renaissance. The urgent need for more and more effective antibiotics in medicine, the demand for ecologically friendly plant protectants in agriculture, “natural” cosmetics and the issue of a sustainable and healthy nutrition in an ageing society have fuelled research into Nature’s treasure chest of “green gold”. Here, redox active secondary metabolites from plants, fungi, bacteria and other (micro-organisms often have been at the forefront of the most interesting developments. These agents provide powerful means to interfere with many, probably most cellular signaling pathways in humans, animals and lower organisms, and therefore can be used to protect, i.e., in form of antioxidants, and to frighten off or even kill, i.e., in form of repellants, antibiotics, fungicides and selective, often catalytic “sensor/effector” anticancer agents. Interestingly, whilst natural product research dates back many decades, in some cases even centuries, and compounds such as allicin and various flavonoids have been investigated thoroughly in the past, it has only recently become possible to investigate their precise interactions and mode(s of action inside living cells. Here, fluorescent staining and labelling on the one side, and appropriate detection, either qualitatively under the microscope or quantitatively in flow cytometers and plate readers, on the other, enable researchers to obtain the various pieces of information necessary to construct a fairly complete puzzle of how such compounds act and interact in living cells. Complemented by the more traditional activity assays and Western Blots, and increasingly joined by techniques such as proteomics, chemogenetic screening and mRNA profiling, these cell based bioanalytical techniques form a powerful platform for “intracellular diagnostics”. In the case of redox active compounds, especially of Reactive Sulfur

  16. Intracellular Localization and Cellular Factors Interaction of HTLV-1 and HTLV-2 Tax Proteins: Similarities and Functional Differences

    Science.gov (United States)

    Bertazzoni, Umberto; Turci, Marco; Avesani, Francesca; Di Gennaro, Gianfranco; Bidoia, Carlo; Romanelli, Maria Grazia

    2011-01-01

    Human T-lymphotropic viruses type 1 (HTLV-1) and type 2 (HTLV-2) present very similar genomic structures but HTLV-1 is more pathogenic than HTLV-2. Is this difference due to their transactivating Tax proteins, Tax-1 and Tax-2, which are responsible for viral and cellular gene activation? Do Tax-1 and Tax-2 differ in their cellular localization and in their interaction pattern with cellular factors? In this review, we summarize Tax-1 and Tax-2 structural and phenotypic properties, their interaction with factors involved in signal transduction and their localization-related behavior within the cell. Special attention will be given to the distinctions between Tax-1 and Tax-2 that likely play an important role in their transactivation activity. PMID:21994745

  17. Intracellular Localization and Cellular Factors Interaction of HTLV-1 and HTLV-2 Tax Proteins: Similarities and Functional Differences

    Directory of Open Access Journals (Sweden)

    Maria Grazia Romanelli

    2011-05-01

    Full Text Available Human T-lymphotropic viruses type 1 (HTLV-1 and type 2 (HTLV-2 present very similar genomic structures but HTLV-1 is more pathogenic than HTLV-2. Is this difference due to their transactivating Tax proteins, Tax-1 and Tax-2, which are responsible for viral and cellular gene activation? Do Tax-1 and Tax-2 differ in their cellular localization and in their interaction pattern with cellular factors? In this review, we summarize Tax-1 and Tax-2 structural and phenotypic properties, their interaction with factors involved in signal transduction and their localization-related behavior within the cell. Special attention will be given to the distinctions between Tax-1 and Tax-2 that likely play an important role in their transactivation activity.

  18. Drug permeation and cellular interaction of amino acid-coated drug combination powders for pulmonary delivery.

    Science.gov (United States)

    Vartiainen, Ville; Bimbo, Luis M; Hirvonen, Jouni; Kauppinen, Esko I; Raula, Janne

    2016-05-17

    The effect of three amino acid coatings (l-leucine, l-valine and l-phenylalanine) on particle integrity, aerosolization properties, cellular interaction, cytocompatibility, and drug permeation properties of drug combination powder particles (beclomethasone dipropionate and salbutamol sulphate) for dry powder inhalation (DPI) was investigated. Particles with crystalline l-leucine coating resulted in intact separated particles, with crystalline l-valine coating in slightly sintered particles and with amorphous l-phenylalanine coating in strongly fused particles. The permeation of beclomethasone dipropionate across a Calu-3 differentiated cell monolayer was increased when compared with its physical mixture. Drug crystal formation was also observed on the Calu-3 cell monolayer. The l-leucine coated particles were further investigated for cytocompatibility in three human pulmonary (Calu-3, A549 and BEAS-2B) and one human macrophage (THP-1) cell lines, where they showed excellent tolerability. The l-leucine coated particles were also examined for their ability to elicit reactive oxygen species in pulmonary BEAS-2B and macrophage THP-1 cell lines. The study showed the influence of the amino acid coatings for particle formation and performance and their feasibility for combination therapy for pulmonary delivery. PMID:27034001

  19. Gelatin-Modified Bone Substitute with Bioactive Molecules Enhance Cellular Interactions and Bone Regeneration.

    Science.gov (United States)

    Teotia, Arun Kumar; Gupta, Ankur; Raina, Deepak Bushan; Lidgren, Lars; Kumar, Ashok

    2016-05-01

    In this work, we have synthesized injectable bone cement incorporated with gelatin to enhance cellular interaction. Human osteosarcoma Saos-2 cells derived bone morphogenetic proteins (BMP's) and a bisphosphonate (zoledronic acid (0.2 mM)) were also incorporated to cement. In vitro studies conducted using Saos-2 demonstrated enhanced cell proliferation on gelatin (0.2%w/v) cement. The differentiation of C2C12 mouse myoblast cells into bone forming cells showed 6-fold increase in ALP levels on gelatin cement. Polymerase chain reaction (PCR) for bone biomarkers showed osteoinductive potential of gelatin cement. We investigated efficacy for local delivery of these bioactive molecules in enhancing bone substitution qualities of bone cements by implanting in 3.5 mm critical size defect in tibial metaphysis of wistar rats. The rats were sacrificed after 12 weeks and 16 weeks post implantation. X-ray, micro-CT, histology, and histomorphometry analysis were performed to check bone healing. The cement materials slowly resorbed from the defect site leaving HAP creating porous matrix providing surface for bone formation. The materials showed high biocompatibility and initial bridging was observed in all the animals but maximum bone formation was observed in animals implanted with cement incorporated with zoledronic acid followed by cement with BMP's compared to other groups. PMID:27077816

  20. Interaction between core protein of classical swine fever virus with cellular IQGAP1 proetin appears essential for virulence in swine

    Science.gov (United States)

    Here we show that IQGAP1, a cellular protein that plays a pivotal role as a regulator of the cytoskeleton affecting cell adhesion, polarization and migration, interacts with Classical Swine Fever Virus (CSFV) Core protein. Sequence analyses identified a defined set of residues within CSFV Core prote...

  1. The role of uncoupling protein 3 regulating calcium ion uptake into mitochondria during sarcopenia

    Science.gov (United States)

    Nikawa, Takeshi; Choi, Inho; Haruna, Marie; Hirasaka, Katsuya; Maita Ohno, Ayako; Kondo Teshima, Shigetada

    Overloaded mitochondrial calcium concentration contributes to progression of mitochondrial dysfunction in aged muscle, leading to sarcopenia. Uncoupling protein 3 (UCP3) is primarily expressed in the inner membrane of skeletal muscle mitochondria. Recently, it has been reported that UCP3 is associated with calcium uptake into mitochondria. However, the mechanisms by which UCP3 regulates mitochondrial calcium uptake are not well understood. Here we report that UCP3 interacts with HS-1 associated protein X-1 (Hax-1), an anti-apoptotic protein that is localized in mitochondria, which is involved in cellular responses to calcium ion. The hydrophilic sequences within the loop 2, matrix-localized hydrophilic domain of mouse UCP3 are necessary for binding to Hax-1 of the C-terminal domain in adjacent to mitochondrial innermembrane. Interestingly, these proteins interaction occur the calcium-dependent manner. Indeed, overexpression of UCP3 significantly enhanced calcium uptake into mitochondria on Hax-1 endogenously expressing C2C12 myoblasts. In addition, Hax-1 knock-down enhanced calcium uptake into mitochondria on both UCP3 and Hax-1 endogenously expressing C2C12 myotubes, but not myoblasts. Finally, the dissociation of UCP3 and Hax-1 enhances calcium uptake into mitochondria in aged muscle. These studies identify a novel UCP3-Hax-1 complex regulates the influx of calcium ion into mitochondria in muscle. Thus, the efficacy of UCP3-Hax-1 in mitochondrial calcium regulation may provide a novel therapeutic approach against mitochondrial dysfunction-related disease containing sarcopenia.

  2. Role of Uncoupling Proteins in Cancer

    International Nuclear Information System (INIS)

    Uncoupling proteins (UCPs) are a family of inner mitochondrial membrane proteins whose function is to allow the re-entry of protons to the mitochondrial matrix, by dissipating the proton gradient and, subsequently, decreasing membrane potential and production of reactive oxygen species (ROS). Due to their pivotal role in the intersection between energy efficiency and oxidative stress, UCPs are being investigated for a potential role in cancer. In this review we compile the latest evidence showing a link between uncoupling and the carcinogenic process, paying special attention to their involvement in cancer initiation, progression and drug chemoresistance

  3. Role of Uncoupling Proteins in Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Valle, Adamo; Oliver, Jordi; Roca, Pilar, E-mail: pilar.roca@uib.es [Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d' Investigació en Ciències de la Salut, Universitat de les Illes Balears/Cra. Valldemossa km 7.5, E-07122, Palma de Mallorca, Illes Balears (Spain)

    2010-04-16

    Uncoupling proteins (UCPs) are a family of inner mitochondrial membrane proteins whose function is to allow the re-entry of protons to the mitochondrial matrix, by dissipating the proton gradient and, subsequently, decreasing membrane potential and production of reactive oxygen species (ROS). Due to their pivotal role in the intersection between energy efficiency and oxidative stress, UCPs are being investigated for a potential role in cancer. In this review we compile the latest evidence showing a link between uncoupling and the carcinogenic process, paying special attention to their involvement in cancer initiation, progression and drug chemoresistance.

  4. Role of Uncoupling Proteins in Cancer

    Directory of Open Access Journals (Sweden)

    Adamo Valle

    2010-04-01

    Full Text Available Uncoupling proteins (UCPs are a family of inner mitochondrial membrane proteins whose function is to allow the re-entry of protons to the mitochondrial matrix, by dissipating the proton gradient and, subsequently, decreasing membrane potential and production of reactive oxygen species (ROS. Due to their pivotal role in the intersection between energy efficiency and oxidative stress, UCPs are being investigated for a potential role in cancer. In this review we compile the latest evidence showing a link between uncoupling and the carcinogenic process, paying special attention to their involvement in cancer initiation, progression and drug chemoresistance.

  5. 30 CFR 56.14215 - Coupling or uncoupling cars.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Coupling or uncoupling cars. 56.14215 Section... Equipment Safety Practices and Operational Procedures § 56.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then moved at...

  6. 30 CFR 57.14215 - Coupling or uncoupling cars.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Coupling or uncoupling cars. 57.14215 Section... and Equipment Safety Practices and Operational Procedures § 57.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and...

  7. *601693 UNCOUPLING PROTEIN 2; UCP2 [OMIM

    Lifescience Database Archive (English)

    Full Text Available FIELD NO 601693 FIELD TI 601693 UNCOUPLING PROTEIN 2; UCP2 FIELD TX CLONING The mitochondrial pr ... els of UCP2 and UCP3 (602044) mRNA in skeletal muscle an d adipose tissue from both lean ... and obese individu ... tion of gene expression observed during fasting in lean ... and obese subjects show that there is no major alt ...

  8. Mitochondrial uncoupling proteins and energy metabolism

    Directory of Open Access Journals (Sweden)

    Rosa Anna Busiello

    2015-02-01

    Full Text Available Understanding the metabolic factors that contribute to energy metabolism (EM is critical for the development of new treatments for obesity and related diseases. Mitochondrial oxidative phosphorylation is not perfectly coupled to ATP synthesis, and the process of proton-leak plays a crucial role. Proton-leak accounts for a significant part of the resting metabolic rate and therefore enhancement of this process represents a potential target for obesity treatment. Since their discovery, uncoupling proteins have stimulated great interest due to their involvement in mitochondrial-inducible proton-leak. Despite the widely accepted uncoupling/thermogenic effect of uncoupling protein one (UCP1, which was the first in this family to be discovered, the reactions catalyzed by its homologue UCP3 and the physiological role remain under debate.This review provides an overview of the role played by UCP1 and UCP3 in mitochondrial uncoupling/functionality as well as EM and suggests that they are a potential therapeutic target for treating obesity and its related diseases such as type II diabetes mellitus.

  9. Increased CO2 uncouples growth from isoprene emission in an agriforest ecosystem

    Science.gov (United States)

    Rosenstiel, Todd N.; Potosnak, Mark J.; Griffin, Kevin L.; Fall, Ray; Monson, Russell K.

    2003-01-01

    The emission of isoprene from the leaves of forest trees is a fundamental component of biosphere-atmosphere interactions, controlling many aspects of photochemistry in the lower atmosphere. As almost all commercial agriforest species emit high levels of isoprene, proliferation of agriforest plantations has significant potential to increase regional ozone pollution and enhance the lifetime of methane, an important determinant of global climate. Here we show that growth of an intact Populus deltoides plantation under increased CO2 (800µmolmol-1 and 1,200µmolmol-1) reduced ecosystem isoprene production by 21% and 41%, while above-ground biomass accumulation was enhanced by 60% and 82%, respectively. Exposure to increased CO2 significantly reduced the cellular content of dimethylallyl diphosphate, the substrate for isoprene synthesis, in both leaves and leaf protoplasts. We identify intracellular metabolic competition for phosphoenolpyruvate as a possible control point in explaining the suppression of isoprene emission under increased CO2. Our results highlight the potential for uncoupling isoprene emission from biomass accumulation in an agriforest species, and show that negative air-quality effects of proliferating agriforests may be offset by increases in CO2.

  10. Detection of regulatory circuits by integrating the cellular networks of protein–protein interactions and transcription regulation

    OpenAIRE

    Yeger-Lotem, Esti; Margalit, Hanah

    2003-01-01

    The post-genomic era is marked by huge amounts of data generated by large-scale functional genomic and proteomic experiments. A major challenge is to integrate the various types of genome-scale information in order to reveal the intra- and inter- relationships between genes and proteins that constitute a living cell. Here we present a novel application of classical graph algorithms to integrate the cellular networks of protein–protein interactions and transcription regulation. We demonstrate ...

  11. Protein-protein interaction networks identify targets which rescue the MPP+ cellular model of Parkinson’s disease

    Science.gov (United States)

    Keane, Harriet; Ryan, Brent J.; Jackson, Brendan; Whitmore, Alan; Wade-Martins, Richard

    2015-11-01

    Neurodegenerative diseases are complex multifactorial disorders characterised by the interplay of many dysregulated physiological processes. As an exemplar, Parkinson’s disease (PD) involves multiple perturbed cellular functions, including mitochondrial dysfunction and autophagic dysregulation in preferentially-sensitive dopamine neurons, a selective pathophysiology recapitulated in vitro using the neurotoxin MPP+. Here we explore a network science approach for the selection of therapeutic protein targets in the cellular MPP+ model. We hypothesised that analysis of protein-protein interaction networks modelling MPP+ toxicity could identify proteins critical for mediating MPP+ toxicity. Analysis of protein-protein interaction networks constructed to model the interplay of mitochondrial dysfunction and autophagic dysregulation (key aspects of MPP+ toxicity) enabled us to identify four proteins predicted to be key for MPP+ toxicity (P62, GABARAP, GBRL1 and GBRL2). Combined, but not individual, knockdown of these proteins increased cellular susceptibility to MPP+ toxicity. Conversely, combined, but not individual, over-expression of the network targets provided rescue of MPP+ toxicity associated with the formation of autophagosome-like structures. We also found that modulation of two distinct proteins in the protein-protein interaction network was necessary and sufficient to mitigate neurotoxicity. Together, these findings validate our network science approach to multi-target identification in complex neurological diseases.

  12. Mystery of the Toxic Flea Dip: An Interactive Approach to Teaching Aerobic Cellular Respiration

    Science.gov (United States)

    Baines, A. T.; McVey, M.; Rybarczyk, B.; Thompson, J. T.; Wilkins, H. R.

    2004-01-01

    We designed an interrupted case study to teach aerobic cellular respiration to major and nonmajor biology students. The case is based loosely on a real-life incident of rotenone poisoning. It places students in the role of a coroner who must determine the cause of death of the victim. The case is presented to the students in four parts. Each part…

  13. *602044 UNCOUPLING PROTEIN 3; UCP3 [OMIM

    Lifescience Database Archive (English)

    Full Text Available FIELD NO 602044 FIELD TI 602044 UNCOUPLING PROTEIN 3; UCP3 FIELD TX CLONING Boss et al. (1997) a ... 3 is expressed as a 2.3-kb message in skeletal muscle an d heart. In rat tissue, UCP3 transcripts were foun ... n the levels of UCP2 and UCP3 mRNA in skeletal muscle an d adipose tissue from both lean ... and obese individu ...

  14. Discovering the cellular-localized functional modules and modular interactions in response to liver cancer

    Institute of Scientific and Technical Information of China (English)

    Zhu Jing; Guo Zheng; Yang Da; Zhang Min; Wang Jing; Wang Chenguang

    2008-01-01

    In this paper, we firstly identify the functional modules enriched with differentially expressed genes (DEGs) and characterized by biological processes in specific cellular locations, based on gene ontology (GO) and microarray data. Then, we further define and filter disease relevant signature modules according to the ranking of the disease discriminating abilities of the pre-selected functional modules. At last, we analyze the potential way by which they cooperate towards human disease. Application of the proposed method to the analysis of a liver cancer dataset shows that, using the same false discovery rate (FDR) threshold, we can find more biologically meaningful and detailed processes by using the cellular localization information. Some biological evidences support the relevancy of our biological modules to the disease mechanism.

  15. Current concepts in chronic inflammatory diseases: Interactions between microbes, cellular metabolism, and inflammation.

    Science.gov (United States)

    Garn, Holger; Bahn, Sabine; Baune, Bernhard T; Binder, Elisabeth B; Bisgaard, Hans; Chatila, Talal A; Chavakis, Triantafyllos; Culmsee, Carsten; Dannlowski, Udo; Gay, Steffen; Gern, James; Haahtela, Tari; Kircher, Tilo; Müller-Ladner, Ulf; Neurath, Markus F; Preissner, Klaus T; Reinhardt, Christoph; Rook, Graham; Russell, Shannon; Schmeck, Bernd; Stappenbeck, Thaddeus; Steinhoff, Ulrich; van Os, Jim; Weiss, Scott; Zemlin, Michael; Renz, Harald

    2016-07-01

    Recent research indicates that chronic inflammatory diseases, including allergies and autoimmune and neuropsychiatric diseases, share common pathways of cellular and molecular dysregulation. It was the aim of the International von-Behring-Röntgen Symposium (October 16-18, 2014, in Marburg, Germany) to discuss recent developments in this field. These include a concept of biodiversity; the contribution of urbanization, lifestyle factors, and nutrition (eg, vitamin D); and new mechanisms of metabolic and immune dysregulation, such as extracellular and intracellular RNAs and cellular and mitochondrial stress. Epigenetic mechanisms contribute further to altered gene expression and therefore to the development of chronic inflammation. These novel findings provide the foundation for further development of preventive and therapeutic strategies. PMID:27373325

  16. Characterization of the Interaction of Lassa Fever Virus with Its Cellular Receptor α-Dystroglycan

    OpenAIRE

    Kunz, Stefan; Rojek, Jillian M.; Perez, Mar; Spiropoulou, Christina F.; Oldstone, Michael B. A.

    2005-01-01

    The cellular receptor for the Old World arenaviruses Lassa fever virus (LFV) and lymphocytic choriomeningitis virus (LCMV) has recently been identified as α-dystroglycan (α-DG), a cell surface receptor that provides a molecular link between the extracellular matrix and the actin-based cytoskeleton. In the present study, we show that LFV binds to α-DG with high affinity in the low-nanomolar range. Recombinant vesicular stomatitis virus pseudotyped with LFV glycoprotein (GP) adopted the recepto...

  17. Comparing the epidermal growth factor interaction with four different cell lines: intriguing effects imply strong dependency of cellular context.

    Directory of Open Access Journals (Sweden)

    Hanna Björkelund

    Full Text Available The interaction of the epidermal growth factor (EGF with its receptor (EGFR is known to be complex, and the common over-expression of EGF receptor family members in a multitude of tumors makes it important to decipher this interaction and the following signaling pathways. We have investigated the affinity and kinetics of (125I-EGF binding to EGFR in four human tumor cell lines, each using four culturing conditions, in real time by use of LigandTracer®.Highly repeatable and precise measurements show that the overall apparent affinity of the (125I-EGF - EGFR interaction is greatly dependent on cell line at normal culturing conditions, ranging from K(D ≈ 200 pM on SKBR3 cells to K(D≈8 nM on A431 cells. The (125I-EGF - EGFR binding curves (irrespective of cell line have strong signs of multiple simultaneous interactions. Furthermore, for the cell lines A431 and SKOV3, gefitinib treatment increases the (125I-EGF - EGFR affinity, in particular when the cells are starved. The (125I-EGF - EGFR interaction on cell line U343 is sensitive to starvation while as on SKBR3 it is insensitive to gefitinib and starvation.The intriguing pattern of the binding characteristics proves that the cellular context is important when deciphering how EGF interacts with EGFR. From a general perspective, care is advisable when generalizing ligand-receptor interaction results across multiple cell-lines.

  18. Towards Inter- and Intra- Cellular Protein Interaction Analysis: Applying the Betweenness Centrality Graph Measure for Node Importance

    Science.gov (United States)

    Barton, Alan J.; Haqqani, Arsalan S.

    2011-11-01

    Three public biological network data sets (KEGG, GeneRIF and Reactome) are collected and described. Two problems are investigated (inter- and intra- cellular interactions) via augmentation of the collected networks to the problem specific data. Results include an estimate of the importance of proteins for the interaction of inflammatory cells with the blood-brain barrier via the computation of Betweenness Centrality. Subsequently, the interactions may be validated from a number of differing perspectives; including comparison with (i) existing biological results, (ii) the literature, and (iii) new hypothesis driven biological experiments. Novel therapeutic and diagnostic targets for inhibiting inflammation at the blood-brain barrier in a number of brain diseases including Alzheimer's disease, stroke and multiple sclerosis are possible. In addition, this methodology may also be applicable towards investigating the breast cancer tumour microenvironment.

  19. Plant-Herbivore Interaction: Dissection of the Cellular Pattern of Tetranychus urticae Feeding on the Host Plant

    Science.gov (United States)

    Bensoussan, Nicolas; Santamaria, M. Estrella; Zhurov, Vladimir; Diaz, Isabel; Grbić, Miodrag; Grbić, Vojislava

    2016-01-01

    The two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), is one of the most polyphagous herbivores feeding on cell contents of over 1100 plant species including more than 150 crops. It is being established as a model for chelicerate herbivores with tools that enable tracking of reciprocal responses in plant-spider mite interactions. However, despite their important pest status and a growing understanding of the molecular basis of interactions with plant hosts, knowledge of the way mites interface with the plant while feeding and the plant damage directly inflicted by mites is lacking. Here, utilizing histology and microscopy methods, we uncovered several key features of T. urticae feeding. By following the stylet path within the plant tissue, we determined that the stylet penetrates the leaf either in between epidermal pavement cells or through a stomatal opening, without damaging the epidermal cellular layer. Our recordings of mite feeding established that duration of the feeding event ranges from several minutes to more than half an hour, during which time mites consume a single mesophyll cell in a pattern that is common to both bean and Arabidopsis plant hosts. In addition, this study determined that leaf chlorotic spots, a common symptom of mite herbivory, do not form as an immediate consequence of mite feeding. Our results establish a cellular context for the plant-spider mite interaction that will support our understanding of the molecular mechanisms and cell signaling associated with spider mite feeding. PMID:27512397

  20. A procedure for noise uncoupling in laser interferometry

    International Nuclear Information System (INIS)

    A numerical procedure for noise recognition and uncoupling is described. The procedure is applied to a Michelson interferometer and is effective in seismic and acoustic noise uncoupling from the output signal of the interferometer. Due to the low data flow coming from the instrumentation this uncoupling can be performed in real time and it is useful as a data quality procedure for interferometer data output

  1. A procedure for noise uncoupling in laser interferometry

    CERN Document Server

    Barone, F; Rosa, R D; Eleuteri, A; Milano, L; Qipiani, K

    2002-01-01

    A numerical procedure for noise recognition and uncoupling is described. The procedure is applied to a Michelson interferometer and is effective in seismic and acoustic noise uncoupling from the output signal of the interferometer. Due to the low data flow coming from the instrumentation this uncoupling can be performed in real time and it is useful as a data quality procedure for interferometer data output.

  2. Noise studies of uncoupled dc-SQUIDs

    International Nuclear Information System (INIS)

    We have performed noise measurements of uncoupled dc SQUIDs with similar square washer geometries. Mappings consisting of hundreds of flux noise measurements at different points of operation have been carried out using a dc SQUID preamplifier and a computer controlled measurement system. The white and low frequency noise, dynamic resistance, and the flux-to-voltage transfer function have been measured. The dc SQUID noise performance is described using equivalent current noise sources, and the voltage noise is observed to be linearly proportional to dynamic resistance Rdyn. (orig.)

  3. Uncoupling proteins of invertebrates: A review.

    Science.gov (United States)

    Slocinska, Malgorzata; Barylski, Jakub; Jarmuszkiewicz, Wieslawa

    2016-09-01

    Uncoupling proteins (UCPs) mediate inducible proton conductance in the mitochondrial inner membrane. Herein, we summarize our knowledge regarding UCPs in invertebrates. Since 2001, the presence of UCPs has been demonstrated in nematodes, mollusks, amphioxi, and insects. We discuss the following important issues concerning invertebrate UCPs: their evolutionary relationships, molecular and functional properties, and physiological impact. Evolutionary analysis indicates that the branch of vertebrate and invertebrate UCP4-5 diverged early in the evolutionary process prior to the divergence of the animal groups. Several proposed physiological roles of invertebrate UCPs are energy control, metabolic balance, and preventive action against oxidative stress. © 2016 IUBMB Life, 68(9):691-699, 2016. PMID:27385510

  4. Genome-wide Mapping of Cellular Protein-RNA Interactions Enabled by Chemical Crosslinking

    Institute of Scientific and Technical Information of China (English)

    Xiaoyu Li; Jinghui Song; Chengqi Yi

    2014-01-01

    RNA-protein interactions influence many biological processes. Identifying the binding sites of RNA-binding proteins (RBPs) remains one of the most fundamental and important chal-lenges to the studies of such interactions. Capturing RNA and RBPs via chemical crosslinking allows stringent purification procedures that significantly remove the non-specific RNA and protein interactions. Two major types of chemical crosslinking strategies have been developed to date, i.e., UV-enabled crosslinking and enzymatic mechanism-based covalent capture. In this review, we com-pare such strategies and their current applications, with an emphasis on the technologies themselves rather than the biology that has been revealed. We hope such methods could benefit broader audi-ence and also urge for the development of new methods to study RNA RBP interactions.

  5. Modelling for near-surface interaction of lithium ceramics and sweep-gas by use of cellular automation

    International Nuclear Information System (INIS)

    Tritium release from the lithium ceramics as a fusion reactor breeder material is strongly affected by the composition of the sweep-gas as result of its influences with the material's surface. The typical surface processes which play important roles are adsorption, desorption and interaction between vacancy site and the constituents of the sweep-gas. Among a large number of studies and models, yet it seems to be difficult to model the overall behaviour of those processes due to its complex time-transient nature. In the present work the coarse grained atomic simulation based on the Cellular Automaton (CA) is used to model the dynamics of near-surface interaction between Li2O surface and sweep-gas that is consisting of a noble gas, hydrogen gas and water vapour. (author)

  6. The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence

    Science.gov (United States)

    Burla, Romina; Carcuro, Mariateresa; Torre, Mattia La; Fratini, Federica; Crescenzi, Marco; D'Apice, Maria Rosaria; Spitalieri, Paola; Raffa, Grazia Daniela; Astrologo, Letizia; Lattanzi, Giovanna; Cundari, Enrico; Raimondo, Domenico; Biroccio, Annamaria; Gatti, Maurizio

    2016-01-01

    AKTIP is a shelterin-interacting protein required for replication of telomeric DNA. Here, we show that AKTIP biochemically interacts with A- and B-type lamins and affects lamin A, but not lamin C or B, expression. In interphase cells, AKTIP localizes at the nuclear rim and in discrete regions of the nucleoplasm just like lamins. Double immunostaining revealed that AKTIP partially co-localizes with lamin B1 and lamin A/C in interphase cells, and that proper AKTIP localization requires functional lamin A. In mitotic cells, AKTIP is enriched at the spindle poles and at the midbody of late telophase cells similar to lamin B1. AKTIP-depleted cells show senescence-associated markers and recapitulate several aspects of the progeroid phenotype. Collectively, our results indicate that AKTIP is a new player in lamin-related processes, including those that govern nuclear architecture, telomere homeostasis and cellular senescence. PMID:27512140

  7. Cellular immunity and pathogen strategies in combative interactions involving Drosophila hosts and their endoparasitic wasps

    Directory of Open Access Journals (Sweden)

    AJ Nappi

    2010-09-01

    Full Text Available Various cellular innate immune responses protect invertebrates from attack by eukaryotic pathogens. In insects, assessments of the factor(s causing, or contributing to, pathogen mortality have long considered as toxic components certain molecules associated with enzyme-mediated melanogenesis. In Drosophila hosts, observations that have prompted additional or alternative considerations are those that document either the survival of certain endoparasitic wasps despite melanotic encapsulation, or the destruction of the parasite with no evidence of this type of host response. Investigations of the production of some reactive intermediates of oxygen and nitrogen during infection provide a basis for proposing that these molecules constitute important elements of the immune arsenal of Drosophila. Studies of the target specificity of virulence factors injected by female wasps during infection that suppress the host immune response will likely facilitate identification of the toxic host molecules, and contribute to a more detailed understanding of the cell-signaling pathways that regulate their synthesis.

  8. Cellular interactions via conditioned media induce in vivo nephron generation from tubular epithelial cells or mesenchymal stem cells

    International Nuclear Information System (INIS)

    Highlights: •We have attempted in vivo nephron generation using conditioned media. •Vascular and tubular cells do cross-talks on cell proliferation and tubular changes. •Tubular cells suppress these changes in mesenchymal stem cells. •Tubular cells differentiate mesenchymal stem cells into tubular cells. •Nephrons can be created from implanted tubular cells or mesenchymal stem cells. -- Abstract: There are some successful reports of kidney generation by utilizing the natural course of kidney development, namely, the use of an artificially treated metanephros, blastocyst or ureteric bud. Under a novel concept of cellular interactions via conditioned media (CMs), we have attempted in vivo nephron generation from tubular epithelial cells (TECs) or mesenchymal stem cells (MSCs). Here we used 10× CMs of vascular endothelial cells (VECs) and TECs, which is the first to introduce a CM into the field of organ regeneration. We first present stimulative cross-talks induced by these CMs between VECs and TECs on cell proliferation and morphological changes. In MSCs, TEC-CM suppressed these changes, however, induced cytokeratin expression, indicating the differentiation of MSCs into TECs. As a result, glomerular and tubular structures were created following the implantation of TECs or MSCs with both CMs. Our findings suggest that the cellular interactions via CMs might induce in vivo nephron generation from TECs or MSCs. As a promoting factor, CMs could also be applied to the regeneration of other organs and tissues

  9. Cellular interactions via conditioned media induce in vivo nephron generation from tubular epithelial cells or mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Machiguchi, Toshihiko, E-mail: machiguchi.toshihiko.23u@st.kyoto-u.ac.jp; Nakamura, Tatsuo, E-mail: nakamura@frontier.kyoto-u.ac.jp

    2013-06-07

    Highlights: •We have attempted in vivo nephron generation using conditioned media. •Vascular and tubular cells do cross-talks on cell proliferation and tubular changes. •Tubular cells suppress these changes in mesenchymal stem cells. •Tubular cells differentiate mesenchymal stem cells into tubular cells. •Nephrons can be created from implanted tubular cells or mesenchymal stem cells. -- Abstract: There are some successful reports of kidney generation by utilizing the natural course of kidney development, namely, the use of an artificially treated metanephros, blastocyst or ureteric bud. Under a novel concept of cellular interactions via conditioned media (CMs), we have attempted in vivo nephron generation from tubular epithelial cells (TECs) or mesenchymal stem cells (MSCs). Here we used 10× CMs of vascular endothelial cells (VECs) and TECs, which is the first to introduce a CM into the field of organ regeneration. We first present stimulative cross-talks induced by these CMs between VECs and TECs on cell proliferation and morphological changes. In MSCs, TEC-CM suppressed these changes, however, induced cytokeratin expression, indicating the differentiation of MSCs into TECs. As a result, glomerular and tubular structures were created following the implantation of TECs or MSCs with both CMs. Our findings suggest that the cellular interactions via CMs might induce in vivo nephron generation from TECs or MSCs. As a promoting factor, CMs could also be applied to the regeneration of other organs and tissues.

  10. Interaction between the human cytomegalovirus‑encoded UL142 and cellular Snapin proteins.

    Science.gov (United States)

    Liu, Chang; Qi, Ying; Ma, Yanping; He, Rong; Sun, Zhengrong; Huang, Yujing; Ji, Yaohua; Ruan, Qiang

    2015-02-01

    Human cytomegalovirus (HCMV) infection can cause severe illness in immunocompromised and immunodeficient individuals. As a novel HCMV‑encoded major histocompatibility complex class I‑related molecule, the UL142‑encoded protein (pUL142) is capable of suppressing natural killer (NK) cell recognition in the course of infection. However, no host factors that directly interact with HCMV pUL142 have been reported so far. In order to understand the interactions between HCMV pUL142 and host proteins, the current study used yeast two‑hybrid screening, a GST pull‑down assay and an immunofluorescence assay. A host protein, the SNARE‑associated protein Snapin, was identified to directly interact and colocalize with HCMV pUL142 in transfected human embryonic kidney‑293 cells. Snapin is abundantly expressed in the majority of cells and mediates the release of neurotransmitters through vesicular transport in the nervous system and vesicle fusion in non‑neuronal cells. It is hypothesized that HCMV pUL142 may have an impact on the neurotransmitter release process and viral dissemination via interaction with Snapin. PMID:25369979

  11. Revealing the sequence and resulting cellular morphology of receptor-ligand interactions during Plasmodium falciparum invasion of erythrocytes.

    Directory of Open Access Journals (Sweden)

    Greta E Weiss

    2015-02-01

    Full Text Available During blood stage Plasmodium falciparum infection, merozoites invade uninfected erythrocytes via a complex, multistep process involving a series of distinct receptor-ligand binding events. Understanding each element in this process increases the potential to block the parasite's life cycle via drugs or vaccines. To investigate specific receptor-ligand interactions, they were systematically blocked using a combination of genetic deletion, enzymatic receptor cleavage and inhibition of binding via antibodies, peptides and small molecules, and the resulting temporal changes in invasion and morphological effects on erythrocytes were filmed using live cell imaging. Analysis of the videos have shown receptor-ligand interactions occur in the following sequence with the following cellular morphologies; 1 an early heparin-blockable interaction which weakly deforms the erythrocyte, 2 EBA and PfRh ligands which strongly deform the erythrocyte, a process dependant on the merozoite's actin-myosin motor, 3 a PfRh5-basigin binding step which results in a pore or opening between parasite and host through which it appears small molecules and possibly invasion components can flow and 4 an AMA1-RON2 interaction that mediates tight junction formation, which acts as an anchor point for internalization. In addition to enhancing general knowledge of apicomplexan biology, this work provides a rational basis to combine sequentially acting merozoite vaccine candidates in a single multi-receptor-blocking vaccine.

  12. Interaction of heavy ions with nuclear chromatin: Spatiotemporal investigations of biological responses in a cellular environment

    International Nuclear Information System (INIS)

    Ion beams offer the possibility to generate strictly localized DNA lesions within subregions of a cell nucleus. The distribution of the ion-induced damage can be indirectly visualized by immunocytochemical detection of repair-related proteins as radiation-induced foci. The proteins analyzed here were the double-strand break marker γ-H2AX, the excision repair and replication protein PCNA and the cell cycle regulator CDKN1A. A newly developed adjustable sample holder is now used to apply an irradiation geometry characterized by a small angle between the plane of the cellular monolayer and the incoming ion beam. This allows the spatial analysis of protein accumulations along ion trajectories, revealing an unexpected clustering after irradiation with low-energy zinc ions. The patterns of protein aggregation observed show considerable intrinsic variability, but similar patterns of protein clustering were obtained for functionally different proteins irrespective of the type of ion beam applied, confirming previous observations for lower and higher LET beams. Foci sizes within ion tracks were found to be larger for γ-H2AX foci in comparison to CDKN1A foci, in agreement with the known histone H2AX phosphorylation response. The results suggest that not the pattern of dose deposition but the underlying chromatin structure determines the distribution of protein clusters along tracks. Therefore, the requirement of time-lapse studies using live cells is emphasized for future studies on chromatin movement as a potential component of the DNA damage response

  13. Characterization of the Interaction of Lassa Fever Virus with Its Cellular Receptor α-Dystroglycan

    Science.gov (United States)

    Kunz, Stefan; Rojek, Jillian M.; Perez, Mar; Spiropoulou, Christina F.; Oldstone, Michael B. A.

    2005-01-01

    The cellular receptor for the Old World arenaviruses Lassa fever virus (LFV) and lymphocytic choriomeningitis virus (LCMV) has recently been identified as α-dystroglycan (α-DG), a cell surface receptor that provides a molecular link between the extracellular matrix and the actin-based cytoskeleton. In the present study, we show that LFV binds to α-DG with high affinity in the low-nanomolar range. Recombinant vesicular stomatitis virus pseudotyped with LFV glycoprotein (GP) adopted the receptor binding characteristics of LFV and depended on α-DG for infection of cells. Mapping of the binding site of LFV on α-DG revealed that LFV binding required the same domains of α-DG that are involved in the binding of LCMV. Further, LFV was found to efficiently compete with laminin α1 and α2 chains for α-DG binding. Together with our previous studies on receptor binding of the prototypic immunosuppressive LCMV isolate LCMV clone 13, these findings indicate a high degree of conservation in the receptor binding characteristics between the highly human-pathogenic LFV and murine-immunosuppressive LCMV isolates. PMID:15857984

  14. Characterization of the interaction of lassa fever virus with its cellular receptor alpha-dystroglycan.

    Science.gov (United States)

    Kunz, Stefan; Rojek, Jillian M; Perez, Mar; Spiropoulou, Christina F; Oldstone, Michael B A

    2005-05-01

    The cellular receptor for the Old World arenaviruses Lassa fever virus (LFV) and lymphocytic choriomeningitis virus (LCMV) has recently been identified as alpha-dystroglycan (alpha-DG), a cell surface receptor that provides a molecular link between the extracellular matrix and the actin-based cytoskeleton. In the present study, we show that LFV binds to alpha-DG with high affinity in the low-nanomolar range. Recombinant vesicular stomatitis virus pseudotyped with LFV glycoprotein (GP) adopted the receptor binding characteristics of LFV and depended on alpha-DG for infection of cells. Mapping of the binding site of LFV on alpha-DG revealed that LFV binding required the same domains of alpha-DG that are involved in the binding of LCMV. Further, LFV was found to efficiently compete with laminin alpha1 and alpha2 chains for alpha-DG binding. Together with our previous studies on receptor binding of the prototypic immunosuppressive LCMV isolate LCMV clone 13, these findings indicate a high degree of conservation in the receptor binding characteristics between the highly human-pathogenic LFV and murine-immunosuppressive LCMV isolates. PMID:15857984

  15. Nutrient-Gene Interaction in Colon Cancer, from the Membrane to Cellular Physiology.

    Science.gov (United States)

    Hou, Tim Y; Davidson, Laurie A; Kim, Eunjoo; Fan, Yang-Yi; Fuentes, Natividad R; Triff, Karen; Chapkin, Robert S

    2016-07-17

    The International Agency for Research on Cancer recently released an assessment classifying red and processed meat as "carcinogenic to humans" on the basis of the positive association between increased consumption and risk for colorectal cancer. Diet, however, can also decrease the risk for colorectal cancer and be used as a chemopreventive strategy. Bioactive dietary molecules, such as n-3 polyunsaturated fatty acids, curcumin, and fermentable fiber, have been proposed to exert chemoprotective effects, and their molecular mechanisms have been the focus of research in the dietary/chemoprevention field. Using these bioactives as examples, this review surveys the proposed mechanisms by which they exert their effects, from the nucleus to the cellular membrane. In addition, we discuss emerging technologies involving the culturing of colonic organoids to study the physiological effects of dietary bioactives. Finally, we address future challenges to the field regarding the identification of additional molecular mechanisms and other bioactive dietary molecules that can be utilized in our fight to reduce the incidence of colorectal cancer. PMID:27431370

  16. iGPCR-drug: a web server for predicting interaction between GPCRs and drugs in cellular networking.

    Directory of Open Access Journals (Sweden)

    Xuan Xiao

    Full Text Available Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs are among the most frequent targets of therapeutic drugs. It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques. Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown. To overcome the situation, a sequence-based classifier, called "iGPCR-drug", was developed to predict the interactions between GPCRs and drugs in cellular networking. In the predictor, the drug compound is formulated by a 2D (dimensional fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity. The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it. It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug - target interaction networks.

  17. Interactions of HIV-1 proteins with their cellular partners : insights from computational methods

    OpenAIRE

    Quy, Vo Cam

    2013-01-01

    HIV-1 attacks vital cells in the human immune system. HIV-1 differs from many viruses since it is characterized by a very high genetic variability. This means that many variants of HIV-1 virus can be generated in a single infected patient in the course of one day. HIV-1 hypervariability causes drug resistance and, consequently, medical treatment failure. Targeting the interactions between proteins from HIV-1 and from Homo sapiens may represent an excellent solution for drug design because it ...

  18. Mitochondrial uncoupler 2, 4-dinitrophenol (DNP) counters radiation induced cell death by stimulating anti-oxidant defence system

    International Nuclear Information System (INIS)

    Mitochondrial uncoupling has been shown to be cyto-protective under various stress conditions and studies with uncouplers suggest that mitochondrial uncoupling could be an attractive approach to promote lifespan extension by preventing the formation of reactive oxygen species (ROS). Our earlier studies have established that uncoupling of mitochondrial respiration to attain high glycolytic rate in cancer cells increased cellular radio-resistance. Therefore, we tested the hypothesis that mild mitochondrial uncoupling using DNP protects normal cells from radiation induced cell death by reducing oxidative stress. Human Embryonic Kidney (HEK293) and Mouse Monocytic (RAW264.7) cells were treated with DNP (10 μM),1 hour prior to radiation exposure (gamma rays, Cobalt-60). Cells treated with DNP before irradiation showed enhanced cell number (1.4 fold) as compared to radiation alone. We also observed 40 % decrease (significant level) in radiation induced ROS, 4 hours after exposure in DNP pre-treated cells with concomitant increase in anti-oxidant defence potential. The decreased ROS production and increased antioxidant defence potential correlated well with enhanced MnSOD and catalase expression. Although, DNP increased mitochondrial biogenesis, radiation induced mitochondrial biogenesis, (a consequence of mitochondrial damage), was not increased further in these cells, thereby suggesting that DNP protects the mitochondria from radiation induced damage, possibly by increasing MnSOD expression. These findings provide evidence that mild mitochondrial uncoupling using DNP attributes to the highly coordinated activation of the anti oxidant defence system in cells and provides survival advantage. Further mechanistic studies to understand the DNP induced radioprotection of cells is under progress. (author)

  19. Cellular polarization: Interaction between extrinsic bounded noises and the wave-pinning mechanism

    Science.gov (United States)

    de Franciscis, Sebastiano; d'Onofrio, Alberto

    2013-09-01

    Cell polarization (cued or uncued) is a fundamental mechanism in cell biology. As an alternative to the classical Turing bifurcation, it has been proposed that the onset of cell polarity might arise by means of the well-known phenomenon of wave-pinning [Gamba , Proc. Natl. Acad. Sci. USAPNASA60027-842410.1073/pnas.0503974102 102, 16927 (2005)]. A particularly simple and elegant deterministic model of cell polarization based on the wave-pinning mechanism has been proposed by Edelstein-Keshet and coworkers [Biophys. J.BIOJAU0006-349510.1529/biophysj.107.120824 94, 3684 (2008)]. This model consists of a small biomolecular network where an active membrane-bound factor interconverts into its inactive form that freely diffuses in the cell cytosol. However, biomolecular networks do communicate with other networks as well as with the external world. Thus, their dynamics must be considered as perturbed by extrinsic noises. These noises may have both a spatial and a temporal correlation, and in any case they must be bounded to preserve the biological meaningfulness of the perturbed parameters. Here we numerically show that the inclusion of external spatiotemporal bounded parametric perturbations in the above wave-pinning-based model of cellular polarization may sometimes destroy the polarized state. The polarization loss depends on both the extent of temporal and spatial correlations and on the kind of noise employed. For example, an increase of the spatial correlation of the noise induces an increase of the probability of cell polarization. However, if the noise is spatially homogeneous then the polarization is lost in the majority of cases. These phenomena are independent of the type of noise. Conversely, an increase of the temporal autocorrelation of the noise induces an effect that depends on the model of noise.

  20. A biophysical study on molecular physiology of the uncoupling proteins of the central nervous system

    OpenAIRE

    Hoang, Tuan; Kuljanin, Miljan; Smith, Matthew D.; Jelokhani-Niaraki, Masoud

    2015-01-01

    Uncoupling proteins (UCP)2, UCP4 and UCP5 transport protons across the inner membrane of mitochondria in the central nervous system (CNS). Novel recombinant protein expression allowed expression of UCPs in Escherichia coli membranes. Functional neuronal UCPs formed multimers in membranes and interacted with various fatty acids (FAs) to transport protons. Self-association and unique ion transport properties of UCPs distinguish their physiological roles in the CNS.

  1. Nanoparticle-allergen interactions mediate human allergic responses: protein corona characterization and cellular responses

    OpenAIRE

    Radauer-Preiml, Isabella; Andosch, Ancuela; Hawranek, Thomas; Luetz-Meindl, Ursula; Wiederstein, Markus; Horejs-Hoeck, Jutta; Himly, Martin; Boyles, Matthew; Duschl, Albert

    2016-01-01

    Background Engineered nanomaterials (ENMs) interact with different biomolecules as soon as they are in contact, resulting in the formation of a biomolecule ‘corona’. Hence, the ‘corona’ defines the biological identity of the ENMs and could affect the response of the immune system to ENM exposure. With up to 40 % of the world population suffering from type I allergy, a possible modulation of allergen effects by binding to ENMs is highly relevant with respect to work place and consumer safety. ...

  2. Uncoupling protein 1 (UCP1 of brown adipocyte, the only uncoupler: historical perspective

    Directory of Open Access Journals (Sweden)

    Daniel eRicquier

    2011-12-01

    Full Text Available Uncoupling protein 1 - UCP1, is a unique mitochondrial membranous protein devoted to adaptive thermogenesis, a specialized function operated by the highly specialized oxidative brown adipocytes. Whereas the family of mitochondrial metabolite carriers comprises ~40 members including UCP1, the UCP1 is specifically identified by its ability to translocate protons through the inner membrane of brown adipocyte mitochondria. Doing that, UCP1 uncouples respiration from ATP synthesis and therefore provokes energy dissipation of oxidative energy as heat while, in parallel it markedly stimulates respiration and activates fatty acid oxidation. UCP1 homologues were identified but they are biochemically and physiologically different from UCP1. Thirty five years after its identification, UCP1 still appears as a fascinating component, and the recent renewal of the interest in human brown adipose tissue makes UCP1 as a potential target for strategies of treatment of metabolic disorders.

  3. iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking

    Directory of Open Access Journals (Sweden)

    Yue-Nong Fan

    2014-03-01

    Full Text Available Nuclear receptors (NRs are closely associated with various major diseases such as cancer, diabetes, inflammatory disease, and osteoporosis. Therefore, NRs have become a frequent target for drug development. During the process of developing drugs against these diseases by targeting NRs, we are often facing a problem: Given a NR and chemical compound, can we identify whether they are really in interaction with each other in a cell? To address this problem, a predictor called “iNR-Drug” was developed. In the predictor, the drug compound concerned was formulated by a 256-D (dimensional vector derived from its molecular fingerprint, and the NR by a 500-D vector formed by incorporating its sequential evolution information and physicochemical features into the general form of pseudo amino acid composition, and the prediction engine was operated by the SVM (support vector machine algorithm. Compared with the existing prediction methods in this area, iNR-Drug not only can yield a higher success rate, but is also featured by a user-friendly web-server established at http://www.jci-bioinfo.cn/iNR-Drug/, which is particularly useful for most experimental scientists to obtain their desired data in a timely manner. It is anticipated that the iNR-Drug server may become a useful high throughput tool for both basic research and drug development, and that the current approach may be easily extended to study the interactions of drug with other targets as well.

  4. Cellular automata (CA) simulation of the interaction of vehicle flows and pedestrian crossings on urban low-grade uncontrolled roads

    Science.gov (United States)

    Chen, Qun; Wang, Yan

    2015-08-01

    This paper discusses the interaction of vehicle flows and pedestrian crossings on uncontrolled low-grade roads or branch roads without separating barriers in cities where pedestrians may cross randomly from any location on both sides of the road. The rules governing pedestrian street crossings are analyzed, and a cellular automata (CA) model to simulate the interaction of vehicle flows and pedestrian crossings is proposed. The influence of the interaction of vehicle flows and pedestrian crossings on the volume and travel time of the vehicle flow and the average wait time for pedestrians to cross is investigated through simulations. The main results of the simulation are as follows: (1) The vehicle flow volume decreases because of interruption from pedestrian crossings, but a small number of pedestrian crossings do not cause a significant delay to vehicles. (2) If there are many pedestrian crossings, slow vehicles will have little chance to accelerate, causing travel time to increase and the vehicle flow volume to decrease. (3) The average wait time for pedestrians to cross generally decreases with a decrease in vehicle flow volume and also decreases with an increase in the number of pedestrian crossings. (4) Temporal and spatial characteristics of vehicle flows and pedestrian flows and some interesting phenomena such as "crossing belt" and "vehicle belt" are found through the simulations.

  5. Seismic coupling and uncoupling at subduction zones

    Science.gov (United States)

    Ruff, L.; Kanamori, H.

    1983-01-01

    Some of the correlations concerning the properties of subduction zones are reviewed. A quantitative global comparison of many subduction zones reveals that the largest earthquakes occur in zones with young lithosphere and fast convergence rates. Maximum earthquake size is directly related to the asperity distribution on the fault plane. This observation can be translated into a simple model of seismic coupling where the horizontal compressive stress between two plates is proportional to the ratio of the summed asperity area to the total area of the contact surface. Plate age and rate can control asperity distribution directly through the horizontal compressive stress associated with the vertical and horizontal velocities of subducting slabs. The basalt to eclogite phase change in the down-going oceanic crust may be largely responsible for the uncoupling of subduction zones below a depth of about 40 km.

  6. Cellular and biophysical evidence for interactions between adenosine triphosphate and P-glycoprotein substrates

    DEFF Research Database (Denmark)

    Abraham, E H; Shrivastav, B; Salikhova, A Y;

    2001-01-01

    P-glycoprotein is involved with the removal of drugs, most of them cations, from the plasma membrane and cytoplasm. Pgp is also associated with movement of ATP, an anion, from the cytoplasm to the extracellular space. The central question of this study is whether drug and ATP transport associated...... with the expression of Pgp are in any way coupled. We have measured the stoichiometry of transport coupling between drug and ATP release. The drug and ATP transport that is inhibitable by the sulfonylurea compound, glyburide (P. E. Golstein, A. Boom, J. van Geffel, P. Jacobs, B. Masereel, and R....... Beauwens, Pfluger's Arch. 437, 652, 1999), permits determination of the transport coupling ratio, which is close to 1:1. In view of this result, we asked whether ATP interacts directly with Pgp substrates. We show by measuring the movement of Pgp substrates in electric fields that ATP and drug movement are...

  7. Suppression of cellular transformation by poly (A binding protein interacting protein 2 (Paip2.

    Directory of Open Access Journals (Sweden)

    Amy B Rosenfeld

    Full Text Available Controlling translation is crucial for the homeostasis of a cell. Its deregulation can facilitate the development and progression of many diseases including cancer. Poly (A binding protein interacting protein 2 (Paip2 inhibits efficient initiation of translation by impairing formation of the necessary closed loop of mRNA. The over production of Paip2 in the presence of a constitutively active form of hRas(V12 can reduce colony formation in a semi-solid matrix and focus formation on a cell monolayer. The ability of Paip2 to bind to Pabp is required to suppress the transformed phenotype mediated by hRas(V12. These observations indicate that Paip2 is able to function as a tumor suppressor.

  8. Mechanism of Laser/light beam interaction at cellular and tissue level and study of the influential factors for the application of low level laser therapy

    OpenAIRE

    Khalid, Muhammad Zeeshan

    2016-01-01

    After the discovery of laser therapy it was realized it has useful application of wound healing and reduce pain, but due to the poor understanding of the mechanism and dose response this technique remained to be controversial for therapeutic applications. In order to understand the working and effectiveness different experiments were performed to determine the laser beam effect at the cellular and tissue level. This article discusses the mechanism of beam interaction at tissues and cellular l...

  9. Interaction of the Papillomavirus E8∧E2C Protein with the Cellular CHD6 Protein Contributes to Transcriptional Repression▿ †

    OpenAIRE

    Fertey, Jasmin; Ammermann, Ingo; Winkler, Michael; Stöger, Reinhard; Iftner, Thomas; Stubenrauch, Frank

    2010-01-01

    Expression of the E6 and E7 oncogenes of high-risk human papillomaviruses (HPV) is controlled by cellular transcription factors and by viral E2 and E8∧E2C proteins, which are both derived from the HPV E2 gene. Both proteins bind to and repress the HPV E6/E7 promoter. Promoter inhibition has been suggested to be due to binding site competition with cellular transcription factors and to interactions of different cellular transcription modulators with the different amino termini of E2 and E8∧E2C...

  10. On the Photonic Cellular Interaction and the Electric Activity of Neurons in the Human Brain

    International Nuclear Information System (INIS)

    The subject of Ultraweak Photon Emission (UPE) by biological systems is very fascinating, and both evidence of its effects and applications are growing rapidly due to improvements in experimental techniques. Since the relevant equipment should be ultrasensitive with high quantum efficiencies and very low noise levels, the subject of UPE is still hotly debated and some of the interpretations need stronger empirical evidence to be accepted at face value. In this paper we first review different types of interactions between light and living systems based on recent publications. We then discuss the feasibility of UPE production in the human brain. The subject of UPE in the brain is still in early stages of development and needs more accurate experimental methods for proper analysis. In this work we also discuss a possible role of mitochondria in the production of UPE in the neurons of the brain and the plausibility of their effects on microtubules (MTs). MTs have been implicated as playing an important role in the signal and information processing taking place in the mammalian (especially human) brain. Finally, we provide a short discussion about the feasible effects of MTs on electric neural activity in the human brain.

  11. An inhibitory interaction between viral and cellular proteins underlies the resistance of tomato to nonadapted tobamoviruses.

    Science.gov (United States)

    Ishibashi, Kazuhiro; Naito, Satoshi; Meshi, Tetsuo; Ishikawa, Masayuki

    2009-05-26

    Any individual virus can infect only a limited range of hosts, and most plant species are "nonhosts" to a given virus; i.e., all members of the species are insusceptible to the virus. In nonhost plants, the factors that control virus resistance are not genetically tractable, and how the host range of a virus is determined remains poorly understood. Tomato (Solanum lycopersicum) is a nonhost species for Tobacco mild green mosaic virus (TMGMV) and Pepper mild mottle virus (PMMoV), members of the genus Tobamovirus. Previously, we identified Tm-1, a resistance gene of tomato to another tobamovirus, Tomato mosaic virus (ToMV), and found that Tm-1 binds to ToMV replication proteins to inhibit RNA replication. Tm-1 is derived from a wild tomato species, S. habrochaites, and ToMV-susceptible tomato cultivars have the allelic gene tm-1. The tm-1 protein can neither bind to ToMV replication proteins nor inhibit ToMV multiplication. Here, we show that transgenic tobacco plants expressing tm-1 exhibit resistance to TMGMV and PMMoV. The tm-1 protein bound to the replication proteins of TMGMV and PMMoV and inhibited their RNA replication in vitro. In one of the tm-1-expressing tobacco plants, a tm-1-insensitive TMGMV mutant emerged. In tomato protoplasts, this mutant TMGMV multiplied as efficiently as ToMV. However, in tomato plants, the mutant TMGMV multiplied with lower efficiency compared to ToMV and caused systemic necrosis. These results suggest that an inhibitory interaction between the replication proteins and tm-1 underlies a multilayered resistance mechanism to TMGMV in tomato. PMID:19423673

  12. Looking for a needle in a haystack: Cellular proteins that may interact with the tyrosine-based sorting signal of the TGEV S protein.

    Science.gov (United States)

    Trincone, Anna; Schwegmann-Weßels, Christel

    2015-04-16

    The spike protein S of transmissible gastroenteritis virus, an Alphacoronavirus, contains a tyrosine-based sorting signal that is responsible for ERGIC retention and may be important for a correct viral assembly process. To find out whether the S protein interacts with cellular proteins via this sorting signal, a pulldown assay with GST fusion proteins was performed. Filamin A has been identified as a putative interaction candidate. Immunofluorescence assays confirmed a co-localization between the TGEV S protein and filamin A. Further experiments have to be performed to prove a significant impact of filamin A on TGEV infection. Different approaches of several researchers for the identification of cellular interaction candidates relevant for coronavirus replication are summarized. These results may help in the future to identify the role of cellular proteins during coronavirus assembly at the ER-Golgi intermediate compartment. PMID:25481285

  13. Molecular chaperones: The modular evolution of cellular networks

    Indian Academy of Sciences (India)

    Tamás Korcsmáros; István A Kovács; Máté S Szalay; Péter Csermely

    2007-04-01

    Molecular chaperones play a prominent role in signaling and transcriptional regulatory networks of the cell. Recent advances uncovered that chaperones act as genetic buffers stabilizing the phenotype of various cells and organisms and may serve as potential regulators of evolvability. Chaperones have weak links, connect hubs, are in the overlaps of network modules and may uncouple these modules during stress, which gives an additional protection for the cell at the network-level. Moreover, after stress chaperones are essential to re-build inter-modular contacts by their low affinity sampling of the potential interaction partners in different modules. This opens the way to the chaperone-regulated modular evolution of cellular networks, and helps us to design novel therapeutic and anti-aging strategies.

  14. Micropatterned co-culture of hepatocyte spheroids layered on non-parenchymal cells to understand heterotypic cellular interactions

    International Nuclear Information System (INIS)

    Microfabrication and micropatterning techniques in tissue engineering offer great potential for creating and controlling cellular microenvironments including cell–matrix interactions, soluble stimuli and cell–cell interactions. Here, we present a novel approach to generate layered patterning of hepatocyte spheroids on micropatterned non-parenchymal feeder cells using microfabricated poly(ethylene glycol) (PEG) hydrogels. Micropatterned PEG-hydrogel-treated substrates with two-dimensional arrays of gelatin circular domains (ϕ = 100 μm) were prepared by photolithographic method. Only on the critical structure of PEG hydrogel with perfect protein rejection, hepatocytes were co-cultured with non-parenchymal cells to be led to enhanced hepatocyte functions. Then, we investigated the mechanism of the functional enhancement in co-culture with respect to the contributions of soluble factors and direct cell–cell interactions. In particular, to elucidate the influence of soluble factors on hepatocyte function, hepatocyte spheroids underlaid with fibroblasts (NIH/3T3 mouse fibroblasts) or endothelial cells (BAECs: bovine aortic endothelial cells) were compared with physically separated co-culture of hepatocyte monospheroids with NIH3T3 or BAEC using trans-well culture systems. Our results suggested that direct heterotypic cell-to-cell contact and soluble factors, both of these between hepatocytes and fibroblasts, significantly enhanced hepatocyte functions. In contrast, direct heterotypic cell-to-cell contact between hepatocytes and endothelial cells only contributed to enhance hepatocyte functions. This patterning technique can be a useful experimental tool for applications in basic science, drug screening and tissue engineering, as well as in the design of artificial liver devices. (paper)

  15. Graphene nanoplatelets spontaneously translocate into the cytosol and physically interact with cellular organelles in the fish cell line PLHC-1

    Energy Technology Data Exchange (ETDEWEB)

    Lammel, Tobias; Navas, José M., E-mail: jmnavas@inia.es

    2014-05-01

    Highlights: • We assessed the cytotoxicity and uptake of graphene nanomaterials in PLHC-1 cells. • GO and CXYG nanoplatelets caused physical injury of the plasma membrane. • GO and CXYG accumulated in the cytosol and interacted with cellular organelles. • PLHC-1 cells exposed to GO/CXYG demonstrated high ROS levels but low cytotoxicity. • ROS formation was related with GO/CXYG-induced structural damage of mitochondria. - Abstract: Graphene and graphene derivatives constitute a novel class of carbon-based nanomaterials being increasingly produced and used in technical and consumer applications. Release of graphene nanoplatelets during the life cycle of these applications may result in human and environmental exposure calling for assessment of their potential to cause harm to humans and wildlife. This study aimed to assess the toxicity of graphene oxide (GO) and carboxyl graphene (CXYG) nanoplatelets to non-mammalian species using the fish cell line PLHC-1 as in vitro model. The cytotoxicity of GO and CXYG was assessed using different assays measuring alterations in plasma membrane integrity, metabolic activity, and lysosomal and mitochondrial function. The induction of oxidative stress was assessed by measuring intracellular reactive oxygen species (ROS) levels. Interaction with the plasma membrane and internalization of nanoplatelets were investigated by electron microscopy. Graphene nanoplatelets spontaneously penetrated through the plasma membrane and accumulated in the cytosol, where they further interacted with mitochondrial and nuclear membranes. PLHC-1 cells demonstrated significantly reduced mitochondrial membrane potential (MMP) and increased ROS levels at 16 μg/ml GO and CXYG (72 h), but barely any decrease in cell viability. The observation of intracellular graphene accumulations not enclosed by membranes suggests that GO and CXYG internalization in fish hepatoma cells occurs through an endocytosis-independent mechanism.

  16. Calcitriol-copper interaction leads to non enzymatic, reactive oxygen species mediated DNA breakage and modulation of cellular redox scavengers in hepatocellular carcinoma.

    Science.gov (United States)

    Rizvi, Asim; Farhan, Mohd; Naseem, Imrana; Hadi, S M

    2016-09-01

    Calcitriol is the metabolically active form of Vitamin D and is known to kill cancer cells. Using the rat model of DEN induced hepatocellular carcinoma we show that there is a marked increase in cellular levels of copper in hepatocellular carcinoma and that calcitriol-copper interaction leads to reactive oxygen species mediated DNA breakage selectively in hepatocellular carcinoma cells. In vivo studies show that calcitriol selectively induces severe fluctuations in cellular enzymatic and non enzymatic scavengers of reactive oxygen species in the malignant tissue. Lipid peroxidation, a well established marker of oxidative stress, was found to increase, and substantial cellular DNA breakage was observed. We propose that calcitriol is a proxidant in the cellular milieu of hepatocellular carcinoma cells, and this copper mediated prooxidant action of calcitriol causes selective DNA breakage in malignant cells, while sparing normal (non malignant) cells. PMID:27343126

  17. Mitochondrial Hormesis in Pancreatic β Cells: Does Uncoupling Protein 2 Play a Role?

    Directory of Open Access Journals (Sweden)

    Ning Li

    2012-01-01

    Full Text Available In pancreatic β cells, mitochondrial metabolism translates glucose sensing into signals regulating insulin secretion. Chronic exposure of β cells to excessive nutrients, namely, glucolipotoxicity, impairs β-cell function. This is associated with elevated ROS production from overstimulated mitochondria. Mitochondria are not only the major source of cellular ROS, they are also the primary target of ROS attacks. The mitochondrial uncoupling protein UCP2, even though its uncoupling properties are debated, has been associated with protective functions against ROS toxicity. Hormesis, an adaptive response to cellular stresses, might contribute to the protection against β-cell death, possibly limiting the development of type 2 diabetes. Mitochondrial hormesis, or mitohormesis, is a defense mechanism observed in ROS-induced stress-responses by mitochondria. In β cells, mitochondrial damages induced by sublethal exogenous H2O2 can induce secondary repair and defense mechanisms. In this context, UCP2 is a marker of mitohormesis, being upregulated following stress conditions. When overexpressed in nonstressed naïve cells, UCP2 confers resistance to oxidative stress. Whether treatment with mitohormetic inducers is sufficient to restore or ameliorate secretory function of β cells remains to be determined.

  18. Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification

    Science.gov (United States)

    Dejonghe, Wim; Kuenen, Sabine; Mylle, Evelien; Vasileva, Mina; Keech, Olivier; Viotti, Corrado; Swerts, Jef; Fendrych, Matyáš; Ortiz-Morea, Fausto Andres; Mishev, Kiril; Delang, Simon; Scholl, Stefan; Zarza, Xavier; Heilmann, Mareike; Kourelis, Jiorgos; Kasprowicz, Jaroslaw; Nguyen, Le Son Long; Drozdzecki, Andrzej; Van Houtte, Isabelle; Szatmári, Anna-Mária; Majda, Mateusz; Baisa, Gary; Bednarek, Sebastian York; Robert, Stéphanie; Audenaert, Dominique; Testerink, Christa; Munnik, Teun; Van Damme, Daniël; Heilmann, Ingo; Schumacher, Karin; Winne, Johan; Friml, Jiří; Verstreken, Patrik; Russinova, Eugenia

    2016-01-01

    ATP production requires the establishment of an electrochemical proton gradient across the inner mitochondrial membrane. Mitochondrial uncouplers dissipate this proton gradient and disrupt numerous cellular processes, including vesicular trafficking, mainly through energy depletion. Here we show that Endosidin9 (ES9), a novel mitochondrial uncoupler, is a potent inhibitor of clathrin-mediated endocytosis (CME) in different systems and that ES9 induces inhibition of CME not because of its effect on cellular ATP, but rather due to its protonophore activity that leads to cytoplasm acidification. We show that the known tyrosine kinase inhibitor tyrphostinA23, which is routinely used to block CME, displays similar properties, thus questioning its use as a specific inhibitor of cargo recognition by the AP-2 adaptor complex via tyrosine motif-based endocytosis signals. Furthermore, we show that cytoplasm acidification dramatically affects the dynamics and recruitment of clathrin and associated adaptors, and leads to reduction of phosphatidylinositol 4,5-biphosphate from the plasma membrane. PMID:27271794

  19. From molecular interaction to acute promyelocytic leukemia: Calculating leukemogenesis and remission from endogenous molecular-cellular network.

    Science.gov (United States)

    Yuan, Ruoshi; Zhu, Xiaomei; Radich, Jerald P; Ao, Ping

    2016-01-01

    Acute promyelocytic leukemia (APL) remains the best example of a malignancy that can be cured clinically by differentiation therapy. We demonstrate that APL may emerge from a dynamical endogenous molecular-cellular network obtained from normal, non-cancerous molecular interactions such as signal transduction and translational regulation under physiological conditions. This unifying framework, which reproduces APL, normal progenitor, and differentiated granulocytic phenotypes as different robust states from the network dynamics, has the advantage to study transition between these states, i.e. critical drivers for leukemogenesis and targets for differentiation. The simulation results quantitatively reproduce microarray profiles of NB4 and HL60 cell lines in response to treatment and normal neutrophil differentiation, and lead to new findings such as biomarkers for APL and additional molecular targets for arsenic trioxide therapy. The modeling shows APL and normal states mutually suppress each other, both in "wiring" and in dynamical cooperation. Leukemogenesis and recovery under treatment may be a consequence of spontaneous or induced transitions between robust states, through "passes" or "dragging" by drug effects. Our approach rationalizes leukemic complexity and constructs a platform towards extending differentiation therapy by performing "dry" molecular biology experiments. PMID:27098097

  20. Interaction of cadmium and zinc on accumulation and sub-cellular distribution in leaves of hyperaccumulator Potentilla griffithii

    Energy Technology Data Exchange (ETDEWEB)

    Qiu Rongliang, E-mail: eesqrl@mail.sysu.edu.cn [School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275 (China); Guangdong Provincial Key Lab of Environmental Pollution Control and Remediation Technology, Guangzhou 510275 (China); Thangavel, Palaniswamy; Hu Pengjie; Senthilkumar, Palaninaicker; Ying Rongrong [School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275 (China); Tang Yetao [School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275 (China); Guangdong Provincial Key Lab of Environmental Pollution Control and Remediation Technology, Guangzhou 510275 (China)

    2011-02-28

    Potentilla griffithii Hook is a newly found hyperaccumulator plant capable of high tolerance and accumulation of Zn and Cd. We investigated the interactive effects between Cd and Zn on accumulation and vacuolar sequestration in P. griffithii. Stimulatory effect of growth was noted at 0.2 mM Cd and 1.25 and 2.5 mM Zn tested. Accumulation of Zn and Cd in roots, petioles and leaves were increased significantly with addition of these metals individually. However, the Zn supplement decreased root Cd accumulation but increased the concentration of Cd in petioles and leaves. The results from sub-cellular distribution showed that up to 94% and 70% of the total Zn and Cd in the leaves were present in the protoplasts, and more than 90% Cd and Zn in the protoplasts were localized in the vacuoles. Nearly, 88% and 85% of total Cd and Zn were extracted in the cell sap of the leaves suggesting that most of the Cd and Zn in the leaves were available in soluble form. The present results indicate that Zn supplement significantly enhanced the petiole accumulation of Cd and further vacuolar sequestration plays an important role in tolerance, detoxification and hyperaccumulation of these metals in P. griffithii.

  1. Interaction of cadmium and zinc on accumulation and sub-cellular distribution in leaves of hyperaccumulator Potentilla griffithii.

    Science.gov (United States)

    Qiu, Rong-Liang; Thangavel, Palaniswamy; Hu, Peng-Jie; Senthilkumar, Palaninaicker; Ying, Rong-Rong; Tang, Ye-Tao

    2011-02-28

    Potentilla griffithii Hook is a newly found hyperaccumulator plant capable of high tolerance and accumulation of Zn and Cd. We investigated the interactive effects between Cd and Zn on accumulation and vacuolar sequestration in P. griffithii. Stimulatory effect of growth was noted at 0.2 mM Cd and 1.25 and 2.5 mM Zn tested. Accumulation of Zn and Cd in roots, petioles and leaves were increased significantly with addition of these metals individually. However, the Zn supplement decreased root Cd accumulation but increased the concentration of Cd in petioles and leaves. The results from sub-cellular distribution showed that up to 94% and 70% of the total Zn and Cd in the leaves were present in the protoplasts, and more than 90% Cd and Zn in the protoplasts were localized in the vacuoles. Nearly, 88% and 85% of total Cd and Zn were extracted in the cell sap of the leaves suggesting that most of the Cd and Zn in the leaves were available in soluble form. The present results indicate that Zn supplement significantly enhanced the petiole accumulation of Cd and further vacuolar sequestration plays an important role in tolerance, detoxification and hyperaccumulation of these metals in P. griffithii. PMID:21211902

  2. A Hsp40 chaperone protein interacts with and modulates the cellular distribution of the primase protein of human cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Yonggang Pei

    Full Text Available Genomic DNA replication is a universal and essential process for all herpesvirus including human cytomegalovirus (HCMV. HCMV UL70 protein, which is believed to encode the primase activity of the viral DNA replication machinery and is highly conserved among herpesviruses, needs to be localized in the nucleus, the site of viral DNA synthesis. No host factors that facilitate the nuclear import of UL70 have been reported. In this study, we provided the first direct evidence that UL70 specifically interacts with a highly conserved and ubiquitously expressed member of the heat shock protein Hsp40/DNAJ family, DNAJB6, which is expressed as two isoforms, a and b, as a result of alternative splicing. The interaction of UL70 with a common region of DNAJB6a and b was identified by both a two hybrid screen in yeast and coimmunoprecipitation in human cells. In transfected cells, UL70 was primarily co-localized with DNAJB6a in the nuclei and with DNAJB6b in the cytoplasm, respectively. The nuclear import of UL70 was increased in cells in which DNAJB6a was up-regulated or DNAJB6b was down-regulated, and was reduced in cells in which DNAJB6a was down-regulated or DNAJB6b was up-regulated. Furthermore, the level of viral DNA synthesis and progeny production was increased in cells in which DNAJB6a was up-regulated or DNAJB6b was down-regulated, and was reduced in cells in which DNAJB6a was down-regulated or DNAJB6b was up-regulated. Thus, DNAJB6a and b appear to enhance the nuclear import and cytoplasmic accumulation of UL70, respectively. Our results also suggest that the relative expression levels of DNAJB6 isoforms may play a key role in regulating the cellular localization of UL70, leading to modulation of HCMV DNA synthesis and lytic infection.

  3. Cellular Interactions and Biological Responses to Titanium Dioxide Nanoparticles in HepG2 and BEAS-2B Cells: Role of Cell Culture Media

    Science.gov (United States)

    ABSTRACT We have shown previously that the composition of the biological medium used in vitro can affect the cellular interaction and biological response of titanium dioxide nanoparticles (nano-TiO2) in human lung epithelial cells. However, it is unclear if these effects are co...

  4. Human papillomavirus 16E6 and NFX1-123 potentiate notch signaling and differentiation without activating cellular arrest

    International Nuclear Information System (INIS)

    High-risk human papillomavirus (HR HPV) oncoproteins bind host cell proteins to dysregulate and uncouple apoptosis, senescence, differentiation, and growth. These pathways are important for both the viral life cycle and cancer development. HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and they collaboratively increase the growth and differentiation master regulator, Notch1. In 16E6 expressing keratinocytes (16E6 HFKs), the Notch canonical pathway genes Hes1 and Hes5 were increased with overexpression of NFX1-123, and their expression was directly linked to the activation or blockade of the Notch1 receptor. Keratinocyte differentiation genes Keratin 1 and Keratin 10 were also increased, but in contrast their upregulation was only indirectly associated with Notch1 receptor stimulation and was fully unlinked to growth arrest, increased p21Waf1/CIP1, or decreased proliferative factor Ki67. This leads to a model of 16E6, NFX1-123, and Notch1 differently regulating canonical and differentiation pathways and entirely uncoupling cellular arrest from increased differentiation. - Highlights: • 16E6 and NFX1-123 increased the Notch canonical pathway through Notch1. • 16E6 and NFX1-123 increased the differentiation pathway indirectly through Notch1. • 16E6 and NFX1-123 increased differentiation gene expression without growth arrest. • Increased NFX1-123 with 16E6 may create an ideal cellular phenotype for HPV

  5. Human papillomavirus 16E6 and NFX1-123 potentiate notch signaling and differentiation without activating cellular arrest

    Energy Technology Data Exchange (ETDEWEB)

    Vliet-Gregg, Portia A.; Hamilton, Jennifer R. [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Katzenellenbogen, Rachel A., E-mail: rkatzen@uw.edu [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Department of Pediatrics, Division of Adolescent Medicine, University of Washington, Seattle WA (United States)

    2015-04-15

    High-risk human papillomavirus (HR HPV) oncoproteins bind host cell proteins to dysregulate and uncouple apoptosis, senescence, differentiation, and growth. These pathways are important for both the viral life cycle and cancer development. HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and they collaboratively increase the growth and differentiation master regulator, Notch1. In 16E6 expressing keratinocytes (16E6 HFKs), the Notch canonical pathway genes Hes1 and Hes5 were increased with overexpression of NFX1-123, and their expression was directly linked to the activation or blockade of the Notch1 receptor. Keratinocyte differentiation genes Keratin 1 and Keratin 10 were also increased, but in contrast their upregulation was only indirectly associated with Notch1 receptor stimulation and was fully unlinked to growth arrest, increased p21{sup Waf1/CIP1}, or decreased proliferative factor Ki67. This leads to a model of 16E6, NFX1-123, and Notch1 differently regulating canonical and differentiation pathways and entirely uncoupling cellular arrest from increased differentiation. - Highlights: • 16E6 and NFX1-123 increased the Notch canonical pathway through Notch1. • 16E6 and NFX1-123 increased the differentiation pathway indirectly through Notch1. • 16E6 and NFX1-123 increased differentiation gene expression without growth arrest. • Increased NFX1-123 with 16E6 may create an ideal cellular phenotype for HPV.

  6. Uncoupled thermoelasticity solutions applied on beam dumps

    Science.gov (United States)

    Ouzia, A.; Antonakakis, T.

    2016-06-01

    In particle accelerators the process of beam absorption is vital. At CERN particle beams are accelerated at energies of the order of TeV. In the event of a system failure or following collisions, the beam needs to be safely absorbed by dedicated protecting blocks. The thermal shock caused by the rapid energy deposition within the absorbing block causes thermal stresses that may rise above critical levels. The present paper provides a convenient expression of such stresses under hypotheses described hereafter. The temperature field caused by the beam energy deposition is assumed to be Gaussian. Such a field models a non-diffusive heat deposition. These effects are described as thermoelastic as long as the stresses remain below the proportional limit and can be analytically modeled by the coupled equations of thermoelasticity. The analytical solution to the uncoupled thermoelastic problem in an infinite domain is presented herein and matched with a finite unit radius sphere. The assumption of zero diffusion as well as the validity of the match with a finite geometry is quantified such that the obtained solutions can be rigorously applied to real problems. Furthermore, truncated series solutions, which are not novel, are used for comparison purposes. All quantities are nondimensional and the problem reduces to a dependence of five dimensionless parameters. The equations of elasticity are presented in the potential formulation where the shear potential is assumed to be nil due to the source being a gradient and the absence of boundaries. Nevertheless equivalent three-dimensional stresses are computed using the compressive potential and optimized using standard analytical optimization methods. An alternative algorithm for finding the critical points of the three-dimensional stress function is presented. Finally, a case study concerning the proton synchrotron booster dump is presented where the aforementioned analytical solutions are used and the preceding assumptions

  7. Mechanism of Laser/light beam interaction at cellular and tissue level and study of the influential factors for the application of low level laser therapy

    CERN Document Server

    Khalid, Muhammad Zeeshan

    2016-01-01

    After the discovery of laser therapy it was realized it has useful application of wound healing and reduce pain, but due to the poor understanding of the mechanism and dose response this technique remained to be controversial for therapeutic applications. In order to understand the working and effectiveness different experiments were performed to determine the laser beam effect at the cellular and tissue level. This article discusses the mechanism of beam interaction at tissues and cellular level with different light sources and dosimetry principles for clinical application of low level laser therapy. Different application techniques and methods currently in use for clinical treatment has also been reviewed.

  8. Direct interaction of cellular hnRNP-F and NS1 of influenza A virus accelerates viral replication by modulation of viral transcriptional activity and host gene expression

    International Nuclear Information System (INIS)

    To investigate novel NS1-interacting proteins, we conducted a yeast two-hybrid analysis, followed by co-immunoprecipitation assays. We identified heterogeneous nuclear ribonucleoprotein F (hnRNP-F) as a cellular protein interacting with NS1 during influenza A virus infection. Co-precipitation assays suggest that interaction between hnRNP-F and NS1 is a common and direct event among human or avian influenza viruses. NS1 and hnRNP-F co-localize in the nucleus of host cells, and the RNA-binding domain of NS1 directly interacts with the GY-rich region of hnRNP-F determined by GST pull-down assays with truncated proteins. Importantly, hnRNP-F expression levels in host cells indicate regulatory role on virus replication. hnRNP-F depletion by small interfering RNA (siRNA) shows 10- to 100-fold increases in virus titers corresponding to enhanced viral RNA polymerase activity. Our results delineate novel mechanism of action by which NS1 accelerates influenza virus replication by modulating normal cellular mRNA processes through direct interaction with cellular hnRNP-F protein.

  9. Image processing with a cellular nonlinear network

    International Nuclear Information System (INIS)

    A cellular nonlinear network (CNN) based on uncoupled nonlinear oscillators is proposed for image processing purposes. It is shown theoretically and numerically that the contrast of an image loaded at the nodes of the CNN is strongly enhanced, even if this one is initially weak. An image inversion can be also obtained without reconfiguration of the network whereas a gray levels extraction can be performed with an additional threshold filtering. Lastly, an electronic implementation of this CNN is presented

  10. Molecular cloning of amphioxus uncoupling protein and assessment of its uncoupling activity using a yeast heterologous expression system

    International Nuclear Information System (INIS)

    Research highlights: → Invertebrates, for example amphioxus, do express uncoupling proteins. → Both the sequence and the uncoupling activity of amphioxus UCP resemble UCP2. → UCP1 is the only UCP that can form dimer on yeast mitochondria. -- Abstract: The present study describes the molecular cloning of a novel cDNA fragment from amphioxus (Branchiostoma belcheri) encoding a 343-amino acid protein that is highly homologous to human uncoupling proteins (UCP), this protein is therefore named amphioxus UCP. This amphioxus UCP shares more homology with and is phylogenetically more related to mammalian UCP2 as compared with UCP1. To further assess the functional similarity of amphioxus UCP to mammalian UCP1 and -2, the amphioxus UCP, rat UCP1, and human UCP2 were separately expressed in Saccharomyces cerevisiae, and the recombinant yeast mitochondria were isolated and assayed for the state 4 respiration rate and proton leak, using pYES2 empty vector as the control. UCP1 increased the state 4 respiration rate by 2.8-fold, and the uncoupling activity was strongly inhibited by GDP, while UCP2 and amphioxus UCP only increased the state 4 respiration rate by 1.5-fold and 1.7-fold in a GDP-insensitive manner, moreover, the proton leak kinetics of amphioxus UCP was very similar to UCP2, but much different from UCP1. In conclusion, the amphioxus UCP has a mild, unregulated uncoupling activity in the yeast system, which resembles mammalian UCP2, but not UCP1.

  11. Molecular cloning of amphioxus uncoupling protein and assessment of its uncoupling activity using a yeast heterologous expression system

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Kun [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Sun, Guoxun [Department of Hematology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001 (China); Lv, Zhiyuan; Wang, Chen [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Jiang, Xueyuan, E-mail: xueyuanjiang@yahoo.com.cn [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Li, Donghai, E-mail: lidonghai@gmail.com [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Zhang, Chenyu, E-mail: cyzhang@nju.edu.cn [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China)

    2010-10-01

    Research highlights: {yields} Invertebrates, for example amphioxus, do express uncoupling proteins. {yields} Both the sequence and the uncoupling activity of amphioxus UCP resemble UCP2. {yields} UCP1 is the only UCP that can form dimer on yeast mitochondria. -- Abstract: The present study describes the molecular cloning of a novel cDNA fragment from amphioxus (Branchiostoma belcheri) encoding a 343-amino acid protein that is highly homologous to human uncoupling proteins (UCP), this protein is therefore named amphioxus UCP. This amphioxus UCP shares more homology with and is phylogenetically more related to mammalian UCP2 as compared with UCP1. To further assess the functional similarity of amphioxus UCP to mammalian UCP1 and -2, the amphioxus UCP, rat UCP1, and human UCP2 were separately expressed in Saccharomyces cerevisiae, and the recombinant yeast mitochondria were isolated and assayed for the state 4 respiration rate and proton leak, using pYES2 empty vector as the control. UCP1 increased the state 4 respiration rate by 2.8-fold, and the uncoupling activity was strongly inhibited by GDP, while UCP2 and amphioxus UCP only increased the state 4 respiration rate by 1.5-fold and 1.7-fold in a GDP-insensitive manner, moreover, the proton leak kinetics of amphioxus UCP was very similar to UCP2, but much different from UCP1. In conclusion, the amphioxus UCP has a mild, unregulated uncoupling activity in the yeast system, which resembles mammalian UCP2, but not UCP1.

  12. Imaging the Breakdown of Molecular Frame Dynamics through Rotational Uncoupling

    CERN Document Server

    Zipp, Lucas J; Bucksbaum, Philip H

    2016-01-01

    We have observed directly in the time domain the uncoupling of electron motion from the molecular frame due to rotational-electronic coupling in a molecular Rydberg system. In contrast to Born- Oppenheimer dynamics, in which the electron is firmly fixed to the molecular frame, there exists a regime of molecular dynamics known as $l$-uncoupling where the motion of a non-penetrating Rydberg electron decouples from the instantaneous alignment of the molecular frame. We have imaged this unusual regime in time-dependent photoelectron angular distributions of a coherently prepared electron wave packet in the 4$f$ manifold of $N_2$.

  13. A cellular stress response (CSR) that interacts with NADPH-P450 reductase (NPR) is a new regulator of hypoxic response.

    Science.gov (United States)

    Oguro, Ami; Koyama, Chika; Xu, Jing; Imaoka, Susumu

    2014-02-28

    NADPH-P450 reductase (NPR) was previously found to contribute to the hypoxic response of cells, but the mechanism was not clarified. In this study, we identified a cellular stress response (CSR) as a new factor interacting with NPR by a yeast two-hybrid system. Overexpression of CSR enhanced the induction of erythropoietin and hypoxia response element (HRE) activity under hypoxia in human hepatocarcinoma cell lines (Hep3B), while knockdown of CSR suppressed them. This new finding regarding the interaction of NPR with CSR provides insight into the function of NPR in hypoxic response. PMID:24491563

  14. N-Terminally Glutamate-Substituted Analogue of Gramicidin A as Protonophore and Selective Mitochondrial Uncoupler

    OpenAIRE

    Alexandra I Sorochkina; Egor Y Plotnikov; Rokitskaya, Tatyana I.; Kovalchuk, Sergei I.; Elena A Kotova; Sergei V Sychev; Zorov, Dmitry B.; Antonenko, Yuri N.

    2012-01-01

    Limited uncoupling of oxidative phosphorylation could be beneficial for cells by preventing excessive generation of reactive oxygen species. Typical uncouplers are weak organic acids capable of permeating across membranes with a narrow gap between efficacy and toxicity. Aimed at designing a nontoxic uncoupler, the protonatable amino acid residue Glu was substituted for Val at the N-terminus of the pentadecapeptide gramicidin A (gA). The modified peptide [Glu1]gA exhibited high uncoupling acti...

  15. Potent non-protonophore uncouplers acting on natural and artificial membranes

    OpenAIRE

    Routaboul, Jean-Marc; Taillandier, Georges; Tissut, Michel

    1994-01-01

    The uncoupling properties of 10 new symmetrical phenylureas, including N,N′-bis-(4-trifluoromethylphenyl)-urea, were investigated. Four compounds were shown to be powerful uncouplers. The result is a proton transfer across the organelle's membrane. These symmetrical phenylureas cannot be classified among the main class of uncouplers (acting through a protonophoric mechanism), due to their inability to exchange protons in a range of pHs between 2 and 9. The most potent uncouplers of the ...

  16. Oxidative stress, thermogenesis and evolution of uncoupling proteins

    OpenAIRE

    Rial, Eduardo; Zardoya, Rafael

    2009-01-01

    The uncoupling protein UCP1 provides eutherian mammals with an efficient thermogenic mechanism. Recent work published in BMC Evolutionary Biology, following the identification of UCP1 orthologs in non-eutherians, concludes that this unique function appeared after sequence divergence and purifying selection that allowed functional co-option.

  17. Uncoupler resistance in E. coli Tuv and Cuv is due to the exclusion of uncoupler by the outer membrane

    DEFF Research Database (Denmark)

    Haworth, Robert S.; Jensen, Peter Ruhdal; Michelsen, Ole;

    1990-01-01

    freely permeable to both TPP+ and hydroxymethylinulin. Tuv and Cuv are able to exclude these compounds. EDTA treatment was necessary prior to measuring membrane potentials in Tuv and Cuv. Under conditions where Δψ could be measured, uncouplers acted to dissipate Δψ with equal potency in all strains...

  18. Failure to interact with Brd4 alters the ability of HPV16 E2 to regulate host genome expression and cellular movement.

    Science.gov (United States)

    Gauson, Elaine J; Wang, Xu; Dornan, Edward S; Herzyk, Pawel; Bristol, Molly; Morgan, Iain M

    2016-01-01

    The E2 protein of the carcinogen human papillomavirus 16 (HPV16) regulates replication and transcription of the viral genome in association with viral and cellular proteins. Our previous work demonstrated that E2 can regulate transcription from the host genome. E2 can activate transcription from adjacent promoters when located upstream using E2 DNA binding sequences and this activation is dependent upon the cellular protein Brd4; this report demonstrates that a Brd4 binding E2 mutant alters host genome expression differently from wild type E2. Of particular note is that highly down regulated genes are mostly not affected by failure to interact with Brd4 suggesting that the E2-Brd4 interaction is more responsible for the transcriptional activation of host genes rather than repression. Therefore failure to interact efficiently with Brd4, or altered levels of Brd4, would alter the ability of E2 to regulate the host genome and could contribute to determining the outcome of infection. PMID:26365679

  19. Accumulated SET protein up-regulates and interacts with hnRNPK, increasing its binding to nucleic acids, the Bcl-xS repression, and cellular proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Luciana O.; Garcia, Cristiana B.; Matos-Silva, Flavia A. [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Curti, Carlos [Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Leopoldino, Andréia M., E-mail: andreiaml@usp.br [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil)

    2014-02-28

    Highlights: • hnRNPK is a new target of SET. • SET regulates hnRNPK. • SET and hnRNPK accumulation promotes tumorigenesis. • SET accumulation is a potential model to study genes regulated by SET-hnRNPK. - Abstract: SET and hnRNPK are proteins involved in gene expression and regulation of cellular signaling. We previously demonstrated that SET accumulates in head and neck squamous cell carcinoma (HNSCC); hnRNPK is a prognostic marker in cancer. Here, we postulate that SET and hnRNPK proteins interact to promote tumorigenesis. We performed studies in HEK293 and HNSCC (HN6, HN12, and HN13) cell lines with SET/hnRNPK overexpression and knockdown, respectively. We found that SET and/or hnRNPK protein accumulation increased cellular proliferation. SET accumulation up-regulated hnRNPK mRNA and total/phosphorylated protein, promoted hnRNPK nuclear location, and reduced Bcl-x mRNA levels. SET protein directly interacted with hnRNPK, increasing both its binding to nucleic acids and Bcl-xS repression. We propose that hnRNPK should be a new target of SET and that SET–hnRNPK interaction, in turn, has potential implications in cell survival and malignant transformation.

  20. Uncoupled dark states can inherit polaritonic properties

    OpenAIRE

    Gonzalez-Ballestero, C.; Feist, J.; Gonzalo-Badia, E.; Moreno, Esteban; Garcia-Vidal, F. J.

    2016-01-01

    When a collection of quantum emitters interacts with an electromagnetic field, the whole system can enter into the collective strong coupling regime in which hybrid light-matter states, i.e., polaritons can be created. Only a small portion of excitations in the emitters are coupled to the light field, and there are many dark states that, in principle, retain their pure excitonic nature. Here we theoretically demonstrate that these dark states can have a delocalized character, which is inheren...

  1. The 3′ Untranslated Region of the Rabies Virus Glycoprotein mRNA Specifically Interacts with Cellular PCBP2 Protein and Promotes Transcript Stability

    OpenAIRE

    Palusa, Saiprasad; Ndaluka, Christina; Bowen, Richard A.; Wilusz, Carol J.; Wilusz, Jeffrey

    2012-01-01

    Viral polymerase entry and pausing at intergenic junctions is predicted to lead to a defined polarity in the levels of rhabdovirus gene expression. Interestingly, we observed that the rabies virus glycoprotein mRNA is differentially over-expressed based on this model relative to other transcripts during infection of 293T cells. During infection, the rabies virus glycoprotein mRNA also selectively interacts with the cellular poly(rC)-binding protein 2 (PCBP2), a factor known to influence mRNA ...

  2. Hydrodynamical simulations of coupled and uncoupled quintessence models II: Galaxy clusters

    CERN Document Server

    Carlesi, Edoardo; Lewis, Geraint F; Yepes, Gustavo

    2014-01-01

    We study the $z=0$ properties of clusters (and large groups) of galaxies within the context of interacting and non-interacting quintessence cosmological models, using a series of adiabatic SPH simulations. Initially, we examine the average properties of groups and clusters, quantifying their differences in LCDM, uncoupled Dark Energy (\\ude) and coupled Dark Energy (\\cde) cosmologies. In particular, we focus upon radial profiles of the gas density, temperature and pressure, and we also investigate how the standard hydrodynamic equilibrium hypothesis holds in quintessence cosmologies. While we are able to confirm previous results about the distribution of baryons, we also find that the main discrepancy (with differences up to $20\\%$) can be seen in cluster pressure profiles. We then switch attention to individual structures, mapping each halo in quintessence cosmology to its \\LCDM\\ counterpart. We are able to identify a series of small correlations between the coupling in the dark sector and halo spin, triaxial...

  3. Arsenate uncoupling of oxidative phosphorylation in isolated plant mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Wickes, W.A.; Wiskich, J.T.

    1976-01-01

    The uncoupling by arsenate of beetroot and cauliflower bud mitochondria showed the following characteristics: arsenate stimulation of respiration above the rate found with phosphate; inhibition of arsenate-stimulated respiration by phosphate; enhancement of arsenate-stimulated respiration by ADP; only partial prevention of this ADP-enhanced respiration by atractyloside; inhibition by oligomycin of the arsenate-stimulated respiration back to the phosphate rate; and the absence of any stimulatory effect of ADP in the presence of oligomycin. These results are qualitatively analogous to those reported for arsenate uncoupling in rat liver mitochondria. Arsenate stimulated malate oxidation, presumably by stimulating malate entry, in both beetroot and cauliflower bud mitochondria; however, high rates of oxidation, and presumably entry, were only sustained with arsenate in beetroot mitochondria. NADH was oxidized rapidly in cauliflower bud mitochondria in the presence of arsenate, showing that arsenate did not inhibit electron transfer processes.

  4. Possible physiological roles of mitochondrial uncoupling proteins-UCPn

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr

    2002-01-01

    Roč. 34, č. 10 (2002), s. 1190-1206. ISSN 1357-2725 R&D Projects: GA AV ČR IAA5011106; GA ČR GA301/02/1215; GA MŠk ME 389 Institutional research plan: CEZ:AV0Z5011922 Keywords : uncoupling proteins * diabetes * obesity Subject RIV: ED - Physiology Impact factor: 3.044, year: 2002

  5. Mitochondrial uncoupling protein is required for efficient photosynthesis

    OpenAIRE

    Sweetlove, Lee J.; Lytovchenko, Anna; Morgan, Megan; Nunes-Nesi, Adriano; Taylor, Nicolas L.; Baxter, Charles J.; Eickmeier, Ira; Fernie, Alisdair R.

    2006-01-01

    Uncoupling proteins (UCPs) occur in the inner mitochondrial membrane and dissipate the proton gradient across this membrane that is normally used for ATP synthesis. Although the catalytic function and regulation of plant UCPs have been described, the physiological purpose of UCP in plants has not been established. Here, biochemical and physiological analyses of an insertional knockout of one of the Arabidopsis UCP genes (AtUCP1) are presented that resolve this issue. Absence of UCP1 results i...

  6. Materials for Chemical-Looping with Oxygen Uncoupling

    OpenAIRE

    Tobias Mattisson

    2013-01-01

    Chemical-looping with oxygen uncoupling (CLOU) is a novel combustion technology with inherent separation of carbon dioxide. The process is a three-step process which utilizes a circulating oxygen carrier to transfer oxygen from the combustion air to the fuel. The process utilizes two interconnected fluidized bed reactors, an air reactor and a fuel reactor. In the fuel reactor, the metal oxide decomposes with the release of gas phase oxygen (step 1), which reacts directly with the fuel through...

  7. Marked over expression of uncoupling protein-2 in beta cells exerts minor effects on mitochondrial metabolism

    International Nuclear Information System (INIS)

    Highlights: ► The impact of UCP-2 over expression on mitochondrial function is controversial. ► We tested mitochondrial functions at defined levels of overexpression. ► We find minor increases of fatty acid oxidation and uncoupling. ► Effects were seen only at high level (fourfold) of over expression. ► Hence it is doubtful whether these effects are of importance in diabetes. -- Abstract: Evidence is conflicting as to the impact of elevated levels of uncoupling protein-2 (UCP-2) on insulin-producing beta cells. Here we investigated effects of a fourfold induction of UCP-2 protein primarily on mitochondrial parameters and tested for replication of positive findings at a lower level of induction. We transfected INS-1 cells to obtain a tet-on inducible cell line. A 48 h exposure to 1 μg/ml of doxycycline (dox) induced UCP-2 fourfold (424 ± 113%, mean ± SEM) and 0.1 μg/ml twofold (178 ± 29%, n = 3). Fourfold induced cells displayed normal viability (MTT, apoptosis), normal cellular insulin contents and, glucose-induced insulin secretion (+27 ± 11%) as well as D-[U-14C]-glucose oxidation (+5 ± 9% at 11 mM glucose). Oxidation of [1-14C]-oleate was increased from 4088 to 5797 fmol/μg prot/2 h at 3.3 mM glucose, p 14C(U)]-glutamine was unaffected. Induction of UCP-2 did not significantly affect measures of mitochondrial membrane potential (Rhodamine 123) or mitochondrial mass (Mitotracker Green) and did not affect ATP levels. Oligomycin-inhibited oxygen consumption (a measure of mitochondrial uncoupling) was marginally increased, the effect being significant in comparison with dox-only treated cells, p < 0.05. Oxygen radicals, assessed by dichlorofluorescin diacetate, were decreased by 30%, p < 0.025. Testing for the lower level of UCP-2 induction did not reproduce any of the positive findings. A fourfold induction of UCP-2 was required to exert minor metabolic effects. These findings question an impact of moderately elevated UCP-2 levels in beta cells as

  8. Marked over expression of uncoupling protein-2 in beta cells exerts minor effects on mitochondrial metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Hals, Ingrid K., E-mail: ingrid.hals@ntnu.no [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Ogata, Hirotaka; Pettersen, Elin [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Ma, Zuheng; Bjoerklund, Anneli [Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm (Sweden); Skorpen, Frank [Department of Laboratory Medicine, NTNU, Trondheim (Norway); Egeberg, Kjartan Wollo [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Grill, Valdemar [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm (Sweden)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer The impact of UCP-2 over expression on mitochondrial function is controversial. Black-Right-Pointing-Pointer We tested mitochondrial functions at defined levels of overexpression. Black-Right-Pointing-Pointer We find minor increases of fatty acid oxidation and uncoupling. Black-Right-Pointing-Pointer Effects were seen only at high level (fourfold) of over expression. Black-Right-Pointing-Pointer Hence it is doubtful whether these effects are of importance in diabetes. -- Abstract: Evidence is conflicting as to the impact of elevated levels of uncoupling protein-2 (UCP-2) on insulin-producing beta cells. Here we investigated effects of a fourfold induction of UCP-2 protein primarily on mitochondrial parameters and tested for replication of positive findings at a lower level of induction. We transfected INS-1 cells to obtain a tet-on inducible cell line. A 48 h exposure to 1 {mu}g/ml of doxycycline (dox) induced UCP-2 fourfold (424 {+-} 113%, mean {+-} SEM) and 0.1 {mu}g/ml twofold (178 {+-} 29%, n = 3). Fourfold induced cells displayed normal viability (MTT, apoptosis), normal cellular insulin contents and, glucose-induced insulin secretion (+27 {+-} 11%) as well as D-[U-{sup 14}C]-glucose oxidation (+5 {+-} 9% at 11 mM glucose). Oxidation of [1-{sup 14}C]-oleate was increased from 4088 to 5797 fmol/{mu}g prot/2 h at 3.3 mM glucose, p < 0.03. Oxidation of L-[{sup 14}C(U)]-glutamine was unaffected. Induction of UCP-2 did not significantly affect measures of mitochondrial membrane potential (Rhodamine 123) or mitochondrial mass (Mitotracker Green) and did not affect ATP levels. Oligomycin-inhibited oxygen consumption (a measure of mitochondrial uncoupling) was marginally increased, the effect being significant in comparison with dox-only treated cells, p < 0.05. Oxygen radicals, assessed by dichlorofluorescin diacetate, were decreased by 30%, p < 0.025. Testing for the lower level of UCP-2 induction did not reproduce any of the

  9. Biomechanics and Thermodynamics of Nanoparticle Interactions with Plasma and Endosomal Membrane Lipids in Cellular Uptake and Endosomal Escape

    OpenAIRE

    Peetla, Chiranjeevi; Jin, Shihua; Weimer, Jonathan; Elegbede, Adekunle; Labhasetwar, Vinod

    2014-01-01

    To be effective for cytoplasmic delivery of therapeutics, nanoparticles (NPs) taken up via endocytic pathways must efficiently transport across the cell membrane and subsequently escape from the secondary endosomes. We hypothesized that the biomechanical and thermodynamic interactions of NPs with plasma and endosomal membrane lipids are involved in these processes. Using model plasma and endosomal lipid membranes, we compared the interactions of cationic NPs composed of poly(d,l-lactide-co-gl...

  10. Cellular and molecular-genetic mechanisms of symbiosis and associative interaction of microorganisms with plants in rhizosphere

    Directory of Open Access Journals (Sweden)

    Lioshina L. G.

    2009-02-01

    Full Text Available The review contains the results of research on symbiotic and associative interaction of microorganisms and plants in rhizosphere. A special attention is given to the process of contact association of microorganisms and plants tissues including the concrete molecular structures and dominant role pertaining to protein-carbohydrate interaction. There are common features and distinctions at formation of arbuscular mycorhiza, rhizobia– legume symbiosis and association of non-leguminous plants with Azospirillum

  11. Interaction of cellular factors related to the Jun oncoprotein with the promoter of a replication-dependent hamster histone H3.2 gene

    International Nuclear Information System (INIS)

    The promoter region of a replication-dependent histone H3.2 gene contains a putative DNA binding site for the Jun oncoprotein within a 32-nucleotide regulatory domain. The hamster sequence differs by one nucleotide from the AP-1 consensus sequence found in several promoters responsive to phorbol 12-myristate 13-acetate. The authors have identified the factors interacting with this region as 42- and 45-kDa proteins by DNA affinity chromatography, immunoblotting, and UV crosslinking. These proteins, which are candidates for conferring high-level expression to the histone promoter, share an antigenic epitope with the DNA-binding domain of Jun but diverge from it at the amino terminus. The interaction of these proteins with the promoter of a replication-dependent cellular gene provides evidence that members of the Jun oncoprotein family may play specific roles in the expression of genes essential for progression of the cell cycle

  12. Systematic Cellular Disease Models Reveal Synergistic Interaction of Trisomy 21 and GATA1 Mutations in Hematopoietic Abnormalities.

    Science.gov (United States)

    Banno, Kimihiko; Omori, Sayaka; Hirata, Katsuya; Nawa, Nobutoshi; Nakagawa, Natsuki; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Sakuma, Tetsushi; Yamamoto, Takashi; Toki, Tsutomu; Ito, Etsuro; Yamamoto, Toshiyuki; Kokubu, Chikara; Takeda, Junji; Taniguchi, Hidetoshi; Arahori, Hitomi; Wada, Kazuko; Kitabatake, Yasuji; Ozono, Keiichi

    2016-05-10

    Chromosomal aneuploidy and specific gene mutations are recognized early hallmarks of many oncogenic processes. However, the net effect of these abnormalities has generally not been explored. We focused on transient myeloproliferative disorder (TMD) in Down syndrome, which is characteristically associated with somatic mutations in GATA1. To better understand functional interplay between trisomy 21 and GATA1 mutations in hematopoiesis, we constructed cellular disease models using human induced pluripotent stem cells (iPSCs) and genome-editing technologies. Comparative analysis of these engineered iPSCs demonstrated that trisomy 21 perturbed hematopoietic development through the enhanced production of early hematopoietic progenitors and the upregulation of mutated GATA1, resulting in the accelerated production of aberrantly differentiated cells. These effects were mediated by dosage alterations of RUNX1, ETS2, and ERG, which are located in a critical 4-Mb region of chromosome 21. Our study provides insight into the genetic synergy that contributes to multi-step leukemogenesis. PMID:27134169

  13. Correlations between cellular resistance to ionizing radiation and other DNA-damaging agents: Patterns of interaction with DFMO

    International Nuclear Information System (INIS)

    The authors evaluated a number of antitumor agents to determine the extent to which cytotoxic responses to these agents correlate with those of x-rays and PUVA. As part of this determination, the authors measured the effect of depletion of cellular levels of polyamines by DFMO on the survival patterns in V79 cells. These studies indicate several agents are cosensitive with x-rays and PUVA in that cell survival is markedly decreased in DFMO treated cells: cis-platinum, nitrogen mustard, mitomycin-C and 4 hydroxycyclophosphamide. The authors data taken in toto suggest common factors in the cytotoxic response of mammalian cells to most DNA-damaging agents whose initial level of damage can be modulated by higher-order chromatin structure

  14. Uncoupling protein 3 expression and intramyocellular lipid accumulation by NMR following local burn trauma.

    Science.gov (United States)

    Zhang, Qunhao; Cao, Haihui; Astrakas, Loukas G; Mintzopoulos, Dionyssios; Mindrinos, Michael N; Schulz, John; Tompkins, Ronald G; Rahme, Laurence G; Tzika, A Aria

    2006-12-01

    Burn trauma is a clinical condition accompanied by muscle wasting that severely impedes rehabilitation in burn survivors. Mitochondrial uncoupling protein 3 (UCP3) is uniformly expressed in myoskeletal mitochondria and its expression has been found to increase in other clinical syndromes that, like burn trauma, are associated with muscle wasting (e.g., starvation, fasting, cancer, sepsis). The aim of this study was to explore the effects of burn trauma on UCP3 expression, intramyocellular lipids, and plasma-free fatty acids. Mice were studied at 6 h, 1 d and 3 d after nonlethal hindlimb burn trauma. Intramyocellular lipids in hindlimb skeletal muscle samples collected from burned and normal mice were measured using 1H NMR spectroscopy on a Bruker 14.1 Tesla spectrometer at 4 degrees C. UCP3 mRNA and protein levels were also measured in these samples. Plasma-free fatty acids were measured in burned and normal mice. Local burn trauma was found to result in: 1) upregulation of UCP3 mRNA and protein expression in hindlimb myoskeletal mitochondria by 6 h postburn; 2) increased intramyocellular lipids; and 3) increased plasma-free fatty acids. Our findings show that the increase in UCP3 after burn trauma may be linked to burn-induced alterations in lipid metabolism. Such a link could reveal novel insights into how processes related to energy metabolism are controlled in burn and suggest that induction of UCP3 by burn in skeletal muscle is protective by either activating cellular redox signaling and/or mitochondrial uncoupling. PMID:17089030

  15. Effect of self-interaction on the phase diagram of a Gibbs-like measure derived by a reversible Probabilistic Cellular Automata

    International Nuclear Information System (INIS)

    Cellular Automata are discrete-time dynamical systems on a spatially extended discrete space which provide paradigmatic examples of nonlinear phenomena. Their stochastic generalizations, i.e., Probabilistic Cellular Automata (PCA), are discrete time Markov chains on lattice with finite single-cell states whose distinguishing feature is the parallel character of the updating rule. We study the ground states of the Hamiltonian and the low-temperature phase diagram of the related Gibbs measure naturally associated with a class of reversible PCA, called the cross PCA. In such a model the updating rule of a cell depends indeed only on the status of the five cells forming a cross centered at the original cell itself. In particular, it depends on the value of the center spin (self-interaction). The goal of the paper is that of investigating the role played by the self-interaction parameter in connection with the ground states of the Hamiltonian and the low-temperature phase diagram of the Gibbs measure associated with this particular PCA

  16. Irradiations of human melanoma cells by 14 MeV neutrons; survival curves interpretation; physical simulation of neutrons interactions in the cellular medium

    International Nuclear Information System (INIS)

    14 MeV neutrons are used to irradiate human melanoma cells in order to study survival curves at low dose and low dose rate. We have simulated with the MCNP code, transport of neutrons through the experimental setup to evaluate the contamination of the primary beam by gamma and electrons, for the feasibility of our experiments. We have shown a rapid decrease of the survival curve in the first cGy followed by a plateau for doses up to 30 cGy; after we observed an exponential decrease. This results are observed for the first time, for neutrons at low dose rate (5 cGy/h). In parallel with this experimental point, we have developed a simulation code which permitted the study of neutrons interactions with the cellular medium for individual cells defined as in our experimental conditions. We show that most of the energy is deposited by protons from neutron interactions with external medium, and by heavy ions for interactions into the cell. On the other hand the code gives a good order of magnitude of the dose rate, compared to the experimental values given by silicon diodes. The first results show that we can, using a theory based on induced repair of cells, give an interpretation of the observed experimental plateau. We can give an estimation of the radial distribution of dose for the tracks of charged ions, we show the possibility of calculate interaction cross sections with cellular organelles. Such a work gives interesting perspectives for the future in radiobiology, radiotherapy or radioprotection. (author)

  17. Cellular automata

    CERN Document Server

    Codd, E F

    1968-01-01

    Cellular Automata presents the fundamental principles of homogeneous cellular systems. This book discusses the possibility of biochemical computers with self-reproducing capability.Organized into eight chapters, this book begins with an overview of some theorems dealing with conditions under which universal computation and construction can be exhibited in cellular spaces. This text then presents a design for a machine embedded in a cellular space or a machine that can compute all computable functions and construct a replica of itself in any accessible and sufficiently large region of t

  18. Detailed Study of the Interaction between Human Herpesvirus 6B Glycoprotein Complex and Its Cellular Receptor, Human CD134

    OpenAIRE

    Tang, Huamin; Wang, Junjie; Mahmoud, Nora F.; Mori, Yasuko

    2014-01-01

    Recently, we identified a novel receptor, CD134, which interacts with the human herpesvirus 6B (HHV-6B) glycoprotein (g)H/gL/gQ1/gQ2 complex and plays a key role in the entry of HHV-6B into target cells. However, details of the interaction between the HHV-6B gH/gL/gQ1/gQ2 complex and CD134 were unknown. In this study, we identified a cysteine-rich domain (CRD), CDR2, of CD134 that is critical for binding to the HHV-6B glycoprotein complex and HHV-6B infection. Furthermore, we found that the e...

  19. Propoxylation of cationic polymers provides a novel approach to controllable modulation of their cellular toxicity and interaction with nucleic acids.

    Science.gov (United States)

    Shevchenko, Vesta D; Salakhieva, Diana V; Yergeshov, Abdulla A; Badeev, Yuriy V; Shtyrlin, Yurii G; Abdullin, Timur I

    2016-12-01

    An effective chemical approach to modulation of biological interactions of cationic polymers was proposed and tested using polyethyleneimine (PEI) as a drug carrier. Branched 25kDa PEI was modified in the reaction with propylene oxide (PO) to produce a series of propoxylated PEIs with NH groups grafted by single or oligomer PO units. Clear relationships between the propoxylation degree and biological effects, such as interaction with plasmid DNA, hemolytic, cytotoxic, and pro-apoptotic activities were revealed for PEIs modified upon PO/NH molar ratio of 0.5, 0.75, 1.0 and 3.0. The partial modification of available cationic centers up to 100% is predominantly accompanied by a significant gradual reduction in polycation adverse effects, while ability of complex formation with plasmid DNA is being preserved. Grafted PEI with 0.75 PO/NH ratio provides better protection from nuclease degradation and transfection activity compared with other modified PEIs. Revealed relationships contribute to the development of safe polymeric systems with controllable physicochemical properties and biological interactions. PMID:27612689

  20. A Saccharomyces cerevisiae Assay System to Investigate Ligand/AdipoR1 Interactions That Lead to Cellular Signaling

    KAUST Repository

    Aouida, Mustapha

    2013-06-07

    Adiponectin is a mammalian hormone that exerts anti-diabetic, anti-cancer and cardioprotective effects through interaction with its major ubiquitously expressed plasma membrane localized receptors, AdipoR1 and AdipoR2. Here, we report a Saccharomyces cerevisiae based method for investigating agonist-AdipoR interactions that is amenable for high-throughput scale-up and can be used to study both AdipoRs separately. Agonist-AdipoR1 interactions are detected using a split firefly luciferase assay based on reconstitution of firefly luciferase (Luc) activity due to juxtaposition of its N- and C-terminal fragments, NLuc and CLuc, by ligand induced interaction of the chimeric proteins CLuc-AdipoR1 and APPL1-NLuc (adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif 1-NLuc) in a S. cerevisiae strain lacking the yeast homolog of AdipoRs (Izh2p). The assay monitors the earliest known step in the adiponectin-AdipoR anti-diabetic signaling cascade. We demonstrate that reconstituted Luc activity can be detected in colonies or cells using a CCD camera and quantified in cell suspensions using a microplate reader. AdipoR1-APPL1 interaction occurs in absence of ligand but can be stimulated specifically by agonists such as adiponectin and the tobacco protein osmotin that was shown to have AdipoR-dependent adiponectin-like biological activity in mammalian cells. To further validate this assay, we have modeled the three dimensional structures of receptor-ligand complexes of membrane-embedded AdipoR1 with cyclic peptides derived from osmotin or osmotin-like plant proteins. We demonstrate that the calculated AdipoR1-peptide binding energies correlate with the peptides\\' ability to behave as AdipoR1 agonists in the split luciferase assay. Further, we demonstrate agonist-AdipoR dependent activation of protein kinase A (PKA) signaling and AMP activated protein kinase (AMPK) phosphorylation in S. cerevisiae, which are homologous to

  1. A Saccharomyces cerevisiae assay system to investigate ligand/AdipoR1 interactions that lead to cellular signaling.

    Directory of Open Access Journals (Sweden)

    Mustapha Aouida

    Full Text Available Adiponectin is a mammalian hormone that exerts anti-diabetic, anti-cancer and cardioprotective effects through interaction with its major ubiquitously expressed plasma membrane localized receptors, AdipoR1 and AdipoR2. Here, we report a Saccharomyces cerevisiae based method for investigating agonist-AdipoR interactions that is amenable for high-throughput scale-up and can be used to study both AdipoRs separately. Agonist-AdipoR1 interactions are detected using a split firefly luciferase assay based on reconstitution of firefly luciferase (Luc activity due to juxtaposition of its N- and C-terminal fragments, NLuc and CLuc, by ligand induced interaction of the chimeric proteins CLuc-AdipoR1 and APPL1-NLuc (adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif 1-NLuc in a S. cerevisiae strain lacking the yeast homolog of AdipoRs (Izh2p. The assay monitors the earliest known step in the adiponectin-AdipoR anti-diabetic signaling cascade. We demonstrate that reconstituted Luc activity can be detected in colonies or cells using a CCD camera and quantified in cell suspensions using a microplate reader. AdipoR1-APPL1 interaction occurs in absence of ligand but can be stimulated specifically by agonists such as adiponectin and the tobacco protein osmotin that was shown to have AdipoR-dependent adiponectin-like biological activity in mammalian cells. To further validate this assay, we have modeled the three dimensional structures of receptor-ligand complexes of membrane-embedded AdipoR1 with cyclic peptides derived from osmotin or osmotin-like plant proteins. We demonstrate that the calculated AdipoR1-peptide binding energies correlate with the peptides' ability to behave as AdipoR1 agonists in the split luciferase assay. Further, we demonstrate agonist-AdipoR dependent activation of protein kinase A (PKA signaling and AMP activated protein kinase (AMPK phosphorylation in S. cerevisiae, which are

  2. Characterization of L1 ORF1p self-interaction and cellular localization using a mammalian two-hybrid system.

    Directory of Open Access Journals (Sweden)

    Mark Sokolowski

    Full Text Available Long INterspersed Element-1 (LINE-1, L1 is an active retrotransposon that mobilizes using a ribonucleoprotein particle (RNP intermediate composed of the full-length bicistronic L1 mRNA and the two proteins (ORF1p and ORF2p encoded by that mRNA. ORF1p and ORF2p demonstrate cis-preference for their encoding mRNA. Previous studies of ORF1p, purified from bacterial and insect cells demonstrated that this protein forms trimers in vitro. While valuable for understanding ORF1p function, these in vitro approaches do not provide any information on ORF1p self-interaction in the context of mammalian cells. We used a mammalian two-hybrid (M2H system in order to study L1 ORF1p self-interaction in human and mouse cells. We demonstrate that the M2H system successfully detects human and mouse ORF1p self-interactions in transiently transfected mammalian cells. We also generated mouse and human ORF1p-specific antibodies to characterize the expression of ORF1p fusion proteins used in the M2H system. Using these antibodies, we demonstrate that ORF1p interaction in trans leads to the formation of heterodimers that are expected to produce a positive signal in the M2H system. Although the role for L1 ORF1p cis-preference in L1 mobilization is established, the impact of ability of ORF1pto interact in trans on the L1 replication cycle is not known. Furthermore, western blot analysis of ORF1p generated by a full-length L1, wild type ORF1, or a codon-optimized ORF1 expression vector is detected in the nucleus. In contrast, the addition of a tag to the N-terminus of the mouse and human ORF1 proteins can significantly alter the subcellular localization in a tag-specific manner. These data support that nuclear localization of ORF1p may contribute to L1 (and potentially the SINE Alu RNP nuclear access in the host cell.

  3. Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination.

    Science.gov (United States)

    Lappe-Siefke, Corinna; Goebbels, Sandra; Gravel, Michel; Nicksch, Eva; Lee, John; Braun, Peter E; Griffiths, Ian R; Nave, Klaus-Armin

    2003-03-01

    Myelination of axons by oligodendrocytes enables rapid impulse propagation in the central nervous system. But long-term interactions between axons and their myelin sheaths are poorly understood. Here we show that Cnp1, which encodes 2',3'-cyclic nucleotide phosphodiesterase in oligodendrocytes, is essential for axonal survival but not for myelin assembly. In the absence of glial cyclic nucleotide phosphodiesterase, mice developed axonal swellings and neurodegeneration throughout the brain, leading to hydrocephalus and premature death. But, in contrast to previously studied myelin mutants, the ultrastructure, periodicity and physical stability of myelin were not altered in these mice. Genetically, the chief function of glia in supporting axonal integrity can thus be completely uncoupled from its function in maintaining compact myelin. Oligodendrocyte dysfunction, such as that in multiple sclerosis lesions, may suffice to cause secondary axonal loss. PMID:12590258

  4. Interaction of Frequency Allocation Schemes and Beam Forming on the Performance of Cellular Communication Systems Based on OFDM

    Directory of Open Access Journals (Sweden)

    R. Gholami

    2013-03-01

    Full Text Available In this study, the interaction of Beam Forming and frequency allocation schemes on an OFDM-based system such as LTE or WiMAX is investigated in order to support the maximum capacity and minimum outage probability. The results of simulation show that rank1 precode scheme based on MISO channel, according to what considered in LTE standard, along with the cell region division in order to allocate OFDM frequency carriers lead to a Considerable interest in the total capacity of the network in different traffics.

  5. D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75

    International Nuclear Information System (INIS)

    Integration of viral-DNA into host chromosome mediated by the viral protein HIV-1 integrase (IN) is an essential step in the HIV-1 life cycle. In this process, Lens epithelium-derived growth factor (LEDGF/p75) is discovered to function as a cellular co-factor for integration. Since LEDGF/p75 plays an important role in HIV integration, disruption of the LEDGF/p75 interaction with IN has provided a special interest for anti-HIV agent discovery. In this work, we reported that a benzoic acid derivative, 4-[(5-bromo-4-{[2,4-dioxo-3-(2-oxo-2-phenylethyl) -1,3-thiazolidin-5-ylidene]methyl}-2-ethoxyphenoxy)methyl]benzoic acid (D77) could potently inhibit the IN-LEDGF/p75 interaction and affect the HIV-1 IN nuclear distribution thus exhibiting antiretroviral activity. Molecular docking with site-directed mutagenesis analysis and surface plasmon resonance (SPR) binding assays has clarified possible binding mode of D77 against HIV-1 integrase. As the firstly discovered small molecular compound targeting HIV-1 integrase interaction with LEDGF/p75, D77 might supply useful structural information for further anti-HIV agent discovery

  6. Sterile α Motif Domain Containing 9 Is a Novel Cellular Interacting Partner to Low-Risk Type Human Papillomavirus E6 Proteins

    Science.gov (United States)

    Wang, Jia; Dupuis, Crystal; Tyring, Stephen K.; Underbrink, Michael P.

    2016-01-01

    Low-risk type human papillomavirus (HPV) 6 and 11 infection causes recurrent respiratory papillomatosis (RRP) and genital warts. RRP is the most common benign tumor of the larynx in children with frequent relapses. Repeated surgeries are often needed to improve vocal function and prevent life-threatening respiratory obstruction. Currently, there are no effective treatments available to completely eliminate these diseases, largely due to limited knowledge regarding their viral molecular pathogenesis. HPV E6 proteins contribute to cell immortalization by interacting with a variety of cellular proteins, which have been well studied for the high-risk type HPVs related to cancer progression. However, the functions of low-risk HPV E6 proteins are largely unknown. In this study, we report GST-pulldown coupled mass spectrometry analysis with low-risk HPV E6 proteins that identified sterile alpha motif domain containing 9 (SAMD9) as a novel interacting partner. We then confirmed the interaction between HPV-E6 and SAMD9 using co-immunoprecipitation, proximity ligation assay, and confocal immunofluorescence staining. The SAMD9 gene is down-regulated in a variety of neoplasms and deleteriously mutated in normophosphatemic familial tumoral calcinosis. Interestingly, SAMD9 also has antiviral functions against poxvirus. Our study adds to the limited knowledge of the molecular properties of low-risk HPVs and describes new potential functions for the low-risk HPV E6 protein. PMID:26901061

  7. Intra-cellular transport by single-headed kinesin KIF1A: effects of single-motor mechano-chemistry and steric interactions

    CERN Document Server

    Greulich, P; Garai, A; Nishinari, K; Schadschneider, A; Chowdhury, Debashish; Garai, Ashok; Greulich, Philip; Nishinari, Katsuhiro; Schadschneider, Andreas

    2006-01-01

    In eukaryotic cells, many motor proteins can move simultaneously on a single microtubule track. This leads to interesting collective phenomena like jamming. Recently we reported ({\\it Phys. Rev. Lett. {\\bf 95}, 118101 (2005)}) a lattice-gas model which describes traffic of unconventional (single-headed) kinesins KIF1A. Here we generalize this model, introducing a novel interaction parameter $c$, to account for an interesting mechano-chemical process which has not been considered in any earlier model. We have been able to extract all the parameters of the model, except $c$, from experimentally measured quantities. In contrast to earlier models of intra-cellular molecular motor traffic, our model assigns distinct ``chemical'' (or, conformational) states to each kinesin to account for the hydrolysis of ATP, the chemical fuel of the motor. Our model makes experimentally testable theoretical predictions. We determine the phase diagram of the model in planes spanned by experimentally controllable parameters, namely...

  8. Study on the Beam Quality of Uncoupled Laser Diode Arrays

    Institute of Scientific and Technical Information of China (English)

    GAO Chunqing; WEI Guanghui

    2001-01-01

    The beam quality of uncoupled laser diode array is studied theoretically and experimentally. By calculating the second order moments of the beam emitted from the laser diode array, the dependence of the M2-factor of the laser diode array on the M2-factor of the single emitter, the ratio of the emitting region to the non-emitting space, and the number of emitters, has been deduced. From the measurement of the beam propagation the M2-factor of a laser diode bar is experimentally determined. The measured M2-factor of the laser diode bar agrees with the theoretical prediction.

  9. An eudesman derivative from Verbesina persicifolia D.C. as a natural mild uncoupler in liver mitochondria. A new potential anti-obesity agent?

    Science.gov (United States)

    Dalla Via, Lisa; García-Argáez, Aída N; Braga, Alessandra; Martínez-Vázquez, Mariano; Grancara, Silvia; Martinis, Pamela; Agostinelli, Enzo; Toninello, Antonio

    2014-01-01

    4β-cinnamoyloxy,1β,3α-dihydroxyeudesm-7,8-ene (CDE) extracted from Verbesina persicifolia induces bioenergetic collapse in rat liver mitochondria (RLM), monitored as a fall in the respiratory control index and ADP/O values. This fall in energy is accompanied by a protonophore effect and membrane potential (Δψ) collapse, demonstrating that CDE behaves as a typical uncoupling agent. However, when examining the effect of CDE in detail, we found that it acts as a "mild" uncoupler because it drops Δψ and increases respiratory state 4. The proposed mechanism is based on the interaction of CDE with membrane protein cytochrome C oxidase, which is implicated in proton permeability, and with the respiratory chain for the generation of reactive oxygen species which mediate and regulate the activity of the above membrane protein. Considering the energy collapse, "mild" uncoupling, and the fact that CDE is largely used in folk medicines, this extract may be viewed as a potentially effective anti-obesity drug and a natural lead compound for developing new natural uncouplers against obesity. PMID:23701541

  10. The influence of receptor-mediated interactions on reaction-diffusion mechanisms of cellular self-organisation.

    Science.gov (United States)

    Klika, Václav; Baker, Ruth E; Headon, Denis; Gaffney, Eamonn A

    2012-04-01

    Understanding the mechanisms governing and regulating self-organisation in the developing embryo is a key challenge that has puzzled and fascinated scientists for decades. Since its conception in 1952 the Turing model has been a paradigm for pattern formation, motivating numerous theoretical and experimental studies, though its verification at the molecular level in biological systems has remained elusive. In this work, we consider the influence of receptor-mediated dynamics within the framework of Turing models, showing how non-diffusing species impact the conditions for the emergence of self-organisation. We illustrate our results within the framework of hair follicle pre-patterning, showing how receptor interaction structures can be constrained by the requirement for patterning, without the need for detailed knowledge of the network dynamics. Finally, in the light of our results, we discuss the ability of such systems to pattern outside the classical limits of the Turing model, and the inherent dangers involved in model reduction. PMID:22072186

  11. Cyclosporine suppression of lymphocyte recruitment, regional blood flow, and vascular permeability at sites of allogeneic cellular interactions

    International Nuclear Information System (INIS)

    Although cyclosporine (CsA) has been thought to act primarily on the afferent phase of the immune response, we can demonstrate that it also acts at the efferent phase. The effect of CsA on lymphocyte recruitment (LR), regional blood flow (RBF), and vascular permeability (VP) was studied in paired, healed, subcutaneously placed urethane sponge grafts inoculated with specifically sensitized lymphocytes (SSLs) and allogeneic target cells. Intravenous injection of 111In-labelled unsensitized lymphocytes, 86RbCl and 125I-labelled albumin were used to assess LR, RBF, and VP, respectively. Suspensions of SSL and targets in CsA at 10 and 1 microgram/ml prior to graft inoculation markedly reduce the preferential increase in LR to the site of interaction between SSLs and targets bearing the sensitizing alloantigen (P less than 0.002 for both). Similarly, CsA blocks the preferential increase in RBF (P . 0.017) and VP (P less than 0.002) to the graft site. These effects persist for at least 24 hours. If SSLs and targets are washed after incubation with CsA, LR is still reduced. These results are consistent with the idea that cell-bound CsA blocks the elaboration of lymphokines which results from the interaction between SSLs and specific alloantigen in vivo. These lymphokines increase RBF and VP and are accompanied by an increase in LR. Inhibition of these vascular effects may prevent the recruitment of additional lymphocytes to the graft site. CsA may, therefore, prevent or interrupt allograft rejection by blocking amplification of the rejection mechanism at the graft site

  12. Lipid-based liquid crystalline nanoparticles as oral drug delivery vehicles for poorly water-soluble drugs: cellular interaction and in vivo absorption

    Directory of Open Access Journals (Sweden)

    Zeng N

    2012-07-01

    Full Text Available Ni Zeng,1,3,* Xiaoling Gao,2,* Quanyin Hu,1 Qingxiang Song,2 Huimin Xia,1 Zhongyang Liu,1 Guangzhi Gu,1 Mengyin Jiang,1,4 Zhiqing Pang,1 Hongzhuan Chen,2 Jun Chen,1 Liang Fang3 1Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, 2Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, 3Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 4School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong People's Republic of China, *These authors contributed equally to this workBackground: Lipid-based liquid crystalline nanoparticles (LCNPs have attracted growing interest as novel drug-delivery systems for improving the bioavailability of both hydrophilic and hydrophobic drugs. However, their cellular interaction and in vivo behavior have not been fully developed and characterized.Methods: In this study, self-assembled LCNPs prepared from soy phosphatidylcholine and glycerol dioleate were developed as a platform for oral delivery of paclitaxel. The particle size of empty LCNPs and paclitaxel-loaded LCNPs was around 80 nm. The phase behavior of the liquid crystalline matrix was characterized using crossed polarized light microscopy and small-angle X-ray scattering, and showed both reversed cubic and hexagonal phase in the liquid crystalline matrix. Transmission electron microscopy and cryofield emission scanning electron microscopy analysis revealed an inner winding water channel in LCNPs and a "ball-like"/"hexagonal" morphology.Results: Cellular uptake of LCNPs in Caco-2 cells was found to be concentration-dependent and time-dependent, with involvement of both clathrin and caveolae/lipid raft-mediated endocytosis. Under confocal laser scanning microscopy, soy phosphatidylcholine was observed to segregate from the internalized LCNPs and

  13. Mapping of immunogenic and protein-interacting regions at the surface of the seven-bladed β-propeller domain of the HIV-1 cellular interactor EED

    Directory of Open Access Journals (Sweden)

    Gouet Patrice

    2008-02-01

    Full Text Available Abstract Background The human EED protein, a member of the superfamily of Polycomb group proteins, is involved in multiple cellular protein complexes. Its C-terminal domain, which is common to the four EED isoforms, contains seven repeats of a canonical WD-40 motif. EED is an interactor of three HIV-1 proteins, matrix (MA, integrase (IN and Nef. An antiviral activity has been found to be associated with isoforms EED3 and EED4 at the late stage of HIV-1 replication, due to a negative effect on virus assembly and genomic RNA packaging. The aim of the present study was to determine the regions of the EED C-terminal core domain which were accessible and available to protein interactions, using three-dimensional (3D protein homology modelling with a WD-40 protein of known structure, and epitope mapping of anti-EED antibodies. Results Our data suggested that the C-terminal domain of EED was folded as a seven-bladed β-propeller protein. During the completion of our work, crystallographic data of EED became available from co-crystals of the EED C-terminal core with the N-terminal domain of its cellular partner EZH2. Our 3D-model was in good congruence with the refined structural model determined from crystallographic data, except for a unique α-helix in the fourth β-blade. More importantly, the position of flexible loops and accessible β-strands on the β-propeller was consistent with our mapping of immunogenic epitopes and sites of interaction with HIV-1 MA and IN. Certain immunoreactive regions were found to overlap with the EZH2, MA and IN binding sites, confirming their accessibility and reactivity at the surface of EED. Crystal structure of EED showed that the two discrete regions of interaction with MA and IN did not overlap with each other, nor with the EZH2 binding pocket, but were contiguous, and formed a continuous binding groove running along the lateral face of the β-propeller. Conclusion Identification of antibody-, MA-, IN- and EZH2

  14. Dietary effects on body composition, glucose metabolism, and longevity are modulated by skeletal muscle mitochondrial uncoupling in mice

    OpenAIRE

    Keipert, Susanne; Voigt, Anja; Klaus, Susanne

    2011-01-01

    Little is known about how diet and energy metabolism interact in determination of lifespan under ad libitum feeding. From 12 weeks of age until death, male and female wild-type (WT) and transgenic (TG) mice with increased skeletal muscle mitochondrial uncoupling (HSA-mUCP1 mice) were fed one of three different semisynthetic diets differing in macronutrient ratio: control (high-carbohydrate/low-fat-HCLF) and two high-fat diets: high-carbohydrate/high-fat (HCHF), and low-carbohydrate/high-fat (...

  15. The Influence of Receptor-Mediated Interactions on Reaction-Diffusion Mechanisms of Cellular Self-organisation

    KAUST Repository

    Klika, Václav

    2011-11-10

    Understanding the mechanisms governing and regulating self-organisation in the developing embryo is a key challenge that has puzzled and fascinated scientists for decades. Since its conception in 1952 the Turing model has been a paradigm for pattern formation, motivating numerous theoretical and experimental studies, though its verification at the molecular level in biological systems has remained elusive. In this work, we consider the influence of receptor-mediated dynamics within the framework of Turing models, showing how non-diffusing species impact the conditions for the emergence of self-organisation. We illustrate our results within the framework of hair follicle pre-patterning, showing how receptor interaction structures can be constrained by the requirement for patterning, without the need for detailed knowledge of the network dynamics. Finally, in the light of our results, we discuss the ability of such systems to pattern outside the classical limits of the Turing model, and the inherent dangers involved in model reduction. © 2011 Society for Mathematical Biology.

  16. Dissecting stromal-epithelial interactions in a 3D in vitro cellularized intestinal model for permeability studies.

    Science.gov (United States)

    Pereira, Carla; Araújo, Francisca; Barrias, Cristina C; Granja, Pedro L; Sarmento, Bruno

    2015-07-01

    Absorption evaluation plays an increasingly important role at the early stage of drug discovery due to its potential to scan the ADME (absorption, distribution, metabolism and excretion) properties of new drug candidates. Therefore, a new three-dimensional (3D) in vitro model replicating the intestinal functioning is herein proposed aiming to dissect the stromal-epithelial interactions and evaluate the permeation of a model drug, insulin. Inspired on the intestinal mucosal architecture, the present model comprises intestinal myofibroblasts (CCD18-Co cells) embedded in Matrigel, onto which epithelial enterocytes (Caco-2 cells) and mucus-producing cells (HT29-MTX cells) were seeded. CCD18-Co myofibroblasts showed to have a central role in the remodeling of the surrounding matrix confirmed by the production of fibronectin. Subsequently, this matrix revealed to be essential to the maintenance of the model architecture by supporting the overlying epithelial cells. In terms of functionality, this model allowed the efficient prediction of insulin permeability in which the presence of mucus, the less tight character between Caco-2 and HT29-MTX epithelial cells and the 3D assembly were critical factors. Concluding, this model constitutes a robust tool in the drug development field with potential to bridge the traditional 2D cell culture models and in vivo animal models. PMID:25934277

  17. Chromatin Assembly at Kinetochores Is Uncoupled from DNA Replication

    Science.gov (United States)

    Shelby, Richard D.; Monier, Karine; Sullivan, Kevin F.

    2000-01-01

    The specification of metazoan centromeres does not depend strictly on centromeric DNA sequences, but also requires epigenetic factors. The mechanistic basis for establishing a centromeric “state” on the DNA remains unclear. In this work, we have directly examined replication timing of the prekinetochore domain of human chromosomes. Kinetochores were labeled by expression of epitope-tagged CENP-A, which stably marks prekinetochore domains in human cells. By immunoprecipitating CENP-A mononucleosomes from synchronized cells pulsed with [3H]thymidine we demonstrate that CENP-A–associated DNA is replicated in mid-to-late S phase. Cytological analysis of DNA replication further demonstrated that centromeres replicate asynchronously in parallel with numerous other genomic regions. In contrast, quantitative Western blot analysis demonstrates that CENP-A protein synthesis occurs later, in G2. Quantitative fluorescence microscopy and transient transfection in the presence of aphidicolin, an inhibitor of DNA replication, show that CENP-A can assemble into centromeres in the absence of DNA replication. Thus, unlike most genomic chromatin, histone synthesis and assembly are uncoupled from DNA replication at the kinetochore. Uncoupling DNA replication from CENP-A synthesis suggests that regulated chromatin assembly or remodeling could play a role in epigenetic centromere propagation. PMID:11086012

  18. Cline coupling and uncoupling in a stickleback hybrid zone.

    Science.gov (United States)

    Vines, Timothy H; Dalziel, Anne C; Albert, Arianne Y K; Veen, Thor; Schulte, Patricia M; Schluter, Dolph

    2016-05-01

    Strong ecological selection on a genetic locus can maintain allele frequency differences between populations in different environments, even in the face of hybridization. When alleles at divergent loci come into tight linkage disequilibrium, selection acts on them as a unit and can significantly reduce gene flow. For populations interbreeding across a hybrid zone, linkage disequilibria between loci can force clines to share the same slopes and centers. However, strong ecological selection on a locus can also pull its cline away from the others, reducing linkage disequilibrium and weakening the barrier to gene flow. We looked for this "cline uncoupling" effect in a hybrid zone between stream resident and anadromous sticklebacks at two genes known to be under divergent natural selection (Eda and ATP1a1) and five morphological traits that repeatedly evolve in freshwater stickleback. These clines were all steep and located together at the top of the estuary, such that we found no evidence for cline uncoupling. However, we did not observe the stepped shape normally associated with steep concordant clines. It thus remains possible that these clines cluster together because their individual selection regimes are identical, but this would be very surprising given their diverse roles in osmoregulation, body armor, and swimming performance. PMID:27061719

  19. Multi-parametric cytometry from a complex cellular sample: Improvements and limits of manual versus computational-based interactive analyses.

    Science.gov (United States)

    Gondois-Rey, F; Granjeaud, S; Rouillier, P; Rioualen, C; Bidaut, G; Olive, D

    2016-05-01

    The wide possibilities opened by the developments of multi-parametric cytometry are limited by the inadequacy of the classical methods of analysis to the multi-dimensional characteristics of the data. While new computational tools seemed ideally adapted and were applied successfully, their adoption is still low among the flow cytometrists. In the purpose to integrate unsupervised computational tools for the management of multi-stained samples, we investigated their advantages and limits by comparison to manual gating on a typical sample analyzed in immunomonitoring routine. A single tube of PBMC, containing 11 populations characterized by different sizes and stained with 9 fluorescent markers, was used. We investigated the impact of the strategy choice on manual gating variability, an undocumented pitfall of the analysis process, and we identified rules to optimize it. While assessing automatic gating as an alternate, we introduced the Multi-Experiment Viewer software (MeV) and validated it for merging clusters and annotating interactively populations. This procedure allowed the finding of both targeted and unexpected populations. However, the careful examination of computed clusters in standard dot plots revealed some heterogeneity, often below 10%, that was overcome by increasing the number of clusters to be computed. MeV facilitated the identification of populations by displaying both the MFI and the marker signature of the dataset simultaneously. The procedure described here appears fully adapted to manage homogeneously high number of multi-stained samples and allows improving multi-parametric analyses in a way close to the classic approach. © 2016 International Society for Advancement of Cytometry. PMID:27059253

  20. Transcriptomic Changes in Osteoblasts Following Endothelial Cell-Cocultivation Suggest a Role of Extracellular Matrix in Cellular Interaction.

    Science.gov (United States)

    Lampert, Florian M; Simunovic, Filip; Finkenzeller, Günter; Pfeifer, Dietmar; Stark, G Björn; Winninger, Oscar; Steiner, Dominik

    2016-08-01

    Vascularization is important for bone development, fracture healing and engineering of artificial bone tissue. In the context of bone tissue engineering, it was shown that coimplantation of human primary umbilical vein endothelial cells (HUVECs) and human osteoblasts (hOBs) results in the formation of functional blood vessels and enhanced bone regeneration. Implanted endothelial cells do not only contribute to blood vessel formation, but also support proliferation, cell survival and osteogenic differentiation of coimplanted hOBs. These effects are partially mediated by direct heterotypic cell contacts. In a previous report we could show that cocultivated hOBs strongly increase the expression of genes involved in extracellular matrix (ECM) formation in HUVECs, suggesting that ECM may be involved in the intercellular communication between hOBs and HUVECs. The present study aimed at investigating whether comparable changes occur in hOBs. We therefore performed a microarray analysis of hOBs cultivated in direct contact with HUVECs, revealing 1,004 differentially expressed genes. The differentially expressed genes could be assigned to the functional clusters ECM, proliferation, apoptosis and osteogenic differentiation. The microarray data could be confirmed by performing quantitative real time RT-PCR on selected genes. Furthermore, we could show that the ECM produced by HUVECs increased the expression of the osteogenic differentiation marker alkaline phosphatase (ALP) in hOBs. In summary, our data demonstrate that HUVECs provoke complex changes in gene expression patterns in cocultivated hOBs and that ECM plays and important role in this interaction. J. Cell. Biochem. 117: 1869-1879, 2016. © 2016 Wiley Periodicals, Inc. PMID:26754918

  1. Metabolically inert perfluorinated fatty acids directly activate uncoupling protein 1 in brown-fat mitochondria.

    Science.gov (United States)

    Shabalina, Irina G; Kalinovich, Anastasia V; Cannon, Barbara; Nedergaard, Jan

    2016-05-01

    The metabolically inert perfluorinated fatty acids perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) can display fatty acid-like activity in biological systems. The uncoupling protein 1 (UCP1) in brown adipose tissue is physiologically (re)activated by fatty acids, including octanoate. This leads to bioenergetically uncoupled energy dissipation (heat production, thermogenesis). We have examined here the possibility that PFOA/PFOS can directly (re)activate UCP1 in isolated mouse brown-fat mitochondria. In wild-type brown-fat mitochondria, PFOS and PFOA overcame GDP-inhibited thermogenesis, leading to increased oxygen consumption and dissipated membrane potential. The absence of this effect in brown-fat mitochondria from UCP1-ablated mice indicated that it occurred through activation of UCP1. A competitive type of inhibition by increased GDP concentrations indicated interaction with the same mechanistic site as that utilized by fatty acids. No effect was observed in heart mitochondria, i.e., in mitochondria without UCP1. The stimulatory effect of PFOA/PFOS was not secondary to non-specific mitochondrial membrane permeabilization or to ROS production. Thus, metabolic effects of perfluorinated fatty acids could include direct brown adipose tissue (UCP1) activation. The possibility that this may lead to unwarranted extra heat production and thus extra utilization of food resources, leading to decreased fitness in mammalian wildlife, is discussed, as well as possible negative effects in humans. However, a possibility to utilize PFOA-/PFOS-like substances for activating UCP1 therapeutically in obesity-prone humans may also be envisaged. PMID:26041126

  2. 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.

  3. Engineering hyaluronic acid hydrogel degradation to control cellular interactions and adult stem cell fate in 3D

    Science.gov (United States)

    Khetan, Sudhir

    The design and implementation of extracellular matrix (ECM)-mimetic hydrogels for tissue engineering (TE) applications requires an intensive understanding of cell-material interactions, including matrix remodeling and stem cell differentiation. However, the influence of microenvironmental cues, e.g., matrix biodegradability, on cell behavior in vitro has not been well studied in the case of direct cell encapsulation within 3-dimensional (3D) hydrogels. To address these issues, a facile sequential crosslinking technique was developed that provides spatial and temporal control of 3D hydrogel degradability to investigate the importance of material design on cell behavior. Specifically, hydrogels were synthesized from hyaluronic acid (HA) macromers in a sequential process: (1) a primary Michael-type addition crosslinking using cell adhesive and matrix metalloprotease (MMP)-degradable oligopeptides to consume a portion of total reactive groups and resulting in "-UV" hydrogels permissive to cell-mediated degradation, followed by (2) a secondary, light initiated free-radical crosslinking to consume remaining reactive groups and "switch" the network to a non-degradable structure ("+UV") via the addition of non-degradable kinetic chains. Using this approach, we demonstrated control of encapsulated hMSC spreading by varying the crosslink type (i.e., the relative hydrogel biodegradability), including with spatial control. Upon incubation with bipotential soluble differentiation factors, these same degradation-mediated spreading cues resulted in an hMSC differentiation fate switch within -UV versus +UV environments. Follow-up studies demonstrated that degradation-mediated traction generation, rather than matrix mechanics or cell morphology, is the critical biophysical signal determining hMSC fate. Sequentially crosslinked HA hydrogels were also studied for the capacity to support remodeling by in vivo and ex vivo tissues, including with spatial control, toward tissue

  4. Changes in GDP binding to brown adipose tissue mitochondria and the uncoupling protein

    International Nuclear Information System (INIS)

    Incubation in vitro of brown adipose tissue (BAT) mitochondria with divalent cations, spermine, or alkaline phosphatase led to a marked increase in the binding of [3H]GDP. The effect of Mg2+ appeared to be the most specific and led to the largest increase in GDP binding. A simplified method was developed for measuring GDP binding to purified uncoupling protein from rat BAT mitochondria. Application of this method indicates that uncoupling protein from cold-acclimated rats binds twice as much GDP as uncoupling protein from cold-acclimated rats that were briefly returned to thermoneutrality, paralleling changes in GDP binding to the mitochondria. Incubation of BAT mitochondria with Mg2+ led to a smaller increase in GDP binding to the subsequently purified uncoupling protein, suggesting that divalent cations may somehow participate in the regulation of the activity of the uncoupling protein

  5. Uncoupling effect of fatty acids in halo- and alkalotolerant bacterium Bacillus pseudofirmus FTU.

    Science.gov (United States)

    Popova, I V; Bodrova, M E; Mokhova, E N; Muntyan, M S

    2004-10-01

    Natural uncouplers of oxidative phosphorylation, long-chain non-esterified fatty acids, cause uncoupling in the alkalo- and halotolerant bacterium Bacillus pseudofirmus FTU. The uncoupling effect in the bacterial cells was manifested as decrease of membrane potential and increase of respiratory activity. The membrane potential decrease was detected only in bacterial cells exhausted by their endogenous substrates. In proteoliposomes containing reconstituted bacterial cytochrome c oxidase, fatty acids caused a "mild" uncoupling effect by reducing membrane potential only at low rate of membrane potential generation. "Free respiration" induced by the "mild" uncouplers, the fatty acids, can be considered as possible mechanism responsible for adaptation of the bacteria to a constantly changed environment. PMID:15527418

  6. Uncoupling and reactive oxygen species (ROS)--a double-edged sword for β-cell function? "Moderation in all things".

    Science.gov (United States)

    Collins, Sheila; Pi, Jingbo; Yehuda-Shnaidman, Einav

    2012-12-01

    The ability of the mitochondrion to (a) manage fuel import to oxidize for adenosine tri-phosphate (ATP) generation while (b) protecting itself and the cellular environment from electron leak, which can generate highly reactive oxygen species (ROS) is a delicate balancing act. ATP is the currency of the cell and as such serves a signaling function as a substrate partner to many kinases and ion channels. While various ROS species have been viewed as a dangerous and toxic group of molecules, it also has a role as a signal derived from mitochondria, as well as other enzymatic sources: a double-edged sword. Current efforts to understand the biochemical mechanisms affected by ROS as a signal--usually noted to be hydrogen peroxide (H(2)O(2))--are exciting, but this duality of ROS effects also pose challenges in managing its levels to protect cells. The mitochondrial uncoupling protein-2 (UCP2), UCP3, and the permeability transition pore have been integral to efforts to try to understand what role mitochondrial-derived ROS have in cells. In this piece we reflect on mitochondrial ROS and uncoupling proteins as signaling regulators. It seems that when it comes to ROS and uncoupling the proverb "Moderation in all things" is apt. PMID:23168277

  7. Effect of Acupuncture on Uncoupling Protein 1 Gene Expression for Brown Adipose Tissue of Obese Rats

    Institute of Scientific and Technical Information of China (English)

    刘志诚; 孙凤岷; 赵东红; 张中成; 孙志; 吴海涛; 徐炳国; 朱苗花; 李朝军

    2003-01-01

    Objective: To explore the effects of acupuncture on the expression of uncoupling protein 1(UCP1) gene of brown adipose tissue (BAT) in obese rats. Methods: The expression of UCP1 gene of BAT was determined with RT-PCR technique. The changes of body weight, Lee′s index, body fat, and the expression of UCP1 gene of BAT in obese rats were observed before and after acupuncture. Resuits:The body weight, Lee′s index, body fat in obese rats were all markedly higher than those in normal rats,but the expression of UCP1 gene of BAT in obese rats was all lower than that in normal rats. There were negative correlation between the obesity index and the expression of UCP1 gene in BAT. After acupuncture the marked effect of weight loss was achieved while the expression of UCP1 gene of BAT obviously increased in obese rats. Conclusion: The abnormal reduction for expression of UCP1 gene of BAT might be an important cause for the obesity. To promote the expression of UCP1 in obese organism might be an important cellular and molecular mechanism in anti-obesity effect by acupuncture.

  8. Cellular Automata

    OpenAIRE

    Bagnoli, Franco

    1998-01-01

    An introduction to cellular automata (both deterministic and probabilistic) with examples. Definition of deterministic automata, dynamical properties, damage spreading and Lyapunov exponents; probabilistic automata and Markov processes, nonequilibrium phase transitions, directed percolation, diffusion; simulation techniques, mean field. Investigation themes: life, epidemics, forest fires, percolation, modeling of ecosystems and speciation. They represent my notes for the school "Dynamical Mod...

  9. Uncoupling primer and releaser responses to pheromone in honey bees

    Science.gov (United States)

    Grozinger, Christina M.; Fischer, Patrick; Hampton, Jacob E.

    2007-05-01

    Pheromones produce dramatic behavioral and physiological responses in a wide variety of species. Releaser pheromones elicit rapid responses within seconds or minutes, while primer pheromones produce long-term changes which may take days to manifest. Honeybee queen mandibular pheromone (QMP) elicits multiple distinct behavioral and physiological responses in worker bees, as both a releaser and primer, and thus produces responses on vastly different time scales. In this study, we demonstrate that releaser and primer responses to QMP can be uncoupled. First, treatment with the juvenile hormone analog methoprene leaves a releaser response (attraction to QMP) intact, but modulates QMP’s primer effects on sucrose responsiveness. Secondly, two components of QMP (9-ODA and 9-HDA) do not elicit a releaser response (attraction) but are as effective as QMP at modulating a primer response, downregulation of foraging-related brain gene expression. These results suggest that different responses to a single pheromone may be produced via distinct pathways.

  10. A new design for reconfigurable XOR function based on cellular neural networks

    Science.gov (United States)

    Liu, Yanyi; Liu, Wenbo

    2014-10-01

    We have described a new method to construct the reconfigurable XOR logic circuit by using the modification of the standard uncoupled cellular neural network (CNN) cells. The modification of the cell is easier to implement in engineering applications. The scheme proposed in this paper, using the modification of standard uncoupled CNN cells, allows less hardware consumption in comparison to the utilisation of chaos computing system or harnessing piecewise-linear systems. The template parameters of the modified cell have been discussed, and the physical circuit implementing the reconfigurable two-input and three-input XOR function has also been presented.

  11. Mitochondrial and cellular mechanisms for managing lipid excess

    Directory of Open Access Journals (Sweden)

    Miguel A Aon

    2014-07-01

    Full Text Available Current scientific debates center on the impact of lipids and mitochondrial function on diverse aspects of human health, nutrition and disease, among them the association of lipotoxicity with the onset of insulin resistance in skeletal muscle, and with heart dysfunction in obesity and diabetes. Mitochondria play a fundamental role in aging and in prevalent acute or chronic diseases. Lipids are main mitochondrial fuels however these molecules can also behave as uncouplers and inhibitors of oxidative phosphorylation. Knowledge about the functional composition of these contradictory effects and their impact on mitochondrial-cellular energetics/redox status is incomplete.Cells store fatty acids (FAs as triacylglycerol and package them into cytoplasmic lipid droplets (LDs. New emerging data shows the LD as a highly dynamic storage pool of FAs that can be used for energy reserve. Lipid excess packaging into LDs can be seen as an adaptive response to fulfilling energy supply without hindering mitochondrial or cellular redox status and keeping low concentration of lipotoxic intermediates.Herein we review the mechanisms of action and utilization of lipids by mitochondria reported in liver, heart and skeletal muscle under relevant physiological situations, e.g. exercise. We report on perilipins, a family of proteins that associate with LDs in response to loading of cells with lipids. Evidence showing that in addition to physical contact, mitochondria and LDs exhibit metabolic interactions is presented and discussed. A hypothetical model of channeled lipid utilization by mitochondria is proposed. Direct delivery and channeled processing of lipids in mitochondria could represent a reliable and efficient way to maintain ROS within levels compatible with signaling while ensuring robust and reliable energy supply.

  12. Hydrodynamical simulations of coupled and uncoupled quintessence models - II. Galaxy clusters

    Science.gov (United States)

    Carlesi, Edoardo; Knebe, Alexander; Lewis, Geraint F.; Yepes, Gustavo

    2014-04-01

    We study the z = 0 properties of clusters (and large groups) of galaxies within the context of interacting and non-interacting quintessence cosmological models, using a series of adiabatic SPH simulations. Initially, we examine the average properties of groups and clusters, quantifying their differences in ΛCold Dark Matter (ΛCDM), uncoupled Dark Energy (uDE) and coupled Dark Energy (cDE) cosmologies. In particular, we focus upon radial profiles of the gas density, temperature and pressure, and we also investigate how the standard hydrodynamic equilibrium hypothesis holds in quintessence cosmologies. While we are able to confirm previous results about the distribution of baryons, we also find that the main discrepancy (with differences up to 20 per cent) can be seen in cluster pressure profiles. We then switch attention to individual structures, mapping each halo in quintessence cosmology to its ΛCDM counterpart. We are able to identify a series of small correlations between the coupling in the dark sector and halo spin, triaxiality and virialization ratio. When looking at spin and virialization of dark matter haloes, we find a weak (5 per cent) but systematic deviation in fifth force scenarios from ΛCDM.

  13. Targeting Cells With MR Imaging Probes: Cellular Interaction And Intracellular Magnetic Iron Oxide Nanoparticles Uptake In Brain Capillary Endothelial and Choroidal Plexus Epithelial Cells

    Science.gov (United States)

    Cambianica, I.; Bossi, M.; Gasco, P.; Gonzalez, W.; Idee, J. M.; Miserocchi, G.; Rigolio, R.; Chanana, M.; Morjan, I.; Wang, D.; Sancini, G.

    2010-10-01

    Magnetic iron oxide nanoparticles (NPs) are considered for various diagnostic and therapeutic applications in brain including their use as contrast agent for magnetic resonance imaging. In delivery application, the critical step is the transport across cell layers and the internalization of NPs into specific cells, a process often limited by poor targeting specificity and low internalization efficiency. The development of the models of brain endothelial cells and choroidal plexus epithelial cells in culture has allowed us to investigate into these mechanisms. Our strategy is aimed at exploring different routes to the entrapment of iron oxide NPs in these brain related cells. Here we demonstrated that not only cells endowed with a good phagocytic activity like activated macrophages but also endothelial brain capillary and choroidal plexus epithelial cells do internalize iron oxide NPs. Our study of the intracellular trafficking of NPs by TEM, and confocal microscopy revealed that NPs are mainly internalized by the endocytic pathway. Iron oxide NPs were dispersed in water and coated with 3,4-dihydroxyl-L-phenylalanine (L-DOPA) using standard procedures. Magnetic lipid NPs were prepared by NANOVECTOR: water in oil in water (W/O/W) microemulsion process has been applied to directly coat different iron based NPs by lipid layer or to encapsulate them into Solid Lipid Nanoparticles (SLNs). By these coating/loading the colloidal stability was improved without strong alteration of the particle size distribution. Magnetic lipid NPs could be reconstituted after freeze drying without appreciable changes in stability. L-DOPA coated NPs are stable in PBS and in MEM (Modified Eagle Medium) medium. The magnetic properties of these NPs were not altered by the coating processes. We investigated the cellular uptake, cytotoxicity, and interaction of these NPs with rat brain capillary endothelial (REB4) and choroidal plexus epithelial (Z310) cells. By means of widefield, confocal

  14. Cellular resilience.

    Science.gov (United States)

    Smirnova, Lena; Harris, Georgina; Leist, Marcel; Hartung, Thomas

    2015-01-01

    Cellular resilience describes the ability of a cell to cope with environmental changes such as toxicant exposure. If cellular metabolism does not collapse directly after the hit or end in programmed cell death, the ensuing stress responses promote a new homeostasis under stress. The processes of reverting "back to normal" and reversal of apoptosis ("anastasis") have been studied little at the cellular level. Cell types show astonishingly similar vulnerability to most toxicants, except for those that require a very specific target, metabolism or mechanism present only in specific cell types. The majority of chemicals triggers "general cytotoxicity" in any cell at similar concentrations. We hypothesize that cells differ less in their vulnerability to a given toxicant than in their resilience (coping with the "hit"). In many cases, cells do not return to the naive state after a toxic insult. The phenomena of "pre-conditioning", "tolerance" and "hormesis" describe this for low-dose exposures to toxicants that render the cell more resistant to subsequent hits. The defense and resilience programs include epigenetic changes that leave a "memory/scar" - an alteration as a consequence of the stress the cell has experienced. These memories might have long-term consequences, both positive (resistance) and negative, that contribute to chronic and delayed manifestations of hazard and, ultimately, disease. This article calls for more systematic analyses of how cells cope with toxic perturbations in the long-term after stressor withdrawal. A technical prerequisite for these are stable (organotypic) cultures and a characterization of stress response molecular networks. PMID:26536287

  15. Hydrophilic interaction liquid chromatography-tandem mass spectrometry quantitative method for the cellular analysis of varying structures of gemini surfactants designed as nanomaterial drug carriers.

    Science.gov (United States)

    Donkuru, McDonald; Michel, Deborah; Awad, Hanan; Katselis, George; El-Aneed, Anas

    2016-05-13

    Diquaternary gemini surfactants have successfully been used to form lipid-based nanoparticles that are able to compact, protect, and deliver genetic materials into cells. However, what happens to the gemini surfactants after they have released their therapeutic cargo is unknown. Such knowledge is critical to assess the quality, safety, and efficacy of gemini surfactant nanoparticles. We have developed a simple and rapid liquid chromatography electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method for the quantitative determination of various structures of gemini surfactants in cells. Hydrophilic interaction liquid chromatography (HILIC) was employed allowing for a short simple isocratic run of only 4min. The lower limit of detection (LLOD) was 3ng/mL. The method was valid to 18 structures of gemini surfactants belonging to two different structural families. A full method validation was performed for two lead compounds according to USFDA guidelines. The HILIC-MS/MS method was compatible with the physicochemical properties of gemini surfactants that bear a permanent positive charge with both hydrophilic and hydrophobic elements within their molecular structure. In addition, an effective liquid-liquid extraction method (98% recovery) was employed surpassing previously used extraction methods. The analysis of nanoparticle-treated cells showed an initial rise in the analyte intracellular concentration followed by a maximum and a somewhat more gradual decrease of the intracellular concentration. The observed intracellular depletion of the gemini surfactants may be attributable to their bio-transformation into metabolites and exocytosis from the host cells. Obtained cellular data showed a pattern that grants additional investigations, evaluating metabolite formation and assessing the subcellular distribution of tested compounds. PMID:27086283

  16. Possible basic and specific functions of plant uncoupling proteins (pUCP)

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr; Borecký, Jiří; Žáčková, Markéta; Costa, A. D. T.; Arruda, P.

    2001-01-01

    Roč. 21, č. 2 (2001), s. 237-245. ISSN 0144-8463 R&D Projects: GA ČR GA301/98/0568; GA AV ČR IAA5011106 Institutional research plan: CEZ:AV0Z5011922 Keywords : fatty acid-induced uncoupling * plant uncoupling mitochondrial protein * plant mitochondria Subject RIV: CE - Biochemistry Impact factor: 0.921, year: 2001

  17. Chronic Alcohol Consumption Leads to a Tissue Specific Expression of Uncoupling Protein-2

    OpenAIRE

    Graw, Jan A.; von Haefen, Clarissa; Poyraz, Deniz; Möbius, Nadine; Sifringer, Marco; Spies, Claudia D.

    2015-01-01

    Uncoupling proteins (UCPs) are anion channels that can decouple the mitochondrial respiratory chain. "Mild uncoupling" of internal respiration reduces free radical production and oxidative cell stress. Chronic alcohol consumption is a potent inducer of oxidative stress in multiple tissues and regulates UCP-2 and -4 expression in the brain. To analyse the impact of chronic alcohol intake on UCP-2 expression in tissues with high endogenous UCP-2 contents, male Wistar rats (n=34) were treated wi...

  18. The Role of Mitochondrial Uncoupling in the Development of Diabetic Nephropathy

    OpenAIRE

    Friederich Persson, Malou

    2012-01-01

    Diabetes is closely associated with increased oxidative stress, especially originating from the mitochondria. A mechanism to reduce increased mitochondria superoxide production is to reduce the mitochondria membrane potential by releasing protons across the mitochondria membrane. This phenomenon is referred to as mitochondria uncoupling since oxygen is consumed independently of ATP being produced and can be mediated by Uncoupling Proteins (UCPs). However, increased oxygen consumption is poten...

  19. A biophysical study on molecular physiology of the uncoupling proteins of the central nervous system.

    Science.gov (United States)

    Hoang, Tuan; Kuljanin, Miljan; Smith, Matthew D; Jelokhani-Niaraki, Masoud

    2015-01-01

    Mitochondrial inner membrane uncoupling proteins (UCPs) facilitate transmembrane (TM) proton flux and consequently reduce the membrane potential and ATP production. It has been proposed that the three neuronal human UCPs (UCP2, UCP4 and UCP5) in the central nervous system (CNS) play significant roles in reducing cellular oxidative stress. However, the structure and ion transport mechanism of these proteins remain relatively unexplored. Recently, we reported a novel expression system for obtaining functionally folded UCP1 in bacterial membranes and applied this system to obtain highly pure neuronal UCPs in high yields. In the present study, we report on the structure and function of the three neuronal UCP homologues. Reconstituted neuronal UCPs were dominantly helical in lipid membranes and transported protons in the presence of physiologically-relevant fatty acid (FA) activators. Under similar conditions, all neuronal UCPs also exhibited chloride transport activities that were partially inhibited by FAs. CD, fluorescence and MS measurements and semi-native gel electrophoresis collectively suggest that the reconstituted proteins self-associate in the lipid membranes. Based on SDS titration experiments and other evidence, a general molecular model for the monomeric, dimeric and tetrameric functional forms of UCPs in lipid membranes is proposed. In addition to their shared structural and ion transport features, neuronal UCPs differ in their conformations and proton transport activities (and possibly mechanism) in the presence of different FA activators. The differences in FA-activated UCP-mediated proton transport could serve as an essential factor in understanding and differentiating the physiological roles of UCP homologues in the CNS. PMID:26182433

  20. Cellulose-Microtubule Uncoupling Proteins Prevent Lateral Displacement of Microtubules during Cellulose Synthesis in Arabidopsis.

    Science.gov (United States)

    Liu, Zengyu; Schneider, Rene; Kesten, Christopher; Zhang, Yi; Somssich, Marc; Zhang, Youjun; Fernie, Alisdair R; Persson, Staffan

    2016-08-01

    Cellulose is the most abundant biopolymer on Earth and is the major contributor to plant morphogenesis. Cellulose is synthesized by plasma membrane-localized cellulose synthase complexes (CSCs). Nascent cellulose microfibrils become entangled in the cell wall, and further catalysis therefore drives the CSC forward through the membrane: a process guided by cortical microtubules via the protein CSI1/POM2. Still, it is unclear how the microtubules can withstand the forces generated by the motile CSCs to effectively direct CSC movement. Here, we identified a family of microtubule-associated proteins, the cellulose synthase-microtubule uncouplings (CMUs), that located as static puncta along cortical microtubules. Functional disruption of the CMUs caused lateral microtubule displacement and compromised microtubule-based guidance of CSC movement. CSCs that traversed the microtubules interacted with the microtubules via CSI1/POM2, which prompted the lateral microtubule displacement. Hence, we have revealed how microtubules can withstand the propulsion of the CSCs during cellulose biosynthesis and thus sustain anisotropic plant cell growth. PMID:27477947

  1. Quantum cellular automata

    Science.gov (United States)

    Porod, Wolfgang; Lent, Craig S.; Bernstein, Gary H.

    1994-06-01

    The Notre Dame group has developed a new paradigm for ultra-dense and ultra-fast information processing in nanoelectronic systems. These Quantum Cellular Automata (QCA's) are the first concrete proposal for a technology based on arrays of coupled quantum dots. The basic building block of these cellular arrays is the Notre Dame Logic Cell, as it has been called in the literature. The phenomenon of Coulomb exclusion, which is a synergistic interplay of quantum confinement and Coulomb interaction, leads to a bistable behavior of each cell which makes possible their use in large-scale cellular arrays. The physical interaction between neighboring cells has been exploited to implement logic functions. New functionality may be achieved in this fashion, and the Notre Dame group invented a versatile majority logic gate. In a series of papers, the feasibility of QCA wires, wire crossing, inverters, and Boolean logic gates was demonstrated. A major finding is that all logic functions may be integrated in a hierarchial fashion which allows the design of complicated QCA structures. The most complicated system which was simulated to date is a one-bit full adder consisting of some 200 cells. In addition to exploring these new concepts, efforts are under way to physically realize such structures both in semiconductor and metal systems. Extensive modeling work of semiconductor quantum dot structures has helped identify optimum design parameters for QCA experimental implementations.

  2. Species-dependent effects of the phenolic herbicide ioxynil with potential thyroid hormone disrupting activity: modulation of its cellular uptake and activity by interaction with serum thyroid hormone-binding proteins

    Institute of Scientific and Technical Information of China (English)

    Sakura Akiyoshi; Gobun Sai; Kiyoshi Yamauchi

    2012-01-01

    Ioxynil,a phenolic herbicide,is known to exert thyroid hormone (TH) disrupting activity by interfering with TH-binding to plasma proteins and a step of the cellular TH-signaling pathway in restricted animal species.However,comparative studies are still lacking on the TH disruption.We investigated the interaction of [125I]ioxynil with serum proteins from rainbow trout,bullfrog,chicken,pig,rat,and mouse,using native polyacrylamide gel electrophoresis.Candidate ioxynil-binding proteins,which included lipoproteins,albumin and transthyretin (TTR),differed among the vertebrates tested.Rainbow trout and bullfrog tadpole serum had the lowest binding activity for ioxynil,whereas the eutherian serum had the highest binding activity.The cellular uptake of,and response to,ioxynil were suppressed by rat serum greater than by tadpole serum.The cellular uptake of [125I]ioxynil competed strongly with phenols with a single ring,but not with THs.Our results suggested that ioxynil interferes with TH homeostasis in plasma and with a step of cellular TH-signaling pathwav other than TH-uptake system in a snecies-specific manner.

  3. Genipin-induced inhibition of uncoupling protein-2 sensitizes drug-resistant cancer cells to cytotoxic agents.

    Directory of Open Access Journals (Sweden)

    Ryan J Mailloux

    Full Text Available Uncoupling protein-2 (UCP2 is known to suppress mitochondrial reactive oxygen species (ROS production and is employed by drug-resistant cancer cells to mitigate oxidative stress. Using the drug-sensitive HL-60 cells and the drug-resistant MX2 subline as model systems, we show that genipin, a UCP2 inhibitor, sensitizes drug-resistant cells to cytotoxic agents. Increased MX2 cell death was observed upon co-treatment with genipin and different doses of menadione, doxorubicin, and epirubicin. DCFH-DA fluorimetry revealed that the increase in MX2 cell death was accompanied by enhanced cellular ROS levels. The drug-induced increase in ROS was linked to genipin-mediated inhibition of mitochondrial proton leak. State 4 and resting cellular respiratory rates were higher in the MX2 cells in comparison to the HL-60 cells, and the increased respiration was readily suppressed by genipin in the MX2 cells. UCP2 accounted for a remarkable 37% of the resting cellular oxygen consumption indicating that the MX2 cells are functionally reliant on this protein. Higher amounts of UCP2 protein were detected in the MX2 versus the HL-60 mitochondria. The observed effects of genipin were absent in the HL-60 cells pointing to the selectivity of this natural product for drug-resistant cells. The specificity of genipin for UCP2 was confirmed using CHO cells stably expressing UCP2 in which genipin induced an ∼22% decrease in state 4 respiration. These effects were absent in empty vector CHO cells expressing no UCP2. Thus, the chemical inhibition of UCP2 with genipin sensitizes multidrug-resistant cancer cells to cytotoxic agents.

  4. Interactive effects of CO2 and trace metals on the proteasome activity and cellular stress response of marine bivalves Crassostrea virginica and Mercenaria mercenaria

    International Nuclear Information System (INIS)

    Highlights: • Elevated PCO2 enhanced accumulation of Cu and Cd in the gills of mollusks. • The proteasome activities were affected by metals but robust to elevated PCO2. • Exposure to Cd and Cu had opposite effects on the proteasome activity. • Combined exposure to Cu and elevated PCO2 negatively affected energy status. - Abstract: Increased anthropogenic emission of CO2 changes the carbonate chemistry and decreases the pH of the ocean. This can affect the speciation and the bioavailability of metals in polluted habitats such as estuaries. However, the effects of acidification on metal accumulation and stress response in estuarine organisms including bivalves are poorly understood. We studied the interactive effects of CO2 and two common metal pollutants, copper (Cu) and cadmium (Cd), on metal accumulation, intracellular ATP/ubiquitin-dependent protein degradation, stress response and energy metabolism in two common estuarine bivalves—Crassostrea virginica (eastern oyster) and Mercenaria mercenaria (hard shell clam). Bivalves were exposed for 4–5 weeks to clean seawater (control) and to either 50 μg L−1 Cu or 50 μg L−1 Cd at one of three partial pressures of CO2 (PCO2 ∼395, ∼800 and ∼1500 μatm) representative of the present-day conditions and projections of the Intergovernmental Panel for Climate Change (IPCC) for the years 2100 and 2250, respectively. Clams accumulated lower metal burdens than oysters, and elevated PCO2 enhanced the Cd and Cu accumulation in mantle tissues in both species. Higher Cd and Cu burdens were associated with elevated mRNA expression of metal binding proteins metallothionein and ferritin. In the absence of added metals, proteasome activities of clams and oysters were robust to elevated PCO2, but PCO2 modulated the proteasome response to metals. Cd exposure stimulated the chymotrypsin-like activity of the oyster proteasome at all CO2 levels. In contrast, trypsin- and caspase-like activities of the oyster proteasome

  5. Interactive effects of CO₂ and trace metals on the proteasome activity and cellular stress response of marine bivalves Crassostrea virginica and Mercenaria mercenaria

    Energy Technology Data Exchange (ETDEWEB)

    Götze, Sandra [Alfred Wegener Institute, Helmholtz Centre for Polar, Marine Research, Functional Ecology, 27570 Bremerhaven (Germany); Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223 (United States); Matoo, Omera B. [Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223 (United States); Beniash, Elia [Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA (United States); Saborowski, Reinhard [Alfred Wegener Institute, Helmholtz Centre for Polar, Marine Research, Functional Ecology, 27570 Bremerhaven (Germany); Sokolova, Inna M., E-mail: isokolov@uncc.edu [Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223 (United States)

    2014-04-01

    Highlights: • Elevated PCO₂ enhanced accumulation of Cu and Cd in the gills of mollusks. • The proteasome activities were affected by metals but robust to elevated PCO₂. • Exposure to Cd and Cu had opposite effects on the proteasome activity. • Combined exposure to Cu and elevated PCO₂ negatively affected energy status. - Abstract: Increased anthropogenic emission of CO₂ changes the carbonate chemistry and decreases the pH of the ocean. This can affect the speciation and the bioavailability of metals in polluted habitats such as estuaries. However, the effects of acidification on metal accumulation and stress response in estuarine organisms including bivalves are poorly understood. We studied the interactive effects of CO₂ and two common metal pollutants, copper (Cu) and cadmium (Cd), on metal accumulation, intracellular ATP/ubiquitin-dependent protein degradation, stress response and energy metabolism in two common estuarine bivalves—Crassostrea virginica (eastern oyster) and Mercenaria mercenaria (hard shell clam). Bivalves were exposed for 4–5 weeks to clean seawater (control) and to either 50 μg L⁻¹ Cu or 50 μg L⁻¹ Cd at one of three partial pressures of CO₂ PCO₂ ~395, ~800 and ~1500 μatm) representative of the present-day conditions and projections of the Intergovernmental Panel for Climate Change (IPCC) for the years 2100 and 2250, respectively. Clams accumulated lower metal burdens than oysters, and elevated PCO₂ enhanced the Cd and Cu accumulation in mantle tissues in both species. Higher Cd and Cu burdens were associated with elevated mRNA expression of metal binding proteins metallothionein and ferritin. In the absence of added metals, proteasome activities of clams and oysters were robust to elevated PCO₂, but PCO₂ modulated the proteasome response to metals. Cd exposure stimulated the chymotrypsin-like activity of the oyster proteasome

  6. Thermodynamics of Anharmonic Systems: Uncoupled Mode Approximations for Molecules.

    Science.gov (United States)

    Li, Yi-Pei; Bell, Alexis T; Head-Gordon, Martin

    2016-06-14

    The partition functions, heat capacities, entropies, and enthalpies of selected molecules were calculated using uncoupled mode (UM) approximations, where the full-dimensional potential energy surface for internal motions was modeled as a sum of independent one-dimensional potentials for each mode. The computational cost of such approaches scales the same with molecular size as standard harmonic oscillator vibrational analysis using harmonic frequencies (HO(hf)). To compute thermodynamic properties, a computational protocol for obtaining the energy levels of each mode was established. The accuracy of the UM approximation depends strongly on how the one-dimensional potentials of each modes are defined. If the potentials are determined by the energy as a function of displacement along each normal mode (UM-N), the accuracies of the calculated thermodynamic properties are not significantly improved versus the HO(hf) model. Significant improvements can be achieved by constructing potentials for internal rotations and vibrations using the energy surfaces along the torsional coordinates and the remaining vibrational normal modes, respectively (UM-VT). For hydrogen peroxide and its isotopologs at 300 K, UM-VT captures more than 70% of the partition functions on average. By contrast, the HO(hf) model and UM-N can capture no more than 50%. For a selected test set of C2 to C8 linear and branched alkanes and species with different moieties, the enthalpies calculated using the HO(hf) model, UM-N, and UM-VT are all quite accurate comparing with reference values though the RMS errors of the HO model and UM-N are slightly higher than UM-VT. However, the accuracies in entropy calculations differ significantly between these three models. For the same test set, the RMS error of the standard entropies calculated by UM-VT is 2.18 cal mol(-1) K(-1) at 1000 K. By contrast, the RMS error obtained using the HO model and UM-N are 6.42 and 5.73 cal mol(-1) K(-1), respectively. For a test set

  7. Uncoupling effect of fatty acids on heart muscle mitochondria and submitochondrial particles.

    Science.gov (United States)

    Dedukhova, V I; Mokhova, E N; Skulachev, V P; Starkov, A A; Arrigoni-Martelli, E; Bobyleva, V A

    1991-12-16

    The effect of ATP/ADP-antiporter inhibitors on palmitate-induced uncoupling was studied in heart muscle mitochondria and inside-out submitochondrial particles. In both systems palmitate is found to decrease the respiration-generated membrane potential. In mitochondria, this effect is specifically abolished by carboxyatractylate (CAtr) a non-penetrating inhibitor of antiporter. In submitochondrial particles, CAtr does not abolish the palmitate-induced potential decrease. At the same time, bongkrekic acid, a penetrating inhibitor of the antiporter, suppresses the palmitate effect on the potential both in mitochondria and particles. Palmitoyl-CoA which is known to inhibit the antiporter in mitochondria as well as in particles decreases the palmitate uncoupling efficiency in both these systems. These data are in agreement with the hypothesis that the ATP/ADP-antiporter is involved in the action of free fatty acids as natural uncouplers of oxidative phosphorylation. PMID:1765167

  8. Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle

    DEFF Research Database (Denmark)

    Fernström, Maria; Tonkonogi, Michail; Sahlin, Kent

    2004-01-01

    increased uncoupled respiration (UCR). Subjects were investigated with muscle biopsies before and after acute exercise (75 min of cycling at 70% of .VO2peak) or 6 weeks endurance training. Mitochondria were isolated and respiration measured in the absence (UCR or state 4) and presence of ADP (coupled...... of CS (a marker of mitochondrial volume) UCP3 and UCR decreased by 54% and 18%(P < 0.05). CS increased by 43% after acute exercise and remained elevated after 3 h of recovery (P < 0.05), whereas the other muscle parameters remained unchanged. An intriguing finding was that acute exercise reversibly......Mitochondrial proteins such as uncoupling protein 3 (UCP3) and adenine nucleotide translocase (ANT) may mediate back-leakage of protons and serve as uncouplers of oxidative phosphorylation. We hypothesized that UCP3 and ANT increase after prolonged exercise and/or endurance training, resulting in...

  9. N-terminally glutamate-substituted analogue of gramicidin A as protonophore and selective mitochondrial uncoupler.

    Directory of Open Access Journals (Sweden)

    Alexandra I Sorochkina

    Full Text Available Limited uncoupling of oxidative phosphorylation could be beneficial for cells by preventing excessive generation of reactive oxygen species. Typical uncouplers are weak organic acids capable of permeating across membranes with a narrow gap between efficacy and toxicity. Aimed at designing a nontoxic uncoupler, the protonatable amino acid residue Glu was substituted for Val at the N-terminus of the pentadecapeptide gramicidin A (gA. The modified peptide [Glu1]gA exhibited high uncoupling activity in isolated mitochondria, in particular, abolishing membrane potential at the inner mitochondrial membrane with the same or even larger efficacy as gA. With mitochondria in cell culture, the depolarizing activity of [Glu1]gA was observed at concentrations by an order of magnitude lower than those of gA. On the contrary, [Glu1]gA was much less potent in forming proton channels in planar lipid bilayers than gA. Remarkably, at uncoupling concentrations, [Glu1]gA did not alter cell morphology and was nontoxic in MTT test, in contrast to gA showing high toxicity. The difference in the behavior of [Glu1]gA and gA in natural and artificial membranes could be ascribed to increased capability of [Glu1]gA to permeate through membranes and/or redistribute between different membranes. Based on the protective role of mild uncoupling, [Glu1]gA and some other proton-conducting gA analogues may be considered as prototypes of prospective therapeutic agents.

  10. N-terminally glutamate-substituted analogue of gramicidin A as protonophore and selective mitochondrial uncoupler.

    Science.gov (United States)

    Sorochkina, Alexandra I; Plotnikov, Egor Y; Rokitskaya, Tatyana I; Kovalchuk, Sergei I; Kotova, Elena A; Sychev, Sergei V; Zorov, Dmitry B; Antonenko, Yuri N

    2012-01-01

    Limited uncoupling of oxidative phosphorylation could be beneficial for cells by preventing excessive generation of reactive oxygen species. Typical uncouplers are weak organic acids capable of permeating across membranes with a narrow gap between efficacy and toxicity. Aimed at designing a nontoxic uncoupler, the protonatable amino acid residue Glu was substituted for Val at the N-terminus of the pentadecapeptide gramicidin A (gA). The modified peptide [Glu1]gA exhibited high uncoupling activity in isolated mitochondria, in particular, abolishing membrane potential at the inner mitochondrial membrane with the same or even larger efficacy as gA. With mitochondria in cell culture, the depolarizing activity of [Glu1]gA was observed at concentrations by an order of magnitude lower than those of gA. On the contrary, [Glu1]gA was much less potent in forming proton channels in planar lipid bilayers than gA. Remarkably, at uncoupling concentrations, [Glu1]gA did not alter cell morphology and was nontoxic in MTT test, in contrast to gA showing high toxicity. The difference in the behavior of [Glu1]gA and gA in natural and artificial membranes could be ascribed to increased capability of [Glu1]gA to permeate through membranes and/or redistribute between different membranes. Based on the protective role of mild uncoupling, [Glu1]gA and some other proton-conducting gA analogues may be considered as prototypes of prospective therapeutic agents. PMID:22911866

  11. Fatty acid circuit as a physiological mechanism of uncoupling of oxidative phosphorylation.

    Science.gov (United States)

    Skulachev, V P

    1991-12-01

    Free fatty acids, natural uncouplers of oxidative phosphorylation, are shown to differ from artificial ones in that they fail to increase conductance of phospholipid bilayers which are permeable for the protonated form of fatty acids but impermeable for their anionic form. Recent studies have revealed that uncoupling by fatty acids in mitochondria is mediated by the ATP/ADP antiporter and, in brown fat, by thermogenin which is structurally very similar to the antiporter. It is suggested that both the ATP/ADP antiporter and thermogenin facilitate translocation of the fatty anions through the mitochondrial membrane. PMID:1756853

  12. Mass, energy, and exergy balance analysis of chemical looping with oxygen uncoupling (CLOU) process

    International Nuclear Information System (INIS)

    Highlights: • A CLOU reactor system using a CuO-based OC and coal as fuel is analyzed. • Possible operational regions for the chosen OC are identified. • Different heat balance scenarios are investigated. • The second-law efficiency of the system is evaluated. • Various design aspects and process modelling relationships are discussed. - Abstract: Chemical looping with oxygen uncoupling (CLOU) is a promising concept for efficient combustion of solid fuels with an inherent capture of the greenhouse gas CO2. This paper presents a CLOU process scheme with stoichiometric mass, energy, and exergy balances. A CLOU reactor system using medium volatile bituminous coal as fuel and silica-supported CuO as an oxygen carrier is analyzed. The analysis includes the estimation of various design and operational parameters, thermal considerations, and evaluation of the overall performance. The operation of a reactor system of two interacting circulating fluidized beds (CFBs) is greatly influenced by the hydrodynamics. For the CuO oxygen carrier, the hydrodynamic operating range appeared feasible considering the maximum solid circulation rates in current CFB boilers. Depending upon the reactor temperatures, oxygen carrier inventories of 400–680 kg/MW in the system were found necessary for stoichiometric combustion of the fuel. The temperature difference between the reactors should not exceed 50 °C, as otherwise, problems may arise with the heat balance. Exergetic efficiencies in the range of 63–70% were obtained for different combinations of relevant design parameters. It is evident that the possible operating conditions in the system are closely related to the properties of the chosen oxygen carrier. However, the calculation procedure and design criteria presented here are applicable to any oxygen carrier to be used in the process

  13. Concentration of rat brown adipose tissue uncoupling protein may not be correlated with 3H-GDP binding

    International Nuclear Information System (INIS)

    Rats fed diets low in protein or exposed to cold show an increase in brown adipose tissue (BAT) mitochondrial 3H-GDP binding. To investigate this phenomenon further, the uncoupling protein associated with BAT function was measured immunochemically on nitrocellulose blots. Quantitation of uncoupling protein was achieved by densitometer scanning with a BioRad densitometer. Peaks were integrated with Chromatochart software and an Apple IIe computer. A standard curve of purified uncoupling protein (50 to 500 ng) was used to calculate uncoupling protein concentration. There is a 1.5-fold increase in uncoupling protein per mg of protein in BAT mitochondria from rats exposed to cold for 15 days. There was no decrease in uncoupling protein from rats exposed to the cold followed by 24 h at 270C although 3H-GDP binding had decreased by half. Rats fed diets containing either 5 or 15% lactalbumin for 3 weeks did not show differences in uncoupling protein concentration although 3H-GDP binding was 1.5-fold greater in BAT mitochondria from the low protein group. These results indicate that GDP binding does not necessarily reflect the concentration of uncoupling protein in BAT mitochondria

  14. Single-cycle immunodeficiency viruses provide strategies for uncoupling in vivo expression levels from viral replicative capacity and for mimicking live-attenuated SIV vaccines

    International Nuclear Information System (INIS)

    To reduce the risks associated with live-attenuated immunodeficiency virus vaccines, single-cycle immunodeficiency viruses (SCIVs) were developed by primer complementation and production of the vaccine in the absence of vif in a vif-independent cell line. After a single intravenous injection of SCIVs into rhesus monkeys, peak viral RNA levels of 103 to 104 copies/ml plasma were observed, indicating efficient expression of SCIV in the vaccinee. After booster immunizations with SCIVs, SIV-specific humoral and cellular immune responses were observed. Although the vaccine doses used in this pilot study could not protect vaccinees from subsequent intravenous challenge with pathogenic SIVmac239, our results demonstrate that the novel SCIV approach allows us to uncouple in vivo expression levels from the viral replicative capacity facilitating the analysis of the relationship between viral expression levels or viral genes and immune responses induced by SIV

  15. Uncoupled achromatic condition of a dog-leg system with the presence of RF cavities

    CERN Document Server

    Geng, Huiping

    2013-01-01

    To merge the beam from either of the two injectors to the main linac, a dog-leg system will be employed in the second Medium Energy Beam Transport (MEBT2) line of the China ADS driving accelerator. The achromatic condition has to be guaranteed to avoid beam center excursion against energy jitter. RF cavities were found indispensable to control the bunch length growth in the dog-leg system of MEBT2. The full uncoupling between transverse and longitudinal plane is desired to minimize the growth of projected rms emittances. The uncoupled achromatic condition of this dogleg system with the presence of RF bunching cavities will be deduced using the method of transfer matrixes. It is found that to fulfil the uncoupling condition, the distance between the bunching cavities is uniquely determined by the maximum energy gain of the RF cavities. The theoretical analysis is verified by the simulation code TraceWin. The space charge effect on the uncoupled achromatic condition and the beam emittance growth will also be di...

  16. Uncoupling of the autonomic and cardiovascular systems in acute brain injury.

    Science.gov (United States)

    Goldstein, B; Toweill, D; Lai, S; Sonnenthal, K; Kimberly, B

    1998-10-01

    We hypothesized that acute brain injury results in decreased heart rate (HR) variability and baroreflex sensitivity indicative of uncoupling of the autonomic and cardiovascular systems and that the degree of uncoupling should be proportional to the degree of neurological injury. We used HR and blood pressure (BP) power spectral analysis to measure neuroautonomic regulation of HR and BP and the transfer function magnitude (TF) between BP and HR as a measure of baroreflex modulation of HR. In 24 brain-injured patients [anoxic/ischemic injury (n = 7), multiple trauma (n = 6), head trauma (n = 5), central nervous system infection (n = 4), and intracranial hemorrhage (n = 2)], neurological injury and survival was associated with low-frequency (0.01-0.15 Hz) HR and BP power and TF. Brain-dead patients showed decreased low-frequency HR power [0. 51 +/- 0.36 (SE) vs. 2.54 +/- 0.14 beats/min2, P = 0.03] and TF [0. 61 +/- 0.16 (SE) vs. 1.29 +/- 0.07 beats . min-1 . mmHg-1, P = 0.05] compared with non-brain-dead patients. We conclude that 1) severity of neurological injury and outcome are inversely associated with HR and BP variability and 2) there is direct evidence for cardiovascular and autonomic uncoupling in acute brain injury with complete uncoupling during brain death. PMID:9756562

  17. Roles of p53 in ionizing radiation-induced cell cycle uncoupling

    International Nuclear Information System (INIS)

    Objective: To explore the roles of p53 in ionizing radiation induced MCF-7 cell cycle uncoupling. Methods: The p53 knock-down models was established in MCF-7 with retrovirus packaged particles from 293T cells through calcium acid phosphate co-precipitation, then Western blot was used to detect the protein expression. Flow cytometry(FCM) was used to analyze the cell cycle uncoupling and polyploid after irradiation. Results: Compared with p53+/+ group, the percentages of G0/G1 cells in p53-/- group decreased, while those of S and G2 + M increased (P0/G1, S cells, and the increase of G2 + M cells. The increase of 2N cells and decrease of 4N and 8N cells were observed in both p53+/+ and p53-/- cells. Compared with p53+/+ + IR group, the decrease of G0/G1 and S cells and the increase of G2 + M cells were significant (P-/- + IR groups. 2N cells decreased, 4N cells increased, but no changes in 8 N cells occurred. Conclusion: Radiation might induce G2 arrest and cycle uncoupling, p53 plays a role in the regulation of G2 arrest, but no role in cycle uncoupling. (authors)

  18. Critical appraisal of the MTT assay in the presence of rottlerin and uncouplers.

    Science.gov (United States)

    Maioli, Emanuela; Torricelli, Claudia; Fortino, Vittoria; Carlucci, Filippo; Tommassini, Valentina; Pacini, Adriana

    2009-01-01

    Rottlerin is a natural product isolated from Mallotus philippinensis. This polyphenolic compound, originally described as a selective inhibitor of PKCδ, can inhibit many other PKC-unrelated kinases and has a number of biological actions, including mitochondrial uncoupling effects. We recently found that Rottlerin inhibits the transcription factor nuclear factor κB in different cell types, causing downregulation of cyclin D1 and growth arrest. The present study was carried out to clarify the surprising lack of effect of Rottlerin on MCF-7 cell viability, assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. We found that Rottlerin causes overestimation of the MTT test, leading to inconsistent results between cell number and cell viability. Rottlerin, however, strongly differs from other antioxidant polyphenols, which directly reduce tetrazolium salts, since it does not exhibit any reactivity toward the tetrazolium salts in vitro nor does it modulate lactate dehydrogenase activity. The interference in the MTT assay occurred only in cultured cells, concomitantly with a decrease in the energy charge. Because the same MTT overestimation was observed in the presence of uncoupling agents, we conclude that the Rottlerin artifact is linked to its uncoupling action that, by accelerating oxidative chain, accidentally results in enhanced MTT reduction. These results suggest caution in the use of the MTT assay in the presence of Rottlerin and uncouplers in general. PMID:19957063

  19. Critical Appraisal of the MTT Assay in the Presence of Rottlerin and Uncouplers

    Directory of Open Access Journals (Sweden)

    Carlucci Filippo

    2009-01-01

    Full Text Available Abstract Rottlerin is a natural product isolated from Mallotus philippinensis. This polyphenolic compound, originally described as a selective inhibitor of PKCδ, can inhibit many other PKC-unrelated kinases and has a number of biological actions, including mitochondrial uncoupling effects. We recently found that Rottlerin inhibits the transcription factor nuclear factor κB in different cell types, causing downregulation of cyclin D1 and growth arrest. The present study was carried out to clarify the surprising lack of effect of Rottlerin on MCF-7 cell viability, assessed by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT test. We found that Rottlerin causes overestimation of the MTT test, leading to inconsistent results between cell number and cell viability. Rottlerin, however, strongly differs from other antioxidant polyphenols, which directly reduce tetrazolium salts, since it does not exhibit any reactivity toward the tetrazolium salts in vitro nor does it modulate lactate dehydrogenase activity. The interference in the MTT assay occurred only in cultured cells, concomitantly with a decrease in the energy charge. Because the same MTT overestimation was observed in the presence of uncoupling agents, we conclude that the Rottlerin artifact is linked to its uncoupling action that, by accelerating oxidative chain, accidentally results in enhanced MTT reduction. These results suggest caution in the use of the MTT assay in the presence of Rottlerin and uncouplers in general.

  20. Critical Appraisal of the MTT Assay in the Presence of Rottlerin and Uncouplers

    Directory of Open Access Journals (Sweden)

    Maioli Emanuela

    2009-12-01

    Full Text Available Abstract Rottlerin is a natural product isolated from Mallotus philippinensis. This polyphenolic compound, originally described as a selective inhibitor of PKCδ, can inhibit many other PKC-unrelated kinases and has a number of biological actions, including mitochondrial uncoupling effects. We recently found that Rottlerin inhibits the transcription factor nuclear factor κB in different cell types, causing downregulation of cyclin D1 and growth arrest. The present study was carried out to clarify the surprising lack of effect of Rottlerin on MCF-7 cell viability, assessed by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT test. We found that Rottlerin causes overestimation of the MTT test, leading to inconsistent results between cell number and cell viability. Rottlerin, however, strongly differs from other antioxidant polyphenols, which directly reduce tetrazolium salts, since it does not exhibit any reactivity toward the tetrazolium salts in vitro nor does it modulate lactate dehydrogenase activity. The interference in the MTT assay occurred only in cultured cells, concomitantly with a decrease in the energy charge. Because the same MTT overestimation was observed in the presence of uncoupling agents, we conclude that the Rottlerin artifact is linked to its uncoupling action that, by accelerating oxidative chain, accidentally results in enhanced MTT reduction. These results suggest caution in the use of the MTT assay in the presence of Rottlerin and uncouplers in general.

  1. SET overexpression in HEK293 cells regulates mitochondrial uncoupling proteins levels within a mitochondrial fission/reduced autophagic flux scenario

    International Nuclear Information System (INIS)

    We hypothesized that SET, a protein accumulated in some cancer types and Alzheimer disease, is involved in cell death through mitochondrial mechanisms. We addressed the mRNA and protein levels of the mitochondrial uncoupling proteins UCP1, UCP2 and UCP3 (S and L isoforms) by quantitative real-time PCR and immunofluorescence as well as other mitochondrial involvements, in HEK293 cells overexpressing the SET protein (HEK293/SET), either in the presence or absence of oxidative stress induced by the pro-oxidant t-butyl hydroperoxide (t-BHP). SET overexpression in HEK293 cells decreased UCP1 and increased UCP2 and UCP3 (S/L) mRNA and protein levels, whilst also preventing lipid peroxidation and decreasing the content of cellular ATP. SET overexpression also (i) decreased the area of mitochondria and increased the number of organelles and lysosomes, (ii) increased mitochondrial fission, as demonstrated by increased FIS1 mRNA and FIS-1 protein levels, an apparent accumulation of DRP-1 protein, and an increase in the VDAC protein level, and (iii) reduced autophagic flux, as demonstrated by a decrease in LC3B lipidation (LC3B-II) in the presence of chloroquine. Therefore, SET overexpression in HEK293 cells promotes mitochondrial fission and reduces autophagic flux in apparent association with up-regulation of UCP2 and UCP3; this implies a potential involvement in cellular processes that are deregulated such as in Alzheimer's disease and cancer. - Highlights: • SET, UCPs and autophagy prevention are correlated. • SET action has mitochondrial involvement. • UCP2/3 may reduce ROS and prevent autophagy. • SET protects cell from ROS via UCP2/3

  2. SET overexpression in HEK293 cells regulates mitochondrial uncoupling proteins levels within a mitochondrial fission/reduced autophagic flux scenario

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Luciana O.; Goto, Renata N. [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Neto, Marinaldo P.C. [Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Sousa, Lucas O. [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Curti, Carlos [Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Leopoldino, Andréia M., E-mail: andreiaml@usp.br [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil)

    2015-03-06

    We hypothesized that SET, a protein accumulated in some cancer types and Alzheimer disease, is involved in cell death through mitochondrial mechanisms. We addressed the mRNA and protein levels of the mitochondrial uncoupling proteins UCP1, UCP2 and UCP3 (S and L isoforms) by quantitative real-time PCR and immunofluorescence as well as other mitochondrial involvements, in HEK293 cells overexpressing the SET protein (HEK293/SET), either in the presence or absence of oxidative stress induced by the pro-oxidant t-butyl hydroperoxide (t-BHP). SET overexpression in HEK293 cells decreased UCP1 and increased UCP2 and UCP3 (S/L) mRNA and protein levels, whilst also preventing lipid peroxidation and decreasing the content of cellular ATP. SET overexpression also (i) decreased the area of mitochondria and increased the number of organelles and lysosomes, (ii) increased mitochondrial fission, as demonstrated by increased FIS1 mRNA and FIS-1 protein levels, an apparent accumulation of DRP-1 protein, and an increase in the VDAC protein level, and (iii) reduced autophagic flux, as demonstrated by a decrease in LC3B lipidation (LC3B-II) in the presence of chloroquine. Therefore, SET overexpression in HEK293 cells promotes mitochondrial fission and reduces autophagic flux in apparent association with up-regulation of UCP2 and UCP3; this implies a potential involvement in cellular processes that are deregulated such as in Alzheimer's disease and cancer. - Highlights: • SET, UCPs and autophagy prevention are correlated. • SET action has mitochondrial involvement. • UCP2/3 may reduce ROS and prevent autophagy. • SET protects cell from ROS via UCP2/3.

  3. Cyanide-induced death of dopaminergic cells is mediated by uncoupling protein-2 up-regulation and reduced Bcl-2 expression

    International Nuclear Information System (INIS)

    Cyanide is a potent inhibitor of mitochondrial oxidative metabolism and produces mitochondria-mediated death of dopaminergic neurons and sublethal intoxications that are associated with a Parkinson-like syndrome. Cyanide toxicity is enhanced when mitochondrial uncoupling is stimulated following up-regulation of uncoupling protein-2 (UCP-2). In this study, the role of a pro-survival protein, Bcl-2, in cyanide-mediated cell death was determined in a rat dopaminergic immortalized mesencephalic cell line (N27 cells). Following pharmacological up-regulation of UCP-2 by treatment with Wy14,643, cyanide reduced cellular Bcl-2 expression by increasing proteasomal degradation of the protein. The increased turnover of Bcl-2 was mediated by an increase of oxidative stress following UCP-2 up-regulation. The oxidative stress involved depletion of mitochondrial glutathione (mtGSH) and increased H2O2 generation. Repletion of mtGSH by loading cells with glutathione ethyl ester reduced H2O2 generation and in turn blocked the cyanide-induced decrease of Bcl-2. To determine if UCP-2 mediated the response, RNAi knock down was conducted. The RNAi decreased cyanide-induced depletion of mtGSH, reduced H2O2 accumulation, and inhibited down-regulation of Bcl-2, thus blocking cell death. To confirm the role of Bcl-2 down-regulation in the cell death, it was shown that over-expression of Bcl-2 by cDNA transfection attenuated the enhancement of cyanide toxicity after UCP-2 up-regulation. It was concluded that UCP-2 up-regulation sensitizes cells to cyanide by increasing cellular oxidative stress, leading to an increase of Bcl-2 degradation. Then the reduced Bcl-2 levels sensitize the cells to cyanide-mediated cell death.

  4. Single nucleotide polymorphisms linked to mitochondrial uncoupling protein genes UCP2 and UCP3 affect mitochondrial metabolism and healthy aging in female nonagenarians.

    Science.gov (United States)

    Kim, Sangkyu; Myers, Leann; Ravussin, Eric; Cherry, Katie E; Jazwinski, S Michal

    2016-08-01

    Energy expenditure decreases with age, but in the oldest-old, energy demand for maintenance of body functions increases with declining health. Uncoupling proteins have profound impact on mitochondrial metabolic processes; therefore, we focused attention on mitochondrial uncoupling protein genes. Alongside resting metabolic rate (RMR), two SNPs in the promoter region of UCP2 were associated with healthy aging. These SNPs mark potential binding sites for several transcription factors; thus, they may affect expression of the gene. A third SNP in the 3'-UTR of UCP3 interacted with RMR. This UCP3 SNP is known to impact UCP3 expression in tissue culture cells, and it has been associated with body weight and mitochondrial energy metabolism. The significant main effects of the UCP2 SNPs and the interaction effect of the UCP3 SNP were also observed after controlling for fat-free mass (FFM) and physical-activity related energy consumption. The association of UCP2/3 with healthy aging was not found in males. Thus, our study provides evidence that the genetic risk factors for healthy aging differ in males and females, as expected from the differences in the phenotypes associated with healthy aging between the two sexes. It also has implications for how mitochondrial function changes during aging. PMID:26965008

  5. A multi-scale approach to colorectal cancer: from a biochemical- interaction signaling-network level, to multi-cellular dynamics of malignant transformation. Interplay with mutations and onco-protein inhibitor drugs.

    Science.gov (United States)

    Tortolina, L; Castagnino, N; De Ambrosi, C; Moran, E; Patrone, F; Ballestrero, A; Parodi, S

    2012-05-01

    This review article is part of a special Current Cancer Drug Targets issue devoted to colorectal cancer and molecularly targeted treatments. In our paper we made an attempt to connect more basic aspects with preclinical, pharmacological / therapeutic and clinical aspects. Reconstruction of a Molecular Interaction Map (MIM) comprising an important part of the G0 - G1 - S cell cycle transition, was a major component of our review. Such a MIM serves also as a convenient / organized database of a large set of important molecular events. The frequency of mutated / altered signaling-proteins indicates the importance of this signaling-network region. We have considered problems at different scale levels. Our MIM works at a biochemical-interaction level. We have also touched the multi-cellular dynamics of normal and aberrant colon crypts. Until recently, dynamic simulations at a biochemical or multi-cellular scale level were considered as a sort of esoteric approach. We tried to convince the reader, also on the basis of a rapidly growing literature, mostly published in high quality journals, that suspicion towards simulations should dissipate, as the limitations and advantages of their application are better appreciated, opening the door to their permanent adoption in everyday research. What is really required is a more interdisciplinary mentality and an interdisciplinary approach. The prize is a level of understanding going beyond mere intuition. PMID:22385511

  6. Screening of cellular proteins that interact with the classical swine fever virus non-structural protein 5A by yeast two-hybrid analysis

    Indian Academy of Sciences (India)

    Chengcheng Zhang; Lei He; Kai Kang; Heng Chen; Lei Xu; Yanming Zhang

    2014-03-01

    Classical swine fever virus (CSFV), the pathogen of classical swine fever (CSF), causes severe hemorrhagic fever and vascular necrosis in domestic pigs and wild boar. A large number of evidence has proven that non-structural 5A (NS5A) is not only a very important part of viral replication complex, but also can regulate host cell’s function; however, the underlying mechanisms remain poorly understood. In the current study, aiming to find more clues in understanding the molecular mechanisms of CSFV NS5A’s function, the yeast two-hybrid (Y2H) system was adopted to screen for CSFV NS5A interactive proteins in the cDNA library of the swine umbilical vein endothelial cell (SUVEC). Alignment with the NCBI database revealed 16 interactive proteins: DDX5, PSMC3, NAV1, PHF5A, GNB2L1, CSDE1, HSPA8, BRMS1, PPP2R3C, AIP, TMED10, POLR1C, TMEM70, METAP2, CHORDC1 and COPS6. These proteins are mostly related to gene transcription, protein folding, protein degradation and metabolism. The interactions detected by the Y2H system should be considered as preliminary results. Since identifying novel pathways and host targets, which play essential roles during infection, may provide potential targets for therapeutic development. The finding of proteins obtained from the SUVEC cDNA library that interact with the CSFV NS5A protein provide valuable information for better understanding the interactions between this viral protein and the host target proteins.

  7. Chapter Three - Ubiquitination and Protein Turnover of G-Protein-Coupled Receptor Kinases in GPCR Signaling and Cellular Regulation.

    Science.gov (United States)

    Penela, P

    2016-01-01

    G-protein-coupled receptors (GPCRs) are responsible for regulating a wide variety of physiological processes, and distinct mechanisms for GPCR inactivation exist to guarantee correct receptor functionality. One of the widely used mechanisms is receptor phosphorylation by specific G-protein-coupled receptor kinases (GRKs), leading to uncoupling from G proteins (desensitization) and receptor internalization. GRKs and β-arrestins also participate in the assembly of receptor-associated multimolecular complexes, thus initiating alternative G-protein-independent signaling events. In addition, the abundant GRK2 kinase has diverse "effector" functions in cellular migration, proliferation, and metabolism homeostasis by means of the phosphorylation or interaction with non-GPCR partners. Altered expression of GRKs (particularly of GRK2 and GRK5) occurs during pathological conditions characterized by impaired GPCR signaling including inflammatory syndromes, cardiovascular disease, and tumor contexts. It is increasingly appreciated that different pathways governing GRK protein stability play a role in the modulation of kinase levels in normal and pathological conditions. Thus, enhanced GRK2 degradation by the proteasome pathway occurs upon GPCR stimulation, what allows cellular adaptation to chronic stimulation in a physiological setting. β-arrestins participate in this process by facilitating GRK2 phosphorylation by different kinases and by recruiting diverse E3 ubiquitin ligase to the receptor complex. Different proteolytic systems (ubiquitin-proteasome, calpains), chaperone activities and signaling pathways influence the stability of GRKs in different ways, thus endowing specificity to GPCR regulation as protein turnover of GRKs can be differentially affected. Therefore, modulation of protein stability of GRKs emerges as a versatile mechanism for feedback regulation of GPCR signaling and basic cellular processes. PMID:27378756

  8. Copper and Zinc Interactions with Cellular Prion Proteins Change Solubility of Full-Length Glycosylated Isoforms and Induce the Occurrence of Heterogeneous Phenotypes

    Science.gov (United States)

    Brim, Svetlana; Groschup, Martin H.; Kuczius, Thorsten

    2016-01-01

    Prion diseases are characterized biochemically by protein aggregation of infectious prion isoforms (PrPSc), which result from the conformational conversion of physiological prion proteins (PrPC). PrPC are variable post-translationally modified glycoproteins, which exist as full length and as aminoterminally truncated glycosylated proteins and which exhibit differential detergent solubility. This implicates the presence of heterogeneous phenotypes, which overlap as protein complexes at the same molecular masses. Although the biological function of PrPC is still enigmatic, evidence reveals that PrPC exhibits metal-binding properties, which result in structural changes and decreased solubility. In this study, we analyzed the yield of PrPC metal binding affiliated with low solubility and changes in protein banding patterns. By implementing a high-speed centrifugation step, the interaction of zinc ions with PrPC was shown to generate large quantities of proteins with low solubility, consisting mainly of full-length glycosylated PrPC; whereas unglycosylated PrPC remained in the supernatants as well as truncated glycosylated proteins which lack of octarepeat sequence necessary for metal binding. This effect was considerably lower when PrPC interacted with copper ions; the presence of other metals tested exhibited no effect under these conditions. The binding of zinc and copper to PrPC demonstrated differentially soluble protein yields within distinct PrPC subtypes. PrPC–Zn2+-interaction may provide a means to differentiate glycosylated and unglycosylated subtypes and offers detailed analysis of metal-bound and metal-free protein conversion assays. PMID:27093554

  9. Genetic Variance in Uncoupling Protein 2 in Relation to Obesity, Type 2 Diabetes, and Related Metabolic Traits

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp

    2011-01-01

    Uncoupling proteins (UCPs) are mitochondrial proteins able to dissipate the proton gradient of the inner mitochondrial membrane when activated. This decreases ATP-generation through oxidation of fuels and may theoretically decrease energy expenditure leading to obesity. Evidence from Ucp...

  10. Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload

    Energy Technology Data Exchange (ETDEWEB)

    Pardo Andreu, G.L. [Centro de Quimica Farmaceutica, Departamento de Investigaciones Biomedicas, Ciudad de La Habana (Cuba); Inada, N.M.; Vercesi, A.E. [Universidade Estadual de Campinas, Departamento de Patologia Clinica, Faculdade de Ciencias Medicas, Campinas, SP (Brazil); Curti, C. [Universidade de Sao Paulo, Departamento de Fisica e Quimica, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, SP (Brazil)

    2009-01-15

    One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron-dextran. The treatment increased the levels of iron in mitochondria (from 21{+-}4 to 130{+-}7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H{sup +} leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria. (orig.)

  11. Uncoupling of reading and IQ over time: empirical evidence for a definition of dyslexia.

    Science.gov (United States)

    Ferrer, Emilio; Shaywitz, Bennett A; Holahan, John M; Marchione, Karen; Shaywitz, Sally E

    2010-01-01

    Developmental dyslexia is defined as an unexpected difficulty in reading in individuals who otherwise possess the intelligence and motivation considered necessary for fluent reading, and who also have had reasonable reading instruction. Identifying factors associated with normative and impaired reading development has implications for diagnosis, intervention, and prevention. We show that in typical readers, reading and IQ development are dynamically linked over time. Such mutual interrelationships are not perceptible in dyslexic readers, which suggests that reading and cognition develop more independently in these individuals. To our knowledge, these findings provide the first empirical demonstration of a coupling between cognition and reading in typical readers and a developmental uncoupling between cognition and reading in dyslexic readers. This uncoupling was the core concept of the initial description of dyslexia and remains the focus of the current definitional model of this learning disability. PMID:20424029

  12. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways

    Science.gov (United States)

    Müller, Sebastian; Balaz, Miroslav; Stefanicka, Patrik; Varga, Lukas; Amri, Ez-Zoubir; Ukropec, Jozef; Wollscheid, Bernd; Wolfrum, Christian

    2016-01-01

    Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. The majority of the 318 proteins with increased abundance in BAT are associated with mitochondrial metabolism and confirm the increased oxidative capacity. In addition to uncoupling protein 1 (UCP1), the main functional effector for uncoupled respiration, we also detected the mitochondrial creatine kinases (CKMT1A/B, CKMT2), as effective modulators of ATP synthase coupled respiration, to be exclusively expressed in BAT. The abundant expression and utilization of both energy expenditure pathways in parallel highlights the complex functional involvement of BAT in human physiology. PMID:27418403

  13. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways.

    Science.gov (United States)

    Müller, Sebastian; Balaz, Miroslav; Stefanicka, Patrik; Varga, Lukas; Amri, Ez-Zoubir; Ukropec, Jozef; Wollscheid, Bernd; Wolfrum, Christian

    2016-01-01

    Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. The majority of the 318 proteins with increased abundance in BAT are associated with mitochondrial metabolism and confirm the increased oxidative capacity. In addition to uncoupling protein 1 (UCP1), the main functional effector for uncoupled respiration, we also detected the mitochondrial creatine kinases (CKMT1A/B, CKMT2), as effective modulators of ATP synthase coupled respiration, to be exclusively expressed in BAT. The abundant expression and utilization of both energy expenditure pathways in parallel highlights the complex functional involvement of BAT in human physiology. PMID:27418403

  14. Uncoupling of M1 muscarinic receptor/G-protein interaction by amyloid beta(1-42)

    Czech Academy of Sciences Publication Activity Database

    Janíčková, Helena; Rudajev, Vladimír; Zimčík, Pavel; Jakubík, Jan; Tanila, H.; El-Fakahany, E. E.; Doležal, Vladimír

    2013-01-01

    Roč. 67, April (2013), s. 272-283. ISSN 0028-3908 R&D Projects: GA ČR(CZ) GA305/09/0681; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) 7E10060 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : Alzheimer ´s Disease * muscarinic receptors * G-proteins Subject RIV: ED - Physiology Impact factor: 4.819, year: 2013

  15. Triglyceride-lowering effect of respiratory uncoupling in white adipose tissue

    Czech Academy of Sciences Publication Activity Database

    Rossmeisl, Martin; Kovář, J.; Syrový, Ivo; Flachs, Pavel; Bobková, D.; Kolář, František; Poledne, R.; Kopecký, Jan

    2005-01-01

    Roč. 13, č. 5 (2005), s. 835-844. ISSN 1071-7323 R&D Projects: GA ČR(CZ) GP303/03/P127; GA ČR(CZ) GA303/02/1220 Institutional research plan: CEZ:AV0Z5011922 Keywords : adipose tissue * uncoupling protein * lipoprotein lipase Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.972, year: 2005

  16. Novel reptilian uncoupling proteins: molecular evolution and gene expression during cold acclimation

    OpenAIRE

    Schwartz, Tonia S.; Murray, Shauna; Seebacher, Frank

    2008-01-01

    Many animals upregulate metabolism in response to cold. Uncoupling proteins (UCPs) increase proton conductance across the mitochondrial membrane and can thereby alleviate damage from reactive oxygen species that may form as a result of metabolic upregulation. Our aim in this study was to determine whether reptiles (Crocodylus porosus) possess UCP genes. If so, we aimed to place reptilian UCP genes within a phylogenetic context and to determine whether the expression of UCP genes is increased ...

  17. Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo

    OpenAIRE

    Hesselink, M.K.C.; Greenhaff, P L; Constantin-Teodosu, D.; Hultman, E; Saris, W. H. M.; Nieuwlaat, R.; Schaart, G.; Kornips, C.F.P.; P. Schrauwen

    2003-01-01

    Phosphocreatine (PCr) resynthesis rate following intense anoxic contraction can be used as a sensitive index of in vivo mitochondrial function. We examined the effect of a diet-induced increase in uncoupling protein 3 (UCP3) expression on postexercise PCr resynthesis in skeletal muscle. Nine healthy male volunteers undertook 20 one-legged maximal voluntary contractions with limb blood flow occluded to deplete muscle PCr stores. Exercise was performed following 7 days consumption of low-fat (L...

  18. Critical Appraisal of the MTT Assay in the Presence of Rottlerin and Uncouplers

    OpenAIRE

    Maioli Emanuela; Torricelli Claudia; Fortino Vittoria; Carlucci Filippo; Tommassini Valentina; Pacini Adriana

    2009-01-01

    Abstract Rottlerin is a natural product isolated from Mallotus philippinensis. This polyphenolic compound, originally described as a selective inhibitor of PKCδ, can inhibit many other PKC-unrelated kinases and has a number of biological actions, including mitochondrial uncoupling effects. We recently found that Rottlerin inhibits the transcription factor nuclear factor κB in different cell types, causing downregulation of cyclin D1 and growth arrest. The present study was carried o...

  19. Inhibition of uncoupling protein 2 with genipin exacerbates palmitate-induced hepatic steatosis

    OpenAIRE

    Ma Shuangtao; Yang Dachun; Li; Tan Yan; Tang Bing; Yang Yongjian

    2012-01-01

    Abstract Background Uncoupling protein 2 (UCP2) was reported to be involved in lipid metabolism through regulating the production of superoxide anion. However, the role of UCP2 in hepatocytes steatosis has not been determined. We hypothesized that UCP2 might regulate hepatic steatosis via suppressing oxidative stress. Results We tested this hypothesis in an in vitro model of hepatocytic steatosis in HepG2 cell lines induced by palmitic acid (PA). We found that treatment with PA induced an obv...

  20. Uncoupling of longevity and paraquat resistance in mutants of the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Fujii, Michihiko; Tanaka, Nanae; Miki, Kensuke; Hossain, Mohammad Nazir; Endoh, Morio; Ayusawa, Dai

    2005-10-01

    To analyze the relationship between resistance to oxidative stress and longevity, we isolated three novel paraquat-resistant mutants, mev-5, mev-6, and mev-7, from the nematode Caenorhabditis elegans. They all showed the Dyf (defective in dye filling) phenotype, but not always resistance to heat or UV. Life-span extension was observed only in the mev-5 mutant at 26 degrees C. These results indicate that longevity is uncoupled with the phenotype of paraquat resistance. PMID:16244463

  1. THE CALCULATION OF INITIAL SHOCK WAVE IN ROCK WITH UNCOUPLING CHARGE BLASTING

    Institute of Scientific and Technical Information of China (English)

    李玉民; 倪芝芳; 黄忆龙

    1997-01-01

    According to the structure of explosive charge in rock blasting, a physical model has been set up in this paper. Based on the model, a methodology for calculating initial shock wave of uncoupling charge has been given. The pressure P3 has been calculated when high explosives act on granite, limestone, marble and shale respectively. Some important conclusions are also gained by the analysis of results.

  2. Human Skeletal Muscle Mitochondrial Uncoupling Is Associated with Cold Induced Adaptive Thermogenesis

    OpenAIRE

    Sander L J Wijers; Schrauwen, Patrick; Saris, Wim H. M.; van Marken Lichtenbelt, Wouter D.

    2008-01-01

    Background Mild cold exposure and overfeeding are known to elevate energy expenditure in mammals, including humans. This process is called adaptive thermogenesis. In small animals, adaptive thermogenesis is mainly caused by mitochondrial uncoupling in brown adipose tissue and regulated via the sympathetic nervous system. In humans, skeletal muscle is a candidate tissue, known to account for a large part of the epinephrine-induced increase in energy expenditure. However, mitochondrial uncoupli...

  3. Augmenting energy expenditure by mitochondrial uncoupling: a role of AMP-activated protein kinase

    Czech Academy of Sciences Publication Activity Database

    Klaus, S.; Keipert, S.; Rossmeisl, Martin; Kopecký, Jan

    2012-01-01

    Roč. 7, č. 3 (2012), s. 369-386. ISSN 1555-8932 R&D Projects: GA MZd(CZ) NS10528; GA MŠk(CZ) 7E10059; GA MŠk(CZ) OC08008 Institutional research plan: CEZ:AV0Z50110509 Keywords : adipose tissue * skeletal muscle * uncoupling protein * transgenic mice * insulin sensitivity Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.329, year: 2012

  4. Mitochondrial uncoupling as a regulator of life-history trajectories in birds: an experimental study in the zebra finch.

    Science.gov (United States)

    Stier, Antoine; Bize, Pierre; Roussel, Damien; Schull, Quentin; Massemin, Sylvie; Criscuolo, François

    2014-10-01

    Mitochondria have a fundamental role in the transduction of energy from food into ATP. The coupling between food oxidation and ATP production is never perfect, but may nevertheless be of evolutionary significance. The 'uncoupling to survive' hypothesis suggests that 'mild' mitochondrial uncoupling evolved as a protective mechanism against the excessive production of damaging reactive oxygen species (ROS). Because resource allocation and ROS production are thought to shape animal life histories, alternative life-history trajectories might be driven by individual variation in the degree of mitochondrial uncoupling. We tested this hypothesis in a small bird species, the zebra finch (Taeniopygia guttata), by treating adults with the artificial mitochondrial uncoupler 2,4-dinitrophenol (DNP) over a 32-month period. In agreement with our expectations, the uncoupling treatment increased metabolic rate. However, we found no evidence that treated birds enjoyed lower oxidative stress levels or greater survival rates, in contrast to previous results in other taxa. In vitro experiments revealed lower sensitivity of ROS production to DNP in mitochondria isolated from skeletal muscles of zebra finch than mouse. In addition, we found significant reductions in the number of eggs laid and in the inflammatory immune response in treated birds. Altogether, our data suggest that the 'uncoupling to survive' hypothesis may not be applicable for zebra finches, presumably because of lower effects of mitochondrial uncoupling on mitochondrial ROS production in birds than in mammals. Nevertheless, mitochondrial uncoupling appeared to be a potential life-history regulator of traits such as fecundity and immunity at adulthood, even with food supplied ad libitum. PMID:25063856

  5. Kidney Function After In Vivo Gene Silencing of Uncoupling Protein-2 in Streptozotocin-Induced Diabetic Rats

    OpenAIRE

    Persson, Malou Friederich; Welch, William. J; Wilcox, Christopher S; Palm, Fredrik

    2013-01-01

    Kidney uncoupling protein 2 (UCP-2) increases in streptozotocin-induced diabetes, resulting in mitochondria uncoupling, i.e., increased oxygen consumption unrelated to active transport. The present study aimed to investigate the role of UCP-2 for normal and diabetic kidney function utilizing small interference RNA (siRNA) to reduce protein expression. Diabetic animals had increased glomerular filtration rate and kidney oxygen consumption, resulting in decreased oxygen tension and transported ...

  6. Dehydrosilybin attenuates the production of ROS in rat cardiomyocyte mitochondria with an uncoupler-like mechanism.

    Science.gov (United States)

    Gabrielová, Eva; Jabůrek, Martin; Gažák, Radek; Vostálová, Jitka; Ježek, Jan; Křen, Vladimír; Modrianský, Martin

    2010-12-01

    Reactive oxygen species (ROS) originating from mitochondria are perceived as a factor contributing to cell aging and means have been sought to attenuate ROS formation with the aim of extending the cell lifespan. Silybin and dehydrosilybin, two polyphenolic compounds, display a plethora of biological effects generally ascribed to their known antioxidant capacity. When investigating the cytoprotective effects of these two compounds in the primary cell cultures of neonatal rat cardiomyocytes, we noted the ability of dehydrosilybin to de-energize the cells by monitoring JC-1 fluorescence. Experiments evaluating oxygen consumption and membrane potential revealed that dehydrosilybin uncouples the respiration of isolated rat heart mitochondria albeit with a much lower potency than synthetic uncouplers. Furthermore, dehydrosilybin revealed a very high potency in suppressing ROS formation in isolated rat heart mitochondria with IC(50) = 0.15 μM. It is far more effective than its effect in a purely chemical system generating superoxide or in cells capable of oxidative burst, where the IC(50) for dehydrosilybin exceeds 50 μM. Dehydrosilybin also attenuated ROS formation caused by rotenone in the primary cultures of neonatal rat cardiomyocytes. We infer that the apparent uncoupler-like activity of dehydrosilybin is the basis of its ROS modulation effect in neonatal rat cardiomyocytes and leads us to propose a hypothesis on natural ischemia preconditioning by dietary polyphenols. PMID:21153691

  7. Activation of AMPKα2 is not crucial for mitochondrial uncoupling-induced metabolic effects but required to maintain skeletal muscle integrity.

    Directory of Open Access Journals (Sweden)

    Mario Ost

    Full Text Available Transgenic (UCP1-TG mice with ectopic expression of UCP1 in skeletal muscle (SM show a phenotype of increased energy expenditure, improved glucose tolerance and increase substrate metabolism in SM. To investigate the potential role of skeletal muscle AMPKα2 activation in the metabolic phenotype of UCP1-TG mice we generated double transgenic (DTG mice, by crossing of UCP1-TG mice with DN-AMPKα2 mice overexpressing a dominant negative α2 subunit of AMPK in SM which resulted in an impaired AMPKα2 activity by 90±9% in SM of DTG mice. Biometric analysis of young male mice showed decreased body weight, lean and fat mass for both UCP1-TG and DTG compared to WT and DN-AMPKα2 mice. Energy intake and weight-specific total energy expenditure were increased, both in UCP1-TG and DTG mice. Moreover, glucose tolerance, insulin sensitivity and fatty acid oxidation were not altered in DTG compared to UCP1-TG. Also uncoupling induced induction and secretion of fibroblast growth factor 21 (FGF21 from SM was preserved in DTG mice. However, voluntary physical cage activity as well as ad libitum running wheel access during night uncovered a severe activity intolerance of DTG mice. Histological analysis showed a progressive degenerative morphology in SM of DTG mice which was not observed in SM of UCP1-TG mice. Moreover, ATP-depletion related cellular stress response via heat shock protein 70 was highly induced, whereas capillarization regulator VEGF was suppressed in DTG muscle. In addition, AMPKα2-mediated induction of mitophagy regulator ULK1 was suppressed in DTG mice, as well as mitochondrial respiratory capacity and content. In conclusion, we demonstrate that AMPKα2 is dispensable for SM mitochondrial uncoupling induced metabolic effects on whole body energy balance, glucose homeostasis and insulin sensitivity. But strikingly, activation of AMPKα2 seems crucial for maintaining SM function, integrity and the ability to compensate chronic metabolic stress

  8. Investigating the consequences of eIF4E2 (4EHP interaction with 4E-transporter on its cellular distribution in HeLa cells.

    Directory of Open Access Journals (Sweden)

    Dorota Kubacka

    Full Text Available In addition to the canonical eIF4E cap-binding protein, eukaryotes have evolved sequence-related variants with distinct features, some of which have been shown to negatively regulate translation of particular mRNAs, but which remain poorly characterised. Mammalian eIF4E proteins have been divided into three classes, with class I representing the canonical cap-binding protein eIF4E1. eIF4E1 binds eIF4G to initiate translation, and other eIF4E-binding proteins such as 4E-BPs and 4E-T prevent this interaction by binding eIF4E1 with the same consensus sequence YX 4Lϕ. We investigate here the interaction of human eIF4E2 (4EHP, a class II eIF4E protein, which binds the cap weakly, with eIF4E-transporter protein, 4E-T. We first show that ratios of eIF4E1:4E-T range from 50:1 to 15:1 in HeLa and HEK293 cells respectively, while those of eIF4E2:4E-T vary from 6:1 to 3:1. We next provide evidence that eIF4E2 binds 4E-T in the yeast two hybrid assay, as well as in pull-down assays and by recruitment to P-bodies in mammalian cells. We also show that while both eIF4E1 and eIF4E2 bind 4E-T via the canonical YX 4Lϕ sequence, nearby downstream sequences also influence eIF4E:4E-T interactions. Indirect immunofluorescence was used to demonstrate that eIF4E2, normally homogeneously localised in the cytoplasm, does not redistribute to stress granules in arsenite-treated cells, nor to P-bodies in Actinomycin D-treated cells, in contrast to eIF4E1. Moreover, eIF4E2 shuttles through nuclei in a Crm1-dependent manner, but in an 4E-T-independent manner, also unlike eIF4E1. Altogether we conclude that while both cap-binding proteins interact with 4E-T, and can be recruited by 4E-T to P-bodies, eIF4E2 functions are likely to be distinct from those of eIF4E1, both in the cytoplasm and nucleus, further extending our understanding of mammalian class I and II cap-binding proteins.

  9. Cellular evidence for nano-scale exosome secretion and interactions with spermatozoa in the epididymis of the Chinese soft-shelled turtle, Pelodiscus sinensis

    Science.gov (United States)

    Chen, Hong; Yang, Ping; Chu, Xiaoya; Huang, Yufei; Liu, Tengfei; Zhang, Qian; Li, Quanfu; Hu, Lisi; Waqas, Yasir; Ahmed, Nisar; Chen, Qiusheng

    2016-01-01

    The epididymis is the location of sperm maturation and sperm storage. Recent studies have shown that nano-scale exosomes play a vital role during these complicated processes. Our aim was to analyze the secretory properties of epididymal exosomes and their ultrastructural interaction with maturing spermatozoa in the Chinese soft-shelled turtle. The exosome marker CD63 was primarily localized to the apices of principal cells throughout the epididymal epithelium. Identification of nano-scale exosomes and their secretory processes were further investigated via transmission electron microscopy. The epithelium secreted epididymal exosomes (50~300 nm in diameter) through apocrine secretion and the multivesicular body (MVB) pathway. Spermatozoa absorbed epididymal exosomes through endocytosis or membrane fusion pathways. This study shows, for the first time, that nano-scale exosomes use two secretion and two absorption pathways in the reptile, which may be contribute to long-term sperm storage. PMID:26992236

  10. Cellular reactions to patterned biointerfaces

    OpenAIRE

    Schulte, Vera Antonie

    2012-01-01

    The subject of this thesis is to study cellular reactions to topographically, mechanically and biochemically tunable polymeric biomaterials. Different aspects of in vitro cell-biomaterial interactions were systematically studied with the murine fibroblast cell line NIH L929 and primary human dermal fibroblasts (HDFs). Besides a general cytocompatibility assessment of the applied materials and the quantification of cell adhesion per se, cell morphological changes (e.g. cell spreading) and intr...

  11. A primary phosphorus-deficient skeletal phenotype in juvenile Atlantic salmon Salmo salar: the uncoupling of bone formation and mineralization.

    Science.gov (United States)

    Witten, P E; Owen, M A G; Fontanillas, R; Soenens, M; McGurk, C; Obach, A

    2016-02-01

    To understand the effect of low dietary phosphorus (P) intake on the vertebral column of Atlantic salmon Salmo salar, a primary P deficiency was induced in post-smolts. The dietary P provision was reduced by 50% for a period of 10 weeks under controlled conditions. The animal's skeleton was subsequently analysed by radiology, histological examination, histochemical detection of minerals in bones and scales and chemical mineral analysis. This is the first account of how a primary P deficiency affects the skeleton in S. salar at the cellular and at the micro-anatomical level. Animals that received the P-deficient diet displayed known signs of P deficiency including reduced growth and soft, pliable opercula. Bone and scale mineral content decreased by c. 50%. On radiographs, vertebral bodies appear small, undersized and with enlarged intervertebral spaces. Contrary to the X-ray-based diagnosis, the histological examination revealed that vertebral bodies had a regular size and regular internal bone structures; intervertebral spaces were not enlarged. Bone matrix formation was continuous and uninterrupted, albeit without traces of mineralization. Likewise, scale growth continues with regular annuli formation, but new scale matrix remains without minerals. The 10 week long experiment generated a homogeneous osteomalacia of vertebral bodies without apparent induction of skeletal malformations. The experiment shows that bone formation and bone mineralization are, to a large degree, independent processes in the fish examined. Therefore, a deficit in mineralization must not be the only cause of the alterations of the vertebral bone structure observed in farmed S. salar. It is discussed how the observed uncoupling of bone formation and mineralization helps to better diagnose, understand and prevent P deficiency-related malformations in farmed S. salar. PMID:26707938

  12. American Ginseng Stimulates Insulin Production and Prevents Apoptosis through Regulation of Uncoupling Protein-2 in Cultured β Cells

    Directory of Open Access Journals (Sweden)

    John Zeqi Luo

    2006-01-01

    Full Text Available American ginseng root displays the ability to achieve glucose homeostasis both experimentally and clinically but the unknown mechanism used by ginseng to achieve its therapeutic effects on diabetes limits its application. Disruption in the insulin secretion of pancreatic β cells is considered the major cause of diabetes. A mitochondrial protein, uncoupling protein-2 (UCP-2 has been found to play a critical role in insulin synthesis and β cell survival. Our preliminary studies found that the extracts of American ginseng inhibit UCP-2 expression which may contribute to the ability of ginseng protecting β cell death and improving insulin synthesis. Therefore, we hypothesized that ginseng extracts suppress UCP-2 in the mitochondria of pancreatic β cells, promoting insulin synthesis and anti-apoptosis (a programmed cell-death mechanism. To test the hypothesis, the serum-deprived quiescent β cells were cultured with or without interleukin-1β (IL-1β, (200 pg ml−1, a cytokine to induce β cell apoptosis and water extracts of American ginseng (25 μg per 5 μl administered to wells of 0.5 ml culture for 24 h. We evaluated effects of ginseng on UCP-2 expression, insulin production, anti-/pro-apoptotic factors Bcl-2/caspase-9 expression and cellular ATP levels. We found that ginseng suppresses UCP-2, down-regulates caspase-9 while increasing ATP and insulin production/secretion and up-regulates Bcl-2, reducing apoptosis. These findings suggest that stimulation of insulin production and prevention of β cell loss by American ginseng extracts can occur via the inhibition of mitochondrial UCP-2, resulting in increase in the ATP level and the anti-apoptotic factor Bcl-2, while down-regulation of pro-apoptotic factor caspase-9 occurs, lowering the occurrence of apoptosis, which support the hypothesis.

  13. Carbon monoxide released by CORM-401 uncouples mitochondrial respiration and inhibits glycolysis in endothelial cells: A role for mitoBKCa channels.

    Science.gov (United States)

    Kaczara, Patrycja; Motterlini, Roberto; Rosen, Gerald M; Augustynek, Bartlomiej; Bednarczyk, Piotr; Szewczyk, Adam; Foresti, Roberta; Chlopicki, Stefan

    2015-10-01

    Carbon monoxide (CO), a product of heme degradation by heme oxygenases, plays an important role in vascular homeostasis. Recent evidence indicates that mitochondria are among a number of molecular targets that mediate the cellular actions of CO. In the present study we characterized the effects of CO released from CORM-401 on mitochondrial respiration and glycolysis in intact human endothelial cells using electron paramagnetic resonance (EPR) oximetry and the Seahorse XF technology. We found that CORM-401 (10-100μM) induced a persistent increase in the oxygen consumption rate (OCR) that was accompanied by inhibition of glycolysis (extracellular acidification rate, ECAR) and a decrease in ATP-turnover. Furthermore, CORM-401 increased proton leak, diminished mitochondrial reserve capacity and enhanced non-mitochondrial respiration. Inactive CORM-401 (iCORM-401) neither induced mitochondrial uncoupling nor inhibited glycolysis, supporting a direct role of CO in the endothelial metabolic response induced by CORM-401. Interestingly, blockade of mitochondrial large-conductance calcium-regulated potassium ion channels (mitoBKCa) with paxilline abolished the increase in OCR promoted by CORM-401 without affecting ECAR; patch-clamp experiments confirmed that CO derived from CORM-401 activated mitoBKCa channels present in mitochondria. Conversely, stabilization of glycolysis by MG132 prevented CORM-401-mediated decrease in ECAR but did not modify the OCR response. In summary, we demonstrated in intact endothelial cells that CO induces a two-component metabolic response: uncoupling of mitochondrial respiration dependent on the activation of mitoBKCa channels and inhibition of glycolysis independent of mitoBKCa channels. PMID:26185029

  14. Shortened leukocyte telomere length in type 2 diabetes mellitus: genetic polymorphisms in mitochondrial uncoupling proteins and telomeric pathways.

    Science.gov (United States)

    Zhou, Yuling; Ning, Zhixin; Lee, Yvonne; Hambly, Brett D; McLachlan, Craig S

    2016-12-01

    Current debate in type 2 diabetes (T2DM) has focused on shortened leukocyte telomere length (LTL) as the result of a number of possible causes, including polymorphisms in mitochondrial uncoupling proteins (UCPs) leading to oxidative stress, telomere regulatory pathway gene polymorphisms, or as a direct result of associated cardiovascular complications inducing tissue organ inflammation and oxidative stress. There is evidence that a heritable shorter telomere trait is a risk factor for development of T2DM. This review discusses the contribution and balance of genetic regulation of UCPs and telomere pathways in the context of T2DM. We discuss genotypes that are well known to influence the shortening of LTL, in particular OBFC1 and telomerase genotypes such as TERC. Interestingly, the interaction between short telomeres and T2DM risk appears to involve mitochondrial dysfunction as an intermediate process. A hypothesis is presented that genetic heterogeneity within UCPs may directly affect oxidative stress that feeds back to influence the fine balance of telomere regulation, cell cycle regulation and diabetes risk and/or metabolic disease progression. PMID:26951191

  15. Epstein–Barr virus nuclear antigen 3C interact with p73: Interplay between a viral oncoprotein and cellular tumor suppressor

    International Nuclear Information System (INIS)

    The p73 protein has structural and functional homology with the tumor suppressor p53, which plays an important role in cell cycle regulation, apoptosis, and DNA repair. The p73 locus encodes both a tumor suppressor (TAp73) and a putative oncogene (ΔNp73). p73 May play a significant role in p53-deficient lymphomas infected with Epstein–Barr virus (EBV). EBV produces an asymptomatic infection in the majority of the global population, but it is associated with several human B-cell malignancies. The EBV-encoded Epstein–Barr virus nuclear antigen 3C (EBNA3C) is thought to disrupt the cell cycle checkpoint by interacting directly with p53 family proteins. Doxorubicin, a commonly used chemotherapeutic agent, induces apoptosis through p53 and p73 signaling such that the lowΔNp73 level promotes the p73-mediated intrinsic pathway of apoptosis. In this report, we investigated the mechanism by which EBV infection counters p73α-induced apoptosis through EBNA3C. - Highlights: • EBV-encoded EBNA3C suppresses doxorubicin-induced apoptosis in B-cell lymphomas. • EBNA3C binds to p73 to suppress its apoptotic effect. • EBNA3C maintains latency by regulating downstream mitochondrial pathways

  16. Epstein–Barr virus nuclear antigen 3C interact with p73: Interplay between a viral oncoprotein and cellular tumor suppressor

    Energy Technology Data Exchange (ETDEWEB)

    Sahu, Sushil Kumar; Mohanty, Suchitra; Kumar, Amit [Division of Infectious Disease Biology, Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar 751023 (India); Kundu, Chanakya N. [School of Biotechnology, KIIT University, Bhubaneswar (India); Verma, Subhash C. [Department of Microbiology and Immunology, University of Nevada, School of Medicine, Reno, NV 89557 (United States); Choudhuri, Tathagata, E-mail: tatha@ils.res.in [Division of Infectious Disease Biology, Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar 751023 (India); Department of Biotechnology, Siksha Bhavana, Visva Bharati, Santiniketan, Bolpur (India)

    2014-01-05

    The p73 protein has structural and functional homology with the tumor suppressor p53, which plays an important role in cell cycle regulation, apoptosis, and DNA repair. The p73 locus encodes both a tumor suppressor (TAp73) and a putative oncogene (ΔNp73). p73 May play a significant role in p53-deficient lymphomas infected with Epstein–Barr virus (EBV). EBV produces an asymptomatic infection in the majority of the global population, but it is associated with several human B-cell malignancies. The EBV-encoded Epstein–Barr virus nuclear antigen 3C (EBNA3C) is thought to disrupt the cell cycle checkpoint by interacting directly with p53 family proteins. Doxorubicin, a commonly used chemotherapeutic agent, induces apoptosis through p53 and p73 signaling such that the lowΔNp73 level promotes the p73-mediated intrinsic pathway of apoptosis. In this report, we investigated the mechanism by which EBV infection counters p73α-induced apoptosis through EBNA3C. - Highlights: • EBV-encoded EBNA3C suppresses doxorubicin-induced apoptosis in B-cell lymphomas. • EBNA3C binds to p73 to suppress its apoptotic effect. • EBNA3C maintains latency by regulating downstream mitochondrial pathways.

  17. Cellular Selenoprotein mRNA Tethering via Antisense Interactions with Ebola and HIV-1 mRNAs May Impact Host Selenium Biochemistry.

    Science.gov (United States)

    Taylor, Ethan Will; Ruzicka, Jan A; Premadasa, Lakmini; Zhao, Lijun

    2016-01-01

    Regulation of protein expression by non-coding RNAs typically involves effects on mRNA degradation and/or ribosomal translation. The possibility of virus-host mRNA-mRNA antisense tethering interactions (ATI) as a gain-of-function strategy, via the capture of functional RNA motifs, has not been hitherto considered. We present evidence that ATIs may be exploited by certain RNA viruses in order to tether the mRNAs of host selenoproteins, potentially exploiting the proximity of a captured host selenocysteine insertion sequence (SECIS) element to enable the expression of virally-encoded selenoprotein modules, via translation of in-frame UGA stop codons as selenocysteine. Computational analysis predicts thermodynamically stable ATIs between several widely expressed mammalian selenoprotein mRNAs (e.g., isoforms of thioredoxin reductase) and specific Ebola virus mRNAs, and HIV-1 mRNA, which we demonstrate via DNA gel shift assays. The probable functional significance of these ATIs is further supported by the observation that, in both viruses, they are located in close proximity to highly conserved in-frame UGA stop codons at the 3' end of open reading frames that encode essential viral proteins (the HIV-1 nef protein and the Ebola nucleoprotein). Significantly, in HIV/AIDS patients, an inverse correlation between serum selenium and mortality has been repeatedly documented, and clinical benefits of selenium in the context of multi-micronutrient supplementation have been demonstrated in several well-controlled clinical trials. Hence, in the light of our findings, the possibility of a similar role for selenium in Ebola pathogenesis and treatment merits serious investigation. PMID:26369818

  18. Cellular Selenoprotein mRNA Tethering via Antisense Interactions with Ebola and HIV-1 mRNAs May Impact Host Selenium Biochemistry

    Science.gov (United States)

    Taylor, Ethan Will; Ruzicka, Jan A.; Premadasa, Lakmini; Zhao, Lijun

    2016-01-01

    Regulation of protein expression by non-coding RNAs typically involves effects on mRNA degradation and/or ribosomal translation. The possibility of virus-host mRNA-mRNA antisense tethering interactions (ATI) as a gain-of-function strategy, via the capture of functional RNA motifs, has not been hitherto considered. We present evidence that ATIs may be exploited by certain RNA viruses in order to tether the mRNAs of host selenoproteins, potentially exploiting the proximity of a captured host selenocysteine insertion sequence (SECIS) element to enable the expression of virally-encoded selenoprotein modules, via translation of in-frame UGA stop codons as selenocysteine. Computational analysis predicts thermodynamically stable ATIs between several widely expressed mammalian selenoprotein mRNAs (e.g., isoforms of thioredoxin reductase) and specific Ebola virus mRNAs, and HIV-1 mRNA, which we demonstrate via DNA gel shift assays. The probable functional significance of these ATIs is further supported by the observation that, in both viruses, they are located in close proximity to highly conserved in-frame UGA stop codons at the 3′ end of open reading frames that encode essential viral proteins (the HIV-1 nef protein and the Ebola nucleoprotein). Significantly, in HIV/AIDS patients, an inverse correlation between serum selenium and mortality has been repeatedly documented, and clinical benefits of selenium in the context of multi-micronutrient supplementation have been demonstrated in several well-controlled clinical trials. Hence, in the light of our findings, the possibility of a similar role for selenium in Ebola pathogenesis and treatment merits serious investigation. PMID:26369818

  19. INTERACT

    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    , and demonstrated in public settings. We then describe INTERACT, a proposed research project that stages the robotic marionettes in a live performance. The interdisciplinary project brings humanities research to bear on scientific and technological inquiry, and culminates in the development a live......This paper considers the impact of visual art and performance on robotics and human-computer interaction and outlines a research project that combines puppetry and live performance with robotics. Kinesics—communication through movement—is the foundation of many theatre and performance traditions...... interaction between a human operator and an artificial actor or agent. We can apply insights from puppetry to develop culturally-aware robots. Here we describe the development of a robotic marionette theatre wherein robotic controllers assume the role of human puppeteers. The system has been built, tested...

  20. Interactions

    DEFF Research Database (Denmark)

    The main theme of this anthology is the unique interaction between mathematics, physics and philosophy during the beginning of the 20th century. Seminal theories of modern physics and new fundamental mathematical structures were discovered or formed in this period. Significant physicists such as...

  1. Cellular responses of BRCA1-defective and triple-negative breast cancer cells and in vitro BRCA1 interactions induced by metallo-intercalator ruthenium(II) complexes containing chloro-substituted phenylazopyridine

    International Nuclear Information System (INIS)

    Triple-negative breast cancer (TNBC) is defined by the absence of expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Breast cancers with a BRCA1 mutation are also frequently triple-negative. Currently, there is a lack of effective therapies and known specific molecular targets for this aggressive breast cancer subtype. To address this concern, we have explored the cellular responses of BRCA1-defective and triple-negative breast cancer cells, and in vitro BRCA1 interactions induced by the ruthenium(II) complexes containing the bidentate ligand, 5-chloro-2-(phenylazo)pyridine. Triple-negative MDA-MB-231, BRCA1-defective HCC1937 and BRCA1-competent MCF-7 breast cancer cell lines were treated with ruthenium(II) complexes. The cytoxoxicity of ruthenium-induced breast cancer cells was evaluated by a real time cellular analyzer (RTCA). Cellular uptake of ruthenium complexes was determined by ICP-MS. Cell cycle progression and apoptosis were assessed using propidium iodide and Annexin V flow cytometry. The N-terminal BRCA1 RING protein was used for conformational and functional studies using circular dichroism and in vitro ubiquitination. HCC1937 cells were significantly more sensitive to the ruthenium complexes than the MDA-MB-231 and MCF-7 cells. Treatment demonstrated a higher degree of cytotoxicity than cisplatin against all three cell lines. Most ruthenium atoms were retained in the nuclear compartment, particularly in HCC1937 cells, after 24 h of incubation, and produced a significant block at the G2/M phase. An increased induction of apoptotic cells as well as an upregulation of p53 mRNA was observed in all tested breast cancer cells. It was of interest that BRCA1 mRNA and replication of BRCA1-defective cells were downregulated. Changes in the conformation and binding constants of ruthenium-BRCA1 adducts were observed, causing inactivation of the RING heterodimer BRCA1/BARD1-mediated E3 ubiquitin ligase activity

  2. Phosphorylation of eIF4E Confers Resistance to Cellular Stress and DNA-Damaging Agents through an Interaction with 4E-T: A Rationale for Novel Therapeutic Approaches.

    Directory of Open Access Journals (Sweden)

    Alba Martínez

    Full Text Available Phosphorylation of the eukaryotic translation initiation factor eIF4E is associated with malignant progression and poor cancer prognosis. Accordingly, here we have analyzed the association between eIF4E phosphorylation and cellular resistance to oxidative stress, starvation, and DNA-damaging agents in vitro. Using immortalized and cancer cell lines, retroviral expression of a phosphomimetic (S209D form of eIF4E, but not phospho-dead (S209A eIF4E or GFP control, significantly increased cellular resistance to stress induced by DNA-damaging agents (cisplatin, starvation (glucose+glutamine withdrawal, and oxidative stress (arsenite. De novo accumulation of eIF4E-containing cytoplasmic bodies colocalizing with the eIF4E-binding protein 4E-T was observed after expression of phosphomimetic S209D, but not S209A or wild-type eIF4E. Increased resistance to cellular stress induced by eIF4E-S209D was lost upon knockdown of endogenous 4E-T or use of an eIF4E-W73A-S209D mutant unable to bind 4E-T. Cancer cells treated with the Mnk1/2 inhibitor CGP57380 to prevent eIF4E phosphorylation and mouse embryonic fibroblasts derived from Mnk1/2 knockout mice were also more sensitive to arsenite and cisplatin treatment. Polysome analysis revealed an 80S peak 2 hours after arsenite treatment in cells overexpressing phosphomimetic eIF4E, indicating translational stalling. Nonetheless, a selective increase was observed in the synthesis of some proteins (cyclin D1, HuR, and Mcl-1. We conclude that phosphorylation of eIF4E confers resistance to various cell stressors and that a direct interaction or regulation of 4E-T by eIF4E is required. Further delineation of this process may identify novel therapeutic avenues for cancer treatment, and these results support the use of modern Mnk1/2 inhibitors in conjunction with standard therapy.

  3. Differences between disease-associated endoplasmic reticulum aminopeptidase 1 (ERAP1) isoforms in cellular expression, interactions with tumour necrosis factor receptor 1 (TNF-R1) and regulation by cytokines.

    Science.gov (United States)

    Yousaf, N; Low, W Y; Onipinla, A; Mein, C; Caulfield, M; Munroe, P B; Chernajovsky, Y

    2015-05-01

    Endoplasmic reticulum aminopeptidase 1 (ERAP1) processes peptides for major histocompatibility complex (MHC) class I presentation and promotes cytokine receptor ectodomain shedding. These known functions of ERAP1 may explain its genetic association with several autoimmune inflammatory diseases. In this study, we identified four novel alternatively spliced variants of ERAP1 mRNA, designated as ΔExon-11, ΔExon-13, ΔExon-14 and ΔExon-15. We also observed a rapid and differential modulation of ERAP1 mRNA levels and spliced variants in different cell types pretreated with lipopolysaccharide (LPS). We have studied three full-length allelic forms of ERAP1 (R127-K528, P127-K528, P127-R528) and one spliced variant (ΔExon-11) and assessed their interactions with tumour necrosis factor receptor 1 (TNF-R1) in transfected cells. We observed variation in cellular expression of different ERAP1 isoforms, with R127-K528 being expressed at a much lower level. Furthermore, the cellular expression of full-length P127-K528 and ΔExon-11 spliced variant was enhanced significantly when co-transfected with TNF-R1. Isoforms P127-K528, P127-R528 and ΔExon-11 spliced variant associated with TNF-R1, and this interaction occurred in a region within the first 10 exons of ERAP1. Supernatant-derived vesicles from transfected cells contained the full-length and ectodomain form of soluble TNF-R1, as well as carrying the full-length ERAP1 isoforms. We observed marginal differences between TNF-R1 ectodomain levels when co-expressed with individual ERAP1 isoforms, and treatment of transfected cells with tumour necrosis factor (TNF), interleukin (IL)-1β and IL-10 exerted variable effects on TNF-R1 ectodomain cleavage. Our data suggest that ERAP1 isoforms may exhibit differential biological properties and inflammatory mediators could play critical roles in modulating ERAP1 expression, leading to altered functional activities of this enzyme. PMID:25545008

  4. Diesel exhaust exposure enhances venoconstriction via uncoupling of eNOS

    International Nuclear Information System (INIS)

    Environmental air pollution is associated with adverse cardiovascular events, including increased hospital admissions due to heart failure and myocardial infarction. The exact mechanism(s) by which air pollution affects the heart and vasculature is currently unknown. Recent studies have found that exposure to air pollution enhances arterial vasoconstriction in humans and animal models. Work in our laboratory has shown that diesel emissions (DE) enhance vasoconstriction of mouse coronary arteries. Thus, we hypothesized that DE could enhance vasoconstriction in arteries and veins through uncoupling of endothelial nitric oxide synthase (eNOS). To test this hypothesis, we first bubbled DE through a physiological saline solution and exposed isolated mesenteric veins. Second, we exposed animals, whole body, to DE at 350 μg/m3 for 4 h, after which mesenteric arteries and veins were isolated. Results from these experiments show that saline bubbled with DE as well as inhaled DE enhances vasoconstriction in veins but not arteries. Exposure to several representative volatile organic compounds found in the DE-exposed saline did not enhance arterial constriction. L-nitro-arginine-methyl-ester (L-NAME), an eNOS inhibitor, normalized the control vessels to the DE-exposed vessels implicating an uncoupling of eNOS as a mechanism for enhanced vasoconstriction. The principal conclusions of this research are 1) veins exhibit endothelial dysfunction following in vivo and ex vivo exposures to DE, 2) veins appear to be more sensitive to DE effects than arteries, and 3) DE components most likely induce endothelial dysfunction through the uncoupling of eNOS

  5. The Tropical Intraseasonal Oscillation in SAMIL Coupled and Uncoupled General Circulation Models

    Institute of Scientific and Technical Information of China (English)

    YANG Jing; BAO Qing; WANG Xiaocong; ZHOU Tianjun

    2012-01-01

    Simulations of tropical intraseasonal oscillation (TISO) in SAMIL,the Spectral Atmospheric Model from the Institute of Atmospheric Physics (IAP) State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics (LASG) coupled and uncoupled general circulation models were comprehensively evaluated in this study.Compared to the uncoupled model,the atmosphere-ocean coupled model improved the TISO simulation in the following aspects:(1) the spectral intensity for the 30-80-day peak eastward periods was more realistic; (2) the eastward propagation signals over western Pacific were stronger; and (3) the variance distribution and stronger signals of Kelvin waves and mixed Rossby gravity waves were more realistic. Better performance in the coupled run was assumed to be associated with a better mean state and a more realistic relationship between precipitation and SST.In both the coupled and uncoupled runs,the unrealistic simulation of the eastward propagation over the equatorial Indian Ocean might have been associated with the biases of the precipitation mean state over the Indian Ocean,and the unrealistic split of maximum TISO precipitation variance over the Pacific might have corresponded to the exaggeration of the double Intertropical Convergence Zone (ITCZ) structure in precipitation mean state.However,whether a better mean state leads to better TISO activity remains questionable.Notably,the northward propagation over the Indian Ocean during summer was not improved in the mean lead-lag correlation analysis,but case studies have shown some strong cases to yield remarkably realistic northward propagation in coupled runs.

  6. Evaluation of the electron transport chain inhibition and uncoupling of mitochondrial bioelectrocatalysis with antibiotics and nitro-based compounds

    International Nuclear Information System (INIS)

    Mitochondrial bioelectrocatalysis can be useful for sensing applications due to the unique metabolic pathways than can be selectively inhibited and uncoupled in mitochondria. This paper details the comparison of different inhibitors and nitro-containing explosive uncouplers in a mitochondria-catalyzed biofuel cell for self-powered explosive sensing. Previous research has reported inhibition of pyruvate oxidation at a mitochondria-modified electrode followed by nitroaromatic uncoupling of current and power. We have previously used oligomycin as the antibiotic and nitrobenzene as the uncoupler of the membrane in the mitochondria-catalyzed biofuel cell, but no comprehensive comparison of various mitochondria inhibitors or explosives has been performed. Results are discussed here for inhibitors targeting complex I, complex III, ATP synthases, adenine nucleotide transport and monocarboxylic acid transport. Reactivation with nitrobenzene was possible in the presence of these inhibitors: oligomycin, 3,3'-diindolylmethane, atractyloside, rotenone, α-cyano-4-hydroxy cinnamic acid and antimycin A. All eleven explosives studied, including: 2,4,6-trinitrotoluene (TNT) and 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), caused uncoupling of the mitochondria function and could be detected by the biosensor.

  7. Modelling cellular behaviour

    Science.gov (United States)

    Endy, Drew; Brent, Roger

    2001-01-01

    Representations of cellular processes that can be used to compute their future behaviour would be of general scientific and practical value. But past attempts to construct such representations have been disappointing. This is now changing. Increases in biological understanding combined with advances in computational methods and in computer power make it possible to foresee construction of useful and predictive simulations of cellular processes.

  8. Macromolecular lesions and cellular radiation chemistry

    International Nuclear Information System (INIS)

    Our studies of the interaction of densely ionizing particles with macromolecules in the living cell may be divided into four parts: characterization of lesions to cellular DNA in the unmodified Bragg ionization curve; characterization of lesions to cellular DNA in the spread Bragg curve as used in radiation therapy; elucidation of the cellular radiation chemistry characteristic of high vs. low LET radiation qualities; and the introduction of novel techniques designed to give a better understanding of the fundamental properties of induction of lesions and their repair potentials in high LET radiation

  9. Synchronization of uncoupled excitable systems induced by white and coloured noise

    International Nuclear Information System (INIS)

    We study, both numerically and experimentally, the synchronization of uncoupled excitable systems due to a common noise. We consider two identical FitzHugh-Nagumo systems, which display both spiking and non-spiking behaviours in chaotic or periodic regimes. An electronic circuit provides a laboratory implementation of these dynamics. Synchronization is tested with both white and coloured noise, showing that coloured noise is more effective in inducing synchronization of the systems. We also study the effects on the synchronization of parameter mismatch and of the presence of intrinsic (not common) noise, and we conclude that the best performance of coloured noise is robust under these distortions.

  10. Genetic analysis on 3'-terminal flanking region of uncoupling protein 3 in different pig breeds

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The 3′-terminal flanking region of porcine uncoupling protein 3 (UCP3) was cloned, the sequence data revealed 15 nucleotide substitutions among Landrace and three Chinese native pig breeds named Neijiang, Minpig and Erhualian. The continuous 9 polymorphic sites were checked by PCR-RFLP, the results indicatedthat Erhualian had extraordinary gene frequency, presented most significant difference by χ2 test compared with Landrace, Largewhite, Neijiang and Minpig respectively, significant level compared with Meishan; and Meishan also had significant difference compared with Landrace and Minpig respectively. These results canbe concluded that Taihu pigs have special genetic characteristics among pig breeds.

  11. Mitochondrial uncoupling protein 2 gene transcript levels are elevated in maturating erythroid cells

    Czech Academy of Sciences Publication Activity Database

    Flachs, Pavel; Šponarová, Jana; Kopecký, P.; Horváth, Ondřej; Šedivá, A.; Nibbelink, M.; Casteilla, L.; Medříková, Daša; Neckář, Jan; Kolář, František; Kopecký, Jan

    2007-01-01

    Roč. 581, č. 6 (2007), s. 1093-1097. ISSN 0014-5793 Grant ostatní: the Wellcome Trust(XE) 070821/Z/03/Z; EARNEST(XE) FOOD-CT-2005-007036 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50520514 Source of funding: N - neverejné zdroje ; R - rámcový projekt EK Keywords : uncoupling protein 2 * erythropoiesis * hypoxia Subject RIV: ED - Physiology Impact factor: 3.263, year: 2007

  12. Antioxidant and regulatory role of mitochondrial uncoupling protein UCP2 in pancreatic beta-cells

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr; Olejár, Tomáš; Smolková, Katarína; Ježek, Jan; Dlasková, Andrea; Plecitá-Hlavatá, Lydie; Zelenka, Jaroslav; Špaček, Tomáš; Engstová, Hana; Reguera Pajuelo, David; Jabůrek, Martin

    2014-01-01

    Roč. 63, Suppl.1 (2014), S73-S91. ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GAP305/12/1247; GA ČR(CZ) GPP304/10/P204; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : mitochondria * uncoupling protein UCP2 * pancreatic beta-cells * reactive oxygen species * glucose-stimulated insulin secretion Subject RIV: EA - Cell Biology Impact factor: 1.293, year: 2014

  13. ADENOVIRUS INTERACTION WITH ITS CELLULAR RECEPTOR CAR.

    Energy Technology Data Exchange (ETDEWEB)

    HOWITT,J.; ANDERSON,C.W.; FREIMUTH,P.

    2001-08-01

    The mechanism of adenovirus attachment to the host cell plasma membrane has been revealed in detail by research over the past 10 years. It has long been known that receptor binding activity is associated with the viral fibers, trimeric spike proteins that protrude radially from the vertices of the icosahedral capsid (Philipson et al. 1968). In some adenovirus serotypes, fiber and other virus structural proteins are synthesized in excess and accumulate in the cell nucleus during late stages of infection. Fiber protein can be readily purified from lysates of cells infected with subgroup C viruses, for example Ad2 and Ad5 (Boulanger and Puvion 1973). Addition of purified fiber protein to virus suspensions during adsorption strongly inhibits infection, indicating that fiber and intact virus particles compete for binding sites on host cells (Philipson et al. 1968; Hautala et al. 1998). Cell binding studies using purified radiolabeled fiber demonstrated that fiber binds specifically and with high affinity to the cell plasma membrane, and that cell lines typically used for laboratory propagation of adenovirus have approximately 10{sup 4} high-affinity receptor sites per cell (Persson et al. 1985; Freimuth 1996). Similar numbers of high-affinity binding sites for radiolabeled intact virus particles also were observed (Seth et al. 1994).

  14. ADENOVIRUS INTERACTION WITH ITS CELLULAR RECEPTOR CAR

    International Nuclear Information System (INIS)

    The mechanism of adenovirus attachment to the host cell plasma membrane has been revealed in detail by research over the past 10 years. It has long been known that receptor binding activity is associated with the viral fibers, trimeric spike proteins that protrude radially from the vertices of the icosahedral capsid (Philipson et al. 1968). In some adenovirus serotypes, fiber and other virus structural proteins are synthesized in excess and accumulate in the cell nucleus during late stages of infection. Fiber protein can be readily purified from lysates of cells infected with subgroup C viruses, for example Ad2 and Ad5 (Boulanger and Puvion 1973). Addition of purified fiber protein to virus suspensions during adsorption strongly inhibits infection, indicating that fiber and intact virus particles compete for binding sites on host cells (Philipson et al. 1968; Hautala et al. 1998). Cell binding studies using purified radiolabeled fiber demonstrated that fiber binds specifically and with high affinity to the cell plasma membrane, and that cell lines typically used for laboratory propagation of adenovirus have approximately 10(sup 4) high-affinity receptor sites per cell (Persson et al. 1985; Freimuth 1996). Similar numbers of high-affinity binding sites for radiolabeled intact virus particles also were observed (Seth et al. 1994)

  15. Mitochondria as pharmacological targets: the discovery of novel anti-obesity mitochondrial uncouplers from Africa's medicinal plants.

    Science.gov (United States)

    Ocloo, Augustine; Dongdem, Julius Tieroyaare

    2012-01-01

    Obesity results from prolonged positive imbalance between energy in take and expenditure. When food intake chronically exceeds the body's energy need, an efficient metabolism results in the storage of the excess energy as fat. Mitochondria are the main centre for energy production in eukaryotic cells. Mitochondrial proton cycling is responsible for a significant proportion of basal or standard metabolic rate, therefore, further uncoupling of mitochondria may be a good way to increase energy expenditure and hence represent a good pharmacological target for the treatment of obesity. This implies that, any chemical agent or photochemical compound that further uncouples the mitochondria in vivo without having any effect on mitochondria activity could be a potential target in finding treatment for obesity. In the past, uncoupling by 2, 4-dinitrophenol has been used this way with notable success. This paper discusses the mitochondria as targets in the discovery of potential plant natural anti-obesity products from Africa's rich rainforests. PMID:23983343

  16. Asiatic acid uncouples respiration in isolated mouse liver mitochondria and induces HepG2 cells death.

    Science.gov (United States)

    Lu, Yapeng; Liu, Siyuan; Wang, Ying; Wang, Dang; Gao, Jing; Zhu, Li

    2016-09-01

    Asiatic acid, one of the triterpenoid components isolated from Centella asiatica, has received increasing attention due to a wide variety of biological activities. To date, little is known about its mechanisms of action. Here we examined the cytotoxic effect of asiatic acid on HepG2 cells and elucidated some of the underlying mechanisms. Asiatic acid induced rapid cell death, as well as mitochondrial membrane potential (MMP) dissipation, ATP depletion and cytochrome c release from mitochondria to the cytosol in HepG2 cells. In mitochondria isolated from mouse liver, asiatic acid treatment significantly stimulated the succinate-supported state 4 respiration rate, dissipated the MMP, increased Ca(2+) release from Ca(2+)-loaded mitochondria, decreased ATP content and promoted cytochrome c release, indicating the uncoupling effect of asiatic acid. Hydrogen peroxide (H2O2) produced by succinate-supported mitochondrial respiration was also significantly inhibited by asiatic acid. In addition, asiatic acid inhibited Ca(2+)-induced mitochondrial swelling but did not induce mitochondrial swelling in hyposmotic potassium acetate medium which suggested that asiatic acid may not act as a protonophoric uncoupler. Inhibition of uncoupling proteins (UCPs) or blockade of adenine nucleotide transporter (ANT) attenuated the effect of asiatic acid on MMP dissipation, Ca(2+) release, mitochondrial respiration and HepG2 cell death. When combined inhibition of UCPs and ANT, asiatic acid-mediated uncoupling effect was noticeably alleviated. These results suggested that both UCPs and ANT partially contribute to the uncoupling properties of asiatic acid. In conclusion, asiatic acid is a novel mitochondrial uncoupler and this property is potentially involved in its toxicity on HepG2 cells. PMID:27288117

  17. The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria.

    Science.gov (United States)

    Long, Jonathan Z; Svensson, Katrin J; Bateman, Leslie A; Lin, Hua; Kamenecka, Theodore; Lokurkar, Isha A; Lou, Jesse; Rao, Rajesh R; Chang, Mi Ra; Jedrychowski, Mark P; Paulo, Joao A; Gygi, Steven P; Griffin, Patrick R; Nomura, Daniel K; Spiegelman, Bruce M

    2016-07-14

    Brown and beige adipocytes are specialized cells that express uncoupling protein 1 (UCP1) and dissipate chemical energy as heat. These cells likely possess alternative UCP1-independent thermogenic mechanisms. Here, we identify a secreted enzyme, peptidase M20 domain containing 1 (PM20D1), that is enriched in UCP1(+) versus UCP1(-) adipocytes. We demonstrate that PM20D1 is a bidirectional enzyme in vitro, catalyzing both the condensation of fatty acids and amino acids to generate N-acyl amino acids and also the reverse hydrolytic reaction. N-acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. Mice with increased circulating PM20D1 have augmented respiration and increased N-acyl amino acids in blood. Lastly, administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure. These data identify an enzymatic node and a family of metabolites that regulate energy homeostasis. This pathway might be useful for treating obesity and associated disorders. PMID:27374330

  18. Radiochemical synthesis and photochemical properites of the uncoupler 2-azido-4-nitrophenol, a versatile photoaffinity labeling

    International Nuclear Information System (INIS)

    2-Amino-4-nitrophenol was tritiated in an acid catalyzed hydrogen exchange reaction. Radioactive 2-azido-4-nitrophenol with a specific radioactivity up to 21 mCi/mmol was synthesized from 2-amino-4-nitrophenol by diazotization and azide coupling. The photochemical properties of the uncoupler, 2-azido-4-nitrophenol, were studied as free solute and as ligand bound to uncoupler binding sites in bovine serum albumin and mitochondria. Based on product analyses, irradiation of free or bound 2-azido-4-nitrophenolate with visible light results in the formation of nitrene intermediates with a singlet to triplet ratio of 6:1 to 9:1. 2-Azido-4-nitrophenolate and bovine serum albumin form a strong 1:1 complex (K/sub D/ = 0.7 μM) which can be converted into a photoproduct with a covalent bond between the label and the protein. The acid dissociation constant of the protein-bound 2-amino-4-nitrophenol moiely is strongly pH dependent. Photoaffinity labeling of mitochondria by 2-azido-4-nitrophenolate follows a pattern expected from equilibrium binding studies using normal and lipid-depleted particles: polypeptides were found to bear 90 to 95% of the radioactive label, and 5 to 10% of the latter was bound to phospholipids. Two polypeptides (approximately 56,000 and 31,000 daltons) were associated with 60% of the label, indicating a high degree of specific photochemical labeling

  19. Explicit thin-lens solution for an arbitrary four by four uncoupled beam transfer matrix

    Energy Technology Data Exchange (ETDEWEB)

    Balandin, V. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Orlov, S. [Moscow State Univ. (Russian Federation). Faculty of Computational Mathematics and Cybernetics

    2011-10-15

    In the design of beam transport lines one often meets the problem of constructing a quadrupole lens system that will produce desired transfer matrices in both the horizontal and vertical planes. Nowadays this problem is typically approached with the help of computer routines, but searching for the numerical solution one has to remember that it is not proven yet that an arbitrary four by four uncoupled beam transfer matrix can be represented by using a finite number of drifts and quadrupoles (representation problem) and the answer to this questions is not known not only for more or less realistic quadrupole field models but also for the both most commonly used approximations of quadrupole focusing, namely thick and thin quadrupole lenses. In this paper we make a step forward in resolving the representation problem and, by giving an explicit solution, we prove that an arbitrary four by four uncoupled beam transfer matrix actually can be obtained as a product of a finite number of thin-lenses and drifts. (orig.)

  20. Uncoupling fertility from fertility-associated pheromones in worker honeybees (Apis mellifera).

    Science.gov (United States)

    Malka, Osnat; Katzav-Gozansky, Tamar; Hefetz, Abraham

    2009-03-01

    Fertility-associated pheromones, chemical signals delineating ovarian development, were favourably selected in the course of evolution because it is in the best interest of both the signallers (in recruiting help from other colony members) and the receivers (in assisting them to reach an informed decision of how to maximize fitness). Such signals therefore should constitute honest, deception-proof indicators of ovarian development, suggesting, theoretically, that the processes of ovarian development and signal production are irreversibly coupled. Here we demonstrate that these processes can be uncoupled by treating queenless (QL) honeybee callow workers with methoprene, a juvenile hormone (JH) analog. While methoprene effectively inhibited ovarian development, it neither inhibited Dufour's fertility signal nor the mandibular glands' dominance signal. In fact, there was even a slight augmentation of both in the methoprene-treated bees. Thus, although fertility and fertility signals are tightly associated, they can be uncoupled by experimental manipulation. These results are consistent with the hypothesis that ovarian development and fertility-associated signal production are triggered by a common event/signal (e.g. queen pheromone disappearance) but comprise different regulatory systems. The evolutionary implication is that these two traits have evolved independently and may have been co-opted to emphasize the reproductive status of workers in the competition for reproduction. PMID:19041321

  1. Heterogeneous cellular networks

    CERN Document Server

    Hu, Rose Qingyang

    2013-01-01

    A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

  2. Cellular Reflectarray Antenna

    Science.gov (United States)

    Romanofsky, Robert R.

    2010-01-01

    The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

  3. Cellular oncogenes in neoplasia.

    OpenAIRE

    Chan, V T; McGee, J O

    1987-01-01

    In recent years cellular homologues of many viral oncogenes have been identified. As these genes are partially homologous to viral oncogenes and are activated in some tumour cell lines they are termed "proto-oncogenes". In tumour cell lines proto-oncogenes are activated by either quantitative or qualitative changes in gene structure: activation of these genes was originally thought to be a necessary primary event in carcinogenesis, but activated cellular oncogenes, unlike viral oncogenes, do ...

  4. Cellular Cardiomyoplasty: Clinical Application

    OpenAIRE

    Chachques, J. (J.); Acar, C; J. Herreros; Trainini, J. (Jorge); Prosper, F.; D’Attellis, N. (N.); Fabiani, J. N.; Carpentier, A

    2004-01-01

    Myocardial regeneration can be induced with the implantation of a variety of myogenic and angiogenic cell types. More than 150 patients have been treated with cellular cardiomyoplasty worldwide, 18 patients have been treated by our group. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit postischemic remodelling, and restore regional myocardial contractility. Techniques for skeletal myoblasts culture and ex vivo expansion using auto...

  5. Quantification of uncoupling protein 2 reveals its main expression in immune cells and selective up-regulation during T-cell proliferation.

    Directory of Open Access Journals (Sweden)

    Anne Rupprecht

    Full Text Available Uncoupling protein 2 (UCP2 is an inner mitochondrial membrane protein. Although the protein was discovered in 1997, its function and even its tissue distribution are still under debate. Here we present a quantitative analysis of mRNA and protein expression in various mice tissues, revealing that UCP2 is mainly expressed in organs and cells associated with the immune system. Although the UCP2 gene is present in the brain, as demonstrated using quantitative RT-PCR, the protein was not detectable in neurons under physiological conditions. Instead, we could detect UCP2 in microglia, which act in the immune defense of the central nervous system. In lymphocytes, activation led to a ten-fold increase of UCP2 protein expression simultaneously to the increase in levels of other mitochondrial proteins, whereas lymphocyte re-stimulation resulted in the selective increase of UCP2. The highest detected level of UCP2 expression in stimulated T-cells (0.54 ng/(µg total cellular protein was approximately 200 times lower than the level of UCP1 in brown adipose tissue from room temperature acclimated mice. Both the UCP2 expression pattern and the time course of up-regulation in stimulated T-cells imply UCP2's involvement in the immune response, probably by controlling the metabolism during cell proliferation.

  6. Oxidase uncoupling in heme monooxygenases: Human cytochrome P450 CYP3A4 in Nanodiscs

    Energy Technology Data Exchange (ETDEWEB)

    Grinkova, Yelena V.; Denisov, Ilia G.; McLean, Mark A. [Departments of Biochemistry and Chemistry, University of Illinois, 505 South Goodwin Avenue (United States); Sligar, Stephen G., E-mail: s-sligar@illinois.edu [Departments of Biochemistry and Chemistry, University of Illinois, 505 South Goodwin Avenue (United States)

    2013-01-25

    Highlights: ► Substantial reducing equivalents are lost in human P450 CYP3A4 via an oxidase channel. ► Substrate binding has a pronounced effect on uncoupling in cytochrome P450. ► Anionic phospholipids improve the overall coupling in CYP3A4 Nanodiscs. -- Abstract: The normal reaction mechanism of cytochrome P450 operates by utilizing two reducing equivalents to reduce atmospheric dioxygen, producing one molecule of water and an oxygenated product in an overall stoichiometry of 2 electrons:1 dioxygen:1 product. However, three alternate unproductive pathways exist where the intermediate iron–oxygen states in the catalytic cycle can yield reduced oxygen products without substrate metabolism. The first involves release of superoxide from the oxygenated intermediate while the second occurs after input of the second reducing equivalent. Superoxide rapidly dismutates and hence both processes produce hydrogen peroxide that can be cytotoxic to the organism. In both cases, the formation of hydrogen peroxide involves the same overall stoichiometry as oxygenases catalysis. The key step in the catalytic cycle of cytochrome P450 involves scission of the oxygen–oxygen bond of atmospheric dioxygen to produce a higher valent iron-oxo state termed “Compound I”. This intermediate initiates a radical reaction in the oxygenase pathway but also can uptake two additional reducing equivalents from reduced pyridine nucleotide (NADPH) and the flavoprotein reductase to produce a second molecule of water. This non-productive decay of Compound I thus yields an overall oxygen to NADPH ratio of 1:2 and does not produce hydrocarbon oxidation. This water uncoupling reaction provides one of a limited means to study the reactivity of the critical Compound I intermediate in P450 catalysis. We measured simultaneously the rates of NADPH and oxygen consumption as a function of substrate concentration during the steady-state hydroxylation of testosterone catalyzed by human P450 CYP3A4

  7. Oxidase uncoupling in heme monooxygenases: Human cytochrome P450 CYP3A4 in Nanodiscs

    International Nuclear Information System (INIS)

    Highlights: ► Substantial reducing equivalents are lost in human P450 CYP3A4 via an oxidase channel. ► Substrate binding has a pronounced effect on uncoupling in cytochrome P450. ► Anionic phospholipids improve the overall coupling in CYP3A4 Nanodiscs. -- Abstract: The normal reaction mechanism of cytochrome P450 operates by utilizing two reducing equivalents to reduce atmospheric dioxygen, producing one molecule of water and an oxygenated product in an overall stoichiometry of 2 electrons:1 dioxygen:1 product. However, three alternate unproductive pathways exist where the intermediate iron–oxygen states in the catalytic cycle can yield reduced oxygen products without substrate metabolism. The first involves release of superoxide from the oxygenated intermediate while the second occurs after input of the second reducing equivalent. Superoxide rapidly dismutates and hence both processes produce hydrogen peroxide that can be cytotoxic to the organism. In both cases, the formation of hydrogen peroxide involves the same overall stoichiometry as oxygenases catalysis. The key step in the catalytic cycle of cytochrome P450 involves scission of the oxygen–oxygen bond of atmospheric dioxygen to produce a higher valent iron-oxo state termed “Compound I”. This intermediate initiates a radical reaction in the oxygenase pathway but also can uptake two additional reducing equivalents from reduced pyridine nucleotide (NADPH) and the flavoprotein reductase to produce a second molecule of water. This non-productive decay of Compound I thus yields an overall oxygen to NADPH ratio of 1:2 and does not produce hydrocarbon oxidation. This water uncoupling reaction provides one of a limited means to study the reactivity of the critical Compound I intermediate in P450 catalysis. We measured simultaneously the rates of NADPH and oxygen consumption as a function of substrate concentration during the steady-state hydroxylation of testosterone catalyzed by human P450 CYP3A4

  8. Stability of a Long Noncoding Viral RNA Depends on a 9-nt Core Element at the RNA 5' End to Interact with Viral ORF57 and Cellular PABPC1

    Directory of Open Access Journals (Sweden)

    Maria J. Massimelli, Jeong-Gu Kang, Vladimir Majerciak, Shu-Yun Le, David J. Liewehr, Seth M. Steinberg, Zhi-Ming Zheng

    2011-01-01

    Full Text Available Kaposi sarcoma-associated herpesvirus (KSHV ORF57, also known as Mta (mRNA transcript accumulation, enhances viral intron-less transcript accumulation and promotes splicing of intron-containing viral RNA transcripts. In this study, we identified KSHV PAN, a long non-coding polyadenylated nuclear RNA as a main target of ORF57 by a genome-wide CLIP (cross-linking and immunoprecipitation approach. KSHV genome lacking ORF57 expresses only a minimal amount of PAN. In cotransfection experiments, ORF57 alone increased PAN expression by 20-30-fold when compared to vector control. This accumulation function of ORF57 was dependent on a structured RNA element in the 5' PAN, named MRE (Mta responsive element, but not much so on an ENE (expression and nuclear retention element in the 3' PAN previously reported by other studies. We showed that the major function of the 5' PAN MRE is increasing the RNA half-life of PAN in the presence of ORF57. Further mutational analyses revealed a core motif consisting of 9 nucleotides in the MRE-II , which is responsible for ORF57 interaction and function. The 9-nt core in the MRE-II also binds cellular PABPC1, but not the E1B-AP5 which binds another region of the MRE-II. In addition, we found that PAN RNA is partially exportable in the presence of ORF57. Together, our data provide compelling evidence as to how ORF57 functions to accumulate a non-coding viral RNA in the course of virus lytic infection.

  9. Cellular metabolic rate is influenced by life-history traits in tropical and temperate birds.

    Directory of Open Access Journals (Sweden)

    Ana Gabriela Jimenez

    Full Text Available In general, tropical birds have a "slow pace of life," lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cells from temperate species of similar body size and common phylogenetic history. We cultured primary dermal fibroblasts from 17 tropical and 17 temperate phylogenetically-paired species of birds in a common nutritive and thermal environment and then examined basal, uncoupled, and non-mitochondrial cellular O2 consumption (OCR, proton leak, and anaerobic glycolysis (extracellular acidification rates [ECAR], using an XF24 Seahorse Analyzer. We found that multiple measures of metabolism in cells from tropical birds were significantly lower than their temperate counterparts. Basal and uncoupled cellular metabolism were 29% and 35% lower in cells from tropical birds, respectively, a decrease closely aligned with differences in whole-animal metabolism between tropical and temperate birds. Proton leak was significantly lower in cells from tropical birds compared with cells from temperate birds. Our results offer compelling evidence that whole-animal metabolism is linked to cellular respiration as a function of an animal's life-history evolution. These findings are consistent with the idea that natural selection has uniquely fashioned cells of long-lived tropical bird species to have lower rates of metabolism than cells from shorter-lived temperate species.

  10. Fatty Acids are Key in 4-Hydroxy-2-Nonenal-Mediated Activation of Uncoupling Proteins 1 and 2

    Czech Academy of Sciences Publication Activity Database

    Malingriaux, E. A.; Rupprecht, A.; Gille, L.; Jovanovic, O.; Ježek, Petr; Jabůrek, Martin; Pohl, E. E.

    2013-01-01

    Roč. 8, č. 10 (2013), e77786. E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP302/10/0346 Institutional support: RVO:67985823 Keywords : mitochondrial uncoupling proteins * 4-hydroxy-2-nonenal * fatty acids Subject RIV: EA - Cell Biology Impact factor: 3.534, year: 2013

  11. Uncoupled correlated variational function in (e, 2e) and (e, 3e) calculations for ionization of the helium atom

    CERN Document Server

    Chuluunbaatar, O; Vinitsky, S I

    2002-01-01

    The uncoupled correlated variational function of the helium atom ground state declared earlier is examined in calculations of differential cross sections of fast electron impact single and double binary ionization processes. An optimal one-parametric set of orthogonal basic functions is generated to provide the considerable coincidence with the experiment and calculations with the alternative multiparametric trial wave functions.

  12. Autocatalytic closure and the evolution of cellular information processing networks

    OpenAIRE

    Decraene, James

    2009-01-01

    Cellular Information Processing Networks (CIPNs) are chemical networks of interacting molecules occurring in living cells. Through complex molecular interactions, CIPNs are able to coordinate critical cellular activities in response to internal and external stimuli. We hypothesise that CIPNs may be abstractly regarded as subsets of collectively autocatalytic (i.e., organisationally closed) reaction networks. These closure properties would subsequently interact with the evolution and adaptatio...

  13. Mitochondrial Uncoupling Protein 2 (UCP2) Regulates Retinal Ganglion Cell Number and Survival.

    Science.gov (United States)

    Barnstable, Colin J; Reddy, Rajini; Li, Hong; Horvath, Tamas L

    2016-04-01

    In the brain, mitochondrial uncoupling protein 2 (UCP2) has emerged as a stress signal associated with neuronal survival. In the retina, UCP2 is expressed primarily by retinal ganglion cells. Here, we investigated the functional relevance of UCP2 in the mouse retina. Increased expression of UCP2 significantly reduced apoptosis during the critical developmental period resulting in elevated numbers of retinal ganglion cells in the adult. Elevated UCP2 levels also protected against excitotoxic cell death induced by intraocular injection of either NMDA or kainic acid. In monolayer cultures of retinal cells, elevated UCP2 levels increased cell survival and rendered the cells independent of the survival-promoting effects of the neurotrophic factors BDNF and CNTF. Taken together, these data implicate UCP2 as an important regulator of retinal neuron survival both during development and in adult animals. PMID:26846222

  14. Thermohaline circulation stability: a box model study - Part I: uncoupled model

    CERN Document Server

    Lucarini, V; Lucarini, Valerio; Stone, Peter H.

    2004-01-01

    A thorough analysis of the stability of the uncoupled Rooth interhemispheric 3-box model of thermohaline circulation (THC) is presented. The model consists of a northern high latitudes box, a tropical box, and a southern high latitudes box, which respectively correspond to the northern, tropical and southern Atlantic ocean. We adopt restoring boundary conditions for the temperature variables and flux boundary conditions for the salinity variables. We study how the strength of THC changes when the system undergoes forcings that are analogous to those of global warming conditions by applying to the equilibrium state perturbations to the moisture and heat fluxes into the three boxes. In each class of experiments, we determine, using suitably de- fined metrics, the boundary dividing the set of forcing scenarios that lead the system to equilibria characterized by a THC pattern similar to the present one, from those that drive the system to equilibria with a reversed THC. Fast increases in the moisture flux into th...

  15. Transverse dynamics of a beam in a chain of uncoupled resonators

    International Nuclear Information System (INIS)

    A method is proposed and realized for full-scale numerical simulation of the transverse dynamics of a train of point charged bunches accelerated in a chain of identical uncoupled resonators. Selfconsistent system of equations of transverse motion of such bunches in a total field of spontaneous transition radiation of the predecessors of each bunch at f11 frequency of defocusing TM110-oscillations of the resonators is reduced to the system of the finite number of algebraic equations for amplitudes of generalized shift moments of such bunches in each resonator. Numerical solutions of this system are presented for a number of specific values of the parameters of the accelerating structure and accelerating beam as well as various starting conditions at the structure's inlet. The obtained results are used for controlling reliability level of the known methods of analytical description of the dynamics under consideration. 6 refs.; 3 figs

  16. Comparison of coupled and uncoupled load simulations on a jacket support structure

    DEFF Research Database (Denmark)

    Haselbach, Philipp Ulrich; Natarajan, Anand; Jiwinangun, Randi Gusto; Branner, Kim

    2013-01-01

    In this article, a comparison of the moments and forces at the joints of a jacket structure is made between fully coupled aerohydroelastic simulations in HAWC2 and uncoupled load predictions in the finite element software Abaqus. The jacket sub structure is modelled in moderate deep waters of 50m......-legged jacket structure similar to the Upwind reference jacket is developed in the Abaqus environment, to which is added the transition piece and tower. The aeroelastic loads determined in normal operating conditions of the turbine is integrated and centralized as nodal forces and moments acting at the tower...... and linking the loads to the components as nodal forces. In both simulation cases, the integrated loads acting on the jacket legs are computed as time series and as damage equivalent loading. The analysis and comparison of the fully coupled and decoupled simulation method show that the results vary...

  17. Coherent population transfer between uncoupled or weakly coupled states in ladder-type superconducting qutrits.

    Science.gov (United States)

    Xu, H K; Song, C; Liu, W Y; Xue, G M; Su, F F; Deng, H; Tian, Ye; Zheng, D N; Han, Siyuan; Zhong, Y P; Wang, H; Liu, Yu-Xi; Zhao, S P

    2016-01-01

    Stimulated Raman adiabatic passage offers significant advantages for coherent population transfer between uncoupled or weakly coupled states and has the potential of realizing efficient quantum gate, qubit entanglement and quantum information transfer. Here we report on the realization of the process in the superconducting Xmon and phase qutrits-two ladder-type three-level systems in which the ground state population is coherently transferred to the second excited state via the dark state subspace. We demonstrate that the population transfer efficiency is no less than 96% and 67% for the two devices, which agree well with the numerical simulation of the master equation. Population transfer via stimulated Raman adiabatic passage is significantly more robust against variations of the experimental parameters compared with that via the conventional resonant π pulse method. Our work opens up a new venue for exploring the process for quantum information processing using the superconducting artificial atoms. PMID:27009972

  18. Irregular Cellular Learning Automata.

    Science.gov (United States)

    Esnaashari, Mehdi; Meybodi, Mohammad Reza

    2015-08-01

    Cellular learning automaton (CLA) is a recently introduced model that combines cellular automaton (CA) and learning automaton (LA). The basic idea of CLA is to use LA to adjust the state transition probability of stochastic CA. This model has been used to solve problems in areas such as channel assignment in cellular networks, call admission control, image processing, and very large scale integration placement. In this paper, an extension of CLA called irregular CLA (ICLA) is introduced. This extension is obtained by removing the structure regularity assumption in CLA. Irregularity in the structure of ICLA is needed in some applications, such as computer networks, web mining, and grid computing. The concept of expediency has been introduced for ICLA and then, conditions under which an ICLA becomes expedient are analytically found. PMID:25291810

  19. Architected Cellular Materials

    Science.gov (United States)

    Schaedler, Tobias A.; Carter, William B.

    2016-07-01

    Additive manufacturing enables fabrication of materials with intricate cellular architecture, whereby progress in 3D printing techniques is increasing the possible configurations of voids and solids ad infinitum. Examples are microlattices with graded porosity and truss structures optimized for specific loading conditions. The cellular architecture determines the mechanical properties and density of these materials and can influence a wide range of other properties, e.g., acoustic, thermal, and biological properties. By combining optimized cellular architectures with high-performance metals and ceramics, several lightweight materials that exhibit strength and stiffness previously unachievable at low densities were recently demonstrated. This review introduces the field of architected materials; summarizes the most common fabrication methods, with an emphasis on additive manufacturing; and discusses recent progress in the development of architected materials. The review also discusses important applications, including lightweight structures, energy absorption, metamaterials, thermal management, and bioscaffolds.

  20. Cellular Homeostasis and Aging.

    Science.gov (United States)

    Hartl, F Ulrich

    2016-06-01

    Aging and longevity are controlled by a multiplicity of molecular and cellular signaling events that interface with environmental factors to maintain cellular homeostasis. Modulation of these pathways to extend life span, including insulin-like signaling and the response to dietary restriction, identified the cellular machineries and networks of protein homeostasis (proteostasis) and stress resistance pathways as critical players in the aging process. A decline of proteostasis capacity during aging leads to dysfunction of specific cell types and tissues, rendering the organism susceptible to a range of chronic diseases. This volume of the Annual Review of Biochemistry contains a set of two reviews addressing our current understanding of the molecular mechanisms underlying aging in model organisms and humans. PMID:27050288

  1. Cortical spreading depression produces a neuroprotective effect activating mitochondrial uncoupling protein-5

    Directory of Open Access Journals (Sweden)

    Viggiano E

    2016-07-01

    Full Text Available Emanuela Viggiano,1,2 Vincenzo Monda,1 Antonietta Messina,1 Fiorenzo Moscatelli,3 Anna Valenzano,3 Domenico Tafuri,4 Giuseppe Cibelli,3 Bruno De Luca,1 Giovanni Messina,1,3 Marcellino Monda1 1Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, Second University of Naples, Naples, 2Department of Medicine, University of Padua, Padua, 3Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 4Department of Motor Sciences and Wellness, University of Naples “Parthenope”, Naples, Italy Abstract: Depression of electrocorticogram propagating over the cortex surface results in cortical spreading depression (CSD, which is probably related to the pathophysiology of stroke, epilepsy, and migraine. However, preconditioning with CSD produces neuroprotection to subsequent ischemic episodes. Such effects require the expression or activation of several genes, including neuroprotective ones. Recently, it has been demonstrated that the expression of the uncoupling proteins (UCPs 2 and 5 is amplified during brain ischemia and their expression exerts a long-term effect upon neuron protection. To evaluate the neuroprotective consequence of CSD, the expression of UCP-5 in the brain cortex was measured following CSD induction. CSD was evoked in four samples of rats, which were sacrificed after 2 hours, 4 hours, 6 hours, and 24 hours. Western blot analyses were carried out to measure UCP-5 concentrations in the prefrontal cortices of both hemispheres, and immunohistochemistry was performed to determine the localization of UCP-5 in the brain cortex. The results showed a significant elevation in UCP-5 expression at 24 hours in all cortical strata. Moreover, UCP-5 was triggered by CSD, indicating that UCP-5 production can have a neuroprotective effect. Keywords: cortical spreading depression, neuroprotective effect, uncoupling protein-5

  2. A novel high-throughput assay for islet respiration reveals uncoupling of rodent and human islets.

    Directory of Open Access Journals (Sweden)

    Jakob D Wikstrom

    Full Text Available BACKGROUND: The pancreatic beta cell is unique in its response to nutrient by increased fuel oxidation. Recent studies have demonstrated that oxygen consumption rate (OCR may be a valuable predictor of islet quality and long term nutrient responsiveness. To date, high-throughput and user-friendly assays for islet respiration are lacking. The aim of this study was to develop such an assay and to examine bioenergetic efficiency of rodent and human islets. METHODOLOGY/PRINCIPAL FINDINGS: The XF24 respirometer platform was adapted to islets by the development of a 24-well plate specifically designed to confine islets. The islet plate generated data with low inter-well variability and enabled stable measurement of oxygen consumption for hours. The F1F0 ATP synthase blocker oligomycin was used to assess uncoupling while rotenone together with myxothiazol/antimycin was used to measure the level of non-mitochondrial respiration. The use of oligomycin in islets was validated by reversing its effect in the presence of the uncoupler FCCP. Respiratory leak averaged to 59% and 49% of basal OCR in islets from C57Bl6/J and FVB/N mice, respectively. In comparison, respiratory leak of INS-1 cells and C2C12 myotubes was measured to 38% and 23% respectively. Islets from a cohort of human donors showed a respiratory leak of 38%, significantly lower than mouse islets. CONCLUSIONS/SIGNIFICANCE: The assay for islet respiration presented here provides a novel tool that can be used to study islet mitochondrial function in a relatively high-throughput manner. The data obtained in this study shows that rodent islets are less bioenergetically efficient than human islets as well as INS1 cells.

  3. Control of mitochondrial pH by uncoupling protein 4 in astrocytes promotes neuronal survival

    KAUST Repository

    Lambert, Hélène Perreten

    2014-09-18

    Brain activity is energetically costly and requires a steady and highly regulated flow of energy equivalents between neural cells. It is believed that a substantial share of cerebral glucose, the major source of energy of the brain, will preferentially be metabolized in astrocytes via aerobic glycolysis. The aim of this study was to evaluate whether uncoupling proteins (UCPs), located in the inner membrane of mitochondria, play a role in setting up the metabolic response pattern of astrocytes. UCPs are believed to mediate the transmembrane transfer of protons, resulting in the uncoupling of oxidative phosphorylation from ATP production. UCPs are therefore potentially important regulators of energy fluxes. The main UCP isoforms expressed in the brain are UCP2, UCP4, and UCP5. We examined in particular the role of UCP4 in neuron-astrocyte metabolic coupling and measured a range of functional metabolic parameters including mitochondrial electrical potential and pH, reactive oxygen species production, NAD/NADH ratio, ATP/ADP ratio, CO2 and lactate production, and oxygen consumption rate. In brief, we found that UCP4 regulates the intramitochondrial pH of astrocytes, which acidifies as a consequence of glutamate uptake, with the main consequence of reducing efficiency of mitochondrial ATP production. The diminished ATP production is effectively compensated by enhancement of glycolysis. This nonoxidative production of energy is not associated with deleterious H2O2 production. We show that astrocytes expressing more UCP4 produced more lactate, which is used as an energy source by neurons, and had the ability to enhance neuronal survival.

  4. Wireless Cellular Mobile Communications

    Directory of Open Access Journals (Sweden)

    V. Zalud

    2002-12-01

    Full Text Available In this article is briefly reviewed the history of wireless cellularmobile communications, examined the progress in current secondgeneration (2G cellular standards and discussed their migration to thethird generation (3G. The European 2G cellular standard GSM and itsevolution phases GPRS and EDGE are described somewhat in detail. Thethird generation standard UMTS taking up on GSM/GPRS core network andequipped with a new advanced access network on the basis of codedivision multiple access (CDMA is investigated too. A sketch of theperspective of mobile communication beyond 3G concludes this article.

  5. Interacting dark energy collapse with matter components separation

    Energy Technology Data Exchange (ETDEWEB)

    Delliou, M. Le [Departamento de Física Matemática, Instituto de Física, Universidade de São Paulo, CP 66.318 — 05314-970, São Paulo, SP (Brazil); Barreiro, T., E-mail: delliou@cii.fc.ul.pt, E-mail: tmbarreiro@ulusofona.pt [Departamento de Matemática da FFMCC, Universidade Lusófona de Humanidades e Tecnologias, Campo Grande, 376 — 1749-024 Lisboa (Portugal)

    2013-02-01

    We use the spherical collapse model of structure formation to investigate the separation in the collapse of uncoupled matter (essentially baryons) and coupled dark matter in an interacting dark energy scenario. Following the usual assumption of a single radius of collapse for all species, we show that we only need to evolve the uncoupled matter sector to obtain the evolution for all matter components. This gives us more information on the collapse with a simplified set of evolution equations compared with the usual approaches. We then apply these results to four quintessence potentials and show how we can discriminate between different quintessence models.

  6. Translating partitioned cellular automata into classical type cellular automata

    OpenAIRE

    Poupet, Victor

    2008-01-01

    Partitioned cellular automata are a variant of cellular automata that was defined in order to make it very simple to create complex automata having strong properties such as number conservation and reversibility (which are often difficult to obtain on cellular automata). In this article we show how a partitioned cellular automaton can be translated into a regular cellular automaton in such a way that these properties are conserved.

  7. Genetic Dominance & Cellular Processes

    Science.gov (United States)

    Seager, Robert D.

    2014-01-01

    In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

  8. Radioactivity of cellular concrete

    International Nuclear Information System (INIS)

    The natural radioactivity of cellular concrete is discussed. Some data on the concentrations of 40K, 226Ra and 232Th in building materials in Poland are given. The results of dose rates measurements in living quarters as well as outside are presented. (A.S.)

  9. The New Cellular Immunology

    Science.gov (United States)

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  10. Cellular Particle Dynamics simulation of biomechanical relaxation processes of multi-cellular systems

    Science.gov (United States)

    McCune, Matthew; Kosztin, Ioan

    2013-03-01

    Cellular Particle Dynamics (CPD) is a theoretical-computational-experimental framework for describing and predicting the time evolution of biomechanical relaxation processes of multi-cellular systems, such as fusion, sorting and compression. In CPD, cells are modeled as an ensemble of cellular particles (CPs) that interact via short range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through numerical integration of their equations of motion. Here we present CPD simulation results for the fusion of both spherical and cylindrical multi-cellular aggregates. First, we calibrate the relevant CPD model parameters for a given cell type by comparing the CPD simulation results for the fusion of two spherical aggregates to the corresponding experimental results. Next, CPD simulations are used to predict the time evolution of the fusion of cylindrical aggregates. The latter is relevant for the formation of tubular multi-cellular structures (i.e., primitive blood vessels) created by the novel bioprinting technology. Work supported by NSF [PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.

  11. Complete nucleotide and derived amino acid sequence of cDNA encoding the mitochondrial uncoupling protein of rat brown adipose tissue: lack of a mitochondrial targeting presequence.

    OpenAIRE

    Ridley, R. G.; Patel, H. V.; Gerber, G E; Morton, R C; Freeman, K. B.

    1986-01-01

    A cDNA clone spanning the entire amino acid sequence of the nuclear-encoded uncoupling protein of rat brown adipose tissue mitochondria has been isolated and sequenced. With the exception of the N-terminal methionine the deduced N-terminus of the newly synthesized uncoupling protein is identical to the N-terminal 30 amino acids of the native uncoupling protein as determined by protein sequencing. This proves that the protein contains no N-terminal mitochondrial targeting prepiece and that a t...

  12. Cellular basis of radiation-induced fibrosis

    International Nuclear Information System (INIS)

    Fibrosis is a common sequela of both cancer treatment by radiotherapy and accidental irradiation and has been described in many tissues including skin, lung, heart and liver. The underlying mechanisms of the radiation-induced fibrosis still remain to be resolved. In the present review we tried to illustrate the basic cellular mechanisms of radiation-induced fibrosis based on the newest findings arising from molecular radiobiology and cell biology. Based on these findings the cellular mechanism of radiation-induced fibrosis can be seen as a multicellular process involving various interacting cell systems in the target organ resulting in the fibrotic phenotype of the fibroblast/fibrocyte cell system

  13. Molecular and Cellular Signaling

    CERN Document Server

    Beckerman, Martin

    2005-01-01

    A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

  14. Magnetic Cellular Switches

    OpenAIRE

    Overby, Darryl R.; Alenghat, Francis J.; Montoya-Zavala, Martín; Bei, HuCheng; Oh, Philmo; Karavitis, John; Ingber, Donald E.

    2004-01-01

    This paper focuses on the development of magnetic cellular switches to enable magnetic control of intracellular functions in living mammalian cells, including receptor signal transduction and gene transcription. Our approach takes advantage of the mechanosensitivity of adenosine 3′,5′-monophosphate (cAMP) induction and downstream transcription controlled by the cAMP regulatory element (CRE) to engineer gene constructs that optically report gene expression in living cells. We activate transcri...

  15. Cellular therapy in Tuberculosis

    Directory of Open Access Journals (Sweden)

    Shreemanta K. Parida

    2015-03-01

    Full Text Available Cellular therapy now offer promise of potential adjunct therapeutic options for treatment of drug-resistant tuberculosis (TB. We review here the role of Mesenchymal stromal cells, (MSCs, as well as other immune effector cells in the therapy of infectious diseases with a focus on TB. MSCs represent a population of tissue-resident non-hematopoietic adult progenitor cells which home into injured tissues increase the proliferative potential of broncho-alveolar stem cells and restore lung epithelium. MSCs have been shown to be immune-modulatory and anti-inflammatory mediated via cell-cell contacts as well as soluble factors. We discuss the functional profile of MSCs and their potential use for adjunct cellular therapy of multi-drug resistant TB, with the aim of limiting tissue damage, and to convert unproductive inflammatory responses into effective anti-pathogen directed immune responses. Adjunct cellular therapy could potentially offer salvage therapy options for patients with drug-resistant TB, increase clinically relevant anti-M.tuberculosis directed immune responses and possibly shorten the duration of anti-TB therapy.

  16. Cellular therapy in tuberculosis.

    Science.gov (United States)

    Parida, Shreemanta K; Madansein, Rajhmun; Singh, Nalini; Padayatchi, Nesri; Master, Iqbal; Naidu, Kantharuben; Zumla, Alimuddin; Maeurer, Markus

    2015-03-01

    Cellular therapy now offer promise of potential adjunct therapeutic options for treatment of drug-resistant tuberculosis (TB). We review here the role of Mesenchymal stromal cells, (MSCs), as well as other immune effector cells in the therapy of infectious diseases with a focus on TB. MSCs represent a population of tissue-resident non-hematopoietic adult progenitor cells which home into injured tissues increase the proliferative potential of broncho-alveolar stem cells and restore lung epithelium. MSCs have been shown to be immune-modulatory and anti-inflammatory mediated via cell-cell contacts as well as soluble factors. We discuss the functional profile of MSCs and their potential use for adjunct cellular therapy of multi-drug resistant TB, with the aim of limiting tissue damage, and to convert unproductive inflammatory responses into effective anti-pathogen directed immune responses. Adjunct cellular therapy could potentially offer salvage therapy options for patients with drug-resistant TB, increase clinically relevant anti-M.tuberculosis directed immune responses and possibly shorten the duration of anti-TB therapy. PMID:25809753

  17. Endothelium negatively modulates the vascular relaxation induced by nitric oxide donor, due to uncoupling NO synthase.

    Science.gov (United States)

    Bonaventura, Daniella; Lunardi, Claure N; Rodrigues, Gerson J; Neto, Mário A; Vercesi, Juliana A; de Lima, Renata G; da Silva, Roberto S; Bendhack, Lusiane M

    2009-10-01

    Nitrosyl ruthenium complexes have been characterized as nitric oxide (NO) donors that induce relaxation in the denuded rat aorta. There are some differences in their vascular relaxation mechanisms compared with sodium nitroprusside. This study investigates whether the endothelium could interfere with the [Ru(terpy)(bdq)NO](3+)-TERPY-induced vascular relaxation, by analyzing the maximal relaxation (Emax) and potency (pD(2)) of TERPY. Vascular reactivity experiments showed that the endothelium negatively modulates (pD(2): 6.17+/-0.07) the TERPY relaxation in intact rat aortic rings compared with the denuded rat aorta (pD(2): 6.65+/-0.07). This effect is abolished by a non-selective NO-synthase (NOS) inhibitor L-NAME (pD(2): 6.46+/-0.10), by the superoxide anion (O(2)(-)) scavenger TIRON (pD(2): 6.49+/-0.08), and by an NOS cofactor BH(4) (pD(2): 6.80+/-0.10). The selective dye for O(2)(-) (DHE) shows that TERPY enhances O(2)(-) concentration in isolated endothelial cells (intensity of fluorescence (IF):11258.00+/-317.75) compared with the basal concentration (IF: 7760.67+/-381.50), and this enhancement is blocked by L-NAME (IF: 8892.33+/-1074.41). Similar results were observed in vascular smooth muscle cells (concentration of superoxide after TERPY: 2.63+/-0.17% and after TERPY+L-NAME: -4.63+/-0.14%). Considering that TERPY could induce uncoupling NOS, thus producing O(2)(-), we have also investigated the involvement of prostanoids in the negative modulation of the endothelium. The non-selective cyclooxygenase (COX) inhibitor indomethacin and the selective tromboxane (TXA(2)) receptor antagonist SQ29548 reduce the effect of the endothelium on TERPY relaxation (pD(2) INDO: 6.80+/-0.17 and SQ29548: 6.85+/-0.15, respectively). However, a selective prostaglandin F(2alpha) receptor antagonist (AH6809) does not change the endothelium effect. Moreover, TERPY enhances the concentration of TXA(2) stable metabolite (TXB(2)), but this effect is blocked by L-NAME and TIRON. The

  18. Environment Aware Cellular Networks

    KAUST Repository

    Ghazzai, Hakim

    2015-02-01

    The unprecedented rise of mobile user demand over the years have led to an enormous growth of the energy consumption of wireless networks as well as the greenhouse gas emissions which are estimated currently to be around 70 million tons per year. This significant growth of energy consumption impels network companies to pay huge bills which represent around half of their operating expenditures. Therefore, many service providers, including mobile operators, are looking for new and modern green solutions to help reduce their expenses as well as the level of their CO2 emissions. Base stations are the most power greedy element in cellular networks: they drain around 80% of the total network energy consumption even during low traffic periods. Thus, there is a growing need to develop more energy-efficient techniques to enhance the green performance of future 4G/5G cellular networks. Due to the problem of traffic load fluctuations in cellular networks during different periods of the day and between different areas (shopping or business districts and residential areas), the base station sleeping strategy has been one of the main popular research topics in green communications. In this presentation, we present several practical green techniques that provide significant gains for mobile operators. Indeed, combined with the base station sleeping strategy, these techniques achieve not only a minimization of the fossil fuel consumption but also an enhancement of mobile operator profits. We start with an optimized cell planning method that considers varying spatial and temporal user densities. We then use the optimal transport theory in order to define the cell boundaries such that the network total transmit power is reduced. Afterwards, we exploit the features of the modern electrical grid, the smart grid, as a new tool of power management for cellular networks and we optimize the energy procurement from multiple energy retailers characterized by different prices and pollutant

  19. p53 regulates expression of uncoupling protein 1 through binding and repression of PPARγ coactivator-1α

    DEFF Research Database (Denmark)

    Hallenborg, Philip; Fjære, Even; Liaset, Bjørn;

    2016-01-01

    1-dependent uncoupled respiration and increased oxidation of glucose and fatty acids in brown or brown-like adipocytes, termed brite or beige, in relation to energy balance and homeostasis has been highlighted recently. UCP1-dependent uncoupled respiration in classic interscapular brown adipose...... tissue is central to cold-induced thermogenesis, whereas brite/beige adipocytes are of special importance in relation to diet-induced thermogenesis, where the importance of UCP1 is only clearly manifested in mice kept at thermoneutrality. We challenged wild-type and TRP53-deficient mice by high......-fat feeding under thermoneutral conditions. Interestingly, mice lacking TRP53 gained less weight compared with their wild-type counterparts. This was related to an increased expression of Ucp1 and other PPARGC1a and PPARGC1b target genes but not Ppargc1a or Ppargc1b in inguinal white adipose tissue of mice...

  20. Cellular bridges: Routes for intercellular communication and cell migration

    OpenAIRE

    Zani, Brett G.; Edelman, Elazer R.

    2010-01-01

    Cell-to-cell communication is the basis of all biology in multicellular organisms, allowing evolution of complex forms and viability in dynamic environments. Though biochemical interactions occur over distances, physical continuity remains the most direct means of cellular interactions. Cellular bridging through thin cytoplasmic channels—plasmodesmata in plants and tunneling nanotubes in animals—creates direct routes for transfer of signals and components, even pathogens, between cells. Recen...

  1. Correlation between uncoupled ATP hydrolysis and heat production by the sarcoplasmic reticulum Ca2+-ATPase: coupling effect of fluoride.

    Science.gov (United States)

    Reis, M; Farage, M; de Souza, A C; de Meis, L

    2001-11-16

    The sarcoplasmic reticulum Ca(2+)-ATPase transports Ca(2+) using the chemical energy derived from ATP hydrolysis. Part of the chemical energy is used to translocate Ca(2+) through the membrane (work) and part is dissipated as heat. The amount of heat produced during catalysis increases after formation of the Ca(2+) gradient across the vesicle membrane. In the absence of gradient (leaky vesicles) the amount of heat produced/mol of ATP cleaved is half of that measured in the presence of the gradient. After formation of the gradient, part of the ATPase activity is not coupled to Ca(2+) transport. We now show that NaF can impair the uncoupled ATPase activity with discrete effect on the ATPase activity coupled to Ca(2+) transport. For the control vesicles not treated with NaF, after formation of the gradient only 20% of the ATP cleaved is coupled to Ca(2+) transport, and the caloric yield of the total ATPase activity (coupled plus uncoupled) is 22.8 kcal released/mol of ATP cleaved. In contrast, the vesicles treated with NaF consume only the ATP needed to maintain the gradient, and the caloric yield of ATP hydrolysis is 3.1 kcal/mol of ATP. The slow ATPase activity measured in vesicles treated with NaF has the same Ca(2+) dependence as the control vesicles. This demonstrates unambiguously that the uncoupled activity is an actual pathway of the Ca(2+)-ATPase rather than a contaminating phosphatase. We conclude that when ATP hydrolysis occurs without coupled biological work most of the chemical energy is dissipated as heat. Thus, uncoupled ATPase activity appears to be the mechanistic feature underlying the ability of the Ca(2+)-ATPase to modulated heat production. PMID:11544263

  2. Mitochondria as Pharmacological Targets: The Discovery of Novel Anti-Obesity Mitochondrial Uncouplers from Africa's Medicinal Plants

    OpenAIRE

    Ocloo, Augustine; Dongdem, Julius Tieroyaare

    2011-01-01

    Obesity results from prolonged positive imbalance between energy in take and expenditure. When food intake chronically exceeds the body's energy need, an efficient metabolism results in the storage of the excess energy as fat. Mitochondria are the main centre for energy production in eukaryotic cells. Mitochondrial proton cycling is responsible for a significant proportion of basal or standard metabolic rate, therefore, further uncoupling of mitochondria may be a good way to increase energy e...

  3. Folic Acid Reverses Nitric Oxide Synthase Uncoupling and Prevents Cardiac Dysfunction in Insulin Resistance: Role of Ca2+/Calmodulin-Activated Protein Kinase II

    OpenAIRE

    Roe, Nathan D.; He, Emily Y.; Wu, Zhenbiao; Ren, Jun

    2013-01-01

    Nitric oxide synthase (NOS) may be uncoupled to produce superoxide rather than nitric oxide (NO) under pathological conditions such as diabetes mellitus and insulin resistance, leading to cardiac contractile anomalies. Nonetheless, the role of NOS uncoupling in insulin resistance-induced cardiac dysfunction remains elusive. Given that folic acid may produce beneficial effect for cardiac insufficiency partially through its NOS recoupling capacity, this study was designed to evaluate the effect...

  4. Cyanide-induced Death of Dopaminergic Cells is Mediated by Uncoupling Protein-2 Up-regulation and Reduced Bcl-2 Expression

    OpenAIRE

    Zhang, X.; Li, L.; Zhang, L.; Borowitz, J.L.; Isom, G.E.

    2009-01-01

    Cyanide is a potent inhibitor of mitochondrial oxidative metabolism and produces mitochondria-mediated death of dopaminergic neurons and sublethal intoxications are associated with a Parkinson-like syndrome. Cyanide toxicity is enhanced when mitochondrial uncoupling is stimulated following up-regulation of uncoupling protein-2 (UCP-2). In this study, the role of a pro-survival protein, Bcl-2, in cyanide-mediated cell death was determined in a rat dopaminergic immortalized mesencephalic cell l...

  5. Inhibition of membrane transport in Streptococcus faecalis by uncouplers of oxidative phosphorylation and its relationship to proton conduction.

    Science.gov (United States)

    Harold, F M; Baarda, J R

    1968-12-01

    We studied the effect of compounds that uncouple oxidative phosphorylation on membrane function in Streptoccocus faecalis, an organism which relies upon glycolysis for the generation of metabolic energy. At low concentrations (ranging from 10(-7) to 10(-4)m), tetrachlorosalicylanilide, tetramethyldipicrylamine, carbonylcyanide m-chlorophenylhydrazone, pentachlorophenol, and dicoumarol strongly inhibited energy-dependent transport of rubidium, phosphate, and certain amino acids. However, these compounds had little effect on the generation of adenosine triphosphate via glycolysis or on its utilization for the synthesis of macromolecules. They also did not seriously inhibit uptake of those monosaccharides and amino acids which do not require concurrent metabolism. It is proposed that the uncouplers interfere with the utilization of metabolic energy for membrane transport. The uncouplers accelerated the translocation of protons across the cytoplasmic membrane. It appears that a proton-impermeable membrane is required for transport, perhaps, because a proton gradient is involved in the coupling of metabolic energy to the translocation of substrates across the membrane. PMID:4177737

  6. An uncoupled dynamical downscaling for the North Sea: Method and evaluation

    Science.gov (United States)

    Mathis, M.; Mayer, B.; Pohlmann, T.

    2013-12-01

    A reliable regional modeling system for uncoupled dynamical downscaling simulations of potential global climate change scenarios in the North Sea is presented. The HAMSOM regional shelf ocean model is forced with results from the MPIOM global ocean model at the open lateral boundaries of the model domain, and with results from the REMO regional atmosphere model at the air-sea interface. The evaluation of the model chain is based on the North Sea regionalization for the period 1951-2000 of the global historic control run 20C3M for the IPCC SRES scenario runs under the CMIP3 model generation. To reproduce reasonable long-term statistics of hydrodynamic conditions in the North Sea, a bias correction method relative to ERA40 reanalysis data and WOA-2001 climatology is applied to the forcing variables. Comparisons of the HAMSOM model results with observational water temperature and salinity climatologies are presented as well as with previously published research of volume transports, residence and flushing times, NAO correlations, surface heat and fresh water fluxes, and thermocline parameters. In general, the model results agree reasonably with the given references, thereby qualifying the presented concept as an appropriate tool for dynamical downscaling of global scenario runs for the North Sea.

  7. Uncoupled organic matter burial and quality in boreal lake sediments over the Holocene

    Science.gov (United States)

    Chmiel, Hannah E.; Niggemann, Jutta; Kokic, Jovana; Ferland, Marie-Ève; Dittmar, Thorsten; Sobek, Sebastian

    2015-09-01

    Boreal lake sediments are important sites of organic carbon (OC) storage, which have accumulated substantial amounts of OC over the Holocene epoch; the temporal evolution and the strength of this Holocene carbon (C) sink is, however, not well constrained. In this study we investigated the temporal record of carbon mass accumulation rates (CMARs) and assessed qualitative changes of terrestrially derived OC in the sediment profiles of seven Swedish boreal lakes, in order to evaluate the variability of boreal lake sediments as a C sink over time. CMARs were resolved on a short-term (centennial) and long-term (i.e., over millennia of the Holocene) timescale, using radioactive lead (210Pb) and carbon (14C) isotope dating. Sources and degradation state of terrestrially derived OC were identified and characterized by molecular analyses of lignin phenols. We found that CMARs varied substantially on both short-term and long-term scales and that the variability was mostly attributed to sedimentation rates and uncoupled from the OC content in the sediment profiles. The lignin phenol analyses revealed that woody material from gymnosperms was a dominant and constant OC source to the sediments over the Holocene. Furthermore, lignin-based degradation indices, such as acid-to-aldehyde ratios, indicated that postdepositional degradation in the sediments was very limited on longer timescales, implying that terrestrial OC is stabilized in the sediments on a permanent basis.

  8. Synthesis of mitochondrial uncoupling protein in brown adipocytes differentiated in cell culture

    International Nuclear Information System (INIS)

    In order to characterize the biogenesis of unique thermogenic mitochondria of brown adipose tissue, differentiation of precursor cells isolated from mouse brown adipose tissue was studied in cell culture. Synthesis of mitochondrial uncoupling protein (UCP), F1-ATPase, and cytochrome oxidase was examined by L-[35S]methionine labeling and immunoblotting. For the first time, synthesis of physiological amounts of the UCP, a key and tissue-specific component of thermogenic mitochondria, was observed in cultures at about confluence (day 6), indicating that a complete differentiation of brown adipocytes was achieved in vitro. In postconfluent cells (day 8) the content of UCP decreased rapidly, in contrast to some other mitochondrial proteins (beta subunit of F1-ATPase, cytochrome oxidase). In these cells, it was possible, by using norepinephrine, to induce specifically the synthesis of the UCP but not of F1-ATPase or cytochrome oxidase. The maximal response was observed at 0.1 microM norepinephrine and the synthesis of UCP remained activated for at least 24 h. Detailed analysis revealed a major role of the beta-adrenergic receptors and elevated intracellular concentration of cAMP in stimulation of UCP synthesis. A quantitative recovery of the newly synthesized UCP in the mitochondrial fraction indicated completed biogenesis of functionally competent thermogenic mitochondria

  9. Specific Heat of Helium in 2 μm3 Boxes, Coupled or Uncoupled?

    International Nuclear Information System (INIS)

    We report on recent measurements of the specific heat of helium confined in pill-boxes 2 μm across and 2 μm deep made lithographically on a silicon wafer. The experimental cells distribute liquid from a bulk reservoir to ∼ 108 boxes by an array of very shallow fill-channels (0.019 μm and 0.010 μm) which represent a negligible volume compared to that of the boxes. Since the channels are so shallow, the helium in them becomes superfluid at a much lower temperature than the liquid in the boxes. Therefore, during the course of the heat capacity measurements, the liquid in the channels in always normal, and the cell would be expected to behave as a system of uncoupled boxes. We compare these measurements with one previously made of a cell where the confinement was to 1 μm boxes with an equivalent fill arrangement. While the shift in the position of the specific heat maximum relative to the 1 μm cell is what one would expect on the basis of finite-size scaling, there are discrepancies in the specific heat amplitude between the 2 μm cell utilizing different depth fill-channels, and with the 1 μm cell. It is possible that the channels, even though normal and of negligible volume, provide a weak coupling between the boxes leading to a collective rather than single-box behavior

  10. Functional and immunochemical characterization of a mutant of Escherichia coli energy uncoupled for lactose transport

    International Nuclear Information System (INIS)

    Right-side-out cytoplasmic membrane vesicles from Escherichia coli ML 308-22, a mutant ''uncoupled'' for beta-galactoside/H+ symport are specifically defective in the ability to catalyze accumulation of methyl 1-thio-beta-D-galactopyranoside (TMG) in the presence of an H+ electrochemical gradient (interior negative and alkaline). Furthermore, the rate of carrier-mediated efflux under nonenergized conditions is slow and unaffected by ambient pH from pH 5.5 to 7.5, and TMG-induced H+ influx is only about 15% of that observed in vesicles containing wild-type lac permease (ML 308-225). Alternatively, ML 308-22 vesicles bind p-nitrophenyl alpha-D-galactopyranoside and monoclonal antibody 4B1 to the same extent as ML 308-225 vesicles and catalyze facilitated diffusion and equilibrium exchange as well as ML 308-225 vesicles. When entrance counterflow is studied with external substrate at saturating and subsaturating concentrations, it is apparent that the mutation simulates the effects of deuterium oxide. That is, the mutation has no effect on the rate or extent of counterflow when external substrate is saturating but stimulates the efficiency of counterflow when external substrate is below the apparent K/sub m/. Moreover, although replacement of protium with deuterium stimulates counterflow in ML 308-225 vesicles when external substrate is subsaturating, the isotope has no effect on the mutant vesicles under the same conditions

  11. Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Bing Ji

    2015-07-01

    Full Text Available Background: Uncoupling protein 2 (UCP2 is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. Methods: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC, and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. Results: TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls. ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. Conclusions: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

  12. Weight loss by Ppc-1, a novel small molecule mitochondrial uncoupler derived from slime mold.

    Science.gov (United States)

    Suzuki, Toshiyuki; Kikuchi, Haruhisa; Ogura, Masato; Homma, Miwako K; Oshima, Yoshiteru; Homma, Yoshimi

    2015-01-01

    Mitochondria play a key role in diverse processes including ATP synthesis and apoptosis. Mitochondrial function can be studied using inhibitors of respiration, and new agents are valuable for discovering novel mechanisms involved in mitochondrial regulation. Here, we screened small molecules derived from slime molds and other microorganisms for their effects on mitochondrial oxygen consumption. We identified Ppc-1 as a novel molecule which stimulates oxygen consumption without adverse effects on ATP production. The kinetic behavior of Ppc-1 suggests its function as a mitochondrial uncoupler. Serial administration of Ppc-1 into mice suppressed weight gain with no abnormal effects on liver or kidney tissues, and no evidence of tumor formation. Serum fatty acid levels were significantly elevated in mice treated with Ppc-1, while body fat content remained low. After a single administration, Ppc-1 distributes into various tissues of individual animals at low levels. Ppc-1 stimulates adipocytes in culture to release fatty acids, which might explain the elevated serum fatty acids in Ppc-1-treated mice. The results suggest that Ppc-1 is a unique mitochondrial regulator which will be a valuable tool for mitochondrial research as well as the development of new drugs to treat obesity. PMID:25668511

  13. Weight loss by Ppc-1, a novel small molecule mitochondrial uncoupler derived from slime mold.

    Directory of Open Access Journals (Sweden)

    Toshiyuki Suzuki

    Full Text Available Mitochondria play a key role in diverse processes including ATP synthesis and apoptosis. Mitochondrial function can be studied using inhibitors of respiration, and new agents are valuable for discovering novel mechanisms involved in mitochondrial regulation. Here, we screened small molecules derived from slime molds and other microorganisms for their effects on mitochondrial oxygen consumption. We identified Ppc-1 as a novel molecule which stimulates oxygen consumption without adverse effects on ATP production. The kinetic behavior of Ppc-1 suggests its function as a mitochondrial uncoupler. Serial administration of Ppc-1 into mice suppressed weight gain with no abnormal effects on liver or kidney tissues, and no evidence of tumor formation. Serum fatty acid levels were significantly elevated in mice treated with Ppc-1, while body fat content remained low. After a single administration, Ppc-1 distributes into various tissues of individual animals at low levels. Ppc-1 stimulates adipocytes in culture to release fatty acids, which might explain the elevated serum fatty acids in Ppc-1-treated mice. The results suggest that Ppc-1 is a unique mitochondrial regulator which will be a valuable tool for mitochondrial research as well as the development of new drugs to treat obesity.

  14. Spatial uncoupling of biodegradation, soil respiration, and PAH concentration in a creosote contaminated soil

    International Nuclear Information System (INIS)

    Hotspots and coldspots of concentration and biodegradation of polycyclic aromatic hydrocarbons (PAHs) marginally overlapped at the 0.5-100 m scale in a creosote contaminated soil in southern Sweden, suggesting that concentration and biodegradation had little spatial co-variation. Biodegradation was substantial and its spatial variability considerable and highly irregular, but it had no spatial autocorrelation. The soil concentration of PAHs explained only 20-30% of the variance of their biodegradation. Soil respiration was spatially autocorrelated. The spatial uncoupling between biodegradation and soil respiration seemed to be governed by the aging of PAHs in the soil, since biodegradation of added 13C phenanthrene covaried with both soil respiration and microbial biomass. The latter two were also correlated with high concentrations of phospholipid fatty acids (PLFAs) that are common in gram-negative bacteria. However, several of the hotspots of biodegradation coincided with hotspots for the distribution of a PLFA indicative of fungal biomass. - Hotspots of PAH biodegradation in a creosote contaminated soil do not coincide with hotspots of PAH concentration, microbial biomass and respiration.

  15. Temporal Uncoupling between Energy Acquisition and Allocation to Reproduction in a Herbivorous-Detritivorous Fish.

    Science.gov (United States)

    Villamarín, Francisco; Magnusson, William E; Jardine, Timothy D; Valdez, Dominic; Woods, Ryan; Bunn, Stuart E

    2016-01-01

    Although considerable knowledge has been gathered regarding the role of fish in cycling and translocation of nutrients across ecosystem boundaries, little information is available on how the energy obtained from different ecosystems is temporally allocated in fish bodies. Although in theory, limitations on energy budgets promote the existence of a trade-off between energy allocated to reproduction and somatic growth, this trade-off has rarely been found under natural conditions. Combining information on RNA:DNA ratios and carbon and nitrogen stable-isotope analyses we were able to achieve novel insights into the reproductive allocation of diamond mullet (Liza alata), a catadromous, widely distributed herbivorous-detritivorous fish. Although diamond mullet were in better condition during the wet season, most reproductive allocation occurred during the dry season when resources are limited and fish have poorer body condition. We found a strong trade-off between reproductive and somatic investment. Values of δ13C from reproductive and somatic tissues were correlated, probably because δ13C in food resources between dry and wet seasons do not differ markedly. On the other hand, data for δ15N showed that gonads are more correlated to muscle, a slow turnover tissue, suggesting long term synthesis of reproductive tissues. In combination, these lines of evidence suggest that L. alata is a capital breeder which shows temporal uncoupling of resource ingestion, energy storage and later allocation to reproduction. PMID:26938216

  16. Low-level lasers affect uncoupling protein gene expression in skin and skeletal muscle tissues

    Science.gov (United States)

    Canuto, K. S.; Sergio, L. P. S.; Paoli, F.; Mencalha, A. L.; Fonseca, A. S.

    2016-03-01

    Wavelength, frequency, power, fluence, and emission mode determine the photophysical, photochemical, and photobiological responses of biological tissues to low-level lasers. Free radicals are involved in these responses acting as second messengers in intracellular signaling processes. Irradiated cells present defenses against these chemical species to avoid unwanted effects, such as uncoupling proteins (UCPs), which are part of protective mechanisms and minimize the effects of free radical generation in mitochondria. In this work UCP2 and UCP3 mRNA gene relative expression in the skin and skeletal muscle tissues of Wistar rats exposed to low-level red and infrared lasers was evaluated. Samples of the skin and skeletal muscle tissue of Wistar rats exposed to low-level red and infrared lasers were withdrawn for total RNA extraction, cDNA synthesis, and the evaluation of gene expression by quantitative polymerase chain reaction. UCP2 and UCP3 mRNA expression was differently altered in skin and skeletal muscle tissues exposed to lasers in a wavelength-dependent effect, with the UCP3 mRNA expression dose-dependent. Alteration on UCP gene expression could be part of the biostimulation effect and is necessary to make cells exposed to red and infrared low-level lasers more resistant or capable of adapting in damaged tissues or diseases.

  17. Intracellular spermine prevents acid-induced uncoupling of Cx43 gap junction channels.

    Science.gov (United States)

    Skatchkov, Serguei N; Bukauskas, Feliksas F; Benedikt, Jan; Inyushin, Mikhail; Kucheryavykh, Yuriy V

    2015-06-17

    Polyamines (PAs), such as spermine and spermidine, modulate the activity of numerous receptors and channels in the central nervous system (CNS) and are stored in glial cells; however, little attention has been paid to their role in the regulation of connexin (Cx)-based gap junction channels. We have previously shown that PAs facilitate diffusion of Lucifer Yellow through astrocytic gap junctions in acute brain slices; therefore, we hypothesized that spermine can regulate Cx43-mediated (as the most abundant Cx in astrocytes) gap junctional communication. We used electrophysiological patch-clamp recording from paired Novikoff cells endogenously expressing Cx43 and HeLaCx43-EGFP transfectants to study pH-dependent modulation of cell-cell coupling in the presence or absence of PAs. Our results showed (i) a higher increase in gap junctional communication at higher concentrations of cytoplasmic spermine, and (ii) that spermine prevented uncoupling of gap junctions at low intracellular pH. Taken together, we conclude that spermine enhances Cx43-mediated gap junctional communication and may preserve neuronal excitability during ischemia and trauma when pH in the brain acidifies. We, therefore, suggest a new role of spermine in the regulation of a Cx43-based network under (patho)physiological conditions. PMID:26011388

  18. Inhibition of uncoupling protein 2 with genipin exacerbates palmitate-induced hepatic steatosis

    Directory of Open Access Journals (Sweden)

    Ma Shuangtao

    2012-11-01

    Full Text Available Abstract Background Uncoupling protein 2 (UCP2 was reported to be involved in lipid metabolism through regulating the production of superoxide anion. However, the role of UCP2 in hepatocytes steatosis has not been determined. We hypothesized that UCP2 might regulate hepatic steatosis via suppressing oxidative stress. Results We tested this hypothesis in an in vitro model of hepatocytic steatosis in HepG2 cell lines induced by palmitic acid (PA. We found that treatment with PA induced an obvious lipid accumulation in HepG2 cells and a significant increase in intracellular triglyceride content. Moreover, the specific inhibition of UCP2 by genipin remarkably exacerbated PA-induced hepatocytes steatosis. Interestingly, the PA-induced superoxide overproduction can also be enhanced by incubation with genipin. In addition, administration with the antioxidant tempol abolished genipin-induced increase in intracellular lipid deposition. We further found that genipin significantly increased the protein expression of fatty acid translocase (FAT/CD36. Conclusions These findings suggest that UCP2 plays a protective role in PA-induced hepatocytic steatosis through ameliorating oxidative stress.

  19. Uncoupling of reactive oxygen species accumulation and defence signalling in the metal hyperaccumulator plant Noccaea caerulescens.

    Science.gov (United States)

    Fones, Helen N; Eyles, Chris J; Bennett, Mark H; Smith, J Andrew C; Preston, Gail M

    2013-09-01

    The metal hyperaccumulator plant Noccaea caerulescens is protected from disease by the accumulation of high concentrations of metals in its aerial tissues, which are toxic to many pathogens. As these metals can lead to the production of damaging reactive oxygen species (ROS), metal hyperaccumulator plants have developed highly effective ROS tolerance mechanisms, which might quench ROS-based signals. We therefore investigated whether metal accumulation alters defence signalling via ROS in this plant. We studied the effect of zinc (Zn) accumulation by N. caerulescens on pathogen-induced ROS production, salicylic acid accumulation and downstream defence responses, such as callose deposition and pathogenesis-related (PR) gene expression, to the bacterial pathogen Pseudomonas syringae pv. maculicola. The accumulation of Zn caused increased superoxide production in N. caerulescens, but inoculation with P. syringae did not elicit the defensive oxidative burst typical of most plants. Defences dependent on signalling through ROS (callose and PR gene expression) were also modified or absent in N. caerulescens, whereas salicylic acid production in response to infection was retained. These observations suggest that metal hyperaccumulation is incompatible with defence signalling through ROS and that, as metal hyperaccumulation became effective as a form of elemental defence, normal defence responses became progressively uncoupled from ROS signalling in N. caerulescens. PMID:23758201

  20. In vivo dissection of the estrogen receptor alpha: uncoupling of its physiological effects and medical perspectives.

    Science.gov (United States)

    Arnal, Jean-François; Gourdy, Pierre; Lenfant, Françoise

    2013-05-01

    Given this widespread role for estrogen in human physiology, it is not surprising that estrogen influence the pathophysiology of numerous diseases, including cancer (of the reproductive tract as breast, endometrial but also colorectal, prostate…), as well as neurodegenerative, inflammatory-immune, cardiovascular and metabolic diseases, and osteoporosis. These actions are mediated by the activation of estrogen receptors (ER) alpha (ERα) and beta (ERβ), which regulate target gene transcription (genomic action) through two independent activation functions (AF)-1 and AF-2, but can also elicit rapid membrane initiated steroid signals (MISS). Targeted ER gene inactivation has shown that although ERβ plays an important role in the central nervous system and in the heart, ERα appears to play a prominent role in most of the other tissues. Pharmacological activation or inhibition of ERα and/or ERβ provides already the basis for many therapeutic interventions, from contraception or hormone replacement at menopause to prevention of the recurrence of breast cancer. However, the use of these estrogens or selective estrogen receptors modulators (SERMs) have also induced undesired effects. Thus, an important challenge consists now to uncouple the beneficial actions from other deleterious ones. We summarize here an in vivo molecular "dissection" that allows to delineate in mouse the role of the main "subfunctions" of the receptor. This could pave the way to an optimization of the ER modulation. PMID:23566615

  1. Isoproterenol Increases Uncoupling, Glycolysis, and Markers of Beiging in Mature 3T3-L1 Adipocytes.

    Directory of Open Access Journals (Sweden)

    Colette N Miller

    Full Text Available Beta-adrenergic activation stimulates uncoupling protein 1 (UCP1, enhancing metabolic rate. In vitro, most work has studied brown adipocytes, however, few have investigated more established adipocyte lines such as the murine 3T3-L1 line. To assess the effect of beta-adrenergic activation, mature 3T3-L1s were treated for 6 or 48 hours with or without isoproterenol (10 and 100 μM following standard differentiation supplemented with thyroid hormone (T3; 1 nM. The highest dose of isoproterenol increased lipid content following 48 hours of treatment. This concentration enhanced UCP1 mRNA and protein expression. The increase in UCP1 following 48 hours of isoproterenol increased oxygen consumption rate. Further, coupling efficiency of the electron transport chain was disturbed and an enhancement of glycolytic rate was measured alongside this, indicating an attempt to meet the energy demands of the cell. Lastly, markers of beige adipocytes (protein content of CD137 and gene transcript of CITED1 were also found to be upregulated at 48 hours of isoproterenol treatment. This data indicates that mature 3T3-L1 adipocytes are responsive to isoproterenol and induce UCP1 expression and activity. Further, this finding provides a model for further pharmaceutical and nutraceutical investigation of UCP1 in 3T3-L1s.

  2. Is there a layer deep in the Earth that uncouples heat from mechanical work?

    Directory of Open Access Journals (Sweden)

    S. J. Burns

    2014-02-01

    Full Text Available The thermal expansion coefficient is presented as the coupling between heat energy and mechanical work. It is shown that when heat and work are uncoupled then very unusual material properties occurs: for example, acoustic p waves are not damped and heat is not generated from mechanical motion. It is found that at pressures defined by the bulk modulus divided by the Anderson–Grüneisen parameter, then the thermal expansion coefficient approaches zero in linear-elastic models. Very large pressures always reduce thermal expansion coefficients; the importance of a very small or even negative thermal expansion coefficient is discussed in relation to physical processes deep in the core and mantle of Earth. Models of the thermal expansion coefficients based on interatomic potentials which are always relegated to isometric conditions preclude any changes in volume due to temperature changes. However, it is known that the pressures in the Earth are large enough to effectively reduce thermal expansion coefficients to near zero which decouples heat from mechanical work.

  3. FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1

    Directory of Open Access Journals (Sweden)

    Michelle M. Kwon

    2015-11-01

    Full Text Available Fibroblast growth factor 21 (FGF21-mediated weight loss and improvements in glucose metabolism correlate with increased uncoupling protein 1 (Ucp1 levels in adipose tissues, suggesting that UCP1-dependent thermogenesis may drive FGF21 action. It was reported that FGF21 is equally effective at reducing body weight and improving glucose homeostasis without UCP1. We find while FGF21 can lower body weight in both wild-type and Ucp1 knockout mice, rapid clearance of glucose by FGF21 is defective in the absence of UCP1. Furthermore, in obese wild-type mice there is a fall in brown adipose tissue (BAT temperature during glucose excursion, and FGF21 improves glucose clearance while preventing the fall in BAT temperature. In Ucp1 knockout mice, the fall in BAT temperature during glucose excursion and FGF21-mediated changes in BAT temperature are lost. We conclude FGF21-mediated improvements in clearance of a glucose challenge require UCP1 and evoke UCP1-dependent thermogenesis as a method to increase glucose disposal.

  4. Widespread uncoupling between transcriptome and translatome variations after a stimulus in mammalian cells

    Directory of Open Access Journals (Sweden)

    Tebaldi Toma

    2012-06-01

    Full Text Available Abstract Background The classical view on eukaryotic gene expression proposes the scheme of a forward flow for which fluctuations in mRNA levels upon a stimulus contribute to determine variations in mRNA availability for translation. Here we address this issue by simultaneously profiling with microarrays the total mRNAs (the transcriptome and the polysome-associated mRNAs (the translatome after EGF treatment of human cells, and extending the analysis to other 19 different transcriptome/translatome comparisons in mammalian cells following different stimuli or undergoing cell programs. Results Triggering of the EGF pathway results in an early induction of transcriptome and translatome changes, but 90% of the significant variation is limited to the translatome and the degree of concordant changes is less than 5%. The survey of other 19 different transcriptome/translatome comparisons shows that extensive uncoupling is a general rule, in terms of both RNA movements and inferred cell activities, with a strong tendency of translation-related genes to be controlled purely at the translational level. By different statistical approaches, we finally provide evidence of the lack of dependence between changes at the transcriptome and translatome levels. Conclusions We propose a model of diffused independency between variation in transcript abundances and variation in their engagement on polysomes, which implies the existence of specific mechanisms to couple these two ways of regulating gene expression.

  5. Failover in cellular automata

    CERN Document Server

    Kumar, Shailesh

    2010-01-01

    A cellular automata (CA) configuration is constructed that exhibits emergent failover. The configuration is based on standard Game of Life rules. Gliders and glider-guns form the core messaging structure in the configuration. The blinker is represented as the basic computational unit, and it is shown how it can be recreated in case of a failure. Stateless failover using primary-backup mechanism is demonstrated. The details of the CA components used in the configuration and its working are described, and a simulation of the complete configuration is also presented.

  6. Cellular-scale hydrodynamics

    DEFF Research Database (Denmark)

    Abkarian, Manouk; Faivre, Magalie; Horton, Renita; Smistrup, Kristian; Best-Popescu, Catherine A; Stone, Howard A.

    2008-01-01

    Microfluidic tools are providing many new insights into the chemical, physical and physicochemical responses of cells. Both suspension-level and single-cell measurements have been studied. We review our studies of these kinds of problems for red blood cells with particular focus on the shapes of ...... mechanical effects on suspended cells can be studied systematically in small devices, and how these features can be exploited to develop methods for characterizing physicochemical responses and possibly for the diagnosis of cellular-scale changes to environmental factors....

  7. Cellular mechanics and motility

    Science.gov (United States)

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

    The term motility defines the movement of a living organism. One widely known example is the motility of sperm cells, or the one of flagellar bacteria. The propulsive element of such organisms is a cilium(or flagellum) that beats. Although cells in our tissues do not have a flagellum in general, they are still able to move, as we will discover in this chapter. In fact, in both cases of movement, with or without a flagellum, cell motility is due to a dynamic re-arrangement of polymers inside the cell. Let us first have a closer look at the propulsion mechanism in the case of a flagellum or a cilium, which is the best known, but also the simplest, and which will help us to define the hydrodynamic general conditions of cell movement. A flagellum is sustained by cellular polymers arranged in semi-flexible bundles and flagellar beating generates cell displacement. These polymers or filaments are part of the cellular skeleton, or "cytoskeleton", which is, in this case, external to the cellular main body of the organism. In fact, bacteria move in a hydrodynamic regime in which viscosity dominates over inertia. The system is thus in a hydrodynamic regime of low Reynolds number (Box 5.1), which is nearly exclusively the case in all cell movements. Bacteria and their propulsion mode by flagella beating are our unicellular ancestors 3.5 billion years ago. Since then, we have evolved to form pluricellular organisms. However, to keep the ability of displacement, to heal our wounds for example, our cells lost their flagellum, since it was not optimal in a dense cell environment: cells are too close to each other to leave enough space for the flagella to accomplish propulsion. The cytoskeleton thus developed inside the cell body to ensure cell shape changes and movement, and also mechanical strength within a tissue. The cytoskeleton of our cells, like the polymers or filaments that sustain the flagellum, is also composed of semi-flexible filaments arranged in bundles, and also in

  8. Radiolabelled Cellular Blood Elements

    International Nuclear Information System (INIS)

    This volume contains the abstracts of the 5th International Symposion on Radiolabelling of Cellular Blood Elements to be held in Vienna, Austria, September 10-14, 1989. The Meeting is the fifth in a series of meetings designed to discuss the basics and clinical application of radiolabelling techniques. In these days, beside the search for new labelling agents and extending the knowledge in clinical use, the use of monoclonal antibodies is a big new challenge. All reviewed contributions that have been accepted for presentation are contained in this volume. (authors) 58 of them are of INIS scope

  9. Cellular Signaling in the Bovine Antral Follicles

    OpenAIRE

    Juan F. Vásquez - Cano; Martha Olivera - A.

    2010-01-01

    Antral follicle development in the ovary of female cattle is the product of a complex of endocrine, paracrine and autocrine relationships. The interactions of the pituitary gonadotropins over granulosa and theca cells prepare the follicle to produce estradiol and for the final stages of maturation of the oocyte and its potencial ovulation or atresia inside subordinate follicles. It is a dynamic event where cellular signaling patterns changes sequentiallyand quickly at different stages of foll...

  10. Integrated cellular systems

    Science.gov (United States)

    Harper, Jason C.

    The generation of new three-dimensional (3D) matrices that enable integration of biomolecular components and whole cells into device architectures, without adversely altering their morphology or activity, continues to be an expanding and challenging field of research. This research is driven by the promise that encapsulated biomolecules and cells can significantly impact areas as diverse as biocatalysis, controlled delivery of therapeutics, environmental and industrial process monitoring, early warning of warfare agents, bioelectronics, photonics, smart prosthetics, advanced physiological sensors, portable medical diagnostic devices, and tissue/organ replacement. This work focuses on the development of a fundamental understanding of the biochemical and nanomaterial mechanisms that govern the cell directed assembly and integration process. It was shown that this integration process relies on the ability of cells to actively develop a pH gradient in response to evaporation induced osmotic stress, which catalyzes silica condensation within a thin 3D volume surrounding the cells, creating a functional bio/nano interface. The mechanism responsible for introducing functional foreign membrane-bound proteins via proteoliposome addition to the silica-lipid-cell matrix was also determined. Utilizing this new understanding, 3D cellular immobilization capabilities were extended using sol-gel matrices endowed with glycerol, trehalose, and media components. The effects of these additives, and the metabolic phase of encapsulated S. cerivisiase cells, on long-term viability and the rate of inducible gene expression was studied. This enabled the entrapment of cells within a novel microfluidic platform capable of simultaneous colorimetric, fluorescent, and electrochemical detection of a single analyte, significantly improving confidence in the biosensor output. As a complementary approach, multiphoton protein lithography was utilized to engineer 3D protein matrices in which to

  11. Multiuser Cellular Network

    CERN Document Server

    Bao, Yi; Chen, Ming

    2011-01-01

    Modern radio communication is faced with a problem about how to distribute restricted frequency to users in a certain space. Since our task is to minimize the number of repeaters, a natural idea is enlarging coverage area. However, coverage has restrictions. First, service area has to be divided economically as repeater's coverage is limited. In this paper, our fundamental method is to adopt seamless cellular network division. Second, underlying physics content in frequency distribution problem is interference between two close frequencies. Consequently, we choose a proper frequency width of 0.1MHz and a relevantly reliable setting to apply one frequency several times. We make a few general assumptions to simplify real situation. For instance, immobile users yield to homogenous distribution; repeaters can receive and transmit information in any given frequency in duplex operation; coverage is mainly decided by antenna height. Two models are built up to solve 1000 users and 10000 users situations respectively....

  12. Modeling and cellular studies

    International Nuclear Information System (INIS)

    Testing the applicability of mathematical models with carefully designed experiments is a powerful tool in the investigations of the effects of ionizing radiation on cells. The modeling and cellular studies complement each other, for modeling provides guidance for designing critical experiments which must provide definitive results, while the experiments themselves provide new input to the model. Based on previous experimental results the model for the accumulation of damage in Chlamydomonas reinhardi has been extended to include various multiple two-event combinations. Split dose survival experiments have shown that models tested to date predict most but not all the observed behavior. Stationary-phase mammalian cells, required for tests of other aspects of the model, have been shown to be at different points in the cell cycle depending on how they were forced to stop proliferating. These cultures also demonstrate different capacities for repair of sublethal radiation damage

  13. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds......, and pharmaceuticals. However, making cells into efficient factories is challenging because cells have evolved robust metabolic networks with hard-wired, tightly regulated lines of communication between molecular pathways that resist efforts to divert resources. Here, we will review the current status and challenges...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  14. Uncoupling High Light Responses from Singlet Oxygen Retrograde Signaling and Spatial-Temporal Systemic Acquired Acclimation.

    Science.gov (United States)

    Carmody, Melanie; Crisp, Peter A; d'Alessandro, Stefano; Ganguly, Diep; Gordon, Matthew; Havaux, Michel; Albrecht-Borth, Verónica; Pogson, Barry J

    2016-07-01

    Distinct ROS signaling pathways initiated by singlet oxygen ((1)O2) or superoxide and hydrogen peroxide have been attributed to either cell death or acclimation, respectively. Recent studies have revealed that more complex antagonistic and synergistic relationships exist within and between these pathways. As specific chloroplastic ROS signals are difficult to study, rapid systemic signaling experiments using localized high light (HL) stress or ROS treatments were used in this study to uncouple signals required for direct HL and ROS perception and distal systemic acquired acclimation (SAA). A qPCR approach was chosen to determine local perception and distal signal reception. Analysis of a thylakoidal ascorbate peroxidase mutant (tapx), the (1)O2-retrograde signaling double mutant (ex1/ex2), and an apoplastic signaling double mutant (rbohD/F) revealed that tAPX and EXECUTER 1 are required for both HL and systemic acclimation stress perception. Apoplastic membrane-localized RBOHs were required for systemic spread of the signal but not for local signal induction in directly stressed tissues. Endogenous ROS treatments revealed a very strong systemic response induced by a localized 1 h induction of (1)O2 using the conditional flu mutant. A qPCR time course of (1)O2 induced systemic marker genes in directly and indirectly connected leaves revealed a direct vascular connection component of both immediate and longer term SAA signaling responses. These results reveal the importance of an EXECUTER-dependent (1)O2 retrograde signal for both local and long distance RBOH-dependent acclimation signaling that is distinct from other HL signaling pathways, and that direct vascular connections have a role in spatial-temporal SAA induction. PMID:27288360

  15. Uncoupling protein-2 mRNA expression in mice subjected to intermittent hypoxia

    Directory of Open Access Journals (Sweden)

    Luciana Rodrigues Vieira

    2015-04-01

    Full Text Available Objective: To investigate the effect of intermittent hypoxia-a model of obstructive sleep apnea (OSA-on pancreatic expression of uncoupling protein-2 (UCP2, as well as on glycemic and lipid profiles, in C57BL mice. Methods: For 8 h/day over a 35-day period, male C57BL mice were exposed to intermittent hypoxia (hypoxia group or to a sham procedure (normoxia group. The intermittent hypoxia condition involved exposing mice to an atmosphere of 92% N and 8% CO2 for 30 s, progressively reducing the fraction of inspired oxygen to 8 ± 1%, after which they were exposed to room air for 30 s and the cycle was repeated (480 cycles over the 8-h experimental period. Pancreases were dissected to isolate the islets. Real-time PCR was performed with TaqMan assays. Results: Expression of UCP2 mRNA in pancreatic islets was 20% higher in the normoxia group than in the hypoxia group (p = 0.11. Fasting serum insulin was higher in the hypoxia group than in the normoxia group (p = 0.01. The homeostasis model assessment of insulin resistance indicated that, in comparison with the control mice, the mice exposed to intermittent hypoxia showed 15% lower insulin resistance (p = 0.09 and 21% higher pancreatic β-cell function (p = 0.01. Immunohistochemical staining of the islets showed no significant differences between the two groups in terms of the area or intensity of α- and β-cell staining for insulin and glucagon. Conclusions: To our knowledge, this is the first report of the effect of intermittent hypoxia on UCP2 expression. Our findings suggest that UCP2 regulates insulin production in OSA. Further study of the role that UCP2 plays in the glycemic control of OSA patients is warranted.

  16. Fruit calcium accumulation coupled and uncoupled from its transpiration in kiwifruit.

    Science.gov (United States)

    Montanaro, Giuseppe; Dichio, Bartolomeo; Lang, Alexander; Mininni, Alba N; Xiloyannis, Cristos

    2015-06-01

    Accumulation of Ca in several fleshy fruit is often supposed to depend, among others, by climatic variables driving fruit transpiration. This study tests the whole causal chain hypothesis: VPD → fruit transpiration → Ca accumulation. Also there are evidences that relationship between fruit transpiration and Ca content is not always clear, hence the hypothesis that low VPD reduces the fraction of xylemic water destined to transpiration was tested by examining the water budget of fruit. Attached fruits of Actinidia deliciosa were subjected to Low (L) and High (H) VPD. Their transpiration was measured from early after fruit-set to day 157 after full bloom (DAFB). Fruits were picked at 70, 130 and 157 DAFB for Ca and K determinations and for water budget analysis. Cumulative transpired water was ∼ 70 g and ∼ 16 g H2O f(-1) in HVPD and LVPD, respectively. Calcium accumulated linearly (R(2) = 0.71) with cumulative transpiration when VPD was high, while correlation was weaker (R(2) = 0.24) under LVPD. Under low VPD the fraction of xylem stream destined to transpiration declined to 40-50%. Results suggest that Ca accumulation is coupled to cumulative transpiration under high VPD because under that condition cumulative transpiration equals xylem stream (which carry the nutrient). At LVPD, Ca gain by fruit is uncoupled from transpiration because ∼ 60% of the xylemic water is needed to sustain fruit growth. Results will apply to most fruits (apples, tomatoes, capsicum, grapes etc.) since most suffer Ca deficiency disorders and grow in changing environments with variable VPD, also they could be supportive for the implementation of fruit quality models accounting also for mineral compositions and for a reinterpretation of certain field practices aimed at naturally improve fruit Ca content. PMID:25982084

  17. Mode Transition and Intermittency in an Acoustically Uncoupled Lean Premixed Swirl-Stabilized Combustor

    KAUST Repository

    LaBry, Zachary A.

    2014-06-16

    The prediction of dynamic instability remains an open and important issue in the development of gas turbine systems, particularly those constrained by emissions limitations. The existence and characteristics of dynamic instability are known to be functions of combustor geometry, flow conditions, and combustion parameters, but the form of dependence is not well understood. By modifying the acoustic boundary conditions, changes in flame and flow structure due to inlet parameters can be studied independent of the acoustic modes with which they couple. This paper examines the effect of equivalence ratio on the flame macrostructure — the relationship between the turbulent flame brush and the dominant flow structures — in an acoustically uncoupled environment. The flame brush is measured using CH* chemiluminescence, and the flow is interrogated using two-dimensional particle image velocimetry. We examine a range of equivalence ratios spanning three distinct macrostructures. The first macrostructure (ϕ = 0.550) is characterized by a diffuse flame brush confined to the interior of the inner recirculation zone. We observe a conical flame in the inner shear layer, continuing along the wall shear layer in the second macrostructure (ϕ = 0.600). The third macrostructure exhibits the same flame brush as the second, with an additional flame brush in the outer shear layer (ϕ = 0.650). Between the second and third macrostructures, we observe a regime in which the flame brush transitions intermittently between the two structures. We use dynamic mode decomposition on the PIV data to show that this transition event, which we call flickering, is linked to vorticity generated by the intermittent expansion of the outer recirculation zone as the flame jumps in and out of the outer shear layer. In a companion paper, we show how the macrostructures described in this paper are linked with dynamic instability [1].

  18. FGF signalling regulates chromatin organisation during neural differentiation via mechanisms that can be uncoupled from transcription.

    Directory of Open Access Journals (Sweden)

    Nishal S Patel

    Full Text Available Changes in higher order chromatin organisation have been linked to transcriptional regulation; however, little is known about how such organisation alters during embryonic development or how it is regulated by extrinsic signals. Here we analyse changes in chromatin organisation as neural differentiation progresses, exploiting the clear spatial separation of the temporal events of differentiation along the elongating body axis of the mouse embryo. Combining fluorescence in situ hybridisation with super-resolution structured illumination microscopy, we show that chromatin around key differentiation gene loci Pax6 and Irx3 undergoes both decompaction and displacement towards the nuclear centre coincident with transcriptional onset. Conversely, down-regulation of Fgf8 as neural differentiation commences correlates with a more peripheral nuclear position of this locus. During normal neural differentiation, fibroblast growth factor (FGF signalling is repressed by retinoic acid, and this vitamin A derivative is further required for transcription of neural genes. We show here that exposure to retinoic acid or inhibition of FGF signalling promotes precocious decompaction and central nuclear positioning of differentiation gene loci. Using the Raldh2 mutant as a model for retinoid deficiency, we further find that such changes in higher order chromatin organisation are dependent on retinoid signalling. In this retinoid deficient condition, FGF signalling persists ectopically in the elongating body, and importantly, we find that inhibiting FGF receptor (FGFR signalling in Raldh2-/- embryos does not rescue differentiation gene transcription, but does elicit both chromatin decompaction and nuclear position change. These findings demonstrate that regulation of higher order chromatin organisation during differentiation in the embryo can be uncoupled from the machinery that promotes transcription and, for the first time, identify FGF as an extrinsic signal that

  19. Expression of PPARα modifies fatty acid effects on insulin secretion in uncoupling protein-2 knockout mice

    Directory of Open Access Journals (Sweden)

    Chan Catherine B

    2007-03-01

    Full Text Available Abstract Aims/hypothesis In uncoupling protein-2 (UCP2 knockout (KO mice, protection of beta cells from fatty acid exposure is dependent upon transcriptional events mediated by peroxisome proliferator-activated receptor-α (PPARα. Methods PPARα expression was reduced in isolated islets from UCP2KO and wild-type (WT mice with siRNA for PPARα (siPPARα overnight. Some islets were also cultured with oleic or palmitic acid, then glucose stimulated insulin secretion (GSIS was measured. Expression of genes was examined by quantitative RT-PCR or immunoblotting. PPARα activation was assessed by oligonucleotide consensus sequence binding. Results siPPARα treatment reduced PPARα protein expression in KO and WT islets by >85%. In siPPARα-treated UCP2KO islets, PA but not OA treatment significantly decreased the insulin response to 16.5 mM glucose. In WT islets, siPPARα treatment did not modify GSIS in PA and OA exposed groups. In WT islets, PA treatment significantly increased UCP2 mRNA and protein expression. Both PA and OA treatment significantly increased PPARα expression in UCP2KO and WT islets but OA treatment augmented PPARα protein expression only in UCP2KO islets (p Conclusion These data show that the negative effect of saturated fatty acid on GSIS is mediated by PPARα/UCP2. Knockout of UCP2 protects beta-cells from PA exposure. However, in the absence of both UCP2 and PPARα even a short exposure (24 h to PA significantly impairs GSIS.

  20. Uncoupling clutch size, prolactin, and luteinizing hormone using experimental egg removal.

    Science.gov (United States)

    Ryan, Calen P; Dawson, Alistair; Sharp, Peter J; Williams, Tony D

    2015-03-01

    Clutch size is a key avian fitness and life history trait. A physiological model for clutch size determination (CSD), involving an anti-gonadal effect of prolactin (PRL) via suppression of luteinizing hormone (LH), was proposed over 20 years ago, but has received scant experimental attention since. The few studies looking at a PRL-based mechanistic hypothesis for CSD have been equivocal, but recent experiments utilizing a pharmacological agent to manipulate PRL in the zebra finch (Taeniopygia guttata) found no support for a role of this hormone in clutch size determination. Here, we take a complementary approach by manipulating clutch size through egg removal, examining co-variation in PRL and LH between two breeding attempts, as well as through experimentally-extended laying. Clutch size increased for egg removal females, but not controls, but this was not correlated with changes in PRL or LH. There were also no differences in PRL between egg removal females and controls, nor did PRL levels during early, mid- or late-laying of supra-normal clutches predict clutch size. By uncoupling PRL, LH and clutch size in our study, several key predictions of the PRL-based mechanistic model for CSD were not supported. However, a positive correlation between PRL levels late in laying and days relative to the last egg (clutch completion) provides an alternative explanation for the equivocal results surrounding the conventional PRL-based physiological model for CSD. We suggest that females coordinate PRL-mediated incubation onset with clutch completion to minimize hatching asynchrony and sibling hierarchy, a behavior that is amplified in females laying larger clutches. PMID:25687742

  1. Dynamic regulation of uncoupling protein 2 expression by microRNA-214 in hepatocellular carcinoma.

    Science.gov (United States)

    Yu, Guangsheng; Wang, Jianlu; Xu, Kesen; Dong, Jiahong

    2016-07-01

    Gemcitabine (GEM), a commonly used chemotherapeutic agent in hepatocellular carcinoma (HCC) patients, uses oxidative stress induction as a common effector pathway. However, GEM alone or in combination with oxaliplatin hardly renders any survival benefits to HCC patients. We have recently shown that this is part due to the overexpression of the mitochondrial uncoupling protein 2 (UCP2) that in turn mediates resistance to GEM in HCC patients. However, not much is known about regulatory mechanisms underlying UCP2 overexpression in HCC. Differential protein expression in HCC cell lines did not show a concomitant change in UCP2 transcript level, indicating post-transcriptional or post-translational regulatory mechanism. In situ analysis revealed that UCP2 is a putative target of miR-214 miR-214 expression is significantly down-regulated in HCC patient samples as compared with normal adjacent tissues and in cell line, human hepatoblastoma cells (HuH6), with high UCP2 protein expression. We demonstrated using miR-214 mimic and antagomir that the miRNA targeted UCP2 expression by directly targeting the wild-type, but not a miR-214 seed mutant, 3' UTR of UCP2 Overexpression of miR-214 significantly attenuated cell proliferation. Finally, analysis in 20 HCC patients revealed an inverse correlation in expression of UCP2 and miR-214 (Pearson's correlation coefficient, r=-0.9792). Cumulatively, our data indicate that in the context of HCC, miR-214 acts as a putative tumour suppressor by targeting UCP2 and defines a novel mechanism of regulation of UCP2. PMID:27129291

  2. Age-related changes of serum mitochondrial uncoupling 1, rumen and rectal temperature in goats.

    Science.gov (United States)

    Arfuso, Francesca; Rizzo, Maria; Giannetto, Claudia; Giudice, Elisabetta; Fazio, Francesco; Piccione, Giuseppe

    2016-07-01

    Thermoregulatory processes are induced not only by exposure to cold or heat but also by a variety of physiological situations including age, fasting and food intake that result in changes in body temperature. The aim of the present study was to evaluate the differences in serum mitochondrial uncoupling protein 1 (UCP1), rumen temperature (TRUMEN) and rectal temperature (TRECTAL) values between adult and kids goats. Ten adult male Maltese goats aged 3-5 years old (Group A) and 30 male kids, raised for meat, were enrolled in this study. The kids were equally divided into 3 groups according to their age: Group B included kids aged 3 months, Group C included kids aged 4 months and Group D included kids aged 5 months. Blood samples and measurements of TRUMEN and TRECTAL were obtained from each animal. One-way repeated measures analysis of variance (ANOVA) was applied to evaluate the effect of age on the studied parameters. Statistically significant higher serum UCP1 levels (P<0.001) were found in Group A as compared to Groups B, C and D. Higher TRUMEN values (P<0.001) were found in Group A than in Groups B, C and D, and in Group B than in Groups C and D. Group A showed lower TRECTAL values (P<0.001) than Groups B, C and D. The Pearson's Correlation test was applied to assess significant relationship among studied parameters showing a statistically significant negative correlation between the values of TRECTAL and serum UCP1 in all studied Groups (P<0.001). These results indicate that goats have good control of body temperature suggesting that further details about the thermogenic capacity and the function of UCP1 in kids and adult goats are worth exploring. PMID:27264887

  3. Combined oxides as oxygen-carrier material for chemical-looping with oxygen uncoupling

    International Nuclear Information System (INIS)

    Highlights: • Manganese-based combined oxides are examined for chemical-looping combustion applications. • Promising compositions includes (MnyFe1−y)Ox, (MnySi1−y)Ox and CaMnO3−δ. • Study includes thermodynamic analysis and overview of current experimental experiences. - Abstract: Oxygen-carrier materials for chemical-looping with oxygen uncoupling (CLOU) must be capable of taking up and releasing gas-phase O2 at conditions relevant for generation of heat and power. In principle, the capability of a certain material to do so is determined by its thermodynamic properties. This paper provides an overview of the possibility to design feasible oxygen carrier materials from combined oxides, i.e. oxides with crystal structures that include several different cations. Relevant literature is reviewed and the thermodynamic properties and key characteristics of a few selected combined oxide systems are calculated and compared to experimental data. The general challenges and opportunities of the combined oxide concept are discussed. The focus is on materials with manganese as one of its components and the following families of compounds and solid solutions have been considered: (MnyFe1−y)Ox, (MnySi1−y)Ox, CaMnO3−δ, (NiyMn1−y)Ox, (MnyCu1−y)Ox and (MnyMg1−y)Ox. In addition to showing promise from a thermodynamic point of view, reactivity data from experimental investigations suggests that the rate of O2 release can be high for all systems. Thus these combined oxides could also be very suitable for practical application

  4. Empirical multiscale networks of cellular regulation.

    Directory of Open Access Journals (Sweden)

    Benjamin de Bivort

    2007-10-01

    Full Text Available Grouping genes by similarity of expression across multiple cellular conditions enables the identification of cellular modules. The known functions of genes enable the characterization of the aggregate biological functions of these modules. In this paper, we use a high-throughput approach to identify the effective mutual regulatory interactions between modules composed of mouse genes from the Alliance for Cell Signaling (AfCS murine B-lymphocyte database which tracks the response of approximately 15,000 genes following chemokine perturbation. This analysis reveals principles of cellular organization that we discuss along four conceptual axes. (1 Regulatory implications: the derived collection of influences between any two modules quantifies intuitive as well as unexpected regulatory interactions. (2 Behavior across scales: trends across global networks of varying resolution (composed of various numbers of modules reveal principles of assembly of high-level behaviors from smaller components. (3 Temporal behavior: tracking the mutual module influences over different time intervals provides features of regulation dynamics such as duration, persistence, and periodicity. (4 Gene Ontology correspondence: the association of modules to known biological roles of individual genes describes the organization of functions within coexpressed modules of various sizes. We present key specific results in each of these four areas, as well as derive general principles of cellular organization. At the coarsest scale, the entire transcriptional network contains five divisions: two divisions devoted to ATP production/biosynthesis and DNA replication that activate all other divisions, an "extracellular interaction" division that represses all other divisions, and two divisions (proliferation/differentiation and membrane infrastructure that activate and repress other divisions in specific ways consistent with cell cycle control.

  5. Characteristics of Middle School Students Learning Actions in Outdoor Mathematical Activities with the Cellular Phone

    Science.gov (United States)

    Daher, Wajeeh; Baya'a, Nimer

    2012-01-01

    Learning in the cellular phone environment enables utilizing the multiple functions of the cellular phone, such as mobility, availability, interactivity, verbal and voice communication, taking pictures or recording audio and video, measuring time and transferring information. These functions together with mathematics-designated cellular phone…

  6. Robust Template Decomposition without Weight Restriction for Cellular Neural Networks Implementing Arbitrary Boolean Functions Using Support Vector Classifiers

    Directory of Open Access Journals (Sweden)

    Yih-Lon Lin

    2013-01-01

    Full Text Available If the given Boolean function is linearly separable, a robust uncoupled cellular neural network can be designed as a maximal margin classifier. On the other hand, if the given Boolean function is linearly separable but has a small geometric margin or it is not linearly separable, a popular approach is to find a sequence of robust uncoupled cellular neural networks implementing the given Boolean function. In the past research works using this approach, the control template parameters and thresholds are restricted to assume only a given finite set of integers, and this is certainly unnecessary for the template design. In this study, we try to remove this restriction. Minterm- and maxterm-based decomposition algorithms utilizing the soft margin and maximal margin support vector classifiers are proposed to design a sequence of robust templates implementing an arbitrary Boolean function. Several illustrative examples are simulated to demonstrate the efficiency of the proposed method by comparing our results with those produced by other decomposition methods with restricted weights.

  7. Illuminating cellular physiology: recent developments.

    Science.gov (United States)

    Brovko, Lubov Y; Griffiths, Mansel W

    2007-01-01

    Bioluminescent methods are gaining more and more attention among scientists due to their sensitivity, selectivity and simplicity; coupled with the fact that the bioluminescence can be monitored both in vitro and in vivo. Since the discovery of bioluminescence in the 19th century, enzymes involved in the bioluminescent process have been isolated and cloned. The bioluminescent reactions in several different organisms have also been fully characterized and used as reporters in a wide variety of biochemical assays. From the 1990s it became clear that bioluminescence can be detected and quantified directly from inside a living cell. This gave rise to numerous possibilities for the in vivo monitoring of intracellular processes non-invasively using bioluminescent molecules as reporters. This review describes recent developments in the area of bioluminescent imaging for cell biology. Newly developed imaging methods allow transcriptional/translational regulation, signal transduction, protein-protein interaction, oncogenic transformation, cell and protein trafficking, and target drug action to be monitored in vivo in real-time with high temporal and spatial resolution; thus providing researchers with priceless information on cellular functions. Advantages and limitations of these novel bioluminescent methods are discussed and possible future developments identified. PMID:17725230

  8. The State of Cellular Probes

    OpenAIRE

    Yim, Youngbin

    2003-01-01

    Cellular probe technology is one of several potentially promising technologies for obtaining accurate travel time information. In 1996, the Federal Communications Commission (FCC) mandated E911 requirements that cellular location be provided when 911 emergency calls come in to emergency management authorities. The E911 requirements allow 50 -300 meters from the emergency call location, depending on the type of cellular phone technology used and whether handset-based or network-based solutions...

  9. Never-ageing cellular senescence

    OpenAIRE

    Ogrunc, Müge; d’Adda di Fagagna, Fabrizio

    2011-01-01

    Cellular senescence was historically discovered as a form of cellular ageing of in vitro cultured cells. It has been under the spotlight following the evidence of oncogene-induced senescence in vivo and its role as a potent tumour suppressor mechanism. Presently, a PubMed search using keywords ‘cellular senescence and cancer’ reveals 8398 number of references (by April 2011) showing that while our knowledge of senescence keeps expanding, the complexity of the phenomenon keeps us – researchers...

  10. Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2

    Directory of Open Access Journals (Sweden)

    Quadros Edward V

    2009-05-01

    Full Text Available Abstract Background Recent evidence suggests that several human cancers are capable of uncoupling of mitochondrial ATP generation in the presence of intact tricarboxylic acid (TCA enzymes. The goal of the current study was to test the hypothesis that ketone bodies can inhibit cell growth in aggressive cancers and that expression of uncoupling protein 2 is a contributing factor. The proposed mechanism involves inhibition of glycolytic ATP production via a Randle-like cycle while increased uncoupling renders cancers unable to produce compensatory ATP from respiration. Methods Seven aggressive human cancer cell lines, and three control fibroblast lines were grown in vitro in either 10 mM glucose medium (GM, or in glucose plus 10 mM acetoacetate [G+AcA]. The cells were assayed for cell growth, ATP production and expression of UCP2. Results There was a high correlation of cell growth with ATP concentration (r = 0.948 in a continuum across all cell lines. Controls demonstrated normal cell growth and ATP with the lowest density of mitochondrial UCP2 staining while all cancer lines demonstrated proportionally inhibited growth and ATP, and over-expression of UCP2 (p Conclusion Seven human cancer cell lines grown in glucose plus acetoacetate medium showed tightly coupled reduction of growth and ATP concentration. The findings were not observed in control fibroblasts. The observed over-expression of UCP2 in cancer lines, but not in controls, provides a plausible molecular mechanism by which acetoacetate spares normal cells but suppresses growth in cancer lines. The results bear on the hypothesized potential for ketogenic diets as therapeutic strategies.

  11. Active Cellular Nematics

    Science.gov (United States)

    Duclos, Guillaume; Erlenkaemper, Christoph; Garcia, Simon; Yevick, Hannah; Joanny, Jean-François; Silberzan, Pascal; Biology inspired physics at mesoscales Team; Physical approach of biological problems Team

    We study the emergence of a nematic order in a two-dimensional tissue of apolar elongated fibroblast cells. Initially, these cells are very motile and the monolayer is characterized by giant density fluctuations, a signature of far-from-equilibrium systems. As the cell density increases because of proliferation, the cells align with each other forming large perfectly oriented domains while the cellular movements slow down and eventually freeze. Therefore topological defects characteristic of nematic phases remain trapped at long times, preventing the development of infinite domains. By analogy with classical non-active nematics, we have investigated the role of boundaries and we have shown that cells confined in stripes of width smaller than typically 500 µm are perfectly aligned in the stripe direction. Experiments performed in cross-shaped patterns show that both the number of cells and the degree of alignment impact the final orientation. Reference: Duclos G., Garcia S., Yevick H.G. and Silberzan P., ''Perfect nematic order in confined monolayers of spindle-shaped cells'', Soft Matter, 10, 14, 2014

  12. Uncoupled responses of Smad4-deficient cancer cells to TNFα result in secretion of monomeric laminin-γ2

    Directory of Open Access Journals (Sweden)

    Schmiegel Wolff

    2010-03-01

    Full Text Available Abstract Background Functional loss of the tumor suppressor Smad4 is involved in pancreatic and colorectal carcinogenesis and has been associated with the acquisition of invasiveness. We have previously demonstrated that the heterotrimeric basement membrane protein laminin-332 is a Smad4 target. Namely, Smad4 functions as a positive transcriptional regulator of all three genes encoding laminin-332; its loss is thus implicated in the reduced or discontinuous deposition of the heterotrimeric basement membrane molecule as evident in carcinomas. Uncoupled expression of laminin genes, on the other hand, namely overexpression of the laminin-γ2 chain is an impressive marker at invasive edges of carcinomas where tumor cells are maximally exposed to signals from stromal cell types like macrophages. As Smad4 is characterized as an integrator of multiple extracellular stimuli in a strongly contextual manner, we asked if loss of Smad4 may also be involved in uncoupled expression of laminin genes in response to altered environmental stimuli. Here, we address Smad4 dependent effects of the prominent inflammatory cytokine TNFα on tumor cells. Results Smad4-reconstituted colon carcinoma cells like adenoma cells respond to TNFα with an increased expression of all three chains encoding laminin-332; coincubation with TGFβ and TNFα leads to synergistic induction and to the secretion of large amounts of the heterotrimer. In contrast, in Smad4-deficient cells TNFα can induce expression of the γ2 and β3 but not the α3 chain. Surprisingly, this uncoupled induction of laminin-332 chains in Smad4-negative cells rather than causing intracellular accumulation is followed by the release of γ2 into the medium, either in a monomeric form or in complexes with as yet unknown proteins. Soluble γ2 is associated with increased cell migration. Conclusions Loss of Smad4 may lead to uncoupled induction of laminin-γ2 in response to TNFα and may therefore represent one of

  13. 47 CFR 22.909 - Cellular markets.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  14. Correspondence Between Uncoupled Flame Macrostructures and Thermoacoustic Instability in Premixed Swirl-Stabilized Combustion

    KAUST Repository

    Taamallah, Soufien

    2014-06-16

    In this paper, we conduct an experimental investigation of a confined premixed swirl-stabilized dump combustor similar to those found in modern gas turbines. We operate the combustor with premixed methane-air in the lean range of equivalence ratio ϕ ∈ [0.5–0.75]. First, we observe different dynamic modes in the lean operating range, as the equivalence ratio is raised, confirming observations made previously in a similar combustor geometry but with a different fuel [1]. Next we examine the correspondence between dynamic mode transitions and changes in the mean flame configuration or macrostructure. We show that each dynamic mode is associated with a specific flame macrostructure. By modifying the combustor length without changing the underlying flow, the resonant frequencies of the geometry are altered allowing for decoupling the heat release fluctuations and the acoustic field, in a certain range of equivalence ratio. Mean flame configurations in the modified (short) combustor and for the same range of equivalence ratio are examined. It is found that not only the same sequence of flame configurations is observed in both combustors (long and short) but also that the set of equivalence ratio where transitions in the flame configuration occur is closely related to the onset of thermo-acoustic instabilities. For both combustor lengths, the flame structure changes at similar equivalence ratio whether thermo-acoustic coupling is allowed or not, suggesting that the flame configuration holds the key to understanding the onset of self-excited thermo-acoustic instability in this range. Finally, we focus on the flame configuration transition that was correlated with the onset of the first dynamically unstable mode ϕ ∈ [0.61–0.64]. Our analysis of this transition in the short, uncoupled combustor shows that it is associated with an intermittent appearance of a flame in the outer recirculation zone (ORZ). The spectral analysis of this “ORZ flame flickering”

  15. Uncoupling protein 2 regulates glucagon-like peptide-1secretion in L-cells

    Institute of Scientific and Technical Information of China (English)

    Yan Chen; Zheng-Yang Li; Yan Yang; Hong-Jie Zhang

    2012-01-01

    AIM:To investigate whether uncoupling protein 2(UCP2) affects oleic acid-induced secretion of glucagonlike peptide-1 (GLP-1) in L-cells.METHODS:mRNA and protein expression of UCP2were analyzed in human NCI-H716 cells,which serve as a model for enteroendocrine L-cells,by quantitative reverse transcription-polymerase chain reaction and Western blotting before and after treatment with oleic acid.Localization of UCP2 and GLP-1 in NCI-H716 cells was assessed by immunofluorescence labeling.NCI-H716cells were transiently transfected with a small interfering RNA (siRNA) that targets UCP2 (siUCP2) or with a nonspecific siRNA using Lipofectamine 2000.The concentrations of bioactive GLP-1 in the medium were measured by enzyme linked immunosorbent assay.RESULTS:Both GLP-1 and UCP2 granules were expressed mainly in the cytoplasm of NCI-H716 cells.NCI-H716 cells that secreted GLP-1 also expressed UCP2.Time-course experiments revealed that release of GLP-1 from NCI-H716 cells into the medium reached a maximum at 120 min and remained stable until at least 180 min after treatment with oleic acid (the level of GLP-1 increased about 2.3-fold as compared with the level of GLP-1 in the control cells,P < 0.05).In an experiment to determine dose dependence,stimulation of NCI-H716 cells with ≤ 8 mmol oleic acid led to a concentration-dependent release of GLP-1 into the medium; 10 mmol oleic acid diminished the release of GLP-1.Furthermore,GLP-1 secretion induced by oleic acid from NCI-H716 cells that were transfected with siUCP2 decreased to 41.8%,as compared with NCI-H716 cells that were transfected with a non-specific siRNA (P < 0.01).CONCLUSION:UCP2 affected GLP-1 secretion induced by oleic acid.UCP2 plays an important role in L-cell secretion that is induced by free fatty acids.

  16. One-rank interaction kernel of the two-nucleon system for medium and high energies

    CERN Document Server

    Bondarenko, S G; Hwang, W-Y Pauchy; Rogochaya, E P

    2008-01-01

    A new version of the separable kernel of the nucleon-nucleon interaction in the Bethe-Salpeter approach is presented. The phase shifts are fitted to recent experimental data for singlet and uncoupled triplet partial waves of the neutron-proton scattering with total angular momenta J=0,1. The results are compared with other model calculations.

  17. Designing beauty the art of cellular automata

    CERN Document Server

    Martínez, Genaro

    2016-01-01

    This fascinating, colourful book offers in-depth insights and first-hand working experiences in the production of art works, using simple computational models with rich morphological behaviour, at the edge of mathematics, computer science, physics and biology. It organically combines ground breaking scientific discoveries in the theory of computation and complex systems with artistic representations of the research results. In this appealing book mathematicians, computer scientists, physicists, and engineers brought together marvelous and esoteric patterns generated by cellular automata, which are arrays of simple machines with complex behavior. Configurations produced by cellular automata uncover mechanics of dynamic patterns formation, their propagation and interaction in natural systems: heart pacemaker, bacterial membrane proteins, chemical rectors, water permeation in soil, compressed gas, cell division, population dynamics, reaction-diffusion media and self-organisation. The book inspires artists to tak...

  18. Quantum features of natural cellular automata

    Science.gov (United States)

    Elze, Hans-Thomas

    2016-03-01

    Cellular automata can show well known features of quantum mechanics, such as a linear rule according to which they evolve and which resembles a discretized version of the Schrödinger equation. This includes corresponding conservation laws. The class of “natural” Hamiltonian cellular automata is based exclusively on integer-valued variables and couplings and their dynamics derives from an Action Principle. They can be mapped reversibly to continuum models by applying Sampling Theory. Thus, “deformed” quantum mechanical models with a finite discreteness scale l are obtained, which for l → 0 reproduce familiar continuum results. We have recently demonstrated that such automata can form “multipartite” systems consistently with the tensor product structures of nonrelativistic many-body quantum mechanics, while interacting and maintaining the linear evolution. Consequently, the Superposition Principle fully applies for such primitive discrete deterministic automata and their composites and can produce the essential quantum effects of interference and entanglement.

  19. Quantum features of natural cellular automata

    CERN Document Server

    Elze, Hans-Thomas

    2016-01-01

    Cellular automata can show well known features of quantum mechanics, such as a linear rule according to which they evolve and which resembles a discretized version of the Schroedinger equation. This includes corresponding conservation laws. The class of "natural" Hamiltonian cellular automata is based exclusively on integer-valued variables and couplings and their dynamics derives from an Action Principle. They can be mapped reversibly to continuum models by applying Sampling Theory. Thus, "deformed" quantum mechanical models with a finite discreteness scale $l$ are obtained, which for $l\\rightarrow 0$ reproduce familiar continuum results. We have recently demonstrated that such automata can form "multipartite" systems consistently with the tensor product structures of nonrelativistic many-body quantum mechanics, while interacting and maintaining the linear evolution. Consequently, the Superposition Principle fully applies for such primitive discrete deterministic automata and their composites and can produce...

  20. Study of the interactivity between mercury and cellular system labeled with carboxymethyl chitosan-coated quantum dots and its application in a real-time in-situ detection of mercury

    Science.gov (United States)

    He, Zhenyu; Zhou, Peijiang; Zhu, Honghao

    2015-03-01

    In this study, canine kidney cells (MDCK) are fluorescently labeled by carboxymethyl chitosan-coated CdTe quantum dots to obtain a stable fluorescence. Fluorescently labeled MDCK cells are incubated with Hg2+ and passed flow cytometer to measure the mean fluorescence intensity, which shows [Hg2+] has a prominent quenching ability on the cells' fluorescence. The dose-dependent relation can be described by Stern-Volmer equation at the concentration range of 5-70 μg/L [Hg2+]. This method can be employed to determine the concentration of Hg2+ in living cells by measuring the changes in fluorescence of the cellular system. The results show a relative standard deviation of 7.16% (n = 11) and a recovery rate ranging from 92% to 103%, indicating a promising prospect of application on real-time in-situ analysis of [Hg2+] and its cytotoxic effects.

  1. Noise in cellular signaling pathways: causes and effects

    OpenAIRE

    Ladbury, John E.; Arold, Stefan T.

    2012-01-01

    Noise caused by stochastic fluctuations in genetic circuits (transcription and translation) is now appreciated as a central aspect of cell function and phenotypic behavior. Noise has also been detected in signaling networks, but the origin of this noise and how it shapes cellular outcomes remain poorly understood. Here, we argue that noise in signaling networks results from the intrinsic promiscuity of protein-protein interactions, and that this noise has shaped cellular signal transduction. ...

  2. Elastomeric Cellular Structure Enhanced by Compressible Liquid Filler

    Science.gov (United States)

    Sun, Yueting; Xu, Xiaoqing; Xu, Chengliang; Qiao, Yu; Li, Yibing

    2016-05-01

    Elastomeric cellular structures provide a promising solution for energy absorption. Their flexible and resilient nature is particularly relevant to protection of human bodies. Herein we develop an elastomeric cellular structure filled with nanoporous material functionalized (NMF) liquid. Due to the nanoscale infiltration in NMF liquid and its interaction with cell walls, the cellular structure has a much enhanced mechanical performance, in terms of loading capacity and energy absorption density. Moreover, it is validated that the structure is highly compressible and self-restoring. Its hyper-viscoelastic characteristics are elucidated.

  3. Elastomeric Cellular Structure Enhanced by Compressible Liquid Filler

    Science.gov (United States)

    Sun, Yueting; Xu, Xiaoqing; Xu, Chengliang; Qiao, Yu; Li, Yibing

    2016-01-01

    Elastomeric cellular structures provide a promising solution for energy absorption. Their flexible and resilient nature is particularly relevant to protection of human bodies. Herein we develop an elastomeric cellular structure filled with nanoporous material functionalized (NMF) liquid. Due to the nanoscale infiltration in NMF liquid and its interaction with cell walls, the cellular structure has a much enhanced mechanical performance, in terms of loading capacity and energy absorption density. Moreover, it is validated that the structure is highly compressible and self-restoring. Its hyper-viscoelastic characteristics are elucidated. PMID:27221079

  4. Mathematical analysis of complex cellular activity

    CERN Document Server

    Bertram, Richard; Teka, Wondimu; Vo, Theodore; Wechselberger, Martin; Kirk, Vivien; Sneyd, James

    2015-01-01

    This book contains two review articles on mathematical physiology that deal with closely related topics but were written and can be read independently. The first article reviews the basic theory of calcium oscillations (common to almost all cell types), including spatio-temporal behaviors such as waves. The second article uses, and expands on, much of this basic theory to show how the interaction of cytosolic calcium oscillators with membrane ion channels can result in highly complex patterns of electrical spiking. Through these examples one can see clearly how multiple oscillatory processes interact within a cell, and how mathematical methods can be used to understand such interactions better. The two reviews provide excellent examples of how mathematics and physiology can learn from each other, and work jointly towards a better understanding of complex cellular processes. Review 1: Richard Bertram, Joel Tabak, Wondimu Teka, Theodore Vo, Martin Wechselberger: Geometric Singular Perturbation Analysis of Burst...

  5. MIMO Communication for Cellular Networks

    CERN Document Server

    Huang, Howard; Venkatesan, Sivarama

    2012-01-01

    As the theoretical foundations of multiple-antenna techniques evolve and as these multiple-input multiple-output (MIMO) techniques become essential for providing high data rates in wireless systems, there is a growing need to understand the performance limits of MIMO in practical networks. To address this need, MIMO Communication for Cellular Networks presents a systematic description of MIMO technology classes and a framework for MIMO system design that takes into account the essential physical-layer features of practical cellular networks. In contrast to works that focus on the theoretical performance of abstract MIMO channels, MIMO Communication for Cellular Networks emphasizes the practical performance of realistic MIMO systems. A unified set of system simulation results highlights relative performance gains of different MIMO techniques and provides insights into how best to use multiple antennas in cellular networks under various conditions. MIMO Communication for Cellular Networks describes single-user,...

  6. Cellular based cancer vaccines

    DEFF Research Database (Denmark)

    Hansen, Morten; Met, O; Svane, I M;

    2012-01-01

    Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....

  7. Molecular identification of uncoupling proteins 2 and 3 in a carnivorous marsupial, the Tasmanian devil (Sarcophilus harrisii).

    Science.gov (United States)

    Kabat, Alexander P; Rose, Randy W; West, Adrian K

    2004-01-01

    This study investigated the expression of uncoupling proteins 2 and 3 (UCP2 and UCP3) in the carnivorous marsupial Sarcophilus harrisii. The current study used molecular techniques to ascertain whether this species expresses UCP2 and/or UCP3. This species increases nonshivering thermogenesis in response to cold exposure and norepinephrine, although our previous study was unable to demonstrate the presence of brown adipose tissue or uncoupling protein 1. Samples of skeletal muscle and white adipose tissues were taken from five S. harrisii pre- and post-cold acclimation (2 degrees -3 degrees C for 2 wk). The tissues were examined for UCP2 and UCP3 expression through Western blots and reverse transcriptase polymerase chain reaction, with subsequent sequencing to ensure identification of the desired gene. These data suggest that S. harrisii expresses UCP2 but not UCP3. The sequencing of the amplified S. harrisii UCP2 cDNA has revealed a 76% homology with human UCP2 cDNA and a 72% homology with rat UCP2 cDNA. The expression of UCP2 but not UCP3 suggests that UCP2 is conserved from a common ancestor to both the Marsupialia and the Eutheria taxa. PMID:15057721

  8. Novel systems of resonant wave interactions

    International Nuclear Information System (INIS)

    A matrix Riemann–Hilbert problem (RHP) is constructed using the dressing method starting from two uncoupled, one-directional linear wave equations; the RHP thus obtained is then used to derive a novel integrable matrix non-local system of equations describing resonant wave interactions, together with its Lax pair. This system is shown to be a matrix generalization of the equations for resonant three-wave interactions and stimulated Raman scattering. Several compatible reductions admitted by this system are also discussed. (paper)

  9. Molecular and cellular neurocardiology: development, and cellular and molecular adaptations to heart disease.

    Science.gov (United States)

    Habecker, Beth A; Anderson, Mark E; Birren, Susan J; Fukuda, Keiichi; Herring, Neil; Hoover, Donald B; Kanazawa, Hideaki; Paterson, David J; Ripplinger, Crystal M

    2016-07-15

    The nervous system and cardiovascular system develop in concert and are functionally interconnected in both health and disease. This white paper focuses on the cellular and molecular mechanisms that underlie neural-cardiac interactions during development, during normal physiological function in the mature system, and during pathological remodelling in cardiovascular disease. The content on each subject was contributed by experts, and we hope that this will provide a useful resource for newcomers to neurocardiology as well as aficionados. PMID:27060296

  10. Co-factor engineering in lactobacilli: Effects of uncoupled ATPase activity on metabolic fluxes in Lactobacillus (L.) plantarum and L. sakei

    DEFF Research Database (Denmark)

    Rud, Ida; Solem, Christian; Jensen, Peter Ruhdal;

    2008-01-01

    The hydrolytic F-1-part of the F1F0-ATPase was over-expressed in Lactobacillus (L.) plantarum NC8 and L. sakei Lb790x during fermentation of glucose or ribose, in order to study how changes in the intracellular levels of ATP and ADP affect the metabolic fluxes. The uncoupled ATPase activity resul...... have approximately 80% control on both the glycolytic and ribolytic flux in L. plantarum under these conditions. In contrast, the glycolytic and ribolytic flux decreased in L. sakei with uncoupled ATPase activity. (C) 2008 Elsevier Inc. All rights reserved....

  11. Uncoupling of sarcoplasmic reticulum Ca²⁺-ATPase by N-arachidonoyl dopamine. Members of the endocannabinoid family as thermogenic drugs

    DEFF Research Database (Denmark)

    Mahmmoud, Yasser Ahmed; Gaster, Michel

    2013-01-01

    -terminal p83C fragment from further cleavage. Moreover, we found a significantly decreased cytoplasmic ATP levels following treatment of skeletal muscle cells with 100 nM NADA. This effect was dependent on the presence of glucose and abolished by pretreatment with the specific SERCA inhibitor thapsigargin......, regardless of the presence of glucose. CONCLUSIONS AND IMPLICATIONS: NADA is an endogenous molecule that may function as SERCA uncoupling agent in vivo. Members of the endocannabinoid family exert concerted actions on several Ca²⁺-handling proteins. Uncoupling of SERCA by exogenous compounds could be a novel...

  12. Actual problems of cellular cardiomyoplasty

    Directory of Open Access Journals (Sweden)

    Bulat Kaupov

    2010-04-01

    Full Text Available The paper provides review of cellular technologies used incardiology, describes types of cellular preparations depending onsources of cells and types of compounding cells. The generalmechanisms of therapies with stem cells applications are described.Use of cellular preparations for treatment of cardiovascular diseasesand is improvement of the forecast at patients with heartinsufficiency of various genesis is considered as alternative topractice with organ transplantations. Efforts of biotechnologicallaboratories are directed on search of optimum population of cellsfor application in cardiology and studying of mechanisms andfactors regulating function of cardiac stem cells.

  13. Performance analysis of coupled and uncoupled hydrodynamic and wave models in the northern Adriatic Sea

    Science.gov (United States)

    Busca, Claudia; Coluccelli, Alessandro; Valentini, Andrea; Benetazzo, Alvise; Bonaldo, Davide; Bortoluzzi, Giovanni; Carniel, Sandro; Falcieri, Francesco; Paccagnella, Tiziana; Ravaioli, Mariangela; Riminucci, Francesco; Sclavo, Mauro; Russo, Aniello

    2014-05-01

    implementations currently running, there is the need to: assess their forecast skill; quantitatively evaluate if the new, coupled systems provide better performances than the uncoupled ones; individuate weaknesses and eventual time trends in the forecasts quality, their causes, and actions to improve the systems. This work presents a first effort aimed to satisfy such need. We employ in situ and remote sensing data collected starting from November 2011, in particular: temperature and salinity data collected during several oceanographic cruises, sea surface temperature derived from satellite measurements, waves, sea level and currents measurements from oceanographic buoys and platforms; specific observational activities funded by the Italian Flagship project RITMARE allowed to collect new measurements in NA coastal areas. Data-model comparison is firstly performed with exploratory qualitative comparisons in order to highlight discrepancies between observed and forecasted data, then a quantitative comparison is performed through the computation of standard statistical scores (root mean square error, mean error, mean bias, standard deviation, cross-correlation). Results are plotted in Taylor diagrams for a rapid evaluation of the overall performances.

  14. Influence of electric field on cellular migration

    Science.gov (United States)

    Guido, Isabella; Bodenschatz, Eberhard

    Cells have the ability to detect continuous current electric fields (EFs) and respond to them with a directed migratory movement. Dictyostelium discoideum (D.d.) cells, a key model organism for the study of eukaryotic chemotaxis, orient and migrate toward the cathode under the influence of an EF. The underlying sensing mechanism and whether it is shared by the chemotactic response pathway remains unknown. Whereas genes and proteins that mediate the electric sensing as well as that define the migration direction have been previously investigated in D.d. cells, a deeper knowledge about the cellular kinematic effects caused by the EF is still lacking. Here we show that besides triggering a directional bias the electric field influences the cellular kinematics by accelerating the movement of cells along their path. We found that the migratory velocity of the cells in an EF increases linearly with the exposure time. Through the analysis of the PI3K and Phg2 distribution in the cytosol and of the cellular adherence to the substrate we aim at elucidating whereas this speed up effect in the electric field is due to either a molecular signalling or the interaction with the substrate. This work is part of the MaxSynBio Consortium which is jointly funded by the Federal Ministry of Education and Research of Germany and the Max Planck Society.

  15. Origami interleaved tube cellular materials

    International Nuclear Information System (INIS)

    A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis. (paper)

  16. Cellular mechanisms during vascular development

    OpenAIRE

    Blum, Yannick

    2012-01-01

    The vascular system is an essential organ in vertebrate animals and provides the organism with enough oxygen and nutrients. It is composed of an interconnected network of blood vessels, which form using a number of different morphogenetic mechanisms. Angiogenesis describes the formation of new blood vessels from preexisting vessels. A number of molecular pathways have been shown to be essential during angiogenesis. However, cellular architecture of blood vessels as well as cellular mechanisms...

  17. Predictive Modelling of Cellular Load

    OpenAIRE

    Carolan, Emmett; McLoone, Seamus; Farrell, Ronan

    2015-01-01

    This work examines the temporal dynamics of cellular load in four Irish regions. Large scale underutilisation of network resources is identified both at the regional level and at the level of individual cells. Cellular load is modeled and prediction intervals are generated. These prediction intervals are used to put an upper bound on usage in a particular cell at a particular time. Opportunities for improvements in network utilization by incorporating these upper bounds on usage are identifie...

  18. Cellular automaton for chimera states

    OpenAIRE

    García-Morales, Vladimir

    2016-01-01

    A minimalistic model for chimera states is presented. The model is a cellular automaton (CA) which depends on only one adjustable parameter, the range of the nonlocal coupling, and is built from elementary cellular automata and the majority (voting) rule. This suggests the universality of chimera-like behavior from a new point of view: Already simple CA rules based on the majority rule exhibit this behavior. After a short transient, we find chimera states for arbitrary initial conditions, the...

  19. Modeling In Vitro Cellular Responses to Silver Nanoparticles

    Directory of Open Access Journals (Sweden)

    Dwaipayan Mukherjee

    2014-01-01

    Full Text Available Engineered nanoparticles (NPs have been widely demonstrated to induce toxic effects to various cell types. In vitro cell exposure systems have high potential for reliable, high throughput screening of nanoparticle toxicity, allowing focusing on particular pathways while excluding unwanted effects due to other cells or tissue dosimetry. The work presented here involves a detailed biologically based computational model of cellular interactions with NPs; it utilizes measurements performed in human cell culture systems in vitro, to develop a mechanistic mathematical model that can support analysis and prediction of in vivo effects of NPs. The model considers basic cellular mechanisms including proliferation, apoptosis, and production of cytokines in response to NPs. This new model is implemented for macrophages and parameterized using in vitro measurements of changes in cellular viability and mRNA levels of cytokines: TNF, IL-1b, IL-6, IL-8, and IL-10. The model includes in vitro cellular dosimetry due to nanoparticle transport and transformation. Furthermore, the model developed here optimizes the essential cellular parameters based on in vitro measurements, and provides a “stepping stone” for the development of more advanced in vivo models that will incorporate additional cellular and NP interactions.

  20. Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

    Science.gov (United States)

    Eldawud, Reem; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha; Zoica Dinu, Cerasela

    2016-02-01

    Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications.

  1. Effect of RNAi p21 gene on uncoupling of EL-4 cells induced by X-irradiation

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of RNAi p21 gene on uncoupling of EL-4 cells induced by X-irradiation. Methods: Construction of RNAi p21 plasmid of pSileneer3.1-H1 neo-p21 was performed. Lipofectamine transfection assay was used to transfer the p21siBNA into EL-4 cells. Fluorescent staining and flow cytometry (FCM) analysis were employed for measurement of protein expression. Fluorescent staining of propidium iodide (PI) and FCM were used for measurement of potyploid cells. Results: In dose-effect experiment it was found that the expression of P21 protein of EL-4 cells increased significantly 24 h after X- irradiation with different doses compared with sham-inadiated control. In time course experiment it was found that the expression of P21 protein of EL-4 cells increased significantly at 8 h to 72 h after 4.0 Gy X-irradiation compared with sham-irradiated control. The results showed that the number of polyploid cells in EL-4 cells was not changed markedly after X-irradiation with doses of 0.5-6.0 Gy. After RNA interference with p21 gene, the expression of P21 protein of EL-4 cells decreased significantly 24 h and 48 h after 4.0 Gy X-irradiation in transfection of plasmid of pSilencer3.1-H1 neo-p21 compared with transfection of plasmid of pSilencer3.1-H1 nco control. And at the same time, the number of polyploid cells in EL-4 cells was increased significantly in transfection of plasmid of pSilencer3.1-H1 neo-p21 compared with transfection of plasmid of pSilencer3.1-H1 nco control. Conclusions: Uncoupling could be induced by X-irradiation in EL-4 cells following BNAi p21 gene, suggesting that P21 protein may play an important role in uncoupling induced by X-rays. (authors)

  2. The 37/67kDa laminin receptor (LR) inhibitor, NSC47924, affects 37/67kDa LR cell surface localization and interaction with the cellular prion protein

    Science.gov (United States)

    Sarnataro, Daniela; Pepe, Anna; Altamura, Gennaro; De Simone, Imma; Pesapane, Ada; Nitsch, Lucio; Montuori, Nunzia; Lavecchia, Antonio; Zurzolo, Chiara

    2016-01-01

    The 37/67 kDa laminin receptor (LR) is a non-integrin protein, which binds both laminin-1 of the extracellular matrix and prion proteins, that hold a central role in prion diseases. The 37/67 kDa LR has been identified as interactor for the prion protein (PrPC) and to be required for pathological PrP (PrPSc) propagation in scrapie-infected neuronal cells, leading to the possibility that 37/67 kDa LR-PrPC interaction is related to the pathogenesis of prion diseases. A relationship between 37/67 kDa LR and PrPC in the presence of specific LR inhibitor compounds has not been investigated yet. We have characterized the trafficking of 37/67 kDa LR in both neuronal and non-neuronal cells, finding the receptor on the cell surface and nuclei, and identified the 67 kDa LR as the almost exclusive isoform interacting with PrPC. Here, we show that the treatment with the 37/67 kDa LR inhibitor, NSC47924, affects both the direct 37/67 kDa LR-PrPC interaction in vitro and the formation of the immunocomplex in live cells, inducing a progressive internalization of 37/67 kDa LR and stabilization of PrPC on the cell surface. These data reveal NSC47924 as a useful tool to regulate PrPC and 37/67 kDa LR trafficking and degradation, representing a novel small molecule to be tested against prion diseases. PMID:27071549

  3. Particles and Patterns in Cellular Automata

    International Nuclear Information System (INIS)

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). Our objective has been to develop tools for studying particle interactions in a class of dynamical systems characterized by discreteness, determinism, local interaction, and an inherently parallel form of evolution. These systems can be described by cellular automata (CA) and the behavior we studied has improved our understanding of the nature of patterns generated by CAs, their ability to perform global computations, and their relationship to continuous dynamical systems. We have also developed a rule-table mathematics that enables one to custom-design CA rule tables to generate patterns of specified types, or to perform specified computational tasks

  4. Total Cellular RNA Modulates Protein Activity.

    Science.gov (United States)

    Majumder, Subhabrata; DeMott, Christopher M; Reverdatto, Sergey; Burz, David S; Shekhtman, Alexander

    2016-08-16

    RNA constitutes up to 20% of a cell's dry weight, corresponding to ∼20 mg/mL. This high concentration of RNA facilitates low-affinity protein-RNA quinary interactions, which may play an important role in facilitating and regulating biological processes. In the yeast Pichia pastoris, the level of ubiquitin-RNA colocalization increases when cells are grown in the presence of dextrose and methanol instead of methanol as the sole carbon source. Total RNA isolated from cells grown in methanol increases β-galactosidase activity relative to that seen with RNA isolated from cells grown in the presence of dextrose and methanol. Because the total cellular RNA content changes with growth medium, protein-RNA quinary interactions can alter in-cell protein biochemistry and may play an important role in cell adaptation, critical to many physiological and pathological states. PMID:27456029

  5. Stimulation of potato tuber respiration by cold stress is associated with an increased capacity of both plant uncoupling mitochondrial protein (PUMP) and alternative oxidase

    Czech Academy of Sciences Publication Activity Database

    Calegario, F. F.; Cosso, R. G.; Fagian, M. M.; Almeida, F. V.; Jardim, W. F.; Ježek, Petr; Arruda, P.; Vercesi, A. E.

    2003-01-01

    Roč. 35, č. 3 (2003), s. 211-220. ISSN 0145-479X R&D Projects: GA ČR GA521/02/0183 Institutional research plan: CEZ:AV0Z5011922 Keywords : potato respiration * plant uncoupling protein * cold adaptation Subject RIV: EF - Botanics Impact factor: 3.424, year: 2003

  6. Probing intra-cellular drug release event using activatable (OFF/ON) CdS:Mn/ZnS quantum dots (Qdots): spectroscopic studies to investigate interaction of Qdots with quencher

    Science.gov (United States)

    Tharkur, Jeremy; Teblum, Andrew; Basumallick, Srijita; Shah, Rikhav; Cantarero, Karishma; Maity, Niharika; Rifai, Sara; Doshi, Mona; Gesquiere, Andre J.; Santra, Swadeshmukul

    2013-02-01

    In recent years, activatable Quantum Dots (AQdots) are gaining popularity in a number of chemical and biological sensing applications. A basic design of AQdot probes involves a suitable quencher which is capable of altering optical properties of the Qdots. In our previous studies we have shown that CdS:Mn/ZnS fluorescence can be effectively quenched using small molecule quenchers (such as dopamine, chemotherapeutic drug) as well as iron oxide nanoparticle via electron/energy transfer process. We have also shown that the quenched Qdot fluorescence can be restored when the Qdots are separated from the quencher. Using Qdot based activatable probes, we detected intracellular drug release event. Qdot fluorescence was restored upon interaction with the intracellular glutathione (GSH). In this paper, we report a GSH induced quenching of water-soluble N-Acetyl Cysteine (NAC) surface-conjugated Cds:Mn/ZnS Qdots. Quenching of NAC-Qdots was due to aggregation of Qdots in solution. This aggregation induced fluorescence quenching phenomenon resembles with the self-quenching phenomenon of traditional organic fluorescence dyes at high concentrations. UV-VIS and fluorescence emission spectroscopy data support the interaction and binding of GSH with the NAC-Qdots. Increase in particle size due to GSH induced aggregation of NAC-Qdots was confirmed by the Dynamic Light Scattering (DLS) data.

  7. Mechanism of mitochondrial uncouplers, inhibitors, and toxins: focus on electron transfer, free radicals, and structure-activity relationships.

    Science.gov (United States)

    Kovacic, Peter; Pozos, Robert S; Somanathan, Ratnasamy; Shangari, Nandita; O'Brien, Peter J

    2005-01-01

    The biology of the mitochondrial electron transport chain is summarized. Our approach to the mechanism of uncouplers, inhibitors, and toxins is based on electron transfer (ET) and reactive oxygen species (ROS). Extensive supporting evidence, which is broadly applicable, is cited. ROS can be generated either endogenously or exogenously. Generally, the reactive entities arise via redox cycling by ET functionalities, such as, quinones (or precursors), metal compounds, imines (or iminiums), and aromatic nitro compounds (or reduced metabolites). In most cases, the ET functions are formed metabolically. The toxic substances belong to many categories, e.g., medicinals, industrial chemicals, abused drugs, and pesticides. Structure-activity relationships are presented from the ET-ROS perspective, and also quantitatively. Evidence for the theoretical framework is provided by the protective effect of antioxidants. Among other topics addressed are proton flux, membrane pores, and apoptosis. There is support for the thesis that mitochondrial insult may contribute to illnesses and aging. PMID:16248817

  8. Hierarchical Cellular Structures in High-Capacity Cellular Communication Systems

    CERN Document Server

    Jain, R K; Agrawal, N K

    2011-01-01

    In the prevailing cellular environment, it is important to provide the resources for the fluctuating traffic demand exactly in the place and at the time where and when they are needed. In this paper, we explored the ability of hierarchical cellular structures with inter layer reuse to increase the capacity of mobile communication network by applying total frequency hopping (T-FH) and adaptive frequency allocation (AFA) as a strategy to reuse the macro and micro cell resources without frequency planning in indoor pico cells [11]. The practical aspects for designing macro- micro cellular overlays in the existing big urban areas are also explained [4]. Femto cells are inducted in macro / micro / pico cells hierarchical structure to achieve the required QoS cost effectively.

  9. Two Phase Flow Simulation Using Cellular Automata

    International Nuclear Information System (INIS)

    The classical mathematical treatment of two-phase flows is based on the average of the conservation equations for each phase.In this work, a complementary approach to the modeling of these systems based on statistical population balances of aut omata sets is presented.Automata are entities defined by mathematical states that change following iterative rules representing interactions with the neighborhood.A model of automata for two-phase flow simulation is presented.This model consists of fie lds of virtual spheres that change their volumes and move around a certain environment.The model is more general than the classical cellular automata in two respects: the grid of cellular automata is dismissed in favor of a trajectory generator, and the rules of interaction involve parameters representing the actual physical interactions between phases.Automata simulation was used to study unsolved two-phase flow problems involving high heat flux rates. One system described in this work consists of a vertical channel with saturated water at normal pressure heated from the lower surface.The heater causes water to boil and starts the bubble production.We used cellular automata to describe two-phase flows and the interaction with the heater.General rule s for such cellular automata representing bubbles moving in stagnant liquid were used, with special attention to correct modeling of different mechanisms of heat transfer.The results of the model were compared to previous experiments and correlations finding good agreement.One of the most important findings is the confirmation of Kutateladze's idea about a close relation between the start of critical heat flux and a change in the flow's topology.This was analyzed using a control volume located in the upper surface of the heater.A strong decrease in the interfacial surface just before the CHF start was encountered.The automata describe quite well some characteristic parameters such as the shape of the local void fraction in the

  10. Simple thermodynamic model of unassisted proton shuttle uncoupling and prediction of activity from calculated speciation, lipophilicity, and molecular geometry.

    Science.gov (United States)

    Martineau, Louis C

    2012-06-21

    A mechanistic model of uncoupling of oxidative phosphorylation by lipophilic weak acids (i.e. proton shuttles) was developed for the purposes of predicting the relative activity of xenobiotics of widely varying structure and of guiding the design of optimized derivatives. The model is based on thermodynamic premises not formulated elsewhere that allow for the calculation of steady-state conditions and of rate of energy dissipation on the basis of acid-dissociation and permeability behavior, the later estimated from partitioning behavior and geometric considerations. Moreover, permeability of either the neutral or of the ionized species is proposed to be effectively enhanced under conditions of asymmetrical molecular distribution. Finally, special considerations were developed to accommodate multi-protic compounds. The comparison of predicted to measured activity for a diverse testset of 48 compounds of natural origin spanning a wide range of activity yielded a Spearman's rho of 0.90. The model was used to tentatively identify several novel proton shuttles, as well as to elucidate core structures particularly conducive to proton shuttle activity from which optimized derivatives can be designed. Principles of design were formulated and examples of derivatives projected to be active at concentrations on the order of 10(-7)M are proposed. Among these are di-protic compounds predicted to shuttle two protons per cycle iteration and proposed to maximally exploit the proton shuttle mechanism. This work promotes the design of highly active, yet easily-metabolized uncouplers for therapeutic applications, namely the indirect activation of AMP-kinase, as well as for various industrial applications where low persistence is desirable. PMID:22425608

  11. Continuum representations of cellular solids

    Energy Technology Data Exchange (ETDEWEB)

    Neilsen, M.K.

    1993-09-01

    Cellular materials consist of interconnected struts or plates which form cells. The struts or plates are constructed from a variety of metals, polymers, ceramics and wood products. Cellular materials are often used in impact limiters for shipping containers to protect the contents from accidental impact events. These materials exhibit a variety of complex behavior when subjected to crushing loads. This research focuses on the development of continuum representations of cellular solids that can be used in the finite element analysis of shipping container accidents. A significant portion of this work is the development of a new methodology to relate localized deformations to appropriate constitutive descriptions. This methodology provides the insight needed to select constitutive descriptions for cellular solids that capture the localized deformations that are observed experimentally. Constitutive relations are developed for two different cellular materials, aluminum honeycomb and polyurethane foam. These constitutive relations are based on plasticity and continuum damage theories. Plasticity is used to describe the permanent deformation exhibited by both aluminum honeycomb and polyurethane foam. Continuum damage is needed to capture the change in elastic parameters due to cracking of the polyurethane cell wall materials. The new constitutive description of polyurethane foam is implemented in both static and dynamic finite element codes, and analytical and numerical predictions are compared with available experimental data.

  12. Prognosis of Different Cellular Generations

    Directory of Open Access Journals (Sweden)

    Preetish Ranjan

    2013-04-01

    Full Text Available Technological advancement in mobile telephony from 1G to 3G, 4G and 5G has a very axiomatic fact that made an entire world a global village. The cellular system employs a different design approach and technology that most commercial radio and television system use. In the cellular system, the service area is divided into cells and a transmitter is designed to serve an individual cell. The system seeks to make efficient use of available channels by using low-power transmitters to allow frequency reuse at a smaller distance. Maximizing the number of times each channel can be reused in a given geographical area is the key to an efficient cellular system design. During the past three decades, the world has seen significant changes in telecommunications industry. There have been some remarkable aspects to the rapid growth in wireless communications, as seen by the large expansion in mobile systems. This paper focuses on “Past, Present & Future of Cellular Telephony” and some light has been thrown upon the technologies of the cellular systems, namely 1G, 2G, 2.5G, 3G and future generations like 4G and 5G systems as well.

  13. Uncoupling the effects of seed predation and seed dispersal by granivorous ants on plant population dynamics.

    Directory of Open Access Journals (Sweden)

    Xavier Arnan

    Full Text Available Secondary seed dispersal is an important plant-animal interaction, which is central to understanding plant population and community dynamics. Very little information is still available on the effects of dispersal on plant demography and, particularly, for ant-seed dispersal interactions. As many other interactions, seed dispersal by animals involves costs (seed predation and benefits (seed dispersal, the balance of which determines the outcome of the interaction. Separate quantification of each of them is essential in order to understand the effects of this interaction. To address this issue, we have successfully separated and analyzed the costs and benefits of seed dispersal by seed-harvesting ants on the plant population dynamics of three shrub species with different traits. To that aim a stochastic, spatially-explicit individually-based simulation model has been implemented based on actual data sets. The results from our simulation model agree with theoretical models of plant response dependent on seed dispersal, for one plant species, and ant-mediated seed predation, for another one. In these cases, model predictions were close to the observed values at field. Nonetheless, these ecological processes did not affect in anyway a third species, for which the model predictions were far from the observed values. This indicates that the balance between costs and benefits associated to secondary seed dispersal is clearly related to specific traits. This study is one of the first works that analyze tradeoffs of secondary seed dispersal on plant population dynamics, by disentangling the effects of related costs and benefits. We suggest analyzing the effects of interactions on population dynamics as opposed to merely analyzing the partners and their interaction strength.

  14. Aging, cellular senescence, and cancer.

    Science.gov (United States)

    Campisi, Judith

    2013-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. PMID:23140366

  15. Novel Materials for Cellular Nanosensors

    DEFF Research Database (Denmark)

    Sasso, Luigi

    The monitoring of cellular behavior is useful for the advancement of biomedical diagnostics, drug development and the understanding of a cell as the main unit of the human body. Micro- and nanotechnology allow for the creation of functional devices that enhance the study of cellular dynamics by...... modifications for electrochemical nanosensors for the detection of analytes released from cells. Two type of materials were investigated, each pertaining to the two different aspects of such devices: peptide nanostructures were studied for the creation of cellular sensing substrates that mimic in vivo surfaces...... and that offer advantages of functionalization, and conducting polymers were used as electrochemical sensor surface modifications for increasing the sensitivity towards relevant analytes, with focus on the detection of dopamine released from cells via exocytosis. Vertical peptide nanowires were...

  16. Cellular-based preemption system

    Science.gov (United States)

    Bachelder, Aaron D. (Inventor)

    2011-01-01

    A cellular-based preemption system that uses existing cellular infrastructure to transmit preemption related data to allow safe passage of emergency vehicles through one or more intersections. A cellular unit in an emergency vehicle is used to generate position reports that are transmitted to the one or more intersections during an emergency response. Based on this position data, the one or more intersections calculate an estimated time of arrival (ETA) of the emergency vehicle, and transmit preemption commands to traffic signals at the intersections based on the calculated ETA. Additional techniques may be used for refining the position reports, ETA calculations, and the like. Such techniques include, without limitation, statistical preemption, map-matching, dead-reckoning, augmented navigation, and/or preemption optimization techniques, all of which are described in further detail in the above-referenced patent applications.

  17. Modeling diffusion of innovations with probabilistic cellular automata

    OpenAIRE

    Boccara, Nino; Fuks, Henryk

    1997-01-01

    We present a family of one-dimensional cellular automata modeling the diffusion of an innovation in a population. Starting from simple deterministic rules, we construct models parameterized by the interaction range and exhibiting a second-order phase transition. We show that the number of individuals who eventually keep adopting the innovation strongly depends on connectivity between individuals.

  18. Two HAP2-GCS1 homologs responsible for gamete interactions in the cellular slime mold with multiple mating types: Implication for common mechanisms of sexual reproduction shared by plants and protozoa and for male-female differentiation.

    Science.gov (United States)

    Okamoto, Marina; Yamada, Lixy; Fujisaki, Yukie; Bloomfield, Gareth; Yoshida, Kentaro; Kuwayama, Hidekazu; Sawada, Hitoshi; Mori, Toshiyuki; Urushihara, Hideko

    2016-07-01

    Fertilization is a central event in sexual reproduction, and understanding its molecular mechanisms has both basic and applicative biological importance. Recent studies have uncovered the molecules that mediate this process in a variety of organisms, making it intriguing to consider conservation and evolution of the mechanisms of sexual reproduction across phyla. The social amoeba Dictyostelium discoideum undergoes sexual maturation and forms gametes under dark and humid conditions. It exhibits three mating types, type-I, -II, and -III, for the heterothallic mating system. Based on proteome analyses of the gamete membranes, we detected expression of two homologs of the plant fertilization protein HAP2-GCS1. When their coding genes were disrupted in type-I and type-II strains, sexual potency was completely lost, whereas disruption in the type-III strain did not affect mating behavior, suggesting that the latter acts as female in complex organisms. Our results demonstrate the highly conserved function of HAP2-GCS1 in gamete interactions and suggest the presence of additional allo-recognition mechanisms in D. discoideum gametes. PMID:27189178

  19. Cellular interactions of human T cell subsets defined by monoclonal antibodies in regulating B cell differentiation: a comparative study in Nocardia water-soluble mitogen- and pokeweed mitogen-stimulated culture systems

    International Nuclear Information System (INIS)

    Two distinct human T cell subsets, OKT4+ cellrich and OKT8+ cellrich populations, were negatively selected with reasonable purity by C-mediated cytolysis with the use of monoclonal OKT4 and OKT8 antibodies. B cells were purified by rigorous depletion of E rosetting cells. Purified B cells responded to pokeweed mitogen (PWM) to yield a negligible number of immunoglobulin-producing cells (lg-PC), which were identified by a direct immunofluorescence method, after 7 days of culture, and to Nocardia water-soluble mitogen (NWSM) with the generation of a few, but a significant number of, lg-PC. Helper function of each T cell subset was measured as the ability of added T cells to restore the generation of lg-PC by B cells after 7 days of culture with NWSM or PWM. Results indicate that although NWSM by itself did not activate suppressor T cells to become effector cells, OKT8+ cells in the NWSM-driven system were able to exert suppressor effect for B cell differentiation only when used in combination with PWM-prestimulated OKT4+ cells. PWM-prestimulated OKT4+ cells had a pivotal role for the expression of suppressor activity by OKT8+ cells in this system, and the ability of these OKT4+ cells to interact with OKT8+ cells appeared to be radiosensitive

  20. Adaptive stochastic cellular automata: Applications

    Science.gov (United States)

    Qian, S.; Lee, Y. C.; Jones, R. D.; Barnes, C. W.; Flake, G. W.; O'Rourke, M. K.; Lee, K.; Chen, H. H.; Sun, G. Z.; Zhang, Y. Q.; Chen, D.; Giles, C. L.

    1990-09-01

    The stochastic learning cellular automata model has been applied to the problem of controlling unstable systems. Two example unstable systems studied are controlled by an adaptive stochastic cellular automata algorithm with an adaptive critic. The reinforcement learning algorithm and the architecture of the stochastic CA controller are presented. Learning to balance a single pole is discussed in detail. Balancing an inverted double pendulum highlights the power of the stochastic CA approach. The stochastic CA model is compared to conventional adaptive control and artificial neural network approaches.

  1. Cellular senescence in aging primates.

    Science.gov (United States)

    Herbig, Utz; Ferreira, Mark; Condel, Laura; Carey, Dee; Sedivy, John M

    2006-03-01

    The aging of organisms is characterized by a gradual functional decline of all organ systems. Mammalian somatic cells in culture display a limited proliferative life span, at the end of which they undergo an irreversible cell cycle arrest known as replicative senescence. Whether cellular senescence contributes to organismal aging has been controversial. We investigated telomere dysfunction, a recently discovered biomarker of cellular senescence, and found that the number of senescent fibroblasts increases exponentially in the skin of aging baboons, reaching >15% of all cells in very old individuals. In addition, the same cells contain activated ataxia-telangiectasia mutated kinase and heterochromatinized nuclei, confirming their senescent status. PMID:16456035

  2. Cellular automaton for chimera states

    Science.gov (United States)

    García-Morales, Vladimir

    2016-04-01

    A minimalistic model for chimera states is presented. The model is a cellular automaton (CA) which depends on only one adjustable parameter, the range of the nonlocal coupling, and is built from elementary cellular automata and the majority (voting) rule. This suggests the universality of chimera-like behavior from a new point of view: Already simple CA rules based on the majority rule exhibit this behavior. After a short transient, we find chimera states for arbitrary initial conditions, the system spontaneously splitting into stable domains separated by static boundaries, some synchronously oscillating and the others incoherent. When the coupling range is local, nontrivial coherent structures with different periodicities are formed.

  3. Prognosis of Different Cellular Generations

    OpenAIRE

    Preetish Ranjan; Prabhat Kumar

    2013-01-01

    Technological advancement in mobile telephony from 1G to 3G, 4G and 5G has a very axiomatic fact that made an entire world a global village. The cellular system employs a different design approach and technology that most commercial radio and television system use. In the cellular system, the service area is divided into cells and a transmitter is designed to serve an individual cell. The system seeks to make efficient use of available channels by using low-power transmitters to allow frequen...

  4. Force control for mechanoinduction of impedance variation in cellular organisms

    International Nuclear Information System (INIS)

    Constantly exposed to various forms of mechanical forces inherent in their physical environment (such as gravity, stress induced by fluid flow or cell–cell interactions, etc), cellular organisms sense such forces and convert them into biochemical signals through the processes of mechanosensing and mechanotransduction that eventually lead to biological changes. The effect of external forces on the internal structures and activities in a cellular organism may manifest in changes its physical properties, such as impedance. Studying variation in the impedance of a cellular organism induced by the application of an external mechanical force represents a meaningful endeavor (from a biosystems perspective) in exploring the complex mechanosensing and mechanotransduction mechanisms that govern the behavior of a cellular organism under the influence of external mechanical stimuli. In this paper we describe the development of an explicit force-feedback control system for exerting an indentation force on a cellular organism while simultaneously measuring its impedance. To demonstrate the effectiveness of this force-control system, we have conducted experiments using zebrafish embryos as a test model of a cellular organism. We report experimental results demonstrating that the application of a properly controlled external force leads to a significant change in the impedance of a zebrafish embryo. These results offer support for a plausible explanation that activities of pore canals in the chorion are responsible for the observed change in impedance.

  5. Repaglinide at a cellular level

    DEFF Research Database (Denmark)

    Krogsgaard Thomsen, M; Bokvist, K; Høy, M;

    2002-01-01

    To investigate the hormonal and cellular selectivity of the prandial glucose regulators, we have undertaken a series of experiments, in which we characterised the effects of repaglinide and nateglinide on ATP-sensitive potassium ion (KATP) channel activity, membrane potential and exocytosis in ra...

  6. Cellular signalling properties in microcircuits

    DEFF Research Database (Denmark)

    Toledo-Rodriguez, Maria; El Manira, Abdeljabbar; Wallén, Peter; Svirskis, Gytis; Hounsgaard, Jørn

    2005-01-01

    Molecules and cells are the signalling elements in microcircuits. Recent studies have uncovered bewildering diversity in postsynaptic signalling properties in all areas of the vertebrate nervous system. Major effort is now being invested in establishing the specialized signalling properties at th...... cellular and molecular levels in microcircuits in specific brain regions. This review is part of the TINS Microcircuits Special Feature....

  7. Quantum Cloning by Cellular Automata

    OpenAIRE

    D'Ariano, G. M.; Macchiavello, C.; M. Rossi

    2012-01-01

    We introduce a quantum cellular automaton that achieves approximate phase-covariant cloning of qubits. The automaton is optimized for 1-to-2N economical cloning. The use of the automaton for cloning allows us to exploit different foliations for improving the performance with given resources.

  8. Analysis of cellular manufacturing systems

    NARCIS (Netherlands)

    Heragu, Sunderesh; Meng, Gang; Zijm, Henk; Ommeren, van Jan-Kees

    2001-01-01

    In this paper, we present an open queuing network modeling approach to estimate performance measures of a cellular manufacturing layout. It is assumed a layout and production data for a planning period of specified length are available. The production data takes into account, processing and handli

  9. Cellular proteins in influenza virus particles.

    Directory of Open Access Journals (Sweden)

    Megan L Shaw

    2008-06-01

    Full Text Available Virions are thought to contain all the essential proteins that govern virus egress from the host cell and initiation of replication in the target cell. It has been known for some time that influenza virions contain nine viral proteins; however, analyses of other enveloped viruses have revealed that proteins from the host cell can also be detected in virions. To address whether the same is true for influenza virus, we used two complementary mass spectrometry approaches to perform a comprehensive proteomic analysis of purified influenza virus particles. In addition to the aforementioned nine virus-encoded proteins, we detected the presence of 36 host-encoded proteins. These include both cytoplasmic and membrane-bound proteins that can be grouped into several functional categories, such as cytoskeletal proteins, annexins, glycolytic enzymes, and tetraspanins. Interestingly, a significant number of these have also been reported to be present in virions of other virus families. Protease treatment of virions combined with immunoblot analysis was used to verify the presence of the cellular protein and also to determine whether it is located in the core of the influenza virus particle. Immunogold labeling confirmed the presence of membrane-bound host proteins on the influenza virus envelope. The identification of cellular constituents of influenza virions has important implications for understanding the interactions of influenza virus with its host and brings us a step closer to defining the cellular requirements for influenza virus replication. While not all of the host proteins are necessarily incorporated specifically, those that are and are found to have an essential role represent novel targets for antiviral drugs and for attenuation of viruses for vaccine purposes.

  10. Probing cellular behaviors through nanopatterned chitosan membranes

    International Nuclear Information System (INIS)

    This paper describes a high-throughput method for developing physically modified chitosan membranes to probe the cellular behavior of MDCK epithelial cells and HIG-82 fibroblasts adhered onto these modified membranes. To prepare chitosan membranes with micro/nanoscaled features, we have demonstrated an easy-to-handle, facile approach that could be easily integrated with IC-based manufacturing processes with mass production potential. These physically modified chitosan membranes were observed by scanning electron microscopy to gain a better understanding of chitosan membrane surface morphology. After MDCK cells and HIG-82 fibroblasts were cultured on these modified chitosan membranes for various culture durations (i.e. 1, 2, 4, 12 and 24 h), they were investigated to decipher cellular behavior. We found that both cells preferred to adhere onto a flat surface rather than on a nanopatterned surface. However, most (> 80%) of the MDCK cells showed rounded morphology and would suspend in the cultured medium instead of adhering onto the planar surface of negatively nanopatterned chitosan membranes. This means different cell types (e.g. fibroblasts versus epithelia) showed distinct capabilities/preferences of adherence for materials of varying surface roughness. We also showed that chitosan membranes could be re-used at least nine times without significant contamination and would provide us consistency for probing cell–material interactions by permitting reuse of the same substrate. We believe these results would provide us better insight into cellular behavior, specifically, microscopic properties and characteristics of cells grown under unique, nanopatterned cell-interface conditions. (paper)

  11. Single-Molecule Imaging of Cellular Signaling

    Science.gov (United States)

    De Keijzer, Sandra; Snaar-Jagalska, B. Ewa; Spaink, Herman P.; Schmidt, Thomas

    Single-molecule microscopy is an emerging technique to understand the function of a protein in the context of its natural environment. In our laboratory this technique has been used to study the dynamics of signal transduction in vivo. A multitude of signal transduction cascades are initiated by interactions between proteins in the plasma membrane. These cascades start by binding a ligand to its receptor, thereby activating downstream signaling pathways which finally result in complex cellular responses. To fully understand these processes it is important to study the initial steps of the signaling cascades. Standard biological assays mostly call for overexpression of the proteins and high concentrations of ligand. This sets severe limits to the interpretation of, for instance, the time-course of the observations, given the large temporal spread caused by the diffusion-limited binding processes. Methods and limitations of single-molecule microscopy for the study of cell signaling are discussed on the example of the chemotactic signaling of the slime-mold Dictyostelium discoideum. Single-molecule studies, as reviewed in this chapter, appear to be one of the essential methodologies for the full spatiotemporal clarification of cellular signaling, one of the ultimate goals in cell biology.

  12. Uncoupled embryonic and extra-embryonic tissues compromise blastocyst development after somatic cell nuclear transfer

    OpenAIRE

    Degrelle, Severine; Jaffrézic, Florence; Campion, Evelyne; Le Cao, Kim-Anh; Le Bourhis, Daniel; Richard, Christophe; Rodde, Nathalie; Fleurot, Renaud; Everts, Robin E.; Lecardonnel, Jérôme; Heyman, Yvan; Vignon, Xavier; Yang, Xiangzhong; Tian, Xiuchun C.; Lewin, Harris A

    2012-01-01

    Somatic cell nuclear transfer (SCNT) is the most efficient cell reprogramming technique available, especially when working with bovine species. Although SCNT blastocysts performed equally well or better than controls in the weeks following embryo transfer at Day 7, elongation and gastrulation defects were observed prior to implantation. To understand the developmental implications of embryonic/extra-embryonic interactions, the morphological and molecular features of elongating and gastrulatin...

  13. Persistent, comorbid pain and anxiety can be uncoupled in a mouse model.

    Science.gov (United States)

    Liu, Yan; Yang, Liu; Yu, Jin; Zhang, Yu-Qiu

    2015-11-01

    Clinically, pain and anxiety frequently coexist; however, these two conditions' interaction is limited and contradictory in animal studies. In this study, we combined social defeat (SD) stress with Freund's adjuvant (CFA)-induced persistent inflammatory pain to investigate the reciprocal relationship between anxiety-like and nociceptive behaviors in two mouse strains. C57BL/6J mice subjected to the 10-day period of SD stress by repeated CD-1 mice aggression exhibited significant social interaction avoidance behaviors in the social interaction (SI) test, which is believed to represent the symptoms of anxiety. These mice also displayed anxiety-like behaviors in elevated plus maze (EPM) and open field (OF) tests. Compared to C57BL/6J mice, FVB/NJNju mice showed less basal social contact, but their behavioral responses to 10-day SD stress were more resilient. CFA-inflammatory mice showed robust mechanical allodynia and thermal hyperalgesia in both strains, but did not develop obvious social avoidance and anxiety-like behaviors 10 days after CFA-inflammation. Interestingly, CFA-inflammatory mice exposed to SD stress were not accompanied by a worsening of pain and anxiety-like behaviors in most tests. In contrast, the SD stress-induced social avoidance was significantly antagonized by combining with CFA-inflammatory pain. These findings suggest that persistent inflammatory pain and SD stress-induced anxiety may not necessarily exacerbate one another in animal models of comorbidity. PMID:26166157

  14. Cellular Automaton Model for Immunology of Tumor Growth

    CERN Document Server

    Voitikova, M

    1998-01-01

    The stochastic discrete space-time model of an immune response on tumor spreading in a two-dimensional square lattice has been developed. The immunity-tumor interactions are described at the cellular level and then transferred into the setting of cellular automata (CA). The multistate CA model for system, in which all statesoflattice sites, composing of both immune and tumor cells populations, are the functions of the states of the 12 nearest neighbors. The CA model incorporates the essential featuresof the immunity-tumor system. Three regimes of neoplastic evolution including metastatic tumor growth and screen effect by inactive immune cells surrounding a tumor have been predicted.

  15. Stochastic properties of disturbed Elementary Cellular Automata

    International Nuclear Information System (INIS)

    Cellular automata are class of simple mathematical systems that generate diverse, often complicated behaviour. Evolution of such a system is given by set of local and deterministic rules. However, in spite of simplicity of 'interactions' it's global behaviour can't be, in general, simply predicted or even can not be predicted in time shorter that time of it's strict evolution. We get as, a systems well known 1-dimensional, Wolfram class automata, and connect it into the reservoir consists of some random source (noise). In our experiment we are interested in: a) numeric verification of ergodicity for such a coupled system. b) finding it's probability distribution and evolution. c) finding some analogous for 'real' quantities and behaviour. d) using the dynamical systems and Markov chains theory to describe the system, and to make any predictions of it's behaviour. (author)

  16. Microsystems for cellular force measurement: a review

    International Nuclear Information System (INIS)

    Microsystems are providing key advances in studying single cell mechanical behavior. The mechanical interaction of cells with their extracellular matrix is fundamentally important for cell migration, division, phagocytosis and aptoptosis. This review reports the development of microsystems on studying cell forces. Microsystems provide advantages of studying single cells since the scale of cells is on the micron level. The components of microsystems provide culture, loading, guiding, trapping and on chip analysis of cellular mechanical forces. This paper gives overviews on how MEMS are advancing in the field of cell biomechno sensory systems. It presents different materials, and mode of studying cell mechanics. Finally, we comment on the future directions and challenges on the state of art techniques

  17. Repair and mutagenesis in procaryotes as cellular responses to ambiental agents

    International Nuclear Information System (INIS)

    The correct and incorrect mechanisms of DNA repair are discussed, as well as the cellular responses induced by the DNA lesions; the reductone mollecular effects; the cellular interactions among irradiated populations of microorganisms and the utilization of microbial assays for the detection of oncogenic activities of chemicals. (M.A.)

  18. The NA+/K+-ATPase controls gap junctions via membrane microdomain interactions in rat smooth muscles.

    DEFF Research Database (Denmark)

    Matchkov, Vladimir; Nilsson, Holger; Aalkjær, Christian

    in rat mesenteric small arteries. Paired cultured rat smooth muscle cells (A7r5) were used as a model for electrical coupling of SMC by measuring membrane capacitance (Cm). PCR, Western blotting and immunohistochemistry were used to identify the membrane transporters. SMCs were uncoupled (evaluated...... by inhibition of vasomotion and desynchronization of [Ca2+]i transients in the vascular wall, or by reduction of Cm measured in paired A7r5 cells) when the Na+/K+-ATPase was inhibited either by a low concentration of ouabain (1-10 µM) or by ATP depletion. Inhibition of the Na+/Ca2+-exchange activity by SEA0400...... or by lowering the extracellular Na+ concentration also uncoupled the cells. Reduction of Na+/K+-ATPase activity by removal of extracellular K+ uncoupled cells, but only after inhibition of KATP channels. This interaction was bidirectional. Depletion of [Na+]i and clamping [Ca2+]i at low levels prevented...

  19. Cellular solidification of transparent monotectics

    Science.gov (United States)

    Kaulker, W. F.

    1986-01-01

    Understanding how liquid phase particles are engulfed or pushed during freezing of a monotectic is addressed. The additional complication is that the solid-liquid interface is nonplanar due to constitutional undercooling. Some evidence of particle pushing where the particles are the liquid phase of the montectic was already observed. Cellular freezing of the succinonitrile-glycerol system also occurred. Only a few compositions were tested at that time. The starting materials were not especially pure so that cellular interface observed was likely due to the presence of unkown impurities, the major portion of which was water. Topics addressed include: the effort of modeling the particle pushing process using the computer, establishing an apparatus for the determination of phase diagrams, and the measurement of the temperature gradients with a specimen which will solidify on the temperature gradient microscope stage.

  20. Cellular ceramics in combustion environments

    Energy Technology Data Exchange (ETDEWEB)

    Fuessel, Alexander; Boettge, Daniela; Adler, Joerg; Marschallek, Felix; Michaelis, Alexander [Fraunhofer Institute for Ceramic Technologies and Systems IKTS, Dresden (Germany)

    2011-11-15

    Cellular materials have become increasingly interesting for applications in combustion environments. Improvements like high power efficiency and low emissions are the main targets of technological development in combustion processes. However, despite scientific and technical success in developing new or improved burner concepts over recent years, a lot of problems remain to be solved in the field of materials science: due to the high power density of the burners the materials are subjected to high loads in terms of thermal shock, temperature and corrosion, especially in so-called porous burner technology. This article shows some examples of research and development strategies and results in developing improved cellular ceramics. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  1. Designing Underwater Cellular Networks Parameters

    Directory of Open Access Journals (Sweden)

    Pejman Khadivi

    2008-09-01

    Full Text Available Oceanographic data collection, pollution monitoring, offshore exploration, disaster prevention, assisted navigation and tactical surveillance are some of the applications of underwater networks. Underwater networks should send the gathered information to other users or an offshore station via a base station in the sea. Since the available bandwidth in underwater is severely limited, frequency reuse and cellular networks concepts are very important. In this paper, after driving the ratio of signal to interference for underwater acoustic channels, the constraints for the cell radius are determined. One of the important results of this work is that, for special parameters like bandwidth, it may be impossible to provide the required signal to interference ratio and bandwidth for the network users. Furthermore, in this paper, number of supportable users, per-user bandwidth, and the user capacity for a cellular underwater network are determined.

  2. Stochastic Nature in Cellular Processes

    Institute of Scientific and Technical Information of China (English)

    刘波; 刘圣君; 王祺; 晏世伟; 耿轶钊; SAKATA Fumihiko; GAO Xing-Fa

    2011-01-01

    The importance of stochasticity in cellular processes is increasingly recognized in both theoretical and experimental studies. General features of stochasticity in gene regulation and expression are briefly reviewed in this article, which include the main experimental phenomena, classification, quantization and regulation of noises. The correlation and transmission of noise in cascade networks are analyzed further and the stochastic simulation methods that can capture effects of intrinsic and extrinsic noise are described.

  3. Xtoys cellular automata on xwindows

    CERN Document Server

    Creutz, M

    1995-01-01

    Xtoys is a collection of xwindow programs for demonstrating simulations of various statistical models. Included are xising, for the two dimensional Ising model, xpotts, for the q-state Potts model, xautomalab, for a fairly general class of totalistic cellular automata, xsand, for the Bak-Tang-Wiesenfield model of self organized criticality, and xfires, a simple forest fire simulation. The programs should compile on any machine supporting xwindows.

  4. Signal processing in cellular clocks

    OpenAIRE

    Forger, Daniel B.

    2011-01-01

    Many biochemical events within a cell need to be timed properly to occur at specific times of day, after other events have happened within the cell or in response to environmental signals. The cellular biochemical feedback loops that time these events have already received much recent attention in the experimental and modeling communities. Here, we show how ideas from signal processing can be applied to understand the function of these clocks. Consider two signals from the network s(t) and r(...

  5. Analysis of cellular manufacturing systems

    OpenAIRE

    Heragu, Sunderesh; Meng, Gang; Zijm, Henk; Ommeren, van, J.C.

    2001-01-01

    In this paper, we present an open queuing network modeling approach to estimate performance measures of a cellular manufacturing layout. It is assumed a layout and production data for a planning period of specified length are available. The production data takes into account, processing and handling set-up times as well as transfer and process batch size information of multiple products that flow through the system. It is assumed that two sets of discrete material handling devices are used fo...

  6. Cellular Dynamics of RNA Modification

    OpenAIRE

    Yi, Chengqi; Pan, Tao

    2011-01-01

    Decades of research have identified over 100 types of ribonucleosides that are post-transcriptionally modified. Many modified nucleosides are conserved in bacteria, archeae and eukaryotes, while some modified nucleosides are unique to each branch of life. However, the cellular and functional dynamics of RNA modifications remains largely unexplored, mostly due to the lack of functional hypotheses and experimental methods for quantification and large scale analysis. Just as many well characteri...

  7. Cellular Dynamics of RNA Modification

    Science.gov (United States)

    Yi, Chengqi; Pan, Tao

    2011-01-01

    Conspectus Decades of research have identified over 100 types of ribonucleosides that are post-transcriptionally modified. Many modified nucleosides are conserved in bacteria, archeae and eukaryotes, while some modified nucleosides are unique to each branch of life. However, the cellular and functional dynamics of RNA modifications remains largely unexplored, mostly due to the lack of functional hypotheses and experimental methods for quantification and large scale analysis. Just as many well characterized protein and DNA modifications, many RNA modifications are not essential for life. Instead, increasingly more evidence indicates that RNA modifications can play regulatory roles in cells, especially in response to stress conditions. In this Account, we review some known examples of RNA modifications that are dynamically controlled in cells and introduce some contemporary technologies and methods that enhance the studies of cellular dynamics of RNA modifications. Examples of RNA modifications discussed in this Account include (Figure 1): (1) 4-thio uridine (s4U) which can act as a cellular sensor of near UV-light; (2) queuosine (Q) which is a potential biomarker for malignancy; (3) N6-methyl adenine (m6A) which is the prevalent modification in eukaryotic mRNAs; and (4) pseudouridine (ψ) which are inducible by nutrient deprivation. Two recent technical advances that stimulated the studies of cellular dynamics of modified ribonucleosides are also described. First, a genome-wide method combines primer extension and microarray to study N1-methyl adenine (m1A) hypomodification in human tRNA. Second, a quantitative mass spectrometric method investigates dynamic changes of a wide range of tRNA modifications under stress conditions in yeast. In addition, we discuss potential mechanisms that control dynamic regulation of RNA modifications, and hypotheses for discovering potential RNA de-modification enzymes. We conclude the Account by highlighting the need to develop new

  8. CELLULAR FETAL MICROCHIMERISM IN PREECLAMPSIA

    OpenAIRE

    Gammill, Hilary S; Aydelotte, Tessa M.; Guthrie, Katherine A.; Nkwopara, Evangelyn C.; Nelson, J. Lee

    2013-01-01

    Previous studies have shown elevated concentrations of free fetal deoxyribonucleic acid and erythroblasts in maternal circulation in preeclampsia compared with normal pregnancy. Pluripotent and immunocompetent fetal cells also transfer to the maternal circulation during pregnancy, but whether concentrations of fetal mononuclear cells also differed in preeclampsia was unknown. We sought to quantify cellular fetal microchimerism in maternal circulation in women with preeclampsia and healthy con...

  9. The Origins of Cellular Life

    OpenAIRE

    Schrum, Jason P.; Zhu, Ting F.; SZOSTAK, JACK W.

    2010-01-01

    Understanding the origin of cellular life on Earth requires the discovery of plausible pathways for the transition from complex prebiotic chemistry to simple biology, defined as the emergence of chemical assemblies capable of Darwinian evolution. We have proposed that a simple primitive cell, or protocell, would consist of two key components: a protocell membrane that defines a spatially localized compartment, and an informational polymer that allows for the replication and inheritance of fun...

  10. Progress of cellular dedifferentiation research

    Institute of Scientific and Technical Information of China (English)

    LIU Hu-xian; HU Da-hai; JIA Chi-yu; FU Xiao-bing

    2006-01-01

    Differentiation, the stepwise specialization of cells, and transdifferentiation, the apparent switching of one cell type into another, capture much of the stem cell spotlight. But dedifferentiation, the developmental reversal of a cell before it reinvents itself, is an important process too. In multicellular organisms, cellular dedifferentiation is the major process underlying totipotency, regeneration and formation of new stem cell lineages. In humans,dedifferentiation is often associated with carcinogenesis.The study of cellular dedifferentiation in animals,particularly early events related to cell fate-switch and determination, is limited by the lack of a suitable,convenient experimental system. The classic example of dedifferentiation is limb and tail regeneration in urodele amphibians, such as salamanders. Recently, several investigators have shown that certain mammalian cell types can be induced to dedifferentiate to progenitor cells when stimulated with the appropriate signals or materials. These discoveries open the possibility that researchers might enhance the endogenous regenerative capacity of mammals by inducing cellular dedifferentiation in vivo.

  11. Expression of human uncoupling protein-3 in insulin-producing cells increases insulin-like peptide (DILP) levels and shortens lifespan

    OpenAIRE

    Humphrey, Dickon M.; Toivonen, Janne M.; Giannakou, Maria; Partridge, Linda; Brand, Martin D.

    2009-01-01

    Abstract Uncoupling proteins (UCPs) can dissipate mitochondrial protonmotive force by increasing the proton conductance of the inner membrane and through this effect could decrease ROS production, ameliorate oxidative stress and extend lifespan. We investigated whether ubiquitous, pan-neuronal or neurosecretory cell-specific expression of human UCP3 (hUCP3) in adult Drosophila melanogaster affected lifespan. Low, ubiquitous expression of hUCP3 at levels found in rodent skeletal mus...

  12. Effects of trans-10, cis-12 conjugated linoleic acid on the expression of uncoupling proteins in hamsters fed an atherogenic diet

    OpenAIRE

    Ribot, Joan; Portillo Baquedano, María Puy; Picó, Catalina; Macarulla Arenaza, María Teresa; Palou, Andreu

    2007-01-01

    It is known that conjugated linoleic acid (CLA) feeding decreases body adiposity but the mechanisms involved are not clear. The aim of this study was to analyse whether alterations in uncoupling protein (UCP) expression in white and brown adipose tissues (WAT and BAT, respectively) and in skeletal muscle may be responsible for the effect of trans-10, cis-12 CLA on the size of body fat depots in hamsters. Animals were divided into three groups and fed an atherogenic diet with different amounts...

  13. Alteration in cardiac uncoupling proteins and eNOS gene expression following high-intensity interval training in favor of increasing mechanical efficiency

    OpenAIRE

    Fallahi, Ali Asghar; Shekarfroush, Shahnaz; Rahimi, Mostafa; Jalali, Amirhossain; Khoshbaten, Ali

    2016-01-01

    Objective(s): High-intensity interval training (HIIT) increases energy expenditure and mechanical energy efficiency. Although both uncoupling proteins (UCPs) and endothelial nitric oxide synthase (eNOS) affect the mechanical efficiency and antioxidant capacity, their effects are inverse. The aim of this study was to determine whether the alterations of cardiac UCP2, UCP3, and eNOS mRNA expression following HIIT are in favor of increased mechanical efficiency or decreased oxidative stress. Mat...

  14. Activating omega-6 polyunsaturated fatty acids and inhibitory purine nucleotides are high affinity ligands for novel mitochondrial uncoupling proteins UCP2 and UCP3

    Czech Academy of Sciences Publication Activity Database

    Žáčková, Markéta; Škobisová, Eva; Urbánková, Eva; Ježek, Petr

    2003-01-01

    Roč. 278, č. 23 (2003), s. 20761-20769. ISSN 0021-9258 R&D Projects: GA AV ČR IAA5011106; GA ČR GA301/02/1215; GA MŠk ME 389 Institutional research plan: CEZ:AV0Z5011922 Keywords : uncoupling protein-2 * polyunsaturated fatty acids * recombinant yeast expression Subject RIV: CE - Biochemistry Impact factor: 6.482, year: 2003

  15. Expression of Uncoupling Protein 1 in Mouse Brown Adipose Tissue Is Thyroid Hormone Receptor-β Isoform Specific and Required for Adaptive Thermogenesis

    OpenAIRE

    Ribeiro, Miriam O.; Bianco, Suzy D. C.; Kaneshige, Masahiro; Schultz, James J.; Cheng, Sheue-yann; Bianco, Antonio C.; Brent, Gregory A.

    2009-01-01

    Cold-induced adaptive (or nonshivering) thermogenesis in small mammals is produced primarily in brown adipose tissue (BAT). BAT has been identified in humans and becomes more active after cold exposure. Heat production from BAT requires sympathetic nervous system stimulation, T3, and uncoupling protein 1 (UCP1) expression. Our previous studies with a thyroid hormone receptor-β (TRβ) isoform-selective agonist demonstrated that after TRβ stimulation alone, adaptive thermogenesis was markedly im...

  16. Interrogating cellular fate decisions with high-throughput arrays of multiplexed cellular communities.

    Science.gov (United States)

    Chen, Sisi; Bremer, Andrew W; Scheideler, Olivia J; Na, Yun Suk; Todhunter, Michael E; Hsiao, Sonny; Bomdica, Prithvi R; Maharbiz, Michel M; Gartner, Zev J; Schaffer, David V

    2016-01-01

    Recreating heterotypic cell-cell interactions in vitro is key to dissecting the role of cellular communication during a variety of biological processes. This is especially relevant for stem cell niches, where neighbouring cells provide instructive inputs that govern cell fate decisions. To investigate the logic and dynamics of cell-cell signalling networks, we prepared heterotypic cell-cell interaction arrays using DNA-programmed adhesion. Our platform specifies the number and initial position of up to four distinct cell types within each array and offers tunable control over cell-contact time during long-term culture. Here, we use the platform to study the dynamics of single adult neural stem cell fate decisions in response to competing juxtacrine signals. Our results suggest a potential signalling hierarchy between Delta-like 1 and ephrin-B2 ligands, as neural stem cells adopt the Delta-like 1 phenotype of stem cell maintenance on simultaneous presentation of both signals. PMID:26754526

  17. Dynamic properties of cellular neural networks

    Directory of Open Access Journals (Sweden)

    Angela Slavova

    1993-01-01

    Full Text Available Dynamic behavior of a new class of information-processing systems called Cellular Neural Networks is investigated. In this paper we introduce a small parameter in the state equation of a cellular neural network and we seek for periodic phenomena. New approach is used for proving stability of a cellular neural network by constructing Lyapunov's majorizing equations. This algorithm is helpful for finding a map from initial continuous state space of a cellular neural network into discrete output. A comparison between cellular neural networks and cellular automata is made.

  18. Cellular communications a comprehensive and practical guide

    CERN Document Server

    Tripathi, Nishith

    2014-01-01

    Even as newer cellular technologies and standards emerge, many of the fundamental principles and the components of the cellular network remain the same. Presenting a simple yet comprehensive view of cellular communications technologies, Cellular Communications provides an end-to-end perspective of cellular operations, ranging from physical layer details to call set-up and from the radio network to the core network. This self-contained source forpractitioners and students represents a comprehensive survey of the fundamentals of cellular communications and the landscape of commercially deployed

  19. Fatty acids as natural uncouplers preventing generation of O2.- and H2O2 by mitochondria in the resting state.

    Science.gov (United States)

    Korshunov, S S; Korkina, O V; Ruuge, E K; Skulachev, V P; Starkov, A A

    1998-09-18

    Both natural (laurate) and artificial (m-chlorocarbonylcyanide phenylhydrazone; CCCP) uncouplers strongly inhibit O2.- and H2O2 formation by rat heart mitochondria oxidizing succinate. Carboxyatractylate, an ATP/ADP antiporter inhibitor, abolishes the laurate inhibition, the CCCP inhibition being unaffected. Atractylate partially releases the inhibition by laurate and decelerates the releasing effect of carboxyatractylate. GDP is much less effective than carboxyatractylate in releasing the laurate inhibition of reactive oxygen species (ROS) formation. Micromolar laurate concentrations arresting the ROS formation cause strong inhibition of reverse electron transfer from succinate to NAD+, whereas State 4 respiration and the transmembrane electric potential difference (delta psi) level are affected only slightly. It is suggested that (i) free fatty acids operate as natural 'mild uncouplers' preventing the transmembrane electrochemical H+ potential difference (delta muH+) from being above a threshold critical for ROS formation by complex I and, to a lesser degree, by complex III of the respiratory chain, and (ii) it is the ATP/ADP-antiporter, rather than uncoupling protein 2, that is mainly involved in this antioxidant mechanism of heart muscle mitochondria. PMID:9762912

  20. A Summary of Coupled, Uncoupled, and Hybrid Tectonic Models for the Yakima Fold Belt--Topical Report

    Energy Technology Data Exchange (ETDEWEB)

    Chamness, Michele A.; Winsor, Kelsey; Unwin, Stephen D.

    2012-08-01

    This document is one in a series of topical reports compiled by the Pacific Northwest National Laboratory to summarize technical information on selected topics important to the performance of a probabilistic seismic hazard analysis of the Hanford Site. The purpose of this report is to summarize the range of opinions and supporting information expressed by the expert community regarding whether a coupled or uncoupled model, or a combination of both, best represents structures in the Yakima Fold Belt. This issue was assessed to have a high level of contention with up to moderate potential for impact on the hazard estimate. This report defines the alternative conceptual models relevant to this technical issue and the arguments and data that support those models. It provides a brief description of the technical issue and principal uncertainties; a general overview on the nature of the technical issue, along with alternative conceptual models, supporting arguments and information, and uncertainties; and finally, suggests some possible approaches for reducing uncertainties regarding this issue.

  1. Conversion of Cn-Unsaturated into Cn-2-Saturated LCFA Can Occur Uncoupled from Methanogenesis in Anaerobic Bioreactors.

    Science.gov (United States)

    Cavaleiro, Ana J; Pereira, Maria Alcina; Guedes, Ana P; Stams, Alfons J M; Alves, M Madalena; Sousa, Diana Z

    2016-03-15

    Fat, oils, and grease present in complex wastewater can be readily converted to methane, but the energy potential of these compounds is not always recyclable, due to incomplete degradation of long chain fatty acids (LCFA) released during lipids hydrolysis. Oleate (C18:1) is generally the dominant LCFA in lipid-containing wastewater, and its conversion in anaerobic bioreactors results in palmitate (C16:0) accumulation. The reason why oleate is continuously converted to palmitate without further degradation via β-oxidation is still unknown. In this work, the influence of methanogenic activity in the initial conversion steps of unsaturated LCFA was studied in 10 bioreactors continuously operated with saturated or unsaturated C16- and C18-LCFA, in the presence or absence of the methanogenic inhibitor bromoethanesulfonate (BrES). Saturated Cn-2-LCFA accumulated both in the presence and absence of BrES during the degradation of unsaturated Cn-LCFA, and represented more than 50% of total LCFA. In the presence of BrES further conversion of saturated intermediates did not proceed, not even when prolonged batch incubation was applied. As the initial steps of unsaturated LCFA degradation proceed uncoupled from methanogenesis, accumulation of saturated LCFA can be expected. Analysis of the active microbial communities suggests a role for facultative anaerobic bacteria in the initial steps of unsaturated LCFA biodegradation. Understanding this role is now imperative to optimize methane production from LCFA. PMID:26810160

  2. Effect of overexpression of uncoupling protein 1 on brown adipose tissue in aP2-Ucp mice

    International Nuclear Information System (INIS)

    The aim of the present study was assess the function of mitochondria in brown fat of the transgenic animals in order to explain the functional involution of brown adipose tissue (BAT). This study was based on measurements of transmembrane electrochemical potential (Δψ) and estimation of [3H]GDP binding to isolated brown fat mitochondria, as well as on immunochemical analysis of trans-gene expression. Fluorescent cationic dye Rhodamine 123 was used to follow the changes in Δψ of isolated brown fat mitochondria. The fluorescence is quenched as the dye is accumulated in mitochondria in response to membrane energization. Titration by the inhibitory ligand of mitochondrial uncoupling protein 1 (UCP1), GDP (in presence of substrate), indicated a 3-fold lower sensitivity to GDP in mitochondria from transgenic compared with non-transgenic animals. Binding of [3H]GDP to both types of brown fat mitochondria was measured. Maximum number of specific GDP-binding sites was estimated from Scatchard plots. In accordance with the activity measurements, number of GDP-binding sites was approximately 3- to 5-fold higher in mitochondria isolated from the transgenic animals. (authors)

  3. Effects of 2 G on adiposity, leptin, lipoprotein lipase, and uncoupling protein-1 in lean and obese Zucker rats

    Science.gov (United States)

    Warren, L. E.; Horwitz, B. A.; Hamilton, J. S.; Fuller, C. A.

    2001-01-01

    Male Zucker rats were exposed to 2 G for 8 wk to test the hypothesis that the leptin regulatory pathway contributes to recovery from effects of 2 G on feeding, growth, and nutrient partitioning. After initial hypophagia, body mass-independent food intake of the lean rats exposed to 2 G surpassed that of the lean rats maintained at 1 G, but food intake of the obese rats exposed to 2 G remained low. After 8 wk at 2 G, body mass and carcass fat were less in both genotypes. Leptin and percent fat were lower in lean rats exposed to 2 G vs. 1 G but did not differ in obese rats exposed to 2 G vs. 1 G. Although exposure to 2 G did not alter uncoupling protein-1 levels, it did elicit white fat pad-specific changes in lipoprotein lipase activity in obese but not lean rats. We conclude that 2 G affects both genotypes but that the lean Zucker rats recover their food intake and growth rate and retain "normal" lipoprotein lipase activity to a greater degree than do the obese rats, emphasizing the importance of a functional leptin regulatory pathway in this acclimation.

  4. Uncoupling of glomerular IgA deposition and disease progression in alymphoplasia mice with IgA nephropathy.

    Directory of Open Access Journals (Sweden)

    Masashi Aizawa

    Full Text Available Previous clinical and experimental studies have indicated that cells responsible for IgA nephropathy (IgAN, at least in part, are localized in bone marrow (BM. Indeed, we have demonstrated that murine IgAN can be experimentally reconstituted by bone marrow transplantation (BMT from IgAN prone mice in not only normal mice, but also in alymphoplasia mice (aly/aly independent of IgA+ cells homing to mucosa or secondary lymphoid tissues. The objective of the present study was to further assess whether secondary lymph nodes (LN contribute to the progression of this disease. BM cells from the several lines of IgAN prone mice were transplanted into aly/aly and wild-type mice (B6. Although the transplanted aly/aly showed the same degree of mesangial IgA and IgG deposition and the same serum elevation levels of IgA and IgA-IgG immune-complexes (IC as B6, even in extent, the progression of glomerular injury was observed only in B6. This uncoupling in aly/aly was associated with a lack of CD4+ T cells and macrophage infiltration, although phlogogenic capacity to nephritogenic IC of renal resident cells was identical between both recipients. It is suggested that secondary LN may be required for the full progression of IgAN after nephritogenic IgA and IgA/IgG IC deposition.

  5. Role and mechanism of uncoupling protein 2 on the fatty acid-induced dysfunction of pancreatic alpha cells in vitro

    Institute of Scientific and Technical Information of China (English)

    SU Jie-ying; LI Hong-liang; YANG Wen-ying; XIAO Jian-zhong; DU Rui-qin; SHEN Xiao-xia; CAI Zhe; ZHANG Lan; SHU Jun

    2010-01-01

    Background Uncoupling protein (UCP) 2 is related to the dysfunction of beta cells induced by fatty acids. However,whether UCP2 has similar effects on alpha cell is still not clear. This study aimed to investigate the effects of UCP2 and its possible mechanisms in lipotoxicity-induced dysfunction of pancreatic alpha cells.Methods The alpha TC1-6 cells were used in this study to evaluate the effects of palmitate and/or UCP2 inhibit factors on the glucagon secretory function, glucagon content, the glucagon mRNA level and the nitrotyrosine level in the supernatant. Meantime, the expression levels of UCP2 and peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1 alpha) were measured by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Furthermore, the possible relationship between UCP2 and insulin signal transduction pathway was analyzed.Results Palmitate stimulated alpha cell glucagon secretion and the expression of UCP2 and PGC-1 alpha, which could be partially decreased by the inhibition of UCP2. Palmitate increased nitrotyrosine level and suppressed insulin signal transduction pathway in alpha cells. Inhibition of UCP2 influenced the effects of free fatty acid on alpha cells and may relate to glucagon secretion.Conclusion UCP2 played an important role on alpha cell dysfunction induced by free fatty acid in vitro, which may be related to its effects on oxidative stress and insulin signal transduction pathway.

  6. Uncoupling protein 2 gene (UCP2) 45-bp I/D polymorphism is associated with adiposity among Malaysian women

    Indian Academy of Sciences (India)

    Yee-How Say; Zi-Lian Ban; Yogambigai Arumugam; Trishal Kaur; Mee-Lay Tan; Phee-Phee Chia; Sook-Ha Fan

    2014-12-01

    This study investigated the association of Uncoupling Protein 2 gene (UCP2) 45-bp I/D polymorphism with obesity and adiposity in 926 Malaysian subjects (416 males; 265 obese; 102/672/152 Malays/Chinese/Indians). The overall minor allele frequency (MAF) was 0.14, while MAFs according to Malay/Chinese/Indian were 0.17/0.12/0.21. The polymorphism was associated with ethnicity, obesity and overall adiposity (total body fat percentage, TBF), but not gender and central adiposity (waist–hip ratio, WHR). Gender- and ethnicity-stratified analysis revealed that within males, the polymorphism was not associated with ethnicity and anthropometric classes. However, within females, significantly more Indians, obese and those with high TBF carried I allele. Logistic regression analysis among females further showed the polymorphism was associated with obesity and overall adiposity; however, when adjusted for age and ethnicity, this association was abolished for obesity but remained significant for overall adiposity [Odds Ratio (OR) for ID genotype =2.02 (CI=1.18, 3.45; =0.01); I allele =1.81 (CI=1.15, 2.84; =0.01)]. Indeed, covariate analysis controlling for age and ethnicity also showed that those carrying ID genotype or I allele had significantly higher TBF than the rest. In conclusion, UCP2 45-bp I/D polymorphism is associated with overall adiposity among Malaysian women.

  7. Ventricular-arterial uncoupling in heart failure with preserved ejection fraction after myocardial infarction in dogs - invasive versus echocardiographic evaluation

    Directory of Open Access Journals (Sweden)

    Bartunek Jozef

    2010-06-01

    Full Text Available Abstract Background Heart failure with preserved left ventricular ejection fraction and abnormal diastolic function is commonly observed after recovery from an acute myocardial infarction. The aim of this study was to investigate the physiopathology of heart failure with preserved ejection fraction in a model of healed myocardial infarction in dogs. Methods Echocardiography, levels of neurohormones and conductance catheter measurements of left ventricular pressure-volume relationships were obtained in 17 beagle dogs 2 months after a coronary artery ligation, and in 6 controls. Results Healed myocardial infarction was associated with preserved echocardiographic left ventricular ejection fraction (0.57 ± 0.01, mean ± SEM and altered Doppler mitral indices of diastolic function. NT-proBNP was increased, aldosterone was decreased, and norepinephrine was unchanged. Invasive measurements showed a markedly decreased end-systolic elastance (2.1 ± 0.2 vs 6.1 ± 0.8, mmHg/ml, p Conclusions In the canine model of healed myocardial infarction induced by coronary ligation, heart failure is essentially characterized by an altered contractility with left ventricular-arterial uncoupling despite vascular compensation rather than by abnormal diastolic function

  8. Effects of rosiglitazone on global ischemia-induced hippocampal injury and expression of mitochondrial uncoupling protein 2

    International Nuclear Information System (INIS)

    We investigate the effect of rosiglitazone, a ligand for peroxisome proliferator-activated receptor-γ (PPARγ) with anti-inflammatory and anti-oxidative actions, on hippocampal injury and its roles in mitochondrial uncoupling protein 2 (UCP2) expression caused by transient global ischemia (TGI) in rats. Increased UCP2 expression was observed in mitochondria of hippocampal CA1 2-24 h after TGI/reperfusion, with maximal expression levels at 6-18 h. Administration of rosiglitazone to hippocampus 30 min prior to the onset of TGI further enhanced mitochondrial UCP2 expression 2-6 h following TGI/reperfusion. Rats subjected to TGI/reperfusion displayed a significant increase in lipid peroxidation, based on increased malondialdehyde (MDA) levels, in hippocampal CA1 mitochondria 2-6 h after reperfusion. Rosiglitazone significantly attenuated TGI/reperfusion-induced lipid peroxidation and suppressed hippocampal CA1 neuronal death based on the surviving neuronal counts. In conclusion, our results provide correlative evidence for the 'PPARγ → UCP2 → neuroprotection' cascade in ischemic brain injury

  9. A comparative approach to understanding tissue-specific expression of uncoupling protein 1 expression in adipose tissue

    Directory of Open Access Journals (Sweden)

    Andrew eShore

    2013-01-01

    Full Text Available The thermoregulatory function of brown adipose tissue (BAT is due to the tissue-specific expression of uncoupling protein 1 (UCP1 which is thought to have evolved in early mammals. We report that a CpG island close to the UCP1 transcription start site is highly conserved in all 29 vertebrates examined apart from the mouse and xenopus. Using methylation sensitive restriction digest and bisulphite mapping we show that the CpG island in both the bovine and human is largely un-methylated and is not related to differences in UCP1 expression between white and brown adipose tissue. Tissue-specific expression of UCP1 has been proposed to be regulated by a conserved 5’ distal enhancer which has been reported to be absent in marsupials. We demonstrate that the enhancer, is also absent in 5 eutherians as well as marsupials, monotremes, amphibians and fish, is present in pigs despite UCP1 having become a pseudogene, and that absence of the enhancer element does not relate to brown adipose tissue-specific UCP1 expression. We identify an additional putative 5’ regulatory unit which is conserved in 14 eutherian species but absent in other eutherians and vertebrates, but again unrelated to UCP1 expression. We conclude that despite clear evidence of conservation of regulatory elements in the UCP1 5’ untranslated region, this does not appear to be related to species or tissues-specific expression of UCP1.

  10. The role of actin networks in cellular mechanosensing

    Science.gov (United States)

    Azatov, Mikheil

    Physical processes play an important role in many biological phenomena, such as wound healing, organ development, and tumor metastasis. During these processes, cells constantly interact with and adapt to their environment by exerting forces to mechanically probe the features of their surroundings and generating appropriate biochemical responses. The mechanisms underlying how cells sense the physical properties of their environment are not well understood. In this thesis, I present my studies to investigate cellular responses to the stiffness and topography of the environment. In order to sense the physical properties of their environment, cells dynamically reorganize the structure of their actin cytoskeleton, a dynamic network of biopolymers, altering the shape and spatial distribution of protein assemblies. Several observations suggest that proteins that crosslink actin filaments may play an important role in cellular mechanosensitivity. Palladin is an actin-crosslinking protein that is found in the lamellar actin network, stress fibers and focal adhesions, cellular structures that are critical for mechanosensing of the physical environment. By virtue of its close interactions with these structures in the cell, palladin may play an important role in cell mechanics. However, the role of actin crosslinkers in general, and palladin in particular, in cellular force generation and mechanosensing is not well known. I have investigated the role of palladin in regulating the plasticity of the actin cytoskeleton and cellular force generation in response to alterations in substrate stiffness. I have shown that the expression levels of palladin modulate the forces exerted by cells and their ability to sense substrate stiffness. Perturbation experiments also suggest that palladin levels in cells altered myosin motor activity. These results suggest that the actin crosslinkers, such as palladin, and myosin motors coordinate for optimal cell function and to prevent aberrant

  11. Cellular interactions during tracheary elements formation and function

    OpenAIRE

    Menard, Delphine; Pesquet, Edouard

    2015-01-01

    The survival of higher plant species on land depends on the development and function of an efficient vascular system distributing water and minerals absorbed by roots to all aerial organs. This conduction and distribution of plant sap relies on specialized cells named tracheary elements (TEs). In contrast to many other cell types in plants, TEs are functionalized by cell death that hollows the cell protoplast to make way for the sap. To maintain a stable conducting function during plant devel...

  12. Microencapsulation of stem cells to study cellular interactions.

    Science.gov (United States)

    Moore, Keith; Vandergriff, Adam; Potts, Jay D

    2013-01-01

    Microencapsulation is a technique used in both controlled delivery of materials over time as well as preservation of these materials while delivery is occurring. The range of materials able to be encapsulated is variable, from drugs to living cells. The latter is described here. Electrospray microencapsulation applies a high-voltage field, through which a polymeric material is extruded. A gelling bath, comprising a cross-linking material, is used to create a stable hydrogel containing secondary substances intended for delivery. Control of extrusion parameters, such as flow rate and voltage, allows for specification of diameter and pore sizes of the microcapsules. PMID:23955738

  13. Numerical simulation of Mach reflection of cellular detonations

    Science.gov (United States)

    Li, J.; Lee, J. H. S.

    2016-07-01

    The Mach reflection of cellular detonation waves on a wedge is investigated numerically in an attempt to elucidate the effect of cellular instabilities on Mach reflection, the dependence of self-similarity on the thickness of a detonation wave, and the initial development of the Mach stem near the wedge apex. A two-step chain-branching reaction model is used to give a thermally neutral induction zone followed by a chemical reaction zone for the detonation wave. A sufficiently large distance of travel of the Mach stem is computed to observe the asymptotic behavior in the far field. Depending on the scale at which the Mach reflection process occurs, it is found that the Mach reflection of a cellular detonation behaves essentially in the same way as a planar ZND detonation wave. The cellular instabilities, however, cause the triple-point trajectory to fluctuate. The fluctuations are due to interactions of the triple point of the Mach stem with the transverse waves of cellular instabilities. In the vicinity of the wedge apex, the Mach reflection is found to be self-similar and corresponds to that of a shock wave of the same strength, since the Mach stem is highly overdriven initially. In the far field, the triple-point trajectory approaches a straight line, indicating that the Mach reflection becomes self-similar asymptotically. The distance of the approach to self-similarity is found to decrease rapidly with decreasing thickness of the detonation front.

  14. A sub-cellular viscoelastic model for cell population mechanics.

    Directory of Open Access Journals (Sweden)

    Yousef Jamali

    Full Text Available Understanding the biomechanical properties and the effect of biomechanical force on epithelial cells is key to understanding how epithelial cells form uniquely shaped structures in two or three-dimensional space. Nevertheless, with the limitations and challenges posed by biological experiments at this scale, it becomes advantageous to use mathematical and 'in silico' (computational models as an alternate solution. This paper introduces a single-cell-based model representing the cross section of a typical tissue. Each cell in this model is an individual unit containing several sub-cellular elements, such as the elastic plasma membrane, enclosed viscoelastic elements that play the role of cytoskeleton, and the viscoelastic elements of the cell nucleus. The cell membrane is divided into segments where each segment (or point incorporates the cell's interaction and communication with other cells and its environment. The model is capable of simulating how cells cooperate and contribute to the overall structure and function of a particular tissue; it mimics many aspects of cellular behavior such as cell growth, division, apoptosis and polarization. The model allows for investigation of the biomechanical properties of cells, cell-cell interactions, effect of environment on cellular clusters, and how individual cells work together and contribute to the structure and function of a particular tissue. To evaluate the current approach in modeling different topologies of growing tissues in distinct biochemical conditions of the surrounding media, we model several key cellular phenomena, namely monolayer cell culture, effects of adhesion intensity, growth of epithelial cell through interaction with extra-cellular matrix (ECM, effects of a gap in the ECM, tensegrity and tissue morphogenesis and formation of hollow epithelial acini. The proposed computational model enables one to isolate the effects of biomechanical properties of individual cells and the

  15. The Madden-Julian Oscillation in ECHAM4 Coupled and Uncoupled GCMs

    Energy Technology Data Exchange (ETDEWEB)

    Sperber, K R; Gualdi, S; Legutke, S; Gayler, V

    2004-10-13

    The Madden-Julian Oscillation (MJO) dominates tropical variability on timescales of 30-70 days. During the boreal winter/spring it is manifested as an eastward propagating disturbance, with a strong convective signature over the eastern hemisphere. The space-time structure of the MJO is analyzed using simulations with the ECHAM4 atmospheric general circulation model run with observed monthly mean sea-surface temperatures, and coupled to three different ocean models. The coherence of the eastward propagation of MJO convection is sensitive to the ocean model to which ECHAM4 is coupled. For ECHAM4/OPYC and ECHO-G, models for which {approx}100 years of daily data is available, Monte Carlo sampling indicates that their metrics of eastward propagation are different at the 1% significance level. The flux-adjusted coupled simulations, ECHAM4/OPYC and ECHO-G, maintain a more realistic mean-state, and have a more realistic MJO simulation than the non-adjusted SINTEX coupled runs. The SINTEX model exhibits a cold bias in Indian Ocean and tropical West Pacific Ocean sea-surface temperature of {approx}0.5 C. This cold bias affects the distribution of time-mean convection over the tropical Eastern Hemisphere. Furthermore, the eastward propagation of MJO convection in this model is not as coherent as in the two models that used flux adjustment or compared to an integration of ECHAM4 with prescribed observed SST. This result suggests that simulating a realistic basic state is at least as important as air-sea interaction for organizing the MJO. While all of the coupled models simulate the warm (cold) SST anomalies that precede (succeed) the MJO convection, the interaction of the components of the net surface heat flux that lead to these anomalies are different over the Indian Ocean. The ECHAM4/OPYC model, in which the atmospheric model is run at a horizontal resolution of T42, has eastward propagating zonal wind anomalies and latent heat flux anomalies. However, the integrations

  16. Roles of Rho GTPases in Intracellular Transport and Cellular Transformation

    Directory of Open Access Journals (Sweden)

    Ji-Long Chen

    2013-03-01

    Full Text Available Rho family GTPases belong to the Ras GTPase superfamily and transduce intracellular signals known to regulate a variety of cellular processes, including cell polarity, morphogenesis, migration, apoptosis, vesicle trafficking, viral transport and cellular transformation. The three best-characterized Rho family members are Cdc42, RhoA and Rac1. Cdc42 regulates endocytosis, the transport between the endoplasmic reticulum and Golgi apparatus, post-Golgi transport and exocytosis. Cdc42 influences trafficking through interaction with Wiskott-Aldrich syndrome protein (N-WASP and the Arp2/3 complex, leading to changes in actin dynamics. Rac1 mediates endocytic and exocytic vesicle trafficking by interaction with its effectors, PI3kinase, synaptojanin 2, IQGAP1 and phospholipase D1. RhoA participates in the regulation of endocytosis through controlling its downstream target, Rho kinase. Interestingly, these GTPases play important roles at different stages of viral protein and genome transport in infected host cells. Importantly, dysregulation of Cdc42, Rac1 and RhoA leads to numerous disorders, including malignant transformation. In some cases, hyperactivation of Rho GTPases is required for cellular transformation. In this article, we review a number of findings related to Rho GTPase function in intracellular transport and cellular transformation.

  17. Cellular host responses to gliomas.

    Directory of Open Access Journals (Sweden)

    Joseph Najbauer

    Full Text Available BACKGROUND: Glioblastoma multiforme (GBM is the most aggressive type of malignant primary brain tumors in adults. Molecular and genetic analysis has advanced our understanding of glioma biology, however mapping the cellular composition of the tumor microenvironment is crucial for understanding the pathology of this dreaded brain cancer. In this study we identified major cell populations attracted by glioma using orthotopic rodent models of human glioma xenografts. Marker-specific, anatomical and morphological analyses revealed a robust influx of host cells into the main tumor bed and tumor satellites. METHODOLOGY/PRINCIPAL FINDINGS: Human glioma cell lines and glioma spheroid orthotopic implants were used in rodents. In both models, the xenografts recruited large numbers of host nestin-expressing cells, which formed a 'network' with glioma. The host nestin-expressing cells appeared to originate in the subventricular zone ipsilateral to the tumor, and were clearly distinguishable from pericytes that expressed smooth muscle actin. These distinct cell populations established close physical contact in a 'pair-wise' manner and migrated together to the deeper layers of tumor satellites and gave rise to tumor vasculature. The GBM biopsy xenografts displayed two different phenotypes: (a low-generation tumors (first in vivo passage in rats were highly invasive and non-angiogenic, and host nestin-positive cells that infiltrated into these tumors displayed astrocytic or elongated bipolar morphology; (b high-generation xenografts (fifth passage had pronounced cellularity, were angiogenic with 'glomerulus-like' microvascular proliferations that contained host nestin-positive cells. Stromal cell-derived factor-1 and its receptor CXCR4 were highly expressed in and around glioma xenografts, suggesting their role in glioma progression and invasion. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a robust migration of nestin-expressing host cells to glioma, which

  18. Modeling cellular effects of coal pollutants

    International Nuclear Information System (INIS)

    The goal of this project is to develop and test models for the dose and dose-rate dependence of biological effects of coal pollutants on mammalian cells in tissue culture. Particular attention is given to the interaction of pollutants with the genetic material (deoxyribonucleic acid, or NDA) in the cell. Unlike radiation, which can interact directly with chromatin, chemical pollutants undergo numerous changes before the ultimate carcinogen becomes covalently bound to the DNA. Synthetic vesicles formed from a phospholipid bilayer are being used to investigate chemical transformations that may occur during the transport of pollutants across cellular membranes. The initial damage to DNA is rapidly modified by enzymatic repair systems in most living organisms. A model has been developed for predicting the effects of excision repair on the survival of human cells exposed to chemical carcinogens. In addition to the excision system, normal human cells also have tolerance mechanisms that permit continued growth and division of cells without removal of the damage. We are investigating the biological effect of damage passed to daughter cells by these tolerance mechanisms

  19. Hydrodynamical simulations of coupled and uncoupled quintessence models I: Halo properties and the cosmic web

    CERN Document Server

    Carlesi, Edoardo; Lewis, Geraint F; Wales, Scott; Yepes, Gustavo

    2014-01-01

    We present the results of a series of adiabatic hydrodynamical simulations of several quintessence models (both with a free and an interacting scalar field) in comparison to a standard \\LCDM\\ cosmology. For each we use $2\\times1024^3$ particles in a $250$\\hMpc\\ periodic box assuming WMAP7 cosmology. In this work we focus on the properties of haloes in the cosmic web at $z=0$. The web is classified into \\emph{voids}, \\emph{sheets}, \\emph{filaments} and \\emph{knots} depending on the eigenvalues of the velocity shear tensor, which are an excellent proxy for the underlying overdensity distribution. We find that the properties of objects classified according to their surrounding environment shows a substantial dependence on the underlying cosmology; for example, while $V_{\\rm max}$ shows average deviations of $\\approx5$ per cent across the different models when considering the full halo sample, comparing objects classified according to their environment, the size of the deviation can be as large as $20$ per cent. ...

  20. New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain.

    Science.gov (United States)

    Venkat, Poornima; Chopp, Michael; Chen, Jieli

    2016-06-30

    The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases. PMID:27374823

  1. Hydrodynamical simulations of coupled and uncoupled quintessence models - I. Halo properties and the cosmic web

    Science.gov (United States)

    Carlesi, Edoardo; Knebe, Alexander; Lewis, Geraint F.; Wales, Scott; Yepes, Gustavo

    2014-04-01

    We present the results of a series of adiabatic hydrodynamical simulations of several quintessence models (both with a free and an interacting scalar field) in comparison to a standard Λ cold dark matter cosmology. For each we use 2 × 10243 particles in a 250 h-1 Mpc periodic box assuming 7-year Wilkinson Microwave Anisotropy Probe cosmology. In this work we focus on the properties of haloes in the cosmic web at z = 0. The web is classified into voids, sheets, filaments and knots depending on the eigenvalues of the velocity shear tensor, which are an excellent proxy for the underlying overdensity distribution. We find that the properties of objects classified according to their surrounding environment show a substantial dependence on the underlying cosmology; for example, while Vmax shows average deviations of ≈5 per cent across the different models when considering the full halo sample, comparing objects classified according to their environment, the size of the deviation can be as large as 20 per cent. We also find that halo spin parameters are positively correlated to the coupling, whereas halo concentrations show the opposite behaviour. Furthermore, when studying the concentration-mass relation in different environments, we find that in all cosmologies underdense regions have a larger normalization and a shallower slope. While this behaviour is found to characterize all the models, differences in the best-fitting relations are enhanced in (coupled) dark energy models, thus providing a clearer prediction for this class of models.

  2. Game of Life Cellular Automata

    CERN Document Server

    Adamatzky, Andrew

    2010-01-01

    In the late 1960s, British mathematician John Conway invented a virtual mathematical machine that operates on a two-dimensional array of square cell. Each cell takes two states, live and dead. The cells' states are updated simultaneously and in discrete time. A dead cell comes to life if it has exactly three live neighbours. A live cell remains alive if two or three of its neighbours are alive, otherwise the cell dies. Conway's Game of Life became the most programmed solitary game and the most known cellular automaton. The book brings together results of forty years of study into computational

  3. Cellular automata a parallel model

    CERN Document Server

    Mazoyer, J

    1999-01-01

    Cellular automata can be viewed both as computational models and modelling systems of real processes. This volume emphasises the first aspect. In articles written by leading researchers, sophisticated massive parallel algorithms (firing squad, life, Fischer's primes recognition) are treated. Their computational power and the specific complexity classes they determine are surveyed, while some recent results in relation to chaos from a new dynamic systems point of view are also presented. Audience: This book will be of interest to specialists of theoretical computer science and the parallelism challenge.

  4. Mathematical Physics of Cellular Automata

    CERN Document Server

    Garcia-Morales, Vladimir

    2012-01-01

    A universal map is derived for all deterministic 1D cellular automata (CA) containing no freely adjustable parameters. The map can be extended to an arbitrary number of dimensions and topologies and its invariances allow to classify all CA rules into equivalence classes. Complexity in 1D systems is then shown to emerge from the weak symmetry breaking of the addition modulo an integer number p. The latter symmetry is possessed by certain rules that produce Pascal simplices in their time evolution. These results elucidate Wolfram's classification of CA dynamics.

  5. Estimation in Cellular Radio Systems

    OpenAIRE

    Blom, Jonas; Gunnarsson, Fredrik; Gustafsson, Fredrik

    1999-01-01

    The problem to track time-varying parameters in cellular radio systems is studied, and the focus is on estimation based only on the signals that are readily available. Previous work have demonstrated very good performance, but were relying on analog measurement that are not available. Most of the information is lost due to quantization and sampling at a rate that might be as low as 2 Hz (GSM case). For that matter a maximum likelihood estimator have been designed and exemplified in the case o...

  6. 'Biomoleculas': cellular metabolism didactic software

    International Nuclear Information System (INIS)

    'Biomoleculas' is a software that deals with topics such as the digestion, cellular metabolism and excretion of nutrients. It is a pleasant, simple and didactic guide, made by and for students. In this program, each biomolecule (carbohydrates, lipids and proteins) is accompanied until its degradation and assimilation by crossing and interrelating the different metabolic channels to finally show the destination of the different metabolites formed and the way in which these are excreted. It is used at present as a teaching-learning process tool by the chair of Physiology and Biophysics at the Facultad de Ingenieria - Universidad Nacional de Entre Rios

  7. Protein accounting in the cellular economy

    Science.gov (United States)

    Vázquez-Laslop, Nora; Mankin, Alexander S.

    2014-01-01

    Knowing the copy number of cellular proteins is critical for understanding cell physiology. By being able to measure the absolute synthesis rates of the majority of cellular proteins, Li et al. (2014) gain insights into key aspects of translation regulation and fundamental principles of cellular strategies to adjust protein synthesis according to the needs. PMID:24766801

  8. Cellular Functions of Transient Receptor Potential channels

    OpenAIRE

    Dadon, Daniela; Minke, Baruch

    2010-01-01

    Transient Receptor Potential channels are polymodal cellular sensors involved in a wide variety of cellular processes, mainly by increasing cellular Ca2+. In this review we focus on the roles of these channels in: i) cell death ii) proliferation and differentiation and iii) synaptic vesicle release.

  9. Universal map for cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    García-Morales, V., E-mail: vmorales@ph.tum.de [Institute for Advanced Study – Technische Universität München, Lichtenbergstr. 2a, D-85748 Garching (Germany)

    2012-08-20

    A universal map is derived for all deterministic 1D cellular automata (CAs) containing no freely adjustable parameters and valid for any alphabet size and any neighborhood range (including non-symmetrical neighborhoods). The map can be extended to an arbitrary number of dimensions and topologies and to arbitrary order in time. Specific CA maps for the famous Conway's Game of Life and Wolfram's 256 elementary CAs are given. An induction method for CAs, based in the universal map, allows mathematical expressions for the orbits of a wide variety of elementary CAs to be systematically derived. -- Highlights: ► A universal map is derived for all deterministic 1D cellular automata (CA). ► The map is generalized to 2D for Von Neumann, Moore and hexagonal neighborhoods. ► A map for all Wolfram's 256 elementary CAs is derived. ► A map for Conway's “Game of Life” is obtained.

  10. Cellular Therapy for Heart Failure.

    Science.gov (United States)

    Psaltis, Peter J; Schwarz, Nisha; Toledo-Flores, Deborah; Nicholls, Stephen J

    2016-01-01

    The pathogenesis of cardiomyopathy and heart failure (HF) is underpinned by complex changes at subcellular, cellular and extracellular levels in the ventricular myocardium. For all of the gains that conventional treatments for HF have brought to mortality and morbidity, they do not adequately address the loss of cardiomyocyte numbers in the remodeling ventricle. Originally conceived to address this problem, cellular transplantation for HF has already gone through several stages of evolution over the past two decades. Various cell types and delivery routes have been implemented to positive effect in preclinical models of ischemic and nonischemic cardiomyopathy, with pleiotropic benefits observed in terms of myocardial remodeling, systolic and diastolic performance, perfusion, fibrosis, inflammation, metabolism and electrophysiology. To a large extent, these salubrious effects are now attributed to the indirect, paracrine capacity of transplanted stem cells to facilitate endogenous cardiac repair processes. Promising results have also followed in early phase human studies, although these have been relatively modest and somewhat inconsistent. This review details the preclinical and clinical evidence currently available regarding the use of pluripotent stem cells and adult-derived progenitor cells for cardiomyopathy and HF. It outlines the important lessons that have been learned to this point in time, and balances the promise of this exciting field against the key challenges and questions that still need to be addressed at all levels of research, to ensure that cell therapy realizes its full potential by adding to the armamentarium of HF management. PMID:27280304

  11. The effect of particle design on cellular internalization pathways

    OpenAIRE

    Gratton, Stephanie E. A.; Ropp, Patricia A.; Pohlhaus, Patrick D.; Luft, J. Christopher; Madden, Victoria J.; Napier, Mary E.; DeSimone, Joseph M.

    2008-01-01

    The interaction of particles with cells is known to be strongly influenced by particle size, but little is known about the interdependent role that size, shape, and surface chemistry have on cellular internalization and intracellular trafficking. We report on the internalization of specially designed, monodisperse hydrogel particles into HeLa cells as a function of size, shape, and surface charge. We employ a top-down particle fabrication technique called PRINT that is able to generate unifor...

  12. On Hardware Implementation of Discrete-Time Cellular Neural Networks

    OpenAIRE

    Malki, Suleyman

    2008-01-01

    Cellular Neural Networks are characterized by simplicity of operation. The network consists of a large number of nonlinear processing units; called cells; that are equally spread in the space. Each cell has a simple function (sequence of multiply-add followed by a single discrimination) that takes an element of a topographic map and then interacts with all cells within a specified sphere of interest through direct connections. Due to their intrinsic parallel computing power, CNNs have attract...

  13. Mimicking a SURF1 allele reveals uncoupling of cytochrome c oxidase assembly from translational regulation in yeast.

    Science.gov (United States)

    Reinhold, Robert; Bareth, Bettina; Balleininger, Martina; Wissel, Mirjam; Rehling, Peter; Mick, David U

    2011-06-15

    Defects in mitochondrial energy metabolism lead to severe human disorders, mainly affecting tissues especially dependent on oxidative phosphorylation, such as muscle and brain. Leigh Syndrome describes a severe encephalomyopathy in infancy, frequently caused by mutations in SURF1. SURF1, termed Shy1 in Saccharomyces cerevisiae, is a conserved assembly factor for the terminal enzyme of the respiratory chain, cytochrome c oxidase. Although the molecular function of SURF1/Shy1 is still enigmatic, loss of function leads to cytochrome c oxidase deficiency and reduced expression of the central subunit Cox1 in yeast. Here, we provide insights into the molecular mechanisms leading to disease through missense mutations in codons of the most conserved amino acids in SURF1. Mutations affecting G(124) do not compromise import of the SURF1 precursor protein but lead to fast turnover of the mature protein within the mitochondria. Interestingly, an Y(274)D exchange neither affects stability nor localization of the protein. Instead, SURF1(Y274D) accumulates in a 200 kDa cytochrome c oxidase assembly intermediate. Using yeast as a model, we demonstrate that the corresponding Shy1(Y344D) is able to overcome the stage where cytochrome c oxidase assembly links to the feedback regulation of mitochondrial Cox1 expression. However, Shy1(Y344D) impairs the assembly at later steps, most apparent at low temperature and exhibits a dominant-negative phenotype upon overexpression. Thus, exchanging the conserved tyrosine (Y(344)) with aspartate in yeast uncouples translational regulation of Cox1 from cytochrome c oxidase assembly and provides evidence for the dual functionality of Shy1. PMID:21470975

  14. Serum levels of mitochondrial uncoupling protein 1, leptin, and lipids during late pregnancy and the early postpartum period in mares.

    Science.gov (United States)

    Arfuso, F; Giannetto, C; Rizzo, M; Fazio, F; Giudice, E; Piccione, G

    2016-09-15

    The aim of this study was to investigate the changes of serum mitochondrial uncoupling protein 1 (UCP1) and leptin levels as well as of lipid and lipoprotein profiles in mares during the peripartum period. Ten pregnant mares (group A) were monitored from 15 ± 3 days of pregnancy until 15 days after foaling, and 10 nonpregnant nonlactating mares constituted the control (group B). In group A, blood sampling was performed on Days 15 ± 3 and 7 ± 3 before foaling, on the day of foaling, and on Days 7 and 15 after foaling. In group B, blood sampling was performed on the same days as in group A. Serum levels were determined for UCP1, leptin, total lipids, phospholipids, triglycerides, total cholesterol (Total-Chol), high-density lipoproteins, low-density lipoproteins (LDLs), and very low-density lipoproteins (VLDLs). Two-way repeated-measures ANOVA was applied to evaluate the effects of peripartum period and group membership. All studied parameters except phospholipid levels (P > 0.05) showed significant changes in group A over the peripartum period (P leptin and total lipids, triglycerides, VLDLs, Total-Chol, and LDLs. These changes observed in mares during the peripartum period could represent a response to hormonal and metabolic adaptations occurring during specific physiological conditions such as late pregnancy and early postpartum. These changes should compensate for the energy loss occurring during these particular life phases and ensure a good body condition to protect mares against negative energy balance. PMID:27165993

  15. [PHYSICAL EXERCISE TRAINING CAN- CELS CONSTITUTIVE NOS UNCOUPLING AND INDUCED VIOLATIONS OF CARDIAC HEMODYNAMICS IN HYPERTENSION (PART III)].

    Science.gov (United States)

    Dorofeyeva, N A; Kotsuruba, A V; Kopjak, B S; Sagach, V F

    2015-01-01

    In the heart and heart mitochondria spontaneously hypertensive rats investigated the effect of physical exercise training (swimming in a moderate and excessive training mode) on the physiological indicators of cardiac hemodynamics and biochemical parameters that characterize the level of oxidative and nitrosative stress. The index of coupling Ca(2+)-dependent constitutive NO-synthases (cNOS = eNOS + nNOS) and biochemical index of dysfunction were calculated. It turned out that both modes of training is completely restored, and even exceed the reference values in untrained rats Wistar conjugate cNOS state and Ca(2+)-dependent synthesis of nitric oxide (NO). Intensity regime of exercise on the border of functionality have been ineffective for improving the functional state of the cardiovascular system and hypertension can provoke it further. Moderate physical training regime, on the contrary, improves the diastolic function of the heart due to an increase dP/dtmin, reducing end-diastolic pressure and a significant reduction in end-diastolic stiffness. Moderate exercise decreased peripheral resistance and cardiac afterload, as indicated by the decrease in end-systolic pressure and arterial stiffness, which contributed to more efficient and energy-saving of heart work. Improve physiological indicators of cardiac hemodynamics and functional state of the heart in moderate mode of training correlated with changes in both the calculated indices. Moderate mode of training is recommended as a simple physiological preconditioning method for the prevention of cardiac dysfunction, hypertension as a result of state uncoupling cNOS and the resulting excessive generation of superoxide and, conversely, inhibition of Ca(2+)-dependent synthesis of NO. PMID:26552300

  16. Interconnectivity of human cellular metabolism and disease prevalence

    International Nuclear Information System (INIS)

    Fluctuations of metabolic reaction fluxes may cause abnormal concentrations of toxic or essential metabolites, possibly leading to metabolic diseases. The mutual binding of enzymatic proteins and ones involving common metabolites enforces distinct coupled reactions, by which local perturbations may spread through the cellular network. Such network effects at the molecular interaction level in human cellular metabolism can reappear in the patterns of disease occurrence. Here we construct the enzyme-reaction network and the metabolite-reaction network, capturing the flux coupling of metabolic reactions caused by the interacting enzymes and the shared metabolites, respectively. Diseases potentially caused by the failure of individual metabolic reactions can be identified by using the known disease–gene association, which allows us to derive the probability of an inactivated reaction causing diseases from the disease records at the population level. We find that the greater the number of proteins that catalyze a reaction, the higher the mean prevalence of its associated diseases. Moreover, the number of connected reactions and the mean size of the avalanches in the networks constructed are also shown to be positively correlated with the disease prevalence. These findings illuminate the impact of the cellular network topology on disease development, suggesting that the global organization of the molecular interaction network should be understood to assist in disease diagnosis, treatment, and drug discovery

  17. A cellular automata evacuation model considering friction and repulsion

    Institute of Scientific and Technical Information of China (English)

    SONG Weiguo; YU Yanfei; FAN Weicheng; Zhang Heping

    2005-01-01

    There exist interactions among pedestrians and between pedestrian and environment in evacuation. These interactions include attraction, repulsion and friction that play key roles in human evacuation behaviors, speed and efficiency. Most former evacuation models focus on the attraction force, while repulsion and friction are not well modeled. As a kind of multi-particle self-driven model, the social force model introduced in recent years can represent those three forces but with low simulation efficiency because it is a continuous model with complex rules. Discrete models such as the cellular automata model and the lattice gas model have simple rules and high simulation efficiency, but are not quite suitable for interactions' simulation. In this paper, a new cellular automata model based on traditional models is introduced in which repulsion and friction are modeled quantitatively. It is indicated that the model can simulate some basic behaviors, e.g.arching and the "faster-is-slower" phenomenon, in evacuation as multi-particle self-driven models, but with high efficiency as the normal cellular automata model and the lattice gas model.

  18. Thermomechanical characterisation of cellular rubber

    Science.gov (United States)

    Seibert, H.; Scheffer, T.; Diebels, S.

    2016-01-01

    This contribution discusses an experimental possibility to characterise a cellular rubber in terms of the influence of multiaxiality, rate dependency under environmental temperature and its behaviour under hydrostatic pressure. In this context, a mixed open and closed cell rubber based on an ethylene propylene diene monomer is investigated exemplarily. The present article intends to give a general idea of the characterisation method and the considerable effects of this special type of material. The main focus lies on the experimental procedure and the used testing devices in combination with the analysis methods such as true three-dimensional digital image correlation. The structural compressibility is taken into account by an approach for a material model using the Theory of Porous Media with additional temperature dependence.

  19. Discrete geodesics and cellular automata

    CERN Document Server

    Arrighi, Pablo

    2015-01-01

    This paper proposes a dynamical notion of discrete geodesics, understood as straightest trajectories in discretized curved spacetime. The notion is generic, as it is formulated in terms of a general deviation function, but readily specializes to metric spaces such as discretized pseudo-riemannian manifolds. It is effective: an algorithm for computing these geodesics naturally follows, which allows numerical validation---as shown by computing the perihelion shift of a Mercury-like planet. It is consistent, in the continuum limit, with the standard notion of timelike geodesics in a pseudo-riemannian manifold. Whether the algorithm fits within the framework of cellular automata is discussed at length. KEYWORDS: Discrete connection, parallel transport, general relativity, Regge calculus.

  20. Cellular compartmentalization of secondary metabolism

    Directory of Open Access Journals (Sweden)

    H. Corby eKistler

    2015-02-01

    Full Text Available Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g. amino acids, acetyl CoA, NADPH, enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported.