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Sample records for cellular function saibo

  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. [Photodynamic modulation of cellular functions].

    Science.gov (United States)

    Li, Yuan; Jiang, Hong-Ning; Cui, Zong-Jie

    2016-08-25

    Photodynamic action, due to the rather limited lifetime (1 μs) and effective reactive distance of singlet oxygen (lysosomes or endoplasmic reticulum can modulate photodynamically subcellular functions and fine-tune protein activity by targeted photooxidation. With the newly emerged active illumination technique, simultaneous photodynamic action localized at multiple sites is now possible, and the contribution of subcellular regions to the whole cell or individual cells to a cell cluster could be quantitated. Photodynamic action with protein photosensitiser will be a powerful tool for nano-manipulation in cell physiology research. PMID:27546513

  3. Mapping functional connectivity in cellular networks

    OpenAIRE

    Buibas, Marius

    2011-01-01

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

  4. 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.)

  5. Cellular Functions of Transient Receptor Potential channels

    OpenAIRE

    Dadon, Daniela; Minke, Baruch

    2010-01-01

    Transient Receptor Potential channels are polymodal cellular sensors involved in a wide variety of cellular processes, mainly by increasing cellular Ca2+. In this review we focus on the roles of these channels in: i) cell death ii) proliferation and differentiation and iii) synaptic vesicle release.

  6. Microgravity and Cellular Consequences in Lymphocyte Function

    Science.gov (United States)

    Pellis, Neal R.; Sundaresan, Alamelu

    2004-01-01

    Mammalian cells adapt to the environment of low gravity and express a series of responses, some possibly from direct effects on cells and others based on environmental conditions created by microgravity. Human lymphocytes in microgravity culture are functionally diminished in activation and locomotion. Both processes are integral to optimal immune response to fight pathogens. The NASA Rotating-wall vessel (RWV) is a well-accepted analog for microgravity culture on the ground. Gene array experiments and immunoblotting identified upstream events in human lymphocytes adapting to microgravity analog culture. Microgravity induces selective changes, many of which are cell membrane related. Results showed that upstream of PKC in the T cell activation cascade, PLC-gamma and LAT are significantly diminished. ZAP 70 which controls LAT activation is also down regulated in modeled microgravity. Thus events governing cell shape might warrant attention in microgravity conditions. The goal of this study is to delineate response suites that are consequential, direct or indirect effects of the microgravity environment and which of these are essential to lymphocytes

  7. 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.

  8. 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.

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

    Science.gov (United States)

    Radbruch, Helena; Bremer, Daniel; Mothes, Ronja; Günther, Robert; Rinnenthal, Jan Leo; Pohlan, Julian; Ulbricht, Carolin; Hauser, Anja E; Niesner, Raluca

    2015-01-01

    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. PMID:26006244

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

    OpenAIRE

    Helena Radbruch; Daniel Bremer; Ronja Mothes; Robert Günther; Jan Leo Rinnenthal; Julian Pohlan; Carolin Ulbricht; Hauser, Anja E.; Raluca Niesner

    2015-01-01

    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 o...

  11. 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.

  12. 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. PMID:26999422

  13. Role of XPD in cellular functions: To TFIIH and beyond.

    Science.gov (United States)

    Houten, Bennett Van; Kuper, Jochen; Kisker, Caroline

    2016-08-01

    XPD, as part of the TFIIH complex, has classically been linked to the damage verification step of nucleotide excision repair (NER). However, recent data indicate that XPD, due to its iron-sulfur center interacts with the iron sulfur cluster assembly proteins, and may interact with other proteins in the cell to mediate a diverse set of biological functions including cell cycle regulation, mitosis, and mitochondrial function. In this perspective, after first reviewing the function and some of the key disease causing variants that affect XPD's interaction with TFIIH and the CDK-activating kinase complex (CAK), we investigate these intriguing cellular roles of XPD and highlight important unanswered questions that provide a fertile ground for further scientific exploration. PMID:27262611

  14. Computer Modeling of the Earliest Cellular Structures and Functions

    Science.gov (United States)

    Pohorille, Andrew

    2000-03-01

    In the absence of extinct or extant record of protocells (the earliest ancestors of contemporary cells), the most direct way to test ourunderstanding of the origin of cellular life is to construct laboratory models of protocells. Such efforts are currently underway in the NASA Astrobiology Program. They are accompanied by computational studies aimed at explaining self-organization of simple molecules into ordered structures and developing designs for molecules that perform protocellular functions. Many of these functions, such as import of nutrients, capture and storage of energy, and response to changes in the environment are carried out by proteins bound to membranes. We will discuss a series of large-scale, molecular-level computer simulations which demonstrate (a) how small proteins (peptides)organize themselves into ordered structures at water-membrane interfaces and insert into membranes, (b) how these peptides aggregate to form membrane-spanning structures (e.g. channels), and (c) by what mechanisms such aggregates perform essential protocellular functions, such as proton transport of protons across cell walls, a key step in cellular bioenergetics. The simulations were performed using the molecular dynamics method, in which Newton's equations of motion for each atom in the system are solved iteratively. The problems of interest required simulations on multi-nanosecond time scales, which corresponded to 10^6-10^8 time steps.

  15. 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.

  16. PEG functionalized luminescent lipid particles for cellular imaging

    Science.gov (United States)

    Rana, Suman; Barick, K. C.; Shetake, Neena G.; Verma, Gunjan; Aswal, V. K.; Panicker, Lata; Pandey, B. N.; Hassan, P. A.

    2016-08-01

    We report here the synthesis, characterization and cellular uptake of luminescent micelle-like particles with phospholipid core and non-ionic PEG based surfactant polysorbate 80 shell. The adsorption of polysorbate 80 at the interface of lipid containing microemulsion droplets and its solidification upon removal of solvent leads to anchoring of PEG chain to the lipid particles. Hydrophobic partitioning of luminescent molecules, sodium 3-hydroxynaphthalene-2-carboxylic acid to the phospholipid core offers additional functionality to these particles. Thus, the cooperative assembly of lipid, non-ionic amphiphile and organic luminescent probe leads to the formation of multifunctional biocompatible particles which are useful for simultaneous imaging and therapy.

  17. Electrostatic bio-manipulation for the modification of cellular functions

    Science.gov (United States)

    Washizu, Masao

    2013-03-01

    The use of electrostatic field effects, including field-induced reversible-breakdown of the membrane and dielectrophoresis (DEP), in microfabricated structures are investigated. With the use of field constriction created by a micro-orifice whose diameter is smaller than the cells, controlled magnitude of pulsed voltage can be applied across the cell membrane regardless of the cell size, shape or orientation. As a result, the breakdown occurs reproducibly and with minimal invasiveness. The breakdown is used for two purposes, electroporation by which foreign substances can be fed into cells, and electrofusion which creates genetic and/or cytoplasmic mixture among two cells. When GFP plasmid is fed into MSC cell, the gene expression started within 2 hours, and finally observed in more than 50% of cells. For cell fusion, several ten percent fusion yield is achieved for most cell types, with the colony formation in several percents. Timing-controlled feeding foreign substances or mixing cellular contents, with high-yield and low-invasiveness, is expected to bring about a new technology for both genetic and epigenetic modifications of cellular functions, in such field as regenerative medicine.

  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 functions of vaults and their involvement in multidrug resistance.

    Science.gov (United States)

    Steiner, E; Holzmann, K; Elbling, L; Micksche, M; Berger, W

    2006-08-01

    Vaults are evolutionary highly conserved ribonucleoprotein (RNP) particles with a hollow barrel-like structure. They are 41 x 73 nm in size and are composed of multiple copies of three proteins and small untranslated RNA (vRNA). The main component of vaults represents the 110 kDa major vault protein (MVP), whereas the two minor vault proteins comprise the 193 kDa vault poly(ADP-ribose) polymerase (VPARP) and the 240 kDa telomerase-associated protein-1 (TEP1). Vaults are abundantly present in the cytoplasm of eukaryotic cells and they were found to be associated with cytoskeletal elements as well as occasionally with the nuclear envelope. Vaults and MVP have been associated with several cellular processes which are also involved in cancer development like cell motility and differentiation. Due to the over-expression of MVP (also termed lung resistance-related protein or LRP) in several P-glycoprotein (P-gp)-negative chemoresistant cancer cell lines, vaults have been linked to multidrug resistance (MDR). Accordingly, high levels of MVP were found in tissues chronically exposed to xenobiotics. In addition, the expression of MVP correlated with the degree of malignancy in certain cancer types, suggesting a direct involvement in tumor development and/or progression. Based on the finding that MVP binds several phosphatases and kinases including PTEN, SHP-2 as well as Erk, evidence is accumulating that MVP might be involved in the regulation of important cell signalling pathways including the PI3K/Akt and the MAPK pathways. In this review we summarize the current knowledge concerning the vault particle and discuss its possible cellular functions, focusing on the role of vaults in chemotherapy resistance. PMID:16918321

  20. 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.

  1. Cellular function of neuropathy target esterase in lysophosphatidylcholine action

    International Nuclear Information System (INIS)

    Neuropathy target esterase (NTE) plays critical roles in embryonic development and maintenance of peripheral axons. It is a secondary target of some organophosphorus toxicants including analogs of insecticides and chemical warfare agents. Although the mechanistic role of NTE in vivo is poorly defined, it is known to hydrolyze lysophosphatidylcholine (LPC) in vitro and may protect cell membranes from cytotoxic accumulation of LPC. To determine the cellular function of NTE, Neuro-2a and COS-7 cells were transfected with a full-length human NTE-containing plasmid yielding recombinant NTE (rNTE). We find the same inhibitor sensitivity and specificity profiles for rNTE assayed with LPC or phenyl valerate (a standard NTE substrate) and that this correlation extends to the LPC hydrolases of human brain, lymphocytes and erythrocytes. All of these LPC hydrolases are therefore very similar to each other in respect to a conserved inhibitor binding site conformation. NTE is expressed in brain and lymphocytes and contributes to LPC hydrolase activities in these tissues. The enzyme or enzymes responsible for erythrocyte LPC hydrolase activity remain to be identified. We also show that rNTE protects Neuro-2a and COS-7 cells from exogenous LPC cytotoxicity. Expression of rNTE in Neuro-2a cells alters their phospholipid balance (analyzed by liquid chromatography-mass spectrometry with single ion monitoring) by lowering LPC-16:0 and LPC-18:0 and elevating glycerophosphocholine without a change in phosphatidylcholine-16:0/18:1 or 16:0/18:2. NTE therefore serves an important function in LPC homeostasis and action

  2. Eukaryotic protein domains as functional units of cellular evolution

    DEFF Research Database (Denmark)

    Jin, Jing; Xie, Xueying; Chen, Chen;

    2009-01-01

    of different domain types to assess the molecular compartment occupied by each domain. This reveals that specific subsets of domains demarcate particular cellular processes, such as growth factor signaling, chromatin remodeling, apoptotic and inflammatory responses, or vesicular trafficking. We suggest...

  3. Cellular interactions during tracheary elements formation and function

    OpenAIRE

    Menard, Delphine; Pesquet, Edouard

    2015-01-01

    The survival of higher plant species on land depends on the development and function of an efficient vascular system distributing water and minerals absorbed by roots to all aerial organs. This conduction and distribution of plant sap relies on specialized cells named tracheary elements (TEs). In contrast to many other cell types in plants, TEs are functionalized by cell death that hollows the cell protoplast to make way for the sap. To maintain a stable conducting function during plant devel...

  4. Leading research on cell proliferation regulation technology; Saibo zoshoku seigyo gijutsu no sendo kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    For developing intelligent material, animal test alternative model, bio-cell analysis equipment, self-controlling bio-reactor and medical material, development of functional cells was studied by cell proliferation regulation technology. In fiscal 1996, the expression analysis and separation technology of specific gene for cell proliferation, and the intracellular regulation technology were surveyed from the viewpoint of intracellular regulation. The cell proliferation regulation technology by specific regulating material of cells, extracellular matrix, coculture system and embryonic cell was surveyed from the viewpoint of extracellular regulation. In addition, based on these survey results, new cell culture/analysis technology, new bio-material, artificial organ system, energy saving bio-reactor, environment purification microorganism, and animal test alternative model were surveyed as applications to industrial basic technologies from a long-term viewpoint. The approach to cell proliferation regulation requires preparation of a concrete proliferation regulation technology system of cells, and concrete application targets. 268 refs., 43 figs., 4 tabs.

  5. Amine functionalized nanodiamond promotes cellular adhesion, proliferation and neurite outgrowth

    International Nuclear Information System (INIS)

    In this study, we report the production of amine functionalized nanodiamond. The amine functionalized nanodiamond forms a conformal monolayer on a negatively charged surface produced via plasma polymerization of acrylic acid. Nanodiamond terminated surfaces were studied as substrates for neuronal cell culture. NG108-15 neuroblastoma-glyoma hybrid cells were successfully cultured upon amine functionalized nanodiamond coated surfaces for between 1 and 7 d. Additionally, primary dorsal root ganglion (DRG) neurons and Schwann cells isolated from Wistar rats were also successfully cultured over a period of 21 d illustrating the potential of the coating for applications in the treatment of peripheral nerve injury. (paper)

  6. 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.

  7. Cellular Functions of NSF: Not Just SNAPs and SNAREs

    OpenAIRE

    Zhao, Chunxia; Slevin, John T.; Whiteheart, Sidney W.

    2007-01-01

    NSF is an AAA protein, broadly required for intracellular membrane fusion. NSF functions as a SNARE chaperone which binds, through SNAPs, to SNARE complexes and utilizes the energy of ATP hydrolysis to disassemble them thus facilitating SNARE recycling. While this is a major function of NSF, it does seem to interact with other proteins, such as the AMPA receptor subunit, GluR2, and β2-AR and is thought to affect their trafficking patterns. New data suggest that NSF may be regulated by transie...

  8. 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.

  9. Multicompartmentalized polymeric systems: towards biomimetic cellular structure and function.

    Science.gov (United States)

    Marguet, Maïté; Bonduelle, Colin; Lecommandoux, Sébastien

    2013-01-21

    The cell is certainly one of the most complex and exciting systems in Nature that scientists are still trying to fully understand. Such a challenge pushes material scientists to seek to reproduce its perfection by building biomimetic materials with high-added value and previously unmatched properties. Thanks to their versatility, their robustness and the current state of polymer chemistry science, we believe polymer-based materials to constitute or represent ideal candidates when addressing the challenge of biomimicry, which defines the focus of this review. The first step consists in mimicking the structure of the cell: its inner compartments, the organelles, with a multicompartmentalized structure, and the rest, i.e. the cytoplasm minus the organelles (mainly cytoskeleton/cytosol) with gels or particular solutions (highly concentrated for example) in one compartment, and finally the combination of both. Achieving this first structural step enables us to considerably widen the gap of possibilities in drug delivery systems. Another powerful property of the cell lies in its metabolic function. The second step is therefore to achieve enzymatic reactions in a compartment, as occurs in the organelles, in a highly controlled, selective and efficient manner. We classify the most exciting polymersome nanoreactors reported in our opinion into two different subsections, depending on their very final concept or purpose of design. We also highlight in a thorough table the experimental sections crucial to such work. Finally, after achieving control over these prerequisites, scientists are able to combine them and push the frontiers of biomimicry further: from cell structure mimics towards a controlled biofunctionality. Such a biomimetic approach in material design and the future research it will stimulate, are believed to bring considerable enrichments to the fields of drug delivery, (bio)sensors, (bio)catalysis and (bio)technology. PMID:23073077

  10. 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. PMID:26277093

  11. The Cellular Bromodomain Protein Brd4 has Multiple Functions in E2-Mediated Papillomavirus Transcription Activation

    OpenAIRE

    Helfer, Christine M.; Junpeng Yan; Jianxin You

    2014-01-01

    The cellular bromodomain protein Brd4 functions in multiple processes of the papillomavirus life cycle, including viral replication, genome maintenance, and gene transcription through its interaction with the viral protein, E2. However, the mechanisms by which E2 and Brd4 activate viral transcription are still not completely understood. In this study, we show that recruitment of positive transcription elongation factor b (P-TEFb), a functional interaction partner of Brd4 in transcription act...

  12. 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.

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

    OpenAIRE

    Griffin, M.; Nayyer, L.; Butler, P. E.; R.G. Palgrave; Seifalian, A. M.; Kalaskar, D. M.

    2016-01-01

    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 s...

  14. 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. PMID:26350218

  15. 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.

  16. 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 recovery, combined with the ability to suppress ATP-demanding cellular functions during hypoxia, may contribute to high resilience of clams to H/R stress and help maintain energy homeostasis during frequent H/R cycles in the intertidal zone. PMID:27252455

  17. 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.

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

    OpenAIRE

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

    2015-01-01

    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, extracel...

  19. 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.

  20. 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

    ABSTRACT 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 PrPC-mediated cell death should be considered, as Ockham's razor theory suggested. PMID:26890218

  1. Cellular functions of p53 and p53 gene family members p63 and p73

    Directory of Open Access Journals (Sweden)

    Nadir Koçak

    2011-12-01

    Full Text Available p53 is a transcription factor that regulates multiple cellular processes that are also important in cellular fates such as cell cycle arrest or programmed cell death. Induction of growth arrest or cell death by p53 prevents the replication of damaged DNA and proliferation of genetically abnormal cells. Therefore, inactivation of p53 by mutation or deletion is also important in ensuring the cellular homeostasis. However, studies showed that p53 deficient mice and cells such as Saos-2 cells are maintaining their life. This situation suggests that p53-related proteins might compensate the functions of p53 in p53 deficient organisms. The identification of two p53-related proteins, p63 and p73 revealed the transcription of p53 responsive genes in p53 deficient organisms. Both p63 and p73 proteins have high homology with the p53 protein and share some of the functions of p53. In contrast to p53, p63 and p73 rarely mutated in human cancers. Here we studied to summarize the current information about the p53 and other p53-related proteins, p63 and p73 that are included into the p53 gene family.

  2. Dual-Modality, Dual-Functional Nanoprobes for Cellular and Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Jyothi U. Menon, Praveen K. Gulaka, Madalyn A. McKay, Sairam Geethanath, Li Liu, Vikram D. Kodibagkar

    2012-01-01

    Full Text Available An emerging need for evaluation of promising cellular therapies is a non-invasive method to image the movement and health of cells following transplantation. However, the use of a single modality to serve this purpose may not be advantageous as it may convey inaccurate or insufficient information. Multi-modal imaging strategies are becoming more popular for in vivo cellular and molecular imaging because of their improved sensitivity, higher resolution and structural/functional visualization. This study aims at formulating Nile Red doped hexamethyldisiloxane (HMDSO nanoemulsions as dual modality (Magnetic Resonance Imaging/Fluorescence, dual-functional (oximetry/detection nanoprobes for cellular and molecular imaging. HMDSO nanoprobes were prepared using a HS15-lecithin combination as surfactant and showed an average radius of 71±39 nm by dynamic light scattering and in vitro particle stability in human plasma over 24 hrs. They were found to readily localize in the cytosol of MCF7-GFP cells within 18 minutes of incubation. As proof of principle, these nanoprobes were successfully used for fluorescence imaging and for measuring pO2 changes in cells by magnetic resonance imaging, in vitro, thus showing potential for in vivo applications.

  3. 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....... Structural changes include an increase in the collagen concentration, a change in the elastic fiber system, and an increase in fat infiltration of skeletal muscle. Biochemical changes include a decreased turnover of collagen with potential accumulation of enzymatically mediated collagen cross-links and a...... buildup of advanced glycation end-product cross-links. Altered mechanotransduction, poorer activation of satellite cells, poorer chemotactic and delayed inflammatory responses, and a change in modulators of the ECM are important cellular changes. It is possible that the structural and biochemical changes...

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

    DEFF Research Database (Denmark)

    Kragstrup, T W; Kjaer, M; Mackey, A L

    2011-01-01

    . Structural changes include an increase in the collagen concentration, a change in the elastic fiber system, and an increase in fat infiltration of skeletal muscle. Biochemical changes include a decreased turnover of collagen with potential accumulation of enzymatically mediated collagen cross......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...... in skeletal muscle ECM contribute to the increased stiffness and impairment in force generated by the contracting muscle fibers seen with aging. The cellular interactions provide and potentially coordinate an adaptation to mechanical loading and ensure successful regeneration after muscle injury. Some...

  5. 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.

  6. The cellular bromodomain protein Brd4 has multiple functions in E2-mediated papillomavirus transcription activation.

    Science.gov (United States)

    Helfer, Christine M; Yan, Junpeng; You, Jianxin

    2014-08-01

    The cellular bromodomain protein Brd4 functions in multiple processes of the papillomavirus life cycle, including viral replication, genome maintenance, and gene transcription through its interaction with the viral protein, E2. However, the mechanisms by which E2 and Brd4 activate viral transcription are still not completely understood. In this study, we show that recruitment of positive transcription elongation factor b (P-TEFb), a functional interaction partner of Brd4 in transcription activation, is important for E2's transcription activation activity. Furthermore, chromatin immunoprecipitation (ChIP) analyses demonstrate that P-TEFb is recruited to the actual papillomavirus episomes. We also show that E2's interaction with cellular chromatin through Brd4 correlates with its papillomavirus transcription activation function since JQ1(+), a bromodomain inhibitor that efficiently dissociates E2-Brd4 complexes from chromatin, potently reduces papillomavirus transcription. Our study identifies a specific function of Brd4 in papillomavirus gene transcription and highlights the potential use of bromodomain inhibitors as a method to disrupt the human papillomavirus (HPV) life cycle. PMID:25140737

  7. The Cellular Bromodomain Protein Brd4 has Multiple Functions in E2-Mediated Papillomavirus Transcription Activation

    Directory of Open Access Journals (Sweden)

    Christine M. Helfer

    2014-08-01

    Full Text Available The cellular bromodomain protein Brd4 functions in multiple processes of the papillomavirus life cycle, including viral replication, genome maintenance, and gene transcription through its interaction with the viral protein, E2. However, the mechanisms by which E2 and Brd4 activate viral transcription are still not completely understood. In this study, we show that recruitment of positive transcription elongation factor b (P-TEFb, a functional interaction partner of Brd4 in transcription activation, is important for E2’s transcription activation activity. Furthermore, chromatin immunoprecipitation (ChIP analyses demonstrate that P-TEFb is recruited to the actual papillomavirus episomes. We also show that E2’s interaction with cellular chromatin through Brd4 correlates with its papillomavirus transcription activation function since JQ1(+, a bromodomain inhibitor that efficiently dissociates E2-Brd4 complexes from chromatin, potently reduces papillomavirus transcription. Our study identifies a specific function of Brd4 in papillomavirus gene transcription and highlights the potential use of bromodomain inhibitors as a method to disrupt the human papillomavirus (HPV life cycle.

  8. 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.

  9. 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.

  10. 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.

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

    Science.gov (United States)

    Liu, Yanyi; Liu, Wenbo

    2014-10-01

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

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

    Science.gov (United States)

    Nikiforov, M. P.; Reukov, V. V.; Thompson, G. L.; Vertegel, A. A.; Guo, S.; Kalinin, S. V.; Jesse, S.

    2009-10-01

    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.

  14. 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.

  15. 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...

  16. The functions of cardiolipin in cellular metabolism-potential modifiers of the Barth syndrome phenotype.

    Science.gov (United States)

    Raja, Vaishnavi; Greenberg, Miriam L

    2014-04-01

    The phospholipid cardiolipin (CL) plays a role in many cellular functions and signaling pathways both inside and outside of mitochondria. This review focuses on the role of CL in energy metabolism. Many reactions of electron transport and oxidative phosphorylation, the transport of metabolites required for these processes, and the stabilization of electron transport chain supercomplexes require CL. Recent studies indicate that CL is required for the synthesis of iron-sulfur (Fe-S) co-factors, which are essential for numerous metabolic pathways. Activation of carnitine shuttle enzymes that are required for fatty acid metabolism is CL dependent. The presence of substantial amounts of CL in the peroxisomal membrane suggests that CL may be required for peroxisomal functions. Understanding the role of CL in energy metabolism may identify physiological modifiers that exacerbate the loss of CL and underlie the variation in symptoms observed in Barth syndrome, a genetic disorder of CL metabolism. PMID:24445246

  17. 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% (P<0.01). Scaffolds 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) (P<0.05) during in vitro analysis. This study provides an effective method of manufacturing mechano-responsive polymeric scaffolds, which can help to customize cellular responses for biomaterial applications. PMID:27013128

  18. Ultrastructure and function of cellular components of the intercentral joint in the percoid vertebral column.

    Science.gov (United States)

    Schmitz, R J

    1995-10-01

    The intervertebral joint of the teleost, Perca flavescens, is formed by opposing amphicoelus centra whose rims are connected by external ligaments. The tissue, located within the space formed by these structures, is derived from the notochord and consists of the elastic externa, the fibrous sheath, and the notochordal cells. The cellular tissue within the joint has many characteristics of a stratified epithelium, and when examined with the transmission electron microscope, at least three morphologically distinct regions can be recognized. First, a peripheral single layer of columnar to squamous-shaped cells lies on a basement membrane immediately deep to the fibrous sheath. Second, several layers of cells, each containing a large central vacuole, occur. Third, in the deepest part of the joint, several layers of attenuated cells surround intracentral fluid-filled lacunae and form a transverse septum across the joint. All cells in this tissue are interconnected by numerous desmosomes. Further, an extensive intermediate filament network exists in all three types of cells. The intermediate filament network in the vacuolated cells is arranged cortically around a membrane-bound vacuole, and suggests that these cells may act as passive cellular hydrostats. The squamous cells surrounding the joint lacunae are structurally similar to mammalian epidermal cells, and the intermediate filament network within them is layered parallel to the surface of the lacunae. The organization of these cells suggests that they are the tensile component of extracellular hydrostats within the intercentral joint. These cellular and extracellular hydrostats within the intercentral joint would function to resist the compressive and tensile stresses encountered during undulatory swimming. PMID:7473764

  19. 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

  20. 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.

  1. 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 pump activity and ATP synthesis decreased significantly. The loss of membrane potential, glucose uptake activity and culturability 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. PMID:16735735

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

    International Nuclear Information System (INIS)

    The epoxy-functionalized mesoporous cellular foams (G-MCFs) with high specific surface area (∼400 m2/g) and large-size mesopores (∼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, N2 adsorption, TG-DTA and 29Si 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 oC 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 Km of 2.1 x 10-2 mol/L lower than that of PGA immobilized on the pure silica MCF (5.0 x 10-2 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-MCF were improved remarkably.

  3. RNase-L Control of Cellular mRNAs: Roles in Biologic Functions and Mechanisms of Substrate Targeting

    OpenAIRE

    Brennan-Laun, Sarah E.; Ezelle, Heather J.; Li, Xiao-Ling; Hassel, Bret A.

    2014-01-01

    RNase-L is a mediator of type 1 interferon-induced antiviral activity that has diverse and critical cellular roles, including the regulation of cell proliferation, differentiation, senescence and apoptosis, tumorigenesis, and the control of the innate immune response. Although RNase-L was originally shown to mediate the endonucleolytic cleavage of both viral and ribosomal RNAs in response to infection, more recent evidence indicates that RNase-L also functions in the regulation of cellular mR...

  4. 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

  5. Functional characterization and cellular dynamics of the CDC-42 - RAC - CDC-24 module in Neurospora crassa.

    Directory of Open Access Journals (Sweden)

    Cynthia L Araujo-Palomares

    Full Text Available Rho-type GTPases are key regulators that control eukaryotic cell polarity, but their role in fungal morphogenesis is only beginning to emerge. In this study, we investigate the role of the CDC-42 - RAC - CDC-24 module in Neurospora crassa. rac and cdc-42 deletion mutants are viable, but generate highly compact colonies with severe morphological defects. Double mutants carrying conditional and loss of function alleles of rac and cdc-42 are lethal, indicating that both GTPases share at least one common essential function. The defects of the GTPase mutants are phenocopied by deletion and conditional alleles of the guanine exchange factor (GEF cdc-24, and in vitro GDP-GTP exchange assays identify CDC-24 as specific GEF for both CDC-42 and RAC. In vivo confocal microscopy shows that this module is organized as membrane-associated cap that covers the hyphal apex. However, the specific localization patterns of the three proteins are distinct, indicating different functions of RAC and CDC-42 within the hyphal tip. CDC-42 localized as confined apical membrane-associated crescent, while RAC labeled a membrane-associated ring excluding the region labeled by CDC42. The GEF CDC-24 occupied a strategic position, localizing as broad apical membrane-associated crescent and in the apical cytosol excluding the Spitzenkörper. RAC and CDC-42 also display distinct localization patterns during branch initiation and germ tube formation, with CDC-42 accumulating at the plasma membrane before RAC. Together with the distinct cellular defects of rac and cdc-42 mutants, these localizations suggest that CDC-42 is more important for polarity establishment, while the primary function of RAC may be maintaining polarity. In summary, this study identifies CDC-24 as essential regulator for RAC and CDC-42 that have common and distinct functions during polarity establishment and maintenance of cell polarity in N. crassa.

  6. 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.

  7. Functional evaluation of DNA repair in human biopsies and their relation to other cellular biomarkers

    Directory of Open Access Journals (Sweden)

    Jana eSlyskova

    2014-05-01

    Full Text Available Thousands of DNA lesions are estimated to occur in each cell every day and almost all are recognized and repaired. DNA repair is an essential system that prevents accumulation of mutations which can lead to serious cellular malfunctions. Phenotypic evaluation of DNA repair activity of individuals is a relatively new approach. Methods to assess base and nucleotide excision repair pathways (BER and NER in peripheral blood cells based on modified comet assay protocols have been widely applied in human epidemiological studies. These provided some interesting observations of individual DNA repair activity being suppressed among cancer patients. However, extension of these results to cancer target tissues requires a different approach. Here we describe the evaluation of BER and NER activities in extracts from deep-frozen colon biopsies using an upgraded version of the in vitro comet-based DNA repair assay in which twelve reactions on one microscope slide can be performed. The aim of this report is to provide a detailed, easy-to-follow protocol together with results of optimization experiments. Additionally, results obtained by functional assays were analysed in the context of other cellular biomarkers, namely single nucleotide polymorphisms and gene expressions. We have shown that measuring DNA repair activity is not easily replaceable by genomic or transcriptomic approaches, but should be applied with the latter techniques in a complementary manner. The ability to measure DNA repair directly in cancer target tissues might finally answer questions about the tissue-specificity of DNA repair processes and their real involvement in the process of carcinogenesis.

  8. 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.

  9. 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.

  10. 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

  11. Cellular functions of p53 and p53 gene family members p63 and p73

    OpenAIRE

    Nadir Koçak; İbrahim Halil Yıldırım; Seval Cing Yıldırım

    2011-01-01

    p53 is a transcription factor that regulates multiple cellular processes that are also important in cellular fates such as cell cycle arrest or programmed cell death. Induction of growth arrest or cell death by p53 prevents the replication of damaged DNA and proliferation of genetically abnormal cells. Therefore, inactivation of p53 by mutation or deletion is also important in ensuring the cellular homeostasis. However, studies showed that p53 deficient mice and cells such as Saos-2 cells are...

  12. Interferon-γ: biological function and application for study of cellular immune response

    Directory of Open Access Journals (Sweden)

    A. A. Lutckii

    2015-01-01

    Full Text Available Cellular immune response plays a central role in control of intracellular pathogens like viruses, some bacteria and parasites. Evaluation of presence, specificity and strength of cellular immune response can be done by investigation of reaction of immune cells to specific stimulus, like antigen. The major cellular reactions to antigen stimulation are production of cytokines, proliferation and cytotoxicity. This review is focused on interferon-gamma as one of the central Th1 cytokines: its biology, immunological role and application as marker of cellular immune response.

  13. Role of cellular prion proteins in the function of macrophages and dendritic cells.

    Science.gov (United States)

    Nitta, Kayako; Sakudo, Akikazu; Masuyama, Jun; Xue, Guangai; Sugiura, Katsuaki; Onodera, Takashi

    2009-01-01

    The cellular isoform of prion proteins (PrPC) is expressed in hematopoietic stem cells, granulocytes, T and B lymphocyte natural killer cells, platelets, monocytes, dendritic cells, and follicular dendritic cells, which may act as carrier cells for the spread of its abnormal isoform (PrPSc) before manifesting transmissible spongiform encephalopathies (TSEs). In particular, macrophages and dendritic cells seem to be involved in the replication of PrPSc after ingestion. In addition, information on the role of PrPC during phagocytotic activity in these cells has been obtained. A recent study showed that resident macrophages from ZrchI PrP gene (Prnp)-deficient (Prnp-/-) mice show augmented phagocytotic activity compared to Prnp+/+ counterparts. In contrast, our study suggests that Rikn Prnp-/- peritoneal macrophages show pseudopodium extension arrest and up-regulation of phagocytotic activity compared to Prnp+/+ cells. Although reports regarding phagocytotic activity in resident and peritoneal macrophages are inconsistent between ZrchI and Rikn Prnp-/- mice, it seems plausible that PrPC in macrophages could contribute to maintain the immunological environment. This review will introduce the recent progress in understanding the functions of PrPC in macrophages and dendritic cells under physiological conditions and its involvement in the pathogenesis of prion diseases. PMID:19275736

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

    Science.gov (United States)

    Chaudhary, Suman; Smith, Carol Anne; del Pino, Pablo; de la Fuente, Jesus M.; Mullin, Margaret; Hursthouse, Andrew; Stirling, David; Berry, Catherine C.

    2013-01-01

    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. PMID:24275948

  15. 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.

  16. 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. PMID:23226257

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

    Directory of Open Access Journals (Sweden)

    Mohamed Hamed

    Full Text Available 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.

  18. Tumor suppressor BTG1 promotes PRMT1-mediated ATF4 function in response to cellular stress

    Science.gov (United States)

    Tijchon, Esther; van Ingen Schenau, Dorette; van Emst, Liesbeth; Levers, Marloes; Palit, Sander A.L.; Rodenbach, Caroline; Poelmans, Geert; Hoogerbrugge, Peter M.; Shan, Jixiu; Kilberg, Michael S.; Scheijen, Blanca; van Leeuwen, Frank N.

    2016-01-01

    Cancer cells are frequently exposed to physiological stress conditions such as hypoxia and nutrient limitation. Escape from stress-induced apoptosis is one of the mechanisms used by malignant cells to survive unfavorable conditions. B-cell Translocation Gene 1 (BTG1) is a tumor suppressor that is frequently deleted in acute lymphoblastic leukemia and recurrently mutated in diffuse large B cell lymphoma. Moreover, low BTG1 expression levels have been linked to poor outcome in several solid tumors. How loss of BTG1 function contributes to tumor progression is not well understood. Here, using Btg1 knockout mice, we demonstrate that loss of Btg1 provides a survival advantage to primary mouse embryonic fibroblasts (MEFs) under stress conditions. This pro-survival effect involves regulation of Activating Transcription Factor 4 (ATF4), a key mediator of cellular stress responses. We show that BTG1 interacts with ATF4 and positively modulates its activity by recruiting the protein arginine methyl transferase PRMT1 to methylate ATF4 on arginine residue 239. We further extend these findings to B-cell progenitors, by showing that loss of Btg1 expression enhances stress adaptation of mouse bone marrow-derived B cell progenitors. In conclusion, we have identified the BTG1/PRMT1 complex as a new modifier of ATF4 mediated stress responses. PMID:26657730

  19. PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Cellular and molecular mechanisms of heat stress related to bovine ovarian function.

    Science.gov (United States)

    Roth, Z

    2015-05-01

    In light of the intensive genetic selection for high milk production and the onset of global warming, it seems that the reduced fertility of lactating cows during the summer will worsen in coming years. Although not entirely clear, the mechanism appears to be multifactorial in nature. It includes alterations in follicular development, depression of follicular dominance, and impairment of steroidogenesis and gonadotropin secretion. Heat-induced perturbations in the physiology of the follicle-enclosed oocyte have also been documented, expressed by impaired cleavage rate and reduced developmental competence. With respect to the oocyte, alterations include an increase in PUFA in the membrane, reactive oxygen species, ceramide formation and caspase activity, and induction of apoptosis via the sphingomyelin and/or mitochondrial pathways. New insight into cellular and molecular alterations has revealed that heat induces perturbations in both nuclear and cytoplasmic maturation events, such as resumption of meiosis, metaphase II plate formation, cytoskeleton rearrangement, and translocation of cortical granules. Alterations in mitochondrial distribution (i.e., low proportion of category I mitochondria) and function (i.e., low membrane potential) have recently been reported for oocytes collected during the summer. These were associated with impaired expression of both nuclear (succinate dehydrogenase subunit [SDHD], adenosine triphosphate [ATP] synthase subunit beta [ATP5B]), mitochondrially NADH dehydrogenase subunit 2 (ND2), and mitochondiral (cytochrome c oxidase subunit II [MT-CO2] and cytochrome b [MT-CYB]) genes that are crucial in the mitochondrial respiratory chain. In addition, season-induced alteration in the stored maternal mRNA has been documented, expressed by reduced transcript levels (oocyte maturation factor MOS [C-MOS], growth differentiation factor 9 [GDF9], POU domain class 5 transcription factor 1 [POU5F1], and glyceraldehyde-3-phosphate dehydrogenase

  20. Serial changes in longitudinal graft function and implications of acute cellular graft rejections during the first year after heart transplantation

    DEFF Research Database (Denmark)

    Clemmensen, Tor Skibsted; Løgstrup, Brian Bridal; Eiskjær, Hans;

    2015-01-01

    AIMS: The aim of this prospective study was to use left ventricular global longitudinal strain (LV-GLS) as a non-invasive tool for the monitoring of graft function in relation to acute cellular rejection (ACR) during the first year after heart transplantation (HTX). METHODS AND RESULTS: The study...

  1. Toxicity of cadmium in Japanese quail: Evaluation of body weight, hepatic and renal function, and cellular immune response

    International Nuclear Information System (INIS)

    Cadmium (Cd) is an environmental pollutant that is able to alter the immune function. Previous studies have shown that, in mammals, chronic exposure to Cd decreases the release of macrophagic cytokines such as IL1 and TNα and decreases phagocytosis activity. On the other hand contradictory results showed an increase in the humoral response. The cellular response could be decreased by exposure to Cd. These alterations were observed in mammals. The present study aimed to investigate some of the toxic effects of Cd exposure in birds. In particular, the main objective of this work was to elucidate the effects of exposure to this pollutant on the cellular immune function of the Japanese quail as a model for the study of toxicity in animals exposed in nature. The animals were exposed to the metal (100 ppm, per os) during development, i.e., from 1 to 28 days old. Body weight, biochemical parameters, and cellular immune response were measured during and at the end of treatment. The results showed that the exposure to Cd for 28 days significantly reduced the body weight and induced hepatic toxicity. The kidney function and cellular immune response were not affected by the Cd exposure

  2. Synthesis and characterization of dual-functionalized core-shell fluorescent microspheres for bioconjugation and cellular delivery.

    Directory of Open Access Journals (Sweden)

    Jonathan M Behrendt

    Full Text Available The efficient transport of micron-sized beads into cells, via a non-endocytosis mediated mechanism, has only recently been described. As such there is considerable scope for optimization and exploitation of this procedure to enable imaging and sensing applications to be realized. Herein, we report the design, synthesis and characterization of fluorescent microsphere-based cellular delivery agents that can also carry biological cargoes. These core-shell polymer microspheres possess two distinct chemical environments; the core is hydrophobic and can be labeled with fluorescent dye, to permit visual tracking of the microsphere during and after cellular delivery, whilst the outer shell renders the external surfaces of the microspheres hydrophilic, thus facilitating both bioconjugation and cellular compatibility. Cross-linked core particles were prepared in a dispersion polymerization reaction employing styrene, divinylbenzene and a thiol-functionalized co-monomer. These core particles were then shelled in a seeded emulsion polymerization reaction, employing styrene, divinylbenzene and methacrylic acid, to generate orthogonally functionalized core-shell microspheres which were internally labeled via the core thiol moieties through reaction with a thiol reactive dye (DY630-maleimide. Following internal labeling, bioconjugation of green fluorescent protein (GFP to their carboxyl-functionalized surfaces was successfully accomplished using standard coupling protocols. The resultant dual-labeled microspheres were visualized by both of the fully resolvable fluorescence emissions of their cores (DY630 and shells (GFP. In vitro cellular uptake of these microspheres by HeLa cells was demonstrated conventionally by fluorescence-based flow cytometry, whilst MTT assays demonstrated that 92% of HeLa cells remained viable after uptake. Due to their size and surface functionalities, these far-red-labeled microspheres are ideal candidates for in vitro, cellular

  3. 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

  4. Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function

    Directory of Open Access Journals (Sweden)

    Aarti eNagayach

    2014-10-01

    Full Text Available Behavioural impairments are the most empirical consequence of diabetes mellitus documented in both humans and animal models, but the underlying causes are still poorly understood. As the cerebellum plays a major role in coordination and execution of the motor functions, we investigated the possible involvement of glial activation, cellular degeneration and glutamate transportation in the cerebellum of rats, rendered diabetic by a single injection of streptozotocin (STZ; 45mg/ kg body weight; intraperitoneally. Motor function alterations were studied using Rotarod test (motor coordination and grip strength (muscle activity at 2nd, 4th, 6th, 8th, 10th and 12th week post diabetic confirmation. Scenario of glial (astroglia and microglia activation, cell death and glutamate transportation was gauged using immunohistochemistry, histological study and image analysis. Cellular degeneration was clearly demarcated in the diabetic cerebellum. Glial cells were showing sequential and marked activation following diabetes in terms of both morphology and cell number. Bergmann glial cells were hypertrophied and distorted. Active caspase-3 positive apoptotic cells were profoundly present in all three cerebellar layers. Reduced co-labelling of GLT-1 and GFAP revealed the altered glutamate transportation in cerebellum following diabetes. These results, exclusively derived from histology, immunohistochemistry and cellular quantification, provide first insight over the associative reciprocity between the glial activation, cellular degeneration and reduced glutamate transportation, which presumably lead to the behavioural alterations following STZ-induced diabetes.

  5. 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 proliferati...

  6. RNase-L control of cellular mRNAs: roles in biologic functions and mechanisms of substrate targeting.

    Science.gov (United States)

    Brennan-Laun, Sarah E; Ezelle, Heather J; Li, Xiao-Ling; Hassel, Bret A

    2014-04-01

    RNase-L is a mediator of type 1 interferon-induced antiviral activity that has diverse and critical cellular roles, including the regulation of cell proliferation, differentiation, senescence and apoptosis, tumorigenesis, and the control of the innate immune response. Although RNase-L was originally shown to mediate the endonucleolytic cleavage of both viral and ribosomal RNAs in response to infection, more recent evidence indicates that RNase-L also functions in the regulation of cellular mRNAs as an important mechanism by which it exerts its diverse biological functions. Despite this growing body of work, many questions remain regarding the roles of mRNAs as RNase-L substrates. This review will survey known and putative mRNA substrates of RNase-L, propose mechanisms by which it may selectively cleave these transcripts, and postulate future clinical applications. PMID:24697205

  7. 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. ...

  8. Study of the influence of microgravity on the biological cells and molecular level; Seitai saibo bunshi level ni okeru bisho juryoku no eikyo ni kansuru kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-03-01

    The shape of osteoblast, gene appearance, gene of rice blast, cellular fusion of plants, gravity acceptance mechanism of unicellular organisms, and physiological and immunity functions of mice were investigated under the microgravity condition. The influence of gravity on the vital reaction and the influence of microgravity on the crystallization of vital substances were also investigated. For the observation of osteoblast, the fluorescence dye reacted with Ca was well taken in the cells. The microgravity affected the stability of rice blast, but hardly affected the protoplast culture of mushroom. The reaction of ciliate against the gravity related to the specific gravity difference between cells and outer liquid. The level of adrenaline in blood of mice increased during the drop. The moving speed of trigger waves of chemical parallel slit formed at the BZ reaction under the microgravity became 60% to 80% of that on the ground. In the case of crystallization at the deposition agent concentration of 1% to 4%, the turbidity showing the degree of crystallization changed complicatedly. Nine processes of crystal growth were recognized. 21 refs., 55 figs., 1 tab.

  9. Mito-Morphosis: Mitochondrial Fusion, Fission, and Cristae Remodeling as Key Mediators of Cellular Function.

    Science.gov (United States)

    Pernas, Lena; Scorrano, Luca

    2016-01-01

    Permanent residency in the eukaryotic cell pressured the prokaryotic mitochondrial ancestor to strategize for intracellular living. Mitochondria are able to autonomously integrate and respond to cellular cues and demands by remodeling their morphology. These processes define mitochondrial dynamics and inextricably link the fate of the mitochondrion and that of the host eukaryote, as exemplified by the human diseases that result from mutations in mitochondrial dynamics proteins. In this review, we delineate the architecture of mitochondria and define the mechanisms by which they modify their shape. Key players in these mechanisms are discussed, along with their role in manipulating mitochondrial morphology during cellular action and development. Throughout, we highlight the evolutionary context in which mitochondrial dynamics emerged and consider unanswered questions whose dissection might lead to mitochondrial morphology-based therapies. PMID:26667075

  10. 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.

  11. 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...

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

    DEFF Research Database (Denmark)

    Choudhary, Chuna Ram; Kumar, Chanchal; Gnad, Florian; Nielsen, Michael L; Rehman, Michael; Walther, Tobias C; Olsen, Jesper V; Mann, Matthias

    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...... lysine acetylation sites on 1750 proteins and quantified acetylation changes in response to the deacetylase inhibitors suberoylanilide hydroxamic acid and MS-275. Lysine acetylation preferentially targets large macromolecular complexes involved in diverse cellular processes, such as chromatin remodeling......, cell cycle, splicing, nuclear transport, and actin nucleation. Acetylation impaired phosphorylation-dependent interactions of 14-3-3 and regulated the yeast cyclin-dependent kinase Cdc28. Our data demonstrate that the regulatory scope of lysine acetylation is broad and comparable with that of other...

  13. Protein adsorption and cellular uptake of cerium oxide nanoparticles as a function of zeta potential

    OpenAIRE

    Patil, Swanand; Sandberg, Amanda; Heckert, Eric; Self, William; Seal, Sudipta

    2007-01-01

    The surface chemistry of biomaterials can have a significant impact on their performance in biological applications. Our recent work suggests that cerium oxide nanoparticles are potent antioxidants in cell culture models and we have evaluated several therapeutic applications of these nanoparticles in different biological systems. Knowledge of protein adsorption and cellular uptake will be very useful in improving the beneficial effects of cerium oxide nanoparticles in biology. In the present ...

  14. BRCA1 function in T lymphocytes: a cellular specificity of a different kind

    OpenAIRE

    Gardner, Kevin; Liu, Edison T

    2000-01-01

    Recent work by Mak et al demonstrates that mice carrying a T-cell-specific disruption of the brca1 gene display markedly impaired T-lymphocyte development and proliferation in the absence of any increased tendency for the formation of tumors. Interestingly, the extent of these defects was found to be highly dependent on cellular context. Contrasting the rather broad tissue expression pattern of brca1 against its exquisitely selective etiologic role in cancers of the breast and ovary, many of ...

  15. Functional evaluation of DNA repair in human biopsies and their relation to other cellular biomarkers

    OpenAIRE

    Slyskova, Jana; Langie, Sabine A. S.; Collins, Andrew R.; Vodicka, Pavel

    2014-01-01

    Thousands of DNA lesions are estimated to occur in each cell every day and almost all are recognized and repaired. DNA repair is an essential system that prevents accumulation of mutations which can lead to serious cellular malfunctions. Phenotypic evaluation of DNA repair activity of individuals is a relatively new approach. Methods to assess base and nucleotide excision repair pathways (BER and NER) in peripheral blood cells based on modified comet assay protocols have been widely applied i...

  16. Elucidating the cellular uptake mechanism of aptamer-functionalized graphene-isolated-Au-nanocrystals with dual-modal imaging.

    Science.gov (United States)

    Wang, Shanshan; Liu, Zhangkun; Zou, Yuxiu; Lai, Xiaofang; Ding, Ding; Chen, Long; Zhang, Liqin; Wu, Yuan; Chen, Zhuo; Tan, Weihong

    2016-05-23

    Elucidating the endocytosis and metabolism of nanoparticles in cells could improve the diagnostic sensitivity and therapeutic efficiency. In this work, we explore the cellular uptake mechanism of a biocompatible nanocrystal nanostructure, graphene-isolated-Au-nanocrystals (GIANs), by monitoring the intrinsic Raman and two-photon luminescence signals of GIANs in live cells. Aptamers functionalized on the GIAN nanostructure through simple, but strong, π-π interactions entered the cells through a clathrin-dependent pathway, while unmodified GIANs mainly entered the cells through a caveolae-mediated endocytosis pathway. Thus, it can be concluded that the mechanism of cellular uptake in these graphene-isolated-Au-nanocrystal nanostructures is determined by the presence or absence of aptamer modification. PMID:27111129

  17. Differential Effects of Polymer-Surface Decoration on Drug Delivery, Cellular Retention, and Action Mechanisms of Functionalized Mesoporous Silica Nanoparticles.

    Science.gov (United States)

    You, Yuanyuan; Hu, Hao; He, Lizhen; Chen, Tianfeng

    2015-12-01

    Polymer-surface decoration has been found to be an effective strategy to enhance the biological activities of nanomedicine. Herein, three different types of polymers with a cancer-targeting ligand Arg-Gly-Asp peptide (RGD) have been used to decorate mesoporous silica nanoparticles (MSNs) and the functionalized nanosystems were used as drug carriers of oxaliplatin (OXA). The results showed that polymer-surface decoration of the MSNs nanosystem by poly(ethylene glycol) (PEG) and polyethyleneimine (PEI) significantly enhanced the anticancer efficacy of OXA, which was much higher than that of chitosan (CTS). This effect was closely related to the enhancement of the cellular uptake and cellular drug retention. Moreover, PEI@MSNs-OXA possessed excellent advantages in penetrating ability and inhibitory effects on SW480 spheroids that were used to simulate the in vivo tumor environments. Therefore, this study provides useful information for the rational design of a cancer-targeted MSNs nanosystem with polymer-surface decoration. PMID:26248202

  18. Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: Implications for regulation and cellular function

    OpenAIRE

    Hubert, Nadia; Hentze, Matthias W.

    2002-01-01

    Divalent metal transporter 1 (DMT1) mediates apical iron uptake into duodenal enterocytes and also transfers iron from the endosome into the cytosol after cellular uptake via the transferrin receptor. Hence, mutations in DMT1 cause systemic iron deficiency and anemia. DMT1 mRNA levels are increased in the duodenum of iron-deficient animals. This regulation has been observed for DMT1 mRNA harboring an iron–responsive element (IRE) in its 3′ UTR, but not for a processing variant lacking a 3′UTR...

  19. 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.

  20. 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

    2016-01-01

    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. PMID:27405011

  1. Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness

    International Nuclear Information System (INIS)

    The evolutionary-conserved interactions between KASH and SUN domain-containing proteins within the perinuclear space establish physical connections, called LINC complexes, between the nucleus and the cytoskeleton. Here, we show that the KASH domains of Nesprins 1, 2 and 3 interact promiscuously with luminal domains of Sun1 and Sun2. These constructs disrupt endogenous LINC complexes as indicated by the displacement of endogenous Nesprins from the nuclear envelope. We also provide evidence that KASH domains most probably fit a pocket provided by SUN domains and that post-translational modifications are dispensable for that interaction. We demonstrate that the disruption of endogenous LINC complexes affect cellular mechanical stiffness to an extent that compares to the loss of mechanical stiffness previously reported in embryonic fibroblasts derived from mouse lacking A-type lamins, a mouse model of muscular dystrophies and cardiomyopathies. These findings support a model whereby physical connections between the nucleus and the cytoskeleton are mediated by interactions between diverse combinations of Sun proteins and Nesprins through their respective evolutionary-conserved domains. Furthermore, they emphasize, for the first time, the relevance of LINC complexes in cellular mechanical stiffness suggesting a possible involvement of their disruption in various laminopathies, a group of human diseases linked to mutations of A-type lamins

  2. 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.

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

    International Nuclear Information System (INIS)

    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

  4. Cellular and molecular mechanism study of declined intestinal transit function in the cholesterol gallstone formation process of the guinea pig

    OpenAIRE

    Fan, Ying; Wu, Shuodong; YIN, ZHENHUA; Fu, Bei-Bei

    2014-01-01

    The aim of this study was to investigate the cellular and molecular mechanisms of declined intestinal transit (IT) function in the cholesterol gallstone (CG) formation process. Forty guinea pigs were divided into an experimental group (EG) and a control group (CoG), and the reverse transcription-polymerase chain reaction (RT-PCR) was performed for the analysis of c-kit and stem cell factor (scf) mRNA expression in the small bowel. In addition, immunofluorescence staining and confocal laser mi...

  5. Cellular composition of periapical granulomas and its function. Histological, immunohistochemical and electronmicroscopic study.

    Science.gov (United States)

    Babál, P; Brozman, M; Jakubovský, J; Basset, F; Jány, Z

    1989-01-01

    Periapical granulomas have been investigated histologically, immunohistologically using polyclonal and monoclonal antibodies, as well as electronmicroscopically. Lesions were formed by inflammatory granulation tissue frequently with foci of purulent exudation and fibrosis. Most numerous were plasma cells usually in cellular regions of the granulation tissue where they were tightly pressed. Of other cellular types were numerous lymphocytes, fibroblasts, less frequent were macrophages, scattered granulocytes and mast cells. More than a half of the plasma cells were IgG positive, about 20% IgA positive, up to 10% IgM, rarely IgE and sporadically IgD positive cells. In the vascular walls and their surrounding as well as in the phagocytes fine granular to granular positivities of C3 and C4 components of the complement were present. The majority of lymphocytes beared markers of T lymphocytes of which the T-suppressor markedly prevailed over the T-helper lymphocytes. In electron microscopy the plasma cells were most frequent. They were usually close to each other, sometimes with a disintegrated cytoplasmic membrane and non-damaged organelles being free around the nucleus. Mast cells were numerous and did not show any signs of marked degranulation. Rich production of immunoglobulins as well as the presence of IgG and IgM positive material in phagocytes, and the presence of positivities of the C3 and C4 components of the complement in the surrounding of the vessels and in phagocytes on the other hand supported the presumption that immune complexes participate in the pathogenesis of periapical granulomas. In spite of the presence of the IgE producing cells the morphological picture of mast cells did not suggest the presence of anaphylactic reaction in periapical lesions. Diffuse distribution of T lymphocytes, moreover with the prevalence of T-suppressor/cytotoxic over T-helper lymphocytes and not numerous macrophages in the inflammatory infiltrates did not suggest the

  6. Transcriptome analysis of Deinagkistrodon acutus venomous gland focusing on cellular structure and functional aspects using expressed sequence tags

    Directory of Open Access Journals (Sweden)

    Qiu Pengxin

    2006-06-01

    Full Text Available Abstract Background The snake venom gland is a specialized organ, which synthesizes and secretes the complex and abundant toxin proteins. Though gene expression in the snake venom gland has been extensively studied, the focus has been on the components of the venom. As far as the molecular mechanism of toxin secretion and metabolism is concerned, we still knew a little. Therefore, a fundamental question being arisen is what genes are expressed in the snake venom glands besides many toxin components? Results To examine extensively the transcripts expressed in the venom gland of Deinagkistrodon acutus and unveil the potential of its products on cellular structure and functional aspects, we generated 8696 expressed sequence tags (ESTs from a non-normalized cDNA library. All ESTs were clustered into 3416 clusters, of which 40.16% of total ESTs belong to recognized toxin-coding sequences; 39.85% are similar to cellular transcripts; and 20.00% have no significant similarity to any known sequences. By analyzing cellular functional transcripts, we found high expression of some venom related genes and gland-specific genes, such as calglandulin EF-hand protein gene and protein disulfide isomerase gene. The transcripts of creatine kinase and NADH dehydrogenase were also identified at high level. Moreover, abundant cellular structural proteins similar to mammalian muscle tissues were also identified. The phylogenetic analysis of two snake venom toxin families of group III metalloproteinase and serine protease in suborder Colubroidea showed an early single recruitment event in the viperids evolutionary process. Conclusion Gene cataloguing and profiling of the venom gland of Deinagkistrodon acutus is an essential requisite to provide molecular reagents for functional genomic studies needed for elucidating mechanisms of action of toxins and surveying physiological events taking place in the very specialized secretory tissue. So this study provides a first

  7. Flavoprotein imaging in the cerebellar cortex in vivo: cellular and metabolic basis and insights into cerebellar function

    Science.gov (United States)

    Gao, Wangcai; Chen, Gang; Ebner, Timothy J.

    2009-02-01

    Flavoprotein autofluorescence is an activity dependent intrinsic signal. Flavoproteins are involved in the electron transport chain and change their fluorescence according to the cellular redox state. We have been using flavoprotein autofluorescence in the cerebellum to examine properties of cerebellar circuits. Studies have also focused on understanding the cellular and metabolic origins of this intrinsic optical signal. Parallel fiber stimulation evokes a beamlike response intersected by bands of decreased fluorescence. The beam response is biphasic, with an early fluorescence increase (light phase) followed by a slower decrease (dark phase). We show this signal originates from flavoproteins as determined by its wavelength selectivity and sensitivity to blockers of the electron transport chain. Selectively blocking glutamate receptors abolished the on-beam light phase with the dark phase remaining intact. This demonstrates that the light phase is due to postsynaptic neuronal activation and suggests the dark phase is primarily due to glial activation. The bands of reduced fluorescence intersecting the beam are primarily neuronal in origin, mediated by GABAergic transmission, and due to the inhibitory action of molecular layer interneurons on Purkinje cells and the interneurons themselves. This parasagittally organized molecular layer inhibition differentially modulates the spatial pattern of cerebellar cortical activity. Flavoprotein imaging also reveals the functional architectures underlying the responses to inferior olive and peripheral whisker pad stimulation. Therefore, flavoprotein autofluorescence imaging is providing new insights into cerebellar cortical function and neurometabolic coupling.

  8. Molecular and cellular mechanisms for the regulation of ovarian follicular function in cows.

    Science.gov (United States)

    Shimizu, Takashi

    2016-08-25

    Ovary is an important organ that houses the oocytes (reproductive cell). Oocyte growth depends on the function of follicular cells such as the granulosa and theca cells. Two-cell two gonadotropin systems are associated with oocyte growth and follicular cell functions. In addition to these systems, it is also known that several growth factors regulate oocyte growth and follicular cell functions. Vascular endothelial growth factor (VEGF) is involved in thecal vasculature during follicular development and the suppression of granulosa cell apoptosis. Metabolic factors such as insulin, growth hormone (GH) and insulin-like growth factor 1 (IGF-1) also play critical roles in the process of follicular development and growth. These factors are associated not only with follicular development, but also with follicular cell function. Steroid hormones (estrogens, androgens, and progestins) that are secreted from follicular cells influence the function of the female genital tract and its affect the susceptibility to bacterial infection. This review covers our current understanding of the mechanisms by which gonadotrophins and/or steroid hormones regulate the growth factors in the follicular cells of the bovine ovary. In addition, this review describes the effect of endotoxin on the function of follicular cells. PMID:27097851

  9. Functional Contributions of Strong and Weak Cellular Oscillators to Synchrony and Light-shifted Phase Dynamics.

    Science.gov (United States)

    Roberts, Logan; Leise, Tanya L; Welsh, David K; Holmes, Todd C

    2016-08-01

    Light is the primary signal that calibrates circadian neural circuits and thus coordinates daily physiological and behavioral rhythms with solar entrainment cues. Drosophila and mammalian circadian circuits consist of diverse populations of cellular oscillators that exhibit a wide range of dynamic light responses, periods, phases, and degrees of synchrony. How heterogeneous circadian circuits can generate robust physiological rhythms while remaining flexible enough to respond to synchronizing stimuli has long remained enigmatic. Cryptochrome is a short-wavelength photoreceptor that is endogenously expressed in approximately half of Drosophila circadian neurons. In a previous study, physiological light response was measured using real-time bioluminescence recordings in Drosophila whole-brain explants, which remain intrinsically light-sensitive. Here we apply analysis of real-time bioluminescence experimental data to show detailed dynamic ensemble representations of whole circadian circuit light entrainment at single neuron resolution. Organotypic whole-brain explants were either maintained in constant darkness (DD) for 6 days or exposed to a phase-advancing light pulse on the second day. We find that stronger circadian oscillators support robust overall circuit rhythmicity in DD, whereas weaker oscillators can be pushed toward transient desynchrony and damped amplitude to facilitate a new state of phase-shifted network synchrony. Additionally, we use mathematical modeling to examine how a network composed of distinct oscillator types can give rise to complex dynamic signatures in DD conditions and in response to simulated light pulses. Simulations suggest that complementary coupling mechanisms and a combination of strong and weak oscillators may enable a robust yet flexible circadian network that promotes both synchrony and entrainment. A more complete understanding of how the properties of oscillators and their signaling mechanisms facilitate their distinct roles

  10. Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function.

    Science.gov (United States)

    Hubert, Nadia; Hentze, Matthias W

    2002-09-17

    Divalent metal transporter 1 (DMT1) mediates apical iron uptake into duodenal enterocytes and also transfers iron from the endosome into the cytosol after cellular uptake via the transferrin receptor. Hence, mutations in DMT1 cause systemic iron deficiency and anemia. DMT1 mRNA levels are increased in the duodenum of iron-deficient animals. This regulation has been observed for DMT1 mRNA harboring an iron-responsive element (IRE) in its 3' UTR, but not for a processing variant lacking a 3'UTR IRE, suggesting that the IRE regulates the expression of DMT1 mRNA in response to iron levels. Here, we show that iron regulation of DMT1 involves the expression of a previously unrecognized upstream 5' exon (exon 1A) of the human and murine DMT1 gene. The expression of this previously uncharacterized 5' exon is tissue-specific and particularly prevalent in the duodenum and kidney. It adds an in-frame AUG translation initiation codon extending the DMT1 ORF by a conserved sequence of 29-31 amino acids. In combination with the IRE- and non-IRE variants in the 3'UTR, our results reveal the existence of four DMT1 mRNA isoforms predicting the synthesis of four different DMT1 proteins. We show that two regulatory regions, the 5' promoter/exon 1A region and the IRE-containing terminal exon participate in iron regulation of DMT1 expression, which operate in a tissue-specific way. These results uncover an unexpected complexity of DMT1 expression and regulation, with implications for understanding the physiology, cell biology, and pathophysiology of mammalian iron metabolism. PMID:12209011

  11. 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 of...... LS can direct how clinicians manage the disease as well as prevent future cancers for the patient and their families. A challenge emerges, however, when a germline missense variant is identified in a MMR gene in a suspected LS patient. The significance of a single amino acid change in these large...

  12. Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system.

    Science.gov (United States)

    Vitlic, Ana; Lord, Janet M; Phillips, Anna C

    2014-06-01

    The immune response is essential for keeping an organism healthy and for defending it from different types of pathogens. It is a complex system that consists of a large number of components performing different functions. The adequate and controlled interaction between these components is necessary for a robust and strong immune response. There are, however, many factors that interfere with the way the immune response functions. Stress and ageing now consistently appear in the literature as factors that act upon the immune system in the way that is often damaging. This review focuses on the role of stress and ageing in altering the robustness of the immune response first separately, and then simultaneously, discussing the effects that emerge from their interplay. The special focus is on the psychological stress and the impact that it has at different levels, from the whole system to the individual molecules, resulting in consequences for physical health. PMID:24562499

  13. Basal cytokeratins and their relationship to the cellular origin and functional classification of breast cancer

    OpenAIRE

    Gusterson, Barry A.; Ross, Douglas T.; Heath, Victoria J; Stein, Torsten

    2005-01-01

    Recent publications have classified breast cancers on the basis of expression of cytokeratin-5 and -17 at the RNA and protein levels, and demonstrated the importance of these markers in defining sporadic tumours with bad prognosis and an association with BRCA1-related breast cancers. These important observations using different technology platforms produce a new functional classification of breast carcinoma. However, it is important in developing hypotheses about the pathogenesis of this tumo...

  14. Bioinspired genotype–phenotype linkages: mimicking cellular compartmentalization for the engineering of functional proteins

    OpenAIRE

    Van Vliet, Liisa D.; Colin, Pierre-Yves; Hollfelder, Florian

    2015-01-01

    The idea of compartmentalization of genotype and phenotype in cells is key for enabling Darwinian evolution. This contribution describes bioinspired systems that use in vitro compartments—water-in-oil droplets and gel-shell beads—for the directed evolution of functional proteins. Technologies based on these principles promise to provide easier access to protein-based therapeutics, reagents for processes involving enzyme catalysis, parts for synthetic biology and materials with biological comp...

  15. 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

    , 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...

  16. 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.

  17. Cellular Functions and X-ray Structure of Anthrolysin O, a Cholesterol-dependent Cytolysin Secreted by Bacillus anthracis

    Energy Technology Data Exchange (ETDEWEB)

    Bourdeau, Raymond W.; Malito, Enrico; Chenal, Alexandre; Bishop, Brian L.; Musch, Mark W.; Villereal, Mitch L.; Chang, Eugene B.; Mosser, Elise M.; Rest, Richard F.; Tang, Wei-Jen; (CNRS-UMR); (Drexel-MED); (UC)

    2009-06-02

    Anthrolysin O (ALO) is a pore-forming, cholesterol-dependent cytolysin (CDC) secreted by Bacillus anthracis, the etiologic agent for anthrax. Growing evidence suggests the involvement of ALO in anthrax pathogenesis. Here, we show that the apical application of ALO decreases the barrier function of human polarized epithelial cells as well as increases intracellular calcium and the internalization of the tight junction protein occludin. Using pharmacological agents, we also found that barrier function disruption requires increased intracellular calcium and protein degradation. We also report a crystal structure of the soluble state of ALO. Based on our analytical ultracentrifugation and light scattering studies, ALO exists as a monomer. Our ALO structure provides the molecular basis as to how ALO is locked in a monomeric state, in contrast to other CDCs that undergo antiparallel dimerization or higher order oligomerization in solution. ALO has four domains and is globally similar to perfringolysin O (PFO) and intermedilysin (ILY), yet the highly conserved undecapeptide region in domain 4 (D4) adopts a completely different conformation in all three CDCs. Consistent with the differences within D4 and at the D2-D4 interface, we found that ALO D4 plays a key role in affecting the barrier function of C2BBE cells, whereas PFO domain 4 cannot substitute for this role. Novel structural elements and unique cellular functions of ALO revealed by our studies provide new insight into the molecular basis for the diverse nature of the CDC family.

  18. Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs.

    Science.gov (United States)

    Pioli, Peter D; Whiteside, Sarah K; Weis, Janis J; Weis, John H

    2016-05-01

    T lymphocytes are essential contributors to the adaptive immune system and consist of multiple lineages that serve various effector and regulatory roles. As such, precise control of gene expression is essential to the proper development and function of these cells. Previously, we identified Snai2 and Snai3 as being essential regulators of immune tolerance partly due to the impaired function of CD4(+) regulatory T cells in Snai2/3 conditional double knockout mice. Here we extend those previous findings using a bone marrow transplantation model to provide an environmentally unbiased view of the molecular changes imparted onto various T lymphocyte populations once Snai2 and Snai3 are deleted. The data presented here demonstrate that Snai2 and Snai3 transcriptionally regulate the cellular fitness and functionality of not only CD4(+) regulatory T cells but effector CD8(α+) and CD4(+) conventional T cells as well. This is achieved through the modulation of gene sets unique to each cell type and includes transcriptional targets relevant to the survival and function of each T cell lineage. As such, Snai2 and Snai3 are essential regulators of T cell immunobiology. PMID:26831822

  19. 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.

  20. Actin—Towards a Deeper Understanding of the Relationship Between Tissue Context, Cellular Function and Tumorigenesis

    International Nuclear Information System (INIS)

    It is well-established that the actin cytoskeleton plays an important role in tumor development yet the contribution made by nuclear actin is ill-defined. In a recent study, nuclear actin was identified as a key mediator through which laminin type III (LN1) acts to control epithelial cell growth. In the breast, epithelial tumors are surrounded by an environment which lacks LN1. These findings point to actin as a potential mediator of tumor development. Here our current understanding of the roles of cytoplasmic and nuclear actin in normal and tumor cell growth is reviewed, relating these functions to cell phenotype in a tissue context

  1. Expression and cellular function of vSNARE proteins in brain astrocytes.

    Science.gov (United States)

    Ropert, N; Jalil, A; Li, D

    2016-05-26

    Gray matter protoplasmic astrocytes, a major type of glial cell in the mammalian brain, extend thin processes ensheathing neuronal synaptic terminals. Albeit electrically silent, astrocytes respond to neuronal activity with Ca(2+) signals that trigger the release of gliotransmitters, such as glutamate, d-serine, and ATP, which modulate synaptic transmission. It has been suggested that the astrocytic processes, together with neuronal pre- and post-synaptic elements, constitute a tripartite synapse, and that astrocytes actively regulate information processing. Astrocytic vesicles expressing VAMP2 and VAMP3 vesicular SNARE (vSNARE) proteins have been suggested to be a key feature of the tripartite synapse and mediate gliotransmitter release through Ca(2+)-regulated exocytosis. However, the concept of exocytotic release of gliotransmitters by astrocytes has been challenged. Here we review studies investigating the expression profile of VAMP2 and VAMP3 vSNARE proteins in rodent astrocytes, and the functional implication of VAMP2/VAMP3 vesicles in astrocyte signaling. We also discuss our recent data suggesting that astrocytic VAMP3 vesicles regulate the trafficking of glutamate transporters at the plasma membrane and glutamate uptake. A better understanding of the functional consequences of the astrocytic vSNARE vesicles on glutamate signaling, neuronal excitability and plasticity, will require the development of new strategies to selectively interrogate the astrocytic vesicles trafficking in vivo. PMID:26518463

  2. 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.

  3. 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.

  4. Effect of Surface Functionalization on the Cellular Uptake and Toxicity of Nanozeolite A.

    Science.gov (United States)

    Męczyńska-Wielgosz, Sylwia; Piotrowska, Agata; Majkowska-Pilip, Agnieszka; Bilewicz, Aleksander; Kruszewski, Marcin

    2016-12-01

    Extensive use of zeolite nanoparticles in many areas, including medicine, has led to the concern about an impact and possible risk of their use for human health and the environment.In our studies, we investigated an uptake, retention, and cytotoxicity of nanozeolite A (BaA) functionalized with aminopropyl or poly(ethylene glycol) (PEG) of different chain lengths using human cervical carcinoma cell line. For internalization studies, nanozeolite was labeled with (133)Ba radionuclide.The results show that in the case of PEG modification, toxicity and uptake depend on the PEG chain length. The highest toxicity has been observed for nanozeolites coated with short-length chain (Ba-silane-PEGm(MW350). Also, amine-modified nanozeolites exhibited high toxicity, while nanozeolites coated with long PEG molecules, BaA-silane-PEGm(MW1000), and BaA-silane-PEGm(MW2000), as well as unmodified nanozeolite, seem to be nontoxic.In conclusion, this study shows that uptake, retention, and toxicity of nanozeolites coated with various length PEG molecules groups depend on the molecular weight of PEG. PMID:26935303

  5. 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. PMID:24903652

  6. 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. PMID:21118962

  7. Cellular uptake of poly(allylamine hydrochloride) microcapsules with different deformability and its influence on cell functions.

    Science.gov (United States)

    Yu, Wei; Zhang, Wenbo; Chen, Ying; Song, Xiaoxue; Tong, Weijun; Mao, Zhengwei; Gao, Changyou

    2016-03-01

    It is important to understand the safety issue and cell interaction pattern of polyelectrolyte microcapsules with different deformability before their use in biomedical applications. In this study, SiO2, poly(sodium-p-styrenesulfonate) (PSS) doped CaCO3 and porous CaCO3 spheres, all about 4μm in diameter, were used as templates to prepare microcapsules with different inner structure and subsequent deformability. As a result, three kinds of covalently assembled poly(allylaminehydrochloride)/glutaraldehyde (PAH/GA) microcapsules with similar size but different deformability under external osmotic pressure were prepared. The impact of different microcapsules on cell viability and functions are studied using smooth muscle cells (SMCs), endothelial cells (ECs) and HepG2 cells. The results demonstrated that viabilities of SMCs, ECs and HepG2 cells were not significantly influenced by either of the three kinds of microcapsules. However, the adhesion ability of SMCs and ECs as well as the mobility of SMCs, ECs and HepG2 cells were significantly impaired after treatment with microcapsules in a deformability dependent manner, especially the microcapsules with lower deformability caused higher impairment on cell functions. The cellular uptake kinetics, uptake pathways, intracellular distribution of microcapsules are further investigated in SMCs to reveal the potential mechanism. The SMCs showed faster uptake rate and exocytosis rate of microcapsules with lower deformability (Cap@CaCO3/PSS and Cap@CaCO3), leading to higher intracellular accumulation of microcapsules with lower deformability and possibly larger retardation of cell functions. The results pointed out that the deformability of microcapsules is an important factor governing the biological performance of microcapsules, which requires careful adjustment for further biomedical applications. PMID:26674230

  8. Effects of p35 Mutations Associated with Mental Retardation on the Cellular Function of p35-CDK5.

    Directory of Open Access Journals (Sweden)

    Shunsuke Takada

    Full Text Available p35 is an activation subunit of the cyclin-dependent kinase 5 (CDK5, which is a Ser/Thr kinase that is expressed predominantly in neurons. Disruption of the CDK5 or p35 (CDK5R1 genes induces abnormal neuronal layering in various regions of the mouse brain via impaired neuronal migration, which may be relevant for mental retardation in humans. Accordingly, mutations in the p35 gene were reported in patients with nonsyndromic mental retardation; however, their effect on the biochemical function of p35 has not been examined. Here, we studied the biochemical effect of mutant p35 on its known properties, i.e., stability, CDK5 activation, and cellular localization, using heterologous expression in cultured cells. We also examined the effect of the mutations on axon elongation in cultured primary neurons and migration of newborn neurons in embryonic brains. However, we did not detect any significant differences in the effects of the mutant forms of p35 compared with wild-type p35. Therefore, we conclude that these p35 mutations are unlikely to cause mental retardation.

  9. 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 (physiologically irrelevant. .

  10. Early impact of cryosurgery ablation on the function of T cellular immunity in tumor-bearing rabbits

    International Nuclear Information System (INIS)

    Objective: To discuss the early impact of cryosurgery ablation on the function of T cellular immunity in tumor-bearing rabbits through observing the changes of T cell subsets after cryosurgery procedure in experimental rabbits. Methods: (1) Thirty tumor-bearing rabbits were randomly and equally divided into 3 groups: group A, receiving cryosurgical treatment; group B, receiving surgical resection; and group C, used as control group. (2) Both the preoperative and the postoperative peripheral blood T cell subsets were determine in all experimental rabbits of three groups, the results were compared and statistically analyzed. Results: After the procedure, CD8 was significantly decreased in all three groups (P < 0.05). CD4 showed an obvious increase in group A (P < 0.05), while a marked decrease in both group B and group C (P < 0.05). The ratio of CD4 /CD8 showed a distinct elevation in group A (P < 0.05), while no change in both group B and group C. Conclusion: The results of this study indicates that cryosurgical ablation is superior to the surgical resection in enhancing the early effect of cell-mediated immunity. (authors)

  11. 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

  12. The preventive effect of vitamin C on the cellular and functional integrity of kidney cells in rats following repeated exposure to paraquat

    OpenAIRE

    Benjamin Nnamdi Okolonkwo; Edna Ogechi Nwachuku; Pascal Chuka Ene; Chukwubuike Udoka Okeke

    2014-01-01

    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 Dvi...

  13. Expansion of colloid and surface chemistry to an interdisciplinary field. Biosimulation by liposome; Koroido kaimen kagaku wa gakusai ryoiki ni hirogaru. Liposome wo mochiite saibo kino ni semaru

    Energy Technology Data Exchange (ETDEWEB)

    Akiyoshi, K. [Kyoto University, Kyoto (Japan)

    1998-07-01

    This paper presents the usefulness of an approach using liposome as cell surface model system (biosimulation by liposome) for clarifying the cell control function of glycolipid. The author and others systematically studied the influence of the aggregation state of ganglioside glycochains on a liposome surface on adhesion and stimulus to cells. Study was also made on the interaction between DPPC liposome including ganglioside and immunocyte, in particular, T cell including an acceptor for glycochains. The interaction was evaluated by laser fluorescence microscope, and an increase in Ca concentration in cells was detected and evaluated by fluorescence probe. An activating rate was also evaluated by counting the number of stimulated cells among nearly 200 cells. As the study result on a degree of adsorption of liposome as fluorescence marker to cells, active systems were strongly adsorbed on cell surfaces, suggesting that signals are transmitted in cells after coupling of active systems with acceptors on cell surfaces. 10 refs., 5 figs.

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

    Science.gov (United States)

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

    2011-01-01

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

  15. 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.

  16. 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)

    Henrik Waldal Holen

    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.

  17. Molecular and Cellular Mechanisms Elucidating Neurocognitive Basis of Functional Impairments Associated with Intellectual Disability in Down Syndrome

    Science.gov (United States)

    Rachidi, Mohammed; Lopes, Carmela

    2010-01-01

    Down syndrome, the most common genetic cause of intellectual disability, is associated with brain disorders due to chromosome 21 gene overdosage. Molecular and cellular mechanisms involved in the neuromorphological alterations and cognitive impairments are reported herein in a global model. Recent advances in Down syndrome research have lead to…

  18. Functionalization of osmium arene anticancer complexes with (poly)arginine: Effect on cellular uptake, internalization, and cytotoxicity

    Czech Academy of Sciences Publication Activity Database

    van Rijt, S.H.; Kostrhunová, Hana; Brabec, Viktor; Sadler, P.J.

    2011-01-01

    Roč. 22, č. 2 (2011), s. 218-226. ISSN 1043-1802 R&D Projects: GA ČR(CZ) GAP301/10/0598 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : osmium * arginine * cellular accumulation Subject RIV: BO - Biophysics Impact factor: 4.930, year: 2011

  19. 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).

  20. Leading research report for fiscal 1998. Research and study of 3-dimensional cell structure module engineering; 1998 nendo sendo chosa kenkyu hokokusho. Sanjigen saibo soshiki module kogaku chosa kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    For the formation of cellular tissues to replace bionic tissues, researches were conducted about technologies of forming bionic tissue modules by culturing various kinds of cells. As for the materials and methods for constructing cellular tissues, researches were conducted about the trends of research and development of 3-dimensional tissue culturing matrices and materials for micromanipulation. As for the development of technologies for the functionalization of 3-dimensionally structured cells, research and study were conducted about the technology of 3-dimensional cell structure organization through application of physical stimulation, the biochemical technology of differentiation inducing, and the differentiation inducing technology for hetero tissue culturing. As for the development of technologies for evaluation using 3-dimensionally structured cells, light CT (computer tomography), analysis and evaluation using spectroscopy and the like, feasibility of the biochemical analysis of the cell state using biosensors, technologies for measuring the secretion of carcinogenic and toxic substances, etc., were studied. In addition, the development of organic models to replace test animals, industrial evolution of 3-dimensional tissue module engineering, etc., were investigated. (NEDO)

  1. 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...... modulation was seen in ADCC. These findings are discussed in the light of our present knowledge of lymphoid NK cells. Udgivelsesdato: 1981-May...

  2. 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 on the...... immune defense and could form the basis of further studies on psychological intervention and immunological status. Udgivelsesdato: 1990-null...

  3. FY 1997 report on the survey of fundamental technologies in the field of brain neuro-biotechnology; 1997 nendo Sendo kenkyu hokokusho (noshinkei saibo kogaku kiban gijutsu no chosa kenkyu)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-03-01

    In Japan with its rapidly aging society, fundamental technologies are required for the development of artificial nerves substituting for or supporting damaged ones, and ultimately constituting artificial neurons based on the knowledge of the brain functions at the molecular and cellular levels. This study defines the fundamental technologies which would be required for the development in the area, and further, evaluates the potential of the technologies to develop the novel industry. The brain function is closely related to the activity in neuronal circuits. In order to repair injured nerves and to develop the advanced technologies of electronics for helping impaired neuronal functions, the most important and urgent is to understand how to work the neuronal circuit system in the brain. Based on these viewpoints, new methodological approaches would make it possible to relieve neural impairment in the sensory input system and the motor system by the use of electronic circuits. They also would improve rehabilitation after injury, and treat neurodegenerative diseases such as Parkinson`s disease. These advances surely create the new types of industry seeds in near future. 77 refs., 29 figs., 2 tabs.

  4. Mms19 protein functions in nucleotide excision repair by sustaining an adequate cellular concentration of the TFIIH component Rad3

    OpenAIRE

    Kou, Haiping; Ying ZHOU; Gorospe, R.M. Charlotte; Wang, Zhigang

    2008-01-01

    Nucleotide excision repair (NER) is a major cellular defense mechanism against DNA damage. We have investigated the role of Mms19 in NER in the yeast Saccharomyces cerevisiae. NER was deficient in the mms19 deletion mutant cell extracts, which was complemented by the NER/transcription factor TFIIH, but not by purified Mms19 protein. In mms19 mutant cells, protein levels of the core TFIIH component Rad3 (XPD homologue) and Ssl2 (XPB homologue) were significantly reduced by up to 3.5- and 2.2-f...

  5. Positive and negative regulatory mechanisms for fine-tuning cellularity and functions of medullary thymic epithelial cells

    Directory of Open Access Journals (Sweden)

    Taishin eAkiyama

    2015-09-01

    Full Text Available 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 mediate these processes. Moreover, cytokines expressed by cells of hematopoietic origin regulate the cellularity of thymic epithelial cells (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, TGF-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.

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

    Institute of Scientific and Technical Information of China (English)

    吴赛珠; 谭家余; 周忠江; 周可祥; 容志毅

    2003-01-01

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

  7. Impact of cadmium on hOGG1 and APE1 as a function of the cellular p53 status

    International Nuclear Information System (INIS)

    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 Polβ. In studies in HCT116 p53−/− 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+/+ 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+/+ cells. In summary, p53 indeed affects the BER pathway directly and indirectly in response to cadmium treatment.

  8. 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

  9. Cellular Automata

    OpenAIRE

    Bagnoli, Franco

    1998-01-01

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

  10. Metabolomics Reveals New Mechanisms for Pathogenesis in Barth Syndrome and Introduces Novel Roles for Cardiolipin in Cellular Function.

    Science.gov (United States)

    Sandlers, Yana; Mercier, Kelly; Pathmasiri, Wimal; Carlson, Jim; McRitchie, Susan; Sumner, Susan; Vernon, Hilary J

    2016-01-01

    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. PMID:27015085

  11. Cellular accumulation and distribution of uranium and lead in osteoblastic cells as a function of their speciation

    International Nuclear Information System (INIS)

    Uranium (U) and lead (Pb) are accumulated and fixed for long periods in bone, impairing remodeling processes. Their toxicity to osteoblasts, the cells responsible for bone formation, is poorly documented. It has been previously shown that cytotoxicity and phenotypic effects of both metals on osteoblasts are highly influenced by metal speciation. Differences in sensitivity between cell types have been underlined as well. In this paper, cellular accumulation of U and Pb in cultured and primary osteoblastic cells was assessed by trace element analysis. Distribution of different species at the cell scale was investigated by electron microscopy. Internalization of both metals was shown to be correlated to cytotoxicity and population growth recovery after exposure. For each metal, the amount of metal uptake leading to 50% cell death was shown to be speciation-dependent. Scanning and transmission electron microscopy showed the formation of precipitates with phosphate in lysosomes for both metals, whose role in toxicity or cell defence remains to be clarified. Although a clear link was established between cytotoxicity and accumulation, differences in sensitivity observed in terms of speciation could not be fully explained and other studies seem necessary

  12. 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

  13. 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

    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 subcultu......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 (<50% lifespan completed) with those of late-passage cells (> 90% lifespan completed). We found a significant reduction in mRNA levels 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 is...

  14. 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. PMID:27442922

  15. Epigenetic regulation of gene expression and cellular functions induced by butyrate, an example of interactions between gene and nutrients

    Science.gov (United States)

    Epigenetics has been defined as ‘the study of heritable changes in genome function that occur without a change in DNA sequence. Research on nutrigenomics, the genome-nutrient interface and epigenomics is in its infancy with respect to livestock species. Feed costs are the single greatest expense t...

  16. 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.

  17. Results from functional and cellular studies using an ovine model to assess response to mesenchymal stem cell therapy after induction of myocardial infarction

    International Nuclear Information System (INIS)

    Full text: Background: Assessing functional and cellular consequences following myocardial infarction (MI) using large animals has advantages of similarity in size, shape and coronary supply to human heart. Aim: To confirm presence of MI and detect recovery of perfusion and function following implantation of ovine bone-marrow derived mesenchymal stem cells (MSC) using intra-myocardial (1M) and intra-coronary (IC) methods. Methods: Eighteen ewes (wt: 45-50kg, LV-EDV: 80-90mL) included, with 10 completing protocol (3=control, 4=IM, 3=IC). MlBI MPI SPECT/CT performed at baseline, 5-7 days post induction of Ml and 6 weeks post cellular therapy with male MSCs. At completion, sheep sacrificed and heart slices reviewed microscopically to confirm Ml, assess neovascularisation and correlate with MPI findings. MPI studies reconstructed using OSEM CT-based AC and analysed using QPS/QGS software. Calculation of Recovery Difference (RD%), Recovery Ratio (RR) and relative change to baseline determined for each study and per segment per study. Results: M I confirmed in 10 of 12 studies (I showed no perfusion abnormality, another pre-existing defect), confirmed anatomically by identification of fibrous scar tissue with lymphoid aggregates, histiocytes and calcium deposits. Reduction in perfusion was 14% to 48%. No improvement in perfusion seen in control (RR=0.8, RD=-16.9) and IC (RR=0.9, RD=-7.1) studies. Significant reperfusion seen on 1M studies, with RR=1.5, RD=1.1 and perfusion recovery 8%, around periphery of infarct zone. Conclusions: Presence of acute Ml identified on MlBl MPI SPECT/CT correlates with anatomical findings. Improvement in perfusion and function at infarct zone seen using 1M method of MSC implantation, correlating with significant neovascularisation identified microscopically.

  18. Specific functions of cFos in the cellular response to UV-irradiation and gene regulation by extracellular stimuli

    International Nuclear Information System (INIS)

    The analysis of TPA-induced expression of known AP-1 dependent genes in cells lacking functional cFos protein revealed three classes of target genes. One class of target genes represents the 92 kD-type IV collagenase whose expression is increased due to the lack of cFos. In contrast, both basal and TPA-induced levels of the interstitial collagenase is significantly reduced in c-fos -/- cells, while expression of other genes (CD44, stromelysin-1 and -2) is not affected differences compared to wild type cells. Using in vivo and in vitro DNA binding studies the molecular mechanism of these differences in target gene expression in c-fos -/- cells was shown to be due to differences in the functional compensation of the lack of cFos by the FosB protein. (orig./AJ)

  19. Membrane texture induced by specific protein binding and receptor clustering: active roles for lipids in cellular function

    OpenAIRE

    Watkins, E. B.; Miller, C.E.; Majewski, J.; Kuhl, T L

    2011-01-01

    Biological membranes are complex, self-organized structures that define boundaries and compartmentalize space in living matter. Composed of a wide variety of lipid and protein molecules, these responsive surfaces mediate transmembrane signaling and material transport within the cell and with its environment. It is well known that lipid membrane properties change as a function of composition and phase state, and that protein-lipid interactions can induce changes in the membrane’s properties an...

  20. Mutually repressing repressor functions and multi-layered cellular heterogeneity regulate the bistable Salmonella fliC census

    OpenAIRE

    Stewart, Mary K.; Cookson, Brad T.

    2014-01-01

    Bistable flagellar and virulence gene expression generates specialized Salmonella subpopulations with distinct functions. Repressing flagellar genes allows Salmonella to evade caspase-1 mediated host defenses and enhances systemic colonization. By definition, bistability arises when intermediate states of gene expression are rendered unstable by the underlying genetic circuitry. We demonstrate sustained bistable fliC expression in virulent Salmonella 14028 and document dynamic control of the ...

  1. Moving Beyond “Good Fat, Bad Fat”: The Complex Roles of Dietary Lipids in Cellular Function and Health12

    OpenAIRE

    Abumrad, Nada A.; Piomelli, Daniele; Yurko-Mauro, Karin; Merrill, Alfred; Clandinin, M. Tom; Serhan, Charles N.

    2012-01-01

    The International Life Science Institute North America and the American Society for Nutrition annual Functional Foods for Health Symposium was held 9 April 2011. Evidence that foods and their components offer health benefits beyond basic nutrition continues to captivate the interest of the scientific community, government agencies, and the general public. This paper is comprised of extended abstracts from the session and addresses issues related to emerging lipid nutrition science, including ...

  2. Hypoxia-inducible factors in T lymphocyte differentiation and function. A Review in the Theme: Cellular Responses to Hypoxia.

    Science.gov (United States)

    Tao, Jin-Hui; Barbi, Joseph; Pan, Fan

    2015-11-01

    Low oxygen concentrations or hypoxia is a trait common to inflamed tissues. Therefore it is not surprising that pathways of hypoxic stress response, largely governed by hypoxia-inducible factors (HIF), are highly relevant to the proper function of immune cells. HIF expression and stabilization in immune cells can be triggered not only by hypoxia, but also by a variety of stimuli and pathological stresses associated with leukocyte activation and inflammation. In addition to its role as a sensor of oxygen scarcity, HIF is also a major regulator of immune cell metabolic function. Rapid progress is being made in elucidating the roles played by HIF in diverse aspects of both innate and adaptive immunity. Here we discuss a number of breakthroughs that have shed light on how HIF expression and activity impact the differentiation and function of diverse T cell populations. The insights gained from these findings may serve as the foundation for future therapies aimed at fine-tuning the immune response. PMID:26354751

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

    Science.gov (United States)

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

    2012-01-01

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

  4. Cellular resilience.

    Science.gov (United States)

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

    2015-01-01

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

  5. Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular potencies against off-target cathepsins and reduced functional selectivity.

    Science.gov (United States)

    Falgueyret, Jean-Pierre; Desmarais, Sylvie; Oballa, Renata; Black, W Cameron; Cromlish, Wanda; Khougaz, Karine; Lamontagne, Sonia; Massé, Frederic; Riendeau, Denis; Toulmond, Sylvie; Percival, M David

    2005-12-01

    The lysosomal cysteine protease cathepsin K is a target for osteoporosis therapy. The aryl-piperazine-containing cathepsin K inhibitor CRA-013783/L-006235 (1) displays greater than 4000-fold selectivity against the lysosomal/endosomal antitargets cathepsin B, L, and S. However, 1 and other aryl-piperazine-containing analogues, including balicatib (10), are approximately 10-100-fold more potent in cell-based enzyme occupancy assays than against each purified enzyme. This phenomenon arises from their basic, lipophilic nature, which results in lysosomal trapping. Consistent with its lysosomotropic nature, 1 accumulates in cells and in rat tissues of high lysosome content. In contrast, nonbasic aryl-morpholino-containing analogues do not exhibit lysosomotropic properties. Increased off-target activities of basic cathepsin K inhibitors were observed in a cell-based cathepsin S antigen presentation assay. No potency increases of basic inhibitors in a functional cathepsin K bone resorption whole cell assay were detected. Therefore, basic cathepsin K inhibitors, such as 1, suffer from reduced functional selectivities compared to those predicted using purified enzyme assays. PMID:16302795

  6. Defects in TRPM7 channel function deregulate thrombopoiesis through altered cellular Mg(2+) homeostasis and cytoskeletal architecture.

    Science.gov (United States)

    Stritt, Simon; Nurden, Paquita; Favier, Remi; Favier, Marie; Ferioli, Silvia; Gotru, Sanjeev K; van Eeuwijk, Judith M M; Schulze, Harald; Nurden, Alan T; Lambert, Michele P; Turro, Ernest; Burger-Stritt, Stephanie; Matsushita, Masayuki; Mittermeier, Lorenz; Ballerini, Paola; Zierler, Susanna; Laffan, Michael A; Chubanov, Vladimir; Gudermann, Thomas; Nieswandt, Bernhard; Braun, Attila

    2016-01-01

    Mg(2+) plays a vital role in platelet function, but despite implications for life-threatening conditions such as stroke or myocardial infarction, the mechanisms controlling [Mg(2+)]i in megakaryocytes (MKs) and platelets are largely unknown. Transient receptor potential melastatin-like 7 channel (TRPM7) is a ubiquitous, constitutively active cation channel with a cytosolic α-kinase domain that is critical for embryonic development and cell survival. Here we report that impaired channel function of TRPM7 in MKs causes macrothrombocytopenia in mice (Trpm7(fl/fl-Pf4Cre)) and likely in several members of a human pedigree that, in addition, suffer from atrial fibrillation. The defect in platelet biogenesis is mainly caused by cytoskeletal alterations resulting in impaired proplatelet formation by Trpm7(fl/fl-Pf4Cre) MKs, which is rescued by Mg(2+) supplementation or chemical inhibition of non-muscle myosin IIA heavy chain activity. Collectively, our findings reveal that TRPM7 dysfunction may cause macrothrombocytopenia in humans and mice. PMID:27020697

  7. Nuclear Factor 90, a cellular dsRNA binding protein inhibits the HIV Rev-export function

    Directory of Open Access Journals (Sweden)

    St-Laurent Georges

    2006-11-01

    Full Text Available Abstract Background The HIV Rev protein is known to facilitate export of incompletely spliced and unspliced viral transcripts to the cytoplasm, a necessary step in virus life cycle. The Rev-mediated nucleo-cytoplasmic transport of nascent viral transcripts, dependents on interaction of Rev with the RRE RNA structural element present in the target RNAs. The C-terminal variant of dsRNA-binding nuclear protein 90 (NF90ctv has been shown to markedly attenuate viral replication in stably transduced HIV-1 target cell line. Here we examined a mechanism of interference of viral life cycle involving Rev-NF90ctv interaction. Results Since Rev:RRE complex formations depend on protein:RNA and protein:protein interactions, we investigated whether the expression of NF90ctv might interfere with Rev-mediated export of RRE-containing transcripts. When HeLa cells expressed both NF90ctv and Rev protein, we observed that NF90ctv inhibited the Rev-mediated RNA transport. In particular, three regions of NF90ctv protein are involved in blocking Rev function. Moreover, interaction of NF90ctv with the RRE RNA resulted in the expression of a reporter protein coding sequences linked to the RRE structure. Moreover, Rev influenced the subcellular localization of NF90ctv, and this process is leptomycin B sensitive. Conclusion The dsRNA binding protein, NF90ctv competes with HIV Rev function at two levels, by competitive protein:protein interaction involving Rev binding to specific domains of NF90ctv, as well as by its binding to the RRE-RNA structure. Our results are consistent with a model of Rev-mediated HIV-1 RNA export that envisions Rev-multimerization, a process interrupted by NF90ctv.

  8. Multi-functional bio-synthetic hybrid nanostructures for enhanced cellular uptake, endosomal escape and targeted delivery toward diagnostics and therapeutics

    Science.gov (United States)

    Shrestha, Ritu

    -assembly of the nanoparticles enhanced cellular uptake and knockdown of nucleolin (a shuttling protein overexpressed at the sites of angiogenesis) and thus inhibiting tumor cell growth. Furthermore, these polymer precursors of the cSCKs were modified with partial to full incorporation of histamines to facilitate their endosomal escape for efficient delivery into the cytosol. The cSCKs were further templated onto high aspect ratio anionic cylinders to form hierarchically-assembled nanostructures that bring together individual components with unique functions, such as one carrying a therapeutic payload and the other with sites for radiolabeling. These higher order nanoobjects enhance circulation in vivo, have capabilities to package nucleic acids electrostatically and contain sites for radiolabeling, providing an overall advantage over the individual components, which could each facilitate only one or the other of the combined functions. Hierarchically-assembled nanostructures were investigated for their cellular uptake, transfection behavior and radiolabeling efficiency, as the next generation of theranostic agents.

  9. Ablation of the cellular prion protein, PrPC, specifically on follicular dendritic cells has no effect on their maturation or function.

    Science.gov (United States)

    McCulloch, Laura; Brown, Karen L; Mabbott, Neil A

    2013-03-01

    Follicular dendritic cells (FDC) are situated in the primary follicles of lymphoid tissues where they maintain the structural integrity of the B-lymphocyte follicle, and help to drive immunoglobulin class-switch recombination, somatic hypermutation and affinity maturation during the germinal centre response. FDC can also provide a reservoir for pathogens that infect germinal centres including HIV and prions. FDC express high levels of the normal cellular form of the prion protein (PrP(C) ), which makes them susceptible to prion infection. The function of PrP(C) is uncertain and it is not known why FDC require such high levels of expression of a protein that is found mainly on cells of the central nervous system. In this study, the function of FDC was assessed in mice that had PrP(C) ablated specifically in their FDC. In mice with FDC-specific PrP(C) ablation, our analysis revealed no observable deficits in lymphoid follicle microarchitecture and FDC status. No effects on FDC ability to trap immune complexes or drive antigen-specific antibody responses and affinity maturation in B lymphocytes were observed. These data clearly demonstrate that PrP(C) expression is dispensable for the functional maturation of FDC and their ability to maintain antigen-specific antibody responses and affinity maturation. PMID:23121447

  10. Natural cytolytic activity in mice with natural or induced cellular defects. I. Differential ability of in vitro interleukin-2 addition to augment natural cytolytic function

    International Nuclear Information System (INIS)

    The ability of in vitro addition of recombinant interleukin 2 (rIL-2) to differentially enhance natural cytotoxicity was assessed using cells from mice with natural and induced cellular defects. In vivo treatment with most immunosuppressive or cytoreductive agents, anti-asialo-GM1 antibody, or gamma irradiation dramatically reduced in vitro cytotoxicity against natural killer (NK) sensitive targets by direct reduction in either percentage specific lysis or lytic units per spleen. In most cases, in vitro addition of rIL-2 (at concentrations causing augmented NK function in cells from naive Balb/C mice) enhanced cytotoxic activity of cells from treatment groups to a normal value but not within the rIL-2-enhanced range of nontreated animals. Additionally, cytotoxic activity of cells from animals treated with certain drugs or gamma irradiation could be augmented by rIL-2 when measured by percentage lysis but not lytic units per spleen. In vivo treatment with cyclosporin A did not affect natural cytotoxic activity and addition of rIL-2 augmented the NK activity in a similar fashion to the profile of naive cells. In experiments using cells from beige (C57Bl/6-bg) mice which have a natural defect in NK activity against YAC-1 targets, addition of rIL-2 (at concentrations causing augmented natural cytotoxic function in cells from C57Bl/6 mice) could not effectively enhance in vitro natural cytotoxic function

  11. Lipid Replacement Therapy: a Functional Food Approach with New Formulations for Reducing Cellular Oxidative Damage, Cancer-Associated Fatigue and the Adverse Effects of Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Garth L. Nicolson

    2011-04-01

    Full Text Available Backgroud:Cancer-associated fatigue and the chronic adverse effects of cancer therapy can be reduced by Lipid Replacement Therapy (LRT using membrane phospholipid mixtures given as food supplements.Methods:This is a review of the published literature on LRT and its uses.Results: LRT significantly reduced fatigue in cancer patients as well as patients suffering from chronic fatiguing illnesses and other medical conditions. It also reduced the adverse effects of chemotherapy, resulting in improvements in incidence of fatigue, nausea, diarrhea, impaired taste, constipation, insomnia and other quality of life indicators. In other diseases, such as chronic fatigue syndrome, fibromyalgia syndrome and other chronic fatiguing illnesses, LRT reduced fatigue by 35.5-43.1% in different clinical trials and increased mitochondrial function.Conclusions: LRT formulations appear to be useful as non-toxic dietary supplements for direct use or placed in functional foods to reduce fatigue and restore mitochondrial and other cellular membrane functions. Formulations of LRT phospholipids are suitable for addition to variousfood products for the treatment of a variety of chronic illnesses as well as their application inanti-aging and other health supplements and products.

  12. Free-fatty acid receptor-4 (GPR120): Cellular and molecular function and its role in metabolic disorders.

    Science.gov (United States)

    Moniri, Nader H

    2016-06-15

    Over the last decade, a subfamily of G protein-coupled receptors that are agonized by endogenous and dietary free-fatty acids (FFA) has been discovered. These free-fatty acid receptors include FFA2 and FFA3, which are agonized by short-chained FFA, as well as FFA1 and FFA4, which are agonized by medium-to-long chained FFA. Ligands for FFA1 and FFA4 comprise the family of long chain polyunsaturated omega-3 fatty acids including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), suggesting that many of the long-known beneficial effects of these fats may be receptor mediated. In this regard, FFA4 has gathered considerable interest due to its role in ameliorating inflammation, promoting insulin sensitization, and regulating energy metabolism in response to FFA ligands. The goal of this review is to summarize the body of evidence in regard to FFA4 signal transduction, its mechanisms of regulation, and its functional role in a variety of tissues. In addition, recent endeavors toward discovery of small molecules that modulate FFA4 activity are also presented. PMID:26827942

  13. Mutually repressing repressor functions and multi-layered cellular heterogeneity regulate the bistable Salmonella fliC census

    Science.gov (United States)

    Stewart, Mary K.; Cookson, Brad T.

    2014-01-01

    Summary Bistable flagellar and virulence gene expression generates specialized Salmonella subpopulations with distinct functions. Repressing flagellar genes allows Salmonella to evade caspase-1 mediated host defenses and enhances systemic colonization. By definition, bistability arises when intermediate states of gene expression are rendered unstable by the underlying genetic circuitry. We demonstrate sustained bistable fliC expression in virulent Salmonella 14028 and document dynamic control of the distribution, or single-cell census, of flagellar gene expression by the mutually repressing repressors YdiV and FliZ. YdiV partitions cells into the fliC-OFF subpopulation, while FliZ partitions cells into the fliC-HIGH subpopulation at late timepoints during growth. Bistability of ΔfliZ populations and ydiV-independent FliZ control of flagellar gene expression provide evidence that the YdiV-FliZ mutually repressing repressor circuit is not required for bistability. Repression and activation by YdiV and FliZ (respectively) can shape the census of fliC expression independently, and bistability collapses into a predominantly intermediate population in the absence of both regulators. Metered expression of YdiV and FliZ reveals variable sensitivity to these regulators and defines conditions where expression of FliZ enhances fliC expression and where FliZ does not alter the fliC census. Thus, this evolved genetic circuitry coordinates multiple layers of regulatory heterogeneity into a binary response. PMID:25315056

  14. Molecular dynamics studies of simple membrane-water interfaces: Structure and functions in the beginnings of cellular life

    Science.gov (United States)

    Pohorille, Andrew; Wilson, Michael A.

    1995-01-01

    Molecular dynamics computer simulations of the structure and functions of a simple membrane are performed in order to examine whether membranes provide an environment capable of promoting protobiological evolution. Our model membrane is composed of glycerol 1-monooleate. It is found that the bilayer surface fluctuates in time and space, occasionally creating thinning defects in the membrane. These defects are essential for passive transport of simple ions across membranes because they reduce the Born barrier to this process by approximately 40%. Negative ions are transferred across the bilayer more readily than positive ions due to favorable interactions with the electric field at the membrane-water interface. Passive transport of neutral molecules is, in general, more complex than predicted by the solubility-diffusion model. In particular, molecules which exhibit sufficient hydrophilicity and lipophilicity concentrate near membrane surfaces and experience 'interfacial resistance' to transport. The membrane-water interface forms an environment suitable for heterogeneous catalysis. Several possible mechanisms leading to an increase of reaction rates at the interface are discussed. We conclude that vesicles have many properties that make them very good candidates for earliest protocells. Some potentially fruitful directions of experimental and theoretical research on this subject are proposed.

  15. Molecular dynamics studies of simple membrane — Water interfaces: Structure and functions in the beginnings of cellular life

    Science.gov (United States)

    Pohorille, Andrew; Wilson, Michael A.

    1995-06-01

    Molecular dynamics computer simulations of the structure and functions of a simple membrane are performed in order to examine whether membranes provide an environment capable of promoting protobiological evolution. Our model membrane is composed of glycerol 1-monooleate. It is found that the bilayer surface fluctuates in time and space, occasionally creating thinning defects in the membrane. These defects are essential for passive transport of simple ions across membranes because they reduce the Bom barrier to this process by approximately 40%. Negative ions are transferred across the bilayer more readily than positive ions due to favorable interactions with the electric field at the membrane-water interface. Passive transport of neutral molecules is, in general, more complex than predicted by the solubility-diffusion model. In particular, molecules which exhibit sufficient hydrophilicity and lipophilicity concentrate near membrane surfaces and experience “interfacial resistance” to transport. The membrane-water interface forms an environment suitable for heterogeneous catalysis. Several possible mechanisms leading to an increase of reaction rates at the interface are discussed. We conclude that vesicles have many properties that make them very good candidates for earliest protocells. Some potentially fruitful directions of experimental and theoretical research on this subject are proposed.

  16. In vivo subsurface morphological and functional cellular and subcellular imaging of the gastrointestinal tract with confocal mini-microscopy

    Institute of Scientific and Technical Information of China (English)

    Martin Goetz; Beena Memadathil; Stefan Biesterfeld; Constantin Schneider; Sebastian Gregor; Peter R Galle; Markus F Neurath; Ralf Kiesslich

    2007-01-01

    AIM: To evaluate a newly developed hand-held confocal probe for in vivo microscopic imaging of the complete gastrointestinal tract in rodents.METHODS: A novel rigid confocal probe (diameter 7 mm) was designed with optical features similar to the flexible endomicroscopy system for use in humans using a 488 nm single line laser for fluorophore excitation.Light emission was detected at 505 to 750 nm. The field of view was 475 μm × 475 μm. Optical slice thickness was 7 μm with a lateral resolution of 0.7 μm. Subsurface serial images at different depths (surface to 250 μm)were generated in real time at 1024 × 1024 pixels (0.8 frames/s) by placing the probe onto the tissue in gentle,stable contact. Tissue specimens were sampled for histopathological correlation.RESULTS: The esophagus, stomach, small and large intestine and meso, liver, pancreas and gall bladder were visualised in vivo at high resolution in n = 48 mice.Real time microscopic imaging with the confocal minimicroscopy probe was easy to achieve. The different staining protocols (fluorescein, acriflavine, FITC-labelled dextran and L. esculentum lectin) each highlighted specific aspects of the tissue, and in vivo imaging correlated excellently with conventional histology. In vivo blood flow monitoring added a functional quality to morphologic imaging.CONCLUSION: Confocal microscopy is feasible in vivo allowing the visualisation of the complete GI tract at high resolution even of subsurface tissue structures.The new confocal probe design evaluated in this study is compatible with laparoscopy and significantly expands the field of possible applications to intra-abdominal organs. It allows immediate testing of new in vivo staining and application options and therefore permits rapid transfer from animal studies to clinical use in patients.

  17. Effects of whole flaxseed, raw soybeans, and calcium salts of fatty acids on measures of cellular immune function of transition dairy cows.

    Science.gov (United States)

    Gandra, J R; Barletta, R V; Mingoti, R D; Verdurico, L C; Freitas, J E; Oliveira, L J; Takiya, C S; Kfoury, J R; Wiltbank, M C; Renno, F P

    2016-06-01

    The objective of the current study was to evaluate the effects of supplemental n-3 and n-6 fatty acid (FA) sources on cellular immune function of transition dairy cows. Animals were randomly assigned to receive 1 of 4 diets: control (n=11); whole flaxseed (n-3 FA source; n=11), 60 and 80g/kg of whole flaxseed [diet dry matter (DM) basis] during pre- and postpartum, respectively; whole raw soybeans (n-6 FA source; n=10), 120 and 160g/kg of whole raw soybeans (diet DM basis) during pre- and postpartum, respectively; and calcium salts of unsaturated FA (Megalac-E, n-6 FA source; n=10), 24 and 32g/kg of calcium salts of unsaturated FA (diet DM basis) during pre- and postpartum, respectively. Supplemental FA did not alter DM intake and milk yield but increased energy balance during the postpartum period. Diets containing n-3 and n-6 FA sources increased phagocytosis capacity of leukocytes and monocytes and phagocytosis activity of monocytes. Furthermore, n-3 FA source increased phagocytic capacity of leukocytes and neutrophils and increased phagocytic activity in monocytes and neutrophils when compared with n-6 FA sources. Supplemental FA effects on adaptive immune system included increased percentage of T-helper cells, T-cytotoxic cells, cells that expressed IL-2 receptors, and CD62 adhesion molecules. The results of this study suggest that unsaturated FA can modulate innate and adaptive cellular immunity and trigger a proinflammatory response. The n-3 FA seems to have a greater effect on phagocytic capacity and activity of leukocytes when compared with n-6 FA. PMID:27060809

  18. Vitamin B6 nutritional status and cellular availability of pyridoxal 5'-phosphate govern the function of the transsulfuration pathway's canonical reactions and hydrogen sulfide production via side reactions.

    Science.gov (United States)

    Gregory, Jesse F; DeRatt, Barbara N; Rios-Avila, Luisa; Ralat, Maria; Stacpoole, Peter W

    2016-07-01

    The transsulfuration pathway (TS) acts in sulfur amino acid metabolism by contributing to the regulation of cellular homocysteine, cysteine production, and the generation of H2S for signaling functions. Regulation of TS pathway kinetics involves stimulation of cystathionine β-synthase (CBS) by S-adenosylmethionine (SAM) and oxidants such as H2O2, and by Michaelis-Menten principles whereby substrate concentrations affect reaction rates. Although pyridoxal phosphate (PLP) serves as coenzyme for both CBS and cystathionine γ-lyase (CSE), CSE exhibits much greater loss of activity than CBS during PLP insufficiency. Thus, cellular and plasma cystathionine concentrations increase in vitamin B6 deficiency mainly due to the bottleneck caused by reduced CSE activity. Because of the increase in cystathionine, the canonical production of cysteine (homocysteine → cystathionine → cysteine) is largely maintained even during vitamin B6 deficiency. Typical whole body transsulfuration flux in humans is 3-7 μmol/h per kg body weight. The in vivo kinetics of H2S production via side reactions of CBS and CSE in humans are unknown but they have been reported for cultured HepG2 cells. In these studies, cells exhibit a pronounced reduction in H2S production capacity and rates of lanthionine and homolanthionine synthesis in deficiency. In humans, plasma concentrations of lanthionine and homolanthionine exhibit little or no mean change due to 4-wk vitamin B6 restriction, nor do they respond to pyridoxine supplementation of subjects in chronically low-vitamin B6 status. Wide individual variation in responses of the H2S biomarkers to such perturbations of human vitamin B6 status suggests that the resulting modulation of H2S production may have physiological consequences in a subset of people. Supported by NIH grant DK072398. This paper refers to data from studies registered at clinicaltrials.gov as NCT01128244 and NCT00877812. PMID:26765812

  19. Receptor complementation and mutagenesis reveal SR-BI as an essential HCV entry factor and functionally imply its intra- and extra-cellular domains.

    Directory of Open Access Journals (Sweden)

    Marlène Dreux

    2009-02-01

    Full Text Available HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and/or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI, a major receptor of high-density lipoprotein (HDL, the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes. Several reports have indicated that HDL promotes HCV entry through interaction with SR-BI. This pathway remains largely elusive, although it was shown that HDL neither associates with HCV particles nor modulates HCV binding to SR-BI. In contrast to CD81 and Claudin-1, the importance of SR-BI has only been addressed indirectly because of lack of cells in which functional complementation assays with mutant receptors could be performed. Here we identified for the first time two cell types that supported HCVpp and HCVcc entry upon ectopic SR-BI expression. Remarkably, the undetectable expression of SR-BI in rat hepatoma cells allowed unambiguous investigation of human SR-BI functions during HCV entry. By expressing different SR-BI mutants in either cell line, our results revealed features of SR-BI intracellular domains that influence HCV infectivity without affecting receptor binding and stimulation of HCV entry induced by HDL/SR-BI interaction. Conversely, we identified positions of SR-BI ectodomain that, by altering HCV binding, inhibit entry. Finally, we characterized alternative ectodomain determinants that, by reducing SR-BI cholesterol uptake and efflux functions, abolish HDL-mediated infection-enhancement. Altogether, we demonstrate that SR-BI is an essential HCV entry factor. Moreover, our results highlight specific SR-BI determinants required during HCV entry and physiological lipid transfer functions hijacked by HCV to favor infection.

  20. Improving cellular function and immune protection via layer-by-layer nanocoating of pancreatic islet β-cell spheroids cocultured with mesenchymal stem cells.

    Science.gov (United States)

    Bhaiji, Tasneem; Zhi, Zheng-Liang; Pickup, John C

    2012-06-01

    Islet transplantation as a therapy for type 1 diabetes is currently limited by lack of primary transplant material from human donors and post-transplantation loss of islets caused by adverse immune and nonimmune reactions. This study aimed to develop a novel strategy to create microenvironment for islets via integration of nanoencapsulation with cell cocultures, thereby enhancing their survival and function. The nanoencapsulation was achieved via layer-by-layer deposition of phosphorycholine-modified poly-L-lysine/heparin leading to the formation of nanometer-thick multilayer coating on islets. Spheroids formed by coculturing MIN6 β-cells with mesenchymal stem cells in suspension were used as the tool for testing encapsulation. Coculturing MSCs with MIN6 cells allowed the cell constructs to enhance structural and morphologic stability with improved insulin secretory function and render them less susceptible to inflammatory cytokine-induced apoptosis. Combining nanoencapsulation with coculture of MSCs/MIN6 resulted in higher glucose responsiveness, and lower antibody binding and apoptosis-inducing effects of cytokines. This strategy of nanoencapsulating islet cocultures appears promising to improve cellular delivery of insulin for treating type 1 diabetes. PMID:22447690

  1. Dancing on damaged chromatin. Functions of ATM and the RAD50/MRE11/NBS1 complex in cellular responses to DNA damage

    International Nuclear Information System (INIS)

    In order to preserve and protect genetic information, eukaryotic cells have developed a signaling or communications network to help the cell respond to DNA damage, and ATM and NBS1 are key players in this network. ATM is a protein kinase which is activated immediately after a DNA double strand break (DSB) is formed, and the resulting signal cascade generated in response to cellular DSBs is regulated by post-translational protein modifications such as phosphorylation and acetylation. In addition, to ensure the efficient functioning of DNA repair and cell cycle checkpoints, the highly ordered structure of eukaryotic chromatin must be appropriately altered to permit access of repair-related factors to DNA. These alterations are termed chromatin remodeling, and are executed by a specific remodeling complex in conjunction with histone modifications. Current advances in the molecular analysis of DNA damage responses have shown that the auto-phosphorylation of ATM and the interaction between ATM and NBS1 are key steps for ATM activation, and that the association of ATM and NBS1 is involved in chromatin remodeling. Identification of novel factors which function in ubiquitination (RNF8, Ubc13, Rap80, etc.) has also enabled us to understand more details of the early stages in DNA repair pathways which respond to DSBs. In this review, the focus is on the role of ATM and the RAD50/MRE11/NBS1 complex in DSB response pathways, and their role in DSB repair and in the regulation of chromatin remodeling. (author)

  2. Magnetic Cellular Switches

    OpenAIRE

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

    2004-01-01

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

  3. International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials.

    Science.gov (United States)

    Galipeau, Jacques; Krampera, Mauro; Barrett, John; Dazzi, Francesco; Deans, Robert J; DeBruijn, Joost; Dominici, Massimo; Fibbe, Willem E; Gee, Adrian P; Gimble, Jeffery M; Hematti, Peiman; Koh, Mickey B C; LeBlanc, Katarina; Martin, Ivan; McNiece, Ian K; Mendicino, Michael; Oh, Steve; Ortiz, Luis; Phinney, Donald G; Planat, Valerie; Shi, Yufang; Stroncek, David F; Viswanathan, Sowmya; Weiss, Daniel J; Sensebe, Luc

    2016-02-01

    Mesenchymal stromal cells (MSCs) as a pharmaceutical for ailments characterized by pathogenic autoimmune, alloimmune and inflammatory processes now cover the spectrum of early- to late-phase clinical trials in both industry and academic sponsored studies. There is a broad consensus that despite different tissue sourcing and varied culture expansion protocols, human MSC-like cell products likely share fundamental mechanisms of action mediating their anti-inflammatory and tissue repair functionalities. Identification of functional markers of potency and reduction to practice of standardized, easily deployable methods of measurements of such would benefit the field. This would satisfy both mechanistic research as well as development of release potency assays to meet Regulatory Authority requirements for conduct of advanced clinical studies and their eventual registration. In response to this unmet need, the International Society for Cellular Therapy (ISCT) addressed the issue at an international workshop in May 2015 as part of the 21st ISCT annual meeting in Las Vegas. The scope of the workshop was focused on discussing potency assays germane to immunomodulation by MSC-like products in clinical indications targeting immune disorders. We here provide consensus perspective arising from this forum. We propose that focused analysis of selected MSC markers robustly deployed by in vitro licensing and metricized with a matrix of assays should be responsive to requirements from Regulatory Authorities. Workshop participants identified three preferred analytic methods that could inform a matrix assay approach: quantitative RNA analysis of selected gene products; flow cytometry analysis of functionally relevant surface markers and protein-based assay of secretome. We also advocate that potency assays acceptable to the Regulatory Authorities be rendered publicly accessible in an "open-access" manner, such as through publication or database collection. PMID:26724220

  4. Quantum cellular automata

    Science.gov (United States)

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

    1994-06-01

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

  5. Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application

    Directory of Open Access Journals (Sweden)

    Alwani S

    2016-02-01

    Full Text Available Saniya Alwani,1 Randeep Kaur,1 Deborah Michel,1 Jackson M Chitanda,2 Ronald E Verrall,3 Chithra Karunakaran,4 Ildiko Badea1 1Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, 2Department of Chemical & Biological Engineering, 3Department of Chemistry, University of Saskatchewan, 4Canadian Light Source, Saskatoon, SK, Canada Purpose: Nanodiamonds (NDs are emerging as an attractive tool for gene therapeutics. To reach their full potential for biological application, NDs should maintain their colloidal stability in biological milieu. This study describes the behavior of lysine-functionalized ND (lys-ND in various dispersion media, with an aim to limit aggregation and improve the colloidal stability of ND-gene complexes called diamoplexes. Furthermore, cellular and macromolecular interactions of lys-NDs are also analyzed in vitro to establish the understanding of ND-mediated gene transfer in cells. Methods: lys-NDs were synthesized earlier through covalent conjugation of lysine amino acid to carboxylated NDs surface generated through re-oxidation in strong oxidizing acids. In this study, dispersions of lys-NDs were prepared in various media, and the degree of sedimentation was monitored for 72 hours. Particle size distributions and zeta potential measurements were performed for a period of 25 days to characterize the physicochemical stability of lys-NDs in the medium. The interaction profile of lys-NDs with fetal bovine serum showed formation of a protein corona, which was evaluated by size and charge distribution measurements. Uptake of lys-NDs in cervical cancer cells was analyzed by scanning transmission X-ray microscopy, flow cytometry, and confocal microscopy. Cellular uptake of diamoplexes (complex of lys-NDs with small interfering RNA was also analyzed using flow cytometry. Results: Aqueous dispersion of lys-NDs showed minimum sedimentation and remained stable over a period of 25 days. Size distributions showed

  6. Regulatory and effector functions of gamma-delta (γδ) T cells and their therapeutic potential in adoptive cellular therapy for cancer.

    Science.gov (United States)

    Paul, Sourav; Lal, Girdhari

    2016-09-01

    γδ T cells are an important innate immune component of the tumor microenvironment and are known to affect the immune response in a wide variety of tumors. Unlike αβ T cells, γδ T cells are capable of spontaneous secretion of IL-17A and IFN-γ without undergoing clonal expansion. Although γδ T cells do not require self-MHC-restricted priming, they can distinguish "foreign" or transformed cells from healthy self-cells by using activating and inhibitory killer Ig-like receptors. γδ T cells were used in several clinical trials to treat cancer patient due to their MHC-unrestricted cytotoxicity, ability to distinguish transformed cells from normal cells, the capacity to secrete inflammatory cytokines and also their ability to enhance the generation of antigen-specific CD8(+) and CD4(+) T cell response. In this review, we discuss the effector and regulatory function of γδ T cells in the tumor microenvironment with special emphasis on the potential for their use in adoptive cellular immunotherapy. PMID:27012367

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

    International Nuclear Information System (INIS)

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

  8. 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.

  9. Comparative genomic analysis of buffalo (Bubalus bubalis NOD1 and NOD2 receptors and their functional role in in-vitro cellular immune response.

    Directory of Open Access Journals (Sweden)

    Biswajit Brahma

    Full Text Available Nucleotide binding and oligomerization domain (NOD-like receptors (NLRs are innate immune receptors that recognize bacterial cell wall components and initiate host immune response. Structure and function of NLRs have been well studied in human and mice, but little information exists on genetic composition and role of these receptors in innate immune system of water buffalo--a species known for its exceptional disease resistance. Here, a comparative study on the functional domains of NOD1 and NOD2 was performed across different species. The NOD mediated in-vitro cellular responses were studied in buffalo peripheral blood mononuclear cells, resident macrophages, mammary epithelial, and fibroblast cells. Buffalo NOD1 (buNOD1 and buNOD2 showed conserved domain architectures as found in other mammals. The domains of buNOD1 and buNOD2 showed analogy in secondary and tertiary conformations. Constitutive expressions of NODs were ubiquitous in different tissues. Following treatment with NOD agonists, peripheral lymphocytes showed an IFN-γ response along-with production of pro-inflammatory cytokines. Alveolar macrophages and mammary epithelial cells showed NOD mediated in-vitro immune response through NF-κB dependent pathway. Fibroblasts showed pro-inflammatory cytokine response following agonist treatment. Our study demonstrates that both immune and non-immune cells could generate NOD-mediated responses to pathogens though the type and magnitude of response depend on the cell types. The structural basis of ligand recognition by buffalo NODs and knowledge of immune response by different cell types could be useful for development of non-infective innate immune modulators and next generation anti-inflammatory compounds.

  10. 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 ...

  11. Actual problems of cellular cardiomyoplasty

    Directory of Open Access Journals (Sweden)

    Bulat Kaupov

    2010-04-01

    Full Text Available The paper provides review of cellular technologies used incardiology, describes types of cellular preparations depending onsources of cells and types of compounding cells. The generalmechanisms of therapies with stem cells applications are described.Use of cellular preparations for treatment of cardiovascular diseasesand is improvement of the forecast at patients with heartinsufficiency of various genesis is considered as alternative topractice with organ transplantations. Efforts of biotechnologicallaboratories are directed on search of optimum population of cellsfor application in cardiology and studying of mechanisms andfactors regulating function of cardiac stem cells.

  12. Different effects of GPR120 and GPR40 on cellular functions stimulated by 12-O-tetradecanoylphorbol-13-acetate in melanoma cells.

    Science.gov (United States)

    Fukushima, Kaori; Takahashi, Kaede; Fukushima, Nobuyuki; Honoki, Kanya; Tsujiuchi, Toshifumi

    2016-06-17

    G-protein-coupled receptor 120 (GPR120) and GPR40 exhibit a variety of biological responses by the binding of free fatty acids. 12-O-Tetradecanoylphorbol-13-acetate (TPA) is a tumor promoting agent of skin carcinogenesis. It is known that TPA treatment stimulates cell motile activity of cancer cells, including melanoma cells. In the present study, we investigated whether GRP120 and GPR40 are involved in regulation of cell motile activity induced by TPA in two melanoma cell lines. A375 and G361 cells were treated with TPA at a concentration of 10 nM for 24 h. The cell motile activity of A375 cells was significantly increased by TPA, correlating with GPR40 expression. In contrast, TPA suppressed the cell motile activity of G361 cells, while GPR120 and GPR40 expressions were increased. The cell motile activity of A375 cells treated with TPA was markedly increased by GPR120 knockdown. In addition, to assess roles of GPR120 and GPR40 in cellular functions of A375 cells by the long-term TPA treatment, cells were treated with TPA (1 nM) for at least 3 months. The long-term TPA treatment induced the high cell motile activity and elevated GPR120 and GPR40 expressions. The high cell motile activity of A375 cells stimulated by the long-term TPA treatment was enhanced by GPR120 knockdown. These results suggest that GPR120 negatively and GPR40 positively regulate cell motile activities induce by TPA in melanoma cells. PMID:27163640

  13. Cellular therapy in Tuberculosis

    Directory of Open Access Journals (Sweden)

    Shreemanta K. Parida

    2015-03-01

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

  14. Cellular therapy in tuberculosis.

    Science.gov (United States)

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

    2015-03-01

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

  15. Aging, cellular senescence, and cancer.

    Science.gov (United States)

    Campisi, Judith

    2013-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. PMID:23140366

  16. Antibody penetration into living cells. V. Interference between two fc gamma receptor-mediated functions: antibody penetration and antibody-dependent cellular cytotoxicity.

    Science.gov (United States)

    Llerena, J M; Ruíz-Argüelles, A; Alarcón-Segovia, D; Llorente, L; Díaz-Jouanen, E

    1981-01-01

    The same Fc gamma receptor appears to be shared for two important phenomena: antibody-dependent cellular cytotoxicity (ADCC) and antibody penetration into living cells. ADCC is inhibited through interaction with the Fc gamma receptor during the antibody penetration process, indicating that both mechanisms may modulate each other in vitro. PMID:6972908

  17. Do calcium-mediated cellular signalling pathways, prostaglandin E2 (PGE2), estrogen or progesterone receptor antagonists, or bacterial endotoxins affect bovine placental function in vitro?

    Science.gov (United States)

    Weems, Y S; Randel, R D; Carstens, G E; Welsh, T H; Weems, C W

    2004-04-01

    .05). Concentrations of PGE2 in media at 4 and 8 h were lower (P or = 0.05). PGF2alpha was increased (P < or = 0.05) by RU-486 at 8h and no other treatment affected PGF2alpha at 4 or 8 h (P < or = 0.05). In conclusion, modulators of cellular calcium signalling pathways given alone do not affect bovine placental progesterone secretion at the days studied and progesterone receptor-mediated events appear to suppress placental progesterone, PGF2alpha, and PGE2 secretion in cattle. In addition, PGE2 does not appear to regulate bovine placental progesterone secretion when the corpus luteum is functional and bacterial endotoxin does not appear to affect bovine placental secretion of PGF2alpha or PGE2. PMID:15287156

  18. Novel Materials for Cellular Nanosensors

    DEFF Research Database (Denmark)

    Sasso, Luigi

    The monitoring of cellular behavior is useful for the advancement of biomedical diagnostics, drug development and the understanding of a cell as the main unit of the human body. Micro- and nanotechnology allow for the creation of functional devices that enhance the study of cellular dynamics by...... modifications for electrochemical nanosensors for the detection of analytes released from cells. Two type of materials were investigated, each pertaining to the two different aspects of such devices: peptide nanostructures were studied for the creation of cellular sensing substrates that mimic in vivo surfaces...... and that offer advantages of functionalization, and conducting polymers were used as electrochemical sensor surface modifications for increasing the sensitivity towards relevant analytes, with focus on the detection of dopamine released from cells via exocytosis. Vertical peptide nanowires were...

  19. Steady-state and time-resolved two-photon fluorescence microscopy: a versatile tool for probing cellular environment and function

    International Nuclear Information System (INIS)

    In the last decade, the two-photon fluorescence laser-scanning microscopy (TPLSM) has become an indispensable tool for the bioscientific and biomedical research. TPLSM techniques as well as their applications are currently experiencing a dramatic evolution and represent the focus of many biophysical research projects. In this work, we compare in detail two steady-state TPLSM techniques, i.e. single-beam scanning microscopy combined with point-detection (SB-PMT) and multi-beam scanning microscopy combined with synchronous detection (MB-CCD), as far as their technical characteristics relevant for the bioscientific research are concerned, i.e. optical performance and imaging speed. We demonstrate that the SB-PMT technique is more adequate for deep-tissue imaging (few 100 μm depth) than the MB-CCD technique, whereas only the MB-CCD technique enables high-speed imaging for characterizing the dynamics of fast biological phenomena. Novel applications of these techniques are additionally discussed. Moreover, we employ a time-resolved TPLSM technique, i.e. biexponential fluorescence lifetime imaging based on the cellular fluorescence of the nicotinamide pyridine dinucleotides NADH and NADPH, which allows us to probe for the first time the redox cellular metabolism of MIN6 cells (mutated insulin producing pancreatic β-cells) as well as to show the potential of this method for the specific and dynamic investigation of NADH- and NADPH-dependent cellular processes

  20. Steady-state and time-resolved two-photon fluorescence microscopy: a versatile tool for probing cellular environment and function

    Science.gov (United States)

    Denicke, Stefan; Ehlers, Jan-Eric; Niesner, Raluca; Quentmeier, Stefan; Gericke, Karl-Heinz

    2007-09-01

    In the last decade, the two-photon fluorescence laser-scanning microscopy (TPLSM) has become an indispensable tool for the bioscientific and biomedical research. TPLSM techniques as well as their applications are currently experiencing a dramatic evolution and represent the focus of many biophysical research projects. In this work, we compare in detail two steady-state TPLSM techniques, i.e. single-beam scanning microscopy combined with point-detection (SB-PMT) and multi-beam scanning microscopy combined with synchronous detection (MB-CCD), as far as their technical characteristics relevant for the bioscientific research are concerned, i.e. optical performance and imaging speed. We demonstrate that the SB-PMT technique is more adequate for deep-tissue imaging (few 100 μm depth) than the MB-CCD technique, whereas only the MB-CCD technique enables high-speed imaging for characterizing the dynamics of fast biological phenomena. Novel applications of these techniques are additionally discussed. Moreover, we employ a time-resolved TPLSM technique, i.e. biexponential fluorescence lifetime imaging based on the cellular fluorescence of the nicotinamide pyridine dinucleotides NADH and NADPH, which allows us to probe for the first time the redox cellular metabolism of MIN6 cells (mutated insulin producing pancreatic β-cells) as well as to show the potential of this method for the specific and dynamic investigation of NADH- and NADPH-dependent cellular processes.

  1. Recent progress in 'bioelectronics' research. Part 2. ; Biocomputer (biological artificial neural networks formed by cultured neurons). Baioerekutoronikusu eno michi (shorai wa saibogu mo) 2. ; Baiokonpyuta (baiyo shinkei saibo ni yoru jinko shinkei kairo)

    Energy Technology Data Exchange (ETDEWEB)

    Kawana, A. (Nippon Telegraph and Telephone Corp., Tokyo (Japan))

    1994-02-20

    A report is made on the study on the functions of neural networks in which cultured neurons are used. A group of brain neurons is taken to pieces once, and restructured in a dish into a neural network. It is possible to observe the behavior of such a neural network. A neurite starts extending from each cell in about a week to form a neural network. The activity of the neural network is then investigated. Many flat microelectrodes are formed instead of acicular electrodes on the substrate where cells are cultivated by microprocessing, and measurement of electrical activity of cells through the electrodes is attempted. In the cultured neural network formed on a micro electrode array, electrical signals can be exchanged with the outside through this electrode. This method seems to be effective for the study of the effect of prolonged stimuli on the functions of the neural network, i.e. mechanism of learning. Formation of a simple neural network is attempted wherein cells exist only on the electrode to form mutual joining. 9 refs., 8 figs.

  2. Predicting Cellular Growth from Gene Expression Signatures

    OpenAIRE

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

    2009-01-01

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

  3. Cellular Dynamics of RNA Modification

    OpenAIRE

    Yi, Chengqi; Pan, Tao

    2011-01-01

    Decades of research have identified over 100 types of ribonucleosides that are post-transcriptionally modified. Many modified nucleosides are conserved in bacteria, archeae and eukaryotes, while some modified nucleosides are unique to each branch of life. However, the cellular and functional dynamics of RNA modifications remains largely unexplored, mostly due to the lack of functional hypotheses and experimental methods for quantification and large scale analysis. Just as many well characteri...

  4. Cellular senescence in aging primates.

    Science.gov (United States)

    Herbig, Utz; Ferreira, Mark; Condel, Laura; Carey, Dee; Sedivy, John M

    2006-03-01

    The aging of organisms is characterized by a gradual functional decline of all organ systems. Mammalian somatic cells in culture display a limited proliferative life span, at the end of which they undergo an irreversible cell cycle arrest known as replicative senescence. Whether cellular senescence contributes to organismal aging has been controversial. We investigated telomere dysfunction, a recently discovered biomarker of cellular senescence, and found that the number of senescent fibroblasts increases exponentially in the skin of aging baboons, reaching >15% of all cells in very old individuals. In addition, the same cells contain activated ataxia-telangiectasia mutated kinase and heterochromatinized nuclei, confirming their senescent status. PMID:16456035

  5. Integrated cellular systems

    Science.gov (United States)

    Harper, Jason C.

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

  6. Penetration of anticancer drugs through tumour tissue as a function of cellular packing density and interstitial fluid pressure and its modification by bortezomib

    Directory of Open Access Journals (Sweden)

    Grantab Rama H

    2012-06-01

    Full Text Available Abstract Background Limited penetration of anticancer drugs in solid tumours is a probable cause of drug resistance. Our previous results indicate that drug penetration depends on cellular packing density and adhesion between cancer cells. Methods We used epithelioid and round cell variants of the HCT-8 human colon carcinoma cell lines to generate tightly and loosely packed xenografts in nude mice. We measured packing density and interstitial fluid pressure (IFP and studied the penetration of anti-cancer drugs through multilayered cell cultures (MCC derived from epithelioid HCT-8 variants, and the distribution of doxorubicin in xenografts with and without pre-treatment with bortezomib. Results We show lower packing density in xenografts established from round cell than epithelioid cell lines, with lower IFP in xenografts. There was better distribution of doxorubicin in xenografts grown from round cell variants, consistent with previous data in MCC. Bortezomib pre-treatment reduced cellular packing density, improved penetration, and enhanced cytotoxcity of several anticancer drugs in MCC derived from epithelioid cell lines. Pre-treatment of xenografts with bortezomib enhanced the distribution of doxorubicin within them. Conclusions Our results provide a rationale for further investigation of agents that enhance the distribution of chemotherapeutic drugs in combination with conventional chemotherapy in solid tumours.

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

    Science.gov (United States)

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

    2016-01-01

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

  8. Structural, molecular and cellular functions of MSH2 and MSH6 during DNA mismatch repair, damage signaling and other noncanonical activities

    International Nuclear Information System (INIS)

    The field of DNA mismatch repair (MMR) has rapidly expanded after the discovery of the MutHLS repair system in bacteria. By the mid 1990s yeast and human homologues to bacterial MutL and MutS had been identified and their contribution to hereditary non-polyposis colorectal cancer (HNPCC; Lynch syndrome) was under intense investigation. The human MutS homologue 6 protein (hMSH6), was first reported in 1995 as a G:T binding partner (GTBP) of hMSH2, forming the hMutSα mismatch-binding complex. Signal transduction from each DNA-bound hMutSα complex is accomplished by the hMutLα heterodimer (hMLH1 and hPMS2). Molecular mechanisms and cellular regulation of individual MMR proteins are now areas of intensive research. This review will focus on molecular mechanisms associated with mismatch binding, as well as emerging evidence that MutSα, and in particular, MSH6, is a key protein in MMR-dependent DNA damage response and communication with other DNA repair pathways within the cell. MSH6 is unstable in the absence of MSH2, however it is the DNA lesion-binding partner of this heterodimer. MSH6, but not MSH2, has a conserved Phe-X-Glu motif that recognizes and binds several different DNA structural distortions, initiating different cellular responses. hMSH6 also contains the nuclear localization sequences required to shuttle hMutSα into the nucleus. For example, upon binding to O6meG:T, MSH6 triggers a DNA damage response that involves altered phosphorylation within the N-terminal disordered domain of this unique protein. While many investigations have focused on MMR as a post-replication DNA repair mechanism, MMR proteins are expressed and active in all phases of the cell cycle. There is much more to be discovered about regulatory cellular roles that require the presence of MutSα and, in particular, MSH6

  9. Structural, molecular and cellular functions of MSH2 and MSH6 during DNA mismatch repair, damage signaling and other noncanonical activities

    Energy Technology Data Exchange (ETDEWEB)

    Edelbrock, Michael A., E-mail: Edelbrock@findlay.edu [The University of Findlay, 1000 North Main Street, Findlay, OH 45840 (United States); Kaliyaperumal, Saravanan, E-mail: Saravanan.Kaliyaperumal@hms.harvard.edu [Division of Comparative Medicine and Pathology, New England Primate Research Center, One Pine Hill Drive, Southborough, MA 01772 (United States); Williams, Kandace J., E-mail: Kandace.williams@utoledo.edu [University of Toledo College of Medicine and Life Sciences, Department of Biochemistry and Cancer Biology, 3000 Transverse Dr., Toledo, OH 43614 (United States)

    2013-03-15

    The field of DNA mismatch repair (MMR) has rapidly expanded after the discovery of the MutHLS repair system in bacteria. By the mid 1990s yeast and human homologues to bacterial MutL and MutS had been identified and their contribution to hereditary non-polyposis colorectal cancer (HNPCC; Lynch syndrome) was under intense investigation. The human MutS homologue 6 protein (hMSH6), was first reported in 1995 as a G:T binding partner (GTBP) of hMSH2, forming the hMutSα mismatch-binding complex. Signal transduction from each DNA-bound hMutSα complex is accomplished by the hMutLα heterodimer (hMLH1 and hPMS2). Molecular mechanisms and cellular regulation of individual MMR proteins are now areas of intensive research. This review will focus on molecular mechanisms associated with mismatch binding, as well as emerging evidence that MutSα, and in particular, MSH6, is a key protein in MMR-dependent DNA damage response and communication with other DNA repair pathways within the cell. MSH6 is unstable in the absence of MSH2, however it is the DNA lesion-binding partner of this heterodimer. MSH6, but not MSH2, has a conserved Phe-X-Glu motif that recognizes and binds several different DNA structural distortions, initiating different cellular responses. hMSH6 also contains the nuclear localization sequences required to shuttle hMutSα into the nucleus. For example, upon binding to O{sup 6}meG:T, MSH6 triggers a DNA damage response that involves altered phosphorylation within the N-terminal disordered domain of this unique protein. While many investigations have focused on MMR as a post-replication DNA repair mechanism, MMR proteins are expressed and active in all phases of the cell cycle. There is much more to be discovered about regulatory cellular roles that require the presence of MutSα and, in particular, MSH6.

  10. HIV-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) -Mediating Antibodies Decline while NK Cell Function Increases during Antiretroviral Therapy (ART)

    DEFF Research Database (Denmark)

    Skov Jensen, Sanne; 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 (<350 cells/μl blood) and the 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...

  11. 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.

    Science.gov (United States)

    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 properties, histometric parameters and sperm dynamics, testis and body weight, testicular cell population and serum testosterone level were analyzed by an acceptable method. Results showed that the mean serum testosterone level was decreased significantly in both treatment groups (50 and 100 mg/Kg b.w) during the experiment time, compared with control group (p < 0.05). However, Rosmarinus officinalis did not change the total count, motility and viability of sperm. In addition, Rosmarinus officinalis at both doses did not change body and testes weight and their ratio. Furthermore, Rosmarinus officinalis increased the number of Spermatogonia at both doses, Spermatocyte at doses of 50 mg/Kg b.w, Leydig cell and Spermatid at dose of 100 mg/Kg b.w significantly (p < 0.05). Rosmarinus officinalis did not significantly affect the number of Spermatozoid and Sertoli cells. In conclusion, it seems that Rosmarinus officinalis may have some hormonal and cellular effects on the testes which can contribute the spermatogenesis process in rat. Rosmarinus officinalis may have antiandrogenic effect potentially indicating the possibility of developing herbal male contraceptive. PMID:24250620

  12. Ceramics adsorbing virus and cells. Uirusu, saibo bunri ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Hiraide, T. (Asahi Optical Co. Ltd., Tokyo (Japan))

    1993-07-01

    It has been reported that hydroxyapatite (HA), which is the main inorganic component of teeth and bones of homo sapiens and used for biomaterials such as artificial tooth roots, adsorbs viruses such as influenza viruses. In this article, the history of development up to now of HA and its adsorption mechanism of protein, virus, etc., are introduced. HA was applied for chromatography in 1956 becoming one of the separating and refining methods of protein and nucleic acid, then after the development of spherical porous HA, it has become applied for high speed liquid chromatography (HPLC). Also by means of a column filled with HA granules, T-cells have been able to be purified in a short time from lymphocyte which was separated from the blood of homo sapiens. Recently it has also been reported that HA granules can adsorb influenza viruses, Japanese encephalitis viruses, polio viruses and hepatitis B viruses, and a cold-preventative mask based upon this report is now on sale. 11 refs., 7 figs.

  13. Cellular Signaling Pathways and Their Clinical Reflections

    Directory of Open Access Journals (Sweden)

    N. Ceren Sumer-Turanligil

    2010-06-01

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

  14. 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. PMID:25225046

  15. Mutations in human C2CD3 cause skeletal dysplasia and provide new insights into phenotypic and cellular consequences of altered C2CD3 function.

    Science.gov (United States)

    Cortés, Claudio R; McInerney-Leo, Aideen M; Vogel, Ida; Rondón Galeano, Maria C; Leo, Paul J; Harris, Jessica E; Anderson, Lisa K; Keith, Patricia A; Brown, Matthew A; Ramsing, Mette; Duncan, Emma L; Zankl, Andreas; Wicking, Carol

    2016-01-01

    Ciliopathies are a group of genetic disorders caused by defective assembly or dysfunction of the primary cilium, a microtubule-based cellular organelle that plays a key role in developmental signalling. Ciliopathies are clinically grouped in a large number of overlapping disorders, including the orofaciodigital syndromes (OFDS), the short rib polydactyly syndromes and Jeune asphyxiating thoracic dystrophy. Recently, mutations in the gene encoding the centriolar protein C2CD3 have been described in two families with a new sub-type of OFDS (OFD14), with microcephaly and cerebral malformations. Here we describe a third family with novel compound heterozygous C2CD3 mutations in two fetuses with a different clinical presentation, dominated by skeletal dysplasia with no microcephaly. Analysis of fibroblast cultures derived from one of these fetuses revealed a reduced ability to form cilia, consistent with previous studies in C2cd3-mutant mouse and chicken cells. More detailed analyses support a role for C2CD3 in basal body maturation; but in contrast to previous mouse studies the normal recruitment of the distal appendage protein CEP164 suggests that this protein is not sufficient for efficient basal body maturation and subsequent axonemal extension in a C2CD3-defective background. PMID:27094867

  16. A Monosaccharide Residue Is Sufficient to Maintain Mouse and Human IgG Subclass Activity and Directs IgG Effector Functions to Cellular Fc Receptors

    Directory of Open Access Journals (Sweden)

    Daniela Kao

    2015-12-01

    Full Text Available Immunoglobulin G (IgG glycosylation modulates antibody activity and represents a major source of heterogeneity within antibody preparations. Depending on their glycosylation pattern, individual IgG glycovariants present in recombinant antibody preparations may trigger effects ranging from enhanced pro-inflammatory activity to increased anti-inflammatory activity. In contrast, reduction of IgG glycosylation beyond the central mannose core is generally believed to result in impaired IgG activity. However, this study reveals that a mono- or disaccharide structure consisting of one N-acetylglucosamine with or without a branching fucose residue is sufficient to retain the activity of the most active human and mouse IgG subclasses in vivo and further directs antibody activity to cellular Fcγ receptors. Notably, the activity of minimally glycosylated antibodies is not predicted by in vitro assays based on a monomeric antibody-Fcγ-receptor interaction analysis, whereas in vitro assay systems using immune complexes are more suitable to predict IgG activity in vivo.

  17. Signal processing in cellular clocks

    OpenAIRE

    Forger, Daniel B.

    2011-01-01

    Many biochemical events within a cell need to be timed properly to occur at specific times of day, after other events have happened within the cell or in response to environmental signals. The cellular biochemical feedback loops that time these events have already received much recent attention in the experimental and modeling communities. Here, we show how ideas from signal processing can be applied to understand the function of these clocks. Consider two signals from the network s(t) and r(...

  18. Comparative Genomic Analysis of Buffalo (Bubalus bubalis) NOD1 and NOD2 Receptors and Their Functional Role in In-Vitro Cellular Immune Response

    OpenAIRE

    Brahma, Biswajit; Kumar, Sushil; De, Bidhan Chandra; Mishra, Purusottam; Patra, Mahesh Chandra; Gaur, Deepak; Chopra, Meenu; Gautam, Devika; Mahanty, Sourav; Malik, Hrudananda; Malakar, Dhruba; Datta, Tirtha Kumar; De, Sachinandan

    2015-01-01

    Nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs) are innate immune receptors that recognize bacterial cell wall components and initiate host immune response. Structure and function of NLRs have been well studied in human and mice, but little information exists on genetic composition and role of these receptors in innate immune system of water buffalo—a species known for its exceptional disease resistance. Here, a comparative study on the functional domains of NOD1 and...

  19. Modelling cellular behaviour

    Science.gov (United States)

    Endy, Drew; Brent, Roger

    2001-01-01

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

  20. Cellular Dynamics of RNA Modification

    Science.gov (United States)

    Yi, Chengqi; Pan, Tao

    2011-01-01

    Conspectus Decades of research have identified over 100 types of ribonucleosides that are post-transcriptionally modified. Many modified nucleosides are conserved in bacteria, archeae and eukaryotes, while some modified nucleosides are unique to each branch of life. However, the cellular and functional dynamics of RNA modifications remains largely unexplored, mostly due to the lack of functional hypotheses and experimental methods for quantification and large scale analysis. Just as many well characterized protein and DNA modifications, many RNA modifications are not essential for life. Instead, increasingly more evidence indicates that RNA modifications can play regulatory roles in cells, especially in response to stress conditions. In this Account, we review some known examples of RNA modifications that are dynamically controlled in cells and introduce some contemporary technologies and methods that enhance the studies of cellular dynamics of RNA modifications. Examples of RNA modifications discussed in this Account include (Figure 1): (1) 4-thio uridine (s4U) which can act as a cellular sensor of near UV-light; (2) queuosine (Q) which is a potential biomarker for malignancy; (3) N6-methyl adenine (m6A) which is the prevalent modification in eukaryotic mRNAs; and (4) pseudouridine (ψ) which are inducible by nutrient deprivation. Two recent technical advances that stimulated the studies of cellular dynamics of modified ribonucleosides are also described. First, a genome-wide method combines primer extension and microarray to study N1-methyl adenine (m1A) hypomodification in human tRNA. Second, a quantitative mass spectrometric method investigates dynamic changes of a wide range of tRNA modifications under stress conditions in yeast. In addition, we discuss potential mechanisms that control dynamic regulation of RNA modifications, and hypotheses for discovering potential RNA de-modification enzymes. We conclude the Account by highlighting the need to develop new

  1. Heterogeneous cellular networks

    CERN Document Server

    Hu, Rose Qingyang

    2013-01-01

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

  2. Cellular Reflectarray Antenna

    Science.gov (United States)

    Romanofsky, Robert R.

    2010-01-01

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

  3. International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials

    OpenAIRE

    Galipeau, Jacques; Krampera, Mauro; Barrett, John; Dazzi, Francesco; Deans, Robert J.; Debruijn, Joost; Dominici, Massimo; Fibbe, Willem E.; Gee, Adrian P.; Gimble, Jeffery M.; Hematti, Peiman; Koh, Mickey B.C.; Leblanc, Katarina; Martin, Ivan; McNiece, Ian K.

    2015-01-01

    Mesenchymal stromal cells (MSCs) as a pharmaceutical for ailments characterized by pathogenic autoimmune, alloimmune and inflammatory processes now cover the spectrum of early- to late-phase clinical trials in both industry and academic sponsored studies. There is a broad consensus that despite different tissue sourcing and varied culture expansion protocols, human MSC-like cell products likely share fundamental mechanisms of action mediating their anti-inflammatory and tissue repair function...

  4. A novel protein-RNA binding assay: functional interactions of the foot-and-mouth disease virus internal ribosome entry site with cellular proteins.

    OpenAIRE

    Stassinopoulos, I A; Belsham, G J

    2001-01-01

    Translation initiation on foot-and-mouth disease virus (FMDV) RNA occurs by a cap-independent mechanism directed by a highly structured element (approximately 435 nt) termed an internal ribosome entry site (IRES). A functional assay to identify proteins that bind to the FMDV IRES and are necessary for FMDV IRES-mediated translation initiation has been developed. In vitro-transcribed polyadenylated RNAs corresponding to the whole or part of the FMDV IRES were immobilized on oligo-dT Dynabeads ...

  5. Adolescence methylphenidate treatment in a rodent model of attention deficit/hyperactivity disorder: Dopamine transporter function and cellular distribution in adulthood

    OpenAIRE

    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 prefr...

  6. Cellular oncogenes in neoplasia.

    OpenAIRE

    Chan, V T; McGee, J O

    1987-01-01

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

  7. Cellular Cardiomyoplasty: Clinical Application

    OpenAIRE

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

    2004-01-01

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

  8. Differential cellular FGF-2 upregulation in the rat facial nucleus following axotomy, functional electrical stimulation and corticosterone: a possible therapeutic target to Bell's palsy

    Directory of Open Access Journals (Sweden)

    Oliveira Gabriela P

    2010-11-01

    Full Text Available Abstract Background The etiology of Bell's palsy can vary but anterograde axonal degeneration may delay spontaneous functional recovery leading the necessity of therapeutic interventions. Corticotherapy and/or complementary rehabilitation interventions have been employed. Thus the natural history of the disease reports to a neurotrophic resistance of adult facial motoneurons leading a favorable evolution however the related molecular mechanisms that might be therapeutically addressed in the resistant cases are not known. Fibroblast growth factor-2 (FGF-2 pathway signaling is a potential candidate for therapeutic development because its role on wound repair and autocrine/paracrine trophic mechanisms in the lesioned nervous system. Methods Adult rats received unilateral facial nerve crush, transection with amputation of nerve branches, or sham operation. Other group of unlesioned rats received a daily functional electrical stimulation in the levator labii superioris muscle (1 mA, 30 Hz, square wave or systemic corticosterone (10 mgkg-1. Animals were sacrificed seven days later. Results Crush and transection lesions promoted no changes in the number of neurons but increased the neurofilament in the neuronal neuropil of axotomized facial nuclei. Axotomy also elevated the number of GFAP astrocytes (143% after crush; 277% after transection and nuclear FGF-2 (57% after transection in astrocytes (confirmed by two-color immunoperoxidase in the ipsilateral facial nucleus. Image analysis reveled that a seven days functional electrical stimulation or corticosterone led to elevations of FGF-2 in the cytoplasm of neurons and in the nucleus of reactive astrocytes, respectively, without astrocytic reaction. Conclusion FGF-2 may exert paracrine/autocrine trophic actions in the facial nucleus and may be relevant as a therapeutic target to Bell's palsy.

  9. 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*

    OpenAIRE

    Chakraborty, Juni; Banerjee, Shuvomoy; Ray, Pallab; Hossain, Dewan Md Sakib; Bhattacharyya, Sankar; Adhikary, Arghya; Chattopadhyay, Sreya; Das, Tanya; Sa, Gaurisankar

    2010-01-01

    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 expressi...

  10. Integrating mitochondrial translation into the cellular context.

    Science.gov (United States)

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

    2015-10-01

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

  11. Nanomechanics of magnetically driven cellular endocytosis

    Science.gov (United States)

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

    2011-10-01

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

  12. Apoptotic regulation of epithelial cellular extrusion

    OpenAIRE

    De Andrade, Daniel,; Rosenblatt, Jody

    2011-01-01

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

  13. Cellular scaling rules for primate brains

    OpenAIRE

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

    2007-01-01

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

  14. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

    Directory of Open Access Journals (Sweden)

    Hwang Jong-Hee

    2008-10-01

    Full Text Available Abstract Background Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. Methods To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. Results Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap, effects on host cell protein processing (ubiquitin ligase, synapse remodeling (Complement 1q, and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease. Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of

  15. Chronic exposure to MDMA (ecstasyinduces DNA damage, impairs functional antioxidant cellular defenses, enhances the lipid peroxidation process and alters testes histopathology in male rat

    Directory of Open Access Journals (Sweden)

    Nadia Gamal Zaki, ** Laila Abdel Kawy

    2013-04-01

    Full Text Available Background : 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy" is consumed mainly by young population. For this reason, it is especially relevant to take into consideration the effects on the reproductive system. The influence of MDMA on the fertility and reproduction of the male rat was assessed in this study. Material and methods: MDMA was administered orally at 0 mg/kg (control, 10 and 30 mg/kg to male rats for 15,30,45 consecutive days followed by 15 days withdrawal. Hormonal, biochemical, histological and testicular were evaluated in the rats. The present study aimed to investigate if daily oral administration of ecstasy at low doses(10mg for 45 days has any deleterious effects on reproductive functions of male rats. Animals were randomly divided into four groups of ten rats each, assigned as control rats, or(0mg ecstasy, rats treated with 10mg ecstasy for, (15,30,45 days, rats treated with 30mg/kg body weight ecstasy for(,15,30,45days by oral gavage. The third group(45 days was followed by 15 withdrawal period(W15. Results: The activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase in testicular homogenate were decreased while the levels of lipid peroxidation increased significantly in the treated rats as compared with the corresponding group of control animals. In group 30mg, only, arachidonic acid was significantly elevated in the testicular homogenate while linoleic acid was decresed when compared to control. Testis DNA fragmentation was observed in 30mg group, but not 10.mg. It is concluded that low doses of ecstasy exposure(10 mg/Kg had moderate detrimental effects on reproductive organ system and more severe effects are likely to be observed at higher dose levels. These results indicate that ecstasy is directly toxic to primary Leydig cells, and that the decreased percentage of normal cells and the increased level of DNA damage in ecstasy -exposed Leydig cells may be responsible for

  16. Irregular Cellular Learning Automata.

    Science.gov (United States)

    Esnaashari, Mehdi; Meybodi, Mohammad Reza

    2015-08-01

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

  17. Architected Cellular Materials

    Science.gov (United States)

    Schaedler, Tobias A.; Carter, William B.

    2016-07-01

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

  18. Cellular Homeostasis and Aging.

    Science.gov (United States)

    Hartl, F Ulrich

    2016-06-01

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

  19. Wireless Cellular Mobile Communications

    Directory of Open Access Journals (Sweden)

    V. Zalud

    2002-12-01

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

  20. Translating partitioned cellular automata into classical type cellular automata

    OpenAIRE

    Poupet, Victor

    2008-01-01

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

  1. Genetic Dominance & Cellular Processes

    Science.gov (United States)

    Seager, Robert D.

    2014-01-01

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

  2. Radioactivity of cellular concrete

    International Nuclear Information System (INIS)

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

  3. The New Cellular Immunology

    Science.gov (United States)

    Claman, Henry N.

    1973-01-01

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

  4. Cellular compartmentalization of secondary metabolism

    Directory of Open Access Journals (Sweden)

    H. Corby eKistler

    2015-02-01

    Full Text Available Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g. amino acids, acetyl CoA, NADPH, enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported.

  5. Cellular fate and functions of glucosylceramide

    NARCIS (Netherlands)

    Wolthoorn, J.

    2006-01-01

    The organization of the synthesis of sphingomyelin and the simple glycosphingolipids in the Golgi appears to be highly important not only for creating sphingolipid/cholesterol rafts in the late Golgi but also for regulating numerous protein glycosylation, processing and sorting steps in the Golgi lu

  6. Cellular fate and functions of glucosylceramide

    OpenAIRE

    Wolthoorn, J.

    2006-01-01

    The organization of the synthesis of sphingomyelin and the simple glycosphingolipids in the Golgi appears to be highly important not only for creating sphingolipid/cholesterol rafts in the late Golgi but also for regulating numerous protein glycosylation, processing and sorting steps in the Golgi lumen via an intricate mechanism of pH regulation. The universal character of this regulatory system predicts that it represents one basic link between very different physiological parameters, sphing...

  7. 玫瑰茄多糖对小鼠体液免疫和细胞免疫功能的影响%Study on the Influence of Hibiscus Sabdariffa Polysaccharide on Humoral Immunity and Cellular Immunity Function in Mice

    Institute of Scientific and Technical Information of China (English)

    张赛男

    2015-01-01

    玫瑰茄多糖设置低、中、高3个剂量组和1个对照组,给(SPF)小鼠连续灌胃4周,以脾淋巴细胞转化功能、迟发性变态反应(DTH)、溶血空斑数、半数溶血值(HC50)等为指标,观察瑰茄多糖对小鼠体液免疫和细胞免疫功能的影响。结果表明:与对照组比较,脾淋巴细胞转化功能、迟发性变态反应(DTH)、溶血空斑数、半数溶血值(HC50)测定实验均有显著提高作用。其中,高剂量组对小鼠迟发型变态反应能力(DTH)影响、半数溶血值(HC50)达到极显著水平(P<0.01),高剂量组对小鼠溶血空斑数的影响达到显著水平(P<0.05)。说明玫瑰茄多糖具有增强小鼠体液免疫功能和细胞免疫功能的作用。%(SPF) Rats were feed with low、 medium、 high dose of Hibiscus Sabdariffa polysaccharide and 1 control group for 4 weeks to observe the humoral immunity and cellular immunity function of Hibiscus Sabdariffa polysaccharides by measurement spleen lymphocyte transform function、 delayed type hypersensitivity (DTH)、 the serum hemolysin concentration、 the serum hemolysin concentration (HC50) . Results, To compared with control group, spleen lymphocyte transform function、 delayed type hypersensitivity (DTH)、 the serum hemolysin concentration、 the serum hemolysin concentration (HC50) were obviously improved. And the influence of high dose group on delayed type hypersensitivity (DTH)、 the serum hemolysin concentration (HC50) reached extremely significant level(P<0.01), the influence of high dose group on the serum hemolysin concentration reached significant level (P<0.05) .Conclusions, Hibiscus Sabdariffa polysaccharide has the role of enhancing humoral immunity and cellular immunity function in mice.

  8. Electromagnetic cellular interactions

    Czech Academy of Sciences Publication Activity Database

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

    2011-01-01

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

  9. Effects of ethanol extraction from pomegranate peel on cellular immune function in mice%石榴皮乙醇提取物对小鼠细胞免疫功能的影响

    Institute of Scientific and Technical Information of China (English)

    吕琴

    2013-01-01

    Objective: To investigate effcts of pomegranate rind ethanol extract on the function of immune cells. Methods:Established immunosuppressed animal models by intraperitoneal injection of cyclophosphamide, the application of pomegranate peel ethanol extract, pomegranate rind total flavonoids extract on mice immunosuppressive treatment to observe the two extracts murine macrophage phagocytosis, spleen lymphocyte transformation function. Results:Middle-dose group and high-dose group and pomegranate rind of pomegranate peel ethanol extract of total flavonoids extracted group can enhance the phagocytic function of mouse peritoneal macrophages, the high-dose group can enhance mouse spleen lymphocyte transformation function (P<0.01). Conclusion:Pomegranate peel ethanol extract on cellular immune function of immunosuppressed mice has improved to some extent.%  目的:探讨石榴皮乙醇提取物对小鼠细胞免疫功能的影响。方法:通过腹腔注射环磷酰胺建立免疫抑制动物模型,应用石榴皮乙醇提取物、石榴皮总黄酮提取物对免疫抑制的小鼠进行治疗,观察两种提取物对小鼠巨噬细胞吞噬功能、脾淋巴细胞转化功能的影响。结果:石榴皮乙醇提取物中剂量组和高剂量组及石榴皮总黄酮提取物组能增强小鼠腹腔巨噬细胞的吞噬功能,高剂量组能够增强小鼠脾淋巴细胞转化功能(P<0.01)。结论:石榴皮乙醇提取物对免疫抑制小鼠的细胞免疫功能具有一定的提高作用。

  10. Environment Aware Cellular Networks

    KAUST Repository

    Ghazzai, Hakim

    2015-02-01

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

  11. Failover in cellular automata

    CERN Document Server

    Kumar, Shailesh

    2010-01-01

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

  12. Cellular-scale hydrodynamics

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  13. Cellular mechanics and motility

    Science.gov (United States)

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

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

  14. Radiolabelled Cellular Blood Elements

    International Nuclear Information System (INIS)

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

  15. Are cellular phone blocking applications effective for novice teen drivers?

    OpenAIRE

    Creaser, J.

    2014-01-01

    Distracted driving is a significant concern for novice teen drivers. Although cellular phone bans are applied in many jurisdictions to restrict cellular phone use, teen drivers often report making calls and texts while driving. Method The Minnesota Teen Driver Study incorporated cellular phone blocking functions via a software application for 182 novice teen drivers in two treatment conditions. The first condition included 92 teens who ran a driver support application on a smartphone that als...

  16. Discrete geodesics and cellular automata

    CERN Document Server

    Arrighi, Pablo

    2015-01-01

    This paper proposes a dynamical notion of discrete geodesics, understood as straightest trajectories in discretized curved spacetime. The notion is generic, as it is formulated in terms of a general deviation function, but readily specializes to metric spaces such as discretized pseudo-riemannian manifolds. It is effective: an algorithm for computing these geodesics naturally follows, which allows numerical validation---as shown by computing the perihelion shift of a Mercury-like planet. It is consistent, in the continuum limit, with the standard notion of timelike geodesics in a pseudo-riemannian manifold. Whether the algorithm fits within the framework of cellular automata is discussed at length. KEYWORDS: Discrete connection, parallel transport, general relativity, Regge calculus.

  17. Aging cellular networks: chaperones as major participants

    OpenAIRE

    Soti, Csaba; Csermely, Peter

    2006-01-01

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

  18. Chaotic behavior in the disorder cellular automata

    International Nuclear Information System (INIS)

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

  19. Software-Defined Cellular Mobile Network Solutions

    Institute of Scientific and Technical Information of China (English)

    Jiandong Li; Peng Liu; Hongyan Li

    2014-01-01

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

  20. Phagocytosis, a cellular immune response in insects

    Directory of Open Access Journals (Sweden)

    C Rosales

    2011-06-01

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

  1. Multiuser Cellular Network

    CERN Document Server

    Bao, Yi; Chen, Ming

    2011-01-01

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

  2. Modeling and cellular studies

    International Nuclear Information System (INIS)

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

  3. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

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

  4. Computer Studies on the Mechanisms Controlling Cellular Proliferation

    International Nuclear Information System (INIS)

    A model of the autoregulation of mitotic and functional activity of the cells is used (R. Tsanev and B. Sendov, J. theoret. Biol. 12 (1966) 327) to study by means of a digital computer the reaction of different cellular systems (a synchronous cellular population, liver and epidermis) to injuring agents disturbing the steady state of the system. The reaction of the cellular models to different kinds of injury was found to imitate adequately some particular features of the real regenerative processes. The model may also be useful to check different hypotheses concerning the mechanisms by which irradiation affects cellular proliferation. (author)

  5. Characteristics of Middle School Students Learning Actions in Outdoor Mathematical Activities with the Cellular Phone

    Science.gov (United States)

    Daher, Wajeeh; Baya'a, Nimer

    2012-01-01

    Learning in the cellular phone environment enables utilizing the multiple functions of the cellular phone, such as mobility, availability, interactivity, verbal and voice communication, taking pictures or recording audio and video, measuring time and transferring information. These functions together with mathematics-designated cellular phone…

  6. Klotho-Dependent Cellular Transport Regulation.

    Science.gov (United States)

    Sopjani, M; Dërmaku-Sopjani, M

    2016-01-01

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

  7. 75 FR 65640 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-10-26

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and... Tumor Vaccines and Biotechnology Branch, Office of Cellular, Tissue and Gene Therapies, Center...

  8. Immunometabolism: Cellular Metabolism Turns Immune Regulator.

    Science.gov (United States)

    Loftus, Róisín M; Finlay, David K

    2016-01-01

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

  9. The State of Cellular Probes

    OpenAIRE

    Yim, Youngbin

    2003-01-01

    Cellular probe technology is one of several potentially promising technologies for obtaining accurate travel time information. In 1996, the Federal Communications Commission (FCC) mandated E911 requirements that cellular location be provided when 911 emergency calls come in to emergency management authorities. The E911 requirements allow 50 -300 meters from the emergency call location, depending on the type of cellular phone technology used and whether handset-based or network-based solutions...

  10. Never-ageing cellular senescence

    OpenAIRE

    Ogrunc, Müge; d’Adda di Fagagna, Fabrizio

    2011-01-01

    Cellular senescence was historically discovered as a form of cellular ageing of in vitro cultured cells. It has been under the spotlight following the evidence of oncogene-induced senescence in vivo and its role as a potent tumour suppressor mechanism. Presently, a PubMed search using keywords ‘cellular senescence and cancer’ reveals 8398 number of references (by April 2011) showing that while our knowledge of senescence keeps expanding, the complexity of the phenomenon keeps us – researchers...

  11. Effect of Phototherapy on Cellular Immune Functions of Newborns with Unconjugated Hyperbilirubinemia%光疗对高未结合胆红素血症新生儿细胞免疫功能的影响

    Institute of Scientific and Technical Information of China (English)

    秦俊; 周四芳; 王瑜; 马洁; 胡向耘; 徐江霞

    2012-01-01

    Objective To investigate the effect and mechanism of phototherapy on the cellular immune functions of newborns with un-conjugated hyperbilirubinemia. Methods One hundred full - term newborns with unconjugated hyperbilirubinemia were randomly divided into 5 groups: Medilac - Vita group (group A ) , Medilac - Vita with continuous phototherapy group (group B ) , Medilac - Vita with intermittent phototherapy group(group C) .continuous phototherapy group(group D) ,and intermittent phototherapy group( group E). Blood samples of the patients in 5 groups were respectively measured of levels of IL - 2, IL - 10 and serum bilirubin at 0 hour before treatment ,24 hours and 48 hours after the treatment to analyze the immune parameters with statistical methodology. Results IL -2 and IL - 10 in group B,group C,group D, group E at 24 hours and 48 hours after treatment were all increased compared with 0 hour before treatment in the same group,and the differences were all statistically significant( Pa < 0.05 ) ; IL - 2 and IL - 10 in group B, group C, group D, group E at 48 hours after treatment were all increased compared with 24 hours after treatment in the same group, and the differences were all statistically significant (Pa < 0.05 ) ; IL -2 and IL - 10 were compared between every two groups at 24 hours after the treatment, which in group B was higher than group C, group D was higher than group E,and the diffe-rences were all significant (Pa <0.001) ;IL -2 in 4 groups were respectively compared at 48 hours after treatment:group B was lower than group C,group D was lower than group E.and the differences were all significant (Pa <0.001) ;IL- 10 in 4 groups were respectively compared at 48 hours after the treatment:group B was higher than group C,group D was higher than group E,and the differences were all very significant ( Pa < 0. 001). Conclusions Phototherapy can stimulate IL - 2 and IL - 10 to affect the immune function of newborns in addition to reduce the neonatal serum

  12. Active Cellular Nematics

    Science.gov (United States)

    Duclos, Guillaume; Erlenkaemper, Christoph; Garcia, Simon; Yevick, Hannah; Joanny, Jean-François; Silberzan, Pascal; Biology inspired physics at mesoscales Team; Physical approach of biological problems Team

    We study the emergence of a nematic order in a two-dimensional tissue of apolar elongated fibroblast cells. Initially, these cells are very motile and the monolayer is characterized by giant density fluctuations, a signature of far-from-equilibrium systems. As the cell density increases because of proliferation, the cells align with each other forming large perfectly oriented domains while the cellular movements slow down and eventually freeze. Therefore topological defects characteristic of nematic phases remain trapped at long times, preventing the development of infinite domains. By analogy with classical non-active nematics, we have investigated the role of boundaries and we have shown that cells confined in stripes of width smaller than typically 500 µm are perfectly aligned in the stripe direction. Experiments performed in cross-shaped patterns show that both the number of cells and the degree of alignment impact the final orientation. Reference: Duclos G., Garcia S., Yevick H.G. and Silberzan P., ''Perfect nematic order in confined monolayers of spindle-shaped cells'', Soft Matter, 10, 14, 2014

  13. 47 CFR 22.909 - Cellular markets.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  14. Exponential Stability for Delayed Cellular Neural Networks

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  15. Cellular Automata Studies of Vertical Silicon Devices

    OpenAIRE

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

    1998-01-01

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

  16. Integrating mitochondrial translation into the cellular context.

    OpenAIRE

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

    2015-01-01

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

  17. Stability of Stochastic Neutral Cellular Neural Networks

    Science.gov (United States)

    Chen, Ling; Zhao, Hongyong

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

  18. Sumo and the cellular stress response

    OpenAIRE

    Enserink, Jorrit M.

    2015-01-01

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

  19. Typhoid fever as cellular microbiological model

    OpenAIRE

    Andrade Dahir Ramos de; Andrade Júnior Dahir Ramos de

    2003-01-01

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

  20. Cellular and synaptic network defects in autism

    OpenAIRE

    Peça, João; Feng, Guoping

    2012-01-01

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

  1. Cellular Automation of Galactic Habitable Zone

    CERN Document Server

    Vukotic, Branislav

    2010-01-01

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

  2. Oxidative stress action in cellular aging

    OpenAIRE

    Monique Cristine de Oliveira; João Paulo Ferreira Schoffen

    2010-01-01

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

  3. Cellular basis of memory for addiction.

    Science.gov (United States)

    Nestler, Eric J

    2013-12-01

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

  4. MIMO Communication for Cellular Networks

    CERN Document Server

    Huang, Howard; Venkatesan, Sivarama

    2012-01-01

    As the theoretical foundations of multiple-antenna techniques evolve and as these multiple-input multiple-output (MIMO) techniques become essential for providing high data rates in wireless systems, there is a growing need to understand the performance limits of MIMO in practical networks. To address this need, MIMO Communication for Cellular Networks presents a systematic description of MIMO technology classes and a framework for MIMO system design that takes into account the essential physical-layer features of practical cellular networks. In contrast to works that focus on the theoretical performance of abstract MIMO channels, MIMO Communication for Cellular Networks emphasizes the practical performance of realistic MIMO systems. A unified set of system simulation results highlights relative performance gains of different MIMO techniques and provides insights into how best to use multiple antennas in cellular networks under various conditions. MIMO Communication for Cellular Networks describes single-user,...

  5. Illuminating cellular physiology: recent developments.

    Science.gov (United States)

    Brovko, Lubov Y; Griffiths, Mansel W

    2007-01-01

    Bioluminescent methods are gaining more and more attention among scientists due to their sensitivity, selectivity and simplicity; coupled with the fact that the bioluminescence can be monitored both in vitro and in vivo. Since the discovery of bioluminescence in the 19th century, enzymes involved in the bioluminescent process have been isolated and cloned. The bioluminescent reactions in several different organisms have also been fully characterized and used as reporters in a wide variety of biochemical assays. From the 1990s it became clear that bioluminescence can be detected and quantified directly from inside a living cell. This gave rise to numerous possibilities for the in vivo monitoring of intracellular processes non-invasively using bioluminescent molecules as reporters. This review describes recent developments in the area of bioluminescent imaging for cell biology. Newly developed imaging methods allow transcriptional/translational regulation, signal transduction, protein-protein interaction, oncogenic transformation, cell and protein trafficking, and target drug action to be monitored in vivo in real-time with high temporal and spatial resolution; thus providing researchers with priceless information on cellular functions. Advantages and limitations of these novel bioluminescent methods are discussed and possible future developments identified. PMID:17725230

  6. Molecular and cellular neurocardiology: development, and cellular and molecular adaptations to heart disease.

    Science.gov (United States)

    Habecker, Beth A; Anderson, Mark E; Birren, Susan J; Fukuda, Keiichi; Herring, Neil; Hoover, Donald B; Kanazawa, Hideaki; Paterson, David J; Ripplinger, Crystal M

    2016-07-15

    The nervous system and cardiovascular system develop in concert and are functionally interconnected in both health and disease. This white paper focuses on the cellular and molecular mechanisms that underlie neural-cardiac interactions during development, during normal physiological function in the mature system, and during pathological remodelling in cardiovascular disease. The content on each subject was contributed by experts, and we hope that this will provide a useful resource for newcomers to neurocardiology as well as aficionados. PMID:27060296

  7. Chromatin chemistry goes cellular.

    OpenAIRE

    W. Fischle; D. Schwarzer; Mootz, H.

    2015-01-01

    Analysing post-translational modifications of histone proteins as they occur within chromatin is challenging due to their large number and chemical diversity. A major step forward has now been achieved by using split intein chemistry to engineer functionalized histones within cells.

  8. Empirical multiscale networks of cellular regulation.

    Directory of Open Access Journals (Sweden)

    Benjamin de Bivort

    2007-10-01

    Full Text Available Grouping genes by similarity of expression across multiple cellular conditions enables the identification of cellular modules. The known functions of genes enable the characterization of the aggregate biological functions of these modules. In this paper, we use a high-throughput approach to identify the effective mutual regulatory interactions between modules composed of mouse genes from the Alliance for Cell Signaling (AfCS murine B-lymphocyte database which tracks the response of approximately 15,000 genes following chemokine perturbation. This analysis reveals principles of cellular organization that we discuss along four conceptual axes. (1 Regulatory implications: the derived collection of influences between any two modules quantifies intuitive as well as unexpected regulatory interactions. (2 Behavior across scales: trends across global networks of varying resolution (composed of various numbers of modules reveal principles of assembly of high-level behaviors from smaller components. (3 Temporal behavior: tracking the mutual module influences over different time intervals provides features of regulation dynamics such as duration, persistence, and periodicity. (4 Gene Ontology correspondence: the association of modules to known biological roles of individual genes describes the organization of functions within coexpressed modules of various sizes. We present key specific results in each of these four areas, as well as derive general principles of cellular organization. At the coarsest scale, the entire transcriptional network contains five divisions: two divisions devoted to ATP production/biosynthesis and DNA replication that activate all other divisions, an "extracellular interaction" division that represses all other divisions, and two divisions (proliferation/differentiation and membrane infrastructure that activate and repress other divisions in specific ways consistent with cell cycle control.

  9. Cytokines as cellular communicators

    Directory of Open Access Journals (Sweden)

    R. Debets

    1996-01-01

    Full Text Available Cytokines and their receptors are involved in the pathophysiology of many diseases. Here we present a detailed review on cytokines, receptors and signalling routes, and show that one important lesson from cytokine biology is the complex and diverse regulation of cytokine activity. The activity of cytokines is controlled at the level of transcription, translation, storage, processing, posttranslational modification, trapping, binding by soluble proteins, and receptor number and/or function. Translation of this diverse regulation in strategies aimed at the control of cytokine activity will result in the development of more specific and selective drugs to treat diseases.

  10. Cellular and molecular basis of cerebellar development

    Science.gov (United States)

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

    2013-01-01

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

  11. Molecular features of cellular reprogramming and development.

    Science.gov (United States)

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

    2016-03-01

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

  12. Cellular and Molecular Basis of Cerebellar Development

    Directory of Open Access Journals (Sweden)

    Salvador eMartinez

    2013-06-01

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

  13. Origami interleaved tube cellular materials

    International Nuclear Information System (INIS)

    A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis. (paper)

  14. Cellular mechanisms during vascular development

    OpenAIRE

    Blum, Yannick

    2012-01-01

    The vascular system is an essential organ in vertebrate animals and provides the organism with enough oxygen and nutrients. It is composed of an interconnected network of blood vessels, which form using a number of different morphogenetic mechanisms. Angiogenesis describes the formation of new blood vessels from preexisting vessels. A number of molecular pathways have been shown to be essential during angiogenesis. However, cellular architecture of blood vessels as well as cellular mechanisms...

  15. Predictive Modelling of Cellular Load

    OpenAIRE

    Carolan, Emmett; McLoone, Seamus; Farrell, Ronan

    2015-01-01

    This work examines the temporal dynamics of cellular load in four Irish regions. Large scale underutilisation of network resources is identified both at the regional level and at the level of individual cells. Cellular load is modeled and prediction intervals are generated. These prediction intervals are used to put an upper bound on usage in a particular cell at a particular time. Opportunities for improvements in network utilization by incorporating these upper bounds on usage are identifie...

  16. Cellular automaton for chimera states

    OpenAIRE

    García-Morales, Vladimir

    2016-01-01

    A minimalistic model for chimera states is presented. The model is a cellular automaton (CA) which depends on only one adjustable parameter, the range of the nonlocal coupling, and is built from elementary cellular automata and the majority (voting) rule. This suggests the universality of chimera-like behavior from a new point of view: Already simple CA rules based on the majority rule exhibit this behavior. After a short transient, we find chimera states for arbitrary initial conditions, the...

  17. Molecular and cellular constraints on proteins

    Science.gov (United States)

    Kortemme, Tanja

    Engineering proteins with new sequences, structures and functions has many exciting practical applications, and provides new ways to dissect design principles for function. Recent successes in computational protein design provide a cause for optimism. Yet many functions are currently too complex to engineer predictively, and successful design of new biological activities also requires an understanding of the functional pressures acting on proteins in the context of cells and organisms. I will present two vignettes describing our progress with dissecting both molecular and cellular constraints on protein function. In the first, we characterized the cost and benefit of protein production upon sequence perturbations in a classic system for gene regulation, the lac operon. Our results were unexpected in light of the common assumption that the dominant fitness costs are due to protein expression. Instead, we discovered a direct linear relationship between cost and lacpermease activity, not protein or mRNA production. The magnitude of the cost of permease activity, relative to protein production, has consequences for regulation. Our model predicts an advantage of direct regulation of protein activity (not just expression), providing a new explanation for the long-known mechanism of ``inducer exclusion'' that inhibits transport through the permease. Similar pressures and cost/benefit tradeoffs may be key to engineering synthetic systems with improved fitness. In the second vignette, I will describe our recent efforts to develop computational approaches that predict protein sequences consistent with multiple functional conformations. We expect such ``multi-constraint'' models to improve predictions of functional sequences determined by deep mutational scanning in bacteria, to provide insights into how the balance between functional conformations shapes sequence space, and to highlight molecular and cellular constraints that cannot be captured by the model.

  18. Elastomeric Cellular Structure Enhanced by Compressible Liquid Filler

    Science.gov (United States)

    Sun, Yueting; Xu, Xiaoqing; Xu, Chengliang; Qiao, Yu; Li, Yibing

    2016-05-01

    Elastomeric cellular structures provide a promising solution for energy absorption. Their flexible and resilient nature is particularly relevant to protection of human bodies. Herein we develop an elastomeric cellular structure filled with nanoporous material functionalized (NMF) liquid. Due to the nanoscale infiltration in NMF liquid and its interaction with cell walls, the cellular structure has a much enhanced mechanical performance, in terms of loading capacity and energy absorption density. Moreover, it is validated that the structure is highly compressible and self-restoring. Its hyper-viscoelastic characteristics are elucidated.

  19. Elastomeric Cellular Structure Enhanced by Compressible Liquid Filler

    Science.gov (United States)

    Sun, Yueting; Xu, Xiaoqing; Xu, Chengliang; Qiao, Yu; Li, Yibing

    2016-01-01

    Elastomeric cellular structures provide a promising solution for energy absorption. Their flexible and resilient nature is particularly relevant to protection of human bodies. Herein we develop an elastomeric cellular structure filled with nanoporous material functionalized (NMF) liquid. Due to the nanoscale infiltration in NMF liquid and its interaction with cell walls, the cellular structure has a much enhanced mechanical performance, in terms of loading capacity and energy absorption density. Moreover, it is validated that the structure is highly compressible and self-restoring. Its hyper-viscoelastic characteristics are elucidated. PMID:27221079

  20. Noise in cellular signaling pathways: causes and effects

    OpenAIRE

    Ladbury, John E.; Arold, Stefan T.

    2012-01-01

    Noise caused by stochastic fluctuations in genetic circuits (transcription and translation) is now appreciated as a central aspect of cell function and phenotypic behavior. Noise has also been detected in signaling networks, but the origin of this noise and how it shapes cellular outcomes remain poorly understood. Here, we argue that noise in signaling networks results from the intrinsic promiscuity of protein-protein interactions, and that this noise has shaped cellular signal transduction. ...

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

    OpenAIRE

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

    2011-01-01

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

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

    OpenAIRE

    Rajachar, Rupak M.; Keat Ghee Ong; Ee Lim Tan; Hal R. Holmes

    2012-01-01

    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 ...

  3. Peroxisomes: a Nexus for Lipid Metabolism and Cellular Signaling

    OpenAIRE

    Lodhi, Irfan J.; Semenkovich, Clay F.

    2014-01-01

    Peroxisomes are often dismissed as the cellular hoi polloi, relegated to cleaning up reactive oxygen chemical debris discarded by other organelles. However, their functions extend far beyond hydrogen peroxide metabolism. Peroxisomes are intimately associated with lipid droplets and mitochondria, and their ability to carry out fatty acid oxidation and lipid synthesis, especially the production of ether lipids, may be critical for generating cellular signals required for normal physiology. Here...

  4. Vertically aligned patterned peptide nanowires for cellulars studies

    DEFF Research Database (Denmark)

    Taskin, Mehmet; Sasso, Luigi; Vedarethinam, Indumathi;

    2012-01-01

    . Recently, our group has demonstrated that vertically aligned diphenylalanine based peptide nanowires (VAPNW) are an useful tool for cellular studies and sensor applications. To expand this study, we patterned VAPNWs into strips of various widths onto an electrode surface to evaluate these structures...... as laminine. Combining this work with other approaches like discrete functionalization of VAPNWs will reveal possible future tools for cellular studies and biosensing....

  5. Hierarchical Cellular Structures in High-Capacity Cellular Communication Systems

    CERN Document Server

    Jain, R K; Agrawal, N K

    2011-01-01

    In the prevailing cellular environment, it is important to provide the resources for the fluctuating traffic demand exactly in the place and at the time where and when they are needed. In this paper, we explored the ability of hierarchical cellular structures with inter layer reuse to increase the capacity of mobile communication network by applying total frequency hopping (T-FH) and adaptive frequency allocation (AFA) as a strategy to reuse the macro and micro cell resources without frequency planning in indoor pico cells [11]. The practical aspects for designing macro- micro cellular overlays in the existing big urban areas are also explained [4]. Femto cells are inducted in macro / micro / pico cells hierarchical structure to achieve the required QoS cost effectively.

  6. Cellular cardiomyoplasty: what have we learned?

    Science.gov (United States)

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

    2009-01-01

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

  7. Cellular Kinetics of Perivascular MSC Precursors

    Directory of Open Access Journals (Sweden)

    William C. W. Chen

    2013-01-01

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

  8. Cellular vs. organ approaches to dose estimates

    International Nuclear Information System (INIS)

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

  9. Continuum representations of cellular solids

    Energy Technology Data Exchange (ETDEWEB)

    Neilsen, M.K.

    1993-09-01

    Cellular materials consist of interconnected struts or plates which form cells. The struts or plates are constructed from a variety of metals, polymers, ceramics and wood products. Cellular materials are often used in impact limiters for shipping containers to protect the contents from accidental impact events. These materials exhibit a variety of complex behavior when subjected to crushing loads. This research focuses on the development of continuum representations of cellular solids that can be used in the finite element analysis of shipping container accidents. A significant portion of this work is the development of a new methodology to relate localized deformations to appropriate constitutive descriptions. This methodology provides the insight needed to select constitutive descriptions for cellular solids that capture the localized deformations that are observed experimentally. Constitutive relations are developed for two different cellular materials, aluminum honeycomb and polyurethane foam. These constitutive relations are based on plasticity and continuum damage theories. Plasticity is used to describe the permanent deformation exhibited by both aluminum honeycomb and polyurethane foam. Continuum damage is needed to capture the change in elastic parameters due to cracking of the polyurethane cell wall materials. The new constitutive description of polyurethane foam is implemented in both static and dynamic finite element codes, and analytical and numerical predictions are compared with available experimental data.

  10. Prognosis of Different Cellular Generations

    Directory of Open Access Journals (Sweden)

    Preetish Ranjan

    2013-04-01

    Full Text Available Technological advancement in mobile telephony from 1G to 3G, 4G and 5G has a very axiomatic fact that made an entire world a global village. The cellular system employs a different design approach and technology that most commercial radio and television system use. In the cellular system, the service area is divided into cells and a transmitter is designed to serve an individual cell. The system seeks to make efficient use of available channels by using low-power transmitters to allow frequency reuse at a smaller distance. Maximizing the number of times each channel can be reused in a given geographical area is the key to an efficient cellular system design. During the past three decades, the world has seen significant changes in telecommunications industry. There have been some remarkable aspects to the rapid growth in wireless communications, as seen by the large expansion in mobile systems. This paper focuses on “Past, Present & Future of Cellular Telephony” and some light has been thrown upon the technologies of the cellular systems, namely 1G, 2G, 2.5G, 3G and future generations like 4G and 5G systems as well.

  11. Cellular membrane trafficking of mesoporous silica nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-01-01

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

  12. Cellular regulation of the dopamine transporter

    DEFF Research Database (Denmark)

    Eriksen, Jacob

    2010-01-01

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

  13. Cellular Scaling Rules for Primate Spinal Cords

    OpenAIRE

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

    2010-01-01

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

  14. Cellular-based preemption system

    Science.gov (United States)

    Bachelder, Aaron D. (Inventor)

    2011-01-01

    A cellular-based preemption system that uses existing cellular infrastructure to transmit preemption related data to allow safe passage of emergency vehicles through one or more intersections. A cellular unit in an emergency vehicle is used to generate position reports that are transmitted to the one or more intersections during an emergency response. Based on this position data, the one or more intersections calculate an estimated time of arrival (ETA) of the emergency vehicle, and transmit preemption commands to traffic signals at the intersections based on the calculated ETA. Additional techniques may be used for refining the position reports, ETA calculations, and the like. Such techniques include, without limitation, statistical preemption, map-matching, dead-reckoning, augmented navigation, and/or preemption optimization techniques, all of which are described in further detail in the above-referenced patent applications.

  15. Adaptive stochastic cellular automata: Applications

    Science.gov (United States)

    Qian, S.; Lee, Y. C.; Jones, R. D.; Barnes, C. W.; Flake, G. W.; O'Rourke, M. K.; Lee, K.; Chen, H. H.; Sun, G. Z.; Zhang, Y. Q.; Chen, D.; Giles, C. L.

    1990-09-01

    The stochastic learning cellular automata model has been applied to the problem of controlling unstable systems. Two example unstable systems studied are controlled by an adaptive stochastic cellular automata algorithm with an adaptive critic. The reinforcement learning algorithm and the architecture of the stochastic CA controller are presented. Learning to balance a single pole is discussed in detail. Balancing an inverted double pendulum highlights the power of the stochastic CA approach. The stochastic CA model is compared to conventional adaptive control and artificial neural network approaches.

  16. Cellular automaton for chimera states

    Science.gov (United States)

    García-Morales, Vladimir

    2016-04-01

    A minimalistic model for chimera states is presented. The model is a cellular automaton (CA) which depends on only one adjustable parameter, the range of the nonlocal coupling, and is built from elementary cellular automata and the majority (voting) rule. This suggests the universality of chimera-like behavior from a new point of view: Already simple CA rules based on the majority rule exhibit this behavior. After a short transient, we find chimera states for arbitrary initial conditions, the system spontaneously splitting into stable domains separated by static boundaries, some synchronously oscillating and the others incoherent. When the coupling range is local, nontrivial coherent structures with different periodicities are formed.

  17. Prognosis of Different Cellular Generations

    OpenAIRE

    Preetish Ranjan; Prabhat Kumar

    2013-01-01

    Technological advancement in mobile telephony from 1G to 3G, 4G and 5G has a very axiomatic fact that made an entire world a global village. The cellular system employs a different design approach and technology that most commercial radio and television system use. In the cellular system, the service area is divided into cells and a transmitter is designed to serve an individual cell. The system seeks to make efficient use of available channels by using low-power transmitters to allow frequen...

  18. Cellular damage of epidermis exposed to ultraviolet light

    International Nuclear Information System (INIS)

    Our studies during the past five years in our department on the cellular damage of epidermis exposed to ultraviolet light, mainly of the lipid peroxide formation of plasma membrane and the usefulness of antioxidant were reviewed. Mitochondria isolated from rat liver were used as a material of plasma membrane. The functional disorders of respiratory chain, surface potential formation and proton ejection were found in parallel with formation of lipid peroxide following ultraviolet exposure. The swelling and the cellular damage of mitochondria were confirmed morphologically by electron microscopic examination. The in vitro and in vivo administrations of antioxidants were found to be useful for preventing the cellular damage and lipid peroxide formation. Electron spin resonance (ESR) spectrum demonstrated that the exposure of ultraviolet light resulted in the increase of free radical and the appearance of typical peroxide radical (ROO.). The lipid peroxide formation in plasma membrane was discussed in the relation to the cellular damage of epidermis. (author)

  19. Repaglinide at a cellular level

    DEFF Research Database (Denmark)

    Krogsgaard Thomsen, M; Bokvist, K; Høy, M;

    2002-01-01

    To investigate the hormonal and cellular selectivity of the prandial glucose regulators, we have undertaken a series of experiments, in which we characterised the effects of repaglinide and nateglinide on ATP-sensitive potassium ion (KATP) channel activity, membrane potential and exocytosis in ra...

  20. Cellular signalling properties in microcircuits

    DEFF Research Database (Denmark)

    Toledo-Rodriguez, Maria; El Manira, Abdeljabbar; Wallén, Peter; Svirskis, Gytis; Hounsgaard, Jørn

    2005-01-01

    Molecules and cells are the signalling elements in microcircuits. Recent studies have uncovered bewildering diversity in postsynaptic signalling properties in all areas of the vertebrate nervous system. Major effort is now being invested in establishing the specialized signalling properties at th...... cellular and molecular levels in microcircuits in specific brain regions. This review is part of the TINS Microcircuits Special Feature....

  1. Quantum Cloning by Cellular Automata

    OpenAIRE

    D'Ariano, G. M.; Macchiavello, C.; M. Rossi

    2012-01-01

    We introduce a quantum cellular automaton that achieves approximate phase-covariant cloning of qubits. The automaton is optimized for 1-to-2N economical cloning. The use of the automaton for cloning allows us to exploit different foliations for improving the performance with given resources.

  2. Analysis of cellular manufacturing systems

    NARCIS (Netherlands)

    Heragu, Sunderesh; Meng, Gang; Zijm, Henk; Ommeren, van Jan-Kees

    2001-01-01

    In this paper, we present an open queuing network modeling approach to estimate performance measures of a cellular manufacturing layout. It is assumed a layout and production data for a planning period of specified length are available. The production data takes into account, processing and handli

  3. Cellular roles of ADAM12 in health and disease

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Albrechtsen, Reidar; Couchman, John R; Wewer, Ulla M

    2008-01-01

    and it is a potential biomarker for breast cancer. It is therefore important to understand ADAM12's functions. Many cellular roles for ADAM12 have been suggested. It is an active metalloprotease, and has been implicated in insulin-like growth factor (IGF) receptor signaling, through cleavage of IGF...... transmitting signals to or from the cell interior. These ADAM12-mediated cellular effects appear to be critical events in both biological and pathological processes. This review presents current knowledge on ADAM12 functions gained from in vitro and in vivo observations, describes ADAM12's role in both normal...... physiology and pathology, particularly in cancer, and discusses important areas for future investigation....

  4. Computing by Temporal Order: Asynchronous Cellular Automata

    Directory of Open Access Journals (Sweden)

    Michael Vielhaber

    2012-08-01

    Full Text Available Our concern is the behaviour of the elementary cellular automata with state set 0,1 over the cell set Z/nZ (one-dimensional finite wrap-around case, under all possible update rules (asynchronicity. Over the torus Z/nZ (n<= 11,we will see that the ECA with Wolfram rule 57 maps any v in F_2^n to any w in F_2^n, varying the update rule. We furthermore show that all even (element of the alternating group bijective functions on the set F_2^n = 0,...,2^n-1, can be computed by ECA57, by iterating it a sufficient number of times with varying update rules, at least for n <= 10. We characterize the non-bijective functions computable by asynchronous rules.

  5. Time scale of diffusion in molecular and cellular biology

    Science.gov (United States)

    Holcman, D.; Schuss, Z.

    2014-05-01

    Diffusion is the driver of critical biological processes in cellular and molecular biology. The diverse temporal scales of cellular function are determined by vastly diverse spatial scales in most biophysical processes. The latter are due, among others, to small binding sites inside or on the cell membrane or to narrow passages between large cellular compartments. The great disparity in scales is at the root of the difficulty in quantifying cell function from molecular dynamics and from simulations. The coarse-grained time scale of cellular function is determined from molecular diffusion by the mean first passage time of molecular Brownian motion to a small targets or through narrow passages. The narrow escape theory (NET) concerns this issue. The NET is ubiquitous in molecular and cellular biology and is manifested, among others, in chemical reactions, in the calculation of the effective diffusion coefficient of receptors diffusing on a neuronal cell membrane strewn with obstacles, in the quantification of the early steps of viral trafficking, in the regulation of diffusion between the mother and daughter cells during cell division, and many other cases. Brownian trajectories can represent the motion of a molecule, a protein, an ion in solution, a receptor in a cell or on its membrane, and many other biochemical processes. The small target can represent a binding site or an ionic channel, a hidden active site embedded in a complex protein structure, a receptor for a neurotransmitter on the membrane of a neuron, and so on. The mean time to attach to a receptor or activator determines diffusion fluxes that are key regulators of cell function. This review describes physical models of various subcellular microdomains, in which the NET coarse-grains the molecular scale to a higher cellular-level, thus clarifying the role of cell geometry in determining subcellular function.

  6. Cellular solidification of transparent monotectics

    Science.gov (United States)

    Kaulker, W. F.

    1986-01-01

    Understanding how liquid phase particles are engulfed or pushed during freezing of a monotectic is addressed. The additional complication is that the solid-liquid interface is nonplanar due to constitutional undercooling. Some evidence of particle pushing where the particles are the liquid phase of the montectic was already observed. Cellular freezing of the succinonitrile-glycerol system also occurred. Only a few compositions were tested at that time. The starting materials were not especially pure so that cellular interface observed was likely due to the presence of unkown impurities, the major portion of which was water. Topics addressed include: the effort of modeling the particle pushing process using the computer, establishing an apparatus for the determination of phase diagrams, and the measurement of the temperature gradients with a specimen which will solidify on the temperature gradient microscope stage.

  7. Cellular ceramics in combustion environments

    Energy Technology Data Exchange (ETDEWEB)

    Fuessel, Alexander; Boettge, Daniela; Adler, Joerg; Marschallek, Felix; Michaelis, Alexander [Fraunhofer Institute for Ceramic Technologies and Systems IKTS, Dresden (Germany)

    2011-11-15

    Cellular materials have become increasingly interesting for applications in combustion environments. Improvements like high power efficiency and low emissions are the main targets of technological development in combustion processes. However, despite scientific and technical success in developing new or improved burner concepts over recent years, a lot of problems remain to be solved in the field of materials science: due to the high power density of the burners the materials are subjected to high loads in terms of thermal shock, temperature and corrosion, especially in so-called porous burner technology. This article shows some examples of research and development strategies and results in developing improved cellular ceramics. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  8. Designing Underwater Cellular Networks Parameters

    Directory of Open Access Journals (Sweden)

    Pejman Khadivi

    2008-09-01

    Full Text Available Oceanographic data collection, pollution monitoring, offshore exploration, disaster prevention, assisted navigation and tactical surveillance are some of the applications of underwater networks. Underwater networks should send the gathered information to other users or an offshore station via a base station in the sea. Since the available bandwidth in underwater is severely limited, frequency reuse and cellular networks concepts are very important. In this paper, after driving the ratio of signal to interference for underwater acoustic channels, the constraints for the cell radius are determined. One of the important results of this work is that, for special parameters like bandwidth, it may be impossible to provide the required signal to interference ratio and bandwidth for the network users. Furthermore, in this paper, number of supportable users, per-user bandwidth, and the user capacity for a cellular underwater network are determined.

  9. Stochastic Nature in Cellular Processes

    Institute of Scientific and Technical Information of China (English)

    刘波; 刘圣君; 王祺; 晏世伟; 耿轶钊; SAKATA Fumihiko; GAO Xing-Fa

    2011-01-01

    The importance of stochasticity in cellular processes is increasingly recognized in both theoretical and experimental studies. General features of stochasticity in gene regulation and expression are briefly reviewed in this article, which include the main experimental phenomena, classification, quantization and regulation of noises. The correlation and transmission of noise in cascade networks are analyzed further and the stochastic simulation methods that can capture effects of intrinsic and extrinsic noise are described.

  10. Xtoys cellular automata on xwindows

    CERN Document Server

    Creutz, M

    1995-01-01

    Xtoys is a collection of xwindow programs for demonstrating simulations of various statistical models. Included are xising, for the two dimensional Ising model, xpotts, for the q-state Potts model, xautomalab, for a fairly general class of totalistic cellular automata, xsand, for the Bak-Tang-Wiesenfield model of self organized criticality, and xfires, a simple forest fire simulation. The programs should compile on any machine supporting xwindows.

  11. Cellular reactions to patterned biointerfaces

    OpenAIRE

    Schulte, Vera Antonie

    2012-01-01

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

  12. Analysis of cellular manufacturing systems

    OpenAIRE

    Heragu, Sunderesh; Meng, Gang; Zijm, Henk; Ommeren, van, J.C.

    2001-01-01

    In this paper, we present an open queuing network modeling approach to estimate performance measures of a cellular manufacturing layout. It is assumed a layout and production data for a planning period of specified length are available. The production data takes into account, processing and handling set-up times as well as transfer and process batch size information of multiple products that flow through the system. It is assumed that two sets of discrete material handling devices are used fo...

  13. CELLULAR FETAL MICROCHIMERISM IN PREECLAMPSIA

    OpenAIRE

    Gammill, Hilary S; Aydelotte, Tessa M.; Guthrie, Katherine A.; Nkwopara, Evangelyn C.; Nelson, J. Lee

    2013-01-01

    Previous studies have shown elevated concentrations of free fetal deoxyribonucleic acid and erythroblasts in maternal circulation in preeclampsia compared with normal pregnancy. Pluripotent and immunocompetent fetal cells also transfer to the maternal circulation during pregnancy, but whether concentrations of fetal mononuclear cells also differed in preeclampsia was unknown. We sought to quantify cellular fetal microchimerism in maternal circulation in women with preeclampsia and healthy con...

  14. The Origins of Cellular Life

    OpenAIRE

    Schrum, Jason P.; Zhu, Ting F.; SZOSTAK, JACK W.

    2010-01-01

    Understanding the origin of cellular life on Earth requires the discovery of plausible pathways for the transition from complex prebiotic chemistry to simple biology, defined as the emergence of chemical assemblies capable of Darwinian evolution. We have proposed that a simple primitive cell, or protocell, would consist of two key components: a protocell membrane that defines a spatially localized compartment, and an informational polymer that allows for the replication and inheritance of fun...

  15. From Cellular Mechanotransduction to Biologically Inspired Engineering

    Science.gov (United States)

    Ingber, Donald E.

    2010-01-01

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

  16. Cellular proteins in influenza virus particles.

    Directory of Open Access Journals (Sweden)

    Megan L Shaw

    2008-06-01

    Full Text Available Virions are thought to contain all the essential proteins that govern virus egress from the host cell and initiation of replication in the target cell. It has been known for some time that influenza virions contain nine viral proteins; however, analyses of other enveloped viruses have revealed that proteins from the host cell can also be detected in virions. To address whether the same is true for influenza virus, we used two complementary mass spectrometry approaches to perform a comprehensive proteomic analysis of purified influenza virus particles. In addition to the aforementioned nine virus-encoded proteins, we detected the presence of 36 host-encoded proteins. These include both cytoplasmic and membrane-bound proteins that can be grouped into several functional categories, such as cytoskeletal proteins, annexins, glycolytic enzymes, and tetraspanins. Interestingly, a significant number of these have also been reported to be present in virions of other virus families. Protease treatment of virions combined with immunoblot analysis was used to verify the presence of the cellular protein and also to determine whether it is located in the core of the influenza virus particle. Immunogold labeling confirmed the presence of membrane-bound host proteins on the influenza virus envelope. The identification of cellular constituents of influenza virions has important implications for understanding the interactions of influenza virus with its host and brings us a step closer to defining the cellular requirements for influenza virus replication. While not all of the host proteins are necessarily incorporated specifically, those that are and are found to have an essential role represent novel targets for antiviral drugs and for attenuation of viruses for vaccine purposes.

  17. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

    Directory of Open Access Journals (Sweden)

    O.Popescu

    1999-01-01

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

  18. Progress of cellular dedifferentiation research

    Institute of Scientific and Technical Information of China (English)

    LIU Hu-xian; HU Da-hai; JIA Chi-yu; FU Xiao-bing

    2006-01-01

    Differentiation, the stepwise specialization of cells, and transdifferentiation, the apparent switching of one cell type into another, capture much of the stem cell spotlight. But dedifferentiation, the developmental reversal of a cell before it reinvents itself, is an important process too. In multicellular organisms, cellular dedifferentiation is the major process underlying totipotency, regeneration and formation of new stem cell lineages. In humans,dedifferentiation is often associated with carcinogenesis.The study of cellular dedifferentiation in animals,particularly early events related to cell fate-switch and determination, is limited by the lack of a suitable,convenient experimental system. The classic example of dedifferentiation is limb and tail regeneration in urodele amphibians, such as salamanders. Recently, several investigators have shown that certain mammalian cell types can be induced to dedifferentiate to progenitor cells when stimulated with the appropriate signals or materials. These discoveries open the possibility that researchers might enhance the endogenous regenerative capacity of mammals by inducing cellular dedifferentiation in vivo.

  19. Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

    Science.gov (United States)

    Eldawud, Reem; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha; Zoica Dinu, Cerasela

    2016-02-01

    Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications.

  20. Dynamic properties of cellular neural networks

    Directory of Open Access Journals (Sweden)

    Angela Slavova

    1993-01-01

    Full Text Available Dynamic behavior of a new class of information-processing systems called Cellular Neural Networks is investigated. In this paper we introduce a small parameter in the state equation of a cellular neural network and we seek for periodic phenomena. New approach is used for proving stability of a cellular neural network by constructing Lyapunov's majorizing equations. This algorithm is helpful for finding a map from initial continuous state space of a cellular neural network into discrete output. A comparison between cellular neural networks and cellular automata is made.

  1. Cellular communications a comprehensive and practical guide

    CERN Document Server

    Tripathi, Nishith

    2014-01-01

    Even as newer cellular technologies and standards emerge, many of the fundamental principles and the components of the cellular network remain the same. Presenting a simple yet comprehensive view of cellular communications technologies, Cellular Communications provides an end-to-end perspective of cellular operations, ranging from physical layer details to call set-up and from the radio network to the core network. This self-contained source forpractitioners and students represents a comprehensive survey of the fundamentals of cellular communications and the landscape of commercially deployed

  2. Engineering Cellular Photocomposite Materials Using Convective Assembly

    Directory of Open Access Journals (Sweden)

    Orlin D. Velev

    2013-05-01

    Full Text Available Fabricating industrial-scale photoreactive composite materials containing living cells, requires a deposition strategy that unifies colloid science and cell biology. Convective assembly can rapidly deposit suspended particles, including whole cells and waterborne latex polymer particles into thin (<10 µm thick, organized films with engineered adhesion, composition, thickness, and particle packing. These highly ordered composites can stabilize the diverse functions of photosynthetic cells for use as biophotoabsorbers, as artificial leaves for hydrogen or oxygen evolution, carbon dioxide assimilation, and add self-cleaning capabilities for releasing or digesting surface contaminants. This paper reviews the non-biological convective assembly literature, with an emphasis on how the method can be modified to deposit living cells starting from a batch process to its current state as a continuous process capable of fabricating larger multi-layer biocomposite coatings from diverse particle suspensions. Further development of this method will help solve the challenges of engineering multi-layered cellular photocomposite materials with high reactivity, stability, and robustness by clarifying how process, substrate, and particle parameters affect coating microstructure. We also describe how these methods can be used to selectively immobilize photosynthetic cells to create biomimetic leaves and compare these biocomposite coatings to other cellular encapsulation systems.

  3. Impaired nonspecific cellular immunity in experimental cholestasis.

    Science.gov (United States)

    Roughneen, P T; Drath, D B; Kulkarni, A D; Rowlands, B J

    1987-11-01

    The abilities of polymorphonuclear leukocytes (PMN) and pulmonary alveolar macrophages (PAM), to demonstrate chemotaxis, phagocytosis, and superoxide release after bile duct ligation in the rat were investigated to determine the effect of cholestasis on nonspecific cellular immune mechanisms. Chemotactic response to C5a and FMLP, phagocytosis of 14C labeled Staphylococcus aureus, and zymosan-induced superoxide release were evaluated 21 days after bile duct ligation (BDL), sham operation, or in normal controls. Serum total bilirubin level was elevated after BDL (p less than 0.01). Chemotactic ability was similar to each group. PMN phagocytic uptake of 14C labeled Staphylococcus aureus was depressed in BDL (p less than 0.05). BDL rats exhibited impaired PAM phagocytic indices and improved PMN superoxide release (p less than 0.03). PAM superoxide release was similar in each study group. Alterations in phagocytic function with cholestasis are important deficits in nonspecific cellular immunity that may contribute to the high incidence of infective complications associated with obstructive jaundice. PMID:2823730

  4. Single-Molecule Imaging of Cellular Signaling

    Science.gov (United States)

    De Keijzer, Sandra; Snaar-Jagalska, B. Ewa; Spaink, Herman P.; Schmidt, Thomas

    Single-molecule microscopy is an emerging technique to understand the function of a protein in the context of its natural environment. In our laboratory this technique has been used to study the dynamics of signal transduction in vivo. A multitude of signal transduction cascades are initiated by interactions between proteins in the plasma membrane. These cascades start by binding a ligand to its receptor, thereby activating downstream signaling pathways which finally result in complex cellular responses. To fully understand these processes it is important to study the initial steps of the signaling cascades. Standard biological assays mostly call for overexpression of the proteins and high concentrations of ligand. This sets severe limits to the interpretation of, for instance, the time-course of the observations, given the large temporal spread caused by the diffusion-limited binding processes. Methods and limitations of single-molecule microscopy for the study of cell signaling are discussed on the example of the chemotactic signaling of the slime-mold Dictyostelium discoideum. Single-molecule studies, as reviewed in this chapter, appear to be one of the essential methodologies for the full spatiotemporal clarification of cellular signaling, one of the ultimate goals in cell biology.

  5. Typhoid fever as cellular microbiological model

    Directory of Open Access Journals (Sweden)

    Andrade Dahir Ramos de

    2003-01-01

    Full Text Available The knowledge about typhoid fever pathogenesis is growing in the last years, mainly about the cellular and molecular phenomena that are responsible by clinical manifestations of this disease. In this article are discussed several recent discoveries, as follows: a Bacterial type III protein secretion system; b The five virulence genes of Salmonella spp. that encoding Sips (Salmonella invasion protein A, B, C, D and E, which are capable of induce apoptosis in macrophages; c The function of Toll R2 and Toll R4 receptors present in the macrophage surface (discovered in the Drosophila. The Toll family receptors are critical in the signalizing mediated by LPS in macrophages in association with LBP and CD14; d The lines of immune defense between intestinal lumen and internal organs; e The fundamental role of the endothelial cells in the inflammatory deviation from bloodstream into infected tissues by bacteria. In addition to above subjects, the authors comment the correlation between the clinical features of typhoid fever and the cellular and molecular phenomena of this disease, as well as the therapeutic consequences of this knowledge.

  6. Typhoid fever as cellular microbiological model.

    Science.gov (United States)

    de Andrade, Dahir Ramos; de Andrade Júnior, Dahir Ramos

    2003-01-01

    The knowledge about typhoid fever pathogenesis is growing in the last years, mainly about the cellular and molecular phenomena that are responsible by clinical manifestations of this disease. In this article are discussed several recent discoveries, as follows: a) Bacterial type III protein secretion system; b) The five virulence genes of Salmonella spp. that encoding Sips (Salmonella invasion protein) A, B, C, D and E, which are capable of induce apoptosis in macrophages; c) The function of Toll R2 and Toll R4 receptors present in the macrophage surface (discovered in the Drosophila). The Toll family receptors are critical in the signalizing mediated by LPS in macrophages in association with LBP and CD14; d) The lines of immune defense between intestinal lumen and internal organs; e) The fundamental role of the endothelial cells in the inflammatory deviation from bloodstream into infected tissues by bacteria. In addition to above subjects, the authors comment the correlation between the clinical features of typhoid fever and the cellular and molecular phenomena of this disease, as well as the therapeutic consequences of this knowledge. PMID:14502344

  7. Regulation of autophagy in oxygen-dependent cellular stress.

    Science.gov (United States)

    Ryter, Stefan W; Choi, Augustine M K

    2013-01-01

    Oxidative stress caused by supraphysiological production of reactive oxygen species (ROS), can cause cellular injury associated with protein and lipid oxidation, DNA damage, and mitochondrial dysfunction. The cellular responses triggered by oxidative stress include the altered regulation of signaling pathways that culminate in the regulation of cell survival or cell death pathways. Recent studies suggest that autophagy, a cellular homeostatic process that governs the turnover of damaged organelles and proteins, may represent a general cellular and tissue response to oxidative stress. The autophagic pathway involves the encapsulation of substrates in double-membraned vesicles, which are subsequently delivered to the lysosome for enzymatic degradation and recycling of metabolic precursors. Autophagy may play multifunctional roles in cellular adaptation to stress, by maintaining mitochondrial integrity, and removing damaged proteins. Additionally, autophagy may play important roles in the regulation of inflammation and immune function. Modulation of the autophagic pathway has been reported in cell culture models of oxidative stress, including altered states of oxygen tension (i.e., hypoxia, hyperoxia), and exposure to oxidants. Furthermore, proteins that regulate autophagy may be subject to redox regulation. The heme oxygenase- 1 (HO)-1 enzyme system may have a role in the regulation of autophagy. Recent studies suggest that carbon monoxide (CO), a reaction product of HO activity which can alter mitochondrial function, may induce autophagy in cultured epithelial cells. In conclusion, current research suggests a central role for autophagy as a mammalian oxidative stress response and its interrelationship to other stress defense systems. PMID:23092322

  8. Performance evaluation of cellular layouts : extension to DRC system contexts

    NARCIS (Netherlands)

    Suresh, NC; Gaalman, GJC

    2000-01-01

    This study involves a comparison of the performance of functional layouts (FL) and cellular manufacturing (CM) systems in a dual-resource-constrained( DRC) system context. Past studies of FL and CM have been based mostly on single-resource-constrained( SRC) systems. Recent studies have included labo

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

    Science.gov (United States)

    Newman, Timothy

    2003-10-01

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

  10. Almost sure exponential stability of delayed cellular neural networks

    Directory of Open Access Journals (Sweden)

    Chuangxia Huang

    2007-03-01

    Full Text Available The stability of stochastic delayed Cellular Neural Networks (DCNN is investigated in this paper. Using suitable Lyapunov functional and the semimartingale convergence theorem, we obtain some sufficient conditions for checking the almost sure exponential stability of the DCNN.

  11. Connecting Photosynthesis and Cellular Respiration: Preservice Teachers' Conceptions

    Science.gov (United States)

    Brown, Mary H.; Schwartz, Renee S.

    2009-01-01

    The biological processes of photosynthesis and plant cellular respiration include multiple biochemical steps, occur simultaneously within plant cells, and share common molecular components. Yet, learners often compartmentalize functions and specialization of cell organelles relevant to these two processes, without considering the interconnections…

  12. Modified Apolipoprotein (apo) A-I by Artificial Sweetener Causes Severe Premature Cellular Senescence and Atherosclerosis with Impairment of Functional and Structural Properties of apoA-I in Lipid-Free and Lipid-Bound State

    OpenAIRE

    Jang, Wookju; Jeoung, Nam Ho; Cho, Kyung-Hyun

    2011-01-01

    Long-term consumption of artificial sweeteners (AS) has been the recent focus of safety concerns. However, the potential risk of the AS in cardiovascular disease and lipoprotein metabolism has not been investigated sufficiently. We compared the influence of AS (aspartame, acesulfame K, and saccharin) and fructose in terms of functional and structural correlations of apolipoprotein (apo) A-I and high-density lipoproteins (HDL), which have atheroprotective effects. Long-term treatment of apoA-I...

  13. Cellular host responses to gliomas.

    Directory of Open Access Journals (Sweden)

    Joseph Najbauer

    Full Text Available BACKGROUND: Glioblastoma multiforme (GBM is the most aggressive type of malignant primary brain tumors in adults. Molecular and genetic analysis has advanced our understanding of glioma biology, however mapping the cellular composition of the tumor microenvironment is crucial for understanding the pathology of this dreaded brain cancer. In this study we identified major cell populations attracted by glioma using orthotopic rodent models of human glioma xenografts. Marker-specific, anatomical and morphological analyses revealed a robust influx of host cells into the main tumor bed and tumor satellites. METHODOLOGY/PRINCIPAL FINDINGS: Human glioma cell lines and glioma spheroid orthotopic implants were used in rodents. In both models, the xenografts recruited large numbers of host nestin-expressing cells, which formed a 'network' with glioma. The host nestin-expressing cells appeared to originate in the subventricular zone ipsilateral to the tumor, and were clearly distinguishable from pericytes that expressed smooth muscle actin. These distinct cell populations established close physical contact in a 'pair-wise' manner and migrated together to the deeper layers of tumor satellites and gave rise to tumor vasculature. The GBM biopsy xenografts displayed two different phenotypes: (a low-generation tumors (first in vivo passage in rats were highly invasive and non-angiogenic, and host nestin-positive cells that infiltrated into these tumors displayed astrocytic or elongated bipolar morphology; (b high-generation xenografts (fifth passage had pronounced cellularity, were angiogenic with 'glomerulus-like' microvascular proliferations that contained host nestin-positive cells. Stromal cell-derived factor-1 and its receptor CXCR4 were highly expressed in and around glioma xenografts, suggesting their role in glioma progression and invasion. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a robust migration of nestin-expressing host cells to glioma, which

  14. Game of Life Cellular Automata

    CERN Document Server

    Adamatzky, Andrew

    2010-01-01

    In the late 1960s, British mathematician John Conway invented a virtual mathematical machine that operates on a two-dimensional array of square cell. Each cell takes two states, live and dead. The cells' states are updated simultaneously and in discrete time. A dead cell comes to life if it has exactly three live neighbours. A live cell remains alive if two or three of its neighbours are alive, otherwise the cell dies. Conway's Game of Life became the most programmed solitary game and the most known cellular automaton. The book brings together results of forty years of study into computational

  15. Cellular automata a parallel model

    CERN Document Server

    Mazoyer, J

    1999-01-01

    Cellular automata can be viewed both as computational models and modelling systems of real processes. This volume emphasises the first aspect. In articles written by leading researchers, sophisticated massive parallel algorithms (firing squad, life, Fischer's primes recognition) are treated. Their computational power and the specific complexity classes they determine are surveyed, while some recent results in relation to chaos from a new dynamic systems point of view are also presented. Audience: This book will be of interest to specialists of theoretical computer science and the parallelism challenge.

  16. Mathematical Physics of Cellular Automata

    CERN Document Server

    Garcia-Morales, Vladimir

    2012-01-01

    A universal map is derived for all deterministic 1D cellular automata (CA) containing no freely adjustable parameters. The map can be extended to an arbitrary number of dimensions and topologies and its invariances allow to classify all CA rules into equivalence classes. Complexity in 1D systems is then shown to emerge from the weak symmetry breaking of the addition modulo an integer number p. The latter symmetry is possessed by certain rules that produce Pascal simplices in their time evolution. These results elucidate Wolfram's classification of CA dynamics.

  17. Estimation in Cellular Radio Systems

    OpenAIRE

    Blom, Jonas; Gunnarsson, Fredrik; Gustafsson, Fredrik

    1999-01-01

    The problem to track time-varying parameters in cellular radio systems is studied, and the focus is on estimation based only on the signals that are readily available. Previous work have demonstrated very good performance, but were relying on analog measurement that are not available. Most of the information is lost due to quantization and sampling at a rate that might be as low as 2 Hz (GSM case). For that matter a maximum likelihood estimator have been designed and exemplified in the case o...

  18. 'Biomoleculas': cellular metabolism didactic software

    International Nuclear Information System (INIS)

    'Biomoleculas' is a software that deals with topics such as the digestion, cellular metabolism and excretion of nutrients. It is a pleasant, simple and didactic guide, made by and for students. In this program, each biomolecule (carbohydrates, lipids and proteins) is accompanied until its degradation and assimilation by crossing and interrelating the different metabolic channels to finally show the destination of the different metabolites formed and the way in which these are excreted. It is used at present as a teaching-learning process tool by the chair of Physiology and Biophysics at the Facultad de Ingenieria - Universidad Nacional de Entre Rios

  19. Area Spectral and Energy Efficiency Analysis of Cellular Networks with Cell DTX

    OpenAIRE

    Chang, Peiliang; Miao, Guowang

    2015-01-01

    Cell discontinuous transmission (DTX) has been proposed as an effective solution to reduce energy consumption of cellular networks. In this paper, we investigate the impact of network traffic load on area spectral efficiency (ASE) and energy efficiency (EE) of cellular networks with cell DTX. Closedform expressions of ASE and EE as functions of traffic load for cellular networks with cell DTX are derived. It is shown that ASE increases monotonically in traffic load, while EE depends on the po...

  20. Signals for the lysosome: a control center for cellular clearance and energy metabolism

    OpenAIRE

    Settembre, Carmine; Fraldi, Alessandro; Medina, Diego L.; Ballabio, Andrea

    2013-01-01

    For a long time lysosomes were considered merely to be cellular “incinerators” involved in the degradation and recycling of cellular waste. However, there is now compelling evidence indicating that lysosomes have a much broader function and that they are involved in fundamental processes such as secretion, plasma membrane repair, signaling and energy metabolism. Furthermore, the essential role of lysosomes in the autophagic pathway puts these organelles at the crossroads of several cellular p...

  1. Cellular and systemic effects of Parkinson’s disease-related LRRK2 mutations: An investigation of cytoskeletal function and the innate immune system in transgenic mice and human LRRK2 mutation carriers

    OpenAIRE

    Caesar, Mareike

    2016-01-01

    Parkinson’s disease (PD) is, after Alzheimer’s disease, the most common neurodegenerative disorder. Mutations in the leucine rich repeat kinase 2 (LRRK2) are the most common known cause of familial PD but also constitute about 3.5 % of all sporadic PD cases. This work focuses on the effects of LRRK2 mutations on cytoskeletal function and on the innate immune system. Findings from animal models were translated to human material to assess their relevance in human disease states. Changes in ...

  2. Simulation of earthquakes with cellular automata

    Directory of Open Access Journals (Sweden)

    P. G. Akishin

    1998-01-01

    Full Text Available The relation between cellular automata (CA models of earthquakes and the Burridge–Knopoff (BK model is studied. It is shown that the CA proposed by P. Bak and C. Tang,although they have rather realistic power spectra, do not correspond to the BK model. We present a modification of the CA which establishes the correspondence with the BK model.An analytical method of studying the evolution of the BK-like CA is proposed. By this method a functional quadratic in stress release, which can be regarded as an analog of the event energy, is constructed. The distribution of seismic events with respect to this “energy” shows rather realistic behavior, even in two dimensions. Special attention is paid to two-dimensional automata; the physical restrictions on compression and shear stiffnesses are imposed.

  3. A cellular automata model for ant trails

    Indian Academy of Sciences (India)

    Sibel Gokce; Ozhan Kayacan

    2013-05-01

    In this study, the unidirectional ant traffic flow with U-turn in an ant trail was investigated using one-dimensional cellular automata model. It is known that ants communicate with each other by dropping a chemical, called pheromone, on the substrate. Apart from the studies in the literature, it was considered in the model that (i) ant colony consists of two kinds of ants, goodand poor-smelling ants, (ii) ants might make U-turn for some special reasons. For some values of densities of good- and poor-smelling ants, the flux and mean velocity of the colony were studied as a function of density and evaporation rate of pheromone.

  4. Protein accounting in the cellular economy

    Science.gov (United States)

    Vázquez-Laslop, Nora; Mankin, Alexander S.

    2014-01-01

    Knowing the copy number of cellular proteins is critical for understanding cell physiology. By being able to measure the absolute synthesis rates of the majority of cellular proteins, Li et al. (2014) gain insights into key aspects of translation regulation and fundamental principles of cellular strategies to adjust protein synthesis according to the needs. PMID:24766801

  5. The Nucleolus Takes Control of Protein Trafficking Under Cellular Stress

    OpenAIRE

    Nalabothula, Narasimharao; Indig, Fred E.; Carrier, France

    2010-01-01

    The nucleolus is a highly dynamic nuclear substructure that was originally described as the site of ribosome biogenesis. The advent of proteomic analysis has now allowed the identification of over 4500 nucleolus associated proteins with only about 30% of them associated with ribogenesis (1). The great number of nucleolar proteins not associated with traditionally accepted nucleolar functions indicates a role for the nucleolus in other cellular functions such as mitosis, cell-cycle progression...

  6. Modified apolipoprotein (apo) A-I by artificial sweetener causes severe premature cellular senescence and atherosclerosis with impairment of functional and structural properties of apoA-I in lipid-free and lipid-bound state.

    Science.gov (United States)

    Jang, Wookju; Jeoung, Nam Ho; Cho, Kyung-Hyun

    2011-05-01

    Long-term consumption of artificial sweeteners (AS) has been the recent focus of safety concerns. However, the potential risk of the AS in cardiovascular disease and lipoprotein metabolism has not been investigated sufficiently. We compared the influence of AS (aspartame, acesulfame K, and saccharin) and fructose in terms of functional and structural correlations of apolipoprotein (apo) A-I and high-density lipoproteins (HDL), which have atheroprotective effects. Long-term treatment of apoA-I with the sweetener at physiological concentration (3 mM for 168 h) resulted in loss of antioxidant and phospholipid binding activities with modification of secondary structure. The AS treated apoA-I exhibited proteolytic cleavage to produce 26 kDa-fragment. They showed pro-atherogenic properties in acetylated LDL phagocytosis of macrophages. Each sweetener alone or sweetener-treated apoA-I caused accelerated senescence in human dermal fibroblasts. These results suggest that long-term consumption of AS might accelerate atherosclerosis and senescence via impairment of function and structure of apoA-I and HDL. PMID:21533907

  7. PM - processing for manufacturing of metals with cellular structures

    International Nuclear Information System (INIS)

    In this review the major Processes about manufacturing of metals with cellular structure are described - based on powder metallurgy, chemical deposition and some other methods (without melting techniques). It can be shown that during the last decade many interesting innovations led to new production methods to design cellular materials. Some of them are used nowadays in industry. Also characterization and properties become more important and have therefore been carried out carefully, because of their strong influence on the functions and applications of such materials. (author)

  8. Absorbed Power Minimization in Cellular Users with Circular Antenna Arrays

    Science.gov (United States)

    Christofilakis, Vasilis; Votis, Constantinos; Tatsis, Giorgos; Raptis, Vasilis; Kostarakis, Panos

    2010-01-01

    Nowadays electromagnetic pollution of non ionizing radiation generated by cellular phones concerns millions of people. In this paper the use of circular antenna array as a means of minimizing the absorbed power by cellular phone users is introduced. In particular, the different characteristics of radiation patterns produced by a helical conventional antenna used in mobile phones operating at 900 MHz and those produced by a circular antenna array, hypothetically used in the same mobile phones, are in detail examined. Furthermore, the percentage of decrement of the power absorbed in the head as a function of direction of arrival is estimated for the circular antenna array.

  9. A NOVEL ARCHITECTURE FOR SDN-BASED CELLULAR NETWORK

    Directory of Open Access Journals (Sweden)

    Md. Humayun Kabir

    2014-12-01

    Full Text Available In this paper, we propose a novel SDN-based cellular network architecture that will be able to utilize the opportunities of centralized administration of today’s emerging mobile network. Our proposed architecture would not depend on a single controller, rather it divides the whole cellular area into clusters, and each cluster is controlled by a separate controller. A number of controller services are provided on top of each controller to manage all the major functionalities of the network and help to make the network programmable and more agile, and create opportunities for policy-driven supervision and more automation.

  10. Cellular Automaton Model for Immunology of Tumor Growth

    CERN Document Server

    Voitikova, M

    1998-01-01

    The stochastic discrete space-time model of an immune response on tumor spreading in a two-dimensional square lattice has been developed. The immunity-tumor interactions are described at the cellular level and then transferred into the setting of cellular automata (CA). The multistate CA model for system, in which all statesoflattice sites, composing of both immune and tumor cells populations, are the functions of the states of the 12 nearest neighbors. The CA model incorporates the essential featuresof the immunity-tumor system. Three regimes of neoplastic evolution including metastatic tumor growth and screen effect by inactive immune cells surrounding a tumor have been predicted.

  11. Universal map for cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    García-Morales, V., E-mail: vmorales@ph.tum.de [Institute for Advanced Study – Technische Universität München, Lichtenbergstr. 2a, D-85748 Garching (Germany)

    2012-08-20

    A universal map is derived for all deterministic 1D cellular automata (CAs) containing no freely adjustable parameters and valid for any alphabet size and any neighborhood range (including non-symmetrical neighborhoods). The map can be extended to an arbitrary number of dimensions and topologies and to arbitrary order in time. Specific CA maps for the famous Conway's Game of Life and Wolfram's 256 elementary CAs are given. An induction method for CAs, based in the universal map, allows mathematical expressions for the orbits of a wide variety of elementary CAs to be systematically derived. -- Highlights: ► A universal map is derived for all deterministic 1D cellular automata (CA). ► The map is generalized to 2D for Von Neumann, Moore and hexagonal neighborhoods. ► A map for all Wolfram's 256 elementary CAs is derived. ► A map for Conway's “Game of Life” is obtained.

  12. Cellular Therapy for Heart Failure.

    Science.gov (United States)

    Psaltis, Peter J; Schwarz, Nisha; Toledo-Flores, Deborah; Nicholls, Stephen J

    2016-01-01

    The pathogenesis of cardiomyopathy and heart failure (HF) is underpinned by complex changes at subcellular, cellular and extracellular levels in the ventricular myocardium. For all of the gains that conventional treatments for HF have brought to mortality and morbidity, they do not adequately address the loss of cardiomyocyte numbers in the remodeling ventricle. Originally conceived to address this problem, cellular transplantation for HF has already gone through several stages of evolution over the past two decades. Various cell types and delivery routes have been implemented to positive effect in preclinical models of ischemic and nonischemic cardiomyopathy, with pleiotropic benefits observed in terms of myocardial remodeling, systolic and diastolic performance, perfusion, fibrosis, inflammation, metabolism and electrophysiology. To a large extent, these salubrious effects are now attributed to the indirect, paracrine capacity of transplanted stem cells to facilitate endogenous cardiac repair processes. Promising results have also followed in early phase human studies, although these have been relatively modest and somewhat inconsistent. This review details the preclinical and clinical evidence currently available regarding the use of pluripotent stem cells and adult-derived progenitor cells for cardiomyopathy and HF. It outlines the important lessons that have been learned to this point in time, and balances the promise of this exciting field against the key challenges and questions that still need to be addressed at all levels of research, to ensure that cell therapy realizes its full potential by adding to the armamentarium of HF management. PMID:27280304

  13. HIV prevalence and cellular immune function analysis among drug addicts in certain area%某地区吸毒者HIV感染状况调查及细胞免疫功能分析

    Institute of Scientific and Technical Information of China (English)

    张丽; 曾汝良

    2012-01-01

    Objective To investigate the prevalence of human immunodeficiency virus(HIV) and immune function among drug addicts in this area. Methods 4 827 cases of drug addicts were surveyed, and detected for anti-HIV antibody and subgroups of T lymphocyte. Results The positive rate of anti-HIV antibody was 1. 28% (62/4 827). Most HIV-positive drug addicts were from other regions[75. 81% (47/62)] , injection drug users[80. 65% (50/62)] , with a history of drug abuse for more than three to five years and at the age of nineteen to less than thirty-five years old. The amount of CD3 +CD4+ T lymphocyte and ratio of CD4+/ CD8+ were both lower than healthy subjects(P5~10)年[67.74%(42/62)]、年龄范围为(19~<35)岁[69.35%(43/62)].HIV阳性者CD3+CD4+T淋巴细胞数及CD4+/CD8+比值均低于健康者(P<0.05).结论 该地区HIV感染吸毒者存在低龄化和地域外来化趋势,需加强相关管理措施,重视健康教育.

  14. Model of Handover and Traffic Based on Cellular Geometry with Smart Antenna

    OpenAIRE

    Zufan Zhang; Jie Zhang; Shaohui Sun

    2014-01-01

    Based on the application of smart antennas in cellular mobile communications, this paper introduces the impact of the width of the antenna beams playing on the dwell time probability density function in cellular geometry with smart antenna. The research results indicate that the smart cell structure can improve the dwell time of users within the cell and improve the traffic system performance.

  15. 尖锐湿疣患者HPV感染类型和细胞免疫功能的分析%Analysis of HPV Infection Types and Cellular Immune Function in Patients With Condyloma

    Institute of Scientific and Technical Information of China (English)

    马晓慧

    2015-01-01

    Objective To investigate condyloma acuminatum (common sexually transmitted disease, CA ) in patients with human papilloma virus ( human papillomavirus, HPV ) genotype infection status and the characteristics of distribution and HPV subtypes, and peripheral blood T lymphocyte subsets and NK cell expression and clinical treatment of ca provide experimental basis.Methods According to the inclusion criteria, the choice of 81 cases of diagnosed patients with Ca, before treatment take rash dander by polymerase chain reaction ( PCR ) method for detection of HPV subtype; in treatment and followed up for 3 months to cut-off point of blood by lfow cytometry analysis of lymphocyte immune function and with the normal population control groups were compared.Results 40 cases ( 49.38% ) were infected by single subtype and 41 cases ( 50.62%) were mixed subtype. Infection in patients with peripheral blood T cells and normal control group comparison, the percentage of CD 4+ cells decreased, P<0.05, had difference statistically significance, CD 8+ cell percentage increased,P<0.05, had difference statistically significance, ratio of CD 4+/CD 8+decreased,P<0.05, had difference statistically significance. Conclusion HPV subtype mixed infection and immune cell function anomaly is prompted condyloma acuminatum patients Infected with human papilloma virus is an important factor.%目的:研究尖锐湿疣(Condyloma Acuminatum,CA)患者感染的人乳头瘤病毒(Human Papilomavirus,HPV)基因型的状况和分布特点,以及HPV亚型和外周血T淋巴细胞亚群和NK细胞的表达情况,分析尖锐湿疣患者感染人乳头瘤病毒亚型与细胞免疫功能的关联性,为临床治疗CA提供实验依据。方法根据纳入标准,选择81例明确诊断CA患者,治疗前取患者皮疹皮屑通过聚合酶链式反应(PCR)方法检测HPV亚型;在治疗和随访3个月的截止点采血,应用流式细胞仪分析淋巴细胞免疫功能,并与

  16. Thermomechanical characterisation of cellular rubber

    Science.gov (United States)

    Seibert, H.; Scheffer, T.; Diebels, S.

    2016-01-01

    This contribution discusses an experimental possibility to characterise a cellular rubber in terms of the influence of multiaxiality, rate dependency under environmental temperature and its behaviour under hydrostatic pressure. In this context, a mixed open and closed cell rubber based on an ethylene propylene diene monomer is investigated exemplarily. The present article intends to give a general idea of the characterisation method and the considerable effects of this special type of material. The main focus lies on the experimental procedure and the used testing devices in combination with the analysis methods such as true three-dimensional digital image correlation. The structural compressibility is taken into account by an approach for a material model using the Theory of Porous Media with additional temperature dependence.

  17. Cellular tolerance to pulsed heating

    Science.gov (United States)

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

    2005-04-01

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

  18. The Pearl Sac Formation in Male and Female Pinctada maxima Host Oysters Implanted With Allograft Saibo

    OpenAIRE

    La Eddy; Ridwan Affandi; Nastiti Kusumorini; Yulvian Sani; Wasmen Manalu

    2015-01-01

    An experiment was conducted to study the effect of male and female host oysters on the pearl sac formation in Pinctada maxima oyster. One hundred sixty oysters were used in a completely randomized design with 2 x 4 factorial arrangement and 20 replications. The 1st factor was that sex of host oyster consisted of two levels that is males and females. The 2nd factor was week after nucleus implantation with four levels that is 1, 2, 3, and 4 weeks. The parameters observed were the percentage of ...

  19. The Pearl Sac Formation in Male and Female Pinctada maxima Host Oysters Implanted With Allograft Saibo

    Directory of Open Access Journals (Sweden)

    La Eddy

    2015-07-01

    Full Text Available An experiment was conducted to study the effect of male and female host oysters on the pearl sac formation in Pinctada maxima oyster. One hundred sixty oysters were used in a completely randomized design with 2 x 4 factorial arrangement and 20 replications. The 1st factor was that sex of host oyster consisted of two levels that is males and females. The 2nd factor was week after nucleus implantation with four levels that is 1, 2, 3, and 4 weeks. The parameters observed were the percentage of successful oysters to form the pearl sac, the speed of pearl sac formation, the percentage of nucleus coverage by the pearl sac, histology of the pearl sac growth and development, and haemolymph glucose, calcium and phosphorus concentrations. Our results showed that the percentages of host oysters that succeeded in forming a pearl sac were 80% and 75% in female and male host oysters, respectively. There was no statistical difference in nucleus rejection and mortality in male and female host oysters but the results indicated that male host oysters showed a numerically higher nucleus rejection. The speed of pearl sac growth and the percentage of nucleus coverage by the pearl sac in female host oysters were better than those in male host oysters. Haemolymph calcium, phosphorus and glucose concentrations, oxygen consumption, and histological development of the pearl sac were not different between male and female host oysters. Pearl sac formation in the female host oysters was better than that in male host oysters.

  20. Oxidative stress action in cellular aging

    Directory of Open Access Journals (Sweden)

    Monique Cristine de Oliveira

    2010-12-01

    Full Text Available Various theories try to explain the biological aging by changing the functions and structure of organic systems and cells. During lifetime, free radicals in the oxidative stress lead to lipid peroxidation of cellular membranes, homeostasis imbalance, chemical residues formation, gene mutations in DNA, dysfunction of certain organelles, and the arise of diseases due to cell death and/or injury. This review describes the action of oxidative stress in the cells aging process, emphasizing the factors such as cellular oxidative damage, its consequences and the main protective measures taken to prevent or delay this process. Tests with antioxidants: vitamins A, E and C, flavonoids, carotenoids and minerals, the practice of caloric restriction and physical exercise, seeking the beneficial effects on human health, increasing longevity, reducing the level of oxidative stress, slowing the cellular senescence and origin of certain diseases, are discussed.Diferentes teorias tentam explicar o envelhecimento biológico através da alteração das funções e estrutura dos sistemas orgânicos e células. Ao longo da vida, os radicais livres presentes no estresse oxidativo conduzem à peroxidação dos lipídios das membranas celulares, desequilíbrio da homeostase, formação de resíduos químicos, mutações gênicas no DNA, disfunção de certas organelas, bem como ao surgimento de doenças devido à lesão e/ou morte celular. Nesta revisão descreve-se a ação do estresse oxidativo no processo de envelhecimento das células, enfatizando fatores como os danos oxidativos celulares, suas conseqüências e as principais medidas protetoras adotadas para se prevenir ou retardar este processo. Testes com antioxidantes: vitaminas A, E e C, flavonóides, carotenóides e minerais; a prática de restrição calórica e exercícios físicos, que buscam efeitos benéficos sobre a saúde humana, aumentando a longevidade, reduzindo o nível de estresse oxidativo

  1. Cellular cardiomyoplasty A preliminary clinical report

    International Nuclear Information System (INIS)

    Background: Cellular cardiomyoplasty is the method of transplanting myogenic cells into injured myocardium to restore the lost heart muscle cells and to improve ventricular function. Method: Three patients, all with a history of coronary heart disease, underwent coronary artery bypass grafting and implantation of autologous satellite cells. A muscle biopsy of 2-4 g from the right vastus lateralis muscle was obtained for satellite cell (myogenic stem cell from skeletal muscle) isolation and proliferation before implanted into the donor's heart. The cells were suspended in serum-free medium and injected into 30-40 sites at and around the ischemic areas just before reversing the hypothermic cardioplegia to eliminate arrhythmia and to improve retention. After recovery, each patient was maintained at the intensive care unit for 3-4 days with ECG monitoring before transferring to the patient floor. Results: All patients survived the procedure with an uneventful recovery and were discharged from the hospital. At 3-4 months follow-up examination, increased left ventricular ejection fraction of 11% (35-46%), 5.4% (40-45.4%) and 1% (40-41%) and decreased left ventricular diastolic diameter of 4, 2 and 9 mm were observed for the patients, respectively. Arrhythmia was not detected during the follow-up evaluation by ECG. Improved perfusion (99mTC-MIBI) and increased metabolic activity (18F-deoxyglucose) were found at the sites of satellite cell implantation. Significant increase of wall thickness and movement at the areas of cell injection was also observed using 2D-echo. Conclusion: Cellular cardiomyoplasty using autologous satellite cells is a safe procedure with encouraging beneficial outcomes in patients

  2. The role of actin networks in cellular mechanosensing

    Science.gov (United States)

    Azatov, Mikheil

    Physical processes play an important role in many biological phenomena, such as wound healing, organ development, and tumor metastasis. During these processes, cells constantly interact with and adapt to their environment by exerting forces to mechanically probe the features of their surroundings and generating appropriate biochemical responses. The mechanisms underlying how cells sense the physical properties of their environment are not well understood. In this thesis, I present my studies to investigate cellular responses to the stiffness and topography of the environment. In order to sense the physical properties of their environment, cells dynamically reorganize the structure of their actin cytoskeleton, a dynamic network of biopolymers, altering the shape and spatial distribution of protein assemblies. Several observations suggest that proteins that crosslink actin filaments may play an important role in cellular mechanosensitivity. Palladin is an actin-crosslinking protein that is found in the lamellar actin network, stress fibers and focal adhesions, cellular structures that are critical for mechanosensing of the physical environment. By virtue of its close interactions with these structures in the cell, palladin may play an important role in cell mechanics. However, the role of actin crosslinkers in general, and palladin in particular, in cellular force generation and mechanosensing is not well known. I have investigated the role of palladin in regulating the plasticity of the actin cytoskeleton and cellular force generation in response to alterations in substrate stiffness. I have shown that the expression levels of palladin modulate the forces exerted by cells and their ability to sense substrate stiffness. Perturbation experiments also suggest that palladin levels in cells altered myosin motor activity. These results suggest that the actin crosslinkers, such as palladin, and myosin motors coordinate for optimal cell function and to prevent aberrant

  3. 海参多糖抗肺癌活性及对T细胞免疫功能调节研究进展%Research and progression on anti-lung neoplasm activity and the regulation of T cellular immune ;function by polysaccharide from sea cucumber

    Institute of Scientific and Technical Information of China (English)

    李甜甜; 王相海; 林存智; 朱新红

    2014-01-01

    肺癌是预后极差的恶性肿瘤之一,已经上升到肿瘤死亡原因的首位,成为严重威胁人类健康的恶性肿瘤。肺癌的早期治疗除了手术、放疗和化疗外,生物治疗已经成为重要的辅助手段。海参多糖具有多种生物活性,它是从海参体内提取的一种糖胺聚糖,具有良好的抗凝血和抗血栓作用。研究显示其具有抗肿瘤活性及细胞免疫调节功能,通过抑制肿瘤新生血管的形成和抗凝血来实现抗肿瘤作用,通过激活T细胞调节机体细胞免疫功能。本文就海参多糖在抗肺癌活性及T细胞免疫功能调节方面的基础研究进展进行综述。%The lung cancer is one of very poor malignant tumors in prognosis. It has reached the top of cause of death and become to threaten the health of human in malignant tumor. The biotherapy has become the important adjunctive therapy method for pulmonary cancer, apart from surgery, chemotherapy and radiotherapy. The polysaccharide which was selectived from sea cucumber has more important biologic activity substance. It has satisfactory effects in anticoagulated blood and anti-thrombosis as biotherapy, and it has the function of cyto-immunity and anti-neoplastic activity. The activity was carried out by inhibiting the form of neovascular of tumor and anti-coagulated blood. It reinforces the cellular immune function by activating T cells. So, we reviewed the progression of grounding research in anti-lung tumor activity and the regulation of T cellular immune function for polysaccharide from sea cucumber.

  4. p53: Biology and role for cellular radiosensitivity

    International Nuclear Information System (INIS)

    Purpose: p53 is the most commonly mutated gene in human tumors with large impact on cellular biology and response to radiation. Many excellent reviews are available on various aspects but for several years none about the role of p53 for radiosensitivity. The latter is the aim of the present paper. Methods: Review of the literature. Results: p53 is a regulator of apoptosis mainly in hematopoetic tissue. In normal tissue and solid tumors presumably other functions have more impact on the cellular response. p53 controls cell-cycle progression after irradiation and also DNA-repair, namely homologous and non-homologous recombination. Mutations of p53 alter these functions which may be responsible for an enhanced cellular and tumor radioresistance. At present only few reports were able to show that under tightly controlled conditions loss of p53 wild-type function leads to enhanced radioresistance. A general proof is still lacking. Conclusion: The emerging picture in the year 2000 shows p53 as a central protein in a multi-enzyme multi-function network which is far from being fully understood. Although p53 appears to be a major regulator it is certainly not the unreplacable component the loss of which uniformly determines radioresistance. Only further understanding of modifiers and cooperators in the cell and in the specific tissue context will elucidate p53's role for radiosensitivity and radiotherapy. (orig.)

  5. Cellular phones: are they detrimental?

    Science.gov (United States)

    Salama, Osama E; Abou El Naga, Randa M

    2004-01-01

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

  6. The mammary cellular hierarchy and breast cancer

    OpenAIRE

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

    2014-01-01

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

  7. A radiation measurement study on cellular phone

    International Nuclear Information System (INIS)

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

  8. Cellular structure in system of interacting particles

    OpenAIRE

    Lev, Bohdan

    2008-01-01

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

  9. Radiation, nitric oxide and cellular death

    International Nuclear Information System (INIS)

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

  10. 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.

  11. The cellular particle swarm optimization algorithm

    International Nuclear Information System (INIS)

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

  12. Optimized Cellular Core for Rotorcraft Project

    Data.gov (United States)

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

  13. 77 FR 73472 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-12-10

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice...

  14. Efficiency of cellular information processing

    CERN Document Server

    Barato, Andre C; Seifert, Udo

    2014-01-01

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

  15. Changes of cellular immune function in children with mycoplasma pneumoniae pneumonia and the adjuvant effect of spleen aminopeptide%肺炎支原体肺炎患儿细胞免疫功能的变化及脾氨肽的辅助治疗作用

    Institute of Scientific and Technical Information of China (English)

    胡晓艳; 钱卫疆; 张双船; 李健雄; 林月钰

    2012-01-01

    Objective To investigate the changes of cellular immune function in children with mycoplasma pneumoniae pneumonia (MPP) and the adjuvant effect of spleen aminopeptide. Methods Sixty-two patients of MPP were randomly divided into group A (n=30) and group B (n=32), and 26 healthy children who had physical examination during the same period were enrolled as the control group. The patients in group A were treated with Azithromy-cin combined with spleen aminopeptide orally, while those in group B were given Azithromycin only. T lymphocyte subgroups of MPP were determined in the acute phase and after treatment, and the recovery of symptoms and signs of MPP were observed. Results The percentage of CD3+, CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes in the acute phase of MPP were significantly lower than those in the control group (P<0.05), while the percentage of CD8+ lymphocytes in the acute phase of MPP was significantly higher than that in the control group (P<0.05). After treatment, the percentage of CD3+, CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes in group A were significantly higher than those in group B (P<0.05), with the percentage of CD8+ lymphocytes significantly lower (P<0.05). The symptoms and signs recovered faster in group A than group B (P<0.05). Conclusion The cellular immune function is depressed in children with MPP. Spleen aminopeptide can improve the cellular immune function of the body, and has a good adjuvant effect for MPP.%目的 探讨肺炎支原体肺炎(MPP)患儿细胞免疫功能的变化及脾氨肽对MPP的辅助治疗作用.方法 62例MPP病例随机分成MPP治疗组30例和MPP对照组32例,并以同期体检的26例健康儿童作为健康对照组.所有MPP病例均予阿奇霉素口服治疗,MPP治疗组同时加用脾氨肽口服治疗.在MPP急性期及治疗后分别进行T淋巴细胞亚群检测,并观察MPP病例临床症状体征恢复的情况.结果 MPP患儿的CD3+、CD4+淋巴细胞比例及CD4+/CD8

  16. Molecular and cellular limits to somatosensory specificity

    Directory of Open Access Journals (Sweden)

    Viana Félix

    2008-04-01

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

  17. Boundedness and exponential stability for nonautonomous cellular neural networks with reaction-diffusion terms

    Energy Technology Data Exchange (ETDEWEB)

    Lou Xuyang [Research Center of Control Science and Engineering, Southern Yangtze University, 1800 Lihu Road, Wuxi, Jiangsu 214122 (China); Cui Baotong [Research Center of Control Science and Engineering, Southern Yangtze University, 1800 Lihu Road, Wuxi, Jiangsu 214122 (China)]. E-mail: btcui@sohu.com

    2007-07-15

    Employing Lyapunov functional method, we analyze the ultimate boundedness and global exponential stability of a class of reaction-diffusion cellular neural networks with time-varying delays. Some new criteria are obtained to ensure ultimate boundedness and global exponential stability of delayed reaction-diffusion cellular neural networks (DRCNNs). Without assuming that the activation functions f {sub ijl}(.) are bounded, the results extend and improve the earlier publications.

  18. A sub-cellular viscoelastic model for cell population mechanics.

    Directory of Open Access Journals (Sweden)

    Yousef Jamali

    Full Text Available Understanding the biomechanical properties and the effect of biomechanical force on epithelial cells is key to understanding how epithelial cells form uniquely shaped structures in two or three-dimensional space. Nevertheless, with the limitations and challenges posed by biological experiments at this scale, it becomes advantageous to use mathematical and 'in silico' (computational models as an alternate solution. This paper introduces a single-cell-based model representing the cross section of a typical tissue. Each cell in this model is an individual unit containing several sub-cellular elements, such as the elastic plasma membrane, enclosed viscoelastic elements that play the role of cytoskeleton, and the viscoelastic elements of the cell nucleus. The cell membrane is divided into segments where each segment (or point incorporates the cell's interaction and communication with other cells and its environment. The model is capable of simulating how cells cooperate and contribute to the overall structure and function of a particular tissue; it mimics many aspects of cellular behavior such as cell growth, division, apoptosis and polarization. The model allows for investigation of the biomechanical properties of cells, cell-cell interactions, effect of environment on cellular clusters, and how individual cells work together and contribute to the structure and function of a particular tissue. To evaluate the current approach in modeling different topologies of growing tissues in distinct biochemical conditions of the surrounding media, we model several key cellular phenomena, namely monolayer cell culture, effects of adhesion intensity, growth of epithelial cell through interaction with extra-cellular matrix (ECM, effects of a gap in the ECM, tensegrity and tissue morphogenesis and formation of hollow epithelial acini. The proposed computational model enables one to isolate the effects of biomechanical properties of individual cells and the

  19. Cognitive Effects of Radiation Emitted by Cellular Phones: A Summary of Three Experiments

    International Nuclear Information System (INIS)

    The widespread use of cellular phones has initiated research regarding the possible biological effects of exposure to Radiofrequency Radiation (RFR). This issue is of particular relevance because a considerable number of people are exposed to cellular RFR emitted in close proximity to their heads. Some studies, recently reviewed by Barth et al.(1), examined whether cognitive functions of human beings are altered while exposed to RFR emitted by cellular phones. This paper summarizes the results of three experiments we conducted in order to examine the effects of exposure to RFR emitted by a standard GSM phone at 890 MHz on human cognitive functions

  20. Cellular and Functional Imaging of Cardiac Transplant Rejection

    Science.gov (United States)

    Wu, Yijen L.; Ye, Qing

    2011-01-01

    Heart transplantation is now an established treatment for patients suffering from end-stage heart diseases. With the advances in immunosuppressive treatment, the survival rate for transplant patients has improved greatly. However, allograft rejection, both acute and chronic, after heart transplantation is still a limitation leading to morbidity and mortality. The current clinical gold standard for screening rejection is endomyocardial biopsy (EMB), which is not only invasive, but also error-prone, due to the limited sample size and the site location of sampling. It would be highly desirable to have reliable and noninvasive alternatives for EMB in monitoring cardiac allograft rejection. The objective of this review is to highlight how cardiovascular imaging can contribute to noninvasively detecting and to evaluating both acute and chronic allograft rejection after heart transplantation, in particular, cardiovascular MRI (CMRI); and how CMRI can assess both immune cell infiltration at the rejecting organ, and the cardiac dysfunctions resulting from allograft rejection. PMID:21359095

  1. Cellular and Functional Imaging of Cardiac Transplant Rejection

    OpenAIRE

    Wu, Yijen L.; Ye, Qing; Ho, Chien

    2011-01-01

    Heart transplantation is now an established treatment for patients suffering from end-stage heart diseases. With the advances in immunosuppressive treatment, the survival rate for transplant patients has improved greatly. However, allograft rejection, both acute and chronic, after heart transplantation is still a limitation leading to morbidity and mortality. The current clinical gold standard for screening rejection is endomyocardial biopsy (EMB), which is not only invasive, but also error-p...

  2. Functionalization and cellular uptake of boron carbide nanoparticles

    DEFF Research Database (Denmark)

    Mortensen, M. W.; Björkdahl, O.; Sørensen, P. G.; Hansen, T.; Jensen, M. R.; Gundersen, Hans Jørgen Gottlieb; Bjørnholm, T.

    2006-01-01

    In this paper we present surface modification strategies of boron carbide nanoparticles, which allow for bioconjugation of the transacting transcriptional activator (TAT) peptide and fluorescent dyes. Coated nanoparticles can be translocated into murine EL4 thymoma cells and B16 F10 malignant...... melanoma cells in amounts as high as 0.3 wt. % and 1 wt. %, respectively. Neutron irradiation of a test system consisting of untreated B16 cells mixed with B16 cells loaded with boron carbide nanoparticles were found to inhibit the proliferative capacity of untreated cells, showing that cells loaded with...... boron-containing nanoparticles can hinder the growth of neighboring cells upon neutron irradiation. This could provide the first step toward a T cell-guided boron neutron capture therapy....

  3. Cut and Paste: restoring cellular function by gene correction

    Institute of Scientific and Technical Information of China (English)

    Guang-Hui Liu; Ignacio Sancho-Martinez; Juan Carlos Izpisua Belmonte

    2012-01-01

    Gene-editing technologies and patient-specific induced pluripotent stem cells (iPSCs) may represent an unprecedented opportunity for merging the stem cell and traditional gene therapy fields to fulfill the promises of regenerative medicine.

  4. The effect of particle design on cellular internalization pathways

    OpenAIRE

    Gratton, Stephanie E. A.; Ropp, Patricia A.; Pohlhaus, Patrick D.; Luft, J. Christopher; Madden, Victoria J.; Napier, Mary E.; DeSimone, Joseph M.

    2008-01-01

    The interaction of particles with cells is known to be strongly influenced by particle size, but little is known about the interdependent role that size, shape, and surface chemistry have on cellular internalization and intracellular trafficking. We report on the internalization of specially designed, monodisperse hydrogel particles into HeLa cells as a function of size, shape, and surface charge. We employ a top-down particle fabrication technique called PRINT that is able to generate unifor...

  5. Nanosensor Data Processor in Quantum-Dot Cellular Automata

    OpenAIRE

    Fenghui Yao; Mohamed Saleh Zein-Sabatto; Guifeng Shao; Mohammad Bodruzzaman; Mohan Malkani

    2014-01-01

    Quantum-dot cellular automata (QCA) is an attractive nanotechnology with the potential alterative to CMOS technology. QCA provides an interesting paradigm for faster speed, smaller size, and lower power consumption in comparison to transistor-based technology, in both communication and computation. This paper describes the design of a 4-bit multifunction nanosensor data processor (NSDP). The functions of NSDP contain (i) sending the preprocessed raw data to high-level processor, (ii) counting...

  6. Chronic pain, perceived stress, and cellular aging: an exploratory study

    OpenAIRE

    Sibille Kimberly T; Langaee Taimour; Burkley Ben; Gong Yan; Glover Toni L; King Chris; Riley Joseph L; Leeuwenburgh Christiaan; Staud Roland; Bradley Laurence A; Fillingim Roger B

    2012-01-01

    Abstract Background Chronic pain conditions are characterized by significant individual variability complicating the identification of pathophysiological markers. Leukocyte telomere length (TL), a measure of cellular aging, is associated with age-related disease onset, psychosocial stress, and health-related functional decline. Psychosocial stress has been associated with the onset of chronic pain and chronic pain is experienced as a physical and psychosocial stressor. However, the utility of...

  7. The GARP complex is required for cellular sphingolipid homeostasis

    DEFF Research Database (Denmark)

    Fröhlich, Florian; Petit, Constance; Kory, Nora;

    2015-01-01

    (GARP) complex, which functions in endosome-to-Golgi retrograde vesicular transport, as a critical player in sphingolipid homeostasis. GARP deficiency leads to accumulation of sphingolipid synthesis intermediates, changes in sterol distribution, and lysosomal dysfunction. A GARP complex mutation...... the phenotypes of GARP-deficient yeast or mammalian cells. Together, these data show that GARP is essential for cellular sphingolipid homeostasis and suggest a therapeutic strategy for the treatment of PCCA2....

  8. Cellular organization of cortical barrel columns is whisker-specific

    OpenAIRE

    Meyer, Hanno S.; Egger, Robert; Guest, Jason M.; Foerster, Rita; Reissl, Stefan; Oberlaender, Marcel

    2013-01-01

    Cortical columns are thought to be the elementary functional building blocks of sensory cortices. Here we show that the cellular architecture of cortical “barrel” columns in rodent somatosensory cortex is not stereotypic, but specific for each whisker on the animals’ snout. Our findings challenge the concepts underlying contemporary simulation efforts that build up large-scale network models of repeatedly occurring identical cortical circuits.

  9. Development and validation of computational models of cellular interaction

    OpenAIRE

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

    2004-01-01

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

  10. Cellular proliferation in the rat pineal gland during postnatal development

    OpenAIRE

    Carvajal, J.C.; Carbajo, S.; Gómez Esteban, M.B.; Alvarez-Morujo Suárez, A.J.; Muñoz Barragan, L.

    1998-01-01

    To establish a possible correlation between the rate of cellular proliferation and already documented functional and morphological characteristics of the rat pineal gland during postnatal development, the bromodeoxyuridine labelling method was used to evaluate the fraction of cells at the S phase of the cell cycle in paraffin sections from I-, 7-, 14- and 28-day-old rats. Numerical density, taken as an indirect measure of cell hypertrophy, was also evaluated. D...

  11. Cellular Chaperonin CCTγ Contributes to Rabies Virus Replication during Infection

    OpenAIRE

    Zhang, Jinyang; Wu, Xiaopeng; Zan, Jie; Wu, Yongping; YE, CHENGJIN; Ruan, Xizhen; Zhou, Jiyong

    2013-01-01

    Rabies, as the oldest known infectious disease, remains a serious threat to public health worldwide. The eukaryotic cytosolic chaperonin TRiC/CCT complex facilitates the folding of proteins through ATP hydrolysis. Here, we investigated the expression, cellular localization, and function of neuronal CCTγ during neurotropic rabies virus (RABV) infection using mouse N2a cells as a model. Following RABV infection, 24 altered proteins were identified by using two-dimensional electrophoresis and ma...

  12. Cellular solid behaviour of liquid crystal colloids. 2. Mechanical properties

    OpenAIRE

    Anderson, V.J.; Terentjev, E. M.

    2000-01-01

    This paper presents the results of a rheological study of thermotropic nematic colloids aggregated into cellular structures. Small sterically stabilised PMMA particles dispersed in a liquid crystal matrix densely pack on cell interfaces, but reversibly mix with the matrix when the system is heated above Tni. We obtain a remarkably high elastic modulus, G'~10^5 Pa, which is a nearly linear function of particle concentration. A characteristic yield stress is required to disrupt the continuity o...

  13. Cellular response after irradiation: Cell cycle control and apoptosis

    International Nuclear Information System (INIS)

    The importance of apoptotic death was assessed in a set of experiments, involving eight human tumour cell lines (breast cancer, bladder carcinoma, medulloblastoma). Various aspects of the quantitative study of apoptosis and methods based on the detection of DNA fragmentation (in situ tailing and comet assay) are described and discussed. Data obtained support the hypothesis that apoptosis is not crucial for cellular radiosensitivity and that the relationship between p53 functionality or clonogenic survival and apoptosis may bee cell type specific. (author)

  14. Development of orally active inhibitors of protein and cellular fucosylation

    OpenAIRE

    Okeley, Nicole M.; Alley, Stephen C.; Anderson, Martha E.; Boursalian, Tamar E.; Burke, Patrick J.; Emmerton, Kim M.; Jeffrey, Scott C.; Klussman, Kerry; Law, Che-Leung; Sussman, Django; Toki, Brian E.; Westendorf, Lori; Zeng, Weiping; Zhang, XinQun; Benjamin, Dennis R.

    2013-01-01

    The key role played by fucose in glycoprotein and cellular function has prompted significant research toward identifying recombinant and biochemical strategies for blocking its incorporation into proteins and membrane structures. Technologies surrounding engineered cell lines have evolved for the inhibition of in vitro fucosylation, but they are not applicable for in vivo use and drug development. To address this, we screened a panel of fucose analogues and identified 2-fluorofucose and 5-alk...

  15. On Hardware Implementation of Discrete-Time Cellular Neural Networks

    OpenAIRE

    Malki, Suleyman

    2008-01-01

    Cellular Neural Networks are characterized by simplicity of operation. The network consists of a large number of nonlinear processing units; called cells; that are equally spread in the space. Each cell has a simple function (sequence of multiply-add followed by a single discrimination) that takes an element of a topographic map and then interacts with all cells within a specified sphere of interest through direct connections. Due to their intrinsic parallel computing power, CNNs have attract...

  16. Pulsed feedback defers cellular differentiation.

    Directory of Open Access Journals (Sweden)

    Joe H Levine

    2012-01-01

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

  17. Virtualized cognitive network architecture for 5G cellular networks

    KAUST Repository

    Elsawy, Hesham

    2015-07-17

    Cellular networks have preserved an application agnostic and base station (BS) centric architecture1 for decades. Network functionalities (e.g. user association) are decided and performed regardless of the underlying application (e.g. automation, tactile Internet, online gaming, multimedia). Such an ossified architecture imposes several hurdles against achieving the ambitious metrics of next generation cellular systems. This article first highlights the features and drawbacks of such architectural ossification. Then the article proposes a virtualized and cognitive network architecture, wherein network functionalities are implemented via software instances in the cloud, and the underlying architecture can adapt to the application of interest as well as to changes in channels and traffic conditions. The adaptation is done in terms of the network topology by manipulating connectivities and steering traffic via different paths, so as to attain the applications\\' requirements and network design objectives. The article presents cognitive strategies to implement some of the classical network functionalities, along with their related implementation challenges. The article further presents a case study illustrating the performance improvement of the proposed architecture as compared to conventional cellular networks, both in terms of outage probability and handover rate.

  18. 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.

  19. Coordination of plant mitochondrial biogenesis: keeping pace with cellular requirements.

    Directory of Open Access Journals (Sweden)

    Elina eWelchen

    2014-01-01

    Full Text Available Plant mitochondria are complex organelles that carry out numerous metabolic processes related with the generation of energy for cellular functions and the synthesis and degradation of several compounds. Mitochondria are semiautonomous and dynamic organelles changing in shape, number and composition depending on tissue or developmental stage. The biogenesis of functional mitochondria requires the coordination of genes present both in the nucleus and the organelle. In addition, due to their central role, all processes held inside mitochondria must be finely coordinated with those in other organelles according to cellular demands. Coordination is achieved by transcriptional control of nuclear genes encoding mitochondrial proteins by specific transcription factors that recognize conserved elements in their promoter regions. In turn, the expression of most of these transcription factors is linked to developmental and environmental cues, according to the availability of nutrients, light-dark cycles and warning signals generated in response to stress conditions. Among the signals impacting in the expression of nuclear genes, retrograde signals that originate inside mitochondria help to adjust mitochondrial biogenesis to organelle demands. Adding more complexity, several nuclear encoded proteins are dual localized to mitochondria and either chloroplasts or the nucleus. Dual targeting might establish a crosstalk between the nucleus and cell organelles to ensure a fine coordination of cellular activities. In this article, we discuss how the different levels of coordination of mitochondrial biogenesis interconnect to optimize the function of the organelle according to both internal and external demands.

  20. Immune cellular response to HPV: current concepts

    Directory of Open Access Journals (Sweden)

    Maria Alice Guimarães Gonçalves

    2004-02-01

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

  1. Mechanisms of cellular transformation by carcinogenic agents

    International Nuclear Information System (INIS)

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

  2. Recent development of cellular manufacturing systems

    Indian Academy of Sciences (India)

    P K Arora; A Haleem; M K Singh

    2013-06-01

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

  3. Mechanisms of cellular transformation by carcinogenic agents

    Energy Technology Data Exchange (ETDEWEB)

    Grunberger, D.; Goff, S.P.

    1987-01-01

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

  4. LMS filters for cellular CDMA overlay

    OpenAIRE

    Wang, J.

    1996-01-01

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

  5. From Cnn Dynamics to Cellular Wave Computers

    Science.gov (United States)

    Roska, Tamas

    2013-01-01

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

  6. Cellular Subcompartments through Cytoplasmic Streaming.

    Science.gov (United States)

    Pieuchot, Laurent; Lai, Julian; Loh, Rachel Ann; Leong, Fong Yew; Chiam, Keng-Hwee; Stajich, Jason; Jedd, Gregory

    2015-08-24

    Cytoplasmic streaming occurs in diverse cell types, where it generally serves a transport function. Here, we examine streaming in multicellular fungal hyphae and identify an additional function wherein regimented streaming forms distinct cytoplasmic subcompartments. In the hypha, cytoplasm flows directionally from cell to cell through septal pores. Using live-cell imaging and computer simulations, we identify a flow pattern that produces vortices (eddies) on the upstream side of the septum. Nuclei can be immobilized in these microfluidic eddies, where they form multinucleate aggregates and accumulate foci of the HDA-2 histone deacetylase-associated factor, SPA-19. Pores experiencing flow degenerate in the absence of SPA-19, suggesting that eddy-trapped nuclei function to reinforce the septum. Together, our data show that eddies comprise a subcellular niche favoring nuclear differentiation and that subcompartments can be self-organized as a consequence of regimented cytoplasmic streaming. PMID:26305593

  7. Roles of Rho GTPases in Intracellular Transport and Cellular Transformation

    Directory of Open Access Journals (Sweden)

    Ji-Long Chen

    2013-03-01

    Full Text Available Rho family GTPases belong to the Ras GTPase superfamily and transduce intracellular signals known to regulate a variety of cellular processes, including cell polarity, morphogenesis, migration, apoptosis, vesicle trafficking, viral transport and cellular transformation. The three best-characterized Rho family members are Cdc42, RhoA and Rac1. Cdc42 regulates endocytosis, the transport between the endoplasmic reticulum and Golgi apparatus, post-Golgi transport and exocytosis. Cdc42 influences trafficking through interaction with Wiskott-Aldrich syndrome protein (N-WASP and the Arp2/3 complex, leading to changes in actin dynamics. Rac1 mediates endocytic and exocytic vesicle trafficking by interaction with its effectors, PI3kinase, synaptojanin 2, IQGAP1 and phospholipase D1. RhoA participates in the regulation of endocytosis through controlling its downstream target, Rho kinase. Interestingly, these GTPases play important roles at different stages of viral protein and genome transport in infected host cells. Importantly, dysregulation of Cdc42, Rac1 and RhoA leads to numerous disorders, including malignant transformation. In some cases, hyperactivation of Rho GTPases is required for cellular transformation. In this article, we review a number of findings related to Rho GTPase function in intracellular transport and cellular transformation.

  8. The Universe as a Cellular System

    CERN Document Server

    Aragón-Calvo, Miguel A

    2014-01-01

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

  9. Molecular and cellular mechanisms of adipogenesis

    Directory of Open Access Journals (Sweden)

    Aleksander Dmitrievich Egorov

    2015-03-01

    Full Text Available The main components of metabolic syndrome include insulin resistance, hypertriglyceridemia and arterial hypertension. Obesity is the cause of metabolic syndrome, mainly as a consequence of the endocrine function of adipose tissue. The volume of adipose tissue depends on the size of individual adipocytes and on their number. The number of adipocytes increases as a result of enhanced adipocyte differentiation. The transcriptional cascade that regulates this differentiation has been well studied. The major adipogenic transcription factor peroxisome proliferator-activated receptor gamma is a ligand-activated nuclear receptor with essential roles in adipogenesis. Its ligands are used to treat metabolic syndrome and type 2 diabetes mellitus. The present article describes the basic molecular and cellular mechanisms of adipogenesis and discusses the impact of insulin, glucocorticoids, cyclic adenosine monophosphate-activating agents, nuclear receptors and transcription factors on the process of adipogenesis. New regulatory regions of the genome that are capable of binding multiple transcription factors are described, and the most promising drug targets for the treatment of metabolic syndrome and obesity, including the homeodomain proteins Pbx1 and Prep1, are discussed.

  10. Cellular pathways controlling integron cassette site folding.

    Science.gov (United States)

    Loot, Céline; Bikard, David; Rachlin, Anna; Mazel, Didier

    2010-08-01

    By mobilizing small DNA units, integrons have a major function in the dissemination of antibiotic resistance among bacteria. The acquisition of gene cassettes occurs by recombination between the attI and attC sites catalysed by the IntI1 integron integrase. These recombination reactions use an unconventional mechanism involving a folded single-stranded attC site. We show that cellular bacterial processes delivering ssDNA, such as conjugation and replication, favour proper folding of the attC site. By developing a very sensitive in vivo assay, we also provide evidence that attC sites can recombine as cruciform structures by extrusion from double-stranded DNA. Moreover, we show an influence of DNA superhelicity on attC site extrusion in vitro and in vivo. We show that the proper folding of the attC site depends on both the propensity to form non-recombinogenic structures and the length of their variable terminal structures. These results draw the network of cell processes that regulate integron recombination. PMID:20628355

  11. Nongenetic functions of the genome.

    Science.gov (United States)

    Bustin, Michael; Misteli, Tom

    2016-05-01

    The primary function of the genome is to store, propagate, and express the genetic information that gives rise to a cell's architectural and functional machinery. However, the genome is also a major structural component of the cell. Besides its genetic roles, the genome affects cellular functions by nongenetic means through its physical and structural properties, particularly by exerting mechanical forces and by serving as a scaffold for binding of cellular components. Major cellular processes affected by nongenetic functions of the genome include establishment of nuclear structure, signal transduction, mechanoresponses, cell migration, and vision in nocturnal animals. We discuss the concept, mechanisms, and implications of nongenetic functions of the genome. PMID:27151873

  12. Interval maps associated to the cellular automaton rule 184

    International Nuclear Information System (INIS)

    We associate to the cellular automaton elementary rule 184 an interval map defined in [0,1]. We show that this interval map is characterized by a functional equation which depends directly on the local rule and also depends on the choice to represent numbers in base 2. The functional equation is the analytical expression of the interval map self-similarity. We also compute a family of transition matrices which characterizes the effect of the interval map on a family of partitions of the interval [0,1]. We show how the family of matrices can be built with a recursive algorithm which depends on the local rule.

  13. Nanosensor Data Processor in Quantum-Dot Cellular Automata

    Directory of Open Access Journals (Sweden)

    Fenghui Yao

    2014-01-01

    Full Text Available Quantum-dot cellular automata (QCA is an attractive nanotechnology with the potential alterative to CMOS technology. QCA provides an interesting paradigm for faster speed, smaller size, and lower power consumption in comparison to transistor-based technology, in both communication and computation. This paper describes the design of a 4-bit multifunction nanosensor data processor (NSDP. The functions of NSDP contain (i sending the preprocessed raw data to high-level processor, (ii counting the number of the active majority gates, and (iii generating the approximate sigmoid function. The whole system is designed and simulated with several different input data.

  14. Cellular computation using classifier systems

    OpenAIRE

    Kelly, Ciaran; Decraene, James, Lobo, Victor; Mitchell, George G.; McMullin, Barry; O'Brien, Darragh

    2006-01-01

    The EU FP6 Integrated Project PACE ('Programmable Artificial Cell Evolution') is investigating the creation, de novo, of chemical 'protocells'. These will be minimal 'wetware' chemical systems integrating molecular information carriers, primitive energy conversion (metabolism) and containment (membrane). Ultimately they should be capable of autonomous reproduction, and be 'programmable' to realise specific desired function. A key objective of PACE is to explore the application of such pro...

  15. Estimating cellular network performance during hurricanes

    International Nuclear Information System (INIS)

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

  16. A Model for Dynamic Cellular Manufacturing System Based on Multi-functional Machines and Multi-skilled Operators%基于多功能机器与多能工的动态单元制造系统模型

    Institute of Scientific and Technical Information of China (English)

    栾世超; 贾国柱; 衣晓蕾; 孔继利

    2015-01-01

    为了成功地实施动态单元制造系统,同时考虑技术性问题(包括生产单元构建和设计、生产单元之间与生产单元内部的物料移动等)和人员问题(包括员工工资、员工雇佣和解雇等),综合研究和分析了多功能机器和多操作技能员工的动态单元制造系统的生产单元构建、生产单元之间与生产单元内部物料移动、库存和延迟生产、员工分配和柔性生产路径,创新性地提出一个整合的混合整数规划模型。通过遗传算法对数值试验求解,结果验证了新模型的可行性和有效性。%In a production environment of high variety and low volume, product mix and demand usually change under a multi-period planning horizon.The dynamic cellular manufacturing system ( DCMS ) is a well known strategy that typically improves manufacturing efficiency in sucha production environment.To implement DCMS successfully both technical issues ( cell formation and design, intercellular and intracel-lular material movements etc) and human issues ( salary, hiring and firing) need to be considered.An in-tegrated mixed-integer model is developed to comprehensively investigate and analyze cell formation, inter-cellular and intracellular materials handling, inventory and backorder holding, operators assignment and flexible production routing considering multi-production planning with multi-functional machines and multi-skilled operators where each period has different demands.The optimum of the numerical example is solved using a genetic algorithm and it proves the proposed model to be feasible and effective.

  17. Modeling integrated cellular machinery using hybrid Petri-Boolean networks.

    Directory of Open Access Journals (Sweden)

    Natalie Berestovsky

    Full Text Available The behavior and phenotypic changes of cells are governed by a cellular circuitry that represents a set of biochemical reactions. Based on biological functions, this circuitry is divided into three types of networks, each encoding for a major biological process: signal transduction, transcription regulation, and metabolism. This division has generally enabled taming computational complexity dealing with the entire system, allowed for using modeling techniques that are specific to each of the components, and achieved separation of the different time scales at which reactions in each of the three networks occur. Nonetheless, with this division comes loss of information and power needed to elucidate certain cellular phenomena. Within the cell, these three types of networks work in tandem, and each produces signals and/or substances that are used by the others to process information and operate normally. Therefore, computational techniques for modeling integrated cellular machinery are needed. In this work, we propose an integrated hybrid model (IHM that combines Petri nets and Boolean networks to model integrated cellular networks. Coupled with a stochastic simulation mechanism, the model simulates the dynamics of the integrated network, and can be perturbed to generate testable hypotheses. Our model is qualitative and is mostly built upon knowledge from the literature and requires fine-tuning of very few parameters. We validated our model on two systems: the transcriptional regulation of glucose metabolism in human cells, and cellular osmoregulation in S. cerevisiae. The model produced results that are in very good agreement with experimental data, and produces valid hypotheses. The abstract nature of our model and the ease of its construction makes it a very good candidate for modeling integrated networks from qualitative data. The results it produces can guide the practitioner to zoom into components and interconnections and investigate them

  18. Macromolecular lesions and cellular radiation chemistry

    International Nuclear Information System (INIS)

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

  19. Cellular and molecular mechanisms in kidney fibrosis

    Science.gov (United States)

    Duffield, Jeremy S.

    2014-01-01

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

  20. Imaging in cellular and tissue engineering

    CERN Document Server

    Yu, Hanry

    2013-01-01

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

  1. Cellular Cell Bifurcation of Cylindrical Detonations

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  2. Cellular chain formation in Escherichia coli biofilms

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk; Klemm, Per

    2009-01-01

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

  3. Interworking of Wireless LANs and Cellular Networks

    CERN Document Server

    Song, Wei

    2012-01-01

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

  4. Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience.

    Science.gov (United States)

    Hall, Catherine N; Howarth, Clare; Kurth-Nelson, Zebulun; Mishra, Anusha

    2016-10-01

    Cognitive neuroscience depends on the use of blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to probe brain function. Although commonly used as a surrogate measure of neuronal activity, BOLD signals actually reflect changes in brain blood oxygenation. Understanding the mechanisms linking neuronal activity to vascular perfusion is, therefore, critical in interpreting BOLD. Advances in cellular neuroscience demonstrating differences in this neurovascular relationship in different brain regions, conditions or pathologies are often not accounted for when interpreting BOLD. Meanwhile, within cognitive neuroscience, the increasing use of high magnetic field strengths and the development of model-based tasks and analyses have broadened the capability of BOLD signals to inform us about the underlying neuronal activity, but these methods are less well understood by cellular neuroscientists. In 2016, a Royal Society Theo Murphy Meeting brought scientists from the two communities together to discuss these issues. Here, we consolidate the main conclusions arising from that meeting. We discuss areas of consensus about what BOLD fMRI can tell us about underlying neuronal activity, and how advanced modelling techniques have improved our ability to use and interpret BOLD. We also highlight areas of controversy in understanding BOLD and suggest research directions required to resolve these issues.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574302

  5. Mitochondrial dysfunction and cellular metabolic deficiency in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Xue-Mei Gu; Han-Chang Huang; Zhao-Feng Jiang

    2012-01-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder.The pathology of AD includes amyloid-β (Aβ) deposits in neuritic plaques and neurofibrillary tangles composed of hyperphosphorylated tau,as well as neuronal loss in specific brain regions.Increasing epidemiological and functional neuroimaging evidence indicates that global and regional disruptions in brain metabolism are involved in the pathogenesis of this disease.Aβ precursor protein is cleaved to produce both extracellular and intracellular Aβ,accumulation of which might interfere with the homeostasis of cellular metabolism.Mitochondria are highly dynamic organelles that not only supply the main energy to the cell but also regulate apoptosis.Mitochondrial dysfunction might contribute to Aβ neurotoxicity.In this review,we summarize the pathways of Aβ generation and its potential neurotoxic effects on cellular metabolism and mitochondrial dysfunction.

  6. Stochastic Models of Vesicular Sorting in Cellular Organelles

    CERN Document Server

    Vagne, Quentin

    2016-01-01

    The proper sorting of membrane components by regulated exchange between cellular organelles is crucial to intra-cellular organization. This process relies on the budding and fusion of transport vesicles, and should be strongly influenced by stochastic fluctuations considering the relatively small size of many organelles. We identify the perfect sorting of two membrane components initially mixed in a single compartment as a first passage process, and we show that the mean sorting time exhibits two distinct regimes as a function of the ratio of vesicle fusion to budding rates. Low ratio values leads to fast sorting, but results in a broad size distribution of sorted compartments dominated by small entities. High ratio values result in two well defined sorted compartments but is exponentially slow. Our results suggests an optimal balance between vesicle budding and fusion for the rapid and efficient sorting of membrane components, and highlight the importance of stochastic effects for the steady-state organizati...

  7. MEMS capacitive force sensors for cellular and flight biomechanics.

    Science.gov (United States)

    Sun, Yu; Nelson, Bradley J

    2007-03-01

    Microelectromechanical systems (MEMS) are playing increasingly important roles in facilitating biological studies. They are capable of providing not only qualitative but also quantitative information on the cellular, sub-cellular and organism levels, which is instrumental to understanding the fundamental elements of biological systems. MEMS force sensors with their high bandwidth and high sensitivity combined with their small size, in particular, have found a role in this domain, because of the importance of quantifying forces and their effect on the function and morphology of many biological structures. This paper describes our research in the development of MEMS capacitive force sensors that have already demonstrated their effectiveness in the areas of cell mechanics and Drosophila flight dynamics studies. PMID:18458415

  8. MEMS capacitive force sensors for cellular and flight biomechanics

    Energy Technology Data Exchange (ETDEWEB)

    Sun Yu [Advanced Micro and Nanosystems Laboratory, University of Toronto, 5 King' s College Road, Toronto M5S 3G8 (Canada); Nelson, Bradley J [Institute of Robotics and Intelligent Systems, Swiss Federal Institute of Technology (ETH-Zuerich), Zurich (Switzerland)

    2007-03-01

    Microelectromechanical systems (MEMS) are playing increasingly important roles in facilitating biological studies. They are capable of providing not only qualitative but also quantitative information on the cellular, sub-cellular and organism levels, which is instrumental to understanding the fundamental elements of biological systems. MEMS force sensors with their high bandwidth and high sensitivity combined with their small size, in particular, have found a role in this domain, because of the importance of quantifying forces and their effect on the function and morphology of many biological structures. This paper describes our research in the development of MEMS capacitive force sensors that have already demonstrated their effectiveness in the areas of cell mechanics and Drosophila flight dynamics studies. (review article)

  9. MEMS capacitive force sensors for cellular and flight biomechanics

    International Nuclear Information System (INIS)

    Microelectromechanical systems (MEMS) are playing increasingly important roles in facilitating biological studies. They are capable of providing not only qualitative but also quantitative information on the cellular, sub-cellular and organism levels, which is instrumental to understanding the fundamental elements of biological systems. MEMS force sensors with their high bandwidth and high sensitivity combined with their small size, in particular, have found a role in this domain, because of the importance of quantifying forces and their effect on the function and morphology of many biological structures. This paper describes our research in the development of MEMS capacitive force sensors that have already demonstrated their effectiveness in the areas of cell mechanics and Drosophila flight dynamics studies. (review article)

  10. 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.

  11. The role of sirtuins in cellular homeostasis.

    Science.gov (United States)

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

    2016-09-01

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

  12. Optimized Cellular Core for Rotorcraft Project

    Data.gov (United States)

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

  13. MILLIMETER-WAVE EMISSIVITY OF CELLULAR SYSTEMS

    Science.gov (United States)

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

  14. A Matrix Construction of Cellular Algebras

    Institute of Scientific and Technical Information of China (English)

    Dajing Xiang

    2005-01-01

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

  15. Probing Cellular Dynamics with Mesoscopic Simulations

    DEFF Research Database (Denmark)

    Shillcock, Julian C.

    2010-01-01

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

  16. Vectorized multisite coding for hydrodynamic cellular automata

    International Nuclear Information System (INIS)

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

  17. 47 CFR 22.911 - Cellular geographic service area.

    Science.gov (United States)

    2010-10-01

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

  18. Line Complexity Asymptotics of Polynomial Cellular Automata

    OpenAIRE

    Stone, Bertrand

    2016-01-01

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

  19. Cellular Restriction Factors of Feline Immunodeficiency Virus

    OpenAIRE

    Carsten Münk; Jörg Zielonka

    2011-01-01

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

  20. Cellular and molecular mechanisms in kidney fibrosis

    OpenAIRE

    Duffield, Jeremy S.

    2014-01-01

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

  1. Building mathematics cellular phone learning communities

    OpenAIRE

    Wajeeh M. Daher

    2011-01-01

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

  2. Directed Percolation arising in Stochastic Cellular Automata

    OpenAIRE

    Regnault, Damien

    2008-01-01

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

  3. Understanding cisplatin resistance using cellular models.

    OpenAIRE

    STORDAL, BRITTA KRISTINA

    2007-01-01

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

  4. Understanding cisplatin resistance using cellular models

    OpenAIRE

    Stordal, Britta; Davey, Mary

    2007-01-01

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

  5. On the Behavior Characteristics of Cellular Automata

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  6. Cellular Hyperproliferation and Cancer as Evolutionary Variables

    OpenAIRE

    Alvarado, Alejandro Sánchez

    2012-01-01

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

  7. Cellular Scaling Rules of Insectivore Brains

    OpenAIRE

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

    2009-01-01

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

  8. Cellular scaling rules of insectivore brains

    OpenAIRE

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

    2009-01-01

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

  9. Stochastic Simulations on the Cellular Wave Computers

    OpenAIRE

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

    2006-01-01

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

  10. Cellular Auxin Transport in Algae

    Science.gov (United States)

    Zhang, Suyun; van Duijn, Bert

    2014-01-01

    The phytohormone auxin is one of the main directors of plant growth and development. In higher plants, auxin is generated in apical plant parts and transported from cell-to-cell in a polar fashion. Auxin is present in all plant phyla, and the existence of polar auxin transport (PAT) is well established in land plants. Algae are a group of relatively simple, autotrophic, photosynthetic organisms that share many features with land plants. In particular, Charophyceae (a taxon of green algae) are closest ancestors of land plants. In the study of auxin function, transport and its evolution, the algae form an interesting research target. Recently, proof for polar auxin transport in Chara species was published and auxin related research in algae gained more attention. In this review we discuss auxin transport in algae with respect to land plants and suggest directions for future studies.

  11. Cellular and molecular biology group

    International Nuclear Information System (INIS)

    Model DNA polymers have been employed to measure physico-chemical effects of X-irradiation and the influence of known base sequences on the transcription by RNA polymerases. These experiments allow quantitative estimates of the fidelity of transcription in the presence of physical and chemical agents. Cells in culture provide the basic system for studying radiation effects on DNA synthesis, organization of DNA in the nucleus, effects of pollutants on genetic information transfer and gene expression, nucleic acid structure, proliferation capacity, histone phosphorylation, and chromatin structure and function. Mathematical models of the immune response have been formulated, and the biochemical properties of the cell surface have been characterized. The use of flow systems to provide rapid karyotype analysis has been established for relatively simple karyotypes, and a series of cell-cycle-dependent, temperature-sensitive mutant mammalian cell lines have been derived and appear useful for cycle progression and mutagenesis studies

  12. Weighted Centroid Correction Localization in Cellular Systems

    Directory of Open Access Journals (Sweden)

    Rong-Zheng Li

    2011-01-01

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

  13. Developing cellular therapies for retinal degenerative diseases.

    Science.gov (United States)

    Bharti, Kapil; Rao, Mahendra; Hull, Sara Chandros; Stroncek, David; Brooks, Brian P; Feigal, Ellen; van Meurs, Jan C; Huang, Christene A; Miller, Sheldon S

    2014-02-01

    Biomedical advances in vision research have been greatly facilitated by the clinical accessibility of the visual system, its ease of experimental manipulation, and its ability to be functionally monitored in real time with noninvasive imaging techniques at the level of single cells and with quantitative end-point measures. A recent example is the development of stem cell-based therapies for degenerative eye diseases including AMD. Two phase I clinical trials using embryonic stem cell-derived RPE are already underway and several others using both pluripotent and multipotent adult stem cells are in earlier stages of development. These clinical trials will use a variety of cell types, including embryonic or induced pluripotent stem cell-derived RPE, bone marrow- or umbilical cord-derived mesenchymal stem cells, fetal neural or retinal progenitor cells, and adult RPE stem cells-derived RPE. Although quite distinct, these approaches, share common principles, concerns and issues across the clinical development pipeline. These considerations were a central part of the discussions at a recent National Eye Institute meeting on the development of cellular therapies for retinal degenerative disease. At this meeting, emphasis was placed on the general value of identifying and sharing information in the so-called "precompetitive space." The utility of this behavior was described in terms of how it could allow us to remove road blocks in the clinical development pipeline, and more efficiently and economically move stem cell-based therapies for retinal degenerative diseases toward the clinic. Many of the ocular stem cell approaches we discuss are also being used more broadly, for nonocular conditions and therefore the model we develop here, using the precompetitive space, should benefit the entire scientific community. PMID:24573369

  14. On the Global Dissipativity of a Class of Cellular Neural Networks with Multipantograph Delays

    Directory of Open Access Journals (Sweden)

    Liqun Zhou

    2011-01-01

    Full Text Available For the first time the global dissipativity of a class of cellular neural networks with multipantograph delays is studied. On the one hand, some delay-dependent sufficient conditions are obtained by directly constructing suitable Lyapunov functionals; on the other hand, firstly the transformation transforms the cellular neural networks with multipantograph delays into the cellular neural networks with constant delays and variable coefficients, and then constructing Lyapunov functionals, some delay-independent sufficient conditions are given. These new sufficient conditions can ensure global dissipativity together with their sets of attraction and can be applied to design global dissipative cellular neural networks with multipantograph delays and easily checked in practice by simple algebraic methods. An example is given to illustrate the correctness of the results.

  15. Structural Basis of Cargo Recognition by Unconventional Myosins in Cellular Trafficking.

    Science.gov (United States)

    Li, Jianchao; Lu, Qing; Zhang, Mingjie

    2016-08-01

    Unconventional myosins are a superfamily of actin-based molecular motors playing diverse roles including cellular trafficking, mechanical supports, force sensing and transmission, etc. The variable neck and tail domains of unconventional myosins function to bind to specific cargoes including proteins and lipid vesicles and thus are largely responsible for the diverse cellular functions of myosins in vivo. In addition, the tail regions, together with their cognate cargoes, can regulate activities of the motor heads. This review outlines the advances made in recent years on cargo recognition and cargo binding-induced regulation of the activity of several unconventional myosins including myosin-I, V, VI and X in cellular trafficking. We approach this topic by describing a series of high-resolution structures of the neck and tail domains of these unconventional myosins either alone or in complex with their specific cargoes, and by discussing potential implications of these structural studies on cellular trafficking of these myosin motors. PMID:26842936

  16. Cellular concrete: a potential load-bearing insulation for cryogenic applications

    International Nuclear Information System (INIS)

    The need for low cost, low thermal conductivity, high strength insulation suitable for cryogenic applications is becoming more evident. An investigation of the potential of cellular concretes to fulfill this function was initiated. A review of the thermal and mechanical characteristics of foamed plastics and cellular concrete is presented along with relative cost comparisons. Test data from preliminary investigations is presented to define the influence of material constituents, density, and temperature on the mechanical and thermal response of cellular concrete. Specimen densities range from 0.64 to 1.44 gr/cc. The influence of temperature variations from 220C to -1960C is reported for selected densities

  17. Potential cellular receptors involved in hepatitis C virus entry into cells

    Directory of Open Access Journals (Sweden)

    Muellhaupt Beat

    2005-04-01

    Full Text Available Abstract Hepatitis C virus (HCV infects hepatocytes and leads to permanent, severe liver damage. Since the genomic sequence of HCV was determined, progress has been made towards understanding the functions of the HCV-encoded proteins and identifying the cellular receptor(s responsible for adsorption and penetration of the virus particle into the target cells. Several cellular receptors for HCV have been proposed, all of which are associated with lipid and lipoprotein metabolism. This article reviews the cellular receptors for HCV and suggests a general model for HCV entry into cells, in which lipoproteins play a crucial role.

  18. 47 CFR 22.970 - Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone...

    Science.gov (United States)

    2010-10-01

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

  19. Cellular resistance to HIV-1 infection in target cells coincides with a rapid induction of X-DING-CD4 mRNA: indication of the unique host innate response to virus regulated through function of the X-DING-CD4 gene.

    Science.gov (United States)

    Shilpi, Rasheda Y; Sachdeva, Rakhee; Simm, Malgorzata

    2012-08-01

    Clinical reports indicate that some infected individuals control HIV-1 replication through undefined mechanisms. Our group reported that a human protein named X-DING-CD4 holds a potent antiviral activity, blocking transcription of HIV-1 LTR through the inhibition of NF-κB/DNA binding. Based on observations that transformed HIV-1 resistant CD4(+) T cells produce higher levels of soluble X-DING-CD4 protein upon their exposure to virus, we hypothesized that resistance to HIV-1 in these cells may be regulated through function of the X-DING-CD4 gene. Real-time PCR evaluations of X-DING-CD4 mRNA expression confirmed our hypothesis; HIV-1 exposure caused rapid up-regulation of X-DING-CD4 mRNA in resistant, but not susceptible, cells; and the burst of X-DING-CD4 mRNA expression correlated with restriction of HIV-1 transcription. Subsequently, we examined the activity of the X-DING-CD4 gene in monocytes and macrophages from (n = 13) HIV-negative donors. The assessment of HIV-1 gag mRNA showed that the majority of cells were permissive to virus replication; however, macrophages from four donors were refractory to HIV-1 infection. In response to virus, these cells up-regulated X-DING-CD4 gene expression by 2- to 1000-fold. These data provide evidence that the X-DING-CD4 gene contributes to early cellular protection from HIV infection in some individuals and this protection depends solely on the unique genetic regulation of the host. PMID:22042911

  20. Oxysterols and Their Cellular Effectors

    Directory of Open Access Journals (Sweden)

    Eija Nissilä

    2012-02-01

    Full Text Available Oxysterols are oxidized 27-carbon cholesterol derivatives or by-products of cholesterol biosynthesis, with a spectrum of biologic activities. Several oxysterols have cytotoxic and pro-apoptotic activities, the ability to interfere with the lateral domain organization, and packing of membrane lipids. These properties may account for their suggested roles in the pathology of diseases such as atherosclerosis, age-onset macular degeneration and Alzheimer’s disease. Oxysterols also have the capacity to induce inflammatory responses and play roles in cell differentiation processes. The functions of oxysterols as intermediates in the synthesis of bile acids and steroid hormones, and as readily transportable forms of sterol, are well established. Furthermore, their actions as endogenous regulators of gene expression in lipid metabolism via liver X receptors and the Insig (insulin-induced gene proteins have been investigated in detail. The cytoplasmic oxysterol-binding protein (OSBP homologues form a group of oxysterol/cholesterol sensors that has recently attracted a lot of attention. However, their mode of action is, as yet, poorly understood. Retinoic acid receptor-related orphan receptors (ROR α and γ, and Epstein-Barr virus induced gene 2 (EBI2 have been identified as novel oxysterol receptors, revealing new physiologic oxysterol effector mechanisms in development, metabolism, and immunity, and evoking enhanced interest in these compounds in the field of biomedicine.

  1. Multispectral Imaging Broadens Cellular Analysis

    Science.gov (United States)

    2007-01-01

    Amnis Corporation, a Seattle-based biotechnology company, developed ImageStream to produce sensitive fluorescence images of cells in flow. The company responded to an SBIR solicitation from Ames Research Center, and proposed to evaluate several methods of extending the depth of field for its ImageStream system and implement the best as an upgrade to its commercial products. This would allow users to view whole cells at the same time, rather than just one section of each cell. Through Phase I and II SBIR contracts, Ames provided Amnis the funding the company needed to develop this extended functionality. For NASA, the resulting high-speed image flow cytometry process made its way into Medusa, a life-detection instrument built to collect, store, and analyze sample organisms from erupting hydrothermal vents, and has the potential to benefit space flight health monitoring. On the commercial end, Amnis has implemented the process in ImageStream, combining high-resolution microscopy and flow cytometry in a single instrument, giving researchers the power to conduct quantitative analyses of individual cells and cell populations at the same time, in the same experiment. ImageStream is also built for many other applications, including cell signaling and pathway analysis; classification and characterization of peripheral blood mononuclear cell populations; quantitative morphology; apoptosis (cell death) assays; gene expression analysis; analysis of cell conjugates; molecular distribution; and receptor mapping and distribution.

  2. Advances in high-resolution imaging – techniques for three-dimensional imaging of cellular structures

    OpenAIRE

    Lidke, Diane S.; Lidke, Keith A.

    2012-01-01

    A fundamental goal in biology is to determine how cellular organization is coupled to function. To achieve this goal, a better understanding of organelle composition and structure is needed. Although visualization of cellular organelles using fluorescence or electron microscopy (EM) has become a common tool for the cell biologist, recent advances are providing a clearer picture of the cell than ever before. In particular, advanced light-microscopy techniques are achieving resolutions below th...

  3. Oxidative stress-induced proteome alterations target different cellular pathways in human myoblasts

    DEFF Research Database (Denmark)

    Baraibar, Martin A; Hyzewicz, Janek; Rogowska-Wrzesinska, Adelina;

    2011-01-01

    Although increased oxidative stress has been associated with the impairment of proliferation and function of adult human muscle stem cells, proteins either involved in the stress response or damaged by oxidation have not been identified. A parallel proteomics approach was performed for analyzing...... are mainly cytosolic and involved in carbohydrate metabolism, cellular assembly, cellular homeostasis, and protein synthesis and degradation. Pathway analysis revealed skeletal and muscular disorders, cell death, and cancer-related as the main molecular networks altered. Interestingly, these pathways...

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  5. A computational study of liposome logic: towards cellular computing from the bottom up

    OpenAIRE

    Smaldon, James; Romero-Campero, Francisco J.; Fernández Trillo, Francisco; Gheorghe, Marian; Alexander, Cameron; Krasnogor, Natalio

    2010-01-01

    In this paper we propose a new bottom-up approach to cellular computing, in which computational chemical processes are encapsulated within liposomes. This “liposome logic” approach (also called vesicle computing) makes use of supra-molecular chemistry constructs, e.g. protocells, chells, etc. as minimal cellular platforms to which logical functionality can be added. Modeling and simulations feature prominently in “top-down” synthetic biology, particularly in the specification, design and impl...

  6. Model of Handover and Traffic Based on Cellular Geometry with Smart Antenna

    Directory of Open Access Journals (Sweden)

    Zufan Zhang

    2014-01-01

    Full Text Available Based on the application of smart antennas in cellular mobile communications, this paper introduces the impact of the width of the antenna beams playing on the dwell time probability density function in cellular geometry with smart antenna. The research results indicate that the smart cell structure can improve the dwell time of users within the cell and improve the traffic system performance.

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

    OpenAIRE

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Siva Prasad Darla

    2014-01-01

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

  9. Shape Memory Alloy-Based Periodic Cellular Structures Project

    Data.gov (United States)

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

  10. Biological Augmentation of Flexor Tendon Repair: A Challenging Cellular Landscape.

    Science.gov (United States)

    Loiselle, Alayna E; Kelly, Meghan; Hammert, Warren C

    2016-01-01

    Advances in surgical technique and rehabilitation have transformed zone II flexor tendon injuries from an inoperable no-man's land to a standard surgical procedure. Despite these advances, many patients develop substantial range of motion-limiting adhesions after primary flexor tendon repair. These suboptimal outcomes may benefit from biologic augmentation or intervention during the flexor tendon healing process. However, there is no consensus biological approach to promote satisfactory flexor tendon healing; we propose that insufficient understanding of the complex cellular milieu in the healing tendon has hindered the development of successful therapies. This article reviews recent advances in our understanding of the cellular components of flexor tendon healing and adhesion formation, including resident tendon cells, synovial sheath, macrophages, and bone marrow-derived cells. In addition, it examines molecular approaches that have been used in translational animal models to improve flexor tendon healing and gliding function, with a specific focus on progress made using murine models of healing. This information highlights the importance of understanding and potentially exploiting the heterogeneity of the cellular environment during flexor tendon healing, to define rational therapeutic approaches to improve healing outcomes. PMID:26652792

  11. Improving Quality of Clustering using Cellular Automata for Information retrieval

    Directory of Open Access Journals (Sweden)

    P. K. Sree

    2008-01-01

    Full Text Available Clustering has been widely applied to Information Retrieval (IR on the grounds of its potential improved effectiveness over inverted file search. Clustering is a mostly unsupervised procedure and the majority of the clustering algorithms depend on certain assumptions in order to define the subgroups present in a data set .A clustering quality measure is a function that, given a data set and its partition into clusters, returns a non-negative real number representing the quality of that clustering. Moreover, they may behave in a different way depending on the features of the data set and their input parameters values. Therefore, in most applications the resulting clustering scheme requires some sort of evaluation as regards its validity. The quality of clustering can be enhanced by using a Cellular Automata Classifier for information retrieval. In this study we take the view that if cellular automata with clustering is applied to search results (query-specific clustering, then it has the potential to increase the retrieval effectiveness compared both to that of static clustering and of conventional inverted file search. We conducted a number of experiments using ten document collections and eight hierarchic clustering methods. Our results show that the effectiveness of query-specific clustering with cellular automata is indeed higher and suggest that there is scope for its application to IR.

  12. The thorny path linking cellular senescence to organismalaging

    Energy Technology Data Exchange (ETDEWEB)

    Patil, Christopher K.; Mian, Saira; Campisi, Judith

    2005-08-09

    Half a century is fast approaching since Hayflick and colleagues formally described the limited ability of normal human cells to proliferate in culture (Hayflick and Moorhead, 1961). This finding--that normal somatic cells, in contrast to cancer cells, cannot divide indefinitely--challenged the prevailing idea that cells from mortal multicellular organisms were intrinsically ''immortal'' (Carrell, 1912). It also spawned two hypotheses, essential elements of which persist today. The first held that the restricted proliferation of normal cells, now termed cellular senescence, suppresses cancer (Hayflick, 1965; Sager, 1991; Campisi, 2001). The second hypothesis, as explained in the article by Lorenzini et al., suggested that the limited proliferation of cells in culture recapitulated aspects of organismal aging (Hayflick, 1965; Martin, 1993). How well have these hypotheses weathered the ensuing decades? Before answering this question, we first consider current insights into the causes and consequences of cellular senescence. Like Lorenzini et al., we limit our discussion to mammals. We also focus on fibroblasts, the cell type studied by Lorenzini et al., but consider other types as well. We suggest that replicative capacity in culture is not a straightforward assessment, and that it correlates poorly with both longevity and body mass. We speculate this is due to the malleable and variable nature of replicative capacity, which renders it an indirect metric of qualitative and quantitative differences among cells to undergo senescence, a response that directly alters cellular phenotype and might indirectly alter tissue structure and function.

  13. Cellular chaperonin CCTγ contributes to rabies virus replication during infection.

    Science.gov (United States)

    Zhang, Jinyang; Wu, Xiaopeng; Zan, Jie; Wu, Yongping; Ye, Chengjin; Ruan, Xizhen; Zhou, Jiyong

    2013-07-01

    Rabies, as the oldest known infectious disease, remains a serious threat to public health worldwide. The eukaryotic cytosolic chaperonin TRiC/CCT complex facilitates the folding of proteins through ATP hydrolysis. Here, we investigated the expression, cellular localization, and function of neuronal CCTγ during neurotropic rabies virus (RABV) infection using mouse N2a cells as a model. Following RABV infection, 24 altered proteins were identified by using two-dimensional electrophoresis and mass spectrometry, including 20 upregulated proteins and 4 downregulated proteins. In mouse N2a cells infected with RABV or cotransfected with RABV genes encoding nucleoprotein (N) and phosphoprotein (P), confocal microscopy demonstrated that upregulated cellular CCTγ was colocalized with viral proteins N and P, which formed a hollow cricoid inclusion within the region around the nucleus. These inclusions, which correspond to Negri bodies (NBs), did not form in mouse N2a cells only expressing the viral protein N or P. Knockdown of CCTγ by lentivirus-mediated RNA interference led to significant inhibition of RABV replication. These results demonstrate that the complex consisting of viral proteins N and P recruits CCTγ to NBs and identify the chaperonin CCTγ as a host factor that facilitates intracellular RABV replication. This work illustrates how viruses can utilize cellular chaperonins and compartmentalization for their own benefit. PMID:23637400

  14. Proton micromachining of substrate scaffolds for cellular and tissue engineering

    International Nuclear Information System (INIS)

    Three dimensional patterns (grooves and ridges) were micromachined in PMMA using a 600 keV proton beam from the nuclear microscopy facility at the Research Centre for Nuclear Microscopy, National University of Singapore. Swiss 3T3 fibroblasts (ATCC CCL92, Rockville, MD) have been seeded onto these patterns, and the following observations have been made: (a) Cells were not found in the grooves (depth 9 μm, width 6.6 μm); (b) Cells were highly aligned and elongated on narrow ridges (4.2 μm wide), with the degree of alignment and elongation reduced for wider ridges. The underlying mechanism responsible of this cellular behaviour is assumed to be induced by the mechanical restrictions imposed by the topographic features on cellular migration, cell adhesion and concomitant changes in the cytoskeletal. The use of topographical stimuli to regulate cell function is an area of high potential, with implications in the engineering of tissue for spare-part surgery. Proton micromachining, which has the unique advantage of being the only technique capable of direct-write 3D micromachining at sub-cellular dimensions has unique advantages in this area of research

  15. Cellular mechanotransduction: putting all the pieces together again.

    Science.gov (United States)

    Ingber, Donald E

    2006-05-01

    Analysis of cellular mechanotransduction, the mechanism by which cells convert mechanical signals into biochemical responses, has focused on identification of critical mechanosensitive molecules and cellular components. Stretch-activated ion channels, caveolae, integrins, cadherins, growth factor receptors, myosin motors, cytoskeletal filaments, nuclei, extracellular matrix, and numerous other structures and signaling molecules have all been shown to contribute to the mechanotransduction response. However, little is known about how these different molecules function within the structural context of living cells, tissues, and organs to produce the orchestrated cellular behaviors required for mechanosensation, embryogenesis, and physiological control. Recent work from a wide range of fields reveals that organ, tissue, and cell anatomy are as important for mechanotransduction as individual mechanosensitive proteins and that our bodies use structural hierarchies (systems within systems) composed of interconnected networks that span from the macroscale to the nanoscale in order to focus stresses on specific mechanotransducer molecules. The presence of isometric tension (prestress) at all levels of these multiscale networks ensures that various molecular scale mechanochemical transduction mechanisms proceed simultaneously and produce a concerted response. Future research in this area will therefore require analysis, understanding, and modeling of tensionally integrated (tensegrity) systems of mechanochemical control. PMID:16675838

  16. The expanding functions of cellular helicases: the tombusvirus RNA replication enhancer co-opts the plant eIF4AIII-like AtRH2 and the DDX5-like AtRH5 DEAD-box RNA helicases to promote viral asymmetric RNA replication.

    Directory of Open Access Journals (Sweden)

    Nikolay Kovalev

    2014-04-01

    Full Text Available Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC, template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3' terminal promoter region in the viral minus-strand (-RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5' proximal RIII(- replication enhancer (REN element in the TBSV (-RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (-RNA could unwind the dsRNA structure within the RIII(- REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(- REN in stimulation of plus-strand (+RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(- REN that promotes bringing the 5' and 3' terminal (-RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+-strand synthesis, thus resulting in asymmetrical viral replication.

  17. Biodegradable Magnetic Particles for Cellular MRI

    Science.gov (United States)

    Nkansah, Michael Kwasi

    Cell transplantation has the potential to treat numerous diseases and injuries. While magnetic particle-enabled, MRI-based cell tracking has proven useful for visualizing the location of cell transplants in vivo, current formulations of particles are either too weak to enable single cell detection or have non-degradable polymer matrices that preclude clinical translation. Furthermore, the off-label use of commercial agents like Feridex®, Bangs beads and ferumoxytol for cell tracking significantly stunts progress in the field, rendering it needlessly susceptible to market externalities. The recent phasing out of Feridex from the market, for example, heightens the need for a dedicated agent specifically designed for MRI-based cell tracking. To this end, we engineered clinically viable, biodegradable particles of iron oxide made using poly(lactide-co-glycolide) (PLGA) and demonstrated their utility in two MRI-based cell tracking paradigms in vivo. Both micro- and nanoparticles (2.1±1.1 μm and 105±37 nm in size) were highly magnetic (56.7-83.7 wt% magnetite), and possessed excellent relaxometry (r2* relaxivities as high as 614.1 s-1mM-1 and 659.1 s -1mM-1 at 4.7 T respectively). Magnetic PLGA micropartides enabled the in vivo monitoring of neural progenitor cell migration to the olfactory bulb in rat brains over 2 weeks at 11.7 T with ˜2-fold greater contrast-to-noise ratio and ˜4-fold better sensitivity at detecting migrated cells in the olfactory bulb than Bangs beads. Highly magnetic PLGA nanoparticles enabled MRI detection (at 11.7 T) of up to 10 rat mesenchymal cells transplanted into rat brain at 100-μm resolution. Highly magnetic PLGA particles were also shown to degrade by 80% in mice liver over 12 weeks in vivo. Moreover, no adverse effects were observed on cellular viability and function in vitro after labeling a wide range of cells. Magnetically labeled rat mesenchymal and neural stem cells retained their ability to differentiate into multiple

  18. Evolving localizations in reaction-diffusion cellular automata

    CERN Document Server

    Adamatzky, Andrew; Collet, Pierre; Sapin, Emmanuel

    2007-01-01

    We consider hexagonal cellular automata with immediate cell neighbourhood and three cell-states. Every cell calculates its next state depending on the integral representation of states in its neighbourhood, i.e. how many neighbours are in each one state. We employ evolutionary algorithms to breed local transition functions that support mobile localizations (gliders), and characterize sets of the functions selected in terms of quasi-chemical systems. Analysis of the set of functions evolved allows to speculate that mobile localizations are likely to emerge in the quasi-chemical systems with limited diffusion of one reagent, a small number of molecules is required for amplification of travelling localizations, and reactions leading to stationary localizations involve relatively equal amount of quasi-chemical species. Techniques developed can be applied in cascading signals in nature-inspired spatially extended computing devices, and phenomenological studies and classification of non-linear discrete systems.

  19. Memory Impairment in Transgenic Alzheimer Mice Requires Cellular Prion Protein

    OpenAIRE

    Gimbel, David A.; Nygaard, Haakon B.; Coffey, Erin E.; Gunther, Erik C.; Laurén, Juha; Gimbel, Zachary A.; Strittmatter, Stephen M.

    2010-01-01

    Soluble oligomers of the amyloid-β (Aβ) peptide are thought to play a key role in the pathophysiology of Alzheimer’s disease (AD). Recently, we reported that synthetic Aβ oligomers bind to cellular prion protein (PrPC) and that this interaction is required for suppression of synaptic plasticity in hippocampal slices by oligomeric Aβ peptide. We hypothesized that PrPC is essential for the ability of brain-derived Aβ to suppress cognitive function. Here, we crossed familial AD transgenes encodi...

  20. The impact of peroxisomes on cellular ageing and death

    Directory of Open Access Journals (Sweden)

    Selvambigai eManivannan

    2012-05-01

    Full Text Available Peroxisomes are ubiquitous eukaryotic organelles, which perform a plethora of functions including hydrogen peroxide metabolism and β-oxidation of fatty acids. Reactive oxygen species produced by peroxisomes are a major contributing factor to cellular oxidative stress, which is supposed to significantly accelerate ageing and cell death according to the free radical theory of ageing. However, relative to mitochondria, the role of the other oxidative organelles, the peroxisomes, in these degenerative pathways has not been extensively investigated. In this contribution we discuss our current knowledge on the role of peroxisomes in ageing and cell death, with focus on studies performed in yeast.