WorldWideScience

Sample records for cellular phosphoinositides profiling

  1. Phosphoinositides and vesicular membrane traffic

    OpenAIRE

    Mayinger, Peter

    2012-01-01

    Phosphoinositide lipids were initially discovered as precursors for specific second messengers involved in signal transduction, but have now taken the center stage in controlling many essential processes at virtually every cellular membrane. In particular, phosphoinositides play a critical role in regulating membrane dynamics and vesicular transport. The unique distribution of certain phosphoinositides at specific intracellular membranes makes these molecules uniquely suited to direct organel...

  2. The phosphoinositide 3-kinase signaling pathway in normal and malignant B cells: activation mechanisms, regulation and impact on cellular functions.

    Science.gov (United States)

    Pauls, Samantha D; Lafarge, Sandrine T; Landego, Ivan; Zhang, Tingting; Marshall, Aaron J

    2012-01-01

    The phosphoinositide 3-kinase (PI3K) pathway is a central signal transduction axis controlling normal B cell homeostasis and activation in humoral immunity. The p110δ PI3K catalytic subunit has emerged as a critical mediator of multiple B cell functions. The activity of this pathway is regulated at multiple levels, with inositol phosphatases PTEN and SHIP both playing critical roles. When deregulated, the PI3K pathway can contribute to B cell malignancies and autoantibody production. This review summarizes current knowledge on key mechanisms that activate and regulate the PI3K pathway and influence normal B cell functional responses including the development of B cell subsets, antigen presentation, immunoglobulin isotype switch, germinal center responses, and maintenance of B cell anergy. We also discuss PI3K pathway alterations reported in select B cell malignancies and highlight studies indicating the functional significance of this pathway in malignant B cell survival and growth within tissue microenvironments. Finally, we comment on early clinical trial results, which support PI3K inhibition as a promising treatment of chronic lymphocytic leukemia. PMID:22908014

  3. Computational studies of the binding profile of phosphoinositide PtdIns (3,4,5) P3 with the pleckstrin homology domain of an oomycete cellulose synthase

    Science.gov (United States)

    Kuang, Guanglin; Bulone, Vincent; Tu, Yaoquan

    2016-02-01

    Saprolegnia monoica is a model organism to investigate Saprolegnia parasitica, an important oomycete which causes considerable loss in aquaculture every year. S. monoica contains cellulose synthases vital for oomycete growth. However, the molecular mechanism of the cellulose biosynthesis process in the oomycete growth is still poorly understood. Some cellulose synthases of S. monoica, such as SmCesA2, are found to contain a plecsktrin homology (PH) domain, which is a protein module widely found in nature and known to bind to phosphoinositides, a class of signaling compounds involved in many biological processes. Understanding the molecular interactions between the PH domain and phosphoinositides would help to unravel the cellulose biosynthesis process of oomycetes. In this work, the binding profile of PtdIns (3,4,5) P3, a typical phosphoinositide, with SmCesA2-PH was studied by molecular docking, molecular dynamics and metadynamics simulations. PtdIns (3,4,5) P3 is found to bind at a specific site located at β1, β2 and β1-β2 loop of SmCesA2-PH. The high affinity of PtdIns (3,4,5) P3 to SmCesA2-PH is contributed by the free phosphate groups, which have electrostatic and hydrogen-bond interactions with Lys88, Lys100 and Arg102 in the binding site.

  4. Phosphoinositides in membrane contact sites.

    Science.gov (United States)

    Raiborg, Camilla; Wenzel, Eva M; Pedersen, Nina M; Stenmark, Harald

    2016-04-15

    Cellular membranes communicate extensively via contact sites that form between two membranes. Such sites allow exchange of specific ions, lipids or proteins between two compartments without content mixing, thereby preserving organellar architecture during the transfer process. Even though the molecular compositions of membrane contact sites are diverse, it is striking that several of these sites, including contact sites between the endoplasmic reticulum (ER) and endosomes, Golgi and the plasma membrane (PM), and contact sites between lysosomes and peroxisomes, contain phosphorylated derivatives of phosphatidylinositol known as phosphoinositides. In this mini-review we discuss the involvement and functions of phosphoinositides in membrane contact sites. PMID:27068950

  5. Cellular profile of bronchoalveolar lavage fluid in Turkish miners

    OpenAIRE

    Kayacan, O.; Beder, S; KARNAK, D.

    2003-01-01

    Pneumoconiosis is still a health problem in Turkey and has a relatively high incidence. Retired underground miners were investigated to document alveolitis, and to observe the difference in the cellular profiles of bronchoalveolar lavage (BAL) fluid with or without pneumoconiosis.

  6. Arabidopsis AtPLC2 Is a Primary Phosphoinositide-Specific Phospholipase C in Phosphoinositide Metabolism and the Endoplasmic Reticulum Stress Response.

    Directory of Open Access Journals (Sweden)

    Kazue Kanehara

    2015-09-01

    Full Text Available Phosphoinositides represent important lipid signals in the plant development and stress response. However, multiple isoforms of the phosphoinositide biosynthetic genes hamper our understanding of the pivotal enzymes in each step of the pathway as well as their roles in plant growth and development. Here, we report that phosphoinositide-specific phospholipase C2 (AtPLC2 is the primary phospholipase in phosphoinositide metabolism and is involved in seedling growth and the endoplasmic reticulum (ER stress responses in Arabidopsis thaliana. Lipidomic profiling of multiple plc mutants showed that the plc2-1 mutant increased levels of its substrates phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate, suggesting that the major phosphoinositide metabolic pathway is impaired. AtPLC2 displayed a distinct tissue expression pattern and localized at the plasma membrane in different cell types, where phosphoinositide signaling occurs. The seedlings of plc2-1 mutant showed growth defect that was complemented by heterologous expression of AtPLC2, suggesting that phosphoinositide-specific phospholipase C activity borne by AtPLC2 is required for seedling growth. Moreover, the plc2-1 mutant showed hypersensitive response to ER stress as evidenced by changes in relevant phenotypes and gene expression profiles. Our results revealed the primary enzyme in phosphoinositide metabolism, its involvement in seedling growth and an emerging link between phosphoinositide and the ER stress response.

  7. Quantum dot multiplexing for the profiling of cellular receptors

    Science.gov (United States)

    Lee-Montiel, Felipe T.; Li, Peter; Imoukhuede, P. I.

    2015-11-01

    The profiling of cellular heterogeneity has wide-reaching importance for our understanding of how cells function and react to their environments in healthy and diseased states. Our ability to interpret and model cell behavior has been limited by the difficulties of measuring cell differences, for example, comparing tumor and non-tumor cells, particularly at the individual cell level. This demonstrates a clear need for a generalizable approach to profile fluorophore sites on cells or molecular assemblies on beads. Here, a multiplex immunoassay for simultaneous detection of five different angiogenic markers was developed. We targeted angiogenic receptors in the vascular endothelial growth factor family (VEGFR1, VEGFR2 and VEGFR3) and Neuropilin (NRP) family (NRP1 and NRP2), using multicolor quantum dots (Qdots). Copper-free click based chemistry was used to conjugate the monoclonal antibodies with 525, 565, 605, 655 and 705 nm CdSe/ZnS Qdots. We tested and performed colocalization analysis of our nanoprobes using the Pearson correlation coefficient statistical analysis. Human umbilical vein endothelial cells (HUVEC) were tested. The ability to easily monitor the molecular indicators of angiogenesis that are a precursor to cancer in a fast and cost effective system is an important step towards personalized nanomedicine.The profiling of cellular heterogeneity has wide-reaching importance for our understanding of how cells function and react to their environments in healthy and diseased states. Our ability to interpret and model cell behavior has been limited by the difficulties of measuring cell differences, for example, comparing tumor and non-tumor cells, particularly at the individual cell level. This demonstrates a clear need for a generalizable approach to profile fluorophore sites on cells or molecular assemblies on beads. Here, a multiplex immunoassay for simultaneous detection of five different angiogenic markers was developed. We targeted angiogenic receptors

  8. Phosphoinositide signaling in somatosensory neurons.

    Science.gov (United States)

    Rohacs, Tibor

    2016-05-01

    Somatosensory neurons of the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are responsible for detecting thermal and tactile stimuli. They are also the primary neurons mediating pain and itch. A large number of cell surface receptors in these neurons couple to phospholipase C (PLC) enzymes leading to the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and the generation of downstream signaling molecules. These neurons also express many different ion channels, several of which are regulated by phosphoinositides. This review will summarize the knowledge on phosphoinositide signaling in DRG neurons, with special focus on effects on sensory and other ion channels. PMID:26724974

  9. Fuel management optimization based on power profile by Cellular Automata

    International Nuclear Information System (INIS)

    Fuel management in PWR nuclear reactors is comprised of a collection of principles and practices required for the planning, scheduling, refueling, and safe operation of nuclear power plants to minimize the total plant and system energy costs to the extent possible. Despite remarkable advancements in optimization procedures, inherent complexities in nuclear reactor structure and strong inter-dependency among the fundamental parameters of the core make it necessary to evaluate the most efficient arrangement of the core. Several patterns have been presented so far to determine the best configuration of fuels in the reactor core by emphasis on minimizing the local power peaking factor (Pq). In this research, a new strategy for optimizing the fuel arrangements in a VVER-1000 reactor core is developed while lowering the Pq is considered as the main target. For this purpose, a Fuel Quality Factor, Z(r), served to depict the reactor core pattern. Mapping to ideal pattern is tracked over the optimization procedure in which the ideal pattern is prepared with considering the Z(r) constraints and their effects on flux and Pq uniformity. For finding the best configuration corresponding to the desired pattern, Cellular Automata (CA) is applied as a powerful and reliable tool on optimization procedure. To obtain the Z(r) constraints, the MCNP code was used and core calculations were performed by WIMS and CITATION codes. The results are compared with the predictions of a Neural Network as a smart optimization method, and the Final Safety Analysis Report (FSAR) as a reference proposed by the designer.

  10. qpure: A tool to estimate tumor cellularity from genome-wide single-nucleotide polymorphism profiles.

    Directory of Open Access Journals (Sweden)

    Sarah Song

    Full Text Available Tumour cellularity, the relative proportion of tumour and normal cells in a sample, affects the sensitivity of mutation detection, copy number analysis, cancer gene expression and methylation profiling. Tumour cellularity is traditionally estimated by pathological review of sectioned specimens; however this method is both subjective and prone to error due to heterogeneity within lesions and cellularity differences between the sample viewed during pathological review and tissue used for research purposes. In this paper we describe a statistical model to estimate tumour cellularity from SNP array profiles of paired tumour and normal samples using shifts in SNP allele frequency at regions of loss of heterozygosity (LOH in the tumour. We also provide qpure, a software implementation of the method. Our experiments showed that there is a medium correlation 0.42 ([Formula: see text]-value=0.0001 between tumor cellularity estimated by qpure and pathology review. Interestingly there is a high correlation 0.87 ([Formula: see text]-value [Formula: see text] 2.2e-16 between cellularity estimates by qpure and deep Ion Torrent sequencing of known somatic KRAS mutations; and a weaker correlation 0.32 ([Formula: see text]-value=0.004 between IonTorrent sequencing and pathology review. This suggests that qpure may be a more accurate predictor of tumour cellularity than pathology review. qpure can be downloaded from https://sourceforge.net/projects/qpure/.

  11. Systematic Characterisation of Cellular Localisation and Expression Profiles of Proteins Containing MHC Ligands

    DEFF Research Database (Denmark)

    Juncker, Agnieszka; Larsen, Mette Voldby; Weinhold, Nils; Nielsen, Morten; Brunak, Søren; Lund, Ole

    2009-01-01

    -scale study, we used a large data set of proteins containing experimentally identified MHC class I or II ligands and examined the proteins according to their expression profiles at the mRNA level and their Gene Ontology (GO) classification within the cellular component ontology. Proteins encoded by highly...

  12. Inositol pentakisphosphate isomers bind PH domains with varying specificity and inhibit phosphoinositide interactions

    Directory of Open Access Journals (Sweden)

    Schultz Carsten

    2011-02-01

    Full Text Available Abstract Background PH domains represent one of the most common domains in the human proteome. These domains are recognized as important mediators of protein-phosphoinositide and protein-protein interactions. Phosphoinositides are lipid components of the membrane that function as signaling molecules by targeting proteins to their sites of action. Phosphoinositide based signaling pathways govern a diverse range of important cellular processes including membrane remodeling, differentiation, proliferation and survival. Myo-Inositol phosphates are soluble signaling molecules that are structurally similar to the head groups of phosphoinositides. These molecules have been proposed to function, at least in part, by regulating PH domain-phosphoinositide interactions. Given the structural similarity of inositol phosphates we were interested in examining the specificity of PH domains towards the family of myo-inositol pentakisphosphate isomers. Results In work reported here we demonstrate that the C-terminal PH domain of pleckstrin possesses the specificity required to discriminate between different myo-inositol pentakisphosphate isomers. The structural basis for this specificity was determined using high-resolution crystal structures. Moreover, we show that while the PH domain of Grp1 does not possess this high degree of specificity, the PH domain of protein kinase B does. Conclusions These results demonstrate that some PH domains possess enough specificity to discriminate between myo-inositol pentakisphosphate isomers allowing for these molecules to differentially regulate interactions with phosphoinositides. Furthermore, this work contributes to the growing body of evidence supporting myo-inositol phosphates as regulators of important PH domain-phosphoinositide interactions. Finally, in addition to expanding our knowledge of cellular signaling, these results provide a basis for developing tools to probe biological pathways.

  13. A Screen for Novel Phosphoinositide 3-kinase Effector Proteins*

    OpenAIRE

    Dixon, Miles J.; Gray, Alexander; Boisvert, François-Michel; Agacan, Mark; Morrice, Nicholas A.; Gourlay, Robert; Leslie, Nicholas R.; Downes, C. Peter; Batty, Ian H.

    2011-01-01

    Class I phosphoinositide 3-kinases exert important cellular effects through their two primary lipid products, phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2). As few molecular targets for PtdIns(3,4)P2 have yet been identified, a screen for PI 3-kinase-responsive proteins that is selective for these is described. This features a tertiary approach incorporating a unique, primary recruitment of target proteins in intact cells to membranes selec...

  14. Comparison of cellular and tissue transcriptional profiles in canine mammary tumor

    OpenAIRE

    Pawlowski, K.M.; Krol, M.; Majewska, A.; Badowska-Kozakiewicz, A.; Mol, J. A.; Malicka, E.; Motyl, T.

    2009-01-01

    J Physiol Pharmacol. 2009 May;60 Suppl 1:85-94. Comparison of cellular and tissue transcriptional profiles in canine mammary tumor. Pawlowski KM, Krol M, Majewska A, Badowska-Kozakiewicz A, Mol JA, Malicka E, Motyl T. Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Poland. Tumor-derived cell lines are widely used as in vitro cancer models. Cell lines historically served as the primary experimental model systems for exploration o...

  15. A new family of phosphoinositide phosphatases in microorganisms: identification and biochemical analysis

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    Bennett Hayley J

    2010-08-01

    Full Text Available Abstract Background Phosphoinositide metabolism is essential to membrane dynamics and impinges on many cellular processes, including phagocytosis. Modulation of phosphoinositide metabolism is important for pathogenicity and virulence of many human pathogens, allowing them to survive and replicate in the host cells. Phosphoinositide phosphatases from bacterial pathogens are therefore key players in this modulation and constitute attractive targets for chemotherapy. MptpB, a virulence factor from Mycobacterium tuberculosis, has phosphoinositide phosphatase activity and a distinct active site P-loop signature HCXXGKDR that shares characteristics with eukaryotic lipid phosphatases and protein tyrosine phosphatases. We used this P-loop signature as a "diagnostic motif" to identify related putative phosphatases with phosphoinositide activity in other organisms. Results We found more than 200 uncharacterised putative phosphatase sequences with the conserved signature in bacteria, with some related examples in fungi and protozoa. Many of the sequences identified belong to recognised human pathogens. Interestingly, no homologues were found in any other organisms including Archaea, plants, or animals. Phylogenetic analysis revealed that these proteins are unrelated to classic eukaryotic lipid phosphatases. However, biochemical characterisation of those from Listeria monocytogenes and Leishmania major, demonstrated that, like MptpB, they have phosphatase activity towards phosphoinositides. Mutagenesis studies established that the conserved Asp and Lys in the P-loop signature (HCXXGKDR are important in catalysis and substrate binding respectively. Furthermore, we provide experimental evidence that the number of basic residues in the P-loop is critical in determining activity towards poly-phosphoinositides. Conclusion This new family of enzymes in microorganisms shows distinct sequence and biochemical characteristics to classic eukaryotic lipid phosphatases

  16. Microfluidic Mobility Shift Profiling of Lysine Acetyltransferases Enables Screening and Mechanistic Analysis of Cellular Acetylation Inhibitors.

    Science.gov (United States)

    Sorum, Alexander W; Shrimp, Jonathan H; Roberts, Allison M; Montgomery, David C; Tiwari, Neil K; Lal-Nag, Madhu; Simeonov, Anton; Jadhav, Ajit; Meier, Jordan L

    2016-03-18

    Lysine acetyltransferases (KATs) are critical regulators of signaling in many diseases, including cancer. A major challenge in establishing the targetable functions of KATs in disease is a lack of well-characterized, cell-active KAT inhibitors. To confront this challenge, here we report a microfluidic mobility shift platform for the discovery and characterization of small molecule KAT inhibitors. Novel fluorescent peptide substrates were developed for four well-known KAT enzymes (p300, Crebbp, Morf, and Gcn5). Enzyme-catalyzed acetylation alters the electrophoretic mobility of these peptides in a microfluidic chip, allowing facile and direct monitoring of KAT activity. A pilot screen was used to demonstrate the utility of microfluidic mobility shift profiling to identify known and novel modulators of KAT activity. Real-time kinetic monitoring of KAT activity revealed that garcinol, a natural product KAT inhibitor used in cellular studies, exhibits time-dependent and detergent-sensitive inhibition, consistent with an aggregation-based mechanism. In contrast, the cell-permeable bisubstrate inhibitor Tat-CoA exhibited potent and time-independent KAT inhibition, highlighting its potential utility as a cellular inhibitor of KAT activity. These studies define microfluidic mobility shift profiling as a powerful platform for the discovery and characterization of small molecule inhibitors of KAT activity, and provide mechanistic insights potentially important for the application of KAT inhibitors in cellular contexts. PMID:26428393

  17. A signature microRNA expression profile for the cellular response to thermal stress

    Science.gov (United States)

    Wilmink, Gerald J.; Roth, Caleb C.; Ketchum, Norma; Ibey, Bennett L.; Waterworth, Angela; Suarez, Maria; Roach, William P.

    2009-02-01

    Recently, an extensive layer of intra-cellular signals was discovered that was previously undetected by genetic radar. It is now known that this layer consists primarily of a class of short noncoding RNA species that are referred to as microRNAs (miRNAs). MiRNAs regulate protein synthesis at the post-transcriptional level, and studies have shown that they are involved in many fundamental cellular processes. In this study, we hypothesized that miRNAs may be involved in cellular stress response mechanisms, and that cells exposed to thermal stress may exhibit a signature miRNA expression profile indicative of their functional involvement in such mechanisms. To test our hypothesis, human dermal fibroblasts were exposed to an established hyperthermic protocol, and the ensuing miRNA expression levels were evaluated 4 hr post-exposure using microRNA microarray gene chips. The microarray data shows that 123 miRNAs were differentially expressed in cells exposed to thermal stress. We collectively refer to these miRNAs as thermalregulated microRNAs (TRMs). Since miRNA research is in its infancy, it is interesting to note that only 27 of the 123 TRMs are currently annotated in the Sanger miRNA registry. Prior to publication, we plan to submit the remaining novel 96 miRNA gene sequences for proper naming. Computational and thermodynamic modeling algorithms were employed to identify putative mRNA targets for the TRMs, and these studies predict that TRMs regulate the mRNA expression of various proteins that are involved in the cellular stress response. Future empirical studies will be conducted to validate these theoretical predictions, and to further examine the specific role that TRMs play in the cellular stress response.

  18. Ion Induced Changes in Phosphoinositide Monolayers at Phisiological Concentrations

    Science.gov (United States)

    Kazadi Badiambile, Adolphe; Forstner, Martin

    2013-03-01

    Phosphoinositides (PIPs) play a crucial role in many cellular process that occur at the plasma membrane such as calcium release, exocytosis or endocytosis. In order to specifically regulate these functions PIPs must segregate in pools at the plasma membrane. A possible mechanism that could induce and regulate such organization of phosphoinositides is their interaction with bivalent cations. Understanding the physicochemical mechanism that can regulate membrane structure is a crucial step in the development of adaptive biomimetic membrane systems. Using Langmuir monolayers, we investigated the effect of calcium and magnesium on the surface pressure-area/lipid isotherm of monolayer of phosphatidylinositol (PI), phosphatidylinositol bisphosphate (PIP2), dioleoylphosphatidylglycerol (DOPG) and palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). It is found that the decrease of area per lipid, i.e. the increase in aggregation, is mostly dependent on the lipid's head group charge but ion specific. In addition, we discuss changes in free energy and compressibility of these monolayer-ion systems. NSF

  19. Biochemistry and structure of phosphoinositide phosphatases

    Directory of Open Access Journals (Sweden)

    Young Yil Bahk

    2013-01-01

    Full Text Available Phosphoinositides are the phosphorylated derivatives ofphosphatidylinositol, and play a very significant role in adiverse range of signaling processes in eukaryotic cells. Anumber of phosphoinositide-metabolizing enzymes, includingphosphoinositide-kinases and phosphatases are involved in thesynthesis and degradation of these phospholipids. Recently,the function of various phosphatases in the phosphatidylinositolsignaling pathway has been of great interest. In thepresent review we summarize the structural insights andbiochemistry of various phosphatases in regulating phosphoinositidemetabolism. [BMB Reports 2013; 46(1: 1-8

  20. Exploiting the ubiquitin and phosphoinositide pathways by the Legionella pneumophila effector, SidC.

    Science.gov (United States)

    Wasilko, David J; Mao, Yuxin

    2016-02-01

    Intracellular bacterial pathogens use secreted effector proteins to alter host cellular processes, with the goal of subverting host defenses and allowing the infection to progress. One such pathogen, Legionella pneumophila, secretes ~300 proteins into its host to alter a number of pathways including intracellular trafficking, phosphoinositide metabolism, and cell signaling. The Legionella effector SidC was previously found to bind to PI(4)P and was responsible for the enrichment of ER proteins and ubiquitinated species on the Legionella-containing vacuoles. Through our recent work, we have discovered that SidC contains a unique N-terminal E3 ubiquitin ligase domain and a C-terminal novel PI(4)P-binding domain. Our results demonstrate that SidC serves to link two distinct cellular pathways, ubiquitin and phosphoinositide. However, how the ubiquitin ligase activity regulates host membrane trafficking events remains to be investigated. PMID:26433729

  1. Phylogenomics of phosphoinositide lipid kinases: perspectives on the evolution of second messenger signaling and drug discovery

    OpenAIRE

    Auger Kurt R; Brown James R

    2011-01-01

    Abstract Background Phosphoinositide lipid kinases (PIKs) generate specific phosphorylated variants of phosatidylinositols (PtdIns) that are critical for second messenger signaling and cellular membrane remodeling. Mammals have 19 PIK isoforms spread across three major families: the PtIns 3-kinases (PI3Ks), PtdIns 4-kinases (PI4Ks), and PtdIns-P (PIP) kinases (PIPKs). Other eukaryotes have fewer yet varying PIK complements. PIKs are also an important, emerging class of drug targets for many t...

  2. Safety Profile of Amnion-Derived Cellular Cytokine Solution (ACCS) Following Topical Skin Application in Patients Receiving Breast Radiotherapy

    OpenAIRE

    Trombetta, Mark; Julian, Thomas B.; Wickerham, D. Lawrence; Steed, David L.

    2015-01-01

    Objective: To establish a safety profile for amnion-derived cellular cytokine solution following topical application in patients undergoing whole breast radiotherapy for breast cancer. Materials and Methods: Twenty female patients with early-stage breast cancer were enrolled in 2 separate cohorts of an institutional review board–approved phase I protocol. Cohort 1 consisted of 10 patients who received topical amnion-derived cellular cytokine solution to the breast immediately following the fi...

  3. Cellular Defense System Gene Expression Profiling of Human Whole Blood: Opportunities to Predict Health Benefits in Response to Diet12

    OpenAIRE

    Drew, Janice E.

    2012-01-01

    Diet is a critical factor in the maintenance of human cellular defense systems, immunity, inflammation, redox regulation, metabolism, and DNA repair that ensure optimal health and reduce disease risk. Assessment of dietary modulation of cellular defense systems in humans has been limited due to difficulties in accessing target tissues. Notably, peripheral blood gene expression profiles associated with nonhematologic disease are detectable. Coupled with recent innovations in gene expression te...

  4. Discovering functional linkages and uncharacterized cellular pathways using phylogenetic profile comparisons: a comprehensive assessment

    Directory of Open Access Journals (Sweden)

    Aravind L

    2007-05-01

    Full Text Available Abstract Background A widely-used approach for discovering functional and physical interactions among proteins involves phylogenetic profile comparisons (PPCs. Here, proteins with similar profiles are inferred to be functionally related under the assumption that proteins involved in the same metabolic pathway or cellular system are likely to have been co-inherited during evolution. Results Our experimentation with E. coli and yeast proteins with 16 different carefully composed reference sets of genomes revealed that the phyletic patterns of proteins in prokaryotes alone could be adequate enough to make reasonably accurate functional linkage predictions. A slight improvement in performance is observed on adding few eukaryotes into the reference set, but a noticeable drop-off in performance is observed with increased number of eukaryotes. Inclusion of most parasitic, pathogenic or vertebrate genomes and multiple strains of the same species into the reference set do not necessarily contribute to an improved sensitivity or accuracy. Interestingly, we also found that evolutionary histories of individual pathways have a significant affect on the performance of the PPC approach with respect to a particular reference set. For example, to accurately predict functional links in carbohydrate or lipid metabolism, a reference set solely composed of prokaryotic (or bacterial genomes performed among the best compared to one composed of genomes from all three super-kingdoms; this is in contrast to predicting functional links in translation for which a reference set composed of prokaryotic (or bacterial genomes performed the worst. We also demonstrate that the widely used random null model to quantify the statistical significance of profile similarity is incomplete, which could result in an increased number of false-positives. Conclusion Contrary to previous proposals, it is not merely the number of genomes but a careful selection of informative genomes in the

  5. Real-time transcriptional profiling of cellular and viral gene expression during lytic cytomegalovirus infection.

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    Lisa Marcinowski

    2012-09-01

    Full Text Available During viral infections cellular gene expression is subject to rapid alterations induced by both viral and antiviral mechanisms. In this study, we applied metabolic labeling of newly transcribed RNA with 4-thiouridine (4sU-tagging to dissect the real-time kinetics of cellular and viral transcriptional activity during lytic murine cytomegalovirus (MCMV infection. Microarray profiling on newly transcribed RNA obtained at different times during the first six hours of MCMV infection revealed discrete functional clusters of cellular genes regulated with distinct kinetics at surprising temporal resolution. Immediately upon virus entry, a cluster of NF-κB- and interferon-regulated genes was induced. Rapid viral counter-regulation of this coincided with a very transient DNA-damage response, followed by a delayed ER-stress response. Rapid counter-regulation of all three clusters indicated the involvement of novel viral regulators targeting these pathways. In addition, down-regulation of two clusters involved in cell-differentiation (rapid repression and cell-cycle (delayed repression was observed. Promoter analysis revealed all five clusters to be associated with distinct transcription factors, of which NF-κB and c-Myc were validated to precisely match the respective transcriptional changes observed in newly transcribed RNA. 4sU-tagging also allowed us to study the real-time kinetics of viral gene expression in the absence of any interfering virion-associated-RNA. Both qRT-PCR and next-generation sequencing demonstrated a sharp peak of viral gene expression during the first two hours of infection including transcription of immediate-early, early and even well characterized late genes. Interestingly, this was subject to rapid gene silencing by 5-6 hours post infection. Despite the rapid increase in viral DNA load during viral DNA replication, transcriptional activity of some viral genes remained remarkably constant until late-stage infection, or was

  6. Interactome profile of the host cellular proteins and the nonstructural protein 2 of porcine reproductive and respiratory syndrome virus.

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    Li Wang

    Full Text Available The nonstructural protein 2 (NSP2 is considered to be one of crucial viral proteins in the replication and pathogenesis of porcine reproductive and respiratory syndrome virus (PRRSV. In the present study, the host cellular proteins that interact with the NSP2 of PRRSV were immunoprecipitated with anti-Myc antibody from the MARC-145 cells infected by a recombinant PRRSV with 3xMyc tag insertion in its NSP2-coding region, and then 285 cellular proteins interacting with NSP2 were identified by LC-MS/MS. The Gene Ontology and enriched KEGG Pathway bioinformatics analyses indicated that the identified proteins could be assigned to different subcellular locations and functional classes. Functional analysis of the interactome profile highlighted cellular pathways associated with infectious disease, translation, immune system, nervous system and signal transduction. Two interested cellular proteins-BCL2-associated athanogene 6 (BAG6 and apoptosis-inducing factor 1 (AIF1 which may involve in transporting of NSP2 to Endoplasmic reticulum (ER or PRRSV-driven apoptosis were validated by Western blot. The interactome data between PRRSV NSP2 and cellular proteins contribute to the understanding of the roles of NSP2 in the replication and pathogenesis of PRRSV, and also provide novel cellular target proteins for elucidating the associated molecular mechanisms of the interaction of host cellular proteins with viral proteins in regulating the viral replication.

  7. Structure, function, and control of phosphoinositide-specific phospholipase C.

    Science.gov (United States)

    Rebecchi, M J; Pentyala, S N

    2000-10-01

    Phosphoinositide-specific phospholipase C (PLC) subtypes beta, gamma, and delta comprise a related group of multidomain phosphodiesterases that cleave the polar head groups from inositol lipids. Activated by all classes of cell surface receptor, these enzymes generate the ubiquitous second messengers inositol 1,4, 5-trisphosphate and diacylglycerol. The last 5 years have seen remarkable advances in our understanding of the molecular and biological facets of PLCs. New insights into their multidomain arrangement and catalytic mechanism have been gained from crystallographic studies of PLC-delta(1), while new modes of controlling PLC activity have been uncovered in cellular studies. Most notable is the realization that PLC-beta, -gamma, and -delta isoforms act in concert, each contributing to a specific aspect of the cellular response. Clues to their true biological roles were also obtained. Long assumed to function broadly in calcium-regulated processes, genetic studies in yeast, slime molds, plants, flies, and mammals point to specific and conditional roles for each PLC isoform in cell signaling and development. In this review we consider each subtype of PLC in organisms ranging from yeast to mammals and discuss their molecular regulation and biological function. PMID:11015615

  8. Profiling human protein degradome delineates cellular responses to proteasomal inhibition and reveals a feedback mechanism in regulating proteasome homeostasis

    OpenAIRE

    Yu, Tao; Tao, Yonghui; Yang, Meiqiang; Chen, Peng; Gao, XiaoBo; Zhang, Yanbo; Zhang,Tao; Chen, Zi; Hou, Jian; Zhang, Yan; Ruan, Kangcheng; Wang, Hongyan; Hu, Ronggui

    2014-01-01

    Global change in protein turnover (protein degradome) constitutes a central part of cellular responses to intrinsic or extrinsic stimuli. However, profiling protein degradome remains technically challenging. Recently, inhibition of the proteasome, e.g., by using bortezomib (BTZ), has emerged as a major chemotherapeutic strategy for treating multiple myeloma and other human malignancies, but systematic understanding of the mechanisms for BTZ drug action and tumor drug resistance is yet to be a...

  9. Multilayer Coating of Tetrandrine-loaded PLGA nanoparticles: Effect of surface charges on cellular uptake rate and drug release profile.

    Science.gov (United States)

    Meng, Rui; Li, Ke; Chen, Zhe; Shi, Chen

    2016-02-01

    The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPNs) was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles' surface with use of poly(styrene sulfonate) sodium salt (PSS) as anionic layer and poly(allylamine hydrochloride) (PAH) as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs (4 layers) exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of-57.8 mV. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles' surface could dramatically influence the drug release profile of TPNs (4 layers vs. 3 layers). In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles' surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery. PMID:26838734

  10. The anti‑dengue virus properties of statins may be associated with alterations in the cellular antiviral profile expression.

    Science.gov (United States)

    Bryan-Marrugo, Owen Lloyd; Arellanos-Soto, Daniel; Rojas-Martinez, Augusto; Barrera-Saldaña, Hugo; Ramos-Jimenez, Javier; Vidaltamayo, Roman; Rivas-Estilla, Ana María

    2016-09-01

    Dengue virus (DENV) susceptibility to cholesterol depleting treatments has been previously reported. There are numerous questions regarding how DENV seizes cellular machinery and cholesterol to improve viral production and the effect of cholesterol sequestering agents on the cellular antiviral response. The aim of the present study was to evaluate the mechanisms involved in the negative regulation of DENV replication induced by agents that diminish intracellular cholesterol levels. Cholesterol synthesis was pharmacologically (fluvastatin, atorvastatin, lovastatin, pravastatin and simvastatin treatment) and genetically (HMGCR‑RNAi) inhibited, in uninfected and DENV2‑infected hepatoma Huh‑7 cells. The cholesterol levels, DENV titer and cellular antiviral expression profile were evaluated. A reduction in the DENV titer, measured as plaque forming units, was observed in DENV‑infected cells following 48 h treatment with 10 µM fluvastatin, 10 µM atorvastatin, 20 µM lovastatin and 20 µM simvastatin, which achieved 70, 70, 65 and 55% DENV2 inhibition, respectively, compared with the untreated cells. In addition, the cytopathic effect was reduced in the statin‑treated DENV‑infected cells. Statins simultaneously reduced cholesterol levels at 48 h, with the exception of DENV2 infected cells. Genetic inhibition of cholesterol synthesis was performed using RNA interference for 3‑hydroxy‑3‑methylglutaryl‑CoA reductase (HMGCR‑siRNA), which indicated a slight reduction in DENV2 titer at 48 h post‑infection, however, with no significant reduction in cholesterol levels. In addition, DENV2 infection was observed to augment the intracellular cholesterol levels in all experimental conditions. Comparison between the cellular antiviral response triggered by DENV2 infection, statin treatment and HMGCR‑siRNA in infected, uninfected, treated and untreated Huh7 cells, showed different expression profiles for the antiviral genes evaluated. All

  11. Role of phosphoinositide 3-kinase in the autophagic death of serum-deprived PC12 cells.

    Science.gov (United States)

    Guillon-Munos, A; van Bemmelen, M X P; Clarke, P G H

    2005-10-01

    The death of serum-deprived undifferentiated PC12 cells shows both autophagic and apoptotic features. Since it is still controversial whether the autophagy is instrumental in the cell death or a mere epiphenomenon, we tested the effects of inhibiting the autophagy by a variety of phosphoinositide 3-kinase inhibitors, and provided evidence that the autophagy, or a related trafficking event, is indeed instrumental in the cell death. Furthermore, by comparing the effects of PI3-K inhibition and caspase-inhibition on autophagic and apoptotic cellular events, we showed that in this case the autophagic and apoptotic mechanisms mediate cell death by parallel pathways and do not act in series. PMID:16151638

  12. Interplay between phosphoinositide lipids and calcium signals at the leading edge of chemotaxing ameboid cells☆

    OpenAIRE

    Falke, Joseph J.; Ziemba, Brian P

    2014-01-01

    The chemotactic migration of eukaryotic ameboid cells up concentration gradients is among the most advanced forms of cellular behavior. Chemotaxis is controlled by a complex network of signaling proteins bound to specific lipids on the cytoplasmic surface of the plasma membrane at the front of the cell, or the leading edge. The central lipid players in this leading edge signaling pathway include the phosphoinositides PI(4,5)P2 (PIP2) and PI(3,4,5)P3 (PIP3), both of which play multiple roles. ...

  13. Autoradiographic imaging of phosphoinositide turnover in the brain

    International Nuclear Information System (INIS)

    With [3H]cytidine as a precursor, phosphoinositide turnover can be localized in brain slices by selective autoradiography of the product [3H]cytidine diphosphate diacylglycerol, which is membrane-bound. In the cerebellum, glutamatergic stimulation elicits an increase of phosphoinositide turnover only in Purkinje cells and the molecular layer. In the hippocampus, both glutamatergic and muscarinic cholinergic stimulation increase phosphoinositide turnover, but with distinct localizations. Cholinergic stimulation affects CA1, CA3, CA4, and subiculum, whereas glutamatergic effects are restricted to the subiculum and CA3. Imaging phosphoinositide turnover in brain slices, which are amenable to electrophysiologic studies, will permit a dynamic localized analysis of regulation of this second messenger in response to synaptic stimulation of specific neuronal pathways

  14. Phosphoinositide signalling in type 2 diabetes: a β-cell perspective.

    Science.gov (United States)

    Rameh, Lucia E; Deeney, Jude T

    2016-02-15

    Type 2 diabetes is a complex disease. It results from a failure of the body to maintain energy homoeostasis. Multicellular organisms have evolved complex strategies to preserve a relatively stable internal nutrient environment, despite fluctuations in external nutrient availability. This complex strategy involves the co-ordinated responses of multiple organs to promote storage or mobilization of energy sources according to the availability of nutrients and cellular bioenergetics needs. The endocrine pancreas plays a central role in these processes by secreting insulin and glucagon. When this co-ordinated effort fails, hyperglycaemia and hyperlipidaemia develops, characterizing a state of metabolic imbalance and ultimately overt diabetes. Although diabetes is most likely a collection of diseases, scientists are starting to identify genetic components and environmental triggers. Genome-wide association studies revealed that by and large, gene variants associated with type 2 diabetes are implicated in pancreatic β-cell function, suggesting that the β-cell may be the weakest link in the chain of events that results in diabetes. Thus, it is critical to understand how environmental cues affect the β-cell. Phosphoinositides are important 'decoders' of environmental cues. As such, these lipids have been implicated in cellular responses to a wide range of growth factors, hormones, stress agents, nutrients and metabolites. Here we will review some of the well-established and potential new roles for phosphoinositides in β-cell function/dysfunction and discuss how our knowledge of phosphoinositide signalling could aid in the identification of potential strategies for treating or preventing type 2 diabetes. PMID:26862218

  15. Thyrotropin Receptor Stimulates Internalization-Independent Persistent Phosphoinositide Signaling

    OpenAIRE

    Boutin, Alisa; Allen, Michael D.; Geras-Raaka, Elizabeth; Huang, Wenwei; Neumann, Susanne; Gershengorn, Marvin C.

    2011-01-01

    The thyrotropin [thyroid-stimulating hormone (TSH)] receptor (TSHR) is known to acutely and persistently stimulate cAMP signaling and at higher TSH concentrations to acutely stimulate phosphoinositide signaling. We measured persistent signaling by stimulating TSHR-expressing human embryonic kidney-EM293 cells with TSH and measuring cAMP or inositol monophosphate (IP1) production, a measure of phosphoinositide signaling, 60 min or longer after TSH removal. In contrast to persistent cAMP produc...

  16. Intensity interrogation near cutoff resonance for label-free cellular profiling

    Science.gov (United States)

    Nazirizadeh, Yousef; Behrends, Volker; Prósz, Aurél; Orgovan, Norbert; Horvath, Robert; Ferrie, Ann M.; Fang, Ye; Selhuber-Unkel, Christine; Gerken, Martina

    2016-04-01

    We report a method enabling intensity-based readout for label-free cellular assays, and realize a reader device with the same footprint as a microtiter plate. For unambiguous resonance intensity measurements in resonance waveguide grating (RWG) sensors, we propose to apply resonances near the substrate cutoff wavelength. This method was validated in bulk refractive index, surface bilayer and G protein-coupled receptor (GPCR) experiments. The significantly reduced size of the reader device opens new opportunities for easy integration into incubators or liquid handling systems.

  17. Phosphoinositide metabolism and adrenergic receptors in astrocytes

    International Nuclear Information System (INIS)

    Agonist-induced phosphoinositide (PI) breakdown functions as a signal generating system. Diacylglycerol, one breakdown product of phosphotidylinositol-4,5-diphosphate hydrolysis, can stimulate protein kinase C, whereas inositol triphosphate, the other product, has been proposed to be a second messenger for Ca++ mobilization. Using purified astrocyte cultures from neonatal rat brain, the effects of adrenergic agonists and antagonists at 10-5 M were measured on PI breakdown. Astrocytes grown in culture were prelabeled with (3H)inositol, and basal (3H) inositol phosphate (IP1) accumulation was measured in the presence of Li+. Epinephrine > norepinephrine (NE) were the most active stimulants of IP1 production. The α1 adrenoreceptor blockers, phentolamine and phenoxybenzamine, added alone had no effect on IP1 production was reduced below basal levels. Propranolol partially blocked the effects of NE. Clonidine and isoproterenol, separately added, reduced IP1 below basal levels and when added together diminished IP1 accumulation even further. The role of adrenergic stimulation in the production of c-AMP

  18. Alterations of idiotypic profiles: The cellular basis of T15 dominance in BALB/c mice

    International Nuclear Information System (INIS)

    Phosphorylcholine (PC) is a component of cell walls and membranes from a variety of widely distributed microorganisms. It is highly immunogenic in mice and most murine strains have circulating anti-PC antibodies which are known to confer protection against certain bacterial infections. BALB/c mice offer a striking example of a high responsiveness to PC, a propensity to generate PC-binding myelomas, and a great restriction of idiotype expression in anti-PC antibodies; in fact, most BALB/c anti-PC IgM antibodies express the T15 idiotype marker. Although it has been suspected that T15 dominance is somewhat related to the continuous antigenic load presented by microorganismal flora found in conventional mice, a complete experimental account of how antigenic selection brings about such extreme idiotypic dominance is not yet available. In the studies presented below, we investigated the role played by the host environment, T cells, and antigen in affecting the generation of the anti-PC T15 idiotype profile in lethally irradiated adoptive hosts reconstituted with syngeneic neonatal liver cells. The results presented herein indicate that the transfer of mature carrier-primed T cells with neonatal liver cells does not influence the generation of the T15 idiotype profile. We also demonstrated that anti-T15 idiotype suppressed mice, used as lethally irradiated hosts of immature immunocompetent cells, allow an increased rate of reconstitution of the anti-PC response when compared to nonsuppressed hosts. Since the administration of a T15+ anti-PC antibody inhibits both reconstitution and idiotype expansion, we conclude that T15+ B cells do not self-promote themselves. In contrast, we observed that exposure of adoptive hosts to PC antigens can enhance the anti-PC response and alter the idiotypic profile in favor of T15-bearing clones

  19. Regulation of calcium and phosphoinositides at endoplasmic reticulum-membrane junctions.

    Science.gov (United States)

    Dickson, Eamonn J; Jensen, Jill B; Hille, Bertil

    2016-04-15

    Effective cellular function requires both compartmentalization of tasks in space and time, and coordination of those efforts. The endoplasmic reticulum's (ER) expansive and ramifying structure makes it ideally suited to serve as a regulatory platform for organelle-organelle communication through membrane contacts. These contact sites consist of two membranes juxtaposed at a distance less than 30 nm that mediate the exchange of lipids and ions without the need for membrane fission or fusion, a process distinct from classical vesicular transport. Membrane contact sites are positioned by organelle-specific membrane-membrane tethering proteins and contain a growing number of additional proteins that organize information transfer to shape membrane identity. Here we briefly review the role of ER-containing membrane junctions in two important cellular functions: calcium signalling and phosphoinositide processing. PMID:27068956

  20. Modulation of phosphoinositide metabolism in aortic smooth muscle cells by allylamine

    International Nuclear Information System (INIS)

    Aortic smooth muscle cells (SMC) modulate from a contractile to a proliferative phenotype upon subchronic exposure to allylamine. The present studies were designed to determine if this phenotypic modulation is associated with alterations in the metabolism of membrane phosphoinositides. 32P incorporation into phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), and phosphatidic acid (PA) was lower by 31, 35, and 22%, respectively, in SMC from allylamine-treated animals relative to controls. In contrast, incorporation of [3H]myoinositol into inositol phosphates did not differ in allylamine cells relative to control cells. Exposure to dibutyryl (db) cAMP (0.2 mM) and theophylline (0.1 mM) reduced 32P incorporation into PIP and PIP2 in SMC from both experimental groups. Under these conditions, a decrease in [3H]myoinositol incorporation into inositol 1-phosphate was only observed in allylamine cells. The effects of db cAMP and theophylline in allylamine and control SMC correlated with a marked decrease in cellular proliferation. These results suggest that alterations in phosphoinositide synthesis and/or degradation contribute to the enhanced proliferation of SMC induced by allylamine. To further examine this concept, the effects of agents which modulate protein kinase C (PKC) activity were evaluated. Sphingosine (125-500 ng/ml), a PKC inhibitor, decreased SMC proliferation in allylamine, but not control cells. 12-O-Tetradecanoylphorbol-13-acetate (1-100 ng/ml), a PKC agonist, stimulated proliferation in control cells, but inhibited proliferation in cells from allylamine-treated animals. We conclude that allylamine-induced phenotypic modulation of SMC is associated with alterations in phosphoinositide metabolism

  1. Modulation of phosphoinositide metabolism in aortic smooth muscle cells by allylamine

    Energy Technology Data Exchange (ETDEWEB)

    Cox, L.R.; Murphy, S.K.; Ramos, K. (Philadelphia College of Pharmacy and Science, PA (USA))

    1990-08-01

    Aortic smooth muscle cells (SMC) modulate from a contractile to a proliferative phenotype upon subchronic exposure to allylamine. The present studies were designed to determine if this phenotypic modulation is associated with alterations in the metabolism of membrane phosphoinositides. 32P incorporation into phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), and phosphatidic acid (PA) was lower by 31, 35, and 22%, respectively, in SMC from allylamine-treated animals relative to controls. In contrast, incorporation of (3H)myoinositol into inositol phosphates did not differ in allylamine cells relative to control cells. Exposure to dibutyryl (db) cAMP (0.2 mM) and theophylline (0.1 mM) reduced 32P incorporation into PIP and PIP2 in SMC from both experimental groups. Under these conditions, a decrease in (3H)myoinositol incorporation into inositol 1-phosphate was only observed in allylamine cells. The effects of db cAMP and theophylline in allylamine and control SMC correlated with a marked decrease in cellular proliferation. These results suggest that alterations in phosphoinositide synthesis and/or degradation contribute to the enhanced proliferation of SMC induced by allylamine. To further examine this concept, the effects of agents which modulate protein kinase C (PKC) activity were evaluated. Sphingosine (125-500 ng/ml), a PKC inhibitor, decreased SMC proliferation in allylamine, but not control cells. 12-O-Tetradecanoylphorbol-13-acetate (1-100 ng/ml), a PKC agonist, stimulated proliferation in control cells, but inhibited proliferation in cells from allylamine-treated animals. We conclude that allylamine-induced phenotypic modulation of SMC is associated with alterations in phosphoinositide metabolism.

  2. Assessing the subcellular distribution of oncogenic phosphoinositide 3-kinase using microinjection into live cells

    Directory of Open Access Journals (Sweden)

    Meredith J. Layton

    2014-04-01

    Full Text Available Oncogenic mutations in PIK3CA lead to an increase in intrinsic phosphoinositide kinase activity, but it is thought that increased access of PI3Kα (phosphoinositide 3-kinase α to its PM (plasma membrane localized substrate is also required for increased levels of downstream PIP3/Akt [phosphoinositide-3,4,5-trisphosphate/also called PKB (protein kinase B] signalling. We have studied the subcellular localization of wild-type and the two most common oncogenic mutants of PI3Kα in cells maintained in growth media, and starved or stimulated cells using a novel method in which PI3Kα is pre-formed as a 1:1 p110α:p85α complex in vitro then introduced into live cells by microinjection. Oncogenic E545K and H1047R mutants did not constitutively interact with membrane lipids in vitro or in cells maintained in 10% (v/v FBS. Following stimulation of RTKs (receptor tyrosine kinases, microinjected PI3Kα was recruited to the PM, but oncogenic forms of PI3Kα were not recruited to the PM to a greater extent and did not reside at the PM longer than the wild-type PI3Kα. Instead, the E545K mutant specifically bound activated Cdc42 in vitro and microinjection of E545K was associated with the formation of cellular protrusions, providing some preliminary evidence that changes in protein–protein interactions may play a role in the oncogenicity of the E545K mutant in addition to the well-known changes in lipid kinase activity.

  3. Focused Metabolite Profiling for Dissecting Cellular and Molecular Processes of Living Organisms in Space Environments

    Science.gov (United States)

    2008-01-01

    Regulatory control in biological systems is exerted at all levels within the central dogma of biology. Metabolites are the end products of all cellular regulatory processes and reflect the ultimate outcome of potential changes suggested by genomics and proteomics caused by an environmental stimulus or genetic modification. Following on the heels of genomics, transcriptomics, and proteomics, metabolomics has become an inevitable part of complete-system biology because none of the lower "-omics" alone provide direct information about how changes in mRNA or protein are coupled to changes in biological function. The challenges are much greater than those encountered in genomics because of the greater number of metabolites and the greater diversity of their chemical structures and properties. To meet these challenges, much developmental work is needed, including (1) methodologies for unbiased extraction of metabolites and subsequent quantification, (2) algorithms for systematic identification of metabolites, (3) expertise and competency in handling a large amount of information (data set), and (4) integration of metabolomics with other "omics" and data mining (implication of the information). This article reviews the project accomplishments.

  4. Lou/C obesity-resistant rat exhibits hyperactivity, hypermetabolism, alterations in white adipose tissue cellularity, and lipid tissue profiles.

    Science.gov (United States)

    Soulage, Christophe; Zarrouki, Bader; Soares, Anisio Francesco; Lagarde, Michel; Geloen, Alain

    2008-02-01

    Lou/C obesity-resistant rat constitutes an original model to understand the phenomena of overweight and obesity. The aim of the present study was to identify metabolic causes for the outstanding leanness of Lou/C rat. To this end, the metabolic profiles (food intake, energy expenditure, and physical activity) and the cellular characteristics of white adipose tissue (lipogenesis, lipolysis, cellularity, and lipid composition) in 30-wk-old Lou/C rats were compared with age-matched Wistar rats. Lou/C rats exhibited a lower body weight (-45%), reduced adiposity (-80%), increased locomotor activity (+95%), and higher energy expenditure (+11%) than Wistar rats. Epididymal adipose tissue of Lou/C rat was twice lower than that of Wistar rat due to both a reduction in both adipocyte size (-25%) and number (three times). Basal lipolysis and sensitivity to noradrenaline were similar; however, the responsiveness to noradrenaline was lower in adipocytes from Lou/C compared with that from Wistar rats. Lipidomic analysis of plasma, adipose tissue, and liver revealed profound differences in lipid composition between the two strains. Of note, the desaturation indexes (ratio C16:1/C16:0 and C18:1/C18:0) were lower in Lou/C, indicating a blunted activity of delta-9-desaturase such as stearoyl-coenzyme A-desaturase-1. Increased physical activity, increased energy expenditure, and white adipose tissue cellularity are in good agreement with previous observations suggesting that a higher sympathetic tone in Lou/C could contribute to its lifelong leanness. PMID:18006635

  5. Establishing cellular stress response profiles as biomarkers of homeodynamics, health, and hormesis

    DEFF Research Database (Denmark)

    Demirovic, Dino; Rattan, Suresh

    2013-01-01

    discuss the main intracellular SR pathways in human cells, and argue for the need to define and establish the immediate and delayed stress response profiles (SRP) during aging. Such SRP are required to be established at several age-points, which can be the molecular biomarkers of homeodynamic space and...... effective strategy, which makes use of SRP for achieving healthy aging and extending the healthspan, is that of strengthening the homeodynamics through repeated mild stress-induced hormesis by physical, biological and nutritional hormetins. Furthermore, SRP can also be the basis for defining health as a...... state of having adequate physical and mental independence of activities of daily living, by identifying a set of measurable parameters at the most fundamental level of biological organization....

  6. COPPER STRESS ON CELLULAR CONTENTS AND FATTY ACID PROFILES IN CHLORELLA SPECIES

    Directory of Open Access Journals (Sweden)

    G. Sibi

    2014-01-01

    Full Text Available Higher photosynthetic efficiency and biomass production with rapid growth makes microalgae as potential candidates over other energy crops in many applications. Heavy metals influence the production of secondary metabolites and lipd content of microalgae in particular. A study was conducted using six Chlorella species under heavy metal exposure to evaluate the copper stress on biomass, cellular and lipid contents. Preliminary growth studies indicated the growth tolerance levels of Chlorella in the presence of copper at 4.0 mg L-1 concentration. The total chlorophyll, protein and lipid content of the isolates were 1.7-3.45%, 0.43-0.70 mg g-1 and 0.02-0.11 mg g-1 respectively. Gas Chromatography-Mass Spectroscopy analysis revealed that the percent composition of fatty acids varied among the species studied and the major group of fatty acids were C16:0, C18:1 and C18:2. Highest percent of fatty acids were found in C. vulgaris, C. protothecoides and C. pyrenoidosa. Copper have an impact on Chlorella species where biomass content was directly proportional to the lipid productivity. The results reflects the fact that copper stress on Chlorella species as the evidence of lipid production in both qualitative and quantitative manner. In conclusion, Chlorella species can be used for the sustainable producion of renewable energy through copper stress and removal of copper from aqueous solutions.

  7. DMPD: Role of phosphoinositide 3-kinase in innate immunity. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17827709 Role of phosphoinositide 3-kinase in innate immunity. Hazeki K, Nigorikawa...sitide 3-kinase in innate immunity. PubmedID 17827709 Title Role of phosphoinositide 3-kinase in innate immunity

  8. Multiple implications of 3-phosphoinositide-dependent protein kinase 1 in human cancer

    Institute of Scientific and Technical Information of China (English)

    Keum-Jin; Yang; Jongsun; Park

    2010-01-01

    3-phosphoinositide-dependent protein kinase-1(PDK1) is a central mediator of cellular signaling between phosphoinositide-3 kinase and various intracellular serine/threonine kinases,including protein kinase B,p70 ribosomal S6 kinase,serum and glucocorticoid-inducible kinase,and protein kinase C.PDK1 activates members of the AGC family of protein kinases by phosphorylating serine/threonine residues in the activation loop.Here,we review the regulatory mechanisms of PDK1 and its roles in cancer.PDK1 is activated by autophosphorylation in the activation loop and other serine residues,as well as by phosphorylation of Tyr-9 and Tyr-373/376.Src appears to recognize PDK1 following tyrosine phosphorylation.The role of heat shock protein 90 in regulating PDK1 stability and PDK1-Src complex formation are also discussed.Furthermore,we summarize the subcellular distribution of PDK1.Finally,an important role for PDK1 in cancer chemotherapy is proposed.In conclusion,a better understanding of its molecular regulatory mechanisms in various signaling pathways will help to explain how PDK1 acts as an oncogenic kinase in various cancers,and will contribute to the development of novel cancer chemotherapies.

  9. Analyzing Protein-Phosphoinositide Interactions with Liposome Flotation Assays.

    Science.gov (United States)

    Busse, Ricarda A; Scacioc, Andreea; Schalk, Amanda M; Krick, Roswitha; Thumm, Michael; Kühnel, Karin

    2016-01-01

    Liposome flotation assays are a convenient tool to study protein-phosphoinositide interactions. Working with liposomes resembles physiological conditions more than protein-lipid overlay assays, which makes this method less prone to detect false positive interactions. However, liposome lipid composition must be well-considered in order to prevent nonspecific binding of the protein through electrostatic interactions with negatively charged lipids like phosphatidylserine. In this protocol we use the PROPPIN Hsv2 (homologous with swollen vacuole phenotype 2) as an example to demonstrate the influence of liposome lipid composition on binding and show how phosphoinositide binding specificities of a protein can be characterized with this method. PMID:26552682

  10. Insulin-stimulated phosphoinositide metabolism in isolated fat cells

    International Nuclear Information System (INIS)

    Treatment of isolated fat cells with insulin produced increases of up to 4.8-fold in the incorporation of [3H]inositol into phosphatidylinositol. This effect of insulin was both time- and dose-dependent with half-maximal stimulation at 30 microunits/ml of insulin. Insulin increased the labeling of phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate but not phosphatidylinositol 4-monophosphate in cells which had been preincubated with [3H]inositol for 90 min. Incubation of the cells in a Ca2+-free buffer increased the basal level of phosphatidylinositol labeling and enhanced the effect of insulin. Glucagon and isoprenaline, both of which stimulate lipolysis, had no effect on phosphatidylinositol labeling but did potentiate insulin-stimulated incorporation of [3H]inositol into phosphatidylinositol. Phosphoinositide breakdown was measured by the accumulation of inositol phosphates. Insulin did not increase the level of the inositol phosphates at all concentrations of the hormone tested. By comparison, phenylephrine and vasopressin were able to stimulate phosphoinositide breakdown. Pretreatment of the cells with insulin enhanced the effect of phenylephrine on inositol phosphates accumulation, suggesting that insulin may potentiate phenylephrine-mediated phosphoinositide turnover. From these data the author conclude that insulin stimulates the de novo synthesis of phosphatidylinositol and phosphatidylinositol 4,5-biphosphate, but has no effect on phosphoinositide breakdown

  11. PI-PLC: Phosphoinositide-Phospholipase C in Plant Signaling

    NARCIS (Netherlands)

    T. Munnik

    2014-01-01

    Historically, phosphoinositide-specific phospholipase C (PI-PLC) catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to generate the second messengers, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG), which release Ca2+ from intracellular stores and activate member

  12. 3-Phosphoinositide-Dependent protein Kinase-1 (PDK1) inhibitors: A review from patent literature

    Science.gov (United States)

    Barile, Elisa; De, Surya K.; Pellecchia, Maurizio

    2016-01-01

    PDK1 (3-Phosphoinositide-dependent kinase 1) is a key member of the AGC protein kinase family. It plays an important role in a variety of cellular functions, leading to the activation of the PI3K signaling pathway, an event often associated with the onset and progression of several human cancers. Numerous recent observations suggest that PDK1 inhibitors may provide novel opportunities for the development of effective classes of therapeutics. On these premises, recent years have witnessed an increased effort by medicinal chemists to develop novel scaffolds to derive potent and selective PDK1 inhibitors. The intent of this review is to update the reader on the recent patent literature covering applications published between June 2008 and September 2011 that report on PDK1 inhibitors. PMID:24236780

  13. The Essential Role of Phosphoinositide 3-Kinases (PI3Ks) in Regulating Pro-Inflammatory Responses and the Progression of Cancer

    Institute of Scientific and Technical Information of China (English)

    Keqiang Chen; Pablo Iribarren; Wanghua Gong; Ji-Ming Wang

    2005-01-01

    Phosphoinositide 3-Kinases (PI3Ks) are proteins coupled to a variety of cell surface receptors and play a key role in signal transduction cascade regulating fundamental cellular functions such as transcription, proliferation, and survival. PI3Ks also are important in disease processes such as inflammation and cancer. The aim of this review is to outline current understandings of the PI3K family, mechanism of their activation, their role in inflammatory responses and the development of malignant tumors.

  14. Characterization, sub-cellular localization and expression profiling of the isoprenylcysteine methylesterase gene family in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Ma Wujun

    2010-09-01

    Full Text Available Abstract Background Isoprenylcysteine methylesterases (ICME demethylate prenylated protein in eukaryotic cell. Until now, knowledge about their molecular information, localization and expression pattern is largely unavailable in plant species. One ICME in Arabidopsis, encoded by At5g15860, has been identified recently. Over-expression of At5g15860 caused an ABA hypersensitive phenotype in transgenic Arabidopsis plants, indicating that it functions as a positive regulator of ABA signaling. Moreover, ABA induced the expression of this gene in Arabidopsis seedlings. The current study extends these findings by examining the sub-cellular localization, expression profiling, and physiological functions of ICME and two other ICME-like proteins, ICME-LIKE1 and ICME-LIKE2, which were encoded by two related genes At1g26120 and At3g02410, respectively. Results Bioinformatics investigations showed that the ICME and other two ICME-like homologs comprise a small subfamily of carboxylesterase (EC 3.1.1.1 in Arabidopsis. Sub-cellular localization of GFP tagged ICME and its homologs showed that the ICME and ICME-like proteins are intramembrane proteins predominantly localizing in the endoplasmic reticulum (ER and Golgi apparatus. Semi-quantitative and real-time quantitative PCR revealed that the ICME and ICME-like genes are expressed in all examined tissues, including roots, rosette leaves, cauline leaves, stems, flowers, and siliques, with differential expression levels. Within the gene family, the base transcript abundance of ICME-LIKE2 gene is very low with higher expression in reproductive organs (flowers and siliques. Time-course analysis uncovered that both ICME and ICME-like genes are up-regulated by mannitol, NaCl and ABA treatment, with ICME showing the highest level of up-regulation by these treatments. Heat stress resulted in up-regulation of the ICME gene significantly but down-regulation of the ICME-LIKE1 and ICME-LIKE2 genes. Cold and dehydration

  15. Effects of sub-lethal high-pressure homogenization treatment on the outermost cellular structures and the volatile-molecule profiles of two strains of probiotic lactobacilli.

    Science.gov (United States)

    Tabanelli, Giulia; Vernocchi, Pamela; Patrignani, Francesca; Del Chierico, Federica; Putignani, Lorenza; Vinderola, Gabriel; Reinheimer, Jorge A; Gardini, Fausto; Lanciotti, Rosalba

    2015-01-01

    Applying sub-lethal levels of high-pressure homogenization (HPH) to lactic acid bacteria has been proposed as a method of enhancing some of their functional properties. Because the principal targets of HPH are the cell-surface structures, the aim of this study was to examine the effect of sub-lethal HPH treatment on the outermost cellular structures and the proteomic profiles of two known probiotic bacterial strains. Moreover, the effect of HPH treatment on the metabolism of probiotic cells within a dairy product during its refrigerated storage was investigated using SPME-GC-MS. Transmission electron microscopy was used to examine the microstructural changes in the outermost cellular structures due to HPH treatment. These alterations may be involved in the changes in some of the technological and functional properties of the strains that were observed after pressure treatment. Moreover, the proteomic profiles of the probiotic strains treated with HPH and incubated at 37°C for various periods showed different peptide patterns compared with those of the untreated cells. In addition, there were differences in the peaks that were observed in the low-mass spectral region (2000-3000 Da) of the spectral profiles of the control and treated samples. Due to pressure treatment, the volatile-molecule profiles of buttermilk inoculated with treated or control cells and stored at 4°C for 30 days exhibited overall changes in the aroma profile and in the production of molecules that improved its sensory profile, although the two different species imparted specific fingerprints to the product. The results of this study will contribute to understanding the changes that occur in the outermost cellular structures and the metabolism of LAB in response to HPH treatment. The findings of this investigation may contribute to elucidating the relationships between these changes and the alterations of the technological and functional properties of LAB induced by pressure treatment. PMID

  16. Anchors for Effectors: Subversion of Phosphoinositide Lipids by Legionella

    OpenAIRE

    Hilbi, Hubert; Weber, Stephen; Finsel, Ivo

    2011-01-01

    The facultative intracellular pathogen Legionella pneumophila replicates in free-living amoebae and macrophages within a distinct compartment, the “Legionella-containing vacuole” (LCV). LCV formation involves phosphoinositide (PI) glycerolipids, which are key factors controlling vesicle trafficking pathways and membrane dynamics of eukaryotic cells. To govern the interactions with host cells, L. pneumophila employs the Icm/Dot type IV secretion system and more than 250 translocated “effector ...

  17. Anchors for effectors: subversion of phosphoinositide lipids by Legionella

    OpenAIRE

    Hubert eHilbi; Stephen eWeber; Ivo eFinsel

    2011-01-01

    The facultative intracellular pathogen Legionella pneumophila replicates in free-living amoebae and macrophages within a distinct compartment, the Legionella-containing vacuole (LCV). LCV formation involves phosphoinositide (PI) glycerolipids, which are key factors controlling vesicle trafficking pathways and membrane dynamics of eukaryotic cells. To govern the interactions with host cells, L. pneumophila employs the Icm/Dot type IV secretion system and more than 250 translocated effector pro...

  18. IQGAP Proteins Reveal an Atypical Phosphoinositide (aPI) Binding Domain with a Pseudo C2 Domain Fold

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, Miles J.; Gray, Alexander; Schenning, Martijn; Agacan, Mark; Tempel, Wolfram; Tong, Yufeng; Nedyalkova, Lyudmila; Park, Hee-Won; Leslie, Nicholas R.; van Aalten, Daan M.F.; Downes, C. Peter; Batty, Ian H. (Toronto); (Dundee)

    2012-10-16

    Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding modules exemplified by select IQGAPs (IQ motif containing GTPase-activating proteins) known to coordinate cellular signaling events and cytoskeletal dynamics. This module is defined by a C-terminal 105-107 amino acid region of which IQGAP1 and -2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). The binding affinity for PtdInsP3, together with other, secondary target-recognition characteristics, are comparable with those of the pleckstrin homology domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP3 effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 pleckstrin homology domain, each tagged with enhanced green fluorescent protein, were both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signaling and constitutes a novel, atypical phosphoinositide binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules.

  19. Phosphoinositide-signaling is one component of a robust plant defense response.

    Directory of Open Access Journals (Sweden)

    Imara Yasmin Perera

    2014-06-01

    Full Text Available The phosphoinositide pathway and inositol-1,4,5-triphosphate (InsP3 have been implicated in plant responses to many abiotic stresses; however, their role in response to biotic stress is not well characterized. In the current study, we show that both basal defense and systemic acquired resistance responses are affected in transgenic plants constitutively expressing the human type I inositol polyphosphate 5-phosphatase (InsP 5-ptase which have greatly reduced InsP3 levels. Flagellin induced Ca2+-release as well as the expressions of some flg22 responsive genes were attenuated in the InsP 5-ptase plants. Furthermore, the InsP 5-ptase plants were more susceptible to virulent and avirulent strains of Pseudomonas syringae pv. tomato (PstDC3000. The InsP 5-ptase plants had lower basal salicylic acid (SA levels and the induction of SAR in systemic leaves was reduced and delayed. Reciprocal exudate experiments showed that although the InsP 5-ptase plants produced equally effective molecules that could trigger PR-1 gene expression in wild type plants, exudates collected from either wild type or InsP 5-ptase plants triggered less PR-1 gene expression in InsP 5-ptase plants. Additionally, expression profiles indicated that several defense genes including PR-1, PR-2, PR-5 and AIG1 were basally down regulated in the InsP 5-ptase plants compared with wild type. Upon pathogen attack, expression of these genes was either not induced or showed delayed induction in systemic leaves. Our study shows that phosphoinositide signaling is one component of the plant defense network and is involved in both basal and systemic responses. The dampening of InsP3-mediated signaling affects Ca2+ release, modulates defense gene expression and compromises plant defense responses.

  20. Sex Hormones Affect Aging Process by Influencing Lipid Profiles,Cellular Immunological Function and Lipid Peroxides and Oxidation System

    Institute of Scientific and Technical Information of China (English)

    吴赛珠; 谭家余; 周忠江; 周可祥; 容志毅

    2003-01-01

    .136、0.532、0.379、0.394、0.234 (P<0.001); HDL - C、HDL - C/TC、HDL - C/LDL - C、CD3 + 、CD4 +/CD8 + 、SOD showed a negatively correlation with E2/T respectively, γequaled - 0.563、 - 0.332、 - 0.654、 -0.1530、-0.4140、-0.236(P<0.001). In women,the serum concentrations of FSH、 LH increased significantly after menopause; PRL increased little with aging; compared with young group, E2 and P in postmenopausal groups reduced obviously, E2/P revealed significant reduce with aging. T enhanced significantly after menopause, but nor did FT. E2, P and the ratio of E2/P were negatively correlated with age respectively by bivariate correlation analysis, and a positive relation between T and age. After 70 years old, the level of TC increased obviously, and so did that of TG after menopause; HDL decreased with aging, but LDL increased after 70, with the result that the ratios of HDL - C/TC and HDL- C/LDL- C all reduced with aging; apoA1 decreased gently after 70, but apoB increased significantly after menopause; correspondingly, the ratio of apoA1/apoB declined obviously. The concentration of GLU increased with aging. CD3 + and CD4 + didn't change until 60, but reduced after 60. Compared with the young groups, CD8 + remained unchanged, CD4 +/CD8 + reduced greatly with aging, CD4 + and CD8 + presented a negatively correlation with age respectively. The value of MDA in serum of women increased notably after 70 years old, but SOD activity already decreased significantly from 60. By partial correlation analysis (controlling BMI, FSH, LH and PRL),HDL- C、 CD4 +、 CD4 +/CD8 + showed a certain correlation with E2/P respectively; γ were 0.245、 0.157、0.154 (P<O.05); TG、 LDL、 apoB、 apoA1/ apoB、SOD presented a negatively correlation with E2/P respectively, γ were 0.452、 0.236、 0.321、 0.135、0.156、0.154、 0.426 (P<0.05). Conclusions The Disequilibrium of SH had correlations with lipid profile, cellular immunological function and lipid

  1. A Role for Phosphoinositides in Regulating Plant Nuclear Functions

    Directory of Open Access Journals (Sweden)

    Catherine B Dieck

    2012-03-01

    Full Text Available Nuclear localized inositol phospholipids and inositol phosphates are important for regulating many essential processes in animal cells such as DNA replication, recombination, RNA processing, mRNA export and cell cycle progression. An overview of the current literature suggests that a nuclear phosphoinositide pathway occurs in plants as well. Inositol phospholipids, inositol phosphates and enzymes of the PI pathway have been identified in plant nuclei and are implicated in DNA replication, chromatin remodeling, stress responses and hormone signaling. It is anticipated that future research will help shed light on the functional significance of the plant nuclear PI pathway.

  2. [Changes in the phosphoinositide metabolism in the blood and tissues of benign and malignant uterine tumors].

    Science.gov (United States)

    Damirov, M M; Sliusar', N N; Kulakov, V I; Bakuleva, I P; Matruk, T A

    1995-01-01

    Measurements of phosphoinositide levels in the blood, immunocompetent cells, and tumors of 105 patients with uterine myomas, 24 patients with cancer of the corpus uteri, and 17 ones with uterine sarcoma showed that the parameters of phosphoinositide metabolism in the blood of patients with tumors of the uterus reliably differed from those in healthy women. The content of phosphatidylinosites and other phosphoinositide fractions in patients with uterine myomas reliably differed from those in patients with malignant tumors of the uterus, this permitting the use of such measurements in the differential diagnosis. Phosphoinositide mechanism of development of tumors of the uterus is discussed, which is related to the "new" phosphoinositides and secondary messengers directly participating in transfer of cell growth signals. PMID:7785738

  3. Effects of sub-lethal high-pressure homogenization treatment on the outermost cellular structures and the volatile-molecule profiles of two strains of probiotic lactobacilli

    OpenAIRE

    Tabanelli, Giulia; Vernocchi, Pamela; Patrignani, Francesca; Del Chierico, Federica; Putignani, Lorenza; Vinderola, Gabriel; Reinheimer, Jorge A.; Gardini, Fausto; Lanciotti, Rosalba

    2015-01-01

    Applying sub-lethal levels of high-pressure homogenization (HPH) to lactic acid bacteria has been proposed as a method of enhancing some of their functional properties. Because the principal targets of HPH are the cell-surface structures, the aim of this study was to examine the effect of sub-lethal HPH treatment on the outermost cellular structures and the proteomic profiles of two known probiotic bacterial strains. Moreover, the effect of HPH treatment on the metabolism of probiotic cells w...

  4. An uncooked vegan diet shifts the profile of human fecal microflora: computerized analysis of direct stool sample gas-liquid chromatography profiles of bacterial cellular fatty acids.

    OpenAIRE

    Peltonen, R; Ling, W H; Hänninen, O.; Eerola, E

    1992-01-01

    The effect of an uncooked extreme vegan diet on fecal microflora was studied by direct stool sample gas-liquid chromatography (GLC) of bacterial cellular fatty acids and by quantitative bacterial culture by using classical microbiological techniques of isolation, identification, and enumeration of different bacterial species. Eighteen volunteers were divided randomly into two groups. The test group received an uncooked vegan diet for 1 month and a conventional diet of mixed Western type for t...

  5. Integrative analysis of large scale expression profiles reveals core transcriptional response and coordination between multiple cellular processes in a cyanobacterium

    Directory of Open Access Journals (Sweden)

    Bhattacharyya-Pakrasi Maitrayee

    2010-08-01

    Full Text Available Abstract Background Cyanobacteria are the only known prokaryotes capable of oxygenic photosynthesis. They play significant roles in global biogeochemical cycles and carbon sequestration, and have recently been recognized as potential vehicles for production of renewable biofuels. Synechocystis sp. PCC 6803 has been extensively used as a model organism for cyanobacterial studies. DNA microarray studies in Synechocystis have shown varying degrees of transcriptome reprogramming under altered environmental conditions. However, it is not clear from published work how transcriptome reprogramming affects pre-existing networks of fine-tuned cellular processes. Results We have integrated 163 transcriptome data sets generated in response to numerous environmental and genetic perturbations in Synechocystis. Our analyses show that a large number of genes, defined as the core transcriptional response (CTR, are commonly regulated under most perturbations. The CTR contains nearly 12% of Synechocystis genes found on its chromosome. The majority of genes in the CTR are involved in photosynthesis, translation, energy metabolism and stress protection. Our results indicate that a large number of differentially regulated genes identified in most reported studies in Synechocystis under different perturbations are associated with the general stress response. We also find that a majority of genes in the CTR are coregulated with 25 regulatory genes. Some of these regulatory genes have been implicated in cellular responses to oxidative stress, suggesting that reactive oxygen species are involved in the regulation of the CTR. A Bayesian network, based on the regulation of various KEGG pathways determined from the expression patterns of their associated genes, has revealed new insights into the coordination between different cellular processes. Conclusion We provide here the first integrative analysis of transcriptome data sets generated in a cyanobacterium. This

  6. Phosphoinositides in the Hepatitis C Virus Life Cycle

    Directory of Open Access Journals (Sweden)

    Aleem Siddiqui

    2012-10-01

    Full Text Available Eukaryotes possess seven different phosphoinositides (PIPs that help form the unique signatures of various intracellular membranes. PIPs serve as docking sites for the recruitment of specific proteins to mediate membrane alterations and integrate various signaling cascades. The spatio-temporal regulation of PI kinases and phosphatases generates distinct intracellular hubs of PIP signaling. Hepatitis C virus (HCV, like other plus-strand RNA viruses, promotes the rearrangement of intracellular membranes to assemble viral replication complexes. HCV stimulates enrichment of phosphatidylinositol 4-phosphate (PI4P pools near endoplasmic reticulum (ER sites by activating PI4KIIIα, the kinase responsible for generation of ER-specific PI4P pools. Inhibition of PI4KIIIα abrogates HCV replication. PI4P, the most abundant phosphoinositide, predominantly localizes to the Golgi and plays central roles in Golgi secretory functions by recruiting effector proteins involved in transport vesicle generation. The PI4P effector proteins also include the lipid-transfer and structural proteins such as ceramide transfer protein (CERT, oxysterol binding protein (OSBP and Golgi phosphoprotein 3 (GOLPH3 that help maintain Golgi-membrane composition and structure. Depletion of Golgi-specific PI4P pools by silencing PI4KIIIβ, expression of dominant negative CERT and OSBP mutants, or silencing GOLPH3 perturb HCV secretion. In this review we highlight the role of PIPs and specifically PI4P in the HCV life cycle.

  7. Integrated analysis of the differential cellular and EBV miRNA expression profiles in microdissected nasopharyngeal carcinoma and non-cancerous nasopharyngeal tissues.

    Science.gov (United States)

    Wan, Xun-Xun; Yi, Hong; Qu, Jia-Quan; He, Qiu-Yan; Xiao, Zhi-Qiang

    2015-11-01

    Nasopharyngeal carcinoma (NPC) is commonly diagnosed in southern Asia. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally. Increasing evidence suggests that the dysregulation of miRNAs promotes NPC tumorigenesis. Epstein-Barr virus (EBV) infection and EBV-encoded miRNAs are also associated with the development of NPC. However, it is unclear how cellular and EBV miRNAs jointly regulate target genes and signaling pathways in NPC. In the present study, we analyzed the differential cellular and EBV miRNA expression profiles in 20 pooled NPC tissues using microarrays. We found that 19 cellular miRNAs and 9 EBV miRNAs were upregulated and 31 cellular miRNAs were downregulated in NPC tissues. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the 19 upregulated miRNAs target mainly the p53 signaling pathway in cancer, whereas the downregulated miRNAs regulate pathways related to cancer, focal adhesion and Erb, and MAPK signaling. In contrast, the upregulated EBV miRNAs target primarily the TGF-β and Wnt signaling pathways. Data also suggested that cellular miR-34b, miR-34c, miR-18a, miR‑200a/b, miR-449a, miR-31 and let-7 may be dysregulated in NPCs, and that the aberrant activation of their target genes in the p53 pathway and cell cycle enhance NPC cell survival and proliferation. In addition, EBV-miRNAs such as BART3 and BART5 target genes in the p53, TGF-β and Wnt signaling pathways to modulate NPC apoptosis and transformation. To better elucidate the interaction between miRNAs and target genes, we constructed an anti-correlated cellular and EBV miRNA/target gene regulatory network. The current findings may help dissect the roles played by cellular and EBV miRNAs during NPC tumorigenesis, and also provide useful biomarkers for the diagnosis and treatment of NPCs. PMID:26330189

  8. TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration.

    Directory of Open Access Journals (Sweden)

    Adrien Rousseau

    2013-12-01

    Full Text Available Tumor necrosis factor (TNF receptor-associated factor 4 (TRAF4 is frequently overexpressed in carcinomas, suggesting a specific role in cancer. Although TRAF4 protein is predominantly found at tight junctions (TJs in normal mammary epithelial cells (MECs, it accumulates in the cytoplasm of malignant MECs. How TRAF4 is recruited and functions at TJs is unclear. Here we show that TRAF4 possesses a novel phosphoinositide (PIP-binding domain crucial for its recruitment to TJs. Of interest, this property is shared by the other members of the TRAF protein family. Indeed, the TRAF domain of all TRAF proteins (TRAF1 to TRAF6 is a bona fide PIP-binding domain. Molecular and structural analyses revealed that the TRAF domain of TRAF4 exists as a trimer that binds up to three lipids using basic residues exposed at its surface. Cellular studies indicated that TRAF4 acts as a negative regulator of TJ and increases cell migration. These functions are dependent from its ability to interact with PIPs. Our results suggest that TRAF4 overexpression might contribute to breast cancer progression by destabilizing TJs and favoring cell migration.

  9. Comparison of the free and bound phenolic profiles and cellular antioxidant activities of litchi pulp extracts from different solvents

    OpenAIRE

    Su, Dongxiao; Zhang, Ruifen; Hou, Fangli; Zhang, Mingwei; Guo, Jinxin; Huang, Fei; Deng, Yuanyuan; Wei, Zhencheng

    2014-01-01

    Background The phenolic contents and antioxidant activities of fruits could be underestimated if the bound phenolic compounds are not considered. In the present study, the extraction efficiencies of various solvents were investigated in terms of the total content of the free and bound phenolic compounds, as well as the phenolic profiles and antioxidant activities of the extracts. Methods Five different solvent mixtures were used to extract the free phenolic compounds from litchi pulp. Alkalin...

  10. Gene Expression Profile Changes and Cellular Responses to Bleomycin-Induced DNA Damage in Human Fibroblast Cells in Space

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Kidane, Yared; Feiveson, Alan; Stodieck, Louis; Karouia, Fathi; Rohde, Larry; Wu, Honglu

    2016-01-01

    Living organisms are constantly exposed to space radiation that consists of energetic protons and other heavier charged particles. In addition, DNA in space can be damaged by toxic chemicals or reactive oxygen species generated due to increased levels of environmental and psychological stresses. Understanding the impact of spaceflight factors, microgravity in particular, on cellular responses to DNA damage affects the accuracy of the radiation risk assessment for astronauts and the mutation rate in microorganisms. Although possible synergistic effects of space radiation and microgravity have been investigated since the early days of the human space program, the published results were mostly conflicting and inconsistent. To investigate the effects of spaceflight on cellular responses to DNA damage, confluent human fibroblast cells (AG1522) flown on the International Space Station (ISS) were treated with bleomycin for three hours in the true microgravity environment, which induced DNA damages including double-strand breaks (DSB). Damages in the DNA were quantified by immunofluorescence staining for ?-H2AX, which showed similar percentages of different types of stained cells between flight and ground. However, there was a slight shift in the distribution of the ?-H2AX foci number in the flown cells with countable foci. Comparison of the cells in confluent and in exponential growth conditions indicated that the proliferation rate between flight and the ground may be responsible for such a shift. A microarray analysis of gene expressions in response to bleomycin treatment was also performed. Comparison of the responsive pathways between the flown and ground cells showed similar responses with the p53 network being the top upstream regulator. Similar responses at the RNA level between different gravity conditions were also observed with a PCR array analysis containing a set of genes involved in DNA damage signaling; with BBC3, CDKN1A, PCNA and PPM1D being significantly

  11. Assessing the subcellular distribution of oncogenic phosphoinositide 3-kinase using microinjection into live cells

    OpenAIRE

    Layton, Meredith J.; Rynkiewicz, Natalie K.; Ivetac, Ivan; Horan, Kristy A.; Mitchell, Christina A.; Phillips, Wayne A.

    2014-01-01

    Oncogenic mutations in PIK3CA lead to an increase in intrinsic phosphoinositide kinase activity, but it is thought that increased access of PI3Kα (phosphoinositide 3-kinase α) to its PM (plasma membrane) localized substrate is also required for increased levels of downstream PIP3/Akt [phosphoinositide-3,4,5-trisphosphate/also called PKB (protein kinase B)] signalling. We have studied the subcellular localization of wild-type and the two most common oncogenic mutants of PI3Kα in cells maintain...

  12. Reconstructing and analysing cellular states, space and time from gene expression profiles of many cells and single cells.

    Science.gov (United States)

    Francesconi, Mirko; Lehner, Ben

    2015-10-01

    Genome-wide gene expression profiling is a fast, cheap and standardised analysis that provides a high dimensional measurement of the state of a biological sample. In this review we describe computational methods that can be applied to identify and interpret sources of variance in gene expression in whole organisms, organs, tissues or single cells. This allows the identification of constituent cell types and states in complex mixtures, the reconstruction of temporal trajectories of development, differentiation and progression, and the reconstruction of spatial patterning. When applied to genetically variable samples, these methods allow the efficient investigation of how genetic variation influences gene expression and biological processes in space and time. PMID:26273952

  13. Ion channel regulation by phosphoinositides analyzed with VSPs – PI(4,5P2 affinity, phosphoinositide selectivity, and PI(4,5P2 pool accessibility

    Directory of Open Access Journals (Sweden)

    Alexandra eRjasanow

    2015-06-01

    Full Text Available The activity of many proteins depends on the phosphoinositide (PI content of the membrane. E.g., dynamic changes of the concentration of PI(4,5P2 are cellular signals that regulate ion channels. The susceptibility of a channel to such dynamics depends on its affinity for PI(4,5P2. Yet, measuring affinities for endogenous PIs has not been possible directly, but has relied largely on the response to soluble analogs, which may not quantitatively reflect binding to native lipids.Voltage-sensitive phosphatases (VSPs turn over PI(4,5P2 to PI(4P when activated by depolarization. In combination with voltage-clamp electrophysiology VSPs are useful tools for rapid and reversible depletion of PI(4,5P2. Because cellular PI(4,5P2 is resynthesized rapidly, steady state PI(4,5P2 changes with the degree of VSP activation and thus depends on membrane potential.Here we show that titration of endogenous PI(4,5P2 with Ci-VSP allows for the quantification of relative PI(4,5P2 affinities of ion channels. The sensitivity of inward rectifier and voltage-gated K+ channels to Ci-VSP allowed for comparison of PI(4,5P2 affinities within and across channel subfamilies and detected changes of affinity in mutant channels. The results also reveal that VSPs are useful only for PI effectors with high binding specificity among PI isoforms, because PI(4,5P2 depletion occurs at constant overall PI level. Thus, Kir6.2, a channel activated by PI(4,5P2 and PI(4P was insensitive to VSP.Surprisingly, despite comparable PI(4,5P2 affinity as determined by Ci-VSP, the Kv7 and Kir channel families strongly differed in their sensitivity to receptor-mediated depletion of PI(4,5P2. While Kv7 members were highly sensitive to activation of PLC by Gq-coupled receptors, Kir channels were insensitive even when PI(4,5P2 affinity was lowered by mutation. We hypothesize that different channels may be associated with distinct pools of PI(4,5P2 that differ in their accessibility to PLC and VSPs.

  14. Phosphoinositide metabolism links cGMP-dependent protein kinase G to essential Ca²⁺ signals at key decision points in the life cycle of malaria parasites.

    Directory of Open Access Journals (Sweden)

    Mathieu Brochet

    2014-03-01

    Full Text Available Many critical events in the Plasmodium life cycle rely on the controlled release of Ca²⁺ from intracellular stores to activate stage-specific Ca²⁺-dependent protein kinases. Using the motility of Plasmodium berghei ookinetes as a signalling paradigm, we show that the cyclic guanosine monophosphate (cGMP-dependent protein kinase, PKG, maintains the elevated level of cytosolic Ca²⁺ required for gliding motility. We find that the same PKG-dependent pathway operates upstream of the Ca²⁺ signals that mediate activation of P. berghei gametocytes in the mosquito and egress of Plasmodium falciparum merozoites from infected human erythrocytes. Perturbations of PKG signalling in gliding ookinetes have a marked impact on the phosphoproteome, with a significant enrichment of in vivo regulated sites in multiple pathways including vesicular trafficking and phosphoinositide metabolism. A global analysis of cellular phospholipids demonstrates that in gliding ookinetes PKG controls phosphoinositide biosynthesis, possibly through the subcellular localisation or activity of lipid kinases. Similarly, phosphoinositide metabolism links PKG to egress of P. falciparum merozoites, where inhibition of PKG blocks hydrolysis of phosphatidylinostitol (4,5-bisphosphate. In the face of an increasing complexity of signalling through multiple Ca²⁺ effectors, PKG emerges as a unifying factor to control multiple cellular Ca²⁺ signals essential for malaria parasite development and transmission.

  15. PPARδ activation acts cooperatively with 3-phosphoinositide-dependent protein kinase-1 to enhance mammary tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Claire B Pollock

    Full Text Available Peroxisome proliferator-activated receptorδ (PPARδ is a transcription factor that is associated with metabolic gene regulation and inflammation. It has been implicated in tumor promotion and in the regulation of 3-phosphoinositide-dependent kinase-1 (PDK1. PDK1 is a key regulator of the AGC protein kinase family, which includes the proto-oncogene AKT/PKB implicated in several malignancies, including breast cancer. To assess the role of PDK1 in mammary tumorigenesis and its interaction with PPARδ, transgenic mice were generated in which PDK1 was expressed in mammary epithelium under the control of the MMTV enhancer/promoter region. Transgene expression increased pT308AKT and pS9GSK3β, but did not alter phosphorylation of mTOR, 4EBP1, ribosomal protein S6 and PKCα. The transgenic mammary gland also expressed higher levels of PPARδ and a gene expression profile resembling wild-type mice maintained on a diet containing the PPARδ agonist, GW501516. Both wild-type and transgenic mice treated with GW501516 exhibited accelerated rates of tumor formation that were more pronounced in transgenic animals. GW501516 treatment was accompanied by a distinct metabolic gene expression and metabolomic signature that was not present in untreated animals. GW501516-treated transgenic mice expressed higher levels of fatty acid and phospholipid metabolites than treated wild-type mice, suggesting the involvement of PDK1 in enhancing PPARδ-driven energy metabolism. These results reveal that PPARδ activation elicits a distinct metabolic and metabolomic profile in tumors that is in part related to PDK1 and AKT signaling.

  16. Kappa opioid receptors stimulate phosphoinositide turnover in rat brain

    International Nuclear Information System (INIS)

    The effects of various subtype-selective opioid agonists and antagonists on the phosphoinositide (PI) turnover response were investigated in the rat brain. The κ-agonists U-50,488H and ketocyclazocine produced a concentration-dependent increase in the accumulation of IP's in hippocampal slices. The other κ-agonists Dynorphin-A (1-13) amide, and its protected analog D[Ala]2-dynorphin-A (1-13) amide also produced a significant increase in the formation of [3H]-IP's, whereas the μ-selective agonists [D-Ala2-N-Me-Phe4-Gly5-ol]-enkephalin and morphine and the δ-selective agonist [D-Pen2,5]-enkephalin were ineffective. The increase in IP's formation elicited by U-50,488H was partially antagonized by naloxone and more completely antagonized by the κ-selective antagonists nor-binaltorphimine and MR 2266. The formation of IP's induced by U-50,488H varies with the regions of the brain used, being highest in hippocampus and amygdala, and lowest in striatum and pons-medullar. The results indicate that brain κ- but neither μ- nor δ- receptors are coupled to the PI turnover response

  17. Kappa opioid receptors stimulate phosphoinositide turnover in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Periyasamy, S.; Hoss, W. (Univ. of Toledo, OH (USA))

    1990-01-01

    The effects of various subtype-selective opioid agonists and antagonists on the phosphoinositide (PI) turnover response were investigated in the rat brain. The {kappa}-agonists U-50,488H and ketocyclazocine produced a concentration-dependent increase in the accumulation of IP's in hippocampal slices. The other {kappa}-agonists Dynorphin-A (1-13) amide, and its protected analog D(Ala){sup 2}-dynorphin-A (1-13) amide also produced a significant increase in the formation of ({sup 3}H)-IP's, whereas the {mu}-selective agonists (D-Ala{sup 2}-N-Me-Phe{sup 4}-Gly{sup 5}-ol)-enkephalin and morphine and the {delta}-selective agonist (D-Pen{sup 2,5})-enkephalin were ineffective. The increase in IP's formation elicited by U-50,488H was partially antagonized by naloxone and more completely antagonized by the {kappa}-selective antagonists nor-binaltorphimine and MR 2266. The formation of IP's induced by U-50,488H varies with the regions of the brain used, being highest in hippocampus and amygdala, and lowest in striatum and pons-medullar. The results indicate that brain {kappa}- but neither {mu}- nor {delta}- receptors are coupled to the PI turnover response.

  18. Exosomal Proteome Profiling: A Potential Multi-Marker Cellular Phenotyping Tool to Characterize Hypoxia-Induced Radiation Resistance in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Stefani N. Thomas

    2013-08-01

    Full Text Available Radiation and drug resistance are significant challenges in the treatment of locally advanced, recurrent and metastatic breast cancer that contribute to mortality. Clinically, radiotherapy requires oxygen to generate cytotoxic free radicals that cause DNA damage and allow that damage to become fixed in the genome rather than repaired. However, approximately 40% of all breast cancers have hypoxic tumor microenvironments that render cancer cells significantly more resistant to irradiation. Hypoxic stimuli trigger changes in the cell death/survival pathway that lead to increased cellular radiation resistance. As a result, the development of noninvasive strategies to assess tumor hypoxia in breast cancer has recently received considerable attention. Exosomes are secreted nanovesicles that have roles in paracrine signaling during breast tumor progression, including tumor-stromal interactions, activation of proliferative pathways and immunosuppression. The recent development of protocols to isolate and purify exosomes, as well as advances in mass spectrometry-based proteomics have facilitated the comprehensive analysis of exosome content and function. Using these tools, studies have demonstrated that the proteome profiles of tumor-derived exosomes are indicative of the oxygenation status of patient tumors. They have also demonstrated that exosome signaling pathways are potentially targetable drivers of hypoxia-dependent intercellular signaling during tumorigenesis. This article provides an overview of how proteomic tools can be effectively used to characterize exosomes and elucidate fundamental signaling pathways and survival mechanisms underlying hypoxia-mediated radiation resistance in breast cancer.

  19. The receptor binding domain of botulinum neurotoxin serotype C binds phosphoinositides.

    Science.gov (United States)

    Zhang, Yanfeng; Varnum, Susan M

    2012-03-01

    Botulinum neurotoxins (BoNTs) are the most toxic proteins known for humans and animals with an extremely low LD(50) of ∼1 ng/kg. BoNTs generally require a protein and a ganglioside on the cell membrane surface for binding, which is known as a "dual receptor" mechanism for host intoxication. Recent studies have suggested that in addition to gangliosides, other membrane lipids such as phosphoinositides may be involved in the interactions with the receptor binding domain (HCR) of BoNTs for better membrane penetration. Using two independent lipid-binding assays, we tested the interactions of BoNT/C-HCR with lipids in vitro domain. BoNT/C-HCR was found to bind negatively charged phospholipids, preferentially phosphoinositides in both assays. Interactions with phosphoinositides may facilitate tighter binding between neuronal membranes and BoNT/C. PMID:22120109

  20. Maitotoxin: Effects on calcium channels, phosphoinositide breakdown, and arachidonate release in pheochromocytoma PC12 cells

    International Nuclear Information System (INIS)

    Maitotoxin (MTX) increases formation of [3H]inositol phosphates from phosphoinositides and release of [3H]arachidonic acid from phospholipids in pheochromocytoma PC12 cells. Formation of [3H]inositol phosphates is detected within 1 min of incubation even with concentrations as low as 0.3 ng/ml (90 pm) MTX, whereas release of [3H]arachidonic acid is not detected until 20 min even with concentrations as high as 1 ng/ml (300 pm) MTX. Stimulation of arachidonic acid release can be detected at 0.03 ng/ml (9 pm) MTX, whereas 0.1 ng/ml (30 pm) MTX is the threshold for detection of phosphoinositide breakdown. Organic and inorganic calcium channel blockers, except Cd2+ and a high concentration of Mn2+, have no effect on MTX-elicited phosphoinositide breakdown, whereas inorganic blockers (e.g., Co2+, Mn2+, Cd2+), but not organic blockers (nifedipine, verapamil, diltiazem), inhibit MTX-stimulated arachidonic acid release. All calcium channel blockers, however, inhibited MTX-elicited influx of 45Ca2+ and the MTX-elicited increase in internal Ca2+ measured with fura-2 was markedly reduced by nifedipine. MTX-elicited phosphoinositide breakdown and arachidonic acid release are abolished or reduced, respectively, in the absence of extracellular calcium plus chelating agent. The calcium ionophore A23187 has little or no effect alone but, in combination with MTX, A23187 inhibits MTX-elicited phosphoinositide breakdown and enhances arachidonic acid release, the latter even in the absence of extracellular calcium. The results suggest that different sites and/or mechanisms are involved in stimulation of calcium influx, breakdown of phosphoinositides, and release of arachidonic acid by MTX

  1. A phosphatidylinositol transfer protein integrates phosphoinositide signaling with lipid droplet metabolism to regulate a developmental program of nutrient stress-induced membrane biogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Jihui; Lin, Coney Pei-Chen; Pathak, Manish C.; Temple, Brenda R.S.; Nile, Aaron H.; Mousley, Carl J.; Duncan, Mara C.; Eckert, Debra M.; Leiker, Thomas J.; Ivanova, Pavlina T.; Myers, David S.; Murphy, Robert C.; Brown, H. Alex; Verdaasdonk, Jolien; Bloom, Kerry S.; Ortlund, Eric A.; Neiman, Aaron M.; Bankaitis, Vytas A. [Emory-MED; (SBU); (TAM); (UNC); (Vanderbilt-MED); (Utah); (UCHSC)

    2014-07-11

    Lipid droplet (LD) utilization is an important cellular activity that regulates energy balance and release of lipid second messengers. Because fatty acids exhibit both beneficial and toxic properties, their release from LDs must be controlled. Here we demonstrate that yeast Sfh3, an unusual Sec14-like phosphatidylinositol transfer protein, is an LD-associated protein that inhibits lipid mobilization from these particles. We further document a complex biochemical diversification of LDs during sporulation in which Sfh3 and select other LD proteins redistribute into discrete LD subpopulations. The data show that Sfh3 modulates the efficiency with which a neutral lipid hydrolase-rich LD subclass is consumed during biogenesis of specialized membrane envelopes that package replicated haploid meiotic genomes. These results present novel insights into the interface between phosphoinositide signaling and developmental regulation of LD metabolism and unveil meiosis-specific aspects of Sfh3 (and phosphoinositide) biology that are invisible to contemporary haploid-centric cell biological, proteomic, and functional genomics approaches.

  2. A phosphatidylinositol transfer protein integrates phosphoinositide signaling with lipid droplet metabolism to regulate a developmental program of nutrient stress-induced membrane biogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Jihui; Lin, Coney Pei-Chen; Pathak, Manish C.; Temple, Brenda R.S.; Nile, Aaron H.; Mousley, Carl J.; Duncan, Mara C.; Eckert, Debra M.; Leiker, Thomas J.; Ivanova, Pavlina T.; Myers, David S.; Murphy, Robert C.; Brown, H. Alex; Verdaasdonk, Jolien; Bloom, Kerry S.; Ortlund, Eric A.; Neiman, Aaron M.; Bankaitis, Vytas A. (Emory-MED); (UNCSM); (UNC); (UCHSC); (TAM); (Vanderbilt-MED); (SBU); (Utah)

    2016-07-06

    Lipid droplet (LD) utilization is an important cellular activity that regulates energy balance and release of lipid second messengers. Because fatty acids exhibit both beneficial and toxic properties, their release from LDs must be controlled. Here we demonstrate that yeast Sfh3, an unusual Sec14-like phosphatidylinositol transfer protein, is an LD-associated protein that inhibits lipid mobilization from these particles. We further document a complex biochemical diversification of LDs during sporulation in which Sfh3 and select other LD proteins redistribute into discrete LD subpopulations. The data show that Sfh3 modulates the efficiency with which a neutral lipid hydrolase-rich LD subclass is consumed during biogenesis of specialized membrane envelopes that package replicated haploid meiotic genomes. These results present novel insights into the interface between phosphoinositide signaling and developmental regulation of LD metabolism and unveil meiosis-specific aspects of Sfh3 (and phosphoinositide) biology that are invisible to contemporary haploid-centric cell biological, proteomic, and functional genomics approaches.

  3. Different phosphoinositide 3-kinase isoforms mediate carrageenan nociception and inflammation.

    Science.gov (United States)

    Pritchard, Rory A; Falk, Lovissa; Larsson, Mathilda; Leinders, Mathias; Sorkin, Linda S

    2016-01-01

    Phosphoinositide 3-kinases (PI3Ks) participate in signal transduction cascades that can directly activate and sensitize nociceptors and enhance pain transmission. They also play essential roles in chemotaxis and immune cell infiltration leading to inflammation. We wished to determine which PI3K isoforms were involved in each of these processes. Lightly anesthetized rats (isoflurane) were injected subcutaneously with carrageenan in their hind paws. This was preceded by a local injection of 1% DMSO vehicle or an isoform-specific antagonist to PI3K-α (compound 15-e), -β (TGX221), -δ (Cal-101), or -γ (AS252424). We measured changes in the mechanical pain threshold and spinal c-Fos expression (4 hours after injection) as indices of nociception. Paw volume, plasma extravasation (Evans blue, 0.3 hours after injection), and neutrophil (myeloperoxidase; 1 hour after injection) and macrophage (CD11b+; 4 hour after injection) infiltration into paw tissue were the measured inflammation endpoints. Only PI3K-γ antagonist before treatment reduced the carrageenan-induced pain behavior and spinal expression of c-Fos (P ≤ 0.01). In contrast, pretreatment with PI3K-α, -δ, and-γ antagonists reduced early indices of inflammation. Plasma extravasation PI3K-α (P ≤ 0.05), -δ (P ≤ 0.05), and -γ (P ≤ 0.01), early (0-2 hour) edema -α (P ≤ 0.05), -δ (P ≤ 0.001), and -γ (P ≤ 0.05), and neutrophil infiltration (all P ≤ 0.001) were all reduced compared to vehicle pretreatment. Later (2-4 hour), edema and macrophage infiltration (P ≤ 0.05) were reduced by only the PI3K-δ and -γ isoform antagonists, with the PI3K-δ antagonist having a greater effect on edema. PI3K-β antagonism was ineffective in all paradigms. These data indicate that pain and clinical inflammation are pharmacologically separable and may help to explain clinical conditions in which inflammation naturally wanes or goes into remission, but pain continues unabated. PMID:26313408

  4. Sec14-like phosphatidylinositol transfer proteins and the biological landscape of phosphoinositide signaling in plants.

    Science.gov (United States)

    Huang, Jin; Ghosh, Ratna; Bankaitis, Vytas A

    2016-09-01

    Phosphoinositides and soluble inositol phosphates are essential components of a complex intracellular chemical code that regulates major aspects of lipid signaling in eukaryotes. These involvements span a broad array of biological outcomes and activities, and cells are faced with the problem of how to compartmentalize and organize these various signaling events into a coherent scheme. It is in the arena of how phosphoinositide signaling circuits are integrated and, and how phosphoinositide pools are functionally defined and channeled to privileged effectors, that phosphatidylinositol (PtdIns) transfer proteins (PITPs) are emerging as critical players. As plant systems offer some unique advantages and opportunities for study of these proteins, we discuss herein our perspectives regarding the progress made in plant systems regarding PITP function. We also suggest interesting prospects that plant systems hold for interrogating how PITPs work, particularly in multi-domain contexts, to diversify the biological outcomes for phosphoinositide signaling. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. PMID:27038688

  5. AGE-RELATED CHANGES IN RECEPTOR-MEDIATED PHOSPHOINOSITIDE HYDROLYSIS IN VARIOUS REGIONS OF RAT BRAIN

    Science.gov (United States)

    The effects of age on cholinergic markers and receptor-stimulated phosphoinositide hydrolysis was dined in the frontal cortex and striatum of male Fischer-344 rats. holine acetyltransferase activity was decreased 27% in the striatum of aged (24 month) rats cared to young (3 month...

  6. Coordinated Expression of Phosphoinositide Metabolic Genes during Development and Aging of Human Dorsolateral Prefrontal Cortex.

    Directory of Open Access Journals (Sweden)

    Stanley I Rapoport

    Full Text Available Phosphoinositides, lipid-signaling molecules, participate in diverse brain processes within a wide metabolic cascade.Gene transcriptional networks coordinately regulate the phosphoinositide cascade during human brain Development and Aging.We used the public BrainCloud database for human dorsolateral prefrontal cortex to examine age-related expression levels of 49 phosphoinositide metabolic genes during Development (0 to 20+ years and Aging (21+ years.We identified three groups of partially overlapping genes in each of the two intervals, with similar intergroup correlations despite marked phenotypic differences between Aging and Development. In each interval, ITPKB, PLCD1, PIK3R3, ISYNA1, IMPA2, INPPL1, PI4KB, and AKT1 are in Group 1, PIK3CB, PTEN, PIK3CA, and IMPA1 in Group 2, and SACM1L, PI3KR4, INPP5A, SYNJ1, and PLCB1 in Group 3. Ten of the genes change expression nonlinearly during Development, suggesting involvement in rapidly changing neuronal, glial and myelination events. Correlated transcription for some gene pairs likely is facilitated by colocalization on the same chromosome band.Stable coordinated gene transcriptional networks regulate brain phosphoinositide metabolic pathways during human Development and Aging.

  7. Arsenite-induced stress signaling: Modulation of the phosphoinositide 3′-kinase/Akt/FoxO signaling cascade

    Directory of Open Access Journals (Sweden)

    Ingrit Hamann

    2013-01-01

    Full Text Available FoxO transcription factors and their regulators in the phosphoinositide 3′-kinase (PI3K/Akt signaling pathway play an important role in the control of cellular processes involved in carcinogenesis, such as proliferation and apoptosis. We have previously demonstrated that physiologically relevant heavy metal ions, such as copper or zinc ions, can stimulate this pathway, triggering phosphorylation and nuclear export of FoxO transcription factors. The present study aims at investigating the effect of arsenite on FoxO transcription factors and the role of PI3K/Akt signaling therein. Exposure of HaCaT human keratinocytes to arsenite resulted in a distinct decrease of glutathione levels only at cytotoxic concentrations. In contrast, a strong phosphorylation of FoxO1a/FoxO3a and Akt was observed at subcytotoxic concentrations of arsenite in HaCaT human keratinocytes. A time- and concentration-dependent increase in phosphorylation of FoxO1a and FoxO3a at sites known to be phosphorylated by Akt as well as phosphorylation of Akt at Ser-473 was detected. These phosphorylations were blunted in the presence of wortmannin, pointing to the involvement of PI3K.

  8. Phosphoinositide and Inositolpolyphosphate Signalling in Defense Responses of Arabidopsis thaliana Challenged by Mechanical Wounding

    Institute of Scientific and Technical Information of China (English)

    Alina Mosblech; Sabine K(o)nig; Irene Stenzel; Peter Grzeganek; Ivo Feussner; Ingo Heilmann

    2008-01-01

    Various biochemical signals are implicated in Arabidopsis wound signalling,including jasmonic acid (JA),salicylic acid,auxin,and Ca2+.Here,we report on cross-talk of phytohormones with phosphoinositide signals not previously implicated in plant wound responses.Within 30 min of mechanical wounding of Arabidopsis rosette-leaves,the levels of the lipid-derived soluble inositolpolyphosphate,inositol 1,4,5-trisphosphate (InsP3),increased four to five-fold.Concomitantly,the precursor lipids,phosphatidylinositol 4,5-bisphosphate,phosphatidylinositol 4-phosphate and phosphatidylinositol transiently depleted,followed by re-synthesis after 30-60 min of stimulation.Increased InsP3 levels with wounding coincided with JA increases over the first hours of stimulation.In dde2-2-mutant plants deficient in JA biosynthesis,no InsP3 increase was observed upon wounding,indicating that JA was required for InsP3 formation,and InsP3 levels increased in wild-type plants challenged with sorbitol,increasing endogenous JA levels.In InsP 5-ptase plants with attenuated phosphoinositide signalling,the induction of wounding-inducible genes was diminished compared with wildtype plants,suggesting a role for phosphoinositide signalling in mediating plant wound responses.The gene-expression patterns suggest that phosphoinositides contribute to both JA-dependent and JA-independent aspects of wound signalling.Weight gain of Plutella xylostella caterpillars feeding on InsPS-ptase plants was increased compared with that of caterpillars feeding on wild-type plants.The ecophysiological relevance of phosphoinositide signals in plant defense responses to herbivory is discussed in light of recent findings of inositolpolyphosphate involvement in phytohormone-receptor function.

  9. 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

  10. Effects of thyroxine and 1-methyl, 2-mercaptoimidazol on phosphoinositides synthesis in rat liver

    Directory of Open Access Journals (Sweden)

    Krasilnikova Oksana A

    2004-12-01

    Full Text Available Abstract Background Phosphoinositides mediate one of the intracellular signal transduction pathways and produce a class of second messengers that are involved in the action of hormones and neurotransmitters on target cells. Thyroid hormones are well known regulators of lipid metabolism and modulators of signal transduction in cells. However, little is known about phosphoinositides cycle regulation by thyroid hormones. The present paper deals with phosphoinositides synthesis de novo and acylation in liver at different thyroid status of rats. Results The experiments were performed in either the rat liver or hepatocytes of 90- and 720-day-old rats. Myo-[3H]inositol, [14C]CH3COONa, [14C]oleic and [3H]arachidonic acids were used to investigate the phosphatidylinositol (PtdIns, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate (PtdInsP2 synthesis. 1-methyl, 2-mercaptoimidazol-induced hypothyroidism was associated with the decrease of myo-[3H]inositol and [3H]arachidonic acids incorporation into liver phosphoinositides and total phospholipids, respectively. The thyroxine (L-T4 injection to hypothyroid animals increased the hormones contents in blood serum and PtdInsP2 synthesis de novo as well as [3H]arachidonic acids incorporation into the PtdIns and PtdInsP2. Under the hormone action, the [14C]oleic acid incorporation into PtdIns reduced in the liver of hypothyroid animals. A single injection of L-T4 to the euthyroid [14C]CH3COONa-pre-treated animals or addition of the hormone to a culture medium of hepatocytes was accompanied by the rapid prominent increase in the levels of the newly synthesized PtdIns and PtdInsP2 and in the mass of phosphatidic acid in the liver or the cells. Conclusions The data obtained have demonstrated that thyroid hormones are of vital importance in the regulation of arachidonate-containing phosphoinositides metabolism in the liver. The drug-induced malfunction of thyroid gland noticeably changed the

  11. Bioactives of Artemisia dracunculus L enhance cellular insulin signaling in primary human skeletal muscle culture

    OpenAIRE

    Wang, Zhong Q.; RIBNICKY, DAVID; Zhang, Xian H.; Raskin, Ilya; Yu, Yongmei; Cefalu, William T.

    2008-01-01

    An alcoholic extract of Artemisia dracunculus L (PMI 5011) has been shown to decrease glucose and improve insulin levels in animal models, suggesting an ability to enhance insulin sensitivity. We sought to assess the cellular mechanism by which this botanical affects carbohydrate metabolism in primary human skeletal muscle culture. We measured basal and insulin-stimulated glucose uptake, glycogen accumulation, phosphoinositide 3 (PI-3) kinase activity, and Akt phosphorylation in primary skele...

  12. Phosphoinositide, Phosphopeptide and Pyridone Interactions of the Abl SH2 Domain

    OpenAIRE

    Tokonzaba, Etienne; Capelluto, Daniel G.S.; Kutateladze, Tatiana G.; Overduin, Michael

    2006-01-01

    Signaling proteins are localized and regulated by Src homology 2 domains which recognize phosphotyrosine-containing sequences. Recently, non-canonical ligands have been proposed for Src homology 2 domains including that of Abl and its breakpoint cluster region fusion, which causes chronic myelogenous leukemia. Here, the Abl Src homology 2 domain’s binding sites and affinities for phosphotyrosine- and phosphoserine-containing motifs, phosphoinositides as well as a pyridone-based peptidomimetic...

  13. The Basal Transcription Complex Component TAF3 Transduces Changes in Nuclear Phosphoinositides into Transcriptional Output

    OpenAIRE

    Stijf-Bultsma, Y.; Sommer, L.; Tauber, M; M. Baalbaki; Giardoglou, P.; D. Jones; Gelato, K.; Pelt, J.; Shah, Z.; Rahnamoun, H.; Toma, C; Anderson, K.(Enrico Fermi Institute, University of Chicago, Chicago, IL, U.S.A.); Hawkins, P; Lauberth, S.; Haramis, A.

    2015-01-01

    Summary Phosphoinositides (PI) are important signaling molecules in the nucleus that influence gene expression. However, if and how nuclear PI directly affects the transcriptional machinery is not known. We report that the lipid kinase PIP4K2B regulates nuclear PI5P and the expression of myogenic genes during myoblast differentiation. A targeted screen for PI interactors identified the PHD finger of TAF3, a TATA box binding protein-associated factor with important roles in transcription regul...

  14. The Receptor Binding Domain of Botulinum Neurotoxin Stereotype C Binds Phosphoinositides

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yanfeng; Varnum, Susan M.

    2012-03-01

    Botulinum neurotoxins (BoNTs) are the most toxic proteins known for humans and animals with an extremely low LD50 of {approx} 1 ng/kg. BoNTs generally require a protein and a ganglioside on the cell membrane surface for binding, which is known as a 'dual receptor' mechanism for host intoxication. Recent studies have suggested that in addition to gangliosides, other membrane lipids such as phosphoinositides may be involved in the interactions with the receptor binding domain (HCR) of BoNTs for better membrane penetration. Here, using two independent lipid-binding assays, we tested the interactions of BoNT/C-HCR with lipids in vitro. BoNT/C-HCR was found to bind negatively charged phospholipids, preferentially phosphoinositides. Additional interactions to phosphoinositides may help BoNT/C bind membrane more tightly and transduct signals for subsequent steps of intoxication. Our results provide new insights into the mechanisms of host cell membrane recognition by BoNTs.

  15. Age-related changes in receptor-mediated phosphoinositide hydrolysis in various regions of rat brain

    International Nuclear Information System (INIS)

    The effects of age on cholinergic markers and receptor-stimulated phosphoinositide hydrolysis was examined in the frontal cortex and striatum of male Fischer-344 rats. Choline acetyltransferase activity was decreased 27% in the striatum of aged rats compared to young controls. Muscarinic receptor density as measured by [3H]-quinuclidinyl benzilate binding showed a similar 26% decrease in the striatum of aged rats. Phosphoinositide hydrolysis was measured by the release of inositol phosphate (IP) from tissue slices prelabeled with [3H]myoinositol in response to carbachol, norepinephrine, and quisqualate. In the cortex, stimulated IP release was significantly greater in slices from aged rats compared to young rats for all three agonists. In contrast, stimulated IP release was significantly decreased in striatal slices from aged rats compared to young for all three agonists. These data indicate a differential effect of age on agonist-stimulated phosphoinositide hydrolysis in the cortex and striatum. The decreased responsiveness in the latter area may result from the age-related loss of postsynaptic receptors

  16. 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...

  17. RAS and RHO Families of GTPases Directly Regulate Distinct Phosphoinositide 3-Kinase Isoforms

    OpenAIRE

    Fritsch, Ralph; de Krijger, Inge; Fritsch, Kornelia; George, Roger; Reason, Beth; Kumar, Madhu S.; Diefenbacher, Markus; Stamp, Gordon; Downward, Julian

    2013-01-01

    Summary RAS proteins are important direct activators of p110α, p110γ, and p110δ type I phosphoinositide 3-kinases (PI3Ks), interacting via an amino-terminal RAS-binding domain (RBD). Here, we investigate the regulation of the ubiquitous p110β isoform of PI3K, implicated in G-protein-coupled receptor (GPCR) signaling, PTEN-loss-driven cancers, and thrombocyte function. Unexpectedly, RAS is unable to interact with p110β, but instead RAC1 and CDC42 from the RHO subfamily of small GTPases bind an...

  18. Heavy metal mediated innate immune responses of the Indian green frog, Euphlyctis hexadactylus (Anura: Ranidae): Cellular profiles and associated Th1 skewed cytokine response.

    Science.gov (United States)

    Jayawardena, Uthpala A; Ratnasooriya, Wanigasekara D; Wickramasinghe, Deepthi D; Udagama, Preethi V

    2016-10-01

    Immune cell and cytokine profiles in relation to metal exposure though much studied in mammals has not been adequately investigated in amphibians, due mainly to lack of suitable reagents for cytokine profiling in non-model species. However, interspecies cross reactivity of cytokines permitted us to assay levels of IFNγ, TNFα, IL6 and IL10in a common anuran, the Indian green frog (Euphlyctis hexadactylus), exposed to heavy metals (Cd, Cr, Cu, Zn and Pb, at ~5ppm each) under field and laboratory settings in Sri Lanka. Enumeration of immune cells in blood and melanomacrophages in the liver, assay of serum and hepatic cytokines, and Th1/Th2 cytokine polarisation were investigated. Immune cell counts indicated overall immunosuppression with decreasing total WBC and splenocyte counts while neutrophil/lymphocyte ratio increased with metal exposure, indicating metal mediated stress. Serum IL6 levels of metal exposed frogs reported the highest (~9360pg/mL) of all cytokines tested. Significantly elevated IFNγ production (Pstress mediated nuclear factor κ-light chain enhancer of activated B cells (NFκB) which enhances the transcription of pro-inflammatory cytokines. Xenobiotic stress has recently imposed an unprecedented level of threat to wildlife, particularly to sensitive species such as amphibians. Therefore, understanding the interactions between physiological stress and related immune responses is fundamental to conserve these environmental sentinels in the face of emerging eco-challenges. PMID:27335164

  19. 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

  20. Stimulation of phosphoinositide hydrolysis by a novel substance partially purified from rat and bovine brain

    International Nuclear Information System (INIS)

    This study demonstrates the partial purification of a potentially novel substance from rat and bovine brain. Whole brains were homogenized in distilled water, then heated at 1000C for 30 min. The water extract was dialyzed and the 3H-inositol monophosphate (3H-IP) using lithium-treated slices of rat cerebral cortex prelabelled with 3H-myo-inositol. A major peak of activity was observed in fractions from the molecular weight range of 800-1300 daltons. Stimulation of phosphoinositide hydrolysis by this material was time-dependent and dose-related. Maximal stimulation of 3H-IP (323% of control) required 10mg/ml of bovine material and was observed at 30 minutes. These effects could not be mimicked by a number of substances of similar molecular weight (e.g. substance P, neurotensin, angiotensin II, bradykinin). Furthermore, the effects of this material were not blocked by antagonist drugs which act at the alpha-adrenoceptor, muscarinic cholinoceptor, 5-HT2 receptor, substance P receptor, or neurotensin receptor. These results indicate that the substance isolated may be a novel neuroactive molecule which has receptors coupled to phosphoinositide hydrolysis in brain

  1. Microwave induced stimulation of 32Pi incorporation into phosphoinositides of rat brain synaptosomes

    International Nuclear Information System (INIS)

    Exposure of synaptosomes to microwave radiation at a power density of 10 mW/sq cm or more produced stimulation of the 32Pi-incorporation into phosphoinositides. The extent of 32Pi incorporation was found to be much more pronounced in phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2) as compared to phosphatidylinositol (PI) and phosphatidic acid (PA). Other lipids were also found to incorporate 32Pi but no significant changes in their labeling were seen after exposure to microwave radiation. Inclusion of 10 mM lithium in the medium reduced the basal labeling of PIP2, PIP and PI and increased PA labeling. Li+ also inhibited the microwave stimulated PIP2, PIP and PI labeling but had no effect on PA labeling. Calcium inophore, A23187, inhibited the basal and microwave stimulated 32Pi labeling of PIP and PIP2, stimulated basal labeling of PA and PI and had no effect on microwave stimulated PA and PI labeling. Calcium chelator, EGTA, on the other hand, had no effect on basal labeling of PA and PI, stimulated basal PIP and PIP2 labeling but did not alter microwave stimulated labeling of these lipids. Exposure of synaptosomes to microwave radiation did not alter the chemical concentration of phosphoinositides indicating that the turnover of these lipids was altered. These results suggest that low frequency microwave radiation alter the metabolism of inositol phospholipids by enhancing their turnover and thus may affect the transmembrane signalling in the nerve endings. (orig.)

  2. Chronic exposure to paclitaxel diminishes phosphoinositide signaling by calpain-mediated neuronal calcium sensor-1 degradation.

    Science.gov (United States)

    Boehmerle, Wolfgang; Zhang, Kun; Sivula, Michael; Heidrich, Felix M; Lee, Yashang; Jordt, Sven-Eric; Ehrlich, Barbara E

    2007-06-26

    Paclitaxel (Taxol) is a well established chemotherapeutic agent for the treatment of solid tumors, but it is limited in its usefulness by the frequent induction of peripheral neuropathy. We found that prolonged exposure of a neuroblastoma cell line and primary rat dorsal root ganglia with therapeutic concentrations of Taxol leads to a reduction in inositol trisphosphate (InsP(3))-mediated Ca(2+) signaling. We also observed a Taxol-specific reduction in neuronal calcium sensor 1 (NCS-1) protein levels, a known modulator of InsP(3) receptor (InsP(3)R) activity. This reduction was also found in peripheral neuronal tissue from Taxol treated animals. We further observed that short hairpin RNA-mediated NCS-1 knockdown had a similar effect on phosphoinositide-mediated Ca(2+) signaling. When NCS-1 protein levels recovered, so did InsP(3)-mediated Ca(2+) signaling. Inhibition of the Ca(2+)-activated protease mu-calpain prevented alterations in phosphoinositide-mediated Ca(2+) signaling and NCS-1 protein levels. We also found that NCS-1 is readily degraded by mu-calpain in vitro and that mu-calpain activity is increased in Taxol but not vehicle-treated cells. From these results, we conclude that prolonged exposure to Taxol activates mu-calpain, which leads to the degradation of NCS-1, which, in turn, attenuates InsP(3)mediated Ca(2+) signaling. These findings provide a previously undescribed approach to understanding and treating Taxol-induced peripheral neuropathy. PMID:17581879

  3. A cellular lipidomic study on the Aβ-induced neurotoxicity and neuroprotective effects of EGCG by using UPLC/MS-based glycerolipids profiling and multivariate analysis.

    Science.gov (United States)

    Zhang, Hongyang; Wang, Jing-Rong; Yau, Lee Fong; Ho, Hing Man; Chan, Chi Leung; Hu, Ping; Liu, Liang; Jiang, Zhi-Hong

    2012-10-30

    The aim of this study was to investigate the cellular lipid metabolism associated with β-amyloid peptide (Aβ)-induced neurotoxicity as well as the neuroprotective effect of (-)-epigallocatechin gallate (EGCG), a major polyphenol in green tea. An ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS)-based lipidomic approach was developed to screen and identify changes of the glycerolipids (GL) upon Aβ treatment with or without the presence of EGCG in PC12 cells. Principle component analysis (PCA) showed that the Aβ-treated group was well separated from the control group, whereas the EGCG group was closer to the control group. The GL levels were significantly elevated in Aβ-treated cells compared with the control group, but were restored near to normal levels after EGCG treatment. The elevated phosphatidylcholines (PCs) levels observed in the Aβ-treated PC12 cells were quite probably the integrated results of the reduced phospholipase A(2) (PLA(2)) activity and the enhanced activity of lysophospholipid acyltransferases. Moreover, an increased liberation of arachidonic acid (AA) from PCs was observed as another important response of PC12 cells to the Aβ aggregates, implying an active inflammatory process occurring in Aβ induced neurotoxicity. EGCG treatment can reverse the deregulated metabolism of PCs, which might be one of the biochemical mechanisms contributing to its neuroprotective effect. Collectively, results obtained from the current lipidomic analyses of PC12 cells provided important insight into the biochemical mechanisms underlying Aβ-induced neurotoxicity and neuro protective effects of EGCG. This is the first report of the lipidomic study on the neuroprotective effect of EGCG. PMID:23032920

  4. Inhibition of the phosphoinositide 3-kinase pathway induces a senescence-like arrest mediated by p27Kip1

    NARCIS (Netherlands)

    Collado, M.; Medema, R.H.; Garcia-Cao, I.; Dubuisson, M.L.N.; Barradas, M.; Glassford, J.; Rivas, C.; Burgering, B.M.T.; Serrano, M.; Lam, E.W.-F.

    2000-01-01

    A senescence-like growth arrest is induced in mouse primary embryo fibroblasts by inhibitors of phosphoinositide 3-kinase (PI3K). We observed that senescence-like growth arrest is correlated with an increase in p27Kip1 but that down-regulation of other cyclin-dependent kinase (CDK) inhibitors, inclu

  5. The yeast VAP homolog Scs2p has a phosphoinositide-binding ability that is correlated with its activity

    International Nuclear Information System (INIS)

    The yeast VAMP-associated protein (VAP) homolog Scs2p is an endoplasmic reticulum (ER)/nuclear membrane protein that binds to an FFAT (diphenylalanine in an acidic tract) motif found in various lipid-metabolic proteins, including Opi1p, a negative regulator of phospholipid biosynthesis. Here, we show that Scs2p is a novel phosphoinositide-binding protein that can bind to phosphatidylinositol monophosphates and bisphosphates in vitro. The phosphoinositide-binding domain was assigned to the N-terminal major sperm protein (MSP) domain which also contains the FFAT-binding domain. When several lysine residues in the MSP domain were substituted for alanine, the resulting mutant Scs2 proteins lost the phosphoinositide-binding ability and failed to complement the inositol auxotrophy of an scs2 deletion strain. However, the mutant proteins still localized in the ER/nuclear membrane, in a similar manner to wild-type Scs2p. These results suggest the possibility that Scs2p activity is regulated by phosphoinositides to coordinate phospholipid biosynthesis in response to changes in phospholipid composition

  6. Salicylic acid modulates levels of phosphoinositide dependent-phospholipase C substrates and products to remodel the Arabidopsis suspension cell transcriptome

    Directory of Open Access Journals (Sweden)

    Eric eRuelland

    2014-11-01

    Full Text Available Basal phosphoinositide-dependent phospholipase C (PI-PLC activity controls gene expression in Arabidopsis suspension cells and seedlings. PI-PLC catalyzes the production of phosphorylated inositol and diacylglycerol (DAG from phosphoinositides. It is not known how PI-PLC regulates the transcriptome although the action of DAG-kinase (DGK on DAG immediately downstream from PI-PLC is responsible for some of the regulation. We previously established a list of genes whose expression is affected in the presence of PI-PLC inhibitors. Here this list of genes was used as a signature in similarity searches of curated plant hormone response transcriptome data. The strongest correlations obtained with the inhibited PI-PLC signature were with salicylic acid (SA treatments. We confirm here that in Arabidopsis suspension cells SA treatment leads to an increase in phosphoinositides, then demonstrate that SA leads to a significant 20% decrease in phosphatidic acid, indicative of a decrease in PI-PLC products. Previous sets of microarray data were re-assessed. The SA response of one set of genes was dependent on phosphoinositides. Alterations in the levels of a second set of genes, mostly SA-repressed genes, could be related to decreases in PI-PLC products that occur in response to SA action. Together, the two groups of genes comprise at least 40% of all SA-responsive genes. Overall these two groups of genes are distinct in the functional categories of the proteins they encode, their promoter cis-elements and their regulation by DGK or phospholipase D. SA-regulated genes dependent on phosphoinositides are typical SA response genes while those with an SA response that is possibly dependent on PI-PLC products are less SA-specific. We propose a model in which SA inhibits PI-PLC activity and alters levels of PI-PLC products and substrates, thereby regulating gene expression divergently.

  7. 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.

  8. 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

  9. Inhibition of platelet thromboxane formation and phosphoinositides breakdown by osthole from Angelica pubescens.

    Science.gov (United States)

    Ko, F N; Wu, T S; Liou, M J; Huang, T F; Teng, C M

    1989-11-24

    Osthole, isolated from Chinese herb Angelica pubescens, inhibited platelet aggregation and ATP release induced by ADP, arachidonic acid, PAF, collagen, ionophore A23187 and thrombin in washed rabbit platelets. It showed a weak activity in platelet-rich plasma. Osthole inhibited the thromboxane B2 formation caused by arachidonic acid, collagen, ionophore A23187 and thrombin in washed platelets, and also the thromboxane B2 formation caused by the incubation of lysed platelet homogenate with arachidonic acid. The generation of inositol phosphates in washed platelets caused by collagen, PAF and thrombin was suppressed by osthole. These data indicate that the inhibitory effect of osthole on platelet aggregation and release reaction was due to the inhibition of thromboxane formation and phosphoinositides breakdown. PMID:2556815

  10. Muscarinic receptor activation of phosphatidylcholine hydrolysis. Relationship to phosphoinositide hydrolysis and diacylglycerol metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Martinson, E.A.; Goldstein, D.; Brown, J.H. (Univ. of California, San Diego, La Jolla (USA))

    1989-09-05

    We examined the relationship between phosphatidylcholine (PC) hydrolysis, phosphoinositide hydrolysis, and diacylglycerol (DAG) formation in response to muscarinic acetylcholine receptor (mAChR) stimulation in 1321N1 astrocytoma cells. Carbachol increases the release of (3H)choline and (3H)phosphorylcholine ((3H)Pchol) from cells containing (3H)choline-labeled PC. The production of Pchol is rapid and transient, while choline production continues for at least 30 min. mAChR-stimulated release of Pchol is reduced in cells that have been depleted of intracellular Ca2+ stores by ionomycin pretreatment, whereas choline release is unaffected by this pretreatment. Phorbol 12-myristate 13-acetate (PMA) increases the release of choline, but not Pchol, from 1321N1 cells, and down-regulation of protein kinase C blocks the ability of carbachol to stimulate choline production. Taken together, these results suggest that Ca2+ mobilization is involved in mAChR-mediated hydrolysis of PC by a phospholipase C, whereas protein kinase C activation is required for mAChR-stimulated hydrolysis of PC by a phospholipase D. Both carbachol and PMA rapidly increase the formation of (3H)phosphatidic acid ((3H)PA) in cells containing (3H)myristate-labeled PC. (3H)Diacylglycerol ((3H)DAG) levels increase more slowly, suggesting that the predominant pathway for PC hydrolysis is via phospholipase D. When cells are labeled with (3H)myristate and (14C)arachidonate such that there is a much greater 3H/14C ratio in PC compared with the phosphoinositides, the 3H/14C ratio in DAG and PA increases with PMA treatment but decreases in response to carbachol.

  11. Expression of phosphoinositide-specific phospholipase C isoforms in native endothelial cells.

    Directory of Open Access Journals (Sweden)

    Delphine M Béziau

    Full Text Available Phospholipase C (PLC comprises a superfamily of enzymes that play a key role in a wide array of intracellular signalling pathways, including protein kinase C and intracellular calcium. Thirteen different mammalian PLC isoforms have been identified and classified into 6 families (PLC-β, γ, δ, ε, ζ and η based on their biochemical properties. Although the expression of PLC isoforms is tissue-specific, concomitant expression of different PLC has been reported, suggesting that PLC family is involved in multiple cellular functions. Despite their critical role, the PLC isoforms expressed in native endothelial cells (ECs remains undetermined. A conventional PCR approach was initially used to elucidate the mRNA expression pattern of PLC isoforms in 3 distinct murine vascular beds: mesenteric (MA, pulmonary (PA and middle cerebral arteries (MCA. mRNA encoding for most PLC isoforms was detected in MA, MCA and PA with the exception of η2 and β2 (only expressed in PA, δ4 (only expressed in MCA, η1 (expressed in all but MA and ζ (not detected in any vascular beds tested. The endothelial-specific PLC expression was then sought in freshly isolated ECs. Interestingly, the PLC expression profile appears to differ across the investigated arterial beds. While mRNA for 8 of the 13 PLC isoforms was detected in ECs from MA, two additional PLC isoforms were detected in ECs from PA and MCA. Co-expression of multiple PLC isoforms in ECs suggests an elaborate network of signalling pathways: PLC isoforms may contribute to the complexity or diversity of signalling by their selective localization in cellular microdomains. However in situ immunofluorescence revealed a homogeneous distribution for all PLC isoforms probed (β3, γ2 and δ1 in intact endothelium. Although PLC isoforms play a crucial role in endothelial signal transduction, subcellular localization alone does not appear to be sufficient to determine the role of PLC in the signalling microdomains found

  12. Phosphoinositide 3-kinase accelerates postoperative tumor growth by inhibiting apoptosis and enhancing resistance to chemotherapy-induced apoptosis. Novel role for an old enemy.

    LENUS (Irish Health Repository)

    Coffey, J Calvin

    2012-02-03

    Tumor removal remains the principal treatment modality in the management of solid tumors. The process of tumor removal may potentiate the resurgent growth of residual neoplastic tissue. Herein, we describe a novel murine model in which flank tumor cytoreduction is followed by accelerated local tumor recurrence. This model held for primary and recurrent tumors generated using a panel of human and murine (LS174T, DU145, SW480, SW640, and 3LL) cell lines and replicated accelerated tumor growth following excisional surgery. In investigating this further, epithelial cells were purified from LS174T primary and corresponding recurrent tumors for comparison. Baseline as well as tumor necrosis factor apoptosis-inducing ligand (TRAIL)-induced apoptosis were significantly reduced in recurrent tumor epithelia. Primary and recurrent tumor gene expression profiles were then compared. This identified an increase and reduction in the expression of p110gamma and p85alpha class Ia phosphoinositide 3-kinase (PI3K) subunits in recurrent tumor epithelia. These changes were further confirmed at the protein level. The targeting of PI3K ex vivo, using LY294002, restored sensitivity to TRAIL in recurrent tumor epithelia. In vivo, adjuvant LY294002 prolonged survival and significantly attenuated recurrent tumor growth by greatly enhancing apoptosis levels. Hence, PI3K plays a role in generating the antiapoptotic and chemoresistant phenotype associated with accelerated local tumor recurrence.

  13. Nuclear Magnetic Resonance Detects Phosphoinositide 3-Kinase/Akt-Independent Traits Common to Pluripotent Murine Embryonic Stem Cells and Their Malignant Counterparts

    Directory of Open Access Journals (Sweden)

    Hanna M. Romanska

    2009-12-01

    Full Text Available Pluripotent embryonic stem (ES cells, a potential source of somatic precursors for cell therapies, cause tumors after transplantation. Studies of mammalian carcinogenesis using nuclear magnetic resonance (NMR spectroscopy have revealed changes in the choline region, particularly increased phosphocholine (PCho content. High PCho levels in murine ES (mES cells have recently been attributed to cell pluripotency. The phosphoinositide 3-kinase (PI3K/Akt pathway has been implicated in tumor-like properties of mES cells. This study aimed to examine a potential link between the metabolic profile associated with choline metabolism of pluripotent mES cells and PI3K/Akt signaling. We used mES (ES-D3 and murine embryonal carcinoma cells (EC-F9 and compared the metabolic profiles of 1 pluripotent mES (ESD0, 2 differentiated mES (ESD14, and 3 pluripotent F9 cells. Involvement of the PI3K/Akt pathway was assessed using LY294002, a selective PI3K inhibitor. Metabolic profiles were characterized in the extracted polar fraction by 1H NMR spectroscopy. Similarities were found between the levels of choline phospholipid metabolites (PCho/total choline and PCho/glycerophosphocholine [GPCho] in ESD0 and F9 cell spectra and a greater-than five-fold decrease of the PCho/GPCho ratio associated with mES cell differentiation. LY294002 caused no significant change in relative PCho levels but led to a greater-than two-fold increase in PCho/GPCho ratios. These results suggest that the PCho/GPCho ratio is a metabolic trait shared by pluripotent and malignant cells and that PI3K does not underlie its development. It is likely that the signature identified here in a mouse model may be relevant for safe therapeutic applications of human ES cells.

  14. Possible mechanism for preterm labor associated with bacterial infection. I. Stimulation of phosphoinositide metabolism by endotoxin in endometrial fibroblasts

    International Nuclear Information System (INIS)

    Growing evidence suggests an association between intra-amniotic infection and premature initiation of parturition. We recently demonstrated that some factor(s) including endotoxin produced by the organism stimulates endogenous phospholipase A2 resulting in liberation of arachidonic acid and prostaglandin formation. The studies presented in this report were designated to evaluate the mechanism for endotoxin to stimulate phospholipase A2 using human endometrial fibroblasts. Exposure of the fibroblasts to endotoxin from Escherichia coli in the presence of [32P] phosphate increased 32P-labeling of phosphatidic acid (PA) and phosphatidyl-inositol (PI) in a dose-dependent and a time-dependent manners. The PA labeling occurred without a measurable lag time. These findings demonstrate that the endotoxin stimulates phosphoinositide metabolism in human endometrial fibroblasts by a receptor-mediated mechanism. Membrane phosphoinositide turnover stimulated by endotoxin results in cytosolic Ca2+ increment, liberation of arachidonic acid, which may be involved in the initiation of parturition

  15. Phosphoinositide 3-Kinase Binds to TRPV1 and Mediates NGF-stimulated TRPV1 Trafficking to the Plasma Membrane

    OpenAIRE

    Stein, Alexander T.; Ufret-Vincenty, Carmen A.; Hua, Li; Santana, Luis F.; Gordon, Sharona E.

    2006-01-01

    Sensitization of the pain-transducing ion channel TRPV1 underlies thermal hyperalgesia by proalgesic agents such as nerve growth factor (NGF). The currently accepted model is that the NGF-mediated increase in TRPV1 function during hyperalgesia utilizes activation of phospholipase C (PLC) to cleave PIP2, proposed to tonically inhibit TRPV1. In this study, we tested the PLC model and found two lines of evidence that directly challenge its validity: (1) polylysine, a cationic phosphoinositide se...

  16. The putative phosphoinositide-specific phospholipase C gene, PLC1, of the yeast Saccharomyces cerevisiae is important for cell growth.

    OpenAIRE

    Yoko-o, T; Matsui, Y; Yagisawa, H; Nojima, H; Uno, I; Toh-E, A

    1993-01-01

    Using the polymerase chain reaction technique, we have isolated a gene that encodes a putative phosphoinositide-specific phospholipase C (PLC) in the yeast Saccharomyces cerevisiae. The nucleotide sequence indicates that the gene encodes a polypeptide of 869 amino acid residues with a calculated molecular mass of 101 kDa. This polypeptide has both the X and Y regions conserved among mammalian PLC-beta, -gamma, and -delta, and the structure is most similar to that of mammalian PLC-delta. This ...

  17. Chronic Restraint Stress Promotes Immune Suppression through Toll-like Receptor 4-Mediated Phosphoinositide 3-kinase Signaling

    OpenAIRE

    Zhang, Yi; Zhang, Ying; Miao, JunYing; Hanley, Gregory; Stuart, Charles; Sun, Xiuli; Chen, Tingting; Yin, Deling

    2008-01-01

    Stress, either psychological or physical, can have a dramatic impact on the immune system. Toll-like receptors (TLRs) play a pivotal role in the induction of innate and adaptive immune response. We have reported that stress modulates the immune response in a TLR4-dependent manner. However, the mechanisms underlying TLR4-mediated signaling in stress modulation of immune system have not been identified. Here, we demonstrate an essential role for the TLR4-mediated phosphoinositide 3-kinase (PI3K...

  18. Expression Analysis of a Stress-Related Phosphoinositide-Specific Phospholipase C Gene in Wheat (Triticum aestivum L.)

    OpenAIRE

    Zhang, Ke; Jin, Congcong; Wu, Lizhu; Hou, Mingyu; Dou, Shijuan; Pan, Yanyun

    2014-01-01

    Plant phosphoinositide-specific phospholipases C (PI-PLCs) function in several essential plant processes associated with either development or environmental stress. In this report, we examined the expression patterns of TaPLC1 under drought and high salinity stress at the transcriptional and post-transcriptional levels. TaPLC1 mRNA was expressed in all wheat organs examined. U73122 and edelfosine, the PLC inhibitor, impaired seedling growth and enhanced seedling sensitivity to drought and hig...

  19. Protection against 1-methyl-4-phenyl pyridinium-induced neurotoxicity in human neuroblastoma SH-SY5Y cells by Soyasaponin I by the activation of the phosphoinositide 3-kinase/AKT/GSK3β pathway.

    Science.gov (United States)

    Guo, Zheng; Cao, Wei; Zhao, Shifeng; Han, Zengtai; Han, Boxiang

    2016-07-01

    Parkinson's disease (PD) can be ascribed to the progressive and selective loss of dopaminergic neurons in the substantia nigra pars compacta, and thus molecules with neuroprotective ability may have therapeutic value against PD. In the current study, the neuroprotective effects and underlying mechanisms of Soyasaponin I (Soya-I), a naturally occurring triterpene extracted from a widely used ingredient in many foods, such as Glycine max (soybean), were evaluated in a widely used cellular PD model in which neurotoxicity was induced by 1-methyl-4-phenyl pyridinium (MPP) in cultured SH-SY5Y cells. We found that Soya-I at 10-40 μM considerably protected against MPP-induced neurotoxicity as evidenced by an increase in cell viability, a decrease in lactate dehydrogenase release, and a reduction in apoptotic nuclei. Moreover, Soya-I effectively inhibited the elevated intracellular accumulation of reactive oxygen species as well as the Bax/Bcl-2 ratio caused by MPP. Most importantly, Soya-I markedly reversed the inhibition of protein expression of phosphorylated AKT and phosphorylated GSK3β caused by MPP. LY294002, the specific inhibitor of phosphoinositide 3-kinase, significantly abrogated the upregulated phosphorylated AKT and phosphorylated GSK3β offered by Soya-I, suggesting that the neuroprotection of Soya-I was mainly dependent on the activation of the phosphoinositide 3-kinase/AKT/GSK3β signaling pathway. The results taken together indicate that Soya-I may be a potential candidate for further preclinical study aimed at the prevention and treatment of PD. PMID:27196724

  20. Effect of albumin-bound DHA on phosphoinositide phosphorylation in collagen stimulated human platelets

    International Nuclear Information System (INIS)

    The effect of exogenous albumin-bound docosahexaenoic acid (22:6n-3) (DHA), arachidonic acid (20:4n-6) (AA), and eicosapendaenoic acid (20:5n-3) (EPA) on phosphoinositide metabolism following collagen stimulation was studied using [3H]inositol prelabelled platelets. Collagen stimulation (3 min, 1.8 micrograms/ml) increased the labelling of both phosphatidylinositol 4-monophosphate (PIP), and phosphatidylinositol 4,5-biphosphate (PIP2). Of the fatty acids tested, only pre-incubation (2 min) with DHA (20 microM) significantly attenuated the collagen-induced increased PIP and PIP2 labelling; EPA was without effect, while AA enhanced PIP labelling. Forty microM DHA was less effective at attenuating the increased PIP and PIP2 labelling even though this concentration of DHA resulted in greater inhibition of platelet aggregation. Neither concentration of DHA attenuated the increased polyphosphoinositide labelling resulting from stimulation by the endoperoxide analogue U46619, or the phorbol ester, PMA. These data suggest that the effect of DHA on attenuating the increased PIP and PIP2 labelling following collagen stimulation likely occurs before thromboxane receptor occupancy, may not occur at the level of protein kinase C activation, and could be mediated in part via a lessened synthesis of thromboxane A2

  1. RAS and RHO families of GTPases directly regulate distinct phosphoinositide 3-kinase isoforms.

    Science.gov (United States)

    Fritsch, Ralph; de Krijger, Inge; Fritsch, Kornelia; George, Roger; Reason, Beth; Kumar, Madhu S; Diefenbacher, Markus; Stamp, Gordon; Downward, Julian

    2013-05-23

    RAS proteins are important direct activators of p110α, p110γ, and p110δ type I phosphoinositide 3-kinases (PI3Ks), interacting via an amino-terminal RAS-binding domain (RBD). Here, we investigate the regulation of the ubiquitous p110β isoform of PI3K, implicated in G-protein-coupled receptor (GPCR) signaling, PTEN-loss-driven cancers, and thrombocyte function. Unexpectedly, RAS is unable to interact with p110β, but instead RAC1 and CDC42 from the RHO subfamily of small GTPases bind and activate p110β via its RBD. In fibroblasts, GPCRs couple to PI3K through Dock180/Elmo1-mediated RAC activation and subsequent interaction with p110β. Cells from mice carrying mutations in the p110β RBD show reduced PI3K activity and defective chemotaxis, and these mice are resistant to experimental lung fibrosis. These findings revise our understanding of the regulation of type I PI3K by showing that both RAS and RHO family GTPases directly regulate distinct ubiquitous PI3K isoforms and that RAC activates p110β downstream of GPCRs. PMID:23706742

  2. Chronic ethanol inhibits receptor-stimulated phosphoinositide hydrolysis in rat liver slices

    Energy Technology Data Exchange (ETDEWEB)

    Gonzales, R.A.; Crews, F.T. (Department of Pharmacology, University of Texas, Austin (USA))

    1991-03-01

    The effects of chronic ethanol feeding on norepinephrine (NE)- and arginine-vasopressin (AVP)-stimulated phosphoinositide (PI) hydrolysis in rat liver slices was determined. The maximum NE-stimulated PI response was significantly reduced by 40% in liver slices from 8-month-old rats which had been treated for 5 months with a liquid diet containing ethanol compared to pair-fed controls. The maximum AVP-stimulated PI response was decreased by 39% in liver slices from the ethanol-fed rats compared to control. EC50 values for NE- and AVP-stimulated PI hydrolysis in liver slices were not affected by the chronic ethanol treatment. Similar reductions in the maximal NE- and AVP-stimulated PI hydrolysis (28% and 27%, respectively) were found in 22-month-old rats which had been maintained on an ethanol containing diet for 5 months compared to pair-fed controls. The binding of (3H)prazosin and (3H)AVP to liver plasma membranes from 8-month-old ethanol-fed rats was not significantly different from binding to liver membranes from sucrose-fed controls. Our data suggest that chronic ethanol ingestion may lead to a reduction in PI-linked signal transduction in liver.

  3. Critical role for phosphoinositide 3-kinase gamma in parasite invasion and disease progression of cutaneous leishmaniasis

    Science.gov (United States)

    Cummings, Hannah E.; Barbi, Joseph; Reville, Patrick; Oghumu, Steve; Zorko, Nicholas; Sarkar, Anasuya; Keiser, Tracy L.; Lu, Bao; Rückle, Thomas; Varikuti, Sanjay; Lezama-Davila, Claudio; Wewers, Mark D.; Whitacre, Caroline; Radzioch, Danuta; Rommel, Christian; Seveau, Stéphanie; Satoskar, Abhay R.

    2012-01-01

    Obligate intracellular pathogens such as Leishmania specifically target host phagocytes for survival and replication. Phosphoinositide 3-kinase γ (PI3Kγ), a member of the class I PI3Ks that is highly expressed by leukocytes, controls cell migration by initiating actin polymerization and cytoskeletal reorganization, which are processes also critical for phagocytosis. In this study, we demonstrate that class IB PI3K, PI3Kγ, plays a critical role in pathogenesis of chronic cutaneous leishmaniasis caused by L. mexicana. Using the isoform-selective PI3Kγ inhibitor, AS-605240 and PI3Kγ gene-deficient mice, we show that selective blockade or deficiency of PI3Kγ significantly enhances resistance against L. mexicana that is associated with a significant suppression of parasite entry into phagocytes and reduction in recruitment of host phagocytes as well as regulatory T cells to the site of infection. Furthermore, we demonstrate that AS-605240 is as effective as the standard antileishmanial drug sodium stibogluconate in treatment of cutaneous leishmaniasis caused by L. mexicana. These findings reveal a unique role for PI3Kγ in Leishmania invasion and establishment of chronic infection, and demonstrate that therapeutic targeting of host pathways involved in establishment of infection may be a viable strategy for treating infections caused by obligate intracellular pathogens such as Leishmania. PMID:22232690

  4. Regulation of platelet activating factor receptor coupled phosphoinositide-specific phospholipase C activity

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, W.J.

    1988-01-01

    The major objectives of this study were two-fold. The first was to establish whether binding of platelet activating factor (PAF) to its receptor was integral to the stimulation of polyphosphoinositide-specific phospholipase C (PLC) in rabbit platelets. The second was to determine regulatory features of this receptor-coupled mechanism. ({sup 3}H)PAF binding demonstrated two binding sites, a high affinity site with a inhibitory constant (Ki) of 2.65 nM and a low affinity site with a Ki of 0.80 {mu}M. PAF receptor coupled activation of phosphoinositide-specific PLC was studied in platelets which were made refractory, by short term pretreatments, to either PAF or thrombin. Saponin-permeabilized rabbit platelets continue to regulate the mechanism(s) coupling PAF receptors to PLC stimulation. However, TRP{gamma}S and GDP{beta}S, which affect guanine nucleotide regulatory protein functions, were unable to modulate the PLC activity to any appreciable extent as compared to PAF. The possible involvement of protein kinase C (PKC) activation in regulating PAF-stimulated PLC activity was studied in rabbit platelets pretreated with staurosporine followed by pretreatments with PAF or phorbol 12-myristate 13-acetate (PMA).

  5. Tyrosol Suppresses Allergic Inflammation by Inhibiting the Activation of Phosphoinositide 3-Kinase in Mast Cells.

    Directory of Open Access Journals (Sweden)

    In-Gyu Je

    Full Text Available Allergic diseases such as atopic dermatitis, rhinitis, asthma, and anaphylaxis are attractive research areas. Tyrosol (2-(4-hydroxyphenylethanol is a polyphenolic compound with diverse biological activities. In this study, we investigated whether tyrosol has anti-allergic inflammatory effects. Ovalbumin-induced active systemic anaphylaxis and immunoglobulin E-mediated passive cutaneous anaphylaxis models were used for the immediate-type allergic responses. Oral administration of tyrosol reduced the allergic symptoms of hypothermia and pigmentation in both animal models. Mast cells that secrete allergic mediators are key regulators on allergic inflammation. Tyrosol dose-dependently decreased mast cell degranulation and expression of inflammatory cytokines. Intracellular calcium levels and activation of inhibitor of κB kinase (IKK regulate cytokine expression and degranulation. Tyrosol blocked calcium influx and phosphorylation of the IKK complex. To define the molecular target for tyrosol, various signaling proteins involved in mast cell activation such as Lyn, Syk, phosphoinositide 3-kinase (PI3K, and Akt were examined. Our results showed that PI3K could be a molecular target for tyrosol in mast cells. Taken together, these findings indicated that tyrosol has anti-allergic inflammatory effects by inhibiting the degranulation of mast cells and expression of inflammatory cytokines; these effects are mediated via PI3K. Therefore, we expect tyrosol become a potential therapeutic candidate for allergic inflammatory disorders.

  6. Ablation of phosphoinositide-3-kinase class II alpha suppresses hepatoma cell proliferation

    International Nuclear Information System (INIS)

    Cancer such as hepatocellular carcinoma (HCC) is characterized by complex perturbations in multiple signaling pathways, including the phosphoinositide-3-kinase (PI3K/AKT) pathways. Herein we investigated the role of PI3K catalytic isoforms, particularly class II isoforms in HCC proliferation. Among the siRNAs tested against the eight known catalytic PI3K isoforms, specific ablation of class II PI3K alpha (PIK3C2α) was the most effective in impairing cell growth and this was accompanied by concomitant decrease in PIK3C2α mRNA and protein levels. Colony formation ability of cells deficient for PIK3C2α was markedly reduced and growth arrest was associated with increased caspase 3 levels. A small but significant difference in gene dosage and expression levels was detected between tumor and non-tumor tissues in a cohort of 19 HCC patients. Taken together, these data suggest for the first time that in addition to class I PI3Ks in cancer, class II PIK3C2α can modulate HCC cell growth.

  7. The basal transcription complex component TAF3 transduces changes in nuclear phosphoinositides into transcriptional output.

    Science.gov (United States)

    Stijf-Bultsma, Yvette; Sommer, Lilly; Tauber, Maria; Baalbaki, Mai; Giardoglou, Panagiota; Jones, David R; Gelato, Kathy A; van Pelt, Jason; Shah, Zahid; Rahnamoun, Homa; Toma, Clara; Anderson, Karen E; Hawkins, Philip; Lauberth, Shannon M; Haramis, Anna-Pavlina G; Hart, Daniel; Fischle, Wolfgang; Divecha, Nullin

    2015-05-01

    Phosphoinositides (PI) are important signaling molecules in the nucleus that influence gene expression. However, if and how nuclear PI directly affects the transcriptional machinery is not known. We report that the lipid kinase PIP4K2B regulates nuclear PI5P and the expression of myogenic genes during myoblast differentiation. A targeted screen for PI interactors identified the PHD finger of TAF3, a TATA box binding protein-associated factor with important roles in transcription regulation, pluripotency, and differentiation. We show that the PI interaction site is distinct from the known H3K4me3 binding region of TAF3 and that PI binding modulates association of TAF3 with H3K4me3 in vitro and with chromatin in vivo. Analysis of TAF3 mutants indicates that TAF3 transduces PIP4K2B-mediated alterations in PI into changes in specific gene transcription. Our study reveals TAF3 as a direct target of nuclear PI and further illustrates the importance of basal transcription components as signal transducers. PMID:25866244

  8. Stimulatory effects of maitotoxin on insulin release in insulinoma HIT cells: Role of calcium uptake and phosphoinositide breakdown

    International Nuclear Information System (INIS)

    In hamster insulinoma (HIT) cells, maitotoxin (MTX) induces a time-dependent and concentration-dependent release of insulin that requires the presence of extracellular calcium. The response is nearly completely blocked by cinnarizine and cadmium, but is not inhibited by the L-type calcium channel blocker nifedipine or by manganese. MTX induces 45Ca+ uptake in these cells in a dose-dependent mode, and the uptake is blocked with cinnarizine, nifedipine and cadmium, and is partially inhibited by manganese. MTX induces phosphoinositide breakdown in HIT cells, and the response is partially blocked by cadmium, but is not affected by nifedipine, cinnarizine or manganese. High concentrations of potassium ions also induce insulin release and calcium uptake in HIT cells. Both effects of potassium are blocked partially by nifedipine, cadmium and cinnarizine. High concentrations of potassium do not induce phosphoinositide breakdown in HIT cells. The results suggest that MTX-elicited release of insulin is attained by two mechanisms: (1) a nifedipine-sensitive action, which results from MTX-induced activation of L-type calcium channels, which can be mimicked with high potassium concentrations; and (2) a nifedipine-insensitive action, which may be initiated by the activation of phosphoinositide breakdown by MTX. Such an activation of phospholipase C would result in the formation of 1,4,5-inositol trisphosphate, a release of intracellular calcium and then release of insulin to the extracellular space. Cinnarizine is proposed to block both MTX-elicited mechanisms, the first by blockade of calcium channels and the second by blocking 1,4,5-inositol trisphosphate-induced release of internal calcium. Either mechanism alone appears capable of eliciting release of insulin

  9. 3-Phosphoinositide-dependent protein kinase-1 as an emerging target in the management of breast cancer

    International Nuclear Information System (INIS)

    It should be noted that 3-phosphoinositide-dependent protein kinase-1 (PDK1) is a protein encoded by the PDPK1 gene, which plays a key role in the signaling pathways activated by several growth factors and hormones. PDK1 is a crucial kinase that functions downstream of phosphoinositide 3-kinase activation and activates members of the AGC family of protein kinases, such as protein kinase B (Akt), protein kinase C (PKC), p70 ribosomal protein S6 kinases, and serum glucocorticoid-dependent kinase, by phosphorylating serine/threonine residues in the activation loop. AGC kinases are known to play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation, and survival. Changes in the expression and activity of PDK1 and several AGC kinases have been linked to human diseases including cancer. Recent data have revealed that the alteration of PDK1 is a critical component of oncogenic phosphoinositide 3-kinase signaling in breast cancer, suggesting that inhibition of PDK1 can inhibit breast cancer progression. Indeed, PDK1 is highly expressed in a majority of human breast cancer cell lines and both PDK1 protein and messenger ribonucleic acid are overexpressed in a majority of human breast cancers. Furthermore, overexpression of PDK1 is sufficient to transform mammary epithelial cells. PDK1 plays an essential role in regulating cell migration, especially in the context of phosphatase and tensin homologue deficiency. More importantly, downregulation of PDK1 levels inhibits migration and experimental metastasis of human breast cancer cells. Thus, targeting PDK1 may be a valuable anticancer strategy that may improve the efficacy of chemotherapeutic strategies in breast cancer patients. In this review, we summarize the evidence that has been reported to support the idea that PDK1 may be a key target in breast cancer management

  10. Cellular transcriptional profiling in influenza A virus-infected lung epithelial cells: The role of the nonstructural NS1 protein in the evasion of the host innate defense and its potential contribution to pandemic influenza

    Science.gov (United States)

    Geiss, Gary K.; Salvatore, Mirella; Tumpey, Terrence M.; Carter, Victoria S.; Wang, Xiuyan; Basler, Christopher F.; Taubenberger, Jeffery K.; Bumgarner, Roger E.; Palese, Peter; Katze, Michael G.; García-Sastre, Adolfo

    2002-08-01

    The NS1 protein of influenza A virus contributes to viral pathogenesis, primarily by enabling the virus to disarm the host cell type IFN defense system. We examined the downstream effects of NS1 protein expression during influenza A virus infection on global cellular mRNA levels by measuring expression of over 13,000 cellular genes in response to infection with wild-type and mutant viruses in human lung epithelial cells. Influenza A/PR/8/34 virus infection resulted in a significant induction of genes involved in the IFN pathway. Deletion of the viral NS1 gene increased the number and magnitude of expression of cellular genes implicated in the IFN, NF-B, and other antiviral pathways. Interestingly, different IFN-induced genes showed different sensitivities to NS1-mediated inhibition of their expression. A recombinant virus with a C-terminal deletion in its NS1 gene induced an intermediate cellular mRNA expression pattern between wild-type and NS1 knockout viruses. Most significantly, a virus containing the 1918 pandemic NS1 gene was more efficient at blocking the expression of IFN-regulated genes than its parental influenza A/WSN/33 virus. Taken together, our results suggest that the cellular response to influenza A virus infection in human lung cells is significantly influenced by the sequence of the NS1 gene, demonstrating the importance of the NS1 protein in regulating the host cell response triggered by virus infection.

  11. Effect of aging on alpha-1 adrenergic stimulation of phosphoinositide hydrolysis in various regions of rat brain

    International Nuclear Information System (INIS)

    The effects of aging were examined on the ability of alpha-1 adrenergic receptor agonists to stimulate phosphoinositide hydrolysis in three brain regions. Tissue minces of thalamus, cerebral cortex and hippocampus from 3-, 18- and 28-month-old male Fischer 344 rats were prelabeled with [3H]myoinositol. Exposure of these prelabeled minces to phenylephrine and (-)-norepinephrine revealed that accumulation of [3H]inositol phosphates was selectively reduced by 20 to 30% in the thalamus and cerebral cortex of the oldest age group. Analysis of concentration-response and competition binding curves indicated that this decrease was due to diminished agonist efficacy rather than diminished receptor affinity. The reduction in responsiveness to phenylephrine and (-)-norepinephrine in the cerebral cortex and the lack of any changes in the hippocampus parallel previously reported changes in the density of alpha-1 adrenergic receptors with aging. These data indicate that the ability of alpha-1 adrenergic receptor agonists to stimulate phosphoinositide hydrolysis is reduced in some, but not all, brain regions of aged Fischer 344 rats

  12. Possible mechanism for preterm labor associated with bacterial infection. I. Stimulation of phosphoinositide metabolism by endotoxin in endometrial fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Khan, A.A.; Imai, A.; Tamaya, T. (Gifu Univ. School of Medicine (Japan))

    1990-07-01

    Growing evidence suggests an association between intra-amniotic infection and premature initiation of parturition. We recently demonstrated that some factor(s) including endotoxin produced by the organism stimulates endogenous phospholipase A2 resulting in liberation of arachidonic acid and prostaglandin formation. The studies presented in this report were designated to evaluate the mechanism for endotoxin to stimulate phospholipase A2 using human endometrial fibroblasts. Exposure of the fibroblasts to endotoxin from Escherichia coli in the presence of ({sup 32}P) phosphate increased {sup 32}P-labeling of phosphatidic acid (PA) and phosphatidyl-inositol (PI) in a dose-dependent and a time-dependent manners. The PA labeling occurred without a measurable lag time. These findings demonstrate that the endotoxin stimulates phosphoinositide metabolism in human endometrial fibroblasts by a receptor-mediated mechanism. Membrane phosphoinositide turnover stimulated by endotoxin results in cytosolic Ca{sup 2+} increment, liberation of arachidonic acid, which may be involved in the initiation of parturition.

  13. DMPD: The p110delta subunit of phosphoinositide 3-kinase is required for thelipopolysaccharide response of mouse B cells. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available polysaccharide response of mouse B cells. Hebeis BJ, Vigorito E, Turner M. Biochem Soc Trans. 2004 Nov;32(Pt...d for thelipopolysaccharide response of mouse B cells. PubmedID 15494016 Title Th...e p110delta subunit of phosphoinositide 3-kinase is required for thelipopolysaccharide response of mouse B c

  14. A P4-ATPase protein interaction network reveals a link between aminophospholipid transport and phosphoinositide metabolism

    NARCIS (Netherlands)

    Puts, C.F.; Lenoir, G.F.; Krijgsveld, J.; WIlliamson, P.L.; Holthuis, J.C.M.

    2009-01-01

    High-throughput analysis of protein-protein interactions can provide unprecedented insight into how cellular processes are integrated at the molecular level. Yet membrane proteins are often overlooked in these studies owing to their hydrophobic nature and low abundance. Here we used a proteomics-bas

  15. Response to platelet-activating factor in human platelets stored and aged in plasma. Decrease in aggregation, phosphoinositide turnover, and receptor affinity

    International Nuclear Information System (INIS)

    Human platelet concentrates were stored in polyolefin bags at 22 to 24 degrees C on a horizontal shaker for up to 8 days. At different intervals, aliquots of platelet-rich plasma (PRP) were removed aseptically and five variables, i.e., platelet counts, morphology, platelet-activating factor (PAF)-stimulated aggregation, phosphoinositide turnover, and [3H]PAF binding to platelet receptors, were studied. The number of platelets did not change during the 8 days of storage. Scanning electron microscopy of the platelets revealed a gradual morphologic change from biconcave flat discs to irregular, crenated forms. The PAF-induced aggregation of platelets declined with time of storage. A decrease to 50 percent of the Day 1 aggregatory response to PAF was evident on Day 2, and there was a further decline to about 20 percent by Day 6. Similarly, PAF receptor-coupled phosphoinositide turnover, as monitored by 32P incorporation into individual phosphoinositides, decreased dramatically with storage. After 2 to 3 days of storage, the phosphoinositide turnover was reduced to 50 percent of the original response, and it continued to decline to about 25 percent of original response by Day 5 or 6. The binding of [3H]PAF to washed human platelets indicated subtle changes between Days 2 and 4, which became more noticeable by Day 6. These results have raised the possibility of changes in the number of the receptors and/or their affinity for the ligand during storage. We conclude that although the number of platelets was maintained during storage for 8 days, a general deterioration of their responses to PAF occurred at the levels of cell surface receptor, transmembrane signaling (phosphoinositide turnover), and response (aggregation)

  16. Emodin negatively affects the phosphoinositide 3-kinase/AKT signalling pathway: a study on its mechanism of action

    DEFF Research Database (Denmark)

    Olsen, Birgitte B; Bjørling-Poulsen, Marina; Guerra, Barbara

    2007-01-01

    The development of selective cell-permeable inhibitors of protein kinases whose aberrant activation contributes to cell transformation is a promising approach in cancer treatment. Emodin is a natural anthraquinone derivative that exhibits anti-proliferative effects in various cancer cell lines by...... efficient induction of apoptosis. The phosphoinositide 3-kinase (PI3K)/AKT pathway has been shown to be central in the promotion of cell survival since the alteration of this signalling cascade is a frequent event in human malignancies. Previous published results indicated that treatment of cells with...... mechanism by which emodin exerts anti-cancer activity and suggest the further investigation of plant polyphenols, such as emodin, as therapeutic and preventive agents for cancer therapy....

  17. Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Medina, Jesus R.; Becker, Christopher J.; Blackledge, Charles W.; Duquenne, Celine; Feng, Yanhong; Grant, Seth W.; Heerding, Dirk; Li, William H.; Miller, William H.; Romeril, Stuart P.; Scherzer, Daryl; Shu, Arthur; Bobko, Mark A.; Chadderton, Antony R.; Dumble, Melissa; Gardiner, Christine M.; Gilbert, Seth; Liu, Qi; Rabindran, Sridhar K.; Sudakin, Valery; Xiang, Hong; Brady, Pat G.; Campobasso, Nino; Ward, Paris; Axten, Jeffrey M. (GSKPA)

    2014-10-02

    Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.

  18. 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.

  19. 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

  20. 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.

  1. 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 ...

  2. 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...

  3. Inhibitory Effects of Isoquinoline Alkaloid Berberine on Ischemia-Induced Apoptosis via Activation of Phosphoinositide 3-Kinase/Protein Kinase B Signaling Pathway

    OpenAIRE

    Kim, Mia; Shin, Mal Soon; Lee, Jae Min; Cho, Han Sam; Kim, Chang Ju; Kim, Young Joon; Choi, Hey Ran; Jeon, Jung Won

    2014-01-01

    Purpose Berberine is a type of isoquinoline alkaloid that has been used to treat various diseases. A neuroprotective effect of berberine against cerebral ischemia has been reported; however, the effects of berberine on apoptosis in relation to reactive astrogliosis and microglia activation under ischemic conditions have not yet been fully evaluated. In the present study, we investigated the effects of berberine on global ischemia-induced apoptosis, and focused on the phosphoinositide 3-kinase...

  4. Ligand-based pharmacophore modeling; atom-based 3D-QSAR analysis and molecular docking studies of phosphoinositide-dependent kinase-1 inhibitors

    Directory of Open Access Journals (Sweden)

    P Kirubakaran

    2012-01-01

    Full Text Available Phosphoinositide-dependent kinase-1 plays a vital role in the PI3-kinase signaling pathway that regulates gene expression, cell cycle growth and proliferation. The common human cancers include lung, breast, blood and prostate possess over stimulation of the phosphoinositide-dependent kinase-1 signaling and making phosphoinositide-dependent kinase-1 an interesting therapeutic target in oncology. A ligand-based pharmacophore and atom-based 3D-QSAR studies were carried out on a set of 82 inhibitors of PDK1. A six point pharmacophore with two hydrogen bond acceptors (A, three hydrogen bond donors (D and one hydrophobic group (H was obtained. The pharmacophore hypothesis yielded a 3D-QSAR model with good partial least square statistics results. The training set correlation is characterized by partial least square factors (R2 = 0.9557, SD = 0.2334, F = 215.5, P = 1.407e-32. The test set correlation is characterized by partial least square factors (Q2 ext = 0.7510, RMSE = 0.5225, Pearson-R =0.8676. The external validation indicated that our QSAR model possess high predictive power with good value of 0.99 and value of 0.88. The docking results show the binding orientations of these inhibitors at active site amino acid residues (Ala162, Thr222, Glu209 and Glu166 of phosphoinositide-dependent kinase-1 protein. The binding free energy interactions of protein-ligand complex have been calculated, which plays an important role in molecular recognition and drug design approach.

  5. Opposing effects of a ras oncogene on growth factor-stimulated phosphoinositide hydrolysis: desensitization to platelet-derived growth factor and enhanced sensitivity to bradykinin

    International Nuclear Information System (INIS)

    Expression of a transforming Harvey or Kirsten ras gene caused opposing effects in the ability of platelet-derived growth factor (PDGF) and bradyknin to activate phospholipase C-mediated phosphoinositide hydrolysis. In [3H]inositol-labeled rat-1 fibroblasts, PDGF resulted in a 2-fold increase in the level of [3H]inositol trisphosphate (InsP3) after 2 min and, in the presence of LiCl, a 3- to 8-fold increase in the level of [3H]inositol monophosphate (InsP1) after 30 min. However, in EJ-ras-transfected rat-1 cells, which exhibit near normal levels of PDGF receptors, PDGF resulted in little or no accumulation of either [3H]InsP3 or [3H]InsP1. Similarly, marked stimulations by PDGF were observed in NIH 3T3 cells, as well as in v-src-transformed 3T3 cells, but not in 3T3 cells transformed by Kirsten sarcoma virus or by transfection with v-Ha-ras DNA. This diminished phosphoinositide response in ras-transformed cells was associated with a markedly attenuated mitogenic response to PDGF. On the other hand, both phosphoinositide metabolism and DNA synthesis in ras-transformed fibroblasts were stimulated several-fold by serum. In NIH 3T3 cells carrying a glucocorticoid-inducible v-Ha-ras gene, a close correlation was found between the expression of p21/sup ras/ and the loss of PDGF-stimulated [3H]InsP1 accumulation. The authors propose that a ras gene product (p21) can, directly or indirectly, influence growth factor-stimulated phosphoinositide hydrolysis, as well as DNA synthesis, via alterations in the properties of specific growth factor receptors

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. rSac3,a novel Sac domain phosphoinositide phosphatase,promotes neurite outgrowth in PC12 cells

    Institute of Scientific and Technical Information of China (English)

    Yiyuan Yuan; Xiang Gao; Ning Guo; Hui Zhang; Zhiqin Xie; Meilei Jin; Baoming Li; Lei yu; Naihe Jing

    2007-01-01

    Sac domain-containing proteins belong to a newly identified family of phosphoinositide phosphatases(the PIPPase family).Despite well-characterized enzymatic activity,the biological functions of this mammalian Sac domain PIPPase family remain largely unknown.We identified a novel Sac domain-containing protein,rat Sac3(rSac3),which iS widely expressed in various tissues and localized to the endoplasmic reticulum,Golgi complex and recycling endosomes.rSac3 displays PIPPase activity with PI(3)P,PI(4)P and PI(3,5)P2 as substrates in vitro,and a mutation in the catalytic core of the Sac domain abolishes its enzymatic activity.The expression of rSac3 iS upregulated during nerve growth factor (NGF)-stimulated PC12 cell neuronal differentiation,and overexpression of this protein promotes neurite outgrowth in PC12 cells.Conversely,inhibition of rSac3 expression by antisense oligonucleotides reduces neurite outgrowth of NGFstimulated PC12 cells,and the active site mutation of rSac3 eliminates its neurite-outgrowth-promoting activity.These results indicate that rSac3 promotes neurite outgrowth in differentiating neurons through its PIPPase activity,suggesting that Sac domain PIPPase proteins may participate in forward membrane trafficking from the endoplasmic reticulum and Golgi complex to the plasma membrane,and may function as regulators of this crucial process of neuronal cell growth and differentiation.

  12. Propofol pretreatment attenuates lipopolysaccharide-induced acute lung injury in rats by activating the phosphoinositide-3-kinase/Akt pathway

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the effect of propofol pretreatment on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway in this procedure. Survival was determined 48 h after LPS injection. At 1 h after LPS challenge, the lung wet- to dry-weight ratio was examined, and concentrations of protein, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method or ELISA. Lung injury was assayed via lung histological examination. PI3K and p-Akt expression levels in the lung tissue were determined by Western blotting. Propofol pretreatment prolonged survival, decreased the concentrations of protein, TNF-α, and IL-6 in BALF, attenuated ALI, and increased PI3K and p-Akt expression in the lung tissue of LPS-challenged rats, whereas treatment with wortmannin, a PI3K/Akt pathway specific inhibitor, blunted this effect. Our study indicates that propofol pretreatment attenuated LPS-induced ALI, partly by activation of the PI3K/Akt pathway

  13. Propofol pretreatment attenuates lipopolysaccharide-induced acute lung injury in rats by activating the phosphoinositide-3-kinase/Akt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, L.L. [Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province (China); Hu, G.C. [Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL (United States); Zhu, S.S. [Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province (China); Li, J.F. [Department of Anesthesiology, Tengzhou Central People' s Hospital, Liaocheng, Shandong Province (China); Liu, G.J. [Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province (China)

    2014-10-14

    The aim of this study was to investigate the effect of propofol pretreatment on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway in this procedure. Survival was determined 48 h after LPS injection. At 1 h after LPS challenge, the lung wet- to dry-weight ratio was examined, and concentrations of protein, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method or ELISA. Lung injury was assayed via lung histological examination. PI3K and p-Akt expression levels in the lung tissue were determined by Western blotting. Propofol pretreatment prolonged survival, decreased the concentrations of protein, TNF-α, and IL-6 in BALF, attenuated ALI, and increased PI3K and p-Akt expression in the lung tissue of LPS-challenged rats, whereas treatment with wortmannin, a PI3K/Akt pathway specific inhibitor, blunted this effect. Our study indicates that propofol pretreatment attenuated LPS-induced ALI, partly by activation of the PI3K/Akt pathway.

  14. Phosphoinositide 3-kinase dependent inhibition as a broad basis for opponent coding in Mammalian olfactory receptor neurons.

    Directory of Open Access Journals (Sweden)

    Kirill Ukhanov

    Full Text Available Phosphoinositide 3-kinase (PI3K signaling has been implicated in mediating inhibitory odorant input to mammalian olfactory receptor neurons (ORNs. To better understand the breadth of such inhibition in odor coding, we screened a panel of odorants representing different chemical classes, as well as odorants known to occur in a natural odor object (tomato, for their ability to rapidly activate PI3K-dependent inhibitory signaling. Odorants were screened on dissociated native rat ORNs before and after pre-incubation with the PI3K-isoform specific blockers AS252424 and TGX221. Many different odorants increased their excitatory strength for particular ORNs following PI3K blockade in a manner consistent with activating PI3K-dependent inhibitory signaling in those cells. The PI3K-dependent inhibitory odorants overlapped with conventional excitatory odorants, but did not share the same bias, indicating partial partitioning of the odor space. Finding that PI3K-dependent inhibition can be activated by a wide range of otherwise conventional excitatory odorants strongly implies PI3K-dependent inhibition provides a broad basis for opponent coding in mammalian ORNs.

  15. Expression analysis of a stress-related phosphoinositide-specific phospholipase C gene in wheat (Triticum aestivum L..

    Directory of Open Access Journals (Sweden)

    Ke Zhang

    Full Text Available Plant phosphoinositide-specific phospholipases C (PI-PLCs function in several essential plant processes associated with either development or environmental stress. In this report, we examined the expression patterns of TaPLC1 under drought and high salinity stress at the transcriptional and post-transcriptional levels. TaPLC1 mRNA was expressed in all wheat organs examined. U73122 and edelfosine, the PLC inhibitor, impaired seedling growth and enhanced seedling sensitivity to drought and high salinity stress. Though TaPLC1 expression in wheat was lowest at the seedling stage, it was strongly induced under conditions of stress. When 6-day-old wheat seedlings were treated with 200 mM NaCl or 20% (w/v PEG 6000 for 6 or 12 h, respectively, the TaPLC1 transcript level increased by 16-fold compared to the control. Western blotting showed that the TaPLC protein concentration was also maintained at a high level from 24 to 48 h during stress treatment. Together, our results indicate the possible biological functions of TaPLC1 in regulating seedling growth and the response to drought and salinity stress.

  16. Phosphoinositides in Ca(2+) signaling and excitation-contraction coupling in skeletal muscle: an old player and newcomers.

    Science.gov (United States)

    Csernoch, Laszlo; Jacquemond, Vincent

    2015-12-01

    Since the postulate, 30 years ago, that phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2) as the precursor of inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3) would be critical for skeletal muscle excitation-contraction (EC) coupling, the issue of whether phosphoinositides (PtdInsPs) may have something to do with Ca(2+) signaling in muscle raised limited interest, if any. In recent years however, the PtdInsP world has expanded considerably with new functions for PtdIns(4,5)P 2 but also with functions for the other members of the PtdInsP family. In this context, the discovery that genetic deficiency in a PtdInsP phosphatase has dramatic consequences on Ca(2+) homeostasis in skeletal muscle came unanticipated and opened up new perspectives in regards to how PtdInsPs modulate muscle Ca(2+) signaling under normal and disease conditions. This review intends to make an update of the established, the questioned, and the unknown regarding the role of PtdInsPs in skeletal muscle Ca(2+) homeostasis and EC coupling, with very specific emphasis given to Ca(2+) signals in differentiated skeletal muscle fibers. PMID:26377756

  17. 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…

  18. 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.)

  19. 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)

  20. Cellular tolerance to pulsed heating

    Science.gov (United States)

    Simanovski, Dimitrii; Sarkar, M.; Irani, A.; O'Connell-Rodwell, C.; Contag, C.; Schwettman, H. Alan; Palanker, D.

    2005-04-01

    Many laser therapies involve significant heating of tissue with pulses varying from picoseconds to minutes in duration. In some of the applications heating is a primary goal, while in others it is an undesirable side effect. In both cases, if a hyperthermia is involved, the knowledge about the threshold temperature leading to irreversible cellular damage is critically important. We study the dependence of the threshold temperature on duration of the heat exposure in the range of 0.3 ms to 5 seconds. Thin layer of cells cultured in a Petri dish was exposed to a pulsed CO2 laser radiation. Laser beam was focused onto sample providing Gaussian intensity distribution in the focal plane with a beam diameter (2w) 2-10 mm. Surface temperature in the central part of the focal spot (1mm in diameter) was measured by thermal infrared (IR) emission from the sample, recorded with a fast IR detector. For pulses shorter than 1 s the temperature profile across the focal spot was found to closely correspond to the radial distribution of the laser beam intensity, thus allowing for accurate determination of temperature at any given distance from the center of the spot. Immediate cellular damage was assessed using vital staining with the live/dead fluorescent assay. Threshold temperatures were found to vary from 65 °C at 5 s of heating to 160 °C at pulses of 0.3 ms in duration. The shorter end of this range was limited by vaporization, which occurs during the laser pulse and results in mechanical damage to cells. Dependence of the maximal temperature on pulse duration could be approximated by Arrhenius law with activation energy being about 1 eV.

  1. 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 ...

  2. 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

  3. 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...

  4. 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.

  5. 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

  6. Analysis of cellular phosphatidylinositol (3,4,5)-trisphosphate levels and distribution using confocal fluorescent microscopy.

    Science.gov (United States)

    Palmieri, Michelle; Nowell, Cameron J; Condron, Melanie; Gardiner, James; Holmes, Andrew B; Desai, Jayesh; Burgess, Antony W; Catimel, Bruno

    2010-11-01

    We have developed an immunocytochemistry method for the semiquantitative detection of phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3) at the cell plasma membrane. This protocol combines the use of a glutathione S-transferase-tagged pleckstrin homology (PH) domain of the general phosphoinositides-1 receptor (GST-GRP1PH) with fluorescence confocal microscopy and image segmentation using cell mask software analysis. This methodology allows the analysis of PI(3,4,5)P3 subcellular distribution in resting and epidermal growth factor (EGF)-stimulated HEK293T cells and in LIM1215 (wild-type phosphoinositide 3-kinase (PI3K)) and LIM2550 (H1047R mutation in PI3K catalytic domain) colonic carcinoma cells. Formation of PI(3,4,5)P3 was observed 5min following EGF stimulation and resulted in an increase of the membrane/cytoplasm fluorescence ratio from 1.03 to 1.53 for HEK293T cells and from 2.2 to 3.3 for LIM1215 cells. Resting LIM2550 cells stained with GST-GRP1PH had an elevated membrane/cytoplasm fluorescence ratio of 9.8, suggesting constitutive PI3K activation. The increase in the membrane/cytoplasm fluorescent ratio was inhibited in a concentration-dependent manner by the PI3K inhibitor LY294002. This cellular confocal imaging assay can be used to directly assess the effects of PI3K mutations in cancer cell lines and to determine the potential specificity and effectiveness of PI3K inhibitors in cancer cells. PMID:20599646

  7. The role of phosphoinositide 3-kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions.

    Science.gov (United States)

    O'Neil, T K; Duffy, L R; Frey, J W; Hornberger, T A

    2009-07-15

    Resistance exercise induces a hypertrophic response in skeletal muscle and recent studies have begun to shed light on the molecular mechanisms involved in this process. For example, several studies indicate that signalling by the mammalian target of rapamycin (mTOR) is necessary for a hypertrophic response. Furthermore, resistance exercise has been proposed to activate mTOR signalling through an upstream pathway involving the phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB); however, this hypothesis has not been thoroughly tested. To test this hypothesis, we first evaluated the temporal pattern of signalling through PI3K-PKB and mTOR following a bout of resistance exercise with eccentric contractions (EC). Our results indicated that the activation of signalling through PI3K-PKB is a transient event (12 h). Furthermore, inhibition of PI3K-PKB activity did not prevent the activation of mTOR signalling by ECs, indicating that PI3K-PKB is not part of the upstream regulatory pathway. These observations led us to investigate an alternative pathway for the activation of mTOR signalling involving the synthesis of phosphatidic acid (PA) by phospholipase D (PLD). Our results demonstrate that ECs induce a sustained elevation in [PA] and inhibiting the synthesis of PA by PLD prevented the activation of mTOR. Furthermore, we determined that similar to ECs, PA activates mTOR signalling through a PI3K-PKB-independent mechanism. Combined, the results of this study indicate that the activation of mTOR following eccentric contractions occurs through a PI3K-PKB-independent mechanism that requires PLD and PA. PMID:19470781

  8. ATP-evoked Ca2+ mobilization and prostanoid release from astrocytes: P2-purinergic receptors linked to phosphoinositide hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Pearce, B.; Murphy, S.; Jeremy, J.; Morrow, C.; Dandona, P.

    1989-03-01

    Astrocyte cultures prelabelled with either (3H)inositol or 45Ca2+ were exposed to ATP and its hydrolysis products. ATP and ADP, but not AMP and adenosine, produced increases in the accumulation of intracellular 3H-labelled inositol phosphates (IP), efflux of 45Ca2+, and release of thromboxane A2 (TXA2). Whereas ATP-stimulated 3H-IP accumulation was unaffected, its ability to promote TXA2 release was markedly reduced by mepacrine, an inhibitor of phospholipase A2 (PLA2). ATP-evoked 3H-IP production was also spared following treatment with the cyclooxygenase inhibitor, indomethacin. We conclude that ATP-induced phosphoinositide (PPI) breakdown and 45Ca2+ mobilization occurred in parallel with, if not preceded, the release of TXA2. Following depletion of intracellular Ca2+ with a brief preexposure to ATP in the absence of extracellular Ca2+, the release of TXA2 in response to a subsequent ATP challenge was greatly reduced when compared with control. These results suggest that mobilization of cytosolic Ca2+ may be the stimulus for PLA2 activation and, thus, TXA2 release. Stimulation of alpha 1-adrenoceptors also caused PPI breakdown and 45Ca2+ efflux but not TXA2 release. The effects of ATP and noradrenaline (NA) on 3H-IP accumulation were additive, but their combined ability to increase 45Ca2+ efflux was not. Interestingly, in the presence of NA, ATP-stimulated TXA2 release was reduced. Our data provide evidence that functional P2-purinergic receptors are present on astrocytes and that ATP is the first physiologically relevant stimulus found to initiate prostanoid release from these cells.

  9. The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide kinase inhibitor PP121

    International Nuclear Information System (INIS)

    Here we explored the potential effect of PP121, a novel dual inhibitor of tyrosine and phosphoinositide kinases, against human esophageal cancer cells. We showed that PP121 exerted potent cytotoxic effect in primary (patient-derived) and established (Eca-109, TE-1 and TE-3 lines) esophageal cancer cells, possibly through activating caspase-3-dependnent apoptosis. PP121 was, however, non-cytotoxic to the normal human esophageal epithelial cells (EECs). At the molecular level, we showed that PP121 blocked Akt-mTOR (mammalian target of rapamycin) activation in esophageal cancer cells, which was restored by introducing a constitutively-active Akt (CA-Akt). Yet, CA-Akt only partly inhibited cytotoxicity by PP121 in Eca-109 cells. Importantly, we showed that PP121 inhibited nuclear factor kappa B (NFκB) signaling activation in esophageal cancer cells, which appeared independent of Akt-mTOR blockage. In vivo, oral administration of PP121 remarkably inhibited Eca-109 xenograft growth in nude mice, and significantly improved mice survival. Further, the immunohistochemistry (IHC) and Western blot assays analyzing xenografted tumors showed that PP121 inhibited Akt-mTOR and NFκB activations in vivo. Together, we demonstrate that PP121 potently inhibits esophageal cancer cells in vitro and in vivo, possibly through concurrently inhibiting Akt-mTOR and NFκB signalings. - Highlights: • PP121 is cytotoxic against primary and established esophageal cancer cells. • PP121 induces caspase-3-dependnent apoptosis in esophageal cancer cells. • PP121 blocks Akt-mTOR activation in esophageal cancer cells. • PP121 inhibits NFκB activation, independent of Akt-mTOR blockage. • PP121 inhibits Eca-109 xenograft growth and Akt-mTOR/NFκB activation in vivo

  10. Leptin Regulated Insulin Secretion via Stimulating IRS2-associated Phosphoinositide 3-kinase Activity in the isolated Rat Pancreatic Islets

    Institute of Scientific and Technical Information of China (English)

    袁莉; 安汉祥; 李卓娅; 邓秀玲

    2003-01-01

    To investigate the molecular mechanism of leptin regulating insulin secretion through determining the regulation of insulin secretion and the insulin receptor substrate (IRS)-2-associated phosphoinositide 3-kinase (PI3K) activity by leptin in the isolated rat pancreatic islets, pancreatic islets were isolated from male SD rats by the collagenase method. The purified islets were incubated with leptin 2 nmol/L for 1 h in the presence of 5.6 mmol/L or 11.1 mmol/L glucose. Insulin release was measured using radioimmunoassay. IRS-2-associated activity of PI3K was determined by immunoprecipitate assay and Western blot. The results showed that in the presence of 5.6 mmol/L glucose, leptin had no significant effect on both insulin secretion and IRS-2-associated PI3K activity, but in the presence of 11.1 mmol/L glucose, insulin release was significantly inhibited after the islets were exposed to leptin for 1 h (P<0. 01). PI3K inhibitor wortmannin blocked the inhibitory regulation of leptin on insulin release (P<0. 05). Western Blot assay revealed that 2 nmol/L leptin could significantly increase the IRS-2-associated activity of PI3K by 51.5 % (P<0. 05) in the presence of 11.1 mmol/L glucose. It was concluded that Leptin could significantly inhibit insulin secretion in the presence of 11.1 mmol/L glucose by stimulating IRS-2-associated activity of PI3K, which might be the molecular mechanism of leptin regulating insulin secretion.

  11. Dual 4- and 5-phosphatase activities regulate SopB-dependent phosphoinositide dynamics to promote bacterial entry.

    Science.gov (United States)

    Piscatelli, Heather L; Li, Menghan; Zhou, Daoguo

    2016-05-01

    Salmonella are able to invade non-phagocytic cells such as intestinal epithelial cells by modulating the host actin cytoskeleton to produce membrane ruffles. Two type III effector proteins SopB and SopE play key roles to this modulation. SopE is a known guanine nucleotide exchange factor (GEF) capable of activating Rac1 and CDC42. SopB is a phosphatidylinositol 4-phosphatase and 5-phosphatase promoting membrane ruffles and invasion of Salmonella through undefined mechanisms. Previous studies have demonstrated that the 4-phosphatase activity of SopB is required for PtdIns-3-phosphate (PtdIns(3)P) accumulation and SopB-mediated invasion. We show here that both the 4-phosphatase as well as the 5-phosphatase activities of SopB are essential in ruffle formation and subsequent invasion. We found that the 5-phosphatase activity of SopB is likely responsible for generating PtdIns-3,4-bisphosphate (PtdIns(3,4)P2 ) and subsequent recruitment of sorting nexin 9 (SNX9), an actin modulating protein. Intriguingly, the 4-phosphatase activity is responsible for the dephosphorylation of PtdIns(3,4)P2 into PtdIns(3)P. Alone, neither activity is sufficient for ruffling but when acting in conjunction with one another, the 4-phosphatase and 5-phosphatase activities led to SNX9-mediated ruffling and Salmonella invasion. This work reveals the unique ability of bacterial effector protein SopB to utilize both its 4- and 5-phosphatase activities to regulate phosphoinositide dynamics to promote bacterial entry. PMID:26537021

  12. The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide kinase inhibitor PP121

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Yi; Zhou, Yajuan [Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan 430071 (China); Cheng, Long [Department of Interventional Radiology, the Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215001 (China); Hu, Desheng; Zhou, Xiaoyi; Wang, Zhaohua [Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan 430071 (China); Xie, Conghua, E-mail: chxie_65@hotmail.com [Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Zhou, Fuxiang, E-mail: ZhouFuxiangwuhan@126.com [Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China)

    2015-09-11

    Here we explored the potential effect of PP121, a novel dual inhibitor of tyrosine and phosphoinositide kinases, against human esophageal cancer cells. We showed that PP121 exerted potent cytotoxic effect in primary (patient-derived) and established (Eca-109, TE-1 and TE-3 lines) esophageal cancer cells, possibly through activating caspase-3-dependnent apoptosis. PP121 was, however, non-cytotoxic to the normal human esophageal epithelial cells (EECs). At the molecular level, we showed that PP121 blocked Akt-mTOR (mammalian target of rapamycin) activation in esophageal cancer cells, which was restored by introducing a constitutively-active Akt (CA-Akt). Yet, CA-Akt only partly inhibited cytotoxicity by PP121 in Eca-109 cells. Importantly, we showed that PP121 inhibited nuclear factor kappa B (NFκB) signaling activation in esophageal cancer cells, which appeared independent of Akt-mTOR blockage. In vivo, oral administration of PP121 remarkably inhibited Eca-109 xenograft growth in nude mice, and significantly improved mice survival. Further, the immunohistochemistry (IHC) and Western blot assays analyzing xenografted tumors showed that PP121 inhibited Akt-mTOR and NFκB activations in vivo. Together, we demonstrate that PP121 potently inhibits esophageal cancer cells in vitro and in vivo, possibly through concurrently inhibiting Akt-mTOR and NFκB signalings. - Highlights: • PP121 is cytotoxic against primary and established esophageal cancer cells. • PP121 induces caspase-3-dependnent apoptosis in esophageal cancer cells. • PP121 blocks Akt-mTOR activation in esophageal cancer cells. • PP121 inhibits NFκB activation, independent of Akt-mTOR blockage. • PP121 inhibits Eca-109 xenograft growth and Akt-mTOR/NFκB activation in vivo.

  13. Pulmonary administration of phosphoinositide 3-kinase inhibitor is a curative treatment for chronic obstructive pulmonary disease by alveolar regeneration.

    Science.gov (United States)

    Horiguchi, Michiko; Oiso, Yuki; Sakai, Hitomi; Motomura, Tomoki; Yamashita, Chikamasa

    2015-09-10

    Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease, causing widespread and irreversible alveoli collapse. The discovery of a low-molecular-weight compound that induces regeneration of pulmonary alveoli is of utmost urgency to cure intractable pulmonary diseases such as COPD. However, a practically useful compound for regenerating pulmonary alveoli is yet to be reported. Previously, we have elucidated that Akt phosphorylation is involved in a differentiation-inducing molecular mechanism of human alveolar epithelial stem cells, which play a role in regenerating pulmonary alveoli. In the present study, we directed our attention to phosphoinositide 3-kinase (PI3K)-Akt signaling and examined whether PI3K inhibitors display the pulmonary alveolus regeneration. Three PI3K inhibitors with different PI3K subtype specificities (Wortmannin, AS605240, PIK-75 hydrochloride) were tested for the differentiation-inducing effect on human alveolar epithelial stem cells, and Wortmannin demonstrated the most potent differentiation-inducing activity. We evaluated Akt phosphorylation in pulmonary tissues of an elastase-induced murine COPD model and found that Akt phosphorylation in the pulmonary tissue was enhanced in the murine COPD model compared with normal mice. Then, the alveolus-repairing effect of pulmonary administration of Wortmannin to murine COPD model was evaluated using X-ray CT analysis and hematoxylin-eosin staining. As a result, alveolar damages were repaired in the Wortmannin-administered group to a similar level of normal mice. Furthermore, pulmonary administration of Wortmannin induced a significant recovery of the respiratory function, compared to the control group. These results indicate that Wortmannin is capable of inducing differentiation of human alveolar epithelial stem cells and represents a promising drug candidate for curative treatment of pulmonary alveolar destruction in COPD. PMID:26160307

  14. Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Van Aller, Glenn S., E-mail: glenn.s.van.aller@gsk.com [Department of Cancer Research, GlaxoSmithKline, Collegeville, PA 19426 (United States); Carson, Jeff D. [Department of Cancer Research, GlaxoSmithKline, Collegeville, PA 19426 (United States); Tang, Wei; Peng, Hao; Zhao, Lin [Discovery Biology, BioDuro, No. 29 Life Science Park Road, Changping, Beijing (China); Copeland, Robert A.; Tummino, Peter J. [Department of Cancer Research, GlaxoSmithKline, Collegeville, PA 19426 (United States); Luo, Lusong [Discovery Biology, BioDuro, No. 29 Life Science Park Road, Changping, Beijing (China)

    2011-03-11

    Research highlights: {yields} Epigallocatechin-3-gallate (EGCG) is an ATP-competitive inhibitor of PI3K and mTOR with Ki values around 300 nM. {yields} EGCG inhibits cell proliferation and AKT phosphorylation at Ser473 in MDA-MB-231and A549 cells. {yields} Molecular docking studies show that EGCG binds well to the PI3K kinase domain active site. {yields} These results suggest another important molecular mechanism for the anticancer activities of EGCG. -- Abstract: The PI3K signaling pathway is activated in a broad spectrum of human cancers, either directly by genetic mutation or indirectly via activation of receptor tyrosine kinases or inactivation of the PTEN tumor suppressor. The key nodes of this pathway have emerged as important therapeutic targets for the treatment of cancer. In this study, we show that (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea, is an ATP-competitive inhibitor of both phosphoinositide-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with K{sub i} values of 380 and 320 nM respectively. The potency of EGCG against PI3K and mTOR is within physiologically relevant concentrations. In addition, EGCG inhibits cell proliferation and AKT phosphorylation at Ser473 in MDA-MB-231 and A549 cells. Molecular docking studies show that EGCG binds well to the PI3K kinase domain active site, agreeing with the finding that EGCG competes for ATP binding. Our results suggest another important molecular mechanism for the anticancer activities of EGCG.

  15. Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor

    International Nuclear Information System (INIS)

    Research highlights: → Epigallocatechin-3-gallate (EGCG) is an ATP-competitive inhibitor of PI3K and mTOR with Ki values around 300 nM. → EGCG inhibits cell proliferation and AKT phosphorylation at Ser473 in MDA-MB-231and A549 cells. → Molecular docking studies show that EGCG binds well to the PI3K kinase domain active site. → These results suggest another important molecular mechanism for the anticancer activities of EGCG. -- Abstract: The PI3K signaling pathway is activated in a broad spectrum of human cancers, either directly by genetic mutation or indirectly via activation of receptor tyrosine kinases or inactivation of the PTEN tumor suppressor. The key nodes of this pathway have emerged as important therapeutic targets for the treatment of cancer. In this study, we show that (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea, is an ATP-competitive inhibitor of both phosphoinositide-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with Ki values of 380 and 320 nM respectively. The potency of EGCG against PI3K and mTOR is within physiologically relevant concentrations. In addition, EGCG inhibits cell proliferation and AKT phosphorylation at Ser473 in MDA-MB-231 and A549 cells. Molecular docking studies show that EGCG binds well to the PI3K kinase domain active site, agreeing with the finding that EGCG competes for ATP binding. Our results suggest another important molecular mechanism for the anticancer activities of EGCG.

  16. Up-regulation of phosphoinositide metabolism in tobacco cells constitutively expressing the human type I inositol polyphosphate 5-phosphatase

    Science.gov (United States)

    Perera, Imara Y.; Love, John; Heilmann, Ingo; Thompson, William F.; Boss, Wendy F.; Brown, C. S. (Principal Investigator)

    2002-01-01

    To evaluate the impact of suppressing inositol 1,4,5-trisphosphate (InsP(3)) in plants, tobacco (Nicotiana tabacum) cells were transformed with the human type I inositol polyphosphate 5-phosphatase (InsP 5-ptase), an enzyme which specifically hydrolyzes InsP(3). The transgenic cell lines showed a 12- to 25-fold increase in InsP 5-ptase activity in vitro and a 60% to 80% reduction in basal InsP(3) compared with wild-type cells. Stimulation with Mas-7, a synthetic analog of the wasp venom peptide mastoparan, resulted in an approximately 2-fold increase in InsP(3) in both wild-type and transgenic cells. However, even with stimulation, InsP(3) levels in the transgenic cells did not reach wild-type basal values, suggesting that InsP(3) signaling is compromised. Analysis of whole-cell lipids indicated that phosphatidylinositol 4,5-bisphosphate (PtdInsP(2)), the lipid precursor of InsP(3), was greatly reduced in the transgenic cells. In vitro assays of enzymes involved in PtdInsP(2) metabolism showed that the activity of the PtdInsP(2)-hydrolyzing enzyme phospholipase C was not significantly altered in the transgenic cells. In contrast, the activity of the plasma membrane PtdInsP 5 kinase was increased by approximately 3-fold in the transgenic cells. In vivo labeling studies revealed a greater incorporation of (32)P into PtdInsP(2) in the transgenic cells compared with the wild type, indicating that the rate of PtdInsP(2) synthesis was increased. These studies show that the constitutive expression of the human type I InsP 5-ptase in tobacco cells leads to an up-regulation of the phosphoinositide pathway and highlight the importance of PtdInsP(2) synthesis as a regulatory step in this system.

  17. 3-Phosphoinositide-dependent Protein Kinase-1 (PDK1) promotes invasion and activation of matrix metalloproteinases

    International Nuclear Information System (INIS)

    Metastasis is a major cause of morbidity and mortality in breast cancer with tumor cell invasion playing a crucial role in the metastatic process. PDK1 is a key molecule that couples PI3K to cell proliferation and survival signals in response to growth factor receptor activation, and is oncogenic when expressed in mouse mammary epithelial cells. We now present evidence showing that PDK1-expressing cells exhibit enhanced anchorage-dependent and -independent cell growth and are highly invasive when grown on Matrigel. These properties correlate with induction of MMP-2 activity, increased MT1-MMP expression and a unique gene expression profile. Invasion assays in Matrigel, MMP-2 zymogram analysis, gene microarray analysis and mammary isografts were used to characterize the invasive and proliferative function of cells expressing PDK1. Tissue microarray analysis of human breast cancers was used to measure PDK1 expression in invasive tumors by IHC. Enhanced invasion on Matrigel in PDK1-expressing cells was accompanied by increased MMP-2 activity resulting from stabilization against proteasomal degradation. Increased MMP-2 activity was accompanied by elevated levels of MT1-MMP, which is involved in generating active MMP-2. Gene microarray analysis identified increased expression of the ECM-associated genes decorin and type I procollagen, whose gene products are substrates of MT1-MMP. Mammary fat pad isografts of PDK1-expressing cells produced invasive adenocarcinomas. Tissue microarray analysis of human invasive breast cancer indicated that PDK1pSer241 was strongly expressed in 90% of samples. These results indicate that PDK1 serves as an important effector of mammary epithelial cell growth and invasion in the transformed phenotype. PDK1 mediates its effect in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and collagen. The presence of increased PDK1 expression in the majority of invasive breast cancers suggests its

  18. Cultural Diagnosis: An Empirical Investigation of Cellular Industry of Pakistan

    Directory of Open Access Journals (Sweden)

    Qamar Ali

    2011-11-01

    Full Text Available This study describes research in five cellular companies operating in Pakistan, aimed at identifying their current and preferred organizational culture. Using Quinn and Rohrbaugh (1983 competing values framework, the overall cultural profiles and dominant characteristics of the organizations and industry are determined through a personally administered survey employing the Organizational Culture Assessment Instrument (OCAI. The results indicate that hierarchy culture is dominating in cellular industry, whereas the clan is found to be the most preferred cultural archetype in majority of cellular companies. This indicates a misalignment between what employees think is needed and what is perceived to exist.

  19. Subtype-specific regulation of P2X3 and P2X2/3 receptors by phosphoinositides in peripheral nociceptors

    Directory of Open Access Journals (Sweden)

    Logothetis Diomedes

    2009-08-01

    Full Text Available Abstract Background P2X3 and P2X2/3 purinergic receptor-channels, expressed in primary sensory neurons that mediate nociception, have been implicated in neuropathic and inflammatory pain responses. The phospholipids phosphatidylinositol 4,5-bisphosphate (PIP2 and phosphatidylinositol 3,4,5-trisphosphate (PIP3 are involved in functional modulation of several types of ion channels. We report here evidence that these phospholipids are able to modulate the function of homomeric P2X3 and heteromeric P2X2/3 purinoceptors expressed in dorsal root ganglion (DRG nociceptors and in heterologous expression systems. Results In dissociated rat DRG neurons, incubation with the PI3K/PI4K inhibitor wortmannin at 35 μM induced a dramatic decrease in the amplitude of ATP- or α,β-meATP-evoked P2X3 currents, while incubation with 100 nM wortmannin (selective PI3K inhibition produced no significant effect. Intracellular application of PIP2 was able to fully reverse the inhibition of P2X3 currents induced by wortmannin. In Xenopus oocytes and in HEK293 cells expressing recombinant P2X3, 35 μM wortmannin incubation induced a significant decrease in the rate of receptor recovery. Native and recombinant P2X2/3 receptor-mediated currents were inhibited by incubation with wortmannin both at 35 μM and 100 nM. The decrease of P2X2/3 current amplitude induced by wortmannin could be partially reversed by application of PIP2 or PIP3, indicating a sensitivity to both phosphoinositides in DRG neurons and Xenopus oocytes. Using a lipid binding assay, we demonstrate that the C-terminus of the P2X2 subunit binds directly to PIP2, PIP3 and other phosphoinositides. In contrast, no direct binding was detected between the C-terminus of P2X3 subunit and phosphoinositides. Conclusion Our findings indicate a functional regulation of homomeric P2X3 and heteromeric P2X2/3 ATP receptors by phosphoinositides in the plasma membrane of DRG nociceptors, based on subtype-specific mechanisms

  20. 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.

  1. 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....

  2. 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

  3. 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

  4. Autophosphorylation of serine 608 in the p85 regulatory subunit of wild type or cancer-associated mutants of phosphoinositide 3-kinase does not affect its lipid kinase activity

    OpenAIRE

    Layton Meredith J; Saad Mirette; Church Nicole L; Pearson Richard B; Mitchell Christina A; Phillips Wayne A

    2012-01-01

    Abstract Background The α-isoform of the Type 1A Phosphoinositide 3-kinases (PI3Kα) has protein kinase activity as well as phosphoinositide lipid kinase activity. The best described substrate for its protein kinase activity is its regulatory subunit, p85α, which becomes phosphorylated on Serine 608. Phosphorylation of Serine 608 has been reported to down-regulate its lipid kinase activity. Results We have assessed whether oncogenic mutants of PI3Kα, which have up-regulated lipid kinase activi...

  5. 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

  6. Class II phosphoinositide 3-kinase C2β regulates a novel signaling pathway involved in breast cancer progression

    Science.gov (United States)

    Abbott, Jonathan J.; Piñeiro, Roberto; Buus, Richard; Iezzi, Manuela; Ricci, Francesca; Bergamaschi, Daniele; Ostano, Paola; Chiorino, Giovanna; Lattanzio, Rossano; Broggini, Massimo; Piantelli, Mauro; Maffucci, Tania; Falasca, Marco

    2016-01-01

    It is now well established that the enzymes phosphoinositide 3-kinases (PI3Ks) have a key role in the development and progression of many cancer types and indeed PI3Ks inhibitors are currently being tested in clinical trials. Although eight distinct PI3K isoforms exist, grouped into three classes, most of the evidence currently available are focused on one specific isoform with very little known about the potential role of the other members of this family in cancer. Here we demonstrate that the class II enzyme PI3K-C2β is overexpressed in several human breast cancer cell lines and in human breast cancer specimens. Our data indicate that PI3K-C2β regulates breast cancer cell growth in vitro and in vivo and that PI3K-C2β expression in breast tissues is correlated with the proliferative status of the tumor. Specifically we show that downregulation of PI3K-C2β in breast cancer cell lines reduces colony formation, induces cell cycle arrest and inhibits tumor growth, in particular in an estrogen-dependent in vivo xenograft. Investigation of the mechanism of the PI3K-C2β-dependent regulation of cell cycle progression and cell growth revealed that PI3K-C2β regulates cyclin B1 protein levels through modulation of microRNA miR-449a levels. Our data further demonstrate that downregulation of PI3K-C2β inhibits breast cancer cell invasion in vitro and breast cancer metastasis in vivo. Consistent with this, PI3K-C2β is highly expressed in lymph-nodes metastases compared to matching primary tumors. These data demonstrate that PI3K-C2β plays a pivotal role in breast cancer progression and in metastasis development. Our data indicate that PI3K-C2β may represent a key molecular switch that regulates a rate-limiting step in breast tumor progression and therefore it may be targeted to limit breast cancer spread. PMID:26934321

  7. Signaling via class IA Phosphoinositide 3-kinases (PI3K in human, breast-derived cell lines.

    Directory of Open Access Journals (Sweden)

    Veronique Juvin

    Full Text Available We have addressed the differential roles of class I Phosphoinositide 3-kinases (PI3K in human breast-derived MCF10a (and iso-genetic derivatives and MDA-MB 231 and 468 cells. Class I PI3Ks are heterodimers of p110 catalytic (α, β, δ and γ and p50-101 regulatory subunits and make the signaling lipid, phosphatidylinositol (3,4,5-trisphosphate (PtdIns(3,4,5P3 that can activate effectors, eg protein kinase B (PKB, and responses, eg migration. The PtdIns(3,4,5P3-3-phosphatase and tumour-suppressor, PTEN inhibits this pathway. p110α, but not other p110s, has a number of onco-mutant variants that are commonly found in cancers. mRNA-seq data shows that MCF10a cells express p110β>>α>δ with undetectable p110γ. Despite this, EGF-stimulated phosphorylation of PKB depended upon p110α-, but not β- or δ- activity. EGF-stimulated chemokinesis, but not chemotaxis, was also dependent upon p110α, but not β- or δ- activity. In the presence of single, endogenous alleles of onco-mutant p110α (H1047R or E545K, basal, but not EGF-stimulated, phosphorylation of PKB was increased and the effect of EGF was fully reversed by p110α inhibitors. Cells expressing either onco-mutant displayed higher basal motility and EGF-stimulated chemokinesis.This latter effect was, however, only partially-sensitive to PI3K inhibitors. In PTEN(-/- cells, basal and EGF-stimulated phosphorylation of PKB was substantially increased, but the p110-dependency was variable between cell types. In MDA-MB 468s phosphorylation of PKB was significantly dependent on p110β, but not α- or δ- activity; in PTEN(-/- MCF10a it remained, like the parental cells, p110α-dependent. Surprisingly, loss of PTEN suppressed basal motility and EGF-stimulated chemokinesis. These results indicate that; p110α is required for EGF signaling to PKB and chemokinesis, but not chemotaxis; onco-mutant alleles of p110α augment signaling in the absence of EGF and may increase motility, in part, via acutely

  8. Differential involvement of phosphoinositide 3-kinase in gonadotrophin-releasing hormone actions in gonadotrophs and somatotrophs of goldfish, Carassius auratus.

    Science.gov (United States)

    Pemberton, Joshua G; Stafford, James L; Yu, Yi; Chang, John P

    2011-08-01

    In goldfish, two endogenous gonadotrophin-releasing hormones (GnRHs) [salmon (s)GnRH and chicken (c)GnRH-II] control maturational gonadotrophin-II [lutenising hormone (LH)] and growth hormone (GH) secretion via Ca(2+)-dependent intracellular signalling pathways. We investigated the involvement of phosphoinositide 3-kinase (PI3K) in GnRH-evoked LH and GH release and associated intracellular Ca(2+) increases ([Ca(2+)](i) ) in goldfish gonadotrophs and somatotrophs. Immunoreactive PI3K p85α, the predominant regulatory subunit for class IA PI3Ks, was detected in goldfish pituitary tissue extracts and both endogenous GnRH isoforms increased phosphorylation of PI3K p85α in excised pituitary fragments. sGnRH- and cGnRH-II-elicited LH release responses from primary cultures of pituitary cells and [Ca(2+)](i) increases in identified gonadotrophs were significantly reduced in the presence of PI3K inhibitors wortmannin (100 nm) and LY294002 (10 μm). Unexpectedly, wortmannin and LY294002 inhibited GnRH-evoked GH release but only attenuated the [Ca(2+)](i) response in identified somatotrophs to cGnRH-II, and not sGnRH. On the other hand, Ca(2+) ionophore-evoked LH and GH secretion remained unaltered in the presence of the PI3K inhibitors, suggesting that general decreases in the releasable hormone pool or sensitivity to [Ca(2+)](i) changes did not underlie the ability of wortmannin and LY294002 to reduce the actions of GnRH. These results provide the first evidence for the presence and involvement of PI3K in GnRH-induced LH and GH release in any primary pituitary cell system. In gonadotrophs, the inhibitory action of PI3K on both sGnRH and cGnRH-II involves the attenuation of their evoked [Ca(2+)](i); in contrast, GnRH isoform-specific effects occur in somatotrophs. PMID:21649760

  9. Phosphoinositide-3-kinases p110alpha and p110beta mediate S phase entry in astroglial cells in the marginal zone of rat neocortex

    Directory of Open Access Journals (Sweden)

    Rabea eMüller

    2013-03-01

    Full Text Available In cells cultured from neocortex of newborn rats, phosphoinositide-3-kinases of class I regulate the DNA synthesis in a subgroup of astroglial cells. We have studied the location of these cells as well as the kinase isoforms which facilitate the S phase entry. Using dominant negative isoforms as well as selective pharmacological inhibitors we quantified S phase entry by nuclear labeling with bromodeoxyuridine. Only in astroglial cells harvested from the marginal zone of the neocortex inhibition of phosphoinositide-3-kinases reduced the nuclear labeling with bromodeoxyuridine, indicating that neocortical astroglial cells differ in the regulation of proliferation. The two kinase isoforms p110 and p110were essential for S phase entry. p110 diminished the level of the p27Kip1 which inactivates the complex of cyclin E and CDK2 necessary for entry into the S phase. p110phosphorylated and inhibited glycogen synthase kinase-3which can prevent S-phase entry. Taken together, both isoforms mediated S phase in a subgroup of neocortical astroglial cells and acted via distinct pathways.

  10. 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....

  11. 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

  12. 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....

  13. Cellular automata simulation of nanometre-scale MOSFETs

    Science.gov (United States)

    Saraniti, M.; Zandler, G.; Formicone, G.; Wigger, S.; Goodnick, S.

    1998-08-01

    We present systematic theoretical cellular automata studies of vertically grown, nanometre-scale, MOSFETs. The predicted drain characteristics and output conductance are in excellent agreement with experimental data from fabricated devices. The inclusion of an inhomogeneous p-doping profiles along the channel is investigated, which is shown to improve current saturation and therefore allows the reduction of the device dimensions.

  14. Cultural Diagnosis: An Empirical Investigation of Cellular Industry of Pakistan

    OpenAIRE

    Qamar Ali; Manqoosh ur Rehman

    2011-01-01

    This study describes research in five cellular companies operating in Pakistan, aimed at identifying their current and preferred organizational culture. Using Quinn and Rohrbaugh (1983) competing values framework, the overall cultural profiles and dominant characteristics of the organizations and industry are determined through a personally administered survey employing the Organizational Culture Assessment Instrument (OCAI). The results indicate that hierarchy culture is dominating in cellul...

  15. 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...

  16. 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...

  17. Computational studies of the binding profile of phosphoinositide PtdIns (3,4,5) P3 with the pleckstrin homology domain of an oomycete cellulose synthase

    OpenAIRE

    Guanglin Kuang; Vincent Bulone; Yaoquan Tu

    2016-01-01

    Saprolegnia monoica is a model organism to investigate Saprolegnia parasitica, an important oomycete which causes considerable loss in aquaculture every year. S. monoica contains cellulose synthases vital for oomycete growth. However, the molecular mechanism of the cellulose biosynthesis process in the oomycete growth is still poorly understood. Some cellulose synthases of S. monoica, such as SmCesA2, are found to contain a plecsktrin homology (PH) domain, which is a protein module widely fou...

  18. Lipid Profile

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Lipid Profile Share this page: Was this page helpful? Also ... as: Lipid Panel; Coronary Risk Panel Formal name: Lipid Profile Related tests: Cholesterol ; HDL Cholesterol ; LDL Cholesterol ; Triglycerides ; ...

  19. 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

  20. 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...

  1. 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,...

  2. Karolinske psychodynamic profile (KAPP)

    DEFF Research Database (Denmark)

    Mathiesen, Birgit Bork; Søgaard, Ulf

    psykologiske testmetoder, assesment, Karolinska psychodynamic profile (KAPP), psykodynamisk profil......psykologiske testmetoder, assesment, Karolinska psychodynamic profile (KAPP), psykodynamisk profil...

  3. Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1)

    DEFF Research Database (Denmark)

    Dettori, Rosalia; Sonzogni, Silvina; Meyer, Lucas;

    2009-01-01

    The members of the AGC kinase family frequently exhibit three conserved phosphorylation sites: the activation loop, the hydrophobic motif (HM), and the zipper (Z)/turn-motif (TM) phosphorylation site. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates the activation loop of...... numerous AGC kinases, including the protein kinase C-related protein kinases (PRKs). Here we studied the docking interaction between PDK1 and PRK2 and analyzed the mechanisms that regulate this interaction. In vivo labeling of recombinant PRK2 by (32)P(i) revealed phosphorylation at two sites, the...... the mechanism that negatively regulates the docking interaction of PRK2 to the upstream kinase PDK1 is directly linked to the activation mechanism of PRK2 itself. Finally, our results indicate that the mechanisms underlying the regulation of the interaction between PRK2 and PDK1 are specific for PRK2...

  4. Nonvesicular sterol movement from plasma membrane to ER requires oxysterol-binding protein–related proteins and phosphoinositides

    OpenAIRE

    Raychaudhuri, Sumana; Im, Young Jun; Hurley, James H.; Prinz, William A.

    2006-01-01

    Sterols are moved between cellular membranes by nonvesicular pathways whose functions are poorly understood. In yeast, one such pathway transfers sterols from the plasma membrane (PM) to the endoplasmic reticulum (ER). We show that this transport requires oxysterol-binding protein (OSBP)–related proteins (ORPs), which are a large family of conserved lipid-binding proteins. We demonstrate that a representative member of this family, Osh4p/Kes1p, specifically facilitates the nonvesicular transf...

  5. 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.

  6. 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)

  7. 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...

  8. 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...

  9. 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...

  10. 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.

  11. Commercialization of cellular immunotherapies for cancer.

    Science.gov (United States)

    Walker, Anthony; Johnson, Robert

    2016-04-15

    Successful commercialization of a cell therapy requires more than proving safety and efficacy to the regulators. The inherent complexity of cellular products delivers particular manufacturing, logistical and reimbursement hurdles that threaten commercial viability for any therapy with a less than spectacular clinical profile that truly changes the standard of care. This is particularly acute for autologous cell therapies where patients receive bespoke treatments manufactured from a sample of their own cells and where economies of scale, which play an important role in containing the production costs for small molecule and antibody therapeutics, are highly limited. Nevertheless, the promise of 'game-changing' efficacy, as exemplified by very high levels of complete responses in refractory haematological malignancies, has attracted capital investments on a vast scale, and the attendant pace of technology development provides promising indicators for future clinical and commercial success. PMID:27068936

  12. A new description of cellular quiescence.

    Directory of Open Access Journals (Sweden)

    Hilary A Coller

    2006-03-01

    Full Text Available Cellular quiescence, defined as reversible growth/proliferation arrest, is thought to represent a homogenous state induced by diverse anti-mitogenic signals. We used transcriptional profiling to characterize human diploid fibroblasts that exited the cell cycle after exposure to three independent signals--mitogen withdrawal, contact inhibition, and loss of adhesion. We show here that each signal caused regulation of a unique set of genes known to be important for cessation of growth and division. Therefore, contrary to expectation, cells enter different quiescent states that are determined by the initiating signal. However, underlying this diversity we discovered a set of genes whose specific expression in non-dividing cells was signal-independent, and therefore representative of quiescence per se, rather than the signal that induced it. This fibroblast "quiescence program" contained genes that enforced the non-dividing state, and ensured the reversibility of the cell cycle arrest. We further demonstrate that one mechanism by which the reversibility of quiescence is insured is the suppression of terminal differentiation. Expression of the quiescence program was not simply a downstream consequence of exit from the cell cycle, because key parts, including those involved in suppressing differentiation, were not recapitulated during the cell cycle arrest caused by direct inhibition of cyclin-dependent kinases. These studies form a basis for understanding the normal biology of cellular quiescence.

  13. Perfil celular e microbiológico do leite de ovelhas Santa Inês no período lactante e pós-desmame Cellular and microbiological profile of Santa Ines ewes in the lactation and the post-weaning period

    Directory of Open Access Journals (Sweden)

    Maiara G. Blagitz

    2008-09-01

    Full Text Available O objetivo deste trabalho foi avaliar o perfil microbiológico e celular do leite no período lactante e de involução ativa de ovelhas da raça Santa Inês. Foram avaliadas amostras lácteas de 12 ovelhas durante estes distintos períodos. Realizou-se o exame físico da mama, sendo as amostras lácteas submetidas à contagem de células somáticas (CCS, ao California Mastitis Test (CMT, ao exame microbiológico e aos testes de sensibilidade in vitro dos patógenos encontrados. Foram observados maiores escores do exame físico, CCS, CMT durante o período de involução ativa, além de uma alta persistência da infecção durante estes períodos. O período de involução ativa não se mostrou como um momento de alta susceptilidade. Os estafilococos coagulase negativa representaram o único gênero isolado das glândulas infectadas. Uma alta sensibilidade dos agentes etiológicos envolvidos frente aos diferentes antimicrobianos in vitro foi também observada.The aim was to evaluate and compare the microbiological and cellular profile of the milk of Santa Ines ewes during the lactation period and the active involution. Milk samples were analyzed from 12 ewes during these distinct periods. Clinical examination of the mammary gland, somatic cell count (SCC, California Mastitis Test (CMT, bacteriologic screening and sensibility of the pathogens in vitro were performed. Most alterations were observed in the active involution period. SCC and CMT were higher in this same period. Besides this, a high persistency of infection occurred. The active involution period did not show high susceptibility. Coagulase-negative staphylococci were the only isolated bacteria. A high antimicrobial sensibility of these pathogens was also encountered.

  14. 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.

  15. Cellular phones and their hazards: the current evidence.

    Science.gov (United States)

    Munshi, Anusheel; Jalali, Rakesh

    2002-01-01

    The past decade has seen an exponential increase globally in the use of cellular phones (popularly known as mobile or cell phones). These phones are convenient and trendy. Discarding the wire means that the communication is through electromagnetic waves, which could have potential hazards. Alarmist reports in the lay press and high profile lawsuits, particularly in the West, have attracted attention to the possible harmful effects of cellular phones. Adverse effects investigated by various clinical trials include the possible link to increased risk of vehicular accidents, leukaemias, sleep disturbances and the more serious brain tumours. Available level II evidence suggests that the only proven side-effect is an increased risk of vehicular accidents. So far, all studies have consistently negated any association between cellular phones and brain tumours. Yet, the final word remains to be said. PMID:12502140

  16. 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.

  17. 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.

  18. Profiling cancer

    DEFF Research Database (Denmark)

    Ciro, Marco; Bracken, Adrian P; Helin, Kristian

    2003-01-01

    In the past couple of years, several very exciting studies have demonstrated the enormous power of gene-expression profiling for cancer classification and prediction of patient survival. In addition to promising a more accurate classification of cancer and therefore better treatment of patients......, gene-expression profiling can result in the identification of novel potential targets for cancer therapy and a better understanding of the molecular mechanisms leading to cancer....

  19. 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

  20. 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...

  1. 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.

  2. Autophosphorylation of serine 608 in the p85 regulatory subunit of wild type or cancer-associated mutants of phosphoinositide 3-kinase does not affect its lipid kinase activity

    Directory of Open Access Journals (Sweden)

    Layton Meredith J

    2012-12-01

    Full Text Available Abstract Background The α-isoform of the Type 1A Phosphoinositide 3-kinases (PI3Kα has protein kinase activity as well as phosphoinositide lipid kinase activity. The best described substrate for its protein kinase activity is its regulatory subunit, p85α, which becomes phosphorylated on Serine 608. Phosphorylation of Serine 608 has been reported to down-regulate its lipid kinase activity. Results We have assessed whether oncogenic mutants of PI3Kα, which have up-regulated lipid kinase activity, have altered levels of Serine 608 phosphorylation compared to wild type PI3Kα, and whether differential phosphorylation of Serine 608 contributes to increased activity of oncogenic forms of PI3Kα with point mutations in the helical or the kinase domains. Despite markedly increased lipid kinase activity, protein kinase activity was not altered in oncogenic compared to wild type forms of PI3Kα. By manipulating levels of phosphorylation of Serine 608 in vitro, we found no evidence that the protein kinase activity of PI3Kα affects its phosphoinositide lipid kinase activity in either wild-type or oncogenic mutants of PI3Kα. Conclusions Phosphorylation of p85α S608 is not a significant regulator of wild-type or oncogenic PI3Kα lipid kinase activity.

  3. 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.

  4. 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

  5. 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.

  6. 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...

  7. Cellular and molecular mechanisms of HGF/Met in the cardiovascular system.

    Science.gov (United States)

    Gallo, Simona; Sala, Valentina; Gatti, Stefano; Crepaldi, Tiziana

    2015-12-01

    Met tyrosine kinase receptor, also known as c-Met, is the HGF (hepatocyte growth factor) receptor. The HGF/Met pathway has a prominent role in cardiovascular remodelling after tissue injury. The present review provides a synopsis of the cellular and molecular mechanisms underlying the effects of HGF/Met in the heart and blood vessels. In vivo, HGF/Met function is particularly important for the protection of the heart in response to both acute and chronic insults, including ischaemic injury and doxorubicin-induced cardiotoxicity. Accordingly, conditional deletion of Met in cardiomyocytes results in impaired organ defence against oxidative stress. After ischaemic injury, activation of Met provides strong anti-apoptotic stimuli for cardiomyocytes through PI3K (phosphoinositide 3-kinase)/Akt and MAPK (mitogen-activated protein kinase) cascades. Recently, we found that HGF/Met is also important for autophagy regulation in cardiomyocytes via the mTOR (mammalian target of rapamycin) pathway. HGF/Met induces proliferation and migration of endothelial cells through Rac1 (Ras-related C3 botulinum toxin substrate 1) activation. In fibroblasts, HGF/Met antagonizes the actions of TGFβ1 (transforming growth factor β1) and AngII (angiotensin II), thus preventing fibrosis. Moreover, HGF/Met influences the inflammatory response of macrophages and the immune response of dendritic cells, indicating its protective function against atherosclerotic and autoimmune diseases. The HGF/Met axis also plays an important role in regulating self-renewal and myocardial regeneration through the enhancement of cardiac progenitor cells. HGF/Met has beneficial effects against myocardial infarction and endothelial dysfunction: the cellular and molecular mechanisms underlying repair function in the heart and blood vessels are common and include pro-angiogenic, anti-inflammatory and anti-fibrotic actions. Thus administration of HGF or HGF mimetics may represent a promising therapeutic agent for the

  8. 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...

  9. 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....

  10. 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.

  11. 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

  12. Perfil microbiológico, celular e fatores de risco associados à mastite subclínica em cabras no semiárido da Paraíba Cellular and microbiological profiles and risk factors for subclinical mastitis in goats in the semi-arid region of Paraíba

    Directory of Open Access Journals (Sweden)

    Patrícia B. Neves

    2010-05-01

    Full Text Available Foi realizado um estudo da mastite subclínica em nove rebanhos de cabras leiteiras no semiárido paraibano com o objetivo de determinar a ocorrência da infecção, avaliar o perfil microbiológico e celular do leite, testar a sensibilidade dos microorganismos isolados frente a antimicrobianos além de identificar os fatores de risco. Foram utilizadas 131 cabras leiteiras das quais foram colhidas 261 amostras de leite para exame microbiológico e 131 para contagem de células somáticas (CCS. Na ocasião das colheitas foi realizado o California Mastitis Test (CMT e aplicado um questionário epidemiológico por propriedade. Houve crescimento bacteriano em 30 amostras (11,49% com 25 (83,33% dos isolados identificados como Staphylococcus coagulase negativa e cinco (16,66% Staphylococcus aureus. A média de CCS foi de 1,39x10(6 células/ml. O CMT apresentou baixa sensibilidade (46,7% e baixa especificidade (60,6% quando comparado ao exame microbiológico. A gentamicina e a associação da neomicina, bacitracina e tetraciclina foram os antimicrobianos contra os quais os microrganismos isolados apresentaram 100% de sensibilidade. Penicilina e ampicilina foram os de maiores índices de resistência (66,67% e 63,89%, respectivamente. A caprinocultura não ser a atividade principal da propriedade e o não isolamento de animais doentes, foram identificados como fatores de risco para a mastite subclínica caprina nas propriedades estudadas. Programas de controle e profilaxia da mastite devem ser implementados enfocando as medidas de higiene na ordenha e correção dos fatores de risco identificados nesse estudo.A subclinical mastitis study was conducted in nine dairy goat herds in the semi-arid region of Paraíba state, Northeastern Brazil, to determine the occurrence of infection, to evaluate microbiological and cellular profiles of the milk, to test the sensitivity of isolated microorganisms to antimicrobials, and to identify risk factors. One hundred

  13. [Changes in the contents of phosphoinositides in formed elements of blood and endometrial tissue in patients with hyperplastic processes and cancer of the endometrium].

    Science.gov (United States)

    Damirov, M M; Kulakov, V I; Sliusar', N N; Bakuleva, L P

    1995-01-01

    The levels of phosphoinositides were measured in blood macrophages, platelets, lymphocytes, granulocytes, neutrophils, and red cells, as well as in endometrial tissue of 175 patients with glandular hyperplasia of the endometrium, atypical hyperplasia, endometrial polyps and cancer. A reliable reduction of the content of phosphatidyl inositides and phosphatidyl inositide-S-phosphates was observed in all formed elements of the blood, the most marked decrease being observed in endometrial cancer. On the contrary, the content of phosphatidyl inositide-4-phosphates and phosphatidyl inositide-4.5-diphosphates in the macrophages, lymphocytes, and granulocytes was reliably increased in the patients as against healthy women. The process of phosphatidylinositide phosphorylation run an absolutely different course in pathologically altered endometrial tissue than in comparison with that in blood cells. A new phosphatidyl inositide-signal mechanism was revealed, which is unrelated to inositol-1.4.5-triphosphate, as a result of which the potentiality of appearance of new secondary messengers actively participating in cell growth increases. PMID:7485761

  14. miR-502 inhibits cell proliferation and tumor growth in hepatocellular carcinoma through suppressing phosphoinositide 3-kinase catalytic subunit gamma

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Suling, E-mail: suling_chen86@163.com [Department of Infectious Disease, Heping Hospital Attached to Changzhi Medical College, Changzhi 046000 (China); Li, Fang; Chai, Haiyun; Tao, Xin [Department of Infectious Disease, Heping Hospital Attached to Changzhi Medical College, Changzhi 046000 (China); Wang, Haili [Department of Hematology, Heping Hospital Attached to Changzhi Medical College, Changzhi 046000 (China); Ji, Aifang [Central Laboratory, Heping Hospital Attached to Changzhi Medical College, Changzhi 046000 (China)

    2015-08-21

    MicroRNAs (miRNAs) play a key role in carcinogenesis and tumor progression in hepatocellular carcinoma (HCC). In the present study, we demonstrated that miR-502 significantly inhibits HCC cell proliferation in vitro and tumor growth in vivo. G1/S cell cycle arrest and apoptosis of HCC cells were induced by miR-502. Phosphoinositide 3-kinase catalytic subunit gamma (PIK3CG) was identified as a direct downstream target of miR-502 in HCC cells. Notably, overexpression of PIK3CG reversed the inhibitory effects of miR-502 in HCC cells. Our findings suggest that miR-502 functions as a tumor suppressor in HCC via inhibition of PI3KCG, supporting its utility as a promising therapeutic gene target for this tumor type. - Highlights: • miR-502 suppresses HCC cell proliferation in vitro and tumorigenicity in vivo. • miR-502 regulates cell cycle and apoptosis in HCC cells. • PIK3CG is a direct target of miR-502. • miR-502 and PIK3CG expression patterns are inversely correlated in HCC tissues.

  15. Melittin stimulates phosphoinositide hydrolysis and placental lactogen release: Arachidonic acid as a link between phospholipase A sub 2 and phospholipase C signal-transduction pathways

    Energy Technology Data Exchange (ETDEWEB)

    Zeitler, P.; Handwerger, S. (Univ. of Cincinnati College of Medicine, OH (USA)); Wu, Y.Q. (Duke Univ. Medical Center, Durham, NC (USA))

    1991-01-01

    Previous investigations from this laboratory have implicated both phospholipase A{sub 2} and phospholipase C in the regulation of human placental lactogen release from human trophoblast. To study further the role of endogenous phospholipase A{sub 2} and the relationship between phospholipase A{sub 2} activation and phosphoinositide metabolism, the authors examined hPL and ({sup 3}H)-inositol release from trophoblast cells in response to agents that stimulate or inhibit the endogenous enzyme. Melittin stimulated rapid, dose-dependent, and reversible increases in the release of hPL, prostaglandin E, and ({sup 3}H)-inositol. Mepacrine inhibited this stimulation. However, mepacrine had no effect on the stimulation of hPL and ({sup 3}H)-inositol release by exogenous arachidonic acid (AA). These results indicate that the stimulation by melittin of phosphoionsitide metabolism and hPL release is mediated by initial activation of phospholipase A{sub 2}. Furthermore, the results support the possibility that AA, released as a consequence of phospholipase A{sub 2} activation, can act as a second messenger linking the two phospholipase pathways.

  16. Eicosapentaenoic acid-enriched phosphatidylcholine isolated from Cucumaria frondosa exhibits anti-hyperglycemic effects via activating phosphoinositide 3-kinase/protein kinase B signal pathway.

    Science.gov (United States)

    Hu, Shiwei; Xu, Leilei; Shi, Di; Wang, Jingfeng; Wang, Yuming; Lou, Qiaoming; Xue, Changhu

    2014-04-01

    Eicosapentaenoic acid-enriched phosphatidylcholine was isolated from the sea cucumber Cucumaria frondosa (Cucumaria-PC) and its effects on streptozotocin (STZ)-induced hyperglycemic rats were investigated. Male Sprague-Dawley rats were randomly divided into normal control, model control (STZ), low- and high-dose Cucumaria-PC groups (STZ + Cucumaria-PC at 25 and 75 mg/Kg·b·wt, intragastrically, respectively). Blood glucose, insulin, glycogen in liver and gastrocnemius were determined over 60 days. Insulin signaling in the rats' gastrocnemius was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. The results showed that Cucumaria-PC significantly decreased blood glucose level, increased insulin secretion and glycogen synthesis in diabetic rats. RT-PCR analysis revealed that Cucumaria-PC significantly promoted the expressions of glycometabolism-related genes of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI3K), protein kinase B (PKB), and glucose transporter 4 (GLUT4) in gastrocnemius. Western blotting assay demonstrated that Cucumaria-PC remarkably enhanced the proteins abundance of IR-β, PI3K, PKB, GLUT4, as well as phosphorylation of Tyr-IR-β, p85-PI3K, Ser473-PKB (P Cucumaria-PC exhibited significant anti-hyperglycemic activities through up-regulating PI3K/PKB signal pathway mediated by insulin. Nutritional supplementation with Cucumaria-PC, if validated for human studies, may offer an adjunctive therapy for diabetes mellitus. PMID:24168893

  17. Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin [alpha]1

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Yufeng; Tempel, Wolfram; Wang, Hui; Yamada, Kaori; Shen, Limin; Senisterra, Guillermo A.; MacKenzie, Farrell; Chishti, Athar H.; Park, Hee-Won (Toronto); (UICM)

    2011-11-07

    Phosphatidylinositol 3,4,5-triphosphate (PIP3) plays a key role in neuronal polarization and axon formation. PIP3-containing vesicles are transported to axon tips by the kinesin KIF13B via an adaptor protein, centaurin {alpha}1 (CENTA1). KIF13B interacts with CENTA1 through its forkhead-associated (FHA) domain. We solved the crystal structures of CENTA1 in ligand-free, KIF13B-FHA domain-bound, and PIP3 head group (IP4)-bound conformations, and the CENTA1/KIF13B-FHA/IP4 ternary complex. The first pleckstrin homology (PH) domain of CENTA1 specifically binds to PIP3, while the second binds to both PIP3 and phosphatidylinositol 3,4-biphosphate (PI(3,4)P2). The FHA domain of KIF13B interacts with the PH1 domain of one CENTA1 molecule and the ArfGAP domain of a second CENTA1 molecule in a threonine phosphorylation-independent fashion. We propose that full-length KIF13B and CENTA1 form heterotetramers that can bind four phosphoinositide molecules in the vesicle and transport it along the microtubule.

  18. Loss of phosphoinositide 3-kinase γ decreases migration and activation of phagocytes but not T cell activation in antigen-induced arthritis

    Directory of Open Access Journals (Sweden)

    Wetzker Reinhard

    2010-04-01

    Full Text Available Abstract Background Phosphoinositide 3-kinase γ (PI3Kγ has been depicted as a major regulator of inflammatory processes, including leukocyte activation and migration towards several chemokines. This study aims to explore the role of PI3Kγ in the murine model of antigen-induced arthritis (AIA. Methods Development of AIA was investigated in wildtype and PI3Kγ-deficient mice as well as in mice treated with a specific inhibitor of PI3Kγ (AS-605240 in comparison to untreated animals. Inflammatory reactions of leukocytes, including macrophage and T cell activation, and macrophage migration, were studied in vivo and in vitro. Results Genetic deletion or pharmacological inhibition of PI3Kγ induced a marked decrease of clinical symptoms in early AIA, together with a considerably diminished macrophage migration and activation (lower production of NO, IL-1β, IL-6. Also, macrophage and neutrophil infiltration into the knee joint were impaired in vivo. However, T cell functions, measured by cytokine production (TNFα, IFNγ, IL-2, IL-4, IL-5, IL-17 in vitro and DTH reaction in vivo were not altered, and accordingly, disease developed normally at later timepoints Conclusion PI3Kγ specifically affects phagocyte function in the AIA model but has no impact on T cell activation.

  19. Berberine induces dedifferentiation by actin cytoskeleton reorganization via phosphoinositide 3-kinase/Akt and p38 kinase pathways in rabbit articular chondrocytes.

    Science.gov (United States)

    Yu, Seon-Mi; Cho, Hongsik; Kim, Gwang-Hoon; Chung, Ki-Wha; Seo, Sung-Yum; Kim, Song-Ja

    2016-04-01

    Osteoarthritis is a nonrheumatologic joint disease characterized by progressive degeneration of the cartilage extracellular matrix. Berberine (BBR) is an isoquinoline alkaloid used in traditional Chinese medicine, the majority of which is extracted from Huang Lian (Coptis chinensis). Although numerous studies have revealed the anticancer activity of BBR, its effects on normal cells, such as chondrocytes, and the molecular mechanisms underlying its actions remain elusive. Therefore, we examined the effects of BBR on rabbit articular chondrocytes, and the underlying molecular mechanisms, focusing on actin cytoskeletal reorganization. BBR induced dedifferentiation by inhibiting activation of phosphoinositide-3(PI3)-kinase/Akt and p38 kinase. Furthermore, inhibition of p38 kinase and PI3-kinase/Akt with SB203580 and LY294002, respectively, accelerated the BBR-induced dedifferentiation. BBR also caused actin cytoskeletal architecture reorganization and, therefore, we investigated if these effects were involved in the dedifferentiation. Disruption of the actin cytoskeleton by cytochalasin D reversed the BBR-induced dedifferentiation by activating PI3-kinase/Akt and p38 kinase. In contrast, the induction of actin filament aggregation by jasplakinolide accelerated the BBR-induced dedifferentiation via PI3-kinase/Akt inhibition and p38 kinase activation. Taken together, these data suggest that BBR strongly induces dedifferentiation, and actin cytoskeletal reorganization is a crucial requirement for this effect. Furthermore, the dedifferentiation activity of BBR appears to be mediated via PI3-kinase/Akt and p38 kinase pathways in rabbit articular chondrocytes. PMID:26851252

  20. The phosphoinositide 3-kinase signaling pathway is involved in the control of modified low-density lipoprotein uptake by human macrophages.

    Science.gov (United States)

    Michael, Daryn R; Davies, Thomas S; Laubertová, Lucia; Gallagher, Hayley; Ramji, Dipak P

    2015-03-01

    The transformation of macrophages into lipid-loaded foam cells is a critical early event in the pathogenesis of atherosclerosis. Both receptor-mediated uptake of modified LDL, mediated primarily by scavenger receptors-A (SR-A) and CD36 along with other proteins such as lipoprotein lipase (LPL), and macropinocytosis contribute to macrophage foam cell formation. The signaling pathways that are involved in the control of foam cell formation are not fully understood. In this study, we have investigated the role of phosphoinositide 3-kinase (PI3K) in relation to foam cell formation in human macrophages. The pan PI3K inhibitor LY294002 attenuated the uptake of modified LDL and macropinocytosis, as measured by Lucifer Yellow uptake, by human macrophages. In addition, the expression of SR-A, CD36 and LPL was attenuated by LY294002. The use of isoform-selective PI3K inhibitors showed that PI3K-β, -γ and -δ were all required for the expression of SR-A and CD36 whereas only PI3K-γ was necessary in the case of LPL. These studies reveal a pivotal role of PI3K in the control of macrophage foam cell formation and provide further evidence for their potential as therapeutic target against atherosclerosis. PMID:25663263

  1. Involvement of class II phosphoinositide 3-kinase α-isoform in antigen-induced degranulation in RBL-2H3 cells.

    Directory of Open Access Journals (Sweden)

    Kiyomi Nigorikawa

    Full Text Available In this study, we present findings that suggest that PI3K-C2α, a member of the class II phosphoinositide 3-kinase (PI3K subfamily, regulates the process of FcεRI-triggered degranulation. RBL-2H3 cells were transfected with shRNA targeting PI3K-C2α. The knockdown impaired the FcεRI-induced release of a lysosome enzyme, β-hexosaminidase, without affecting the intracellular Ca2+ mobilization. The release of mRFP-tagged neuropeptide-Y, a reporter for the regulated exocytosis, was also decreased in the PI3K-C2α-deficient cells. The release was increased significantly by the expression of the siRNA-resistant version of PI3K-C2α. In wild-type cells, FcεRI stimulation induced the formation of large vesicles, which were associated with CD63, a marker protein of secretory granules. On the vesicles, the existence of PI3K-C2α and PtdIns(3,4P2 was observed. These results indicated that PI3K-C2α and its product PtdIns(3,4P2 may play roles in the secretory process.

  2. Phosphoinositide 3-kinase γ affects LPS-induced disturbance of blood-brain barrier via lipid kinase-independent control of cAMP in microglial cells.

    Science.gov (United States)

    Frister, Adrian; Schmidt, Caroline; Schneble, Nadine; Brodhun, Michael; Gonnert, Falk A; Bauer, Michael; Hirsch, Emilio; Müller, Jörg P; Wetzker, Reinhard; Bauer, Reinhard

    2014-12-01

    The breakdown of the blood-brain barrier (BBB) is a key event in the development of sepsis-induced brain damage. BBB opening allows blood-born immune cells to enter the CNS to provoke a neuroinflammatory response. Abnormal expression and activation of matrix metalloproteinases (MMP) was shown to contribute to BBB opening. Using different mouse genotypes in a model of LPS-induced systemic inflammation, our present report reveals phosphoinositide 3-kinase γ (PI3Kγ) as a mediator of BBB deterioration and concomitant generation of MMP by microglia. Unexpectedly, microglia expressing lipid kinase-deficient mutant PI3Kγ exhibited similar MMP regulation as wild-type cells. Our data suggest kinase-independent control of cAMP phosphodiesterase activity by PI3Kγ as a crucial mediator of microglial cell activation, MMP expression and subsequent BBB deterioration. The results identify the suppressive effect of PI3Kγ on cAMP as a critical mediator of immune cell functions. PMID:25033932

  3. Profile video

    Science.gov (United States)

    Voglewede, Paul E.; Zampieron, Jeffrey

    2009-05-01

    For unattended persistent surveillance there is a need for a system which provides the following information: target classification, target quantity estimate, cargo presence and characterization, direction of travel, and action. Over highly bandwidth restricted links, such as Iridium, SATCOM or HF, the data rates of common techniques are too high, even after aggressive compression, to deliver the required intelligence in a timely, low power manner. We propose the following solution to this data rate problem: Profile Video. Profile video is a new technique which provides all of the required information in a very low data-rate package.

  4. Movies of cellular and sub-cellular motion by digital holographic microscopy

    Directory of Open Access Journals (Sweden)

    Yu Lingfeng

    2006-03-01

    Full Text Available Abstract Background Many biological specimens, such as living cells and their intracellular components, often exhibit very little amplitude contrast, making it difficult for conventional bright field microscopes to distinguish them from their surroundings. To overcome this problem phase contrast techniques such as Zernike, Normarsky and dark-field microscopies have been developed to improve specimen visibility without chemically or physically altering them by the process of staining. These techniques have proven to be invaluable tools for studying living cells and furthering scientific understanding of fundamental cellular processes such as mitosis. However a drawback of these techniques is that direct quantitative phase imaging is not possible. Quantitative phase imaging is important because it enables determination of either the refractive index or optical thickness variations from the measured optical path length with sub-wavelength accuracy. Digital holography is an emergent phase contrast technique that offers an excellent approach in obtaining both qualitative and quantitative phase information from the hologram. A CCD camera is used to record a hologram onto a computer and numerical methods are subsequently applied to reconstruct the hologram to enable direct access to both phase and amplitude information. Another attractive feature of digital holography is the ability to focus on multiple focal planes from a single hologram, emulating the focusing control of a conventional microscope. Methods A modified Mach-Zender off-axis setup in transmission is used to record and reconstruct a number of holographic amplitude and phase images of cellular and sub-cellular features. Results Both cellular and sub-cellular features are imaged with sub-micron, diffraction-limited resolution. Movies of holographic amplitude and phase images of living microbes and cells are created from a series of holograms and reconstructed with numerically adjustable

  5. Profile counting

    International Nuclear Information System (INIS)

    In ''profile counting'', a counter is moved progressively along the whole length of the body, and is so collimated that, at each position, it records the radioisotope content of the whole width of the body, but of only a short section of its length. If the counting rate at each position is plotted against the distance of the counter from the vertex of the head, the ''profile'' so obtained gives a rapid and quantitative measure of the radioisotope distribution throughout the body. When a suitable isotope is selectively concentrated in certain organs or tissues of the body, the profile will show peaks indicative of the sites and extent of such concentration, the organs concerned being identified by two-dimensional mapping, and profile counts continued to follow the turnover or changes of concentration in these organs. This technique has been used in the study of I131 concentration and metabolism in thyroid carcinomata, and its value in the management of the radioiodine treatment of such tumours will be discussed. It has also been used in examining the distribution of labelled thyroxine and triiodothyronine after intravenous administration, and of yttrium-90 oxide particles after intrapulmonary artery injection; and of other isotopes by gamma radiation or bremsstrahlung. The method gives a clinically convenient simplification of whole body mapping which lends itself particularly to the quantitative comparison of isotope distribution at different intervals after a radioisotope dose, or after successive doses. (author)

  6. 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.

  7. 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)

  8. 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.

  9. 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.

  10. 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.

  11. 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...

  12. 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(...

  13. 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...

  14. 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...

  15. 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

  16. 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...

  17. 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...

  18. 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.

  19. 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.

  20. 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

  1. Insulin and insulin-like growth factor-1 can modulate the phosphoinositide-3-kinase/Akt/FoxO1 pathway in SZ95 sebocytes in vitro.

    Science.gov (United States)

    Mirdamadi, Yasaman; Thielitz, Anja; Wiede, Antje; Goihl, Alexander; Papakonstantinou, Eleni; Hartig, Roland; Zouboulis, Christos C; Reinhold, Dirk; Simeoni, Luca; Bommhardt, Ursula; Quist, Sven; Gollnick, Harald

    2015-11-01

    A recent hypothesis suggests that a high glycaemic load diet-associated increase of insulin-like growth factor-1 (IGF-1) and insulin may promote acne by reducing nuclear localization of the forkhead box-O1 (FoxO1) transcription factor via activation of the phosphoinositide-3-kinase (PI3K)/Akt pathway. Using SZ95 sebocytes as a model, we investigated the effect of the most important insulinotropic western dietary factors, IGF-1 and insulin on acne. SZ95 sebocytes were stimulated with different concentrations of IGF-1 and insulin (0.001, 0.01, 0.1 and 1 μM) for 15 to 120 min ± PI3K inhibitor LY294002 (50 μM). Cytoplasmic and nuclear protein expression of p-Akt and p-FoxO1 as well as FoxO transcriptional activity was analysed. In addition, the proliferation and differentiation of sebocytes and their TLR2/4 expression were determined. We found that high concentrations of IGF-1 and insulin differentially stimulate the PI3K/Akt/FoxO1 pathway by an early up-regulation of cytoplasmic p-Akt and delayed up-regulation of p-FoxO1 resulting in FoxO1 shift to the cytoplasm and the reduction of FoxO transcriptional activity, physiological serum concentration had no effect. IGF-1 at concentrations of 0.1 and 1 μM significantly reduced proliferation but increased differentiation of sebocytes to a greater extent than insulin (0.1 and 1 μM), but up-regulated TLR2/4 expression to comparable extent. These data provide the first in vitro evidence that FoxO1 principally might be involved in the regulation of growth-factor-stimulatory effects on sebaceous lipogenesis and inflammation in the pathological condition of acne. However, the in vivo significance under physiological conditions remains to be elucidated. PMID:26257240

  2. Phosphoinositide-3-kinase/akt - dependent signaling is required for maintenance of [Ca2+]i,ICa, and Ca2+ transients in HL-1 cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Graves Bridget M

    2012-06-01

    Full Text Available Abstract The phosphoinositide 3-kinases (PI3K/Akt dependent signaling pathway plays an important role in cardiac function, specifically cardiac contractility. We have reported that sepsis decreases myocardial Akt activation, which correlates with cardiac dysfunction in sepsis. We also reported that preventing sepsis induced changes in myocardial Akt activation ameliorates cardiovascular dysfunction. In this study we investigated the role of PI3K/Akt on cardiomyocyte function by examining the role of PI3K/Akt-dependent signaling on [Ca2+]i, Ca2+ transients and membrane Ca2+ current, ICa, in cultured murine HL-1 cardiomyocytes. LY294002 (1–20 μM, a specific PI3K inhibitor, dramatically decreased HL-1 [Ca2+]i, Ca2+ transients and ICa. We also examined the effect of PI3K isoform specific inhibitors, i.e. α (PI3-kinase α inhibitor 2; 2–8 nM; β (TGX-221; 100 nM and γ (AS-252424; 100 nM, to determine the contribution of specific isoforms to HL-1 [Ca2+]i regulation. Pharmacologic inhibition of each of the individual PI3K isoforms significantly decreased [Ca2+]i, and inhibited Ca2+ transients. Triciribine (1–20 μM, which inhibits AKT downstream of the PI3K pathway, also inhibited [Ca2+]i, and Ca2+ transients and ICa. We conclude that the PI3K/Akt pathway is required for normal maintenance of [Ca2+]i in HL-1 cardiomyocytes. Thus, myocardial PI3K/Akt-PKB signaling sustains [Ca2+]i required for excitation-contraction coupling in cardiomyoctyes.

  3. Hepatoprotective Effect of Quercetin on Endoplasmic Reticulum Stress and Inflammation after Intense Exercise in Mice through Phosphoinositide 3-Kinase and Nuclear Factor-Kappa B

    Directory of Open Access Journals (Sweden)

    Yuhan Tang

    2016-01-01

    Full Text Available The mechanisms underlying intense exercise-induced liver damage and its potential treatments remain unclear. We explored the hepatoprotection and mechanisms of quercetin, a naturally occurring flavonoid, in strenuous exercise-derived endoplasmic reticulum stress (ERS and inflammation. Intense exercise (28 m/min at a 5° slope for 90 min resulted in the leakage of aminotransferases in the BALB/C mice. The hepatic ultrastructural malformations and oxidative stress levels were attenuated by quercetin (100 mg/kg·bw. Intense exercise and thapsigargin- (Tg- induced ERS (glucose-regulated protein 78, GRP78 and inflammatory cytokines levels (IL-6 and TNF-α were decreased with quercetin. Furthermore, quercetin resulted in phosphoinositide 3-kinase (PI3K induction, Ca2+ restoration, and blockade of the activities of Jun N-terminal kinase (JNK, activating transcription factor 6 (ATF6 and especially NF-κB (p65 and p50 nuclear translocation. A PI3K inhibitor abrogated the protection of quercetin on ERS and inflammation of mouse hepatocytes. SP600125 (JNK inhibitor, AEBSF (ATF6 inhibitor, and especially PDTC (NF-κB inhibitor enhanced the quercetin-induced protection against Tg stimulation. Collectively, intense exercise-induced ERS and inflammation were attenuated by quercetin. PI3K/Akt activation and JNK, ATF6, and especially NF-κB suppression were involved in the protection. Our results highlight a novel preventive strategy for treating ERS and inflammation-mediated liver damage induced by intense exercise using natural phytochemicals.

  4. Hepatoprotective Effect of Quercetin on Endoplasmic Reticulum Stress and Inflammation after Intense Exercise in Mice through Phosphoinositide 3-Kinase and Nuclear Factor-Kappa B

    Science.gov (United States)

    Tang, Yuhan; Li, Juan; Gao, Chao; Xu, Yanyan; Li, Yanyan; Yu, Xiao; Wang, Jing; Liu, Liegang

    2016-01-01

    The mechanisms underlying intense exercise-induced liver damage and its potential treatments remain unclear. We explored the hepatoprotection and mechanisms of quercetin, a naturally occurring flavonoid, in strenuous exercise-derived endoplasmic reticulum stress (ERS) and inflammation. Intense exercise (28 m/min at a 5° slope for 90 min) resulted in the leakage of aminotransferases in the BALB/C mice. The hepatic ultrastructural malformations and oxidative stress levels were attenuated by quercetin (100 mg/kg·bw). Intense exercise and thapsigargin- (Tg-) induced ERS (glucose-regulated protein 78, GRP78) and inflammatory cytokines levels (IL-6 and TNF-α) were decreased with quercetin. Furthermore, quercetin resulted in phosphoinositide 3-kinase (PI3K) induction, Ca2+ restoration, and blockade of the activities of Jun N-terminal kinase (JNK), activating transcription factor 6 (ATF6) and especially NF-κB (p65 and p50 nuclear translocation). A PI3K inhibitor abrogated the protection of quercetin on ERS and inflammation of mouse hepatocytes. SP600125 (JNK inhibitor), AEBSF (ATF6 inhibitor), and especially PDTC (NF-κB inhibitor) enhanced the quercetin-induced protection against Tg stimulation. Collectively, intense exercise-induced ERS and inflammation were attenuated by quercetin. PI3K/Akt activation and JNK, ATF6, and especially NF-κB suppression were involved in the protection. Our results highlight a novel preventive strategy for treating ERS and inflammation-mediated liver damage induced by intense exercise using natural phytochemicals. PMID:27504150

  5. The Arabidopsis DREB2 genetic pathway is constitutively repressed by basal phosphoinositide-dependent phospholipase C coupled to diacylglycerol kinase in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Nabila eDjafi

    2013-08-01

    Full Text Available Phosphoinositide-dependent phospholipases C (PI-PLCs are activated in response to various stimuli. They utilize substrates provided by type III-Phosphatidylinositol-4 kinases (PI4KIII to produce inositol triphosphate and diacylglycerol (DAG that is phosphorylated into phosphatidic acid (PA by DAG-kinases (DGKs. The roles of PI4KIIIs, PI-PLCs and DGKs in basal signalling are poorly understood. We investigated the control of gene expression by basal PI-PLC pathway in Arabidopsis thaliana suspension cells. A transcriptome-wide analysis allowed the identification of genes whose expression was altered by edelfosine, 30 µM wortmannin or R59022, inhibitors of PI-PLCs, PI4KIIIs and DGKs, respectively. We found that a gene responsive to one of these molecules is more likely to be similarly regulated by the other two inhibitors. The common action of these agents is to inhibit PA formation, showing that basal PI-PLCs act, in part, on gene expression through their coupling to DGKs. Amongst the genes up-regulated in presence of the inhibitors, were some DREB2 genes, in suspension cells and in seedlings. The DREB2 genes encode transcription factors with major roles in responses to environmental stresses, including dehydration. They bind to C-repeat motifs, known as Drought-Responsive Elements, that are indeed enriched in the promoters of genes up-regulated by PI-PLC pathway inhibitors. PA can also be produced by phospholipases D (PLDs. We show that the DREB2 genes that are up-regulated by PI-PLC inhibitors are positively or negatively regulated, or indifferent, to PLD basal activity. Our data show that the DREB2 genetic pathway is constitutively repressed in resting conditions and that DGK coupled to PI-PLC is active in this process, in suspension cells and seedlings. We discuss how this basal negative regulation of DREB2 genes is compatible with their stress-triggered positive regulation.

  6. Definition of the binding mode of phosphoinositide 3-kinase α-selective inhibitor A-66S through molecular dynamics simulation.

    Science.gov (United States)

    Bian, Xiaoli; Dong, Wangqing; Zhao, Yang; Sun, Rui; Kong, Wanjun; Li, Yiping

    2014-04-01

    Activation of the phosphatidylinositol 3-kinase α (PI3Kα) is commonly observed in human cancer and is critical for tumor progression, which has made PI3Kα an attractive target for anticancer drug discovery. To systematically investigate the binding mode of A-66S, a new selective PI3Kα inhibitor for PI3Kα, molecular docking, molecular dynamics simulation and ensuing energetic analysis were performed. The binding free energy between PI3Kα and A-66S is -11.27 kcal•mol⁻¹ using MMPBSA method, while -14.67 kcal•mol⁻¹ using MMGBSA method, which is beneficial for the binding, and the van der Waals/hydrophobic and electrostatic interactions are critical for the binding. The conserved hydrophobic adenine region of PI3Kα made up of Met772, Pro778, Ile800, Tyr836, Ile848, Val850, Val851, Met922, Phe930 and Ile932 accommodates the flat 2-tert-butyl-4'-methyl-4,5'-bithiazol moiety of A-66S, and the NH of Val851 forms a hydrogen with the nitrogen atom embedded in the aminothiazole ring of A-66S. The (S)-pyrrolidine carboxamide urea moiety especially extends toward the region of the binding site wall (Ser854-Gln859) defined by the C-terminal lobe, and has three hydrogen-bond arms with the backbone of Ser854 and the side chain of Gln859. Notably the interaction between the non-conserved residue Gln859 and A-66S is responsible for the selectivity profile of A-66S. The binding mode of A-66S for PI3Kα presented in this study should aid in the design of a new highly selective PI3Kα inhibitor. PMID:24633771

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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...

  12. '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

  13. 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

  14. 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.

  15. Bacterial Cellular Engineering by Genome Editing and Gene Silencing

    Directory of Open Access Journals (Sweden)

    Nobutaka Nakashima

    2014-02-01

    Full Text Available Genome editing is an important technology for bacterial cellular engineering, which is commonly conducted by homologous recombination-based procedures, including gene knockout (disruption, knock-in (insertion, and allelic exchange. In addition, some new recombination-independent approaches have emerged that utilize catalytic RNAs, artificial nucleases, nucleic acid analogs, and peptide nucleic acids. Apart from these methods, which directly modify the genomic structure, an alternative approach is to conditionally modify the gene expression profile at the posttranscriptional level without altering the genomes. This is performed by expressing antisense RNAs to knock down (silence target mRNAs in vivo. This review describes the features and recent advances on methods used in genomic engineering and silencing technologies that are advantageously used for bacterial cellular engineering.

  16. MPI Profiling

    Energy Technology Data Exchange (ETDEWEB)

    Han, D K; Jones, T R

    2005-02-11

    The Message Passing Interface (MPI) is the de facto message-passing standard for massively parallel programs. It is often the case that application performance is a crucial factor, especially for solving grand challenge problems. While there have been many studies on the scalability of applications, there have not been many focusing on the specific types of MPI calls being made and their impact on application performance. Using a profiling tool called mpiP, a large spectrum of parallel scientific applications were surveyed and their performance results analyzed.

  17. Gene expression profiles of mouse spermatogenesis during recovery from irradiation

    DEFF Research Database (Denmark)

    Shah, Fozia J; Tanaka, Masami; Nielsen, John E;

    2009-01-01

    cellular changes that happen during recovery from irradiation by means of histology. We have earlier generated gene expression profiles during induction of spermatogenesis in mouse postnatal developing testes and found a correlation between profiles and the expressing cell types. The aim of the present...... work was to utilize the link between expression profile and cell types to follow the cellular changes that occur during post-irradiation recovery of spermatogenesis in order to describe recovery by means of gene expression. METHODS: Adult mouse testes were subjected to irradiation with 1 Gy or a...

  18. 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.

  19. 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

  20. Nuclear and cytoplasmic signalling in the cellular response to ionising radiation

    International Nuclear Information System (INIS)

    DNA is the universal primary target for ionising radiation; however, the cellular response is highly diversified not only by differential DNA repair ability. The monitoring system for the ionising radiation-inflicted DNA damage consists of 3 apparently independently acting enzymes which are activated by DNA breaks: two protein kinases, ATM (ataxia telangiectasia mutated) and DNA-PK (DNA-dependent protein kinase) and a poly(ADP-ribose) polymerase, PARP-1. These 3 enzymes are the source of alarm signals, which affect to various extents DNA repair, progression through the cell cycle and eventually the pathway to cell death. Their functions probably are partly overlapping. On the side of DNA repair their role consists in recruiting and/or activating the repair enzymes, as well as preventing illegitimate recombination of the damaged sites. A large part of the nuclear signalling pathway, including the integrating role of TP53 has been revealed. Two main signalling pathways start at the plasma membrane: the MAPK/ERK (mitogen and extracellular signal regulated protein kinase family) 'survival pathway' and the SAPK/JNK (stress-activated protein kinase/c-Jun N-terminal kinase) 'cell death pathway'. The balance between them is likely to determine the cell's fate. An additional important 'survival pathway' starts at the insulin-like growth factor type I receptor (IGF-IR), involves phosphoinositide- 3 kinase and Akt kinase and is targeted at inactivation of the pro-apoptotic BAD protein. Interestingly, over-expression of IGF-IR almost entirely abrogates the extreme radiation sensitivity of ataxia telangiectasia cells. When DNA break rejoining is impaired, the cell is unconditionally radiation sensitive. The fate of a repair-competent cell is determined by the time factor: the cell cycle arrest should be long enough to ensure the completion of repair. Incomplete repair or misrepair may be tolerated, when generation of the death signal is prevented. So, the character and timing

  1. In silico studies of the effect of phenolic compounds from grape seed extracts on the activity of phosphoinositide 3-kinase (PI3K) and the farnesoid x receptor (FXR)

    OpenAIRE

    Vaqué Marquès, Montserrat

    2007-01-01

    In silico studies of the effect of phenolic compounds from grape seed extracts on the activity of phosphoinositide 3-kinase (PI3K) and farnesoid X receptor (FXR)Montserrat Vaqué Marquès En aquesta tesis es pretén aplicar metodologies computacionals (generació de farmacòfors i docking proteïna lligand) en l'àmbit de la nutigenòmica (ciència que pretén entendre, a nivell molecular, com els nutrients afecten la salut). S'aplicaran metodologies in silico per entendre a nivell molecular com produc...

  2. Molecular profiling of neurons based on connectivity.

    Science.gov (United States)

    Ekstrand, Mats I; Nectow, Alexander R; Knight, Zachary A; Latcha, Kaamashri N; Pomeranz, Lisa E; Friedman, Jeffrey M

    2014-05-22

    The complexity and cellular heterogeneity of neural circuitry presents a major challenge to understanding the role of discrete neural populations in controlling behavior. While neuroanatomical methods enable high-resolution mapping of neural circuitry, these approaches do not allow systematic molecular profiling of neurons based on their connectivity. Here, we report the development of an approach for molecularly profiling projective neurons. We show that ribosomes can be tagged with a camelid nanobody raised against GFP and that this system can be engineered to selectively capture translating mRNAs from neurons retrogradely labeled with GFP. Using this system, we profiled neurons projecting to the nucleus accumbens. We then used an AAV to selectively profile midbrain dopamine neurons projecting to the nucleus accumbens. By comparing the captured mRNAs from each experiment, we identified a number of markers specific to VTA dopaminergic projection neurons. The current method provides a means for profiling neurons based on their projections. PMID:24855954

  3. 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.

  4. 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.

  5. 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.

  6. Alpha 1-adrenergic receptor-mediated phosphoinositide hydrolysis and prostaglandin E2 formation in Madin-Darby canine kidney cells. Possible parallel activation of phospholipase C and phospholipase A2

    International Nuclear Information System (INIS)

    alpha 1-Adrenergic receptors mediate two effects on phospholipid metabolism in Madin-Darby canine kidney (MDCK-D1) cells: hydrolysis of phosphoinositides and arachidonic acid release with generation of prostaglandin E2 (PGE2). The similarity in concentration dependence for the agonist (-)-epinephrine in eliciting these two responses implies that they are mediated by a single population of alpha 1-adrenergic receptors. However, we find that the kinetics of the two responses are quite different, PGE2 production occurring more rapidly and transiently than the hydrolysis of phosphoinositides. The antibiotic neomycin selectively decreases alpha 1-receptor-mediated phosphatidylinositol 4,5-bisphosphate hydrolysis without decreasing alpha 1-receptor-mediated arachidonic acid release and PGE2 generation. In addition, receptor-mediated inositol trisphosphate formation is independent of extracellular calcium, whereas release of labeled arachidonic acid is largely calcium-dependent. Moreover, based on studies obtained with labeled arachidonic acid, receptor-mediated generation of arachidonic acid cannot be accounted for by breakdown of phosphatidylinositol monophosphate, phosphatidylinositol bisphosphate, or phosphatidic acid. Further studies indicate that epinephrine produces changes in formation or turnover of several classes of membrane phospholipids in MDCK cells. We conclude that alpha 1-adrenergic receptors in MDCK cells appear to regulate phospholipid metabolism by the parallel activation of phospholipase C and phospholipase A2. This parallel activation of phospholipases contrasts with models described in other systems which imply sequential activation of phospholipase C and diacylglycerol lipase or phospholipase A2

  7. Cellular phones: are they detrimental?

    Science.gov (United States)

    Salama, Osama E; Abou El Naga, Randa M

    2004-01-01

    The issue of possible health effects of cellular phones is very much alive in the public's mind where the rapid increase in the number of the users of cell phones in the last decade has increased the exposure of people to the electromagnetic fields (EMFs). Health consequences of long term use of mobile phones are not known in detail but available data indicates the development of non specific annoying symptoms on acute exposure to mobile phone radiations. In an attempt to determine the prevalence of such cell phones associated health manifestations and the factors affecting their occurrence, a cross sectional study was conducted in five randomly selected faculties of Alexandria University. Where, 300 individuals including teaching staff, students and literate employee were equally allocated and randomly selected among the five faculties. Data about mobile phone's users and their medical history, their pattern of mobile usage and the possible deleterious health manifestations associated with cellular phone use was collected. The results revealed 68% prevalence of mobile phone usage, nearly three quarters of them (72.5%) were complainers of the health manifestations. They suffered from headache (43%), earache (38.3%), sense of fatigue (31.6%), sleep disturbance (29.5%), concentration difficulty (28.5%) and face burning sensation (19.2%). Both univariate and multivariate analysis were consistent in their findings. Symptomatic users were found to have significantly higher frequency of calls/day, longer call duration and longer total duration of mobile phone usage/day than non symptomatic users. For headache both call duration and frequency of calls/day were the significant predicting factors for its occurrence (chi2 = 18.208, p = 0.0001). For earache, in addition to call duration, the longer period of owning the mobile phone were significant predictors (chi2 = 16.996, p = 0.0002). Sense of fatigue was significantly affected by both call duration and age of the user

  8. The mammary cellular hierarchy and breast cancer

    OpenAIRE

    Oakes, Samantha R.; Gallego-Ortega, David; Ormandy, Christopher J.

    2014-01-01

    Advances in the study of hematopoietic cell maturation have paved the way to a deeper understanding the stem and progenitor cellular hierarchy in the mammary gland. The mammary epithelium, unlike the hematopoietic cellular hierarchy, sits in a complex niche where communication between epithelial cells and signals from the systemic hormonal milieu, as well as from extra-cellular matrix, influence cell fate decisions and contribute to tissue homeostasis. We review the discovery, definition and ...

  9. A radiation measurement study on cellular phone

    International Nuclear Information System (INIS)

    This paper will explain the radiation level produced by various selected cellular phone from various models and brands available in the market. The result obtained from this study will also recommend whether a cellular phone is safe for public usage or it might cause any effect on public health. Finally, a database of radiation measurement level produced by selected various cellular phone will also be developed and exhibited in this paper. (Author)

  10. Predicting Cellular Growth from Gene Expression Signatures

    OpenAIRE

    Dunham, Maitreya J.; Troyanskaya, Olga G.; Airoldi, Edoardo; Broach, James R.; Caudy, Amy A.; Gresham, David; Botstein, David; Huttenhower, Curtis; Lu, Charles

    2009-01-01

    Maintaining balanced growth in a changing environment is a fundamental systems-level challenge for cellular physiology, particularly in microorganisms. While the complete set of regulatory and functional pathways supporting growth and cellular proliferation are not yet known, portions of them are well understood. In particular, cellular proliferation is governed by mechanisms that are highly conserved from unicellular to multicellular organisms, and the disruption of these processes in metazo...

  11. 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 ...

  12. Radiation, nitric oxide and cellular death

    International Nuclear Information System (INIS)

    The mechanisms of radiation induced cellular death constitute an objective of research ever since the first biological effects of radiation were first observed. The explosion of information produced in the last 20 years calls for a careful analysis due to the apparent contradictory data related to the cellular system studied and the range of doses used. This review focuses on the role of the active oxygen species, in particular the nitric oxides, in its relevance as potential mediator of radiation induced cellular death

  13. Autophagy and mitophagy in cellular damage control

    Directory of Open Access Journals (Sweden)

    Jianhua Zhang

    2013-01-01

    Full Text Available Autophagy and mitophagy are important cellular processes that are responsible for breaking down cellular contents, preserving energy and safeguarding against accumulation of damaged and aggregated biomolecules. This graphic review gives a broad summary of autophagy and discusses examples where autophagy is important in controlling protein degradation. In addition we highlight how autophagy and mitophagy are involved in the cellular responses to reactive species and mitochondrial dysfunction. The key signaling pathways for mitophagy are described in the context of bioenergetic dysfunction.

  14. The cellular particle swarm optimization algorithm

    International Nuclear Information System (INIS)

    This work presents a variant of the Particle Swarm Optimization (PSO) original algorithm, the Cellular-PSO. Inspired by the cellular Genetic Algorithm (GA), particles in Cellular-PSO are arranged into a matrix of cells interconnected according to a given topology. Such topology defines particle's neighborhood, inside which social adaptation may occur. As a consequence, population diversity is increased and the optimization process becomes more efficient and robust. The proposed Cellular-PSO has been applied to the nuclear reactor core design optimization problem and comparative experiments demonstrated that it is superior to the standard PSO. (author)

  15. Optimized Cellular Core for Rotorcraft Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Patz Materials and Technologies proposes to develop a unique structural cellular core material to improve mechanical performance, reduce platform weight and lower...

  16. 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

  17. Efficiency of cellular information processing

    CERN Document Server

    Barato, Andre C; Seifert, Udo

    2014-01-01

    We show that a rate of conditional Shannon entropy reduction, characterizing the learning of an internal process about an external process, is bounded by the thermodynamic entropy production. This approach allows for the definition of an informational efficiency that can be used to study cellular information processing. We analyze three models of increasing complexity inspired by the E. coli sensory network, where the external process is an external ligand concentration jumping between two values. We start with a simple model for which ATP must be consumed so that a protein inside the cell can learn about the external concentration. With a second model for a single receptor we show that the rate at which the receptor learns about the external environment can be nonzero even without any dissipation inside the cell since chemical work done by the external process compensates for this learning rate. The third model is more complete, also containing adaptation. For this model we show inter alia that a bacterium i...

  18. Probabilistically determining the cellular source of DNA derived from differential extractions in sexual assault scenarios.

    Science.gov (United States)

    Taylor, Duncan

    2016-09-01

    Sexual assault cases are the type of case that often produces questions about the cellular source of DNA. In these cases multiple findings of microscopy, DNA profiling and presumptive testing need to be considered when addressing source level propositions. In this work, I consider a line of questioning that has been raised a number of times in the recent past, where in court it was disputed that low levels of sperm seen on a microscope slide were the cellular source of the male DNA profile component generated from the sperm fraction of a differential DNA extraction. I demonstrate how the cell scoring results and DNA profiling results can be considered together, in helping address this source level question through the use of Bayesian Networks. PMID:27388428

  19. Pulsed feedback defers cellular differentiation.

    Directory of Open Access Journals (Sweden)

    Joe H Levine

    2012-01-01

    Full Text Available Environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well-characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable "polyphasic" positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a "timer" that operates over timescales much longer than a cell cycle.

  20. Immune cellular response to HPV: current concepts

    Directory of Open Access Journals (Sweden)

    Maria Alice Guimarães Gonçalves

    2004-02-01

    Full Text Available Although cellular immunity is essential for the elimination of human papillomavirus (HPV, the mechanisms involved are still poorly understood. We summarize the main mechanisms involved in cellular immune response to infections caused by HPV. Immunotherapies for HPV-related cancers require the disruption of T-cell response control mechanisms, associated with the stimulation of the Th1 cytokine response.

  1. Mechanisms of cellular transformation by carcinogenic agents

    International Nuclear Information System (INIS)

    This book contains 14 chapters. Some of the chapter titles are: DNA Modification by Chemical Carcinogens; Role of DNA Lesions and Repair in the Transformation of Human Cells; The Induction and Regulation of Radiogenic Transformation In Vitro: Cellular and Molecular Mechanisms; Cellular Transformation by Adenoviruses; and The fos Gene

  2. Recent development of cellular manufacturing systems

    Indian Academy of Sciences (India)

    P K Arora; A Haleem; M K Singh

    2013-06-01

    Cellular manufacturing system has been proved a vital approach for batch and job shop production systems. Group technology has been an essential tool for developing a cellular manufacturing system. The paper aims to discuss various cell formation techniques and highlights the significant research work done in past over the years and attempts to points out the gap in research.

  3. Mechanisms of cellular transformation by carcinogenic agents

    Energy Technology Data Exchange (ETDEWEB)

    Grunberger, D.; Goff, S.P.

    1987-01-01

    This book contains 14 chapters. Some of the chapter titles are: DNA Modification by Chemical Carcinogens; Role of DNA Lesions and Repair in the Transformation of Human Cells; The Induction and Regulation of Radiogenic Transformation In Vitro: Cellular and Molecular Mechanisms; Cellular Transformation by Adenoviruses; and The fos Gene.

  4. LMS filters for cellular CDMA overlay

    OpenAIRE

    Wang, J.

    1996-01-01

    This paper extends and complements previous research we have performed on the performance of nonadaptive narrowband suppression filters when used in cellular CDMA overlay situations. In this paper, an adaptive LMS filter is applied to cellular CDMA overlay situations in order to reject narrowband interference.

  5. From Cnn Dynamics to Cellular Wave Computers

    Science.gov (United States)

    Roska, Tamas

    2013-01-01

    Embedded in a historical overview, the development of the Cellular Wave Computing paradigm is presented, starting from the standard CNN dynamics. The theoretical aspects, the physical implementation, the innovation process, as well as the biological relevance are discussed in details. Finally, the latest developments, the physical versus virtual cellular machines, as well as some open questions are presented.

  6. The Universe as a Cellular System

    CERN Document Server

    Aragón-Calvo, Miguel A

    2014-01-01

    Cellular systems are observed everywhere in nature, from crystal domains in metals, soap froth and cucumber cells to the network of cosmological voids. Surprisingly, despite their disparate scale and origin all cellular systems follow certain scaling laws relating their geometry, topology and dynamics. Using a cosmological N-body simulation we found that the Cosmic Web, the largest known cellular system, follows the same scaling relations seen elsewhere in nature. Our results extend the validity of scaling relations in cellular systems by over 30 orders of magnitude in scale with respect to previous studies. The dynamics of cellular systems can be used to interpret local observations such as the local velocity anomaly as the result of a collapsing void in our cosmic backyard. Moreover, scaling relations depend on the curvature of space, providing an independent measure of geometry.

  7. Syphilis Profiles, 2012

    Science.gov (United States)

    ... STD on Facebook Data & Statistics Sexually Transmitted Diseases Syphilis Profiles, 2012 Recommend on Facebook Tweet Share Compartir ... Profiles The following profiles provide an overview of syphilis morbidity in each of the 50 states, the ...

  8. Markers of cellular senescence. Telomere shortening as a marker of cellular senescence.

    Science.gov (United States)

    Bernadotte, Alexandra; Mikhelson, Victor M; Spivak, Irina M

    2016-01-01

    The cellular senescence definition comes to the fact of cells irreversible proliferation disability. Besides the cell cycle arrest, senescent cells go through some morphological, biochemical, and functional changes which are the signs of cellular senescence. The senescent cells (including replicative senescence and stress-induced premature senescence) of all the tissues look alike. They are metabolically active and possess the set of characteristics in vitro and in vivo, which are known as biomarkers of aging and cellular senescence. Among biomarkers of cellular senescence telomere shortening is a rather elegant frequently used biomarker. Validity of telomere shortening as a marker for cellular senescence is based on theoretical and experimental data. PMID:26805432

  9. HOPWA Performance Profiles

    Data.gov (United States)

    Department of Housing and Urban Development — HOPWA Performance Profiles are generated quarterly for all agencies receiving HOPWA formula or competitive grants. Performance Profiles are available at the...

  10. Estimating cellular network performance during hurricanes

    International Nuclear Information System (INIS)

    Cellular networks serve a critical role during and immediately after a hurricane, allowing citizens to contact emergency services when land-line communication is lost and serving as a backup communication channel for emergency responders. However, due to their ubiquitous deployment and limited design for extreme loading events, basic network elements, such as cellular towers and antennas are prone to failures during adverse weather conditions such as hurricanes. Accordingly, a systematic and computationally feasible approach is required for assessing and improving the reliability of cellular networks during hurricanes. In this paper we develop a new multi-disciplinary approach to efficiently and accurately assess cellular network reliability during hurricanes. We show how the performance of a cellular network during and immediately after future hurricanes can be estimated based on a combination of hurricane wind field models, structural reliability analysis, Monte Carlo simulation, and cellular network models and simulation tools. We then demonstrate the use of this approach for assessing the improvement in system reliability that can be achieved with discrete topological changes in the system. Our results suggest that adding redundancy, particularly through a mesh topology or through the addition of an optical fiber ring around the perimeter of the system can be an effective way to significantly increase the reliability of some cellular systems during hurricanes.

  11. Molecular and cellular limits to somatosensory specificity

    Directory of Open Access Journals (Sweden)

    Viana Félix

    2008-04-01

    involved primarily in nerve impulse generation can also influence the gating of transducing channels, dramatically modifying their activation profile. Thus, we propose that the capacity exhibited by the different functional types of somatosensory receptor neurons to preferentially detect and encode specific stimuli into a discharge of nerve impulses, appears to result of a characteristic combinatorial expression of different ion channels in each neuronal type that finally determines their transduction and impulse firing properties. Transduction channels don't operate in isolation and their cellular context should also be taken into consideration to fully understand their function. Moreover, the inhomogeneous distribution of transduction and voltage-gated channels at soma, axonal branches and peripheral endings of primary sensory neurons influences the characteristics of the propagated impulse discharge that encodes the properties of the stimulus. Alteration of this concerted operation of ion channels in pathological conditions may underlie the changes in excitability accompanying peripheral sensory neuron injuries.

  12. 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

  13. Integrating mitochondrial translation into the cellular context.

    Science.gov (United States)

    Richter-Dennerlein, Ricarda; Dennerlein, Sven; Rehling, Peter

    2015-10-01

    Mitochondrial-encoded subunits of the oxidative phosphorylation system assemble with nuclear-encoded subunits into enzymatic complexes. Recent findings showed that mitochondrial translation is linked to other mitochondrial functions, as well as to cellular processes. The supply of mitochondrial-encoded proteins is coordinated by the coupling of mitochondrial protein synthesis with assembly of respiratory chain complexes. MicroRNAs imported from the cytoplasm into mitochondria were, surprisingly, found to act as regulators of mitochondrial translation. In turn, translation in mitochondria controls cellular proliferation, and mitochondrial ribosomal subunits contribute to the cytoplasmic stress response. Thus, translation in mitochondria is apparently integrated into cellular processes. PMID:26535422

  14. Cellular and molecular mechanisms in kidney fibrosis

    Science.gov (United States)

    Duffield, Jeremy S.

    2014-01-01

    Fibrosis is a characteristic feature of all forms of chronic kidney disease. Deposition of pathological matrix in the interstitial space and within the walls of glomerular capillaries as well as the cellular processes resulting in this deposition are increasingly recognized as important factors amplifying kidney injury and accelerating nephron demise. Recent insights into the cellular and molecular mechanisms of fibrogenesis herald the promise of new therapies to slow kidney disease progression. This review focuses on new findings that enhance understanding of cellular and molecular mechanisms of fibrosis, the characteristics of myofibroblasts, their progenitors, and molecular pathways regulating both fibrogenesis and its resolution. PMID:24892703

  15. Nanomechanics of magnetically driven cellular endocytosis

    Science.gov (United States)

    Zablotskii, V.; Lunov, O.; Dejneka, A.; Jastrabík, L.; Polyakova, T.; Syrovets, T.; Simmet, Th.

    2011-10-01

    Being essential for many pharmacodynamic and pharmacokinetic processes and playing a crucial role in regulating substrate detachment that enables cellular locomotion, endocytotic mechanisms in many aspects still remain a mystery and therefore can hardly be controlled. Here, we report on experimental and modeling studies of the magnetically assisted endocytosis of functionalized superparamagnetic iron oxide nanoparticles by prostate cancer cells (PC-3) and characterize the time and force scales of the cellular uptake machinery. The results indicate how the cellular uptake rate could be controlled by applied magnetic field, membrane elasticity, and nanoparticle magnetic moment.

  16. Cellular Signaling Pathways and Their Clinical Reflections

    Directory of Open Access Journals (Sweden)

    N. Ceren Sumer-Turanligil

    2010-06-01

    Full Text Available Cellular signaling pathways have important roles in cellular growth, differentiation, inflammatory response and apoptosis and in regulation of cellular responses under various chemical stimulators. Different proteins which belong to these pathways may be exposed to loss-of-function or gain-of-function mutations; this may lead to many clinical phenotypes including primarily cancer. In this review information about basic working principles of these pathways and diseases related to them are included. [Archives Medical Review Journal 2010; 19(3.000: 180-191

  17. Imaging in cellular and tissue engineering

    CERN Document Server

    Yu, Hanry

    2013-01-01

    Details on specific imaging modalities for different cellular and tissue engineering applications are scattered throughout articles and chapters in the literature. Gathering this information into a single reference, Imaging in Cellular and Tissue Engineering presents both the fundamentals and state of the art in imaging methods, approaches, and applications in regenerative medicine. The book underscores the broadening scope of imaging applications in cellular and tissue engineering. It covers a wide range of optical and biological applications, including the repair or replacement of whole tiss

  18. Cellular Cell Bifurcation of Cylindrical Detonations

    Institute of Scientific and Technical Information of China (English)

    HAN Gui-Lai; JIANG Zong-Lin; WANG Chun; ZHANG Fan

    2008-01-01

    Cellular cell pattern evolution of cylindrically-diverging detonations is numerically simulated successfully by solving two-dimensional Euler equations implemented with an improved two-step chemical kinetic model. From the simulation, three cell bifurcation modes are observed during the evolution and referred to as concave front focusing, kinked and wrinkled wave front instability, and self-merging of cellular cells. Numerical research demonstrates that the wave front expansion resulted from detonation front diverging plays a major role in the cellular cell bifurcation, which can disturb the nonlinearly self-sustained mechanism of detonations and finally lead to cell bifurcations.

  19. Cellular chain formation in Escherichia coli biofilms

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk; Klemm, Per

    2009-01-01

    In this study we report on a novel structural phenotype in Escherichia coli biofilms: cellular chain formation. Biofilm chaining in E. coli K-12 was found to occur primarily by clonal expansion, but was not due to filamentous growth. Rather, chain formation was the result of intercellular......; type I fimbriae expression significantly reduced cellular chain formation, presumably by steric hindrance. Cellular chain formation did not appear to be specific to E coli K-12. Although many urinary tract infection (UTI) isolates were found to form rather homogeneous, flat biofilms, three isolates...

  20. Interworking of Wireless LANs and Cellular Networks

    CERN Document Server

    Song, Wei

    2012-01-01

    The next-generation of wireless communications are envisioned to be supported by heterogeneous networks by using various wireless access technologies. The popular cellular networks and wireless local area networks (WLANs) present perfectly complementary characteristics in terms of service capacity, mobility support, and quality-of-service (QoS) provisioning. The cellular/WLAN interworking is an effective way to promote the evolution of wireless networks. "Interworking of Wireless LANs and Cellular Networks" focuses on three aspects, namely access selection, call admission control and

  1. 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

  2. The role of sirtuins in cellular homeostasis.

    Science.gov (United States)

    Kupis, Wioleta; Pałyga, Jan; Tomal, Ewa; Niewiadomska, Ewa

    2016-09-01

    Sirtuins are evolutionarily conserved nicotinamide adenine dinucleotide (NAD(+))-dependent lysine deacylases or ADP-ribosyltransferases. These cellular enzymes are metabolic sensors sensitive to NAD(+) levels that maintain physiological homeostasis in the animal and plant cells. PMID:27154583

  3. Optimized Cellular Core for Rotorcraft Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Patz Materials and Technologies has developed, produced and tested, as part of the Phase-I SBIR, a new form of composite cellular core material, named Interply...

  4. MILLIMETER-WAVE EMISSIVITY OF CELLULAR SYSTEMS

    Science.gov (United States)

    A general analysis has been presented of the millimeter-wave and farinfrared spectroscopic properties of in vivo cellular systems, and of the boson radiative equilibrium with steady-state nonequilibrium molecular systems. The frequency threshhold of spectroscopic properties assoc...

  5. A Matrix Construction of Cellular Algebras

    Institute of Scientific and Technical Information of China (English)

    Dajing Xiang

    2005-01-01

    In this paper, we give a concrete method to construct cellular algebras from matrix algebras by specifying certain fixed matrices for the data of inflations. In particular,orthogonal matrices can be chosen for such data.

  6. Probing Cellular Dynamics with Mesoscopic Simulations

    DEFF Research Database (Denmark)

    Shillcock, Julian C.

    2010-01-01

    Cellular processes span a huge range of length and time scales from the molecular to the near-macroscopic. Understanding how effects on one scale influence, and are themselves influenced by, those on lower and higher scales is a critical issue for the construction of models in Systems Biology....... Advances in computing hardware and software now allow explicit simulation of some aspects of cellular dynamics close to the molecular scale. Vesicle fusion is one example of such a process. Experiments, however, typically probe cellular behavior from the molecular scale up to microns. Standard particle...... soon be coupled to Mass Action models allowing the parameters in such models to be continuously tuned according to the finer resolution simulation. This will help realize the goal of a computational cellular simulation that is able to capture the dynamics of membrane-associated processes such as...

  7. Vectorized multisite coding for hydrodynamic cellular automata

    International Nuclear Information System (INIS)

    Simulating eight lattices for Pomeau's cellular automata simultaneously through bit-per-bit operations, a vectorized Fortran program reached 30 million updates per second and per Cray YMP processor. They authors give the full innermost loops

  8. 47 CFR 22.911 - Cellular geographic service area.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular geographic service area. 22.911... PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.911 Cellular geographic service area. The Cellular Geographic Service Area (CGSA) of a cellular system is the geographic area considered by the...

  9. Line Complexity Asymptotics of Polynomial Cellular Automata

    OpenAIRE

    Stone, Bertrand

    2016-01-01

    Cellular automata are discrete dynamical systems that consist of patterns of symbols on a grid, which change according to a locally determined transition rule. In this paper, we will consider cellular automata that arise from polynomial transition rules, where the symbols in the automaton are integers modulo some prime $p$. We are principally concerned with the asymptotic behavior of the line complexity sequence $a_T(k)$, which counts, for each $k$, the number of coefficient strings of length...

  10. Cellular Restriction Factors of Feline Immunodeficiency Virus

    OpenAIRE

    Carsten Münk; Jörg Zielonka

    2011-01-01

    Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors) or inhibit viral replication (restriction factors). Similar to Human immunodeficiency virus type 1 (HIV-1), the cat lentivirus Feline immunodeficiency virus (FIV) is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating...

  11. Cellular and molecular mechanisms in kidney fibrosis

    OpenAIRE

    Duffield, Jeremy S.

    2014-01-01

    Fibrosis is a characteristic feature of all forms of chronic kidney disease. Deposition of pathological matrix in the interstitial space and within the walls of glomerular capillaries as well as the cellular processes resulting in this deposition are increasingly recognized as important factors amplifying kidney injury and accelerating nephron demise. Recent insights into the cellular and molecular mechanisms of fibrogenesis herald the promise of new therapies to slow kidney disease progressi...

  12. Building mathematics cellular phone learning communities

    OpenAIRE

    Wajeeh M. Daher

    2011-01-01

    Researchers emphasize the importance of maintaining learning communities and environments. This article describes the building and nourishment of a learning community, one comprised of middle school students who learned mathematics out-of-class using the cellular phone. The building of the learning community was led by three third year pre-service teachers majoring in mathematics and computers. The pre-service teachers selected thirty 8th grade students to learn mathematics with the cellular ...

  13. Directed Percolation arising in Stochastic Cellular Automata

    OpenAIRE

    Regnault, Damien

    2008-01-01

    Cellular automata are both seen as a model of computation and as tools to model real life systems. Historically they were studied under synchronous dynamics where all the cells of the system are updated at each time step. Meanwhile the question of probabilistic dynamics emerges: on the one hand, to develop cellular automata which are capable of reliable computation even when some random errors occur; on the other hand, because synchronous dynamics is not a reasonable assumption to simulate re...

  14. Apoptotic regulation of epithelial cellular extrusion

    OpenAIRE

    De Andrade, Daniel,; Rosenblatt, Jody

    2011-01-01

    Cellular extrusion is a mechanism that removes dying cells from epithelial tissues to prevent compromising their barrier function. Extrusion occurs in all observed epithelia in vivo and can be modeled in vitro by inducing apoptosis in cultured epithelial monolayers. We established that actin and myosin form a ring that contracts in the surrounding cells that drives cellular extrusion. It is not clear, however, if all apoptotic pathways lead to extrusion and how apoptosis and extrusion are mol...

  15. Understanding cisplatin resistance using cellular models.

    OpenAIRE

    STORDAL, BRITTA KRISTINA

    2007-01-01

    PUBLISHED Many mechanisms of cisplatin resistance have been proposed from studies of cellular models of resistance including changes in cellular drug accumulation, detoxification of the drug, inhibition of apoptosis and repair of the DNA adducts. A series of resistant models were developed from CCRF-CEM leukaemia cells with increasing doses of cisplatin from 100 ng/ml. This produced increasing resistance up to 7-fold with a treatment dose of 1.6 ?g/ml. Cisplatin resistance i...

  16. Understanding cisplatin resistance using cellular models

    OpenAIRE

    Stordal, Britta; Davey, Mary

    2007-01-01

    Many mechanisms of cisplatin resistance have been proposed from studies of cellular models of resistance including changes in cellular drug accumulation, detoxification of the drug, inhibition of apoptosis and repair of the DNA adducts. A series of resistant models were developed from CCRF-CEM leukaemia cells with increasing doses of cisplatin from 100 ng/ml. This produced increasing resistance up to 7-fold with a treatment dose of 1.6 microg/ml. Cisplatin resistance in these cells correlated...

  17. On the Behavior Characteristics of Cellular Automata

    Institute of Scientific and Technical Information of China (English)

    CHEN Jin-cai; ZHANG Jiang-ling; FENG Dan

    2005-01-01

    In this paper, the inherent relationships between the running regulations and behavior characteristics of cellular automata are presented; an imprecise taxonomy of such systems is put forward; the three extreme cases of stable systems are discussed; and the illogicalness of evolutional strategies of cellular automata is analyzed. The result is suitable for the emulation and prediction of behavior of discrete dynamics systems; especially it can be taken as an important analysis means of dynamic performance of complex networks.

  18. Cellular Hyperproliferation and Cancer as Evolutionary Variables

    OpenAIRE

    Alvarado, Alejandro Sánchez

    2012-01-01

    Technological advances in biology have begun to dramatically change the way we think about evolution, development, health and disease. The ability to sequence the genomes of many individuals within a population, and across multiple species, has opened the door to the possibility of answering some long-standing and perplexing questions about our own genetic heritage. One such question revolves around the nature of cellular hyperproliferation. This cellular behavior is used to effect wound heal...

  19. Cellular Scaling Rules of Insectivore Brains

    OpenAIRE

    Sarko, Diana K.; Catania, Kenneth C.; Leitch, Duncan B.; Kaas, Jon H.; Herculano-Houzel, Suzana

    2009-01-01

    Insectivores represent extremes in mammalian body size and brain size, retaining various “primitive” morphological characteristics, and some species of Insectivora are thought to share similarities with small-bodied ancestral eutherians. This raises the possibility that insectivore brains differ from other taxa, including rodents and primates, in cellular scaling properties. Here we examine the cellular scaling rules for insectivore brains and demonstrate that insectivore scaling rules overla...

  20. Cellular scaling rules of insectivore brains

    OpenAIRE

    Sarko, Diana K.; Catania, Kenneth C.; Leitch, Duncan B.; Kaas, Jon H.; Suzana Herculano-Houzel

    2009-01-01

    Insectivores represent extremes in mammalian body size and brain size, retaining various “primitive” morphological characteristics, and some species of Insectivora are thought to share similarities with small-bodied ancestral eutherians. This raises the possibility that insectivore brains differ from other taxa, including rodents and primates, in cellular scaling properties. Here we examine the cellular scaling rules for insectivore brains and demonstrate that insectivore scaling ...

  1. Cellular scaling rules for primate brains

    OpenAIRE

    Herculano-Houzel, Suzana; Collins, Christine E.; Wong, Peiyan; Kaas, Jon H.

    2007-01-01

    Primates are usually found to have richer behavioral repertoires and better cognitive abilities than rodents of similar brain size. This finding raises the possibility that primate brains differ from rodent brains in their cellular composition. Here we examine the cellular scaling rules for primate brains and show that brain size increases approximately isometrically as a function of cell numbers, such that an 11× larger brain is built with 10× more neurons and ≈12× more nonneuronal cells of ...

  2. Stochastic Simulations on the Cellular Wave Computers

    OpenAIRE

    Ercsey-Ravasz, M.; Roska, T.; Néda, Z.

    2006-01-01

    The computational paradigm represented by Cellular Neural/nonlinear Networks (CNN) and the CNN Universal Machine (CNN-UM) as a Cellular Wave Computer, gives new perspectives for computational physics. Many numerical problems and simulations can be elegantly addressed on this fully parallelized and analogic architecture. Here we study the possibility of performing stochastic simulations on this chip. First a realistic random number generator is implemented on the CNN-UM, and then as an example...

  3. Weighted Centroid Correction Localization in Cellular Systems

    Directory of Open Access Journals (Sweden)

    Rong-Zheng Li

    2011-01-01

    Full Text Available Problem statement: There is a large demand for wireless Location-Based Service (LBS and it is provided by many wireless cellular systems. In process of positioning a Mobile Station (MS, the computing speed is as important as the positioning accuracy and the algorithm should also be resistant to environmental influences. Approach: A new positioning method based on Weighted Centroid Correction Localization (WCCL for wireless cellular systems is introduced in this article. Firstly, referring to the receiving-state of an MS in cellular systems, it computes a weighted centroid of surrounding Base Stations (BSs as a rough approximate position of the MS. Then, according to the distances between the MS and the BSs being less or bigger than the computed distances between the BSs and the weighted centroid, it corrects the coordinate of the weighted centroid towards the directions of the BSs by moving it closer or farther in turn. Results: According to our experiments, WCCL improves the positioning accuracy, as well as to provide a better resistance to environmental influences. Conclusion: As a modified centroid-based localization algorithm, WCCL obtains weighting factors from the receiving-state of MS in multi-cells structured cellular systems and obtains a better positioning result in cellular systems without updating the network equipment. Therefore, for the cellular positioning problem, WCCL algorithm can be an alternate solution.

  4. Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma.

    Science.gov (United States)

    Pelaia, Girolamo; Vatrella, Alessandro; Busceti, Maria Teresa; Gallelli, Luca; Calabrese, Cecilia; Terracciano, Rosa; Maselli, Rosario

    2015-01-01

    Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper (Th)2 cell-derived cytokines, whilst neutrophilic asthma is mostly dependent on Th17 cell-induced mechanisms. These immune-inflammatory profiles develop as a consequence of a functional impairment of T regulatory (Treg) lymphocytes, which promotes the activation of dendritic cells directing the differentiation of distinct Th cell subsets. The recent advances in the knowledge of the cellular and molecular mechanisms underlying asthmatic inflammation are contributing to the identification of novel therapeutic targets, potentially suitable for the implementation of future improvements in antiasthma pharmacologic treatments. PMID:25878402

  5. Cellular Mechanisms Underlying Eosinophilic and Neutrophilic Airway Inflammation in Asthma

    Directory of Open Access Journals (Sweden)

    Girolamo Pelaia

    2015-01-01

    Full Text Available Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper (Th2 cell-derived cytokines, whilst neutrophilic asthma is mostly dependent on Th17 cell-induced mechanisms. These immune-inflammatory profiles develop as a consequence of a functional impairment of T regulatory (Treg lymphocytes, which promotes the activation of dendritic cells directing the differentiation of distinct Th cell subsets. The recent advances in the knowledge of the cellular and molecular mechanisms underlying asthmatic inflammation are contributing to the identification of novel therapeutic targets, potentially suitable for the implementation of future improvements in antiasthma pharmacologic treatments.

  6. Reinforced aerodynamic profile

    DEFF Research Database (Denmark)

    2010-01-01

    The present invention relates to the prevention of deformations in an aerodynamic profile caused by lack of resistance to the bending moment forces that are created when such a profile is loaded in operation. More specifically, the invention relates to a reinforcing element inside an aerodynamic ...... profile and a method for the construction thereof. The profile is intended for, but not limited to, useas a wind turbine blade, an aerofoil device or as a wing profile used in the aeronautical industry....

  7. 47 CFR 22.970 - Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone...

    Science.gov (United States)

    2010-10-01

    .... Except as provided in 47 CFR 90.617(k), unacceptable interference to non-cellular part 90 licensees in...-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. 22.970 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.970 Unacceptable interference to part 90...

  8. Cellular reprogramming through mitogen-activated protein kinases

    Directory of Open Access Journals (Sweden)

    Justin eLee

    2015-10-01

    Full Text Available Mitogen-activated protein kinase (MAPK cascades are conserved eukaryote signaling modules where MAPKs, as the final kinases in the cascade, phosphorylate protein substrates to regulate cellular processes. While some progress in the identification of MAPK substrates has been made in plants, the knowledge on the spectrum of substrates and their mechanistic action is still fragmentary. In this focused review, we discuss the biological implications of the data in our original paper (Sustained mitogen-activated protein kinase activation reprograms defense metabolism and phosphoprotein profile in Arabidopsis thaliana; Frontiers in Plant Science 5: 554 in the context of related research. In our work, we mimicked in vivo activation of two stress-activated MAPKs, MPK3 and MPK6, through transgenic manipulation of Arabidopsis thaliana and used phosphoproteomics analysis to identify potential novel MAPK substrates. Here, we plotted the identified putative MAPK substrates (and downstream phosphoproteins as a global protein clustering network. Based on a highly stringent selection confidence level, the core networks highlighted a MAPK-induced cellular reprogramming at multiple levels of gene and protein expression – including transcriptional, post-transcriptional, translational, post-translational (such as protein modification, folding and degradation steps, and also protein re-compartmentalization. Additionally, the increase in putative substrates/phosphoproteins of energy metabolism and various secondary metabolite biosynthesis pathways coincides with the observed accumulation of defense antimicrobial substances as detected by metabolome analysis. Furthermore, detection of protein networks in phospholipid or redox elements suggests activation of downstream signaling events. Taken in context with other studies, MAPKs are key regulators that reprogram cellular events to orchestrate defense signaling in eukaryotes.

  9. Cellular Recycling of Proteins in Seed Dormancy Alleviation and Germination.

    Science.gov (United States)

    Oracz, Krystyna; Stawska, Marlena

    2016-01-01

    Each step of the seed-to-seed cycle of plant development including seed germination is characterized by a specific set of proteins. The continual renewal and/or replacement of these biomolecules are crucial for optimal plant adaptation. As proteins are the main effectors inside the cells, their levels need to be tightly regulated. This is partially achieved by specific proteolytic pathways via multicatalytic protease complexes defined as 20S and 26S proteasomes. In plants, the 20S proteasome is responsible for degradation of carbonylated proteins, while the 26S being a part of ubiquitin-proteasome pathway is known to be involved in proteolysis of phytohormone signaling regulators. On the other hand, the role of translational control of plant development is also well-documented, especially in the context of pollen tube growth and light signaling. Despite the current progress that has been made in seed biology, the sequence of cellular events that determine if the seed can germinate or not are still far from complete understanding. The role and mechanisms of regulation of proteome composition during processes occurring in the plant's photosynthetic tissues have been well-characterized since many years, but in non-photosynthetic seeds it has emerged as a tempting research task only since the last decade. This review discusses the recent discoveries providing insights into the role of protein turnover in seed dormancy alleviation, and germination, with a focus on the control of translation and proteasomal proteolysis. The presented novel data of translatome profiling in seeds highlighted that post-transcriptional regulation of germination results from a timely regulated initiation of translation. In addition, the importance of 26S proteasome in the degradation of regulatory elements of cellular signaling and that of the 20S complex in proteolysis of specific carbonylated proteins in hormonal- and light-dependent processes occurring in seeds is discussed. Based on the

  10. A cellular automata-based mathematical model for thymocyte development.

    Directory of Open Access Journals (Sweden)

    Hallan Souza-e-Silva

    Full Text Available Intrathymic T cell development is an important process necessary for the normal formation of cell-mediated immune responses. Importantly, such a process depends on interactions of developing thymocytes with cellular and extracellular elements of the thymic microenvironment. Additionally, it includes a series of oriented and tunely regulated migration events, ultimately allowing mature cells to cross endothelial barriers and leave the organ. Herein we built a cellular automata-based mathematical model for thymocyte migration and development. The rules comprised in this model take into account the main stages of thymocyte development, two-dimensional sections of the normal thymic microenvironmental network, as well as the chemokines involved in intrathymic cell migration. Parameters of our computer simulations with further adjusted to results derived from previous experimental data using sub-lethally irradiated mice, in which thymus recovery can be evaluated. The model fitted with the increasing numbers of each CD4/CD8-defined thymocyte subset. It was further validated since it fitted with the times of permanence experimentally ascertained in each CD4/CD8-defined differentiation stage. Importantly, correlations using the whole mean volume of young normal adult mice revealed that the numbers of cells generated in silico with the mathematical model fall within the range of total thymocyte numbers seen in these animals. Furthermore, simulations made with a human thymic epithelial network using the same mathematical model generated similar profiles for temporal evolution of thymocyte developmental stages. Lastly, we provided in silico evidence that the thymus architecture is important in the thymocyte development, since changes in the epithelial network result in different theoretical profiles for T cell development/migration. This model likely can be used to predict thymocyte evolution following therapeutic strategies designed for recovery of the

  11. Cellular Transport Mechanisms of Cytotoxic Metallodrugs: An Overview beyond Cisplatin

    Directory of Open Access Journals (Sweden)

    Sarah Spreckelmeyer

    2014-09-01

    Full Text Available The field of medicinal inorganic chemistry has grown consistently during the past 50 years; however, metal-containing coordination compounds represent only a minor proportion of drugs currently on the market, indicating that research in this area has not yet been thoroughly realized. Although platinum-based drugs as cancer chemotherapeutic agents have been widely studied, exact knowledge of the mechanisms governing their accumulation in cells is still lacking. However, evidence suggests active uptake and efflux mechanisms are involved; this may be involved also in other experimental metal coordination and organometallic compounds with promising antitumor activities in vitro and in vivo, such as ruthenium and gold compounds. Such knowledge would be necessary to elucidate the balance between activity and toxicity profiles of metal compounds. In this review, we present an overview of the information available on the cellular accumulation of Pt compounds from in vitro, in vivo and clinical studies, as well as a summary of reports on the possible accumulation mechanisms for different families of experimental anticancer metal complexes (e.g., Ru Au and Ir. Finally, we discuss the need for rationalization of the investigational approaches available to study metallodrug cellular transport.

  12. Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Lovelace, Erica S.; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard; Zink, Erika M.; Kim, Young-Mo; Kyle, Jennifer E.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Metz, Thomas O.; Farin, Federico; Oberlies, Nicholas H.; Polyak, Steve

    2015-08-28

    Silymarin (SM), a natural product, is touted as a liver protectant and preventer of both chronic inflammation and diseases. To define how SM elicits these effects at a systems level, we performed transcriptional profiling, metabolomics, and signaling studies in human liver and T cell lines. Multiple pathways associated with cellular stress and metabolism were modulated by SM treatment within 0.5 to four hours: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed suppression of glycolytic, TCA cycle, and amino acid metabolism by SM treatment. Antiinflammatory effects arose with prolonged (i.e. 24 hours) SM exposure, with suppression of multiple proinflammatory mRNAs and nuclear factor kappa B (NF-κB) and forkhead box O (FOXO) signaling. Studies with murine knock out cells revealed that SM inhibition of both mTOR and NF-κB was partially AMPK dependent, while SM inhibition of the mTOR pathway in part required DDIT4. Thus, SM activates stress and repair responses that culminate in an anti-inflammatory phenotype. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Therefore, natural products like SM may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation.

  13. Optimization of Inter Cellular Movement of Parts in Cellular Manufacturing System Using Genetic Algorithm

    OpenAIRE

    Siva Prasad Darla; C.D. Naiju; Polu Vidya Sagar; B. Venkat Likhit

    2014-01-01

    In the modern manufacturing environment, Cellular Manufacturing Systems (CMS) have gained greater importance in job shop or batch-type production to gain economic advantage similar to those of mass production. Successful implementation of CMS highly depends on the determination of part families; machine cells and minimizing inter cellular movement. This study considers machine component grouping problems namely inter-cellular movement and cell load variation by developing a mathematical model...

  14. Early Cellular Responses of Purine Nucleoside-mediated Protection of Hypoxia-induced Injuries of Neuronal PC12 Cells

    Directory of Open Access Journals (Sweden)

    Bettina Tomaselli

    2005-01-01

    Full Text Available Hypoxia in brain may lead to cell death by apoptosis and necrosis. In parallel adenosine, a powerful endogenous neuroprotectant is formed. We wanted to investigate the effect of adenosine and its purine nucleoside relatives, inosine and guanosine on early cellular responses to hypoxia. O2-sensitive neuronal PC12-cells were subjected to chemical hypoxia induced with rotenone, an inhibitor of mitochondrial complex I. Loss of viability after hypoxic insult was impressively rescued by adenosine, guanosine and inosine. PC12-cells mainly express the A2A adenosine receptor. Its inhibition with a specific antagonist (CSC induced cell death of PC12-cells, which could be salvaged by adenosine but not with guanosine or inosine. We have previously demonstrated the important role of mitogen activated protein kinases 1/2 (p42/44 MAPK in purine-mediated rescue. In this study we were interested in the involvement of protein kinases whose activities mediate these processes, including protein kinase A (PKA, phosphoinositide 3-kinase (PI3-K and protein kinase C-related kinases (PRK 1/2. Pharmacological inhibition of PKA and PI3-K increased hypoxia-induced toxicity and likewise also affected the rescue by purine nucleosides. Nerve growth factor (NGF and purine nucleosides induced an activation of PRK 1/2, which to our knowledge indicates for the first time that these kinases are potentially involved in purine nucleoside-mediated rescue of hypoxic neuronal cells. Results suggest that A2A receptor expressing cells are mainly dependent on the purine nucleoside adenosine for their rescue after hypoxic insult. In addition to PKA, PI3-K is an important effector molecule in A2A-mediated signaling and for the rescue of PC12-cells after hypoxic insult.

  15. Optimization of Inter Cellular Movement of Parts in Cellular Manufacturing System Using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Siva Prasad Darla

    2014-01-01

    Full Text Available In the modern manufacturing environment, Cellular Manufacturing Systems (CMS have gained greater importance in job shop or batch-type production to gain economic advantage similar to those of mass production. Successful implementation of CMS highly depends on the determination of part families; machine cells and minimizing inter cellular movement. This study considers machine component grouping problems namely inter-cellular movement and cell load variation by developing a mathematical model and optimizing the solution using Genetic Algorithm to arrive at a cell formation to minimize the inter-cellular movement and cell load variation. The results are presented with a numerical example.

  16. The cellular composition of the human immune system is shaped by age and cohabitation.

    Science.gov (United States)

    Carr, Edward J; Dooley, James; Garcia-Perez, Josselyn E; Lagou, Vasiliki; Lee, James C; Wouters, Carine; Meyts, Isabelle; Goris, An; Boeckxstaens, Guy; Linterman, Michelle A; Liston, Adrian

    2016-04-01

    Detailed population-level description of the human immune system has recently become achievable. We used a 'systems-level' approach to establish a resource of cellular immune profiles of 670 healthy individuals. We report a high level of interindividual variation, with low longitudinal variation, at the level of cellular subset composition of the immune system. Despite the profound effects of antigen exposure on individual antigen-specific clones, the cellular subset structure proved highly elastic, with transient vaccination-induced changes followed by a return to the individual's unique baseline. Notably, the largest influence on immunological variation identified was cohabitation, with 50% less immunological variation between individuals who share an environment (as parents) than between people in the wider population. These results identify local environmental conditions as a key factor in shaping the human immune system. PMID:26878114

  17. Laboratory testing of a building envelope segment based on cellular concrete

    Science.gov (United States)

    Fořt, Jan; Pavlík, Zbyšek; Černý, Robert

    2016-07-01

    Hygrothermal performance of a building envelope based on cellular concrete blocks is studied in the paper. Simultaneously, the strain fields induced by the heat and moisture changes are monitored. The studied wall is exposed to the climatic load corresponding to the winter climatic conditions of the moderate year for Prague. The winter climatic exposure is chosen in order to simulate the critical conditions of the building structure from the point of view of material performance and temperature and humidity loading. The evaluation of hygrothermal performance of a researched wall is done on the basis of relative humidity and temperature profiles measured along the cross section of the cellular concrete blocks. Strain gauges are fixed on the wall surface in expected orientation of the blocks expansion. The obtained results show a good hygrothermal function of the analyzed cellular concrete wall and its insignificant strain.

  18. Shape Memory Alloy-Based Periodic Cellular Structures Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This SBIR Phase I effort will develop and demonstrate an innovative shape memory alloy (SMA) periodic cellular structural technology. Periodic cellular structures...

  19. Cellular fibronectin response to supervised moderate aerobic training in patients with type 2 diabetes.

    Science.gov (United States)

    Alghadir, Ahmad H; Gabr, Sami A; Al-Eisa, Einas

    2016-04-01

    [Purpose] Physical activity is one of the most pivotal targets for the prevention and management of vascular complications, especially endothelial dysfunctions. Cellular fibronectin is an endothelium-derived protein involved in subendothelial matrix assembly. Its plasma levels reflect matrix alterations and vessel wall destruction in patients with type II diabetes. This study investigated the influence of 12 weeks of supervised aerobic training on cellular fibronectin and its relationship with insulin resistance and body weight in type II diabetic subjects. [Subjects and Methods] This study included 50 men with type II diabetes who had a mean age of 48.8 ± 14.6 years and were randomly divided into two groups: an aerobic exercise group (12 weeks, three 50 minutes sessions per week) and control group. To examine changes in cellular fibronectin, glycosylated hemoglobin, insulin resistance, fasting insulin, fasting blood sugar, and lipid profile, 5 ml of blood was taken from the brachial vein of patients before and 48 hours after completion of the exercise period and after 12 hours of fasting at rest. Data analysis was performed using the SPSS-16 software with the independent and paired t-tests. [Results] A significant decrease was observed in body mass index and body fat percentage in the experimental group. Compared with the control group, the aerobic exercise group showed a significant decrease in cellular fibronectin, glycosylated hemoglobin, insulin resistance, fasting insulin, fasting blood sugar, and lipid profile after 12 weeks of aerobic exercise. The change in cellular fibronectin showed positive significant correlation with body mass index, diabetic biomarkers, and physical activity level. [Conclusion] The results showed that supervised aerobic exercise as a stimulus can change the levels of cellular fibronectin as matrix metalloproteinase protein a long with improvement of insulin sensitivity and glycosylated hemoglobin in order to prevent

  20. Cellular Levels of Oxidative Stress Affect the Response of Cervical Cancer Cells to Chemotherapeutic Agents

    OpenAIRE

    Maria Filippova; Valery Filippov; Williams, Vonetta M; Kangling Zhang; Anatolii Kokoza; Svetlana Bashkirova; Penelope Duerksen-Hughes

    2014-01-01

    Treatment of advanced and relapsed cervical cancer is frequently ineffective, due in large part to chemoresistance. To examine the pathways responsible, we employed the cervical carcinoma-derived SiHa and CaSki cells as cellular models of resistance and sensitivity, respectively, to treatment with chemotherapeutic agents, doxorubicin, and cisplatin. We compared the proteomic profiles of SiHa and CaSki cells and identified pathways with the potential to contribute to the differential response....

  1. Cellular and temporal expression of NADPH oxidase (NOX) isotypes after brain injury

    OpenAIRE

    Cooney, Sean J.; Bermudez-Sabogal, Sara L; Byrnes, Kimberly R.

    2013-01-01

    Background Brain injury results in an increase in the activity of the reactive oxygen species generating NADPH oxidase (NOX) enzymes. Preliminary studies have shown that NOX2, NOX3, and NOX4 are the most prominently expressed NOX isotypes in the brain. However, the cellular and temporal expression profile of these isotypes in the injured and non-injured brain is currently unclear. Methods Double immunofluorescence for NOX isotypes and brain cell types was performed at acute (24 hours), sub-ac...

  2. Evolution of secondary cellular circulation flow above submarine bedforms imaged by remote sensing techniques

    OpenAIRE

    Hennings, Ingo; Herbers, Dagmar

    2013-01-01

    Normalized radar cross section (NRCS) modulation and acoustic Doppler current profiler (ADCP) measurements above submarine sand ribbons and sand waves are presented. The two study areas are located in the Southern Bight of the North Sea at the Birkenfels wreck and in the sand wave field of the Lister Tief in the German Bight of the North Sea. These measurements reveal the developments of secondary cellular circulations in tidally induced coastal sea areas. Secondary circulation cells can deve...

  3. Cellular Responses during Morphological Transformation in Azospirillum brasilense and Its flcA Knockout Mutant

    OpenAIRE

    Hou, Xingsheng; McMillan, Mary; Joëlle V. F. Coumans; Poljak, Anne; Raftery, Mark J.; Pereg, Lily

    2014-01-01

    FlcA is a response regulator controlling flocculation and the morphological transformation of Azospirillum cells from vegetative to cyst-like forms. To understand the cellular responses of Azospirillum to conditions that cause morphological transformation, proteins differentially expressed under flocculation conditions in A. brasilense Sp7 and its flcA knockout mutant were investigated. Comparison of 2-DE protein profiles of wild-type (Sp7) and a flcA deletion mutant (Sp7-flcAΔ) revealed a to...

  4. Spin Echo Studies on Cellular Water

    CERN Document Server

    Chang, D C; Nichols, B L; Rorschach, H E

    2014-01-01

    Previous studies indicated that the physical state of cellular water could be significantly different from pure liquid water. To experimentally investigate this possibility, we conducted a series of spin-echo NMR measurements on water protons in rat skeletal muscle. Our result indicated that the spin-lattice relaxation time and the spin-spin relaxation time of cellular water protons are both significantly shorter than that of pure water (by 4.3-fold and 34-fold, respectively). Furthermore, the spin diffusion coefficient of water proton is almost 1/2 of that of pure water. These data suggest that cellular water is in a more ordered state in comparison to pure water.

  5. Software-Defined Cellular Mobile Network Solutions

    Institute of Scientific and Technical Information of China (English)

    Jiandong Li; Peng Liu; Hongyan Li

    2014-01-01

    The emergency relating to software-defined networking (SDN), especially in terms of the prototype associated with OpenFlow, pro-vides new possibilities for innovating on network design. Researchers have started to extend SDN to cellular networks. Such new programmable architecture is beneficial to the evolution of mobile networks and allows operators to provide better services. The typical cellular network comprises radio access network (RAN) and core network (CN); hence, the technique roadmap diverges in two ways. In this paper, we investigate SoftRAN, the latest SDN solution for RAN, and SoftCell and MobileFlow, the latest solu-tions for CN. We also define a series of control functions for CROWD. Unlike in the other literature, we emphasize only software-defined cellular network solutions and specifications in order to provide possible research directions.

  6. Cellular Signaling in Health and Disease

    CERN Document Server

    Beckerman, Martin

    2009-01-01

    In today’s world, three great classes of non-infectious diseases – the metabolic syndromes (such as type 2 diabetes and atherosclerosis), the cancers, and the neurodegenerative disorders – have risen to the fore. These diseases, all associated with increasing age of an individual, have proven to be remarkably complex and difficult to treat. This is because, in large measure, when the cellular signaling pathways responsible for maintaining homeostasis and health of the body become dysregulated, they generate equally stable disease states. As a result the body may respond positively to a drug, but only for a while and then revert back to the disease state. Cellular Signaling in Health and Disease summarizes our current understanding of these regulatory networks in the healthy and diseased states, showing which molecular components might be prime targets for drug interventions. This is accomplished by presenting models that explain in mechanistic, molecular detail how a particular part of the cellular sign...

  7. Cellular automatons applied to gas dynamic problems

    Science.gov (United States)

    Long, Lyle N.; Coopersmith, Robert M.; McLachlan, B. G.

    1987-06-01

    This paper compares the results of a relatively new computational fluid dynamics method, cellular automatons, with experimental data and analytical results. This technique has been shown to qualitatively predict fluidlike behavior; however, there have been few published comparisons with experiment or other theories. Comparisons are made for a one-dimensional supersonic piston problem, Stokes first problem, and the flow past a normal flat plate. These comparisons are used to assess the ability of the method to accurately model fluid dynamic behavior and to point out its limitations. Reasonable results were obtained for all three test cases, but the fundamental limitations of cellular automatons are numerous. It may be misleading, at this time, to say that cellular automatons are a computationally efficient technique. Other methods, based on continuum or kinetic theory, would also be very efficient if as little of the physics were included.

  8. Infrared image enhancement using Cellular Automata

    Science.gov (United States)

    Qi, Wei; Han, Jing; Zhang, Yi; Bai, Lian-fa

    2016-05-01

    Image enhancement is a crucial technique for infrared images. The clear image details are important for improving the quality of infrared images in computer vision. In this paper, we propose a new enhancement method based on two priors via Cellular Automata. First, we directly learn the gradient distribution prior from the images via Cellular Automata. Second, considering the importance of image details, we propose a new gradient distribution error to encode the structure information via Cellular Automata. Finally, an iterative method is applied to remap the original image based on two priors, further improving the quality of enhanced image. Our method is simple in implementation, easy to understand, extensible to accommodate other vision tasks, and produces more accurate results. Experiments show that the proposed method performs better than other methods using qualitative and quantitative measures.

  9. Cellular automatons applied to gas dynamic problems

    Science.gov (United States)

    Long, Lyle N.; Coopersmith, Robert M.; Mclachlan, B. G.

    1987-01-01

    This paper compares the results of a relatively new computational fluid dynamics method, cellular automatons, with experimental data and analytical results. This technique has been shown to qualitatively predict fluidlike behavior; however, there have been few published comparisons with experiment or other theories. Comparisons are made for a one-dimensional supersonic piston problem, Stokes first problem, and the flow past a normal flat plate. These comparisons are used to assess the ability of the method to accurately model fluid dynamic behavior and to point out its limitations. Reasonable results were obtained for all three test cases, but the fundamental limitations of cellular automatons are numerous. It may be misleading, at this time, to say that cellular automatons are a computationally efficient technique. Other methods, based on continuum or kinetic theory, would also be very efficient if as little of the physics were included.

  10. Parametric study of double cellular detonation structure

    Science.gov (United States)

    Khasainov, B.; Virot, F.; Presles, H.-N.; Desbordes, D.

    2013-05-01

    A parametric numerical study is performed of a detonation cellular structure in a model gaseous explosive mixture whose decomposition occurs in two successive exothermic reaction steps with markedly different characteristic times. Kinetic and energetic parameters of both reactions are varied in a wide range in the case of one-dimensional steady and two-dimensional (2D) quasi-steady self-supported detonations. The range of governing parameters of both exothermic steps is defined where a "marked" double cellular structure exists. It is shown that the two-level cellular structure is completely governed by the kinetic parameters and the local overdrive ratio of the detonation front propagating inside large cells. Furthermore, since it is quite cumbersome to use detailed chemical kinetics in unsteady 2D case, the proposed work should help to identify the mixtures and the domain of their equivalence ratio where double detonation structure could be observed.

  11. Online isolation of defects in cellular nanocomputers

    Institute of Scientific and Technical Information of China (English)

    Teijiro Isokawa; Shin'ya Kowada; Ferdinand Peper; Naotake Kamiura; Nobuyuki Matsui

    2007-01-01

    Unreliability will be a major issue for computers built from components at nanometer scales.Thus,it's to be expected that such computers will need a high degree of defect-tolerance to overcome components' defects which have arisen during the process of manufacturing.This paper presents a novel approach to defect-tolerance that is especially geared towards nanocomputers based on asynchronous cellular automata.According to this approach,defective cells are detected and isolated by small configurations that move around randomly in cellular space.These configurations,called random flies,will attach to configurations that are static,which is typical for configurations that contain defective cells.On the other hand,dynamic configurations,like those that conduct computations,will not be isolated from the rest of the cellular space by the random flies,and will be able to continue their operations unaffectedly.

  12. Phagocytosis, a cellular immune response in insects

    Directory of Open Access Journals (Sweden)

    C Rosales

    2011-06-01

    Full Text Available Insects like many other organisms are exposed to a wide range of infectious agents. Defense against these agents is provided by innate immune systems, which include physical barriers, humoral responses, and cellular responses. The humoral responses are characterized by the production of antimicrobial peptides, while the cellular defense responses include nodulation, encapsulation, melanization and phagocytosis. The phagocytic process, whereby cells ingest large particles, is of fundamental importance for insects’ development and survival. Phagocytic cells recognize foreign particles through a series of receptors on their cell membrane for pathogen-associated molecules. These receptors in turn initiate a series of signaling pathways that instruct the cell to ingest and eventually destroy the foreign particle. This review describes insect innate humoral and cellular immune functions with emphasis on phagocytosis. Recent advances in our understanding of the phagocytic cell types in various insect species; the receptors involved and the signaling pathways activated during phagocytosis are discussed.

  13. Alleviate Cellular Congestion Through Opportunistic Trough Filling

    Directory of Open Access Journals (Sweden)

    Yichuan Wang

    2014-04-01

    Full Text Available The demand for cellular data service has been skyrocketing since the debut of data-intensive smart phones and touchpads. However, not all data are created equal. Many popular applications on mobile devices, such as email synchronization and social network updates, are delay tolerant. In addition, cellular load varies significantly in both large and small time scales. To alleviate network congestion and improve network performance, we present a set of opportunistic trough filling schemes that leverage the time-variation of network congestion and delay-tolerance of certain traffic in this paper. We consider average delay, deadline, and clearance time as the performance metrics. Simulation results show promising performance improvement over the standard schemes. The work shed lights on addressing the pressing issue of cellular overload.

  14. Cellular Stress Response to Engineered Nanoparticles: Effect of Size, Surface Coating, and Cellular Uptake

    Science.gov (United States)

    CELLULAR STRESS RESPONSE TO ENGINEERED NANOPARTICLES: EFFECT OF SIZE, SURFACE COATING, AND CELLULAR UPTAKE RY Prasad 1, JK McGee2, MG Killius1 D Ackerman2, CF Blackman2 DM DeMarini2 , SO Simmons2 1 Student Services Contractor, US EPA, RTP, NC 2 US EPA, RTP, NC The num...

  15. About the embedding of one dimensional cellular automata into hyperbolic cellular automata

    OpenAIRE

    Margenstern, Maurice

    2010-01-01

    In this paper, we look at two ways to implement determinisitic one dimensional cellular automata into hyperbolic cellular automata in three contexts: the pentagrid, the heptagrid and the dodecagrid, these tilings being classically denoted by $\\{5,4\\}$, $\\{7,3\\}$ and $\\{5,3,4\\}$ respectively.

  16. DNA profiles from fingermarks.

    Science.gov (United States)

    Templeton, Jennifer E L; Linacre, Adrian

    2014-11-01

    Criminal investigations would be considerably improved if DNA profiles could be routinely generated from single fingermarks. Here we report a direct DNA profiling method that was able to generate interpretable profiles from 71% of 170 fingermarks. The data are based on fingermarks from all 5 digits of 34 individuals. DNA was obtained from the fingermarks using a swab moistened with Triton-X, and the fibers were added directly to one of two commercial DNA profiling kits. All profiles were obtained without increasing the number of amplification cycles; therefore, our method is ideally suited for adoption by the forensic science community. We indicate the use of the technique in a criminal case in which a DNA profile was generated from a fingermark on tape that was wrapped around a drug seizure. Our direct DNA profiling approach is rapid and able to generate profiles from touched items when current forensic practices have little chance of success. PMID:25391915

  17. Microwave Radiometer Profiler

    Data.gov (United States)

    Oak Ridge National Laboratory — The microwave radiometer profiler (MWRP) provides vertical profiles of temperature, humidity, and cloud liquid water content as a function of height or pressure at...

  18. Cellularity of certain quantum endomorphism algebras

    DEFF Research Database (Denmark)

    Andersen, Henning Haahr; Lehrer, Gus; Zhang, Ruibin

    2015-01-01

    For any ring A˜ such that Z[q±1∕2]⊆A˜⊆Q(q1∕2), let ΔA˜(d) be an A˜-form of the Weyl module of highest weight d∈N of the quantised enveloping algebra UA˜ of sl2. For suitable A˜, we exhibit for all positive integers r an explicit cellular structure for EndUA˜(ΔA˜(d)⊗r). This algebra and its cellul...... we independently recover the weight multiplicities of indecomposable tilting modules for Uζ(sl2) from the decomposition numbers of the endomorphism algebras, which are known through cellular theory....

  19. Rapid Cellular Turnover in Adipose Tissue

    OpenAIRE

    Alessandra Rigamonti; Kristen Brennand; Frank Lau; Cowan, Chad A.

    2011-01-01

    It was recently shown that cellular turnover occurs within the human adipocyte population. Through three independent experimental approaches — dilution of an inducible histone 2B-green fluorescent protein (H2BGFP), labeling with the cell cycle marker Ki67 and incorporation of BrdU — we characterized the degree of cellular turnover in murine adipose tissue. We observed rapid turnover of the adipocyte population, finding that 4.8% of preadipocytes are replicating at any time and that between 1–...

  20. Cellular effects of LRRK2 mutations

    OpenAIRE

    Cookson, Mark R.

    2012-01-01

    Mutations in leucine-rich repeat kinase 2 (LRRK2) are a relatively common cause of inherited Parkinson's disease (PD) but the mechanism(s) by which mutations lead to disease are poorly understood. Here, I will discuss what is known about LRRK2 in cellular models, focusing on specifically on assays that have been used to tease apart the effects of LRRK2 mutations on cellular phenotypes. LRRK2 expression has been suggested to cause loss of neuronal viability, although because it also has a stro...

  1. Toxicology and cellular effect of manufactured nanomaterials

    Science.gov (United States)

    Chen, Fanqing

    2014-07-22

    The increasing use of nanotechnology in consumer products and medical applications underlies the importance of understanding its potential toxic effects to people and the environment. Herein are described methods and assays to predict and evaluate the cellular effects of nanomaterial exposure. Exposing cells to nanomaterials at cytotoxic doses induces cell cycle arrest and increases apoptosis/necrosis, activates genes involved in cellular transport, metabolism, cell cycle regulation, and stress response. Certain nanomaterials induce genes indicative of a strong immune and inflammatory response within skin fibroblasts. Furthermore, the described multiwall carbon nanoonions (MWCNOs) can be used as a therapeutic in the treatment of cancer due to its cytotoxicity.

  2. 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

  3. The cellular decision between apoptosis and autophagy

    Directory of Open Access Journals (Sweden)

    Yong-Jun Fan

    2013-03-01

    Full Text Available Apoptosis and autophagy are important molecular processes that maintain organismal and cellular homeostasis, respectively. While apoptosis fulfills its role through dismantling damaged or unwanted cells, autophagy maintains cellular homeostasis through recycling selective intracellular organelles and molecules. Yet in some conditions, autophagy can lead to cell death. Apoptosis and autophagy can be stimulated by the same stresses. Emerging evidence indicates an interplay between the core proteins in both pathways, which underlies the molecular mechanism of the crosstalk between apoptosis and autophagy. This review summarizes recent literature on molecules that regulate both the apoptotic and autophagic processes.

  4. Chaotic behavior in the disorder cellular automata

    International Nuclear Information System (INIS)

    Disordered cellular automata (DCA) represent an intermediate class between elementary cellular automata and the Kauffman network. Recently, Rule 126 of DCA has been explicated: the system can be accurately described by a discrete probability function. However, a means of extending to other rules has not been developed. In this investigation, a density map of the dynamical behavior of DCA is formulated based on Rule 22 and other totalistic rules. The numerical results reveal excellent agreement between the model and original automata. Furthermore, the inhomogeneous situation is also discussed

  5. External insulation with cellular plastic materials

    DEFF Research Database (Denmark)

    Sørensen, Lars Schiøtt; Nielsen, Anker

    2014-01-01

    External thermal insulation composite systems (ETICS) can be used as extra insulation of existing buildings. The system can be made of cellular plastic materials or mineral wool. There is a European Technical guideline, ETAG 004, that describe the tests that shall be conducted on such systems....... This paper gives a comparison of systems with mineral wool and cellular plastic, based on experience from practice and literature. It is important to look at the details in the system and at long time stability of the properties such as thermal insulation, moisture and fire. Investigation of fire properties...

  6. Modification of an acetone-sodium dodecyl sulfate disruption method for cellular protein extraction from neuropathogenic Clostridium botulinum

    Science.gov (United States)

    An acetone-sodium dodecyl sulfate (SDS) disruption method was used for the extraction of cellular proteins from neurotoxigenic Clostridium botulinum. The amount of protein extracted per gram of dry weight and the protein profile as revealed by polyacrylamide gel electrophoresis (PAGE) was comparabl...

  7. Gene expression profiles in irradiated cancer cells

    International Nuclear Information System (INIS)

    Knowledge of the molecular and genetic mechanisms underlying cellular response to radiation may provide new avenues to develop innovative predictive tests of radiosensitivity of tumours and normal tissues and to improve individual therapy. Nowadays very few studies describe molecular changes induced by hadrontherapy treatments, therefore this field has to be explored and clarified. High-throughput methodologies, such as DNA microarray, allow us to analyse mRNA expression of thousands of genes simultaneously in order to discover new genes and pathways as targets of response to hadrontherapy. Our aim is to elucidate the molecular networks involved in the sensitivity/resistance of cancer cell lines subjected to hadrontherapy treatments with a genomewide approach by using cDNA microarray technology to identify gene expression profiles and candidate genes responsible of differential cellular responses

  8. Recognition of chemical compounds in contaminated water using time-dependent multiple dose cellular responses

    International Nuclear Information System (INIS)

    Highlights: ► Dose- and time-dependent cellular responses are used to evaluate the cytotoxicity. ► The CI can reflect the cell number, cell viability, morphological change, etc. ► The CSVID can capture the dynamic information after cells exposed to toxins. ► The multi-class classification can distinguish the compounds using multi-doses. ► The majority vote strategy (fingerprint) can improve the classification accuracy. - Abstract: An early determination of toxicant compounds of water contaminations can gain critical time to protect citizens’ health and save substantial amounts of medical costs. To determine toxins in real time, a multi-dose classification algorithm using cellular state variable identification (CSVID) is developed in this paper. First, the dynamic cytotoxicity response profiles of living cells are measured using a real-time cell electronic sensing (RT-CES) system. Changes in cell number expressed as cell index (CI) are recorded on-line as time series. Then CSVID, which reflects the cell killing, cell lysis and certain cellular pathological changes, is extracted from those dynamic cellular responses. Finally, a support vector machine (SVM) algorithm based on CSVID is employed to classify chemical compounds and determine their analogous cellular response pathway. In order to increase the classification accuracy, a majority vote of the class labels is also proposed. Several validation studies demonstrate that CSVID-based classification algorithm has great potential in distinguishing the cytotoxicity response of the cells in the presence of toxins.

  9. On reversibility of cellular automata with periodic boundary conditions

    Energy Technology Data Exchange (ETDEWEB)

    Nobe, Atsushi [Graduate School of Engineering Science, Osaka University, Machikaneyama-cho 1-3, Toyonaka, Osaka 560-8531 (Japan); Yura, Fumitaka [Imai Quantum Computing and Information Project, ERATO, JST, Daini Hongo White Bldg 201, 5-28-3 Hongo, Bunkyo, Tokyo 113-0033 (Japan)

    2004-06-04

    Reversibility of one-dimensional cellular automata with periodic boundary conditions is discussed. It is shown that there exist exactly 16 reversible elementary cellular automaton rules for infinitely many cell sizes by means of a correspondence between elementary cellular automaton and the de Bruijn graph. In addition, a sufficient condition for reversibility of three-valued and two-neighbour cellular automaton is given.

  10. 47 CFR 22.905 - Channels for cellular service.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Channels for cellular service. 22.905 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.905 Channels for cellular service. The following frequency bands are allocated for assignment to service providers in the Cellular Radiotelephone Service....

  11. 47 CFR 22.923 - Cellular system configuration.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular system configuration. 22.923 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.923 Cellular system configuration. Mobile stations... directly or through cellular repeaters. Auxiliary test stations may communicate with base or...

  12. Cellular automata and self-organized criticality

    OpenAIRE

    Creutz, Michael

    1996-01-01

    Cellular automata provide a fascinating class of dynamical systems capable of diverse complex behavior. These include simplified models for many phenomena seen in nature. Among other things, they provide insight into self-organized criticality, wherein dissipative systems naturally drive themselves to a critical state with important phenomena occurring over a wide range of length and time scales.

  13. Cellular Automata Rules and Linear Numbers

    OpenAIRE

    Nayak, Birendra Kumar; Sahoo, Sudhakar; Biswal, Sagarika

    2012-01-01

    In this paper, linear Cellular Automta (CA) rules are recursively generated using a binary tree rooted at "0". Some mathematical results on linear as well as non-linear CA rules are derived. Integers associated with linear CA rules are defined as linear numbers and the properties of these linear numbers are studied.

  14. Building mathematics cellular phone learning communities

    Directory of Open Access Journals (Sweden)

    Wajeeh M. Daher

    2011-04-01

    Full Text Available Researchers emphasize the importance of maintaining learning communities and environments. This article describes the building and nourishment of a learning community, one comprised of middle school students who learned mathematics out-of-class using the cellular phone. The building of the learning community was led by three third year pre-service teachers majoring in mathematics and computers. The pre-service teachers selected thirty 8th grade students to learn mathematics with the cellular phone and be part of a learning community experimenting with this learning. To analyze the building and development stages of the cellular phone learning community, two models of community building stages were used; first the team development model developed by Tuckman (1965, second the life cycle model of a virtual learning community developed by Garber (2004. The research findings indicate that a learning community which is centered on a new technology has five 'life' phases of development: Pre-birth, birth, formation, performing, and maturity. Further, the research finding indicate that the norms that were encouraged by the preservice teachers who initiated the cellular phone learning community resulted in a community which developed, nourished and matured to be similar to a community of experienced applied mathematicians who use mathematical formulae to study everyday phenomena.

  15. Phosphoproteomics: new insights into cellular signaling

    OpenAIRE

    Mumby, Marc; Brekken, Deirdre

    2005-01-01

    Developments in the field of phosphoproteomics have been fueled by the need simultaneously to monitor many different phosphoproteins within the signaling networks that coordinate responses to changes in the cellular environment. This article presents a brief review of phosphoproteomics with an emphasis on the biological insights that have been derived so far.

  16. Cellular grafts in management of leucoderma

    Directory of Open Access Journals (Sweden)

    Mysore Venkataram

    2009-01-01

    Full Text Available Cellular grafting methods constitute important advances in the surgical management of leucoderma. Different methods such as noncultured epidermal suspensions, melanocyte cultures, and melanocyte-keratinocyte cultures have all been shown to be effective. This article reviews these methods.

  17. Cellular basis of memory for addiction.

    Science.gov (United States)

    Nestler, Eric J

    2013-12-01

    DESPITE THE IMPORTANCE OF NUMEROUS PSYCHOSOCIAL FACTORS, AT ITS CORE, DRUG ADDICTION INVOLVES A BIOLOGICAL PROCESS: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. Here, we review the types of molecular and cellular adaptations that occur in specific brain regions to mediate addiction-associated behavioral abnormalities. These include alterations in gene expression achieved in part via epigenetic mechanisms, plasticity in the neurophysiological functioning of neurons and synapses, and associated plasticity in neuronal and synaptic morphology mediated in part by altered neurotrophic factor signaling. Each of these types of drug-induced modifications can be viewed as a form of "cellular or molecular memory." Moreover, it is striking that most addiction-related forms of plasticity are very similar to the types of plasticity that have been associated with more classic forms of "behavioral memory," perhaps reflecting the finite repertoire of adaptive mechanisms available to neurons when faced with environmental challenges. Finally, addiction-related molecular and cellular adaptations involve most of the same brain regions that mediate more classic forms of memory, consistent with the view that abnormal memories are important drivers of addiction syndromes. The goal of these studies which aim to explicate the molecular and cellular basis of drug addiction is to eventually develop biologically based diagnostic tests, as well as more effective treatments for addiction disorders. PMID:24459410

  18. Cellular dosimetry in nuclear medicine imaging: training

    International Nuclear Information System (INIS)

    The radionuclides used in nuclear medicine imaging emit not only diagnostically useful photons, but also energy electron emissions, responsible for dose heterogeneity at the cellular level. The mean dose delivered to the cell nucleus by electron emissions of 99mTc, 123I, 111In, 67Ga, and 201Tl, has been calculated, for the cell nucleus, a cytoplasmic and a cell membrane distribution of radioactivity. This model takes into account both the self-dose which results from the radionuclide located in the target cell, and the cross-dose, which comes from the surrounding cells. The results obtained by cellular dosimetry (Dcel) have been compared with those obtained with conventional dosimetry (Dconv), by assuming the same amount of radioactivity per cell. Cellular dosimetry shows, for a cytoplasmic and a cell membrane distributions of radioactivity, that the main contribution to the dose to the cell nucleus, comes from the surrounding cells. On the other hand, for a cell nucleus distribution of radioactivity, the self-dose is not negligible and may be the main contribution. The comparison between cellular and conventional dosimetry shows that Dcel/Dconv ratio ranges from 0.61 and O.89, in case of a cytoplasmic and a cell membrane distributions of radioactivity, depending on the radionuclide and cell dimensions. Thus, conventional dosimetry slightly overestimates the mean dose to the cell nucleus. On the other hand, Dcel/Dconv ranges from 1.1 to 75, in case of a cell nucleus distribution of radioactivity. Conventional dosimetry may strongly underestimates the absorbed dose to the nucleus, when radioactivity is located in the nucleus. The study indicates that in nuclear medicine imaging, cellular dosimetry may lead to a better understanding of biological effects of radiopharmaceuticals. (authors)

  19. Klotho-Dependent Cellular Transport Regulation.

    Science.gov (United States)

    Sopjani, M; Dërmaku-Sopjani, M

    2016-01-01

    Klotho is a transmembrane protein that in humans is encoded by the hKL gene. This protein is known to have aging suppressor effects and is predominantly expressed in the distal convoluted tubule of the kidney, parathyroid glands, and choroid plexus of the brain. The Klotho protein exists in both full-length membrane form and a soluble secreted form, which exerts numerous distinct functions. The extracellular domain of Klotho can be enzymatically cleaved off and released into the systemic circulation where it functions as β-glucuronidase and a hormone. Soluble Klotho is a multifunction protein present in the biological fluids including blood, urine, and cerebrospinal fluid of mammals. Klotho deficiency leads to multiple organ failure accompanied by early appearance of multiple age-related disorders and early death, whereas overexpression of Klotho results in the opposite effects. Klotho, an enzyme and hormone, has been reported to participate in the regulation of cellular transport processes across the plasma membrane either indirectly through inhibiting calcitriol (1,25(OH)2D3) formation or other mechanism, or by directly affecting transporter proteins, including ion channels, cellular carriers, and Na(+)/K(+)-ATPase. Accordingly, Klotho protein serves as a powerful regulator of cellular transport across the plasma membrane. Importantly, Klotho-dependent cellular transport regulation implies stimulatory or inhibitory effects. Klotho has been shown to play a key role in the regulation of multiple calcium and potassium ion channels, and various cellular carriers including the Na(+)-coupled cotransporters such as NaPi-IIa, NaPi-IIb, EAAT3, and EAAT4, CreaT1 as well as Na(+)/K(+)-ATPase. These regulations are parts of the antiaging function of Klotho, which will be discussing throughout this chapter. Clearly, further experimental efforts are required to investigate the effect of Klotho on other transport proteins and underlying molecular mechanisms by which Klotho

  20. Cellular glutathione prevents cytolethality of monomethylarsonic acid

    International Nuclear Information System (INIS)

    Inorganic arsenicals are clearly toxicants and carcinogens in humans. In mammals, including humans, inorganic arsenic often undergoes methylation, forming compounds such as monomethylarsonic acid (MMAsV) and dimethylarsinic acid (DMAsV). However, much less information is available on the in vitro toxic potential or mechanisms of these methylated arsenicals, especially MMAsV. We studied the molecular mechanisms of in vitro cytolethality of MMAsV using a rat liver epithelial cell line (TRL 1215). MMAsV was not cytotoxic in TRL 1215 cells even at concentrations exceeding 10 mM, but it became weakly cytotoxic and induced both necrotic and apoptotic cell death when cellular reduced glutathione (GSH) was depleted with the glutathione synthase inhibitor, L-buthionine-[S,R]-sulfoximine (BSO), or the glutathione reductase inhibitor, carmustine. Similar results were observed in the other mammalian cells, such as human skin TIG-112 cells, chimpanzee skin CRT-1609 cells, and mouse metallothionein (MT) positive and MT negative embryonic cells. Ethacrynic acid (EA), an inhibitor of glutathione S-transferase (GST) that catalyses GSH-substrate conjugation, also enhanced the cytolethality of MMAsV, but aminooxyacetic acid (AOAA), an inhibitor of β-lyase that catalyses the final breakdown of GSH-substrate conjugates, had no effect. Both the cellular GSH levels and the cellular GST activity were increased by the exposure to MMAsV in TRL 1215 cells. On the other hand, the addition of exogenous extracellular GSH enhanced the cytolethality of MMAsV, although cellular GSH levels actually prevented the cytolethality of combined MMAsV and exogenous GSH. These findings indicate that human arsenic metabolite MMAsV is not a highly toxic compound in mammalian cells, and the level of cellular GSH is critical to its eventual toxic effects

  1. HPV16 E2 could act as down-regulator in cellular genes implicated in apoptosis, proliferation and cell differentiation

    Directory of Open Access Journals (Sweden)

    Valencia-Hernández Armando

    2011-05-01

    Full Text Available Abstract Background Human Papillomavirus (HPV E2 plays several important roles in the viral cycle, including the transcriptional regulation of the oncogenes E6 and E7, the regulation of the viral genome replication by its association with E1 helicase and participates in the viral genome segregation during mitosis by its association with the cellular protein Brd4. It has been shown that E2 protein can regulate negative or positively the activity of several cellular promoters, although the precise mechanism of this regulation is uncertain. In this work we constructed a recombinant adenoviral vector to overexpress HPV16 E2 and evaluated the global pattern of biological processes regulated by E2 using microarrays expression analysis. Results The gene expression profile was strongly modified in cells expressing HPV16 E2, finding 1048 down-regulated genes, and 581 up-regulated. The main cellular pathway modified was WNT since we found 28 genes down-regulated and 15 up-regulated. Interestingly, this pathway is a convergence point for regulating the expression of genes involved in several cellular processes, including apoptosis, proliferation and cell differentiation; MYCN, JAG1 and MAPK13 genes were selected to validate by RT-qPCR the microarray data as these genes in an altered level of expression, modify very important cellular processes. Additionally, we found that a large number of genes from pathways such as PDGF, angiogenesis and cytokines and chemokines mediated inflammation, were also modified in their expression. Conclusions Our results demonstrate that HPV16 E2 has regulatory effects on cellular gene expression in HPV negative cells, independent of the other HPV proteins, and the gene profile observed indicates that these effects could be mediated by interactions with cellular proteins. The cellular processes affected suggest that E2 expression leads to the cells in to a convenient environment for a replicative cycle of the virus.

  2. Molecular and cellular pathophysiology of preclinical Alzheimer's disease.

    Science.gov (United States)

    Mufson, Elliott J; Ikonomovic, Milos D; Counts, Scott E; Perez, Sylvia E; Malek-Ahmadi, Michael; Scheff, Stephen W; Ginsberg, Stephen D

    2016-09-15

    Although the two pathological hallmarks of Alzheimer's disease (AD), senile plaques composed of amyloid-β (Aβ) peptides and neurofibrillary tangles (NFTs) consisting of hyperphosphorylated tau, have been studied extensively in postmortem AD and relevant animal and cellular models, the pathogenesis of AD remains unknown, particularly in the early stages of the disease where therapies presumably would be most effective. We and others have demonstrated that Aβ plaques and NFTs are present in varying degrees before the onset and throughout the progression of dementia. In this regard, aged people with no cognitive impairment (NCI), mild cognitive impairment (MCI, a presumed prodromal AD transitional state, and AD all present at autopsy with varying levels of pathological hallmarks. Cognitive decline, a requisite for the clinical diagnosis of dementia associated with AD, generally correlates better with NFTs than Aβ plaques. However, correlations are even higher between cognitive decline and synaptic loss. In this review, we illustrate relevant clinical pathological research in preclinical AD and throughout the progression of dementia in several areas including Aβ and tau pathobiology, single population expression profiling of vulnerable hippocampal and basal forebrain neurons, neuroplasticity, neuroimaging, cerebrospinal fluid (CSF) biomarker studies and their correlation with antemortem cognitive endpoints. In each of these areas, we provide evidence for the importance of studying the pathological hallmarks of AD not in isolation, but rather in conjunction with other molecular, cellular, and imaging markers to provide a more systematic and comprehensive assessment of the multiple changes that occur during the transition from NCI to MCI to frank AD. PMID:27185734

  3. Cellular toxicity (High-Throughput Cellular Assays for Modeling Toxicity in the Fish Reproductive System)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The purpose of this project is to adapt cellular in vitro assay systems of the rainbow trout pituitary, liver and ovary for high-throughput screening (HTS) of...

  4. Expression Profiling of Exosomal miRNAs Derived from Human Esophageal Cancer Cells by Solexa High-Throughput Sequencing

    OpenAIRE

    Juan Liao; Ran Liu; Lihong Yin; Yuepu Pu

    2014-01-01

    Cellular genetic materials, such as microRNAs (miRNAs), mRNAs and proteins, are packaged inside exosomes, small membrane vesicles of endocytic origin that are released into the extracellular environment. These cellular genetic materials can be delivered into recipient cells, where they exert their respective biological effects. However, the miRNA profiles and biological functions of exosomes secreted by cancer cells remain unknown. The present study explored the miRNA expression profile and d...

  5. Cellular Dynamic Simulator: An Event Driven Molecular Simulation Environment for Cellular Physiology

    OpenAIRE

    Byrne, Michael J.; Waxham, M. Neal; Kubota, Yoshihisa

    2010-01-01

    In this paper, we present the Cellular Dynamic Simulator (CDS) for simulating diffusion and chemical reactions within crowded molecular environments. CDS is based on a novel event driven algorithm specifically designed for precise calculation of the timing of collisions, reactions and other events for each individual molecule in the environment. Generic mesh based compartments allow the creation / importation of very simple or detailed cellular structures that exist in a 3D environment. Multi...

  6. Synthesis of New Styrylquinoline Cellular Dyes, Fluorescent Properties, Cellular Localization and Cytotoxic Behavior

    OpenAIRE

    Rams-Baron, Marzena; Dulski, Mateusz; Mrozek-Wilczkiewicz, Anna; Korzec, Mateusz; Cieslik, Wioleta; Spaczyńska, Ewelina; Bartczak, Piotr; Ratuszna, Alicja; Polanski, Jaroslaw; Musiol, Robert

    2016-01-01

    New styrylquinoline derivatives with their photophysical constants are described. The synthesis was achieved via Sonogashira coupling using the newly developed heterogeneous nano-Pd/Cu catalyst system, which provides an efficient synthesis of high purity products. The compounds were tested in preliminary fluorescent microscopy studies to in order to identify their preferable cellular localization, which appeared to be in the lipid cellular organelles. The spectroscopic properties of the compo...

  7. Cellular and molecular introduction to brain development.

    Science.gov (United States)

    Jiang, Xiangning; Nardelli, Jeannette

    2016-08-01

    Advances in the study of brain development over the last decades, especially recent findings regarding the evolutionary expansion of the human neocortex, and large-scale analyses of the proteome/transcriptome in the human brain, have offered novel insights into the molecular mechanisms guiding neural maturation, and the pathophysiology of multiple forms of neurological disorders. As a preamble to reviews of this issue, we provide an overview of the cellular, molecular and genetic bases of brain development with an emphasis on the major mechanisms associated with landmarks of normal neural development in the embryonic stage and early postnatal life, including neural stem/progenitor cell proliferation, cortical neuronal migration, evolution and folding of the cerebral cortex, synaptogenesis and neural circuit development, gliogenesis and myelination. We will only briefly depict developmental disorders that result from perturbations of these cellular or molecular mechanisms, and the most common perinatal brain injuries that could disturb normal brain development. PMID:26184894

  8. Cellular and molecular basis of cerebellar development

    Science.gov (United States)

    Martinez, Salvador; Andreu, Abraham; Mecklenburg, Nora; Echevarria, Diego

    2013-01-01

    Historically, the molecular and cellular mechanisms of cerebellar development were investigated through structural descriptions and studying spontaneous mutations in animal models and humans. Advances in experimental embryology, genetic engineering, and neuroimaging techniques render today the possibility to approach the analysis of molecular mechanisms underlying histogenesis and morphogenesis of the cerebellum by experimental designs. Several genes and molecules were identified to be involved in the cerebellar plate regionalization, specification, and differentiation of cerebellar neurons, as well as the establishment of cellular migratory routes and the subsequent neuronal connectivity. Indeed, pattern formation of the cerebellum requires the adequate orchestration of both key morphogenetic signals, arising from distinct brain regions, and local expression of specific transcription factors. Thus, the present review wants to revisit and discuss these morphogenetic and molecular mechanisms taking place during cerebellar development in order to understand causal processes regulating cerebellar cytoarchitecture, its highly topographically ordered circuitry and its role in brain function. PMID:23805080

  9. 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...

  10. A Modified Sensitive Driving Cellular Automaton Model

    Institute of Scientific and Technical Information of China (English)

    GE Hong-Xia; DAI Shi-Qiang; DONG Li-Yun; LEI Li

    2005-01-01

    A modified cellular automaton model for traffic flow on highway is proposed with a novel concept about the variable security gap. The concept is first introduced into the original Nagel-Schreckenberg model, which is called the non-sensitive driving cellular automaton model. And then it is incorporated with a sensitive driving NaSch model,in which the randomization brake is arranged before the deterministic deceleration. A parameter related to the variable security gap is determined through simulation. Comparison of the simulation results indicates that the variable security gap has different influence on the two models. The fundamental diagram obtained by simulation with the modified sensitive driving NaSch model shows that the maximumflow are in good agreement with the observed data, indicating that the presented model is more reasonable and realistic.

  11. 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.

  12. Mobile Node Localization in Cellular Networks

    Directory of Open Access Journals (Sweden)

    Yasir Malik

    2012-01-01

    Full Text Available Location information is the major component in location based applications. This information is used in different safety and service oriented applications to provide users with services according to their Geolocation. There are many approaches to locate mobile nodes in indoor and outdoor environments. In thispaper, we are interested in outdoor localization particularly in cellular networks of mobile nodes andpresented a localization method based on cell and user location information. Our localization method is based on hello message delay (sending and receiving time and coordinate information of Base Transceiver Station (BTSs. To validate our method across cellular network, we implemented and simulated our method in two scenarios i.e. maintaining database of base stations in centralize and distributed system. Simulation results show the effectiveness of our approach and its implementation applicability in telecommunication systems.

  13. Cellular automata in image processing and geometry

    CERN Document Server

    Adamatzky, Andrew; Sun, Xianfang

    2014-01-01

    The book presents findings, views and ideas on what exact problems of image processing, pattern recognition and generation can be efficiently solved by cellular automata architectures. This volume provides a convenient collection in this area, in which publications are otherwise widely scattered throughout the literature. The topics covered include image compression and resizing; skeletonization, erosion and dilation; convex hull computation, edge detection and segmentation; forgery detection and content based retrieval; and pattern generation. The book advances the theory of image processing, pattern recognition and generation as well as the design of efficient algorithms and hardware for parallel image processing and analysis. It is aimed at computer scientists, software programmers, electronic engineers, mathematicians and physicists, and at everyone who studies or develops cellular automaton algorithms and tools for image processing and analysis, or develops novel architectures and implementations of mass...

  14. SELF-ORGANIZED CRITICALITY AND CELLULAR AUTOMATA

    Energy Technology Data Exchange (ETDEWEB)

    CREUTZ,M.

    2007-01-01

    Cellular automata provide a fascinating class of dynamical systems based on very simple rules of evolution yet capable of displaying highly complex behavior. These include simplified models for many phenomena seen in nature. Among other things, they provide insight into self-organized criticality, wherein dissipative systems naturally drive themselves to a critical state with important phenomena occurring over a wide range of length and the scales. This article begins with an overview of self-organized criticality. This is followed by a discussion of a few examples of simple cellular automaton systems, some of which may exhibit critical behavior. Finally, some of the fascinating exact mathematical properties of the Bak-Tang-Wiesenfeld sand-pile model [1] are discussed.

  15. Molecular features of cellular reprogramming and development.

    Science.gov (United States)

    Smith, Zachary D; Sindhu, Camille; Meissner, Alexander

    2016-03-01

    Differentiating somatic cells are progressively restricted to specialized functions during ontogeny, but they can be experimentally directed to form other cell types, including those with complete embryonic potential. Early nuclear reprogramming methods, such as somatic cell nuclear transfer (SCNT) and cell fusion, posed significant technical hurdles to precise dissection of the regulatory programmes governing cell identity. However, the discovery of reprogramming by ectopic expression of a defined set of transcription factors, known as direct reprogramming, provided a tractable platform to uncover molecular characteristics of cellular specification and differentiation, cell type stability and pluripotency. We discuss the control and maintenance of cellular identity during developmental transitions as they have been studied using direct reprogramming, with an emphasis on transcriptional and epigenetic regulation. PMID:26883001

  16. Stochastic Simulations on the Cellular Wave Computers

    CERN Document Server

    Ercsey-Ravasz, M; Neda, Z

    2006-01-01

    The computational paradigm represented by Cellular Neural/nonlinear Networks (CNN) and the CNN Universal Machine (CNN-UM) as a Cellular Wave Computer, gives new perspectives for computational physics. Many numerical problems and simulations can be elegantly addressed on this fully parallelized and analogic architecture. Here we study the possibility of performing stochastic simulations on this chip. First a realistic random number generator is implemented on the CNN-UM, and then as an example the two-dimensional Ising model is studied by Monte Carlo type simulations. The results obtained on an experimental version of the CNN-UM with 128 * 128 cells are in good agreement with the results obtained on digital computers. Computational time measurements suggests that the developing trend of the CNN-UM chips - increasing the lattice size and the number of local logic memories - will assure an important advantage for the CNN-UM in the near future.

  17. Cellular and Molecular Basis of Cerebellar Development

    Directory of Open Access Journals (Sweden)

    Salvador eMartinez

    2013-06-01

    Full Text Available Historically, the molecular and cellular mechanisms of cerebellar development were investigated through structural descriptions and studying spontaneous mutations in animal models and humans. Advances in experimental embryology, genetic engineering and neuroimaging techniques render today the possibility to approach the analysis of molecular mechanisms underlying histogenesis and morphogenesis of the cerebellum by experimental designs. Several genes and molecules were identified to be involved in the cerebellar plate regionalization, specification and differentiation of cerebellar neurons, as well as the establishment of cellular migratory routes and the subsequent neuronal connectivity. Indeed, pattern formation of the cerebellum requires the adequate orchestration of both key morphogenetic signals, arising from distinct brain regions, and local expression of specific transcription factors. Thus, the present review wants to revisit and discuss these morphogenetic and molecular mechanisms taking place during cerebellar development in order to understand causal processes regulating cerebellar cytoarchitecture, its highly topographically ordered circuitry and its role in brain function.

  18. 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...

  19. Exponential Stability for Delayed Cellular Neural Networks

    Institute of Scientific and Technical Information of China (English)

    YANG Jin-xiang; ZHONG Shou-ming; YAN Ke-yu

    2005-01-01

    The exponential stability of the delayed cellular neural networks (DCNN's) is investigated. By dividing the network state variables into some parts according to the characters of the neural networks, some new sufficient conditions of exponential stability are derived via constructing a Liapunov function. It is shown that the conditions differ from previous ones. The new conditions, which are associated with some initial value, are represented by some blocks of the interconnection matrix.

  20. A framework for understanding cellular manufacturing systems

    OpenAIRE

    Silva, Sílvio Carmo; Alves, Anabela Carvalho

    2002-01-01

    Many practical benefits, such as superior quality of products and short manufacturing lead times, are usually associated with Cellular Manufacturing. These and other benefits can lead to important competitive advantages of companies. However, to fully achieve these benefits there is a need for an evolution from the traditional concept of CM to the more comprehensive one, which we call Product Oriented Manufacturing. Here systems are dynamically reconfigured for total manufac...

  1. Spectrum sharing for future mobile cellular systems

    OpenAIRE

    Bennis, M

    2009-01-01

    Abstract Spectrum sharing has become a high priority research area over the past few years. The motivation behind this lies in the fact that the limited spectrum is currently inefficiently utilized. As recognized by the World radio communication conference (WRC)-07, the amount of identified spectrum is not large enough to support large bandwidths for a substantial number of operators. Therefore, it is paramount for future mobile cellular systems to share the frequency spectrum and coexist ...

  2. Clinical applications of cellular therapy products

    OpenAIRE

    Serpil Yanbakan

    2015-01-01

    Adult stem cells have the potential to differentiate into multiple cell types and have usage about lots of regenerative medicine research fields. Especially bone marrow-derived mesenchymal stem cells have a wide range of case presentation. New discoveries about stem cell biology will progress new options about cellular therapy products and isolation of different stem cell types will increase hope for treatment of important illness such as Parkinson’s disease, diabetes, malign brain tumors. It...

  3. Cellular Automata Studies of Vertical Silicon Devices

    OpenAIRE

    M. Saraniti; G. Zandler; G. Formicone; S. Goodnick

    1998-01-01

    We present systematic theoretical Cellular Automata (CA) studies of a novel nanometer scale Si device, namely vertically grown Metal Oxide Field Effect Transistors (MOSFET) with channel lengths between 65 and 120 nm. The CA simulations predict drain characteristics and output conductance as a function of gate length. The excellent agreement with available experimental data indicates a high quality oxide/semiconductor interface. Impact ionization is shown to be of minor importance. For inhomog...

  4. Mapping functional connectivity in cellular networks

    OpenAIRE

    Buibas, Marius

    2011-01-01

    My thesis is a collection of theoretical and practical techniques for mapping functional or effective connectivity in cellular neuronal networks, at the cell scale. This is a challenging scale to work with, primarily because of the difficulty in labeling and measuring the activities of networks of cells. It is also important as it underlies behavior, function, and complex diseases. I present methods to measure and quantify the dynamic activities of cells using the optical flow technique, whic...

  5. Integrating mitochondrial translation into the cellular context.

    OpenAIRE

    Richter-Dennerlein, R.; Dennerlein Sven, S.; Rehling, P

    2015-01-01

    Mitochondrial-encoded subunits of the oxidative phosphorylation system assemble with nuclear-encoded subunits into enzymatic complexes. Recent findings showed that mitochondrial translation is linked to other mitochondrial functions, as well as to cellular processes. The supply of mitochondrial- encoded proteins is coordinated by the coupling of mitochondrial protein synthesis with assembly of respiratory chain complexes. MicroRNAs imported from the cytoplasm into mitochondria were, surprisin...

  6. Stability of Stochastic Neutral Cellular Neural Networks

    Science.gov (United States)

    Chen, Ling; Zhao, Hongyong

    In this paper, we study a class of stochastic neutral cellular neural networks. By constructing a suitable Lyapunov functional and employing the nonnegative semi-martingale convergence theorem we give some sufficient conditions ensuring the almost sure exponential stability of the networks. The results obtained are helpful to design stability of networks when stochastic noise is taken into consideration. Finally, two examples are provided to show the correctness of our analysis.

  7. Cognitive resource management for heterogeneous cellular networks

    CERN Document Server

    Liu, Yongkang

    2014-01-01

    This Springer Brief focuses on cognitive resource management in heterogeneous cellular networks (Het Net) with small cell deployment for the LTE-Advanced system. It introduces the Het Net features, presents practical approaches using cognitive radio technology in accommodating small cell data relay and optimizing resource allocation and examines the effectiveness of resource management among small cells given limited coordination bandwidth and wireless channel uncertainty. The authors introduce different network characteristics of small cell, investigate the mesh of small cell access points in

  8. Cellular responses to environmental DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    1994-08-01

    This volume contains the proceedings of the conference entitled Cellular Responses to Environmental DNA Damage held in Banff,Alberta December 1--6, 1991. The conference addresses various aspects of DNA repair in sessions titled DNA repair; Basic Mechanisms; Lesions; Systems; Inducible Responses; Mutagenesis; Human Population Response Heterogeneity; Intragenomic DNA Repair Heterogeneity; DNA Repair Gene Cloning; Aging; Human Genetic Disease; and Carcinogenesis. Individual papers are represented as abstracts of about one page in length.

  9. Imaging cellular and molecular biological functions

    Energy Technology Data Exchange (ETDEWEB)

    Shorte, S.L. [Institut Pasteur, 75 - Paris (France). Plateforme d' Imagerie Dynamique PFID-Imagopole; Frischknecht, F. (eds.) [Heidelberg Univ. Medical School (Germany). Dept. of Parasitology

    2007-07-01

    'Imaging cellular and molecular biological function' provides a unique selection of essays by leading experts, aiming at scientist and student alike who are interested in all aspects of modern imaging, from its application and up-scaling to its development. Indeed the philosophy of this volume is to provide student, researcher, PI, professional or provost the means to enter this applications field with confidence, and to construct the means to answer their own specific questions. (orig.)

  10. 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.

  11. Sumo and the cellular stress response

    OpenAIRE

    Enserink, Jorrit M.

    2015-01-01

    The ubiquitin family member Sumo has important functions in many cellular processes including DNA repair, transcription and cell division. Numerous studies have shown that Sumo is essential for maintaining cell homeostasis when the cell encounters endogenous or environmental stress, such as osmotic stress, hypoxia, heat shock, genotoxic stress, and nutrient stress. Regulation of transcription is a key component of the Sumo stress response, and multiple mechanisms have been described by which ...

  12. Aging cellular networks: chaperones as major participants

    OpenAIRE

    Soti, Csaba; Csermely, Peter

    2006-01-01

    We increasingly rely on the network approach to understand the complexity of cellular functions. Chaperones (heat shock proteins) are key "networkers", which have among their functions to sequester and repair damaged protein. In order to link the network approach and chaperones with the aging process, we first summarize the properties of aging networks suggesting a "weak link theory of aging". This theory suggests that age-related random damage primarily affects the overwhelming majority of t...

  13. Typhoid fever as cellular microbiological model

    OpenAIRE

    Andrade Dahir Ramos de; Andrade Júnior Dahir Ramos de

    2003-01-01

    The knowledge about typhoid fever pathogenesis is growing in the last years, mainly about the cellular and molecular phenomena that are responsible by clinical manifestations of this disease. In this article are discussed several recent discoveries, as follows: a) Bacterial type III protein secretion system; b) The five virulence genes of Salmonella spp. that encoding Sips (Salmonella invasion protein) A, B, C, D and E, which are capable of induce apoptosis in macrophages; c) The function of ...

  14. Cellular immune findings in Lyme disease.

    OpenAIRE

    Sigal, L. H.; Moffat, C. M.; Steere, A. C.; Dwyer, J. M.

    1984-01-01

    From 1981 through 1983, we did the first testing of cellular immunity in Lyme disease. Active established Lyme disease was often associated with lymphopenia, less spontaneous suppressor cell activity than normal, and a heightened response of lymphocytes to phytohemagglutinin and Lyme spirochetal antigens. Thus, a major feature of the immune response during active disease seems to be a lessening of suppression, but it is not yet known whether this response plays a role in the pathophysiology o...

  15. Introduction to Tissular and Cellular Engineering

    Institute of Scientific and Technical Information of China (English)

    JF; STOLTZ

    2005-01-01

    Most human tissues do not regenerate spontaneously, which is why cellular therapies and tissular engineering are promising alternatives. The principle is simple: cells are sampled in a patient and introduced in the damaged tissue or in a tridimentional porous support and cultivated in a bioreactor in which the physico-chemical and mechanical parameters are controlled. Once the tissues (or the cells) are mature they may be implanted. In parallel, the development of biotherapies with stem cells is a field of ...

  16. Cellular mechanisms of nociception in the frog

    Czech Academy of Sciences Publication Activity Database

    Kuffler, D. P.; Lyfenko, Alla; Vyklický st., Ladislav; Vlachová, Viktorie

    2002-01-01

    Roč. 88, č. 4 (2002), s. 1843-1850. ISSN 0022-3077 R&D Projects: GA ČR GA305/00/1639; GA MŠk LN00B122 Grant ostatní: NATO(XX) Grant 977062 Institutional research plan: CEZ:AV0Z5011922 Keywords : cellular mechanisms of nociception * frog Subject RIV: FH - Neurology Impact factor: 3.743, year: 2002

  17. Heterogeneous Force Chains in Cellularized Biopolymer Network

    OpenAIRE

    Liang, Long; Jones, Christopher; Sun, Bo; Jiao, Yang

    2015-01-01

    Biopolymer Networks play an important role in coordinating and regulating collective cellular dynamics via a number of signaling pathways. Here, we investigate the mechanical response of a model biopolymer network due to the active contraction of embedded cells. Specifically, a graph (bond-node) model derived from confocal microscopy data is used to represent the network microstructure, and cell contraction is modeled by applying correlated displacements at specific nodes, representing the fo...

  18. Cellular and synaptic network defects in autism

    OpenAIRE

    Peça, João; Feng, Guoping

    2012-01-01

    Many candidate genes are now thought to confer susceptibility to autism spectrum disorders (ASDs). Here we review four interrelated complexes, each composed of multiple families of genes that functionally coalesce on common cellular pathways. We illustrate a common thread in the organization of glutamatergic synapses and suggest a link between genes involved in Tuberous Sclerosis Complex, Fragile X syndrome, Angelman syndrome and several synaptic ASD candidate genes. When viewed in this conte...

  19. Cellular events and biomarkers of wound healing

    OpenAIRE

    Shah Jumaat Mohd Yussof; Effat Omar; Pai, Dinker R.; Suneet Sood

    2012-01-01

    Researchers have identified several of the cellular events associated with wound healing. Platelets, neutrophils, macrophages, and fibroblasts primarily contribute to the process. They release cytokines including interleukins (ILs) and TNF-α, and growth factors, of which platelet-derived growth factor (PDGF) is perhaps the most important. The cytokines and growth factors manipulate the inflammatory phase of healing. Cytokines are chemotactic for white cells and fibroblasts, while the growth f...

  20. Cellular Automation of Galactic Habitable Zone

    CERN Document Server

    Vukotic, Branislav

    2010-01-01

    We present a preliminary results of our Galactic Habitable Zone (GHZ) 2D probabilistic cellular automata models. The relevant time-scales (emergence of life, it's diversification and evolution influenced with the global risk function) are modeled as the probability matrix elements and are chosen in accordance with the Copernican principle to be well-represented by the data inferred from the Earth's fossil record. With Fermi's paradox as a main boundary condition the resulting histories of astrobiological landscape are discussed.

  1. Cellular factors required for papillomavirus DNA replication.

    OpenAIRE

    Melendy, T; Sedman, J; Stenlund, A

    1995-01-01

    In vitro replication of papillomavirus DNA has been carried out with a combination of purified proteins and partially purified extracts made from human cells. DNA synthesis requires the viral E1 protein and the papillomavirus origin of replication. The E2 protein stimulates DNA synthesis in a binding site-independent manner. Papillomavirus DNA replication is also dependent on the cellular factors replication protein A, replication factor C, and proliferating-cell nuclear antigen as well as a ...

  2. 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

  3. Animal and cellular models of human disease

    OpenAIRE

    Arends, Mark; White, Eric; Whitelaw, Christopher

    2016-01-01

    In this eighteenth (2016) Annual Review Issue of The Journal of Pathology, we present a collection of 19 invited review articles that cover different aspects of cellular and animal models of disease. These include genetically-engineered models, chemically-induced models, naturally-occurring models, and combinations thereof, with the focus on recent methodological and conceptual developments across a wide range of human diseases.

  4. Oxidative stress action in cellular aging

    OpenAIRE

    Monique Cristine de Oliveira; João Paulo Ferreira Schoffen

    2010-01-01

    Various theories try to explain the biological aging by changing the functions and structure of organic systems and cells. During lifetime, free radicals in the oxidative stress lead to lipid peroxidation of cellular membranes, homeostasis imbalance, chemical residues formation, gene mutations in DNA, dysfunction of certain organelles, and the arise of diseases due to cell death and/or injury. This review describes the action of oxidative stress in the cells aging process, emphasizing the fac...

  5. 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...

  6. Cellular-based sea level gauge

    Digital Repository Service at National Institute of Oceanography (India)

    Desai, R.G.P.; Joseph, A.

    treaties with greater transparency. Among the various communication technologies used for real-time transmission of sea-level data are the wired telephone connection, VHF/UHF transceivers, satellite transmit terminals and cellular connectivity. Wired... telephone connections are severely susceptible to loss of connectivity during natural disasters such as storm surges, primarily because of telephone line breakage. Communication via VHF/UHF transceivers is limited by line-of-sight distance between...

  7. The flow of forces through cellular materials

    OpenAIRE

    Berger, Mitchell A.

    2012-01-01

    Describing and measuring the elastic properties of cellular materials such as honeycombs and foams can be a difficult problem when the cell structure is disordered. This paper suggests that tracking the flow of forces through the material can help in visualizing and understanding how the geometry of the cell structure affects the elastic behaviour. The mean strain tensor for a sample of material can be calculated by summing over the force paths, weighted by the strengths of the paths. This me...

  8. Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow.

    Science.gov (United States)

    Watanabe, Hiroshi; Okahara, Kyohei; Naito-Matsui, Yuko; Abe, Mitsuhiro; Go, Shinji; Inokuchi, Jinichi; Okazaki, Toshiro; Kobayashi, Toshihide; Kozutsumi, Yasunori; Oka, Shogo; Takematsu, Hiromu

    2016-07-01

    Endomitosis is a special type of mitosis in which only cytokinesis-the final step of the cell division cycle-is defective, resulting in polyploid cells. Although endomitosis is biologically important, its regulatory aspects remain elusive. Psychosine, a lysogalactosylceramide, prevents proper cytokinesis when supplemented to proliferating cells. Cytokinetic inhibition by psychosine does not inhibit genome duplication. Consequently cells undergo multiple rounds of endomitotic cell cycles, resulting in the formation of giant multiploid cells. Here we successfully quantified psychosine-triggered multiploid cell formation, showing that membrane sphingolipids ratios modulate psychosine-triggered polyploidy in Namalwa cells. Among enzymes that experimentally remodel cellular sphingolipids, overexpression of glucosylceramide synthase to biosynthesize glycosylsphingolipids (GSLs) and neutral sphingomyelinase 2 to hydrolyze sphingomyelin (SM) additively enhanced psychosine-triggered multiploidy; almost all of the cells became polyploid. In the presence of psychosine, Namalwa cells showed attenuated cell surface SM clustering and suppression of phosphatidylinositol 4,5-bisphosphate production at the cleavage furrow, both important processes for cytokinesis. Depending on the sphingolipid balance between GSLs and SM, Namalwa cells could be effectively converted to viable multiploid cells with psychosine. PMID:27170180

  9. Dynamic Channel Allocation in Sectored Cellular Systems

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    It is known that dynamic channel assignment(DCA) strategy outperforms the fixed channel assignment(FCA) strategy in omni-directional antenna cellular systems. One of the most important methods used in DCA was channel borrowing. But with the emergence of cell sectorization and spatial division multiple access(SDMA) which are used to increase the capacity of cellular systems, the channel assignment faces a series of new problems. In this paper, a dynamic channel allocation scheme based on sectored cellular systems is proposed. By introducing intra-cell channel borrowing (borrowing channels from neighboring sectors) and inter-cell channel borrowing (borrowing channels from neighboring cells) methods, previous DCA strategies, including compact pattern based channel borrowing(CPCB) and greedy based dynamic channel assignment(GDCA) schemes proposed by the author, are improved significantly. The computer simulation shows that either intra-cell borrowing scheme or inter-cell borrowing scheme is efficient enough to uniform and non-uniform traffic service distributions.

  10. 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.

  11. Cellular cardiomyoplasty: what have we learned?

    Science.gov (United States)

    Kao, Race L; Browder, William; Li, Chuanfu

    2009-01-01

    Restoring blood flow, improving perfusion, reducing clinical symptoms, and augmenting ventricular function are the goals after acute myocardial infarction. Other than cardiac transplantation, no standard clinical procedure is available to restore damaged myocardium. Since we first reported cellular cardiomyoplasty in 1989, successful outcomes have been confirmed by experimental and clinical studies, but definitive long-term efficacy requires large-scale placebo-controlled double-blind randomized trials. On meta-analysis, stem cell-treated groups had significantly improved left ventricular ejection fraction, reduced infarct scar size, and decreased left ventricular end-systolic volume. Fewer myocardial infarctions, deaths, readmissions for heart failure, and repeat revascularizations were additional benefits. Encouraging clinical findings have been reported using satellite or bone marrow stem cells, but understanding of the benefit mechanisms demands additional studies. Adult mammalian ventricular myocardium lacks adequate regeneration capability, and cellular cardiomyoplasty offers a new way to overcome this; the poor retention and engraftment rate and high apoptotic rate of the implanted stem cells limit outcomes. The ideal type and number of cells, optimal timing of cell therapy, and ideal cell delivery method depend on determining the beneficial mechanisms. Cellular cardiomyoplasty has progressed rapidly in the last decade. A critical review may help us to better plan the future direction. PMID:19515892

  12. Cellular Kinetics of Perivascular MSC Precursors

    Directory of Open Access Journals (Sweden)

    William C. W. Chen

    2013-01-01

    Full Text Available Mesenchymal stem/stromal cells (MSCs and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration.

  13. HDACi: cellular effects, opportunities for restorative dentistry.

    LENUS (Irish Health Repository)

    Duncan, H F

    2011-12-01

    Acetylation of histone and non-histone proteins alters gene expression and induces a host of cellular effects. The acetylation process is homeostatically balanced by two groups of cellular enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HAT activity relaxes the structure of the human chromatin, rendering it transcriptionally active, thereby increasing gene expression. In contrast, HDAC activity leads to gene silencing. The enzymatic balance can be \\'tipped\\' by histone deacetylase inhibitors (HDACi), leading to an accumulation of acetylated proteins, which subsequently modify cellular processes including stem cell differentiation, cell cycle, apoptosis, gene expression, and angiogenesis. There is a variety of natural and synthetic HDACi available, and their pleiotropic effects have contributed to diverse clinical applications, not only in cancer but also in non-cancer areas, such as chronic inflammatory disease, bone engineering, and neurodegenerative disease. Indeed, it appears that HDACi-modulated effects may differ between \\'normal\\' and transformed cells, particularly with regard to reactive oxygen species accumulation, apoptosis, proliferation, and cell cycle arrest. The potential beneficial effects of HDACi for health, resulting from their ability to regulate global gene expression by epigenetic modification of DNA-associated proteins, also offer potential for application within restorative dentistry, where they may promote dental tissue regeneration following pulpal damage.

  14. Literature Review on Dynamic Cellular Manufacturing System

    Science.gov (United States)

    Nouri Houshyar, A.; Leman, Z.; Pakzad Moghadam, H.; Ariffin, M. K. A. M.; Ismail, N.; Iranmanesh, H.

    2014-06-01

    In previous decades, manufacturers faced a lot of challenges because of globalization and high competition in markets. These problems arise from shortening product life cycle, rapid variation in demand of products, and also rapid changes in manufcaturing technologies. Nowadays most manufacturing companies expend considerable attention for improving flexibility and responsiveness in order to overcome these kinds of problems and also meet customer's needs. By considering the trend toward the shorter product life cycle, the manufacturing environment is towards manufacturing a wide variety of parts in small batches [1]. One of the major techniques which are applied for improving manufacturing competitiveness is Cellular Manufacturing System (CMS). CMS is type of manufacturing system which tries to combine flexibility of job shop and also productivity of flow shop. In addition, Dynamic cellular manufacturing system which considers different time periods for the manufacturing system becomes an important topic and attracts a lot of attention to itself. Therefore, this paper made attempt to have a brief review on this issue and focused on all published paper on this subject. Although, this topic gains a lot of attention to itself during these years, none of previous researchers focused on reviewing the literature of that which can be helpful and useful for other researchers who intend to do the research on this topic. Therefore, this paper is the first study which has focused and reviewed the literature of dynamic cellular manufacturing system.

  15. Cellular vs. organ approaches to dose estimates

    International Nuclear Information System (INIS)

    The cellular distribution of tissue-incorporated radionuclides has generally been neglected in the dosimetry of internal emitters. Traditional dosimetry assumes homogeneous distribution of radionuclides in organs of interest, while presuming that the ranges of particulate radiations are large relative to typical cell diameters. The macroscopic distribution of dose thus calculated has generally served as a sufficient approximation for the energy deposited within radiosensitive sites. However, with the increasing utilization of intracellular agents, such as thallium-201, it has become necessary to examine the microscopic distribution of energy at the cellular level. This is particularly important in the instance of radionuclides that decay by electron capture or by internal conversion with the release of Auger and Coster-Kronig electrons. In many instances, these electrons are released as a dense shower of low-energy particles with ranges of subcellular dimensions. The high electron density in the immediate vicinity of the decaying atom produces a focal deposition of energy that far exceeds the average dose taken over several cell diameters. These studies point out the increasing need to take into account the microscopic distribution of dose on the cellular level as radionuclides distributed in cells become more commonplace, especially if the decay involves electron capture or internal conversion. As radiotracers are developed for the measurement of intracellular functions these factors should be given greater consideration. 16 references, 5 figures, 5 tables

  16. YOUNG ATHLETES' MOTIVATIONAL PROFILES

    Directory of Open Access Journals (Sweden)

    Juan Antonio Moreno Murcia

    2007-06-01

    Full Text Available The aim of this study was to examine the relationship between motivational characteristics and dispositional flow. In order to accomplish this goal, motivational profiles emerging from key constructs within Achievement Goal Theory and Self-Determination Theory were related to the dispositional flow measures. A sample of 413 young athletes (Age range 12 to 16 years completed the PMCSQ-2, POSQ, SMS and DFS measures. Cluster analysis results revealed three profiles: a "self-determined profile" characterised by higher scores on the task-involving climate perception and on the task orientation; a "non-self-determined profile", characterised by higher scores on ego-involving climate perception and ego orientation; and a "low self-determined and low non-self-determined profile" which had the lowest dispositional flow. No meaningful differences were found between the "self-determined profile" and the "non-self-determined profile" in dispositional flow. The "self-determined profile" was more commonly associated with females, athletes practising individual sports and those training more than three days a week. The "non-self-determined profile" was more customary of males and athletes practising team sports as well as those training just two or three days a week

  17. Single-Cell Cytokine Profiling to Investigate Cellular Functional Diversity in Hematopoietic Malignancies.

    Science.gov (United States)

    Chen, Jonathan J; Kwak, Minsuk; Fan, Rong

    2016-01-01

    Single-cell analysis of cytokine production is increasingly recognized as an important method to understand the inflammatory microenvironment and hematopoietic disease state. Certain cytokines are critical to the regulation of lineage specification, and the aberrant production of these cytokines can contribute to lineage reprogramming. Here, we describe of a platform combining subnanoliter microchambers and a high-density antibody barcode array for the study of single-cell cytokine secretions in hematopoietic cancer cell populations. PMID:27581152

  18. Cellular fatty acid composition, protein profile and antimicrobial activity of Bacillus sp., isolated from fish gut

    Directory of Open Access Journals (Sweden)

    Pushparaj Sujith

    2014-01-01

    Full Text Available Objective: To purify and partially characterize the antimicrobial compounds from bacteria Bacillus sp., isolated from fish gut. Methods: Protein and fatty acids were isolated from the bacteria and checked for the presence of antibacterial activity. Protein has been purified to apparent homogeneity from the supernatants of culture by means of ammonium sulphate precipitation followed by dialysis. Fourier transform infrared spectroscopy analyses were performed for proteins to identify the functional groups. Results: Protein showed an apparent molecular mass 56, 47 and 39 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Fatty acids were extracted and subjected to gas chromatographic analysis. Conclusions: The antimicrobial activity of the bacteria might be due to the presence of fatty acids and proteins which holds promise for the development of new drugs.

  19. Cellular fatty acid composition, protein profile and antimicrobial activity of Bacillus sp., isolated from fish gut

    Institute of Scientific and Technical Information of China (English)

    Pushparaj Sujith; Baskaran Rohini; Singaram Jayalakshmi

    2014-01-01

    Objective: To purify and partially characterize the antimicrobial compounds from bacteriaBacillus sp., isolated from fish gut. Methods: Protein and fatty acids were isolated from the bacteria and checked for the presence of antibacterial activity. Protein has been purified to apparent homogeneity from the supernatants of culture by means of ammonium sulphate precipitation followed by dialysis. Fourier transform infrared spectroscopy analyses were performed for proteins to identify the functional groups.Results:sulfate polyacrylamide gel electrophoresis. Fatty acids were extracted and subjected to gas chromatographic analysis.Conclusions:Protein showed an apparent molecular mass 56, 47 and 39 kDa on sodium dodecyl acids and proteins which holds promise for the development of new drugs. The antimicrobial activity of the bacteria might be due to the presence of fatty acids and proteins which holds promise for the development of new drugs.

  20. Selective peptide inhibitors of antiapoptotic cellular and viral Bcl-2 proteins lead to cytochrome c release during latent Kaposi’s sarcoma-associated herpesvirus infection

    OpenAIRE

    Burrer, Christine M.; Foight, Glenna W.; Keating, Amy E.; Chan, Gary C.

    2015-01-01

    Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with B-cell lymphomas including primary effusion lymphoma and multicentric Castleman’s disease. KSHV establishes latency within B cells by modulating or mimicking the antiapoptotic Bcl-2 family of proteins to promote cell survival. Our previous BH3 profiling analysis, a functional assay that assesses the contribution of Bcl-2 proteins towards cellular survival, identified two Bcl-2 proteins, cellular Mcl-1 and viral KsBcl-2, as pote...

  1. Cellular membrane trafficking of mesoporous silica nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Fang, I-Ju [Iowa State Univ., Ames, IA (United States)

    2012-01-01

    This dissertation mainly focuses on the investigation of the cellular membrane trafficking of mesoporous silica nanoparticles. We are interested in the study of endocytosis and exocytosis behaviors of mesoporous silica nanoparticles with desired surface functionality. The relationship between mesoporous silica nanoparticles and membrane trafficking of cells, either cancerous cells or normal cells was examined. Since mesoporous silica nanoparticles were applied in many drug delivery cases, the endocytotic efficiency of mesoporous silica nanoparticles needs to be investigated in more details in order to design the cellular drug delivery system in the controlled way. It is well known that cells can engulf some molecules outside of the cells through a receptor-ligand associated endocytosis. We are interested to determine if those biomolecules binding to cell surface receptors can be utilized on mesoporous silica nanoparticle materials to improve the uptake efficiency or govern the mechanism of endocytosis of mesoporous silica nanoparticles. Arginine-glycine-aspartate (RGD) is a small peptide recognized by cell integrin receptors and it was reported that avidin internalization was highly promoted by tumor lectin. Both RGD and avidin were linked to the surface of mesoporous silica nanoparticle materials to investigate the effect of receptor-associated biomolecule on cellular endocytosis efficiency. The effect of ligand types, ligand conformation and ligand density were discussed in Chapter 2 and 3. Furthermore, the exocytosis of mesoporous silica nanoparticles is very attractive for biological applications. The cellular protein sequestration study of mesoporous silica nanoparticles was examined for further information of the intracellular pathway of endocytosed mesoporous silica nanoparticle materials. The surface functionality of mesoporous silica nanoparticle materials demonstrated selectivity among the materials and cancer and normal cell lines. We aimed to determine

  2. Household electricity demand profiles

    DEFF Research Database (Denmark)

    Marszal, Anna Joanna; Heiselberg, Per Kvols; Larsen, Olena Kalyanova

    2016-01-01

    Highlights •A 1-min resolution household electricity load model is presented. •Model adapts a bottom-up approach with single appliance as the main building block. •Load profiles are used to analyse the flexibility potential of household appliances. •Load profiles can be applied in other domains, e...

  3. Polar measurements on profiles

    Energy Technology Data Exchange (ETDEWEB)

    Althaus, D.

    1985-03-01

    Wind tunnel models with a profile depth of t=0.5 m were measured in a laminar wind tunnel by the usual measuring processes. The profile resistance was determined by integration along the width of span. The smooth profiles were examined at Re=0.7/1.0 and 1.5 million. At Re=1.0 million, the position of the changeover points were determined with a stethoscope. Also at this Reynolds number measurements were taken with a trip wire of d=2 mm diameter, directly on the profile nose. The tables contain the co-ordinates of the profiles, the contours, the theoretical speed distributions for 4 different angles of attack, the csub(a)-csub(w) polar measurements and changeover points, and the torque coefficients around the t/4 point. (BR).

  4. Shape Memory Alloy-Based Periodic Cellular Structures Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This SBIR Phase II effort will continue to develop and demonstrate an innovative shape memory alloy (SMA) periodic cellular structural technology. Periodic cellular...

  5. ISBT 128 coding and labeling for cellular therapy products

    OpenAIRE

    Slaper-Cortenbach, Ineke

    2010-01-01

    This paper describes the development of the ISBT 128 coding and labeling for cellular therapy products. It is published on behalf of the international Cellular Therapy Coding and Labeling Advisory Group (see www.ICCBBA.org)

  6. 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.

  7. Mapping of cellular iron using hyperspectral fluorescence imaging in a cellular model of Parkinson's disease

    Science.gov (United States)

    Oh, Eung Seok; Heo, Chaejeong; Kim, Ji Seon; Lee, Young Hee; Kim, Jong Min

    2013-05-01

    Parkinson's disease (PD) is characterized by progressive dopaminergic cell loss in the substantianigra (SN) and elevated iron levels demonstrated by autopsy and with 7-Tesla magnetic resonance imaging. Direct visualization of iron with live imaging techniques has not yet been successful. The aim of this study is to visualize and quantify the distribution of cellular iron using an intrinsic iron hyperspectral fluorescence signal. The 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of PD was established in SHSY5Y cells. The cells were exposed to iron by treatment with ferric ammonium citrate (FAC, 100 μM) for up to 6 hours. The hyperspectral fluorescence imaging signal of iron was examined usinga high- resolution dark-field optical microscope system with signal absorption for the visible/ near infrared (VNIR) spectral range. The 6-hour group showed heavy cellular iron deposition compared with the small amount of iron accumulation in the 1-hour group. The cellular iron was dispersed in a small, particulate form, whereas extracellular iron was detected in an aggregated form. In addition, iron particles were found to be concentrated on the cell membrane/edge of shrunken cells. The cellular iron accumulation readily occurred in MPP+-induced cells, which is consistent with previous studies demonstrating elevated iron levels in the SN in PD. This direct iron imaging methodology could be applied to analyze the physiological role of iron in PD, and its application might be expanded to various neurological disorders involving other metals, such as copper, manganese or zinc.

  8. Cellular Dynamic Simulator: An Event Driven Molecular Simulation Environment for Cellular Physiology

    Science.gov (United States)

    Byrne, Michael J.; Waxham, M. Neal; Kubota, Yoshihisa

    2010-01-01

    In this paper, we present the Cellular Dynamic Simulator (CDS) for simulating diffusion and chemical reactions within crowded molecular environments. CDS is based on a novel event driven algorithm specifically designed for precise calculation of the timing of collisions, reactions and other events for each individual molecule in the environment. Generic mesh based compartments allow the creation / importation of very simple or detailed cellular structures that exist in a 3D environment. Multiple levels of compartments and static obstacles can be used to create a dense environment to mimic cellular boundaries and the intracellular space. The CDS algorithm takes into account volume exclusion and molecular crowding that may impact signaling cascades in small sub-cellular compartments such as dendritic spines. With the CDS, we can simulate simple enzyme reactions; aggregation, channel transport, as well as highly complicated chemical reaction networks of both freely diffusing and membrane bound multi-protein complexes. Components of the CDS are generally defined such that the simulator can be applied to a wide range of environments in terms of scale and level of detail. Through an initialization GUI, a simple simulation environment can be created and populated within minutes yet is powerful enough to design complex 3D cellular architecture. The initialization tool allows visual confirmation of the environment construction prior to execution by the simulator. This paper describes the CDS algorithm, design implementation, and provides an overview of the types of features available and the utility of those features are highlighted in demonstrations. PMID:20361275

  9. Defining the cellular precursors to human breast cancer

    Science.gov (United States)

    Keller, Patricia J.; Arendt, Lisa M.; Skibinski, Adam; Logvinenko, Tanya; Klebba, Ina; Dong, Shumin; Smith, Avi E.; Prat, Aleix; Perou, Charles M.; Gilmore, Hannah; Schnitt, Stuart; Naber, Stephen P.; Garlick, Jonathan A.; Kuperwasser, Charlotte

    2012-01-01

    Human breast cancers are broadly classified based on their gene-expression profiles into luminal- and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM+) and basal/myoepithelial (CD10+). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer. Here we report that transformation of EpCAM+ epithelial cells results in the formation of common forms of human breast cancer, including estrogen receptor-positive and estrogen receptor-negative tumors with luminal and basal-like characteristics, respectively, whereas transformation of CD10+ cells results in the development of rare metaplastic tumors reminiscent of the claudin-low subtype. We also demonstrate the existence of CD10+ breast cells with metaplastic traits that can give rise to skin and epidermal tissues. Furthermore, we show that the development of metaplastic breast cancer is attributable, in part, to the transformation of these metaplastic breast epithelial cells. These findings identify normal cellular precursors to human breast cancers and reveal the existence of a population of cells with epidermal progenitor activity within adult human breast tissues. PMID:21940501

  10. Quantifying a cellular automata simulation of electric vehicles

    Science.gov (United States)

    Hill, Graeme; Bell, Margaret; Blythe, Phil

    2014-12-01

    Within this work the Nagel-Schreckenberg (NS) cellular automata is used to simulate a basic cyclic road network. Results from SwitchEV, a real world Electric Vehicle trial which has collected more than two years of detailed electric vehicle data, are used to quantify the results of the NS automata, demonstrating similar power consumption behavior to that observed in the experimental results. In particular the efficiency of the electric vehicles reduces as the vehicle density increases, due in part to the reduced efficiency of EVs at low speeds, but also due to the energy consumption inherent in changing speeds. Further work shows the results from introducing spatially restricted speed restriction. In general it can be seen that induced congestion from spatially transient events propagates back through the road network and alters the energy and efficiency profile of the simulated vehicles, both before and after the speed restriction. Vehicles upstream from the restriction show a reduced energy usage and an increased efficiency, and vehicles downstream show an initial large increase in energy usage as they accelerate away from the speed restriction.

  11. A nanotube based electron microbeam cellular irradiator for radiobiology research

    OpenAIRE

    Bordelon, David E.; Zhang, Jian; Graboski, Sarah; Cox, Adrienne; Schreiber, Eric; Zhou, Otto Z.; Chang, Sha

    2008-01-01

    A prototype cellular irradiator utilizing a carbon nanotube (CNT) based field emission electron source has been developed for microscopic image-guided cellular region irradiation. The CNT cellular irradiation system has shown great potential to be a high temporal and spatial resolution research tool to enable researchers to gain a better understanding of the intricate cellular and intercellular microprocesses occurring following radiation deposition, which is essential to improving radiothera...

  12. Molecular and cellular mechanisms of cadmium carcinogenesis

    International Nuclear Information System (INIS)

    Cadmium is a heavy metal, which is widely used in industry, affecting human health through occupational and environmental exposure. In mammals, it exerts multiple toxic effects and has been classified as a human carcinogen by the International Agency for Research on Cancer. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Cd2+ does not catalyze Fenton-type reactions because it does not accept or donate electrons under physiological conditions, and it is only weakly genotoxic. Hence, indirect mechanisms are implicated in the carcinogenicity of cadmium. In this review multiple mechanisms are discussed, such as modulation of gene expression and signal transduction, interference with enzymes of the cellular antioxidant system and generation of reactive oxygen species (ROS), inhibition of DNA repair and DNA methylation, role in apoptosis and disruption of E-cadherin-mediated cell-cell adhesion. Cadmium affects both gene transcription and translation. The major mechanisms of gene induction by cadmium known so far are modulation of cellular signal transduction pathways by enhancement of protein phosphorylation and activation of transcription and translation factors. Cadmium interferes with antioxidant defense mechanisms and stimulates the production of reactive oxygen species, which may act as signaling molecules in the induction of gene expression and apoptosis. The inhibition of DNA repair processes by cadmium represents a mechanism by which cadmium enhances the genotoxicity of other agents and may contribute to the tumor initiation by this metal. The disruption of E-cadherin-mediated cell-cell adhesion by cadmium probably further stimulates the development of tumors. It becomes clear that there exist multiple mechanisms which contribute to the carcinogenicity of cadmium, although the relative weights of these contributions are difficult to estimate

  13. From Cellular Mechanotransduction to Biologically Inspired Engineering

    Science.gov (United States)

    Ingber, Donald E.

    2010-01-01

    This article is based on a lecture I presented as the recipient of the 2009 Pritzker Distinguished Lecturer Award at the Biomedical Engineering Society annual meeting in October 2009. Here, I review more than thirty years of research from my laboratory, beginning with studies designed to test the theory that cells use tensegrity (tensional integrity) architecture to stabilize their shape and sense mechanical signals, which I believed to be critical for control of cell function and tissue development. Although I was trained as a cell biologist, I found that the tools I had at my disposal were insufficient to experimentally test these theories, and thus I ventured into engineering to find critical solutions. This path has been extremely fruitful as it has led to confirmation of the critical role that physical forces play in developmental control, as well as how cells sense and respond to mechanical signals at the molecular level through a process known as cellular mechanotransduction. Many of the predictions of the cellular tensegrity model relating to cell mechanical behaviors have been shown to be valid, and this vision of cell structure led to discovery of the central role that transmembrane adhesion receptors, such as integrins, and the cytoskeleton play in mechanosensing and mechanochemical conversion. In addition, these fundamental studies have led to significant unexpected technology fallout, including development of micromagnetic actuators for non-invasive control of cellular signaling, microfluidic systems as therapeutic extracorporeal devices for sepsis therapy, and new DNA-based nanobiotechnology approaches that permit construction of artificial tensegrities that mimic properties of living materials for applications in tissue engineering and regenerative medicine. PMID:20140519

  14. 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.

  15. 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)

  16. Traffic Engineering of Cellular Wireless Communication Systems

    DEFF Research Database (Denmark)

    Iversen, Villy Bæk

    2002-01-01

    In mobile communications an efficient utilisation of the channels is of great importance. In this paper we describe the basic principles for obtaining the maximum utilisation and study strategies for obtaining these limits. In general a high degree of sharing is efficient, but requires service...... protection mechanisms to guarantee the Quality of Service for all services. We study cellular systems with hierarchical cells, and the effect of overlapping cells, and we show that by call packing we obtain a very high utilisation. The models are generalisations of the Erlang-B formula, and include general...

  17. Propagation Mechanism of Cylindrical Cellular Detonation

    Science.gov (United States)

    Han, Wen-Hu; Wang, Cheng; Ning, Jian-Guo

    2012-10-01

    We investigate the evolution of cylindrical cellular detonation with different instabilities. The numerical results show that with decreasing initial temperature, detonation becomes more unstable and the cells of the cylindrical detonation tend to be irregular. For stable detonation, a divergence of cylindrical detonation cells is formed eventually due to detonation instability resulting from a curved detonation front. For mildly unstable detonation, local overdriven detonation occurs. The detonation cell diverges and its size decreases. For highly unstable detonation, locally driven detonation is more obvious and the front is highly wrinkled. As a result, the diverging cylindrical detonation cell becomes highly irregular.

  18. Imaging Cellular Architecture with X-rays

    OpenAIRE

    Larabell, Carolyn A.; Nugent, Keith A.

    2010-01-01

    X-ray imaging of biological samples is progressing rapidly. In this paper we review the progress to date in high resolution imaging of cellular architecture. In particular we survey the progress in soft X-ray tomography and argue that the field is coming of age and that important biological insights are starting to emerge. We then review the new ideas based on coherent diffraction. These methods are at a much earlier stage of development but, as they eliminate the need for X-ray optics, have ...

  19. Single spin measurement using cellular automata techniques

    CERN Document Server

    Perez-Delgado, C A; Cory, D G; Mosca, M; Cappellaro, Paola; Cory, David G.; Mosca, Michele; Perez-Delgado, Carlos A.

    2006-01-01

    We propose an approach for single spin measurement. Our method uses techniques from the theory of quantum cellular automata to correlate a large amount of ancillary spins to the one to be measured. It has the distinct advantage of being efficient, and to a certain extent fault-tolerant. Under ideal conditions, it requires the application of only order of cube root of N steps (each requiring a constant number of rf pulses) to create a system of N correlated spins. It is also fairly robust against pulse errors, imperfect initial polarization of the ancilla spin system, and does not rely on entanglement. We study the scalability of our scheme through numerical simulation.

  20. Single spin measurement using cellular automata techniques

    OpenAIRE

    Perez-Delgado, Carlos A.; Mosca, Michele; Cappellaro, Paola; Cory, David G.

    2006-01-01

    We propose an approach for single spin measurement. Our method uses techniques from the theory of quantum cellular automata to correlate a large amount of ancillary spins to the one to be measured. It has the distinct advantage of being efficient, and to a certain extent fault-tolerant. Under ideal conditions, it requires the application of only order of cube root of N steps (each requiring a constant number of rf pulses) to create a system of N correlated spins. It is also fairly robust agai...

  1. Wireless communications, cellular phones and relay antennas

    International Nuclear Information System (INIS)

    Wireless communications using radiofrequency fields (RF) have seen an increasing use with the massive deployment of cellular systems GSM, UMTS and now LTE. In parallel, public concerns have been raised about possible health effects. During the last decade, about 10 million Euros per year have been dedicated to research. In vivo, in vitro, animal and human studies have been carried out. This paper gives an overview of the subject. The applicable limits and regulation as well as the typical human exposure are presented. The state of knowledge on biological and health effect is summarized. The recent classification of RF by the IARC and some sociological aspects are also discussed. (authors)

  2. Effect of cellular mobility on immune response

    Science.gov (United States)

    Pandey, R. B.; Mannion, R.; Ruskin, H. J.

    2000-08-01

    Mobility of cell types in our HIV immune response model is subject to an intrinsic mobility and an explicit directed mobility, which is governed by Pmob. We investigate how restricting the explicit mobility, while maintaining the innate mobility of a viral-infected cell, affects the model's results. We find that increasing the explicit mobility of the immune system cells leads to viral dominance for certain levels of viral mutation. We conclude that increasing immune system cellular mobility indirectly increases the virus’ inherent mobility.

  3. Cellular regulation of the dopamine transporter

    DEFF Research Database (Denmark)

    Eriksen, Jacob

    2010-01-01

    The dopamine transporter (DAT) mediates reuptake of dopamine from the synaptic cleft and is a target for widely abused psychostimulants such as cocaine and amphetamine. Nonetheless, little is known about the cellular distribution and trafficking of natively expressed DAT. DAT and its trafficking...... single-membrane spanning protein Tac, thereby creating an extracellular antibody epitope. Upon expression in HEK293 cells this TacDAT fusion protein displayed functional properties similar to the wild type transporter. In an ELISA based internalization assay, TacDAT intracellular accumulation was...

  4. Cellular spaces, null spaces and homotopy localization

    CERN Document Server

    Farjoun, Emmanuel Dror

    1996-01-01

    In this monograph we give an exposition of some recent development in homotopy theory. It relates to advances in periodicity in homotopy localization and in cellular spaces. The notion of homotopy localization is treated quite generally and encompasses all the known idempotent homotopy functors. It is applied to K-theory localizations, to Morava-theories, to Hopkins-Smith theory of types. The method of homotopy colimits is used heavily. It is written with an advanced graduate student in topology and research homotopy theorist in mind.

  5. Cellular automata modelling of hantarvirus infection

    International Nuclear Information System (INIS)

    Hantaviruses are a group of viruses which have been identified as being responsible for the outbreak of diseases such as the hantavirus pulmonary syndrome. In an effort to understand the characteristics and dynamics of hantavirus infection, mathematical models based on differential equations have been developed and widely studied. However, such models neglect the local characteristics of the spreading process and do not include variable susceptibility of individuals. In this paper, we develop an alternative approach based on cellular automata to analyze and study the spatiotemporal patterns of hantavirus infection.

  6. Cellular automata modelling of hantarvirus infection

    Energy Technology Data Exchange (ETDEWEB)

    Abdul Karim, Mohamad Faisal [School of Distance Education, Universiti Sains Malaysia, Minden 11800, Penang (Malaysia)], E-mail: faisal@usm.my; Md Ismail, Ahmad Izani [School of Mathematical Sciences, Universiti Sains Malaysia, Minden 11800, Penang (Malaysia)], E-mail: izani@cs.usm.my; Ching, Hoe Bee [School of Mathematical Sciences, Universiti Sains Malaysia, Minden 11800, Penang (Malaysia)], E-mail: Bee_Ching_Janice_Hoe@dell.com

    2009-09-15

    Hantaviruses are a group of viruses which have been identified as being responsible for the outbreak of diseases such as the hantavirus pulmonary syndrome. In an effort to understand the characteristics and dynamics of hantavirus infection, mathematical models based on differential equations have been developed and widely studied. However, such models neglect the local characteristics of the spreading process and do not include variable susceptibility of individuals. In this paper, we develop an alternative approach based on cellular automata to analyze and study the spatiotemporal patterns of hantavirus infection.

  7. Rapid Cellular Identification by Dynamic Electromechanical Response

    Energy Technology Data Exchange (ETDEWEB)

    Nikiforov, Maxim [ORNL; Jesse, Stephen [ORNL; Kalinin, Sergei V [ORNL; Reukov, Vladimir V [ORNL; Vertegel, Alexey [ORNL; Thompson, Gary L [ORNL

    2009-01-01

    Coupling between electrical and mechanical phenomena is ubiquitous in living systems. Here, we demonstrate rapid identification of cellular organisms using difference in electromechanical activity in a broad frequency range. Principal component analysis of the dynamic electromechanical response spectra bundled with neural network based recognition provides a robust identification algorithm based on their electromechanical signature, and allows unambiguous differentiation of model Micrococcus Lysodeikticus and Pseudomonas Fluorescens system. This methodology provides a universal pathway for biological identification obviating the need for well-defined analytical models of Scanning Probe Microscopy response.

  8. Immunometabolism: Cellular Metabolism Turns Immune Regulator.

    Science.gov (United States)

    Loftus, Róisín M; Finlay, David K

    2016-01-01

    Immune cells are highly dynamic in terms of their growth, proliferation, and effector functions as they respond to immunological challenges. Different immune cells can adopt distinct metabolic configurations that allow the cell to balance its requirements for energy, molecular biosynthesis, and longevity. However, in addition to facilitating immune cell responses, it is now becoming clear that cellular metabolism has direct roles in regulating immune cell function. This review article describes the distinct metabolic signatures of key immune cells, explains how these metabolic setups facilitate immune function, and discusses the emerging evidence that intracellular metabolism has an integral role in controlling immune responses. PMID:26534957

  9. Quantumness of discrete Hamiltonian cellular automata

    Directory of Open Access Journals (Sweden)

    Elze Hans-Thomas

    2014-01-01

    Full Text Available We summarize a recent study of discrete (integer-valued Hamiltonian cellular automata (CA showing that their dynamics can only be consistently defined, if it is linear in the same sense as unitary evolution described by the Schrödinger equation. This allows to construct an invertible map between such CA and continuous quantum mechanical models, which incorporate a fundamental scale. Presently, we emphasize general aspects of these findings, the construction of admissible CA observables, and the existence of solutions of the modified dispersion relation for stationary states.

  10. Conference on radionuclide labelled cellular blood elements

    International Nuclear Information System (INIS)

    The South African Medical Research Council presented this conference on radionuclide labelled cellular blood elements with application in atherosclerosis and thrombosis. The conference was held in Bloemfontein from 3-6 February 1986. This work only consists of the abstracts of the seminars that were delivered on the conference. The radioisotopes that occur most of the time in the abstracts include Indium 111, Indium 114, Chromium 51, Iodine 125, Iodine 131 and Carbon 14. Especially Indium 111 seems to be the method of choice for all labelling

  11. Cellular Scaling Rules for Primate Spinal Cords

    OpenAIRE

    Burish, Mark J.; Peebles, J. Klint; Baldwin, Mary K.; Tavares, Luciano; Kaas, Jon H.; Herculano-Houzel, Suzana

    2010-01-01

    The spinal cord can be considered a major sensorimotor interface between the body and the brain. How does the spinal cord scale with body and brain mass, and how are its numbers of neurons related to the number of neurons in the brain across species of different body and brain sizes? Here we determine the cellular composition of the spinal cord in eight primate species and find that its number of neurons varies as a linear function of cord length, and accompanies body mass raised to an expone...

  12. 47 CFR 32.5003 - Cellular mobile revenue.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular mobile revenue. 32.5003 Section 32... SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions For Revenue Accounts § 32.5003 Cellular mobile revenue. This account shall include message revenue derived from cellular...

  13. 47 CFR 22.901 - Cellular service requirements and limitations.

    Science.gov (United States)

    2010-10-01

    ... accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies of the standard may be purchased from Global... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular service requirements and limitations... SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.901 Cellular service requirements...

  14. 47 CFR 22.917 - Emission limitations for cellular equipment.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Emission limitations for cellular equipment. 22... SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.917 Emission limitations for cellular equipment. The rules in this section govern the spectral characteristics of emissions in the...

  15. Non-invasive imaging of phosphoinositide-3-kinase-catalytic-subunit-alpha (PIK3CA promoter modulation in small animal models.

    Directory of Open Access Journals (Sweden)

    Snehal M Gaikwad

    Full Text Available Activation of the PI3K/Akt pathway, a critical step for survival in cancer cells is often associated with decreased sensitivity to several chemotherapeutic drugs. PIK3CA gene amplification is observed in 16-24% of epithelial ovarian cancer (EOC patients in conjunction with p53 mutations. A 900 bp long PIK3CA promoter is shown to be negatively regulated by p53 in ovarian surface epithelial cells but the consequence of chemotherapeutic drug treatments on this promoter in ovarian cancer cells is largely unknown. We aim to study the modulation of this promoter by cisplatin using an improved fusion reporter in ovarian cancer cells and tumor xenografts by non-invasive imaging approach. A PIK3CA sensor was developed using a bi-fusion reporter from a newly constructed library of bi- and tri-fusion vectors comprising of two mutant far red fluorescent proteins (mcherry/mch and tdTomato/tdt, a mutant firefly luciferase (fluc2, and a PET reporter protein (ttk. In vivo imaging of mice implanted with 293T cells transiently expressing these bi- and tri-fusion reporters along with respective controls revealed comparable activity of each reporter in the fusion background and fluc2-tdt as the most sensitive one. Repression of the PIK3CA sensor by drugs was inversely proportional to cellular p53 level in a germline (PA1 and in an EOC (A2780 cell line but not in a p53 deficient EOC (SKOV3 cell line. Bioluminescence imaging of tumor xenografts stably expressing the PIK3CA sensor in PA1 and A2780 cells exhibited attenuating activity without any change in SKOV3 tumors expressing the PIK3CA sensor after cisplatin treatment. Sequential mutation at p53 binding sites showed gradual increase in promoter activity and decreased effects of the drugs. These newly developed PIK3CA-fluc2-tdt and the mutant reporter sensors thus would be extremely useful for screening new drugs and for functional assessment of PIK3CA expression from intact cells to living subjects.

  16. Using a cDNA microarray to study cellular gene expression altered by Mycobacterium tuberculosis

    Institute of Scientific and Technical Information of China (English)

    徐永忠; 谢建平; 李瑶; 乐军; 陈建平; 淳于利娟; 王洪海

    2003-01-01

    Objective To examine the global effects of Mycobacterium tuberculosis (M.tuberculosis) infection on macrophages. Methods The gene expression profiling of macrophage U937, in response to infection with M.tuberculosis H37Ra, was monitored using a high-density cDNA microarray. Results M.tuberculosis infection caused 463 differentially expressed genes, of which 366 genes are known genes registered in the Gene Bank. These genes function in various cellular processes including intracellular signalling, cytoskeletal rearrangement, apoptosis, transcriptional regulation, cell surface receptors, cell-mediated immunity as well as a variety of cellular metabolic pathways, and may play key roles in M.tuberculosis infection and intracellular survival. Conclusions M.tuberculosis infection alters the expression of host-cell genes, and these genes will provide a foundation for understanding the infection process of M.tuberculosis. The cDNA microarray is a powerful tool for studying pathogen-host cell interaction.

  17. Voluntary accreditation of cellular therapies: Foundation for the Accreditation of Cellular Therapy (FACT).

    Science.gov (United States)

    Warkentin, P I

    2003-01-01

    Voluntary accreditation of cells, tissues, and cellular and tissue-based products intended for human transplantation is an important mechanism for improving quality in cellular therapy. The Foundation for the Accreditation of Cellular Therapy (FACT) has developed and implemented programs of voluntary inspection and accreditation for hematopoietic cellular therapy, and for cord blood banking. These programs are based on the standards of the clinical and laboratory professionals of the American Society of Blood and Marrow Transplantation (ASBMT), the International Society for Cellular Therapy (ISCT), and NETCORD. FACT has collaborated with European colleagues in the development of the Joint Accreditation Committee in Europe (jACIE). FACT has published standards documents, a guidance manual, accreditation checklists, and inspection documents; and has trained as inspectors over 300 professionals active in the field. All inspectors have a minimum of 5 years' experience in the area they inspect. Since the incorporation of FACT in 1996, 215 hematopoietic progenitor cell facilities have applied for FACT accreditation. Of these facilities, 113 are fully accredited; the others are in the process of document submission or inspection. Significant opportunities and challenges exist for FACT in the future, including keeping standards and guidance materials current and relevant, recruiting and retaining expert inspectors, and establishing collaborations to develop standards and accreditation systems for new cellular products. The continuing dialogue with the Food and Drug Administration (FDA) is also important to ensure that they are aware of the accomplishments of voluntary accreditation, and keep FACT membership alerted to FDA intentions for the future. Other potential avenues of communication and cooperation with FDA and other regulatory agencies are being investigated and evaluated. PMID:12944235

  18. 植物细胞中磷酸肌醇和磷脂酶C介导的信号转导%Signal Transduction by Phosphoinositides and Phospholipase C in Plant Cells

    Institute of Scientific and Technical Information of China (English)

    李莉; 井文; 章文华

    2015-01-01

    磷酸肌醇(PIs)是磷脂酰肌醇(PtdIns)单、双、三磷酸化产物的总称。磷脂酶C (PLC)水解磷脂酰肌醇-4,5-二磷酸[Pt-dIns(4,5)P2]产生二酰甘油(DAG)和肌醇三磷酸(InsP3),此双信使系统的靶蛋白分别是蛋白激酶C (PKC)和InsP3受体(钙通道蛋白)。此经典的信号途径是从动物细胞中发现的。到目前为止,植物中没有发现PKC或InsP3受体,但有其独特的磷酸肌醇信号组分和途径。与动物不同,植物PI含量最高的是磷脂酰肌醇-4-磷酸(PtdIns4P),最多可达PtdIns(4,5)P2的100倍;而DAG磷酸化产物磷脂酸(PA)和InsP3磷酸化产物肌醇六磷酸(InsP6)也被证明是植物中重要的信号分子。本文通过比较动、植物细胞中PI和PLC信号途径的差异,综述了植物细胞中PI和PLC途径的独特作用和调控机理。%Phosphoinositides (PIs) are mono-, bis-, or tris-phosphorylated derivatives of phosphatidylinositol (PtdIns). Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] can be hydrolyzed by phospholipase C (PLC) to produce diacylglycerol (DAG) and inositol trisphosphates (InsP3). In animal cells, DAG and InsP3 are important second messengers that activate protein kinase C (PKC) and InsP3 receptor (Ca2+ channel), respectively. How-ever, neither PKC nor InsP3 receptor has been found in plant cells. Instead, there are unique phosphoinositide signaling pathways in plant cells. In plants, PtdIns4P is the most abundant PI, and the ratio of phosphatidyli-nositol 4-phosphate (PtdIns4P) to PtdIns(4,5)P2 is as high as 100 to 1. The phosphorylated products of DAG and InsP3, phosphatidic acid (PA) and inositol hexakisphosphate (InsP6), respectively, are as signaling mole-cules in plants. This paper compared the PI and PLC signalings between plant and animal cells, and summa-rized the unique mechanism of PI and PLC pathways in plant cells.

  19. Qualitative Value Profiling

    DEFF Research Database (Denmark)

    Duus, Henrik Johannsen; Bjerre, Mogens

    2015-01-01

    allows the development of 1) profiles of the target country in which operations are to take place, 2) profiles of the buying center (i.e. the group of decision makers) in the partner company, and 3) profiles of the product/service offering. It also allows the development of a semantic scaling method for...... International Business. This comparison suggests that QVP on most accounts provides deeper insights than alternative methods and thus lays the foundation for better strategic planning in international business-to-business markets. Hence, it is a valuable addition to the toolbox of business strategists and...

  20. Profiling the Mobile Customer

    DEFF Research Database (Denmark)

    Jessen, Pernille Wegener; King, Nancy J.

    2010-01-01

    Mobile customers are increasingly being tracked and profiled by behavioural advertisers to enhance delivery of personalized advertising. This type of profiling relies on automated processes that mine databases containing personally-identifying or anonymous consumer data, and it raises a host of...... significant concerns about privacy and data protection. This second article in a two part series on "Profiling the Mobile Customer" explores how to best protect consumers' privacy and personal data through available mechanisms that include industry self-regulation, privacy-enhancing technologies and...