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Sample records for controlling cellular function

  1. Leading research on artificial techniques controlling cellular function; Saibo zoshoku seigyo gijutsu no sendo kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-03-01

    Advanced research and its applicability were surveyed to apply the advanced functional cells to industry. The basic target was set to develop, produce, control and utilize the functional cells, such as intelligent materials and self-regulation bioreactors. The regulation factors regarding apotosis, which is a process of cell suicide programmed within the cell itself of multicellular organisms, cell cycle and aging/ageless were investigated. Furthermore, the function of regulatory factors was investigated at the protein level. Injection of factors regulating cellular function and tissue engineering required for the regulation of cell proliferation were investigated. Tissue engineering is considered to be the intracellular regulation by gene transduction and the extracellular regulation by culture methods, such as coculture. Analysis methods for cell proliferation and function of living cells were investigated using the probes recognizing molecular structure. Novel biomaterials, artificial organ systems, cellular therapy and useful materials were investigated for utilizing the regulation techniques of cell proliferation. 425 refs., 85 figs., 9 tabs.

  2. Remote Control of Cellular Functions: The Role of Smart Nanomaterials in the Medicine of the Future.

    Science.gov (United States)

    Genchi, Giada Graziana; Marino, Attilio; Grillone, Agostina; Pezzini, Ilaria; Ciofani, Gianni

    2017-05-01

    The remote control of cellular functions through smart nanomaterials represents a biomanipulation approach with unprecedented potential applications in many fields of medicine, ranging from cancer therapy to tissue engineering. By actively responding to external stimuli, smart nanomaterials act as real nanotransducers able to mediate and/or convert different forms of energy into both physical and chemical cues, fostering specific cell behaviors. This report describes those classes of nanomaterials that have mostly paved the way to a "wireless" control of biological phenomena, focusing the discussion on some examples close to the clinical practice. In particular, magnetic fields, light irradiation, ultrasound, and pH will be presented as means to manipulate the cellular fate, due to the peculiar physical/chemical properties of some smart nanoparticles, thus providing realistic examples of "nanorobots" approaching the visionary ideas of Richard Feynman. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Conducting polymer scaffolds for electrical control of cellular functions (Conference Presentation)

    Science.gov (United States)

    Inal, Sahika; Wan, Alwin M.; Williams, Tiffany V.; Giannelis, Emmanuel P.; Fischbach-Teschl, Claudia; Gourdon, Delphine; Owens, Róisín. M.; Malliaras, George G.

    2016-09-01

    Considering the limited physiological relevance of 2D cell culture experiments, significant effort was devoted to the development of materials that could more accurately recreate the in vivo cellular microenvironment, and support 3D cell cultures in vitro. (1) One such class of materials is conducting polymers, which are promising due to their compliant mechanical properties, compatibility with biological systems, mixed electrical and ionic conductivity, and ability to form porous structures. (2) In this work, we report the fabrication of a single component, macroporous scaffold made from poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) via an ice-templating method. (3) PEDOT:PSS scaffolds offer tunable pore size, morphology and shape through facile changes in preparation conditions, and are capable of supporting 3D cell cultures due to their biocompatibility and tissue-like elasticity. Moreover, these materials are functional: they exhibit excellent electrochemical switching behavior and significantly lower impedance compared to films. Their electrochemical activity enables their use in the active channel of a state of the art diagnostic tool in the field of bioelectronics, i.e., the organic electrochemical transistor (OECT). The inclusion of cells within the porous architecture affects the impedance of the electrically-conducting polymer network and, thus, may be used as a method to quantify cell growth. The adhesion and pro-angiogenic secretions of mouse fibroblasts cultured within the scaffolds can be controlled by switching the electrochemical state of the polymer prior to cell-seeding. In summary, these smart materials hold promise not only as extracellular matrix-mimicking structures for cell culture, but also as high-performance bioelectronic tools for diagnostic and signaling applications. References [1] M. Holzwarth, P. X. Ma, Journal of Materials Chemistry, 21, 10243-10251 (2011). [2] L. H. Jimison, J. Rivnay, R. M. Owens, in Organic

  4. Development of mechano-responsive polymeric scaffolds using functionalized silica nano-fillers for the control of cellular functions.

    Science.gov (United States)

    Griffin, Michelle; Nayyer, Leila; Butler, Peter E; Palgrave, Robert G; Seifalian, Alexander M; Kalaskar, Deepak M

    2016-08-01

    We demonstrate an efficient method to produce mechano-responsive polymeric scaffolds which can alter cellular functions using two different functionalized (OH and NH2) silica nano-fillers. Fumed silica-hydroxyl and fumed silica-amine nano-fillers were mixed with a biocompatible polymer (POSS-PCU) at various wt% to produce scaffolds. XPS and mechanical testing demonstrate that bulk mechanical properties are modified without changing the scaffold's surface chemistry. Mechanical testing showed significant change in bulk properties of POSS-PCU scaffolds with an addition of silica nanofillers as low as 1% (PScaffolds modified with NH2 silica showed significantly higher bulk mechanical properties compared to the one modified with the OH group. Enhanced cell adhesion, proliferation and collagen production over 14days were observed on scaffolds with higher bulk mechanical properties (NH2) compared to those with lower ones (unmodified and OH modified) (Ppolymeric scaffolds, which can help to customize cellular responses for biomaterial applications.

  5. c-Myc and AMPK Control Cellular Energy Levels by Cooperatively Regulating Mitochondrial Structure and Function.

    Directory of Open Access Journals (Sweden)

    Lia R Edmunds

    Full Text Available The c-Myc (Myc oncoprotein and AMP-activated protein kinase (AMPK regulate glycolysis and oxidative phosphorylation (Oxphos although often for different purposes. Because Myc over-expression depletes ATP with the resultant activation of AMPK, we explored the potential co-dependency of and cross-talk between these proteins by comparing the consequences of acute Myc induction in ampk+/+ (WT and ampk-/- (KO murine embryo fibroblasts (MEFs. KO MEFs showed a higher basal rate of glycolysis than WT MEFs and an appropriate increase in response to activation of a Myc-estrogen receptor (MycER fusion protein. However, KO MEFs had a diminished ability to increase Oxphos, mitochondrial mass and reactive oxygen species in response to MycER activation. Other differences between WT and KO MEFs, either in the basal state or following MycER induction, included abnormalities in electron transport chain function, levels of TCA cycle-related oxidoreductases and cytoplasmic and mitochondrial redox states. Transcriptional profiling of pathways pertinent to glycolysis, Oxphos and mitochondrial structure and function also uncovered significant differences between WT and KO MEFs and their response to MycER activation. Finally, an unbiased mass-spectrometry (MS-based survey capable of quantifying ~40% of all mitochondrial proteins, showed about 15% of them to be AMPK- and/or Myc-dependent in their steady state. Significant differences in the activities of the rate-limiting enzymes pyruvate kinase and pyruvate dehydrogenase, which dictate pyruvate and acetyl coenzyme A abundance, were also differentially responsive to Myc and AMPK and could account for some of the differences in basal metabolite levels that were also detected by MS. Thus, Myc and AMPK are highly co-dependent and appear to engage in significant cross-talk across numerous pathways which support metabolic and ATP-generating functions.

  6. Cellular functions of the microprocessor.

    Science.gov (United States)

    Macias, Sara; Cordiner, Ross A; Cáceres, Javier F

    2013-08-01

    The microprocessor is a complex comprising the RNase III enzyme Drosha and the double-stranded RNA-binding protein DGCR8 (DiGeorge syndrome critical region 8 gene) that catalyses the nuclear step of miRNA (microRNA) biogenesis. DGCR8 recognizes the RNA substrate, whereas Drosha functions as an endonuclease. Recent global analyses of microprocessor and Dicer proteins have suggested novel functions for these components independent of their role in miRNA biogenesis. A HITS-CLIP (high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation) experiment designed to identify novel substrates of the microprocessor revealed that this complex binds and regulates a large variety of cellular RNAs. The microprocessor-mediated cleavage of several classes of RNAs not only regulates transcript levels, but also modulates alternative splicing events, independently of miRNA function. Importantly, DGCR8 can also associate with other nucleases, suggesting the existence of alternative DGCR8 complexes that may regulate the fate of a subset of cellular RNAs. The aim of the present review is to provide an overview of the diverse functional roles of the microprocessor.

  7. Enrichment from birth accelerates the functional and cellular development of a motor control area in the mouse.

    Directory of Open Access Journals (Sweden)

    Teresa Simonetti

    Full Text Available BACKGROUND: There is strong evidence that sensory experience in early life has a profound influence on the development of sensory circuits. Very little is known, however, about the role of experience in the early development of striatal networks which regulate both motor and cognitive function. To address this, we have investigated the influence of early environmental enrichment on motor development. METHODOLOGY/PRINCIPAL FINDINGS: Mice were raised in standard or enriched housing from birth. For animals assessed as adults, half of the mice had their rearing condition reversed at weaning to enable the examination of the effects of pre- versus post-weaning enrichment. We found that exclusively pre-weaning enrichment significantly improved performance on the Morris water maze compared to non-enriched mice. The effects of early enrichment on the emergence of motor programs were assessed by performing behavioural tests at postnatal day 10. Enriched mice traversed a significantly larger region of the test arena in an open-field test and had improved swimming ability compared to non-enriched cohorts. A potential cellular correlate of these changes was investigated using Wisteria-floribunda agglutinin (WFA staining to mark chondroitin-sulfate proteoglycans (CSPGs. We found that the previously reported transition of CSPG staining from striosome-associated clouds to matrix-associated perineuronal nets (PNNs is accelerated in enriched mice. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration that the early emergence of exploratory as well as coordinated movement is sensitive to experience. These behavioural changes are correlated with an acceleration of the emergence of striatal PNNs suggesting that they may consolidate the neural circuits underlying these behaviours. Finally, we confirm that pre-weaning experience can lead to life long changes in the learning ability of mice.

  8. Redox control of cellular signalling

    NARCIS (Netherlands)

    Putker, M.

    2014-01-01

    Reactive oxygen species (ROS) are natural by-products of cellular energy production. Consequently, mammalian cells encounter them on a daily basis. Increased ROS levels are associated with the onset of cancer and accelerated ageing, and historically, ROS are therefore considered harmful molecules.

  9. 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.

  10. Cellular mechanisms that control mistranslation

    DEFF Research Database (Denmark)

    Reynolds, Noah M; Lazazzera, Beth A; Ibba, Michael

    2010-01-01

    Mistranslation broadly encompasses the introduction of errors during any step of protein synthesis, leading to the incorporation of an amino acid that is different from the one encoded by the gene. Recent research has vastly enhanced our understanding of the mechanisms that control mistranslation...

  11. Molecular kinesis in cellular function and plasticity.

    Science.gov (United States)

    Tiedge, H; Bloom, F E; Richter, D

    2001-06-19

    Intracellular transport and localization of cellular components are essential for the functional organization and plasticity of eukaryotic cells. Although the elucidation of protein transport mechanisms has made impressive progress in recent years, intracellular transport of RNA remains less well understood. The National Academy of Sciences Colloquium on Molecular Kinesis in Cellular Function and Plasticity therefore was devised as an interdisciplinary platform for participants to discuss intracellular molecular transport from a variety of different perspectives. Topics covered at the meeting included RNA metabolism and transport, mechanisms of protein synthesis and localization, the formation of complex interactive protein ensembles, and the relevance of such mechanisms for activity-dependent regulation and synaptic plasticity in neurons. It was the overall objective of the colloquium to generate momentum and cohesion for the emerging research field of molecular kinesis.

  12. 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.)

  13. Distinguishing between biochemical and cellular function: Are there peptide signatures for cellular function of proteins?

    Science.gov (United States)

    Jain, Shruti; Bhattacharyya, Kausik; Bakshi, Rachit; Narang, Ankita; Brahmachari, Vani

    2017-04-01

    The genome annotation and identification of gene function depends on conserved biochemical activity. However, in the cell, proteins with the same biochemical function can participate in different cellular pathways and cannot complement one another. Similarly, two proteins of very different biochemical functions are put in the same class of cellular function; for example, the classification of a gene as an oncogene or a tumour suppressor gene is not related to its biochemical function, but is related to its cellular function. We have taken an approach to identify peptide signatures for cellular function in proteins with known biochemical function. ATPases as a test case, we classified ATPases (2360 proteins) and kinases (517 proteins) from the human genome into different cellular function categories such as transcriptional, replicative, and chromatin remodelling proteins. Using publicly available tool, MEME, we identify peptide signatures shared among the members of a given category but not between cellular functional categories; for example, no motif sharing is seen between chromatin remodelling and transporter ATPases, similarly between receptor Serine/Threonine Kinase and Receptor Tyrosine Kinase. There are motifs shared within each category with significant E value and high occurrence. This concept of signature for cellular function was applied to developmental regulators, the polycomb and trithorax proteins which led to the prediction of the role of INO80, a chromatin remodelling protein, in development. This has been experimentally validated earlier for its role in homeotic gene regulation and its interaction with regulatory complexes like the Polycomb and Trithorax complex. Proteins 2017; 85:682-693. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Tandem E2F binding sites in the promoter of the p107 cell cycle regulator control p107 expression and its cellular functions.

    Directory of Open Access Journals (Sweden)

    Deborah L Burkhart

    2010-06-01

    Full Text Available The retinoblastoma tumor suppressor (Rb is a potent and ubiquitously expressed cell cycle regulator, but patients with a germline Rb mutation develop a very specific tumor spectrum. This surprising observation raises the possibility that mechanisms that compensate for loss of Rb function are present or activated in many cell types. In particular, p107, a protein related to Rb, has been shown to functionally overlap for loss of Rb in several cellular contexts. To investigate the mechanisms underlying this functional redundancy between Rb and p107 in vivo, we used gene targeting in embryonic stem cells to engineer point mutations in two consensus E2F binding sites in the endogenous p107 promoter. Analysis of normal and mutant cells by gene expression and chromatin immunoprecipitation assays showed that members of the Rb and E2F families directly bound these two sites. Furthermore, we found that these two E2F sites controlled both the repression of p107 in quiescent cells and also its activation in cycling cells, as well as in Rb mutant cells. Cell cycle assays further indicated that activation of p107 transcription during S phase through the two E2F binding sites was critical for controlled cell cycle progression, uncovering a specific role for p107 to slow proliferation in mammalian cells. Direct transcriptional repression of p107 by Rb and E2F family members provides a molecular mechanism for a critical negative feedback loop during cell cycle progression and tumorigenesis. These experiments also suggest novel therapeutic strategies to increase the p107 levels in tumor cells.

  15. The CORVET complex: compositions, function, and impact on cellular behaviour

    NARCIS (Netherlands)

    Jonker, CTH

    2016-01-01

    The endolysosomal system is positioned on the crossroad of the intracellular and extracellular environment and is therefore crucial to regulate many cellular processes. Proper function of the endolysosomal system greatly depends on the concept of membrane identity; the controlled protein and lipid

  16. Cellular strategies for regulating functional and nonfunctional protein aggregation.

    Science.gov (United States)

    Gsponer, Jörg; Babu, M Madan

    2012-11-29

    Growing evidence suggests that aggregation-prone proteins are both harmful and functional for a cell. How do cellular systems balance the detrimental and beneficial effect of protein aggregation? We reveal that aggregation-prone proteins are subject to differential transcriptional, translational, and degradation control compared to nonaggregation-prone proteins, which leads to their decreased synthesis, low abundance, and high turnover. Genetic modulators that enhance the aggregation phenotype are enriched in genes that influence expression homeostasis. Moreover, genes encoding aggregation-prone proteins are more likely to be harmful when overexpressed. The trends are evolutionarily conserved and suggest a strategy whereby cellular mechanisms specifically modulate the availability of aggregation-prone proteins to (1) keep concentrations below the critical ones required for aggregation and (2) shift the equilibrium between the monomeric and oligomeric/aggregate form, as explained by Le Chatelier's principle. This strategy may prevent formation of undesirable aggregates and keep functional assemblies/aggregates under control.

  17. Call Admission Control in Mobile Cellular Networks

    CERN Document Server

    Ghosh, Sanchita

    2013-01-01

    Call Admission Control (CAC) and Dynamic Channel Assignments (DCA) are important decision-making problems in mobile cellular communication systems. Current research in mobile communication considers them as two independent problems, although the former greatly depends on the resulting free channels obtained as the outcome of the latter. This book provides a solution to the CAC problem, considering DCA as an integral part of decision-making for call admission. Further, current technical resources ignore movement issues of mobile stations and fluctuation in network load (incoming calls) in the control strategy used for call admission. In addition, the present techniques on call admission offers solution globally for the entire network, instead of considering the cells independently.      CAC here has been formulated by two alternative approaches. The first approach aimed at handling the uncertainty in the CAC problem by employing fuzzy comparators.  The second approach is concerned with formulation of CAC ...

  18. Natural Products as Tools for Defining How Cellular Metabolism Influences Cellular Immune and Inflammatory Function during Chronic Infection

    Directory of Open Access Journals (Sweden)

    Erica S. Lovelace

    2015-11-01

    Full Text Available Chronic viral infections like those caused by hepatitis C virus (HCV and human immunodeficiency virus (HIV cause disease that establishes an ongoing state of chronic inflammation. While there have been tremendous improvements towards curing HCV with directly acting antiviral agents (DAA and keeping HIV viral loads below detection with antiretroviral therapy (ART, there is still a need to control inflammation in these diseases. Recent studies indicate that many natural products like curcumin, resveratrol and silymarin alter cellular metabolism and signal transduction pathways via enzymes such as adenosine monophosphate kinase (AMPK and mechanistic target of rapamycin (mTOR, and these pathways directly influence cellular inflammatory status (such as NF-κB and immune function. Natural products represent a vast toolkit to dissect and define how cellular metabolism controls cellular immune and inflammatory function.

  19. Cellular metabolic and autophagic pathways: traffic control by redox signaling.

    Science.gov (United States)

    Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua

    2013-10-01

    It has been established that the key metabolic pathways of glycolysis and oxidative phosphorylation are intimately related to redox biology through control of cell signaling. Under physiological conditions glucose metabolism is linked to control of the NADH/NAD redox couple, as well as providing the major reductant, NADPH, for thiol-dependent antioxidant defenses. Retrograde signaling from the mitochondrion to the nucleus or cytosol controls cell growth and differentiation. Under pathological conditions mitochondria are targets for reactive oxygen and nitrogen species and are critical in controlling apoptotic cell death. At the interface of these metabolic pathways, the autophagy-lysosomal pathway functions to maintain mitochondrial quality and generally serves an important cytoprotective function. In this review we will discuss the autophagic response to reactive oxygen and nitrogen species that are generated from perturbations of cellular glucose metabolism and bioenergetic function.

  20. Performance comparison of virtual cellular manufacturing with functional and cellular layouts in DRC settings

    NARCIS (Netherlands)

    Suresh, N.; Slomp, J.

    2005-01-01

    This study investigates the performance of virtual cellular manufacturing (VCM) systems, comparing them with functional layouts (FL) and traditional, physical cellular layout (CL), in a dual-resource-constrained (DRC) system context. VCM systems employ logical cells, retaining the process layouts of

  1. Using RNA as Molecular Code for Programming Cellular Function.

    Science.gov (United States)

    Kushwaha, Manish; Rostain, William; Prakash, Satya; Duncan, John N; Jaramillo, Alfonso

    2016-08-19

    RNA is involved in a wide-range of important molecular processes in the cell, serving diverse functions: regulatory, enzymatic, and structural. Together with its ease and predictability of design, these properties can lead RNA to become a useful handle for biological engineers with which to control the cellular machinery. By modifying the many RNA links in cellular processes, it is possible to reprogram cells toward specific design goals. We propose that RNA can be viewed as a molecular programming language that, together with protein-based execution platforms, can be used to rewrite wide ranging aspects of cellular function. In this review, we catalogue developments in the use of RNA parts, methods, and associated computational models that have contributed to the programmability of biology. We discuss how RNA part repertoires have been combined to build complex genetic circuits, and review recent applications of RNA-based parts and circuitry. We explore the future potential of RNA engineering and posit that RNA programmability is an important resource for firmly establishing an era of rationally designed synthetic biology.

  2. Functional characterization of calliphorid cell death genes and cellularization gene promoters for controlling gene expression and cell viability in early embryos.

    Science.gov (United States)

    Edman, R M; Linger, R J; Belikoff, E J; Li, F; Sze, S-H; Tarone, A M; Scott, M J

    2015-02-01

    The New World screwworm fly, Cochliomyia hominivorax, and the Australian sheep blow fly, Lucilia cuprina, are major pests of livestock. The sterile insect technique was used to eradicate C. hominivorax from North and Central America. This involved area-wide releases of male and female flies that had been sterilized by radiation. Genetic systems have been developed for making 'male-only' strains that would improve the efficiency of genetic control of insect pests. One system involves induction of female lethality in embryos through activation of a pro-apoptotic gene by the tetracycline-dependent transactivator. Sex-specific expression is achieved using an intron from the transformer gene, which we previously isolated from several calliphorids. In the present study, we report the isolation of the promoters from the C. hominivorax slam and Lucilia sericata bnk cellularization genes and show that these promoters can drive expression of a GFP reporter gene in early embryos of transgenic L. cuprina. Additionally, we report the isolation of the L. sericata pro-apoptotic hid and rpr genes, identify conserved motifs in the encoded proteins and determine the relative expression of these genes at different stages of development. We show that widespread expression of the L. sericata pro-apoptotic genes was lethal in Drosophila melanogaster. The isolated gene promoters and pro-apoptotic genes could potentially be used to build transgenic embryonic sexing strains of calliphorid livestock pests.

  3. Multistructural biomimetic substrates for controlled cellular differentiation

    Science.gov (United States)

    Orza, Anamaria I.; Mihu, Carmen; Soritau, Olga; Diudea, Mircea; Florea, Adrian; Matei, Horea; Balici, Stefana; Mudalige, Thilak; Kanarpardy, Ganesh K.; Biris, Alexandru S.

    2014-02-01

    Multidimensional scaffolds are considered to be ideal candidates for regenerative medicine and tissue engineering based on their potential to provide an excellent microenvironment and direct the fate of the cultured cells. More recently, the use of stem cells in medicine has opened a new technological opportunity for controlled tissue formation. However, the mechanism through which the substrate directs the differentiation of stem cells is still rather unclear. Data concerning its specific surface chemistry, topology, and its signaling ability need to be further understood and analyzed. In our study, atomic force microscopy was used to study the stiffness, roughness, and topology of the collagen (Coll) and metallized collagen (MC) substrates, proposed as an excellent substrate for regenerative medicine. The importance of signaling molecules was studied by constructing a new hybrid signaling substrate that contains both collagen and laminin extracellular matrix (ECM) proteins. The cellular response—such as attachment capability, proliferation and cardiac and neuronal phenotype expression on the metallized and non-metallized hybrid substrates (collagen + laminin)—was studied using MTT viability assay and immunohistochemistry studies. Our findings indicate that such hybrid materials could play an important role in the regeneration of complex tissues.

  4. Controlled cellular energy conversion in brown adipose tissue thermogenesis

    Science.gov (United States)

    Horowitz, J. M.; Plant, R. E.

    1978-01-01

    Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.

  5. Cellular Functions Regulated by Phosphorylation of EGFR on Tyr845

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    Ken-ichi Sato

    2013-05-01

    Full Text Available The Src gene product (Src and the epidermal growth factor receptor (EGFR are prototypes of oncogene products and function primarily as a cytoplasmic non-receptor tyrosine kinase and a transmembrane receptor tyrosine kinase, respectively. The identification of Src and EGFR, and the subsequent extensive investigations of these proteins have long provided cutting edge research in cancer and other molecular and cellular biological studies. In 1995, we reported that the human epidermoid carcinoma cells, A431, contain a small fraction of Src and EGFR in which these two kinase were in physical association with each other, and that Src phosphorylates EGFR on tyrosine 845 (Y845 in the Src-EGFR complex. Y845 of EGFR is located in the activation segment of the kinase domain, where many protein kinases contain kinase-activating autophosphorylation sites (e.g., cAMP-dependent protein kinase, Src family kinases, transmembrane receptor type tyrosine kinases or trans-phosphorylation sites (e.g., cyclin-dependent protein kinase, mitogen-activated protein kinase, Akt protein kinase. A number of studies have demonstrated that Y845 phosphorylation serves an important role in cancer as well as normal cells. Here we compile the experimental facts involving Src phosphorylation of EGFR on Y845, by which cell proliferation, cell cycle control, mitochondrial regulation of cell metabolism, gamete activation and other cellular functions are regulated. We also discuss the physiological relevance, as well as structural insights of the Y845 phosphorylation.

  6. Modeling and simulation for train control system using cellular automata

    Institute of Scientific and Technical Information of China (English)

    LI; KePing; GAO; ZiYou; YANG; LiXing

    2007-01-01

    Train control system plays a key role in railway traffic. Its function is to manage and control the train movement on railway networks. In our previous works, based on the cellular automata (CA) model, we proposed several models and algorithms for simulating the train movement under different control system conditions. However, these models are only suitable for some simple traffic conditions. Some basic factors, which are important for train movement, are not considered. In this paper, we extend these models and algorithms and give a unified formula. Using the proposed method, we analyze and discuss the space-time diagram of railway traffic flow and the trajectories of the train movement. The numerical simulation and analytical results demonstrate that the unified CA model is an effective tool for simulating the train control system.

  7. Cellular Mechanisms of Ciliary Length Control

    Directory of Open Access Journals (Sweden)

    Jacob Keeling

    2016-01-01

    Full Text Available Cilia and flagella are evolutionarily conserved, membrane-bound, microtubule-based organelles on the surface of most eukaryotic cells. They play important roles in coordinating a variety of signaling pathways during growth, development, cell mobility, and tissue homeostasis. Defects in ciliary structure or function are associated with multiple human disorders called ciliopathies. These diseases affect diverse tissues, including, but not limited to the eyes, kidneys, brain, and lungs. Many processes must be coordinated simultaneously in order to initiate ciliogenesis. These include cell cycle, vesicular trafficking, and axonemal extension. Centrioles play a central role in both cell cycle progression and ciliogenesis, making the transition between basal bodies and mitotic spindle organizers integral to both processes. The maturation of centrioles involves a functional shift from cell division toward cilium nucleation which takes place concurrently with its migration and fusion to the plasma membrane. Several proteinaceous structures of the distal appendages in mother centrioles are required for this docking process. Ciliary assembly and maintenance requires a precise balance between two indispensable processes; so called assembly and disassembly. The interplay between them determines the length of the resulting cilia. These processes require a highly conserved transport system to provide the necessary substances at the tips of the cilia and to recycle ciliary turnover products to the base using a based microtubule intraflagellar transport (IFT system. In this review; we discuss the stages of ciliogenesis as well as mechanisms controlling the lengths of assembled cilia.

  8. Power Control in Multi-Layer Cellular Networks

    CERN Document Server

    Davaslioglu, Kemal

    2012-01-01

    We investigate the possible performance gains of power control in multi-layer cellular systems where microcells and picocells are distributed within macrocells. Although multilayers in cellular networks help increase system capacity and coverage, and can reduce total energy consumption; they cause interference, reducing the performance of the network. Therefore, downlink transmit power levels of multi-layer hierarchical cellular networks need to be controlled in order to fully exploit their benefits. In this work, we present an analytical derivation to determine optimum power levels for two-layer cellular networks and generalize our solution to multi-layer cellular networks. We also simulate our results in a typical multi-layer network setup and observe significant power savings compared to single-layer cellular networks.

  9. To Be or Not to Be: Controlling Cellular Suicide | Center for Cancer Research

    Science.gov (United States)

    When a cell is damaged and can no longer function properly, a complex series of molecular steps is triggered that allows it to die in a controlled manner. This cellular suicide is called programmed cell death, or apoptosis.

  10. Cellular regulation of the structure and function of aortic valves

    Directory of Open Access Journals (Sweden)

    Ismail El-Hamamsy

    2010-01-01

    Full Text Available The aortic valve was long considered a passive structure that opens and closes in response to changes in transvalvular pressure. Recent evidence suggests that the aortic valve performs highly sophisticated functions as a result of its unique microscopic structure. These functions allow it to adapt to its hemodynamic and mechanical environment. Understanding the cellular and molecular mechanisms involved in normal valve physiology is essential to elucidate the mechanisms behind valve disease. We here review the structure and developmental biology of aortic valves; we examine the role of its cellular parts in regulating its function and describe potential pathophysiological and clinical implications.

  11. Steganography by using Logistic Map Function and Cellular Automata

    Directory of Open Access Journals (Sweden)

    Mehdi Alirezanejad

    2012-12-01

    Full Text Available A tradeoff between the hiding capacity of a cover image and the quality of a stego-image in steganographic schemes is inevitable. In this study a hybrid model of cellular automata and chaotic function is proposed for steganography. In this method, N-bits mask is used for choosing a pixel position in main image which is suitable for hiding one bit of secret data. This mask is generated in each stage by cellular automat and logistic map function. Using cellular automata and logistic map function cause more security and safety in proposed method. Studying the obtained results of the performed experiments, high resistance of the proposed method against brute-force and statistical invasions is obviously illustrated.

  12. Controlling Cellular Endocytosis at the Nanoscale

    Science.gov (United States)

    Battaglia, Giuseppe

    2011-03-01

    One of the most challenging aspects of drug delivery is the intra-cellular delivery of active agents. Several drugs and especially nucleic acids all need to be delivered within the cell interior to exert their therapeutic action. Small hydrophobic molecules can permeate cell membranes with relative ease, but hydrophilic molecules and especially large macromolecules such as proteins and nucleic acids require a vector to assist their transport across the cell membrane. This must be designed so as to ensure intracellular delivery without compromising cell viability. We have recently achieved this by using pH-sensitive poly(2-(methacryloyloxy)ethyl-phosphorylcholine)- co -poly(2-(diisopropylamino)ethyl methacrylate) (PMPC-PDPA) and poly(ethylene oxide)-co- poly(2-(diisopropylamino)ethyl methacrylate) (PEO-PDPA) diblock copolymers that self-assemble to form vesicles in aqueous solution. These vesicles combine a non-fouling PMPC or PEO block with a pH-sensitive PDPA block and have the ability to encapsulate both hydrophobic molecules within the vesicular membrane and hydrophilic molecules within their aqueous cores. The pH sensitive nature of the PDPA blocks make the diblock copolymers forming stable vesicles at physiological pH but that rapid dissociation of these vesicles occurs between pH 5 and pH 6 to form molecularly dissolved copolymer chains (unimers). We used these vesicles to encapsulate small and large macromolecules and these were successfully delivered intracellularly including nucleic acid, drugs, quantum dots, and antibodies. Dynamic light scattering, zeta potential measurements, and transmission electron microscopy were used to study and optimise the encapsulation processes. Confocal laser scanning microscopy, fluorescence flow cytometry and lysates analysis were used to quantify cellular uptake and to study the kinetics of this process in vitro and in vivo. We show the effective cytosolic delivery of nucleic acids, proteins, hydrophobic molecules

  13. DNA origami: Nanorobots grab cellular control

    Science.gov (United States)

    Elbaz, Johann; Willner, Itamar

    2012-04-01

    Self-assembled barrel-like DNA nanostructures carrying active payloads and pre-programmed with logic operations to reconfigure in response to cell-surface cues can trigger a variety of intracellular functions.

  14. Design of a bistable switch to control cellular uptake.

    Science.gov (United States)

    Oyarzún, Diego A; Chaves, Madalena

    2015-12-06

    Bistable switches are widely used in synthetic biology to trigger cellular functions in response to environmental signals. All bistable switches developed so far, however, control the expression of target genes without access to other layers of the cellular machinery. Here, we propose a bistable switch to control the rate at which cells take up a metabolite from the environment. An uptake switch provides a new interface to command metabolic activity from the extracellular space and has great potential as a building block in more complex circuits that coordinate pathway activity across cell cultures, allocate metabolic tasks among different strains or require cell-to-cell communication with metabolic signals. Inspired by uptake systems found in nature, we propose to couple metabolite import and utilization with a genetic circuit under feedback regulation. Using mathematical models and analysis, we determined the circuit architectures that produce bistability and obtained their design space for bistability in terms of experimentally tuneable parameters. We found an activation-repression architecture to be the most robust switch because it displays bistability for the largest range of design parameters and requires little fine-tuning of the promoters' response curves. Our analytic results are based on on-off approximations of promoter activity and are in excellent qualitative agreement with simulations of more realistic models. With further analysis and simulation, we established conditions to maximize the parameter design space and to produce bimodal phenotypes via hysteresis and cell-to-cell variability. Our results highlight how mathematical analysis can drive the discovery of new circuits for synthetic biology, as the proposed circuit has all the hallmarks of a toggle switch and stands as a promising design to control metabolic phenotypes across cell cultures. © 2015 The Author(s).

  15. Regulation of mammalian microRNA processing and function by cellular signaling and subcellular localization

    OpenAIRE

    2008-01-01

    For many microRNAs, in many normal tissues and in cancer cells, the cellular levels of mature microRNAs are not simply determined by transcription of microRNA genes. This mini-review will discuss how microRNA biogenesis and function can be regulated by various nuclear and cytoplasmic processing events, including emerging evidence that microRNA pathway components can be selectively regulated by control of their subcellular localization and by modifications that occur during dynamic cellular si...

  16. Kinetic Adaptations of Myosins for Their Diverse Cellular Functions.

    Science.gov (United States)

    Heissler, Sarah M; Sellers, James R

    2016-08-01

    Members of the myosin superfamily are involved in all aspects of eukaryotic life. Their function ranges from the transport of organelles and cargos to the generation of membrane tension, and the contraction of muscle. The diversity of physiological functions is remarkable, given that all enzymatically active myosins follow a conserved mechanoenzymatic cycle in which the hydrolysis of ATP to ADP and inorganic phosphate is coupled to either actin-based transport or tethering of actin to defined cellular compartments. Kinetic capacities and limitations of a myosin are determined by the extent to which actin can accelerate the hydrolysis of ATP and the release of the hydrolysis products and are indispensably linked to its physiological tasks. This review focuses on kinetic competencies that - together with structural adaptations - result in myosins with unique mechanoenzymatic properties targeted to their diverse cellular functions.

  17. Methods for Determining the Cellular Functions of Vimentin Intermediate Filaments.

    Science.gov (United States)

    Ridge, Karen M; Shumaker, Dale; Robert, Amélie; Hookway, Caroline; Gelfand, Vladimir I; Janmey, Paul A; Lowery, Jason; Guo, Ming; Weitz, David A; Kuczmarski, Edward; Goldman, Robert D

    2016-01-01

    The type III intermediate filament protein vimentin was once thought to function mainly as a static structural protein in the cytoskeleton of cells of mesenchymal origin. Now, however, vimentin is known to form a dynamic, flexible network that plays an important role in a number of signaling pathways. Here, we describe various methods that have been developed to investigate the cellular functions of the vimentin protein and intermediate filament network, including chemical disruption, photoactivation and photoconversion, biolayer interferometry, soluble bead binding assay, three-dimensional substrate experiments, collagen gel contraction, optical-tweezer active microrheology, and force spectrum microscopy. Using these techniques, the contributions of vimentin to essential cellular processes can be probed in ever further detail.

  18. A Cellular Perspective on Brain Energy Metabolism and Functional Imaging

    KAUST Repository

    Magistretti, Pierre J.

    2015-05-01

    The energy demands of the brain are high: they account for at least 20% of the body\\'s energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and pointat a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales. © 2015 Elsevier Inc.

  19. Representing and analysing molecular and cellular function using the computer.

    Science.gov (United States)

    van Helden, J; Naim, A; Mancuso, R; Eldridge, M; Wernisch, L; Gilbert, D; Wodak, S J

    2000-01-01

    Determining the biological function of a myriad of genes, and understanding how they interact to yield a living cell, is the major challenge of the post genome-sequencing era. The complexity of biological systems is such that this cannot be envisaged without the help of powerful computer systems capable of representing and analysing the intricate networks of physical and functional interactions between the different cellular components. In this review we try to provide the reader with an appreciation of where we stand in this regard. We discuss some of the inherent problems in describing the different facets of biological function, give an overview of how information on function is currently represented in the major biological databases, and describe different systems for organising and categorising the functions of gene products. In a second part, we present a new general data model, currently under development, which describes information on molecular function and cellular processes in a rigorous manner. The model is capable of representing a large variety of biochemical processes, including metabolic pathways, regulation of gene expression and signal transduction. It also incorporates taxonomies for categorising molecular entities, interactions and processes, and it offers means of viewing the information at different levels of resolution, and dealing with incomplete knowledge. The data model has been implemented in the database on protein function and cellular processes 'aMAZE' (http://www.ebi.ac.uk/research/pfbp/), which presently covers metabolic pathways and their regulation. Several tools for querying, displaying, and performing analyses on such pathways are briefly described in order to illustrate the practical applications enabled by the model.

  20. The phosphate makes a difference: cellular functions of NADP.

    Science.gov (United States)

    Agledal, Line; Niere, Marc; Ziegler, Mathias

    2010-01-01

    Recent research has unraveled a number of unexpected functions of the pyridine nucleotides. In this review, we will highlight the variety of known physiological roles of NADP. In its reduced form (NADPH), this molecule represents a universal electron donor, not only to drive biosynthetic pathways. Perhaps even more importantly, NADPH is the unique provider of reducing equivalents to maintain or regenerate the cellular detoxifying and antioxidative defense systems. The roles of NADPH in redox sensing and as substrate for NADPH oxidases to generate reactive oxygen species further extend its scope of functions. NADP(+), on the other hand, has acquired signaling functions. Its conversion to second messengers in calcium signaling may have critical impact on important cellular processes. The generation of NADP by NAD kinases is a key determinant of the cellular NADP concentration. The regulation of these enzymes may, therefore, be critical to feed the diversity of NADP-dependent processes adequately. The increasing recognition of the multiple roles of NADP has thus led to exciting new insights in this expanding field.

  1. Membrane-Based Functions in the Origin of Cellular Life

    Science.gov (United States)

    Chipot, Christophe; New, Michael H.; Schweighofer, Karl; Pohorille, Andrew; Wilson, Michael A.

    1999-01-01

    Our objective is to help explain how the earliest ancestors of contemporary cells (protocells) performed their essential functions employing only the molecules available in the protobiological milieu. Our hypothesis is that vesicles, built of amphiphilic, membrane-forming materials, emerged early in protobiological evolution and served as precursors to protocells. We further assume that the cellular functions associated with contemporary membranes, such as capturing and, transducing of energy, signaling, or sequestering organic molecules and ions, evolved in these membrane environments. An alternative hypothesis is that these functions evolved in different environments and were incorporated into membrane-bound structures at some later stage of evolution. We focus on the application of the fundamental principles of physics and chemistry to determine how they apply to the formation of a primitive, functional cell. Rather than attempting to develop specific models for cellular functions and to identify the origin of the molecules which perform these functions, our goal is to define the structural and energetic conditions that any successful model must fulfill, therefore providing physico-chemical boundaries for these models. We do this by carrying out large-scale, molecular level computer simulations on systems of interest.

  2. Functional and cellular adaptations of rodent skeletal muscle to weightlessness

    Science.gov (United States)

    Caiozzo, Vincent J.; Haddad, Fadia; Baker, Michael J.; Baldwin, Kenneth M.

    1995-01-01

    This paper describes the affects of microgravity upon three key cellular levels (functional, protein, and mRNA) that are linked to one another. It is clear that at each of these levels, microgravity produces rapid and substantial alterations. One of the key challenges facing the life science community is the development of effective countermeasures that prevent the loss of muscle function as described in this paper. The development of optimal countermeasures, however, awaits a clearer understanding of events occurring at the levels of transcription, translation, and degradation.

  3. Simulation of Power Control and Diversity of Cellular CDMA

    Institute of Scientific and Technical Information of China (English)

    RomanPichna; QiangWang; 等

    1995-01-01

    This paper presents a software package developed by the authors for the simulation of a cellular code division multiple access(CDMA)system.In the simulated system,a number of fac-tors are taken into account including time-correlated fading and shadowing,delays in power control and diversity ,errors in power control commands,soft hand-off,base station diversity,and pilots and diversity transmissions,contributions to the interference.

  4. Cellular and Humoral Mechanisms Involved in the Control of Tuberculosis

    Directory of Open Access Journals (Sweden)

    Joaquin Zuñiga

    2012-01-01

    Full Text Available Mycobacterium tuberculosis (Mtb infection is a major international public health problem. One-third of the world's population is thought to have latent tuberculosis, a condition where individuals are infected by the intracellular bacteria without active disease but are at risk for reactivation, if their immune system fails. Here, we discuss the role of nonspecific inflammatory responses mediated by cytokines and chemokines induced by interaction of innate receptors expressed in macrophages and dendritic cells (DCs. We also review current information regarding the importance of several cytokines including IL-17/IL-23 in the development of protective cellular and antibody-mediated protective responses against Mtb and their influence in containment of the infection. Finally, in this paper, emphasis is placed on the mechanisms of failure of Mtb control, including the immune dysregulation induced by the treatment with biological drugs in different autoimmune diseases. Further functional studies, focused on the mechanisms involved in the early host-Mtb interactions and the interplay between host innate and acquired immunity against Mtb, may be helpful to improve the understanding of protective responses in the lung and in the development of novel therapeutic and prophylactic tools in TB.

  5. Contrast agents for functional and cellular MRI of the kidney

    Energy Technology Data Exchange (ETDEWEB)

    Grenier, Nicolas [ERT CNRS ' Imagerie Moleculaire et Fonctionnelle' , Universite Victor Segalen-Bordeaux 2, Bordeaux (France) and Service d' Imagerie Diagnostique et Interventionnelle de l' Adulte, Groupe Hospitalier Pellegrin, Place Amelie Raba-Leon, 33076 Bordeaux Cedex (France)]. E-mail: nicolas.grenier@chu-bordeaux.fr; Pedersen, Michael [MR Research Center, Aarhus University Hospital, Aarhus (Denmark); Hauger, Olivier [ERT CNRS ' Imagerie Moleculaire et Fonctionnelle' , Universite Victor Segalen-Bordeaux 2, Bordeaux (France); Service d' Imagerie Diagnostique et Interventionnelle de l' Adulte, Groupe Hospitalier Pellegrin, Place Amelie Raba-Leon, 33076 Bordeaux Cedex (France)

    2006-12-15

    Low-molecular-weight gadolinium (Gd) chelates are glomerular tracers but their role in evaluation of renal function with magnetic resonance (MR) imaging is still marginal. Because of their small size, they diffuse freely into the interstitium and the relationship between measured signal intensity and concentration is complex. New categories of contrast agents, such as large Gd-chelates or iron oxide particules, with different pharmacokinetic and magnetic properties have been developed. These large molecules could be useful for both functional (quantification of perfusion, quantification of glomerular filtration rate, estimation of tubular function) and cellular imaging (intrarenal phagocytosis in inflammatory renal diseases). Continuous development of new contrast agents remains worthwhile to get the best adequacy between the physiological phenomenon of interest and the pharmacokinetic of the agent.

  6. Fluxomics links cellular functional analyses to whole-plant phenotyping.

    Science.gov (United States)

    Salon, Christophe; Avice, Jean-Christophe; Colombié, Sophie; Dieuaide-Noubhani, Martine; Gallardo, Karine; Jeudy, Christian; Ourry, Alain; Prudent, Marion; Voisin, Anne-Sophie; Rolin, Dominique

    2017-04-01

    Fluxes through metabolic pathways reflect the integration of genetic and metabolic regulations. While it is attractive to measure all the mRNAs (transcriptome), all the proteins (proteome), and a large number of the metabolites (metabolome) in a given cellular system, linking and integrating this information remains difficult. Measurement of metabolome-wide fluxes (termed the fluxome) provides an integrated functional output of the cell machinery and a better tool to link functional analyses to plant phenotyping. This review presents and discusses sets of methodologies that have been developed to measure the fluxome. First, the principles of metabolic flux analysis (MFA), its 'short time interval' version Inst-MFA, and of constraints-based methods, such as flux balance analysis and kinetic analysis, are briefly described. The use of these powerful methods for flux characterization at the cellular scale up to the organ (fruits, seeds) and whole-plant level is illustrated. The added value given by fluxomics methods for unravelling how the abiotic environment affects flux, the process, and key metabolic steps are also described. Challenges associated with the development of fluxomics and its integration with 'omics' for thorough plant and organ functional phenotyping are discussed. Taken together, these will ultimately provide crucial clues for identifying appropriate target plant phenotypes for breeding. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. Intravital FRET: Probing Cellular and Tissue Function in Vivo

    Directory of Open Access Journals (Sweden)

    Helena Radbruch

    2015-05-01

    Full Text Available The development of intravital Förster Resonance Energy Transfer (FRET is required to probe cellular and tissue function in the natural context: the living organism. Only in this way can biomedicine truly comprehend pathogenesis and develop effective therapeutic strategies. Here we demonstrate and discuss the advantages and pitfalls of two strategies to quantify FRET in vivo—ratiometrically and time-resolved by fluorescence lifetime imaging—and show their concrete application in the context of neuroinflammation in adult mice.

  8. Controlled inflation of voids in cellular polymer ferroelectrets: Optimizing electromechanical transducer properties

    Science.gov (United States)

    Wegener, M.; Wirges, W.; Gerhard-Multhaupt, R.; Dansachmüller, M.; Schwödiauer, R.; Bauer-Gogonea, S.; Bauer, S.; Paajanen, M.; Minkkinen, H.; Raukola, J.

    2004-01-01

    When exposed to sufficiently high electric fields, polymer-foam electret materials with closed cells exhibit ferroelectric-like behavior and may therefore be called ferroelectrets. In cellular ferroelectrets, the influence of the cell size and shape distributions on the application-relevant properties is not yet understood. Therefore, controlled inflation experiments were carried out on cellular polypropylene films, and the resulting elastical and electromechanical parameters were determined. The elastic modulus in the thickness direction shows a minimum with a corresponding maximum in the electromechanical transducer coefficient. The resonance frequency shifts as a function of the elastic modulus and the relative density of the inflated cellular films. Therefore, the transducer properties of cellular ferroelectrets can be optimized by means of controlled inflation.

  9. Optimum Transmitter Power Control in WCDMA Cellular Systems

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Power control is an important technique in WCDMA mobile systems for both increasing system capacity and guaranteeing the required QoS (time delay and wireless link transmission quality) of multimedia services. The optimum power control for narrow band CDMA cellular systems is a problem of single threshold optimization. Because these systems have only one type of traffic and have the same QoS requirement. However, WCDMA mobile systems should provide multimedia services and different types of traffic have different QoS requirements. Thus, the power control in WCDMA mobile systems doesn't be a problem of single threshold optimizing, but turns into the optimizing problem of multi-thresholds. In this paper, we analyze the power control problem in WCDMA cellular mobile systems and propose the optimum transmitter power control algorithm. Three criteria to optimize transmitter power levels of multi-thresholds based on grading the priority orders of multimedia services are proposed. Simulation results show that the proposed algorithms are more effective than conventional algorithms and can provide better performance for WCDMA cellular mobile systems.

  10. Control functions in MFM

    DEFF Research Database (Denmark)

    Lind, Morten

    2011-01-01

    Multilevel Flow Modeling (MFM) has been proposed as a tool for representing goals and functions of complex industrial plants and suggested as a basis for reasoning about control situations. Lind presents an introduction to MFM but do not describe how control functions are used in the modeling....... The purpose of the present paper is to serve as a companion paper to this introduction by explaining the basic principles used in MFM for representation of control functions. A theoretical foundation for modeling control functions is presented and modeling examples are given for illustration....

  11. Eukaryotic protein domains as functional units of cellular evolution

    DEFF Research Database (Denmark)

    Jin, Jing; Xie, Xueying; Chen, Chen

    2009-01-01

    Modular protein domains are functional units that can be modified through the acquisition of new intrinsic activities or by the formation of novel domain combinations, thereby contributing to the evolution of proteins with new biological properties. Here, we assign proteins to groups with related...... biological processes. Evolutionary jumps are associated with a domain that coordinately acquires a new intrinsic function and enters new domain clubs, thereby providing the modified domain with access to a new cellular microenvironment. We also coordinately analyzed the covalent and noncovalent interactions...... that domains, and the proteins in which they reside, are selected during evolution through reciprocal interactions with protein domains in their local microenvironment. Based on this scheme, we propose a mechanism by which Tudor domains may have evolved to support different modes of epigenetic regulation...

  12. Fabrication of Biocompatible, Vibrational Magnetoelastic Materials for Controlling Cellular Adhesion

    Directory of Open Access Journals (Sweden)

    Rupak M. Rajachar

    2012-02-01

    Full Text Available This paper describes the functionalization of magnetoelastic (ME materials with Parylene-C coating to improve the surface reactivity to cellular response. Previous study has demonstrated that vibrating ME materials were capable of modulating cellular adhesion when activated by an externally applied AC magnetic field. However, since ME materials are not inherently biocompatible, surface modifications are needed for their implementation in biological settings. Here, the long-term stability of the ME material in an aqueous and biological environment is achieved by chemical-vapor deposition of a conformal Parylene-C layer, and further functionalized by methods of oxygen plasma etching and protein adsorption. In vitro cytotoxicity measurement and characterization of the vibrational behavior of the ME materials showed that Parylene-C coatings of 10 µm or greater could prevent hydrolytic degradation without sacrificing the vibrational behavior of the ME material. This work allows for long-term durability and functionality of ME materials in an aqueous and biological environment and makes the potential use of this technology in monitoring and modulating cellular behavior at the surface of implantable devices feasible.

  13. Control of Cellular Structural Networks Through Unstructured Protein Domains

    Science.gov (United States)

    2016-07-01

    structural and mechanical networks in cells. The research plan seeks to determine the role of molecular­scale steric forces on the assembly, mechanics...Distribution Unlimited UU UU UU UU 01-07-2016 1-Oct-2009 30-Sep-2015 Final Report: WHITEPAPER; Research Area 8; Control of cellular structural networks ...any other aspect of this collection of information, including suggesstions for reducing this burden, to Washington Headquarters Services , Directorate

  14. A self-learning call admission control scheme for CDMA cellular networks.

    Science.gov (United States)

    Liu, Derong; Zhang, Yi; Zhang, Huaguang

    2005-09-01

    In the present paper, a call admission control scheme that can learn from the network environment and user behavior is developed for code division multiple access (CDMA) cellular networks that handle both voice and data services. The idea is built upon a novel learning control architecture with only a single module instead of two or three modules in adaptive critic designs (ACDs). The use of adaptive critic approach for call admission control in wireless cellular networks is new. The call admission controller can perform learning in real-time as well as in offline environments and the controller improves its performance as it gains more experience. Another important contribution in the present work is the choice of utility function for the present self-learning control approach which makes the present learning process much more efficient than existing learning control methods. The performance of our algorithm will be shown through computer simulation and compared with existing algorithms.

  15. Linear matrix inequality approach for synchronization control of fuzzy cellular neural networks with mixed time delays

    Institute of Scientific and Technical Information of China (English)

    P. Balasubramaniam; M. Kalpana; R. Rakkiyappan

    2012-01-01

    Fuzzy cellular neural networks (FCNNs) are special kinds of cellular neural networks (CNNs).Each cell in an FCNN contains fuzzy operating abilities.The entire network is governed by cellular computing laws.The design of FCNNs is based on fuzzy local rules.In this paper,a linear matrix inequality (LMI) approach for synchronization control of FCNNs with mixed delays is investigated.Mixed delays include discrete time-varying delays and unbounded distributed delays.A dynamic control scheme is proposed to achieve the synchronization between a drive network and a response network.By constructing the Lyapunov-Krasovskii functional which contains a triple-integral term and the free-weighting matrices method an improved delay-dependent stability criterion is derived in terms of LMIs.The controller can be easily obtained by solving the derived LMIs.A numerical example and its simulations are presented to illustrate the effectiveness of the proposed method.

  16. Rejuvenating cellular respiration for optimizing respiratory function: targeting mitochondria.

    Science.gov (United States)

    Agrawal, Anurag; Mabalirajan, Ulaganathan

    2016-01-15

    Altered bioenergetics with increased mitochondrial reactive oxygen species production and degradation of epithelial function are key aspects of pathogenesis in asthma and chronic obstructive pulmonary disease (COPD). This motif is not unique to obstructive airway disease, reported in related airway diseases such as bronchopulmonary dysplasia and parenchymal diseases such as pulmonary fibrosis. Similarly, mitochondrial dysfunction in vascular endothelium or skeletal muscles contributes to the development of pulmonary hypertension and systemic manifestations of lung disease. In experimental models of COPD or asthma, the use of mitochondria-targeted antioxidants, such as MitoQ, has substantially improved mitochondrial health and restored respiratory function. Modulation of noncoding RNA or protein regulators of mitochondrial biogenesis, dynamics, or degradation has been found to be effective in models of fibrosis, emphysema, asthma, and pulmonary hypertension. Transfer of healthy mitochondria to epithelial cells has been associated with remarkable therapeutic efficacy in models of acute lung injury and asthma. Together, these form a 3R model--repair, reprogramming, and replacement--for mitochondria-targeted therapies in lung disease. This review highlights the key role of mitochondrial function in lung health and disease, with a focus on asthma and COPD, and provides an overview of mitochondria-targeted strategies for rejuvenating cellular respiration and optimizing respiratory function in lung diseases. Copyright © 2016 the American Physiological Society.

  17. Photothermal cellular stimulation in functional bio-polymer interfaces

    Science.gov (United States)

    Martino, Nicola; Feyen, Paul; Porro, Matteo; Bossio, Caterina; Zucchetti, Elena; Ghezzi, Diego; Benfenati, Fabio; Lanzani, Guglielmo; Antognazza, Maria Rosa

    2015-03-01

    Hybrid interfaces between organic semiconductors and living tissues represent a new tool for in-vitro and in-vivo applications, bearing a huge potential, from basic researches to clinical applications. In particular, light sensitive conjugated polymers can be exploited as a new approach for optical modulation of cellular activity. In this work we focus on light-induced changes in the membrane potential of Human Embryonic Kidney (HEK-293) cells grown on top of a poly(3-hexylthiophene) (P3HT) thin film. On top of a capacitive charging of the polymer interface, we identify and fully characterize two concomitant mechanisms, leading to membrane depolarization and hyperpolarisation, both mediated by a thermal effect. Our results can be usefully exploited in the creation of a new platform for light-controlled cell manipulation, with possible applications in neuroscience and medicine.

  18. Persistent cellular motion control and trapping using mechanotactic signaling.

    Directory of Open Access Journals (Sweden)

    Xiaoying Zhu

    Full Text Available Chemotactic signaling and the associated directed cell migration have been extensively studied owing to their importance in emergent processes of cellular aggregation. In contrast, mechanotactic signaling has been relatively overlooked despite its potential for unique ways to artificially signal cells with the aim to effectively gain control over their motile behavior. The possibility of mimicking cellular mechanotactic signals offers a fascinating novel strategy to achieve targeted cell delivery for in vitro tissue growth if proven to be effective with mammalian cells. Using (i optimal level of extracellular calcium ([Ca(2+]ext = 3 mM we found, (ii controllable fluid shear stress of low magnitude (σ < 0.5 Pa, and (iii the ability to swiftly reverse flow direction (within one second, we are able to successfully signal Dictyostelium discoideum amoebae and trigger migratory responses with heretofore unreported control and precision. Specifically, we are able to systematically determine the mechanical input signal required to achieve any predetermined sequences of steps including straightforward motion, reversal and trapping. The mechanotactic cellular trapping is achieved for the first time and is associated with a stalling frequency of 0.06 ~ 0.1 Hz for a reversing direction mechanostimulus, above which the cells are effectively trapped while maintaining a high level of directional sensing. The value of this frequency is very close to the stalling frequency recently reported for chemotactic cell trapping [Meier B, et al. (2011 Proc Natl Acad Sci USA 108:11417-11422], suggesting that the limiting factor may be the slowness of the internal chemically-based motility apparatus.

  19. Controllability of time-varying cellular neural networks

    Directory of Open Access Journals (Sweden)

    Wadie Aziz

    2005-11-01

    Full Text Available In this work, we consider the model of Cellular Neural Network (CNN introduced by Chua and Yang in 1988, but with the cloning templates $omega$-periodic in time. By imposing periodic boundary conditions the matrices involved in the system become circulant and $omega$-periodic. We show some results on the controllability of the linear model using a Theorem by Brunovsky for the case of linear and $omega$-periodic system. Also we use this approach in image detection, specifically foreground, background and contours of figures in different scales of grey.

  20. Membrane-Based Functions in the Origin of Cellular Life

    Science.gov (United States)

    Wilson, Michael A.

    2003-01-01

    How simple membrane peptides performed such essential proto-cellular functions as transport of ions and organic matter across membranes separating the interior of the cell from the environment, capture and utilization of energy, and transduction of environmental signals, is a key question in protobiological evolution. On the basis of detailed, molecular-level computer simulations we investigate how these peptides insert into membranes, self-assemble into higher-order structures and acquire functions. We have studied the insertion of an a-helical peptide containing leucine (L) and serine (S) of the form (LSLLLSL)S into a model membrane. The transmembrane state is metastable, and approximately 15 kcal/mol is required to insert the peptide into the membrane. Investigations of dimers formed by (LSLLLSL)S and glycophorin A demonstrate how the favorable free energy of helix association can offset the unfavorable free energy of insertion, leading to self- assembly of peptide helices in the membrane. An example of a self-assembled structure is the tetrameric transmembrane pore of the influenza virus M2 protein, which is an efficient and selective voltage-gated proton channel. Our simulations explain the gating mechanism and provide guidelines how to reengineering the channel to act as a simple proton pump. In general, emergence of integral membrane proteins appears to be quite feasible and may be easier to envision than the emergence of water-soluble proteins.

  1. Purification, Cellular Levels, and Functional Domains of LMF1

    Science.gov (United States)

    Babilonia-Rosa, Melissa; Neher, Saskia B.

    2014-01-01

    Over a third of the US adult population has hypertriglyceridemia, resulting in an increased risk of atherosclerosis, pancreatitis, and metabolic syndrome. Lipoprotein lipase (LPL)1, a dimeric enzyme, is the main lipase responsible for TG clearance from the blood after food intake. LPL requires an endoplasmic reticulum (ER)-resident, transmembrane protein known as lipase maturation factor 1 (LMF1) for secretion and enzymatic activity. LMF1 is believed to act as a client specific chaperone for dimeric lipases, but the precise mechanism by which LMF1 functions is not understood. Here, we examine which domains of LMF1 contribute to dimeric lipase maturation by assessing the function of truncation variants. N-terminal truncations of LMF1 show that all the domains are necessary for LPL maturation. Fluorescence microscopy and protease protection assays confirmed that these variants were properly oriented in the ER. We measured cellular levels of LMF1 and found that it is expressed at low levels and each molecule of LMF1 promotes the maturation of 50 or more molecules of LPL. Thus we provide evidence for the critical role of the N-terminus of LMF1 for the maturation of LPL and relevant ratio of chaperone to substrate. PMID:24909692

  2. A structural and functional homolog supports a general role for frataxin in cellular iron chemistry.

    Science.gov (United States)

    Qi, Wenbin; Cowan, J A

    2010-02-07

    Bacillus subtilis YdhG lacks sequence homology, but demonstrates structural and functional similarity to the frataxin family, supporting a general cellular role for frataxin-type proteins in cellular iron homeostasis.

  3. Energy-efficient power control for OFDMA cellular networks

    KAUST Repository

    Sboui, Lokman

    2016-12-24

    In this paper, we study the energy efficiency (EE) of orthogonal frequency-division multiple access (OFDMA) cellular networks. Our objective is to present a power allocation scheme that maximizes the EE of downlink communications. We propose a novel explicit expression of the optimal power allocation to each subcarrier. We also present the power control when the transmit power is limited by power budget constraint or/and minimal rate constraint and we highlight the occurrence of some transmission outage events depending on the constraints\\' parameters. In the numerical results, we show that our proposed power control improves the EE especially at high power budget regime and low minimal rate regime. In addition, we show that having a higher number of subcarriers enhances the OFDMA EE.

  4. Service-Aware Retransmission Control in Cellular Networks

    Directory of Open Access Journals (Sweden)

    Nadhir Ben Halima

    2010-01-01

    Full Text Available This paper proposes a service-aware cross-layer approach between application/transport layers on the mobile terminal and link layer on the wireless base station to enable dynamic control on the level of per-packet error protection for multimedia data streams. Specifically, in the context of cellular networks, the proposed scheme enables the mobile terminal to specify to the base station the desired level of Hybrid ARQ (HARQ protection by using an in-band control feedback channel. Such protection is dynamically adapted on a per-packet basis and depends on the perceptual importance of different packets as well as on the reception history of the flow. Experimental results demonstrate the potential benefits deriving from the proposed strategy either for audio and video real-time streams as well as for TCP-based data transfers.

  5. Insights into the physiological function of cellular prion protein

    Directory of Open Access Journals (Sweden)

    Martins V.R.

    2001-01-01

    Full Text Available Prions have been extensively studied since they represent a new class of infectious agents in which a protein, PrPsc (prion scrapie, appears to be the sole component of the infectious particle. They are responsible for transmissible spongiform encephalopathies, which affect both humans and animals. The mechanism of disease propagation is well understood and involves the interaction of PrPsc with its cellular isoform (PrPc and subsequently abnormal structural conversion of the latter. PrPc is a glycoprotein anchored on the cell surface by a glycosylphosphatidylinositol moiety and expressed in most cell types but mainly in neurons. Prion diseases have been associated with the accumulation of the abnormally folded protein and its neurotoxic effects; however, it is not known if PrPc loss of function is an important component. New efforts are addressing this question and trying to characterize the physiological function of PrPc. At least four different mouse strains in which the PrP gene was ablated were generated and the results regarding their phenotype are controversial. Localization of PrPc on the cell membrane makes it a potential candidate for a ligand uptake, cell adhesion and recognition molecule or a membrane signaling molecule. Recent data have shown a potential role for PrPc in the metabolism of copper and moreover that this metal stimulates PrPc endocytosis. Our group has recently demonstrated that PrPc is a high affinity laminin ligand and that this interaction mediates neuronal cell adhesion and neurite extension and maintenance. Moreover, PrPc-caveolin-1 dependent coupling seems to trigger the tyrosine kinase Fyn activation. These data provide the first evidence for PrPc involvement in signal transduction.

  6. Simultaneous characterization of cellular RNA structure and function with in-cell SHAPE-Seq.

    Science.gov (United States)

    Watters, Kyle E; Abbott, Timothy R; Lucks, Julius B

    2016-01-29

    Many non-coding RNAs form structures that interact with cellular machinery to control gene expression. A central goal of molecular and synthetic biology is to uncover design principles linking RNA structure to function to understand and engineer this relationship. Here we report a simple, high-throughput method called in-cell SHAPE-Seq that combines in-cell probing of RNA structure with a measurement of gene expression to simultaneously characterize RNA structure and function in bacterial cells. We use in-cell SHAPE-Seq to study the structure-function relationship of two RNA mechanisms that regulate translation in Escherichia coli. We find that nucleotides that participate in RNA-RNA interactions are highly accessible when their binding partner is absent and that changes in RNA structure due to RNA-RNA interactions can be quantitatively correlated to changes in gene expression. We also characterize the cellular structures of three endogenously expressed non-coding RNAs: 5S rRNA, RNase P and the btuB riboswitch. Finally, a comparison between in-cell and in vitro folded RNA structures revealed remarkable similarities for synthetic RNAs, but significant differences for RNAs that participate in complex cellular interactions. Thus, in-cell SHAPE-Seq represents an easily approachable tool for biologists and engineers to uncover relationships between sequence, structure and function of RNAs in the cell.

  7. Mnk kinase pathway: Cellular functions and biological outcomes

    Institute of Scientific and Technical Information of China (English)

    Sonali; Joshi; Leonidas; C; Platanias

    2014-01-01

    The mitogen-activated protein kinase(MAPK) interacting protein kinases 1 and 2(Mnk1 and Mnk2) play important roles in controlling signals involved in mRNA translation. In addition to the MAPKs(p38 or Erk), multiple studies suggest that the Mnk kinases can be regulated by other known kinases such as Pak2 and/or other unidentified kinases by phosphorylation of residues distinct from the sites phosphorylated by the MAPKs. Several studies have established multiple Mnk protein targets, including PSF, heterogenous nuclear ribonucleoprotein A1, Sprouty 2 and have lead to the identification of distinct biological functions and substrate specificity for the Mnk kinases. In this review we discuss the pathways regulating the Mnk kinases, their known substrates as well as the functional consequences of engagement of pathways controlled by Mnk kinases. These kinases play an important role in mRNA translation via their regulation of eukaryotic initiation factor 4E(eIF4E) and their functions have important implications in tumor biology as well as the regulation of drug resistance to anti-oncogenic therapies. Other studies have identified a role for the Mnk kinases in cap-independent mRNA translation, suggesting that the Mnk kinases can exert important functional effects independently of the phosphorylation of eIF4 E. The role of Mnk kinases in inflammation and inflammationinduced malignancies is also discussed.

  8. Quantifying the entropic cost of cellular growth control

    Science.gov (United States)

    De Martino, Daniele; Capuani, Fabrizio; De Martino, Andrea

    2017-07-01

    Viewing the ways a living cell can organize its metabolism as the phase space of a physical system, regulation can be seen as the ability to reduce the entropy of that space by selecting specific cellular configurations that are, in some sense, optimal. Here we quantify the amount of regulation required to control a cell's growth rate by a maximum-entropy approach to the space of underlying metabolic phenotypes, where a configuration corresponds to a metabolic flux pattern as described by genome-scale models. We link the mean growth rate achieved by a population of cells to the minimal amount of metabolic regulation needed to achieve it through a phase diagram that highlights how growth suppression can be as costly (in regulatory terms) as growth enhancement. Moreover, we provide an interpretation of the inverse temperature β controlling maximum-entropy distributions based on the underlying growth dynamics. Specifically, we show that the asymptotic value of β for a cell population can be expected to depend on (i) the carrying capacity of the environment, (ii) the initial size of the colony, and (iii) the probability distribution from which the inoculum was sampled. Results obtained for E. coli and human cells are found to be remarkably consistent with empirical evidence.

  9. Cellular functions of gamma-secretase-related proteins.

    Science.gov (United States)

    Haffner, Christof; Haass, Christian

    2006-01-01

    Amyloid-beta peptide (Abeta) is generated by gamma-secretase, a membrane protein complex with an unusual aspartyl protease activity consisting of the four components presenilin, nicastrin, APH-1 and PEN-2. Presenilin is considered the catalytic subunit of this complex since it represents the prototype of the new family of intramembrane-cleaving GxGD-type aspartyl proteases. Recently, five novel members of this family and a nicastrin-like protein were identified. Whereas one of the GxGD-type proteins was shown to be identical with signal peptide peptidase (SPP), the function of the others, now called SPP-like proteins (SPPLs), is not known. We therefore analyzed SPPL2b and SPPL3 and demonstrated that they localize to different subcellular compartments suggesting nonredundant functions. This was supported by different phenotypes obtained in knockdown studies in zebrafish embryos. In addition, these phenotypes could be phenocopied by ectopic expression of putative active site mutants, providing strong evidence for a proteolytic function of SPPL2b and SPPL3. We also identified and characterized the nicastrin-like protein nicalin which, together with the 130-kDa protein NOMO (Nodal modulator), forms a membrane protein complex different from gamma-secretase. We found that during zebrafish embryogenesis this complex is involved in the patterning of the axial mesendoderm, a process controlled by the Nodal signaling pathway.

  10. Prion protein modulates cellular iron uptake: a novel function with implications for prion disease pathogenesis.

    Directory of Open Access Journals (Sweden)

    Ajay Singh

    Full Text Available Converging evidence leaves little doubt that a change in the conformation of prion protein (PrP(C from a mainly alpha-helical to a beta-sheet rich PrP-scrapie (PrP(Sc form is the main event responsible for prion disease associated neurotoxicity. However, neither the mechanism of toxicity by PrP(Sc, nor the normal function of PrP(C is entirely clear. Recent reports suggest that imbalance of iron homeostasis is a common feature of prion infected cells and mouse models, implicating redox-iron in prion disease pathogenesis. In this report, we provide evidence that PrP(C mediates cellular iron uptake and transport, and mutant PrP forms alter cellular iron levels differentially. Using human neuroblastoma cells as models, we demonstrate that over-expression of PrP(C increases intra-cellular iron relative to non-transfected controls as indicated by an increase in total cellular iron, the cellular labile iron pool (LIP, and iron content of ferritin. As a result, the levels of iron uptake proteins transferrin (Tf and transferrin receptor (TfR are decreased, and expression of iron storage protein ferritin is increased. The positive effect of PrP(C on ferritin iron content is enhanced by stimulating PrP(C endocytosis, and reversed by cross-linking PrP(C on the plasma membrane. Expression of mutant PrP forms lacking the octapeptide-repeats, the membrane anchor, or carrying the pathogenic mutation PrP(102L decreases ferritin iron content significantly relative to PrP(C expressing cells, but the effect on cellular LIP and levels of Tf, TfR, and ferritin is complex, varying with the mutation. Neither PrP(C nor the mutant PrP forms influence the rate or amount of iron released into the medium, suggesting a functional role for PrP(C in cellular iron uptake and transport to ferritin, and dysfunction of PrP(C as a significant contributing factor of brain iron imbalance in prion disorders.

  11. Circadian clock-coupled lung cellular and molecular functions in chronic airway diseases.

    Science.gov (United States)

    Sundar, Isaac K; Yao, Hongwei; Sellix, Michael T; Rahman, Irfan

    2015-09-01

    Airway diseases are associated with abnormal circadian rhythms of lung function, reflected in daily changes of airway caliber, airway resistance, respiratory symptoms, and abnormal immune-inflammatory responses. Circadian rhythms are generated at the cellular level by an autoregulatory feedback loop of interlocked transcription factors collectively referred to as clock genes. The molecular clock is altered by cigarette smoke, LPS, and bacterial and viral infections in mouse and human lungs and in patients with chronic airway diseases. Stress-mediated post-translational modification of molecular clock proteins, brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (BMAL1) and PERIOD 2, is associated with a reduction in the activity/level of the deacetylase sirtuin 1 (SIRT1). Similarly, the levels of the nuclear receptor REV-ERBα and retinoic acid receptor-related orphan receptor α (ROR α), critical regulators of Bmal1 expression, are altered by environmental stresses. Molecular clock dysfunction is implicated in immune and inflammatory responses, DNA damage response, and cellular senescence. The molecular clock in the lung also regulates the timing of glucocorticoid sensitivity and phasic responsiveness to inflammation. Herein, we review our current understanding of clock-controlled cellular and molecular functions in the lungs, the impact of clock dysfunction in chronic airway disease, and the response of the pulmonary clock to different environmental perturbations. Furthermore, we discuss the evidence for candidate signaling pathways, such as the SIRT1-BMAL1-REV-ERBα axis, as novel targets for chronopharmacological management of chronic airway diseases.

  12. Molecular and cellular functions of the FANCJ DNA helicase defective in cancer and in Fanconi Anemia

    Directory of Open Access Journals (Sweden)

    Robert M. Brosh

    2014-10-01

    Full Text Available The FANCJ DNA helicase is mutated in hereditary breast and ovarian cancer as well as the progressive bone marrow failure disorder Fanconi anemia (FA. FANCJ is linked to cancer suppression and DNA double strand break (DSB repair through its direct interaction with the hereditary breast cancer associated gene product, BRCA1. FANCJ also operates in the FA pathway of interstrand cross-link (ICL repair and contributes to homologous recombination (HR. FANCJ collaborates with a number of DNA metabolizing proteins implicated in DNA damage detection and repair, and plays an important role in cell cycle checkpoint control. In addition to its role in the classical FA pathway, FANCJ is believed to have other functions that are centered on alleviating replication stress. FANCJ resolves G-quadruplex (G4 DNA structures that are known to affect cellular replication and transcription, and potentially plays a role in the preservation and functionality of chromosomal structures such as telomeres. Recent studies suggest that FANCJ helps to maintain chromatin structure and preserve epigenetic stability by facilitating smooth progression of the replication fork when it encounters DNA damage or an alternate DNA structure such as a G4. Ongoing studies suggest a prominent but still not well-understood role of FANCJ in transcriptional regulation, chromosomal structure and function, and DNA damage repair to maintain genomic stability. This review will synthesize our current understanding of the molecular and cellular functions of FANCJ that are critical for chromosomal integrity.

  13. YAP/TEAD-mediated transcription controls cellular senescence

    National Research Council Canada - National Science Library

    Xie, Qi; Chen, Jing; Feng, Han; Peng, Shengyi; Adams, Ursula; Bai, Yujie; Huang, Li; Li, Ji; Huang, Junjian; Meng, Songshu; Yuan, Zengqiang

    2013-01-01

    .... Silencing of YAP inhibits cell proliferation and induces premature senescence. In additional experiments, we observe that cellular senescence induced by YAP deficiency is TEAD- and Rb/p16/p53-dependent...

  14. YAP/TEAD-mediated transcription controls cellular senescence.

    Science.gov (United States)

    Xie, Qi; Chen, Jing; Feng, Han; Peng, Shengyi; Adams, Ursula; Bai, Yujie; Huang, Li; Li, Ji; Huang, Junjian; Meng, Songshu; Yuan, Zengqiang

    2013-06-15

    Transcription coactivator Yes-associated protein (YAP) plays an important role in the regulation of cell proliferation and apoptosis. Here, we identify a new role of YAP in the regulation of cellular senescence. We find that the expression levels of YAP proteins decrease following the replication-induced cellular senescence in IMR90 cells. Silencing of YAP inhibits cell proliferation and induces premature senescence. In additional experiments, we observe that cellular senescence induced by YAP deficiency is TEAD- and Rb/p16/p53-dependent. Furthermore, we show that Cdk6 is a direct downstream target gene of YAP in the regulation of cellular senescence, and the expression of Cdk6 is through the YAP-TEAD complex. Ectopic expression of Cdk6 rescued YAP knockdown-induced senescence. Finally, we find that downregulation of YAP in tumor cells increases senescence in response to chemotherapeutic agents, and YAP or Cdk6 expression rescues cellular senescence. Taken together, our findings define the critical role of YAP in the regulation of cellular senescence and provide a novel insight into a potential chemotherapeutic avenue for tumor suppression. ©2013 AACR.

  15. Guaranteed Cost Control for Exponential Synchronization of Cellular Neural Networks with Mixed Time-Varying Delays via Hybrid Feedback Control

    Directory of Open Access Journals (Sweden)

    T. Botmart

    2013-01-01

    Full Text Available The problem of guaranteed cost control for exponential synchronization of cellular neural networks with interval nondifferentiable and distributed time-varying delays via hybrid feedback control is considered. The interval time-varying delay function is not necessary to be differentiable. Based on the construction of improved Lyapunov-Krasovskii functionals is combined with Leibniz-Newton's formula and the technique of dealing with some integral terms. New delay-dependent sufficient conditions for the exponential synchronization of the error systems with memoryless hybrid feedback control are first established in terms of LMIs without introducing any free-weighting matrices. The optimal guaranteed cost control with linear error hybrid feedback is turned into the solvable problem of a set of LMIs. A numerical example is also given to illustrate the effectiveness of the proposed method.

  16. H(2)S signaling in redox regulation of cellular functions.

    Science.gov (United States)

    Ju, Youngjun; Zhang, Weihua; Pei, Yanxi; Yang, Guangdong

    2013-01-01

    Hydrogen sulfide (H(2)S) is traditionally recognized as a toxic gas with a rotten-egg smell. In just the last few decades, H(2)S has been found to be one of a family of gasotransmitters, together with nitric oxide and carbon monoxide, and various physiologic effects of H(2)S have been reported. Among the most acknowledged molecular mechanisms for the cellular effects of H(2)S is the regulation of intracellular redox homeostasis and post-translational modification of proteins through S-sulfhydration. On the one side, H(2)S can promote an antioxidant effect and is cytoprotective; on the other side, H(2)S stimulates oxidative stress and is cytotoxic. This review summarizes our current knowledge of the antioxidant versus pro-oxidant effects of H(2)S in mammalian cells and describes the Janus-faced properties of this novel gasotransmitter. The redox regulation for the cellular effects of H(2)S through S-sulfhydration and the role of H(2)S in glutathione generation is also recapitulated. A better understanding of H(2)S-regualted redox homeostasis will pave the way for future design of novel pharmacological and therapeutic interventions for various diseases.

  17. 2D spatially controlled polymer micro patterning for cellular behavior studies

    Science.gov (United States)

    Dinca, V.; Palla-Papavlu, A.; Paraico, I.; Lippert, T.; Wokaun, A.; Dinescu, M.

    2011-04-01

    A simple and effective method to functionalize glass surfaces that enable polymer micropatterning and subsequent spatially controlled adhesion of cells is reported in this paper. The method involves the application of laser induced forward transfer (LIFT) to achieve polymer patterning in a single step onto cell repellent substrates (i.e. polyethyleneglycol (PEG)). This approach was used to produce micron-size polyethyleneimine (PEI)-patterns alternating with cell-repellent areas. The focus of this work is the ability of SH-SY5Y human neuroblastoma cells to orient, migrate, and produce organized cellular arrangements on laser generated PEI patterns.

  18. Cellular Automaton Models of Highway Traffic Flow Considering Lane-Control and Speed-Control

    Institute of Scientific and Technical Information of China (English)

    钱勇生; 李文俊; 曾俊伟; 王敏; 杜加伟; 广晓平

    2011-01-01

    As two kinds of management modes of highway tramc control, lane-control, and speed-control produce different effect under different conditions. In this paper, traffic flow cellular automaton models for four-lane highway system with two opposing directions under the above two modes are established considering car and truck mixed running. Through computer numerical simulating, the fundamental diagrams with different parameters are obtained, and after the analysis of density-flux diagrams, the variation discipline of flux with traffic density under different control models is gained. The results indicate that, compared with lane-control, utilization ratio of road can be further improved with speed-control when the truck number increases. The research result is of great significance for reasonable providing theoretical guidance for highway traffic control.

  19. Improved cellular uptake of functionalized single-walled carbon nanotubes

    Science.gov (United States)

    Antonelli, A.; Serafini, S.; Menotta, M.; Sfara, C.; Pierigé, F.; Giorgi, L.; Ambrosi, G.; Rossi, L.; Magnani, M.

    2010-10-01

    Single-walled carbon nanotubes (SWNTs) due to their unique structural and physicochemical properties, have been proposed as delivery systems for a variety of diagnostic and therapeutic agents. However, SWNTs have proven difficult to solubilize in aqueous solution, limiting their use in biological applications. In an attempt to improve SWNTs' solubility, biocompatibility, and to increase cell penetration we have thoroughly investigated the construction of carbon scaffolds coated with aliphatic carbon chains and phospholipids to obtain micelle-like structures. At first, oxidized SWNTs (2370 ± 30 nmol mg - 1 of SWNTs) were covalently coupled with an alcoholic chain (stearyl alcohol, C18H37OH; 816 nmol mg - 1 of SWNTs). Subsequently, SWNTs-COOC18H37 derivatives were coated with phosphatidylethanolamine (PE) or -serine (PS) phospholipids obtaining micelle-like structures. We found that cellular uptake of these constructs by phagocytic cells occurs via an endocytotic mechanism for constructs larger than 400 nm while occurs via diffusion through the cell membrane for constructs up to 400 nm. The material that enters the cell by phagocytosis is actively internalized by macrophages and localizes inside endocytotic vesicles. In contrast the material that enters the cells by diffusion is found in the cell cytosol. In conclusion, we have realized new biomimetic constructs based on alkylated SWNTs coated with phospholipids that are efficiently internalized by different cell types only if their size is lower than 400 nm. These constructs are not toxic to the cells and could now be explored as delivery systems for non-permeant cargoes.

  20. p53 Cellular Localization and Function in Neuroblastoma

    Science.gov (United States)

    Tweddle, Deborah A.; Malcolm, Archie J.; Cole, Michael; Pearson, Andrew D.J.; Lunec, John

    2001-01-01

    This study investigated the hypothesis that p53 accumulation in neuroblastoma, in the absence of mutation, is associated with functional inactivation, which interferes with downstream mediators of p53 function. To test this hypothesis, p53 expression, location, and functional integrity was examined in neuroblastoma by irradiating 6 neuroblastoma cell lines and studying the effects on p53 transcriptional function, cell cycle arrest, and induction of apoptosis, together with the transcriptional function of p53 after irradiation in three ex vivo primary, untreated neuroblastoma tumors. p53 sequencing showed five neuroblastoma cell lines, two of which were MYCN-amplified, and that all of the tumors were wild-type for p53. p53 was found to be predominantly nuclear before and after irradiation and to up-regulate the p53 responsive genes WAF1 and MDM2 in wild-type p53 cell lines and a poorly-differentiated neuroblastoma, but not a differentiating neuroblastoma or the ganglioneuroblastoma part of a nodular ganglioneuroblastoma in short term culture. This suggests intact p53 transcriptional activity in proliferating neuroblastoma. Irradiation of wild-type p53 neuroblastoma cell lines led to G1 cell cycle arrest in cell lines without MYCN amplification, but not in those with MYCN amplification, despite induction of WAF1. This suggests MYCN amplification may alter downstream mediators of p53 function in neuroblastoma. PMID:11395384

  1. Improved cellular uptake of functionalized single-walled carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Antonelli, A; Serafini, S; Menotta, M; Sfara, C; Pierige, F; Rossi, L; Magnani, M [Department of Biomolecular Sciences, University of Urbino ' Carlo Bo' , Via Saffi 2, 61029 Urbino (Italy); Giorgi, L; Ambrosi, G, E-mail: antonella.antonelli@uniurb.it, E-mail: sonja.serafini@erydel.com, E-mail: michele.menotta@uniurb.it, E-mail: carla.sfara@uniurb.it, E-mail: francesca.pierige@uniurb.it, E-mail: luca.giorgi@uniurb.it, E-mail: gianluca.ambrosi@uniurb.it, E-mail: luigia.rossi@uniurb.it, E-mail: mauro.magnani@uniurb.it [Department of Mathematics, Physics and Informatics, University of Urbino ' Carlo Bo' , Via S Chiara 27, 61029 Urbino (Italy)

    2010-10-22

    Single-walled carbon nanotubes (SWNTs) due to their unique structural and physicochemical properties, have been proposed as delivery systems for a variety of diagnostic and therapeutic agents. However, SWNTs have proven difficult to solubilize in aqueous solution, limiting their use in biological applications. In an attempt to improve SWNTs' solubility, biocompatibility, and to increase cell penetration we have thoroughly investigated the construction of carbon scaffolds coated with aliphatic carbon chains and phospholipids to obtain micelle-like structures. At first, oxidized SWNTs (2370 {+-} 30 nmol mg{sup -1} of SWNTs) were covalently coupled with an alcoholic chain (stearyl alcohol, C{sub 18}H{sub 37}OH; 816 nmol mg{sup -1} of SWNTs). Subsequently, SWNTs-COOC{sub 18}H{sub 37} derivatives were coated with phosphatidylethanolamine (PE) or -serine (PS) phospholipids obtaining micelle-like structures. We found that cellular uptake of these constructs by phagocytic cells occurs via an endocytotic mechanism for constructs larger than 400 nm while occurs via diffusion through the cell membrane for constructs up to 400 nm. The material that enters the cell by phagocytosis is actively internalized by macrophages and localizes inside endocytotic vesicles. In contrast the material that enters the cells by diffusion is found in the cell cytosol. In conclusion, we have realized new biomimetic constructs based on alkylated SWNTs coated with phospholipids that are efficiently internalized by different cell types only if their size is lower than 400 nm. These constructs are not toxic to the cells and could now be explored as delivery systems for non-permeant cargoes.

  2. Control of Cellular Arrangement by Surface Topography Induced by Plastic Deformation

    Directory of Open Access Journals (Sweden)

    Aira Matsugaki

    2016-06-01

    Full Text Available The anisotropic microstructure of bone tissue is crucial for appropriate mechanical and biological functions of bone. We recently revealed that the construction of oriented bone matrix is established by osteoblast alignment; there is a quite unique correlation between cell alignment and cell-produced bone matrix orientation governed by the molecular interactions between material surface and cells. Titanium and its alloys are one of the most attractive materials for biomedical applications. We previously succeeded in controlling cellular arrangement using the dislocations of a crystallographic slip system in titanium single crystals with hexagonal close-packing (hcp crystal lattice. Here, we induced a specific surface topography by deformation twinning and dislocation motion to control cell orientation. Dislocation and deformation twinning were introduced into α-titanium polycrystals in compression, inducing a characteristic surface structure involving nanometer-scale highly concentrated twinning traces. The plastic deformation-induced surface topography strongly influenced osteoblast orientation, causing them to align preferentially along the slip and twinning traces. This surface morphology, exhibiting a characteristic grating structure, controlled the localization of focal adhesions and subsequent elongation of stress fibers in osteoblasts. These results indicate that cellular responses against dislocation and deformation twinning are useful for controlling osteoblast alignment and the resulting bone matrix anisotropy.

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

    Science.gov (United States)

    Kolhar, Poornima

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

  4. New Functions for Oxysterols and Their Cellular Receptors

    Directory of Open Access Journals (Sweden)

    Vesa M. Olkkonen

    2008-01-01

    Full Text Available Oxysterols are naturally occurring oxidized derivatives of cholesterol, or by-products of cholesterol biosynthesis, with multiple biologic functions. These compounds display cytotoxic, pro-apoptotic, and pro-inflammatory activities and may play a role in the pathology of atherosclerosis. Their functions as intermediates in the synthesis of bile acids and steroid hormones, and as readily transportable forms of sterol are well established. During the past decade, however, novel physiologic activities of oxysterols have emerged. They are now thought to act as endogenous regulators of gene expression in lipid metabolism. Recently, new intracellular oxysterol receptors have been identified and novel functions of oxysterols in cell signaling discovered, evoking novel interest in these compounds in several branches of biomedical research.

  5. Dual Biochemical Oscillators May Control Cellular Reversals in Myxococcus xanthus

    Science.gov (United States)

    Eckhert, Erik; Rangamani, Padmini; Davis, Annie E.; Oster, George; Berleman, James E.

    2014-01-01

    Myxococcus xanthus is a Gram-negative, soil-dwelling bacterium that glides on surfaces, reversing direction approximately once every 6 min. Motility in M. xanthus is governed by the Che-like Frz pathway and the Ras-like Mgl pathway, which together cause the cell to oscillate back and forth. Previously, Igoshin et al. (2004) suggested that the cellular oscillations are caused by cyclic changes in concentration of active Frz proteins that govern motility. In this study, we present a computational model that integrates both the Frz and Mgl pathways, and whose downstream components can be read as motor activity governing cellular reversals. This model faithfully reproduces wildtype and mutant behaviors by simulating individual protein knockouts. In addition, the model can be used to examine the impact of contact stimuli on cellular reversals. The basic model construction relies on the presence of two nested feedback circuits, which prompted us to reexamine the behavior of M. xanthus cells. We performed experiments to test the model, and this cell analysis challenges previous assumptions of 30 to 60 min reversal periods in frzCD, frzF, frzE, and frzZ mutants. We demonstrate that this average reversal period is an artifact of the method employed to record reversal data, and that in the absence of signal from the Frz pathway, Mgl components can occasionally reverse the cell near wildtype periodicity, but frz- cells are otherwise in a long nonoscillating state. PMID:25468349

  6. Molecular design and nanoparticle-mediated intracellular delivery of functional proteins to target cellular pathways

    Science.gov (United States)

    Shah, Dhiral Ashwin

    Intracellular delivery of specific proteins and peptides represents a novel method to influence stem cells for gain-of-function and loss-of-function. Signaling control is vital in stem cells, wherein intricate control of and interplay among critical pathways directs the fate of these cells into either self-renewal or differentiation. The most common route to manipulate cellular function involves the introduction of genetic material such as full-length genes and shRNA into the cell to generate (or prevent formation of) the target protein, and thereby ultimately alter cell function. However, viral-mediated gene delivery may result in relatively slow expression of proteins and prevalence of oncogene insertion into the cell, which can alter cell function in an unpredictable fashion, and non-viral delivery may lead to low efficiency of genetic delivery. For example, the latter case plagues the generation of induced pluripotent stem cells (iPSCs) and hinders their use for in vivo applications. Alternatively, introducing proteins into cells that specifically recognize and influence target proteins, can result in immediate deactivation or activation of key signaling pathways within the cell. In this work, we demonstrate the cellular delivery of functional proteins attached to hydrophobically modified silica (SiNP) nanoparticles to manipulate specifically targeted cell signaling proteins. In the Wnt signaling pathway, we have targeted the phosphorylation activity of glycogen synthase kinase-3beta (GSK-3beta) by designing a chimeric protein and delivering it in neural stem cells. Confocal imaging indicates that the SiNP-chimeric protein conjugates were efficiently delivered to the cytosol of human embryonic kidney cells and rat neural stem cells, presumably via endocytosis. This uptake impacted the Wnt signaling cascade, indicated by the elevation of beta-catenin levels, and increased transcription of Wnt target genes, such as c-MYC. The results presented here suggest that

  7. Intermittent hypoxia leads to functional reorganization of mitochondria and affects cellular bioenergetics in marine molluscs.

    Science.gov (United States)

    Ivanina, Anna V; Nesmelova, Irina; Leamy, Larry; Sokolov, Eugene P; Sokolova, Inna M

    2016-06-01

    Fluctuations in oxygen (O2) concentrations represent a major challenge to aerobic organisms and can be extremely damaging to their mitochondria. Marine intertidal molluscs are well-adapted to frequent O2 fluctuations, yet it remains unknown how their mitochondrial functions are regulated to sustain energy metabolism and prevent cellular damage during hypoxia and reoxygenation (H/R). We used metabolic control analysis to investigate the mechanisms of mitochondrial responses to H/R stress (18 h at <0.1% O2 followed by 1 h of reoxygenation) using hypoxia-tolerant intertidal clams Mercenaria mercenaria and hypoxia-sensitive subtidal scallops Argopecten irradians as models. We also assessed H/R-induced changes in cellular energy balance, oxidative damage and unfolded protein response to determine the potential links between mitochondrial dysfunction and cellular injury. Mitochondrial responses to H/R in scallops strongly resembled those in other hypoxia-sensitive organisms. Exposure to hypoxia followed by reoxygenation led to a strong decrease in the substrate oxidation (SOX) and phosphorylation (PHOS) capacities as well as partial depolarization of mitochondria of scallops. Elevated mRNA expression of a reactive oxygen species-sensitive enzyme aconitase and Lon protease (responsible for degradation of oxidized mitochondrial proteins) during H/R stress was consistent with elevated levels of oxidative stress in mitochondria of scallops. In hypoxia-tolerant clams, mitochondrial SOX capacity was enhanced during hypoxia and continued rising during the first hour of reoxygenation. In both species, the mitochondrial PHOS capacity was suppressed during hypoxia, likely to prevent ATP wastage by the reverse action of FO,F1-ATPase. The PHOS capacity recovered after 1 h of reoxygenation in clams but not in scallops. Compared with scallops, clams showed a greater suppression of energy-consuming processes (such as protein turnover and ion transport) during hypoxia, indicated

  8. a Cellular Automaton Modeling the Struggle to Control the Media

    Science.gov (United States)

    Boccara, N.

    A free and fair press is an essential condition for democracy. In many western countries, the media production, distribution, ownership, and funding are dominated by corporations, and therefore governed by the idea of maximizing profits for the investors making freedom and fairness of the press very questionable. There exist, however, a number of political activists who, by writing books and articles, and giving talks, are fighting to free the media from the influence of big corporations. This paper presents a simple cellular automaton model of this struggle.

  9. Adaptive Posttranslational Control in Cellular Stress Response Pathways and Its Relationship to Toxicity Testing and Safety Assessment.

    Science.gov (United States)

    Zhang, Qiang; Bhattacharya, Sudin; Pi, Jingbo; Clewell, Rebecca A; Carmichael, Paul L; Andersen, Melvin E

    2015-10-01

    Although transcriptional induction of stress genes constitutes a major cellular defense program against a variety of stressors, posttranslational control directly regulating the activities of preexisting stress proteins provides a faster-acting alternative response. We propose that posttranslational control is a general adaptive mechanism operating in many stress pathways. Here with the aid of computational models, we first show that posttranslational control fulfills two roles: (1) handling small, transient stresses quickly and (2) stabilizing the negative feedback transcriptional network. We then review the posttranslational control pathways for major stress responses-oxidative stress, metal stress, hyperosmotic stress, DNA damage, heat shock, and hypoxia. Posttranslational regulation of stress protein activities occurs by reversible covalent modifications, allosteric or non-allosteric enzymatic regulations, and physically induced protein structural changes. Acting in feedback or feedforward networks, posttranslational control may establish a threshold level of cellular stress. Sub-threshold stresses are handled adequately by posttranslational control without invoking gene transcription. With supra-threshold stress levels, cellular homeostasis cannot be maintained and transcriptional induction of stress genes and other gene programs, eg, those regulating cell metabolism, proliferation, and apoptosis, takes place. The loss of homeostasis with consequent changes in cellular function may lead to adverse cellular outcomes. Overall, posttranslational and transcriptional control pathways constitute a stratified cellular defense system, handling stresses coherently across time and intensity. As cell-based assays become a focus for chemical testing anchored on toxicity pathways, examination of proteomic and metabolomic changes as a result of posttranslational control occurring in the absence of transcriptomic alterations deserves more attention. © The Author 2015

  10. Power Control for D2D Underlay Cellular Networks With Channel Uncertainty

    KAUST Repository

    Memmi, Amen

    2016-12-26

    Device-to-device (D2D) communications underlying the cellular infrastructure are a technology that have been proposed recently as a promising solution to enhance cellular network capabilities. It improves spectrum utilization, overall throughput, and energy efficiency while enabling new peer-to-peer and location-based applications and services. However, interference is the major challenge, since the same resources are shared by both systems. Therefore, interference management techniques are required to keep the interference under control. In this paper, in order to mitigate interference, we consider centralized and distributed power control algorithms in a one-cell random network model. Existing results on D2D underlay networks assume perfect channel state information (CSI). This assumption is usually unrealistic in practice due to the dynamic nature of wireless channels. Thus, it is of great interest to study and evaluate achievable performances under channel uncertainty. Differently from previous works, we are assuming that the CSI may be imperfect and include estimation errors. In the centralized approach, we derive the optimal powers that maximize the coverage probability and the rate of the cellular user while scheduling as many D2D links as possible. These powers are computed at the base station (BS) and then delivered to the users, and hence the name “centralized”. For the distributed method, the ON–OFF power control and the truncated channel inversion are proposed. Expressions of coverage probabilities are established in the function of D2D links intensity, pathloss exponent, and estimation error variance. Results show the important influence of CSI error on achievable performances and thus how crucial it is to consider it while designing networks and evaluating performances.

  11. Magnetogenetics: Remote Control of Cellular Signaling with Magnetic Fields

    Science.gov (United States)

    Sauer, Jeremy P.

    Means for temporally regulating gene expression and cellular activity are invaluable for elucidating the underlying physiological processes and have therapeutic implications. Here we report the development of a system for remote regulation of gene expression by low frequency radiowaves (RF) or by a static magnetic field. We accomplished this by first adding iron oxide nanoparticles - either exogenously or as genetically encoded ferritin/ferric oxyhydroxide particle. These particles have been designed with affinity to the plasma membrane ion channel Transient Receptor Potential Vanilloid 1 (TRPV1) by a conjugated antibody. Application of a magnetic field stimulates the particle to gate the ion channel and this, in turn, initiates calcium-dependent transgene expression. We first demonstrated in vitro that TRPV1 can be actuated to cause calcium flux into the cell by directly applying a localized magnetic field. In mice expressing these genetically encoded components, application of external magnetic field caused remote stimulation of insulin transgene expression and significantly lowered blood glucose. In addition, we are investigating mechanisms by which iron oxide nanoparticles can absorb RF, and transduce this energy to cause channel opening. This robust, repeatable method for remote cellular regulation in vivo may ultimately have applications in basic science, as well as in technology and therapeutics.

  12. GO-2D: identifying 2-dimensional cellular-localized functional modules in Gene Ontology

    Directory of Open Access Journals (Sweden)

    Yang Da

    2007-01-01

    Full Text Available Abstract Background Rapid progress in high-throughput biotechnologies (e.g. microarrays and exponential accumulation of gene functional knowledge make it promising for systematic understanding of complex human diseases at functional modules level. Based on Gene Ontology, a large number of automatic tools have been developed for the functional analysis and biological interpretation of the high-throughput microarray data. Results Different from the existing tools such as Onto-Express and FatiGO, we develop a tool named GO-2D for identifying 2-dimensional functional modules based on combined GO categories. For example, it refines biological process categories by sorting their genes into different cellular component categories, and then extracts those combined categories enriched with the interesting genes (e.g., the differentially expressed genes for identifying the cellular-localized functional modules. Applications of GO-2D to the analyses of two human cancer datasets show that very specific disease-relevant processes can be identified by using cellular location information. Conclusion For studying complex human diseases, GO-2D can extract functionally compact and detailed modules such as the cellular-localized ones, characterizing disease-relevant modules in terms of both biological processes and cellular locations. The application results clearly demonstrate that 2-dimensional approach complementary to current 1-dimensional approach is powerful for finding modules highly relevant to diseases.

  13. Regulation of REGγ cellular distribution and function by SUMO modification

    Institute of Scientific and Technical Information of China (English)

    Yan Wu; Honglin Luo; Xiaotao Li; Lu Wang; Ping Zhou; Guangqiang Wang; Yu Zeng; Ying Wang; Jian Liu; Bianhong Zhang; Shuang Liu

    2011-01-01

    Discovery of emerging REGy-regulated proteins has accentuated the RECry-proteasome as an important pathway in multiple biological processes, including cell growth, cell cycle regulation, and apoptosis. However, little is known about the regulation of the REGy-proteasome pathway. Here we demonstrate that REGγ can be SUMOylated in vitro and in vivo by SUMO-1, SUMO-2, and SUMO-3. The SUMO-E3 protein inhibitor of activated STAT(PIAS)1physically associates with REGy and promotes SUMOylation of REGy. SUMOylation of RECry was found to occur at multiple sites, including K6, K14, and K12. Mutation analysis indicated that these SUMO sites simultaneously contributed to the SUMOylation status of REGy in cells. Posttranslational modification of REGγ by SUMO conjugation was revealed to mediate cytosolic translocation of REGγ and to cause increased stability of this proteasome activator.SUMOylation-deficient REGγ displayed attenuated ability to degrade p21waf//Cipl due to reduced affinity of the REGγ SUMOylation-defective mutant for p21. Taken together, we report a previously unrecognized mechanism regulating the activity of the proteasome activator REGy. This regulatory mechanism may enable REGy to function as a more potent factor in protein degradation with a broader substrate spectrum.

  14. The liver X receptor : Control of cellular lipid homeostasis and beyond Implications for drug design

    NARCIS (Netherlands)

    Oosterveer, Maaike H.; Grefhorst, Aldo; Groen, Albert K.; Kuipers, Folkert

    2010-01-01

    Liver X receptor (LXR) alpha and beta are nuclear receptors that control cellular metabolism. LXRs modulate the expression of genes involved in cholesterol and lipid metabolism in response to changes in cellular cholesterol status. Because of their involvement in cholesterol homeostasis, LXRs have e

  15. Cellular Controlled Short-Range Communication for Cooperative P2P Networking

    DEFF Research Database (Denmark)

    Fitzek, Frank H. P.; Katz, Marcos; Zhang, Qi

    2009-01-01

    This article advocates a novel communication architecture and associated collaborative framework for future wireless communication systems. In contrast to the dominating cellular architecture and the upcoming peer-to-peer architecture, the new approach envisions a cellular controlled short-range ...

  16. GAME THEORY BASED INTERFERENCE CONTROL AND POWER CONTROL FOR D2D COMMUNICATION IN CELLULAR NETWORKS

    Directory of Open Access Journals (Sweden)

    Fa-Bin Li

    2016-09-01

    Full Text Available With the current development of mobile communication services, people need personal communication of high speed, excellent service, high quality and low latency,however, limited spectrum resources become the most important factor to hamper improvement of cellular systems. As big amount of data traffic will cause greater local consumption of spectrum resources, future networks are required to have appropriate techniques to better support such forms of communication. D2D (Device-to-device communication technology in a cellular network makes full use of spectrum resources underlaying, reduces the load of the base station, minimizes transmit power of the terminals and the base stations, thereby enhances the overall throughput of the networks. Due to the use of multiplexing D2D UE (User equipment resources and spectrum, and the interference caused by the sharing of resources between adjacent cells, it has become a major factor affecting coexisting of cellular subscribers and D2D users. When D2D communication multiplexes the uplink resources, the base-stations are easily to be disturbed; when the downlink resources are multiplexed, the users of downlink are susceptible to interference. In order to build a high-efficient mobile network, we can meet the QoS requirements by controlling the power to suppress the interference between the base station and a terminal user.

  17. Embryonic MicroRNA-369 Controls Metabolic Splicing Factors and Urges Cellular Reprograming.

    Directory of Open Access Journals (Sweden)

    Masamitsu Konno

    Full Text Available Noncoding microRNAs inhibit translation and lower the transcript stability of coding mRNA, however miR-369 s, in aberrant silencing genomic regions, stabilizes target proteins under cellular stress. We found that in vitro differentiation of embryonic stem cells led to chromatin methylation of histone H3K4 at the miR-369 region on chromosome 12qF in mice, which is expressed in embryonic cells and is critical for pluripotency. Proteomic analyses revealed that miR-369 stabilized translation of pyruvate kinase (Pkm2 splicing factors such as HNRNPA2B1. Overexpression of miR-369 stimulated Pkm2 splicing and enhanced induction of cellular reprogramming by induced pluripotent stem cell factors, whereas miR-369 knockdown resulted in suppression. Furthermore, immunoprecipitation analysis showed that the Argonaute complex contained the fragile X mental retardation-related protein 1 and HNRNPA2B1 in a miR-369-depedent manner. Our findings demonstrate a unique role of the embryonic miR-369-HNRNPA2B1 axis in controlling metabolic enzyme function, and suggest a novel pathway linking epigenetic, transcriptional, and metabolic control in cell reprogramming.

  18. Serum cortisol level in cerebral infarction patients with infection and its correlation with nerve function, humoral immunity and cellular immunity

    Institute of Scientific and Technical Information of China (English)

    Jie-Min Zhai; Hui-Qi Li; Jian-Bo He; Hai-Guo Wang

    2016-01-01

    Objective:To analyze the serum cortisol level in cerebral infarction patients with infection and its correlation with nerve function, humoral immunity and cellular immunity.Methods:A total of 86 patients with cerebral infarction were divided into observation group (cerebral infarction combined with infection) (n=40) and control group (cerebral infarction alone) (n=46) according to the combination of infection. Serum content of cortisol, nerve function-related indexes and humoral immunity indexes as well as peripheral blood levels of cellular immunity indexes of two groups of patients were determined on admission, and the correlation between serum cortisol level and the above illness-related indexes in cerebral infarction patients with infection was further analyzed.Results: Serum cortisol content of observation group was significantly higher than that of control group; serum nerve function indexes S100β, GFAP, Hcy and HO1 content were significantly higher than those of control group while IGF-1 content was significantly lower than that of control group; humoral immunity indexes IgA, IgM, IgG, C3 and C4 content in serum were significantly lower than those of control group; cellular immunity indexes CD3+, CD4+ and CD54+T lymphocyte content in peripheral blood were significantly lower than those of control group while CD19+T lymphocyte content and CD4+/CD8+ level were significantly higher than those of control group; hemodynamic indexes rCBF and rCBV levels were significantly lower than those of control group while MTT, TTP and DLY levels were significantly higher than those of control group. Serum cortisol level in cerebral infarction patients with infection was directly correlated with the levels of nerve function, humoral immunity, cellular immunity and other illness-related indexes. Conclusions:The high cortisol state in cerebral infarction patients with infection is the visual sign of severe nerve function damage and suppressed immune function, and it can be a

  19. Study on the Functional Dynamic Changes of Peri-Operative Cellular Immunity in Esophageal and Cardiac Cancer

    Institute of Scientific and Technical Information of China (English)

    Chen Sheng; Li Shiting; Fang Youping

    2014-01-01

    Objective: To explore the systemic and local cellular immune function of patients with esophageal carcinoma or cardiac cancer. Methods: The distribution of tumor-infiltrating lymphocyte (TIL) and cancer-associated macrophage (TAM) in local tumor tissues of 52 patients with esophageal cancer or cardiac cancer were observed by immunehistochemical method. The level of peripheral SIL-2R and TNF-α of preoperative and postoperative 1, 2, 3 weeks were detected by ELISA and ABC-ELISA methods respectively, then the acquired results were compared with 30 cases of normal control group. Results:The peritumor inifltration densities of TIL and TAM was greater than that of cancer nest stroma (P<0.05). Compared with the normal control group, the levels of sIL-2R and TNF-α increased signiifcantly (P<0.01). Immune function could be suppressed by operative wound in a short time of post-operation, whose damage severity was closely associated with tumor TNM stages. Conclusion: Patients with esophageal or cardiac cancer have cellular immune function disorders. Dynamic testing of peripheral sIL-2R and TNT-α level in patients with esophageal or cardiac cancer has positive clinical signiifcance in the evaluation of cellular immune function, tumor lesion degree and curative effect.

  20. Physiological enzymology: The next frontier in understanding protein structure and function at the cellular level.

    Science.gov (United States)

    Lee, Irene; Berdis, Anthony J

    2016-01-01

    Historically, the study of proteins has relied heavily on characterizing the activity of a single purified protein isolated from other cellular components. This classic approach allowed scientists to unambiguously define the intrinsic kinetic and chemical properties of that protein. The ultimate hope was to extrapolate this information toward understanding how the enzyme or receptor behaves within its native cellular context. These types of detailed in vitro analyses were necessary to reduce the innate complexities of measuring the singular activity and biochemical properties of a specific enzyme without interference from other enzymes and potential competing substrates. However, recent developments in fields encompassing cell biology, molecular imaging, and chemical biology now provide the unique chemical tools and instrumentation to study protein structure, function, and regulation in their native cellular environment. These advancements provide the foundation for a new field, coined physiological enzymology, which quantifies the function and regulation of enzymes and proteins at the cellular level. In this Special Edition, we explore the area of Physiological Enzymology and Protein Function through a series of review articles that focus on the tools and techniques used to measure the cellular activity of proteins inside living cells. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions.

  1. Cell patch seeding and functional analysis of cellularized scaffolds for tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, P R Anil [Division of Implant Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012 (India); Varma, H K [Bioceramics Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012 (India); Kumary, T V [Division of Implant Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012 (India)

    2007-03-01

    Cell seeding has a direct impact on the final structure and function of tissue constructs, especially for applications like tissue engineering and regeneration. In this study seeding cell patches retrieved from the thermoresponsive poly(N-isopropylacrylamide) surface were used to generate in vitro tissue constructs. Porous and dense bone substitute materials were cellularized using osteoblast cells by a patch transfer and a trypsin method. The function and proliferation of cells was analyzed after 7 days of culture. The relative cell growth rate was found to be higher in cellularized porous hydroxyapatite (PHA) than in dense hydroxyapatite. Live-dead staining confirmed viable cells inside the pores of PHA. Increased alkaline phosphatase activity of cells transferred by the cell patch over the trypsin method revealed the significance of cell patch seeding. This novel method of generating tissue constructs by cell patch seeding was successful in cellularizing scaffolds with intact cell function.

  2. Cell patch seeding and functional analysis of cellularized scaffolds for tissue engineering.

    Science.gov (United States)

    Anil Kumar, P R; Varma, H K; Kumary, T V

    2007-03-01

    Cell seeding has a direct impact on the final structure and function of tissue constructs, especially for applications like tissue engineering and regeneration. In this study seeding cell patches retrieved from the thermoresponsive poly(N-isopropylacrylamide) surface were used to generate in vitro tissue constructs. Porous and dense bone substitute materials were cellularized using osteoblast cells by a patch transfer and a trypsin method. The function and proliferation of cells was analyzed after 7 days of culture. The relative cell growth rate was found to be higher in cellularized porous hydroxyapatite (PHA) than in dense hydroxyapatite. Live-dead staining confirmed viable cells inside the pores of PHA. Increased alkaline phosphatase activity of cells transferred by the cell patch over the trypsin method revealed the significance of cell patch seeding. This novel method of generating tissue constructs by cell patch seeding was successful in cellularizing scaffolds with intact cell function.

  3. Quantitative, Phenotypical, and Functional Characterization of Cellular Immunity in Children and Adolescents With Down Syndrome.

    Science.gov (United States)

    Schoch, Justine; Rohrer, Tilman R; Kaestner, Michael; Abdul-Khaliq, Hashim; Gortner, Ludwig; Sester, Urban; Sester, Martina; Schmidt, Tina

    2017-05-15

    Infections and autoimmune disorders are more frequent in Down syndrome, suggesting abnormality of adaptive immunity. Although the role of B cells and antibodies is well characterized, knowledge regarding T cells is limited. Lymphocyte subpopulations of 40 children and adolescents with Down syndrome and 51 controls were quantified, and phenotype and functionality of antigen-specific effector T cells were analyzed with flow cytometry after polyclonal and pathogen-specific stimulation (with varicella-zoster virus [VZV] and cytomegalovirus [CMV]). Results were correlated with immunoglobulin (Ig) G responses. Apart from general alterations in the percentage of lymphocytes, regulatory T cells, and T-helper 1 and 17 cells, all major T-cell subpopulations showed higher expression of the inhibitory receptor PD-1. Polyclonally stimulated effector CD4+ T-cell frequencies were significantly higher in subjects with Down syndrome, whereas their inhibitory receptor expression (programmed cell death 1 [PD-1] and cytotoxic T-lymphocyte antigen 4 [CTLA-4]) was similar to that of controls and cytokine expression profiles were only marginally altered. Pathogen-specific immunity showed age-appropriate levels of endemic infection, with correlation of CMV-specific cellular and humoral immunity in all subjects. Among VZV IgG-positive individuals, a higher percentage of VZV-specific T-cell-positive subjects was seen in those with Down syndrome. Despite alterations in lymphocyte subpopulations, individuals with Down syndrome can mount effector T-cell responses with similar phenotype and functionality as controls but may require higher effector T-cell frequencies to ensure pathogen control.

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

    Science.gov (United States)

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

    2016-02-01

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

  5. Localization of RhoGEF2 during Drosophila cellularization is developmentally controlled by Slam.

    Science.gov (United States)

    Wenzl, Christian; Yan, Shuling; Laupsien, Philip; Grosshans, Jörg

    2010-01-01

    Essential for proper function of small GTPases of the Rho family, which control many aspects of cytoskeletal and membrane dynamics, is their temporal and spatial control by activating GDP exchange factors (GEFs) and deactivating GTPase-activating-proteins (GAPs). The regulatory mechanisms controlling these factors are not well understood, especially during development, when the organization and behaviour of cells change in a stage dependent manner. During Drosophila cellularization Rho signalling and RhoGEF2 are involved in furrow canal formation and the organization of actin and myosin. Here we analyze, how RhoGEF2 is localized at the sites of membrane invagination. We show that the PDZ domain is necessary for localization and function of RhoGEF2 and identify Slam as a factor that is necessary for RhoGEF2 localization. We also demonstrate that Slam can recruit RhoGEF2 to ectopic sites. Furthermore we find that the PDZ domain of RhoGEF2 can form a complex with Slam invivo and that Slam transcripts and protein colocalize at the furrow canal and in basal particles. Based on these findings, we propose that accumulation of slam mRNA and protein at the presumptive invagination site provides a spatial and temporal trigger for RhoGEF2-Rho1 signalling.

  6. Control of in vivo (cellular) phleomycin sensitivity by nuclear genotype, growth phase, and metal ions

    Energy Technology Data Exchange (ETDEWEB)

    Moore, C.W.

    1982-03-01

    Nuclear genotype, growth phase, and the presence of metal ions all proved to be important in controlling the lethal effects of phleomycin in eukaryotic Saccharomyces cerevisiae. Among 120 normal and radiation-sensitive strains compared for their sensitivities to lethal effects of phleomycin, all mutant strains exhibiting enhanced sensitivities to phleomycin killing were also sensitive to killing by ionizing radiation. Mutants exhibiting sensitivities to phleomycin similar to normal strains of the same ploidy were sensitive to ultraviolet radiation. We conclude that cellular recovery from phleomycin-induced damage in yeast depends upon the function of some or all of 13 independent genes and upon at least some of the same steps in cellular pathways for the biological repair of damage by ionizing radiation. In this respect, the action of phleomycin is similar to the action of its structurally similar analog, bleomycin, even though phleomycin was substantially more cytotoxic. Stationary-phase haploid yeast cells were more sensitive than exponentially growing cells to killing by phleomycin. Survival of stationary-phase yeast was reduced to 0.3 +/- 0.07% (S.E.) after 20-min exposures to phleomycin (1 microgram/ml; approximately 6.7 x 10(-7) M), but lethal effects of phleomycin were completely eradicated (98% survival) by the presence of 0.05 M ethylenediaminetetraacetate during the treatment period. The inactivation indicates an important role for one or more metal ion(s) in the in vivo toxicity of the phleomycin-bleomycin group of anticancer antibiotics.

  7. Controlled cellular fusion using optically trapped plasmonic nano-heaters

    Science.gov (United States)

    Bahadori, Azra; Lund, Andreas R.; Semsey, Szabolcs; Oddershede, Lene B.; Bendix, Poul M.

    2016-09-01

    Optically trapped plasmonic nano-heaters are used to mediate efficient and controlled fusion of biological membranes. The fusion method is demonstrated by optically trapping plasmonic nanoparticles located in between vesicle membranes leading to rapid lipid and content mixing. As an interesting application we show how direct control over fusion can be used for studying diffusion of peripheral membrane proteins and their interactions with membranes and for studying protein reactions. Membrane proteins encapsulated in an inert vesicle can be transferred to a vesicle composed of negative lipids by optically induced fusion. Mixing of the two membranes results in a fused vesicle with a high affinity for the protein and we observe immediate membrane tubulation due to the activity of the protein. Fusion of distinct membrane compartments also has applications in small scale chemistry for realizing pico-liter reactions and offers many exciting applications within biology which are discussed here.

  8. Global functional analyses of cellular responses to pore-forming toxins.

    Directory of Open Access Journals (Sweden)

    Cheng-Yuan Kao

    2011-03-01

    Full Text Available Here we present the first global functional analysis of cellular responses to pore-forming toxins (PFTs. PFTs are uniquely important bacterial virulence factors, comprising the single largest class of bacterial protein toxins and being important for the pathogenesis in humans of many Gram positive and Gram negative bacteria. Their mode of action is deceptively simple, poking holes in the plasma membrane of cells. The scattered studies to date of PFT-host cell interactions indicate a handful of genes are involved in cellular defenses to PFTs. How many genes are involved in cellular defenses against PFTs and how cellular defenses are coordinated are unknown. To address these questions, we performed the first genome-wide RNA interference (RNAi screen for genes that, when knocked down, result in hypersensitivity to a PFT. This screen identifies 106 genes (∼0.5% of genome in seven functional groups that protect Caenorhabditis elegans from PFT attack. Interactome analyses of these 106 genes suggest that two previously identified mitogen-activated protein kinase (MAPK pathways, one (p38 studied in detail and the other (JNK not, form a core PFT defense network. Additional microarray, real-time PCR, and functional studies reveal that the JNK MAPK pathway, but not the p38 MAPK pathway, is a key central regulator of PFT-induced transcriptional and functional responses. We find C. elegans activator protein 1 (AP-1; c-jun, c-fos is a downstream target of the JNK-mediated PFT protection pathway, protects C. elegans against both small-pore and large-pore PFTs and protects human cells against a large-pore PFT. This in vivo RNAi genomic study of PFT responses proves that cellular commitment to PFT defenses is enormous, demonstrates the JNK MAPK pathway as a key regulator of transcriptionally-induced PFT defenses, and identifies AP-1 as the first cellular component broadly important for defense against large- and small-pore PFTs.

  9. Reciprocal Control of the Circadian Clock and Cellular Redox State - a Critical Appraisal.

    Science.gov (United States)

    Putker, Marrit; O'Neill, John Stuart

    2016-01-01

    Redox signalling comprises the biology of molecular signal transduction mediated by reactive oxygen (or nitrogen) species. By specific and reversible oxidation of redox-sensitive cysteines, many biological processes sense and respond to signals from the intracellular redox environment. Redox signals are therefore important regulators of cellular homeostasis. Recently, it has become apparent that the cellular redox state oscillates in vivo and in vitro, with a period of about one day (circadian). Circadian time-keeping allows cells and organisms to adapt their biology to resonate with the 24-hour cycle of day/night. The importance of this innate biological time-keeping is illustrated by the association of clock disruption with the early onset of several diseases (e.g. type II diabetes, stroke and several forms of cancer). Circadian regulation of cellular redox balance suggests potentially two distinct roles for redox signalling in relation to the cellular clock: one where it is regulated by the clock, and one where it regulates the clock. Here, we introduce the concepts of redox signalling and cellular timekeeping, and then critically appraise the evidence for the reciprocal regulation between cellular redox state and the circadian clock. We conclude there is a substantial body of evidence supporting circadian regulation of cellular redox state, but that it would be premature to conclude that the converse is also true. We therefore propose some approaches that might yield more insight into redox control of cellular timekeeping.

  10. The interplay between p16 serine phosphorylation and arginine methylation determines its function in modulating cellular apoptosis and senescence

    OpenAIRE

    Lu, Yang; Ma, Wenlong; Li, Zhongwei; Lu, Jun; Wang, Xiuli

    2017-01-01

    Cyclin-dependent kinase inhibitor p16INK4a (p16) primarily functions as a negative regulator of the retinoblastoma protein (Rb) -E2F pathway, thus plays critical role in cell cycle progression, cellular senescence and apoptosis. In this study, we showed that the methylation of Arg 138 and the phosphorylation of Ser 140 on p16 were critical for the control of cell proliferation and apoptosis. Compared to wild type p16, mutant p16R138K possessed improved function in preventing cell proliferatio...

  11. The FPGA realization of the general cellular automata based cryptographic hash functions: Performance and effectiveness

    Directory of Open Access Journals (Sweden)

    P. G. Klyucharev

    2014-01-01

    Full Text Available In the paper the author considers hardware implementation of the GRACE-H family general cellular automata based cryptographic hash functions. VHDL is used as a language and Altera FPGA as a platform for hardware implementation. Performance and effectiveness of the FPGA implementations of GRACE-H hash functions were compared with Keccak (SHA-3, SHA-256, BLAKE, Groestl, JH, Skein hash functions. According to the performed tests, performance of the hardware implementation of GRACE-H family hash functions significantly (up to 12 times exceeded performance of the hardware implementation of previously known hash functions, and effectiveness of that hardware implementation was also better (up to 4 times.

  12. Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

    DEFF Research Database (Denmark)

    Kragstrup, Tue Wenzel; Kjaer, M; Mackey, A L

    2011-01-01

    The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging...

  13. High-order sliding mode control of a DC motor drive via a switched controlled multi-cellular converter

    Science.gov (United States)

    Djemaï, M.; Busawon, K.; Benmansour, K.; Marouf, A.

    2011-11-01

    In this article, we present a high-order sliding mode controller of a DC motor drive connected to a multi-cellular converter. More specifically, we design a second-order (super-twisting) control algorithm for the speed regulation of a DC motor. For this, a switching control for the multi-cellular converter is derived in order to supply the correct reference value for the speed regulation. A practical implementation of the controller is realised using a laboratory set-up. The performance and the validity of the controller are shown experimentally.

  14. Performance Evaluation of Road Traffic Control Using a Fuzzy Cellular Model

    CERN Document Server

    Płaczek, Bartłomiej

    2011-01-01

    In this paper a method is proposed for performance evaluation of road traffic control systems. The method is designed to be implemented in an on-line simulation environment, which enables optimisation of adaptive traffic control strategies. Performance measures are computed using a fuzzy cellular traffic model, formulated as a hybrid system combining cellular automata and fuzzy calculus. Experimental results show that the introduced method allows the performance to be evaluated using imprecise traffic measurements. Moreover, the fuzzy definitions of performance measures are convenient for uncertainty determination in traffic control decisions.

  15. A new method for the re-implementation of threshold logic functions with cellular neural networks.

    Science.gov (United States)

    Bénédic, Y; Wira, P; Mercklé, J

    2008-08-01

    A new strategy is presented for the implementation of threshold logic functions with binary-output Cellular Neural Networks (CNNs). The objective is to optimize the CNNs weights to develop a robust implementation. Hence, the concept of generative set is introduced as a convenient representation of any linearly separable Boolean function. Our analysis of threshold logic functions leads to a complete algorithm that automatically provides an optimized generative set. New weights are deduced and a more robust CNN template assuming the same function can thus be implemented. The strategy is illustrated by a detailed example.

  16. Function of Membrane Rafts in Viral Lifecycles and Host Cellular Response

    Directory of Open Access Journals (Sweden)

    Tadanobu Takahashi

    2011-01-01

    Full Text Available Membrane rafts are small (10–200 nm sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Membrane rafts play an important role in viral infection cycles and viral virulence. Viruses are divided into four main classes, enveloped DNA virus, enveloped RNA virus, nonenveloped DNA virus, and nonenveloped RNA virus. General virus infection cycle is also classified into two sections, the early stage (entry process and the late stage (assembly, budding, and release processes of virus particles. In the viral cycle, membrane rafts act as a scaffold of many cellular signal transductions, which are associated with symptoms caused by viral infections. In this paper, we describe the functions of membrane rafts in viral lifecycles and host cellular response according to each virus classification, each stage of the virus lifecycle, and each virus-induced signal transduction.

  17. A novel adaptive joint power control algorithm with channel estimation in a CDMA cellular system

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Joint power control has advantages of multi-user detection and power control; and it can combat the multi-access interference and the near-far problem. A novel adaptive joint power control algorithm with channel estimation in a CDMA cellular system was designed. Simulation results show that the algorithm can control the power not only quickly but also precisely with a time change. The method is useful for increasing system capacity.

  18. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins.

    Science.gov (United States)

    Michishita, Eriko; Park, Jean Y; Burneskis, Jenna M; Barrett, J Carl; Horikawa, Izumi

    2005-10-01

    Sir2 is a NAD+-dependent protein deacetylase that extends lifespan in yeast and worms. This study examines seven human proteins homologous to Sir2 (SIRT1 through SIRT7) for cellular localization, expression profiles, protein deacetylation activity, and effects on human cell lifespan. We found that: 1) three nuclear SIRT proteins (SIRT1, SIRT6, and SIRT7) show different subnuclear localizations: SIRT6 and SIRT7 are associated with heterochromatic regions and nucleoli, respectively, where yeast Sir2 functions; 2) SIRT3, SIRT4, and SIRT5 are localized in mitochondria, an organelle that links aging and energy metabolism; 3) cellular p53 is a major in vivo substrate of SIRT1 deacetylase, but not the other six SIRT proteins; 4) SIRT1, but not the other two nuclear SIRT proteins, shows an in vitro deacetylase activity on histone H4 and p53 peptides; and 5) overexpression of any one of the seven SIRT proteins does not extend cellular replicative lifespan in normal human fibroblasts or prostate epithelial cells. This study supports the notion that multiple human SIRT proteins have evolutionarily conserved and nonconserved functions at different cellular locations and reveals that the lifespan of normal human cells, in contrast to that of lower eukaryotes, cannot be manipulated by increased expression of a single SIRT protein.

  19. SCA1+ Cells from the Heart Possess a Molecular Circadian Clock and Display Circadian Oscillations in Cellular Functions

    Directory of Open Access Journals (Sweden)

    Bastiaan C. Du Pré

    2017-09-01

    Full Text Available Stem cell antigen 1-positive (SCA1+ cells (SPCs have been investigated in cell-based cardiac repair and pharmacological research, although improved cardiac function after injection has been variable and the mode of action remains unclear. Circadian (24-hr rhythms are biorhythms regulated by molecular clocks that play an important role in (pathophysiology. Here, we describe (1 the presence of a molecular circadian clock in SPCs and (2 circadian rhythmicity in SPC function. We isolated SPCs from human fetal heart and found that these cells possess a molecular clock based on typical oscillations in core clock components BMAL1 and CRY1. Functional analyses revealed that circadian rhythmicity also governs SPC proliferation, stress tolerance, and growth factor release, with large differences between peaks and troughs. We conclude that SPCs contain a circadian molecular clock that controls crucial cellular functions. Taking circadian rhythms into account may improve reproducibility and outcome of research and therapies using SPCs.

  20. Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich ataxia.

    Directory of Open Access Journals (Sweden)

    Sara Anjomani Virmouni

    Full Text Available Friedreich ataxia (FRDA is an autosomal recessive neurodegenerative disorder, caused by a GAA repeat expansion mutation within intron 1 of the FXN gene. We have previously established and performed preliminary characterisation of several human FXN yeast artificial chromosome (YAC transgenic FRDA mouse models containing GAA repeat expansions, Y47R (9 GAA repeats, YG8R (90 and 190 GAA repeats and YG22R (190 GAA repeats.We now report extended cellular, molecular and functional characterisation of these FXN YAC transgenic mouse models. FXN transgene copy number analysis of the FRDA mice demonstrated that the YG22R and Y47R lines each have a single copy of the FXN transgene while the YG8R line has two copies. Single integration sites of all transgenes were confirmed by fluorescence in situ hybridisation (FISH analysis of metaphase and interphase chromosomes. We identified significant functional deficits, together with a degree of glucose intolerance and insulin hypersensitivity, in YG8R and YG22R FRDA mice compared to Y47R and wild-type control mice. We also confirmed increased somatic GAA repeat instability in the cerebellum and brain of YG22R and YG8R mice, together with significantly reduced levels of FXN mRNA and protein in the brain and liver of YG8R and YG22R compared to Y47R.Together these studies provide a detailed characterisation of our GAA repeat expansion-based YAC transgenic FRDA mouse models that will help investigations of FRDA disease mechanisms and therapy.

  1. Active Control of Cellular Orientation through In-Situ Stress in the Substrate

    Institute of Scientific and Technical Information of China (English)

    WU Heng-An; WANG Xiu-Xi; YAN Shun-Ping

    2007-01-01

    We investigate the orientation of cells on substrates to find possible methods for controlling the cellular orientation.The force dipole model is employed in our modelling and simulation.The elastic interaction between cells as well as the elastic interaction between the cell and in-situ stress field in the substrate are found to be the two main physical mechanisms to control the cellular orientation,The former interaction dominates the cellular orientation when the in-situ stress is small.while the later dominates when the in-situ stress is large enough.Two cells tend to align perpendicularly on a free substrate,but the cellular orientation varies with the increasing in-situ stress.Two cells tend to align in parallel when the normal stress is large enough.Their direction is perpendicular to the extension stress direction or parallel to the compression stress direction.When the positive in-situ shear stress is large enough,the two cells tend to align at-45°.Based on this theoretical simulation,it is believed that the cellular orientation on substrates can be controlled by the in-situ stresses.

  2. The Cellular Prion Protein Controls Notch Signaling in Neural Stem/Progenitor Cells.

    Science.gov (United States)

    Martin-Lannerée, Séverine; Halliez, Sophie; Hirsch, Théo Z; Hernandez-Rapp, Julia; Passet, Bruno; Tomkiewicz, Céline; Villa-Diaz, Ana; Torres, Juan-Maria; Launay, Jean-Marie; Béringue, Vincent; Vilotte, Jean-Luc; Mouillet-Richard, Sophie

    2017-03-01

    The prion protein is infamous for its involvement in a group of neurodegenerative diseases known as Transmissible Spongiform Encephalopathies. In the longstanding quest to decipher the physiological function of its cellular isoform, PrP(C) , the discovery of its participation to the self-renewal of hematopoietic and neural stem cells has cast a new spotlight on its potential role in stem cell biology. However, still little is known on the cellular and molecular mechanisms at play. Here, by combining in vitro and in vivo murine models of PrP(C) depletion, we establish that PrP(C) deficiency severely affects the Notch pathway, which plays a major role in neural stem cell maintenance. We document that the absence of PrP(C) in a neuroepithelial cell line or in primary neurospheres is associated with drastically reduced expression of Notch ligands and receptors, resulting in decreased levels of Notch target genes. Similar alterations of the Notch pathway are recovered in the neuroepithelium of Prnp(-/-) embryos during a developmental window encompassing neural tube closure. In addition, in line with Notch defects, our data show that the absence of PrP(C) results in altered expression of Nestin and Olig2 as well as N-cadherin distribution. We further provide evidence that PrP(C) controls the expression of the epidermal growth factor receptor (EGFR) downstream from Notch. Finally, we unveil a negative feedback action of EGFR on both Notch and PrP(C) . As a whole, our study delineates a molecular scenario through which PrP(C) takes part to the self-renewal of neural stem and progenitor cells. Stem Cells 2017;35:754-765.

  3. Effect of liniment levamisole on cellular immune functions of patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Ke-Xia Wang; Li-Hua Zhang; Jiang-Long Peng; Yong Liang; Xue-Feng Wang; Hui Zhi; Xiang-Xia Wang; Huan-Xiong Geng

    2005-01-01

    AIM: To explore the effects of liniment levamisole on cellular immune functions of patients with chronic hepatitis B.METHODS: The levels of T lymphocyte subsets and mlL-2R in peripheral blood mononuclear cells (PBMCs)were measured by biotin-streptavidin (BSA) technique in patients with chronic hepatitis B before and after the treatment with liniment levamisole.RESULTS: After one course of treatment with liniment levamisole, the levels of CD3+, CD4+, and the ratio of CD4+/CD8+ increased as compared to those before the treatment but the level of CD8+ decreased. The total expression level of mIL-2R in PBMCs increased before and after the treatment with liniment levamisole.CONCLUSION: Liniment levamisole may reinforce cellular immune functions of patients with chronic hepatitis B.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  5. Least dissipation cost as a design principle for robustness and function of cellular networks

    Science.gov (United States)

    Han, Bo; Wang, Jin

    2008-03-01

    From a study of the budding yeast cell cycle, we found that the cellular network evolves to have the least cost for realizing its biological function. We quantify the cost in terms of the dissipation or heat loss characterized through the steady-state properties: the underlying landscape and the associated flux. We found that the dissipation cost is intimately related to the stability and robustness of the network. With the least dissipation cost, the network becomes most stable and robust under mutations and perturbations on the sharpness of the response from input to output as well as self-degradations. The least dissipation cost may provide a general design principle for the cellular network to survive from the evolution and realize the biological function.

  6. Copper transporters and chaperones: Their function on angiogenesis and cellular signalling

    Indian Academy of Sciences (India)

    SR BHARATHI DEVI; DHIVYA M ALOYSIUS; KN SULOCHANA

    2016-09-01

    Copper, although known as a micronutrient, has a pivotal role in modulating the cellular metabolism. Many studieshave reported the role of copper in angiogenesis. Copper chaperones are intracellular proteins that mediate coppertrafficking to various cell organelles. However, the role and function of copper chaperones in relation to angiogenesishas to be further explored. The intracellular copper levels when in excess are deleterious and certain mutations ofcopper chaperones have been shown to induce cell death and influence various cellular metabolisms. The study ofthese chaperones will be helpful in understanding the players in the cascade of events in angiogenesis and their role incellular metabolic pathways. In this review we have briefly listed the copper chaperones associated with angiogenicand metabolic signalling and their function.

  7. Cellular therapy of tumor angiogenesis : morphological and functional imaging using MRI and videomicroscopy

    OpenAIRE

    Faye, Nathalie

    2011-01-01

    Introduction : Tumor angiogenesis leads to the development of new vessels enabling the growth of the tumor. Tumor vessels are characterized by abnormalities including mural cells (perivascular muscular cells) responsible for abnormal vessel function and maturation. In this thesis, we studied cellular therapy in a tumor model by injection of mural cells using MRI and fluorescence videomicroscopy. Materiels and methods: Nude mice were injected with squamous cell TC1 tumors and animals were divi...

  8. Power Control for D2D Underlay Cellular Networks with Imperfect CSI

    KAUST Repository

    Memmi, Amen

    2017-02-09

    Device-to-Device communications underlying the cellular infrastructure is a technology that has recently been proposed as a promising solution to enhance cellular network capabilities. However, interference is the major challenge since the same resources are shared by both systems. Therefore, interference management techniques are required to keep the interference under control. In this work, in order to mitigate interference, we consider centralized and distributed power control algorithms in a one-cell random network model. Differently from previous works, we are assuming that the channel state information may be imperfect and include estimation errors. We evaluate how this uncertainty impacts performances. In the centralized approach, we derive the optimal powers that maximize the coverage probability and the rate of the cellular user while scheduling as many D2D links as possible. These powers are computed at the base station (BS) and then delivered to the users, and hence the name

  9. Therapeutic intervention at cellular quality control systems in Alzheimer's and Parkinson's diseases.

    Science.gov (United States)

    Arduino, Daniela M; Esteves, A Raquel; Silva, Diana F F; Martins-Branco, Diogo; Santos, Daniel; Pimentel, Diana F Gomes; Cardoso, Sandra M

    2011-01-01

    Cellular homeostasis relies on quality control systems so that damaged biologic structures are either repaired or degraded and entirely replaced by newly formed proteins or even organelles. The clearance of dysfunctional cellular structures in long-lived postmitotic cells, like neurons, is essential to eliminate, per example, defective mitochondria, lipofuscin-loaded lysosomes and oxidized proteins. Short-lived proteins are degraded mainly by proteases and proteasomes whether most long-lived proteins and all organelles are digested by autophagy in the lysosomes. Recently, it an interplay was established between the ubiquitin-proteasome system and macroautophagy, so that both degradative mechanisms compensate for each other. In this article we describe each of these clearance systems and their contribution to neuronal quality control. We will highlight some of the findings that provide evidence for the dysfunction of these systems in Alzheimer's and Parkinson's diseases. Ultimately, we provide an outline on potential therapeutic interventions based on the modulation of cellular degradative systems.

  10. Cell size control - a mechanism for maintaining fitness and function.

    Science.gov (United States)

    Miettinen, Teemu P; Caldez, Matias J; Kaldis, Philipp; Björklund, Mikael

    2017-09-01

    The maintenance of cell size homeostasis has been studied for years in different cellular systems. With the focus on 'what regulates cell size', the question 'why cell size needs to be maintained' has been largely overlooked. Recent evidence indicates that animal cells exhibit nonlinear cell size dependent growth rates and mitochondrial metabolism, which are maximal in intermediate sized cells within each cell population. Increases in intracellular distances and changes in the relative cell surface area impose biophysical limitations on cells, which can explain why growth and metabolic rates are maximal in a specific cell size range. Consistently, aberrant increases in cell size, for example through polyploidy, are typically disadvantageous to cellular metabolism, fitness and functionality. Accordingly, cellular hypertrophy can potentially predispose to or worsen metabolic diseases. We propose that cell size control may have emerged as a guardian of cellular fitness and metabolic activity. © 2017 WILEY Periodicals, Inc.

  11. Soil restoration with organic amendments: linking cellular functionality and ecosystem processes

    Science.gov (United States)

    Bastida, F.; Selevsek, N.; Torres, I. F.; Hernández, T.; García, C.

    2015-10-01

    A hot topic in recent decades, the application of organic amendments to arid-degraded soils has been shown to benefit microbially-mediated processes. However, despite the importance of soils for global sustainability, a gap has not been addressed yet in soil science: is there any connection between ecosystem-community processes, cellular functionality, and microbial lifestyles (i.e. oligotrophy-copiotrophy) in restored soils? Together with classical ecosystem indicators (fatty-acids, extracellular-enzyme activities, basal respiration), state-of-the-art metaproteomics was applied to fill this gap in a model-restoration experiment initiated 10-years ago by the addition of sewage-sludge and compost. Organic amendment strongly impacted ecosystem processes. Furthermore, the type of material used induced differences in the cellular functionalities through variations in the percentages of proteins involved in translation, transcription, energy production and C-fixation. We conclude that the long-term impact of organic restoration goes beyond ecosystem processes and affects cellular functionalities and phyla-lifestyles coupled with differences in microbial-community structures.

  12. Functions of the cellular prion protein, the end of Moore's law, and Ockham's razor theory.

    Science.gov (United States)

    del Río, José A; Gavín, Rosalina

    2016-01-01

    Since its discovery the cellular prion protein (encoded by the Prnp gene) has been associated with a large number of functions. The proposed functions rank from basic cellular processes such as cell cycle and survival to neural functions such as behavior and neuroprotection, following a pattern similar to that of Moore's law for electronics. In addition, particular interest is increasing in the participation of Prnp in neurodegeneration. However, in recent years a redefinition of these functions has begun, since examples of previously attributed functions were increasingly re-associated with other proteins. Most of these functions are linked to so-called "Prnp-flanking genes" that are close to the genomic locus of Prnp and which are present in the genome of some Prnp mouse models. In addition, their role in neuroprotection against convulsive insults has been confirmed in recent studies. Lastly, in recent years a large number of models indicating the participation of different domains of the protein in apoptosis have been uncovered. However, after more than 10 years of molecular dissection our view is that the simplest mechanistic model in PrP(C)-mediated cell death should be considered, as Ockham's razor theory suggested.

  13. Cellular protein quality control and the evolution of aggregates in spinocerebellar ataxia type 3 (SCA3)

    NARCIS (Netherlands)

    Seidel, K.; Meister, M.; Dugbartey, G. J.; Zijlstra, M. P.; Vinet, J.; Brunt, E. R. P.; van Leeuwen, F. W.; Rueb, U.; Kampinga, H. H.; den Dunnen, W. F. A.

    2012-01-01

    K. Seidel, M. Meister, G. J. Dugbartey, M. P. Zijlstra, J. Vinet, E. R. P. Brunt, F. W. van Leeuwen, U. Rub, H. H. Kampinga and W. F. A. den Dunnen (2012) Neuropathology and Applied Neurobiology38, 548558 Cellular protein quality control and the evolution of aggregates in spinocerebellar ataxia type

  14. Robust Template Decomposition without Weight Restriction for Cellular Neural Networks Implementing Arbitrary Boolean Functions Using Support Vector Classifiers

    Directory of Open Access Journals (Sweden)

    Yih-Lon Lin

    2013-01-01

    Full Text Available If the given Boolean function is linearly separable, a robust uncoupled cellular neural network can be designed as a maximal margin classifier. On the other hand, if the given Boolean function is linearly separable but has a small geometric margin or it is not linearly separable, a popular approach is to find a sequence of robust uncoupled cellular neural networks implementing the given Boolean function. In the past research works using this approach, the control template parameters and thresholds are restricted to assume only a given finite set of integers, and this is certainly unnecessary for the template design. In this study, we try to remove this restriction. Minterm- and maxterm-based decomposition algorithms utilizing the soft margin and maximal margin support vector classifiers are proposed to design a sequence of robust templates implementing an arbitrary Boolean function. Several illustrative examples are simulated to demonstrate the efficiency of the proposed method by comparing our results with those produced by other decomposition methods with restricted weights.

  15. Coordinated function of cellular DEAD-box helicases in suppression of viral RNA recombination and maintenance of viral genome integrity.

    Directory of Open Access Journals (Sweden)

    Chingkai Chuang

    2015-02-01

    Full Text Available The intricate interactions between viruses and hosts include an evolutionary arms race and adaptation that is facilitated by the ability of RNA viruses to evolve rapidly due to high frequency mutations and genetic RNA recombination. In this paper, we show evidence that the co-opted cellular DDX3-like Ded1 DEAD-box helicase suppresses tombusviral RNA recombination in yeast model host, and the orthologous RH20 helicase functions in a similar way in plants. In vitro replication and recombination assays confirm the direct role of the ATPase function of Ded1p in suppression of viral recombination. We also present data supporting a role for Ded1 in facilitating the switch from minus- to plus-strand synthesis. Interestingly, another co-opted cellular helicase, the eIF4AIII-like AtRH2, enhances TBSV recombination in the absence of Ded1/RH20, suggesting that the coordinated actions of these helicases control viral RNA recombination events. Altogether, these helicases are the first co-opted cellular factors in the viral replicase complex that directly affect viral RNA recombination. Ded1 helicase seems to be a key factor maintaining viral genome integrity by promoting the replication of viral RNAs with correct termini, but inhibiting the replication of defective RNAs lacking correct 5' end sequences. Altogether, a co-opted cellular DEAD-box helicase facilitates the maintenance of full-length viral genome and suppresses viral recombination, thus limiting the appearance of defective viral RNAs during replication.

  16. One-way hash function based on hyper-chaotic cellular neural network

    Institute of Scientific and Technical Information of China (English)

    Yang Qun-Ting; Gao Tie-Gang

    2008-01-01

    The design of an efficient one-way hash function with good performance is a hot spot in modern cryptography researches. In this paper, a hash function construction method based on cell neural network with hyper-chaos characteristics is proposed. First, the chaos sequence is gotten by iterating cellular neural network with Runge-Kutta algorithm, and then the chaos sequence is iterated with the message. The hash code is obtained through the corresponding transform of the latter chaos sequence. Simulation and analysis demonstrate that the new method has the merit of convenience, high sensitivity to initial values, good hash performance, especially the strong stability.

  17. Picornaviruses and nuclear functions: targeting a cellular compartment distinct from the replication site of a positive-strand RNA virus

    Directory of Open Access Journals (Sweden)

    Dylan eFlather

    2015-06-01

    Full Text Available The compartmentalization of DNA replication and gene transcription in the nucleus and protein production in the cytoplasm is a defining feature of eukaryotic cells. The nucleus functions to maintain the integrity of the nuclear genome of the cell and to control gene expression based on intracellular and environmental signals received through the cytoplasm. The spatial separation of the major processes that lead to the expression of protein-coding genes establishes the necessity of a transport network to allow biomolecules to translocate between these two regions of the cell. The nucleocytoplasmic transport network is therefore essential for regulating normal cellular functioning. The Picornaviridae virus family is one of many viral families that disrupt the nucleocytoplasmic trafficking of cells to promote viral replication. Picornaviruses contain positive-sense, single-stranded RNA genomes and replicate in the cytoplasm of infected cells. As a result of the limited coding capacity of these viruses, cellular proteins are required by these intracellular parasites for both translation and genomic RNA replication. Being of messenger RNA polarity, a picornavirus genome can immediately be translated upon entering the cell cytoplasm. However, the replication of viral RNA requires the activity of RNA-binding proteins, many of which function in host gene expression, and are consequently localized to the nucleus. As a result, picornaviruses disrupt nucleocytoplasmic trafficking to exploit protein functions normally localized to a different cellular compartment from which they translate their genome to facilitate efficient replication. Furthermore, picornavirus proteins are also known to enter the nucleus of infected cells to limit host-cell transcription and down-regulate innate antiviral responses. The interactions of picornavirus proteins and host-cell nuclei are extensive, required for a productive infection, and are the focus of this review.

  18. Picornaviruses and nuclear functions: targeting a cellular compartment distinct from the replication site of a positive-strand RNA virus.

    Science.gov (United States)

    Flather, Dylan; Semler, Bert L

    2015-01-01

    The compartmentalization of DNA replication and gene transcription in the nucleus and protein production in the cytoplasm is a defining feature of eukaryotic cells. The nucleus functions to maintain the integrity of the nuclear genome of the cell and to control gene expression based on intracellular and environmental signals received through the cytoplasm. The spatial separation of the major processes that lead to the expression of protein-coding genes establishes the necessity of a transport network to allow biomolecules to translocate between these two regions of the cell. The nucleocytoplasmic transport network is therefore essential for regulating normal cellular functioning. The Picornaviridae virus family is one of many viral families that disrupt the nucleocytoplasmic trafficking of cells to promote viral replication. Picornaviruses contain positive-sense, single-stranded RNA genomes and replicate in the cytoplasm of infected cells. As a result of the limited coding capacity of these viruses, cellular proteins are required by these intracellular parasites for both translation and genomic RNA replication. Being of messenger RNA polarity, a picornavirus genome can immediately be translated upon entering the cell cytoplasm. However, the replication of viral RNA requires the activity of RNA-binding proteins, many of which function in host gene expression, and are consequently localized to the nucleus. As a result, picornaviruses disrupt nucleocytoplasmic trafficking to exploit protein functions normally localized to a different cellular compartment from which they translate their genome to facilitate efficient replication. Furthermore, picornavirus proteins are also known to enter the nucleus of infected cells to limit host-cell transcription and down-regulate innate antiviral responses. The interactions of picornavirus proteins and host-cell nuclei are extensive, required for a productive infection, and are the focus of this review.

  19. Calibrating floor field cellular automaton models for pedestrian dynamics by using likelihood function optimization

    Science.gov (United States)

    Lovreglio, Ruggiero; Ronchi, Enrico; Nilsson, Daniel

    2015-11-01

    The formulation of pedestrian floor field cellular automaton models is generally based on hypothetical assumptions to represent reality. This paper proposes a novel methodology to calibrate these models using experimental trajectories. The methodology is based on likelihood function optimization and allows verifying whether the parameters defining a model statistically affect pedestrian navigation. Moreover, it allows comparing different model specifications or the parameters of the same model estimated using different data collection techniques, e.g. virtual reality experiment, real data, etc. The methodology is here implemented using navigation data collected in a Virtual Reality tunnel evacuation experiment including 96 participants. A trajectory dataset in the proximity of an emergency exit is used to test and compare different metrics, i.e. Euclidean and modified Euclidean distance, for the static floor field. In the present case study, modified Euclidean metrics provide better fitting with the data. A new formulation using random parameters for pedestrian cellular automaton models is also defined and tested.

  20. Controlling Cell Function with Geometry

    Science.gov (United States)

    Mrksich, Milan

    2012-02-01

    This presentation will describe the use of patterned substrates to control cell shape with examples that illustrate the ways in which cell shape can regulate cell function. Most cells are adherent and must attach to and spread on a surface in order to survive, proliferate and function. In tissue, this surface is the extracellular matrix (ECM), an insoluble scaffold formed by the assembly of several large proteins---including fibronectin, the laminins and collagens and others---but in the laboratory, the surface is prepared by adsorbing protein to glass slides. To pattern cells, gold-coated slides are patterned with microcontact printing to create geometric features that promote cell attachment and that are surrounded by inert regions. Cells attach to these substrates and spread to adopt the shape defined by the underlying pattern and remain stable in culture for several days. Examples will be described that used a series of shapes to reveal the relationship between the shape of the cell and the structure of its cytoskeleton. These geometric cues were used to control cell polarity and the tension, or contractility, present in the cytoskeleton. These rules were further used to control the shapes of mesenchymal stem cells and in turn to control the differentiation of these cells into specialized cell types. For example, stem cells that were patterned into a ``star'' shape preferentially differentiated into bone cells whereas those that were patterned into a ``flower'' shape preferred a fat cell fate. These influences of shape on differentiation depend on the mechanical properties of the cytoskeleton. These examples, and others, reveal that shape is an important cue that informs cell function and that can be combined with the more common soluble cues to direct and study cell function.

  1. New structural and functional defects in polyphosphate deficient bacteria: A cellular and proteomic study

    Directory of Open Access Journals (Sweden)

    Chávez Francisco P

    2010-01-01

    Full Text Available Abstract Background Inorganic polyphosphate (polyP, a polymer of tens or hundreds of phosphate residues linked by ATP-like bonds, is found in all organisms and performs a wide variety of functions. PolyP is synthesized in bacterial cells by the actions of polyphosphate kinases (PPK1 and PPK2 and degraded by exopolyphosphatase (PPX. Bacterial cells with polyP deficiencies due to knocking out the ppk1 gene are affected in many structural and important cellular functions such as motility, quorum sensing, biofilm formation and virulence among others. The cause of this pleiotropy is not entirely understood. Results The overexpression of exopolyphosphatase in bacteria mimicked some pleitropic defects found in ppk1 mutants. By using this approach we found new structural and functional defects in the polyP-accumulating bacteria Pseudomonas sp. B4, which are most likely due to differences in the polyP-removal strategy. Colony morphology phenotype, lipopolysaccharide (LPS structure changes and cellular division malfunction were observed. Finally, we used comparative proteomics in order to elucidate the cellular adjustments that occurred during polyP deficiency in this bacterium and found some clues that helped to understand the structural and functional defects observed. Conclusions The results obtained suggest that during polyP deficiency energy metabolism and particularly nucleoside triphosphate (NTP formation were affected and that bacterial cells overcame this problem by increasing the flux of energy-generating metabolic pathways such as tricarboxilic acid (TCA cycle, β-oxidation and oxidative phosphorylation and by reducing energy-consuming ones such as active transporters and amino acid biosynthesis. Furthermore, our results suggest that a general stress response also took place in the cell during polyP deficiency.

  2. Emerging Microfluidic Tools for Functional Cellular Immunophenotyping: A New Potential Paradigm for Immune Status Characterization

    Directory of Open Access Journals (Sweden)

    Weiqiang eChen

    2013-04-01

    Full Text Available Rapid, accurate, and quantitative characterization of immune status of patients is of utmost importance for disease diagnosis and prognosis, evaluating efficacy of immunotherapeutics and tailoring drug treatments. Immune status of patients is often dynamic and patient-specific, and such complex heterogeneity has made accurate, real-time measurements of patient immune status challenging in the clinical setting. Recent advances in microfluidics have demonstrated promising applications of microfluidics for immune monitoring with minimum sample requirement and rapid functional immunophenotyping capability. This review will highlight recent developments of microfluidic platforms that can perform rapid and accurate cellular functional assays on patient immune cells. We will also discuss the future potential of integrated microfluidics to perform rapid, accurate, and sensitive cellular functional assays at a single-cell resolution on different types or subpopulations of immune cells, to provide an unprecedented level of information depth on the distribution of immune cell functionalities. We envision that such microfluidic immunophenotyping tools will allow comprehensive and systems-level immunomonitoring, unlocking the potential to transform experimental clinical immunology into an information-rich science.

  3. The interplay between p16 serine phosphorylation and arginine methylation determines its function in modulating cellular apoptosis and senescence.

    Science.gov (United States)

    Lu, Yang; Ma, Wenlong; Li, Zhongwei; Lu, Jun; Wang, Xiuli

    2017-01-25

    Cyclin-dependent kinase inhibitor p16(INK4a) (p16) primarily functions as a negative regulator of the retinoblastoma protein (Rb) -E2F pathway, thus plays critical role in cell cycle progression, cellular senescence and apoptosis. In this study, we showed that the methylation of Arg 138 and the phosphorylation of Ser 140 on p16 were critical for the control of cell proliferation and apoptosis. Compared to wild type p16, mutant p16R138K possessed improved function in preventing cell proliferation and inducing apoptosis, while the Ser 140 mutation (p16S140A) exhibited the opposite alteration. We also demonstrated that H2O2 was able to induce the phosphorylation of p16, which facilitated the interaction between CDK4 (Cyclin-dependent protein kinase) and p16, in 293T (human emborynic kidney) cells. Furthermore, the elevated arginine methylation in p16S140A mutant and increased serine phosphorylation in p16R138K mutant suggest that a antagonizing mechanism coordinating Arg 138 methylation and Ser 140 phosphorylation to regulates p16 function as well as cellular apoptosis and senescence. These findings will therefore contribute to therapeutic treatment for p16-related gene therapy by providing theoretical and experimental evidence.

  4. Generation and precise control of dynamic biochemical gradients for cellular assays

    CERN Document Server

    Saka, Yasushi; Giuraniuc, Claudiu V

    2016-01-01

    Spatial gradients of diffusible signalling molecules play crucial roles in controlling diverse cellular behaviour such as cell differentiation, tissue patterning and chemotaxis. Here we present a microfluidic platform for cellular assays that can generate and control diffusion-based gradients dynamically. A unique design of the device eliminates cross-flow between the source and sink channels, thereby stabilising gradients by passive diffusion. The platform also enables quick and flexible control of chemical concentration that makes highly dynamic gradients in diffusion chambers. Budding yeast cells cultured in a gradient of a chemical inducer expressed a reporter fluorescence protein in a concentration-dependent manner. This microfluidic platform serves as a versatile prototype applicable to a broad range of biomedical investigations.

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

    Directory of Open Access Journals (Sweden)

    Thomas Wallach

    2013-03-01

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

  6. Hijacking of host cellular functions by an intracellular parasite, the microsporidian Anncaliia algerae.

    Science.gov (United States)

    Panek, Johan; El Alaoui, Hicham; Mone, Anne; Urbach, Serge; Demettre, Edith; Texier, Catherine; Brun, Christine; Zanzoni, Andreas; Peyretaillade, Eric; Parisot, Nicolas; Lerat, Emmanuelle; Peyret, Pierre; Delbac, Frederic; Biron, David G

    2014-01-01

    Intracellular pathogens including bacteria, viruses and protozoa hijack host cell functions to access nutrients and to bypass cellular defenses and immune responses. These strategies have been acquired through selective pressure and allowed pathogens to reach an appropriate cellular niche for their survival and growth. To get new insights on how parasites hijack host cellular functions, we developed a SILAC (Stable Isotope Labeling by Amino Acids in Cell culture) quantitative proteomics workflow. Our study focused on deciphering the cross-talk in a host-parasite association, involving human foreskin fibroblasts (HFF) and the microsporidia Anncaliia algerae, a fungus related parasite with an obligate intracellular lifestyle and a strong host dependency. The host-parasite cross-talk was analyzed at five post-infection times 1, 6, 12 and 24 hours post-infection (hpi) and 8 days post-infection (dpi). A significant up-regulation of four interferon-induced proteins with tetratricopeptide repeats IFIT1, IFIT2, IFIT3 and MX1 was observed at 8 dpi suggesting a type 1 interferon (IFN) host response. Quantitative alteration of host proteins involved in biological functions such as signaling (STAT1, Ras) and reduction of the translation activity (EIF3) confirmed a host type 1 IFN response. Interestingly, the SILAC approach also allowed the detection of 148 A. algerae proteins during the kinetics of infection. Among these proteins many are involved in parasite proliferation, and an over-representation of putative secreted effectors proteins was observed. Finally our survey also suggests that A. algerae could use a transposable element as a lure strategy to escape the host innate immune system.

  7. Hijacking of host cellular functions by an intracellular parasite, the microsporidian Anncaliia algerae.

    Directory of Open Access Journals (Sweden)

    Johan Panek

    Full Text Available Intracellular pathogens including bacteria, viruses and protozoa hijack host cell functions to access nutrients and to bypass cellular defenses and immune responses. These strategies have been acquired through selective pressure and allowed pathogens to reach an appropriate cellular niche for their survival and growth. To get new insights on how parasites hijack host cellular functions, we developed a SILAC (Stable Isotope Labeling by Amino Acids in Cell culture quantitative proteomics workflow. Our study focused on deciphering the cross-talk in a host-parasite association, involving human foreskin fibroblasts (HFF and the microsporidia Anncaliia algerae, a fungus related parasite with an obligate intracellular lifestyle and a strong host dependency. The host-parasite cross-talk was analyzed at five post-infection times 1, 6, 12 and 24 hours post-infection (hpi and 8 days post-infection (dpi. A significant up-regulation of four interferon-induced proteins with tetratricopeptide repeats IFIT1, IFIT2, IFIT3 and MX1 was observed at 8 dpi suggesting a type 1 interferon (IFN host response. Quantitative alteration of host proteins involved in biological functions such as signaling (STAT1, Ras and reduction of the translation activity (EIF3 confirmed a host type 1 IFN response. Interestingly, the SILAC approach also allowed the detection of 148 A. algerae proteins during the kinetics of infection. Among these proteins many are involved in parasite proliferation, and an over-representation of putative secreted effectors proteins was observed. Finally our survey also suggests that A. algerae could use a transposable element as a lure strategy to escape the host innate immune system.

  8. Comprehensive interrogation of the cellular response to fluorescent, detonation and functionalized nanodiamonds

    Science.gov (United States)

    Moore, Laura; Grobárová, Valéria; Shen, Helen; Man, Han Bin; Míčová, Júlia; Ledvina, Miroslav; Štursa, Jan; Nesladek, Milos; Fišerová, Anna; Ho, Dean

    2014-09-01

    Nanodiamonds (NDs) are versatile nanoparticles that are currently being investigated for a variety of applications in drug delivery, biomedical imaging and nanoscale sensing. Although initial studies indicate that these small gems are biocompatible, there is a great deal of variability in synthesis methods and surface functionalization that has yet to be evaluated. Here we present a comprehensive analysis of the cellular compatibility of an array of nanodiamond subtypes and surface functionalization strategies. These results demonstrate that NDs are well tolerated by multiple cell types at both functional and gene expression levels. In addition, ND-mediated delivery of daunorubicin is less toxic to multiple cell types than treatment with daunorubicin alone, thus demonstrating the ability of the ND agent to improve drug tolerance and decrease therapeutic toxicity. Overall, the results here indicate that ND biocompatibility serves as a promising foundation for continued preclinical investigation.

  9. Comprehensive interrogation of the cellular response to fluorescent, detonation and functionalized nanodiamonds.

    Science.gov (United States)

    Moore, Laura; Grobárová, Valéria; Shen, Helen; Man, Han Bin; Míčová, Júlia; Ledvina, Miroslav; Štursa, Jan; Nesladek, Milos; Fišerová, Anna; Ho, Dean

    2014-10-21

    Nanodiamonds (NDs) are versatile nanoparticles that are currently being investigated for a variety of applications in drug delivery, biomedical imaging and nanoscale sensing. Although initial studies indicate that these small gems are biocompatible, there is a great deal of variability in synthesis methods and surface functionalization that has yet to be evaluated. Here we present a comprehensive analysis of the cellular compatibility of an array of nanodiamond subtypes and surface functionalization strategies. These results demonstrate that NDs are well tolerated by multiple cell types at both functional and gene expression levels. In addition, ND-mediated delivery of daunorubicin is less toxic to multiple cell types than treatment with daunorubicin alone, thus demonstrating the ability of the ND agent to improve drug tolerance and decrease therapeutic toxicity. Overall, the results here indicate that ND biocompatibility serves as a promising foundation for continued preclinical investigation.

  10. Cellular and functional aspects of the renal kallikrein system in health and disease.

    Science.gov (United States)

    Vio, C P; Olavarría, V; González, C; Nazal, L; Córdova, M; Balestrini, C

    1998-01-01

    The kallikrein kinin system is a tissue-derived system with potent renal and cardiovascular effects. Within the kidney, the components of the kallikrein kinin system (kallikrein, kininogen, kinins, kininases, kinin receptors and mediators/modulators) originate from or are located in discrete segments of the nephron in highly specialized cells which determine its physiological effects. The kallikrein system acts on the kidney in a paracrine fashion in two anatomical microenvironments where the system regulates glomerular function, renal hemodynamics, and salt and water excretion. Impairment of the renal kallikrein system contributes to the development of hypertension, in particular to the salt-sensitive hypertension, and other pathologies like diabetes. There are several links between the vasodepressor kallikrein system and the vasopressor renin system which are relevant to normal renal function and to the pathophysiology of hypertension and renal diseases. Local induction of kininase II or angiotensin converting enzyme in the kidney could be a novel mechanism contributing to the renal damage in hypertension and other renal diseases. This review evaluates cellular and functional aspects of the renal kallikrein system with emphasis placed on the cellular localization of its components along the nephron, the links to other vasoactive systems, and the contribution of the system to the pathogenesis of hypertension.

  11. Functional recognition imaging using artificial neural networks: applications to rapid cellular identification via broadband electromechanical response

    Energy Technology Data Exchange (ETDEWEB)

    Nikiforov, M P; Guo, S; Kalinin, S V; Jesse, S [Oak Ridge National Laboratory (ORNL), Oak Ridge, TN 37831 (United States); Reukov, V V; Thompson, G L; Vertegel, A A, E-mail: sergei2@ornl.go [Department of Bioengineering, Clemson University, Clemson, SC 29634 (United States)

    2009-10-07

    Functional recognition imaging in scanning probe microscopy (SPM) using artificial neural network identification is demonstrated. This approach utilizes statistical analysis of complex SPM responses at a single spatial location to identify the target behavior, which is reminiscent of associative thinking in the human brain, obviating the need for analytical models. We demonstrate, as an example of recognition imaging, rapid identification of cellular organisms using the difference in electromechanical activity over a broad frequency range. Single-pixel identification of model Micrococcus lysodeikticus and Pseudomonas fluorescens bacteria is achieved, demonstrating the viability of the method.

  12. Short-term plasticity in thalamocortical pathways: cellular mechanisms and functional roles.

    Science.gov (United States)

    Castro-Alamancos, M A

    1997-01-01

    Information reaches the neocortex through different types of thalamocortical pathways. These differ in many morphological and physiological properties. One interesting aspect in which thalamocortical pathways differ is in their temporal dynamics, such as their short-term plasticity. Primary pathways display frequency-dependent depression, while secondary pathways display frequency-dependent enhancement. The cellular mechanisms underlying these dynamic responses involve pre- and post-synaptic and circuit properties. They may serve to synchronize, amplify and/or filter neural activity in neocortex depending on behavioral demands, and thus to adapt each pathway to its specific function.

  13. II. Unbound versus total serum gold concentration: pharmacological actions on cellular function.

    Science.gov (United States)

    Lorber, A; Kunishima, D H; Harralson, A F; Simon, T M

    1983-08-01

    Unbound serum gold (UBSG) has received little attention, possibly because of rapid in vivo decay and in vivo concentration below the range of existing analytical procedures. We have recently developed a methodology enabling quantitation and study of UBSG during chrysotherapy to assess effects on cellular functions. UBSG after gold administration is labile, declining rapidly after attaining peak values at which lymphocyte mitogen response and polymorphonuclear phagocytosis were observed to be suppressed. Oral gold, i.e., auranofin, 3 mg BID as compared to systemic chrysotherapy 50 mg/wk, resulted in a higher percentage of UBSG to total serum gold.

  14. Effect of Compound Glycyrrhizin Injection on Liver Function and Cellular Immunity of Children with Infectious Mononucleosis Complicated Liver Impairment

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To investigate the effects of Compound Glycyrrhizin Injection (CGI) on liver function and cellular immunity of children with infectious mononucleosis complicated liver impairment (IM-LI) and to explore its clinical therapeutic effect. Methods: Forty-two patients with IM-LI were randomly assigned, according to the randomizing number table, to two groups, 20 in the control group and 22 in the treated group.All the patients were treated with conventional treatment, but to those in the treated group, CGI was given additionally once a day, at the dosage of 10 ml for children aged below 2 years, 20 ml for 2-4 years old, 30 ml for 5-7 years old and 40 ml for 8- 12 years old, in 100-200 ml of 5% glucose solution by intravenous dripping. The treatment lasted for 2 weeks. T lymphocyte subsets and serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) were detected before and after treatment. Besides, a normal control group consisting of 20 healthy children was also set up. Results: Baseline of the percentage of CD3 + , CD8 + lymphocyte and serum levels of ALT, AST, TBiL in the children with IM-LI were markedly higher, while the percentage of CD4 + lymphocyte and the CD4 +/CD8 + ratio was markedly lower in IM-LI children as compared with the corresponding indices in the healthy children ( P<0.01 ). These indices were improved after treatment in both groups of patients, but the improvement in the treated group was better than that in the control group (P<0.01). Conclusion: Cellular immunity dysfunction often occurs in patients with IM-LI, and CGI treatment can not only obviously promote the recovery of liver function, but also regulate the immune function in organism.

  15. Generation and precise control of dynamic biochemical gradients for cellular assays

    Science.gov (United States)

    Saka, Yasushi; MacPherson, Murray; Giuraniuc, Claudiu V.

    2017-03-01

    Spatial gradients of diffusible signalling molecules play crucial roles in controlling diverse cellular behaviour such as cell differentiation, tissue patterning and chemotaxis. In this paper, we report the design and testing of a microfluidic device for diffusion-based gradient generation for cellular assays. A unique channel design of the device eliminates cross-flow between the source and sink channels, thereby stabilizing gradients by passive diffusion. The platform also enables quick and flexible control of chemical concentration that makes highly dynamic gradients in diffusion chambers. A model with the first approximation of diffusion and surface adsorption of molecules recapitulates the experimentally observed gradients. Budding yeast cells cultured in a gradient of a chemical inducer expressed a reporter fluorescence protein in a concentration-dependent manner. This microfluidic platform serves as a versatile prototype applicable to a broad range of biomedical investigations.

  16. Cellular oxido-reductive proteins of Chlamydomonas reinhardtii control the biosynthesis of silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Barwal Indu

    2011-12-01

    Full Text Available Abstract Background Elucidation of molecular mechanism of silver nanoparticles (SNPs biosynthesis is important to control its size, shape and monodispersity. The evaluation of molecular mechanism of biosynthesis of SNPs is of prime importance for the commercialization and methodology development for controlling the shape and size (uniform distribution of SNPs. The unicellular algae Chlamydomonas reinhardtii was exploited as a model system to elucidate the role of cellular proteins in SNPs biosynthesis. Results The C. reinhardtii cell free extract (in vitro and in vivo cells mediated synthesis of silver nanoparticles reveals SNPs of size range 5 ± 1 to 15 ± 2 nm and 5 ± 1 to 35 ± 5 nm respectively. In vivo biosynthesized SNPs were localized in the peripheral cytoplasm and at one side of flagella root, the site of pathway of ATP transport and its synthesis related enzymes. This provides an evidence for the involvement of oxidoreductive proteins in biosynthesis and stabilization of SNPs. Alteration in size distribution and decrease of synthesis rate of SNPs in protein-depleted fractions confirmed the involvement of cellular proteins in SNPs biosynthesis. Spectroscopic and SDS-PAGE analysis indicate the association of various proteins on C. reinhardtii mediated in vivo and in vitro biosynthesized SNPs. We have identified various cellular proteins associated with biosynthesized (in vivo and in vitro SNPs by using MALDI-MS-MS, like ATP synthase, superoxide dismutase, carbonic anhydrase, ferredoxin-NADP+ reductase, histone etc. However, these proteins were not associated on the incubation of pre-synthesized silver nanoparticles in vitro. Conclusion Present study provides the indication of involvement of molecular machinery and various cellular proteins in the biosynthesis of silver nanoparticles. In this report, the study is mainly focused towards understanding the role of diverse cellular protein in the synthesis and capping of silver

  17. Identifying disease feature genes based on cellular localized gene functional modules and regulation networks

    Institute of Scientific and Technical Information of China (English)

    ZHANG Min; ZHU Jing; GUO Zheng; LI Xia; YANG Da; WANG Lei; RAO Shaoqi

    2006-01-01

    Identifying disease-relevant genes and functional modules, based on gene expression profiles and gene functional knowledge, is of high importance for studying disease mechanisms and subtyping disease phenotypes. Using gene categories of biological process and cellular component in Gene Ontology, we propose an approach to selecting functional modules enriched with differentially expressed genes, and identifying the feature functional modules of high disease discriminating abilities. Using the differentially expressed genes in each feature module as the feature genes, we reveal the relevance of the modules to the studied diseases. Using three datasets for prostate cancer, gastric cancer, and leukemia, we have demonstrated that the proposed modular approach is of high power in identifying functionally integrated feature gene subsets that are highly relevant to the disease mechanisms. Our analysis has also shown that the critical disease-relevant genes might be better recognized from the gene regulation network, which is constructed using the characterized functional modules, giving important clues to the concerted mechanisms of the modules responding to complex disease states. In addition, the proposed approach to selecting the disease-relevant genes by jointly considering the gene functional knowledge suggests a new way for precisely classifying disease samples with clear biological interpretations, which is critical for the clinical diagnosis and the elucidation of the pathogenic basis of complex diseases.

  18. Surface charge and cellular processing of covalently functionalized multiwall carbon nanotubes determine pulmonary toxicity.

    Science.gov (United States)

    Li, Ruibin; Wang, Xiang; Ji, Zhaoxia; Sun, Bingbing; Zhang, Haiyuan; Chang, Chong Hyun; Lin, Sijie; Meng, Huan; Liao, Yu-Pei; Wang, Meiying; Li, Zongxi; Hwang, Angela A; Song, Tze-Bin; Xu, Run; Yang, Yang; Zink, Jeffrey I; Nel, André E; Xia, Tian

    2013-03-26

    Functionalized carbon nanotubes (f-CNTs) are being produced in increased volume because of the ease of dispersion and maintenance of the pristine material physicochemical properties when used in composite materials as well as for other commercial applications. However, the potential adverse effects of f-CNTs have not been quantitatively or systematically explored. In this study, we used a library of covalently functionalized multiwall carbon nanotubes (f-MWCNTs), established from the same starting material, to assess the impact of surface charge in a predictive toxicological model that relates the tubes' pro-inflammatory and pro-fibrogenic effects at cellular level to the development of pulmonary fibrosis. Carboxylate (COOH), polyethylene glycol (PEG), amine (NH2), sidewall amine (sw-NH2), and polyetherimide (PEI)-modified MWCNTs were successfully established from raw or as-prepared (AP-) MWCNTs and comprehensively characterized by TEM, XPS, FTIR, and DLS to obtain information about morphology, length, degree of functionalization, hydrodynamic size, and surface charge. Cellular screening in BEAS-2B and THP-1 cells showed that, compared to AP-MWCNTs, anionic functionalization (COOH and PEG) decreased the production of pro-fibrogenic cytokines and growth factors (including IL-1β, TGF-β1, and PDGF-AA), while neutral and weak cationic functionalization (NH2 and sw-NH2) showed intermediary effects. In contrast, the strongly cationic PEI-functionalized tubes induced robust biological effects. These differences could be attributed to differences in cellular uptake and NLRP3 inflammasome activation, which depends on the propensity toward lysosomal damage and cathepsin B release in macrophages. Moreover, the in vitro hazard ranking was validated by the pro-fibrogenic potential of the tubes in vivo. Compared to pristine MWCNTs, strong cationic PEI-MWCNTs induced significant lung fibrosis, while carboxylation significantly decreased the extent of pulmonary fibrosis. These

  19. Sterol regulation of acetyl coenzyme A carboxylase: a mechanism for coordinate control of cellular lipid.

    OpenAIRE

    Lopez, J.M.; Bennett, M K; Sanchez, H B; Rosenfeld, J M; Osborne, T E

    1996-01-01

    Transcription from the housekeeping promoter for the acetyl coenzyme A carboxylase (ACC) gene, which encodes the rate-controlling enzyme of fatty acid biosynthesis, is shown to be regulated by cellular sterol levels through novel binding sites for the sterol-sensitive sterol regulatory element binding protein (SREBP)-1 transcription factor. The position of the SREBP sites relative to those for the ubiquitous auxiliary transcription factor Sp1 is reminiscent of that previously described for th...

  20. Resveratrol against Arcobacter butzleri and Arcobacter cryaerophilus: activity and effect on cellular functions.

    Science.gov (United States)

    Ferreira, Susana; Silva, Filomena; Queiroz, João A; Oleastro, Mónica; Domingues, Fernanda C

    2014-06-16

    The frequent isolation of Arcobacter butzleri and Arcobacter cryaerophilus from food samples makes it imperative to search for potential compounds able to inhibit the development of these bacteria. Taking this into consideration, this study focuses on the antimicrobial activity of resveratrol and its mechanism of action against A. butzleri and A. cryaerophilus. The activity of resveratrol was assessed by a microdilution method and time-kill curves. Resveratrol effect on cellular functions was assessed by flow cytometry evaluating intracellular DNA content and metabolic activity. Ethidium bromide (EtBr) accumulation in the presence of resveratrol was also evaluated, as well as the susceptibility to resveratrol in the presence of phenylalanine-arginine β-naphthylamide (PAβN). Scanning electron microscopy (SEM) was used to further evaluate cell damage caused by resveratrol. Resveratrol presented MIC values of 100 and 50μg/mL to A. butzleri and A. cryaerophilus, respectively. Based on the time-kill curves, resveratrol exhibited bactericidal activity, leading to a ≥3log10CFU/mL reduction of initial inoculums, for A. butzleri exponential phase cells incubated for 6h with 1× MIC or with 2× MIC after 24h for stationary phase cells. For A. cryaerophilus cells in exponential growth phase, 99.9% killing was achieved after 24h incubation with 2× MIC, whereas, for stationary phase cells, bactericidal activity was only detected after incubation with 4× MIC. Incubation with resveratrol led to a decrease in both intracellular DNA content and metabolic activity. An increase in the accumulation of EtBr was observed in the presence of resveratrol, and the efflux pump inhibitor PAβN reduced the MIC of resveratrol. SEM analysis revealed disintegration of A. butzleri cells treated with resveratrol, whereas no morphological alteration was observed for A. cryaerophilus cells. Resveratrol has a good anti-Arcobacter activity, and the results obtained suggest that this compound

  1. [Functional activity of peritonal macrophages in liver immune damage of cellular and antibody genesis in mice].

    Science.gov (United States)

    Martynova, T V; Aleksieieva, I M

    2009-01-01

    The aim of present work was to compare the functional activity of peritoneal macrophages (Mf) at T-cellular and antibody induced hepatitis in mice of CBA line. T-cellular hepatitis was caused by concanavalin A (ConA), antibody-induced hepatitis was caused by administration of xenogenic anti-liver antibodies: gamma-globulin fractions of antihepatocytotoxic serum (gamma-AHCS). It was found that single injection of ConA or gamma-AHCS caused damage of liver with cytolytic syndrome through 20 hours. Functional activity of Mf in these conditions was significantly different. Application of ConA resulted in the decrease in phagocytosis of latex particles and oxygen-dependent metabolism; application of gamma-AHCS--to increase of these processes. Weakening of Mf activity may be one of the reasons for the decrease of dead cell eliminations that results in the maintenance of inflammatory reaction. At the same time significant amplification of phagocytic Mf activity may be one of the pathways of free radical endogenic sources increase that causes cell alteration and plays its role as mediators at inflammation.

  2. Cardiac function in an endothermic fish: cellular mechanisms for overcoming acute thermal challenges during diving.

    Science.gov (United States)

    Shiels, H A; Galli, G L J; Block, B A

    2015-02-07

    Understanding the physiology of vertebrate thermal tolerance is critical for predicting how animals respond to climate change. Pacific bluefin tuna experience a wide range of ambient sea temperatures and occupy the largest geographical niche of all tunas. Their capacity to endure thermal challenge is due in part to enhanced expression and activity of key proteins involved in cardiac excitation-contraction coupling, which improve cardiomyocyte function and whole animal performance during temperature change. To define the cellular mechanisms that enable bluefin tuna hearts to function during acute temperature change, we investigated the performance of freshly isolated ventricular myocytes using confocal microscopy and electrophysiology. We demonstrate that acute cooling and warming (between 8 and 28°C) modulates the excitability of the cardiomyocyte by altering the action potential (AP) duration and the amplitude and kinetics of the cellular Ca(2+) transient. We then explored the interactions between temperature, adrenergic stimulation and contraction frequency, and show that when these stressors are combined in a physiologically relevant way, they alter AP characteristics to stabilize excitation-contraction coupling across an acute 20°C temperature range. This allows the tuna heart to maintain consistent contraction and relaxation cycles during acute thermal challenges. We hypothesize that this cardiac capacity plays a key role in the bluefin tunas' niche expansion across a broad thermal and geographical range. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  3. Immobilization of penicillin G acylase on paramagnetic aldehyde-functionalized mesostructured cellular foams.

    Science.gov (United States)

    Yang, Ling; Gao, Zhenyuan; Guo, Yanglong; Zhan, Wangcheng; Guo, Yun; Wang, Yunsong; Lu, Guanzhong

    2014-06-10

    Paramagnetic aldehyde-functionalized mesostructured cellular foams (PAMCFs), synthesized by grafting 3-aminopropyltriethoxysilane modified Fe3O4 (NH2-Fe3O4) nanoparticles with larger particle size than the window pore size of MCFs on the outer surface of aldehyde-functionalized mesostructured cellular foams (AMCFs), were investigated as efficient supports for immobilization of penicillin G acylase (PGA). The results show that NH2-Fe3O4 nanoparticles were successfully grafted on the outer surface of AMCFs and PGA molecules were mainly immobilized covalently on the inner surface of PAMCFs, which was because amino groups of NH2-Fe3O4 nanoparticles or PGA molecules reacted with aldehyde groups of AMCFs or PAMCFs to form imine bonds. PGA/PAMCFs-15 showed a rather high initial activity of 9563Ug(-1) and retained 89.1% of its initial activity after recycled for 10 times. PGA/PAMCFs are easily recycled by magnetic field in order to replace tedious separation of high-speed centrifugation for mesoporous materials.

  4. Lactose-Functionalized Dendrimers Arbitrate the Interaction of Galectin-3/MUC1 Mediated Cancer Cellular Aggregation

    Science.gov (United States)

    Michel, Anna K.; Nangia-Makker, Pratima; Raz, Avraham

    2015-01-01

    By using lactose-functionalized poly(amidoamine) dendrimers as a tunable multivalent platform, we studied cancer cell aggregation in three different cell lines (A549, DU-145, and HT-1080) with galectin-3. We found that small lactose-functionalized G(2)-dendrimer 1 inhibited galectin-3-induced aggregation of the cancer cells. In contrast, dendrimer 4 (a larger, generation 6 dendrimer with 100 carbohydrate end groups) caused cancer cells to aggregate through a galectin-3 pathway. This study indicates that inhibition of cellular aggregation occurred because 1 provided competitive binding sites for galectin-3 (compared to its putative cancer cell ligand, TF-antigen on MUC1). Dendrimer 4, in contrast, provided an excess of ligands for galectin-3 binding; this caused crosslinking and aggregation of cells to be increased. PMID:25138772

  5. Non-specific cellular uptake of surface-functionalized quantum dots

    CERN Document Server

    Kelf, T A; Sun, J; Kim, E J; Goldys, E M; Zvyagin, A V; 10.1088/0957-4484/21/28/285105

    2010-01-01

    We report a systematic empirical study of nanoparticle internalization into cells via non-specific pathways. The nanoparticles were comprised of commercial quantum dots (QDs) that were highly visible under a fluorescence confocal microscope. Surface-modified QDs with basic biologically-significant moieties, e.g. carboxyl, amino, streptavidin were used, in combination with the surface derivatization with polyethylene glycol (PEG) in a range of immortalized cell lines. Internalization rates were derived from image analysis and a detailed discussion about the effect of nanoparticle size, charge and surface groups is presented. We find that PEG-derivatization dramatically suppresses the non-specific uptake while PEG-free carboxyl and amine functional groups promote QD internalization. These uptake variations displayed a remarkable consistency across different cell types. The reported results are important for experiments concerned with cellular uptake of surface-functionalized nanomaterials, both when non-specifi...

  6. Neurotransmitter Specific, Cellular-Resolution Functional Brain Mapping Using Receptor Coated Nanoparticles: Assessment of the Possibility.

    Directory of Open Access Journals (Sweden)

    Ebrahim Forati

    Full Text Available Receptor coated resonant nanoparticles and quantum dots are proposed to provide a cellular-level resolution image of neural activities inside the brain. The functionalized nanoparticles and quantum dots in this approach will selectively bind to different neurotransmitters in the extra-synaptic regions of neurons. This allows us to detect neural activities in real time by monitoring the nanoparticles and quantum dots optically. Gold nanoparticles (GNPs with two different geometries (sphere and rod and quantum dots (QDs with different sizes were studied along with three different neurotransmitters: dopamine, gamma-Aminobutyric acid (GABA, and glycine. The absorption/emission spectra of GNPs and QDs before and after binding of neurotransmitters and their corresponding receptors are reported. The results using QDs and nanorods with diameter 25nm and aspect rations larger than three were promising for the development of the proposed functional brain mapping approach.

  7. Neurotransmitter Specific, Cellular-Resolution Functional Brain Mapping Using Receptor Coated Nanoparticles: Assessment of the Possibility

    Science.gov (United States)

    Forati, Ebrahim; Sabouni, Abas; Ray, Supriyo; Head, Brian; Schoen, Christian; Sievenpiper, Dan

    2015-01-01

    Receptor coated resonant nanoparticles and quantum dots are proposed to provide a cellular-level resolution image of neural activities inside the brain. The functionalized nanoparticles and quantum dots in this approach will selectively bind to different neurotransmitters in the extra-synaptic regions of neurons. This allows us to detect neural activities in real time by monitoring the nanoparticles and quantum dots optically. Gold nanoparticles (GNPs) with two different geometries (sphere and rod) and quantum dots (QDs) with different sizes were studied along with three different neurotransmitters: dopamine, gamma-Aminobutyric acid (GABA), and glycine. The absorption/emission spectra of GNPs and QDs before and after binding of neurotransmitters and their corresponding receptors are reported. The results using QDs and nanorods with diameter 25nm and aspect rations larger than three were promising for the development of the proposed functional brain mapping approach. PMID:26717196

  8. Cellular Signaling Networks Function as Generalized Wiener-Kolmogorov Filters to Suppress Noise

    Science.gov (United States)

    Hinczewski, Michael; Thirumalai, D.

    2014-10-01

    Cellular signaling involves the transmission of environmental information through cascades of stochastic biochemical reactions, inevitably introducing noise that compromises signal fidelity. Each stage of the cascade often takes the form of a kinase-phosphatase push-pull network, a basic unit of signaling pathways whose malfunction is linked with a host of cancers. We show that this ubiquitous enzymatic network motif effectively behaves as a Wiener-Kolmogorov optimal noise filter. Using concepts from umbral calculus, we generalize the linear Wiener-Kolmogorov theory, originally introduced in the context of communication and control engineering, to take nonlinear signal transduction and discrete molecule populations into account. This allows us to derive rigorous constraints for efficient noise reduction in this biochemical system. Our mathematical formalism yields bounds on filter performance in cases important to cellular function—such as ultrasensitive response to stimuli. We highlight features of the system relevant for optimizing filter efficiency, encoded in a single, measurable, dimensionless parameter. Our theory, which describes noise control in a large class of signal transduction networks, is also useful both for the design of synthetic biochemical signaling pathways and the manipulation of pathways through experimental probes such as oscillatory input.

  9. Cellular Signaling Networks Function as Generalized Wiener-Kolmogorov Filters to Suppress Noise

    Directory of Open Access Journals (Sweden)

    Michael Hinczewski

    2014-10-01

    Full Text Available Cellular signaling involves the transmission of environmental information through cascades of stochastic biochemical reactions, inevitably introducing noise that compromises signal fidelity. Each stage of the cascade often takes the form of a kinase-phosphatase push-pull network, a basic unit of signaling pathways whose malfunction is linked with a host of cancers. We show that this ubiquitous enzymatic network motif effectively behaves as a Wiener-Kolmogorov optimal noise filter. Using concepts from umbral calculus, we generalize the linear Wiener-Kolmogorov theory, originally introduced in the context of communication and control engineering, to take nonlinear signal transduction and discrete molecule populations into account. This allows us to derive rigorous constraints for efficient noise reduction in this biochemical system. Our mathematical formalism yields bounds on filter performance in cases important to cellular function—such as ultrasensitive response to stimuli. We highlight features of the system relevant for optimizing filter efficiency, encoded in a single, measurable, dimensionless parameter. Our theory, which describes noise control in a large class of signal transduction networks, is also useful both for the design of synthetic biochemical signaling pathways and the manipulation of pathways through experimental probes such as oscillatory input.

  10. The eukaryotic Pso2/Snm1/Artemis proteins and their function as genomic and cellular caretakers

    Directory of Open Access Journals (Sweden)

    D. Bonatto

    2005-03-01

    Full Text Available DNA double-strand breaks (DSBs represent a major threat to the genomic stability of eukaryotic cells. DNA repair mechanisms such as non-homologous end joining (NHEJ are responsible for the maintenance of eukaryotic genomes. Dysfunction of one or more of the many protein complexes that function in NHEJ can lead to sensitivity to DNA damaging agents, apoptosis, genomic instability, and severe combined immunodeficiency. One protein, Pso2p, was shown to participate in the repair of DSBs induced by DNA inter-strand cross-linking (ICL agents such as cisplatin, nitrogen mustard or photo-activated bi-functional psoralens. The molecular function of Pso2p in DNA repair is unknown, but yeast and mammalian cell line mutants for PSO2 show the same cellular responses as strains with defects in NHEJ, e.g., sensitivity to ICLs and apoptosis. The Pso2p human homologue Artemis participates in V(DJ recombination. Mutations in Artemis induce a variety of immunological deficiencies, a predisposition to lymphomas, and an increase in chromosomal aberrations. In order to better understand the role of Pso2p in the repair of DSBs generated as repair intermediates of ICLs, an in silico approach was used to characterize the catalytic domain of Pso2p, which led to identification of novel Pso2p homologues in other organisms. Moreover, we found the catalytic core of Pso2p fused to different domains. In plants, a specific ATP-dependent DNA ligase I contains the catalytic core of Pso2p, constituting a new DNA ligase family, which was named LIG6. The possible functions of Pso2p/Artemis/Lig6p in NHEJ and V(DJ recombination and in other cellular metabolic reactions are discussed.

  11. Role of Mitochondrial Reactive Oxygen Species in the Activation of Cellular Signals, Molecules, and Function

    DEFF Research Database (Denmark)

    Indo, Hiroko P.; Hawkins, Clare L; Nakanishi, Ikuo

    2017-01-01

    Mitochondria are a major source of intracellular energy and reactive oxygen species in cells, but are also increasingly being recognized as a controller of cell death. Here, we review evidence of signal transduction control by mitochondrial superoxide generation via the nuclear factor-κB (NF......-κB) and GATA signaling pathways. We have also reviewed the effects of ROS on the activation of MMP and HIF. There is significant evidence to support the hypothesis that mitochondrial superoxide can initiate signaling pathways following transport into the cytosol. In this study, we provide evidence of TATA...... signal transductions by mitochondrial superoxide. Oxidative phosphorylation via the electron transfer chain, glycolysis, and generation of superoxide from mitochondria could be important factors in regulating signal transduction, cellular homeostasis, and cell death....

  12. Influence of D-net (European GSM-Standard) cellular phones on pacemaker function in 50 patients with permanent pacemakers.

    Science.gov (United States)

    Wilke, A; Grimm, W; Funck, R; Maisch, B

    1996-10-01

    The widespread use of cellular phones in the last years has prompted some recent studies to suggest an interference of pacemaker function by cellular phone usage. To determine the risk of pacemaker patients using D-net cellular phones, we tested 50 patients with permanent pacemakers after routine pacemaker check by short phone calls using a cellular phone (Ericsson, D-net, frequency 890-915 MHz, digital information coding, equivalent to the European Groupe Systemes Mobiles standard). A six-channel surface ECG was continuously recorded from each patient to detect any interactions between pacemakers and cellular phones. Phone calls were repeated during the following pacemaker settings: (1) preexisting setting; (2) minimum ventricular rate of 90 beats/min and preexisting sensitivity; and (3) minimum ventricular rate of 90 beats/min and maximum sensitivity without T wave oversensing. Only 2 (4%) of 50 patients repeatedly showed intermittent pacemaker inhibition during calls with the cellular phone. Both pacemakers had unipolar sensing. Therefore, although interactions between cellular phone use and pacemaker function appear to be rare in our study, pacemaker dependent patients in particular should avoid the use of cellular phones.

  13. Forward Link Power Control Strategy and its Optimum Issue in CDMA Cellular Networks

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In this paper, we propose a theoretical method in order to estimate the forward link outage probability and user capacity of a cellular system which are based on IS-95 CDMA standard, especialy impact of power control strategy and voice activity monitoring in the system under long-term fading effects, in which the light and heavy fadings are considered. According to the numerical results obtained in this paper, the power control strategy leads to approximately the threefold user capacity in contrast to the situation without power control strategy. The reults are compared with Interference-to-Signal Ratio (ISR) driven power control scheme[6][9] which can be used only for simulation of the system. The power control strategy not only improves the desired signal to the interference ratio in the reference user's receiver, but also offers uniform service to the user wherever it is located in the cell.

  14. Adhesion GPCRs CD97 and GPR56: From structural regulation to cellular function

    NARCIS (Netherlands)

    Hsiao, C.-C.

    2015-01-01

    Cells correspond with their environment through receptors that translate extracellular signals into intracellular messages. Members of the large superfamily of G protein-coupled receptors (GPCRs) control various physiological functions and have been implicated in numerous diseases. Adhesion GPCRs

  15. A Biologically-Inspired Power Control Algorithm for Energy-Efficient Cellular Networks

    Directory of Open Access Journals (Sweden)

    Hyun-Ho Choi

    2016-03-01

    Full Text Available Most of the energy used to operate a cellular network is consumed by a base station (BS, and reducing the transmission power of a BS can therefore afford a substantial reduction in the amount of energy used in a network. In this paper, we propose a distributed transmit power control (TPC algorithm inspired by bird flocking behavior as a means of improving the energy efficiency of a cellular network. Just as each bird in a flock attempts to match its velocity with the average velocity of adjacent birds, in the proposed algorithm, each mobile station (MS in a cell matches its rate with the average rate of the co-channel MSs in adjacent cells by controlling the transmit power of its serving BS. We verify that this bio-inspired TPC algorithm using a local rate-average process achieves an exponential convergence and maximizes the minimum rate of the MSs concerned. Simulation results show that the proposed TPC algorithm follows the same convergence properties as the flocking algorithm and also effectively reduces the power consumption at the BSs while maintaining a low outage probability as the inter-cell interference increases; in so doing, it significantly improves the energy efficiency of a cellular network.

  16. On mode selection and power control for uplink D2D communication in cellular networks

    KAUST Repository

    Ali, Konpal S.

    2015-06-08

    Device-to-device (D2D) communication enables users lying in close proximity to bypass the cellular base station (BS) and transmit to one another directly. This offloads traffic from the cellular network, improves spatial frequency reuse and energy efficiency in the network. We present a comprehensive and tractable analytical framework for D2D-enabled uplink cellular networks with two different flexible mode-selection schemes. The power-control cutoff thresholds of the two communication modes have been decoupled unlike past work on the subject. We find that for a given network, an optimal value exists not only for the biased mode selection criterion, but also for r, the ratio of the power-control cutoff thresholds of the two communication modes, which maximizes spatial spectral efficiency. Also, r turns out to be a more robust parameter for optimizing network performance. Further, it is shown that the second scheme, which prioritizes spatial frequency reuse over the per-user achievable performance compared to the first scheme, achieves almost the same overall network performance; thereby trading per user performance to serve a larger number of users.

  17. Cellular Controlled Short-Range Communication for Cooperative P2P Networking

    DEFF Research Database (Denmark)

    Fitzek, Frank H. P.; Katz, Marcos; Zhang, Qi

    2009-01-01

    This article advocates a novel communication architecture and associated collaborative framework for future wireless communication systems. In contrast to the dominating cellular architecture and the upcoming peer-to-peer architecture, the new approach envisions a cellular controlled short......-range communication network among cooperating mobile and wireless devices. The role of the mobile device will change, from being an agnostic entity in respect to the surrounding world to a cognitive device. This cognitive device is capable of being aware of the neighboring devices as well as on the possibility...... to establish cooperation with them. The novel architecture together with several possible cooperative strategies will bring clear benefits for the network and service providers, mobile device manufacturers and also end users....

  18. A Current View of Functional Biomaterials for Wound Care, Molecular and Cellular Therapies

    Directory of Open Access Journals (Sweden)

    Francesco Piraino

    2015-01-01

    Full Text Available The intricate process of wound healing involves activation of biological pathways that work in concert to regenerate a tissue microenvironment consisting of cells and external cellular matrix (ECM with enzymes, cytokines, and growth factors. Distinct stages characterize the mammalian response to tissue injury: hemostasis, inflammation, new tissue formation, and tissue remodeling. Hemostasis and inflammation start right after the injury, while the formation of new tissue, along with migration and proliferation of cells within the wound site, occurs during the first week to ten days after the injury. In this review paper, we discuss approaches in tissue engineering and regenerative medicine to address each of these processes through the application of biomaterials, either as support to the native microenvironment or as delivery vehicles for functional hemostatic, antibacterial, or anti-inflammatory agents. Molecular therapies are also discussed with particular attention to drug delivery methods and gene therapies. Finally, cellular treatments are reviewed, and an outlook on the future of drug delivery and wound care biomaterials is provided.

  19. Viral and cellular SOS-regulated motor proteins: dsDNA translocation mechanisms with divergent functions.

    Science.gov (United States)

    Wolfe, Annie; Phipps, Kara; Weitao, Tao

    2014-01-01

    DNA damage attacks on bacterial cells have been known to activate the SOS response, a transcriptional response affecting chromosome replication, DNA recombination and repair, cell division and prophage induction. All these functions require double-stranded (ds) DNA translocation by ASCE hexameric motors. This review seeks to delineate the structural and functional characteristics of the SOS response and the SOS-regulated DNA translocases FtsK and RuvB with the phi29 bacteriophage packaging motor gp16 ATPase as a prototype to study bacterial motors. While gp16 ATPase, cellular FtsK and RuvB are similarly comprised of hexameric rings encircling dsDNA and functioning as ATP-driven DNA translocases, they utilize different mechanisms to accomplish separate functions, suggesting a convergent evolution of these motors. The gp16 ATPase and FtsK use a novel revolution mechanism, generating a power stroke between subunits through an entropy-DNA affinity switch and pushing dsDNA inward without rotation of DNA and the motor, whereas RuvB seems to employ a rotation mechanism that remains to be further characterized. While FtsK and RuvB perform essential tasks during the SOS response, their roles may be far more significant as SOS response is involved in antibiotic-inducible bacterial vesiculation and biofilm formation as well as the perspective of the bacteria-cancer evolutionary interaction.

  20. [Effects of electromagnetic field from cellular phones on selected central nervous system functions: a literature review].

    Science.gov (United States)

    Bak, Marek; Zmyślony, Marek

    2010-01-01

    In the opinion of some experts, a growing emission of man-made electromagnetic fields (EMF), also known as electromagnetic is a source of continuously increasing health hazards to the general population. Due to their large number and very close proximity to the user's head, mobile phones deserve special attention. This work is intended to give a systematic review of objective studies, assessing the effects of mobile phone EMF on the functions of the central nervous system (CNS) structures. Our review shows that short exposures to mobile phone EMF, experienced by telephone users during receiving calls, do not affect the cochlear function. Effects of GSM mobile phone EMF on the conduction of neural impulses from the inner car neurons to the brainstem auditory centres have not been detected either. If Picton's principle, saying that P300 amplitude varies with the improbability of the targets and its latency varies with difficulty of discriminating the target stimulus from standard stimuli, is true, EMF changes the improbability of the targets without hindering their discrimination. Experiments with use of indirect methods do not enable unequivocal verification of EMF effects on the cognitive functions due to the CNS anatomical and functional complexity. Thus, it seems advisable to develop a model of EMF effects on the excitable brain structures at the cellular level.

  1. Recycling of inorganic waste in monolithic and cellular glass-based materials for structural and functional applications.

    Science.gov (United States)

    Rincón, Acacio; Marangoni, Mauro; Cetin, Suna; Bernardo, Enrico

    2016-07-01

    The stabilization of inorganic waste of various nature and origin, in glasses, has been a key strategy for environmental protection for the last decades. When properly formulated, glasses may retain many inorganic contaminants permanently, but it must be acknowledged that some criticism remains, mainly concerning costs and energy use. As a consequence, the sustainability of vitrification largely relies on the conversion of waste glasses into new, usable and marketable glass-based materials, in the form of monolithic and cellular glass-ceramics. The effective conversion in turn depends on the simultaneous control of both starting materials and manufacturing processes. While silica-rich waste favours the obtainment of glass, iron-rich wastes affect the functionalities, influencing the porosity in cellular glass-based materials as well as catalytic, magnetic, optical and electrical properties. Engineered formulations may lead to important reductions of processing times and temperatures, in the transformation of waste-derived glasses into glass-ceramics, or even bring interesting shortcuts. Direct sintering of wastes, combined with recycled glasses, as an example, has been proven as a valid low-cost alternative for glass-ceramic manufacturing, for wastes with limited hazardousness. The present paper is aimed at providing an up-to-date overview of the correlation between formulations, manufacturing technologies and properties of most recent waste-derived, glass-based materials. © 2016 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

  2. 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

  3. Studying the Effects of Matrix Stiffness on Cellular Function using Acrylamide-based Hydrogels

    Science.gov (United States)

    Cretu, Alexandra; Castagnino, Paola; Assoian, Richard

    2010-01-01

    Tissue stiffness is an important determinant of cellular function, and changes in tissue stiffness are commonly associated with fibrosis, cancer and cardiovascular disease1-11. Traditional cell biological approaches to studying cellular function involve culturing cells on a rigid substratum (plastic dishes or glass coverslips) which cannot account for the effect of an elastic ECM or the variations in ECM stiffness between tissues. To model in vivo tissue compliance conditions in vitro, we and others use ECM-coated hydrogels. In our laboratory, the hydrogels are based on polyacrylamide which can mimic the range of tissue compliances seen biologically12. "Reactive" cover slips are generated by incubation with NaOH followed by addition of 3-APTMS. Glutaraldehyde is used to cross-link the 3-APTMS and the polyacrylamide gel. A solution of acrylamide (AC), bis-acrylamide (Bis-AC) and ammonium persulfate is used for the polymerization of the hydrogel. N-hydroxysuccinimide (NHS) is incorporated into the AC solution to crosslink ECM protein to the hydrogel. Following polymerization of the hydrogel, the gel surface is coated with an ECM protein of choice such as fibronectin, vitronectin, collagen, etc. The stiffness of a hydrogel can be determined by rheology or atomic force microscopy (AFM) and adjusted by varying the percentage of AC and/or bis-AC in the solution12. In this manner, substratum stiffness can be matched to the stiffness of biological tissues which can also be quantified using rheology or AFM. Cells can then be seeded on these hydrogels and cultured based upon the experimental conditions required. Imaging of the cells and their recovery for molecular analysis is straightforward. For this article, we define soft substrata as those having elastic moduli (E) 20,000 Pascal. PMID:20736914

  4. Flow-cytometric study of vital cellular functions in Escherichia coli during solar disinfection (SODIS).

    Science.gov (United States)

    Berney, Michael; Weilenmann, Hans-Ulrich; Egli, Thomas

    2006-06-01

    The effectiveness of solar disinfection (SODIS), a low-cost household water treatment method for developing countries, was investigated with flow cytometry and viability stains for the enteric bacterium Escherichia coli. A better understanding of the process of injury or death of E. coli during SODIS could be gained by investigating six different cellular functions, namely: efflux pump activity (Syto 9 plus ethidium bromide), membrane potential [bis-(1,3-dibutylbarbituric acid)trimethine oxonol; DiBAC4(3)], membrane integrity (LIVE/DEAD BacLight), glucose uptake activity (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose; 2-NBDG), total ATP concentration (BacTiter-Glo) and culturability (pour-plate method). These variables were measured in E. coli K-12 MG1655 cells that were exposed to either sunlight or artificial UVA light. The inactivation pattern of cellular functions was very similar for both light sources. A UVA light dose (fluence) of 80 % of the cells was observed at a fluence of approximately 1500 kJ m(-2), and the cytoplasmic membrane of bacterial cells became permeable at a fluence of >2500 kJ m(-2). Culturable counts of stressed bacteria after anaerobic incubation on sodium pyruvate-supplemented tryptic soy agar closely correlated with the loss of membrane potential. The results strongly suggest that cells exposed to >1500 kJ m(-2) solar UVA (corresponding to 530 W m(-2) global sunlight intensity for 6 h) were no longer able to repair the damage and recover. Our study confirms the lethal effect of SODIS with cultivation-independent methods and gives a detailed picture of the 'agony' of E. coli when it is stressed with sunlight.

  5. Epoxy-functionalized mesostructured cellular foams as effective support for covalent immobilization of penicillin G acylase

    Energy Technology Data Exchange (ETDEWEB)

    Xue Ping [Key Laboratory of Energy Resources and Chemical Engineering, Ningxia University, Yinchuan 750021 (China)], E-mail: Ping@nxu.edu.cn; Xu Fang [Department of Molecule Biology, Ningxia Medical College, Yinchuan 750021 (China); Xu Lidong [Key Laboratory of Energy Resources and Chemical Engineering, Ningxia University, Yinchuan 750021 (China)

    2008-12-30

    The epoxy-functionalized mesoporous cellular foams (G-MCFs) with high specific surface area ({approx}400 m{sup 2}/g) and large-size mesopores ({approx}17 nm) were obtained by condensation of 3-glycidoxypropyltriethoxysilane (GPTS) and the surface silanol groups of mesoporous cellular foams (MCFs) and used as the support for immobilization of penicillin G acylase (PGA). The structural properties of G-MCF were characterized by FT-IR, N{sub 2} adsorption, TG-DTA and {sup 29}Si MAS NMR. The studies indicated that the glycidoxypropyl groups were chemically bonded to the silicon atoms on the surface of MCF. The epoxy-functionalized mesoporous cellular foams can provide the microenvironments suitable for the immobilization of PGA, and the enzyme molecules could be immobilized covalently onto the G-MCF under mild conditions by reaction between the amino groups of the enzyme molecules and the epoxy groups on the surface of G-MCF. The PGA immobilized on G-MCF (PGA/G-MCF) exhibited the apparent activity of 1782 IU/g and 46.6% of activity recovery for hydrolyzing penicillin G potassium to produce 6-aminopenicillanic acid at 37 {sup o}C which were higher than that of PGA on pure silica MCF (1521 IU/g and 39.8%, respectively). The kinetic study also indicated that PGA immobilized on G-MCF has a K{sub m} of 2.1 x 10{sup -2} mol/L lower than that of PGA immobilized on the pure silica MCF (5.0 x 10{sup -2} mol/L). These may be attributed to the enhanced surface affinity between G-MCF support and the substrate molecules. Due to the covalent immobilization of PGA molecules on the surface of G-MCF, the immobilized PGA with considerable operational stability was achieved. The activity of PGA/G-MCF is still about 91.4% of its initial activity at the 10th cycle reuse while that of PGA/MCF only remains 41.5% of its initial activity at the same reuse numbers. In addition, the investigation results show the thermal stability and durability on acid or basic medium of PGA immobilized on G

  6. Patient-controlled paravertebral block in optimizing cellular immune function after radical resection of pulmonary carcinoma performed via video-assisted thoracoscope%胸腔镜肺癌根治术后病人自控椎旁神经阻滞对细胞免疫功能的优化程度

    Institute of Scientific and Technical Information of China (English)

    冯芳; 李娟; 刘兴慧; 康芳; 张林杰

    2015-01-01

    目的 评价胸腔镜肺癌根治术后病人自控椎旁神经阻滞(PCPB)对细胞免疫功能的优化程度.方法 择期胸腔镜肺癌根治术病人41例,年龄50 ~ 64岁,BMI 20~25 kg/m2,ASA分级Ⅰ或Ⅱ级,TNM分期Ⅰ或Ⅱ期,性别不限,采用随机数字表法,将其分为2组:PCIA组(n=21)和PCPB组(n=20),PCIA组药液配方:舒芬太尼2μg/kg,生理盐水稀释至100 ml,背景输注速率2 ml/h,锁定时间15 min,PCA剂量2 ml;PCPB组术毕于患侧T5椎旁注射0.2%罗哌卡因5 ml,随后行PCPB,药液配方:0.75%罗哌卡因67 ml,生理盐水稀释至250 ml,背景输注速率5 ml/h,锁定时间15 min,PCA剂量5 ml,维持VAS评分≤3分,镇痛至术后50 h.分别于麻醉诱导前即刻(基础状态)、术毕、术后1、3、5d时采集静脉血样,检测调节性T细胞、自然杀伤细胞和自然杀伤T细胞的水平,并检测血浆白细胞介素-10和转化生长因子-β浓度.结果 与PCIA组比较,PCPB组术后1、3d时调节性T细胞水平降低,自然杀伤细胞水平和自然杀伤T细胞水平升高,血浆白细胞介素-10及转化生长因子-β的浓度降低(P<0.05或0.01),术后细胞免疫功能低下率差异无统计学意义(p>0.05).结论 胸腔镜肺癌根治术后PCPB对细胞免疫功能的优化程度无临床意义.%Objective To evaluate the patient-controlled paravertebral block (PCPB) in optimizing the cellular immune function when used after radical resection of pulmonary carcinoma performed via video-assisted thoracoscope in patients.Methods Forty-one ASA physical status Ⅰ or Ⅱ patients of both sexes,aged 50-64 yr,with body mass index of 20-25 kg/m2,of TNM staging Ⅰ or Ⅱ,undergoing radical resection of pulmonary carcinoma performed via video-assisted thoracoscope,were randomly divided into 2 groups using a random number table:PCIA group (n =21) and PCPB group (n =20).PCIA solution contained sufentanil 2 μg/kg in 100 ml of normal saline.The PCIA pump was set up to deliver a 2 ml bolus dose

  7. Cellular localization of ATBF1 protein and its functional implication in breast epithelial cells.

    Science.gov (United States)

    Li, Mei; Zhang, Chi; Zhong, Yi; Zhao, Jiyuan

    2017-08-19

    ATBF1, a large transcription factor, was normally localized in nuclei, and its mislocalization to cytoplasm was reported in multiple cancers. However, localization of ATBF1 in breast epithelial cells and its potential functions were unknown. Here, we investigated ATBF1 localization via immunofluorescence staining in different kinds of breast epithelial cells. In MCF10A cells and normal mice mammary gland tissues, ATBF1 was mainly localized in nuclei. Knockdown of ATBF1 expression in MCF10A cells by siRNA promoted cell proliferation. Moreover, ATBF1 was co-localized with chromosome during mitosis, indicating its potential function in mitosis. In an estrogen receptor (ER)-positive breast cancer cell line (MCF7), estrogen induced ATBF1 translocation from cytoplasm to nuclei in an ER dependent pathway. In ER-negative cells (Hs578T and MDA-MB-231), ATBF1 was co-localized with GM130 in cytoplasm, indicating ATBF1 localization was associated with protein modification in golgi body. The results were beneficial for intensive investigation of ATBF1's function with different cellular localization in breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Multi-functional MIMO communication in multi-hop cellular systems

    Science.gov (United States)

    Roger, Sandra; Calabuig, Daniel; Monserrat, Jose F.; Cardona, Narcis

    2014-12-01

    In the context of multi-hop cellular communications, user equipment devices (UEs) with relaying capabilities provide a virtual infrastructure that can enhance the cell spectral efficiency. UE relays, which are generally transparent to the destination user and lack channel state information, mainly operate in an open-loop mode. Most open-loop transmission techniques for relaying are based on orthogonal space-time block coding (OSTBC), which offers a good trade-off between performance and complexity. In this paper, we consider the concept of multi-functional multiple-input multiple-output (MIMO) transmission, which combines OSTBC with beamforming techniques. This concept is applied to networks with multiple relays, which can offer a high number of antennas to implement multi-functional MIMO techniques. The proposed schemes are shown to reduce the bit error rate of the destination user with respect to a direct transmission from the base station (BS). Furthermore, the multi-functional setup exhibits better performance than conventional OSTBC at high transmission rates.

  9. Admission Control Scheme for Multi-class Services in QoS-based Mobile Cellular Networks

    Institute of Scientific and Technical Information of China (English)

    YINZhiming; XIEJianying

    2004-01-01

    Call admission control (CAC) is one of the key schemes to guarantee Quality of service (QoS) in mobile cellular networks. In this paper, we propose an optimal CAC scheme based on Semi-Markov decision processes (SMDP) theory to support multi-class services for QoS wireless networks. Linear programming formulation is used to find the optimal solution, which maximizes the channel utilization while meeting the requirements of QoS constraints. The numerical results show that the performance of our scheme outperforms DCAC scheme.

  10. Electrically Controlled "Sponge Effect" of PEDOT:PSS Governs Membrane Potential and Cellular Growth.

    Science.gov (United States)

    Amorini, Fabrizio; Zironi, Isabella; Marzocchi, Marco; Gualandi, Isacco; Calienni, Maria; Cramer, Tobias; Fraboni, Beatrice; Castellani, Gastone

    2017-03-01

    PSS is a highly conductive material with good thermal and chemical stability and enhanced biocompatibility that make it suitable for bioengineering applications. The electrical control of the oxidation state of PEDOT:PSS films allows modulation of peculiar physical and chemical properties of the material, such as topography, wettability, and conductivity, and thus offers a possible route for controlling cellular behavior. Through the use of (i) the electrophysiological response of the plasma membrane as a biosensor of the ionic availability; (ii) relative abundance around the cells via X-ray spectroscopy; and (iii) atomic force microscopy to monitor PEDOT:PSS film thickness relative to its oxidation state, we demonstrate that redox processes confer to PEDOT:PSS the property to modify the ionic environment at the film-liquid interface through a "sponge-like" effect on ions. Finally, we show how this property offers the capability to electrically control central cellular properties such as viability, substrate adhesion, and growth, paving the way for novel bioelectronics and biotechnological applications.

  11. Symptoms of Problematic Cellular Phone Use, Functional Impairment and Its Association with Depression among Adolescents in Southern Taiwan

    Science.gov (United States)

    Yen, Cheng-Fang; Tang, Tze-Chun; Yen, Ju-Yu; Lin, Huang-Chi; Huang, Chi-Fen; Liu, Shu-Chun; Ko, Chih-Hung

    2009-01-01

    The aims of this study were: (1) to examine the prevalence of symptoms of problematic cellular phone use (CPU); (2) to examine the associations between the symptoms of problematic CPU, functional impairment caused by CPU and the characteristics of CPU; (3) to establish the optimal cut-off point of the number of symptoms for functional impairment…

  12. Symptoms of Problematic Cellular Phone Use, Functional Impairment and Its Association with Depression among Adolescents in Southern Taiwan

    Science.gov (United States)

    Yen, Cheng-Fang; Tang, Tze-Chun; Yen, Ju-Yu; Lin, Huang-Chi; Huang, Chi-Fen; Liu, Shu-Chun; Ko, Chih-Hung

    2009-01-01

    The aims of this study were: (1) to examine the prevalence of symptoms of problematic cellular phone use (CPU); (2) to examine the associations between the symptoms of problematic CPU, functional impairment caused by CPU and the characteristics of CPU; (3) to establish the optimal cut-off point of the number of symptoms for functional impairment…

  13. Effects of HIV-1 protease on cellular functions and their potential applications in antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Yang Hailiu

    2012-09-01

    fission yeast as a possible surrogate system to study the effects of HIV-1 protease on cellular functions and to explore its utility as a HTS system to search for new PIs to battle HIV-1 resistant strains.

  14. Identification, cellular distribution and potential function of the metalloprotease-disintegrin MDC9 in the kidney.

    Science.gov (United States)

    Mahimkar, R M; Baricos, W H; Visaya, O; Pollock, A S; Lovett, D H

    2000-04-01

    The complex interactions of glomerular and tubular epithelial cells with the basal laminae play a critical role in renal function. Disruption of these interactions has been widely implicated in glomerular diseases and acute renal failure. MDC are a large family of membrane-bound proteins containing metalloprotease, disintegrin (integrin interaction sites), and cysteine-rich domains. Little information is available concerning the presence of MDC in the kidney or their role in renal pathophysiology. Using degenerate PCR primers for the conserved metalloprotease and disintegrin domains of this protein family, cDNA templates from tubules, whole glomeruli, and glomerular epithelial cells (GEC) yielded a single, 195-bp product, which on sequence analysis corresponded to a region in the disintegrin domain of MDC9. Northern analysis of poly(A)+ RNA from tubules, whole glomeruli, and GEC revealed a 3.9-kb transcript, identical to that of mouse MDC9. Using antibodies generated against a 21-amino acid peptide present in the metalloprotease domain of MDC9, Western analysis of concanavalin A-enriched glomerular microsomal extracts demonstrated both processed (76 kD) and unprocessed (116 kD) forms of MDC9, which upon reduction changed to the corresponding 84- and 124-kD forms. Histochemical studies revealed a basolateral localization of intrinsic MDC9 protein in renal cortical tubule cells and glomerular visceral epithelial cells, which colocalized with the beta1 integrin chain. Expression of green fluorescence protein MDC9 chimeric constructs in GEC or polarized Madin-Darby canine kidney epithelial cells revealed a similar punctate basolateral surface localization. Transient overexpression of the soluble disintegrin domain-green fluorescence protein chimera in GEC led to dramatic changes in cellular morphology with rounding and detachment from cell monolayers. These studies document the presence of MDC9 in renal epithelial cells and suggest an important role for MDC9 in renal

  15. Effect of adenosine cyclophosphate combined with vitamin C on cellular immune function of children with viral myocarditis

    Institute of Scientific and Technical Information of China (English)

    Xiu Chang; Lan-Hui Jiu

    2016-01-01

    Objective:To investigate the curative effect of adenosine cyclophosphate combined with vitamin C on children with viral myocarditis andon cellular immune function.Methods:A total of96 cases of children with viral myocarditis were randomly divided into control group and observation group, 48 cases in each. The control group received routine treatment for viral myocarditis. The observation group received routine treatment for viral myocarditis as well as vitamin C and adenosine cyclophosphate.Results:The total effective rate of observation group 89.59% was higher than that of control group 64.58%, and differences were statistical significant. The electrocardiogram total effective rate of observation group 91.67% was higher than that of control group 68.75%, and differences were statistical significant. After treatment, the level of CD3+ (65.09±10.35)%, the level of CD4+ (42.93±6.22)%, the level of CD8+ (29.55±4.87)% and the level of NK (47.37±8.52)% of observation group were higher than the level of CD3+ (51.85±9.33)%, the level of CD4+ (35.18±5.73)%, the level of CD8+(24.46±4.03)% and the level of NK (35.64±7.72)% of control group, and differences were statistical significant. After treatment, myocardial enzyme indexes lactate dehydrogenase (329.65±19.76) U/L, creatine phosphate kinase (126.36±12.92) U/L, hydroxybutyrate dehydrogenase (271.68±14.73) U/L, glutamic oxaloacetic transaminase (31.22±3.76) U/L and creatine kinase (185.28±13.83) U/L of observation group were lower than lactate dehydrogenase (348.06±20.51) U/L, creatine phosphate kinase (163.19±13.15) U/L, hydroxybutyrate dehydrogenase (305.50±16.42) U/L, glutamic oxaloacetic transaminase (37.87±4.07) U/L and creatine kinase (202.79±15.47) U/L of control group, and differences were statistical significant. After treatment, heart function indexes CI, FS and EF levels of observation group were higher than those of control group, and differences were statistical significant

  16. Expanding Internal Control Functionality Scope

    Directory of Open Access Journals (Sweden)

    Mykola M. Vuitsiv

    2012-08-01

    Full Text Available The article reviews the influence of «western» concepts of the information needs of management process provisions on forming and developing the up-to-date model of Internal Control. An attempt has been made to develop the approach to solve urgent management tasks by applying the ideas of controlling and management accounting via the traditional national approach to the content of control. The place of control in the enterprise management information system has also been reviewed.

  17. Cellular and molecular function of mucolipins (TRPML) and polycystin 2 (TRPP2).

    Science.gov (United States)

    Qian, Feng; Noben-Trauth, Konrad

    2005-10-01

    Mucolipins (transient receptor potential mucolipin, TRPML) and polycystin-2 proteins (transient receptor potential polycystin, TRPP) constitute two small families of cation channels with motif and sequence similarities to the transient receptor potential (TRP) class of non-selective cation channels. Genetic defects in TRPML1 and TRPML3 in humans and in animal models cause the accumulation of large vacuoles, leading to a variety of cellular phenotypes including neurological and neurosensory deficiencies. TRPML1 is a Ca(2+)-, K(+)-, and Na(+)-permeable cation channel sensitive to pH changes, and regulates a critical step in the maturation of late endosomes to lysosomes. Mutations of TRPP2 in humans result in autosomal dominant polycystic kidney disease. Molecular studies have demonstrated that TRPP2 and TRPP3 proteins function as Ca(2+)-regulated, non-selective cation channels. During embryogenesis TRPP2 is active in node monocilia and plays a role in the establishment of left-right asymmetry. Recent results have indicated that TRPP2 interacts with polycystin-1 and that their interaction is important for their function as mechanosensitive channels at the primary cilium of renal epithelial cells. The interaction of polycystin family members appears to be conserved and is critical for fertilization and mating behavior. An emerging concept from the studies of the polycystin family is that they function as cation-influx based devices for sensing extracellular signals on ciliated structures. Here we review the function of TRPML1 and TRPP2 as representative members of these families, focusing on the genetics, physiology, and biochemistry.

  18. Much to know about proteolysis: intricate proteolytic machineries compromise essential cellular functions.

    Science.gov (United States)

    Marfany, Gemma; Farràs, Rosa; Salido, Eduardo; Xirodimas, Dimitris P; Rodríguez, Manuel S

    2008-10-01

    Proteolysis has traditionally been considered as a radical way to terminate the function of a protein. However, protein destruction also is the starting point for many processes as they can only occur when the way has been cleared for the action of other proteins. Protein destruction can occur virtually in all compartments and organelles of the cell, associated with cell membranes or large protein complexes, it determines subcellular partitioning, association with positive or negative regulators which conditions the action of many critical cellular factors. The third intracellular proteolysis meeting held by the University La Laguna, Canary Islands, Spain, included speakers working with some of the most important proteolytic systems present in higher eukaryotes, such as the UPS (ubiquitin-proteasome system) and autophagy. Owing to the fact that these pathways directly or indirectly regulate many cell functions, this meeting brought together an audience with a wide range of research interests, including genetic, cell biological, biochemical and structural aspects of protein degradation. Some of these topics inspired interesting discussions and a significant number of these are developed in the issues reviewed herein.

  19. Cellular functions of the ADF/cofilin family at a glance.

    Science.gov (United States)

    Kanellos, Georgios; Frame, Margaret C

    2016-09-01

    The actin depolymerizing factor (ADF)/cofilin family comprises small actin-binding proteins with crucial roles in development, tissue homeostasis and disease. They are best known for their roles in regulating actin dynamics by promoting actin treadmilling and thereby driving membrane protrusion and cell motility. However, recent discoveries have increased our understanding of the functions of these proteins beyond their well-characterized roles. This Cell Science at a Glance article and the accompanying poster serve as an introduction to the diverse roles of the ADF/cofilin family in cells. The first part of the article summarizes their actions in actin treadmilling and the main mechanisms for their intracellular regulation; the second part aims to provide an outline of the emerging cellular roles attributed to the ADF/cofilin family, besides their actions in actin turnover. The latter part discusses an array of diverse processes, which include regulation of intracellular contractility, maintenance of nuclear integrity, transcriptional regulation, nuclear actin monomer transfer, apoptosis and lipid metabolism. Some of these could, of course, be indirect consequences of actin treadmilling functions, and this is discussed.

  20. Non-specific cellular uptake of surface-functionalized quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Kelf, T A; Sreenivasan, V K A; Sun, J; Goldys, E M; Zvyagin, A V [MQ Photonics Centre, Faculty of Science, Macquarie University, Sydney (Australia); Kim, E J, E-mail: azvyagin@science.mq.edu.au [Department of Science Education-Chemical Education Major, Daegu University, Gyeonbuk (Korea, Republic of)

    2010-07-16

    We report a systematic empirical study of nanoparticle internalization into cells via non-specific pathways. The nanoparticles were comprised of commercial quantum dots (QDs) that were highly visible under a fluorescence confocal microscope. Surface-modified QDs with basic biologically significant moieties, e.g. carboxyl, amino, and streptavidin, were used, in combination with surface derivatization with polyethylene glycol (PEG) for a range of immortalized cell lines. Internalization rates were derived from image analysis and a detailed discussion about the effect of nanoparticle size, charge and surface groups is presented. We find that PEG derivatization dramatically suppresses the non-specific uptake while PEG-free carboxyl and amine functional groups promote QD internalization. These uptake variations displayed a remarkable consistency across different cell types. The reported results are important for experiments concerned with cellular uptake of surface-functionalized nanomaterials, both when non-specific internalization is undesirable and when it is intended for material to be internalized as efficiently as possible.

  1. Cocaine and MDMA Induce Cellular and Molecular Changes in Adult Neurogenic Systems: Functional Implications

    Directory of Open Access Journals (Sweden)

    Vivian Capilla-Gonzalez

    2011-06-01

    Full Text Available The capacity of the brain to generate new adult neurons is a recent discovery that challenges the old theory of an immutable adult brain. A new and fascinating field of research now focuses on this regenerative process. The two brain systems that constantly produce new adult neurons, known as the adult neurogenic systems, are the dentate gyrus (DG of the hippocampus and the lateral ventricules/olfactory bulb system. Both systems are involved in memory and learning processes. Different drugs of abuse, such as cocaine and MDMA, have been shown to produce cellular and molecular changes that affect adult neurogenesis. This review summarizes the effects that these drugs have on the adult neurogenic systems. The functional relevance of adult neurogenesis is obscured by the functions of the systems that integrate adult neurons. Therefore, we explore the effects that cocaine and MDMA produce not only on adult neurogenesis, but also on the DG and olfactory bulbs. Finally, we discuss the possible role of new adult neurons in cocaine- and MDMA-induced impairments. We conclude that, although harmful drug effects are produced at multiple physiological and anatomical levels, the specific consequences of reduced hippocampus neurogenesis are unclear and require further exploration.

  2. Insights into the cellular function of YhdE, a nucleotide pyrophosphatase from Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Jin Jin

    Full Text Available YhdE, a Maf-like protein in Escherichia coli, exhibits nucleotide pyrophosphatase (PPase activity, yet its cellular function remains unknown. Here, we characterized the PPase activity of YhdE on dTTP, UTP and TTP and determined two crystal structures of YhdE, revealing 'closed' and 'open' conformations of an adaptive active site. Our functional studies demonstrated that YhdE retards cell growth by prolonging the lag and log phases, particularly under stress conditions. Morphology studies showed that yhdE-knockout cells transformed the normal rod shape of wild-type cells to a more spherical form, and the cell wall appeared to become more flexible. In contrast, YhdE overexpression resulted in filamentous cells. This study reveals the previously unknown involvement of YhdE in cell growth inhibition under stress conditions, cell-division arrest and cell-shape maintenance, highlighting YhdE's important role in E. coli cell-cycle checkpoints.

  3. 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

  4. A NOVEL CALL ADMISSION CONTROL SCHEME IN CELLULAR/WLAN INTEGRATION AND PERFORMANCE ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    Xia Weiwei; Shen Lianfeng

    2009-01-01

    In order to achieve the Quality of Service (QoS) provisioning and efficient resource utilization in cellular network and Wireless Local Area Network (WLAN) integration, an Integrated Service-Based Call Admission Control (ISB-CAC) scheme is proposed in this paper. The integrated network is modeled by using multi-dimensional Markov chains. The numerical analysis is presented to evaluate the important performance measures such as the blocking probability of originating calls, the dropping probability, and the average transfer time, etc. The steady-state probabilities of the multi-dimensional Markov chains are obtained by using an iterative approach, and the CAC parameters are optimally designed. The analytical model is validated by the computer simulation. It is shown that compared with the conventional WLAN-First Call Admission Control (WF-CAC) scheme, the proposed ISB-CAC scheme not only provides better QoS for mobile users but also utilizes the bandwidth resources more efficiently.

  5. SELF-ADAPTIVE CONTROLS OF A COMPLEX CELLULAR SIGNALING TRANSDUCTION SYSTEM

    Institute of Scientific and Technical Information of China (English)

    LI Hong; ZHOU Zhiyuan; DAI Rongyang; LUO Bo; ZHENG Xiaoli; YANG Wenli; HE Tao; WU Minglu

    2004-01-01

    In cells, the interactions of distinct signaling transduction pathways originating from cross-talkings between signaling molecules give rise to the formation of signaling transduction networks, which contributes to the changes (emergency) of kinetic behaviors of signaling system compared with single molecule or pathway. Depending on the known experimental data, we have constructed a model for complex cellular signaling transduction system, which is derived from signaling transduction of epidermal growth factor receptor in neuron. By the computational simulating methods, the self-adaptive controls of this system have been investigated. We find that this model exhibits a relatively stable selfadaptive system, especially to over-stimulation of agonist, and the amplitude and duration of signaling intermediates in it could be controlled by multiple self-adaptive effects, such as "signal scattering", "positive feedback", "negative feedback" and "B-Raf shunt". Our results provide an approach to understanding the dynamic behaviors of complex biological systems.

  6. Monoaminergic Control of Cellular Glucose Utilization by Glycogenolysis in Neocortex and Hippocampus.

    Science.gov (United States)

    DiNuzzo, Mauro; Giove, Federico; Maraviglia, Bruno; Mangia, Silvia

    2015-12-01

    Brainstem nuclei are the principal sites of monoamine (MA) innervation to major forebrain structures. In the cortical grey matter, increased secretion of MA neuromodulators occurs in response to a wealth of environmental and homeostatic challenges, whose onset is associated with rapid, preparatory changes in neural activity as well as with increases in energy metabolism. Blood-borne glucose is the main substrate for energy production in the brain. Once entered the tissue, interstitial glucose is equally accessible to neurons and astrocytes, the two cell types accounting for most of cellular volume and energy metabolism in neocortex and hippocampus. Astrocytes also store substantial amounts of glycogen, but non-stimulated glycogen turnover is very small. The rate of cellular glucose utilization in the brain is largely determined by hexokinase, which under basal conditions is more than 90 % inhibited by its product glucose-6-phosphate (Glc-6-P). During rapid increases in energy demand, glycogen is a primary candidate in modulating the intracellular level of Glc-6-P, which can occur only in astrocytes. Glycogenolysis can produce Glc-6-P at a rate higher than uptake and phosphorylation of glucose. MA neurotransmitter are released extrasinaptically by brainstem neurons projecting to neocortex and hippocampus, thus activating MA receptors located on both neuronal and astrocytic plasma membrane. Importantly, MAs are glycogenolytic agents and thus they are exquisitely suitable for regulation of astrocytic Glc-6-P concentration, upstream substrate flow through hexokinase and hence cellular glucose uptake. Conforming to such mechanism, Gerald A. Dienel and Nancy F. Cruz recently suggested that activation of noradrenergic locus coeruleus might reversibly block astrocytic glucose uptake by stimulating glycogenolysis in these cells, thereby anticipating the rise in glucose need by active neurons. In this paper, we further develop the idea that the whole monoaminergic system

  7. Monoaminergic control of cellular glucose utilization by glycogenolysis in neocortex and hippocampus

    Science.gov (United States)

    DiNuzzo, Mauro; Giove, Federico; Maraviglia, Bruno; Mangia, Silvia

    2016-01-01

    Brainstem nuclei are the principal sites of monoamine (MA) innervation to major forebrain structures. In the cortical grey matter, increased secretion of MA neuromodulators occurs in response to a wealth of environmental and homeostatic challenges, whose onset is associated with rapid, preparatory changes in neural activity as well as with increases in energy metabolism. Blood-borne glucose is the main substrate for energy production in the brain. Once entered the tissue, interstitial glucose is equally accessible to neurons and astrocytes, the two cell types accounting for most of cellular volume and energy metabolism in neocortex and hippocampus. Astrocytes also store substantial amounts of glycogen, but non-stimulated glycogen turnover is very small. The rate of cellular glucose utilization in the brain is largely determined by hexokinase, which under basal conditions is more than 90% inhibited by its product glucose-6-phosphate (Glc-6-P). During rapid increases in energy demand, glycogen is a primary candidate in modulating the intracellular level of Glc-6-P, which can occur only in astrocytes. Glycogenolysis can produce Glc-6-P at a rate higher than uptake and phosphorylation of glucose. MA neurotransmitter are released extrasinaptically by brainstem neurons projecting to neocortex and hippocampus, thus activating MA receptors located on both neuronal and astrocytic plasma membrane. Importantly, MAs are glycogenolytic agents and thus they are exquisitely suitable for regulation of astrocytic Glc-6-P concentration, upstream substrate flow through hexokinase and hence cellular glucose uptake. Conforming to such mechanism, Gerald A. Dienel and Nancy F. Cruz recently suggested that activation of noradrenergic locus coeruleus might reversibly block astrocytic glucose uptake by stimulating glycogenolysis in these cells, thereby anticipating the rise in glucose need by active neurons. In this paper, we further develop the idea that the whole monoaminergic system

  8. Boron dipyrromethene (BODIPY) functionalized carbon nano-onions for high resolution cellular imaging

    Science.gov (United States)

    Bartelmess, Juergen; de Luca, Elisa; Signorelli, Angelo; Baldrighi, Michele; Becce, Michele; Brescia, Rosaria; Nardone, Valentina; Parisini, Emilio; Echegoyen, Luis; Pompa, Pier Paolo; Giordani, Silvia

    2014-10-01

    Carbon nano-onions (CNOs) are an exciting class of carbon nanomaterials, which have recently demonstrated a facile cell-penetration capability. In the present work, highly fluorescent boron dipyrromethene (BODIPY) dyes were covalently attached to the surface of CNOs. The introduction of this new carbon nanomaterial-based imaging platform, made of CNOs and BODIPY fluorophores, allows for the exploration of synergetic effects between the two building blocks and for the elucidation of its performance in biological applications. The high fluorescence intensity exhibited by the functionalized CNOs translates into an excellent in vitro probe for the high resolution imaging of MCF-7 human breast cancer cells. It was also found that the CNOs, internalized by the cells by endocytosis, localized in the lysosomes and did not show any cytotoxic effects. The presented results highlight CNOs as excellent platforms for biological and biomedical studies due to their low toxicity, efficient cellular uptake and low fluorescence quenching of attached probes.Carbon nano-onions (CNOs) are an exciting class of carbon nanomaterials, which have recently demonstrated a facile cell-penetration capability. In the present work, highly fluorescent boron dipyrromethene (BODIPY) dyes were covalently attached to the surface of CNOs. The introduction of this new carbon nanomaterial-based imaging platform, made of CNOs and BODIPY fluorophores, allows for the exploration of synergetic effects between the two building blocks and for the elucidation of its performance in biological applications. The high fluorescence intensity exhibited by the functionalized CNOs translates into an excellent in vitro probe for the high resolution imaging of MCF-7 human breast cancer cells. It was also found that the CNOs, internalized by the cells by endocytosis, localized in the lysosomes and did not show any cytotoxic effects. The presented results highlight CNOs as excellent platforms for biological and biomedical

  9. A functional screen for copper homeostasis genes identifies a pharmacologically tractable cellular system.

    Science.gov (United States)

    Schlecht, Ulrich; Suresh, Sundari; Xu, Weihong; Aparicio, Ana Maria; Chu, Angela; Proctor, Michael J; Davis, Ronald W; Scharfe, Curt; St Onge, Robert P

    2014-04-05

    Copper is essential for the survival of aerobic organisms. If copper is not properly regulated in the body however, it can be extremely cytotoxic and genetic mutations that compromise copper homeostasis result in severe clinical phenotypes. Understanding how cells maintain optimal copper levels is therefore highly relevant to human health. We found that addition of copper (Cu) to culture medium leads to increased respiratory growth of yeast, a phenotype which we then systematically and quantitatively measured in 5050 homozygous diploid deletion strains. Cu's positive effect on respiratory growth was quantitatively reduced in deletion strains representing 73 different genes, the function of which identify increased iron uptake as a cause of the increase in growth rate. Conversely, these effects were enhanced in strains representing 93 genes. Many of these strains exhibited respiratory defects that were specifically rescued by supplementing the growth medium with Cu. Among the genes identified are known and direct regulators of copper homeostasis, genes required to maintain low vacuolar pH, and genes where evidence supporting a functional link with Cu has been heretofore lacking. Roughly half of the genes are conserved in man, and several of these are associated with Mendelian disorders, including the Cu-imbalance syndromes Menkes and Wilson's disease. We additionally demonstrate that pharmacological agents, including the approved drug disulfiram, can rescue Cu-deficiencies of both environmental and genetic origin. A functional screen in yeast has expanded the list of genes required for Cu-dependent fitness, revealing a complex cellular system with implications for human health. Respiratory fitness defects arising from perturbations in this system can be corrected with pharmacological agents that increase intracellular copper concentrations.

  10. A celiac cellular phenotype, with altered LPP sub-cellular distribution, is inducible in controls by the toxic gliadin peptide P31-43.

    Directory of Open Access Journals (Sweden)

    Merlin Nanayakkara

    Full Text Available Celiac disease (CD is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Undigested gliadin peptides P31-43 and P57-68 induce innate and adaptive T cell-mediated immune responses, respectively. Alterations in the cell shape and actin cytoskeleton are present in celiac enterocytes, and gliadin peptides induce actin rearrangements in both the CD mucosa and cell lines. Cell shape is maintained by the actin cytoskeleton and focal adhesions, sites of membrane attachment to the extracellular matrix. The locus of the human Lipoma Preferred Partner (LPP gene was identified as strongly associated with CD using genome-wide association studies (GWAS. The LPP protein plays an important role in focal adhesion architecture and acts as a transcription factor in the nucleus. In this study, we examined the hypothesis that a constitutive alteration of the cell shape and the cytoskeleton, involving LPP, occurs in a cell compartment far from the main inflammation site in CD fibroblasts from skin explants. We analyzed the cell shape, actin organization, focal adhesion number, focal adhesion proteins, LPP sub-cellular distribution and adhesion to fibronectin of fibroblasts obtained from CD patients on a Gluten-Free Diet (GFD and controls, without and with treatment with A-gliadin peptide P31-43. We observed a "CD cellular phenotype" in these fibroblasts, characterized by an altered cell shape and actin organization, increased number of focal adhesions, and altered intracellular LPP protein distribution. The treatment of controls fibroblasts with gliadin peptide P31-43 mimics the CD cellular phenotype regarding the cell shape, adhesion capacity, focal adhesion number and LPP sub-cellular distribution, suggesting a close association between these alterations and CD pathogenesis.

  11. Peptide-independent stabilization of MHC class I molecules breaches cellular quality control.

    Science.gov (United States)

    Hein, Zeynep; Uchtenhagen, Hannes; Abualrous, Esam Tolba; Saini, Sunil Kumar; Janßen, Linda; Van Hateren, Andy; Wiek, Constanze; Hanenberg, Helmut; Momburg, Frank; Achour, Adnane; Elliott, Tim; Springer, Sebastian; Boulanger, Denise

    2014-07-01

    The intracellular trafficking of major histocompatibility complex class I (MHC-I) proteins is directed by three quality control mechanisms that test for their structural integrity, which is correlated to the binding of high-affinity antigenic peptide ligands. To investigate which molecular features of MHC-I these quality control mechanisms detect, we have followed the hypothesis that suboptimally loaded MHC-I molecules are characterized by their conformational mobility in the F-pocket region of the peptide-binding site. We have created a novel variant of an MHC-I protein, K(b)-Y84C, in which two α-helices in this region are linked by a disulfide bond that mimics the conformational and dynamic effects of bound high-affinity peptide. K(b)-Y84C shows a remarkable increase in the binding affinity to its light chain, beta-2 microglobulin (β2m), and bypasses all three cellular quality control steps. Our data demonstrate (1) that coupling between peptide and β2m binding to the MHC-I heavy chain is mediated by conformational dynamics; (2) that the folded conformation of MHC-I, supported by β2m, plays a decisive role in passing the ER-to-cell-surface transport quality controls; and (3) that β2m association is also tested by the cell surface quality control that leads to MHC-I endocytosis.

  12. Analytical modeling of mode selection and power control for underlay D2D communication in cellular networks

    KAUST Repository

    Elsawy, Hesham

    2014-11-01

    Device-to-device (D2D) communication enables the user equipments (UEs) located in close proximity to bypass the cellular base stations (BSs) and directly connect to each other, and thereby, offload traffic from the cellular infrastructure. D2D communication can improve spatial frequency reuse and energy efficiency in cellular networks. This paper presents a comprehensive and tractable analytical framework for D2D-enabled uplink cellular networks with a flexible mode selection scheme along with truncated channel inversion power control. The developed framework is used to analyze and understand how the underlaying D2D communication affects the cellular network performance. Through comprehensive numerical analysis, we investigate the expected performance gains and provide guidelines for selecting the network parameters.

  13. Cellular functions of genetically imprinted genes in human and mouse as annotated in the gene ontology.

    Science.gov (United States)

    Hamed, Mohamed; Ismael, Siba; Paulsen, Martina; Helms, Volkhard

    2012-01-01

    By analyzing the cellular functions of genetically imprinted genes as annotated in the Gene Ontology for human and mouse, we found that imprinted genes are often involved in developmental, transport and regulatory processes. In the human, paternally expressed genes are enriched in GO terms related to the development of organs and of anatomical structures. In the mouse, maternally expressed genes regulate cation transport as well as G-protein signaling processes. Furthermore, we investigated if imprinted genes are regulated by common transcription factors. We identified 25 TF families that showed an enrichment of binding sites in the set of imprinted genes in human and 40 TF families in mouse. In general, maternally and paternally expressed genes are not regulated by different transcription factors. The genes Nnat, Klf14, Blcap, Gnas and Ube3a contribute most to the enrichment of TF families. In the mouse, genes that are maternally expressed in placenta are enriched for AP1 binding sites. In the human, we found that these genes possessed binding sites for both, AP1 and SP1.

  14. Interneurons. Fast-spiking, parvalbumin⁺ GABAergic interneurons: from cellular design to microcircuit function.

    Science.gov (United States)

    Hu, Hua; Gan, Jian; Jonas, Peter

    2014-08-01

    The success story of fast-spiking, parvalbumin-positive (PV(+)) GABAergic interneurons (GABA, γ-aminobutyric acid) in the mammalian central nervous system is noteworthy. In 1995, the properties of these interneurons were completely unknown. Twenty years later, thanks to the massive use of subcellular patch-clamp techniques, simultaneous multiple-cell recording, optogenetics, in vivo measurements, and computational approaches, our knowledge about PV(+) interneurons became more extensive than for several types of pyramidal neurons. These findings have implications beyond the "small world" of basic research on GABAergic cells. For example, the results provide a first proof of principle that neuroscientists might be able to close the gaps between the molecular, cellular, network, and behavioral levels, representing one of the main challenges at the present time. Furthermore, the results may form the basis for PV(+) interneurons as therapeutic targets for brain disease in the future. However, much needs to be learned about the basic function of these interneurons before clinical neuroscientists will be able to use PV(+) interneurons for therapeutic purposes.

  15. Cellular and functional specificity among ferritin-like proteins in the multicellular cyanobacterium Nostoc punctiforme.

    Science.gov (United States)

    Ekman, Martin; Sandh, Gustaf; Nenninger, Anja; Oliveira, Paulo; Stensjö, Karin

    2014-03-01

    Ferritin-like proteins constitute a remarkably heterogeneous protein family, including ferritins, bacterioferritins and Dps proteins. The genome of the filamentous heterocyst-forming cyanobacterium Nostoc punctiforme encodes five ferritin-like proteins. In the present paper, we report a multidimensional characterization of these proteins. Our phylogenetic and bioinformatics analyses suggest both structural and physiological differences among the ferritin-like proteins. The expression of these five genes responded differently to hydrogen peroxide treatment, with a significantly higher rise in transcript level for Npun_F3730 as compared with the other four genes. A specific role for Npun_F3730 in the cells tolerance against hydrogen peroxide was also supported by the inactivation of Npun_F3730, Npun_R5701 and Npun_R6212; among these, only the ΔNpun_F3730 strain showed an increased sensitivity to hydrogen peroxide compared with wild type. Analysis of promoter-GFP reporter fusions of the ferritin-like genes indicated that Npun_F3730 and Npun_R5701 were expressed in all cell types of a diazotrophic culture, while Npun_F6212 was expressed specifically in heterocysts. Our study provides the first comprehensive analysis combining functional differentiation and cellular specificity within this important group of proteins in a multicellular cyanobacterium. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

  16. Elucidating the Function of Penetratin and a Static Magnetic Field in Cellular Uptake of Magnetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    David Stirling

    2013-02-01

    Full Text Available Nanotechnology plays an increasingly important role in the biomedical arena. In particular, magnetic nanoparticles (mNPs have become important tools in molecular diagnostics, in vivo imaging and improved treatment of disease, with the ultimate aim of producing a more theranostic approach. Due to their small sizes, the nanoparticles can cross most of the biological barriers such as the blood vessels and the blood brain barrier, thus providing ubiquitous access to most tissues. In all biomedical applications maximum nanoparticle uptake into cells is required. Two promising methods employed to this end include functionalization of mNPs with cell-penetrating peptides to promote efficient translocation of cargo into the cell and the use of external magnetic fields for enhanced delivery. This study aimed to compare the effect of both penetratin and a static magnetic field with regards to the cellular uptake of 200 nm magnetic NPs and determine the route of uptake by both methods. Results demonstrated that both techniques increased particle uptake, with penetratin proving more cell specific. Clathrin- medicated endocytosis appeared to be responsible for uptake as shown via PCR and western blot, with Pitstop 2 (known to selectively block clathrin formation blocking particle uptake. Interestingly, it was further shown that a magnetic field was able to reverse or overcome the blocking, suggesting an alternative route of uptake.

  17. On the Quest of Cellular Functions of PEA-15 and the Therapeutic Opportunities

    Directory of Open Access Journals (Sweden)

    Yufeng Wei

    2015-07-01

    Full Text Available Phosphoprotein enriched in astrocytes, 15 KDa (PEA-15, a ubiquitously expressed small protein in all mammals, is known for decades for its potent interactions with various protein partners along distinct biological pathways. Most notable interacting partners of PEA-15 include extracellular signal-regulated kinase 1 and 2 (ERK1/2 in the mitogen activated protein kinase (MAPK pathway, the Fas-associated death domain (FADD protein involving in the formation of the death-inducing signaling complex (DISC, and the phospholipase D1 (PLD1 affecting the insulin sensitivity. However, the actual cellular functions of PEA-15 are still mysterious, and the question why this protein is expressed in almost all cell and tissue types remains unanswered. Here we synthesize the most recent structural, biological, and clinical studies on PEA-15 with emphases on its anti-apoptotic, anti-proliferative, and anti-inflammative properties, and propose a converged protective role of PEA-15 that maintains the balance of death and survival in different cell types. Under conditions that this delicate balance is unsustainable, PEA-15 may become pathological and lead to various diseases, including cancers and diabetes. Targeting PEA-15 interactions, or the use of PEA-15 protein as therapeutics, may provide a wider window of opportunities to treat these diseases.

  18. Functional DNA-containing nanomaterials: cellular applications in biosensing, imaging, and targeted therapy.

    Science.gov (United States)

    Liang, Hao; Zhang, Xiao-Bing; Lv, Yifan; Gong, Liang; Wang, Ruowen; Zhu, Xiaoyan; Yang, Ronghua; Tan, Weihong

    2014-06-17

    CONSPECTUS: DNA performs a vital function as a carrier of genetic code, but in the field of nanotechnology, DNA molecules can catalyze chemical reactions in the cell, that is, DNAzymes, or bind with target-specific ligands, that is, aptamers. These functional DNAs with different modifications have been developed for sensing, imaging, and therapeutic systems. Thus, functional DNAs hold great promise for future applications in nanotechnology and bioanalysis. However, these functional DNAs face challenges, especially in the field of biomedicine. For example, functional DNAs typically require the use of cationic transfection reagents to realize cellular uptake. Such reagents enter the cells, increasing the difficulty of performing bioassays in vivo and potentially damaging the cell's nucleus. To address this obstacle, nanomaterials, such as metallic, carbon, silica, or magnetic materials, have been utilized as DNA carriers or assistants. In this Account, we describe selected examples of functional DNA-containing nanomaterials and their applications from our recent research and those of others. As models, we have chosen to highlight DNA/nanomaterial complexes consisting of gold nanoparticles, graphene oxides, and aptamer-micelles, and we illustrate the potential of such complexes in biosensing, imaging, and medical diagnostics. Under proper conditions, multiple ligand-receptor interactions, decreased steric hindrance, and increased surface roughness can be achieved from a high density of DNA that is bound to the surface of nanomaterials, resulting in a higher affinity for complementary DNA and other targets. In addition, this high density of DNA causes a high local salt concentration and negative charge density, which can prevent DNA degradation. For example, DNAzymes assembled on gold nanoparticles can effectively catalyze chemical reactions even in living cells. And it has been confirmed that DNA-nanomaterial complexes can enter cells more easily than free single

  19. Novel metastasis-related gene CIM functions in the regulation of multiple cellular stress-response pathways.

    Science.gov (United States)

    Yanagisawa, Kiyoshi; Konishi, Hiroyuki; Arima, Chinatsu; Tomida, Shuta; Takeuchi, Toshiyuki; Shimada, Yukako; Yatabe, Yasushi; Mitsudomi, Tetsuya; Osada, Hirotaka; Takahashi, Takashi

    2010-12-01

    Various stresses of the tumor microenvironment produced by insufficient nutrients, pH, and oxygen can contribute to the generation of altered metabolic and proliferative states that promote the survival of metastatic cells. Among many cellular stress-response pathways activated under such conditions are the hypoxia-inducible factor (HIF) pathway and the unfolded protein response (UPR), which is elicited as a response to endoplasmic reticulum (ER) stress. In this study, we report the identification of a novel cancer invasion and metastasis-related gene (hereafter referred to as CIM, also called ERLEC1), which influences both of these stress-response pathways to promote metastasis. CIM was identified by comparing the gene expression profile of a highly metastatic human lung cancer cell line with its weakly metastatic parental clone. We showed that CIM is critical for metastatic properties in this system. Proteomic approaches combined with bioinformatic analyses revealed that CIM has multifaceted roles in controlling the response to hypoxia and ER stress. Specifically, CIM sequestered OS-9 from the HIF-1α complex and PHD2, permitting HIF-1α accumulation by preventing its degradation. Ectopic expression of CIM in lung cancer cells increased their tolerance to hypoxia. CIM also modulated UPR through interaction with the key ER stress protein BiP, influencing cell proliferation under ER stress conditions. Our findings shed light on how tolerance to multiple cellular stresses at a metastatic site can be evoked by an integrated mechanism involving CIM, which can function to coordinate those responses in a manner that promotes metastatic cell survival.

  20. Small-molecule control of protein function through Staudinger reduction

    Science.gov (United States)

    Luo, Ji; Liu, Qingyang; Morihiro, Kunihiko; Deiters, Alexander

    2016-11-01

    Using small molecules to control the function of proteins in live cells with complete specificity is highly desirable, but challenging. Here we report a small-molecule switch that can be used to control protein activity. The approach uses a phosphine-mediated Staudinger reduction to activate protein function. Genetic encoding of an ortho-azidobenzyloxycarbonyl amino acid using a pyrrolysyl transfer RNA synthetase/tRNACUA pair in mammalian cells enables the site-specific introduction of a small-molecule-removable protecting group into the protein of interest. Strategic placement of this group renders the protein inactive until deprotection through a bioorthogonal Staudinger reduction delivers the active wild-type protein. This developed methodology was applied to the conditional control of several cellular processes, including bioluminescence (luciferase), fluorescence (enhanced green fluorescent protein), protein translocation (nuclear localization sequence), DNA recombination (Cre) and gene editing (Cas9).

  1. Adaptive call admission control and resource allocation in multi server wireless/cellular network

    Science.gov (United States)

    Jain, Madhu; Mittal, Ragini

    2016-11-01

    The ever increasing demand of the subscribers has put pressure on the capacity of wireless networks around the world. To utilize the scare resources, in the present paper we propose an optimal allocation scheme for an integrated wireless/cellular model with handoff priority and handoff guarantee services. The suggested algorithm optimally allocates the resources in each cell and dynamically adjust threshold to control the admission. To give the priority to handoff calls over the new calls, the provision of guard channels and subrating scheme is taken into consideration. The handoff voice call may balk and renege from the system while waiting in the buffer. An iterative algorithm is implemented to generate the arrival rate of the handoff calls in each cell. Various performance indices are established in term of steady state probabilities. The sensitivity analysis has also been carried out to examine the tractability of algorithms and to explore the effects of system descriptors on the performance indices.

  2. Combined Base Station Association and Power Control in Multi-channel Cellular Networks

    CERN Document Server

    Singh, Chandramani; Sundaresan, Rajesh

    2011-01-01

    A combined base station association and power control problem is studied for the uplink of multichannel multicell cellular networks, in which each channel is used by exactly one cell (i.e., base station). A distributed association and power update algorithm is proposed and shown to converge to a Nash equilibrium of a noncooperative game. We consider network models with discrete mobiles (yielding an atomic congestion game), as well as a continuum of mobiles (yielding a population game). We find that the equilibria need not be Pareto efficient, nor need they be system optimal. To address the lack of system optimality, we propose pricing mechanisms. It is shown that these mechanisms can be implemented in a distributed fashion.

  3. Joint Mode Selection and Resource Allocation for Cellular Controlled Short-Range Communication in OFDMA Networks

    Science.gov (United States)

    Deng, Hui; Tao, Xiaoming; Ge, Ning; Lu, Jianhua

    This letter studies cellular controlled short-range communication in OFDMA networks. The network needs to decide when to allow direct communication between a closely located device-to-device (D2D) pair instead of conveying data from one device to the other via the base station and when not to, in addition to subchannel and power allocation. Our goal is to maximize the total network throughput while guaranteeing the rate requirements of all users. For that purpose, we formulate an optimization problem subject to subchannel and power constraints. A scheme which combines a joint mode selection and subchannel allocation algorithm based on equal power allocation with a power reallocation scheme is proposed. Simulation results show that our proposed scheme can improve the network throughput and outage probability compared with other schemes.

  4. Cellular function and pathological role of ATP13A2 and related P-type transport ATPases in Parkinson's disease and other neurological disorders.

    Science.gov (United States)

    van Veen, Sarah; Sørensen, Danny M; Holemans, Tine; Holen, Henrik W; Palmgren, Michael G; Vangheluwe, Peter

    2014-01-01

    Mutations in ATP13A2 lead to Kufor-Rakeb syndrome, a parkinsonism with dementia. ATP13A2 belongs to the P-type transport ATPases, a large family of primary active transporters that exert vital cellular functions. However, the cellular function and transported substrate of ATP13A2 remain unknown. To discuss the role of ATP13A2 in neurodegeneration, we first provide a short description of the architecture and transport mechanism of P-type transport ATPases. Then, we briefly highlight key P-type ATPases involved in neuronal disorders such as the copper transporters ATP7A (Menkes disease), ATP7B (Wilson disease), the Na(+)/K(+)-ATPases ATP1A2 (familial hemiplegic migraine) and ATP1A3 (rapid-onset dystonia parkinsonism). Finally, we review the recent literature of ATP13A2 and discuss ATP13A2's putative cellular function in the light of what is known concerning the functions of other, better-studied P-type ATPases. We critically review the available data concerning the role of ATP13A2 in heavy metal transport and propose a possible alternative hypothesis that ATP13A2 might be a flippase. As a flippase, ATP13A2 may transport an organic molecule, such as a lipid or a peptide, from one membrane leaflet to the other. A flippase might control local lipid dynamics during vesicle formation and membrane fusion events.

  5. Cellular function and pathological role of ATP13A2 and related P-type transport ATPases in Parkinson’s disease and other neurological disorders

    Directory of Open Access Journals (Sweden)

    Sarah evan Veen

    2014-05-01

    Full Text Available Mutations in ATP13A2 lead to Kufor-Rakeb syndrome, a parkinsonism with dementia. ATP13A2 belongs to the P-type transport ATPases, a large family of primary active transporters that exert vital cellular functions. However, the cellular function and transported substrate of ATP13A2 remain unknown. To discuss the role of ATP13A2 in neurodegeneration, we first provide a short description of the architecture and transport mechanism of P-type transport ATPases. Then, we briefly highlight key P-type ATPases involved in neuronal disorders such as the copper transporters ATP7A (Menkes disease, ATP7B (Wilson disease, the Na+/K+-ATPases ATP1A2 (familial hemiplegic migraine and ATP1A3 (rapid-onset dystonia parkinsonism. Finally, we review the recent literature of ATP13A2 and discuss ATP13A2’s putative cellular function in the light of what is known concerning the functions of other, better-studied P-type ATPases. We critically review the available data concerning the role of ATP13A2 in heavy metal transport and propose a possible alternative hypothesis that ATP13A2 might be a flippase. As a flippase, ATP13A2 may transport an organic molecule, such as a lipid or a peptide, from one membrane leaflet to the other. A flippase might control local lipid dynamics during vesicle formation and membrane fusion events.

  6. Traffic Accident Propagation Properties and Control Measures for Urban Links Based on Cellular Automata

    Directory of Open Access Journals (Sweden)

    Xian-sheng Li

    2013-01-01

    Full Text Available With the rapid development of urban transport and the sharp increase in vehicle population, traffic accidents form one of the most important causes of urban traffic congestion other than the imbalance between traffic supply and demand. Traffic congestion causes severe problems, such as environment contamination and energy dissipation. Therefore, it would be useful to analyze the congestion propagation characteristics after traffic accidents. Numerical analysis and computer simulation were two of the typical methods used at present to study the traffic congestion propagation properties. The latter was more widespread as it is more consistent with the actual traffic flow and more visual than the former. In this paper, an improved cellular automata (CA model was presented to analyze traffic congestion propagation properties and to evaluate control strategies. In order to apply them to urban traffic flow simulation, the CA models have been improved and expanded on. Computer simulations were built for congestion not only extending to the upstream intersection, but also the upstream intersection and the entire road network, respectively. Congestion propagation characteristics after road traffic accidents were obtained, and controls of different severities and durations were analyzed. The results provide the theoretical foundation and practical means for the control of congestion.

  7. Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Ling Yang

    2016-01-01

    Full Text Available Calorie restriction (CR retards aging, acts as a hormetic intervention, and increases serum corticosterone and HSP70 expression in rodents. However, less is known regarding the effects of CR on these factors in humans. Serum cortisol and molecular chaperones and autophagic proteins were measured in the skeletal muscle of subjects on CR diets for 3–15 years and in control volunteers. Serum cortisol was higher in the CR group than in age-matched sedentary and endurance athlete groups (15.6 ± 4.6 ng/dl versus 12.3 ± 3.9 ng/dl and 11.2 ± 2.7 ng/dl, respectively; p ≤ 0.001. HSP70, Grp78, beclin-1, and LC3 mRNA and/or protein levels were higher in the skeletal muscle of the CR group compared to controls. Our data indicate that CR in humans is associated with sustained rises in serum cortisol, reduced inflammation, and increases in key molecular chaperones and autophagic mediators involved in cellular protein quality control and removal of dysfunctional proteins and organelles.

  8. Functional Divergence of Hsp90 Genetic Interactions in Biofilm and Planktonic Cellular States.

    Directory of Open Access Journals (Sweden)

    Stephanie Diezmann

    Full Text Available Candida albicans is among the most prevalent opportunistic fungal pathogens. Its capacity to cause life-threatening bloodstream infections is associated with the ability to form biofilms, which are intrinsically drug resistant reservoirs for dispersal. A key regulator of biofilm drug resistance and dispersal is the molecular chaperone Hsp90, which stabilizes many signal transducers. We previously identified 226 C. albicans Hsp90 genetic interactors under planktonic conditions, of which 56 are involved in transcriptional regulation. Six of these transcriptional regulators have previously been implicated in biofilm formation, suggesting that Hsp90 genetic interactions identified in planktonic conditions may have functional significance in biofilms. Here, we explored the relationship between Hsp90 and five of these transcription factor genetic interactors: BCR1, MIG1, TEC1, TUP1, and UPC2. We deleted each transcription factor gene in an Hsp90 conditional expression strain, and assessed biofilm formation and morphogenesis. Strikingly, depletion of Hsp90 conferred no additional biofilm defect in the mutants. An interaction was observed in which deletion of BCR1 enhanced filamentation upon reduction of Hsp90 levels. Further, although Hsp90 modulates expression of TEC1, TUP1, and UPC2 in planktonic conditions, it has no impact in biofilms. Lastly, we probed for physical interactions between Hsp90 and Tup1, whose WD40 domain suggests that it might interact with Hsp90 directly. Hsp90 and Tup1 formed a stable complex, independent of temperature or developmental state. Our results illuminate a physical interaction between Hsp90 and a key transcriptional regulator of filamentation and biofilm formation, and suggest that Hsp90 has distinct genetic interactions in planktonic and biofilm cellular states.

  9. Controller Chips Preserve Microprocessor Function

    Science.gov (United States)

    2012-01-01

    Above the Atlantic Ocean, off the coast of Brazil, there is a dip in the Earth s surrounding magnetic field called the South Atlantic Anomaly. Here, space radiation can reach into Earth s upper atmosphere to interfere with the functioning of satellites, aircraft, and even the International Space Station. "The South Atlantic Anomaly is a hot spot of radiation that the space station goes through at a certain point in orbit," Miria Finckenor, a physicist at Marshall Space Flight Center, describes, "If there s going to be a problem with the electronics, 90 percent of that time, it is going to be in that spot." Space radiation can cause physical damage to microchips and can actually change the software commands in computers. When high-energy particles penetrate a satellite or other spacecraft, the electrical components can absorb the energy and temporarily switch off. If the energy is high enough, it can cause the device to enter a hung state, which can only be addressed by restarting the system. When space radiation affects the operational status of microprocessors, the occurrence is called single event functional interrupt (SEFI). SEFI happens not only to the computers onboard spacecraft in Earth orbit, but to the computers on spacecraft throughout the solar system. "One of the Mars rovers had this problem in the radiation environment and was rebooting itself several times a day. On one occasion, it rebooted 40 times in one day," Finckenor says. "It s hard to obtain any data when you have to constantly reboot and start over."

  10. Effects of electromagnetic interference on the functional usage of medical equipment by 2G/3G/4G cellular phones: A revie

    National Research Council Canada - National Science Library

    Periyasamy M. Mariappan; Dhanasekaran R. Raghavan; Shady H.E. Abdel Aleem; Ahmed F. Zobaa

    2016-01-01

    .... The most commonly used device is the cellular phone, which emits strong electromagnetic energy affecting thereby the functionality of the vital medical equipment such as ventilators, ECG monitors...

  11. Regulation of cellular function via electromagnetic field frequency and extracellular environment: A theoretical- experimental approach

    Science.gov (United States)

    Taghian, Toloo; Sheikh, Abdul; Narmoneva, Daria; Kogan, Andrei

    2015-03-01

    Application of external electric field (EF) as a non-pharmacological, non-invasive tool to control cell function is of great therapeutic interest. We developed a theoretical-experimental approach to investigate the biophysical mechanisms of EF interaction with cells in electrode-free physiologically-relevant configuration. Our numerical results demonstrated that EF frequency is the major parameter to control cell response to EF. Non-oscillating or low-frequency EF leads to charge accumulation on the cell surface membrane that may mediate membrane initiated cell responses. In contrast, high-frequency EF penetrates the cell membrane and reaches cell cytoplasm, where it may directly activate intracellular responses. The theoretical predictions were confirmed in our experimental studies of the effects of applied EF on vascular cell function. Results show that non-oscillating EF increases vascular endothelial growth factor (VEGF) expression while field polarity controls cell adhesion rate. High-frequency, but not low frequency, EF provides differential regulation of cytoplasmic focal adhesion kinase and VEGF expression depending on the substrate, with increased expression in cells cultured on RGD-rich synthetic hydrogels, and decreased expression for matrigel culture. The authors acknowledge the financial support from the NSF (DMR-1206784 & DMR-0804199 to AK); the NIH (1R21 DK078814-01A1 to DN) and the University of Cincinnati (Interdisciplinary Faculty Research Support Grant to DN and AK).

  12. Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G.

    Directory of Open Access Journals (Sweden)

    Robert A Eagle

    very different cellular localisations that are likely to reflect unique functionality.

  13. Glycosaminoglycan-functionalized poly-lactide-co-glycolide nanoparticles: synthesis, characterization, cytocompatibility, and cellular uptake

    Directory of Open Access Journals (Sweden)

    Lamichhane SP

    2015-01-01

    Full Text Available Surya P Lamichhane,1 Neha Arya,1,2 Nirdesh Ojha,3 Esther Kohler,1 V Prasad Shastri1,2,41Institute for Macromolecular Chemistry, University of Freiburg, Freiburg, 2Helmholtz Virtual Institute on “Multifunctional Biomaterials for Medicine”, 3Laboratory for Process Technology, Department of Microsystems Engineering, University of Freiburg, Freiburg, 4Centre for Biological Signaling Studies (BIOSS, University of Freiburg, Freiburg, GermanyAbstract: The efficient delivery of chemotherapeutics to the tumor via nanoparticle (NP-based delivery systems remains a significant challenge. This is compounded by the fact that the tumor is highly dynamic and complex environment composed of a plurality of cell types and extracellular matrix. Since glycosaminoglycan (GAG production is altered in many diseases (or pathologies, NPs bearing GAG moieties on the surface may confer some unique advantages in interrogating the tumor microenvironment. In order to explore this premise, in the study reported here poly-lactide-co-glycolide (PLGA NPs in the range of 100–150 nm bearing various proteoglycans were synthesized by a single-step nanoprecipitation and characterized. The surface functionalization of the NPs with GAG moieties was verified using zeta potential measurements and X-ray photoelectron spectroscopy. To establish these GAG-bearing NPs as carriers of therapeutics, cellular toxicity assays were undertaken in lung epithelial adenocarcinoma (A549 cells, human pulmonary microvascular endothelial cells (HPMEC, and renal proximal tubular epithelial cells. In general NPs were well tolerated over a wide concentration range (100–600 µg/mL by all cell types and were taken up to appreciable extents without any adverse cell response in A549 cells and HPMEC. Further, GAG-functionalized PLGA NPs were taken up to different extents in A459 cells and HPMEC. In both cell systems, the uptake of heparin-modified NPs was diminished by 50%–65% in comparison to that of

  14. Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair.

    Science.gov (United States)

    Du, Fengxia; Zhang, Minjie; Li, Xiaohua; Yang, Caiyun; Meng, Hao; Wang, Dong; Chang, Shuang; Xu, Ye; Price, Brendan; Sun, Yingli

    2014-10-03

    The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair.

  15. SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease.

    Science.gov (United States)

    Rivat, Christine; Booth, Claire; Alonso-Ferrero, Maria; Blundell, Michael; Sebire, Neil J; Thrasher, Adrian J; Gaspar, H Bobby

    2013-02-14

    X-linked lymphoproliferative disease (XLP1) arises from mutations in the gene encoding SLAM-associated protein (SAP) and leads to abnormalities of NKT-cell development, NK-cell cytotoxicity, and T-dependent humoral function. Curative treatment is limited to allogeneic hematopoietic stem cell (HSC) transplantation. We tested whether HSC gene therapy could correct the multilineage defects seen in SAP(-/-) mice. SAP(-/-) murine HSCs were transduced with lentiviral vectors containing either SAP or reporter gene before transplantation into irradiated recipients. NKT-cell development was significantly higher and NK-cell cytotoxicity restored to wild-type levels in mice receiving the SAP vector in comparison to control mice. Baseline immunoglobulin levels were significantly increased and T-dependent humoral responses to NP-CGG, including germinal center formation, were restored in SAP-transduced mice.We demonstrate for the first time that HSC gene transfer corrects the cellular and humoral defects in SAP(-/-) mice providing proof of concept for gene therapy in XLP1.

  16. Control of human trophoblast function

    Directory of Open Access Journals (Sweden)

    Biondi Carla

    2007-02-01

    Full Text Available Abstract The trophoblast, i.e. the peripheral part of the human conceptus, exerts a crucial role in implantation and placentation. Both processes properly occur as a consequence of an intimate dialogue between fetal and maternal tissues, fulfilled by membrane ligands and receptors, as well as by hormone and local factor release. During blastocyst implantation, generation of distinct trophoblast cell types begins, namely the villous and the extravillous trophoblast, the former of which is devoted to fetal-maternal exchanges and the latter binds the placental body to the uterine wall. Physiological placentation is characterized by the invasion of the uterine spiral arteries by extravillous trophoblast cells arising from anchoring villi. Due to this invasion, the arterial structure is replaced by amorphous fibrinoid material and endovascular trophoblastic cells. This transformation establishes a low-resistance, high-capacity perfusion system from the radial arteries to the intervillous space, in which the villous tree is embedded. The physiology of pregnancy depends upon the orderly progress of structural and functional changes of villous and extravillous trophoblast, whereas a derangement of such processes can lead to different types of complications of varying degrees of gravity, including possible pregnancy loss and maternal life-threatening diseases. In this review we describe the mechanisms which regulate trophoblast differentiation, proliferation, migration and invasiveness, and the alterations in these mechanisms which lead to pathological conditions. Furthermore, based on the growing evidence that proper inflammatory changes and oxidative balance are needed for successful gestation, we explain the mechanisms by which agents able to influence such processes may be useful in the prevention and treatment of pregnancy disorders.

  17. Cellular transport of l-arginine determines renal medullary blood flow in control rats, but not in diabetic rats despite enhanced cellular uptake capacity.

    Science.gov (United States)

    Persson, Patrik; Fasching, Angelica; Teerlink, Tom; Hansell, Peter; Palm, Fredrik

    2017-02-01

    Diabetes mellitus is associated with decreased nitric oxide bioavailability thereby affecting renal blood flow regulation. Previous reports have demonstrated that cellular uptake of l-arginine is rate limiting for nitric oxide production and that plasma l-arginine concentration is decreased in diabetes. We therefore investigated whether regional renal blood flow regulation is affected by cellular l-arginine uptake in streptozotocin-induced diabetic rats. Rats were anesthetized with thiobutabarbital, and the left kidney was exposed. Total, cortical, and medullary renal blood flow was investigated before and after renal artery infusion of increasing doses of either l-homoarginine to inhibit cellular uptake of l-arginine or N(ω)-nitro- l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase. l-Homoarginine infusion did not affect total or cortical blood flow in any of the groups, but caused a dose-dependent reduction in medullary blood flow. l-NAME decreased total, cortical and medullary blood flow in both groups. However, the reductions in medullary blood flow in response to both l-homoarginine and l-NAME were more pronounced in the control groups compared with the diabetic groups. Isolated cortical tubular cells displayed similar l-arginine uptake capacity whereas medullary tubular cells isolated from diabetic rats had increased l-arginine uptake capacity. Diabetics had reduced l-arginine concentrations in plasma and medullary tissue but increased l-arginine concentration in cortical tissue. In conclusion, the reduced l-arginine availability in plasma and medullary tissue in diabetes results in reduced nitric oxide-mediated regulation of renal medullary hemodynamics. Cortical blood flow regulation displays less dependency on extracellular l-arginine and the upregulated cortical tissue l-arginine may protect cortical hemodynamics in diabetes.

  18. Extensive natural variation for cellular hydrogen peroxide release is genetically controlled.

    Directory of Open Access Journals (Sweden)

    Homa Attar

    Full Text Available Natural variation in DNA sequence contributes to individual differences in quantitative traits. While multiple studies have shown genetic control over gene expression variation, few additional cellular traits have been investigated. Here, we investigated the natural variation of NADPH oxidase-dependent hydrogen peroxide (H(2O(2 release, which is the joint effect of reactive oxygen species (ROS production, superoxide metabolism and degradation, and is related to a number of human disorders. We assessed the normal variation of H(2O(2 release in lymphoblastoid cell lines (LCL in a family-based 3-generation cohort (CEPH-HapMap, and in 3 population-based cohorts (KORA, GenCord, HapMap. Substantial individual variation was observed, 45% of which were associated with heritability in the CEPH-HapMap cohort. We identified 2 genome-wide significant loci of Hsa12 and Hsa15 in genome-wide linkage analysis. Next, we performed genome-wide association study (GWAS for the combined KORA-GenCord cohorts (n = 279 using enhanced marker resolution by imputation (>1.4 million SNPs. We found 5 significant associations (p<5.00×10-8 and 54 suggestive associations (p<1.00×10-5, one of which confirmed the linked region on Hsa15. To replicate our findings, we performed GWAS using 58 HapMap individuals and ∼2.1 million SNPs. We identified 40 genome-wide significant and 302 suggestive SNPs, and confirmed genome signals on Hsa1, Hsa12, and Hsa15. Genetic loci within 900 kb from the known candidate gene p67phox on Hsa1 were identified in GWAS in both cohorts. We did not find replication of SNPs across all cohorts, but replication within the same genomic region. Finally, a highly significant decrease in H(2O(2 release was observed in Down Syndrome (DS individuals (p<2.88×10-12. Taken together, our results show strong evidence of genetic control of H(2O(2 in LCL of healthy and DS cohorts and suggest that cellular phenotypes, which themselves are also complex, may be

  19. On stochastic geometry modeling of cellular uplink transmission with truncated channel inversion power control

    KAUST Repository

    Elsawy, Hesham

    2014-08-01

    Using stochastic geometry, we develop a tractable uplink modeling paradigm for outage probability and spectral efficiency in both single and multi-tier cellular wireless networks. The analysis accounts for per user equipment (UE) power control as well as the maximum power limitations for UEs. More specifically, for interference mitigation and robust uplink communication, each UE is required to control its transmit power such that the average received signal power at its serving base station (BS) is equal to a certain threshold ρo. Due to the limited transmit power, the UEs employ a truncated channel inversion power control policy with a cutoff threshold of ρo. We show that there exists a transfer point in the uplink system performance that depends on the following tuple: BS intensity λ, maximum transmit power of UEs Pu, and ρo. That is, when Pu is a tight operational constraint with respect to (w.r.t.) λ and ρo, the uplink outage probability and spectral efficiency highly depend on the values of λ and ρo. In this case, there exists an optimal cutoff threshold ρ*o, which depends on the system parameters, that minimizes the outage probability. On the other hand, when Pu is not a binding operational constraint w.r.t. λ and ρo, the uplink outage probability and spectral efficiency become independent of λ and ρo. We obtain approximate yet accurate simple expressions for outage probability and spectral efficiency, which reduce to closed forms in some special cases. © 2002-2012 IEEE.

  20. Potential for Natural Killer Cell-Mediated Antibody-Dependent Cellular Cytotoxicity for Control of Human Cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Rebecca J. Aicheler

    2013-12-01

    Full Text Available Human cytomegalovirus (HCMV is an important pathogen that infects the majority of the population worldwide, yet, currently, there is no licensed vaccine. Despite HCMV encoding at least seven Natural Killer (NK cell evasion genes, NK cells remain critical for the control of infection in vivo. Classically Antibody-Dependent Cellular Cytotoxicity (ADCC is mediated by CD16, which is found on the surface of the NK cell in a complex with FcεRI-γ chains and/or CD3ζ chains. Ninety percent of NK cells express the Fc receptor CD16; thus, they have the potential to initiate ADCC. HCMV has a profound effect on the NK cell repertoire, such that up to 10-fold expansions of NKG2C+ cells can be seen in HCMV seropositive individuals. These NKG2C+ cells are reported to be FcεRI-γ deficient and possess variable levels of CD16+, yet have striking ADCC functions. A subset of HCMV cell surface proteins will induce robust antibody responses that could render cells susceptible to ADCC. We will consider how the strong anti-HCMV function of NKG2C+ FcεRI-γ-deficient NK cells could potentially be harnessed in the clinic to treat patients suffering from HCMV disease and in the development of an efficacious HCMV vaccine.

  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. Cellular and biochemical responses of the oyster Crassostrea gigas to controlled exposures to metals and Alexandrium minutum

    Energy Technology Data Exchange (ETDEWEB)

    Haberkorn, Hansy; Lambert, Christophe; Le Goïc, Nelly [Laboratoire des Sciences de l‘Environnement Marin, UMR 6539, Institut Universitaire Européen de la Mer, Université de Bretagne Occidentale, Place Copernic, Technopôle Brest-Iroise, 29280 Plouzané (France); Quéré, Claudie [IFREMER Centre de Brest, Laboratoire de Physiologie des Invertébrés, Unité Physiologie Fonctionnelle des Organismes Marins, BP 70, 29280 Plouzané (France); Bruneau, Audrey; Riso, Ricardo; Auffret, Michel [Laboratoire des Sciences de l‘Environnement Marin, UMR 6539, Institut Universitaire Européen de la Mer, Université de Bretagne Occidentale, Place Copernic, Technopôle Brest-Iroise, 29280 Plouzané (France); Soudant, Philippe, E-mail: Philippe.Soudant@univ-brest.fr [Laboratoire des Sciences de l‘Environnement Marin, UMR 6539, Institut Universitaire Européen de la Mer, Université de Bretagne Occidentale, Place Copernic, Technopôle Brest-Iroise, 29280 Plouzané (France)

    2014-02-15

    Highlights: •Oysters, C. gigas, were exposed to both metals and PST-producer A. minutum. •Oysters exposed to metals accumulated about thirty-six times less PSTs. •Exposure to both metals and A. minutum induced antagonistic or synergetic effects. -- Abstract: Effects of simultaneous exposure of Pacific oyster, Crassostrea gigas, to both a harmful dinoflagellate that produces Paralytic Shellfish Toxins (PST), Alexandrium minutum, and cadmium (Cd) and copper (Cu), were assessed. Oysters were exposed to a mix of Cd–Cu with two different diets (i.e. A. minutum or Tisochrysis lutea) and compared to control oysters fed A. minutum or T. lutea, respectively, without metal addition. Metals and PST accumulations, digestive gland lipid composition, and cellular and biochemical hemolymph variables were measured after 4 days of exposure. Oysters exposed to Cd–Cu accumulated about thirty-six times less PSTs than oysters exposed to A. minutum alone. Exposure to Cd–Cu induced significant changes in neutral lipids (increase in diacylglycerol – DAG – and decrease in sterols) and phospholipids (decreases in phosphatidylcholine, phosphatidylethanolamine, cardiolipin and ceramide aminoethylphosphonate) of digestive gland suggesting that lipid metabolism disruptions and/or lipid peroxidation have occurred. Simultaneously, concentrations, percentages of dead cells and phenoloxidase activity of hemocytes increased in oysters exposed to metals while reactive oxygen species production of hemocytes decreased. Feeding on the harmful dinoflagellate A. minutum resulted in significant decreases in monoacylglycerol (MAG) and DAG and ether glycerides (EG), as well as significant increases in hemocyte concentration and phagocytic activity as compared to oysters fed T. lutea. Finally, the present study revealed that short-term, simultaneous exposure to Cd–Cu and A. minutum may induce antagonistic (i.e. hemocyte concentration and phagocytosis) or synergic (i.e. DAG content in

  3. Lysine acetylation targets protein complexes and co-regulates major cellular functions

    DEFF Research Database (Denmark)

    Choudhary, Chuna Ram; Kumar, Chanchal; Gnad, Florian;

    2009-01-01

    Lysine acetylation is a reversible posttranslational modification of proteins and plays a key role in regulating gene expression. Technological limitations have so far prevented a global analysis of lysine acetylation's cellular roles. We used high-resolution mass spectrometry to identify 3600...

  4. Transfer Function Control for Biometric Monitoring System

    Science.gov (United States)

    Chmiel, Alan J. (Inventor); Humphreys, Bradley T. (Inventor); Grodinsky, Carlos M. (Inventor)

    2015-01-01

    A modular apparatus for acquiring biometric data may include circuitry operative to receive an input signal indicative of a biometric condition, the circuitry being configured to process the input signal according to a transfer function thereof and to provide a corresponding processed input signal. A controller is configured to provide at least one control signal to the circuitry to programmatically modify the transfer function of the modular system to facilitate acquisition of the biometric data.

  5. Cellular function and pathological role of ATP13A2 and related P-type transport ATPases in Parkinson's disease and other neurological disorders

    DEFF Research Database (Denmark)

    van Veen, Sarah; Sørensen, Danny M.; Holemans, Tine

    2014-01-01

    Mutations in ATP13A2 lead to Kufor-Rakeb syndrome, a parkinsonism with dementia. ATP13A2 belongs to the P-type transport ATPases, a large family of primary active transporters that exert vital cellular functions. However, the cellular function and transported substrate of ATP13A2 remain unknown. ...

  6. Control of flux by narrow passages and hidden targets in cellular biology.

    Science.gov (United States)

    Holcman, D; Schuss, Z

    2013-07-01

    Critical biological processes, such as synaptic plasticity and transmission, activation of genes by transcription factors, or double-strained DNA break repair, are controlled by diffusion in structures that have both large and small spatial scales. These may be small binding sites inside or on the surface of the cell, or narrow passages between subcellular compartments. The great disparity in spatial scales is the key to controlling cell function by structure. We report here recent progress on resolving analytical and numerical difficulties in extracting properties from experimental data, from biophysical models, and from Brownian dynamics simulations of diffusion in multi-scale structures. This progress is achieved by developing an analytical approximation methodology for solving the model equations. The reported results are applied to analysis and simulations of subcellular processes and to the quantification of their biological functions.

  7. Functional adaptation and phenotypic plasticity at the cellular and whole plant level

    Indian Academy of Sciences (India)

    Karl J Niklas

    2009-10-01

    The ability to adaptively alter morphological, anatomical, or physiological functional traits to local environmental variations using external environmental cues is especially well expressed by all terrestrial and most aquatic plants. A ubiquitous cue eliciting these plastic phenotypic responses is mechanical perturbation (MP), which can evoke dramatic differences in the size, shape, or mechanical properties of conspecifics. Current thinking posits that MP is part of a very ancient ``stress-perception response system” that involves receptors located at the cell membrane/cell wall interface capable of responding to a broad spectrum of stress-inducing factors. This hypothesis is explored here from the perspective of cell wall evolution and the control of cell wall architecture by unicellular and multicellular plants. Among the conclusions that emerge from this exploration is the perspective that the plant cell is phenotypically plastic.

  8. Control of acrobot based on Lyapunov function

    Institute of Scientific and Technical Information of China (English)

    赖旭芝; 吴敏; 佘锦华

    2004-01-01

    Fuzzy control based on Lyapunov function was employed to control the posture and the energy of an acrobot to make the transition from upswing control to balance control smoothly and stably. First, a control law based on Lyapunov function was used to control the angle and the angular velocity of the second link towards zero when the energy of the acrobot reaches the potential energy at the unstable straight-up equilibrium position in the upswing process. The controller based on Lyapunov function makes the second link straighten nature relatively to the first link. At the same time, a fuzzy controller was designed to regulate the parameters of the upper control law to keep the change of the energy of the acrobot to a minimum, so that the switching from upswing to balance can be properly carried out and the acrobot can enter the balance quickly. The results of simulation show that the switching from upswing to balance can be completed smoothly, and the control effect of the acrobot is improved greatly.

  9. Functional and genetic deconstruction of the cellular origin in liver cancer

    DEFF Research Database (Denmark)

    Marquardt, Jens U; Andersen, Jesper B; Thorgeirsson, Snorri S

    2015-01-01

    During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation......, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance...... of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, we emphasize the importance and complexity of the cellular origin in tumour initiation and progression, and attempt to integrate this aspect with recent discoveries in tumour genomics and the contribution...

  10. Conserved and novel functions of programmed cellular senescence during vertebrate development

    Science.gov (United States)

    Davaapil, Hongorzul; Brockes, Jeremy P.

    2017-01-01

    Cellular senescence, a form of stable cell cycle arrest that is traditionally associated with tumour suppression, has been recently found to occur during mammalian development. Here, we show that cell senescence is an intrinsic part of the developmental programme in amphibians. Programmed senescence occurs in specific structures during defined time windows during amphibian development. It contributes to the physiological degeneration of the amphibian pronephros and to the development of the cement gland and oral cavity. In both contexts, senescence depends on TGFβ but is independent of ERK/MAPK activation. Furthermore, elimination of senescent cells through temporary TGFβ inhibition leads to developmental defects. Our findings uncover conserved and new roles of senescence in vertebrate organogenesis and support the view that cellular senescence may have arisen in evolution as a developmental mechanism. PMID:27888193

  11. A Pedestrian Navigation System Using Cellular Phone Video-Conferencing Functions

    Directory of Open Access Journals (Sweden)

    Akihiko Sugiura

    2012-01-01

    Full Text Available A user’s position-specific field has been developed using the Global Positioning System (GPS technology. To determine the position using cellular phones, a device was developed, in which a pedestrian navigation unit carries the GPS. However, GPS cannot specify a position in a subterranean environment or indoors, which is beyond the reach of transmitted signals. In addition, the position-specification precision of GPS, that is, its resolution, is on the order of several meters, which is deemed insufficient for pedestrians. In this study, we proposed and evaluated a technique for locating a user’s 3D position by setting up a marker in the navigation space detected in the image of a cellular phone. By experiment, we verified the effectiveness and accuracy of the proposed method. Additionally, we improved the positional precision because we measured the position distance using numerous markers.

  12. Evolutionarily Conserved and Nonconserved Cellular Localizations and Functions of Human SIRT Proteins

    OpenAIRE

    Michishita, Eriko; Park, Jean Y.; Burneskis, Jenna M.; Barrett, J. Carl; Horikawa, Izumi

    2005-01-01

    Sir2 is a NAD+-dependent protein deacetylase that extends lifespan in yeast and worms. This study examines seven human proteins homologous to Sir2 (SIRT1 through SIRT7) for cellular localization, expression profiles, protein deacetylation activity, and effects on human cell lifespan. We found that: 1) three nuclear SIRT proteins (SIRT1, SIRT6, and SIRT7) show different subnuclear localizations: SIRT6 and SIRT7 are associated with heterochromatic regions and nucleoli, respectively, where yeast...

  13. [Regulatory role of mechanical stress response in cellular function: development of new drugs and tissue engineering].

    Science.gov (United States)

    Momose, Kazutaka; Matsuda, Takehisa; Oike, Masahiro; Obara, Kazuo; Laher, Ismail; Sugiura, Seiryo; Ohata, Hisayuki; Nakayama, Koichi

    2003-02-01

    The investigation of mechanotransduction in the cardiovascular system is essentially important for elucidating the cellular and molecular mechanisms involved in not only the maintenance of hemodynamic homeostasis but also etiology of cardiovascular diseases including arteriosclerosis. The present review summarizes the latest research performed by six academic groups, and presented at the 75th Annual Meeting of the Japanese Pharmacological Society. Technology of cellular biomechanics is also required for research and clinical application of a vascular hybrid tissue responding to pulsatile stress. 1) Vascular tissue engineering: Design of pulsatile stress-responsive scaffold and in vivo vascular wall reconstruction (T. Matsuda); 2) Cellular mechanisms of mechanosensitive calcium transients in vascular endothelium (M. Oike et al.); 3) Cross-talk of stimulation with fluid flow and lysophosphatidic acid in vascular endothelial cells (K. Momose et al.); 4) Mechanotransduction of vascular smooth muscles: Rate-dependent stretch-induced protein phosphorylations and contractile activation (K. Obara et al.); 5) Lipid mediators in vascular myogenic tone (I. Laher et al.); and 6) Caldiomyocyte regulates its mechanical output in response to mechanical load (S. Sugiura et al.).

  14. Performance of joint dual links dynamic power control and smart antenna for TDMA/TDD cellular mobile communications

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Interference cancellation is made available by using smart antenna at cellular base stations. Well-distribut ed cumulative probability of signal-to-interference plus noise power ratio appears to be vital for cellular mobile multi media communications. A scenario of dual links dynamic power control combined to a solution of smart antenna is pro posed to adjust the instant transmission power in terms of the disparity from the favorite range. Simulation results show that this method is quite effective to improve the cumulative distribution probability performance. Meanwhile, accom panying low power consumption is also obtained at both base stations and mobile stations.

  15. Design and Performance Evaluation of Cooperative Retransmission Scheme for Reliable Multicast Services in Cellular Controlled P2P Networks

    DEFF Research Database (Denmark)

    Zhang, Qi; Fitzek, F.H.P.; Iversen, Villy Bæk

    2007-01-01

    communication architecture. It is referred to as cellular controlled peer-to- peer network, where the mobile devices communicate directly with each other to perform cooperative retransmissions using their short-range communication capabilities in addition to their cellular links. Based on the cooperative...... architecture a novel retransmission scheme is proposed exploiting the short-range retransmission in this paper. The state of the art, the non-cooperative error recovery schemes (e.g., ARQ, Layered FEC and Integrated FEC II) and the proposed scheme are compared with each other in terms of energy consumption...... to show the benefit of the newly introduced scheme....

  16. Continuous Control Artificial Potential Function Methods and Optimal Control

    Science.gov (United States)

    2014-03-27

    Method, namely r̈VDSVAPF = −K̇SKR∇φ−KSK̇R∇φ−KSKRH(φ)ṙ −KD (KSKR∇φ+ ṙ) . The above dynamics are very nonlinear due to the trigonometric functions (inside...constraints (on KS and θ) and the deletion of trigonometric functions . The suspected reasons for the larger computa- tional expense are twofold. First, this...Continuous Control Artificial Potential Function Methods and Optimal Control THESIS R. Andrew Fields, Civ, USAF AFIT-ENY-14-M-20 DEPARTMENT OF THE

  17. Analyses of Dynein Heavy Chain Mutations Reveal Complex Interactions Between Dynein Motor Domains and Cellular Dynein Functions

    Science.gov (United States)

    Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Razafsky, David S.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

    2012-01-01

    Cytoplasmic dynein transports cargoes for a variety of crucial cellular functions. However, since dynein is essential in most eukaryotic organisms, the in-depth study of the cellular function of dynein via genetic analysis of dynein mutations has not been practical. Here, we identify and characterize 34 different dynein heavy chain mutations using a genetic screen of the ascomycete fungus Neurospora crassa, in which dynein is nonessential. Interestingly, our studies show that these mutations segregate into five different classes based on the in vivo localization of the mutated dynein motors. Furthermore, we have determined that the different classes of dynein mutations alter vesicle trafficking, microtubule organization, and nuclear distribution in distinct ways and require dynactin to different extents. In addition, biochemical analyses of dynein from one mutant strain show a strong correlation between its in vitro biochemical properties and the aberrant intracellular function of that altered dynein. When the mutations were mapped to the published dynein crystal structure, we found that the three-dimensional structural locations of the heavy chain mutations were linked to particular classes of altered dynein functions observed in cells. Together, our data indicate that the five classes of dynein mutations represent the entrapment of dynein at five separate points in the dynein mechanochemical and transport cycles. We have developed N. crassa as a model system where we can dissect the complexities of dynein structure, function, and interaction with other proteins with genetic, biochemical, and cell biological studies. PMID:22649085

  18. Poly(methyl vinyl ether-alt-maleic acid)-functionalized porous silicon nanoparticles for enhanced stability and cellular internalization.

    Science.gov (United States)

    Shahbazi, Mohammad-Ali; Almeida, Patrick V; Mäkilä, Ermei; Correia, Alexandra; Ferreira, Mónica P A; Kaasalainen, Martti; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

    2014-03-01

    Currently, developing a stable nanocarrier with high cellular internalization and low toxicity is a key bottleneck in nanomedicine. Here, we have developed a successful method to covalently conjugate poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of (3-aminopropyl)triethoxysilane-functionalized thermally carbonized porous silicon nanoparticles (APSTCPSi NPs), forming a surface negatively charged nanovehicle with unique properties. This polymer conjugated NPs could modify surface smoothness, charge, and hydrophilicity of the developed NPs, leading to considerable improvement in the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion. Furthermore, despite the surface negative charge of the polymer-conjugated NPs, the cellular internalization was increased in both MDA-MB-231 and MCF-7 breast cancer cells. These results provide a proof-of-concept evidence that such polymer-based PSi nanocomposite can be extensively used as a promising candidate for intracellular drug delivery.

  19. Contextual Control by Function and Form of Transfer of Functions

    Science.gov (United States)

    Perkins, David R.; Dougher, Michael J.; Greenway, David E.

    2007-01-01

    This study investigated conditions leading to contextual control by stimulus topography over transfer of functions. Three 4-member stimulus equivalence classes, each consisting of four (A, B, C, D) topographically distinct visual stimuli, were established for 5 college students. Across classes, designated A stimuli were open-ended linear figures,…

  20. Whole-body microwave exposure emitted by cellular phones and testicular function of rats.

    Science.gov (United States)

    Dasdag, S; Ketani, M A; Akdag, Z; Ersay, A R; Sari, I; Demirtas, O C; Celik, M S

    1999-06-01

    This study investigated whether there are adverse effects due to microwave exposure emitted by cellular phones in male rats. Eighteen Wistar Albino rats were separated into three groups, a sham group and two experimental groups. The rats were confined in Plexiglas cages and cellular phones were placed 0.5 cm under the cages. In the first experimental group, cellular phones were in standby position for 2 h. In the second experimental group, phones were turned to the speech position three times each for 1 min duration over 2 h. Rats in the first and second experimental groups were exposed to microwaves emitted by phones for 2 h/day for a duration of 1 month. After the last exposure the rats were killed. Brain, eyes, ears, liver, heart, lungs, stomach, kidneys, testes, small and large intestines and skin of the rats were observed histologically. The decrease of epididymal sperm counts in the speech groups were not found to be significant (P > 0.05). Differences in terms of normal and abnormal sperm forms were not observed (P > 0.05). Histological changes were especially observed in the testes of rats of the speech groups. Seminiferous tubular diameter of rat testes in the standby and speech groups was found to be lower than the sham group (P < 0.05). Rectal temperatures of rats in the speech group were found to be higher than the sham and standby groups (P < 0.05). The rectal temperatures of rats before and after exposure were also found to be significantly higher in the speech group (P < 0.05). Specific absorption rate (SAR) was determined as 0.141 W/kg.

  1. Cellular and behavioral outcomes of dorsal striatonigral neuron ablation: new insights into striatal functions.

    Science.gov (United States)

    Révy, Delphine; Jaouen, Florence; Salin, Pascal; Melon, Christophe; Chabbert, Dorian; Tafi, Elisiana; Concetta, Lena; Langa, Francina; Amalric, Marianne; Kerkerian-Le Goff, Lydia; Marie, Hélène; Beurrier, Corinne

    2014-10-01

    The striatum is the input structure of the basal ganglia network that contains heterogeneous neuronal populations, including two populations of projecting neurons called the medium spiny neurons (MSNs), and different types of interneurons. We developed a transgenic mouse model enabling inducible ablation of the striatonigral MSNs constituting the direct pathway by expressing the human diphtheria toxin (DT) receptor under the control of the Slc35d3 gene promoter, a gene enriched in striatonigral MSNs. DT injection into the striatum triggered selective elimination of the majority of striatonigral MSNs. DT-mediated ablation of striatonigral MSNs caused selective loss of cholinergic interneurons in the dorsal striatum but not in the ventral striatum (nucleus accumbens), suggesting a region-specific critical role of the direct pathway in striatal cholinergic neuron homeostasis. Mice with DT injection into the dorsal striatum showed altered basal and cocaine-induced locomotion and dramatic reduction of L-DOPA-induced dyskinesia in the parkinsonian condition. In addition, these mice exhibited reduced anxiety, revealing a role of the dorsal striatum in the modulation of behaviors involving an emotional component, behaviors generally associated with limbic structures. Altogether, these results highlight the implication of the direct striatonigral pathway in the regulation of heterogeneous functions from cell survival to regulation of motor and emotion-associated behaviors.

  2. BACE1 regulates the proliferation and cellular functions of Schwann cells.

    Science.gov (United States)

    Hu, Xiangyou; Hou, Hailong; Bastian, Chinthasagar; He, Wanxia; Qiu, Shupeng; Ge, Yingying; Yin, Xinhua; Kidd, Grahame J; Brunet, Sylvain; Trapp, Bruce D; Baltan, Selva; Yan, Riqiang

    2017-05-01

    BACE1 is an indispensable enzyme for generating β-amyloid peptides, which are excessively accumulated in brains of Alzheimer's patients. However, BACE1 is also required for proper myelination of peripheral nerves, as BACE1-null mice display hypomyelination. To determine the precise effects of BACE1 on myelination, here we have uncovered a role of BACE1 in the control of Schwann cell proliferation during development. We demonstrate that BACE1 regulates the cleavage of Jagged-1 and Delta-1, two membrane-bound ligands of Notch. BACE1 deficiency induces elevated Jag-Notch signaling activity, which in turn facilitates proliferation of Schwann cells. This increase in proliferation leads to shortened internodes and decreased Schmidt-Lanterman incisures. Functionally, evoked compound action potentials in BACE1-null nerves were significantly smaller and slower, with a clear decrease in excitability. BACE1-null nerves failed to effectively use lactate as an alternative energy source under conditions of increased physiological activity. Correlatively, BACE1-null mice showed reduced performance on rotarod tests. Collectively, our data suggest that BACE1 deficiency enhances proliferation of Schwann cell due to the elevated Jag1/Delta1-Notch signaling, but fails to myelinate axons efficiently due to impaired the neuregulin1-ErbB signaling, which has been documented.

  3. The Effect of Bifidobacterium animalis ssp. lactis HN019 on Cellular Immune Function in Healthy Elderly Subjects: Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Larry E. Miller

    2017-02-01

    Full Text Available Elderly people have increased susceptibility to infections and cancer that are associated with decline in cellular immune function. The objective of this work was to determine the efficacy of Bifidobacterium (B. animalis ssp. lactis HN019 (HN019 supplementation on cellular immune activity in healthy elderly subjects. We conducted a systematic review of Medline and Embase for controlled trials that reported polymorphonuclear (PMN cell phagocytic capacity or natural killer (NK cell tumoricidal activity following B. lactis HN019 consumption in the elderly. A random effects meta-analysis was performed with standardized mean difference (SMD and 95% confidence interval between probiotic and control groups for each outcome. A total of four clinical trials were included in this analysis. B. lactis HN019 supplementation was highly efficacious in increasing PMN phagocytic capacity with an SMD of 0.74 (95% confidence interval: 0.38 to 1.11, p < 0.001 and moderately efficacious in increasing NK cell tumoricidal activity with an SMD of 0.43 (95% confidence interval: 0.08 to 0.78, p = 0.02. The main limitations of this research were the small number of included studies, short-term follow-up, and assessment of a single probiotic strain. In conclusion, daily consumption of B. lactis HN019 enhances NK cell and PMN function in healthy elderly adults.

  4. Experimental studies on extremely low frequency pulsed magnetic field inhibiting sarcoma and enhancing cellular immune functions

    Institute of Scientific and Technical Information of China (English)

    张沪生; 叶晖; 张传清; 曾繁清; 黄兴鼎; 张晴川; 李宗山; 杜碧

    1997-01-01

    The previous observation with an electron microscope showed that extremely low frequency (ELF) pulsed magnetic field (PMF) (with the maximum intensity of 0. 6-2. 0 T, gradient of 10-100 T. M-1, pulse width of 20-200 ms and frequency of 0. 16-1. 34 Hz) inhibited the growth of S-180 sarcoma in mice and enhanced the ability of immune cell’s dissolving sarcoma cells. In this study, the DNA contents of nuclei were assayed by using Faulgen Staining method. With an electron microscope and cell stereoscopy technology it was observed that magnetic field affected the sarcoma cell’s metabolism, lowered its malignancy, and restrained its rapid and heteromorphic growth. The magnetic field enhanced the cellular immune ability and the reaction of lymphocytes and plasma. Since ELF pulsed magnetic fields can inhibit the growth of sarcomas and enhance the cellular immune ability, it is possible to use it as a new method to treat cancer.

  5. Multi-functionality Redefined with Colloidal Carotene Carbon Nanoparticles for Synchronized Chemical Imaging, Enriched Cellular Uptake and Therapy

    Science.gov (United States)

    Misra, Santosh K.; Mukherjee, Prabuddha; Chang, Huei-Huei; Tiwari, Saumya; Gryka, Mark; Bhargava, Rohit; Pan, Dipanjan

    2016-07-01

    Typically, multiplexing high nanoparticle uptake, imaging, and therapy requires careful integration of three different functions of a multiscale molecular-particle assembly. Here, we present a simpler approach to multiplexing by utilizing one component of the system for multiple functions. Specifically, we successfully synthesized and characterized colloidal carotene carbon nanoparticle (C3-NP), in which a single functional molecule served a threefold purpose. First, the presence of carotene moieties promoted the passage of the particle through the cell membrane and into the cells. Second, the ligand acted as a potent detrimental moiety for cancer cells and, finally, the ligands produced optical contrast for robust microscopic detection in complex cellular environments. In comparative tests, C3-NP were found to provide effective intracellular delivery that enables both robust detection at cellular and tissue level and presents significant therapeutic potential without altering the mechanism of intracellular action of β-carotene. Surface coating of C3 with phospholipid was used to generate C3-Lipocoat nanoparticles with further improved function and biocompatibility, paving the path to eventual in vivo studies.

  6. Functional Neuroanatomy for Posture and Gait Control

    OpenAIRE

    Takakusaki, Kaoru

    2017-01-01

    Here we argue functional neuroanatomy for posture-gait control. Multi-sensory information such as somatosensory, visual and vestibular sensation act on various areas of the brain so that adaptable posture-gait control can be achieved. Automatic process of gait, which is steady-state stepping movements associating with postural reflexes including headeye coordination accompanied by appropriate alignment of body segments and optimal level of postural muscle tone, is mediated by the descending p...

  7. Both viral E2 protein and the cellular factor PEBP2 regulate transcription via E2 consensus sites within the bovine papillomavirus type 4 long control region.

    OpenAIRE

    Jackson, M E; Campo, M S

    1995-01-01

    The bovine papillomavirus type 4 (BPV4) long control region (LCR) contains three consensus binding sites, E2(1), E2(2), and E2(3) (ACCN6GGT), for the viral E2 transcription factor and a fourth degenerate site, dE2 (ATCN6GGT), which lies 3 bp upstream of E2(3). The E2(2) site was found to bind the cellular transcription factor PEBP2, and mutations at this site reduced basal promoter activity by as much as 60%, indicating an important role for PEBP2 in LCR function. Mutation of the E2(3) or dE2...

  8. Controlled functionalization of nanoparticles & practical applications

    Science.gov (United States)

    Rashwan, Khaled

    With the increasing use of nanoparticles in both science and industry, their chemical modification became a significant part of nanotechnology. Unfortunately, most commonly used procedures provide just randomly functionalized materials. The long-term objective of our work is site- and stoichiometrically-controlled functionalization of nanoparticles with the utilization of solid supports and other nanostructures. On the examples of silica nanoparticles and titanium dioxide nanorods, we have obtained results on the solid-phase chemistry, method development, and modeling, which advanced us toward this goal. At the same time, we explored several applications of nanoparticles that will benefit from the controlled functionalization: imaging of titanium-dioxide-based photocatalysts, bioimaging by fluorescent nanoparticles, drug delivery, assembling of bone implants, and dental compositions. Titanium dioxide-based catalysts are known for their catalytic activity and their application in solar energy utilization such as photosplitting of water. Functionalization of titanium dioxide is essential for enhancing bone-titanium dioxide nanotube adhesion, and, therefore, for its application as an interface between titanium implants and bones. Controlled functionalization of nanoparticles should enhance sensitivity and selectivity of nanoassemblies for imaging and drug delivery applications. Along those lines, we studied the relationship between morphology and surface chemistry of nanoparticles, and their affinity to organic molecules (salicylic and caffeic acid) using Langmuir adsorption isotherms, and toward material surfaces using SEM- and TEM-imaging. We focused on commercial samples of titanium dioxide, titanium dioxide nanorods with and without oleic acid ligands, and differently functionalized silica nanoparticles. My work included synthesis, functionalization, and characterization of several types of nanoparticles, exploring their application in imaging, dentistry, and bone

  9. Genes encoding Cher-TPR fusion proteins are predominantly found in gene clusters encoding chemosensory pathways with alternative cellular functions.

    Science.gov (United States)

    Muñoz-Martínez, Francisco; García-Fontana, Cristina; Rico-Jiménez, Miriam; Alfonso, Carlos; Krell, Tino

    2012-01-01

    Chemosensory pathways correspond to major signal transduction mechanisms and can be classified into the functional families flagellum-mediated taxis, type four pili-mediated taxis or pathways with alternative cellular functions (ACF). CheR methyltransferases are core enzymes in all of these families. CheR proteins fused to tetratricopeptide repeat (TPR) domains have been reported and we present an analysis of this uncharacterized family. We show that CheR-TPRs are widely distributed in GRAM-negative but almost absent from GRAM-positive bacteria. Most strains contain a single CheR-TPR and its abundance does not correlate with the number of chemoreceptors. The TPR domain fused to CheR is comparatively short and frequently composed of 2 repeats. The majority of CheR-TPR genes were found in gene clusters that harbor multidomain response regulators in which the REC domain is fused to different output domains like HK, GGDEF, EAL, HPT, AAA, PAS, GAF, additional REC, HTH, phosphatase or combinations thereof. The response regulator architectures coincide with those reported for the ACF family of pathways. Since the presence of multidomain response regulators is a distinctive feature of this pathway family, we conclude that CheR-TPR proteins form part of ACF type pathways. The diversity of response regulator output domains suggests that the ACF pathways form a superfamily which regroups many different regulatory mechanisms, in which all CheR-TPR proteins appear to participate. In the second part we characterize WspC of Pseudomonas putida, a representative example of CheR-TPR. The affinities of WspC-Pp for S-adenosylmethionine and S-adenosylhomocysteine were comparable to those of prototypal CheR, indicating that WspC-Pp activity is in analogy to prototypal CheRs controlled by product feed-back inhibition. The removal of the TPR domain did not impact significantly on the binding constants and consequently not on the product feed-back inhibition. WspC-Pp was found to be

  10. Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair

    Energy Technology Data Exchange (ETDEWEB)

    Du, Fengxia [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); Zhang, Minjie [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Li, Xiaohua; Yang, Caiyun [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); Meng, Hao; Wang, Dong; Chang, Shuang [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Xu, Ye [Department of Radiation Oncology, Division of Genomic Stability, Dana Farber Cancer Institute, Harvard Medical School, MA 02134 (United States); Price, Brendan, E-mail: Brendan_Price@dfci.harvard.edu [Department of Radiation Oncology, Division of Genomic Stability, Dana Farber Cancer Institute, Harvard Medical School, MA 02134 (United States); Sun, Yingli, E-mail: sunyl@big.ac.cn [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China)

    2014-10-03

    Highlights: • ATM phosphorylates the opposite strand of the dimer in response to DNA damage. • The PETPVFRLT box of ATM plays a key role in its dimer dissociation in DNA repair. • The dephosphorylation of ATM is critical for dimer re-formation after DNA repair. - Abstract: The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair.

  11. Shock-induced damage to mitochondrial function and some cellular antioxidant mechanisms in humans.

    Science.gov (United States)

    Corbucci, G G; Gasparetto, A; Candiani, A; Crimi, G; Antonelli, M; Bufi, M; De Blasi, R A; Cooper, M B; Gohil, K

    1985-01-01

    The effects of circulatory shock on skeletal muscle mitochondrial oxidative activity in various substrates and cytochrome oxidase activity have been investigated using samples of muscle obtained by the needle biopsy technique from human subjects. The effect of shock on superoxide dismutase activity and glutathione content of skeletal muscle was also examined. The results show that there is a large decrease in cytochrome oxidase activity during shock and also in the capacity of the mitochondria to oxidize either succinate, or pyruvate, or palmitoyl carnitine. There is a fall in the tissue content of superoxide dismutase and in the total glutathione present. Furthermore, an increased oxidized glutathione content causes a decrease in the molar ratio of reduced to oxidized glutathione present in the muscle. These findings suggest that mitochondrial electron transport chain (ETC) oxidative damage can play a relevant role in the pathogenesis of circulatory shock and support the hypothesis of oxygen-free radical involvement in the cellular injury.

  12. Mechanics and dynamics of triglyceride-phospholipid model membranes: Implications for cellular properties and function.

    Science.gov (United States)

    Pakkanen, Kirsi I; Duelund, Lars; Qvortrup, Klaus; Pedersen, Jan S; Ipsen, John H

    2011-08-01

    We demonstrate here that triolein alters the mechanical properties of phospholipid membranes and induces extraordinary conformational dynamics. Triolein containing membranes exhibit fluctuations up to size range of 100μm and with the help of these are e.g. able to squeeze through narrow passages between neighbouring structures. Triolein-phosphatidylcholine membranes were found to have bending rigidity significantly lower than that of corresponding pure phosphatidylcholine membrane. Moreover, the triolein containing membranes were found to be reluctant to fuse, which is in good accordance with larger lamellar distances observed in the TOPOPC membranes. These findings suggest repulsion between adjacent membranes. We provide a comprehensive discussion on the possible explanations for the observed mechanics and dynamics in the TOPOPC system and on their potential cellular implications. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Functional Proteomics Defines the Molecular Switch Underlying FGF Receptor Trafficking and Cellular Outputs

    DEFF Research Database (Denmark)

    Francavilla, Chiara; Rigbolt, Kristoffer T.G.; Emdal, Kristina B

    2013-01-01

    The stimulation of fibroblast growth factor receptors (FGFRs) with distinct FGF ligands generates specific cellular responses. However, the mechanisms underlying this paradigm have remained elusive. Here, we show that FGF-7 stimulation leads to FGFR2b degradation and, ultimately, cell proliferation......, whereas FGF-10 promotes receptor recycling and cell migration. By combining mass-spectrometry-based quantitative proteomics with fluorescence microscopy and biochemical methods, we find that FGF-10 specifically induces the rapid phosphorylation of tyrosine (Y) 734 on FGFR2b, which leads to PI3K and SH3BP4...... recruitment. This complex is crucial for FGFR2b recycling and responses, given that FGF-10 stimulation of either FGFR2b_Y734F mutant- or SH3BP4-depleted cells switches the receptor endocytic route to degradation, resulting in decreased breast cancer cell migration and the inhibition of epithelial branching...

  14. Sub-cellular localisation studies may spuriously detect the Yes-associated protein, YAP, in nucleoli leading to potentially invalid conclusions of its function.

    Science.gov (United States)

    Finch, Megan L; Passman, Adam M; Strauss, Robyn P; Yeoh, George C; Callus, Bernard A

    2015-01-01

    The Yes-associated protein (YAP) is a potent transcriptional co-activator that functions as a nuclear effector of the Hippo signaling pathway. YAP is oncogenic and its activity is linked to its cellular abundance and nuclear localisation. Activation of the Hippo pathway restricts YAP nuclear entry via its phosphorylation by Lats kinases and consequent cytoplasmic retention bound to 14-3-3 proteins. We examined YAP expression in liver progenitor cells (LPCs) and surprisingly found that transformed LPCs did not show an increase in YAP abundance compared to the non-transformed LPCs from which they were derived. We then sought to ascertain whether nuclear YAP was more abundant in transformed LPCs. We used an antibody that we confirmed was specific for YAP by immunoblotting to determine YAP's sub-cellular localisation by immunofluorescence. This antibody showed diffuse staining for YAP within the cytosol and nuclei, but, noticeably, it showed intense staining of the nucleoli of LPCs. This staining was non-specific, as shRNA treatment of cells abolished YAP expression to undetectable levels by Western blot yet the nucleolar staining remained. Similar spurious YAP nucleolar staining was also seen in mouse embryonic fibroblasts and mouse liver tissue, indicating that this antibody is unsuitable for immunological applications to determine YAP sub-cellular localisation in mouse cells or tissues. Interestingly nucleolar staining was not evident in D645 cells suggesting the antibody may be suitable for use in human cells. Given the large body of published work on YAP in recent years, many of which utilise this antibody, this study raises concerns regarding its use for determining sub-cellular localisation. From a broader perspective, it serves as a timely reminder of the need to perform appropriate controls to ensure the validity of published data.

  15. Optically controlled reconfigurable antenna for 5G future broadband cellular communication networks

    DEFF Research Database (Denmark)

    Costa, I.F. da; Spadoti, D. H.; Cerqueira Sodre Jr., Arismar

    2017-01-01

    the lightly licensed 28 GHz and 38 GHz frequency bands, useful for future mobile 5G broadband cellular communication networks. Experimental results with the reconfigurable antenna on 16-QAM and 32-QAM wireless transmission supported by photonic downconversion are successfully reported under 78 dB link budget...

  16. Small regulatory RNAs control the multi-cellular adhesive lifestyle of Escherichia coli

    DEFF Research Database (Denmark)

    Jørgensen, Mikkel Girke; Nielsen, Jesper Sejrup; Boysen, Anders

    2012-01-01

    Small regulatory RNA molecules have recently been recognized as important regulatory elements of developmental processes in both eukaryotes and bacteria. We here describe a striking example in Escherichia coli that can switch between a single-cell motile lifestyle and a multi-cellular, sessile...

  17. Control of Directional Macromolecular Trafficking Across Specific Cellular Boundaries: A Key to Integrative Plant Biology

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    There is now solid evidence that cell-to-cell trafficking of certain proteins and RNAs plays a critical role in trans-cellular regulation of gene expression to coordinate cellular differentiation and development. Such trafficking also is critical for viral infection and plant defense. The mechanisms of trafficking remain poorly understood. Although some proteins may move between cells by diffusion, many proteins and RNAs move in a highly regulated fashion. Regulation is likely achieved through interactions between distinct protein or RNA motifs and cellular factors. Some motifs and factors have been identified. One of the major focuses for future studies is to identify all motifs and their cognate factors and further elucidate their roles in trafficking between specific cells. With increasing information from such studies, we should be able to develop an understanding of the mechanisms that regulate trafficking of various proteins and RNAs across all and specific cellular boundaries. On the basis of such mechanistic knowledge, we can further investigate how the trafficking machinery has evolved to regulate developmental and physiological processes in a plant, how pathogens have co-evolved to use this machinery for systemic spread in a plant, and how plants use this machinery for counterdefense.

  18. Early stages of HIV replication: how to hijack cellular functions for a successful infection.

    Science.gov (United States)

    Lehmann-Che, Jacqueline; Saïb, Ali

    2004-01-01

    From the cell surface to the nucleus, the human immunodeficiency virus type 1 (HIV-1) will face multiple obstacles, crossing the plasma and nuclear membranes, but also finding its path within the cytoplasm in which elements from the cytoskeleton, organelles, and high a protein concentration, limit intracellular movements. At the same time, HIV-1 has to counteract cellular defenses--known as restriction factors--interfering with early steps of the virus cycle. Although the general outcomes of these early stages have been identified since several decades, the stepwise interactions taking place between cellular and viral components during this early journey, which will transform the incoming viral-RNA genome into a double-strand DNA competent for integration, remain largely unknown. In that sense, the uncoating process and the molecular basis of intracellular trafficking of preintegration complexes (PICs) are still poorly defined. Additionally, other key stages, which have been the focus of many reports, still require some clarifications, as is the case for the precise determinants of nuclear import of PICs. Finally, whereas the molecular mechanisms of integration, the last event of the early phase of retroviral life cycle, are now well understood, the choice of the integration site remains mysterious. Fully elucidating the early steps of HIV-1 replication is therefore crucial, not only for developing new antiretroviral drugs, but also for improving the design of lentiviral vectors for gene therapy. Since the mechanisms of HIV-1 entry and innate cell defenses were recently the topic of excellent reviews, we will focus here on uncoating and intracellular trafficking of HIV-1.

  19. Calcium and ATP control multiple vital functions

    Science.gov (United States)

    Verkhratsky, Alexei

    2016-01-01

    Life on Planet Earth, as we know it, revolves around adenosine triphosphate (ATP) as a universal energy storing molecule. The metabolism of ATP requires a low cytosolic Ca2+ concentration, and hence tethers these two molecules together. The exceedingly low cytosolic Ca2+ concentration (which in all life forms is kept around 50–100 nM) forms the basis for a universal intracellular signalling system in which Ca2+ acts as a second messenger. Maintenance of transmembrane Ca2+ gradients, in turn, requires ATP-dependent Ca2+ transport, thus further emphasizing the inseparable links between these two substances. Ca2+ signalling controls the most fundamental processes in the living organism, from heartbeat and neurotransmission to cell energetics and secretion. The versatility and plasticity of Ca2+ signalling relies on cell specific Ca2+ signalling toolkits, remodelling of which underlies adaptive cellular responses. Alterations of these Ca2+ signalling toolkits lead to aberrant Ca2+ signalling which is fundamental for the pathophysiology of numerous diseases from acute pancreatitis to neurodegeneration. This paper introduces a theme issue on this topic, which arose from a Royal Society Theo Murphy scientific meeting held in March 2016. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377728

  20. Deep networks for motor control functions

    Directory of Open Access Journals (Sweden)

    Max eBerniker

    2015-03-01

    Full Text Available The motor system generates time-varying commands to move our limbs and body. Conventional descriptions of motor control and learning rely on dynamical representations of our body’s state (forward and inverse models, and control policies that must be integrated forward to generate feedforward time-varying commands; thus these are representations across space, but not time. Here we examine a new approach that directly represents both time-varying commands and the resulting state trajectories with a function; a representation across space and time. Since the output of this function includes time, it necessarily requires more parameters than a typical dynamical model. To avoid the problems of local minima these extra parameters introduce, we exploit recent advances in machine learning to build our function using a stacked autoencoder, or deep network. With initial and target states as inputs, this deep network can be trained to output an accurate temporal profile of the optimal command and state trajectory for a point-to-point reach of a nonlinear limb model, even when influenced by varying force fields. In a manner that mirrors motor babble, the network can also teach itself to learn through trial and error. Lastly, we demonstrate how this network can learn to optimize a cost objective. This functional approach to motor control is a sharp departure from the standard dynamical approach, and may offer new insights into the neural implementation of motor control.

  1. Effects of acamprosate on attentional set-shifting and cellular function in the prefrontal cortex of chronic alcohol-exposed mice

    Science.gov (United States)

    Hu, Wei

    Background: The medial prefrontal cortex (mPFC) inhibits impulsive and compulsive behaviors that characterize drug abuse and dependence. Acamprosate is the leading medication approved for the maintenance of abstinence, shown to reduce craving and relapse in animal models and human alcoholics. Whether acamprosate can modulate executive functions that are impaired by chronic ethanol exposure is unknown. Here we explored the effects of acamprosate on an attentional set-shifting task, and tested whether these behavioral effects are correlated with modulation of glutamatergic synaptic transmission and intrinsic excitability of mPFC neurons. Methods: We induced alcohol dependence in mice via chronic intermittent ethanol (CIE) exposure in vapor chambers and measured changes in alcohol consumption in a limited access 2-bottle choice paradigm. Impairments of executive function were assessed in an attentional set-shifting task. Acamprosate was applied subchronically for 2 days during withdrawal before the final behavioral test. Alcohol-induced changes in cellular function of layer 5/6 pyramidal neurons, and the potential modulation of these changes by acamprosate, were measured using patch clamp recordings in brain slices. Results: Chronic ethanol exposure impaired cognitive flexibility in the attentional set-shifting task. Acamprosate improved overall performance and reduced perseveration. Recordings of mPFC neurons showed that chronic ethanol exposure increased use-dependent presynaptic transmitter release and enhanced postsynaptic N-methyl-D-aspartate receptor (NMDAR) function. Moreover, CIE-treatment lowered input resistance, and decreased the threshold and the afterhyperpolarization (AHP) of action potentials, suggesting chronic ethanol exposure also impacted membrane excitability of mPFC neurons. However, acamprosate treatment did not reverse these ethanol-induced changes cellular function. Conclusion: Acamprosate improved attentional control of ethanol exposed animals

  2. SURFACE TEXTURE ANALYSIS FOR FUNCTIONALITY CONTROL

    DEFF Research Database (Denmark)

    De Chiffre, Leonardo; Andreasen, Jan Lasson; Tosello, Guido

    This document is used in connection with three exercises of 3 hours duration as a part of the course VISION ONLINE – One week course on Precision & Nanometrology. The exercises concern surface texture analysis for functionality control, in connection with three different case stories. This docume...... contains a short description of each case story, 3-D roughness parameters analysis and relation with the product’s functionality.......This document is used in connection with three exercises of 3 hours duration as a part of the course VISION ONLINE – One week course on Precision & Nanometrology. The exercises concern surface texture analysis for functionality control, in connection with three different case stories. This document...

  3. Root Cause Analysis and New Practical Schemes for better Accessing and Establishing of Dedicated Control Channel in Cellular Networks

    Directory of Open Access Journals (Sweden)

    Mohammad Rasoul Tanhatalab

    2013-12-01

    Full Text Available The Dedicated Control Channel (DCCH plays an important role in all generations of cellular networks, such as, GSM , HSPA and LTE ; through this logical channel, some information between user equipment and network can be carried. It should be considered that accessing to the DCCH is the entry gate of entrance to the every cellular network; and without a successful DCCH access call-setup process will not be possible. Hence, DCCH channel accessing is one of the most critical issues that RF planner and optimization engineers must consider. More than this, these schemes can contribute to achieve some algorithms in SON for ameliorating the DCCH accessing and serving better services at 4G. In this paper, a real fundamentally established cellular network (GSM is surveyed and its radio frequency network performance is evaluated and presented on the basis of KPI parameters in general. Furthermore, the DCCH Access Success in particular and different issues, findings, trials and improvements have been summarized. Also, recommendations have been listed to correlate the practical aspects of RF optimization, which affect the improvement of DCCH Access Success rate in cellular networks.

  4. A paradigm shift in neurobiology: peripheral nerves deliver cellular material and control development.

    Science.gov (United States)

    Ivashkin, Evgeny; Voronezhskaya, Elena E; Adameyko, Igor

    2014-10-01

    Living beings are extremely complex. Multiple structures, especially evolutionarily young ones, develop or take their final shape during late stages of embryonic development, when the body of an embryo is large and comprised of a huge number of cells. Yet, these late structures frequently need cellular sources from other locations and, sometimes, developmental stages. During recent years it became obvious that nerves provide a perfect solution for transporting and hosting multipotent cells that are later recruited to become new cellular sources in the innervated organs. Moreover, the role of nerves and nerve-dwelling cells in morphogenesis and regeneration seems to be much broader than was previously appreciated in invertebrate and vertebrate animals. In a broader view, nerves can provide material for morphological plasticity and evolutional diversity.

  5. Design and Evaluation of IP Header Compression for Cellular-Controlled P2P Networks

    DEFF Research Database (Denmark)

    Madsen, T.K.; Zhang, Qi; Fitzek, F.H.P.

    2007-01-01

    In this paper we advocate to exploit terminal cooperation to stabilize IP communication using header compression. The terminal cooperation is based on direct communication between terminals using short range communication and simultaneously being connected to the cellular service access point....... The short range link is than used to provide first aid information to heal the decompressor state of the neighboring node in case of a packet loss on the cellular link. IP header compression schemes are used to increase the spectral and power efficiency loosing robustness of the communication compared...... to the uncompressed version. By introducing the terminal cooperation supporting header compression the robustness is increased. Within this article we will show that header compression should be applied to reduce the energy consumption of the terminals and moreover the header compression should be supported...

  6. JAK/STAT signaling in Drosophila muscles controls the cellular immune response against parasitoid infection.

    Science.gov (United States)

    Yang, Hairu; Kronhamn, Jesper; Ekström, Jens-Ola; Korkut, Gül Gizem; Hultmark, Dan

    2015-12-01

    The role of JAK/STAT signaling in the cellular immune response of Drosophila is not well understood. Here, we show that parasitoid wasp infection activates JAK/STAT signaling in somatic muscles of the Drosophila larva, triggered by secretion of the cytokines Upd2 and Upd3 from circulating hemocytes. Deletion of upd2 or upd3, but not the related os (upd1) gene, reduced the cellular immune response, and suppression of the JAK/STAT pathway in muscle cells reduced the encapsulation of wasp eggs and the number of circulating lamellocyte effector cells. These results suggest that JAK/STAT signaling in muscles participates in a systemic immune defense against wasp infection.

  7. Inhibiting the NF-kappaB pathway to assess its function in the cellular response to space radiation

    Science.gov (United States)

    Koch, Kristina; Baumstark-Khan, Christa; Hellweg, Christine; Testard, Isabelle; Reitz, Guenther

    2012-07-01

    Radiation is regarded as one of the limiting factors for space missions. Therefore the cellular radiation response needs to be studied in order to estimate risks and to develop appropriate countermeasures. Exposure of human cells to ionizing radiation can provoke cell cycle arrest, leading to cellular senescence or premature differentiation, and different types of cell death. Previous heavy ion experiments have shown that the Nuclear Factor κB (NF-κB) pathway is activated by fluences that can be reached during long-term missions and thereby NF-κB was identified as an important modulating factor in the cellular radiation response. It could improve cellular survival after exposure to high radiation doses and influence the cancer risk of astronauts. The classical and the genotoxic stress induced NF-κB pathway result in nuclear translocation of the p65/p50 dimer. Both pathways might contribute to the cellular radiation response. Chemical inhibitors were tested to suppress the NF-κB pathway in recombinant HEK-pNF-κB-d2EGFP/Neo cells. The efficacy and cytotoxicity of the inhibitors targeting different elements of the NF-κB pathway were analyzed and found mostly inappropriate as inhibitors were partly cytotoxic or unspecific. Alternatively a functional knock-out of RelA (p65) was used to identify the contribution of the NF-κB pathway to different cellular outcomes. Small hairpin RNA constructs (shRNA) were transfected into the HEK-pNF-κB-d2EGFP/Neo cell line. Their functionality was assessed by quantitative Reverse Transcriptase real-time PCR (qRT-PCR) to verify that the RelA mRNA amount was reduced by more than 80% in the knock-down cells The original cell line had been stably transfected with a reporter system to monitor NF-κB activation by measuring destabilized Enhanced Green Fluorescent Protein (d2EGFP)-expression. It was shown that after 18 hours d2EGFP reaches its highest expression level after activation of NF-κB and can be measured by FACS analysis

  8. Functional characterization of water transport and cellular localization of three aquaporin paralogs in the salmonid intestine

    DEFF Research Database (Denmark)

    Madsen, Steffen S; Olesen, Jesper H; Bedal, Konstanze

    2011-01-01

    Intestinal water absorption is greatly enhanced in salmonids upon acclimation from freshwater (FW) to seawater (SW); however, the molecular mechanism for water transport is unknown. We conducted a pharmacological characterization of water absorption in the rainbow trout intestine along with an in......Intestinal water absorption is greatly enhanced in salmonids upon acclimation from freshwater (FW) to seawater (SW); however, the molecular mechanism for water transport is unknown. We conducted a pharmacological characterization of water absorption in the rainbow trout intestine along...... with an investigation of the distribution and cellular localization of three aquaporins (Aqp1aa, -1ab, and -8ab) in pyloric caeca, middle (M), and posterior (P) intestine of the Atlantic salmon. In vitro iso-osmotic water absorption (J(v)) was higher in SW than FW-trout and was inhibited by (mmol L(-1)): 0.1 KCN (41......%), 0.1 ouabain (72%), and 0.1 bumetanide (82%) suggesting that active transport, Na(+), K(+)-ATPase and Na(+), K(+), 2Cl(-)-co-transport are involved in establishing the driving gradient for water transport. J(v) was also inhibited by 1 mmol L(-1) HgCl(2), serosally (23% in M and 44% in P), mucosally...

  9. Functional domains and sub-cellular distribution of the Hedgehog transducing protein Smoothened in Drosophila.

    Science.gov (United States)

    Nakano, Y; Nystedt, S; Shivdasani, A A; Strutt, H; Thomas, C; Ingham, P W

    2004-06-01

    The Hedgehog signalling pathway is deployed repeatedly during normal animal development and its inappropriate activity is associated with various tumours in human. The serpentine protein Smoothened (Smo) is essential for cells to respond to the Hedeghog (Hh) signal; oncogenic forms of Smo have been isolated from human basal cell carcinomas. Despite similarities with ligand binding G-protein coupled receptors, the molecular basis of Smo activity and its regulation remains unclear. In non-responding cells, Smo is suppressed by the activity of another multipass membrane spanning protein Ptc, which acts as the Hh receptor. In Drosophila, binding of Hh to Ptc has been shown to cause an accumulation of phosphorylated Smo protein and a concomitant stabilisation of the activated form of the Ci transcription factor. Here, we identify domains essential for Smo activity and investigate the sub-cellular distribution of the wild type protein in vivo. We find that deletion of the amino terminus and the juxtamembrane region of the carboxy terminus of the protein result in the loss of normal Smo activity. Using Green Fluorescent Protein (GFP) and horseradish peroxidase fusion proteins we show that Smo accumulates in the plasma membrane of cells in which Ptc activity is abrogated by Hh but is targeted to the degradative pathway in cells where Ptc is active. We further demonstrate that Smo accumulation is likely to be a cause, rather than a consequence, of Hh signal transduction.

  10. ECM signaling regulates collective cellular dynamics to control pancreas branching morphogenesis

    OpenAIRE

    2015-01-01

    During pancreas development, epithelial buds undergo branching morphogenesis to form an exocrine and endocrine gland. Proper morphogenesis is necessary for correct lineage allocation of pancreatic progenitors; however, the cellular events underlying pancreas morphogenesis are unknown. Here, we employed time-lapse microscopy and fluorescent labeling of cells to analyze cell behaviors associated with pancreas morphogenesis. We observed that outer bud cells adjacent to the basement membrane are ...

  11. When "altering brain function" becomes "mind control".

    Science.gov (United States)

    Koivuniemi, Andrew; Otto, Kevin

    2014-01-01

    Functional neurosurgery has seen a resurgence of interest in surgical treatments for psychiatric illness. Deep brain stimulation (DBS) technology is the preferred tool in the current wave of clinical experiments because it allows clinicians to directly alter the functions of targeted brain regions, in a reversible manner, with the intent of correcting diseases of the mind, such as depression, addiction, anorexia nervosa, dementia, and obsessive compulsive disorder. These promising treatments raise a critical philosophical and humanitarian question. "Under what conditions does 'altering brain function' qualify as 'mind control'?" In order to answer this question one needs a definition of mind control. To this end, we reviewed the relevant philosophical, ethical, and neurosurgical literature in order to create a set of criteria for what constitutes mind control in the context of DBS. We also outline clinical implications of these criteria. Finally, we demonstrate the relevance of the proposed criteria by focusing especially on serendipitous treatments involving DBS, i.e., cases in which an unintended therapeutic benefit occurred. These cases highlight the importance of gaining the consent of the subject for the new therapy in order to avoid committing an act of mind control.

  12. The Surface Charge and Cellular Processing of Covalently Functionalized Multiwall Carbon Nanotubes Determine Pulmonary Toxicity

    OpenAIRE

    Li, Ruibin; Wang,Xiang; Ji, Zhaoxia; Sun, Bingbing; Zhang, Haiyuan; Chang, Chong Hyun; Lin, Sijie; Meng, Huan; Liao, Yu-Pei; Wang, Meiying; Li, Zongxi; Hwang, Angela; Song, Tze-Bin; Xu, Run; Yang, Yang

    2013-01-01

    Functionalized carbon nanotubes (f-CNTs) are being produced in increased volume because of the ease of dispersion and maintenance of the pristine material physicochemical properties when used in composite materials as well as for other commercial applications. However, the potential adverse effects of f-CNTs have not been quantitatively or systematically explored, and in this study we used a library of covalently functionalized multiwall carbon nanotubes (f-MWCNTs), established from the same ...

  13. Case-control study on the use of cellular and cordless phones and the risk for malignant brain tumours.

    Science.gov (United States)

    Hardell, L; Mild, K H; Carlberg, M

    2002-10-01

    To investigate the use of cellular and cordless phones and the risk for malignant brain tumours. A case-control study was performed on 649 patients aged 20-80 years of both sexes with malignant brain tumour diagnosed from 1 January 1997 to 30 June 2000. All patients were alive during the time of the study and had histopathology verified brain tumours. One matched control to each case was selected from the Swedish Population Register. The study area was the Uppsala-Orebro, Stockholm, Linköping and Göteborg medical regions of Sweden. Exposure was assessed by a questionnaire answered by 588 (91%) cases and 581 (90%) controls. Phone usage was defined as 'ever use' and usage starting within 1 year before diagnosis was disregarded. Overall, no significantly increased risks were found: analogue cellular phones yielded an odds ratio (OR)=1.13, 95% confidence interval (CI)=0.82-1.57, digital cellular phones OR=1.13, CI=0.86-1.48, and cordless phones OR=1.13, CI=0.85-1.50. For ipsilateral (same side) radiofrequency exposure, analogue mobile phones gave OR=1.85, CI=1.16-2.96, for all malignant brain tumours. For astrocytoma, this risk was OR=1.95, CI=1.12-3.39. For all malignant brain tumours, digital mobile phones yielded OR=1.59, CI=1.05-2.41, and cordless phones yielded OR=1.46, CI=0.96-2.23, in the analysis of ipsilateral exposure. The ipsilateral use of an analogue cellular phone yielded a significantly increased risk for malignant brain tumours.

  14. Alumina-zirconia composites functionalized with laminin-1 and laminin-5 for dentistry: effect of protein adsorption on cellular response.

    Science.gov (United States)

    Vallée, A; Faga, M G; Mussano, F; Catalano, F; Tolosano, E; Carossa, S; Altruda, F; Martra, G

    2014-02-01

    The present paper describes a study on laminin interaction with the surface of two alumina-zirconia composites with different percentages of ZrO2, both with submicrometric grain size. As major molecules within the basement membrane (BM), laminins are important protein fragments for epithelial cell adhesion and migration. On the other hand, alumina-zirconia composites are very attractive materials for dental applications due to their esthetic and mechanical properties. X-Ray photoelectron spectroscopy and atomic force microscopy were used to study the adsorption of two types of laminin, laminin-1 (Ln-1) and laminin-5 (Ln-5), onto the ceramics surfaces. The in vitro cell response was determined by intracellular phosphorylation of major kinases. Ceramics samples functionalized with laminins showed better cellular activation than untreated specimens; furthermore, cellular activation was found to be greater for the composite with higher percentage in zirconia when functionalized with Ln-5, whereas the adsorption of Ln-1 resulted in a greater activation for the alumina-rich oxide.

  15. Algebras of holomorphic functions and control theory

    CERN Document Server

    Sasane, Amol

    2009-01-01

    This accessible, undergraduate-level text illustrates the role of algebras of holomorphic functions in the solution of an important engineering problem: the stabilization of a linear control system. Its concise and self-contained treatment avoids the use of higher mathematics and forms a bridge to more advanced treatments. The treatment consists of two components: the algebraic framework, which serves as the abstract language for posing and solving the problem of stabilization; and the analysis component, which examines properties of specific rings of holomorphic functions. Elementary, self-co

  16. Functional Neuroanatomy for Posture and Gait Control.

    Science.gov (United States)

    Takakusaki, Kaoru

    2017-01-01

    Here we argue functional neuroanatomy for posture-gait control. Multi-sensory information such as somatosensory, visual and vestibular sensation act on various areas of the brain so that adaptable posture-gait control can be achieved. Automatic process of gait, which is steady-state stepping movements associating with postural reflexes including headeye coordination accompanied by appropriate alignment of body segments and optimal level of postural muscle tone, is mediated by the descending pathways from the brainstem to the spinal cord. Particularly, reticulospinal pathways arising from the lateral part of the mesopontine tegmentum and spinal locomotor network contribute to this process. On the other hand, walking in unfamiliar circumstance requires cognitive process of postural control, which depends on knowledges of self-body, such as body schema and body motion in space. The cognitive information is produced at the temporoparietal association cortex, and is fundamental to sustention of vertical posture and construction of motor programs. The programs in the motor cortical areas run to execute anticipatory postural adjustment that is optimal for achievement of goal-directed movements. The basal ganglia and cerebellum may affect both the automatic and cognitive processes of posturegait control through reciprocal connections with the brainstem and cerebral cortex, respectively. Consequently, impairments in cognitive function by damages in the cerebral cortex, basal ganglia and cerebellum may disturb posture-gait control, resulting in falling.

  17. Functional Neuroanatomy for Posture and Gait Control

    Directory of Open Access Journals (Sweden)

    Kaoru Takakusaki

    2017-01-01

    Full Text Available Here we argue functional neuroanatomy for posture- gait control. Multi-sensory information such as somatosensory, visual and vestibular sensation act on various areas of the brain so that adaptable posture- gait control can be achieved. Automatic process of gait, which is steady-state stepping movements associating with postural reflexes including headeye coordination accompanied by appropriate alignment of body segments and optimal level of postural muscle tone, is mediated by the descending pathways from the brainstem to the spinal cord. Particularly, reticulospinal pathways arising from the lateral part of the mesopontine tegmentum and spinal locomotor network contribute to this process. On the other hand, walking in unfamiliar circumstance requires cognitive process of postural control, which depends on knowledges of self-body, such as body schema and body motion in space. The cognitive information is produced at the temporoparietal association cortex, and is fundamental to sustention of vertical posture and construction of motor programs. The programs in the motor cortical areas run to execute anticipatory postural adjustment that is optimal for achievement of goal-directed movements. The basal ganglia and cerebellum may affect both the automatic and cognitive processes of posturegait control through reciprocal connections with the brainstem and cerebral cortex, respectively. Consequently, impairments in cognitive function by damages in the cerebral cortex, basal ganglia and cerebellum may disturb posture-gait control, resulting in falling.

  18. Functional Neuroanatomy for Posture and Gait Control

    Science.gov (United States)

    Takakusaki, Kaoru

    2017-01-01

    Here we argue functional neuroanatomy for posture-gait control. Multi-sensory information such as somatosensory, visual and vestibular sensation act on various areas of the brain so that adaptable posture-gait control can be achieved. Automatic process of gait, which is steady-state stepping movements associating with postural reflexes including headeye coordination accompanied by appropriate alignment of body segments and optimal level of postural muscle tone, is mediated by the descending pathways from the brainstem to the spinal cord. Particularly, reticulospinal pathways arising from the lateral part of the mesopontine tegmentum and spinal locomotor network contribute to this process. On the other hand, walking in unfamiliar circumstance requires cognitive process of postural control, which depends on knowledges of self-body, such as body schema and body motion in space. The cognitive information is produced at the temporoparietal association cortex, and is fundamental to sustention of vertical posture and construction of motor programs. The programs in the motor cortical areas run to execute anticipatory postural adjustment that is optimal for achievement of goal-directed movements. The basal ganglia and cerebellum may affect both the automatic and cognitive processes of posturegait control through reciprocal connections with the brainstem and cerebral cortex, respectively. Consequently, impairments in cognitive function by damages in the cerebral cortex, basal ganglia and cerebellum may disturb posture-gait control, resulting in falling. PMID:28122432

  19. Aryl Hydrocarbon Receptor Activation in Hematopoietic Stem/Progenitor Cells Alters Cell Function and Pathway-Specific Gene Modulation Reflecting Changes in Cellular Trafficking and MigrationS⃞

    OpenAIRE

    Casado, Fanny L.; Singh, Kameshwar P.; Gasiewicz, Thomas A.

    2011-01-01

    The aryl hydrocarbon receptor (AhR) is a transcription factor belonging to the Per-ARNT-Sim family of proteins. These proteins sense molecules and stimuli from the cellular/tissue environment and initiate signaling cascades to elicit appropriate cellular responses. Recent literature reports suggest an important function of AhR in hematopoietic stem cell (HSC) biology. However, the molecular mechanisms by which AhR signaling regulates HSC functions are unknown. In previous studies, we and othe...

  20. Liapunov Functions and Stability in Control Theory

    CERN Document Server

    Bacciotti, Andrea

    2005-01-01

    This book presents a modern and self-contained treatment of the Liapunov method for stability analysis, in the framework of mathematical nonlinear control theory. A Particular focus is on the problem of the existence of Liapunov functions (converse Liapunov theorems) and their regularity, whose interest is especially motivated by applications to automatic control. Many recent results in this area have been collected and presented in a systematic way. Some of them are given in extended, unified versions and with new, simpler proofs. In the 2nd edition of this successful book several new section

  1. Chondroitin sulfate proteoglycan 4 functions as the cellular receptor for Clostridium difficile toxin B.

    Science.gov (United States)

    Yuan, Pengfei; Zhang, Hongmin; Cai, Changzu; Zhu, Shiyou; Zhou, Yuexin; Yang, Xiaozhou; He, Ruina; Li, Chan; Guo, Shengjie; Li, Shan; Huang, Tuxiong; Perez-Cordon, Gregorio; Feng, Hanping; Wei, Wensheng

    2015-02-01

    As a gram-positive, spore-forming anaerobic bacillus, Clostridium difficile (C. difficile) is responsible for severe and fatal pseudomembranous colitis, and poses the most urgent antibiotic resistance threat worldwide. Epidemic C. difficile is the leading cause of antibiotic-associated diarrhoea globally, especially diarrhoea due to the emergence of hypervirulent strains associated with high mortality and morbidity. TcdB, one of the key virulence factors secreted by this bacterium, enters host cells through a poorly understood mechanism to elicit its pathogenic effect. Here we report the first identification of the TcdB cellular receptor, chondroitin sulfate proteoglycan 4 (CSPG4). CSPG4 was initially isolated from a whole-genome human shRNAmir library screening, and its role was confirmed by both TALEN- and CRISPR/Cas9-mediated gene knockout in human cells. CSPG4 is critical for TcdB binding to the cell surface, inducing cytoskeleton disruption and cell death. A direct interaction between the N-terminus of CSPG4 and the C-terminus of TcdB was confirmed, and the soluble peptide of the toxin-binding domain of CSPG4 could protect cells from the action of TcdB. Notably, the complete loss of CSPG4/NG2 decreased TcdB-triggered interleukin-8 induction in mice without significantly affecting animal mortality. Based on both the in vitro and in vivo studies, we propose a dual-receptor model for TcdB endocytosis. The discovery of the first TcdB receptor reveals a previously unsuspected role for CSPG4 and provides a new therapeutic target for the treatment of C. difficile infection.

  2. TRPV4 is necessary for trigeminal irritant pain and functions as a cellular formalin receptor.

    Science.gov (United States)

    Chen, Yong; Kanju, Patrick; Fang, Quan; Lee, Suk Hee; Parekh, Puja K; Lee, Whasil; Moore, Carlene; Brenner, Daniel; Gereau, Robert W; Wang, Fan; Liedtke, Wolfgang

    2014-12-01

    Detection of external irritants by head nociceptor neurons has deep evolutionary roots. Irritant-induced aversive behavior is a popular pain model in laboratory animals. It is used widely in the formalin model, where formaldehyde is injected into the rodent paw, eliciting quantifiable nocifensive behavior that has a direct, tissue-injury-evoked phase, and a subsequent tonic phase caused by neural maladaptation. The formalin model has elucidated many antipain compounds and pain-modulating signaling pathways. We have adopted this model to trigeminally innervated territories in mice. In addition, we examined the involvement of TRPV4 channels in formalin-evoked trigeminal pain behavior because TRPV4 is abundantly expressed in trigeminal ganglion (TG) sensory neurons, and because we have recently defined TRPV4's role in response to airborne irritants and in a model for temporomandibular joint pain. We found TRPV4 to be important for trigeminal nocifensive behavior evoked by formalin whisker pad injections. This conclusion is supported by studies with Trpv4(-/-) mice and TRPV4-specific antagonists. Our results imply TRPV4 in MEK-ERK activation in TG sensory neurons. Furthermore, cellular studies in primary TG neurons and in heterologous TRPV4-expressing cells suggest that TRPV4 can be activated directly by formalin to gate Ca(2+). Using TRPA1-blocker and Trpa1(-/-) mice, we found that both TRP channels co-contribute to the formalin trigeminal pain response. These results imply TRPV4 as an important signaling molecule in irritation-evoked trigeminal pain. TRPV4-antagonistic therapies can therefore be envisioned as novel analgesics, possibly for specific targeting of trigeminal pain disorders, such as migraine, headaches, temporomandibular joint, facial, and dental pain, and irritation of trigeminally innervated surface epithelia.

  3. Transient receptor potential ion channel function in sensory transduction and cellular signaling cascades underlying visceral hypersensitivity.

    Science.gov (United States)

    Balemans, Dafne; Boeckxstaens, Guy E; Talavera, Karel; Wouters, Mira M

    2017-06-01

    Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders including functional dyspepsia, irritable bowel syndrome, and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family. A variety of TRP channels are present in the gastrointestinal tract (TRPV1, TRPV3, TRPV4, TRPA1, TRPM2, TRPM5, and TRPM8), and modulation of their function by increased activation or sensitization (decreased activation threshold) or altered expression in visceral afferents have been reported in visceral hypersensitivity. TRP channels directly detect or transduce osmotic, mechanical, thermal, and chemosensory stimuli. In addition, pro-inflammatory mediators released in tissue damage or inflammation can activate receptors of the G protein-coupled receptor superfamily leading to TRP channel sensitization and activation, which amplify pain and neurogenic inflammation. In this review, we highlight the present knowledge on the functional roles of neuronal TRP channels in visceral hypersensitivity and discuss the signaling pathways that underlie TRP channel modulation. We propose that a better understanding of TRP channels and their modulators may facilitate the development of more selective and effective therapies to treat visceral hypersensitivity. Copyright © 2017 the American Physiological Society.

  4. Controlling Functional Group Architecture in Artificial Cells

    Science.gov (United States)

    2015-07-02

    further enable enzyme encapsulation to improve the efficiency of light-driven hydrogen fuel production. 5. Changes in key personnel, if applicable : -None ...Controlling Functional Group Architecture in Artificial Cells 5a. CONTRACT NUMBER W9132T-14-2-0002 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...cycloadditions to modify reactive groups within the phospholipid membrane structure and how the nature of the reactive elements, the copper catalyst

  5. Determining the functional significance of mismatch repair gene missense variants using biochemical and cellular assays

    DEFF Research Database (Denmark)

    Heinen, Christopher D; Juel Rasmussen, Lene

    2012-01-01

    provided an important experimental tool for studying the functional consequences of VUS. However, beyond this repair assay, a number of other experimental methods have been developed that allow us to test the effect of a VUS on discrete biochemical steps or other aspects of MMR function. Here, we describe......ABSTRACT: With the discovery that the hereditary cancer susceptibility disease Lynch syndrome (LS) is caused by deleterious germline mutations in the DNA mismatch repair (MMR) genes nearly 20 years ago, genetic testing can now be used to diagnose this disorder in patients. A definitive diagnosis...

  6. Hsp70 chaperone systems: diversity of cellular functions and mechanism of action.

    Science.gov (United States)

    Mayer, M P; Bukau, B

    1998-03-01

    Hsp70 chaperone systems play an essential role in the life cycle of many proteins not only in an hostile environment but also under normal growth conditions. In the course of evolution the diversification of functions was accompanied by an amplification of components of the Hsp70 system. Here strategies are reviewed how different Hsp70 systems work independently or cooperate with each other in a functional network to perform their housekeeping tasks even under stress conditions. We further discuss how co-chaperones which act as targeting factors regulate the cycle of substrate binding and release upon which the Hsp70 chaperone activity depends.

  7. The complex and important cellular and metabolic functions of saturated fatty acids.

    Science.gov (United States)

    Legrand, Philippe; Rioux, Vincent

    2010-10-01

    This review summarizes recent findings on the metabolism and biological functions of saturated fatty acids (SFA). Some of these findings show that SFA may have important and specific roles in the cells. Elucidated biochemical mechanisms like protein acylation (N-myristoylation, S-palmitoylation) and regulation of gene transcription are presented. In terms of physiology, SFA are involved for instance in lipogenesis, fat deposition, polyunsaturated fatty acids bioavailability and apoptosis. The variety of their functions demonstrates that SFA should no longer be considered as a single group.

  8. Pre-analytical and post-analytical evaluation in the era of molecular diagnosis of sexually transmitted diseases: cellularity control and internal control

    Directory of Open Access Journals (Sweden)

    Loria Bianchi

    2014-06-01

    Full Text Available Background. Increase of molecular tests performed on DNA extracted from various biological materials should not be carried out without an adequate standardization of the pre-analytical and post-analytical phase. Materials and Methods. Aim of this study was to evaluate the role of internal control (IC to standardize pre-analytical phase and the role of cellularity control (CC in the suitability evaluation of biological matrices, and their influence on false negative results. 120 cervical swabs (CS were pre-treated and extracted following 3 different protocols. Extraction performance was evaluated by amplification of: IC, added in each mix extraction; human gene HPRT1 (CC with RT-PCR to quantify sample cellularity; L1 region of HPV with SPF10 primers. 135 urine, 135 urethral swabs, 553 CS and 332 ThinPrep swabs (TP were tested for C. trachomatis (CT and U. parvum (UP with RT-PCR and for HPV by endpoint-PCR. Samples were also tested for cellularity. Results. Extraction protocol with highest average cellularity (Ac/sample showed lowest number of samples with inhibitors; highest HPV positivity was achieved by protocol with greatest Ac/PCR. CS and TP under 300.000 cells/sample showed a significant decrease of UP (P<0.01 and HPV (P<0.005 positivity. Female urine under 40.000 cells/mL were inadequate to detect UP (P<0.05. Conclusions. Our data show that IC and CC allow optimization of pre-analytical phase, with an increase of analytical quality. Cellularity/sample allows better sample adequacy evaluation, crucial to avoid false negative results, while cellularity/PCR allows better optimization of PCR amplification. Further data are required to define the optimal cut-off for result normalization.

  9. The Functional Connectome of Speech Control.

    Science.gov (United States)

    Fuertinger, Stefan; Horwitz, Barry; Simonyan, Kristina

    2015-07-01

    In the past few years, several studies have been directed to understanding the complexity of functional interactions between different brain regions during various human behaviors. Among these, neuroimaging research installed the notion that speech and language require an orchestration of brain regions for comprehension, planning, and integration of a heard sound with a spoken word. However, these studies have been largely limited to mapping the neural correlates of separate speech elements and examining distinct cortical or subcortical circuits involved in different aspects of speech control. As a result, the complexity of the brain network machinery controlling speech and language remained largely unknown. Using graph theoretical analysis of functional MRI (fMRI) data in healthy subjects, we quantified the large-scale speech network topology by constructing functional brain networks of increasing hierarchy from the resting state to motor output of meaningless syllables to complex production of real-life speech as well as compared to non-speech-related sequential finger tapping and pure tone discrimination networks. We identified a segregated network of highly connected local neural communities (hubs) in the primary sensorimotor and parietal regions, which formed a commonly shared core hub network across the examined conditions, with the left area 4p playing an important role in speech network organization. These sensorimotor core hubs exhibited features of flexible hubs based on their participation in several functional domains across different networks and ability to adaptively switch long-range functional connectivity depending on task content, resulting in a distinct community structure of each examined network. Specifically, compared to other tasks, speech production was characterized by the formation of six distinct neural communities with specialized recruitment of the prefrontal cortex, insula, putamen, and thalamus, which collectively forged the formation

  10. The Functional Connectome of Speech Control.

    Directory of Open Access Journals (Sweden)

    Stefan Fuertinger

    2015-07-01

    Full Text Available In the past few years, several studies have been directed to understanding the complexity of functional interactions between different brain regions during various human behaviors. Among these, neuroimaging research installed the notion that speech and language require an orchestration of brain regions for comprehension, planning, and integration of a heard sound with a spoken word. However, these studies have been largely limited to mapping the neural correlates of separate speech elements and examining distinct cortical or subcortical circuits involved in different aspects of speech control. As a result, the complexity of the brain network machinery controlling speech and language remained largely unknown. Using graph theoretical analysis of functional MRI (fMRI data in healthy subjects, we quantified the large-scale speech network topology by constructing functional brain networks of increasing hierarchy from the resting state to motor output of meaningless syllables to complex production of real-life speech as well as compared to non-speech-related sequential finger tapping and pure tone discrimination networks. We identified a segregated network of highly connected local neural communities (hubs in the primary sensorimotor and parietal regions, which formed a commonly shared core hub network across the examined conditions, with the left area 4p playing an important role in speech network organization. These sensorimotor core hubs exhibited features of flexible hubs based on their participation in several functional domains across different networks and ability to adaptively switch long-range functional connectivity depending on task content, resulting in a distinct community structure of each examined network. Specifically, compared to other tasks, speech production was characterized by the formation of six distinct neural communities with specialized recruitment of the prefrontal cortex, insula, putamen, and thalamus, which collectively

  11. Functional characterization of water transport and cellular localization of three aquaporin paralogs in the salmonid intestine.

    Directory of Open Access Journals (Sweden)

    Steffen S Madsen

    2011-09-01

    Full Text Available Intestinal water absorption is greatly enhanced in salmonids upon acclimation from freshwater (FW to seawater (SW; however, the molecular mechanism for water transport is unknown. We conducted a pharmacological characterization of water absorption in the rainbow trout intestine along with an investigation of the distribution and cellular localization of 3 aquaporins (Aqp1aa, -1ab and -8ab in pyloric caeca, middle (M and posterior (P intestine of the Atlantic salmon. In vitro iso-osmotic water absorption (Jv was higher in SW than FW-trout and was inhibited by (mmol L-1: 0.1 KCN (41%, 0.1 ouabain (72% and 0.1 bumetanide (82% suggesting that active transport, Na+,K+-ATPase and Na+,K+,2Cl--cotransport are involved in establishing the driving gradient for water transport. Jv was also inhibited by 1 mmol L-1 HgCl2, serosally (23% in M and 44% in P, mucosally (27% in M or both (61% in M and 58% in P, suggesting involvement of both apical and basolateral aquaporins in water transport. The inhibition was antagonized by 5 mmol L-1 mercaptoethanol. By comparison, 10 mmol L-1 mucosal tetraethylammonium, an inhibitor of certain aquaporins, inhibited Jv by 20%. In the presence of glucose, mucosal addition of phloridzin inhibited water transport by 20%, suggesting that water transport is partially linked to the Na+-glucose cotransporter. Using polyclonal antibodies against salmon Aqp1aa, -1ab and -8ab, we detected Aqp1aa, and -1ab immunoreactivity in the brush border and sub-apical region of enterocytes in all intestinal segments. The Aqp8ab antibody showed a particularly strong immunoreaction in the brush border and sub-apical region of enterocytes throughout the intestine and also stained lateral membranes and peri-nuclear regions though at lower intensity. The present localization of 3 aquaporins in both apical and lateral membranes of salmonid enterocytes facilitates a model for transcellular water transport in the intestine of SW-acclimated salmonids.

  12. Mitigating Handoff Call Dropping in Wireless Cellular Networks: A Call Admission Control Technique

    Science.gov (United States)

    Ekpenyong, Moses Effiong; Udoh, Victoria Idia; Bassey, Udoma James

    2016-06-01

    Handoff management has been an important but challenging issue in the field of wireless communication. It seeks to maintain seamless connectivity of mobile users changing their points of attachment from one base station to another. This paper derives a call admission control model and establishes an optimal step-size coefficient (k) that regulates the admission probability of handoff calls. An operational CDMA network carrier was investigated through the analysis of empirical data collected over a period of 1 month, to verify the performance of the network. Our findings revealed that approximately 23 % of calls in the existing system were lost, while 40 % of the calls (on the average) were successfully admitted. A simulation of the proposed model was then carried out under ideal network conditions to study the relationship between the various network parameters and validate our claim. Simulation results showed that increasing the step-size coefficient degrades the network performance. Even at optimum step-size (k), the network could still be compromised in the presence of severe network crises, but our model was able to recover from these problems and still functions normally.

  13. Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells

    Science.gov (United States)

    Corsaro, Alessandro; Bajetto, Adriana; Thellung, Stefano; Begani, Giulia; Villa, Valentina; Nizzari, Mario; Pattarozzi, Alessandra; Solari, Agnese; Gatti, Monica; Pagano, Aldo; Würth, Roberto; Daga, Antonio; Barbieri, Federica; Florio, Tullio

    2016-01-01

    Prion protein (PrPC) is a cell surface glycoprotein whose misfolding is responsible for prion diseases. Although its physiological role is not completely defined, several lines of evidence propose that PrPC is involved in self-renewal, pluripotency gene expression, proliferation and differentiation of neural stem cells. Moreover, PrPC regulates different biological functions in human tumors, including glioblastoma (GBM). We analyzed the role of PrPC in GBM cell pathogenicity focusing on tumor-initiating cells (TICs, or cancer stem cells, CSCs), the subpopulation responsible for development, progression and recurrence of most malignancies. Analyzing four GBM CSC-enriched cultures, we show that PrPC expression is directly correlated with the proliferation rate of the cells. To better define its role in CSC biology, we knocked-down PrPC expression in two of these GBM-derived CSC cultures by specific lentiviral-delivered shRNAs. We provide evidence that CSC proliferation rate, spherogenesis and in vivo tumorigenicity are significantly inhibited in PrPC down-regulated cells. Moreover, PrPC down-regulation caused loss of expression of the stemness and self-renewal markers (NANOG, Sox2) and the activation of differentiation pathways (i.e. increased GFAP expression). Our results suggest that PrPC controls the stemness properties of human GBM CSCs and that its down-regulation induces the acquisition of a more differentiated and less oncogenic phenotype. PMID:27229535

  14. A functional overview of conservation biological control

    DEFF Research Database (Denmark)

    Begg, Graham S; Cook, Samantha M; Dye, Richard

    2017-01-01

    and their biological control function across local and regional scales, and consider the interactions, interdependencies and constraints that determine the outcome of CBC strategies. Conservation measures are often effective in supporting natural enemy populations but their success cannot be guaranteed; the greatest...... limitation to the development of effective CBC is due to a failure to adequately direct biological control services to achieve suppression of the target pests. By considering the performance of these and other components of CBC within the context of an integrated system, we believe that the limiting factors......Conservation biological control (CBC) is a sustainable approach to pest management that can contribute to a reduction in pesticide use as part of an Integrated Pest Management (IPM) strategy. CBC is based on the premise that countering habitat loss and environmental disturbance associated...

  15. Structure and function of tetrameric hemoglobins and their mutants at a molecular and cellular level.

    OpenAIRE

    Balsamo, Anna

    2011-01-01

    The present Ph.D. thesis has focused on tetrameric hemoglobins (Hbs), both recombinant and natural, both from human origin and Antarctic fish, using a multidisciplinary approach based on spectroscopic, crystallographic and computational techniques. In particular the main scope of the research has been the elucidation of two still unsolved problems in the chemistry of tetrameric Hbs: 1) the role of the bis-histidyl heme coordination in the Hb function and oxidation process and 2) the role of t...

  16. The complex and important cellular and metabolic functions of saturated fatty acids

    OpenAIRE

    Legrand, Philippe; Rioux, Vincent

    2010-01-01

    This review summarizes recent findings on the metabolism and biological functions of saturated fatty acids (SFA). Some of these findings show that SFA may have important and specific roles in the cells. Elucidated biochemical mechanisms like protein acylation (N-myristoylation, S-palmitoylation) and regulation of gene transcription are presented. In terms of physiology, SFA are involved for instance in lipogenesis, fat deposition, polyunsaturated fatty acids bioavailability and apoptosis. The...

  17. Lifelong maintenance of composition, function and cellular/subcellular distribution of proteasomes in human liver.

    Science.gov (United States)

    Bellavista, Elena; Martucci, Morena; Vasuri, Francesco; Santoro, Aurelia; Mishto, Michele; Kloss, Alexander; Capizzi, Elisa; Degiovanni, Alessio; Lanzarini, Catia; Remondini, Daniel; Dazzi, Alessandro; Pellegrini, Sara; Cescon, Matteo; Capri, Miriam; Salvioli, Stefano; D'Errico-Grigioni, Antonia; Dahlmann, Burkhardt; Grazi, Gian Luca; Franceschi, Claudio

    2014-01-01

    Owing to organ shortage, livers from old donors are increasingly used for transplantation. The function and duration of such transplanted livers are apparently comparable to those from young donors, suggesting that, despite some morphological and structural age-related changes, no major functional changes do occur in liver with age. We tested this hypothesis by performing a comprehensive study on proteasomes, major cell organelles responsible for proteostasis, in liver biopsies from heart-beating donors. Oxidized and poly-ubiquitin conjugated proteins did not accumulate with age and the three major proteasome proteolytic activities were similar in livers from young and old donors. Analysis of proteasomes composition showed an age-related increased of β5i/α4 ratio, suggesting a shift toward proteasomes containing inducible subunits and a decreased content of PA28α subunit, mainly in the cytosol of hepatocytes. Thus our data suggest that, proteasomes activity is well preserved in livers from aged donors, concomitantly with subtle changes in proteasome subunit composition which might reflect the occurrence of a functional remodelling to maintain an efficient proteostasis. Gender differences are emerging and they deserve further investigations owing to the different aging trajectories between men and women. Finally, our data support the safe use of livers from old donors for transplantation.

  18. Tissue architecture and function: dynamic reciprocity via extra- and intra-cellular matrices

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ren; Boudreau, Aaron; Bissell, Mina J

    2008-12-23

    Mammary gland development, functional differentiation, and homeostasis are orchestrated and sustained by a balance of biochemical and biophysical cues from the organ's microenvironment. The three-dimensional microenvironment of the mammary gland, predominantly 'encoded' by a collaboration between the extracellular matrix (ECM), hormones, and growth factors, sends signals from ECM receptors through the cytoskeletal intracellular matrix to nuclear and chromatin structures resulting in gene expression; the ECM in turn is regulated and remodeled by signals from the nucleus. In this chapter, we discuss how coordinated ECM deposition and remodeling is necessary for mammary gland development, how the ECM provides structural and biochemical cues necessary for tissue-specific function, and the role of the cytoskeleton in mediating the extra - to intracellular dialogue occurring between the nucleus and the microenvironment. When operating normally, the cytoskeletal-mediated dynamic and reciprocal integration of tissue architecture and function directs mammary gland development, tissue polarity, and ultimately, tissue-specific gene expression. Cancer occurs when these dynamic interactions go awry for an extended time.

  19. Auxin-binding pocket of ABP1 is crucial for its gain-of-function cellular and developmental roles.

    Science.gov (United States)

    Grones, Peter; Chen, Xu; Simon, Sibu; Kaufmann, Walter A; De Rycke, Riet; Nodzyński, Tomasz; Zažímalová, Eva; Friml, Jiří

    2015-08-01

    The plant hormone auxin is a key regulator of plant growth and development. Auxin levels are sensed and interpreted by distinct receptor systems that activate a broad range of cellular responses. The Auxin-Binding Protein1 (ABP1) that has been identified based on its ability to bind auxin with high affinity is a prime candidate for the extracellular receptor responsible for mediating a range of auxin effects, in particular, the fast non-transcriptional ones. Contradictory genetic studies suggested prominent or no importance of ABP1 in many developmental processes. However, how crucial the role of auxin binding to ABP1 is for its functions has not been addressed. Here, we show that the auxin-binding pocket of ABP1 is essential for its gain-of-function cellular and developmental roles. In total, 16 different abp1 mutants were prepared that possessed substitutions in the metal core or in the hydrophobic amino acids of the auxin-binding pocket as well as neutral mutations. Their analysis revealed that an intact auxin-binding pocket is a prerequisite for ABP1 to activate downstream components of the ABP1 signalling pathway, such as Rho of Plants (ROPs) and to mediate the clathrin association with membranes for endocytosis regulation. In planta analyses demonstrated the importance of the auxin binding pocket for all known ABP1-mediated postembryonic developmental processes, including morphology of leaf epidermal cells, root growth and root meristem activity, and vascular tissue differentiation. Taken together, these findings suggest that auxin binding to ABP1 is central to its function, supporting the role of ABP1 as auxin receptor.

  20. Stochastic fluctuations and distributed control of gene expression impact cellular memory.

    Directory of Open Access Journals (Sweden)

    Guillaume Corre

    Full Text Available Despite the stochastic noise that characterizes all cellular processes the cells are able to maintain and transmit to their daughter cells the stable level of gene expression. In order to better understand this phenomenon, we investigated the temporal dynamics of gene expression variation using a double reporter gene model. We compared cell clones with transgenes coding for highly stable mRNA and fluorescent proteins with clones expressing destabilized mRNA-s and proteins. Both types of clones displayed strong heterogeneity of reporter gene expression levels. However, cells expressing stable gene products produced daughter cells with similar level of reporter proteins, while in cell clones with short mRNA and protein half-lives the epigenetic memory of the gene expression level was completely suppressed. Computer simulations also confirmed the role of mRNA and protein stability in the conservation of constant gene expression levels over several cell generations. These data indicate that the conservation of a stable phenotype in a cellular lineage may largely depend on the slow turnover of mRNA-s and proteins.

  1. Cellular factors controlling neuronal vulnerability in the brain: a lesson from the striatum.

    Science.gov (United States)

    Calabresi, P; Centonze, D; Bernardi, G

    2000-11-14

    In many acute and chronic neurologic disorders, both deficits in energy metabolism and defects in glutamate-mediated excitatory synaptic transmission have been proposed as important pathogenic factors. Brain cells, however, express variable vulnerability to these insults, as indicated by the fact that certain brain areas and even different cell types in the same area are preferentially spared until the very late stages of various diseases. This can be clearly seen in the striatum, where GABAergic projection cells but not cholinergic interneurons are precociously damaged in the course of both acute metabolic insults (such as hypoxia, hypoglycemia, and ischemia) and chronic neurodegenerative disorders (such as Huntington's disease). A well-mapped pattern of cell loss, in fact, is a common finding in the striatum of patients suffering from these pathologic conditions. Physiologic and molecular studies have been directed in recent years to the identification of the cellular mechanisms underlying the cell-type specific vulnerability of striatal cells. These studied recognized that, in striatal spiny and aspiny cells, specific membrane ion channels, glutamate receptor subtypes and subunits, and intracellular enzymatic activities are involved in the cascade of events responsible for opposite responses and vulnerabilities to oxygen or glucose deprivation and to glutamate receptor-mediated toxicity. Specific molecules able to target these cellular factors might be employed as therapeutic agents during acute and chronic neurologic disorders affecting this brain area.

  2. Longevity of guard cell chloroplasts in falling leaves: implication for stomatal function and cellular aging

    Energy Technology Data Exchange (ETDEWEB)

    Zeiger, E.; Schwartz, A.

    1982-11-12

    Guard cell chloroplasts in senescing leaves from 12 species of perennial trees and three species of annual plants survived considerably longer than their mesophyll counterparts. In Ginkgo biloba, stomata from yellow leaves opened during the day and closed at night; guard cell chloroplasts from these leaves showed fluorescence transients associated with electron transport and photophosphorylation. These findings indicate that guard cell chloroplasts are highly conserved throughout the life-span of the leaf and that leaves retain stomatal control during senescence.

  3. Pressuromodulation at the cell membrane as the basis for small molecule hormone and peptide regulation of cellular and nuclear function.

    Science.gov (United States)

    Sarin, Hemant

    2015-11-26

    Building on recent knowledge that the specificity of the biological interactions of small molecule hydrophiles and lipophiles across microvascular and epithelial barriers, and with cells, can be predicted on the basis of their conserved biophysical properties, and the knowledge that biological peptides are cell membrane impermeant, it has been further discussed herein that cellular, and thus, nuclear function, are primarily regulated by small molecule hormone and peptide/factor interactions at the cell membrane (CM) receptors. The means of regulating cellular, and thus, nuclear function, are the various forms of CM Pressuromodulation that exist, which include Direct CM Receptor-Mediated Stabilizing Pressuromodulation, sub-classified as Direct CM Receptor-Mediated Stabilizing Shift Pressuromodulation (Single, Dual or Tri) or Direct CM Receptor-Mediated Stabilizing Shift Pressuromodulation (Single, Dual or Tri) cum External Cationomodulation (≥3+ → 1+); which are with respect to acute CM receptor-stabilizing effects of small biomolecule hormones, growth factors or cytokines, and also include Indirect CM- or CM Receptor-Mediated Pressuromodulation, sub-classified as Indirect 1ary CM-Mediated Shift Pressuromodulation (Perturbomodulation), Indirect 2ary CM Receptor-Mediated Shift Pressuromodulation (Tri or Quad Receptor Internal Pseudo-Cationomodulation: SS 1+), Indirect 3ary CM Receptor-Mediated Shift Pressuromodulation (Single or Dual Receptor Endocytic External Cationomodulation: 2+) or Indirect (Pseudo) 3ary CM Receptor-Mediated Shift Pressuromodulation (Receptor Endocytic Hydroxylocarbonyloetheroylomodulation: 0), which are with respect to sub-acute CM receptor-stabilizing effects of small biomolecules, growth factors or cytokines. As a generalization, all forms of CM pressuromodulation decrease CM and nuclear membrane (NM) compliance (whole cell compliance), due to pressuromodulation of the intracellular microtubule network and increases the exocytosis of pre

  4. Stochastic asymptotical synchronization of chaotic Markovian jumping fuzzy cellular neural networks with mixed delays and the Wiener process based on sampled-data control

    Institute of Scientific and Technical Information of China (English)

    M.Kalpana; P.Balasubramaniam

    2013-01-01

    We investigate the stochastic asymptotical synchronization of chaotic Markovian jumping fuzzy cellular neural networks (MJFCNNs) with discrete,unbounded distributed delays,and the Wiener process based on sampled-data control using the linear matrix inequality (LMI) approach.The Lyapunov-Krasovskii functional combined with the input delay approach as well as the free-weighting matrix approach is employed to derive several sufficient criteria in terms of LMIs to ensure that the delayed MJFCNNs with the Wiener process is stochastic asymptotical synchronous.Restrictions (e.g.,time derivative is smaller than one) are removed to obtain a proposed sampled-data controller.Finally,a numerical example is provided to demonstrate the reliability of the derived results.

  5. Prion Protein Modulates Cellular Iron Uptake: A Novel Function with Implications for Prion Disease Pathogenesis

    OpenAIRE

    2009-01-01

    Converging evidence leaves little doubt that a change in the conformation of prion protein (PrP(C)) from a mainly alpha-helical to a beta-sheet rich PrP-scrapie (PrP(Sc)) form is the main event responsible for prion disease associated neurotoxicity. However, neither the mechanism of toxicity by PrP(Sc), nor the normal function of PrP(C) is entirely clear. Recent reports suggest that imbalance of iron homeostasis is a common feature of prion infected cells and mouse models, implicating redox-i...

  6. Inseparable tandem: evolution chooses ATP and Ca2+ to control life, death and cellular signalling.

    Science.gov (United States)

    Plattner, Helmut; Verkhratsky, Alexei

    2016-08-05

    From the very dawn of biological evolution, ATP was selected as a multipurpose energy-storing molecule. Metabolism of ATP required intracellular free Ca(2+) to be set at exceedingly low concentrations, which in turn provided the background for the role of Ca(2+) as a universal signalling molecule. The early-eukaryote life forms also evolved functional compartmentalization and vesicle trafficking, which used Ca(2+) as a universal signalling ion; similarly, Ca(2+) is needed for regulation of ciliary and flagellar beat, amoeboid movement, intracellular transport, as well as of numerous metabolic processes. Thus, during evolution, exploitation of atmospheric oxygen and increasingly efficient ATP production via oxidative phosphorylation by bacterial endosymbionts were a first step for the emergence of complex eukaryotic cells. Simultaneously, Ca(2+) started to be exploited for short-range signalling, despite restrictions by the preset phosphate-based energy metabolism, when both phosphates and Ca(2+) interfere with each other because of the low solubility of calcium phosphates. The need to keep cytosolic Ca(2+) low forced cells to restrict Ca(2+) signals in space and time and to develop energetically favourable Ca(2+) signalling and Ca(2+) microdomains. These steps in tandem dominated further evolution. The ATP molecule (often released by Ca(2+)-regulated exocytosis) rapidly grew to be the universal chemical messenger for intercellular communication; ATP effects are mediated by an extended family of purinoceptors often linked to Ca(2+) signalling. Similar to atmospheric oxygen, Ca(2+) must have been reverted from a deleterious agent to a most useful (intra- and extracellular) signalling molecule. Invention of intracellular trafficking further increased the role for Ca(2+) homeostasis that became critical for regulation of cell survival and cell death. Several mutually interdependent effects of Ca(2+) and ATP have been exploited in evolution, thus turning an originally

  7. When Altering Brain Function Becomes Mind Control

    Directory of Open Access Journals (Sweden)

    Andrew Sanford Koivuniemi

    2014-10-01

    Full Text Available Functional neurosurgery has seen a resurgence of interest in surgical treatments for psychiatric illness. Deep brain stimulation (DBS technology is the preferred tool in the current wave of clinical experiments because it allows clinicians to directly alter the functions of targeted brain regions, in a reversible manner, with the intent of correcting diseases of the mind, such as depression, addiction, anorexia nervosa, dementia, and obsessive compulsive disorder. These promising treatments raise a critical philosophical and humanitarian question. Under what conditions does ‘altering brain function’ qualify as ‘mind control’? In order to answer this question one needs a definition of mind control. To this end, we reviewed the relevant philosophical, ethical, and neurosurgical literature in order to create a set of criteria for what constitutes mind control in the context of DBS. We also outline clinical implications of these criteria. Finally, we demonstrate the relevance of the proposed criteria by focusing especially on serendipitous treatments involving DBS, i.e., cases in which an unintended therapeutic benefit occurred. These cases highlight the importance of gaining the consent of the subject for the new therapy in order to avoid committing an act of mind control.

  8. Cellular thiamine status is coupled to function of mitochondrial 2-oxoglutarate dehydrogenase.

    Science.gov (United States)

    Mkrtchyan, G; Graf, A; Bettendorff, L; Bunik, V

    2016-12-01

    Decreased thiamine and reduced activity of thiamine diphosphate (ThDP)-dependent 2-oxoglutarate dehydrogenase (OGDH) cause neurodegeneration. We hypothesized on concerted cell-specific regulation of the thiamine metabolism and ThDP-dependent reactions. We identified a smaller thiamine pool, a lower expression of the mitochondrial ThDP transporter, and a higher expression of OGDH in rat astrocytes versus neuroblastoma N2A. According to the data, the astrocytic OGDH may be up-regulated by an increase in intracellular ThDP, while the neuroblastomal OGDH functions at full ThDP saturation. Indeed, in rat astrocytes and brain cortex, OGDH inhibition by succinyl phosphonate (SP) enlarged the pool of thiamine compounds. Increased ThDP level in response to the OGDH inhibition presumably up-regulated the enzyme to compensate for a decrease in reducing power which occurred in SP-treated astrocytes. Under the same SP treatment of N2A cells, their thiamine pool and reducing power were unchanged, although SP action was evident from accumulation of glutamate. The presented data indicate that functional interplay between OGDH, other proteins of the tricarbocylic acid cycle and proteins of thiamine metabolism is an important determinant of physiology-specific networks and their homeostatic mechanisms.

  9. Acute morphine treatment alters cellular immune function in the lungs of healthy rats.

    Science.gov (United States)

    Coussons-Read, M E; Giese, S

    2001-08-01

    Previous work has shown that morphine suppresses the pulmonary immune response to infection and reduces pulmonary inflammation. No published studies have addressed the impact of morphine on lymphocyte function in the lungs without infection. This study addressed this question by assessing the impact of acute morphine treatment on proliferation, cytokine production, and natural killer (NK) cell activity in resident pulmonary lymphocytes from healthy rats. Male Lewis rats received either a single 15 mg/kg morphine sulfate or vehicle injection 1 h prior to sacrifice. Lungs were minced and passed through wire mesh following collagenase digestion. The resulting cell preparations were pooled (2 rats/pool) to yield sufficient cell numbers for the functional assays, and a portion of these suspensions were separated using a density gradient. Crude and purified cell suspensions were used in assays of NK cell activity and mitogen-induced proliferation and cytokine production. Morphine significantly suppressed lymphocyte proliferation and cytokine production in whole cell suspensions, but not in purified cultures. NK activity was enhanced by morphine treatment in purified treated cultures. Studies of nitrate/nitrite levels in crude and purified cultures suggest that macrophage-derived nitric oxide may be a mechanism of the suppression observed in whole cell suspensions following morphine treatment. These data are consistent with previous work showing that morphine suppresses mitogenic responsiveness and NK activity in the spleen and peripheral blood, and may do so through a macrophage-derived nitric oxide mechanism.

  10. Next-generation biomedical implants using additive manufacturing of complex, cellular and functional mesh arrays.

    Science.gov (United States)

    Murr, L E; Gaytan, S M; Medina, F; Lopez, H; Martinez, E; Machado, B I; Hernandez, D H; Martinez, L; Lopez, M I; Wicker, R B; Bracke, J

    2010-04-28

    In this paper, we examine prospects for the manufacture of patient-specific biomedical implants replacing hard tissues (bone), particularly knee and hip stems and large bone (femoral) intramedullary rods, using additive manufacturing (AM) by electron beam melting (EBM). Of particular interest is the fabrication of complex functional (biocompatible) mesh arrays. Mesh elements or unit cells can be divided into different regions in order to use different cell designs in different areas of the component to produce various or continually varying (functionally graded) mesh densities. Numerous design elements have been used to fabricate prototypes by AM using EBM of Ti-6Al-4V powders, where the densities have been compared with the elastic (Young) moduli determined by resonant frequency and damping analysis. Density optimization at the bone-implant interface can allow for bone ingrowth and cementless implant components. Computerized tomography (CT) scans of metal (aluminium alloy) foam have also allowed for the building of Ti-6Al-4V foams by embedding the digital-layered scans in computer-aided design or software models for EBM. Variations in mesh complexity and especially strut (or truss) dimensions alter the cooling and solidification rate, which alters the alpha-phase (hexagonal close-packed) microstructure by creating mixtures of alpha/alpha' (martensite) observed by optical and electron metallography. Microindentation hardness measurements are characteristic of these microstructures and microstructure mixtures (alpha/alpha') and sizes.

  11. ATR controls cellular adaptation to hypoxia through positive regulation of hypoxia-inducible factor 1 (HIF-1) expression.

    Science.gov (United States)

    Fallone, F; Britton, S; Nieto, L; Salles, B; Muller, C

    2013-09-12

    Tumor cells adaptation to severe oxygen deprivation (hypoxia) plays a major role in tumor progression. The transcription factor HIF-1 (hypoxia-inducible factor 1), whose α-subunit is stabilized under hypoxic conditions is a key component of this process. Recent studies showed that two members of the phosphoinositide 3-kinase-related kinases (PIKKs) family, ATM (ataxia telangiectasia mutated) and DNA-PK (DNA-dependent protein kinase), regulate the hypoxic-dependent accumulation of HIF-1. These proteins initiate cellular stress responses when DNA damage occurs. In addition, it has been demonstrated that extreme hypoxia induces a replicative stress resulting in regions of single-stranded DNA at stalled replication forks and the activation of ATR (ataxia telangiectasia and Rad3 related protein), another member of the PIKKs family. Here, we show that even less severe hypoxia (0.1% O2) also induces activation of ATR through replicative stress. Importantly, in using either transiently silenced ATR cells, cells expressing an inactive form of ATR or cells exposed to an ATR inhibitor (CGK733), we demonstrate that hypoxic ATR activation positively regulates the key transcription factor HIF-1 independently of the checkpoint kinase Chk1. We show that ATR kinase activity regulates HIF-1α at the translational level and we find that the elements necessary for the regulation of HIF-1α translation are located within the coding region of HIF-1α mRNA. Finally, by using three independent cellular models, we clearly show that the loss of ATR expression and/or kinase activity results in the decrease of HIF-1 DNA binding under hypoxia and consequently affects protein expression levels of two HIF-1 target genes, GLUT-1 and CAIX. Taken together, our data show a new function for ATR in cellular adaptation to hypoxia through regulation of HIF-1α translation. Our work offers new prospect for cancer therapy using ATR inhibitors with the potential to decrease cellular adaptation in hypoxic

  12. Macromitophagy is a longevity assurance process that in chronologically aging yeast limited in calorie supply sustains functional mitochondria and maintains cellular lipid homeostasis

    Science.gov (United States)

    Burstein, Michelle T.; Koupaki, Olivia; Gomez-Perez, Alejandra; Levy, Sean; Pluska, Lukas; Mattie, Sevan; Rafeh, Rami; Iouk, Tatiana; Sheibani, Sara; Greenwood, Michael; Vali, Hojatollah; Titorenko, Vladimir I.

    2013-01-01

    Macromitophagy controls mitochondrial quality and quantity. It involves the sequestration of dysfunctional or excessive mitochondria within double-membrane autophagosomes, which then fuse with the vacuole/lysosome to deliver these mitochondria for degradation. To investigate a physiological role of macromitophagy in yeast, we examined how the atg32Δ-dependent mutational block of this process influences the chronological lifespan of cells grown in a nutrient-rich medium containing low (0.2%) concentration of glucose. Under these longevity-extending conditions of caloric restriction (CR) yeast cells are not starving. We also assessed a role of macromitophagy in lifespan extension by lithocholic acid (LCA), a bile acid that prolongs yeast longevity under CR conditions. Our findings imply that macromitophagy is a longevity assurance process underlying the synergistic beneficial effects of CR and LCA on yeast lifespan. Our analysis of how the atg32Δ mutation influences mitochondrial morphology, composition and function revealed that macromitophagy is required to maintain a network of healthy mitochondria. Our comparative analysis of the membrane lipidomes of organelles purified from wild-type and atg32Δ cells revealed that macromitophagy is required for maintaining cellular lipid homeostasis. We concluded that macromitophagy defines yeast longevity by modulating vital cellular processes inside and outside of mitochondria. PMID:23553280

  13. Optically-controlled platforms for transfection and single- and sub-cellular surgery

    DEFF Research Database (Denmark)

    Villangca, Mark Jayson; Casey, Duncan; Glückstad, Jesper

    2015-01-01

    , unpredictable failures or mutations in individual cells can lead to serious downstream conditions across the whole organism. The traditional tools of biochemistry struggle to observe such processes: the vast majority are based upon ensemble approaches analysing the properties of bulk populations, which means...... and specificity of optical trapping in conjunction with other modalities to perform single and sub-cellular surgery. These tools form highly tuneable platforms for the delivery or removal of material from cells of interest, but can simultaneously excite fluorescent probes for imaging purposes or plasmonic...... structures for very local heating. We discuss both the history and recent applications of the field, highlighting the key findings and developments over the last 40 years of biophotonics research....

  14. Strategizing the clone wars: pharmacological control of cellular sensitivity to radiation.

    Science.gov (United States)

    Kimple, Randall J

    2010-12-01

    The combined administration of ionizing radiation and systemic chemotherapy is an accepted standard of care for numerous cancers. Improved efficacy through the combination of therapies reflects several interrelated processes, including DNA damage, inhibition of DNA synthesis, alteration of cell cycle distribution, and impaired DNA repair. Insights into cellular responses to radiation have led to the use of drugs that target specific intracellular signaling pathways to sensitize cells to radiation. Combinations of chemotherapy and radiation continue to be optimized, based on preclinical and early-phase clinical data that indicate the ideal sequencing of therapies, the best combinations of agents (including radiosensitizers), and the most reliable biological markers for predicting patient responsiveness. This review summarizes our current understanding of radiosensitization as it relates to preclinical drug development and discusses the potential benefits of judiciously incorporating both traditional and targeted chemotherapy into radiation regimens.

  15. Multiple Applications of Alamar Blue as an Indicator of Metabolic Function and Cellular Health in Cell Viability Bioassays

    Directory of Open Access Journals (Sweden)

    Sephra N. Rampersad

    2012-09-01

    Full Text Available Accurate prediction of the adverse effects of test compounds on living systems, detection of toxic thresholds, and expansion of experimental data sets to include multiple toxicity end-point analysis are required for any robust screening regime. Alamar Blue is an important redox indicator that is used to evaluate metabolic function and cellular health. The Alamar Blue bioassay has been utilized over the past 50 years to assess cell viability and cytotoxicity in a range of biological and environmental systems and in a number of cell types including bacteria, yeast, fungi, protozoa and cultured mammalian and piscine cells. It offers several advantages over other metabolic indicators and other cytotoxicity assays. However, as with any bioassay, suitability must be determined for each application and cell model. This review seeks to highlight many of the important considerations involved in assay use and design in addition to the potential pitfalls.

  16. Structural Aberrations of Cellular Sialic Acids and TheirFunctions in Cancer Metastases

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Sialic acids (neuraminic acids) are a special series of 9-carbon ring negatively charged carbohydrates, which has been found to be selectively changed in malignant cells from structures (both synthesis and structure modifications) to functions (up and down regulation in cells). Sialic acids, in single forms or conjugates, have been systematically studied both in lab and in clinics by GC, GCMS, NMR, HPTLC, HPLC and other modern analytical means. Sialic acids and related conjugates are predicted to be used in cancer diagnosis, cancer prognostic forecasting, designing of cancer chemotherapy regimens, uncovering carcinogenetic processes and neoplasm metastasis. Tumor cell regulative systems and pathways are correlated with sialic acids, which can be applied to prognostic evaluation of cancer patients, and antimetastatic chemotherapy by sialic acid derivatives and analogues. Searching for new biological characteristics of sialic acids in cells have also been extensively studied these days. In this paper, main stream discoveries and advancements are provided , also discussions of possible mechanisms and hypotheses are invoked.

  17. Fluorescent chitosan functionalized magnetic polymeric nanoparticles: Cytotoxicity and in vitro evaluation of cellular uptake.

    Science.gov (United States)

    Kaewsaneha, Chariya; Jangpatarapongsa, Kulachart; Tangchaikeeree, Tienrat; Polpanich, Duangporn; Tangboriboonrat, Pramuan

    2014-11-01

    Nanoparticles possessing magnetic and fluorescent properties were fabricated by the covalent attachment of fluorescein isothiocyanate onto magnetic polymeric nanoparticles functionalized by chitosan. The synthesized magnetic polymeric nanoparticles-chitosan/fluorescein isothiocyanate were successfully used for labeling the living organ and blood-related cancer cells, i.e., HeLa, Hep G2, and K562 cells. The cytotoxicity test of nanoparticles at various incubation times indicated the high cell viability (>90%) without morphological change. The confocal microscopy revealed that they could pass through cell membrane within 2 h for K562 cells and 3 h for HeLa and Hep G2 cells and then confine inside cytoplasm of all types of tested cells for at least 24 h. Therefore, the synthesized magnetic polymeric nanoparticles-chitosan/fluorescein isothiocyanate would potentially be used as cell tracking in theranostic applications.

  18. Scaffolds, levers, rods and springs: diverse cellular functions of long coiled-coil proteins.

    Science.gov (United States)

    Rose, A; Meier, I

    2004-08-01

    Long alpha-helical coiled-coil proteins are involved in a variety of organizational and regulatory processes in eukaryotic cells. They provide cables and networks in the cyto- and nucleoskeleton, molecular scaffolds that organize membrane systems, motors, levers, rotating arms and possibly springs. A growing number of human diseases are found to be caused by mutations in long coiled-coil proteins. This review summarizes our current understanding of the multifaceted group of long coiled-coil proteins in the cytoskeleton, nucleus, Golgi and cell division apparatus. The biophysical features of coiled-coil domains provide first clues toward their contribution to the diverse protein functions and promise potential future applications in the area of nanotechnology. Combining the power of fully sequenced genomes and structure prediction algorithms, it is now possible to comprehensively summarize and compare the complete inventory of coiled-coil proteins of different organisms.

  19. Heparan sulfate proteoglycans on the cell surface: versatile coordinators of cellular functions

    DEFF Research Database (Denmark)

    Tumova, S; Woods, A; Couchman, J R

    2000-01-01

    Heparan sulfate proteoglycans are complex molecules composed of a core protein with covalently attached glycosaminoglycan chains. While the protein part determines localization of the proteoglycan on the cell surfaces or in the extracellular matrix, the glycosaminoglycan component, heparan sulfate......, mediates interactions with a variety of extracellular ligands such as growth factors and adhesion molecules. Through these interactions, heparan sulfate proteoglycans participate in many events during cell adhesion, migration, proliferation and differentiation. We are determining the multitude...... of proteoglycan functions, as their intricate roles in many pathways are revealed. They act as coreceptors for growth factors, participate in signalling during cell adhesion, modulate the activity of a broad range of molecules, and partake in many developmental and pathological processes, including tumorigenesis...

  20. Role of Mitochondria in Cerebral Vascular Function: Energy Production, Cellular Protection, and Regulation of Vascular Tone.

    Science.gov (United States)

    Busija, David W; Rutkai, Ibolya; Dutta, Somhrita; Katakam, Prasad V

    2016-06-13

    Mitochondria not only produce energy in the form of ATP to support the activities of cells comprising the neurovascular unit, but mitochondrial events, such as depolarization and/or ROS release, also initiate signaling events which protect the endothelium and neurons against lethal stresses via pre-/postconditioning as well as promote changes in cerebral vascular tone. Mitochondrial depolarization in vascular smooth muscle (VSM), via pharmacological activation of the ATP-dependent potassium channels on the inner mitochondrial membrane (mitoKATP channels), leads to vasorelaxation through generation of calcium sparks by the sarcoplasmic reticulum and subsequent downstream signaling mechanisms. Increased release of ROS by mitochondria has similar effects. Relaxation of VSM can also be indirectly achieved via actions of nitric oxide (NO) and other vasoactive agents produced by endothelium, perivascular and parenchymal nerves, and astroglia following mitochondrial activation. Additionally, NO production following mitochondrial activation is involved in neuronal preconditioning. Cerebral arteries from female rats have greater mitochondrial mass and respiration and enhanced cerebral arterial dilation to mitochondrial activators. Preexisting chronic conditions such as insulin resistance and/or diabetes impair mitoKATP channel relaxation of cerebral arteries and preconditioning. Surprisingly, mitoKATP channel function after transient ischemia appears to be retained in the endothelium of large cerebral arteries despite generalized cerebral vascular dysfunction. Thus, mitochondrial mechanisms may represent the elusive signaling link between metabolic rate and blood flow as well as mediators of vascular change according to physiological status. Mitochondrial mechanisms are an important, but underutilized target for improving vascular function and decreasing brain injury in stroke patients. © 2016 American Physiological Society. Compr Physiol 6:1529-1548, 2016.

  1. High-density lipoprotein maintains skeletal muscle function by modulating cellular respiration in mice.

    Science.gov (United States)

    Lehti, Maarit; Donelan, Elizabeth; Abplanalp, William; Al-Massadi, Omar; Habegger, Kirk M; Weber, Jon; Ress, Chandler; Mansfeld, Johannes; Somvanshi, Sonal; Trivedi, Chitrang; Keuper, Michaela; Ograjsek, Teja; Striese, Cynthia; Cucuruz, Sebastian; Pfluger, Paul T; Krishna, Radhakrishna; Gordon, Scott M; Silva, R A Gangani D; Luquet, Serge; Castel, Julien; Martinez, Sarah; D'Alessio, David; Davidson, W Sean; Hofmann, Susanna M

    2013-11-26

    Abnormal glucose metabolism is a central feature of disorders with increased rates of cardiovascular disease. Low levels of high-density lipoprotein (HDL) are a key predictor for cardiovascular disease. We used genetic mouse models with increased HDL levels (apolipoprotein A-I transgenic [apoA-I tg]) and reduced HDL levels (apoA-I-deficient [apoA-I ko]) to investigate whether HDL modulates mitochondrial bioenergetics in skeletal muscle. ApoA-I ko mice exhibited fasting hyperglycemia and impaired glucose tolerance test compared with wild-type mice. Mitochondria isolated from gastrocnemius muscle of apoA-I ko mice displayed markedly blunted ATP synthesis. Endurance capacity during exercise exhaustion test was impaired in apoA-I ko mice. HDL directly enhanced glucose oxidation by increasing glycolysis and mitochondrial respiration rate in C2C12 muscle cells. ApoA-I tg mice exhibited lower fasting glucose levels, improved glucose tolerance test, increased lactate levels, reduced fat mass, associated with protection against age-induced decline of endurance capacity compared with wild-type mice. Circulating levels of fibroblast growth factor 21, a novel biomarker for mitochondrial respiratory chain deficiencies and inhibitor of white adipose lipolysis, were significantly reduced in apoA-I tg mice. Consistent with an increase in glucose utilization of skeletal muscle, genetically increased HDL and apoA-I levels in mice prevented high-fat diet-induced impairment of glucose homeostasis. In view of impaired mitochondrial function and decreased HDL levels in type 2 diabetes mellitus, our findings indicate that HDL-raising therapies may preserve muscle mitochondrial function and address key aspects of type 2 diabetes mellitus beyond cardiovascular disease.

  2. Control and Functions of Fixational Eye Movements

    Science.gov (United States)

    Rucci, Michele; Poletti, Martina

    2016-01-01

    Humans and other species explore a visual scene by rapidly shifting their gaze 2-3 times every second. Although the eyes may appear immobile in the brief intervals in between saccades, microscopic (fixational) eye movements are always present, even when attending to a single point. These movements occur during the very periods in which visual information is acquired and processed and their functions have long been debated. Recent technical advances in controlling retinal stimulation during normal oculomotor activity have shed new light on the visual contributions of fixational eye movements and their degree of control. The emerging body of evidence, reviewed in this article, indicates that fixational eye movements are important components of the strategy by which the visual system processes fine spatial details, enabling both precise positioning of the stimulus on the retina and encoding of spatial information into the joint space-time domain.

  3. Stability and Control of Functional Differential Equations

    CERN Document Server

    Peet, M M

    2006-01-01

    This thesis addresses the question of stability of systems defined by differential equations which contain nonlinearity and delay. In particular, we analyze the stability of a well-known delayed nonlinear implementation of a certain Internet congestion control protocol. We also describe a generalized methodology for proving stability of time-delay systems through the use of semidefinite programming. In Chapters 4 and 5, we consider an Internet congestion control protocol based on the decentralized gradient projection algorithm. For a certain class of utility function, this algorithm was shown to be globally convergent for some sufficiently small value of a gain parameter. Later work gave an explicit bound on this gain for a linearized version of the system. This thesis proves that this bound also implies stability of the original system. In Chapter 7, we describe a general methodology for proving stability of linear time-delay systems by computing solutions to an operator-theoretic version of the Lyapunov ine...

  4. Study Design for a Case Control Investigation of Cellular Telephones and Other Risk Factors for Brain Tumors in Adults

    Energy Technology Data Exchange (ETDEWEB)

    Inskip, P.D.; Hatch, E.E.; Stewart, P.A.; Heineman, E.F.; Ziegler, R.G.; Dosemeci, M.; Parry, D.; Rothman, N.; Boice, J.D. Jr.; Wilcosky, T.C.; Watson, D.J.; Shapiro, W.R.; Selker, R.G.; Fine, H.A.; Black, P. McL.; Loeffler, J.S.; Linet, M.S

    1999-07-01

    The aetiology of brain tumours is poorly understood. Due, in part, to public concern about a postulated relationship between the use of cellular telephones or other increasingly prevalent environmental exposures and the incidence of brain cancer in adults, the National Cancer Institute is collaborating with three US hospitals in a comprehensive case control study of malignant and benign brain tumours. Factors under consideration include use of cellular phones and other wireless communication devices, workplace exposures to chemical agents and electromagnetic fields, dietary factors, family history of tumours, genetic determinants of susceptibility, home appliance use, reproductive history and hormonal exposures, viruses, medical and dental exposure to ionising radiation, and other aspects of medical history. Approximately 800 newly diagnosed brain tumour cases and 800 controls were enrolled at hospitals in Boston, Phoenix and Pittsburgh from 1994 to 1998. Cases include all adults (age {>=} 18 y) newly diagnosed with a histologically confirmed intracranial glioma, histologically confirmed intracranial meningioma or acoustic neuroma. Controls are patients admitted to the same hospitals as the cases, and treated for any of a variety of non-malignant conditions. Key features of the study include its large size, the emphasis on rapid ascertainment of incident cases and interview of study subjects rather than surrogate respondents, the use of detailed, job-specific questions developed by industrial hygienists to ascertain occupational exposures, and the storage of blood samples for future evaluation of inherited susceptibility, biomarkers of exposure and gene environment interactions. (author)

  5. Automating the purchasing and inventory control functions.

    Science.gov (United States)

    Hughes, T W

    1985-05-01

    Factors involved in computerizing the purchasing and inventory control functions in hospital pharmacies are described. When initiating an automated purchasing and inventory control system, a feasibility study should first be conducted to determine the extent of automation needed to develop a cost-effective system. The design of the system will depend on the extent to which the department of materials management is involved with other hospital departments. The advantages and disadvantages of decentralized versus centralized systems are discussed, and criteria for selecting hardware and software vendors are presented. A return-on-investment analysis should be performed to validate the benefits or savings expected from implementing the new automated system. Factors to consider during implementation of the new system and future developments affecting purchasing and inventory control systems, such as bar coding, are discussed. With the current concern about rapidly rising health-care costs and the need to enhance productivity, the development and implementation of automated purchasing and inventory control systems are important strategies for institutions to pursue now.

  6. Role of Myeloperoxidase Oxidants in the Modulation of Cellular Lysosomal Enzyme Function

    DEFF Research Database (Denmark)

    Ismael, Fahd O; Barrett, Tessa J; Sheipouri, Diba

    2016-01-01

    with the development of atherosclerosis. In this study, we examined the effect of HOCl, HOSCN and LDL pre-treated with these oxidants on the function of lysosomal enzymes responsible for protein catabolism and lipid hydrolysis in murine macrophage-like J774A.1 cells. In each case, the cells were exposed to HOCl...... or HOSCN or LDL pre-treated with these oxidants. Lysosomal cathepsin (B, L and D) and acid lipase activities were quantified, with cathepsin and LAMP-1 protein levels determined by Western blotting. Exposure of J774A.1 cells to HOCl or HOSCN resulted in a significant decrease in the activity of the Cys......-dependent cathepsins B and L, but not the Asp-dependent cathepsin D. Cathepsins B and L were also inhibited in macrophages exposed to HOSCN-modified, and to a lesser extent, HOCl-modified LDL. No change was seen in cathepsin D activity or the expression of the cathepsin proteins or lysosomal marker protein LAMP-1...

  7. In-vitro cytotoxicity and cellular uptake studies of luminescent functionalized core-shell nanospheres.

    Science.gov (United States)

    Ansari, Anees A; Hasan, T N; Syed, N A; Labis, J P; Alshatwi, Ali A

    2017-09-01

    Monodispersed luminescent functionalized core-shell nanospheres (LFCSNs) were successfully synthesized and investigated for their cyto-toxic effect on human liver hepatocellular carcinoma cell line (HepG2 cells) by adopting MTT, DNA Ladder, TUNEL assay and qPCR based gene expressions through mRNA quantifications. The TUNEL and DNA ladder assays suggested an insignificant apoptosis in HepG2 cells due to the LFCSNs treatment. Further, the qPCR results also show that the mRNA expressions of cell cycle checkpoint gene p53 and apoptosis related gene (caspase-9) was up-regulated, while the antiapoptotic gene BCl-2 and apoptosis related genes FADD and CAS-3 (apoptosis effecter gene) were down-regulated in the LFCSNs treated cells. The nanospheres that were loaded into the cells confirm their intracellular uptake by light and fluorescent spectro-photometry and microscopy imaging analysis. The loaded nanospheres demonstrate an absolute resistance to photo-bleaching, which were applied for dynamic imaging to real-time tracking in-vitro cell migratory activity for continuous 24 and 48 h durations using a time-lapsed fluorescent microscope. These properties of LFCSNs could therefore promote applications in the area of fluorescent protein biolabeling and drug-delivery.

  8. An improved, non-functionalized route to plasmonic nanoparticle based cellular probing through osmolyte mediation (Conference Presentation)

    Science.gov (United States)

    Siddhanta, Soumik; Barman, Ishan

    2017-02-01

    Engineering nanostructured probes for ultra-sensitive detection of specific molecular species, our research seeks to capture the complex changes in cells and tissues that can predict disease progression in an individual. While such nanoparticle-based platforms are rapidly gaining a foothold in cancer diagnostics, one of the most concerning factors is the vulnerability of cells to the interaction with functional nanoparticles thereby raising the specter of systemic toxicity. The nanoparticles end up damaging the cells and disrupting cellular functions thereby impeding their imaging aim. Furthermore, PEGylation, and similar routes, force a tradeoff between desired nanoparticle properties (recognition, uptake, and reduced toxicity) and sensitivity of plasmon-enhanced spectroscopic sensing methods, such as surface-enhanced Raman spectroscopy (SERS) where the proximal presence of noble metal NP and the organic molecule of interest is key. In this work, we report a trehalose-mediated, non-surface functionalized route for cell-nanoparticle interactions that maintains cell viability while allowing selective interaction of the nanoparticle with the cell surface receptors and subsequent internalization. Through careful electron microscopy of nanoparticle-prostate cancer cells interactions, we elucidated that there exists a dynamic equilibrium between "free" cytosolic diffusion of the nanoparticles and endocytosis through vesicle formation - and trehalose tilts the scale in favor of the latter to mask the toxic effects of the nanoparticles. The precise molecular interpretation of this behavior was further probed through SERS, which directly points towards the protein stabilization properties of trehalose mediation during interaction of the nanoparticles with the plasma membrane components.

  9. Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Ji P

    2016-03-01

    Full Text Available Peng Ji, Tong Yu, Ying Liu, Jie Jiang, Jie Xu, Ying Zhao, Yanna Hao, Yang Qiu, Wenming Zhao, Chao WuCollege of Pharmacy, Liaoning Medical University, Jinzhou, Liaoning Province, People’s Republic of ChinaAbstract: Naringenin (NRG, a flavonoid compound, had been reported to exhibit extensive pharmacological effects, but its water solubility and oral bioavailability are only ~46±6 µg/mL and 5.8%, respectively. The purpose of this study is to design and develop NRG-loaded solid lipid nanoparticles (NRG-SLNs to provide prolonged and sustained drug release, with improved stability, involving nontoxic nanocarriers, and increase the bioavailability by means of pulmonary administration. Initially, a group contribution method was used to screen the best solid lipid matrix for the preparation of SLNs. NRG-SLNs were prepared by an emulsification and low-temperature solidification method and optimized using an orthogonal experiment approach. The morphology was examined by transmission electron microscopy, and the particle size and zeta potential were determined by photon correlation spectroscopy. The total drug content of NRG-SLNs was measured by high-performance liquid chromatography, and the encapsulation efficiency (EE was determined by Sephadex gel-50 chromatography and high-performance liquid chromatography. The in vitro NRG release studies were carried out using a dialysis bag. The best cryoprotectant to prepare NRG-SLN lyophilized powder for future structural characterization was selected using differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. The short-term stability, 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT assay, cellular uptake, and pharmacokinetics in rats were studied after pulmonary administration of NRG-SLN lyophilized powder. Glycerol monostearate was selected to prepare SLNs, and the optimal formulation of NRG-SLNs was spherical in shape, with a particle

  10. Effect of the sequential therapy of lamivudine and α-interferon on cellular immune function as well as serum PD-1 and Tin-3 levels in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Yan Jin; Ting Qiu; Yi-Fei Lyu; Chun-Ying Yan; Xue Wang; Tian-Jiao Duan; Rong Zhang; Gui-Sheng Liu

    2016-01-01

    Objective:To analyze the effect of the sequential therapy of lamivudine and α-interferon on cellular immune function as well as serum PD-1 and Tin-3 levels in patients with chronic hepatitis B. Methods: A total of 92 cases of patients with chronic hepatitis B who were treated in our hospital from May 2012 to May 2015 were selected as the research subjects and divided into observation group and control group (n=46) according to the random number table. Control group received lamivudine treatment alone, observation group received the sequential therapy of lamivudine and α-interferon, and then differences in ultrasound-related indexes, cellular immune function as well as PD-1 and Tin-3 levels were compared between two groups. Results:After observation group received the sequential therapy of lamivudine andα-interferon, ultrasonic major diameter of left hepatic lobe and PVM values were greater than those of control group, and internal diameter of portal vein was lower than that of control group; CD4+T and CD4+T/ CD8+T values of observation group were higher than those of control group, and CD8+T value was lower than that of control group;circulating blood CD8+T cell PD-1 and Tim-3 expression levels of observation group were lower than those of control group. Conclusion:Sequential therapy of lamivudine andα-interferon can optimize the cellular immune function of patients with chronic hepatitis B and inhibit the negative regulation process of immune function, and it helps to inhibit hepatitis B virus activity and disease control.

  11. An acetylation switch controls TDP-43 function and aggregation propensity

    Science.gov (United States)

    Cohen, Todd J.; Hwang, Andrew W.; Restrepo, Clark R.; Yuan, Chao-Xing; Trojanowski, John Q.; Lee, Virginia M.Y.

    2015-01-01

    TDP-43 pathology is a disease hallmark that characterizes amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP). Although a critical role for TDP-43 as an RNA-binding protein has emerged, the regulation of TDP-43 function is poorly understood. Here we identify lysine acetylation as a novel post-translational modification controlling TDP-43 function and aggregation. We provide evidence that TDP-43 acetylation impairs RNA-binding and promotes accumulation of insoluble, hyper-phosphorylated TDP-43 species that largely resemble pathological inclusions in ALS and FTLD-TDP. Moreover, biochemical and cell-based assays identify oxidative stress as a signaling cue that promotes acetylated TDP-43 aggregates that are readily engaged by the cellular defense machinery. Importantly, acetylated TDP-43 lesions are found in ALS patient spinal cord, indicating that aberrant TDP-43 acetylation and loss of RNA binding are linked to TDP-43 proteinopathy. Thus, modulating TDP-43 acetylation represents a plausible strategy to fine-tune TDP-43 activity, which could provide new therapeutic avenues for TDP-43 proteinopathies. PMID:25556531

  12. ECM Signaling Regulates Collective Cellular Dynamics to Control Pancreas Branching Morphogenesis.

    Science.gov (United States)

    Shih, Hung Ping; Panlasigui, Devin; Cirulli, Vincenzo; Sander, Maike

    2016-01-12

    During pancreas development, epithelial buds undergo branching morphogenesis to form an exocrine and endocrine gland. Proper morphogenesis is necessary for correct lineage allocation of pancreatic progenitors; however, the cellular events underlying pancreas morphogenesis are unknown. Here, we employed time-lapse microscopy and fluorescent labeling of cells to analyze cell behaviors associated with pancreas morphogenesis. We observed that outer bud cells adjacent to the basement membrane are pleomorphic and rearrange frequently; additionally, they largely remain in the outer cell compartment even after mitosis. These cell behaviors and pancreas branching depend on cell contacts with the basement membrane, which induce actomyosin cytoskeleton remodeling via integrin-mediated activation of FAK/Src signaling. We show that integrin signaling reduces E-cadherin-mediated cell-cell adhesion in outer cells and provide genetic evidence that this regulation is necessary for initiation of branching. Our study suggests that regulation of cell motility and adhesion by local niche cues initiates pancreas branching morphogenesis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. ECM Signaling Regulates Collective Cellular Dynamics to Control Pancreas Branching Morphogenesis

    Directory of Open Access Journals (Sweden)

    Hung Ping Shih

    2016-01-01

    Full Text Available During pancreas development, epithelial buds undergo branching morphogenesis to form an exocrine and endocrine gland. Proper morphogenesis is necessary for correct lineage allocation of pancreatic progenitors; however, the cellular events underlying pancreas morphogenesis are unknown. Here, we employed time-lapse microscopy and fluorescent labeling of cells to analyze cell behaviors associated with pancreas morphogenesis. We observed that outer bud cells adjacent to the basement membrane are pleomorphic and rearrange frequently; additionally, they largely remain in the outer cell compartment even after mitosis. These cell behaviors and pancreas branching depend on cell contacts with the basement membrane, which induce actomyosin cytoskeleton remodeling via integrin-mediated activation of FAK/Src signaling. We show that integrin signaling reduces E-cadherin-mediated cell-cell adhesion in outer cells and provide genetic evidence that this regulation is necessary for initiation of branching. Our study suggests that regulation of cell motility and adhesion by local niche cues initiates pancreas branching morphogenesis.

  14. Directed Ligand Passage Over the Surface of Diffusion-Controlled Enzymes: A Cellular Automata Model

    CERN Document Server

    Ghaemi, M; Sarbolouki, M N; Ghaemi, Mehrdad; Rezaei-Ghaleh, Nasrollah; Sarbolouki, Mohammad-Nabi

    2004-01-01

    The rate-limiting step of some enzymatic reactions is a physical step, i.e. diffusion. The efficiency of such reactions can be improved through an increase in the arrival rate of the substrate molecules, e.g. by a directed passage of substrate (ligand) to active site after its random encounter with the enzyme surface. Herein, we introduce a cellular automata model simulating the ligand passage over the protein surface to its destined active site. The system is simulated using the lattice gas automata with probabilistic transition rules. Different distributions of amino acids over the protein surface are examined. For each distribution, the hydration pattern is achieved and the mean number of iteration steps needed for the ligand to arrive at the active site calculated. Comparison of results indicates that the rate at which ligand arrives at the active site is clearly affected by the distribution of amino acids outside the active side. Such a process can facilitate the ligand diffusion towards the active site ...

  15. Contribution of glutathione to the control of cellular redox homeostasis under toxic metal and metalloid stress.

    Science.gov (United States)

    Hernández, Luis E; Sobrino-Plata, Juan; Montero-Palmero, M Belén; Carrasco-Gil, Sandra; Flores-Cáceres, M Laura; Ortega-Villasante, Cristina; Escobar, Carolina

    2015-05-01

    The accumulation of toxic metals and metalloids, such as cadmium (Cd), mercury (Hg), or arsenic (As), as a consequence of various anthropogenic activities, poses a serious threat to the environment and human health. The ability of plants to take up mineral nutrients from the soil can be exploited to develop phytoremediation technologies able to alleviate the negative impact of toxic elements in terrestrial ecosystems. However, we must select plant species or populations capable of tolerating exposure to hazardous elements. The tolerance of plant cells to toxic elements is highly dependent on glutathione (GSH) metabolism. GSH is a biothiol tripeptide that plays a fundamental dual role: first, as an antioxidant to mitigate the redox imbalance caused by toxic metal(loid) accumulation, and second as a precursor of phytochelatins (PCs), ligand peptides that limit the free ion cellular concentration of those pollutants. The sulphur assimilation pathway, synthesis of GSH, and production of PCs are tightly regulated in order to alleviate the phytotoxicity of different hazardous elements, which might induce specific stress signatures. This review provides an update on mechanisms of tolerance that depend on biothiols in plant cells exposed to toxic elements, with a particular emphasis on the Hg-triggered responses, and considering the contribution of hormones to their regulation.

  16. Nrf2 impacts cellular bioenergetics by controlling substrate availability for mitochondrial respiration

    Directory of Open Access Journals (Sweden)

    Kira M. Holmström

    2013-06-01

    Transcription factor Nrf2 and its repressor Keap1 regulate a network of cytoprotective genes involving more than 1% of the genome, their best known targets being drug-metabolizing and antioxidant genes. Here we demonstrate a novel role for this pathway in directly regulating mitochondrial bioenergetics in murine neurons and embryonic fibroblasts. Loss of Nrf2 leads to mitochondrial depolarisation, decreased ATP levels and impaired respiration, whereas genetic activation of Nrf2 increases the mitochondrial membrane potential and ATP levels, the rate of respiration and the efficiency of oxidative phosphorylation. We further show that Nrf2-deficient cells have increased production of ATP in glycolysis, which is then used by the F1Fo-ATPase for maintenance of the mitochondrial membrane potential. While the levels and in vitro activities of the respiratory complexes are unaffected by Nrf2 deletion, their activities in isolated mitochondria and intact live cells are substantially impaired. In addition, the rate of regeneration of NADH after inhibition of respiration is much slower in Nrf2-knockout cells than in their wild-type counterparts. Taken together, these results show that Nrf2 directly regulates cellular energy metabolism through modulating the availability of substrates for mitochondrial respiration. Our findings highlight the importance of efficient energy metabolism in Nrf2-mediated cytoprotection.

  17. Location-based admission control for differentiated services in 3G cellular networks

    NARCIS (Netherlands)

    Núñez-Queija, R.; Tan, H.-P.

    2006-01-01

    Third generation wireless systems can simultaneously accommodate flow transmissions of users with widely heterogeneous applications. As resources are limited (particularly in the air interface), admission control is necessary to ensure that all active users are accommodated with sufficient capacity

  18. Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics.

    Science.gov (United States)

    Ji, Peng; Yu, Tong; Liu, Ying; Jiang, Jie; Xu, Jie; Zhao, Ying; Hao, Yanna; Qiu, Yang; Zhao, Wenming; Wu, Chao

    2016-01-01

    Naringenin (NRG), a flavonoid compound, had been reported to exhibit extensive pharmacological effects, but its water solubility and oral bioavailability are only~46±6 µg/mL and 5.8%, respectively. The purpose of this study is to design and develop NRG-loaded solid lipid nanoparticles (NRG-SLNs) to provide prolonged and sustained drug release, with improved stability, involving nontoxic nanocarriers, and increase the bioavailability by means of pulmonary administration. Initially, a group contribution method was used to screen the best solid lipid matrix for the preparation of SLNs. NRG-SLNs were prepared by an emulsification and low-temperature solidification method and optimized using an orthogonal experiment approach. The morphology was examined by transmission electron microscopy, and the particle size and zeta potential were determined by photon correlation spectroscopy. The total drug content of NRG-SLNs was measured by high-performance liquid chromatography, and the encapsulation efficiency (EE) was determined by Sephadex gel-50 chromatography and high-performance liquid chromatography. The in vitro NRG release studies were carried out using a dialysis bag. The best cryoprotectant to prepare NRG-SLN lyophilized powder for future structural characterization was selected using differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. The short-term stability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, cellular uptake, and pharmacokinetics in rats were studied after pulmonary administration of NRG-SLN lyophilized powder. Glycerol monostearate was selected to prepare SLNs, and the optimal formulation of NRG-SLNs was spherical in shape, with a particle size of 98 nm, a polydispersity index of 0.258, a zeta potential of -31.4 mV, a total drug content of 9.76 mg, an EE of 79.11%, and a cumulative drug release of 80% in 48 hours with a sustained profile. In addition, 5% mannitol (w

  19. From Cellular Attractor Selection to Adaptive Signal Control for Traffic Networks.

    Science.gov (United States)

    Tian, Daxin; Zhou, Jianshan; Sheng, Zhengguo; Wang, Yunpeng; Ma, Jianming

    2016-03-14

    The management of varying traffic flows essentially depends on signal controls at intersections. However, design an optimal control that considers the dynamic nature of a traffic network and coordinates all intersections simultaneously in a centralized manner is computationally challenging. Inspired by the stable gene expressions of Escherichia coli in response to environmental changes, we explore the robustness and adaptability performance of signalized intersections by incorporating a biological mechanism in their control policies, specifically, the evolution of each intersection is induced by the dynamics governing an adaptive attractor selection in cells. We employ a mathematical model to capture such biological attractor selection and derive a generic, adaptive and distributed control algorithm which is capable of dynamically adapting signal operations for the entire dynamical traffic network. We show that the proposed scheme based on attractor selection can not only promote the balance of traffic loads on each link of the network but also allows the global network to accommodate dynamical traffic demands. Our work demonstrates the potential of bio-inspired intelligence emerging from cells and provides a deep understanding of adaptive attractor selection-based control formation that is useful to support the designs of adaptive optimization and control in other domains.

  20. From Cellular Attractor Selection to Adaptive Signal Control for Traffic Networks

    Science.gov (United States)

    Tian, Daxin; Zhou, Jianshan; Sheng, Zhengguo; Wang, Yunpeng; Ma, Jianming

    2016-03-01

    The management of varying traffic flows essentially depends on signal controls at intersections. However, design an optimal control that considers the dynamic nature of a traffic network and coordinates all intersections simultaneously in a centralized manner is computationally challenging. Inspired by the stable gene expressions of Escherichia coli in response to environmental changes, we explore the robustness and adaptability performance of signalized intersections by incorporating a biological mechanism in their control policies, specifically, the evolution of each intersection is induced by the dynamics governing an adaptive attractor selection in cells. We employ a mathematical model to capture such biological attractor selection and derive a generic, adaptive and distributed control algorithm which is capable of dynamically adapting signal operations for the entire dynamical traffic network. We show that the proposed scheme based on attractor selection can not only promote the balance of traffic loads on each link of the network but also allows the global network to accommodate dynamical traffic demands. Our work demonstrates the potential of bio-inspired intelligence emerging from cells and provides a deep understanding of adaptive attractor selection-based control formation that is useful to support the designs of adaptive optimization and control in other domains.

  1. Impact of cadmium on hOGG1 and APE1 as a function of the cellular p53 status

    Energy Technology Data Exchange (ETDEWEB)

    Hamann, Ingrit [Institut fuer Angewandte Biowissenschaften, Abteilung Lebensmittelchemie und Toxikologie, Karlsruher Institut fuer Technologie (KIT), 76131 Karlsruhe (Germany); Fachgebiet Lebensmittelchemie und Toxikologie, Institut fuer Lebensmitteltechnologie und Lebensmittelchemie, Technische Universitaet Berlin, 13355 Berlin (Germany); Faculty for Pharmacy and Pharmaceutical Sciences, University of Alberta, 3126 Dentistry/Pharmacy Centre, Edmonton, Alberta, Canada T6G 2N8 (Canada); Koenig, Charlotte; Richter, Constanze [Fachgebiet Lebensmittelchemie und Toxikologie, Institut fuer Lebensmitteltechnologie und Lebensmittelchemie, Technische Universitaet Berlin, 13355 Berlin (Germany); Jahnke, Gunnar [Institut fuer Angewandte Biowissenschaften, Abteilung Lebensmittelchemie und Toxikologie, Karlsruher Institut fuer Technologie (KIT), 76131 Karlsruhe (Germany); Fachgebiet Lebensmittelchemie und Toxikologie, Institut fuer Lebensmitteltechnologie und Lebensmittelchemie, Technische Universitaet Berlin, 13355 Berlin (Germany); Hartwig, Andrea, E-mail: andrea.hartwig@kit.edu [Institut fuer Angewandte Biowissenschaften, Abteilung Lebensmittelchemie und Toxikologie, Karlsruher Institut fuer Technologie (KIT), 76131 Karlsruhe (Germany); Fachgebiet Lebensmittelchemie und Toxikologie, Institut fuer Lebensmitteltechnologie und Lebensmittelchemie, Technische Universitaet Berlin, 13355 Berlin (Germany)

    2012-08-01

    The tumor suppressor protein p53, often called the guardian of the genome, is involved in important cellular processes, such as cell cycle control, apoptosis and DNA repair. With respect to BER, p53 might physically interact with and affect the transcription of different BER proteins such as hOGG1, APE1 or Pol{beta}. In studies in HCT116 p53{sup -/-} cells previously published, activity and mRNA expression of hOGG1 were found to be significantly decreased, while down-regulation of APE1 mRNA and protein levels in response to genotoxic stress were only described in HCT116 p53{sup +/+} cells, but not in the isogenic p53 knockout cell line. The predominantly indirect genotoxic carcinogen cadmium inhibits the BER pathway and potentially interferes with zinc binding proteins such as p53. Therefore, this study was accomplished to investigate whether p53 is involved in the cadmium-induced inhibition of BER activity. To address this issue we applied a non-radioactive cleavage test system based on a Cy5-labeled oligonucleotide. We present evidence that p53 is not essential for hOGG1 and APE1 gene expression as well as OGG and APE activity in unstressed HCT116 cells; however, it plays an important role in the cellular response to cadmium treatment. Here, a direct involvement of p53 was only observed with respect to APE1 gene expression contributing to an altered APE activity, while OGG activity was presumably affected indirectly due to a stronger accumulation of cadmium in HCT116 p53{sup +/+} cells. In summary, p53 indeed affects the BER pathway directly and indirectly in response to cadmium treatment.

  2. System-level insights into the cellular interactome of a non-model organism: inferring, modelling and analysing functional gene network of soybean (Glycine max).

    Science.gov (United States)

    Xu, Yungang; Guo, Maozu; Zou, Quan; Liu, Xiaoyan; Wang, Chunyu; Liu, Yang

    2014-01-01

    Cellular interactome, in which genes and/or their products interact on several levels, forming transcriptional regulatory-, protein interaction-, metabolic-, signal transduction networks, etc., has attracted decades of research focuses. However, such a specific type of network alone can hardly explain the various interactive activities among genes. These networks characterize different interaction relationships, implying their unique intrinsic properties and defects, and covering different slices of biological information. Functional gene network (FGN), a consolidated interaction network that models fuzzy and more generalized notion of gene-gene relations, have been proposed to combine heterogeneous networks with the goal of identifying functional modules supported by multiple interaction types. There are yet no successful precedents of FGNs on sparsely studied non-model organisms, such as soybean (Glycine max), due to the absence of sufficient heterogeneous interaction data. We present an alternative solution for inferring the FGNs of soybean (SoyFGNs), in a pioneering study on the soybean interactome, which is also applicable to other organisms. SoyFGNs exhibit the typical characteristics of biological networks: scale-free, small-world architecture and modularization. Verified by co-expression and KEGG pathways, SoyFGNs are more extensive and accurate than an orthology network derived from Arabidopsis. As a case study, network-guided disease-resistance gene discovery indicates that SoyFGNs can provide system-level studies on gene functions and interactions. This work suggests that inferring and modelling the interactome of a non-model plant are feasible. It will speed up the discovery and definition of the functions and interactions of other genes that control important functions, such as nitrogen fixation and protein or lipid synthesis. The efforts of the study are the basis of our further comprehensive studies on the soybean functional interactome at the genome

  3. Associations of IL-4, IL-6, and IL-12 levels in peripheral blood with lung function, cellular immune function, and quality of life in children with moderate-to-severe asthma

    Science.gov (United States)

    Cui, Ai-Hua; Zhao, Jing; Liu, Shu-Xiang; Hao, Ying-Shuang

    2017-01-01

    Abstract Background: Pediatric asthma has gained increasing concerns with poorly understood pathogenesis. The purpose of this study was to explore the associations of interleukin-4 (IL-4), IL-6, and IL-12 levels in peripheral blood (PB) with lung function, cellular immune function, and children's quality of life (QOL) with moderate-to-severe asthma. Methods: A total of 1158 children with moderate-to-severe asthma (the experimental group) and 1075 healthy children (the control group) were recruited for our study. Enzyme-linked immunosorbent assay was used to detect IL-4, IL-6, and IL-12 levels. T lymphocytes were detected by alkaline phosphatase antialkaline phosphatase, and erythrocyte immune was measured by red blood cell C 3b receptor (RBC-C3bR) rosette-forming test. The forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) were detected, after which FEV1/forced vital capacity (FVC) was calculated before and after treatment. PedsQL3.0 was used to measure the effect of asthma on QOL of children, and the correlation between IL-4, IL-6, and IL-12 levels and the lung function and QOL was measured. Logistic regression analysis was applied to detect related factors of moderate-to-severe asthma of children. Results: After treatment, the decreased IL-4 and IL-6 levels and increased IL-12 level were revealed in the experimental group. The cellular immune function's disorder was significantly decreased, and an elevated CD3, CD4, CD8, and declined CD4/CD8 level was performed in T lymphocytes. RBC-C3bR was increased, and red blood cell immune complex (RBC-IC) was reduced in erythrocyte immune in comparison with those before treatment. Lung function parameters all increased. After treatment, the symptoms of asthma in children reduced with scores of increased QOL. IL-4 was positively related to RBC-IC, but negatively associated with the QOL score. IL-6 showed negative connection with CD4/CD8, RBC-C3bR, FEV1/FVC, and QOL score, and had positive connection

  4. Associations of IL-4, IL-6, and IL-12 levels in peripheral blood with lung function, cellular immune function, and quality of life in children with moderate-to-severe asthma.

    Science.gov (United States)

    Cui, Ai-Hua; Zhao, Jing; Liu, Shu-Xiang; Hao, Ying-Shuang

    2017-03-01

    Pediatric asthma has gained increasing concerns with poorly understood pathogenesis. The purpose of this study was to explore the associations of interleukin-4 (IL-4), IL-6, and IL-12 levels in peripheral blood (PB) with lung function, cellular immune function, and children's quality of life (QOL) with moderate-to-severe asthma. A total of 1158 children with moderate-to-severe asthma (the experimental group) and 1075 healthy children (the control group) were recruited for our study. Enzyme-linked immunosorbent assay was used to detect IL-4, IL-6, and IL-12 levels. T lymphocytes were detected by alkaline phosphatase antialkaline phosphatase, and erythrocyte immune was measured by red blood cell C 3b receptor (RBC-C3bR) rosette-forming test. The forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) were detected, after which FEV1/forced vital capacity (FVC) was calculated before and after treatment. PedsQL3.0 was used to measure the effect of asthma on QOL of children, and the correlation between IL-4, IL-6, and IL-12 levels and the lung function and QOL was measured. Logistic regression analysis was applied to detect related factors of moderate-to-severe asthma of children. After treatment, the decreased IL-4 and IL-6 levels and increased IL-12 level were revealed in the experimental group. The cellular immune function's disorder was significantly decreased, and an elevated CD3, CD4, CD8, and declined CD4/CD8 level was performed in T lymphocytes. RBC-C3bR was increased, and red blood cell immune complex (RBC-IC) was reduced in erythrocyte immune in comparison with those before treatment. Lung function parameters all increased. After treatment, the symptoms of asthma in children reduced with scores of increased QOL. IL-4 was positively related to RBC-IC, but negatively associated with the QOL score. IL-6 showed negative connection with CD4/CD8, RBC-C3bR, FEV1/FVC, and QOL score, and had positive connection with PEF. In addition, IL-12 was

  5. The problem of determining the range of innovation controlling functions

    Directory of Open Access Journals (Sweden)

    N.M. Mykhaylychenko

    2012-03-01

    Full Text Available The article analyzes the concept of controlling of innovation, examines the various approaches to defining the range of functions of innovation controlling subsystem and determines its place in the system of company controlling and the management system as a whole. It provides the authors definition of controlling of innovation, defines the circle of functions to be performed by controlling of innovation the coordination, analytical, methodical functions and the function of information management of innovation processes in the enterprise.

  6. Metabolomics Reveals New Mechanisms for Pathogenesis in Barth Syndrome and Introduces Novel Roles for Cardiolipin in Cellular Function.

    Directory of Open Access Journals (Sweden)

    Yana Sandlers

    Full Text Available Barth Syndrome is the only known Mendelian disorder of cardiolipin remodeling, with characteristic clinical features of cardiomyopathy, skeletal myopathy, and neutropenia. While the primary biochemical defects of reduced mature cardiolipin and increased monolysocardiolipin are well-described, much of the downstream biochemical dysregulation has not been uncovered, and biomarkers are limited. In order to further expand upon the knowledge of the biochemical abnormalities in Barth Syndrome, we analyzed metabolite profiles in plasma from a cohort of individuals with Barth Syndrome compared to age-matched controls via 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. A clear distinction between metabolite profiles of individuals with Barth Syndrome and controls was observed, and was defined by an array of metabolite classes including amino acids and lipids. Pathway analysis of these discriminating metabolites revealed involvement of mitochondrial and extra-mitochondrial biochemical pathways including: insulin regulation of fatty acid metabolism, lipid metabolism, biogenic amine metabolism, amino acid metabolism, endothelial nitric oxide synthase signaling, and tRNA biosynthesis. Taken together, this data indicates broad metabolic dysregulation in Barth Syndrome with wide cellular effects.

  7. New Concepts and Theories For Intelligent Control of Cellular Manufacturing Systems

    DEFF Research Database (Denmark)

    Langer, Gilad

    1996-01-01

    This paper will present some new theories such as biological manufacturing system, the fractal factory theory, holonic manufacturing systems, and multi-agent theory in the context of manufacturing systems. The objective of the paper is to show how these theories can contribute to develop the new...... concepts that are required for controlling the manufacturing systems of the future. Thereafter it will present the potential for improvement of the manufacturing system by introduction and implementation of these theories. The paper tries to encapsulate the main area of my Ph.D. thesis research which...... will evolve around the idea of integrating intelligent elements into the control systems of the manufacturing systems. The research will concentrate on integration of manufacturing units by use of intelligent control mechanisms, information technology and the material handling as the key integrators....

  8. New Concepts and Theories For Intelligent Control of Cellular Manufacturing Systems

    DEFF Research Database (Denmark)

    Langer, Gilad

    1996-01-01

    concepts that are required for controlling the manufacturing systems of the future. Thereafter it will present the potential for improvement of the manufacturing system by introduction and implementation of these theories. The paper tries to encapsulate the main area of my Ph.D. thesis research which......This paper will present some new theories such as biological manufacturing system, the fractal factory theory, holonic manufacturing systems, and multi-agent theory in the context of manufacturing systems. The objective of the paper is to show how these theories can contribute to develop the new...... will evolve around the idea of integrating intelligent elements into the control systems of the manufacturing systems. The research will concentrate on integration of manufacturing units by use of intelligent control mechanisms, information technology and the material handling as the key integrators....

  9. Dynamical Allocation of Cellular Resources as an Optimal Control Problem: Novel Insights into Microbial Growth Strategies

    Science.gov (United States)

    Giordano, Nils; Mairet, Francis; Gouzé, Jean-Luc

    2016-01-01

    Microbial physiology exhibits growth laws that relate the macromolecular composition of the cell to the growth rate. Recent work has shown that these empirical regularities can be derived from coarse-grained models of resource allocation. While these studies focus on steady-state growth, such conditions are rarely found in natural habitats, where microorganisms are continually challenged by environmental fluctuations. The aim of this paper is to extend the study of microbial growth strategies to dynamical environments, using a self-replicator model. We formulate dynamical growth maximization as an optimal control problem that can be solved using Pontryagin’s Maximum Principle. We compare this theoretical gold standard with different possible implementations of growth control in bacterial cells. We find that simple control strategies enabling growth-rate maximization at steady state are suboptimal for transitions from one growth regime to another, for example when shifting bacterial cells to a medium supporting a higher growth rate. A near-optimal control strategy in dynamical conditions is shown to require information on several, rather than a single physiological variable. Interestingly, this strategy has structural analogies with the regulation of ribosomal protein synthesis by ppGpp in the enterobacterium Escherichia coli. It involves sensing a mismatch between precursor and ribosome concentrations, as well as the adjustment of ribosome synthesis in a switch-like manner. Our results show how the capability of regulatory systems to integrate information about several physiological variables is critical for optimizing growth in a changing environment. PMID:26958858

  10. Control of spatially heterogeneous and time-varying cellular reaction networks: a new summation law

    NARCIS (Netherlands)

    Peletier, M.A.; Westerhoff, H.V.; Kholodenko, B.N.

    2002-01-01

    A hallmark of a plethora of intracellular signaling pathways is the spatial separation of activation and deactivation processes that potentially results in precipitous gradients of activated proteins. The classical Metabolic Control Analysis (MCA), which quantifies the influence of an individual pro

  11. Dynamical Allocation of Cellular Resources as an Optimal Control Problem: Novel Insights into Microbial Growth Strategies.

    Directory of Open Access Journals (Sweden)

    Nils Giordano

    2016-03-01

    Full Text Available Microbial physiology exhibits growth laws that relate the macromolecular composition of the cell to the growth rate. Recent work has shown that these empirical regularities can be derived from coarse-grained models of resource allocation. While these studies focus on steady-state growth, such conditions are rarely found in natural habitats, where microorganisms are continually challenged by environmental fluctuations. The aim of this paper is to extend the study of microbial growth strategies to dynamical environments, using a self-replicator model. We formulate dynamical growth maximization as an optimal control problem that can be solved using Pontryagin's Maximum Principle. We compare this theoretical gold standard with different possible implementations of growth control in bacterial cells. We find that simple control strategies enabling growth-rate maximization at steady state are suboptimal for transitions from one growth regime to another, for example when shifting bacterial cells to a medium supporting a higher growth rate. A near-optimal control strategy in dynamical conditions is shown to require information on several, rather than a single physiological variable. Interestingly, this strategy has structural analogies with the regulation of ribosomal protein synthesis by ppGpp in the enterobacterium Escherichia coli. It involves sensing a mismatch between precursor and ribosome concentrations, as well as the adjustment of ribosome synthesis in a switch-like manner. Our results show how the capability of regulatory systems to integrate information about several physiological variables is critical for optimizing growth in a changing environment.

  12. Retinol-binding protein 4 and its membrane receptor STRA6 control adipogenesis by regulating cellular retinoid homeostasis and retinoic acid receptor α activity.

    Science.gov (United States)

    Muenzner, Matthias; Tuvia, Neta; Deutschmann, Claudia; Witte, Nicole; Tolkachov, Alexander; Valai, Atijeh; Henze, Andrea; Sander, Leif E; Raila, Jens; Schupp, Michael

    2013-10-01

    Retinoids are vitamin A (retinol) derivatives and complex regulators of adipogenesis by activating specific nuclear receptors, including the retinoic acid receptor (RAR) and retinoid X receptor (RXR). Circulating retinol-binding protein 4 (RBP4) and its membrane receptor STRA6 coordinate cellular retinol uptake. It is unknown whether retinol levels and the activity of RAR and RXR in adipocyte precursors are linked via RBP4/STRA6. Here, we show that STRA6 is expressed in precursor cells and, dictated by the apo- and holo-RBP4 isoforms, mediates bidirectional retinol transport that controls RARα activity and subsequent adipocyte differentiation. Mobilization of retinoid stores in mice by inducing RBP4 secretion from the liver activated RARα signaling in the precursor cell containing the stromal-vascular fraction of adipose tissue. Retinol-loaded holo-RBP4 blocked adipocyte differentiation of cultured precursors by activating RARα. Remarkably, retinol-free apo-RBP4 triggered retinol efflux that reduced cellular retinoids, RARα activity, and target gene expression and enhanced adipogenesis synergistically with ectopic STRA6. Thus, STRA6 in adipocyte precursor cells links nuclear RARα activity to the circulating RBP4 isoforms, whose ratio in obese mice was shifted toward limiting the adipogenic potential of their precursors. This novel cross talk identifies a retinol-dependent metabolic function of RBP4 that may have important implications for the treatment of obesity.

  13. Cellular localization of adenine receptors in the rat kidney and their functional significance in the inner medullary collecting duct.

    Science.gov (United States)

    Kishore, Bellamkonda K; Zhang, Yue; Gevorgyan, Haykanush; Kohan, Donald E; Schiedel, Anke C; Müller, Christa E; Peti-Peterdi, János

    2013-11-01

    The Gi-coupled adenine receptor (AdeR) binds adenine with high affinity and potentially reduces cellular cAMP levels. Since cAMP is an important second messenger in the renal transport of water and solutes, we localized AdeR in the rat kidney. Real-time RT-PCR showed higher relative expression of AdeR mRNA in the cortex and outer medulla compared with the inner medulla. Immunoblots using a peptide-derived and affinity-purified rabbit polyclonal antibody specific for an 18-amino acid COOH-terminal sequence of rat AdeR, which we generated, detected two bands between ∼30 and 40 kDa (molecular mass of native protein: 37 kDa) in the cortex, outer medulla, and inner medulla. These bands were ablated by preadsorption of the antibody with the immunizing peptide. Immunofluorescence labeling showed expression of AdeR protein in all regions of the kidney. Immunoperoxidase revealed strong labeling of AdeR protein in the cortical vasculature, including the glomerular arterioles, and less intense labeling in the cells of the collecting duct system. Confocal immunofluorescence imaging colocalized AdeR with aquaporin-2 protein to the apical plasma membrane in the collecting duct. Functionally, adenine (10 μM) significantly decreased (P < 0.01) 1-deamino-8-d-arginine vasopressin (10 nM)-induced cAMP production in ex vivo preparations of inner medullary collecting ducts, which was reversed by PSB-08162 (20 μM, P < 0.01), a selective antagonist of AdeR. Thus, we demonstrated the expression of AdeR in the renal vasculature and collecting ducts and its functional relevance. This study may open a new avenue for the exploration of autocrine/paracrine regulation of renal vascular and tubular functions by the nucleobase adenine in health and disease.

  14. The cellular chaperone hsc70 is specifically recruited to reovirus viral factories independently of its chaperone function.

    Science.gov (United States)

    Kaufer, Susanne; Coffey, Caroline M; Parker, John S L

    2012-01-01

    Mammalian orthoreoviruses replicate and assemble in the cytosol of infected cells. A viral nonstructural protein, μNS, forms large inclusion-like structures called viral factories (VFs) in which assembling viral particles can be identified. Here we examined the localization of the cellular chaperone Hsc70 and found that it colocalizes with VFs in infected cells and also with viral factory-like structures (VFLs) formed by ectopically expressed μNS. Small interfering RNA (siRNA)-mediated knockdown of Hsc70 did not affect the formation or maintenance of VFLs. We further showed that dominant negative mutants of Hsc70 were also recruited to VFLs, indicating that Hsc70 recruitment to VFLs is independent of the chaperone function. In support of this finding, μNS was immunoprecipitated with wild-type Hsc70, with a dominant negative mutant of Hsc70, and with the minimal substrate-binding site of Hsc70 (amino acids 395 to 540). We identified a minimal region of μNS between amino acids 222 and 271 that was sufficient for the interaction with Hsc70. This region of μNS has not been assigned any function previously. However, neither point mutants with alterations in this region nor the complete deletion of this domain abrogated the μNS-Hsc70 interaction, indicating that a second portion of μNS also interacts with Hsc70. Taken together, these findings suggest a specific chaperone function for Hsc70 within viral factories, the sites of reovirus replication and assembly in cells.

  15. Solid lipid nanoparticles for oral drug delivery: chitosan coating improves stability, controlled delivery, mucoadhesion and cellular uptake.

    Science.gov (United States)

    Luo, Yangchao; Teng, Zi; Li, Ying; Wang, Qin

    2015-05-20

    The poor stability of solid lipid nanoparticles (SLN) under acidic condition resulted in large aggregation in gastric environment, limiting their application as oral delivery systems. In this study, a series of SLN was prepared to investigate the effects of surfactant/cosurfactant and chitosan coating on their physicochemical properties as well as cellular uptake. SLN was prepared from Compritol 888 ATO using a low-energy method combining the solvent-diffusion and hot homogenization technique. Poloxamer 188 and polyethylene glycol (PEG) were effective emulsifiers to produce SLN with better physicochemical properties than SLN control. Chitosan-coated SLN exhibited the best stability under acidic condition by forming a thick layer around the lipid core, as clearly observed by transmission electron microscope. The intermolecular interactions in different formulations were monitored by Fourier transform infrared spectroscopy. Chitosan coating also significantly improved the mucoadhesive property of SLN as determined by Quartz Crystal Microbalance. In vitro drug delivery assays, cytotoxicity, and cellular uptake of SLN were studied by incorporating coumarin 6 as a fluorescence probe. Overall, chitosan-coated SLN was superior to other formulations and held promising features for its application as a potential oral drug delivery system for hydrophobic drugs.

  16. New Concepts and Theories For Intelligent Control of Cellular Manufacturing Systems

    DEFF Research Database (Denmark)

    Langer, Gilad

    1996-01-01

    This paper will present some new theories such as biological manufacturing system, the fractal factory theory, holonic manufacturing systems, agile manufacturing, object orientation, multi-agent theory, artificial intelligence, and artificial life in the context of manufacturing systems....... The paper tries to encapsulate the main area of my Ph.D. thesis research which will evolve around the idea of integrating intelligent elements into the control systems of the manufacturing systems. Furthermore it intends to show how the curriculum and discussions of the IPS Ph.D. course will and have...... contributed to my research. The research will concentrate on integration of manufacturing units by use of intelligent control mechanisms, information technology and the material handling as the key integrators....

  17. New Concepts and Theories For Intelligent Control of Cellular Manufacturing Systems

    DEFF Research Database (Denmark)

    Langer, Gilad

    1996-01-01

    . The objective of the paper is to show how these theories can contribute to develop the new concepts that are required for controlling the manufacturing systems of the future. Thereafter it will present the potential for improvement of the manufacturing system by introduction and implementation of these theories......This paper will present some new theories such as biological manufacturing system, the fractal factory theory, holonic manufacturing systems, agile manufacturing, object orientation, multi-agent theory, artificial intelligence, and artificial life in the context of manufacturing systems...... contributed to my research. The research will concentrate on integration of manufacturing units by use of intelligent control mechanisms, information technology and the material handling as the key integrators....

  18. Cellular nucleic acid binding protein binds G-rich single-stranded nucleic acids and may function as a nucleic acid chaperone.

    Science.gov (United States)

    Armas, Pablo; Nasif, Sofía; Calcaterra, Nora B

    2008-02-15

    Cellular nucleic acid binding protein (CNBP) is a small single-stranded nucleic acid binding protein made of seven Zn knuckles and an Arg-Gly rich box. CNBP is strikingly conserved among vertebrates and was reported to play broad-spectrum functions in eukaryotic cells biology. Neither its biological function nor its mechanisms of action were elucidated yet. The main goal of this work was to gain further insights into the CNBP biochemical and molecular features. We studied Bufo arenarum CNBP (bCNBP) binding to single-stranded nucleic acid probes representing the main reported CNBP putative targets. We report that, although bCNBP is able to bind RNA and single-stranded DNA (ssDNA) probes in vitro, it binds RNA as a preformed dimer whereas both monomer and dimer are able to bind to ssDNA. A systematic analysis of variant probes shows that the preferred bCNBP targets contain unpaired guanosine-rich stretches. These data expand the knowledge about CNBP binding stoichiometry and begins to dissect the main features of CNBP nucleic acid targets. Besides, we show that bCNBP presents a highly disordered predicted structure and promotes the annealing and melting of nucleic acids in vitro. These features are typical of proteins that function as nucleic acid chaperones. Based on these data, we propose that CNBP may function as a nucleic acid chaperone through binding, remodeling, and stabilizing nucleic acids secondary structures. This novel CNBP biochemical activity broadens the field of study about its biological function and may be the basis to understand the diverse ways in which CNBP controls gene expression.

  19. Optically controlled reconfigurable antenna for 5G future broadband cellular communication networks

    DEFF Research Database (Denmark)

    da Costa, Igor; Cerqueira Sodre Jr., Arismar; Gustavo da Silva, Luis

    to higher frequency solutions, such as E-and W-band solutions. We present two key elements for the project: a broadband horn antenna for millimetre-wave and an optically controlled reconfigurable antenna, which can adapt its frequency response and radiation pattern by using photonics technology....... Experimental results on 16-QAM and 32-QAM wireless transmission supported by photonic downconversion are successfully reported by using the developed antennas under 78 dB link budget requirement....

  20. Community control in cellular protein production: consequences for amino acid starvation.

    Science.gov (United States)

    Heldt, Frank S; Brackley, Chris A; Grebogi, Celso; Thiel, Marco

    2015-12-13

    Deprivation of essential nutrients can have stark consequences for many processes in a cell. We consider amino acid starvation, which can result in bottlenecks in mRNA translation when ribosomes stall due to lack of resources, i.e. tRNAs charged with the missing amino acid. Recent experiments also show less obvious effects such as increased charging of other (non-starved) tRNA species and selective charging of isoaccepting tRNAs. We present a mechanism which accounts for these observations and shows that production of some proteins can actually increase under starvation. One might assume that such responses could only be a result of sophisticated control pathways, but here we show that these effects can occur naturally due to changes in the supply and demand for different resources, and that control can be accomplished through selective use of rare codons. We develop a model for translation which includes the dynamics of the charging and use of aminoacylated tRNAs, explicitly taking into account the effect of specific codon sequences. This constitutes a new control mechanism in gene regulation which emerges at the community level, i.e. via resources used by all ribosomes.

  1. Longitudinal structural, functional, and cellular myocardial alterations with chronic centrifugal continuous-flow left ventricular assist device support.

    Science.gov (United States)

    Muthiah, Kavitha; Humphreys, David T; Robson, Desiree; Dhital, Kumud; Spratt, Phillip; Jansz, Paul; Macdonald, Peter S; Hayward, Christopher S

    2017-07-01

    Left ventricular assist device (LVAD) support triggers adaptations within failing hearts. The HeartWare (HeartWare International, Inc., Framingham, MA) LVAD exhibits different flow profiles and afterload dependence compared with previous-generation devices, which may alter remodelling patterns. We sought to characterize myocardial adaptation to third-generation centrifugal-flow LVADs at a functional, hemodynamic, and structural level in addition to profiling transcriptomal changes using next-generation sequencing platforms. We studied 37 patients supported with the HeartWare device with paired measurements of invasive hemodynamics, serial longitudinal left ventricular (LV) and right ventricular (RV) 3-dimensional echocardiography, and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) measurements. Paired samples for comparison of histologic myocardial cellular size and transcriptomal profiling were performed on specimens taken at pump implant and transplantation. The mean support duration was 280 ± 163 days. Mechanical unloading after HeartWare support resulted in reduced filling pressures (mean pulmonary capillary wedge pressure 27.1 ± 6.6 to 14.8 ± 5.1 mm Hg, p hypertrophy, and an improvement in LV and RV ejection fractions. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  2. Gall-forming root-knot nematodes hijack key plant cellular functions to induce multinucleate and hypertrophied feeding cells.

    Science.gov (United States)

    Favery, Bruno; Quentin, Michaël; Jaubert-Possamai, Stéphanie; Abad, Pierre

    2016-01-01

    Among plant-parasitic nematodes, the root-knot nematodes (RKNs) of the Meloidogyne spp. are the most economically important genus. RKN are root parasitic worms able to infect nearly all crop species and have a wide geographic distribution. During infection, RKNs establish and maintain an intimate relationship with the host plant. This includes the creation of a specialized nutritional structure composed of multinucleate and hypertrophied giant cells, which result from the redifferentiation of vascular root cells. Giant cells constitute the sole source of nutrients for the nematode and are essential for growth and reproduction. Hyperplasia of surrounding root cells leads to the formation of the gall or root-knot, an easily recognized symptom of plant infection by RKNs. Secreted effectors produced in nematode salivary glands and injected into plant cells through a specialized feeding structure called the stylet play a critical role in the formation of giant cells. Here, we describe the complex interactions between RKNs and their host plants. We highlight progress in understanding host plant responses, focusing on how RKNs manipulate key plant processes and functions, including cell cycle, defence, hormones, cellular scaffold, metabolism and transport.

  3. Investigation of potential effects of cellular phones on human auditory function by means of distortion product otoacoustic emissions.

    Science.gov (United States)

    Janssen, Thomas; Boege, Paul; von Mikusch-Buchberg, Jutta; Raczek, Johannes

    2005-03-01

    Outer hair cells (OHC) are thought to act like piezoelectric transducers that amplify low sounds and hence enable the ear's exquisite sensitivity. Distortion product otoacoustic emissions (DPOAE) reflect OHC function. The present study investigated potential effects of electromagnetic fields (EMF) of GSM (Global System for Mobile Communication) cellular phones on OHCs by means of DPOAEs. DPOAE measurements were performed during exposure, i.e., between consecutive GSM signal pulses, and during sham exposure (no EMF) in 28 normally hearing subjects at tone frequencies around 4 kHz. For a reliable DPOAE measurement, a 900-MHz GSM-like signal was used where transmission pause was increased from 4.034 ms (GSM standard) to 24.204 ms. Peak transmitter power was set to 20 W, corresponding to a specific absorption rate (SAR) of 0.1 W/kg. No significant change in the DPOAE level in response to the EMF exposure was found. However, when undesired side effects on DPOAEs were compensated, in some subjects an extremely small EMF-exposure-correlated change in the DPOAE level (< 1 dB) was observed. In view of the very large dynamic range of hearing in humans (120 dB), it is suggested that this observation is physiologically irrelevant.

  4. Generating multiplex gradients of biomolecules for controlling cellular adhesion in parallel microfluidic channels.

    Science.gov (United States)

    Didar, Tohid Fatanat; Tabrizian, Maryam

    2012-11-07

    Here we present a microfluidic platform to generate multiplex gradients of biomolecules within parallel microfluidic channels, in which a range of multiplex concentration gradients with different profile shapes are simultaneously produced. Nonlinear polynomial gradients were also generated using this device. The gradient generation principle is based on implementing parrallel channels with each providing a different hydrodynamic resistance. The generated biomolecule gradients were then covalently functionalized onto the microchannel surfaces. Surface gradients along the channel width were a result of covalent attachments of biomolecules to the surface, which remained functional under high shear stresses (50 dyn/cm(2)). An IgG antibody conjugated to three different fluorescence dyes (FITC, Cy5 and Cy3) was used to demonstrate the resulting multiplex concentration gradients of biomolecules. The device enabled generation of gradients with up to three different biomolecules in each channel with varying concentration profiles. We were also able to produce 2-dimensional gradients in which biomolecules were distributed along the length and width of the channel. To demonstrate the applicability of the developed design, three different multiplex concentration gradients of REDV and KRSR peptides were patterned along the width of three parallel channels and adhesion of primary human umbilical vein endothelial cell (HUVEC) in each channel was subsequently investigated using a single chip.

  5. The deiodinases and the control of intracellular thyroid hormone signaling during cellular differentiation☆

    Science.gov (United States)

    Dentice, Monica; Marsili, Alessandro; Zavacki, AnnMarie; Larsen, P. Reed; Salvatore, Domenico

    2013-01-01

    Background Thyroid hormone influences gene expression in virtually all vertebrates. Its action is initiated by the activation of T4 to T3, an outer ring deiodination reaction that is catalyzed by the type 1 or the type 2 iodothyronine selenodeiodinases (D1 or D2). Inactivation of T4 and T3 occurs via inner ring deiodination catalyzed by the type 3 iodothyronine selenodeiodinases (D3). The T4 concentration is generally quite stable in human plasma, with T3 levels also remaining constant. Deiodinase actions are tightly regulated in both pre- and post-natal life when they are required to make local adjustments of intracellular T3 concentrations in a precise spatio- and temporal manner. Although all the signals governing the dynamic expression of deiodinases in specific cell types are not known, many important regulatory factors have been deciphered. Scope of review This review provides striking examples from the recent literature illustrating how the expression of D2 and D3 is finely tuned during maturation of different organs, and how their action play a critical role in different settings to control intracellular T3 availability. Major conclusions Emerging evidence indicates that in various cell contexts, D2 and D3 are expressed in a dynamic balance, in which the expression of one enzyme is coordinately regulated with that of the other to tightly control intracellular T3 levels commensurate with cell requirements at that time. General significance Deiodinases control TH action in a precise spatio-temporal fashion thereby providing a novel mechanism for the local paracrine and autocrine regulation of TH action. This remarkable tissue-specific regulation of intracellular thyroid status remains hidden due to the maintenance of constant circulating TH concentrations by the hypothalamic–pituitary–thyroid axis. This article is part of a Special Issue entitled Thyroid hormone signalling. PMID:22634734

  6. Temporal and fluoride control of secondary metabolism regulates cellular organofluorine biosynthesis.

    Science.gov (United States)

    Walker, Mark C; Wen, Miao; Weeks, Amy M; Chang, Michelle C Y

    2012-09-21

    Elucidating mechanisms of natural organofluorine biosynthesis is essential for a basic understanding of fluorine biochemistry in living systems as well as for expanding biological methods for fluorine incorporation into small molecules of interest. To meet this goal we have combined massively parallel sequencing technologies, genetic knockout, and in vitro biochemical approaches to investigate the fluoride response of the only known genetic host of an organofluorine-producing pathway, Streptomyces cattleya. Interestingly, we have discovered that the major mode of S. cattleya's resistance to the fluorinated toxin it produces, fluoroacetate, may be due to temporal control of production rather than the ability of the host's metabolic machinery to discriminate between fluorinated and non-fluorinated molecules. Indeed, neither the acetate kinase/phosphotransacetylase acetate assimilation pathway nor the TCA cycle enzymes (citrate synthase and aconitase) exclude fluorinated substrates based on in vitro biochemical characterization. Furthermore, disruption of the fluoroacetate resistance gene encoding a fluoroacetyl-CoA thioesterase (FlK) does not appear to lead to an observable growth defect related to organofluorine production. By showing that a switch in central metabolism can mediate and control molecular fluorine incorporation, our findings reveal a new potential strategy toward diversifying simple fluorinated building blocks into more complex products.

  7. Understanding Control Function and Failure From a Process Perspective

    DEFF Research Database (Denmark)

    Heussen, Kai; Lind, Morten

    2012-01-01

    In control design, fault-identification and fault tolerant control, the controlled process is usually perceived as a dynamical process, captured in a mathematical model. The design of a control system for a complex process, however, begins typically long before these mathematical models become...... behaviour and its function. This paper presents a formal methodology for the qualitative representation of control functions in relation to their process context. Different types of relevant process and control abstractions are introduced and their application to formal analysis of control failure modes...... relevant and available. To consider the role of control functions in process design, a good qualitative understanding of the process as well as of control functions is required. As the purpose of a control function is closely tied to the process functions, its failure has a direct effects on the process...

  8. Shroom3 functions downstream of planar cell polarity to regulate myosin II distribution and cellular organization during neural tube closure

    Directory of Open Access Journals (Sweden)

    Erica M. McGreevy

    2015-01-01

    Full Text Available Neural tube closure is a critical developmental event that relies on actomyosin contractility to facilitate specific processes such as apical constriction, tissue bending, and directional cell rearrangements. These complicated processes require the coordinated activities of Rho-Kinase (Rock, to regulate cytoskeletal dynamics and actomyosin contractility, and the Planar Cell Polarity (PCP pathway, to direct the polarized cellular behaviors that drive convergent extension (CE movements. Here we investigate the role of Shroom3 as a direct linker between PCP and actomyosin contractility during mouse neural tube morphogenesis. In embryos, simultaneous depletion of Shroom3 and the PCP components Vangl2 or Wnt5a results in an increased liability to NTDs and CE failure. We further show that these pathways intersect at Dishevelled, as Shroom3 and Dishevelled 2 co-distribute and form a physical complex in cells. We observed that multiple components of the Shroom3 pathway are planar polarized along mediolateral cell junctions in the neural plate of E8.5 embryos in a Shroom3 and PCP-dependent manner. Finally, we demonstrate that Shroom3 mutant embryos exhibit defects in planar cell arrangement during neural tube closure, suggesting a role for Shroom3 activity in CE. These findings support a model in which the Shroom3 and PCP pathways interact to control CE and polarized bending of the neural plate and provide a clear illustration of the complex genetic basis of NTDs.

  9. Shroom3 functions downstream of planar cell polarity to regulate myosin II distribution and cellular organization during neural tube closure.

    Science.gov (United States)

    McGreevy, Erica M; Vijayraghavan, Deepthi; Davidson, Lance A; Hildebrand, Jeffrey D

    2015-01-16

    Neural tube closure is a critical developmental event that relies on actomyosin contractility to facilitate specific processes such as apical constriction, tissue bending, and directional cell rearrangements. These complicated processes require the coordinated activities of Rho-Kinase (Rock), to regulate cytoskeletal dynamics and actomyosin contractility, and the Planar Cell Polarity (PCP) pathway, to direct the polarized cellular behaviors that drive convergent extension (CE) movements. Here we investigate the role of Shroom3 as a direct linker between PCP and actomyosin contractility during mouse neural tube morphogenesis. In embryos, simultaneous depletion of Shroom3 and the PCP components Vangl2 or Wnt5a results in an increased liability to NTDs and CE failure. We further show that these pathways intersect at Dishevelled, as Shroom3 and Dishevelled 2 co-distribute and form a physical complex in cells. We observed that multiple components of the Shroom3 pathway are planar polarized along mediolateral cell junctions in the neural plate of E8.5 embryos in a Shroom3 and PCP-dependent manner. Finally, we demonstrate that Shroom3 mutant embryos exhibit defects in planar cell arrangement during neural tube closure, suggesting a role for Shroom3 activity in CE. These findings support a model in which the Shroom3 and PCP pathways interact to control CE and polarized bending of the neural plate and provide a clear illustration of the complex genetic basis of NTDs.

  10. Tailoring the ligand shell for the control of cellular uptake and optical properties of nanocrystals

    Directory of Open Access Journals (Sweden)

    Johannes Ostermann

    2015-01-01

    Full Text Available In this short review, the main challenges in the use of hydrophobic nanoparticles in biomedical application are addressed. It is shown how to overcome the different issues by the use of a polymeric encapsulation system, based on an amphiphilic polyisoprene-block-poly(ethylene glycol diblock copolymer. On the basis of this simple molecule, the development of a versatile and powerful phase transfer strategy is summarized, focusing on the main advantages like the adjustable size, the retained properties, the excellent shielding and the diverse functionalization properties of the encapsulated nanoparticles. Finally, the extraordinary properties of these encapsulated nanoparticles in terms of toxicity and specificity in a broad in vitro test is demonstrated.

  11. Specific Human and Candida Cellular Interactions Lead to Controlled or Persistent Infection Outcomes during Granuloma-Like Formation.

    Science.gov (United States)

    Misme-Aucouturier, Barbara; Albassier, Marjorie; Alvarez-Rueda, Nidia; Le Pape, Patrice

    2017-01-01

    A delayed type of multicellular process could be crucial during chronic candidiasis in determining the course of infection. This reaction, consisting of organized immune cells surrounding the pathogen, initiates an inflammatory response to avoid fungal dissemination. The goal of the present study was to examine, at an in vitro cellular scale, Candida and human immune cell interaction dynamics during a long-term period. By challenging human peripheral blood immune cells from 10 healthy donors with 32 Candida albicans and non-albicans (C. glabrata, C. tropicalis, C. parapsilosis, C. dubliniensis, C. lusitaniae, C. krusei, and C. kefyr) clinical isolates, we showed that Candida spp. induced the formation of granuloma-like structures within 6 days after challenge, but their sizes and the respective fungal burdens differed according to the Candida species. These two parameters are positively correlated. Phenotypic characteristics, such as hypha formation and higher axenic growth rate, seem to contribute to yeast persistence within granuloma-like structures. We showed an interindividual variability of the human response against Candida spp. Higher proportions of neutrophils and elevated CD4(+)/CD8(+) T cell ratios during the first days after challenge were correlated with early production of gamma interferon (IFN-γ) and associated with controlled infection. In contrast, the persistence of Candida could result from upregulation of proinflammatory cytokines such as interleukin-6 (IL-6), IFN-γ, and tumor necrosis factor alpha (TNF-α) and a poor anti-inflammatory negative feedback (IL-10). Importantly, regulatory subsets of NK cells and CD4(lo) CD8(hi) doubly positive (DP) lymphocytes at late stage infiltrate granuloma-like structures and could correlate with the IL-10 and TNF-α production. These data offer a base frame to explain cellular events that guide infection control or fungal persistence. Copyright © 2016 Misme-Aucouturier et al.

  12. Autonomic and endocrine control of cardiovascular function

    Institute of Scientific and Technical Information of China (English)

    Richard; Gordan; Judith; K; Gwathmey; Lai-Hua; Xie

    2015-01-01

    The function of the heart is to contract and pump oxygenated blood to the body and deoxygenated blood to the lungs.To achieve this goal,a normal human heart must beat regularly and continuously for one’s entire life.Heartbeats originate from the rhythmic pacing discharge from the sinoatrial(SA) node within the heart itself.In the absence of extrinsic neural or hormonal influences,the SA node pacing rate would be about 100 beats per minute.Heart rate and cardiac output,however,must vary in response to the needs of the body’s cells for oxygen and nutrients under varying conditions.In order to respond rapidly to the changing requirements of the body’s tissues,the heart rate and contractility are regulated by the nervous system,hormones,and other factors.Here we review how the cardiovascular system is controlled and influenced by not only a unique intrinsic system,but is also heavily influenced by the autonomic nervous system as well as the endocrine system.

  13. Small regulatory RNAs control the multi-cellular adhesive lifestyle of Escherichia coli

    DEFF Research Database (Denmark)

    Jørgensen, Mikkel Girke; Nielsen, Jesper Sejrup; Boysen, Anders;

    2012-01-01

    . Our demonstration that basal expression of each of the three RNA species is sufficient to downregulate CsgD synthesis and prevent curli formation indicates that all play a prominent role in the curli regulatory network. Our findings provide the first clue as to how the Rcs signalling pathway...... and adhesive state that enables biofilm formation on surfaces. For this, the bacterium needs to reprogramme its gene expression, and in many E. coli and Salmonella strains the lifestyle shift relies on control cascades that inhibit flagellar expression and activate the synthesis of curli, extracellular...... adhesive fibres important for co-aggregation of cells and adhesion to biotic and abiotic surfaces. By combining bioinformatics, genetic and biochemical analysis we identified three small RNAs that act by an antisense mechanism to downregulate translation of CsgD, the master regulator of curli synthesis...

  14. Depolymerizing kinesins Kip3 and MCAK shape cellular microtubule architecture by differential control of catastrophe.

    Science.gov (United States)

    Gardner, Melissa K; Zanic, Marija; Gell, Christopher; Bormuth, Volker; Howard, Jonathon

    2011-11-23

    Microtubules are dynamic filaments whose ends alternate between periods of slow growth and rapid shortening as they explore intracellular space and move organelles. A key question is how regulatory proteins modulate catastrophe, the conversion from growth to shortening. To study this process, we reconstituted microtubule dynamics in the absence and presence of the kinesin-8 Kip3 and the kinesin-13 MCAK. Surprisingly, we found that, even in the absence of the kinesins, the microtubule catastrophe frequency depends on the age of the microtubule, indicating that catastrophe is a multistep process. Kip3 slowed microtubule growth in a length-dependent manner and increased the rate of aging. In contrast, MCAK eliminated the aging process. Thus, both kinesins are catastrophe factors; Kip3 mediates fine control of microtubule length by narrowing the distribution of maximum lengths prior to catastrophe, whereas MCAK promotes rapid restructuring of the microtubule cytoskeleton by making catastrophe a first-order random process.

  15. Cognitive memory: cellular and network machineries and their top-down control.

    Science.gov (United States)

    Miyashita, Yasushi

    2004-10-15

    A brain-wide distributed network orchestrates cognitive memorizing and remembering of explicit memory (i.e., memory of facts and events). The network was initially identified in humans and is being systematically investigated in molecular/genetic, single-unit, lesion, and imaging studies in animals. The types of memory identified in humans are extended into animals as episodic-like (event) memory or semantic-like (fact) memory. The unique configurational association between environmental stimuli and behavioral context, which is likely the basis of episodic-like memory, depends on neural circuits in the medial temporal lobe, whereas memory traces representing repeated associations, which is likely the basis of semantic-like memory, are consolidated in the domain-specific regions in the temporal cortex. These regions are reactivated during remembering and contribute to the contents of a memory. Two types of retrieval signal reach the cortical representations. One runs from the frontal cortex for active (or effortful) retrieval (top-down signal), and the other spreads backward from the medial temporal lobe for automatic retrieval. By sending the top-down signal to the temporal cortex, frontal regions manipulate and organize to-be-remembered information, devise strategies for retrieval, and also monitor the outcome, with dissociated frontal regions making functionally separate contributions. The challenge is to understand the hierarchical interactions between these multiple cortical areas, not only with a correlational analysis but also with an interventional study demonstrating the causal necessity and the direction of the causality.

  16. Mitochondrial respiration controls lysosomal function during inflammatory T cell responses

    Science.gov (United States)

    Baixauli, Francesc; Acín-Pérez, Rebeca; Villarroya-Beltrí, Carolina; Mazzeo, Carla; Nuñez-Andrade, Norman; Gabandé-Rodriguez, Enrique; Dolores Ledesma, Maria; Blázquez, Alberto; Martin, Miguel Angel; Falcón-Pérez, Juan Manuel; Redondo, Juan Miguel; Enríquez, Jose Antonio; Mittelbrunn, Maria

    2016-01-01

    Summary The endolysosomal system is critical for the maintenance of cellular homeostasis. However, how endolysosomal compartment is regulated by mitochondrial function is largely unknown. We have generated a mouse model with defective mitochondrial function in CD4+ T lymphocytes by genetic deletion of the mitochondrial transcription factor A (Tfam). Mitochondrial respiration-deficiency impairs lysosome function, promotes p62 and sphingomyelin accumulation and disrupts endolysosomal trafficking pathways and autophagy, thus linking a primary mitochondrial dysfunction to a lysosomal storage disorder. The impaired lysosome function in Tfam-deficient cells subverts T cell differentiation toward pro-inflammatory subsets and exacerbates the in vivo inflammatory response. Restoration of NAD+ levels improves lysosome function and corrects the inflammatory defects in Tfam-deficient T cells. Our results uncover a mechanism by which mitochondria regulate lysosome function to preserve T cell differentiation and effector functions, and identify novel strategies for intervention in mitochondrial-related diseases. PMID:26299452

  17. Long-time tails of the velocity autocorrelation function in 2D and 3D lattice gas cellular automata: a test of mode-coupling theory

    NARCIS (Netherlands)

    Hoef, M.A. van der; Frenkel, D.

    1990-01-01

    We report simulations of the velocity autocorrelation function (VACF) of a tagged particle in two- and three-dimensional lattice-gas cellular automata, using a new technique that is about a million times more efficient than the conventional techniques. The simulations clearly show the algebraic t-D/

  18. Mesenchymal progenitor cells differentiate into an endothelial phenotype, enhance vascular density and improve heart function in a rat cellular cardiomyoplasty model

    Institute of Scientific and Technical Information of China (English)

    SDAVANI; NMERSIN; BROYER; BKANTELIP; JPKANTELIP

    2004-01-01

    AIM: Cellular cardiomyoplasty is promising for improving postinfarcted cardiac function. Over the past decade, a variety of cell types have been proposed including mononuclear bone marrow cells. The latter contains different lineages including mesenchymal stem cells (MSCs). The aim of this study was to analyse the differentiation pathways of engrafted syngenic mesenchymal progenitor cells (MPCs) obtained in culture from bone marrow

  19. Effect of psychological intervention in the form of relaxation and guided imagery on cellular immune function in normal healthy subjects. An overview

    DEFF Research Database (Denmark)

    Zachariae, R; Kristensen, J S; Hokland, P;

    1991-01-01

    The present study measured the effects of relaxation and guided imagery on cellular immune function. During a period of 10 days 10 healthy subjects were given one 1-hour relaxation procedure and one combined relaxation and guided imagery procedure, instructing the subjects to imagine their immune...

  20. Working memory dysfunction associated with brain functional deficits and cellular metabolic changes in patients with generalized anxiety disorder.

    Science.gov (United States)

    Moon, Chung-Man; Sundaram, Thirunavukkarasu; Choi, Nam-Gil; Jeong, Gwang-Woo

    2016-08-30

    Generalized anxiety disorder (GAD) is associated with brain functional and morphological changes in connected with emotional dysregulation and cognitive deficit. This study dealt with the neural functional deficits and metabolic abnormalities in working memory (WM) task with emotion-inducing distractors in patients with GAD. Fourteen patients with GAD and 14 healthy controls underwent functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy ((1)H-MRS) at 3T. In response to the emotional distractors in WM tasks, the patients concurrently showed higher activity in the hippocampus and lower activities in the superior occipital gyrus, superior parietal gyrus, dorsolateral prefrontal cortex (DLPFC) and precentral gyrus compared to the controls. MRS revealed significantly lower choline/creatine (Cho/Cr) and choline/N-acetylaspartate (Cho/NAA) ratios in the DLPFC. In particular, the Cho ratios were positively correlated with the brain activities based on blood oxygenation level-dependent signal change in the DLPFC. This study provides the first evidence for the association between the metabolic alterations and functional deficit in WM processing with emotion-inducing distractors in GAD. These findings will be helpful to understand the neural dysfunction in connection with WM impairment in GAD.

  1. Rhizobial exopolysaccharides: genetic control and symbiotic functions

    Directory of Open Access Journals (Sweden)

    Mazur Andrzej

    2006-02-01

    Full Text Available Abstract Specific complex interactions between soil bacteria belonging to Rhizobium, Sinorhizobium, Mesorhizobium, Phylorhizobium, Bradyrhizobium and Azorhizobium commonly known as rhizobia, and their host leguminous plants result in development of root nodules. Nodules are new organs that consist mainly of plant cells infected with bacteroids that provide the host plant with fixed nitrogen. Proper nodule development requires the synthesis and perception of signal molecules such as lipochitooligosaccharides, called Nod factors that are important for induction of nodule development. Bacterial surface polysaccharides are also crucial for establishment of successful symbiosis with legumes. Sugar polymers of rhizobia are composed of a number of different polysaccharides, such as lipopolysaccharides (LPS, capsular polysaccharides (CPS or K-antigens, neutral β-1, 2-glucans and acidic extracellular polysaccharides (EPS. Despite extensive research, the molecular function of the surface polysaccharides in symbiosis remains unclear. This review focuses on exopolysaccharides that are especially important for the invasion that leads to formation of indetermined (with persistent meristem type of nodules on legumes such as clover, vetch, peas or alfalfa. The significance of EPS synthesis in symbiotic interactions of Rhizobium leguminosarum with clover is especially noticed. Accumulating data suggest that exopolysaccharides may be involved in invasion and nodule development, bacterial release from infection threads, bacteroid development, suppression of plant defense response and protection against plant antimicrobial compounds. Rhizobial exopolysaccharides are species-specific heteropolysaccharide polymers composed of common sugars that are substituted with non-carbohydrate residues. Synthesis of repeating units of exopolysaccharide, their modification, polymerization and export to the cell surface is controlled by clusters of genes, named exo/exs, exp or

  2. Telmisartan enhances mitochondrial activity and alters cellular functions in human coronary artery endothelial cells via AMP-activated protein kinase pathway.

    Science.gov (United States)

    Kurokawa, Hirofumi; Sugiyama, Seigo; Nozaki, Toshimitsu; Sugamura, Koichi; Toyama, Kensuke; Matsubara, Junichi; Fujisue, Koichiro; Ohba, Keisuke; Maeda, Hirofumi; Konishi, Masaaki; Akiyama, Eiichi; Sumida, Hitoshi; Izumiya, Yasuhiro; Yasuda, Osamu; Kim-Mitsuyama, Shokei; Ogawa, Hisao

    2015-04-01

    Mitochondrial dysfunction plays an important role in cellular senescence and impaired function of vascular endothelium, resulted in cardiovascular diseases. Telmisartan is a unique angiotensin II type I receptor blocker that has been shown to prevent cardiovascular events in high risk patients. AMP-activated protein kinase (AMPK) plays a critical role in mitochondrial biogenesis and endothelial function. This study assessed whether telmisartan enhances mitochondrial function and alters cellular functions via AMPK in human coronary artery endothelial cells (HCAECs). In cultured HCAECs, telmisartan significantly enhanced mitochondrial activity assessed by mitochondrial reductase activity and intracellular ATP production and increased the expression of mitochondria related genes. Telmisartan prevented cellular senescence and exhibited the anti-apoptotic and pro-angiogenic properties. The expression of genes related anti-oxidant and pro-angiogenic properties were increased by telmisartan. Telmisartan increased endothelial NO synthase and AMPK phosphorylation. Peroxisome proliferator-activated receptor gamma signaling was not involved in telmisartan-induced improvement of mitochondrial function. All of these effects were abolished by inhibition of AMPK. Telmisartan enhanced mitochondrial activity and exhibited anti-senescence effects and improving endothelial function through AMPK in HCAECs. Telmisartan could provide beneficial effects on vascular diseases via enhancement of mitochondrial activity and modulating endothelial function through AMPK activation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Metabolic Control of Dendritic Cell Activation and Function: Recent Advances and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Bart eEverts

    2014-05-01

    Full Text Available Dendritic cells (DCs are key regulators of both immunity and tolerance by controlling activation and polarization of effector T helper cell and regulatory T cell responses. Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to profound changes in cellular metabolism. Over the past decade there is a growing appreciation that these metabolic changes also underlie the capacity of immune cells to perform particular functions. This has led to the concept that the manipulation of cellular metabolism can be used to shape innate and adaptive immune responses. While most of our understanding in this area has been gained from studies with T cells and macrophages, evidence is emerging that the activation and function of DCs are also dictated by the type of metabolism these cells commit to. We here discuss these new insights and explore whether targeting of metabolic pathways in DCs could hold promise as a novel approach to manipulate the functional properties of DCs for clinical purposes.

  4. Lyapunov function-based control laws for revolute robot arms - Tracking control, robustness, and adaptive control

    Science.gov (United States)

    Wen, John T.; Kreutz-Delgado, Kenneth; Bayard, David S.

    1992-01-01

    A new class of joint level control laws for all-revolute robot arms is introduced. The analysis is similar to a recently proposed energy-like Liapunov function approach, except that the closed-loop potential function is shaped in accordance with the underlying joint space topology. This approach gives way to a much simpler analysis and leads to a new class of control designs which guarantee both global asymptotic stability and local exponential stability. When Coulomb and viscous friction and parameter uncertainty are present as model perturbations, a sliding mode-like modification of the control law results in a robustness-enhancing outer loop. Adaptive control is formulated within the same framework. A linear-in-the-parameters formulation is adopted and globally asymptotically stable adaptive control laws are derived by simply replacing unknown model parameters by their estimates (i.e., certainty equivalence adaptation).

  5. Lyapunov function-based control laws for revolute robot arms - Tracking control, robustness, and adaptive control

    Science.gov (United States)

    Wen, John T.; Kreutz-Delgado, Kenneth; Bayard, David S.

    1992-01-01

    A new class of joint level control laws for all-revolute robot arms is introduced. The analysis is similar to a recently proposed energy-like Liapunov function approach, except that the closed-loop potential function is shaped in accordance with the underlying joint space topology. This approach gives way to a much simpler analysis and leads to a new class of control designs which guarantee both global asymptotic stability and local exponential stability. When Coulomb and viscous friction and parameter uncertainty are present as model perturbations, a sliding mode-like modification of the control law results in a robustness-enhancing outer loop. Adaptive control is formulated within the same framework. A linear-in-the-parameters formulation is adopted and globally asymptotically stable adaptive control laws are derived by simply replacing unknown model parameters by their estimates (i.e., certainty equivalence adaptation).

  6. Key requirements for future control room functionality

    DEFF Research Database (Denmark)

    Tornelli, Carlo; Zuelli, Roberto; Marinelli, Mattia

    2016-01-01

    This internal report provides the key requirements for the future control centres. R8.1 represents the starting point of WP8 activities and wants to achieve a double objective. On the one hand it collects general requirements on future control centres emerging from the general trends in power...... system operation as well as experiences and results from other European projects. On the other hand, it analyses what requirements for future control rooms arise from the ELECTRA proposed control solutions. Hence, different points of view are taken into account. The ELECTRA Use Cases (UCs...... requirements for the future control centres discussed within this report. The analysis of what happened before the European system disturbance occurred on 4th November 2006 and of the existing trends by vendors helped T8.1 in the definition of the requirements for the future control centres. Volunteer...

  7. Machine function based control code algebras

    NARCIS (Netherlands)

    Bergstra, J.A.

    2008-01-01

    Machine functions have been introduced by Earley and Sturgis in [6] in order to provide a mathematical foundation of the use of the T-diagrams proposed by Bratman in [5]. Machine functions describe the operation of a machine at a very abstract level. A theory of hardware and software based on machin

  8. Cellular immune responses to HIV

    Science.gov (United States)

    McMichael, Andrew J.; Rowland-Jones, Sarah L.

    2001-04-01

    The cellular immune response to the human immunodeficiency virus, mediated by T lymphocytes, seems strong but fails to control the infection completely. In most virus infections, T cells either eliminate the virus or suppress it indefinitely as a harmless, persisting infection. But the human immunodeficiency virus undermines this control by infecting key immune cells, thereby impairing the response of both the infected CD4+ T cells and the uninfected CD8+ T cells. The failure of the latter to function efficiently facilitates the escape of virus from immune control and the collapse of the whole immune system.

  9. Identification of Cellular Targets of MicroRNA-181a in HepG2 Cells: A New Approach for Functional Analysis of MicroRNAs.

    Science.gov (United States)

    Tan, Jane Yi Lin; Habib, Nagy A; Chuah, York Wieo; Yau, Yin Hoe; Geifman-Shochat, Susana; Chen, Wei Ning

    2015-01-01

    MicroRNAs (miRNAs) are known to play a part in regulating important cellular processes. They generally perform their regulatory function through their binding with mRNAs, ultimately leading to a repression of target protein expression levels. However, their roles in cellular processes are poorly understood due to the limited understanding of their specific cellular targets. Aberrant levels of miRNAs have been found in hepatocellular carcinoma (HCC) including miR-181a. Using bioinformatics analysis, cyclin-dependent kinase inhibitor 1B (CDKN1β) and transcriptional factor E2F7 were identified as potential targets of miR-181a. Validation analysis using surface plasmon resonance (SPR) showed a positive binding between miR-181a and the 3'UTRs of these two potential mRNA targets. In vivo luciferase assay further confirmed the positive miR-181a:mRNA bindings, where a significant decrease in luciferase activity was detected when HepG2 cells were co-transfected with the 3'UTR-containing reporter plasmids and miR-181a. The potential impact of miR-181a binding to its specific targets on the general cellular behavior was further investigated. Results showed that miR-181a significantly activated the MAPK/JNK pathway which regulates cell proliferation, supporting our recently reported findings. Inhibition of miR-181a, on the other hand, abolished the observed activation. Our findings open up a new approach in designing targeted functional analysis of miRNAs in cellular processes, through the identification of their cellular targets.

  10. Effects of electromagnetic interference on the functional usage of medical equipment by 2G/3G/4G cellular phones: A revie

    Directory of Open Access Journals (Sweden)

    Periyasamy M. Mariappan

    2016-09-01

    Full Text Available There has been an increase in the potential use of wireless devices in healthcare domain for a variety of reasons. The most commonly used device is the cellular phone, which emits strong electromagnetic energy affecting thereby the functionality of the vital medical equipment such as ventilators, ECG monitors, cardiac monitors, and defibrillators. This prompted the healthcare concerns to restrict the use of these phones in the proximity of critical and non-critical care medical equipment. Due to the developments made in the design of medical equipment to comply with the EMC standards, the restriction had been slowly laid off. Still, the researchers are concerned about the electromagnetic interference with medical devices by cellular phones in the healthcare domain and recommend for conducting continuous research to study their interaction with medical equipment. This paper overviews the certain investigations carried out in the recent years to study the electromagnetic interference between medical devices and 2G/3G/4G LTE cellular phones. During the initial development of cellular phones, the 2G cellular phones had caused more interference that affects the function and operation of some medical devices. The possibility of interference from 3G cellular phones with medical devices was considerably lower than the 2G phones, but still exists. Furthermore, almost all of the 4G phones have little to no interference with the medical devices. Currently, with the development of the medical devices industry, the current medical devices are designed to operate safely under any conditions of usage. Finally, a careful analysis would require statistics on the frequency of adverse events across the healthcare system, which apparently do not exist.

  11. HIV-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) -Mediating Antibodies Decline while NK Cell Function Increases during Antiretroviral Therapy (ART).

    Science.gov (United States)

    Jensen, Sanne Skov; Fomsgaard, Anders; Borggren, Marie; Tingstedt, Jeanette Linnea; Gerstoft, Jan; Kronborg, Gitte; Rasmussen, Line Dahlerup; Pedersen, Court; Karlsson, Ingrid

    2015-01-01

    Understanding alterations in HIV-specific immune responses during antiretroviral therapy (ART), such as antibody-dependent cellular cytotoxicity (ADCC), is important in the development of novel strategies to control HIV-1 infection. This study included 53 HIV-1 positive individuals. We evaluated the ability of effector cells and antibodies to mediate ADCC separately and in combination using the ADCC-PanToxiLux assay. The ability of the peripheral blood mononuclear cells (PBMCs) to mediate ADCC was significantly higher in individuals who had been treated with ART before seroconversion, compared to the individuals initiating ART at a low CD4+ T cell count (ART-naïve individuals. The frequency of CD16 expressing natural killer (NK) cells correlated with both the duration of ART and Granzyme B (GzB) activity. In contrast, the plasma titer of antibodies mediating ADCC declined during ART. These findings suggest improved cytotoxic function of the NK cells if initiating ART early during infection, while the levels of ADCC mediating antibodies declined during ART.

  12. System-level insights into the cellular interactome of a non-model organism: inferring, modelling and analysing functional gene network of soybean (Glycine max.

    Directory of Open Access Journals (Sweden)

    Yungang Xu

    Full Text Available Cellular interactome, in which genes and/or their products interact on several levels, forming transcriptional regulatory-, protein interaction-, metabolic-, signal transduction networks, etc., has attracted decades of research focuses. However, such a specific type of network alone can hardly explain the various interactive activities among genes. These networks characterize different interaction relationships, implying their unique intrinsic properties and defects, and covering different slices of biological information. Functional gene network (FGN, a consolidated interaction network that models fuzzy and more generalized notion of gene-gene relations, have been proposed to combine heterogeneous networks with the goal of identifying functional modules supported by multiple interaction types. There are yet no successful precedents of FGNs on sparsely studied non-model organisms, such as soybean (Glycine max, due to the absence of sufficient heterogeneous interaction data. We present an alternative solution for inferring the FGNs of soybean (SoyFGNs, in a pioneering study on the soybean interactome, which is also applicable to other organisms. SoyFGNs exhibit the typical characteristics of biological networks: scale-free, small-world architecture and modularization. Verified by co-expression and KEGG pathways, SoyFGNs are more extensive and accurate than an orthology network derived from Arabidopsis. As a case study, network-guided disease-resistance gene discovery indicates that SoyFGNs can provide system-level studies on gene functions and interactions. This work suggests that inferring and modelling the interactome of a non-model plant are feasible. It will speed up the discovery and definition of the functions and interactions of other genes that control important functions, such as nitrogen fixation and protein or lipid synthesis. The efforts of the study are the basis of our further comprehensive studies on the soybean functional

  13. Cellular versus acellular matrix devices in treatment of diabetic foot ulcers: study protocol for a comparative efficacy randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Lev-Tov Hadar

    2013-01-01

    Full Text Available Abstract Background Diabetic foot ulcers (DFUs represent a significant source of morbidity and an enormous financial burden. Standard care for DFUs involves systemic glucose control, ensuring adequate perfusion, debridement of nonviable tissue, off-loading, control of infection, local wound care and patient education, all administered by a multidisciplinary team. Unfortunately, even with the best standard of care (SOC available, only 24% or 30% of DFUs will heal at weeks 12 or 20, respectively. The extracellular matrix (ECM in DFUs is abnormal and its impairment has been proposed as a key target for new therapeutic devices. These devices intend to replace the aberrant ECM by implanting a matrix, either devoid of cells or enhanced with fibroblasts, keratinocytes or both as well as various growth factors. These new bioengineered skin substitutes are proposed to encourage angiogenesis and in-growth of new tissue, and to utilize living cells to generate cytokines needed for wound repair. To date, the efficacy of bioengineered ECM containing live cellular elements for improving healing above that of a SOC control group has not been compared with the efficacy of an ECM devoid of cells relative to the same SOC. Our hypothesis is that there is no difference in the improved healing effected by either of these two product types relative to SOC. Methods/Design To test this hypothesis we propose a randomized, single-blind, clinical trial with three arms: SOC, SOC plus Dermagraft® (bioengineered ECM containing living fibroblasts and SOC plus Oasis® (ECM devoid of living cells in patients with nonhealing DFUs. The primary outcome is the percentage of subjects that achieved complete wound closure by week 12. Discussion If our hypothesis is correct, then immense cost savings could be realized by using the orders-of-magnitude less expensive acellular ECM device without compromising patient health outcomes. The article describes the protocol proposed to test

  14. Control of Colloid Surface Chemistry through Matrix Confinement: Facile Preparation of Stable Antibody Functionalized Silver Nanoparticles

    Science.gov (United States)

    Skewis, Lynell R.; Reinhard, Björn M.

    2010-01-01

    Here we describe a simple yet efficient gel matrix assisted preparation method which improves synthetic control over the interface between inorganic nanomaterials and biopolymers and yields stable biofunctionalized silver nanoparticles. Covalent functionalization of the noble metal surface is aided by the confinement of polyethylene glycol acetate functionalized silver nanoparticles in thin slabs of a 1% agarose gel. The gel confined nanoparticles can be transferred between reaction and washing media simply by immersing the gel slab in the solution of interest. The agarose matrix retains nanoparticles but is swiftly penetrated by the antibodies of interest. The antibodies are covalently anchored to the nanoparticles using conventional crosslinking strategies, and the resulting antibody functionalized nanoparticles are recovered from the gel through electroelution. We demonstrate the efficacy of this nanoparticle functionalization approach by labeling specific receptors on cellular surfaces with functionalized silver nanoparticles that are stable under physiological conditions. PMID:20161660

  15. Minimal model for complex dynamics in cellular processes.

    Science.gov (United States)

    Suguna, C; Chowdhury, K K; Sinha, S

    1999-11-01

    Cellular functions are controlled and coordinated by the complex circuitry of biochemical pathways regulated by genetic and metabolic feedback processes. This paper aims to show, with the help of a minimal model of a regulated biochemical pathway, that the common nonlinearities and control structures present in biomolecular interactions are capable of eliciting a variety of functional dynamics, such as homeostasis, periodic, complex, and chaotic oscillations, including transients, that are observed in various cellular processes.

  16. Influence of postoperative enteral nutrition on cellular immunity. A random double-blinded placebo controlled clinical trial

    DEFF Research Database (Denmark)

    Beier-Holgersen, R; Brandstrup, B

    2012-01-01

    The aim of this study was to discover if the cellular immunological response is different in patients receiving early postoperative enteral nutrition compared to patients who only receive "water".......The aim of this study was to discover if the cellular immunological response is different in patients receiving early postoperative enteral nutrition compared to patients who only receive "water"....

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

    Directory of Open Access Journals (Sweden)

    Maria Grazia Romanelli

    2011-05-01

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

  18. Foxd1-dependent signals control cellularity in the renal capsule, a structure required for normal renal development.

    Science.gov (United States)

    Levinson, Randy S; Batourina, Ekatherina; Choi, Christopher; Vorontchikhina, Marina; Kitajewski, Jan; Mendelsohn, Cathy L

    2005-02-01

    Development of the metanephric kidney involves the establishment of discrete zones of induction and differentiation that are crucial to the future radial patterning of the organ. Genetic deletion of the forkhead transcription factor, Foxd1, results in striking renal abnormalities, including the loss of these discrete zones and pelvic fused kidneys. We have investigated the molecular and cellular basis of the kidney phenotypes displayed by Foxd1-null embryos and report here that they are likely to be caused by a failure in the correct formation of the renal capsule. Unlike the single layer of Foxd1-positive stroma that comprises the normal renal capsule, the mutant capsule contains heterogeneous layers of cells, including Bmp4-expressing cells, which induce ectopic phospho-Smad1 signaling in nephron progenitors. This missignaling disrupts their early patterning, which, in turn, causes mispatterning of the ureteric tree, while delaying and disorganizing nephrogenesis. In addition, the defects in capsule formation prevent the kidneys from detaching from the body wall, thus explaining their fusion and pelvic location. For the first time, functions have been ascribed to the renal capsule that include delineation of the organ and acting as a barrier to inappropriate exogenous signals, while providing a source of endogenous signals that are crucial to the establishment of the correct zones of induction and differentiation.

  19. Power Control and Performance Analysis of Outage-Limited Cellular Network with MUD-SIC and Macro-Diversity

    CERN Document Server

    Ng, Derrick Wing Kwan

    2010-01-01

    In this paper, we analyze the uplink goodput (bits/sec/Hz successfully decoded) and per-user packet outage in a cellular network using multi-user detection with successive interference cancellation (MUD-SIC). We consider non-ergodic fading channels where microscopic fading channel information is not available at the transmitters. As a result, packet outage occurs whenever the data rate of packet transmissions exceeds the instantaneous mutual information even if powerful channel coding is applied for protection. We are interested to study the role of macro-diversity (MDiv) between multiple base stations on the MUD-SIC performance where the effect of potential error-propagation during the SIC processing is taken into account. While the jointly optimal power and decoding order in the MUD-SIC are NP hard problem, we derive a simple on/off power control and asymptotically optimal decoding order with respect to the transmit power. Based on the information theoretical framework, we derive the closed-form expressions...

  20. Oma1 Links Mitochondrial Protein Quality Control and TOR Signaling To Modulate Physiological Plasticity and Cellular Stress Responses.

    Science.gov (United States)

    Bohovych, Iryna; Kastora, Stavroula; Christianson, Sara; Topil, Danelle; Kim, Heejeong; Fangman, Teresa; Zhou, You J; Barrientos, Antoni; Lee, Jaekwon; Brown, Alistair J P; Khalimonchuk, Oleh

    2016-09-01

    A network of conserved proteases known as the intramitochondrial quality control (IMQC) system is central to mitochondrial protein homeostasis and cellular health. IMQC proteases also appear to participate in establishment of signaling cues for mitochondrion-to-nucleus communication. However, little is known about this process. Here, we show that in Saccharomyces cerevisiae, inactivation of the membrane-bound IMQC protease Oma1 interferes with oxidative-stress responses through enhanced production of reactive oxygen species (ROS) during logarithmic growth and reduced stress signaling via the TORC1-Rim15-Msn2/Msn4 axis. Pharmacological or genetic prevention of ROS accumulation in Oma1-deficient cells restores this defective TOR signaling. Additionally, inactivation of the Oma1 ortholog in the human fungal pathogen Candida albicans also alters TOR signaling and, unexpectedly, leads to increased resistance to neutrophil killing and virulence in the invertebrate animal model Galleria mellonella Our findings reveal a novel and evolutionarily conserved link between IMQC and TOR-mediated signaling that regulates physiological plasticity and pancellular oxidative-stress responses.

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

    Directory of Open Access Journals (Sweden)

    Samantha D Pauls

    2012-08-01

    Full Text Available 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, immunogloblulin 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.

  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.

  3. Controlling Function and Structure with DNA

    DEFF Research Database (Denmark)

    Tørring, Thomas

    2011-01-01

    In this thesis, the research on three different topics will be described. The overall area of the research is DNA nanotechnology, and the first chapter is therefore an introduction to DNA, and its advantages as a building material. The first research topic is the development of a new method...... investigated on a two dimensional DNA origami platform. This was done by incorporating functional groups on the surface of the origami, and reacting these with biotin analogues carrying the complementary functional groups. Successful reactions could then be observed using atomic force microscopy after addition...... of the protein streptavidin. While the implementation of chemical functionalities on origami can be achieved during automated DNA synthesis, this is laborious and costly. In a separate research project we aimed at improving the accessibility by applying an enzymatic labelling method. We demonstrated that the DNA...

  4. Epitope-based vaccines with the Anaplasma marginale MSP1a functional motif induce a balanced humoral and cellular immune response in mice.

    Directory of Open Access Journals (Sweden)

    Paula S Santos

    Full Text Available Bovine anaplasmosis is a hemoparasitic disease that causes considerable economic loss to the dairy and beef industries. Cattle immunized with the Anaplasma marginale MSP1 outer membrane protein complex presents a protective humoral immune response; however, its efficacy is variable. Immunodominant epitopes seem to be a key-limiting factor for the adaptive immunity. We have successfully demonstrated that critical motifs of the MSP1a functional epitope are essential for antibody recognition of infected animal sera, but its protective immunity is yet to be tested. We have evaluated two synthetic vaccine formulations against A. marginale, using epitope-based approach in mice. Mice infection with bovine anaplasmosis was demonstrated by qPCR analysis of erythrocytes after 15-day exposure. A proof-of-concept was obtained in this murine model, in which peptides conjugated to bovine serum albumin were used for immunization in three 15-day intervals by intraperitoneal injections before challenging with live bacteria. Blood samples were analyzed for the presence of specific IgG2a and IgG1 antibodies, as well as for the rickettsemia analysis. A panel containing the cytokines' transcriptional profile for innate and adaptive immune responses was carried out through qPCR. Immunized BALB/c mice challenged with A. marginale presented stable body weight, reduced number of infected erythrocytes, and no mortality; and among control groups mortality rates ranged from 15% to 29%. Additionally, vaccines have significantly induced higher IgG2a than IgG1 response, followed by increased expression of pro-inflammatory cytokines. This is a successful demonstration of epitope-based vaccines, and protection against anaplasmosis may be associated with elicitation of effector functions of humoral and cellular immune responses in murine model.

  5. Controllability of impulsive functional differential systems with nonlocal conditions

    Directory of Open Access Journals (Sweden)

    Yansheng Liu

    2013-08-01

    Full Text Available In this article, we study the controllability of impulsive functional differential equations with nonlocal conditions. We establish sufficient conditions for controllability, via the measure of noncompactness and Monch fixed point theorem.

  6. Approximate controllability of neutral functional differential system with unbounded delay

    Directory of Open Access Journals (Sweden)

    Jong Yeoul Park

    2001-01-01

    Full Text Available We consider a class of control systems governed by the neutral functional differential equation with unbounded delay and study the approximate controllability of the system. An example is given to illustrate the result.

  7. The preventive effect of vitamin C on the cellular and functional integrity of kidney cells in rats following repeated exposure to paraquat

    Directory of Open Access Journals (Sweden)

    Benjamin Nnamdi Okolonkwo

    2014-11-01

    Full Text Available Paraquat (PQ is a bipyridylium herbicide that is applied around trees in orchards and between crop rows to control broad-leaved and grassy weeds. Its oxidation results in the formation of superoxides which causes damage to cellular components. In this study, we determined the antioxidant effect vitamin C has on the cellular integrity of kidney function in rats following repeated exposure to PQ. Ninety-six male rats, grouped twelve rats per subgroup (A, Avit.c, B, Bvit.c, C, Cvit.c, D and Dvit.c were intraperitoneally injected with different sublethal increasing doses (0, 0, 2, 2, 4, 4, 6 and 6 mg/kg body weight of PQ respectively on biweekly (14 days intervals over a period of three months (84 days. Subsequently, the subgrouped animals (Avit.c, Bvit.c, Cvit.c and Dvit.c were maintained orally with 1 g/L vitamin C, while the other subgrouped animals (A, B, C and D received drinking water with negligible vitamin content throughout the study period. At the end of each monthly (28 days treatment, four animals per subgroup were selected. Urine samples were collected from each of the selected rats, after which each of the animals were anaesthetized with gaseous isoflurane and 5 mL of blood samples were collected using cardiac puncture procedure. The animals were later decapitated and their kidneys harvested. The samples collected were analyzed for urine [specific gravity (SG, pH, protein and glucose], blood (urea, creatinine, total protein and glucose, and the histological studies on kidney slides. The dose and exposure- time dependent PQ toxicity resulted in the reduction in urinary pH, elevation in urinary SG, and the detectable presence of protein and glucose in urine. It also caused marked elevation in serum urea and creatinine levels with reduction in serum protein and glucose levels and alterations in the cellular integrity of the renal architecture, especially the glomeruli and tubular tissues. Treatments on the PQ insulted animals with vitamin

  8. Controller design for TS models using delayed nonquadratic Lyapunov functions.

    Science.gov (United States)

    Lendek, Zsofia; Guerra, Thierry-Marie; Lauber, Jimmy

    2015-03-01

    In the last few years, nonquadratic Lyapunov functions have been more and more frequently used in the analysis and controller design for Takagi-Sugeno fuzzy models. In this paper, we developed relaxed conditions for controller design using nonquadratic Lyapunov functions and delayed controllers and give a general framework for the use of such Lyapunov functions. The two controller design methods developed in this framework outperform and generalize current state-of-the-art methods. The proposed methods are extended to robust and H∞ control and α -sample variation.

  9. Engineering invitro cellular microenvironment using polyelectrolyte multilayer films to control cell adhesion and for drug delivery applications

    Science.gov (United States)

    Kidambi, Srivatsan

    Over the past decades, the development of new methods for fabricating thin films that provide precise control of the three-dimensional topography and cell adhesion has generated lots of interest. These films could lead to significant advances in the fields of tissue engineering, drug delivery and biosensors which have become increasingly germane areas of research in the field of chemical engineering. The ionic layer-by-layer (LbL) assembly technique called "Polyelectrolyte Multilayers (PEMs)", introduced by Decher in 1991, has emerged as a versatile and inexpensive method of constructing polymeric thin films, with nanometer-scale control of ionized species. PEMs have long been utilized in such applications as sensors, eletrochromics, and nanomechanical thin films but recently they have also been shown to be excellent candidates for biomaterial applications. In this thesis, we engineered these highly customizable PEM thin films to engineer in vitro cellular microenvironments to control cell adhesion and for drug delivery applications. PEM films were engineered to control the adhesion of primary hepatocytes and primary neurons without the aid of adhesive proteins/ligands. We capitalized upon the differential cell attachment and spreading of primary hepatocytes and neurons on poly(diallyldimethylammoniumchloride) (PDAC) and sulfonated polystyrene (SPS) surfaces to make patterned co-cultures of primary hepatocytes/fibroblasts and primary neurons/astrocytes on the PEM surfaces. In addition, we developed self-assembled monolayer (SAM) patterns of m-d-poly(ethylene glycol) (m-dPEG) acid molecules onto PEMs. The created m-dPEG acid monolayer patterns on PEMs acted as resistive templates, and thus prevented further deposits of consecutive poly(anion)/poly(cation) pairs of charged particles and resulted in the formation of three-dimensional (3-D) patterned PEM films or selective particle depositions atop the original multilayer thin films. These new patterned and structured

  10. Highly Ordered 1D Fullerene Crystals for Concurrent Control of Macroscopic Cellular Orientation and Differentiation toward Large-Scale Tissue Engineering.

    Science.gov (United States)

    Minami, Kosuke; Kasuya, Yuki; Yamazaki, Tomohiko; Ji, Qingmin; Nakanishi, Waka; Hill, Jonathan P; Sakai, Hideki; Ariga, Katsuhiko

    2015-07-15

    A highly aligned 1D fullerene whisker (FW) scaffold in a centimeter area is fabricated by interfacial alignment. The resulting aligned FW scaffold enables concurrent control over cellular orientation and differentiation to muscle cells. This aligned FW scaffold is made by a facile method, and hence the substrate is a promising alternative to other cell scaffolds for tissue engineering.

  11. Cellular mechanisms regulating neuronal excitability: Functional implications and in epilepsy | Mecanismos celulares reguladores de la excitabilidad celular: Implicaciones funcionales y en epilepsia

    OpenAIRE

    Cabezas-Fernández, C.; Martín-Montiel, E. D.; Buño, W

    2003-01-01

    Introduction and method. The cellular mechanisms that regulate neuronal excitability and the propagation of electrical signals in the dendrites of pyramidal neurons are incompletely understood and of key functional and pathological importance. The capacity of dendrites to actively propagate action potentials is vital in processes related to memory and learning. The deregulation of dendritic excitability may also contribute to epilepsy. The contributions of ionic conductances that regulate neu...

  12. From a Global View to Focused Examination:Understanding Cellular Function of Lipid Kinase VPS34-Beclin 1 Complex in Autophagy

    Institute of Scientific and Technical Information of China (English)

    Zhenyu Yue; Yun Zhong

    2010-01-01

    @@ Autophagy is a cell'self-digestion'process via lysosomal degradation.The bestknown type of autophagy is macroauto phagy(hereafter referred to as auto phagy).Which involves the formation,delivery and degradation of autophago somes.The physiological function of autophagy is the controI of cellular nutrient and organelle homeostasis and can be regulated by various extracellular and intracellular cues(Klionsky and Emr,2000;Levine and Klionsky.2004).

  13. Myosin II controls cellular branching morphogenesis and migration in three dimensions by minimizing cell-surface curvature.

    Science.gov (United States)

    Elliott, Hunter; Fischer, Robert S; Myers, Kenneth A; Desai, Ravi A; Gao, Lin; Chen, Christopher S; Adelstein, Robert S; Waterman, Clare M; Danuser, Gaudenz

    2015-02-01

    In many cases, cell function is intimately linked to cell shape control. We used endothelial cell branching morphogenesis as a model to understand the role of myosin II in shape control of invasive cells migrating in 3D collagen gels. We applied principles of differential geometry and mathematical morphology to 3D image sets to parameterize cell branch structure and local cell-surface curvature. We find that Rho/ROCK-stimulated myosin II contractility minimizes cell-scale branching by recognizing and minimizing local cell-surface curvature. Using microfabrication to constrain cell shape identifies a positive feedback mechanism in which low curvature stabilizes myosin II cortical association, where it acts to maintain minimal curvature. The feedback between regulation of myosin II by curvature and control of curvature by myosin II drives cycles of localized cortical myosin II assembly and disassembly. These cycles in turn mediate alternating phases of directionally biased branch initiation and retraction to guide 3D cell migration.

  14. [Senescence and cellular immortality].

    Science.gov (United States)

    Trentesaux, C; Riou, J-F

    2010-11-01

    Senescence was originally described from the observation of the limited ability of normal cells to grow in culture, and may be generated by telomere erosion, accumulation of DNA damages, oxidative stress and modulation of oncogenes or tumor suppressor genes. Senescence corresponds to a cellular response aiming to control tumor progression by limiting cell proliferation and thus constitutes an anticancer barrier. Senescence is observed in pre-malignant tumor stages and disappears from malignant tumors. Agents used in standard chemotherapy also have the potential to induce senescence, which may partly explain their therapeutic activities. It is possible to restore senescence in tumors using targeted therapies that triggers telomere dysfunction or reactivates suppressor genes functions, which are essential for the onset of senescence.

  15. Function complex for automated system of coke machinery remote control

    Energy Technology Data Exchange (ETDEWEB)

    Simonov, N.F.; Pankrat' ev, O.N.; Bannikov, L.S.; Slatin, E.I.; Parfenov, G.I.

    1979-05-01

    this paper discusses a functional control system for remote control of coking plants introduced at the KBAiM of the Giprokoks. The control block allows for three modes of operation: fully automatic, by predesignated program according to oven design and technology; semi-automatic, in which individual programs perform automatically, checked and initiated by the operator; and remote, in which the operator controls each operation from the control console. The functions of selecting the location for the coke machinery, signal transmission and control selection have been incorporated as three autonomous but interfacing systems. (In Russian)

  16. A Retroviral Promoter and a Cellular Enhancer Define a Bipartite Element Which Controls env ERVWE1 Placental Expression

    Science.gov (United States)

    Prudhomme, Sarah; Oriol, Guy; Mallet, François

    2004-01-01

    The HERV-W family contains hundreds of loci diversely expressed in several physiological and pathological contexts. A unique locus termed ERVWE1 encodes an envelope glycoprotein (syncytin) involved in hominoid placental physiology. Here we show that syncytin expression is regulated by a bipartite element consisting of a cyclic AMP (cAMP)-inducible long terminal repeat (LTR) retroviral promoter adjacent to a cellular enhancer conferring a high level of expression and placental tropism. Deletion mutant analysis showed that the ERVWE1 5′ LTR contains binding sites essential for basal placental activity in the region from positions +1 to +125. The region from positions +125 to +310 represents a cAMP-responsive core HERV-W promoter active in all cell types. Site-directed mutagenesis analysis highlighted the complexity of U3 regulation. ERVWE1 placenta-specific positive (e.g., T240) and negative (e.g., G71) regulatory sites were identified, as were essential sites required for basic activity (e.g., A247). The flanking sequences of the ERVWE1 provirus contain several putative regulatory elements. The upstream HERV-H and HERV-P LTRs were found to be inactive. Conversely, the 436-bp region located between the HERV-P LTR and ERVWE1 was shown to be an upstream regulatory element (URE) which is significantly active in placenta cells. This URE acts as a tissue-specific enhancer. Genetic and functional analyses of hominoid UREs revealed large differences between UREs of members of the Hominidae and the Hylobatidae. These data allowed the identification of a positive regulatory region from positions −436 to −128, a mammalian apparent LTR retrotransposon negative regulatory region from positions −128 to −67, and a trophoblast-specific enhancer (TSE) from positions −67 to −35. Putative AP-2, Sp-1, and GCMa binding sites are essential constituents of the 33-bp TSE. PMID:15507602

  17. 仔猪痢清对动物细胞免疫功能影响的研究%Preliminary Study on the Effects of Zizhuliqing on Animal Cellular Immune Function

    Institute of Scientific and Technical Information of China (English)

    洪伟鸣; 邢晓玲; 郁杰; 葛竹兴; 王妲妲

    2008-01-01

    [Objective] The study aimed to explore the effects of Zizhuliqing Oral Liquid on animal cellular immune function. [Method] MTT method and phagocytizing natural red method were used to determine the effects of Zizhuliqing Oral Liquid on piglet lymphocyte transformation and the phagocytosis of mouse peritoneal macrophages respectively. [Result] The lymphocyte transformation rates of piglets in medicated groups were significantly higher than that in control group; the difference of mouse peritoneal macrophage activities between the medicated groups and the control group was obvious. [Conclusion] Zizhuliqing Oral Liquid could promote the transformation of piglet T lymphocytes induced by ConA and the phagocytosis of mouse peritoneal macrophages to natural red, indicating its good immune enhancement function.

  18. Molecular cloning and analysis of functional cDNA and genomic clones encoding bovine cellular retinoic acid-binding protein.

    Science.gov (United States)

    Shubeita, H E; Sambrook, J F; McCormick, A M

    1987-08-01

    A recombinant cDNA clone, pCRABP-HS1, encoding cellular retinoic acid-binding protein was isolated from a bovine adrenal cDNA library. COS-7 cells transfected with pCRABP-HS1 produced a biologically active retinoic acid-binding protein molecule of the expected molecular mass (15.5 kDa). RNA blot hybridization analysis using pCRABP-HS1 as a probe revealed a single 1050-nucleotide mRNA species in bovine adrenal, uterus, and testis, tissues that contain the highest levels of retinoic acid-binding activity. No hybridization was detected in RNA extracted from ovary, spleen, kidney, or liver, which contain relatively low levels of cellular retinoic acid-binding protein activity. Analysis of genomic clones isolated from an EcoRI bovine genomic library demonstrated that the bovine cellular retinoic acid-binding protein gene is composed of four exons and three introns. Two putative promoter sequences were identified in the cloned 5' sequence of the gene.

  19. Stabilization of nonlinear systems based on robust control Lyapunov function

    Institute of Scientific and Technical Information of China (English)

    CAI Xiu-shan; HAN Zheng-zhi; LU Gan-yun

    2007-01-01

    This paper deals with the robust stabilization problem for a class of nonlinear systems with structural uncertainty. Based on robust control Lyapunov function, a sufficient and necessary condition for a function to be a robust control Lyapunov function is given. From this condition, simply sufficient condition for the robust stabilization (robust practical stabilization) is deduced. Moreover, if the equilibrium of the closed-loop system is unique, the existence of such a robust control Lyapunov function will also imply robustly globally asymptotical stabilization. Then a continuous state feedback law can be constructed explicitly. The simulation shows the effectiveness of the method.

  20. miR-221/222 Promotes S-Phase Entry and Cellular Migration in Control of Basal-Like Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yuan Li

    2014-05-01

    Full Text Available The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a much higher expression of miR-221/222 in highly invasive basal-like breast cancer (BLBC cells than that in non-invasive luminal cells. A microRNA dataset from breast cancer patients indicated an elevated expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was associated with the induction of miR-221/222 expression. miRNA inhibitors specially targeting miR-221 or miR-222 both significantly suppressed cellular migration, invasion and G1/S transition of the cell cycle in BLBC cell types. Proteomic analysis demonstrated the down-regulation of two tumor suppressor genes, suppressor of cytokine signaling 1 (SOCS1 and cyclin-dependent kinase inhibit 1B (CDKN1B, by miR-221/222. This is the first report to reveal miR-221/222 regulation of G1/S transition of the cell cycle. These findings demonstrate that miR-221/222 contribute to the aggressiveness in control of BLBC.

  1. IQGAP1 and its binding proteins control diverse biological functions.

    Science.gov (United States)

    White, Colin D; Erdemir, Huseyin H; Sacks, David B

    2012-04-01

    IQGAP proteins have been identified in a wide spectrum of organisms, ranging from yeast to humans. The most extensively studied family member is the ubiquitously expressed scaffold protein IQGAP1, which participates in multiple essential aspects of mammalian biology. IQGAP1 mediates these effects by binding to and regulating the function of numerous interacting proteins. Over ninety proteins have been reported to associate with IQGAP1, either directly or as part of a larger complex. In this review, we summarise those IQGAP1 binding partners that have been identified in the last five years. The molecular mechanisms by which these interactions contribute to the functions of receptors and their signalling cascades, small GTPase function, cytoskeletal dynamics, neuronal regulation and intracellular trafficking are evaluated. The evidence that has accumulated recently validates the role of IQGAP1 as a scaffold protein and expands the repertoire of cellular activities in which it participates.

  2. On a useful functional representation of control system structure

    Science.gov (United States)

    Malchow, Harvey L.

    1988-01-01

    An alternative structure for control systems is proposed. The structure is represented by a three-element block diagram and three functional definitions. It is argued that the three functional elements form a canonical set. The set includes the functions description, estimation and control. General overlay of the structure on parallel state and nested-state control systems is discussed. Breakdown of two real nested-state control systems into the proposed functional format is displayed. Application of the process to the mapping of complex control systems R and D efforts is explained with the Mars Rover Sample and Return mission as an example. A previous application of this basic functional structure to Space Station performance requirements organization is discussed.

  3. Using Lyapunov function to design optimal controller for AQM routers

    Institute of Scientific and Technical Information of China (English)

    ZHANG Peng; YE Cheng-qing; MA Xue-ying; CHEN Yan-hua; LI Xin

    2007-01-01

    It was shown that active queue management schemes implemented in the routers of communication networks supporting transmission control protocol (TCP) flows can be modelled as a feedback control system. In this paper based on Lyapunov function we developed an optimal controller to improve active queue management (AQM) router's stability and response time,which are often in conflict with each other in system performance. Ns-2 simulations showed that optimal controller outperforms PI controller significantly.

  4. Effect of psychological intervention in the form of relaxation and guided imagery on cellular immune function in normal healthy subjects. An overview

    DEFF Research Database (Denmark)

    Zachariae, R; Kristensen, J S; Hokland, P

    1991-01-01

    The present study measured the effects of relaxation and guided imagery on cellular immune function. During a period of 10 days 10 healthy subjects were given one 1-hour relaxation procedure and one combined relaxation and guided imagery procedure, instructing the subjects to imagine their immune...... system becoming very effective. Even though no major changes in the composition of the major mononuclear leukocyte subsets could be demonstrated a significant increase in natural killer function was demonstrated. These data suggest that relaxation and guided imagery might have a beneficial effect...

  5. Stabilization of discrete nonlinear systems based on control Lyapunov functions

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The stabilization of discrete nonlinear systems is studied.Based on control Lyapunov functions,asufficient and necessary condition for a quadratic function to be a control Lyapunov function is given.From this condition,a continuous state feedback law is constructed explicitly.It can globally asymptotically stabilize the equilibrium of the closed-loop system.A simulation example shows the effectiveness of the proposed method.

  6. Function approximation for learning control : a key sample based approach

    NARCIS (Netherlands)

    Kruif, de Bastiaan Johannes

    2004-01-01

    Two function approximators are introduced in this thesis for use in learning control. These function approximators identify a relation between input and output based on samples. Two different, but closely related function approximators are introduced: the key sample machine and the recursive key sam

  7. Function approximation for learning control : a key sample based approach

    OpenAIRE

    2004-01-01

    Two function approximators are introduced in this thesis for use in learning control. These function approximators identify a relation between input and output based on samples. Two different, but closely related function approximators are introduced: the key sample machine and the recursive key sample machine.

  8. Catalog of Window Taper Functions for Sidelobe Control

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin W.

    2017-04-01

    Window taper functions of finite apertures are well-known to control undesirable sidelobes, albeit with performance trades. A plethora of various taper functions have been developed over the years to achieve various optimizations. We herein catalog a number of window functions, and com pare principal characteristics.

  9. Control of beam halo-chaos by sample function

    Institute of Scientific and Technical Information of China (English)

    Bai Long; Zhang Rong; Weng Jia-Qiang; Luo Xiao-Shu; Fang Jin-Qing

    2006-01-01

    The K-V beam through an axisymmetric uniform-focusing channel is studied using the particle-core model. The beam halo-chaos is found, and a sample function controller is proposed based on mechanism of halo formation and strategy of controlling halo-chaos. We perform multiparticle simulation to control the halo by using the sample function controller. The numerical results show that our control method is effective. We also find that the radial ion density changes when the ion beam is in the channel: not only can the halo-chaos and its regeneration be eliminated by using the sample function control method, but also the density uniformity can be found at the beam's centre as long as an appropriate control method is chosen.

  10. Molecular cloning and analysis of functional cDNA and genomic clones encoding bovine cellular retinoic acid-binding protein.

    OpenAIRE

    Shubeita, H E; Sambrook, J F; McCormick, A M

    1987-01-01

    A recombinant cDNA clone, pCRABP-HS1, encoding cellular retinoic acid-binding protein was isolated from a bovine adrenal cDNA library. COS-7 cells transfected with pCRABP-HS1 produced a biologically active retinoic acid-binding protein molecule of the expected molecular mass (15.5 kDa). RNA blot hybridization analysis using pCRABP-HS1 as a probe revealed a single 1050-nucleotide mRNA species in bovine adrenal, uterus, and testis, tissues that contain the highest levels of retinoic acid-bindin...

  11. Enhanced NF-κB activation and cellular function in macrophages lacking IκB kinase 1 (IKK1)

    Science.gov (United States)

    Li, Qiutang; Lu, Qingxian; Bottero, Virginie; Estepa, Gabriela; Morrison, Lisa; Mercurio, Frank; Verma, Inder M.

    2005-01-01

    IκB kinase (IKK) complex plays a key regulatory role in macrophages for NF-κB activation during both innate and adaptive immune responses. Because IKK1–/– mice died at birth, we differentiated functional macrophages from embryonic day 15.5 IKK1 mutant embryonic liver. The embryonic liver-derived macrophage (ELDM) showed enhanced phagocytotic clearance of bacteria, more efficient antigen-presenting capacity, elevated secretion of several key proinflammatory cytokines and chemokines, and known NFκB target genes. Increased NFκB activity in IKK1 mutant ELDM was the result of prolonged degradation of IκBα in response to infectious pathogens. The delayed restoration of IκBα in pathogen-activated IKK1–/– ELDM was a direct consequence of uncontrolled IKK2 kinase activity. We hypothesize that IKK1 plays a checkpoint role in the proper control of IκBα kinase activity in innate and adaptive immunity. PMID:16116086

  12. Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes.

    Science.gov (United States)

    Schreiner, Sabrina; Bürck, Carolin; Glass, Mandy; Groitl, Peter; Wimmer, Peter; Kinkley, Sarah; Mund, Andreas; Everett, Roger D; Dobner, Thomas

    2013-04-01

    Death domain-associated protein (Daxx) cooperates with X-linked α-thalassaemia retardation syndrome protein (ATRX), a putative member of the sucrose non-fermentable 2 family of ATP-dependent chromatin-remodelling proteins, acting as the core ATPase subunit in this complex, whereas Daxx is the targeting factor, leading to histone deacetylase recruitment, H3.3 deposition and transcriptional repression of cellular promoters. Despite recent findings on the fundamental importance of chromatin modification in host-cell gene regulation, it remains unclear whether adenovirus type 5 (Ad5) transcription is regulated by cellular chromatin remodelling to allow efficient virus gene expression. Here, we focus on the repressive role of the Daxx/ATRX complex during Ad5 replication, which depends on intact protein-protein interaction, as negative regulation could be relieved with a Daxx mutant that is unable to interact with ATRX. To ensure efficient viral replication, Ad5 E1B-55K protein inhibits Daxx and targets ATRX for proteasomal degradation in cooperation with early region 4 open reading frame protein 6 and cellular components of a cullin-dependent E3-ubiquitin ligase. Our studies illustrate the importance and diversity of viral factors antagonizing Daxx/ATRX-mediated repression of viral gene expression and shed new light on the modulation of cellular chromatin remodelling factors by Ad5. We show for the first time that cellular Daxx/ATRX chromatin remodelling complexes play essential roles in Ad gene expression and illustrate the importance of early viral proteins to counteract cellular chromatin remodelling.

  13. Fuzzy Control Method with Application for Functional Neuromuscular Stimulation System

    Institute of Scientific and Technical Information of China (English)

    吴怀宇; 周兆英; 熊沈蜀

    2001-01-01

    A fuzzy control technique is applied to a functional neuromuscular stimulation (FNS) physicalmultiarticular muscle control system. The FNS multiarticular muscle control system based on the fuzzy controllerwas developed with the fuzzy control rule base. Simulation experiments were then conducted for the joint angletrajectories of both the elbow flexion and the wrist flexion using the proposed fuzzy control algorithm and aconventional PID control algorithm with the FNS physical multiarticular muscle control system. The simulationresults demonstrated that the proposed fuzzy control method is more suitable for the physiologicalcharacteristics than conventional PID control. In particular, both the trajectory-following and the stability of theFNS multiarticular muscle control system were greatly improved. Furthermore, the stimulating pulse trainsgenerated by the fuzzy controller were stable and smooth.``

  14. Three cdg operons control cellular turnover of cyclic di-GMP in Acetobacter xylinum: genetic organization and occurrence of conserved domains in isoenzymes.

    Science.gov (United States)

    Tal, R; Wong, H C; Calhoon, R; Gelfand, D; Fear, A L; Volman, G; Mayer, R; Ross, P; Amikam, D; Weinhouse, H; Cohen, A; Sapir, S; Ohana, P; Benziman, M

    1998-09-01

    Cyclic di-GMP (c-di-GMP) is the specific nucleotide regulator of beta-1,4-glucan (cellulose) synthase in Acetobacter xylinum. The enzymes controlling turnover of c-di-GMP are diguanylate cyclase (DGC), which catalyzes its formation, and phosphodiesterase A (PDEA), which catalyzes its degradation. Following biochemical purification of DGC and PDEA, genes encoding isoforms of these enzymes have been isolated and found to be located on three distinct yet highly homologous operons for cyclic diguanylate, cdg1, cdg2, and cdg3. Within each cdg operon, a pdeA gene lies upstream of a dgc gene. cdg1 contains two additional flanking genes, cdg1a and cdg1d. cdg1a encodes a putative transcriptional activator, similar to AadR of Rhodopseudomonas palustris and FixK proteins of rhizobia. The deduced DGC and PDEA proteins have an identical motif structure of two lengthy domains in their C-terminal regions. These domains are also present in numerous bacterial proteins of undefined function. The N termini of the DGC and PDEA deduced proteins contain putative oxygen-sensing domains, based on similarity to domains on bacterial NifL and FixL proteins, respectively. Genetic disruption analyses demonstrated a physiological hierarchy among the cdg operons, such that cdg1 contributes 80% of cellular DGC and PDEA activities and cdg2 and cdg3 contribute 15 and 5%, respectively. Disruption of dgc genes markedly reduced in vivo cellulose production, demonstrating that c-di-GMP controls this process.

  15. Next Generation Nuclear Plant Resilient Control System Functional Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lynne M. Stevens

    2010-07-01

    Control Systems and their associated instrumentation must meet reliability, availability, maintainability, and resiliency criteria in order for high temperature gas-cooled reactors (HTGRs) to be economically competitive. Research, perhaps requiring several years, may be needed to develop control systems to support plant availability and resiliency. This report functionally analyzes the gaps between traditional and resilient control systems as applicable to HTGRs, which includes the Next Generation Nuclear Plant; defines resilient controls; assesses the current state of both traditional and resilient control systems; and documents the functional gaps existing between these two controls approaches as applicable to HTGRs. This report supports the development of an overall strategy for applying resilient controls to HTGRs by showing that control systems with adequate levels of resilience perform at higher levels, respond more quickly to disturbances, increase operational efficiency, and increase public protection.

  16. The Na+/Glucose Cotransporter Inhibitor Canagliflozin Activates AMPK by Inhibiting Mitochondrial Function and Increasing Cellular AMP Levels.

    Science.gov (United States)

    Hawley, Simon A; Ford, Rebecca J; Smith, Brennan K; Gowans, Graeme J; Mancini, Sarah J; Pitt, Ryan D; Day, Emily A; Salt, Ian P; Steinberg, Gregory R; Hardie, D Grahame

    2016-09-01

    Canagliflozin, dapagliflozin, and empagliflozin, all recently approved for treatment of type 2 diabetes, were derived from the natural product phlorizin. They reduce hyperglycemia by inhibiting glucose reuptake by sodium/glucose cotransporter (SGLT) 2 in the kidney, without affecting intestinal glucose uptake by SGLT1. We now report that canagliflozin also activates AMPK, an effect also seen with phloretin (the aglycone breakdown product of phlorizin), but not to any significant extent with dapagliflozin, empagliflozin, or phlorizin. AMPK activation occurred at canagliflozin concentrations measured in human plasma in clinical trials and was caused by inhibition of Complex I of the respiratory chain, leading to increases in cellular AMP or ADP. Although canagliflozin also inhibited cellular glucose uptake independently of SGLT2, this did not account for AMPK activation. Canagliflozin also inhibited lipid synthesis, an effect that was absent in AMPK knockout cells and that required phosphorylation of acetyl-CoA carboxylase (ACC) 1 and/or ACC2 at the AMPK sites. Oral administration of canagliflozin activated AMPK in mouse liver, although not in muscle, adipose tissue, or spleen. Because phosphorylation of ACC by AMPK is known to lower liver lipid content, these data suggest a potential additional benefit of canagliflozin therapy compared with other SGLT2 inhibitors. © 2016 by the American Diabetes Association.

  17. Positive and Negative Regulatory Mechanisms for Fine-Tuning Cellularity and Functions of Medullary Thymic Epithelial Cells

    Science.gov (United States)

    Akiyama, Taishin; Tateishi, Ryosuke; Akiyama, Nobuko; Yoshinaga, Riko; Kobayashi, Tetsuya J.

    2015-01-01

    Self-tolerant T cells and regulatory T cells develop in the thymus. A wide variety of cell–cell interactions in the thymus is required for the differentiation, proliferation, and repertoire selection of T cells. Various secreted and cell surface molecules expressed in thymic epithelial cells (TECs) mediate these processes. Moreover, cytokines expressed by cells of hematopoietic origin regulate the cellularity of TECs. Tumor necrosis factor (TNF) family RANK ligand, lymphotoxin, and CD40 ligand, expressed in T cells and innate lymphoid cells (ILCs), promote the differentiation and proliferation of medullary TECs (mTECs) that play critical roles in the induction of immune tolerance. A recent study suggests that interleukin-22 (IL-22) produced by ILCs promotes regeneration of TECs after irradiation. Intriguingly, tumor growth factor-β and osteoprotegerin limit cellularity of mTECs, thereby attenuating regulatory T cell generation. We will review recent insights into the molecular basis for cell–cell interactions regulating differentiation and proliferation of mTECs and also discuss about a perspective on use of mathematical models for understanding this complicated system. PMID:26441966

  18. Arrhenius parameter determination as a function of heating method and cellular microenvironment based on spatial cell viability analysis.

    Science.gov (United States)

    Whitney, Jon; Carswell, William; Rylander, Nichole

    2013-06-01

    Predictions of injury in response to photothermal therapy in vivo are frequently made using Arrhenius parameters obtained from cell monolayers exposed to laser or water bath heating. However, the impact of different heating methods and cellular microenvironments on Arrhenius predictions has not been thoroughly investigated. This study determined the influence of heating method (water bath and laser irradiation) and cellular microenvironment (cell monolayers and tissue phantoms) on Arrhenius parameters and spatial viability. MDA-MB-231 cells seeded in monolayers and sodium alginate phantoms were heated with a water bath for 3-20 min at 46, 50, and 54 °C or laser irradiated (wavelength of 1064 nm and fluences of 40 W/cm(2) or 3.8 W/cm(2) for 0-4 min) in combination with photoabsorptive carbon nanohorns. Spatial viability was measured using digital image analysis of cells stained with calcein AM and propidium iodide and used to determine Arrhenius parameters. The influence of microenvironment and heating method on Arrhenius parameters and capability of parameters derived from more simplistic experimental conditions (e.g. water bath heating of monolayers) to predict more physiologically relevant systems (e.g. laser heating of phantoms) were assessed. Arrhenius predictions of the treated area (Arrhenius parameters, with heating method having the greater impact.

  19. Controllability of Impulsive Neutral Functional Differential Inclusions in Banach Spaces

    Directory of Open Access Journals (Sweden)

    X. J. Wan

    2013-01-01

    Full Text Available We investigate the controllability of impulsive neutral functional differential inclusions in Banach spaces. Our main aim is to find an effective method to solve the controllability problem of impulsive neutral functional differential inclusions with multivalued jump sizes in Banach spaces. Based on a fixed point theorem with regard to condensing map, sufficient conditions for the controllability of the impulsive neutral functional differential inclusions in Banach spaces are derived. Moreover, a remark is given to explain less conservative criteria for special cases, and work is improved in the previous literature.

  20. Transfer Function Model of Multirate Feedback Control Systems

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Based on the suitably defined multivariable version of Krancoperators and the extended input and output vectors, the multirate sampling plant is transformed to a equivalent time invariant single rate one, then the transfer function model of the multivariable multirate sampling plant is obtained. By combining this plant model with the time invariant description of the multirate controller in terms of extended vectors, the closed-loop transfer function model of the multirate feedback control system can be determinated. This transfer function model has a very simple structure, and can be used as a basis for the analysis and synthesis of the multirate sampling feedback control systems in the frequency domain.

  1. Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial.

    Science.gov (United States)

    Paulsen, Gøran; Cumming, Kristoffer T; Holden, Geir; Hallén, Jostein; Rønnestad, Bent Ronny; Sveen, Ole; Skaug, Arne; Paur, Ingvild; Bastani, Nasser E; Østgaard, Hege Nymo; Buer, Charlotte; Midttun, Magnus; Freuchen, Fredrik; Wiig, Havard; Ulseth, Elisabeth Tallaksen; Garthe, Ina; Blomhoff, Rune; Benestad, Haakon B; Raastad, Truls

    2014-04-15

    In this double-blind, randomised, controlled trial, we investigated the effects of vitamin C and E supplementation on endurance training adaptations in humans. Fifty-four young men and women were randomly allocated to receive either 1000 mg of vitamin C and 235 mg of vitamin E or a placebo daily for 11 weeks. During supplementation, the participants completed an endurance training programme consisting of three to four sessions per week (primarily of running), divided into high-intensity interval sessions [4-6 × 4-6 min; >90% of maximal heart rate (HRmax)] and steady state continuous sessions (30-60 min; 70-90% of HRmax). Maximal oxygen uptake (VO2 max ), submaximal running and a 20 m shuttle run test were assessed and blood samples and muscle biopsies were collected, before and after the intervention. Participants in the vitamin C and E group increased their VO2 max (mean ± s.d.: 8 ± 5%) and performance in the 20 m shuttle test (10 ± 11%) to the same degree as those in the placebo group (mean ± s.d.: 8 ± 5% and 14 ± 17%, respectively). However, the mitochondrial marker cytochrome c oxidase subunit IV (COX4) and cytosolic peroxisome proliferator-activated receptor-γ coactivator 1 α (PGC-1α) increased in the m. vastus lateralis in the placebo group by 59 ± 97% and 19 ± 51%, respectively, but not in the vitamin C and E group (COX4: -13 ± 54%; PGC-1α: -13 ± 29%; P ≤ 0.03, between groups). Furthermore, mRNA levels of CDC42 and mitogen-activated protein kinase 1 (MAPK1) in the trained muscle were lower in the vitamin C and E group than in the placebo group (P ≤ 0.05). Daily vitamin C and E supplementation attenuated increases in markers of mitochondrial biogenesis following endurance training. However, no clear interactions were detected for improvements in VO2 max and running performance. Consequently, vitamin C and E supplementation hampered cellular adaptations in the exercised muscles, and although this did not translate to the performance tests

  2. Control architecture of power systems: Modeling of purpose and function

    DEFF Research Database (Denmark)

    Heussen, Kai; Saleem, Arshad; Lind, Morten

    2009-01-01

    for semantically consistent modeling of control architecture is presented. The method, called Multilevel Flow Modeling (MFM), is applied to the case of system balancing. It was found that MFM is capable of capturing implicit control knowledge, which is otherwise difficult to formalize. The method has possible...... of power systems and it is necessary to identify requirements and functions. How does new control architecture fit with the old architecture? How can power system functions be specified independent of technology? What is the purpose of control in power systems? In this paper, a method suitable...

  3. Cellular Telephone

    Institute of Scientific and Technical Information of China (English)

    杨周

    1996-01-01

    Cellular phones, used in automobiles, airliners, and passenger trains, are basically low-power radiotelephones. Calls go through radio transmitters that are located within small geographical units called cells. Because each cell’s signals are too weak to interfere with those of other cells operating on the same fre-

  4. Elucidation of the Ebola virus VP24 cellular interactome and disruption of virus biology through targeted inhibition of host-cell protein function.

    Science.gov (United States)

    García-Dorival, Isabel; Wu, Weining; Dowall, Stuart; Armstrong, Stuart; Touzelet, Olivier; Wastling, Jonathan; Barr, John N; Matthews, David; Carroll, Miles; Hewson, Roger; Hiscox, Julian A

    2014-11-07

    Viral pathogenesis in the infected cell is a balance between antiviral responses and subversion of host-cell processes. Many viral proteins specifically interact with host-cell proteins to promote virus biology. Understanding these interactions can lead to knowledge gains about infection and provide potential targets for antiviral therapy. One such virus is Ebola, which has profound consequences for human health and causes viral hemorrhagic fever where case fatality rates can approach 90%. The Ebola virus VP24 protein plays a critical role in the evasion of the host immune response and is likely to interact with multiple cellular proteins. To map these interactions and better understand the potential functions of VP24, label-free quantitative proteomics was used to identify cellular proteins that had a high probability of forming the VP24 cellular interactome. Several known interactions were confirmed, thus placing confidence in the technique, but new interactions were also discovered including one with ATP1A1, which is involved in osmoregulation and cell signaling. Disrupting the activity of ATP1A1 in Ebola-virus-infected cells with a small molecule inhibitor resulted in a decrease in progeny virus, thus illustrating how quantitative proteomics can be used to identify potential therapeutic targets.

  5. A cellular reporter to evaluate CRM1 nuclear export activity: functional analysis of the cancer-related mutant E571K.

    Science.gov (United States)

    García-Santisteban, Iraia; Arregi, Igor; Alonso-Mariño, Marián; Urbaneja, María A; Garcia-Vallejo, Juan J; Bañuelos, Sonia; Rodríguez, Jose A

    2016-12-01

    The exportin CRM1 binds nuclear export signals (NESs), and mediates active transport of NES-bearing proteins from the nucleus to the cytoplasm. Structural and biochemical analyses have uncovered the molecular mechanisms underlying CRM1/NES interaction. CRM1 binds NESs through a hydrophobic cleft, whose open or closed conformation facilitates NES binding and release. Several cofactors allosterically modulate the conformation of the NES-binding cleft through intramolecular interactions involving an acidic loop and a C-terminal helix in CRM1. This current model of CRM1-mediated nuclear export has not yet been evaluated in a cellular setting. Here, we describe SRV100, a cellular reporter to interrogate CRM1 nuclear export activity. Using this novel tool, we provide evidence further validating the model of NES binding and release by CRM1. Furthermore, using both SRV100-based cellular assays and in vitro biochemical analyses, we investigate the functional consequences of a recurrent cancer-related mutation, which targets a residue near CRM1 NES-binding cleft. Our data indicate that this mutation does not necessarily abrogate the nuclear export activity of CRM1, but may increase its affinity for NES sequences bearing a more negatively charged C-terminal end.

  6. Moderate-intensity resistance exercise alters skeletal muscle molecular and cellular structure and function in inactive older adults with knee osteoarthritis.

    Science.gov (United States)

    Miller, Mark S; Callahan, Damien M; Tourville, Timothy W; Slauterbeck, James R; Kaplan, Anna; Fiske, Brad R; Savage, Patrick D; Ades, Philip A; Beynnon, Bruce D; Toth, Michael J

    2017-04-01

    High-intensity resistance exercise (REX) training increases physical capacity, in part, by improving muscle cell size and function. Moderate-intensity REX, which is more feasible for many older adults with disease and/or disability, also increases physical function, but the mechanisms underlying such improvements are not understood. Therefore, we measured skeletal muscle structure and function from the molecular to the tissue level in response to 14 wk of moderate-intensity REX in physically inactive older adults with knee osteoarthritis (n = 17; 70 ± 1 yr). Although REX training increased quadriceps muscle cross-sectional area (CSA), average single-fiber CSA was unchanged because of reciprocal changes in myosin heavy chain (MHC) I and IIA fibers. Intermyofibrillar mitochondrial content increased with training because of increases in mitochondrial size in men, but not women, with no changes in subsarcolemmal mitochondria in either sex. REX increased whole muscle contractile performance similarly in men and women. In contrast, adaptations in single-muscle fiber force production per CSA (i.e., tension) and contractile velocity varied between men and women in a fiber type-dependent manner, with adaptations being explained at the molecular level by differential changes in myosin-actin cross-bridge kinetics and mechanics and single-fiber MHC protein expression. Our results are notable compared with studies of high-intensity REX because they show that the effects of moderate-intensity REX in older adults on muscle fiber size/structure and myofilament function are absent or modest. Moreover, our data highlight unique sex-specific adaptations due to differential cellular and subcellular structural and functional changes.NEW & NOTEWORTHY Moderate-intensity resistance training causes sex-specific adaptations in skeletal muscle structure and function at the cellular and molecular levels in inactive older adult men and women with knee osteoarthritis. However, these responses

  7. Malignant monoblasts can function as effector cells in natural killer cell and antibody-dependent cellular cytotoxicity assays

    DEFF Research Database (Denmark)

    Hokland, P; Hokland, M; Ellegaard, J

    1981-01-01

    This is the first report describing natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) of malignant monoblasts. Pure acute monoblastic leukemia was diagnosed in bone marrow aspirations from two patients by use of conventional cytochemical methods as well as multiple immunologic...... techniques including detection of ALL antigens and terminal transferase. The malignant cells were subsequently found to be potent effectors in NK and ADCC assays. Addition of partially purified alpha-interferon to the in vitro cultures was found to have an enhancing effect on NK activity, whereas...... no modulation was seen in ADCC. These findings are discussed in the light of our present knowledge of lymphoid NK cells. Udgivelsesdato: 1981-May...

  8. Integrated Control Strategies Supporting Autonomous Functionalities in Mobile Robots

    Science.gov (United States)

    2005-01-01

    Integrated Control Strategies Supporting Autonomous Functionalities in Mobile Robots B. Sightsa, H.R. Everetta, E. Biagtan Pacisa, G. Koguta M...TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Integrated Control Strategies Supporting Autonomous Functionalities in Mobile Robots 5a...calculation methods using encoder counts, wheel radius, and the robot’s wheelbase, as described in Sensors For Mobile Robots [5]. On top of this

  9. Energy Management and Control System: Desired Capabilities and Functionality

    Energy Technology Data Exchange (ETDEWEB)

    Hatley, Darrel D.; Meador, Richard J.; Katipamula, Srinivas; Brambley, Michael R.; Wouden, Carl

    2005-04-29

    This document discusses functions and capabilities of a typical building/facility energy management and control systems (EMCS). The overall intent is to provide a building operator, manager or engineer with basic background information and recommended functions, capabilities, and good/best practices that will enable the control systems to be fully utilized/optimized, resulting in improved building occupant quality of life and more reliable, energy efficient facilities.

  10. HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans.

    Science.gov (United States)

    Chen, Huan-Da; Kao, Cheng-Yuan; Liu, Bang-Yu; Huang, Shin-Whei; Kuo, Cheng-Ju; Ruan, Jhen-Wei; Lin, Yen-Hung; Huang, Cheng-Rung; Chen, Yu-Hung; Wang, Horng-Dar; Aroian, Raffi V; Chen, Chang-Shi

    2017-02-01

    Autophagy is an evolutionarily conserved intracellular system that maintains cellular homeostasis by degrading and recycling damaged cellular components. The transcription factor HLH-30/TFEB-mediated autophagy has been reported to regulate tolerance to bacterial infection, but less is known about the bona fide bacterial effector that activates HLH-30 and autophagy. Here, we reveal that bacterial membrane pore-forming toxin (PFT) induces autophagy in an HLH-30-dependent manner in Caenorhabditis elegans. Moreover, autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C. elegans. These results demonstrate that autophagic pathways and autophagy are induced partly at the transcriptional level through HLH-30 activation and are required to protect metazoan upon PFT intoxication. Together, our data show a new and powerful connection between HLH-30-mediated autophagy and epithelium intrinsic cellular defense against the single most common mode of bacterial attack in vivo.

  11. Dual Functional Nanocarrier for Cellular Imaging and Drug Delivery in Cancer Cells Based on π-Conjugated Core and Biodegradable Polymer Arms.

    Science.gov (United States)

    Kulkarni, Bhagyashree; Surnar, Bapurao; Jayakannan, Manickam

    2016-03-14

    Multipurpose polymer nanoscaffolds for cellular imaging and delivery of anticancer drug are urgently required for the cancer therapy. The present investigation reports a new polymer drug delivery concept based on biodegradable polycaprolactone (PCL) and highly luminescent π-conjugated fluorophore as dual functional nanocarrier for cellular imaging and delivery vehicles for anticancer drug to cancer cells. To accomplish this goal, a new substituted caprolactone monomer was designed, and it was subjected to ring opening polymerization using a blue luminescent bishydroxyloligo-phenylenevinylene (OPV) fluorophore as an initiator. A series of A-B-A triblock copolymer building blocks with a fixed OPV π-core and variable chain biodegradable PCL arm length were tailor-made. These triblocks self-assembled in organic solvents to produce well-defined helical nanofibers, whereas in water they produced spherical nanoparticles (size ∼150 nm) with blue luminescence. The hydrophobic pocket of the polymer nanoparticle was found to be an efficient host for loading water insoluble anticancer drug such as doxorubicin (DOX). The photophysical studies revealed that there was no cross-talking between the OPV and DOX chromophores, and their optical purity was retained in the nanoparticle assembly for cellular imaging. In vitro studies revealed that the biodegradable PCL arm was susceptible to enzymatic cleavage at the intracellular lysosomal esterase under physiological conditions to release the loaded drugs. The nascent nanoparticles were found to be nontoxic to cancer cells, whereas the DOX-loaded nanoparticles accomplished more than 80% killing in HeLa cells. Confocal microscopic analysis confirmed the cell penetrating ability of the blue luminescent polymer nanoparticles and their accumulation preferably in the cytoplasm. The DOX loaded red luminescent polymer nanoparticles were also taken up by the cells, and the drug was found to be accumulated at the perinuclear environment

  12. Hydrogen peroxide sensors for cellular imaging based on horse radish peroxidase reconstituted on polymer-functionalized TiO2 nanorods

    Science.gov (United States)

    Tahir, Muhammad Nawaz; André, Rute; Sahoo, Jugal Kishore; Jochum, Florian D.; Theato, Patrick; Natalio, Filipe; Berger, Rüdiger; Branscheid, Robert; Kolb, Ute; Tremel, Wolfgang

    2011-09-01

    We describe the reconstitution of apo-horse radish peroxidase (apo-HRP) onto TiO2 nanorods functionalized with a multifunctional polymer. After functionalization, the horse radish peroxidase (HRP) functionalized TiO2 nanorods were well dispersible in aqueous solution, catalytically active and biocompatible, and they could be used to quantify and image H2O2 which is a harmful secondary product of cellular metabolism. The shape, size and structure of TiO2 nanorods (anatase) were analyzed by transmission electron microscopy (TEM), high resolution TEM (HRTEM), electron diffraction (ED) and X-ray diffraction (XRD). The surface functionalization, HRP reconstitution and catalytic activity were confirmed by UV-Vis, FT-IR, CLSM and atomic force microscopy (AFM). Biocompatibility and cellular internalization of active HRP reconstituted TiO2 nanorods were confirmed by a classical MTT cytotoxicity assay and confocal laser scanning microscopy (CLSM) imaging, respectively. The intracellular localization allowed H2O2 detection, imaging and quantification in HeLa cells. The polymer functionalized hybrid system creates a complete sensor including a ``cell positioning system'' in each single particle. The flexible synthetic concept with functionalization by post-polymerization modification allows introduction of various dyes for sensitisation at different wavelengths and introduction of various anchor groups for anchoring on different particles.We describe the reconstitution of apo-horse radish peroxidase (apo-HRP) onto TiO2 nanorods functionalized with a multifunctional polymer. After functionalization, the horse radish peroxidase (HRP) functionalized TiO2 nanorods were well dispersible in aqueous solution, catalytically active and biocompatible, and they could be used to quantify and image H2O2 which is a harmful secondary product of cellular metabolism. The shape, size and structure of TiO2 nanorods (anatase) were analyzed by transmission electron microscopy (TEM), high

  13. Phg1/TM9 proteins control intracellular killing of bacteria by determining cellular levels of the Kil1 sulfotransferase in Dictyostelium.

    Directory of Open Access Journals (Sweden)

    Marion Le Coadic

    Full Text Available Dictyostelium discoideum has largely been used to study phagocytosis and intracellular killing of bacteria. Previous studies have shown that Phg1A, Kil1 and Kil2 proteins are necessary for efficient intracellular killing of Klebsiella bacteria. Here we show that in phg1a KO cells, cellular levels of lysosomal glycosidases and lysozyme are decreased, and lysosomal pH is increased. Surprisingly, overexpression of Kil1 restores efficient killing in phg1a KO cells without correcting these lysosomal anomalies. Conversely, kil1 KO cells are defective for killing, but their enzymatic content and lysosomal pH are indistinguishable from WT cells. The killing defect of phg1a KO cells can be accounted for by the observation that in these cells the stability and the cellular amount of Kil1 are markedly reduced. Since Kil1 is the only sulfotransferase characterized in Dictyostelium, an (unidentified sulfated factor, defective in both phg1a and kil1 KO cells, may play a key role in intracellular killing of Klebsiella bacteria. In addition, Phg1B plays a redundant role with Phg1A in controlling cellular amounts of Kil1 and intracellular killing. Finally, cellular levels of Kil1 are unaffected in kil2 KO cells, and Kil1 overexpression does not correct the killing defect of kil2 KO cells, suggesting that Kil2 plays a distinct role in intracellular killing.

  14. Irreversibility of cellular senescence: dual roles of p16INK4a/Rb-pathway in cell cycle control

    Directory of Open Access Journals (Sweden)

    Hara Eiji

    2007-03-01

    Full Text Available Abstract The retinoblastoma (Rb tumor suppressor gene product, pRb, has an established role in the implementation of cellular senescence, the state of irreversible G1 cell cycle arrest provoked by diverse oncogenic stresses. In murine cells, senescence cell cycle arrest can be reversed by subsequent inactivation of pRb, indicating that pRb is required not only for the onset of cellular senescence, but also for the maintenance of senescence program in murine cells. However, in human cells, once pRb is fully activated by p16INK4a, senescence cell cycle arrest becomes irreversible and is no longer revoked by subsequent inactivation of pRb, suggesting that p16INK4a/Rb-pathway activates an alternative mechanism to irreversibly block the cell cycle in human senescent cells. Here, we discuss the molecular mechanism underlying the irreversibility of senescence cell cycle arrest and its potential towards tumor suppression.

  15. Evaluation of an Aqueous-Ethanolic Extract from Rosmarinus officinalis (Rosemary) for its Activity on the Hormonal and Cellular Function of Testes in Adult Male Rat

    OpenAIRE

    Heidari-Vala, Hamed; Ebrahimi Hariry, Reza; Sadeghi, Mohammad Reza; Akhondi, Mohammad Mehdi; Ghaffari Novin, Marefat; Heidari, Mahnaz

    2013-01-01

    Rosmarinus officinalis has been used in traditional medicine extensively. This study evaluated the hormonal and cellular effects of Rosmarinus officinalis extract on testes of adult rats. Thirty male Wistar rats (in three groups) received 50 or 100 mg/Kg b.w of Rosmarinus officinalis extract (made from the plant’s leaves, flower and stem) (treatment groups) and 10 mL/Kg b.w normal saline (control group) respectively, on a daily bases by gavage route for 60 days. Then, spermatological properti...

  16. Predictive functional control based on fuzzy T-S model for HVAC systems temperature control

    Institute of Scientific and Technical Information of China (English)

    Hongli L(U); Lei JIA; Shulan KONG; Zhaosheng ZHANG

    2007-01-01

    In heating,ventilating and air-conditioning(HVAC)systems,there exist severe nonlinearity,time-varying nature,disturbances and uncertainties.A new predictive functional control based on Takagi-Sugeno(T-S)fuzzy model was proposed to control HVAC systems.The T-S fuzzy model of stabilized controlled process was obtained using the least squares method,then on the basis of global linear predictive model from T-S fuzzy model,the process was controlled by the predictive functional controller.Especially the feedback regulation part was developed to compensate uncertainties of fuzzy predictive model.Finally simulation test results in HVAC systems control applications showed that the proposed fuzzy model predictive functional control improves tracking effect and robustness.Compared with the conventional PID controller,this control strategy has the advantages of less overshoot and shorter setting time,etc.

  17. GREEN‘S FUNCTION APPROACH IN APPROXIMATE CONTROLLABILITY PROBLEMS

    Directory of Open Access Journals (Sweden)

    Avetisyan A. S.

    2016-06-01

    Full Text Available A mathematical approach based on Green‘s function approach allowing to construct controls providing approximate controllability is suggested in the present paper. Representing the solution of governing system via Green’s formula and substituting it in prescribed terminal conditions, we obtain control functions providing approximate controllability of the system under study in explicit form. Choosing appropriate controls, we can provide required accuracy of approximation for prescribed conditions. Examples illustrating the procedure are described. Particularly, infinite string, controlled by a concentrated force, semi-infinite rod heated by a point heat source, finite rod heated from its boundary and parameter optimization for electrical circuit are considered. Results of computsations are brought.

  18. Controlled stochastic networks in heavy traffic: Convergence of value functions

    CERN Document Server

    Budhiraja, Amarjit; 10.1214/11-AAP784

    2012-01-01

    Scheduling control problems for a family of unitary networks under heavy traffic with general interarrival and service times, probabilistic routing and an infinite horizon discounted linear holding cost are studied. Diffusion control problems, that have been proposed as approximate models for the study of these critically loaded controlled stochastic networks, can be regarded as formal scaling limits of such stochastic systems. However, to date, a rigorous limit theory that justifies the use of such approximations for a general family of controlled networks has been lacking. It is shown that, under broad conditions, the value function of the suitably scaled network control problem converges to that of the associated diffusion control problem. This scaling limit result, in addition to giving a precise mathematical basis for the above approximation approach, suggests a general strategy for constructing near optimal controls for the physical stochastic networks by solving the associated diffusion control problem...

  19. Neural networks for function approximation in nonlinear control

    Science.gov (United States)

    Linse, Dennis J.; Stengel, Robert F.

    1990-01-01

    Two neural network architectures are compared with a classical spline interpolation technique for the approximation of functions useful in a nonlinear control system. A standard back-propagation feedforward neural network and a cerebellar model articulation controller (CMAC) neural network are presented, and their results are compared with a B-spline interpolation procedure that is updated using recursive least-squares parameter identification. Each method is able to accurately represent a one-dimensional test function. Tradeoffs between size requirements, speed of operation, and speed of learning indicate that neural networks may be practical for identification and adaptation in a nonlinear control environment.

  20. Gain of cellular adaptation due to prolonged p53 impairment leads to functional switchover from p53 to p73 during DNA damage in acute myeloid leukemia cells.

    Science.gov (United States)

    Chakraborty, Juni; Banerjee, Shuvomoy; Ray, Pallab; Hossain, Dewan Md Sakib; Bhattacharyya, Sankar; Adhikary, Arghya; Chattopadhyay, Sreya; Das, Tanya; Sa, Gaurisankar

    2010-10-22

    Tumor suppressor p53 plays the central role in regulating apoptosis in response to genotoxic stress. From an evolutionary perspective, the activity of p53 has to be backed up by other protein(s) in case of any functional impairment of this protein, to trigger DNA damage-induced apoptosis in cancer cells. We adopted multiple experimental approaches to demonstrate that in p53-impaired cancer cells, DNA damage caused accumulation of p53 paralogue p73 via Chk-1 that strongly impacted Bax expression and p53-independent apoptosis. On the contrary, when p53 function was restored by ectopic expression, Chk-2 induced p53 accumulation that in turn overshadowed p73 activity, suggesting an antagonistic interaction between p53 family members. To understand such interaction better, p53-expressing cells were impaired differentially for p53 activity. In wild-type p53-expressing cancer cells that were silenced for p53 for several generations, p73 was activated, whereas no such trend was observed when p53 was transiently silenced. Prolonged p53 interference, even in functional p53 settings, therefore, leads to the "gain of cellular adaptation" in a way that alters the cellular microenvironment in favor of p73 activation by altering p73-regulatory proteins, e.g. Chk1 activation and dominant negative p73 down-regulation. These findings not only unveil a hitherto unexplained mechanism underlying the functional switchover from p53 to p73, but also validate p73 as a promising and potential target for cancer therapy in the absence of functional p53.

  1. Allele-specific Gene Silencing of Mutant mRNA Restores Cellular Function in Ullrich Congenital Muscular Dystrophy Fibroblasts

    Directory of Open Access Journals (Sweden)

    Satoru Noguchi

    2014-01-01

    Full Text Available Ullrich congenital muscular dystrophy (UCMD is an inherited muscle disorder characterized clinically by muscle weakness, distal joint hyperlaxity, and proximal joint contractures. Sporadic and recessive mutations in the three collagen VI genes, COL6A1, COL6A2, and COL6A3, are reported to be causative. In the sporadic forms, a heterozygous point mutation causing glycine substitution in the triple helical domain has been identified in higher rate. In this study, we examined the efficacy of siRNAs, which target point mutation site, on specific knockdown toward transcripts from mutant allele and evaluated consequent cellular phenotype of UCMD fibroblasts. We evaluated the effect of siRNAs targeted to silence-specific COL6A1 alleles in UCMD fibroblasts, where simultaneous expression of both wild-type and mutant collagen VI resulted in defective collagen localization. Addition of mutant-specific siRNAs allowed normal extracellular localization of collagen VI surrounding fibroblasts, suggesting selective inhibition of mutant collagen VI. Targeting the single-nucleotide COL6A1 c.850G>A (p.G284R mutation responsible a sporadic autosomal dominant form of UCMD can potently and selectively block expression of mutant collagen VI. These results suggest that allele-specific knockdown of the mutant mRNA can potentially be considered as a therapeutic procedure in UCMD due to COL6A1 point mutations.

  2. Stem cell function and stress response are controlled by protein synthesis.

    Science.gov (United States)

    Blanco, Sandra; Bandiera, Roberto; Popis, Martyna; Hussain, Shobbir; Lombard, Patrick; Aleksic, Jelena; Sajini, Abdulrahim; Tanna, Hinal; Cortés-Garrido, Rosana; Gkatza, Nikoletta; Dietmann, Sabine; Frye, Michaela

    2016-06-15

    Whether protein synthesis and cellular stress response pathways interact to control stem cell function is currently unknown. Here we show that mouse skin stem cells synthesize less protein than their immediate progenitors in vivo, even when forced to proliferate. Our analyses reveal that activation of stress response pathways drives both a global reduction of protein synthesis and altered translational programmes that together promote stem cell functions and tumorigenesis. Mechanistically, we show that inhibition of post-transcriptional cytosine-5 methylation locks tumour-initiating cells in this distinct translational inhibition programme. Paradoxically, this inhibition renders stem cells hypersensitive to cytotoxic stress, as tumour regeneration after treatment with 5-fluorouracil is blocked. Thus, stem cells must revoke translation inhibition pathways to regenerate a tissue or tumour.

  3. Treatment with 1,25-dihydroxyvitamin D3 reduces impairment of human osteoblast functions during cellular aging in culture

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Rattan, Suresh; Clark, Brian F.C.

    2001-01-01

    of alkaline phosphatase (AP: 68%), osteocalcin (OC: 67%), and collagen type I (ColI: 76%) in in vitro senescent late-passage cells compared to early-passage cells, suggesting an in vitro age-related impairment of osteoblast functions. We hypothesized that decreased osteoblast functions with in vitro aging......Adequate responses to various hormones, such as 1,25-dihydroxyvitamin D(3) (calcitriol) are a prerequisite for optimal osteoblast functions. We have previously characterized several human diploid osteoblastic cell lines that exhibit typical in vitro aging characteristics during long......-term subculturing. In order to study in vitro age-related changes in osteoblast functions, we compared constitutive mRNA levels of osteoblast-specific genes in early-passage ( 90% lifespan completed). We found a significant reduction in mRNA levels...

  4. CONTROLLED ANIONIC SYNTHESIS OF FUNCTIONALIZED AND STAR-BRANCHED POLYMERS

    Institute of Scientific and Technical Information of China (English)

    RODERIC P. QUIRK; YIN Jian; GUO Shaohua; HU Xiaowei; GABRIEL SUMMERS; KIM Jungahn; ZHU Linfang; LAUREL E. SCHOCK

    1990-01-01

    The use of living, alkyllithium-initiated anionic polymerization to prepare chain-end functionalized polymers and heteroarm, star- branched polymers is discussed. The scope and limitations of specific termination reactions with a variety of electrophilic species are illustrated for carbonation, hydroxyethylation,amination, and sulfonation. The methodology of using substituted 1,1- diphenylethylenes to provide a general, quantitative functionalization procedure is outlined and illustrated with examples of amine and phenol end-functionalization. A methodology is described for the synthesis of functionalized,star-branched copolymers with compositionally heterogeneous arms of controlled molecular weight and narrow molecular weight distribution using 1, 3-bis (1-phenylethenyl) benzene.

  5. Store-operated Ca2+ entry does not control proliferation in primary cultures of human metastatic renal cellular carcinoma.

    Science.gov (United States)

    Dragoni, Silvia; Turin, Ilaria; Laforenza, Umberto; Potenza, Duilio Michele; Bottino, Cinzia; Glasnov, Toma N; Prestia, Martina; Ferulli, Federica; Saitta, Anna; Mosca, Alessandra; Guerra, Germano; Rosti, Vittorio; Luinetti, Ombretta; Ganini, Carlo; Porta, Camillo; Pedrazzoli, Paolo; Tanzi, Franco; Montagna, Daniela; Moccia, Francesco

    2014-01-01

    Store-operated Ca(2+) entry (SOCE) is activated following depletion of the inositol-1,4,5-trisphosphate (InsP3)-sensitive Ca(2+) pool to regulate proliferation in immortalized cell lines established from either primary or metastatic lesions. The molecular nature of SOCE may involve both Stim1, which senses Ca(2+) levels within the endoplasmic reticulum (ER) Ca(2+) reservoir, and a number of a Ca(2+)-permeable channels on the plasma membrane, including Orai1, Orai3, and members of the canonical transient receptor (TRPC1-7) family of ion channels. The present study was undertaken to assess whether SOCE is expressed and controls proliferation in primary cultures isolated from secondary lesions of heavily pretreated metastatic renal cell carcinoma (mRCC) patients. SOCE was induced following pharmacological depletion of the ER Ca(2+) store, but not by InsP3-dependent Ca(2+) release. Metastatic RCC cells express Stim1-2, Orai1-3, and TRPC1-7 transcripts and proteins. In these cells, SOCE was insensitive to BTP-2, 10 µM Gd(3+) and Pyr6, while it was inhibited by 100 µM Gd(3+), 2-APB, and carboxyamidotriazole (CAI). Neither Gd(3+) nor 2-APB or CAI impaired mRCC cell proliferation. Consistently, no detectable Ca(2+) signal was elicited by growth factor stimulation. Therefore, a functional SOCE is expressed but does not control proliferation of mRCC cells isolated from patients resistant to multikinase inhibitors.

  6. Store-Operated Ca2+ Entry Does Not Control Proliferation in Primary Cultures of Human Metastatic Renal Cellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Silvia Dragoni

    2014-01-01

    Full Text Available Store-operated Ca2+ entry (SOCE is activated following depletion of the inositol-1,4,5-trisphosphate (InsP3-sensitive Ca2+ pool to regulate proliferation in immortalized cell lines established from either primary or metastatic lesions. The molecular nature of SOCE may involve both Stim1, which senses Ca2+ levels within the endoplasmic reticulum (ER Ca2+ reservoir, and a number of a Ca2+-permeable channels on the plasma membrane, including Orai1, Orai3, and members of the canonical transient receptor (TRPC1–7 family of ion channels. The present study was undertaken to assess whether SOCE is expressed and controls proliferation in primary cultures isolated from secondary lesions of heavily pretreated metastatic renal cell carcinoma (mRCC patients. SOCE was induced following pharmacological depletion of the ER Ca2+ store, but not by InsP3-dependent Ca2+ release. Metastatic RCC cells express Stim1-2, Orai1–3, and TRPC1–7 transcripts and proteins. In these cells, SOCE was insensitive to BTP-2, 10 µM Gd3+ and Pyr6, while it was inhibited by 100 µM Gd3+, 2-APB, and carboxyamidotriazole (CAI. Neither Gd3+ nor 2-APB or CAI impaired mRCC cell proliferation. Consistently, no detectable Ca2+ signal was elicited by growth factor stimulation. Therefore, a functional SOCE is expressed but does not control proliferation of mRCC cells isolated from patients resistant to multikinase inhibitors.

  7. Test-specific control conditions for functional analyses.

    Science.gov (United States)

    Fahmie, Tara A; Iwata, Brian A; Querim, Angie C; Harper, Jill M

    2013-01-01

    Most functional analyses of problem behavior include a common condition (play or noncontingent reinforcement) as a control for both positive and negative reinforcement. However, test-specific conditions that control for each potential source of reinforcement may be beneficial occasionally. We compared responding during alone, ignore, play, and differential reinforcement of other behavior (DRO) control conditions for individuals whose problem behavior was maintained by positive or negative reinforcement. Results showed that all of the conditions were effective controls for problem behavior maintained by positive reinforcement; however, the DRO condition was consistently ineffective as a control for problem behavior maintained by negative reinforcement. Implications for the design of functional analyses and future research are discussed.

  8. Cellular function and pathological role of ATP13A2 and related P-type transport ATPases in Parkinson's disease and other neurological disorders

    DEFF Research Database (Denmark)

    van Veen, Sarah; Sørensen, Danny M.; Holemans, Tine;

    2014-01-01

    . To discuss the role of ATP13A2 in neurodegeneration, we first provide a short description of the architecture and transport mechanism of P-type transport ATPases. Then, we briefly highlight key P-type ATPases involved in neuronal disorders such as the copper transporters ATP7A (Menkes disease), ATP7B (Wilson...... disease), the Na+/K+-ATPases ATP1A2 (familial hemiplegic migraine) and ATP1A3 (rapid-onset dystonia parkinsonism). Finally, we review the recent literature of ATP13A2 and discuss ATP13A2's putative cellular function in the light of what is known concerning the functions of other, better-studied P...

  9. The study of non-fouling and non-specific cellular binding on functionalized surface for mammalian cell identification and manipulation

    Science.gov (United States)

    Zainudin, Nor Syuhada; Hambali, Nor Azura Malini Ahmad; Wahid, Mohamad Halim Abd; Retnasamy, Vithyacharan; Shahimin, Mukhzeer Mohamad

    2017-04-01

    Surface functionalization has emerged as a powerful tool for mapping limitless surface-cell membrane interaction in diverse biomolecular applications. Inhibition of non-specific biomolecular and cellular adhesion to solid surfaces is critical in improving the performance of some biomedical devices, particularly for in vitro bioassays. Some factors have to be paid particular attention in determining the right surface modification which are the types of surface, the methods and chemical solution that being used during the experimentation and also tools for analyzing the results. Improved surface functionalization technologies that provide better non-fouling performance in conjunction with specific attachment chemistries are sought for these applications. Hence, this paper serves as a review for multiple surface treatment methods including PEG grafting, adsorptive chemistries, self-assembled monolayers (SAMs) and plasma treatments.

  10. Functionalized graphene oxide serves as a novel vaccine nano-adjuvant for robust stimulation of cellular immunity

    Science.gov (United States)

    Xu, Ligeng; Xiang, Jian; Liu, Ye; Xu, Jun; Luo, Yinchan; Feng, Liangzhu; Liu, Zhuang; Peng, Rui

    2016-02-01

    Benefiting from their unique physicochemical properties, graphene derivatives have attracted great attention in biomedicine. In this study, we carefully engineered graphene oxide (GO) as a vaccine adjuvant for immunotherapy using urease B (Ure B) as the model antigen. Ure B is a specific antigen for Helicobacter pylori, which is a class I carcinogen for gastric cancer. Polyethylene glycol (PEG) and various types of polyethylenimine (PEI) were used as coating polymers. Compared with single-polymer modified GOs (GO-PEG and GO-PEI), certain dual-polymer modified GOs (GO-PEG-PEI) can act as a positive modulator to promote the maturation of dendritic cells (DCs) and enhance their cytokine secretion through the activation of multiple toll-like receptor (TLR) pathways while showing low toxicity. Moreover, this GO-PEG-PEI can serve as an antigen carrier to effectively shuttle antigens into DCs. These two advantages enable GO-PEG-PEI to serve as a novel vaccine adjuvant. In the subsequent in vivo experiments, compared with free Ure B and clinically used aluminum-adjuvant-based vaccine (Alum-Ure B), GO-PEG-PEI-Ure B induces stronger cellular immunity via intradermal administration, suggesting promising applications in cancer immunotherapy. Our work not only presents a novel, highly effective GO-based vaccine nano-adjuvant, but also highlights the critical roles of surface chemistry for the rational design of nano-adjuvants.Benefiting from their unique physicochemical properties, graphene derivatives have attracted great attention in biomedicine. In this study, we carefully engineered graphene oxide (GO) as a vaccine adjuvant for immunotherapy using urease B (Ure B) as the model antigen. Ure B is a specific antigen for Helicobacter pylori, which is a class I carcinogen for gastric cancer. Polyethylene glycol (PEG) and various types of polyethylenimine (PEI) were used as coating polymers. Compared with single-polymer modified GOs (GO-PEG and GO-PEI), certain dual

  11. Investigation of microgravity effects on basic imune functions on the cellular level - The TRIPLELUX-B experiment

    Science.gov (United States)

    Unruh, Eckehardt; Hansen, Peter-Diedrich

    Hemocytes are the primary defence of the Blue Mussel against invading microorganisms and foreign particles. The hemocytes of mussels as part of the immune system of invertebrates has not been studied so far in space. The choice of the phagocytes from invertebrates is justified by the claim to study the universal validity of innate immune responses. The hemocytes of mussels have a lot in common with macrophages of higher organisms. They are able to detect the presence of microorganisms and kill these microorganisms by phagocytosis. The phagocy-tosis related production of ROS will be stimulated with opsonised zymosan. The hemocytes will be stored frozen and reconstituted in-flight for the experiment. The signals of the im-muno cellular responses are translated into luminescence as a rapid optical reporter system. The primary aim of Triplelux B is to investigate under space flight conditions the effect of microgravity on the ability of isolated Blue Mussel hemocytes to perform phagocytosis. As a secondery objectiv, the results expected will allow to conclude whether the observed responses are caused by microgravity and/or radiation (change in permeability, endpoints in genotoxicity: DNA unwinding). The TRIPLELUX-B Experiment contributes to risk assessment concerning immunotoxicity under space flight conditions. The components of the fully automated AEC (Advanced Experimental Containment) will be demonstrated. The AEC of the TRIPLELUX-B experiment will contribute to a real time operational monitoring for immunotoxicity testing for earth. Blue mussels have been used repeatedly for monitoring imunotoxicity and genotoxicity in coastal waters. Based on the AEC an automatet measuring device will allow "real time monitoring" providing observations of immunotoxicity in coastal and inland waters.

  12. Qualitative Functional Decomposition Analysis of Evolved Neuromorphic Flight Controllers

    Directory of Open Access Journals (Sweden)

    Sanjay K. Boddhu

    2012-01-01

    Full Text Available In the previous work, it was demonstrated that one can effectively employ CTRNN-EH (a neuromorphic variant of EH method methodology to evolve neuromorphic flight controllers for a flapping wing robot. This paper describes a novel frequency grouping-based analysis technique, developed to qualitatively decompose the evolved controllers into explainable functional control blocks. A summary of the previous work related to evolving flight controllers for two categories of the controller types, called autonomous and nonautonomous controllers, is provided, and the applicability of the newly developed decomposition analysis for both controller categories is demonstrated. Further, the paper concludes with appropriate discussion of ongoing work and implications for possible future work related to employing the CTRNN-EH methodology and the decomposition analysis techniques presented in this paper.

  13. A Goal-Function Approach to Analysis of Control Situations

    DEFF Research Database (Denmark)

    Lind, Morten

    2010-01-01

    The concept of situations plays a central role in all theories of meaning and context. and serve to frame or group events and other occurrences into coherent meaningful wholes. Situations are typed, may be interconnected and organized into higher level structures. In operation of industrial...... processes situations should identify operational aspects relevant for control agent’s decision making in plant supervision and control. Control situations can be understood as recurrent and interconnected patterns of control with important implications for control and HMI design. Goal-Function approaches...... to systems modeling like Multilevel Flow Modeling can be used to represent control situations. The paper will describe an action theoretical foundation for MFM and its use for the development of a theory of control situations....

  14. Adolescence methylphenidate treatment in a rodent model of attention deficit/hyperactivity disorder: Dopamine transporter function and cellular distribution in adulthood

    Science.gov (United States)

    Somkuwar, Sucharita S.; Darna, Mahesh; Kantak, Kathleen M.; Dwoskin, Linda P.

    2013-01-01

    Attention deficit/hyperactivity disorder (ADHD) is attributed to dysfunction of the prefrontal cortex. Methylphenidate, an inhibitor of dopamine and norepinephrine transporters (DAT and NET, respectively), is a standard treatment for ADHD. The Spontaneously Hypertensive Rat (SHR) is a well-established animal model of ADHD. Our previous results showed that methylphenidate treatment in adolescent SHR enhanced cocaine self-administration during adulthood, and alterations in DAT function in prefrontal cortex play a role in this response. Importantly, prefrontal cortex subregions, orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC), have been shown to have distinct roles in ADHD and cocaine self-administration. In the current study, SHR, Wistar-Kyoto (WKY) and Wistar (WIS) rats received a therapeutically relevant dose of methylphenidate (1.5 mg/kg, p.o.) or vehicle during adolescence and then OFC and mPFC DAT function and cellular expression were assessed during adulthood. In both OFC and mPFC, no strain differences in Vmax or Km for dopamine uptake into synaptosomes were found between vehicle-treated SHR, WKY and WIS. Methylphenidate increased DAT Vmax in SHR mPFC and decreased DAT Vmax in WKY OFC. Also, methylphenidate decreased DAT Km in WIS OFC. Further, methylphenidate did not alter DAT cellular localization, indicating that methylphenidate treatment during adolescence regulated DAT function in SHR mPFC in a traffickingindependent manner. Thus, the increase in mPFC DAT function was an SHR-specific long term consequence of methylphenidate treatment during adolescence, which may be responsible for the treatment-induced alterations in behavior including the observed increases in cocaine self-administration. PMID:23623751

  15. Predictive functional control of integrating process based on impulse response

    Institute of Scientific and Technical Information of China (English)

    Bin ZHANG; Ping LI; Weidong ZHANG

    2004-01-01

    The predictive model is built according to the characteristics of the impulse response of integrating process. In order to eliminate the permanent offset between the setpoint and the process output in the presence of the load disturbance, a novel error compensation method is proposed. Then predictive functional control of integrating process is designed. The method given generates a simple control structure, which can significantly reduce online computation. Furthermore, the tuning of the controller is fairly straightforward. Simulation results indicate that the designed control system is relatively robust to the parameters variation of the process.

  16. Understanding the Form, Function, and Logic of Clandestine Cellular Networks: The First Step in Effective Counternetwork Operations

    Science.gov (United States)

    2009-04-01

    form, function, and logic is derived from Gilles Deleuze and Felix Guattari, A Thousand Plateaus; Capitalism and Schizophreni, (Minneapolis: University...February 8, 2009]. Deleuze , Gilles and Felix Guattari. A Thousand Plateaus; Capitalism and Schizophrenia. Minneapolis: University of Minnesota Press, 1987

  17. The Kunitz-protease inhibitor domain in amyloid precursor protein reduces cellular mitochondrial enzymes expression and function.

    Science.gov (United States)

    Chua, Li-Min; Lim, Mei-Li; Wong, Boon-Seng

    2013-08-09

    Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD) and this can be contributed by aberrant metabolic enzyme function. But, the mechanism causing this enzymatic impairment is unclear. Amyloid precursor protein (APP) is known to be alternatively spliced to produce three major isoforms in the brain (APP695, APP751, APP770). Both APP770 and APP751 contain the Kunitz Protease Inhibitory (KPI) domain, but the former also contain an extra OX-2 domain. APP695 on the other hand, lacks both domains. In AD, up-regulation of the KPI-containing APP isoforms has been reported. But the functional contribution of this elevation is unclear. In the present study, we have expressed and compared the effect of the non-KPI containing APP695 and the KPI-containing APP751 on mitochondrial function. We found that the KPI-containing APP751 significantly decreased the expression of three major mitochondrial metabolic enzymes; citrate synthase, succinate dehydrogenase and cytochrome c oxidase (COX IV). This reduction lowers the NAD(+)/NADH ratio, COX IV activity and mitochondrial membrane potential. Overall, this study demonstrated that up-regulation of the KPI-containing APP isoforms is likely to contribute to the impairment of metabolic enzymes and mitochondrial function in AD. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. From understanding cellular function to novel drug discovery: the role of planar patch-clamp array chip technology

    Directory of Open Access Journals (Sweden)

    Christophe ePy

    2011-10-01

    Full Text Available All excitable cell functions rely upon ion channels that are embedded in their plasma membrane. Perturbations of ion channel structure or function result in pathologies ranging from cardiac dysfunction to neurodegenerative disorders. Consequently, to understand the functions of excitable cells and to remedy their pathophysiology, it is important to understand the ion channel functions under various experimental conditions – including exposure to novel drug targets. Glass pipette patch-clamp is the state of the art technique to monitor the intrinsic and synaptic properties of neurons. However, this technique is labor-intensive and has low data throughput. Planar patch-clamp chips, integrated into automated systems, offer high throughputs but are limited to isolated cells from suspensions, resulting in questionable models of true physiological function, and are unsuitable for studies involving neuronal communication. Multi-electrode arrays (MEA, in contrast, have the ability to monitor network activity by measuring local field potentials from multiple extracellular sites, but specific ion channel activity is challenging to extract from these multiplexed signals. Here we describe a novel planar patch-clamp chip technology that enables the simultaneous high resolution electrophysiological interrogation of individual neurons at multiple sites in synaptically connected neuronal networks, thereby combining the advantages of MEA and patch-clamp techniques. Each neuron can be probed through an aperture that connects to a dedicated subterranean microfluidic channel. Neurons growing in networks are aligned to the apertures by physisorbed or chemisorbed chemical cues. In this review, we describe the design and fabrication process of these chips, the approach to the chemical patterning for cell placement, and present physiological data from cultured neuronal cells.

  19. The impulse influence function for de-centralized control

    Institute of Scientific and Technical Information of China (English)

    ZHONG Wanxie

    2004-01-01

    Impulse influence matrix function is introduced based on that the de-centralized control analysis is analogous to the sub-structural analysis in structural mechanics. The static sub-structural analysis is analogous to the usual de-centralized control, whereas the dynamic sub-structural analysis corresponds to the de-centralized control theory. The reciprocal symmetry for the impulse influence matrix function is proved, and is solved by the precise integration method for time invariant system, giving the results up to computer precision. Based on the impulse influence functions of subsystems, the combination of subsystems can lead to a set of integral equations and be solved numerically. Numerical example demonstrates the effectiveness of the method.

  20. Generation of Polynomial Control Function and Polynomial Lyapunov Function on a Simplex and Simplicial Complex

    DEFF Research Database (Denmark)

    Ribard, Nicolas; Wisniewski, Rafael; Sloth, Christoffer

    2016-01-01

    In the paper, we strive to develop an algorithm that simultaneously computes a polynomial control and a polynomial Lyapunov function. This ensures asymptotic stability of the designed feedback system. The above problem is translated to a certificate of positivity. To this end, we use the represen......In the paper, we strive to develop an algorithm that simultaneously computes a polynomial control and a polynomial Lyapunov function. This ensures asymptotic stability of the designed feedback system. The above problem is translated to a certificate of positivity. To this end, we use...... the representation of the given control sy