WorldWideScience

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. Cellular functions of the microprocessor.

    Science.gov (United States)

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

    2013-08-01

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

  3. Molecular kinesis in cellular function and plasticity.

    Science.gov (United States)

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

    2001-06-19

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

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

    NARCIS (Netherlands)

    Suresh, N.; Slomp, J.

    2005-01-01

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

  6. 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.

  7. Steganography by using Logistic Map Function and Cellular Automata

    Directory of Open Access Journals (Sweden)

    Mehdi Alirezanejad

    2012-12-01

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

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

    Science.gov (United States)

    Heissler, Sarah M; Sellers, James R

    2016-08-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  10. 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.

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

    Science.gov (United States)

    Gsponer, Jörg; Babu, M Madan

    2012-11-29

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

  12. Eukaryotic protein domains as functional units of cellular evolution

    DEFF Research Database (Denmark)

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

    2009-01-01

    domain compositions and functional properties, termed "domain clubs," which we use to compare multiple eukaryotic proteomes. This analysis shows that different domain types can take distinct evolutionary trajectories, which correlate with the conservation, gain, expansion, or decay of particular...... 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...

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

    Science.gov (United States)

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

    2000-01-01

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

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

    Science.gov (United States)

    Agledal, Line; Niere, Marc; Ziegler, Mathias

    2010-01-01

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

  15. 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.

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

    Science.gov (United States)

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

    1995-01-01

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

  17. 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.

  18. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-12-15

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

  20. 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.

  1. Cellular Functions Regulated by Phosphorylation of EGFR on Tyr845

    Directory of Open Access Journals (Sweden)

    Ken-ichi Sato

    2013-05-01

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

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

    Science.gov (United States)

    Babilonia-Rosa, Melissa; Neher, Saskia B.

    2014-01-01

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

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

    Science.gov (United States)

    Wilson, Michael A.

    2003-01-01

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

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

    Science.gov (United States)

    Qi, Wenbin; Cowan, J A

    2010-02-01

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

  5. Insights into the physiological function of cellular prion protein

    Directory of Open Access Journals (Sweden)

    Martins V.R.

    2001-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  7. Photothermal cellular stimulation in functional bio-polymer interfaces

    Science.gov (United States)

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

    2015-03-01

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

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

    Science.gov (United States)

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

    2010-10-01

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

  9. p53 Cellular Localization and Function in Neuroblastoma

    Science.gov (United States)

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

    2001-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-10-22

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

  11. 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.

  12. 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.

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

    Science.gov (United States)

    Haffner, Christof; Haass, Christian

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yang Da

    2007-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

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

    OpenAIRE

    2008-01-01

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

  17. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-03-01

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

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

    Science.gov (United States)

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

    2007-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Cheng-Yuan Kao

    2011-03-01

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

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

    Directory of Open Access Journals (Sweden)

    P. G. Klyucharev

    2014-01-01

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

  2. 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...

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

    Science.gov (United States)

    Bénédic, Y; Wira, P; Mercklé, J

    2008-08-01

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

  4. 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.

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

    Science.gov (United States)

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

    2005-10-01

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

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

    Science.gov (United States)

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

    2016-01-29

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

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

    Science.gov (United States)

    Han, Bo; Wang, Jin

    2008-03-01

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

  8. 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.

  9. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    OpenAIRE

    Faye, Nathalie

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ajay Singh

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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

    del Río, José A; Gavín, Rosalina

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Yang Qun-Ting; Gao Tie-Gang

    2008-01-01

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

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

    Science.gov (United States)

    Lovreglio, Ruggiero; Ronchi, Enrico; Nilsson, Daniel

    2015-11-01

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

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Robert M. Brosh

    2014-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Weiqiang eChen

    2013-04-01

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

  20. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  2. 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.

  3. 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.

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

    Science.gov (United States)

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

    2014-10-21

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

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

    Science.gov (United States)

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

    1998-01-01

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

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

    Science.gov (United States)

    Castro-Alamancos, M A

    1997-01-01

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

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

    Science.gov (United States)

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

    1983-08-01

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

  8. 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.

  9. 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.

  10. 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.

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

    Science.gov (United States)

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

    2013-03-26

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

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

    Science.gov (United States)

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

    2014-06-10

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

  13. 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...

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    D. Bonatto

    2005-03-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

    Shah, Dhiral Ashwin

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

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

    Science.gov (United States)

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

    1996-10-01

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

  20. 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

  1. 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.

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

    Science.gov (United States)

    Wolfe, Annie; Phipps, Kara; Weitao, Tao

    2014-01-01

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

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

    Science.gov (United States)

    Bak, Marek; Zmyślony, Marek

    2010-01-01

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

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

    Science.gov (United States)

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

    2006-06-01

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

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

    Science.gov (United States)

    Cretu, Alexandra; Castagnino, Paola; Assoian, Richard

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-12-30

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

  7. 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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

  10. 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.

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

    Science.gov (United States)

    Qian, Feng; Noben-Trauth, Konrad

    2005-10-01

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

  12. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-07-16

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

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

    Science.gov (United States)

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

    2008-10-01

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

  15. 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.

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

    Science.gov (United States)

    Kanellos, Georgios; Frame, Margaret C

    2016-09-01

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

  17. 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

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

    Science.gov (United States)

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

    2014-10-01

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

  19. 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.

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

    Science.gov (United States)

    Hu, Hua; Gan, Jian; Jonas, Peter

    2014-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Yufeng Wei

    2015-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Sara Anjomani Virmouni

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

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

    Science.gov (United States)

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

    2014-06-17

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

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

    Directory of Open Access Journals (Sweden)

    Stephanie Diezmann

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

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

    Science.gov (United States)

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

    2014-10-03

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

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

    Directory of Open Access Journals (Sweden)

    Robert A Eagle

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

  7. 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

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Science.gov (United States)

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

    2014-06-16

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

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

    Institute of Scientific and Technical Information of China (English)

    Chen Sheng; Li Shiting; Fang Youping

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  12. 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.

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

    Science.gov (United States)

    Davaapil, Hongorzul; Brockes, Jeremy P.

    2017-01-01

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

  14. 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...

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

    OpenAIRE

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2003-02-01

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

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

    OpenAIRE

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2014-03-01

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

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

    Science.gov (United States)

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

    1999-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Chingkai Chuang

    2015-02-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    1997-01-01

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

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

    Science.gov (United States)

    Flather, Dylan; Semler, Bert L

    2015-01-01

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

  5. 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.

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

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

    1985-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2017-01-25

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

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

    Science.gov (United States)

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

    2012-07-01

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

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

    Science.gov (United States)

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

    2004-06-01

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

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

    OpenAIRE

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2014-02-01

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

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

    OpenAIRE

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2015-02-01

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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

    Legrand, Philippe; Rioux, Vincent

    2010-10-01

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

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

    Science.gov (United States)

    Mayer, M P; Bukau, B

    1998-03-01

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

  19. 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)

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

    OpenAIRE

    Legrand, Philippe; Rioux, Vincent

    2010-01-01

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

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

    OpenAIRE

    Balsamo, Anna

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  5. 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.

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

    Science.gov (United States)

    Sarin, Hemant

    2015-11-26

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

  7. 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.

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

    OpenAIRE

    2009-01-01

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

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Science.gov (United States)

    Coussons-Read, M E; Giese, S

    2001-08-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Sephra N. Rampersad

    2012-09-01

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

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

    Science.gov (United States)

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

    2014-11-01

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

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

    Science.gov (United States)

    Rose, A; Meier, I

    2004-08-01

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

  15. 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.

  16. 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.

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

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

    Science.gov (United States)

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

    2016-06-13

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

  19. 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.

  20. 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.

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

    Science.gov (United States)

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

    2017-05-01

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

  2. 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.

  3. Cellular localization of adenine receptors in the rat kidney and their functional significance in the inner medullary collecting duct.

    Science.gov (United States)

    Kishore, Bellamkonda K; Zhang, Yue; Gevorgyan, Haykanush; Kohan, Donald E; Schiedel, Anke C; Müller, Christa E; Peti-Peterdi, János

    2013-11-01

    The Gi-coupled adenine receptor (AdeR) binds adenine with high affinity and potentially reduces cellular cAMP levels. Since cAMP is an important second messenger in the renal transport of water and solutes, we localized AdeR in the rat kidney. Real-time RT-PCR showed higher relative expression of AdeR mRNA in the cortex and outer medulla compared with the inner medulla. Immunoblots using a peptide-derived and affinity-purified rabbit polyclonal antibody specific for an 18-amino acid COOH-terminal sequence of rat AdeR, which we generated, detected two bands between ∼30 and 40 kDa (molecular mass of native protein: 37 kDa) in the cortex, outer medulla, and inner medulla. These bands were ablated by preadsorption of the antibody with the immunizing peptide. Immunofluorescence labeling showed expression of AdeR protein in all regions of the kidney. Immunoperoxidase revealed strong labeling of AdeR protein in the cortical vasculature, including the glomerular arterioles, and less intense labeling in the cells of the collecting duct system. Confocal immunofluorescence imaging colocalized AdeR with aquaporin-2 protein to the apical plasma membrane in the collecting duct. Functionally, adenine (10 μM) significantly decreased (P < 0.01) 1-deamino-8-d-arginine vasopressin (10 nM)-induced cAMP production in ex vivo preparations of inner medullary collecting ducts, which was reversed by PSB-08162 (20 μM, P < 0.01), a selective antagonist of AdeR. Thus, we demonstrated the expression of AdeR in the renal vasculature and collecting ducts and its functional relevance. This study may open a new avenue for the exploration of autocrine/paracrine regulation of renal vascular and tubular functions by the nucleobase adenine in health and disease.

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

    Science.gov (United States)

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

    2013-02-14

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

  5. Gall-forming root-knot nematodes hijack key plant cellular functions to induce multinucleate and hypertrophied feeding cells.

    Science.gov (United States)

    Favery, Bruno; Quentin, Michaël; Jaubert-Possamai, Stéphanie; Abad, Pierre

    2016-01-01

    Among plant-parasitic nematodes, the root-knot nematodes (RKNs) of the Meloidogyne spp. are the most economically important genus. RKN are root parasitic worms able to infect nearly all crop species and have a wide geographic distribution. During infection, RKNs establish and maintain an intimate relationship with the host plant. This includes the creation of a specialized nutritional structure composed of multinucleate and hypertrophied giant cells, which result from the redifferentiation of vascular root cells. Giant cells constitute the sole source of nutrients for the nematode and are essential for growth and reproduction. Hyperplasia of surrounding root cells leads to the formation of the gall or root-knot, an easily recognized symptom of plant infection by RKNs. Secreted effectors produced in nematode salivary glands and injected into plant cells through a specialized feeding structure called the stylet play a critical role in the formation of giant cells. Here, we describe the complex interactions between RKNs and their host plants. We highlight progress in understanding host plant responses, focusing on how RKNs manipulate key plant processes and functions, including cell cycle, defence, hormones, cellular scaffold, metabolism and transport.

  6. 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

  7. Mesenchymal progenitor cells differentiate into an endothelial phenotype, enhance vascular density and improve heart function in a rat cellular cardiomyoplasty model

    Institute of Scientific and Technical Information of China (English)

    SDAVANI; NMERSIN; BROYER; BKANTELIP; JPKANTELIP

    2004-01-01

    AIM: Cellular cardiomyoplasty is promising for improving postinfarcted cardiac function. Over the past decade, a variety of cell types have been proposed including mononuclear bone marrow cells. The latter contains different lineages including mesenchymal stem cells (MSCs). The aim of this study was to analyse the differentiation pathways of engrafted syngenic mesenchymal progenitor cells (MPCs) obtained in culture from bone marrow

  8. Long-time tails of the velocity autocorrelation function in 2D and 3D lattice gas cellular automata: a test of mode-coupling theory

    NARCIS (Netherlands)

    Hoef, M.A. van der; Frenkel, D.

    1990-01-01

    We report simulations of the velocity autocorrelation function (VACF) of a tagged particle in two- and three-dimensional lattice-gas cellular automata, using a new technique that is about a million times more efficient than the conventional techniques. The simulations clearly show the algebraic t-D/

  9. 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...

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

    Directory of Open Access Journals (Sweden)

    Teresa Simonetti

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

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

    Science.gov (United States)

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

    2012-01-01

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

  12. Identification of Cellular Targets of MicroRNA-181a in HepG2 Cells: A New Approach for Functional Analysis of MicroRNAs.

    Science.gov (United States)

    Tan, Jane Yi Lin; Habib, Nagy A; Chuah, York Wieo; Yau, Yin Hoe; Geifman-Shochat, Susana; Chen, Wei Ning

    2015-01-01

    MicroRNAs (miRNAs) are known to play a part in regulating important cellular processes. They generally perform their regulatory function through their binding with mRNAs, ultimately leading to a repression of target protein expression levels. However, their roles in cellular processes are poorly understood due to the limited understanding of their specific cellular targets. Aberrant levels of miRNAs have been found in hepatocellular carcinoma (HCC) including miR-181a. Using bioinformatics analysis, cyclin-dependent kinase inhibitor 1B (CDKN1β) and transcriptional factor E2F7 were identified as potential targets of miR-181a. Validation analysis using surface plasmon resonance (SPR) showed a positive binding between miR-181a and the 3'UTRs of these two potential mRNA targets. In vivo luciferase assay further confirmed the positive miR-181a:mRNA bindings, where a significant decrease in luciferase activity was detected when HepG2 cells were co-transfected with the 3'UTR-containing reporter plasmids and miR-181a. The potential impact of miR-181a binding to its specific targets on the general cellular behavior was further investigated. Results showed that miR-181a significantly activated the MAPK/JNK pathway which regulates cell proliferation, supporting our recently reported findings. Inhibition of miR-181a, on the other hand, abolished the observed activation. Our findings open up a new approach in designing targeted functional analysis of miRNAs in cellular processes, through the identification of their cellular targets.

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

    Directory of Open Access Journals (Sweden)

    Periyasamy M. Mariappan

    2016-09-01

    Full Text Available There has been an increase in the potential use of wireless devices in healthcare domain for a variety of reasons. The most commonly used device is the cellular phone, which emits strong electromagnetic energy affecting thereby the functionality of the vital medical equipment such as ventilators, ECG monitors, cardiac monitors, and defibrillators. This prompted the healthcare concerns to restrict the use of these phones in the proximity of critical and non-critical care medical equipment. Due to the developments made in the design of medical equipment to comply with the EMC standards, the restriction had been slowly laid off. Still, the researchers are concerned about the electromagnetic interference with medical devices by cellular phones in the healthcare domain and recommend for conducting continuous research to study their interaction with medical equipment. This paper overviews the certain investigations carried out in the recent years to study the electromagnetic interference between medical devices and 2G/3G/4G LTE cellular phones. During the initial development of cellular phones, the 2G cellular phones had caused more interference that affects the function and operation of some medical devices. The possibility of interference from 3G cellular phones with medical devices was considerably lower than the 2G phones, but still exists. Furthermore, almost all of the 4G phones have little to no interference with the medical devices. Currently, with the development of the medical devices industry, the current medical devices are designed to operate safely under any conditions of usage. Finally, a careful analysis would require statistics on the frequency of adverse events across the healthcare system, which apparently do not exist.

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

    Directory of Open Access Journals (Sweden)

    Sarah evan Veen

    2014-05-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  16. 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...

  17. Cellular mechanisms regulating neuronal excitability: Functional implications and in epilepsy | Mecanismos celulares reguladores de la excitabilidad celular: Implicaciones funcionales y en epilepsia

    OpenAIRE

    Cabezas-Fernández, C.; Martín-Montiel, E. D.; Buño, W

    2003-01-01

    Introduction and method. The cellular mechanisms that regulate neuronal excitability and the propagation of electrical signals in the dendrites of pyramidal neurons are incompletely understood and of key functional and pathological importance. The capacity of dendrites to actively propagate action potentials is vital in processes related to memory and learning. The deregulation of dendritic excitability may also contribute to epilepsy. The contributions of ionic conductances that regulate neu...

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

    DEFF Research Database (Denmark)

    Jensen, Sanne Skov; Fomsgaard, Anders; Borggren, Marie

    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...... during ART. These findings suggest improved cytotoxic function of the NK cells if initiating ART early during infection, while the levels of ADCC mediating antibodies declined during ART....

  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. Molecular cloning and analysis of functional cDNA and genomic clones encoding bovine cellular retinoic acid-binding protein.

    Science.gov (United States)

    Shubeita, H E; Sambrook, J F; McCormick, A M

    1987-08-01

    A recombinant cDNA clone, pCRABP-HS1, encoding cellular retinoic acid-binding protein was isolated from a bovine adrenal cDNA library. COS-7 cells transfected with pCRABP-HS1 produced a biologically active retinoic acid-binding protein molecule of the expected molecular mass (15.5 kDa). RNA blot hybridization analysis using pCRABP-HS1 as a probe revealed a single 1050-nucleotide mRNA species in bovine adrenal, uterus, and testis, tissues that contain the highest levels of retinoic acid-binding activity. No hybridization was detected in RNA extracted from ovary, spleen, kidney, or liver, which contain relatively low levels of cellular retinoic acid-binding protein activity. Analysis of genomic clones isolated from an EcoRI bovine genomic library demonstrated that the bovine cellular retinoic acid-binding protein gene is composed of four exons and three introns. Two putative promoter sequences were identified in the cloned 5' sequence of the gene.

  1. Molecular cloning and analysis of functional cDNA and genomic clones encoding bovine cellular retinoic acid-binding protein.

    OpenAIRE

    Shubeita, H E; Sambrook, J F; McCormick, A M

    1987-01-01

    A recombinant cDNA clone, pCRABP-HS1, encoding cellular retinoic acid-binding protein was isolated from a bovine adrenal cDNA library. COS-7 cells transfected with pCRABP-HS1 produced a biologically active retinoic acid-binding protein molecule of the expected molecular mass (15.5 kDa). RNA blot hybridization analysis using pCRABP-HS1 as a probe revealed a single 1050-nucleotide mRNA species in bovine adrenal, uterus, and testis, tissues that contain the highest levels of retinoic acid-bindin...

  2. The Na+/Glucose Cotransporter Inhibitor Canagliflozin Activates AMPK by Inhibiting Mitochondrial Function and Increasing Cellular AMP Levels.

    Science.gov (United States)

    Hawley, Simon A; Ford, Rebecca J; Smith, Brennan K; Gowans, Graeme J; Mancini, Sarah J; Pitt, Ryan D; Day, Emily A; Salt, Ian P; Steinberg, Gregory R; Hardie, D Grahame

    2016-09-01

    Canagliflozin, dapagliflozin, and empagliflozin, all recently approved for treatment of type 2 diabetes, were derived from the natural product phlorizin. They reduce hyperglycemia by inhibiting glucose reuptake by sodium/glucose cotransporter (SGLT) 2 in the kidney, without affecting intestinal glucose uptake by SGLT1. We now report that canagliflozin also activates AMPK, an effect also seen with phloretin (the aglycone breakdown product of phlorizin), but not to any significant extent with dapagliflozin, empagliflozin, or phlorizin. AMPK activation occurred at canagliflozin concentrations measured in human plasma in clinical trials and was caused by inhibition of Complex I of the respiratory chain, leading to increases in cellular AMP or ADP. Although canagliflozin also inhibited cellular glucose uptake independently of SGLT2, this did not account for AMPK activation. Canagliflozin also inhibited lipid synthesis, an effect that was absent in AMPK knockout cells and that required phosphorylation of acetyl-CoA carboxylase (ACC) 1 and/or ACC2 at the AMPK sites. Oral administration of canagliflozin activated AMPK in mouse liver, although not in muscle, adipose tissue, or spleen. Because phosphorylation of ACC by AMPK is known to lower liver lipid content, these data suggest a potential additional benefit of canagliflozin therapy compared with other SGLT2 inhibitors.

  3. Positive and Negative Regulatory Mechanisms for Fine-Tuning Cellularity and Functions of Medullary Thymic Epithelial Cells

    Science.gov (United States)

    Akiyama, Taishin; Tateishi, Ryosuke; Akiyama, Nobuko; Yoshinaga, Riko; Kobayashi, Tetsuya J.

    2015-01-01

    Self-tolerant T cells and regulatory T cells develop in the thymus. A wide variety of cell–cell interactions in the thymus is required for the differentiation, proliferation, and repertoire selection of T cells. Various secreted and cell surface molecules expressed in thymic epithelial cells (TECs) mediate these processes. Moreover, cytokines expressed by cells of hematopoietic origin regulate the cellularity of TECs. Tumor necrosis factor (TNF) family RANK ligand, lymphotoxin, and CD40 ligand, expressed in T cells and innate lymphoid cells (ILCs), promote the differentiation and proliferation of medullary TECs (mTECs) that play critical roles in the induction of immune tolerance. A recent study suggests that interleukin-22 (IL-22) produced by ILCs promotes regeneration of TECs after irradiation. Intriguingly, tumor growth factor-β and osteoprotegerin limit cellularity of mTECs, thereby attenuating regulatory T cell generation. We will review recent insights into the molecular basis for cell–cell interactions regulating differentiation and proliferation of mTECs and also discuss about a perspective on use of mathematical models for understanding this complicated system. PMID:26441966

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

    Energy Technology Data Exchange (ETDEWEB)

    Hamann, Ingrit [Institut fuer Angewandte Biowissenschaften, Abteilung Lebensmittelchemie und Toxikologie, Karlsruher Institut fuer Technologie (KIT), 76131 Karlsruhe (Germany); Fachgebiet Lebensmittelchemie und Toxikologie, Institut fuer Lebensmitteltechnologie und Lebensmittelchemie, Technische Universitaet Berlin, 13355 Berlin (Germany); Faculty for Pharmacy and Pharmaceutical Sciences, University of Alberta, 3126 Dentistry/Pharmacy Centre, Edmonton, Alberta, Canada T6G 2N8 (Canada); Koenig, Charlotte; Richter, Constanze [Fachgebiet Lebensmittelchemie und Toxikologie, Institut fuer Lebensmitteltechnologie und Lebensmittelchemie, Technische Universitaet Berlin, 13355 Berlin (Germany); Jahnke, Gunnar [Institut fuer Angewandte Biowissenschaften, Abteilung Lebensmittelchemie und Toxikologie, Karlsruher Institut fuer Technologie (KIT), 76131 Karlsruhe (Germany); Fachgebiet Lebensmittelchemie und Toxikologie, Institut fuer Lebensmitteltechnologie und Lebensmittelchemie, Technische Universitaet Berlin, 13355 Berlin (Germany); Hartwig, Andrea, E-mail: andrea.hartwig@kit.edu [Institut fuer Angewandte Biowissenschaften, Abteilung Lebensmittelchemie und Toxikologie, Karlsruher Institut fuer Technologie (KIT), 76131 Karlsruhe (Germany); Fachgebiet Lebensmittelchemie und Toxikologie, Institut fuer Lebensmitteltechnologie und Lebensmittelchemie, Technische Universitaet Berlin, 13355 Berlin (Germany)

    2012-08-01

    The tumor suppressor protein p53, often called the guardian of the genome, is involved in important cellular processes, such as cell cycle control, apoptosis and DNA repair. With respect to BER, p53 might physically interact with and affect the transcription of different BER proteins such as hOGG1, APE1 or Pol{beta}. In studies in HCT116 p53{sup -/-} cells previously published, activity and mRNA expression of hOGG1 were found to be significantly decreased, while down-regulation of APE1 mRNA and protein levels in response to genotoxic stress were only described in HCT116 p53{sup +/+} cells, but not in the isogenic p53 knockout cell line. The predominantly indirect genotoxic carcinogen cadmium inhibits the BER pathway and potentially interferes with zinc binding proteins such as p53. Therefore, this study was accomplished to investigate whether p53 is involved in the cadmium-induced inhibition of BER activity. To address this issue we applied a non-radioactive cleavage test system based on a Cy5-labeled oligonucleotide. We present evidence that p53 is not essential for hOGG1 and APE1 gene expression as well as OGG and APE activity in unstressed HCT116 cells; however, it plays an important role in the cellular response to cadmium treatment. Here, a direct involvement of p53 was only observed with respect to APE1 gene expression contributing to an altered APE activity, while OGG activity was presumably affected indirectly due to a stronger accumulation of cadmium in HCT116 p53{sup +/+} cells. In summary, p53 indeed affects the BER pathway directly and indirectly in response to cadmium treatment.

  5. Cellular Telephone

    Institute of Scientific and Technical Information of China (English)

    杨周

    1996-01-01

    Cellular phones, used in automobiles, airliners, and passenger trains, are basically low-power radiotelephones. Calls go through radio transmitters that are located within small geographical units called cells. Because each cell’s signals are too weak to interfere with those of other cells operating on the same fre-

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

    Science.gov (United States)

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

    2015-01-01

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

  7. Dual Functional Nanocarrier for Cellular Imaging and Drug Delivery in Cancer Cells Based on π-Conjugated Core and Biodegradable Polymer Arms.

    Science.gov (United States)

    Kulkarni, Bhagyashree; Surnar, Bapurao; Jayakannan, Manickam

    2016-03-14

    Multipurpose polymer nanoscaffolds for cellular imaging and delivery of anticancer drug are urgently required for the cancer therapy. The present investigation reports a new polymer drug delivery concept based on biodegradable polycaprolactone (PCL) and highly luminescent π-conjugated fluorophore as dual functional nanocarrier for cellular imaging and delivery vehicles for anticancer drug to cancer cells. To accomplish this goal, a new substituted caprolactone monomer was designed, and it was subjected to ring opening polymerization using a blue luminescent bishydroxyloligo-phenylenevinylene (OPV) fluorophore as an initiator. A series of A-B-A triblock copolymer building blocks with a fixed OPV π-core and variable chain biodegradable PCL arm length were tailor-made. These triblocks self-assembled in organic solvents to produce well-defined helical nanofibers, whereas in water they produced spherical nanoparticles (size ∼150 nm) with blue luminescence. The hydrophobic pocket of the polymer nanoparticle was found to be an efficient host for loading water insoluble anticancer drug such as doxorubicin (DOX). The photophysical studies revealed that there was no cross-talking between the OPV and DOX chromophores, and their optical purity was retained in the nanoparticle assembly for cellular imaging. In vitro studies revealed that the biodegradable PCL arm was susceptible to enzymatic cleavage at the intracellular lysosomal esterase under physiological conditions to release the loaded drugs. The nascent nanoparticles were found to be nontoxic to cancer cells, whereas the DOX-loaded nanoparticles accomplished more than 80% killing in HeLa cells. Confocal microscopic analysis confirmed the cell penetrating ability of the blue luminescent polymer nanoparticles and their accumulation preferably in the cytoplasm. The DOX loaded red luminescent polymer nanoparticles were also taken up by the cells, and the drug was found to be accumulated at the perinuclear environment

  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. Gain of cellular adaptation due to prolonged p53 impairment leads to functional switchover from p53 to p73 during DNA damage in acute myeloid leukemia cells.

    Science.gov (United States)

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

    2010-10-22

    Tumor suppressor p53 plays the central role in regulating apoptosis in response to genotoxic stress. From an evolutionary perspective, the activity of p53 has to be backed up by other protein(s) in case of any functional impairment of this protein, to trigger DNA damage-induced apoptosis in cancer cells. We adopted multiple experimental approaches to demonstrate that in p53-impaired cancer cells, DNA damage caused accumulation of p53 paralogue p73 via Chk-1 that strongly impacted Bax expression and p53-independent apoptosis. On the contrary, when p53 function was restored by ectopic expression, Chk-2 induced p53 accumulation that in turn overshadowed p73 activity, suggesting an antagonistic interaction between p53 family members. To understand such interaction better, p53-expressing cells were impaired differentially for p53 activity. In wild-type p53-expressing cancer cells that were silenced for p53 for several generations, p73 was activated, whereas no such trend was observed when p53 was transiently silenced. Prolonged p53 interference, even in functional p53 settings, therefore, leads to the "gain of cellular adaptation" in a way that alters the cellular microenvironment in favor of p73 activation by altering p73-regulatory proteins, e.g. Chk1 activation and dominant negative p73 down-regulation. These findings not only unveil a hitherto unexplained mechanism underlying the functional switchover from p53 to p73, but also validate p73 as a promising and potential target for cancer therapy in the absence of functional p53.

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

    Directory of Open Access Journals (Sweden)

    Yana Sandlers

    Full Text Available Barth Syndrome is the only known Mendelian disorder of cardiolipin remodeling, with characteristic clinical features of cardiomyopathy, skeletal myopathy, and neutropenia. While the primary biochemical defects of reduced mature cardiolipin and increased monolysocardiolipin are well-described, much of the downstream biochemical dysregulation has not been uncovered, and biomarkers are limited. In order to further expand upon the knowledge of the biochemical abnormalities in Barth Syndrome, we analyzed metabolite profiles in plasma from a cohort of individuals with Barth Syndrome compared to age-matched controls via 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. A clear distinction between metabolite profiles of individuals with Barth Syndrome and controls was observed, and was defined by an array of metabolite classes including amino acids and lipids. Pathway analysis of these discriminating metabolites revealed involvement of mitochondrial and extra-mitochondrial biochemical pathways including: insulin regulation of fatty acid metabolism, lipid metabolism, biogenic amine metabolism, amino acid metabolism, endothelial nitric oxide synthase signaling, and tRNA biosynthesis. Taken together, this data indicates broad metabolic dysregulation in Barth Syndrome with wide cellular effects.

  11. Shroom3 functions downstream of planar cell polarity to regulate myosin II distribution and cellular organization during neural tube closure

    Directory of Open Access Journals (Sweden)

    Erica M. McGreevy

    2015-01-01

    Full Text Available Neural tube closure is a critical developmental event that relies on actomyosin contractility to facilitate specific processes such as apical constriction, tissue bending, and directional cell rearrangements. These complicated processes require the coordinated activities of Rho-Kinase (Rock, to regulate cytoskeletal dynamics and actomyosin contractility, and the Planar Cell Polarity (PCP pathway, to direct the polarized cellular behaviors that drive convergent extension (CE movements. Here we investigate the role of Shroom3 as a direct linker between PCP and actomyosin contractility during mouse neural tube morphogenesis. In embryos, simultaneous depletion of Shroom3 and the PCP components Vangl2 or Wnt5a results in an increased liability to NTDs and CE failure. We further show that these pathways intersect at Dishevelled, as Shroom3 and Dishevelled 2 co-distribute and form a physical complex in cells. We observed that multiple components of the Shroom3 pathway are planar polarized along mediolateral cell junctions in the neural plate of E8.5 embryos in a Shroom3 and PCP-dependent manner. Finally, we demonstrate that Shroom3 mutant embryos exhibit defects in planar cell arrangement during neural tube closure, suggesting a role for Shroom3 activity in CE. These findings support a model in which the Shroom3 and PCP pathways interact to control CE and polarized bending of the neural plate and provide a clear illustration of the complex genetic basis of NTDs.

  12. Shroom3 functions downstream of planar cell polarity to regulate myosin II distribution and cellular organization during neural tube closure.

    Science.gov (United States)

    McGreevy, Erica M; Vijayraghavan, Deepthi; Davidson, Lance A; Hildebrand, Jeffrey D

    2015-01-16

    Neural tube closure is a critical developmental event that relies on actomyosin contractility to facilitate specific processes such as apical constriction, tissue bending, and directional cell rearrangements. These complicated processes require the coordinated activities of Rho-Kinase (Rock), to regulate cytoskeletal dynamics and actomyosin contractility, and the Planar Cell Polarity (PCP) pathway, to direct the polarized cellular behaviors that drive convergent extension (CE) movements. Here we investigate the role of Shroom3 as a direct linker between PCP and actomyosin contractility during mouse neural tube morphogenesis. In embryos, simultaneous depletion of Shroom3 and the PCP components Vangl2 or Wnt5a results in an increased liability to NTDs and CE failure. We further show that these pathways intersect at Dishevelled, as Shroom3 and Dishevelled 2 co-distribute and form a physical complex in cells. We observed that multiple components of the Shroom3 pathway are planar polarized along mediolateral cell junctions in the neural plate of E8.5 embryos in a Shroom3 and PCP-dependent manner. Finally, we demonstrate that Shroom3 mutant embryos exhibit defects in planar cell arrangement during neural tube closure, suggesting a role for Shroom3 activity in CE. These findings support a model in which the Shroom3 and PCP pathways interact to control CE and polarized bending of the neural plate and provide a clear illustration of the complex genetic basis of NTDs.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    . To discuss the role of ATP13A2 in neurodegeneration, we first provide a short description of the architecture and transport mechanism of P-type transport ATPases. Then, we briefly highlight key P-type ATPases involved in neuronal disorders such as the copper transporters ATP7A (Menkes disease), ATP7B (Wilson...... disease), the Na+/K+-ATPases ATP1A2 (familial hemiplegic migraine) and ATP1A3 (rapid-onset dystonia parkinsonism). Finally, we review the recent literature of ATP13A2 and discuss ATP13A2's putative cellular function in the light of what is known concerning the functions of other, better-studied P...

  14. 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

  15. Investigation of microgravity effects on basic imune functions on the cellular level - The TRIPLELUX-B experiment

    Science.gov (United States)

    Unruh, Eckehardt; Hansen, Peter-Diedrich

    Hemocytes are the primary defence of the Blue Mussel against invading microorganisms and foreign particles. The hemocytes of mussels as part of the immune system of invertebrates has not been studied so far in space. The choice of the phagocytes from invertebrates is justified by the claim to study the universal validity of innate immune responses. The hemocytes of mussels have a lot in common with macrophages of higher organisms. They are able to detect the presence of microorganisms and kill these microorganisms by phagocytosis. The phagocy-tosis related production of ROS will be stimulated with opsonised zymosan. The hemocytes will be stored frozen and reconstituted in-flight for the experiment. The signals of the im-muno cellular responses are translated into luminescence as a rapid optical reporter system. The primary aim of Triplelux B is to investigate under space flight conditions the effect of microgravity on the ability of isolated Blue Mussel hemocytes to perform phagocytosis. As a secondery objectiv, the results expected will allow to conclude whether the observed responses are caused by microgravity and/or radiation (change in permeability, endpoints in genotoxicity: DNA unwinding). The TRIPLELUX-B Experiment contributes to risk assessment concerning immunotoxicity under space flight conditions. The components of the fully automated AEC (Advanced Experimental Containment) will be demonstrated. The AEC of the TRIPLELUX-B experiment will contribute to a real time operational monitoring for immunotoxicity testing for earth. Blue mussels have been used repeatedly for monitoring imunotoxicity and genotoxicity in coastal waters. Based on the AEC an automatet measuring device will allow "real time monitoring" providing observations of immunotoxicity in coastal and inland waters.

  16. Understanding the Form, Function, and Logic of Clandestine Cellular Networks: The First Step in Effective Counternetwork Operations

    Science.gov (United States)

    2009-04-01

    form, function, and logic is derived from Gilles Deleuze and Felix Guattari, A Thousand Plateaus; Capitalism and Schizophreni, (Minneapolis: University...February 8, 2009]. Deleuze , Gilles and Felix Guattari. A Thousand Plateaus; Capitalism and Schizophrenia. Minneapolis: University of Minnesota Press, 1987

  17. 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.

  18. From understanding cellular function to novel drug discovery: the role of planar patch-clamp array chip technology

    Directory of Open Access Journals (Sweden)

    Christophe ePy

    2011-10-01

    Full Text Available All excitable cell functions rely upon ion channels that are embedded in their plasma membrane. Perturbations of ion channel structure or function result in pathologies ranging from cardiac dysfunction to neurodegenerative disorders. Consequently, to understand the functions of excitable cells and to remedy their pathophysiology, it is important to understand the ion channel functions under various experimental conditions – including exposure to novel drug targets. Glass pipette patch-clamp is the state of the art technique to monitor the intrinsic and synaptic properties of neurons. However, this technique is labor-intensive and has low data throughput. Planar patch-clamp chips, integrated into automated systems, offer high throughputs but are limited to isolated cells from suspensions, resulting in questionable models of true physiological function, and are unsuitable for studies involving neuronal communication. Multi-electrode arrays (MEA, in contrast, have the ability to monitor network activity by measuring local field potentials from multiple extracellular sites, but specific ion channel activity is challenging to extract from these multiplexed signals. Here we describe a novel planar patch-clamp chip technology that enables the simultaneous high resolution electrophysiological interrogation of individual neurons at multiple sites in synaptically connected neuronal networks, thereby combining the advantages of MEA and patch-clamp techniques. Each neuron can be probed through an aperture that connects to a dedicated subterranean microfluidic channel. Neurons growing in networks are aligned to the apertures by physisorbed or chemisorbed chemical cues. In this review, we describe the design and fabrication process of these chips, the approach to the chemical patterning for cell placement, and present physiological data from cultured neuronal cells.

  19. 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...... cells inhibited their proliferation by 57 +/- 1% and stimulated steady state mRNA levels of AP (1.7 +/- 0.1-fold) and OC (1.8 +/- 0.2-fold). Similarly, calcitriol treatment increased mRNA levels of AP (1.7 +/- 0.2-fold) and OC (3.0 +/- 0.3-fold) in late-passage osteoblastic cells. Thus, in vitro...

  20. Multiple Functional Domains and Complexes of the Two Nonstructural Proteins of Human Respiratory Syncytial Virus Contribute to Interferon Suppression and Cellular Location▿

    Science.gov (United States)

    Swedan, Samer; Andrews, Joel; Majumdar, Tanmay; Musiyenko, Alla; Barik, Sailen

    2011-01-01

    Human respiratory syncytial virus (RSV), a major cause of severe respiratory diseases, efficiently suppresses cellular innate immunity, represented by type I interferon (IFN), using its two unique nonstructural proteins, NS1 and NS2. In a search for their mechanism, NS1 was previously shown to decrease levels of TRAF3 and IKKε, whereas NS2 interacted with RIG-I and decreased TRAF3 and STAT2. Here, we report on the interaction, cellular localization, and functional domains of these two proteins. We show that recombinant NS1 and NS2, expressed in lung epithelial A549 cells, can form homo- as well as heteromers. Interestingly, when expressed alone, substantial amounts of NS1 and NS2 localized to the nuclei and to the mitochondria, respectively. However, when coexpressed with NS2, as in RSV infection, NS1 could be detected in the mitochondria as well, suggesting that the NS1-NS2 heteromer localizes to the mitochondria. The C-terminal tetrapeptide sequence, DLNP, common to both NS1 and NS2, was required for some functions, but not all, whereas only the NS1 N-terminal region was important for IKKε reduction. Finally, NS1 and NS2 both interacted specifically with host microtubule-associated protein 1B (MAP1B). The contribution of MAP1B in NS1 function was not tested, but in NS2 it was essential for STAT2 destruction, suggesting a role of the novel DLNP motif in protein-protein interaction and IFN suppression. PMID:21795342

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

    Directory of Open Access Journals (Sweden)

    Samantha D Pauls

    2012-08-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  3. Regulation of the hypertonic stress response and other cellular functions by the Rel-like transcription factor NFAT5.

    Science.gov (United States)

    Aramburu, José; Drews-Elger, Katherine; Estrada-Gelonch, Anaïs; Minguillón, Jordi; Morancho, Beatriz; Santiago, Verónica; López-Rodríguez, Cristina

    2006-11-30

    Stress, be it from environmental factors or intrinsic to the cell as result of growth and metabolism, can be harmful to cells. Mammalian cells have developed numerous mechanisms to respond to diverse forms of stress. These mechanisms combine signaling cascades and activation of gene expression programs to orchestrate an adaptive response that will allow the cell to survive and resume its normal functioning. In this review we will focus on the transcription factor NFAT5, a fundamental regulator of the response to osmotic stress in mammalian cells. Identified in 1999, NFAT5 is the latest addition to the Rel family, which comprises the NF-kappaB and NFATc proteins. Though in some of its structural and functional features NFAT5 is a hybrid between these two major groups of Rel proteins, it has unique characteristics that make it stand on its own as a third type of Rel transcription factor. Since its discovery, NFAT5 has been studied mostly in the context of the hypertonicity stress response. The advent of mouse models deficient in NFAT5 and other recent advances have confirmed a fundamental osmoprotective role for this factor in mammals, but also revealed features that suggest it may have a wider range of functions.

  4. Integrative analysis of miRNA and mRNA paired expression profiling of primary fibroblast derived from diabetic foot ulcers reveals multiple impaired cellular functions.

    Science.gov (United States)

    Liang, Liang; Stone, Rivka C; Stojadinovic, Olivera; Ramirez, Horacio; Pastar, Irena; Maione, Anna G; Smith, Avi; Yanez, Vanessa; Veves, Aristides; Kirsner, Robert S; Garlick, Jonathan A; Tomic-Canic, Marjana

    2016-11-01

    Diabetic foot ulcers (DFUs) are one of the major complications of diabetes. Its molecular pathology remains poorly understood, impeding the development of effective treatments. Although it has been established that multiple cell types, including fibroblasts, keratinocytes, macrophages, and endothelial cells, all contribute to inhibition of healing, less is known regarding contributions of individual cell type. Thus, we generated primary fibroblasts from nonhealing DFUs and evaluated their cellular and molecular properties in comparison to nondiabetic foot fibroblasts (NFFs). Specifically, we analyzed both micro-RNA and mRNA expression profiles of primary DFU fibroblasts. Paired genomic analyses identified a total of 331 reciprocal miRNA-mRNA pairs including 21 miRNAs (FC > 2.0) along with 239 predicted target genes (FC > 1.5) that are significantly and differentially expressed. Of these, we focused on three miRNAs (miR-21-5p, miR-34a-5p, miR-145-5p) that were induced in DFU fibroblasts as most differentially regulated. The involvement of these microRNAs in wound healing was investigated by testing the expression of their downstream targets as well as by quantifying cellular behaviors in prospectively collected and generated cell lines from 15 patients (seven DFUF and eight NFF samples). We found large number of downstream targets of miR-21-5p, miR-34a-5p, miR-145-5p to be coordinately regulated in mRNA profiles, which was confirmed by quantitative real-time PCR. Pathway analysis on paired miRNA-mRNA profiles predicted inhibition of cell movement and cell proliferation, as well as activation of cell differentiation and senescence in DFU fibroblasts, which was confirmed by cellular assays. We concluded that induction of miR-21-5p, miR-34a-5p, miR-145-5p in DFU dermal fibroblasts plays an important role in impairing multiple cellular functions, thus contributing to overall inhibition of healing in DFUs.

  5. The effect of natural and synthetic fatty acids on membrane structure, microdomain organization, cellular functions and human health.

    Science.gov (United States)

    Ibarguren, Maitane; López, David J; Escribá, Pablo V

    2014-06-01

    This review deals with the effects of synthetic and natural fatty acids on the biophysical properties of membranes, and on their implication on cell function. Natural fatty acids are constituents of more complex lipids, like triacylglycerides or phospholipids, which are used by cells to store and obtain energy, as well as for structural purposes. Accordingly, natural and synthetic fatty acids may modify the structure of the lipid membrane, altering its microdomain organization and other physical properties, and provoking changes in cell signaling. Therefore, by modulating fatty acids it is possible to regulate the structure of the membrane, influencing the cell processes that are reliant on this structure and potentially reverting pathological cell dysfunctions that may provoke cancer, diabetes, hypertension, Alzheimer's and Parkinson's disease. The so-called Membrane Lipid Therapy offers a strategy to regulate the membrane composition through drug administration, potentially reverting pathological processes by re-adapting cell membrane structure. Certain fatty acids and their synthetic derivatives are described here that may potentially be used in such therapies, where the cell membrane itself can be considered as a target to combat disease. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.

  6. Beneficial effects of beta-blockers on left ventricular function and cellular energy reserve in patients with heart failure.

    Science.gov (United States)

    Spoladore, Roberto; Fragasso, Gabriele; Perseghin, Gianluca; De Cobelli, Francesco; Esposito, Antonio; Maranta, Francesco; Calori, Giliola; Locatelli, Massimo; Lattuada, Guido; Scifo, Paola; Del Maschio, Alessandro; Margonato, Alberto

    2013-08-01

    Beta-blockers have been shown to improve left ventricular (LV) function in patients with heart failure. The aim of this study is to non-invasively assess, by means of in vivo 31P-magnetic resonance spectroscopy (31P-MRS), the effects of beta-blockers on LV cardiac phosphocreatine and adenosine triphosphate (PCr/ATP) ratio in patients with heart failure. Ten heart failure patients on full medical therapy were beta-blocked by either carvedilol or bisoprolol. Before and after 3 months of treatment, exercise testing, 2D echocardiography, MRS, New York Heart Association (NYHA) class, ejection fraction (EF), maximal rate-pressure product and exercise metabolic equivalent system (METS) were evaluated. Relative concentrations of PCr and ATP were determined by cardiac 31P-MRS. After beta-blockade, NYHA class decreased (from 2.2 ± 0.54 to 1.9 ± 0.52, P = 0.05), whereas EF (from 33 ± 7 to 44 ± 6%, P = 0.0009) and METS (from 6.74 ± 2.12 to 8.03 ± 2.39, P = 0.01) increased. Accordingly, the mean cardiac PCr/ATP ratio increased by 33% (from 1.48 ± 0.22 to 1.81 ± 0.48, P = 0.03). Beta-blockade-induced symptomatic and functional improvement in patients with heart failure is associated to increased PCr/ATP ratio, indicating preservation of myocardial high-energy phosphate levels.

  7. Epigenetics and Cellular Metabolism

    Science.gov (United States)

    Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well. PMID:27695375

  8. 'P-cadherin functional role is dependent on E-cadherin cellular context: a proof of concept using the breast cancer model'.

    Science.gov (United States)

    2016-05-01

    This article corrects: P-cadherin functional role is dependent on E-cadherin cellular context: a proof of concept using the breast cancer model Volume 229, Issue 5, 705–718, Article first published online: 24 January 2013. By Ana Sofia Ribeiro, Bárbara Sousa, Laura Carreto, Nuno Mendes, Ana Rita Nobre, Sara Ricardo, André Albergaria, Jorge F Cameselle-Teijeiro, Rene Gerhard, Ola Söderberg, Raquel Seruca, Manuel A Santos, Fernando Schmitt and Joana Paredes, J Pathol 2013; 229: 708–718. DOI: 10.1002/path.4143. The above article, published online on 24 January 2013 on Wiley Online Library (wileyonlinelibrary.com). The funding information, “This work was also funded by FEDER funds through the Operational Programme for Competitiveness Factors - COMPETE (FCOMP-01-0124-FEDER-021209).” was omitted from the Acknowledgements section. We apologise for any inconvenience caused.

  9. Moving beyond "good fat, bad fat": the complex roles of dietary lipids in cellular function and health: session abstracts.

    Science.gov (United States)

    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 active roles of lipids in modulating physiological pathways. Identified pathways underlie the development of obesity, cognitive development, and inflammation, the latter of which is thought to relate to multiple disease processes. These data point to a new way of thinking about the role of lipids in health and disease.

  10. Widening Spectrum of Cellular and Subcellular Expression of Human GLUD1 and GLUD2 Glutamate Dehydrogenases Suggests Novel Functions.

    Science.gov (United States)

    Spanaki, Cleanthe; Kotzamani, Dimitra; Plaitakis, Andreas

    2017-01-01

    Mammalian glutamate dehydrogenase1 (GDH1) (E.C. 1.4.1.3) is a mitochondrial enzyme that catalyzes the reversible oxidative deamination of glutamate to α-ketoglutarate and ammonia while reducing NAD+ and/or NADP+ to NADH and/or NADPH. It links amino acid with carbohydrate metabolism, contributing to Krebs cycle anaplerosis, energy production, ammonia handling and redox homeostasis. Although GDH1 was one of the first major metabolic enzymes to be studied decades ago, its role in cell biology is still incompletely understood. There is however growing interest in a novel GDH2 isoenzyme that emerged via duplication in primates and underwent rapid evolutionary selection concomitant with prefrontal human cortex expansion. Also, the anaplerotic function of GDH1 and GDH2 is currently under sharp focus as this relates to the biology of glial tumors and other neoplasias. Here we used antibodies specific for human GDH1 (hGDH1) and human GDH2 (hGDH2) to study the expression of these isoenzymes in human tissues. Results revealed that both hGDH1 and hGDH2 are expressed in human brain, kidney, testis and steroidogenic organs. However, distinct hGDH1 and hGDH2 expression patterns emerged. Thus, while the Sertoli cells of human testis were strongly positive for hGDH2, they were negative for hGDH1. Conversely, hGDH1 showed very high levels of expression in human liver, but hepatocytes were virtually devoid of hGDH2. In human adrenals, both hGDHs were densely expressed in steroid-producing cells, with hGDH2 expression pattern matching that of the cholesterol side chain cleavage system involved in steroid synthesis. Similarly in human ovaries and placenta, both hGDH1 and hGDH2 were densely expressed in estrogen producing cells. In addition, hGDH1, being a housekeeping enzyme, was also expressed in cells that lack endocrine function. Regarding human brain, study of cortical sections using immunofluorescence (IF) with confocal microscopy revealed that hGDH1 and hGDH2 were both expressed

  11. 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.

  12. Functional and cellular characterization of human Retinoic Acid Induced 1 (RAI1 mutations associated with Smith-Magenis Syndrome

    Directory of Open Access Journals (Sweden)

    Carmona-Mora Paulina

    2010-08-01

    Full Text Available Abstract Background Smith-Magenis Syndrome is a contiguous gene syndrome in which the dosage sensitive gene has been identified: the Retinoic Acid Induced 1 (RAI1. Little is known about the function of human RAI1. Results We generated the full-length cDNA of the wild type protein and five mutated forms: RAI1-HA 2687delC, RAI1-HA 3103delC, RAI1 R960X, RAI1-HA Q1562R, and RAI1-HA S1808N. Four of them have been previously associated with SMS clinical phenotype. Molecular weight, subcellular localization and transcription factor activity of the wild type and mutant forms were studied by western blot, immunofluorescence and luciferase assays respectively. The wild type protein and the two missense mutations presented a higher molecular weight than expected, localized to the nucleus and activated transcription of a reporter gene. The frameshift mutations generated a truncated polypeptide with transcription factor activity but abnormal subcellular localization, and the same was true for the 1-960aa N-terminal half of RAI1. Two different C-terminal halves of the RAI1 protein (1038aa-end and 1229aa-end were able to localize into the nucleus but had no transactivation activity. Conclusion Our results indicate that transcription factor activity and subcellular localization signals reside in two separate domains of the protein and both are essential for the correct functionality of RAI1. The pathogenic outcome of some of the mutated forms can be explained by the dissociation of these two domains.

  13. System-level insights into the cellular interactome of a non-model organism: inferring, modelling and analysing functional gene network of soybean (Glycine max).

    Science.gov (United States)

    Xu, Yungang; Guo, Maozu; Zou, Quan; Liu, Xiaoyan; Wang, Chunyu; Liu, Yang

    2014-01-01

    Cellular interactome, in which genes and/or their products interact on several levels, forming transcriptional regulatory-, protein interaction-, metabolic-, signal transduction networks, etc., has attracted decades of research focuses. However, such a specific type of network alone can hardly explain the various interactive activities among genes. These networks characterize different interaction relationships, implying their unique intrinsic properties and defects, and covering different slices of biological information. Functional gene network (FGN), a consolidated interaction network that models fuzzy and more generalized notion of gene-gene relations, have been proposed to combine heterogeneous networks with the goal of identifying functional modules supported by multiple interaction types. There are yet no successful precedents of FGNs on sparsely studied non-model organisms, such as soybean (Glycine max), due to the absence of sufficient heterogeneous interaction data. We present an alternative solution for inferring the FGNs of soybean (SoyFGNs), in a pioneering study on the soybean interactome, which is also applicable to other organisms. SoyFGNs exhibit the typical characteristics of biological networks: scale-free, small-world architecture and modularization. Verified by co-expression and KEGG pathways, SoyFGNs are more extensive and accurate than an orthology network derived from Arabidopsis. As a case study, network-guided disease-resistance gene discovery indicates that SoyFGNs can provide system-level studies on gene functions and interactions. This work suggests that inferring and modelling the interactome of a non-model plant are feasible. It will speed up the discovery and definition of the functions and interactions of other genes that control important functions, such as nitrogen fixation and protein or lipid synthesis. The efforts of the study are the basis of our further comprehensive studies on the soybean functional interactome at the genome

  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. Enhanced NF-κB activation and cellular function in macrophages lacking IκB kinase 1 (IKK1)

    Science.gov (United States)

    Li, Qiutang; Lu, Qingxian; Bottero, Virginie; Estepa, Gabriela; Morrison, Lisa; Mercurio, Frank; Verma, Inder M.

    2005-01-01

    IκB kinase (IKK) complex plays a key regulatory role in macrophages for NF-κB activation during both innate and adaptive immune responses. Because IKK1–/– mice died at birth, we differentiated functional macrophages from embryonic day 15.5 IKK1 mutant embryonic liver. The embryonic liver-derived macrophage (ELDM) showed enhanced phagocytotic clearance of bacteria, more efficient antigen-presenting capacity, elevated secretion of several key proinflammatory cytokines and chemokines, and known NFκB target genes. Increased NFκB activity in IKK1 mutant ELDM was the result of prolonged degradation of IκBα in response to infectious pathogens. The delayed restoration of IκBα in pathogen-activated IKK1–/– ELDM was a direct consequence of uncontrolled IKK2 kinase activity. We hypothesize that IKK1 plays a checkpoint role in the proper control of IκBα kinase activity in innate and adaptive immunity. PMID:16116086

  16. 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.

  17. 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.

  18. Functional clustering and lineage markers: insights into cellular differentiation and gene function from large-scale microarray studies of purified primary cell populations.

    Science.gov (United States)

    Hume, David A; Summers, Kim M; Raza, Sobia; Baillie, J Kenneth; Freeman, Thomas C

    2010-06-01

    Very large microarray datasets showing gene expression across multiple tissues and cell populations provide a window on the transcriptional networks that underpin the differences in functional activity between biological systems. Clusters of co-expressed genes provide lineage markers, candidate regulators of cell function and, by applying the principle of guilt by association, candidate functions for genes of currently unknown function. We have analysed a dataset comprising pure cell populations from hemopoietic and non-hemopoietic cell types (http://biogps.gnf.org). Using a novel network visualisation and clustering approach, we demonstrate that it is possible to identify very tight expression signatures associated specifically with embryonic stem cells, mesenchymal cells and hematopoietic lineages. Selected examples validate the prediction that gene function can be inferred by co-expression. One expression cluster was enriched in phagocytes, which, alongside endosome-lysosome constituents, contains genes that may make up a 'pathway' for phagocyte differentiation. Promoters of these genes are enriched for binding sites for the ETS/PU.1 and MITF families. Another cluster was associated with the production of a specific extracellular matrix, with high levels of gene expression shared by cells of mesenchymal origin (fibroblasts, adipocytes, osteoblasts and myoblasts). We discuss the limitations placed upon such data by the presence of alternative promoters with distinct tissue specificity within many protein-coding genes.

  19. Cellular nucleic acid binding protein binds G-rich single-stranded nucleic acids and may function as a nucleic acid chaperone.

    Science.gov (United States)

    Armas, Pablo; Nasif, Sofía; Calcaterra, Nora B

    2008-02-15

    Cellular nucleic acid binding protein (CNBP) is a small single-stranded nucleic acid binding protein made of seven Zn knuckles and an Arg-Gly rich box. CNBP is strikingly conserved among vertebrates and was reported to play broad-spectrum functions in eukaryotic cells biology. Neither its biological function nor its mechanisms of action were elucidated yet. The main goal of this work was to gain further insights into the CNBP biochemical and molecular features. We studied Bufo arenarum CNBP (bCNBP) binding to single-stranded nucleic acid probes representing the main reported CNBP putative targets. We report that, although bCNBP is able to bind RNA and single-stranded DNA (ssDNA) probes in vitro, it binds RNA as a preformed dimer whereas both monomer and dimer are able to bind to ssDNA. A systematic analysis of variant probes shows that the preferred bCNBP targets contain unpaired guanosine-rich stretches. These data expand the knowledge about CNBP binding stoichiometry and begins to dissect the main features of CNBP nucleic acid targets. Besides, we show that bCNBP presents a highly disordered predicted structure and promotes the annealing and melting of nucleic acids in vitro. These features are typical of proteins that function as nucleic acid chaperones. Based on these data, we propose that CNBP may function as a nucleic acid chaperone through binding, remodeling, and stabilizing nucleic acids secondary structures. This novel CNBP biochemical activity broadens the field of study about its biological function and may be the basis to understand the diverse ways in which CNBP controls gene expression.

  20. Suppression of Transforming Growth Factor-β Signaling Delays Cellular Senescence and Preserves the Function of Endothelial Cells Derived From Human Pluripotent Stem Cells.

    Science.gov (United States)

    Bai, Hao; Gao, Yongxing; Hoyle, Dixie L; Cheng, Tao; Wang, Zack Z

    2016-09-20

    : Transplantation of vascular cells derived from human pluripotent stem cells (hPSCs) offers an attractive noninvasive method for repairing the ischemic tissues and for preventing the progression of vascular diseases. Here, we found that in a serum-free condition, the proliferation rate of hPSC-derived endothelial cells is quickly decreased, accompanied with an increased cellular senescence, resulting in impaired gene expression of endothelial nitric oxide synthase (eNOS) and impaired vessel forming capability in vitro and in vivo. To overcome the limited expansion of hPSC-derived endothelial cells, we screened small molecules for specific signaling pathways and found that inhibition of transforming growth factor-β (TGF-β) signaling significantly retarded cellular senescence and increased a proliferative index of hPSC-derived endothelial cells. Inhibition of TGF-β signaling extended the life span of hPSC-derived endothelial and improved endothelial functions, including vascular network formation on Matrigel, acetylated low-density lipoprotein uptake, and eNOS expression. Exogenous transforming growth factor-β1 increased the gene expression of cyclin-dependent kinase inhibitors, p15(Ink4b), p16(Ink4a), and p21(CIP1), in endothelial cells. Conversely, inhibition of TGF-β reduced the gene expression of p15(Ink4b), p16(Ink4a), and p21(CIP1). Our findings demonstrate that the senescence of newly generated endothelial cells from hPSCs is mediated by TGF-β signaling, and manipulation of TGF-β signaling offers a potential target to prevent vascular aging.

  1. 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.

  2. Neisserial outer membrane vesicles bind the coinhibitory receptor carcinoembryonic antigen-related cellular adhesion molecule 1 and suppress CD4+ T lymphocyte function.

    Science.gov (United States)

    Lee, Hannah S W; Boulton, Ian C; Reddin, Karen; Wong, Henry; Halliwell, Denise; Mandelboim, Ofer; Gorringe, Andrew R; Gray-Owen, Scott D

    2007-09-01

    Pathogenic Neisseria bacteria naturally liberate outer membrane "blebs," which are presumed to contribute to pathology, and the detergent-extracted outer membrane vesicles (OMVs) from Neisseria meningitidis are currently employed as meningococcal vaccines in humans. While the composition of these vesicles reflects the bacteria from which they are derived, the functions of many of their constituent proteins remain unexplored. The neisserial colony opacity-associated Opa proteins function as adhesins, the majority of which mediate bacterial attachment to human carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs). Herein, we demonstrate that the Opa proteins within OMV preparations retain the capacity to bind the immunoreceptor tyrosine-based inhibitory motif-containing coinhibitory receptor CEACAM1. When CD4(+) T lymphocytes were exposed to OMVs from Opa-expressing bacteria, their activation and proliferation in response to a variety of stimuli were effectively halted. This potent immunosuppressive effect suggests that localized infection will generate a "zone of inhibition" resulting from the diffusion of membrane blebs into the surrounding tissues. Moreover, it demonstrates that OMV-based vaccines must be developed from strains that lack CEACAM1-binding Opa variants.

  3. Cellular rehabilitation of photobiomodulation

    Science.gov (United States)

    Liu, Timon Cheng-Yi; Yuan, Jian-Qin; Wang, Yan-Fang; Xu, Xiao-Yang; Liu, Song-Hao

    2007-05-01

    Homeostasis is a term that refers to constancy in a system. A cell in homeostasis normally functions. There are two kinds of processes in the internal environment and external environment of a cell, the pathogenic processes (PP) which disrupts the old homeostasis (OH), and the sanogenetic processes (SP) which restores OH or establishes a new homeostasis (NH). Photobiomodualtion (PBM), the cell-specific effects of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems, is a kind of modulation on PP or SP so that there is no PBM on a cell in homeostasis. There are two kinds of pathways mediating PBM, the membrane endogenetic chromophores mediating pathways which often act through reactive oxygen species, and membrane proteins mediating pathways which often enhance cellular SP so that it might be called cellular rehabilitation. The cellular rehabilitation of PBM will be discussed in this paper. It is concluded that PBM might modulate the disruption of cellular homeostasis induced by pathogenic factors such as toxin until OH has been restored or NH has been established, but can not change homeostatic processes from one to another one.

  4. System-level insights into the cellular interactome of a non-model organism: inferring, modelling and analysing functional gene network of soybean (Glycine max.

    Directory of Open Access Journals (Sweden)

    Yungang Xu

    Full Text Available Cellular interactome, in which genes and/or their products interact on several levels, forming transcriptional regulatory-, protein interaction-, metabolic-, signal transduction networks, etc., has attracted decades of research focuses. However, such a specific type of network alone can hardly explain the various interactive activities among genes. These networks characterize different interaction relationships, implying their unique intrinsic properties and defects, and covering different slices of biological information. Functional gene network (FGN, a consolidated interaction network that models fuzzy and more generalized notion of gene-gene relations, have been proposed to combine heterogeneous networks with the goal of identifying functional modules supported by multiple interaction types. There are yet no successful precedents of FGNs on sparsely studied non-model organisms, such as soybean (Glycine max, due to the absence of sufficient heterogeneous interaction data. We present an alternative solution for inferring the FGNs of soybean (SoyFGNs, in a pioneering study on the soybean interactome, which is also applicable to other organisms. SoyFGNs exhibit the typical characteristics of biological networks: scale-free, small-world architecture and modularization. Verified by co-expression and KEGG pathways, SoyFGNs are more extensive and accurate than an orthology network derived from Arabidopsis. As a case study, network-guided disease-resistance gene discovery indicates that SoyFGNs can provide system-level studies on gene functions and interactions. This work suggests that inferring and modelling the interactome of a non-model plant are feasible. It will speed up the discovery and definition of the functions and interactions of other genes that control important functions, such as nitrogen fixation and protein or lipid synthesis. The efforts of the study are the basis of our further comprehensive studies on the soybean functional

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

    Directory of Open Access Journals (Sweden)

    Benjamin Nnamdi Okolonkwo

    2014-11-01

    Full Text Available Paraquat (PQ is a bipyridylium herbicide that is applied around trees in orchards and between crop rows to control broad-leaved and grassy weeds. Its oxidation results in the formation of superoxides which causes damage to cellular components. In this study, we determined the antioxidant effect vitamin C has on the cellular integrity of kidney function in rats following repeated exposure to PQ. Ninety-six male rats, grouped twelve rats per subgroup (A, Avit.c, B, Bvit.c, C, Cvit.c, D and Dvit.c were intraperitoneally injected with different sublethal increasing doses (0, 0, 2, 2, 4, 4, 6 and 6 mg/kg body weight of PQ respectively on biweekly (14 days intervals over a period of three months (84 days. Subsequently, the subgrouped animals (Avit.c, Bvit.c, Cvit.c and Dvit.c were maintained orally with 1 g/L vitamin C, while the other subgrouped animals (A, B, C and D received drinking water with negligible vitamin content throughout the study period. At the end of each monthly (28 days treatment, four animals per subgroup were selected. Urine samples were collected from each of the selected rats, after which each of the animals were anaesthetized with gaseous isoflurane and 5 mL of blood samples were collected using cardiac puncture procedure. The animals were later decapitated and their kidneys harvested. The samples collected were analyzed for urine [specific gravity (SG, pH, protein and glucose], blood (urea, creatinine, total protein and glucose, and the histological studies on kidney slides. The dose and exposure- time dependent PQ toxicity resulted in the reduction in urinary pH, elevation in urinary SG, and the detectable presence of protein and glucose in urine. It also caused marked elevation in serum urea and creatinine levels with reduction in serum protein and glucose levels and alterations in the cellular integrity of the renal architecture, especially the glomeruli and tubular tissues. Treatments on the PQ insulted animals with vitamin

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

    Science.gov (United States)

    Jensen, Sanne Skov; Fomsgaard, Anders; Borggren, Marie; Tingstedt, Jeanette Linnea; Gerstoft, Jan; Kronborg, Gitte; Rasmussen, Line Dahlerup; Pedersen, Court; Karlsson, Ingrid

    2015-01-01

    Understanding alterations in HIV-specific immune responses during antiretroviral therapy (ART), such as antibody-dependent cellular cytotoxicity (ADCC), is important in the development of novel strategies to control HIV-1 infection. This study included 53 HIV-1 positive individuals. We evaluated the ability of effector cells and antibodies to mediate ADCC separately and in combination using the ADCC-PanToxiLux assay. The ability of the peripheral blood mononuclear cells (PBMCs) to mediate ADCC was significantly higher in individuals who had been treated with ART before seroconversion, compared to the individuals initiating ART at a low CD4+ T cell count (ART-naïve individuals. The frequency of CD16 expressing natural killer (NK) cells correlated with both the duration of ART and Granzyme B (GzB) activity. In contrast, the plasma titer of antibodies mediating ADCC declined during ART. These findings suggest improved cytotoxic function of the NK cells if initiating ART early during infection, while the levels of ADCC mediating antibodies declined during ART.

  7. The role of the Frank-Starling law in the transduction of cellular work to whole organ pump function: a computational modeling analysis.

    Directory of Open Access Journals (Sweden)

    Steven A Niederer

    2009-04-01

    Full Text Available We have developed a multi-scale biophysical electromechanics model of the rat left ventricle at room temperature. This model has been applied to investigate the relative roles of cellular scale length dependent regulators of tension generation on the transduction of work from the cell to whole organ pump function. Specifically, the role of the length dependent Ca(2+ sensitivity of tension (Ca(50, filament overlap tension dependence, velocity dependence of tension, and tension dependent binding of Ca(2+ to Troponin C on metrics of efficient transduction of work and stress and strain homogeneity were predicted by performing simulations in the absence of each of these feedback mechanisms. The length dependent Ca(50 and the filament overlap, which make up the Frank-Starling Law, were found to be the two dominant regulators of the efficient transduction of work. Analyzing the fiber velocity field in the absence of the Frank-Starling mechanisms showed that the decreased efficiency in the transduction of work in the absence of filament overlap effects was caused by increased post systolic shortening, whereas the decreased efficiency in the absence of length dependent Ca(50 was caused by an inversion in the regional distribution of strain.

  8. The role of the Frank-Starling law in the transduction of cellular work to whole organ pump function: a computational modeling analysis.

    Science.gov (United States)

    Niederer, Steven A; Smith, Nicolas P

    2009-04-01

    We have developed a multi-scale biophysical electromechanics model of the rat left ventricle at room temperature. This model has been applied to investigate the relative roles of cellular scale length dependent regulators of tension generation on the transduction of work from the cell to whole organ pump function. Specifically, the role of the length dependent Ca(2+) sensitivity of tension (Ca(50)), filament overlap tension dependence, velocity dependence of tension, and tension dependent binding of Ca(2+) to Troponin C on metrics of efficient transduction of work and stress and strain homogeneity were predicted by performing simulations in the absence of each of these feedback mechanisms. The length dependent Ca(50) and the filament overlap, which make up the Frank-Starling Law, were found to be the two dominant regulators of the efficient transduction of work. Analyzing the fiber velocity field in the absence of the Frank-Starling mechanisms showed that the decreased efficiency in the transduction of work in the absence of filament overlap effects was caused by increased post systolic shortening, whereas the decreased efficiency in the absence of length dependent Ca(50) was caused by an inversion in the regional distribution of strain.

  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. 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.

  11. 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 ...

  12. Cellular systems biology profiling applied to cellular models of disease.

    Science.gov (United States)

    Giuliano, Kenneth A; Premkumar, Daniel R; Strock, Christopher J; Johnston, Patricia; Taylor, Lansing

    2009-11-01

    Building cellular models of disease based on the approach of Cellular Systems Biology (CSB) has the potential to improve the process of creating drugs as part of the continuum from early drug discovery through drug development and clinical trials and diagnostics. This paper focuses on the application of CSB to early drug discovery. We discuss the integration of protein-protein interaction biosensors with other multiplexed, functional biomarkers as an example in using CSB to optimize the identification of quality lead series compounds.

  13. Energy Landscape of Cellular Networks

    Science.gov (United States)

    Wang, Jin

    2008-03-01

    Cellular Networks are in general quite robust and perform their biological functions against the environmental perturbations. Progresses have been made from experimental global screenings, topological and engineering studies. However, there are so far few studies of why the network should be robust and perform biological functions from global physical perspectives. In this work, we will explore the global properties of the network from physical perspectives. The aim of this work is to develop a conceptual framework and quantitative physical methods to study the global nature of the cellular network. The main conclusion of this presentation is that we uncovered the underlying energy landscape for several small cellular networks such as MAPK signal transduction network and gene regulatory networks, from the experimentally measured or inferred inherent chemical reaction rates. The underlying dynamics of these networks can show bi-stable as well as oscillatory behavior. The global shapes of the energy landscapes of the underlying cellular networks we have studied are robust against perturbations of the kinetic rates and environmental disturbances through noise. We derived a quantitative criterion for robustness of the network function from the underlying landscape. It provides a natural explanation of the robustness and stability of the network for performing biological functions. We believe the robust landscape is a global universal property for cellular networks. We believe the robust landscape is a quantitative realization of Darwinian principle of natural selection at the cellular network level. It may provide a novel algorithm for optimizing the network connections, which is crucial for the cellular network design and synthetic biology. Our approach is general and can be applied to other cellular networks.

  14. Study on The Progress of Relationship Between Cellular Immunological Function and Primary Liver Cancer%细胞免疫功能变化与肝癌的关系研究进展

    Institute of Scientific and Technical Information of China (English)

    莫世发; 贾乾斌

    2012-01-01

    目的 总结细胞免疫功能变化与肝癌的关系及免疫治疗的作用.方法 通过复习国内、外文献,回顾性分析肝癌与细胞免疫功能变化的关系及肝癌免疫治疗在临床应用中的研究现状.结果 肝癌患者均存在着细胞免疫功能异常,肝癌的发生和发展与细胞免疫功能状态密切相关.细胞免疫功能低下是肝癌患者难以治愈和复发、转移的重要因素.免疫治疗通过调整机体的免疫功能,在肝癌的治疗中发挥着重要作用.结论 细胞免疫功能变化与肝癌的发生和发展关系密切,肝癌免疫治疗有望为肝癌治疗提供新的途径,可作为辅助治疗重要手段.%To summarize the role of the relationship between liver cancer and cellular immunological function, and the role of immune therapy in clinical application. Methods To analyze the relationship between liver cancer and cellular immunological function, and the present research situation of immune therapy for liver cancer in clinical application retrospectively via review the related domestic and foreign literatures. Results The cellular immune dysfunction existed in all liver cancer patients. The state of body's cellular immunological function is closely related with the arising and development of liver cancer, and the lowness of cellular immunological function is an important factor of hepatocellular carcinoma hard to cure or recurrence and metastasis. Immune therapy plays an important role in the treatment of liver cancer by adjusting the body's cellular immunological function. Conclusions Liver cancer is closely related with the body's cellular immunological function. Immune therapy is expected to offer a new way for the treatment of liver cancer, which can also be used as an important auxiliary treatment way.

  15. Spectrum-efficiency and energy-efficiency functions of green cellular networks%绿色蜂窝网络的频谱效率与能效函数

    Institute of Scientific and Technical Information of China (English)

    朱近康; 许莉

    2013-01-01

      为了给绿色蜂窝网络的研究和设计提供一个基本的基准或判断依据,对存在多小区干扰和越区切换情况下蜂窝网络的网络传输能力(网络频谱效率)和能量效率函数(能效函数)进行了研究,揭示了蜂窝网络的功率开销与频谱效率之间的关系。首先,给出了蜂窝网络能效函数的定义,并在此基础上提出了小区干扰深度和越区切换的动力学模型,进而论证了存在多小区干扰和越区切换情况下的蜂窝网络频谱效率,并推证了数学表达式。最后,求解了蜂窝网络的能效函数,讨论了相关参数对它的影响和数值结果分析,为绿色蜂窝网络的研究和设计,提供了有益的分析依据和基础。%To provide a research and design standard for green cellular networks with the presence of multi-cell interfer-ence and handover cases, the network transmission capacity (network spectral efficiency) and energy efficiency functions of the cellular network was researched, and the relationship between the power consumption and the spectrum efficiency in the cellular networks was revealed. First, the energy efficiency function of the cellular networks was defined. Based on this, the cell interference depth and the handoff dynamic model of cellular networks were proposed, and then the network spectrum-efficiency of the cellular networks was analyzed in the presence of multi-cell interference and handoff, and its mathematical expression was derived. Finally, the energy-efficiency function of the cellular networks and its numerical results were deducted and discussed. These results will provide a useful theoretical basis for green design of cellular net-works.

  16. The Coxsackievirus-Adenovirus Receptor Protein Can Function as a Cellular Attachment Protein for Adenovirus Serotypes from Subgroups A, C, D, E, and F

    OpenAIRE

    Roelvink, Peter W.; Lizonova, Alena; Lee, Jennifer G. M.; Li, Yuan; Bergelson, Jeffrey M.; Finberg, Robert W.; Douglas E Brough; Kovesdi, Imre; Wickham, Thomas J.

    1998-01-01

    Attachment of an adenovirus (Ad) to a cell is mediated by the capsid fiber protein. To date, only the cellular fiber receptor for subgroup C serotypes 2 and 5, the so-called coxsackievirus-adenovirus receptor (CAR) protein, has been identified and cloned. Previous data suggested that the fiber of the subgroup D serotype Ad9 also recognizes CAR, since Ad9 and Ad2 fiber knobs cross-blocked each other’s cellular binding. Recombinant fiber knobs and 3H-labeled Ad virions from serotypes representi...

  17. Enhanced cellular uptake of albumin-based lyophilisomes when functionalized with cell-penetrating peptide TAT in HeLa cells.

    Directory of Open Access Journals (Sweden)

    Etienne van Bracht

    Full Text Available Lyophilisomes are a novel class of biodegradable proteinaceous nano/micrometer capsules with potential use as drug delivery carrier. Cell-penetrating peptides (CPPs including the TAT peptide have been successfully implemented for intracellular delivery of a broad variety of cargos including various nanoparticulate pharmaceutical carriers. In the present study, lyophilisomes were modified using CPPs in order to achieve enhanced cellular uptake. Lyophilisomes were prepared by a freezing, annealing, and lyophilization method and a cystein-elongated TAT peptide was conjugated to the lyophilisomes using a heterobifunctional linker. Fluorescent-activated cell sorting (FACS was utilized to acquire a lyophilisome population with a particle diameter smaller than 1000 nm. Cultured HeLa, OVCAR-3, Caco-2 and SKOV-3 cells were exposed to unmodified lyophilisomes and TAT-conjugated lyophilisomes and examined with FACS. HeLa cells were investigated in more detail using a trypan blue quenching assay, confocal microscopy, and transmission electron microscopy. TAT-conjugation strongly increased binding and cellular uptake of lyophilisomes in a time-dependent manner in vitro, as assessed by FACS. These results were confirmed by confocal microscopy. Transmission electron microscopy indicated rapid cellular uptake of TAT-conjugated lyophilisomes via phagocytosis and/or macropinocytosis. In conclusion, TAT-peptides conjugated to albumin-based lyophilisomes are able to enhance cellular uptake of lyophilisomes in HeLa cells.

  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...... 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 synthesized from...

  19. Mathematical Modeling of Cellular Metabolism.

    Science.gov (United States)

    Berndt, Nikolaus; Holzhütter, Hermann-Georg

    2016-01-01

    Cellular metabolism basically consists of the conversion of chemical compounds taken up from the extracellular environment into energy (conserved in energy-rich bonds of organic phosphates) and a wide array of organic molecules serving as catalysts (enzymes), information carriers (nucleic acids), and building blocks for cellular structures such as membranes or ribosomes. Metabolic modeling aims at the construction of mathematical representations of the cellular metabolism that can be used to calculate the concentration of cellular molecules and the rates of their mutual chemical interconversion in response to varying external conditions as, for example, hormonal stimuli or supply of essential nutrients. Based on such calculations, it is possible to quantify complex cellular functions as cellular growth, detoxification of drugs and xenobiotic compounds or synthesis of exported molecules. Depending on the specific questions to metabolism addressed, the methodological expertise of the researcher, and available experimental information, different conceptual frameworks have been established, allowing the usage of computational methods to condense experimental information from various layers of organization into (self-) consistent models. Here, we briefly outline the main conceptual frameworks that are currently exploited in metabolism research.

  20. Fisetin attenuates hydrogen peroxide-induced cell damage by scavenging reactive oxygen species and activating protective functions of cellular glutathione system.

    Science.gov (United States)

    Kang, Kyoung Ah; Piao, Mei Jing; Kim, Ki Cheon; Cha, Ji Won; Zheng, Jian; Yao, Cheng Wen; Chae, Sungwook; Hyun, Jin Won

    2014-01-01

    Hydrogen peroxide (H2O2) can induce cell damage by generating reactive oxygen species (ROS), resulting in DNA damage and cell death. The aim of this study is to elucidate the protective effects of fisetin (3,7,3',4',-tetrahydroxy flavone) against H2O2-induced cell damage. Fisetin reduced the level of superoxide anion, hydroxyl radical in cell free system, and intracellular ROS generated by H2O2. Moreover, fisetin protected against H2O2-induced membrane lipid peroxidation, cellular DNA damage, and protein carbonylation, which are the primary cellular outcomes of H2O2 treatment. Furthermore, fisetin increased the level of reduced glutathione (GSH) and expression of glutamate-cysteine ligase catalytic subunit, which is decreased by H2O2. Conversely, a GSH inhibitor abolished the cytoprotective effect of fisetin against H2O2-induced cells damage. Taken together, our results suggest that fisetin protects against H2O2-induced cell damage by inhibiting ROS generation, thereby maintaining the protective role of the cellular GSH system.

  1. HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans.

    Science.gov (United States)

    Chen, Huan-Da; Kao, Cheng-Yuan; Liu, Bang-Yu; Huang, Shin-Whei; Kuo, Cheng-Ju; Ruan, Jhen-Wei; Lin, Yen-Hung; Huang, Cheng-Rung; Chen, Yu-Hung; Wang, Horng-Dar; Aroian, Raffi V; Chen, Chang-Shi

    2017-02-01

    Autophagy is an evolutionarily conserved intracellular system that maintains cellular homeostasis by degrading and recycling damaged cellular components. The transcription factor HLH-30/TFEB-mediated autophagy has been reported to regulate tolerance to bacterial infection, but less is known about the bona fide bacterial effector that activates HLH-30 and autophagy. Here, we reveal that bacterial membrane pore-forming toxin (PFT) induces autophagy in an HLH-30-dependent manner in Caenorhabditis elegans. Moreover, autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C. elegans. These results demonstrate that autophagic pathways and autophagy are induced partly at the transcriptional level through HLH-30 activation and are required to protect metazoan upon PFT intoxication. Together, our data show a new and powerful connection between HLH-30-mediated autophagy and epithelium intrinsic cellular defense against the single most common mode of bacterial attack in vivo.

  2. Flat Cellular (UMTS) Networks

    NARCIS (Netherlands)

    Bosch, H.G.P.; Samuel, L.G.; Mullender, S.J.; Polakos, P.; Rittenhouse, G.

    2007-01-01

    Traditionally, cellular systems have been built in a hierarchical manner: many specialized cellular access network elements that collectively form a hierarchical cellular system. When 2G and later 3G systems were designed there was a good reason to make system hierarchical: from a cost-perspective i

  3. Evaluation of an Aqueous-Ethanolic Extract from Rosmarinus officinalis (Rosemary) for its Activity on the Hormonal and Cellular Function of Testes in Adult Male Rat

    OpenAIRE

    Heidari-Vala, Hamed; Ebrahimi Hariry, Reza; Sadeghi, Mohammad Reza; Akhondi, Mohammad Mehdi; Ghaffari Novin, Marefat; Heidari, Mahnaz

    2013-01-01

    Rosmarinus officinalis has been used in traditional medicine extensively. This study evaluated the hormonal and cellular effects of Rosmarinus officinalis extract on testes of adult rats. Thirty male Wistar rats (in three groups) received 50 or 100 mg/Kg b.w of Rosmarinus officinalis extract (made from the plant’s leaves, flower and stem) (treatment groups) and 10 mL/Kg b.w normal saline (control group) respectively, on a daily bases by gavage route for 60 days. Then, spermatological properti...

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

  5. 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.

  6. 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 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 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.

  7. Glycosylation regulates prestin cellular activity.

    Science.gov (United States)

    Rajagopalan, Lavanya; Organ-Darling, Louise E; Liu, Haiying; Davidson, Amy L; Raphael, Robert M; Brownell, William E; Pereira, Fred A

    2010-03-01

    Glycosylation is a common post-translational modification of proteins and is implicated in a variety of cellular functions including protein folding, degradation, sorting and trafficking, and membrane protein recycling. The membrane protein prestin is an essential component of the membrane-based motor driving electromotility changes (electromotility) in the outer hair cell (OHC), a central process in auditory transduction. Prestin was earlier identified to possess two N-glycosylation sites (N163, N166) that, when mutated, marginally affect prestin nonlinear capacitance (NLC) function in cultured cells. Here, we show that the double mutant prestin(NN163/166AA) is not glycosylated and shows the expected NLC properties in the untreated and cholesterol-depleted HEK 293 cell model. In addition, unlike WT prestin that readily forms oligomers, prestin(NN163/166AA) is enriched as monomers and more mobile in the plasma membrane, suggesting that oligomerization of prestin is dependent on glycosylation but is not essential for the generation of NLC in HEK 293 cells. However, in the presence of increased membrane cholesterol, unlike the hyperpolarizing shift in NLC seen with WT prestin, cells expressing prestin(NN163/166AA) exhibit a linear capacitance function. In an attempt to explain this finding, we discovered that both WT prestin and prestin(NN163/166AA) participate in cholesterol-dependent cellular trafficking. In contrast to WT prestin, prestin(NN163/166AA) shows a significant cholesterol-dependent decrease in cell-surface expression, which may explain the loss of NLC function. Based on our observations, we conclude that glycosylation regulates self-association and cellular trafficking of prestin(NN163/166AA). These observations are the first to implicate a regulatory role for cellular trafficking and sorting in prestin function. We speculate that the cholesterol regulation of prestin occurs through localization to and internalization from membrane microdomains by

  8. 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.

  9. 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.

  10. 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

  11. Reversible quantum cellular automata

    CERN Document Server

    Schumacher, B

    2004-01-01

    We define quantum cellular automata as infinite quantum lattice systems with discrete time dynamics, such that the time step commutes with lattice translations and has strictly finite propagation speed. In contrast to earlier definitions this allows us to give an explicit characterization of all local rules generating such automata. The same local rules also generate the global time step for automata with periodic boundary conditions. Our main structure theorem asserts that any quantum cellular automaton is structurally reversible, i.e., that it can be obtained by applying two blockwise unitary operations in a generalized Margolus partitioning scheme. This implies that, in contrast to the classical case, the inverse of a nearest neighbor quantum cellular automaton is again a nearest neighbor automaton. We present several construction methods for quantum cellular automata, based on unitaries commuting with their translates, on the quantization of (arbitrary) reversible classical cellular automata, on quantum c...

  12. 仔猪痢清对动物细胞免疫功能影响的研究%Preliminary Study on the Effects of Zizhuliqing on Animal Cellular Immune Function

    Institute of Scientific and Technical Information of China (English)

    洪伟鸣; 邢晓玲; 郁杰; 葛竹兴; 王妲妲

    2008-01-01

    [Objective] The study aimed to explore the effects of Zizhuliqing Oral Liquid on animal cellular immune function. [Method] MTT method and phagocytizing natural red method were used to determine the effects of Zizhuliqing Oral Liquid on piglet lymphocyte transformation and the phagocytosis of mouse peritoneal macrophages respectively. [Result] The lymphocyte transformation rates of piglets in medicated groups were significantly higher than that in control group; the difference of mouse peritoneal macrophage activities between the medicated groups and the control group was obvious. [Conclusion] Zizhuliqing Oral Liquid could promote the transformation of piglet T lymphocytes induced by ConA and the phagocytosis of mouse peritoneal macrophages to natural red, indicating its good immune enhancement function.

  13. RNA interference-mediated targeting of human cytomegalovirus immediate-early or early gene products inhibits viral replication with differential effects on cellular functions.

    Science.gov (United States)

    Xiaofei, E; Stadler, Bradford M; Debatis, Michelle; Wang, Shixia; Lu, Shan; Kowalik, Timothy F

    2012-05-01

    Viral drug toxicity, resistance, and an increasing immunosuppressed population warrant continued research into new avenues for limiting diseases associated with human cytomegalovirus (HCMV). In this study, a small interfering RNA (siRNA), siX3, was designed to target coding sequences within shared exon 3 of UL123 and UL122 transcripts encoding IE1 and IE2 immediate-early proteins of HCMV. Pretreatment of cells with siX3 reduced the levels of viral protein expression, DNA replication, and progeny virus production compared to control siRNA. Two siRNAs against UL54 and overlapping transcripts (UL55-57) were compared to siX3 in HCMV infection and were also found to be effective at inhibiting HCMV replication. Further investigation into the effects of the siRNAs on viral replication showed that pretreatment with each of the siRNAs resulted in an inhibition in the formation of mature replication compartments. The ability of these siRNAs to prevent or reduce certain cytopathic effects associated with HCMV infection was also examined. Infected cells pretreated with siX3, but not siUL54, retained promyelocytic leukemia (PML) protein in cellular PML bodies, an essential component of this host intrinsic antiviral defense. DNA damage response proteins, which are localized in nuclear viral replication compartments, were reduced in the siX3- and siUL54-treated cells. siX3, but not siUL54, prevented DNA damage response signaling early after infection. Therapeutic efficacy was demonstrated by treating cells with siRNAs after HCMV replication had commenced. Together, these findings suggest that siRNAs targeting exon 3 of the major IE genes or the UL54-57 transcripts be further studied for their potential development into anti-HCMV therapeutics.

  14. 基于神经网络模型的双混沌 Hash 函数构造%A Dual Chaotic Hash Function Based on Cellular Neural Network

    Institute of Scientific and Technical Information of China (English)

    刘慧; 赵耿; 白健

    2014-01-01

    高效快速的单向Hash函数是当前安全技术研究的热点。文章采用神经网络结构构造了一种Hash函数,由Logistic映射和Chebyshev映射结合起来的双混沌系统产生该神经网络的参数,将明文信息逐块进行处理,并最终通过异或产生128 bit的Hash值。经实验数据和仿真分析可知:文章提出的方案满足单向Hash函数所要求的混乱和置换特性,并且具有很好的弱碰撞性和初值敏感性;另外,该方案结构简单容易实现。%The Hash function with high speed and efifciency has been a hotspot of security. In this paper, a new Hash function based on cellular neural network was proposed. The parameters of the cellular neural network were produced by a unique system which combined the Logistic map with the Chebyshev map. The function can handle the plaintext by the block, and the ifnal 128 Hash value is the xor of every block’s Hash value. The experimental data and simulated analysis show that the proposed algorithm can satisfy the requirements of a secure hash function, and it has some good properties such as diffusion, confusion, weak collision and sensitivity to initial conditions. What’s more, the construction of the scheme can be achieved easily.

  15. 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

  16. SR-BI as target in atherosclerosis and cardiovascular disease - A comprehensive appraisal of the cellular functions of SR-BI in physiology and disease.

    Science.gov (United States)

    Hoekstra, Menno

    2017-01-31

    High-density lipoprotein (HDL) is considered an anti-atherogenic lipoprotein species due to its role in reverse cholesterol transport. HDL delivers cholesterol esters to the liver through selective uptake by scavenger receptor class B type I (SR-BI). In line with the protective role for HDL in the context of cardiovascular disease, studies in mice and recently also in humans have shown that a disruption of normal SR-BI function predisposes subjects to the development of atherosclerotic lesions and cardiovascular disease. Although SR-BI function has been studied primarily in the liver, it should be acknowledged that the SR-BI protein is expressed in multiple tissues and cell types across the body, albeit at varying levels between the different tissues. Given that SR-BI is widely expressed throughout the body, multiple cell types and tissues can theoretically contribute to the atheroprotective effect of SR-BI. In this review the different functions of SR-BI in normal physiology are highlighted and the (potential) consequences of cell type-specific disruption of SR-BI function for atherosclerosis and cardiovascular disease susceptibility discussed. It appears that hepatocyte and platelet SR-BI inhibit respectively the development of atherosclerotic lesions and thrombosis, suggesting that SR-BI located on these cell compartments should be regarded as being a protective factor in the context of cardiovascular disease. The relative contribution of SR-BI present on endothelial cells, steroidogenic cells, adipocytes and macrophages to the pathogenesis of atherosclerosis and cardiovascular disease remains less clear, although proper SR-BI function in these cells does appear to influence multiple processes that impact on cardiovascular disease susceptibility.

  17. The insect cellular immune response

    Institute of Scientific and Technical Information of China (English)

    Michael R. Strand

    2008-01-01

    The innate immune system of insects is divided into humoral defenses that include the production of soluble effector molecules and cellular defenses like phagocytosis and encapsulation that are mediated by hemocytes. This review summarizes current understanding of the cellular immune response. Insects produce several terminally differentiated types of hemocytes that are distinguished by morphology, molecular and antigenic markers, and function. The differentiated hemocytes that circulate in larval or nymphal stage insects arise from two sources: progenitor cells produced during embryogenesis and mesodermally derived hematopoietic organs. Regulation of hematopoiesis and hemocyte differentiation also involves several different signaling pathways. Phagocytosis and encapsulation require that hemocytes first recognize a given target as foreign followed by activation of downstream signaling and effector responses. A number of humoral and cellular receptors have been identified that recognize different microbes and multicellular parasites. In turn, activation of these receptors stimulates a number of signaling pathways that regulate different hemocyte functions. Recent studies also identify hemocytes as important sources of a number of humoral effector molecules required for killing different foreign invaders.

  18. Investigation of molecular and cellular events associated with beta cell function and elucidation of extracellular RNAs as potential biomarker for diabetes

    OpenAIRE

    Rani, Sweta

    2009-01-01

    Diabetes is a chronic disorder of glucose metabolism and a major cause of premature mortality. The potential use of replacement beta cells as therapy for diabetes requires an ability to culture such cells while maintaining their functional status. Glucose stimulated insulin secretion (GSIS) is lost in long-term cultured MIN6 heterogeneous cells. MIN6 B1, a clonal sub-line derived from MIN6, has been described as highly glucose-responsive. This study aimed to investigate the GSIS functio...

  19. The Functional Landscape of Hsp27 Reveals New Cellular Processes such as DNA Repair and Alternative Splicing and Proposes Novel Anticancer Targets*

    Science.gov (United States)

    Katsogiannou, Maria; Andrieu, Claudia; Baylot, Virginie; Baudot, Anaïs; Dusetti, Nelson J.; Gayet, Odile; Finetti, Pascal; Garrido, Carmen; Birnbaum, Daniel; Bertucci, François; Brun, Christine; Rocchi, Palma

    2014-01-01

    Previously, we identified the stress-induced chaperone, Hsp27, as highly overexpressed in castration-resistant prostate cancer and developed an Hsp27 inhibitor (OGX-427) currently tested in phase I/II clinical trials as a chemosensitizing agent in different cancers. To better understand the Hsp27 poorly-defined cytoprotective functions in cancers and increase the OGX-427 pharmacological safety, we established the Hsp27-protein interaction network using a yeast two-hybrid approach and identified 226 interaction partners. As an example, we showed that targeting Hsp27 interaction with TCTP, a partner protein identified in our screen increases therapy sensitivity, opening a new promising field of research for therapeutic approaches that could decrease or abolish toxicity for normal cells. Results of an in-depth bioinformatics network analysis allying the Hsp27 interaction map into the human interactome underlined the multifunctional character of this protein. We identified interactions of Hsp27 with proteins involved in eight well known functions previously related to Hsp27 and uncovered 17 potential new ones, such as DNA repair and RNA splicing. Validation of Hsp27 involvement in both processes in human prostate cancer cells supports our system biology-predicted functions and provides new insights into Hsp27 roles in cancer cells. PMID:25277244

  20. The functional landscape of Hsp27 reveals new cellular processes such as DNA repair and alternative splicing and proposes novel anticancer targets.

    Science.gov (United States)

    Katsogiannou, Maria; Andrieu, Claudia; Baylot, Virginie; Baudot, Anaïs; Dusetti, Nelson J; Gayet, Odile; Finetti, Pascal; Garrido, Carmen; Birnbaum, Daniel; Bertucci, François; Brun, Christine; Rocchi, Palma

    2014-12-01

    Previously, we identified the stress-induced chaperone, Hsp27, as highly overexpressed in castration-resistant prostate cancer and developed an Hsp27 inhibitor (OGX-427) currently tested in phase I/II clinical trials as a chemosensitizing agent in different cancers. To better understand the Hsp27 poorly-defined cytoprotective functions in cancers and increase the OGX-427 pharmacological safety, we established the Hsp27-protein interaction network using a yeast two-hybrid approach and identified 226 interaction partners. As an example, we showed that targeting Hsp27 interaction with TCTP, a partner protein identified in our screen increases therapy sensitivity, opening a new promising field of research for therapeutic approaches that could decrease or abolish toxicity for normal cells. Results of an in-depth bioinformatics network analysis allying the Hsp27 interaction map into the human interactome underlined the multifunctional character of this protein. We identified interactions of Hsp27 with proteins involved in eight well known functions previously related to Hsp27 and uncovered 17 potential new ones, such as DNA repair and RNA splicing. Validation of Hsp27 involvement in both processes in human prostate cancer cells supports our system biology-predicted functions and provides new insights into Hsp27 roles in cancer cells.

  1. Ankrd6 is a mammalian functional homolog of Drosophila planar cell polarity gene diego and regulates coordinated cellular orientation in the mouse inner ear.

    Science.gov (United States)

    Jones, Chonnettia; Qian, Dong; Kim, Sun Myoung; Li, Shuangding; Ren, Dongdong; Knapp, Lindsey; Sprinzak, David; Avraham, Karen B; Matsuzaki, Fumio; Chi, Fanglu; Chen, Ping

    2014-11-01

    The coordinated polarization of neighboring cells within the plane of the tissue, known as planar cell polarity (PCP), is a recurring theme in biology. It is required for numerous developmental processes for the form and function of many tissues and organs across species. The genetic pathway regulating PCP was first discovered in Drosophila, and an analogous but distinct pathway is emerging in vertebrates. It consists of membrane protein complexes known as core PCP proteins that are conserved across species. Here we report that the over-expression of the murine Ankrd6 (mAnkrd6) gene that shares homology with Drosophila core PCP gene diego causes a typical PCP phenotype in Drosophila, and mAnkrd6 can rescue the loss of function of diego in Drosophila. In mice, mAnkrd6 protein is asymmetrically localized in cells of the inner ear sensory organs, characteristic of components of conserved core PCP complexes. The loss of mAnkrd6 causes PCP defects in the inner ear sensory organs. Moreover, canonical Wnt signaling is significantly increased in mouse embryonic fibroblasts from mAnkrd6 knockout mice in comparison to wild type controls. Together, these results indicated that mAnkrd6 is a functional homolog of the Drosophila diego gene for mammalian PCP regulation and act to suppress canonical Wnt signaling.

  2. Nanostructured cellular networks.

    Science.gov (United States)

    Moriarty, P; Taylor, M D R; Brust, M

    2002-12-01

    Au nanocrystals spin-coated onto silicon from toluene form cellular networks. A quantitative statistical crystallography analysis shows that intercellular correlations drive the networks far from statistical equilibrium. Spin-coating from hexane does not produce cellular structure, yet a strong correlation is retained in the positions of nanocrystal aggregates. Mechanisms based on Marangoni convection alone cannot account for the variety of patterns observed, and we argue that spinodal decomposition plays an important role in foam formation.

  3. 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.

  4. 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

    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...

  5. Dimerization and thiol sensitivity of the salicylic acid binding thimet oligopeptidases TOP1 and TOP2 define their functions in redox-sensitive cellular pathways

    Directory of Open Access Journals (Sweden)

    Timothy James Westlake

    2015-05-01

    Full Text Available A long-term goal in plant research is to understand how plants integrate signals from multiple environmental stressors. The importance of salicylic acid (SA in plant response to biotic and abiotic stress is known, yet the molecular details of the SA-mediated pathways are insufficiently understood. Our recent work identified the peptidases TOP1 and TOP2 as critical components in plant response to pathogens and programmed cell death. In this study, we investigated the characteristics of TOPs related to the regulation of their enzymatic activity and function in oxidative stress response. We determined that TOP1 and TOP2 interact with themselves and each other and their ability to associate in dimers is influenced by SA. Biochemical characterization of the organellar TOP1 indicated sensitivity to redox changes and robust activity under a range of pH values. Treatments of top mutants with Methyl Viologen (MV revealed TOP1 and TOP2 as a modulators of the plant tolerance to MV, and that exogenous SA alleviates the toxicity of MV in top background. Finally, we generated a TOP-centered computational model of a plant cell whose simulation outputs replicate experimental findings and predict novel functions of TOP1 and TOP2. Altogether, our work indicates that TOP1 and TOP2 mediate plant responses to oxidative stress through spatially separated pathways and positions proteolysis in a network for plant response to diverse stressors.

  6. Cellular immune function change and chronic obstructive pulmonary disease%细胞免疫功能变化与慢性阻塞性肺疾病

    Institute of Scientific and Technical Information of China (English)

    姜素丽; 李亚; 李建生

    2012-01-01

    目前研究显示机体的免疫功能降低或紊乱在慢性阻塞性肺疾病的发生、发展过程中起着重要作用,执行非特异性免疫的细胞主要包括巨噬细胞、中性粒细胞、自然杀伤细胞、树突状细胞等,特异性免疫主要有T细胞和B细胞介导.参与免疫功能的细胞与慢性阻塞性肺疾病发生发展密切相关.%The current study shows that the body's immune function or disorders play an important role in the development and progression of chronic obstructive pulmonary disease (COPD).In which the non-specific immune cells include alveolar macrophage,polymorphonuclear,natural killer cells,dendritic cell,while the specific immunity are mediated by T lymphocytes and B lymphocyte cells. The cells involved in immune function are closely related with the development of COPD.

  7. Regulation of Vascular Tone, Angiogenesis and Cellular Bioenergetics by the 3-Mercaptopyruvate Sulfurtransferase/H2S Pathway: Functional Impairment by Hyperglycemia and Restoration by DL-α-Lipoic Acid.

    Science.gov (United States)

    Coletta, Ciro; Módis, Katalin; Szczesny, Bartosz; Brunyánszki, Attila; Oláh, Gábor; Rios, Ester C S; Yanagi, Kazunori; Ahmad, Akbar; Papapetropoulos, Andreas; Szabo, Csaba

    2015-02-18

    Hydrogen sulfide (H2S), as a reducing agent and an antioxidant molecule, exerts protective effects against hyperglycemic stress in the vascular endothelium. The mitochondrial enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is an important biological source of H2S. We have recently demonstrated that 3-MST activity is inhibited by oxidative stress in vitro and speculated that this may have an adverse effect on cellular homeostasis. In the current study, given the importance of H2S as a vasorelaxant, angiogenesis stimulator and cellular bioenergetic mediator, we first determined whether the 3-MST/H2S system plays a physiological regulatory role in endothelial cells. Next, we tested whether a dysfunction of this pathway develops during the development of hyperglycemia and μmol/L to diabetes-associated vascular complications. Intraperitoneal (IP) 3-MP (1 mg/kg) raised plasma H2S levels in rats. 3-MP (10 1 mmol/L) promoted angiogenesis in vitro in bEnd3 microvascular endothelial cells and in vivo in a Matrigel assay in mice (0.3-1 mg/kg). In vitro studies with bEnd3 cell homogenates demonstrated that the 3-MP-induced increases in H2S production depended on enzymatic activity, although at higher concentrations (1-3 mmol/L) there was also evidence for an additional nonenzymatic H2S production by 3-MP. In vivo, 3-MP facilitated wound healing in rats, induced the relaxation of dermal microvessels and increased mitochondrial bioenergetic function. In vitro hyperglycemia or in vivo streptozotocin diabetes impaired angiogenesis, attenuated mitochondrial function and delayed wound healing; all of these responses were associated with an impairment of the proangiogenic and bioenergetic effects of 3-MP. The antioxidants DL-α-lipoic acid (LA) in vivo, or dihydrolipoic acid (DHLA) in vitro restored the ability of 3-MP to stimulate angiogenesis, cellular bioenergetics and wound healing in hyperglycemia and diabetes. We conclude that diabetes leads to an impairment of the 3-MST

  8. Association of oxidative DNA damage, protein oxidation and antioxidant function with oxidative stress induced cellular injury in pre-eclamptic/eclamptic mothers during fetal circulation.

    Science.gov (United States)

    Negi, Reena; Pande, Deepti; Karki, Kanchan; Kumar, Ashok; Khanna, Ranjana S; Khanna, Hari D

    2014-02-05

    Pre-eclampsia is a devastating multi system syndrome and a major cause of maternal, fetal, neonatal morbidity and mortality. Pre-eclampsia is associated with oxidative stress in the maternal circulation. To have an insight on the effect of pre-eclampsia/eclampsia on the neonates, the study was made to explore the oxidative status by quantification of byproducts generated during protein oxidation and oxidative DNA damage and deficient antioxidant activity in umbilical cord blood of pre-eclamptic/eclamptic mothers during fetal circulation. Umbilical cord blood during delivery from neonates born to 19 pre-eclamptic mothers, 14 eclamptic mothers and 18 normotensive mothers (uncomplicated pregnancy) as control cases was collected. 8-OHdG (8-hydroxy-2-deoxyguanosine), protein carbonyl, nitrite, catalase, non-enzymatic antioxidants (vitamin A, E, C), total antioxidant status and iron status were determined. Significant elevation in the levels of 8-OHdG, protein carbonyl, nitrite and iron along with decreased levels of catalase, vitamin A, E, C, total antioxidant status were observed in the umbilical cord blood of pre-eclamptic and eclamptic pregnancies. These parameters might be influential variables for the risk of free radical damage in infants born to pre-eclamptic/eclamptic pregnancies. Increased oxidative stress causes oxidation of DNA and protein which alters antioxidant function. Excess iron level and decreased unsaturated iron binding capacity may be the important factor associated with oxidative stress and contribute in the pathogenesis of pre-eclampsia/eclampsia which is reflected in fetal circulation.

  9. Cellular and Molecular Mechanisms of TSLP Function in Human Allergic Disorders - TSLP Programs the “Th2 code” in Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Tomoki Ito

    2012-01-01

    Full Text Available Thymic stromal lymphopoietin (TSLP has been recently implicated as a key molecule for initiating allergic inflammation at the epithelial cell-dendritic cell (DC interface. In humans, aberrant TSLP expression is observed in allergic tissues, such as lesional skins of atopic dermatitis, lungs of asthmatics, nasal mucosa of atopic rhinitis and nasal polyps, and ocular surface of allergic keratoconjunctivitis. TSLP is produced predominantly by damaged epithelial cells and stimulates myeloid DCs (mDCs. TSLP-activated mDCs can promote the differentiation of naive CD4+ T cells into a Th2 phenotype and the expansion of CD4+ Th2 memory cells in a unique manner dependent on OX40L, one of the tumor necrosis factor superfamily members with Th2-promoting function, and lack of production of IL-12. From a genetic point of view, multiple genome-wide association studies have repeatedly identified the TSLP gene as one of the loci associated with susceptibility to allergic diseases. Thus, TSLP is a rational therapeutic target for the treatment of allergic disorders. Elucidating the mechanisms that regulate TSLP expression and the effects of TSLP on orchestrating the immune response toward a Th2 phenotype is essential for developing anti-TSLP therapy.

  10. Cellular function of microRNA-15 family%microRNA-15家族功能研究进展

    Institute of Scientific and Technical Information of China (English)

    刘丽凤; 王禹

    2012-01-01

    微小RNA (microRNAs,miRNAs)是一类具有转录后调节作用的短小的内源性非编码RNA,其中miR-15家族参与凋亡、细胞分化与周期调控、应激等重要细胞功能活动的调节,并与多种人类疾病如肿瘤、心血管疾病、神经退行性疾病等相关,具有潜在的治疗前景及干预价值.本文就miR- 15家族的重要功能及治疗应用前景作一综述.%micro RNAs (miRNAs) are non-coding endogenous short RNAs which are involved in regulating gene expression at the post-transcriptional level. miR-15 family is increasingly found to play great roles in important cell processes, such as apoptosis, cell differentiation and stress response. Growing evidence indicates that miR-15 family members are implicated in tumor, cardiovascular disease and neurodegenerative disease. miRNAs have emerged as a new promising subset of therapeutic targets. The present paper re viewed the important function of miR-15 family and new approaches for miRNA-based therapy.

  11. 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.

  12. A novel, live-attenuated vesicular stomatitis virus vector displaying conformationally intact, functional HIV-1 envelope trimers that elicits potent cellular and humoral responses in mice.

    Directory of Open Access Journals (Sweden)

    Svetlana Rabinovich

    Full Text Available Though vaccination with live-attenuated SIV provides the greatest protection from progressive disease caused by SIV challenge in rhesus macaques, attenuated HIV presents safety concerns as a vaccine; therefore, live viral vectors carrying HIV immunogens must be considered. We have designed a replication-competent vesicular stomatitis virus (VSV displaying immunogenic HIV-1 Env trimers and attenuating quantities of the native surface glycoprotein (G. The clade B Env immunogen is an Env-VSV G hybrid (EnvG in which the transmembrane and cytoplasmic tail regions are derived from G. Relocation of the G gene to the 5'terminus of the genome and insertion of EnvG into the natural G position induced a ∼1 log reduction in surface G, significant growth attenuation compared to wild-type, and incorporation of abundant EnvG. Western blot analysis indicated that ∼75% of incorporated EnvG was a mature proteolytically processed form. Flow cytometry showed that surface EnvG bound various conformationally- and trimer-specific antibodies (Abs, and in-vitro growth assays on CD4+CCR5+ cells demonstrated EnvG functionality. Neither intranasal (IN or intramuscular (IM administration in mice induced any observable pathology and all regimens tested generated potent Env-specific ELISA titers of 10(4-10(5, with an IM VSV prime/IN VSV boost regimen eliciting the highest binding and neutralizing Ab titers. Significant quantities of Env-specific CD4+ T cells were also detected, which were augmented as much as 70-fold by priming with IM electroporated plasmids encoding EnvG and IL-12. These data suggest that our novel vector can achieve balanced safety and immunogenicity and should be considered as an HIV vaccine platform.

  13. Cellular Functions and Gene and Protein Expression Profiles in Endothelial Cells Derived from Moyamoya Disease-Specific iPS Cells

    Science.gov (United States)

    Hamauchi, Shuji; Shichinohe, Hideo; Uchino, Haruto; Yamaguchi, Shigeru; Nakayama, Naoki; Kazumata, Ken; Osanai, Toshiya; Abumiya, Takeo; Houkin, Kiyohiro; Era, Takumi

    2016-01-01

    Background and purpose Moyamoya disease (MMD) is a slow, progressive steno-occlusive disease, arising in the terminal portions of the cerebral internal carotid artery. However, the functions and characteristics of the endothelial cells (ECs) in MMD are unknown. We analyzed these features using induced pluripotent stem cell (iPSC)-derived ECs. Methods iPSC lines were established from the peripheral blood of three patients with MMD carrying the variant RNF213 R4810K, and three healthy persons used as controls. After the endothelial differentiation of iPSCs, CD31+CD144+ cells were purified as ECs using a cell sorter. We analyzed their proliferation, angiogenesis, and responses to some angiogenic factors, namely VEGF, bFGF, TGF-β, and BMP4. The ECs were also analyzed using DNA microarray and proteomics to perform comprehensive gene and protein expression analysis. Results Angiogenesis was significantly impaired in MMD regardless of the presence of any angiogenic factor. On the contrary, endothelial proliferation was not significant between control- and MMD-derived cells. Regarding DNA microarray, pathway analysis illustrated that extracellular matrix (ECM) receptor-related genes, including integrin β3, were significantly downregulated in MMD. Proteomic analysis revealed that cytoskeleton-related proteins were downregulated and splicing regulation-related proteins were upregulated in MMD. Conclusions Downregulation of ECM receptor-related genes may be associated with impaired angiogenic activity in ECs derived from iPSCs from patients with MMD. Upregulation of splicing regulation-related proteins implied differences in splicing patterns between control and MMD ECs. PMID:27662211

  14. Cellular immune responses to HIV

    Science.gov (United States)

    McMichael, Andrew J.; Rowland-Jones, Sarah L.

    2001-04-01

    The cellular immune response to the human immunodeficiency virus, mediated by T lymphocytes, seems strong but fails to control the infection completely. In most virus infections, T cells either eliminate the virus or suppress it indefinitely as a harmless, persisting infection. But the human immunodeficiency virus undermines this control by infecting key immune cells, thereby impairing the response of both the infected CD4+ T cells and the uninfected CD8+ T cells. The failure of the latter to function efficiently facilitates the escape of virus from immune control and the collapse of the whole immune system.

  15. ING proteins in cellular senescence.

    Science.gov (United States)

    Menéndez, Camino; Abad, María; Gómez-Cabello, Daniel; Moreno, Alberto; Palmero, Ignacio

    2009-05-01

    Cellular senescence is an effective anti-tumor barrier that acts by restraining the uncontrolled proliferation of cells carrying potentially oncogenic alterations. ING proteins are putative tumor suppressor proteins functionally linked to the p53 pathway and to chromatin regulation. ING proteins exert their tumor-protective action through different types of responses. Here, we review the evidence on the participation of ING proteins, mainly ING1 and ING2, in the implementation of the senescent response. The currently available data support an important role of ING proteins as regulators of senescence, in connection with the p53 pathway and chromatin organization.

  16. Cellular blue naevus

    Directory of Open Access Journals (Sweden)

    Mittal R

    2001-01-01

    Full Text Available A 31-year-old man had asymptomatic, stationary, 1.5X2 cm, shiny, smooth, dark blue nodule on dorsum of right hand since 12-14 years. In addition he had developed extensive eruption of yellow to orange papulonodular lesions on extensors of limbs and buttocks since one and half months. Investigations confirmed that yellow papules were xanthomatosis and he had associated diabetes mellitus and hyperlipidaemia. Biopsy of blue nodule confirmed the clinical diagnosis of cellular blue naevus. Cellular blue naevus is rare and its association with xanthomatosis and diabetes mellitus were interesting features of above patients which is being reported for its rarity.

  17. 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

  18. 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

  19. Cellular Response to Irradiation

    Institute of Scientific and Technical Information of China (English)

    LIU Bo; YAN Shi-Wei

    2011-01-01

    To explore the nonlinear activities of the cellular signaling system composed of one transcriptional arm and one protein-interaction arm, we use an irradiation-response module to study the dynamics of stochastic interactions.It is shown that the oscillatory behavior could be described in a unified way when the radiation-derived signal and noise are incorporated.

  20. Cellular compartmentalization of secondary metabolism

    Directory of Open Access Journals (Sweden)

    H. Corby eKistler

    2015-02-01

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

  1. Expression pattern, ethanol-metabolizing activities, and cellular localization of alcohol and aldehyde dehydrogenases in human large bowel: association of the functional polymorphisms of ADH and ALDH genes with hemorrhoids and colorectal cancer.

    Science.gov (United States)

    Chiang, Chien-Ping; Jao, Shu-Wen; Lee, Shiao-Pieng; Chen, Pei-Chi; Chung, Chia-Chi; Lee, Shou-Lun; Nieh, Shin; Yin, Shih-Jiun

    2012-02-01

    Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal enzymes responsible for metabolism of ethanol. Functional polymorphisms of ADH1B, ADH1C, and ALDH2 genes occur among racial populations. The goal of this study was to systematically determine the functional expressions and cellular localization of ADHs and ALDHs in human rectal mucosa, the lesions of adenocarcinoma and hemorrhoid, and the genetic association of allelic variations of ADH and ALDH with large bowel disorders. Twenty-one surgical specimens of rectal adenocarcinoma and the adjacent normal mucosa, including 16 paired tissues of rectal tumor, normal mucosae of rectum and sigmoid colon from the same individuals, and 18 surgical mixed hemorrhoid specimens and leukocyte DNA samples from 103 colorectal cancer patients, 67 hemorrhoid patients, and 545 control subjects recruited in previous study, were investigated. The isozyme/allozyme expression patterns of ADH and ALDH were identified by isoelectric focusing and the activities were assayed spectrophotometrically. The protein contents of ADH/ALDH isozymes were determined by immunoblotting using the corresponding purified class-specific antibodies; the cellular activity and protein localizations were detected by immunohistochemistry and histochemistry, respectively. Genotypes of ADH1B, ADH1C, and ALDH2 were determined by polymerase chain reaction-restriction fragment length polymorphisms. At 33mM ethanol, pH 7.5, the activity of ADH1C*1/1 phenotypes exhibited 87% higher than that of the ADH1C*1/*2 phenotypes in normal rectal mucosa. The activity of ALDH2-active phenotypes of rectal mucosa was 33% greater than ALDH2-inactive phenotypes at 200μM acetaldehyde. The protein contents in normal rectal mucosa were in the following order: ADH1>ALDH2>ADH3≈ALDH1A1, whereas those of ADH2, ADH4, and ALDH3A1 were fairly low. Both activity and content of ADH1 were significantly decreased in rectal tumors, whereas the ALDH activity remained

  2. 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

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

    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。

  4. 芪杞参颗粒对小鼠的细胞免疫和体液免疫功能的影响%The Influence of Qiqishen Granules on the Cellular and Humoral Immune Function

    Institute of Scientific and Technical Information of China (English)

    李宏; 戴学文; 房志仲; 高卫真

    2013-01-01

      目的研究芪杞参颗粒对小鼠的细胞免疫和体液免疫功能的影响。方法6周龄昆明种小鼠分空白对照组、芪杞参颗粒高、中、低剂量组,小鼠腹腔注射鸡红细胞混悬液,观察芪杞参颗粒对小鼠腹腔巨噬细胞吞噬功能的影响;制备绵羊红细胞(SRBC),观察血球凝集程度,测定血清溶血素;以靶细胞(YAC-1细胞)与脾细胞(效应细胞)的反应检测芪杞参颗粒对小鼠自然杀伤(NK)细胞活性的影响;采用淋巴细胞转化法观察芪杞参颗粒对细胞免疫的影响;计算小鼠胸腺质量/体质量及脾脏质量/体质量为脏器系数观察芪杞参颗粒对小鼠脏器的影响。结果与对照组比较,芪杞参颗粒显著增加小鼠腹腔巨噬细胞吞噬功能;对小鼠体液免疫功能有一定的增强作用;可增强小鼠NK细胞活性;对刀豆蛋白(Con)A诱导下的小鼠淋巴细胞转化有增强作用;对脏器系数没有显著的影响。结论芪杞参颗粒具有明显的免疫调节作用,预示其有良好的应用前景。%Objective To study the influence of qiqishen granules on the cellular and humoral immune functions in model mice. Methods Six-week-old mice were divided into control group and qiqishen granule (high, medium and low dose) groups. The suspension of chicken red blood cells was injected into the mouse abdominal cavity. The influence of qiq-ishen granules on the phagocytic function of the macrophages in mouse abdominal cavity was observed. The sheep red blood cells (SRBC) were prepared. The blood corpuscle coagulation was observed, and the serum hemolysin was detected. The ac-tivity of the mouse natural killer (NK) cells were detected by the interaction between the target cell (YAC-1) and spleen cell (the response cell). The influence of qiqishen granules on the cellular immunity was detected by the lymphocyte transforming assay. The influence of qiqishen granules on organ/body weight ratio

  5. Cellular communication through light.

    Directory of Open Access Journals (Sweden)

    Daniel Fels

    Full Text Available Information transfer is a fundamental of life. A few studies have reported that cells use photons (from an endogenous source as information carriers. This study finds that cells can have an influence on other cells even when separated with a glass barrier, thereby disabling molecule diffusion through the cell-containing medium. As there is still very little known about the potential of photons for intercellular communication this study is designed to test for non-molecule-based triggering of two fundamental properties of life: cell division and energy uptake. The study was performed with a cellular organism, the ciliate Paramecium caudatum. Mutual exposure of cell populations occurred under conditions of darkness and separation with cuvettes (vials allowing photon but not molecule transfer. The cell populations were separated either with glass allowing photon transmission from 340 nm to longer waves, or quartz being transmittable from 150 nm, i.e. from UV-light to longer waves. Even through glass, the cells affected cell division and energy uptake in neighboring cell populations. Depending on the cuvette material and the number of cells involved, these effects were positive or negative. Also, while paired populations with lower growth rates grew uncorrelated, growth of the better growing populations was correlated. As there were significant differences when separating the populations with glass or quartz, it is suggested that the cell populations use two (or more frequencies for cellular information transfer, which influences at least energy uptake, cell division rate and growth correlation. Altogether the study strongly supports a cellular communication system, which is different from a molecule-receptor-based system and hints that photon-triggering is a fine tuning principle in cell chemistry.

  6. Cellular automata: structures

    OpenAIRE

    Ollinger, Nicolas

    2002-01-01

    Jury : François Blanchard (Rapporteur), Marianne Delorme (Directeur), Jarkko Kari (Président), Jacques Mazoyer (Directeur), Dominique Perrin, Géraud Sénizergues (Rapporteur); Cellular automata provide a uniform framework to study an important problem of "complex systems" theory: how and why do system with a easily understandable -- local -- microscopic behavior can generate a more complicated -- global -- macroscopic behavior? Since its introduction in the 40s, a lot of work has been done to ...

  7. 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...... 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....

  8. 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.

  9. 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.

  10. Refining cellular automata with routing constraints

    OpenAIRE

    Millo, Jean-Vivien; De Simone, Robert

    2012-01-01

    A cellular automaton (CA) is an infinite array of cells, each containing the same automaton. The dynamics of a CA is distributed over the cells where each computes its next state as a function of the previous states of its neighborhood. Thus, the transmission of such states between neighbors is considered as feasible directly, in no time. When considering the implementation of a cellular automaton on a many-cores System-on-Chip (SoC), this state transmission is no longer abstract and instanta...

  11. Effects of mild perioperative hypothermia on cellular immune function in patients undergoing surgery for rectal cancer%轻度低温对直肠癌根治术患者细胞免疫功能的影响

    Institute of Scientific and Technical Information of China (English)

    赵敏; 赵光瑜; 戴春宇; 张毅

    2012-01-01

    Objective To investigate the effects of mild pefioperative hypothermia on cellular immune function in patients undergoing surgery for rectal cancer.Methods Fifty ASA Ⅰ or Ⅱ patients aged 30-64 yr undergoing surgery for rectal cancer were randomly divided into 2 groups ( n =25 each):mild hypothermia group and normal body temperature group.Anesthesia was induced with midazolam,fentanyl,etomidate and vecuronium and maintained with propofol,remifentanil and vecuronium.The patients were mechanically ventilated after tracheal intubation.PET CO2 was maintained at 35-45 mm Hg.The venous blood samples were taken from peripheral vein at 1 h before anesthesia (T1 ),at the end of operation (T2),at 24 h after operation (T3),and on 7th day after operation (T4) to measure the serum Th1 and Th2 cytokines levels and Th1/Th2 cytokines balance was observed.Results Compared with the baseline value at T1,the serum Th2 cytokines level was significantly decreased and Th1/Th2 ratio was significantly increased at T4 in normal body temperature group,and the serum Th1 cytokines level and Th1/Th2 ratio were significantly decreased and the serum Th2 cytokines level was significantly increased at T2.3 in mild hypothermia group ( P < 0.05).Compared with normal body temperature group,the serum Th1 cytokines level and Th1/Th2 ratio were significantly decreased and the serum Th2 cytokines level was significantly increased at T2-4 in mild hypothermia group ( P < 0.05).Conclusion Mild perioperative hypothermia can depress cellular immune function in patients undergoing surgery for rectal cancer.%目的 评价轻度低温对直肠癌根治术患者细胞免疫功能的影响.方法 择期拟行直肠癌根治术患者50例,ASA分级Ⅰ或Ⅱ级,年龄30~64岁,采用随机数字表法,将其随机分为轻度低温组和常温组,每组25例.分别于麻醉前1 h(T1)、手术结束时(T2)、术后24 h(T3)及术后第7天(T4)采用流式细胞仪测定血清Th1型、Th2

  12. 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.

  13. Crack Propagation in Bamboo's Hierarchical Cellular Structure

    Science.gov (United States)

    Habibi, Meisam K.; Lu, Yang

    2014-07-01

    Bamboo, as a natural hierarchical cellular material, exhibits remarkable mechanical properties including excellent flexibility and fracture toughness. As far as bamboo as a functionally graded bio-composite is concerned, the interactions of different constituents (bamboo fibers; parenchyma cells; and vessels.) alongside their corresponding interfacial areas with a developed crack should be of high significance. Here, by using multi-scale mechanical characterizations coupled with advanced environmental electron microscopy (ESEM), we unambiguously show that fibers' interfacial areas along with parenchyma cells' boundaries were preferred routes for crack growth in both radial and longitudinal directions. Irrespective of the honeycomb structure of fibers along with cellular configuration of parenchyma ground, the hollow vessels within bamboo culm affected the crack propagation too, by crack deflection or crack-tip energy dissipation. It is expected that the tortuous crack propagation mode exhibited in the present study could be applicable to other cellular natural materials as well.

  14. Astrocytes and mitochondria from adrenoleukodystrophy protein (ABCD1)-deficient mice reveal that the adrenoleukodystrophy-associated very long-chain fatty acids target several cellular energy-dependent functions.

    Science.gov (United States)

    Kruska, Nicol; Schönfeld, Peter; Pujol, Aurora; Reiser, Georg

    2015-05-01

    X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative disorder resulting from defective ABCD1 transport protein. ABCD1 mediates peroxisomal uptake of free very-long-chain fatty acids (VLCFA) as well as their CoA-esters. Consequently, VLCFA accumulate in patients' plasma and tissues, which is considered as pathogenic X-ALD triggering factor. Clinical symptoms are mostly manifested in neural tissues and adrenal gland. Here, we investigate astrocytes from wild-type control and a genetic X-ALD mouse model (Abcd1-knockout), exposed to supraphysiological VLCFA (C22:0, C24:0 and C26:0) concentrations. They exhibit multiple impairments of energy metabolism. Furthermore, brain mitochondria from Abcd1(-/-) mice and wild-type control respond similarly to VLCFA with increased ROS generation, impaired oxidative ATP synthesis and diminished Ca(2+) uptake capacity, suggesting that a defective ABCD1 exerts no adaptive pressure on mitochondria. In contrast, astrocytes from Abcd1(-/-) mice respond more sensitively to VLCFA than wild-type control astrocytes. Moreover, long-term application of VLCFA induces high ROS generation, and strong in situ depolarization of mitochondria, and, in Abcd1(-/-) astrocytes, severely diminishes the capability to revert oxidized pyridine nucleotides to NAD(P)H. In addition, observed differences in responses of mitochondria and astrocytes to the hydrocarbon chain length of VLCFA suggest that detrimental VLCFA activities in astrocytes involve defective cellular functions other than mitochondria. In summary, we clearly demonstrate that VLCFA increase the vulnerability of Abcd1(-/-) astrocytes.

  15. Cellular image classification

    CERN Document Server

    Xu, Xiang; Lin, Feng

    2017-01-01

    This book introduces new techniques for cellular image feature extraction, pattern recognition and classification. The authors use the antinuclear antibodies (ANAs) in patient serum as the subjects and the Indirect Immunofluorescence (IIF) technique as the imaging protocol to illustrate the applications of the described methods. Throughout the book, the authors provide evaluations for the proposed methods on two publicly available human epithelial (HEp-2) cell datasets: ICPR2012 dataset from the ICPR'12 HEp-2 cell classification contest and ICIP2013 training dataset from the ICIP'13 Competition on cells classification by fluorescent image analysis. First, the reading of imaging results is significantly influenced by one’s qualification and reading systems, causing high intra- and inter-laboratory variance. The authors present a low-order LP21 fiber mode for optical single cell manipulation and imaging staining patterns of HEp-2 cells. A focused four-lobed mode distribution is stable and effective in optical...

  16. 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....

  17. Engineering Cellular Metabolism.

    Science.gov (United States)

    Nielsen, Jens; Keasling, Jay D

    2016-03-10

    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.

  18. Characterizing heterogeneous cellular responses to perturbations.

    Science.gov (United States)

    Slack, Michael D; Martinez, Elisabeth D; Wu, Lani F; Altschuler, Steven J

    2008-12-01

    Cellular populations have been widely observed to respond heterogeneously to perturbation. However, interpreting the observed heterogeneity is an extremely challenging problem because of the complexity of possible cellular phenotypes, the large dimension of potential perturbations, and the lack of methods for separating meaningful biological information from noise. Here, we develop an image-based approach to characterize cellular phenotypes based on patterns of signaling marker colocalization. Heterogeneous cellular populations are characterized as mixtures of phenotypically distinct subpopulations, and responses to perturbations are summarized succinctly as probabilistic redistributions of these mixtures. We apply our method to characterize the heterogeneous responses of cancer cells to a panel of drugs. We find that cells treated with drugs of (dis-)similar mechanism exhibit (dis-)similar patterns of heterogeneity. Despite the observed phenotypic diversity of cells observed within our data, low-complexity models of heterogeneity were sufficient to distinguish most classes of drug mechanism. Our approach offers a computational framework for assessing the complexity of cellular heterogeneity, investigating the degree to which perturbations induce redistributions of a limited, but nontrivial, repertoire of underlying states and revealing functional significance contained within distinct patterns of heterogeneous responses.

  19. 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…

  20. Cellular bioluminescence imaging.

    Science.gov (United States)

    Welsh, David K; Noguchi, Takako

    2012-08-01

    Bioluminescence imaging of live cells has recently been recognized as an important alternative to fluorescence imaging. Fluorescent probes are much brighter than bioluminescent probes (luciferase enzymes) and, therefore, provide much better spatial and temporal resolution and much better contrast for delineating cell structure. However, with bioluminescence imaging there is virtually no background or toxicity. As a result, bioluminescence can be superior to fluorescence for detecting and quantifying molecules and their interactions in living cells, particularly in long-term studies. Structurally diverse luciferases from beetle and marine species have been used for a wide variety of applications, including tracking cells in vivo, detecting protein-protein interactions, measuring levels of calcium and other signaling molecules, detecting protease activity, and reporting circadian clock gene expression. Such applications can be optimized by the use of brighter and variously colored luciferases, brighter microscope optics, and ultrasensitive, low-noise cameras. This article presents a review of how bioluminescence differs from fluorescence, its applications to cellular imaging, and available probes, optics, and detectors. It also gives practical suggestions for optimal bioluminescence imaging of single cells.

  1. Cellular neurothekeoma with melanocytosis.

    Science.gov (United States)

    Wu, Ren-Chin; Hsieh, Yi-Yueh; Chang, Yi-Chin; Kuo, Tseng-Tong

    2008-02-01

    Cellular neurothekeoma (CNT) is a benign dermal tumor mainly affecting the head and neck and the upper extremities. It is characterized histologically by interconnecting fascicles of plump spindle or epithelioid cells with ample cytoplasm infiltrating in the reticular dermis. The histogenesis of CNT has been controversial, although it is generally regarded as an immature counterpart of classic/myxoid neurothekeoma, a tumor with nerve sheath differentiation. Two rare cases of CNT containing melanin-laden cells were described. Immunohistochemical study with NKI/C3, vimentin, epithelial membrane antigen, smooth muscle antigen, CD34, factor XIIIa, collagen type IV, S100 protein and HMB-45 was performed. Both cases showed typical growth pattern of CNT with interconnecting fascicles of epithelioid cells infiltrating in collagenous stroma. One of the nodules contained areas exhibiting atypical cytological features. Melanin-laden epithelioid or dendritic cells were diffusely scattered throughout one nodule, and focally present in the peripheral portion of the other nodule. Both nodules were strongly immunoreactive to NKI/C3 and vimentin, but negative to all the other markers employed. CNT harboring melanin-laden cells may pose diagnostic problems because of their close resemblance to nevomelanocytic lesions and other dermal mesenchymal tumors. These peculiar cases may also provide further clues to the histogenesis of CNT.

  2. 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...

  3. Minimal model for complex dynamics in cellular processes.

    Science.gov (United States)

    Suguna, C; Chowdhury, K K; Sinha, S

    1999-11-01

    Cellular functions are controlled and coordinated by the complex circuitry of biochemical pathways regulated by genetic and metabolic feedback processes. This paper aims to show, with the help of a minimal model of a regulated biochemical pathway, that the common nonlinearities and control structures present in biomolecular interactions are capable of eliciting a variety of functional dynamics, such as homeostasis, periodic, complex, and chaotic oscillations, including transients, that are observed in various cellular processes.

  4. 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.

  5. Free fall and cellular automata

    Directory of Open Access Journals (Sweden)

    Pablo Arrighi

    2016-03-01

    Full Text Available Three reasonable hypotheses lead to the thesis that physical phenomena can be described and simulated with cellular automata. In this work, we attempt to describe the motion of a particle upon which a constant force is applied, with a cellular automaton, in Newtonian physics, in Special Relativity, and in General Relativity. The results are very different for these three theories.

  6. About Strongly Universal Cellular Automata

    Directory of Open Access Journals (Sweden)

    Maurice Margenstern

    2013-09-01

    Full Text Available In this paper, we construct a strongly universal cellular automaton on the line with 11 states and the standard neighbourhood. We embed this construction into several tilings of the hyperbolic plane and of the hyperbolic 3D space giving rise to strongly universal cellular automata with 10 states.

  7. Reactive Programming of Cellular Automata

    OpenAIRE

    Boussinot, Frédéric

    2004-01-01

    Implementation of cellular automata using reactive programming gives a way to code cell behaviors in an abstract and modular way. Multiprocessing also becomes possible. The paper describes the implementation of cellular automata with the reactive programming language LOFT, a thread-based extension of C. Self replicating loops considered in artificial life are coded to show the interest of the approach.

  8. Changes of cellular immune function with Chaihulongmu decoction in Lewis mice with iumg cancer%柴胡龙牡汤对Lewis肺癌小鼠细胞免疫功能的影响

    Institute of Scientific and Technical Information of China (English)

    潘玉真; 殷东风; 周立江; 朱颖

    2011-01-01

    Objective To study effects of Chaihulongmu decoction on cellular immune function such as T lymphocyte subgroup,NK cell activeness,IL-lO and γ-intefferon of Lewis mice with lung cancer. Methods The cells of Lewis lung cancer were planted in the right axilla of C57BL/6J inbred strain mice subcutaneously. The mice with cancer were randomly divided into model group ( MG), herbal group ( HG), DDP group (DG) and combination group (CG). The tumors were weighed when the mice were sacrificed in each group. Then the inhibition rate of tumor was calculated. The experiment of the lactic dehydrogenase (LDH) releasing was used to detect the activity of NK cell in the mouse spleens. The method of enzyme-linked immuno sorbent assay (ELISA) was used to detect the IL-10, γ-intefferon in the supernatant fluid of spleen. The rates of CD4, CD8 and the ratio of CD4/CD8 were detected by the flow cytometry (FCM) in the way of PE/FITC fluorescent staining in the spleens of mice. Results The inhibited effectiveness of CG was optimal, and the inhibition rate of tumor was 62.4%. There was significant difference comparing to DG and HG( P <0. 01 ). The activity of NK cell in HG was highest,and the difference was obvious comparing to MG, DG and CG( P < 0. 01 ). The content of IFN-γ was 65.78 ± 17. 68 in HG, which was higher than that in DG ( P < 0. 05 ). The content of IL-10 in MG was highest( 153. 30 ± 33. 14).In HG it was lower than MG, DG and CG( P < 0. 05 ). The figure of CD4 ± and the ratio of CD4 ± / CD8 ± in HG were the highest.Comparing to the MG and the DG, the difference was extremely obvious. (P <0.01 ). While the percentage of CD8 ± cell in each post-treatment group had no obvious changes. Conclusion The prescription of Chaihulongmu decoction can inhibit tumor and improve the cellular immune function through raising the level of IFN-γ, reducing the superior expression of IL-10, strengthening the activity of the NK cell, obviously elevating the percentage of the

  9. 星状神经节阻滞对糖尿病大鼠细胞免疫功能的影响%Effect of stellate ganglion block on cellular immune function in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    郎海丽; 胡小兰; 陈勇; 周志东; 蔡俊赢; 余树春; 徐国海

    2016-01-01

    目的 评价星状神经节阻滞对糖尿病大鼠细胞免疫功能的影响.方法 健康雄性SD大鼠,3月龄,体重240~ 280 g,采用腹腔注射1%链脲佐菌素60 mg/kg制备糖尿病模型.取糖尿病模型制备成功的大鼠48只,采用随机数字表法分为2组(n=24):糖尿病组(DM组)和星状神经节阻滞组(SGB组);另取健康同龄大鼠24只作为对照组(C组).SGB组于糖尿病模型制备成功1周后行右颈交感干离断术,C组和DM组仅分离右颈交感干.分别于颈交感干离断术前(T0)、术后1、3、7d(T13)时,随机取6只大鼠,采集下腔静脉血样,测定血糖浓度,采用ELISA法检测血浆去甲肾上腺素(NE)浓度,采用FACSCalibur流式细胞仪检测全血T淋巴细胞亚群CD3+、CD4+和CD8+的水平,计算CD4+/CD8+比值;处死前称重,解剖分离胸腺组织称重,计算胸腺指数(胸腺重量÷大鼠体重).结果 与C组比较,DM组和SGB组T0-3时血糖升高,全血CD3+和CD4+的水平、CD4+/CD8+比值和胸腺指数降低(P<0.05),CD8+水平差异无统计学意义(P>0.05),SGB组T1-3时血浆NE浓度降低(P<0.05),DM组血浆NE浓度差异无统计学意义(P>0.05);与DM组比较,SGB组T1-3时血糖及血浆NE浓度降低,全血CD3+和CD4+的水平、CD4+/CD8+比值和胸腺指数升高(P<0.05),CD8+水平差异无统计学意义(P>0.05).结论 星状神经节阻滞可改善糖尿病大鼠细胞免疫功能.%Objective To evaluate the effect of stellate ganglion block (SGB) on cellular immune function in diabetic rats.Methods Healthy male Sprague-Dawley rats,aged 3 months,weighing 240-280 g,were used in this study.Diabetes mellitus was induced by intraperitoneal 1% streptozotocin 60 mg/kg and confirmed by blood glucose ≥ 16.7 mmol/L 3 days later.Forty-eight rats with diabetes mellitus were randomly divided into 2 groups (n=24 each) using a random number table:diabetes mellitus group (group DM) and group SGB.Another 24 healthy rats,aged 3 months,were selected and served as

  10. 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,...

  11. The origins of cellular life.

    Science.gov (United States)

    Schrum, Jason P; Zhu, Ting F; Szostak, Jack W

    2010-09-01

    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 functional information. Recent studies of vesicles composed of fatty-acid membranes have shed considerable light on pathways for protocell growth and division, as well as means by which protocells could take up nutrients from their environment. Additional work with genetic polymers has provided insight into the potential for chemical genome replication and compatibility with membrane encapsulation. The integration of a dynamic fatty-acid compartment with robust, generalized genetic polymer replication would yield a laboratory model of a protocell with the potential for classical Darwinian biological evolution, and may help to evaluate potential pathways for the emergence of life on the early Earth. Here we discuss efforts to devise such an integrated protocell model.

  12. The cellular toxicity of aluminium.

    Science.gov (United States)

    Exley, C; Birchall, J D

    1992-11-07

    Aluminium is a serious environmental toxicant and is inimical to biota. Omnipresent, it is linked with a number of disorders in man including Alzheimer's disease, Parkinson's dementia and osteomalacia. Evidence supporting aluminium as an aetiological agent in such disorders is not conclusive and suffers principally from a lack of consensus with respect to aluminium's toxic mode of action. Obligatory to the elucidation of toxic mechanisms is an understanding of the biological availability of aluminium. This describes the fate of and response to aluminium in any biological system and is thus an important influence of the toxicity of aluminium. A general theme in much aluminium toxicity is an accelerated cell death. Herein mechanisms are described to account for cell death from both acute and chronic aluminium challenges. Aluminium associations with both extracellular surfaces and intracellular ligands are implicated. The cellular response to aluminium is found to be biphasic having both stimulatory and inhibitory components. In either case the disruption of second messenger systems is observed and GTPase cycles are potential target sites. Specific ligands for aluminium at these sites are unknown though are likely to be proteins upon which oxygen-based functional groups are orientated to give exceptionally strong binding with the free aluminium ion.

  13. 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.

  14. 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.

  15. Cellular circadian clocks in mood disorders.

    Science.gov (United States)

    McCarthy, Michael J; Welsh, David K

    2012-10-01

    Bipolar disorder (BD) and major depressive disorder (MDD) are heritable neuropsychiatric disorders associated with disrupted circadian rhythms. The hypothesis that circadian clock dysfunction plays a causal role in these disorders has endured for decades but has been difficult to test and remains controversial. In the meantime, the discovery of clock genes and cellular clocks has revolutionized our understanding of circadian timing. Cellular circadian clocks are located in the suprachiasmatic nucleus (SCN), the brain's primary circadian pacemaker, but also throughout the brain and peripheral tissues. In BD and MDD patients, defects have been found in SCN-dependent rhythms of body temperature and melatonin release. However, these are imperfect and indirect indicators of SCN function. Moreover, the SCN may not be particularly relevant to mood regulation, whereas the lateral habenula, ventral tegmentum, and hippocampus, which also contain cellular clocks, have established roles in this regard. Dysfunction in these non-SCN clocks could contribute directly to the pathophysiology of BD/MDD. We hypothesize that circadian clock dysfunction in non-SCN clocks is a trait marker of mood disorders, encoded by pathological genetic variants. Because network features of the SCN render it uniquely resistant to perturbation, previous studies of SCN outputs in mood disorders patients may have failed to detect genetic defects affecting non-SCN clocks, which include not only mood-regulating neurons in the brain but also peripheral cells accessible in human subjects. Therefore, reporters of rhythmic clock gene expression in cells from patients or mouse models could provide a direct assay of the molecular gears of the clock, in cellular clocks that are likely to be more representative than the SCN of mood-regulating neurons in patients. This approach, informed by the new insights and tools of modern chronobiology, will allow a more definitive test of the role of cellular circadian clocks

  16. 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.

  17. Elements of the Cellular Metabolic Structure

    Directory of Open Access Journals (Sweden)

    Ildefonso Martínez De La Fuente

    2015-04-01

    Full Text Available A large number of studies have shown the existence of metabolic covalent modifications in different molecular structures, able to store biochemical information that is not encoded by the DNA. Some of these covalent mark patterns can be transmitted across generations (epigenetic changes. Recently, the emergence of Hopfield-like attractor dynamics has been observed in the self-organized enzymatic networks, which have the capacity to store functional catalytic patterns that can be correctly recovered by the specific input stimuli. The Hopfield-like metabolic dynamics are stable and can be maintained as a long-term biochemical memory. In addition, specific molecular information can be transferred from the functional dynamics of the metabolic networks to the enzymatic activity involved in the covalent post-translational modulation so that determined functional memory can be embedded in multiple stable molecular marks. Both the metabolic dynamics governed by Hopfield-type attractors (functional processes and the enzymatic covalent modifications of determined molecules (structural dynamic processes seem to represent the two stages of the dynamical memory of cellular metabolism (metabolic memory. Epigenetic processes appear to be the structural manifestation of this cellular metabolic memory. Here, a new framework for molecular information storage in the cell is presented, which is characterized by two functionally and molecularly interrelated systems: a dynamic, flexible and adaptive system (metabolic memory and an essentially conservative system (genetic memory. The molecular information of both systems seems to coordinate the physiological development of the whole cell.

  18. [Cellular and molecular mechanisms of memory].

    Science.gov (United States)

    Laroche, Serge

    2010-01-01

    A defining characteristic of the brain is its remarkable capacity to undergo activity-dependent functional and morphological remodelling via mechanisms of plasticity that form the basis of our capacity to encode and retain memories. Today, it is generally accepted that one key neurobiological mechanism underlying the formation of memories reside in activity-driven modifications of synaptic strength and structural remodelling of neural networks activated during learning. The discovery and detailed report of the phenomenon generally known as long-term potentiation, a long-lasting activity-dependent form of synaptic strengthening, opened a new chapter in the study of the neurobiological substrate of memory in the vertebrate brain, and this form of synaptic plasticity has now become the dominant model in the search for the cellular bases of learning and memory. To date, the key events in the cellular and molecular mechanisms underlying synaptic plasticity and memory formation are starting to be identified. They require the activation of specific receptors and of several molecular cascades to convert extracellular signals into persistent functional changes in neuronal connectivity. Accumulating evidence suggests that the rapid activation of neuronal gene programs is a key mechanism underlying the enduring modification of neural networks required for the laying down of memory. The recent developments in the search for the cellular and molecular mechanisms of memory storage are reviewed.

  19. 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.

  20. WD40 proteins propel cellular networks.

    Science.gov (United States)

    Stirnimann, Christian U; Petsalaki, Evangelia; Russell, Robert B; Müller, Christoph W

    2010-10-01

    Recent findings indicate that WD40 domains play central roles in biological processes by acting as hubs in cellular networks; however, they have been studied less intensely than other common domains, such as the kinase, PDZ or SH3 domains. As suggested by various interactome studies, they are among the most promiscuous interactors. Structural studies suggest that this property stems from their ability, as scaffolds, to interact with diverse proteins, peptides or nucleic acids using multiple surfaces or modes of interaction. A general scaffolding role is supported by the fact that no WD40 domain has been found with intrinsic enzymatic activity despite often being part of large molecular machines. We discuss the WD40 domain distributions in protein networks and structures of WD40-containing assemblies to demonstrate their versatility in mediating critical cellular functions.

  1. A Course in Cellular Bioengineering.

    Science.gov (United States)

    Lauffenburger, Douglas A.

    1989-01-01

    Gives an overview of a course in chemical engineering entitled "Cellular Bioengineering," dealing with how chemical engineering principles can be applied to molecular cell biology. Topics used are listed and some key references are discussed. Listed are 85 references. (YP)

  2. Lipids, lipid droplets and lipoproteins in their cellular context; an ultrastructural approach

    NARCIS (Netherlands)

    Mesman, R.J.

    2013-01-01

    Lipids are essential for cellular life, functioning either organized as bilayer membranes to compartmentalize cellular processes, as signaling molecules or as metabolic energy storage. Our current knowledge on lipid organization and cellular lipid homeostasis is mainly based on biochemical data. How

  3. Functional aspects of cilia and tumor suppressors

    NARCIS (Netherlands)

    Basten, S.G.

    2013-01-01

    Sensing the cellular environment and responding accordingly is pivotal for tissue development and homeostasis. One cellular structure that functions almost exclusively as a sensory organelle is the nearly ubiquitously present primary cilium, that has been implicated in orchestrating cellular respons

  4. Effects of intrathecal tramadol on cellular immune functions in rats%鞘内注射曲马多对大鼠细胞免疫功能的影响

    Institute of Scientific and Technical Information of China (English)

    邹望远; 郭曲练; 王锷; 蔡进; 刘瑶

    2008-01-01

    tramadol infusion 5 % formalin 50 μl was injected subcutaneously into the plantar surface of the left hlndpaw. The number of flinches, lickings and total time of licking were recorded for 60 min. Pain intensity scores (PIS) (0 = no pain, 3 = severe pain) were recorded to assess the antinociceptive effects of IT tramadol. The animals were killed after evaluation of pain intensity. Body weight and spleen weight were measured. Spleen index (spleen weight/body weight) was calculated. T-lymphocyte function was evaluated based on Concanavalin A (ConA)-induced splenocyte proliferation. A modified lactic acid dehydrogeuase (LDH) release assay was used to assess NK cell activity. Results The PISs were significantly lower in group T1, T2 and T3 than in control group. The spleen index and spleenocyte proliferation induced by ConA were significantly suppressed in group T1, but there was no significant difference between control group and group T2 and T3. There was no significant difference in NK cell activity between the control group and the 3 tramadol groups. Conclusion IT tramadol has significant antinociceptive effect. Tramadol 50μg/h IT infusion can suppress cellular immune function.

  5. Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity

    Science.gov (United States)

    Dalmasso, Giovanni; Marin Zapata, Paula Andrea; Brady, Nathan Ryan; Hamacher-Brady, Anne

    2017-01-01

    Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis) and the removal of damaged mitochondria by selective autophagy (mitophagy). While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM) to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1) mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2) restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3) maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4) our model suggests sources of, and stress conditions amplifying

  6. 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.

  7. Quantitative, functional and biochemical alterations in the peritoneal cells of mice exposed to whole-body gamma-irradiation. 1. Changes in cellular protein, adherence properties and enzymatic activities associated with platelet-activating factor formation and inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Steel, L.K.; Hughes, H.N.; Walden, T.L. Jr.

    1988-06-01

    Changes in total number, differentials, cell protein, adherence properties, acetyl-CoA transferase and acetylhydrolase activities, prostaglandin E/sub 2/ and leukotriene C/sub 4/ production, as well as Ca/sup 2+/ ionophore A23187 stimulation were examined in resident peritoneal cells isolated from mice 2 h to 10 days postexposure to a single dose (7, 10 or 12 Gy) of gamma-radiation. Radiation dose-related reductions in macrophage and lymphocyte numbers and increases in cellular protein and capacity to adhere to plastic surfaces were evident. In vivo irradiation also elevated the activities of acetyltransferase and acetyl-CoA hydrolase (catalysing platelet-activating factor biosynthesis and inactivation, respectively) in adherent and nonadherent peritoneal cells, particularly 3-4 days postexposure. Blood plasma from irradiated animals did not reflect the increased cellular acetyl-hydrolase activity. Prostaglandin E/sub 2/ and leukotriene C/sub 4/ synthesis were elevated postexposure, suggesting increased substrate (arachidonate) availability and increased cyclooxygenase and lipoxygenase activities. Ionophore stimulation of enzyme activities and eicosanoid release also differed in irradiated peritoneal cells.

  8. 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.

  9. Coordination of autophagy with other cellular activities

    Institute of Scientific and Technical Information of China (English)

    Yan WANG; Zheng-hong QIN

    2013-01-01

    The cell biological phenomenon of autophagy has attracted increasing attention in recent years,partly as a consequence of the discovery of key components of its cellular machinery.Autophagy plays a crucial role in a myriad of cellular functions.Autophagy has its own regulatory mechanisms,but this process is not isolated.Autophagy is coordinated with other cellular activities to maintain cell homeostasis.Autophagy is critical for a range of human physiological processes.The multifunctional roles of autophagy are explained by its ability to interact with several key components of various cell pathways.In this review,we focus on the coordination between autophagy and other physiological processes,including the ubiquitin-proteasome system (UPS),energy homeostasis,aging,programmed cell death,the immune responses,microbial invasion and inflammation.The insights gained from investigating autophagic networks should increase our understanding of their roles in human diseases and their potential as targets for therapeutic intervention.

  10. Classifying cellular automata using grossone

    Science.gov (United States)

    D'Alotto, Louis

    2016-10-01

    This paper proposes an application of the Infinite Unit Axiom and grossone, introduced by Yaroslav Sergeyev (see [7] - [12]), to the development and classification of one and two-dimensional cellular automata. By the application of grossone, new and more precise nonarchimedean metrics on the space of definition for one and two-dimensional cellular automata are established. These new metrics allow us to do computations with infinitesimals. Hence configurations in the domain space of cellular automata can be infinitesimally close (but not equal). That is, they can agree at infinitely many places. Using the new metrics, open disks are defined and the number of points in each disk computed. The forward dynamics of a cellular automaton map are also studied by defined sets. It is also shown that using the Infinite Unit Axiom, the number of configurations that follow a given configuration, under the forward iterations of cellular automaton maps, can now be computed and hence a classification scheme developed based on this computation.

  11. 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.

  12. Cellular senescence mediates fibrotic pulmonary disease

    Science.gov (United States)

    Schafer, Marissa J.; White, Thomas A.; Iijima, Koji; Haak, Andrew J.; Ligresti, Giovanni; Atkinson, Elizabeth J.; Oberg, Ann L.; Birch, Jodie; Salmonowicz, Hanna; Zhu, Yi; Mazula, Daniel L.; Brooks, Robert W.; Fuhrmann-Stroissnigg, Heike; Pirtskhalava, Tamar; Prakash, Y. S.; Tchkonia, Tamara; Robbins, Paul D.; Aubry, Marie Christine; Passos, João F.; Kirkland, James L.; Tschumperlin, Daniel J.; Kita, Hirohito; LeBrasseur, Nathan K.

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by interstitial remodelling, leading to compromised lung function. Cellular senescence markers are detectable within IPF lung tissue and senescent cell deletion rejuvenates pulmonary health in aged mice. Whether and how senescent cells regulate IPF or if their removal may be an efficacious intervention strategy is unknown. Here we demonstrate elevated abundance of senescence biomarkers in IPF lung, with p16 expression increasing with disease severity. We show that the secretome of senescent fibroblasts, which are selectively killed by a senolytic cocktail, dasatinib plus quercetin (DQ), is fibrogenic. Leveraging the bleomycin-injury IPF model, we demonstrate that early-intervention suicide-gene-mediated senescent cell ablation improves pulmonary function and physical health, although lung fibrosis is visibly unaltered. DQ treatment replicates benefits of transgenic clearance. Thus, our findings establish that fibrotic lung disease is mediated, in part, by senescent cells, which can be targeted to improve health and function. PMID:28230051

  13. 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

  14. Cellular trafficking of nicotinic acetylcholine receptors

    Institute of Scientific and Technical Information of China (English)

    Paul A ST JOHN

    2009-01-01

    Nicotinic acetylcholine receptors (nAChRs) play critical roles throughout the body. Precise regulation of the cellular location and availability of nAChRs on neurons and target cells is critical to their proper function. Dynamic, post-translational regulation of nAChRs, particularly control of their movements among the different compartments of cells, is an important aspect of that regulation. A combination of new information and new techniques has the study of nAChR trafficking poised for new breakthroughs.

  15. Cellular models for Parkinson's disease.

    Science.gov (United States)

    Falkenburger, Björn H; Saridaki, Theodora; Dinter, Elisabeth

    2016-10-01

    Developing new therapeutic strategies for Parkinson's disease requires cellular models. Current models reproduce the two most salient changes found in the brains of patients with Parkinson's disease: The degeneration of dopaminergic neurons and the existence of protein aggregates consisting mainly of α-synuclein. Cultured cells offer many advantages over studying Parkinson's disease directly in patients or in animal models. At the same time, the choice of a specific cellular model entails the requirement to focus on one aspect of the disease while ignoring others. This article is intended for researchers planning to use cellular models for their studies. It describes for commonly used cell types the aspects of Parkinson's disease they model along with technical advantages and disadvantages. It might also be helpful for researchers from other fields consulting literature on cellular models of Parkinson's disease. Important models for the study of dopaminergic neuron degeneration include Lund human mesencephalic cells and primary neurons, and a case is made for the use of non-dopaminergic cells to model pathogenesis of non-motor symptoms of Parkinson's disease. With regard to α-synuclein aggregates, this article describes strategies to induce and measure aggregates with a focus on fluorescent techniques. Cellular models reproduce the two most salient changes of Parkinson's disease, the degeneration of dopaminergic neurons and the existence of α-synuclein aggregates. This article is intended for researchers planning to use cellular models for their studies. It describes for commonly used cell types and treatments the aspects of Parkinson's disease they model along with technical advantages and disadvantages. Furthermore, this article describes strategies to induce and measure aggregates with a focus on fluorescent techniques. This article is part of a special issue on Parkinson disease.

  16. Cellular basis of Alzheimer's disease.

    Science.gov (United States)

    Bali, Jitin; Halima, Saoussen Ben; Felmy, Boas; Goodger, Zoe; Zurbriggen, Sebastian; Rajendran, Lawrence

    2010-12-01

    Alzheimer's disease (AD) is the most common form of neurodegenerative disease. A characteristic feature of the disease is the presence of amyloid-β (Aβ) which either in its soluble oligomeric form or in the plaque-associated form is causally linked to neurodegeneration. Aβ peptide is liberated from the membrane-spanning -amyloid precursor protein by sequential proteolytic processing employing β- and γ-secretases. All these proteins involved in the production of Aβ peptide are membrane associated and hence, membrane trafficking and cellular compartmentalization play important roles. In this review, we summarize the key cellular events that lead to the progression of AD.

  17. On Cellular MIMO Channel Capacity

    Science.gov (United States)

    Adachi, Koichi; Adachi, Fumiyuki; Nakagawa, Masao

    To increase the transmission rate without bandwidth expansion, the multiple-input multiple-output (MIMO) technique has recently been attracting much attention. The MIMO channel capacity in a cellular system is affected by the interference from neighboring co-channel cells. In this paper, we introduce the cellular channel capacity and evaluate its outage capacity, taking into account the frequency-reuse factor, path loss exponent, standard deviation of shadowing loss, and transmission power of a base station (BS). Furthermore, we compare the cellular MIMO downlink channel capacity with those of other multi-antenna transmission techniques such as single-input multiple-output (SIMO) and space-time block coded multiple-input single-output (STBC-MISO). We show that the optimum frequency-reuse factor F that maximizes 10%-outage capacity is 3 and both 50%- and 90%-outage capacities is 1 irrespective of the type of multi-antenna transmission technique, where q%-outage capacity is defined as the channel capacity that gives an outage probability of q%. We also show that the cellular MIMO channel capacity is always higher than those of SIMO and STBC-MISO.

  18. Cellular uptake of metallated cobalamins

    DEFF Research Database (Denmark)

    Tran, MQT; Stürup, Stefan; Lambert, Ian H.;

    2016-01-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN(-...

  19. Functional

    Directory of Open Access Journals (Sweden)

    Fedoua Gandia

    2014-07-01

    Full Text Available The study was carried out to investigate the effects of inhaled Mg alone and associated with F in the treatment of bronchial hyperresponsiveness. 43 male Wistar rats were randomly divided into four groups and exposed to inhaled NaCl 0.9%, MeCh, MgSO4 and MgF2. Pulmonary changes were assessed by means of functional tests and quantitative histological examination of lungs and trachea. Results revealed that delivery of inhaled Mg associated with F led to a significant decrease of total lung resistance better than inhaled Mg alone (p < 0.05. Histological examinations illustrated that inhaled Mg associated with F markedly suppressed muscular hypertrophy (p = 0.034 and bronchoconstriction (p = 0.006 in MeCh treated rats better than inhaled Mg alone. No histological changes were found in the trachea. This study showed that inhaled Mg associated with F attenuated the main principle of the central components of changes in MeCh provoked experimental asthma better than inhaled Mg alone, potentially providing a new therapeutic approach against asthma.

  20. Cellular roles of ADAM12 in health and disease

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Albrechtsen, Reidar; Couchman, John R;

    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-binding proteins...... 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...

  1. Protein S-palmitoylation in cellular differentiation

    Science.gov (United States)

    Zhang, Mingzi M.

    2017-01-01

    Reversible protein S-palmitoylation confers spatiotemporal control of protein function by modulating protein stability, trafficking and activity, as well as protein–protein and membrane–protein associations. Enabled by technological advances, global studies revealed S-palmitoylation to be an important and pervasive posttranslational modification in eukaryotes with the potential to coordinate diverse biological processes as cells transition from one state to another. Here, we review the strategies and tools to analyze in vivo protein palmitoylation and interrogate the functions of the enzymes that put on and take off palmitate from proteins. We also highlight palmitoyl proteins and palmitoylation-related enzymes that are associated with cellular differentiation and/or tissue development in yeasts, protozoa, mammals, plants and other model eukaryotes. PMID:28202682

  2. 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.

  3. Threshold effects and cellular recognition. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Rando, R R

    1980-01-01

    In the first year we focused on developing the techniques required for the successful incorporation of synthetic glycolipids into cells. To these ends a new water-soluble spacer group (8-amino-3-6-dioxaoctanoic acid) was developed and incorporated into the cholesterol based synthetic glycolipids. These glycolipids could be incorporated into liposomes, rendering them susceptible to aggregation by the appropriate lectin. They also allowed us to define the minimal distance between the sugar moiety and membrane required for agglutination. Finally and most importantly, we were able to functionally incorporate these new glycolipids in cells and render them agglutinable with the appropriate lectins. Functional incorporation does not occur with glycolipids bearing hydropholic spacer groups. We are now in a position to begin using the new glycolipids to answer questions about the roles of cell surface sugars in cellular recognition, which is the subject of this renewal proposal.

  4. 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.

  5. Reversibly assembled cellular composite materials.

    Science.gov (United States)

    Cheung, Kenneth C; Gershenfeld, Neil

    2013-09-13

    We introduce composite materials made by reversibly assembling a three-dimensional lattice of mass-produced carbon fiber-reinforced polymer composite parts with integrated mechanical interlocking connections. The resulting cellular composite materials can respond as an elastic solid with an extremely large measured modulus for an ultralight material (12.3 megapascals at a density of 7.2 milligrams per cubic centimeter). These materials offer a hierarchical decomposition in modeling, with bulk properties that can be predicted from component measurements and deformation modes that can be determined by the placement of part types. Because site locations are locally constrained, structures can be produced in a relative assembly process that merges desirable features of fiber composites, cellular materials, and additive manufacturing.

  6. 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.

  7. Cellular fiber–reinforced concrete

    OpenAIRE

    Isachenko S.; Kodzoev M.

    2016-01-01

    Methods disperse reinforcement of concrete matrix using polypropylene, glass, basalt and metal fibers allows to make the construction of complex configuration, solve the problem of frost products. Dispersed reinforcement reduces the overall weight of the structures. The fiber replaces the secondary reinforcement, reducing the volume of use of structural steel reinforcement. Cellular Fiber concretes are characterized by high-performance properties, especially increased bending strength and...

  8. Identification of Nonstationary Cellular Automata

    Institute of Scientific and Technical Information of China (English)

    AndrewI.Adamatzky

    1992-01-01

    The principal feature of nonstationary cellular automata(NCA) is that a local transitiol rule of each cell is changed at each time step depending on neighborhood configuration at previous time step.The identification problem for NCA is extraction of local transition rules and the establishment of mechanism for changing these rules using sequence of NCA configurations.We present serial and parallel algorithms for identification of NCA.

  9. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

    OpenAIRE

    Popescu, O.; Sumanovski, L. T.; I. Checiu; Elisabeta Popescu; G. N. Misevic

    1999-01-01

    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...

  10. 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

  11. 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.

  12. Structure and Function of Human Carcinoembryonic Antigen-related Cellular Adhesion Molecule 1%人体癌胚抗原相关细胞黏附分子1的结构与功能

    Institute of Scientific and Technical Information of China (English)

    叶秋芳

    2012-01-01

    人癌胚抗原相关细胞黏附分子1(CEACAMl)是广泛表达于中性粒细胞、巨噬细胞、内皮细胞、上皮细胞及淋巴细胞表面的Ⅰ型跨膜糖蛋白,属癌胚抗原家族免疫球蛋白超家族分子,胞膜外区有Ig样结构域,CEACAM1-L型具有两个免疫受体酪氨酸抑制性基序,其生物学功能包括免疫调节、促进血管形成、调节血管重构、参与细胞凋亡调控、促进腺体管腔形成及调控胰岛素的清除,同时CEACAM1也是致病微生物的黏着受体.%Human carcinoembryonic antigen-related cellular adhesion molenile l( CEACAM1 )is a member of the carcinoembryonir antigen iamily(CEA )whirh is a type I-transmembrane glycoprotein broadly expressed on the surface oi cells including: macrophages, neutrophilic granulocyte, lymphocyte, epithelial, and endothelial cells. It is an adhesion molecule oi immunoglobulin superfamily. The extiacellulai' domain oi CEACAM 1 contains IgG-like stmctuie. The long form oi CEACAM1 protein has two immunoieceptoi tinosine-based inhibitoiy motiis( ITIMs )that have crucial roles in immu no-regulation, vascular neogenesis, vascular remolding, cell apoptosis regulation, gland lumen formation and insulin clearance. CEACAM1 is also a receptor for pathogenic bacteria and viruses.

  13. Scalable asynchronous execution of cellular automata

    Science.gov (United States)

    Folino, Gianluigi; Giordano, Andrea; Mastroianni, Carlo

    2016-10-01

    The performance and scalability of cellular automata, when executed on parallel/distributed machines, are limited by the necessity of synchronizing all the nodes at each time step, i.e., a node can execute only after the execution of the previous step at all the other nodes. However, these synchronization requirements can be relaxed: a node can execute one step after synchronizing only with the adjacent nodes. In this fashion, different nodes can execute different time steps. This can be a notable advantageous in many novel and increasingly popular applications of cellular automata, such as smart city applications, simulation of natural phenomena, etc., in which the execution times can be different and variable, due to the heterogeneity of machines and/or data and/or executed functions. Indeed, a longer execution time at a node does not slow down the execution at all the other nodes but only at the neighboring nodes. This is particularly advantageous when the nodes that act as bottlenecks vary during the application execution. The goal of the paper is to analyze the benefits that can be achieved with the described asynchronous implementation of cellular automata, when compared to the classical all-to-all synchronization pattern. The performance and scalability have been evaluated through a Petri net model, as this model is very useful to represent the synchronization barrier among nodes. We examined the usual case in which the territory is partitioned into a number of regions, and the computation associated with a region is assigned to a computing node. We considered both the cases of mono-dimensional and two-dimensional partitioning. The results show that the advantage obtained through the asynchronous execution, when compared to the all-to-all synchronous approach is notable, and it can be as large as 90% in terms of speedup.

  14. 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

  15. Cellular and molecular connections between sleep and synaptic plasticity.

    Science.gov (United States)

    Benington, Joel H; Frank, Marcos G

    2003-02-01

    The hypothesis that sleep promotes learning and memory has long been a subject of active investigation. This hypothesis implies that sleep must facilitate synaptic plasticity in some way, and recent studies have provided evidence for such a function. Our knowledge of both the cellular neurophysiology of sleep states and of the cellular and molecular mechanisms underlying synaptic plasticity has expanded considerably in recent years. In this article, we review findings in these areas and discuss possible mechanisms whereby the neurophysiological processes characteristic of sleep states may serve to facilitate synaptic plasticity. We address this issue first on the cellular level, considering how activation of T-type Ca(2+) channels in nonREM sleep may promote either long-term depression or long-term potentiation, as well as how cellular events of REM sleep may influence these processes. We then consider how synchronization of neuronal activity in thalamocortical and hippocampal-neocortical networks in nonREM sleep and REM sleep could promote differential strengthening of synapses according to the degree to which activity in one neuron is synchronized with activity in other neurons in the network. Rather than advocating one specific cellular hypothesis, we have intentionally taken a broad approach, describing a range of possible mechanisms whereby sleep may facilitate synaptic plasticity on the cellular and/or network levels. We have also provided a general review of evidence for and against the hypothesis that sleep does indeed facilitate learning, memory, and synaptic plasticity.

  16. 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; Dinu, Cerasela Zoica

    2016-02-26

    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.

  17. 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.

  18. The Algorithm of Continuous Optimization Based on the Modified Cellular Automaton

    Directory of Open Access Journals (Sweden)

    Oleg Evsutin

    2016-08-01

    Full Text Available This article is devoted to the application of the cellular automata mathematical apparatus to the problem of continuous optimization. The cellular automaton with an objective function is introduced as a new modification of the classic cellular automaton. The algorithm of continuous optimization, which is based on dynamics of the cellular automaton having the property of geometric symmetry, is obtained. The results of the simulation experiments with the obtained algorithm on standard test functions are provided, and a comparison between the analogs is shown.

  19. Diabetes mellitus: channeling care through cellular discovery.

    Science.gov (United States)

    Maiese, Kenneth; Shang, Yan Chen; Chong, Zhao Zhong; Hou, Jinling

    2010-02-01

    Diabetes mellitus (DM) impacts a significant portion of the world's population and care for this disorder places an economic burden on the gross domestic product for any particular country. Furthermore, both Type 1 and Type 2 DM are becoming increasingly prevalent and there is increased incidence of impaired glucose tolerance in the young. The complications of DM are protean and can involve multiple systems throughout the body that are susceptible to the detrimental effects of oxidative stress and apoptotic cell injury. For these reasons, innovative strategies are necessary for the implementation of new treatments for DM that are generated through the further understanding of cellular pathways that govern the pathological consequences of DM. In particular, both the precursor for the coenzyme beta-nicotinamide adenine dinucleotide (NAD(+)), nicotinamide, and the growth factor erythropoietin offer novel platforms for drug discovery that involve cellular metabolic homeostasis and inflammatory cell control. Interestingly, these agents and their tightly associated pathways that consist of cell cycle regulation, protein kinase B, forkhead transcription factors, and Wnt signaling also function in a broader sense as biomarkers for disease onset and progression.

  20. Alpha-synuclein is a cellular ferrireductase.

    Directory of Open Access Journals (Sweden)

    Paul Davies

    Full Text Available α-synuclein (αS is a cellular protein mostly known for the association of its aggregated forms with a variety of diseases that include Parkinson's disease and Dementia with Lewy Bodies. While the role of αS in disease is well documented there is currently no agreement on the physiological function of the normal isoform of the protein. Here we provide strong evidence that αS is a cellular ferrireductase, responsible for reducing iron (III to bio available iron (II. The recombinant form of the protein has a V(Max of 2.72 nmols/min/mg and K(m 23 µM. This activity is also evident in lysates from neuronal cell lines overexpressing αS. This activity is dependent on copper bound to αS as a cofactor and NADH as an electron donor. Overexpression of α-synuclein by cells significantly increases the percentage of iron (II in cells. The common disease mutations associated with increased susceptibility to PD show no [corrected] differences in activity or iron (II levels. This discovery may well provide new therapeutic targets for PD and Lewy body dementias.

  1. Filovirus tropism: Cellular molecules for viral entry

    Directory of Open Access Journals (Sweden)

    Ayato eTakada

    2012-02-01

    Full Text Available In human and nonhuman primates, filoviruses (Ebola and Marburg viruses cause severe hemorrhagic fever.Recently, other animals such as pigs and some species of fruit bats have also been shown to be susceptible to these viruses. While having a preference for some cell types such as hepatocytes, endothelial cells, dendritic cells, monocytes, and macrophages, filoviruses are known to be pantropic in infection of primates. The envelope glycoprotein (GP is responsible for both receptor binding and fusion of the virus envelope with the host cell membrane. It has been demonstrated that filovirus GP interacts with multiple molecules for entry into host cells, whereas none of the cellular molecules so far identified as a receptor/coreceptor fully explains filovirus tissue tropism and host range. Available data suggest that the mucin-like region (MLR on GP plays an important role in attachment to the preferred target cells, whose infection is likely involved in filovirus pathogenesis, whereas the MLR is not essential for the fundamental function of the GP in viral entry into cells in vitro. Further studies elucidating the mechanisms of cellular entry of filoviruses may shed light on the development of strategies for prophylaxis and treatment of Ebola and Marburg hemorrhagic fevers.

  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. Dynamics of active cellular response under stress

    Science.gov (United States)

    de, Rumi; Zemel, Assaf; Safran, Samuel

    2008-03-01

    Forces exerted by and on adherent cells are important for many physiological processes such as wound healing and tissue formation. In addition, recent experiments have shown that stem cell differentiation is controlled, at least in part, by the elasticity of the surrounding matrix. Using a simple theoretical model that includes the forces due to both the mechanosensitive nature of cells and the elastic response of the matrix, we predict the dynamics of orientation of cells. The model predicts many features observed in measurements of cellular forces and orientation including the increase with time of the forces generated by cells in the absence of applied stress and the consequent decrease of the force in the presence of quasi-static stresses. We also explain the puzzling observation of parallel alignment of cells for static and quasi-static stresses and of nearly perpendicular alignment for dynamically varying stresses. In addition, we predict the response of the cellular orientation to a sinusoidally varying applied stress as a function of frequency. The dependence of the cell orientation angle on the Poisson ratio of the surrounding material can be used to distinguish systems in which cell activity is controlled by stress from those where cell activity is controlled by strain. Reference: Nature Physics, vol. 3, pp 655 (2007).

  4. Characteristics of cellular composition of periodontal pockets

    Science.gov (United States)

    Hasiuk, Petro; Hasiuk, Nataliya; Kindiy, Dmytro; Ivanchyshyn, Victoriya; Kalashnikov, Dmytro; Zubchenko, Sergiy

    2016-01-01

    Purpose The development of inflammatory periodontal disease in young people is an urgent problem of today's periodontology, and requires a development of new methods that would give an opportunity not only to diagnose but also for prognosis of periodontitis course in a given patients contingent. Results Cellular structure of periodontal pockets is presented by hematogenous and epithelial cells. Our results are confirmed by previous studies, and show that the penetration of periodontal pathogens leads to formation in periodontal tissue of a highly active complex compounds—cytokines that are able to modify the activity of neutrophils and reduce their specific antibacterial properties. Cytokines not only adversely affect the periodontal tissues, but also cause further activation of cells that synthesized them, and inhibit tissue repair and process of resynthesis of connective tissue by fibroblasts. Conclusion Neutrophilic granulocytes present in each of the types of smear types, but their functional status and quantitative composition is different. The results of our cytological study confirmed the results of immunohistochemical studies, and show that in generalized periodontitis, an inflammatory cellular elements with disorganized epithelial cells and connective tissue of the gums and periodontium, and bacteria form specific types of infiltration in periodontal tissues. PMID:28180007

  5. A metabolic-transcriptional network links sleep and cellular energetics in the brain.

    Science.gov (United States)

    Wisor, Jonathan P

    2012-01-01

    This review proposes a mechanistic link between cellular metabolic status, transcriptional regulatory changes and sleep. Sleep loss is associated with changes in cellular metabolic status in the brain. Metabolic sensors responsive to cellular metabolic status regulate the circadian clock transcriptional network. Modifications of the transcriptional activity of circadian clock genes affect sleep/wake state changes. Changes in sleep state reverse sleep loss-induced changes in cellular metabolic status. It is thus proposed that the regulation of circadian clock genes by cellular metabolic sensors is a critical intermediate step in the link between cellular metabolic status and sleep. Studies of this regulatory relationship may offer insights into the function of sleep at the cellular level.

  6. Iron Oxide Nanoparticles Stimulates Extra-Cellular Matrix Production in Cellular Spheroids

    Directory of Open Access Journals (Sweden)

    Megan Casco

    2017-01-01

    Full Text Available Nanotechnologies have been integrated into drug delivery, and non-invasive imaging applications, into nanostructured scaffolds for the manipulation of cells. The objective of this work was to determine how the physico-chemical properties of magnetic nanoparticles (MNPs and their spatial distribution into cellular spheroids stimulated cells to produce an extracellular matrix (ECM. The MNP concentration (0.03 mg/mL, 0.1 mg/mL and 0.3 mg/mL, type (magnetoferritin, shape (nanorod—85 nm × 425 nm and incorporation method were studied to determine each of their effects on the specific stimulation of four ECM proteins (collagen I, collagen IV, elastin and fibronectin in primary rat aortic smooth muscle cell. Results demonstrated that as MNP concentration increased there was up to a 6.32-fold increase in collagen production over no MNP samples. Semi-quantitative Immunohistochemistry (IHC results demonstrated that MNP type had the greatest influence on elastin production with a 56.28% positive area stain compared to controls and MNP shape favored elastin stimulation with a 50.19% positive area stain. Finally, there are no adverse effects of MNPs on cellular contractile ability. This study provides insight on the stimulation of ECM production in cells and tissues, which is important because it plays a critical role in regulating cellular functions.

  7. The impact of peroxisomes on cellular aging and death

    NARCIS (Netherlands)

    Manivannan, Selvambigai; Scheckhuber, Christian Quintus; Veenhuis, Marten; Klei, Ida Johanna van der; Côrte-Real, Manuela

    2012-01-01

    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 significan

  8. CYCLIC VECTORS AND CELLULAR INDECOMPOSABLE OPERATORS ON Qp SPACES

    Institute of Scientific and Technical Information of China (English)

    Ye Shanli; Lou Zengjian

    2011-01-01

    We identify the functions whose polynomial multiples are weak* dense in Qp spaces and prove that if |f(z)|≥|g(z)| and g is cyclic in Qp, then f is cyclic in Qp. We also show that the multiplication operator Mz on Qp spaces is cellular indecomposable.

  9. 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

  10. 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…

  11. Simulating Quantitative Cellular Responses Using Asynchronous Threshold Boolean Network Ensembles

    Science.gov (United States)

    With increasing knowledge about the potential mechanisms underlying cellular functions, it is becoming feasible to predict the response of biological systems to genetic and environmental perturbations. Due to the lack of homogeneity in living tissues it is difficult to estimate t...

  12. An Ontology for Collaborative Construction and Analysis of Cellular Pathways

    NARCIS (Netherlands)

    Demir, E.; Babur, O.; Dogrusoz, U.; Gursoy, A.; Ayaz, A.; Güleşir, G.; Nisanci, G.; Cetin-Atalay, R.

    2004-01-01

    Motivation: As the scientific curiosity in genome studies shifts toward identification of functions of the genomes in large scale, data produced about cellular processes at molecular level has been accumulating with an accelerating rate. In this regard, it is essential to be able to store, integrate

  13. A novel hNIS/tdTomato fusion reporter for visualizing the relationship between the cellular localization of sodium iodide symporter and its iodine uptake function under heat shock treatment.

    Science.gov (United States)

    Yeom, Chan Joo; Chung, Taemoon; Youn, Hyewon; Kang, Keon Wook; Lee, Dong Soo; Chung, June-Key

    2015-01-01

    The function of membrane-localized sodium iodide symporter (NIS) determines the efficacy of radioiodine therapy in thyroid cancer. Here, we describe a dual mode reporter fused with human NIS (hNIS) and a red fluorescent protein named tandem dimeric Tomato (tdTomato) for the in vitro and in vivo imaging of hNIS protein expression, localization, and iodide uptake function. Human cervical epithelial adenocarcinoma cell line (HeLa)-hNIS/tdTomato cells were established by transducing a fusion gene expressing hNIS/tdTomato under the control of a cytomegalovirus promoter. Fluorescence imaging, confocal microscopy, and an 125I uptake assay were performed to validate the integrity of the fusion protein. Actinomycin D and cycloheximide were used to block newly synthesized hNIS proteins. In vivo images were acquired using a gamma camera and a Maestro fluorescence imaging device. The fluorescence intensity of membrane-localized hNIS and 125I uptake both were increased after heat shock. Scintigraphy and fluorescence imaging indicated specific accumulation of the hNIS/tdTomato fusion protein in xenografted tumors, supporting the utility of this system for in vivo monitoring of hNIS expression and activity. We developed a novel hNIS/tdTomato dual mode reporter that enables visualization of the expression, localization, and iodine uptake function of hNIS in vitro and in vivo.

  14. 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 rat...... pancreatic alpha-cells and somatotrophs. We found a pharmacological dissociation between the actions on KATP channels and exocytosis and suggest that compounds that, unlike repaglinide, have direct stimulatory effects on exocytosis in somatotrophs and alpha- and beta-cells, such as sulphonylureas...

  15. 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

  16. 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.

  17. Cellular Analogs of Operant Behavior.

    Science.gov (United States)

    1992-07-31

    ing of single units can be demonstrated, does such a cellular subset of neighboring pyramidal cells and interneurons as well as process contribute...excite dopamine neurons by -hyperpolarization of local interneurons . J. Neurosci. 12:483-488; 1992. Kosterlitz, H. W. Biosynthesis of morphine in the...II 197 1 1 ocation preltereite iindiis- HOIdlod VA. artdo \\M I . \\.ill I ’’’’i i R i l’)89) ( pioid mediationl lserilI1 reintoree-Cd bK amlphetcamine

  18. 5G Ultra-Dense Cellular Networks

    OpenAIRE

    Ge, Xiaohu; Tu, Song; Mao, Guoqiang; Wang, Cheng-xiang; Han, Tao

    2015-01-01

    Traditional ultra-dense wireless networks are recommended as a complement for cellular networks and are deployed in partial areas, such as hotspot and indoor scenarios. Based on the massive multiple-input multi-output (MIMO) antennas and the millimeter wavecommunication technologies, the 5G ultra-dense cellular network is proposed to deploy in overall cellular scenarios. Moreover, a distribution network architecture is presented for 5G ultra-dense cellular networks. Furthermore, the backhaul ...

  19. 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.

  20. Cellular regulation of the dopamine transporter

    DEFF Research Database (Denmark)

    Eriksen, Jacob

    2010-01-01

    -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 increased by inhibitors......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...... to natively expressed transporter, DAT was visualized directly in cultured DA neurons using the fluorescent cocaine analog JHC 1-64. These data showed pronounced colocalization upon constitutive internalization with Lysotracker, a late endosomal/lysosomal marker; however only little cololization was observed...

  1. 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.

  2. Cellular nanotechnology: making biological interfaces smarter.

    Science.gov (United States)

    Mendes, Paula M

    2013-12-21

    Recently, there has been an outburst of research on engineered cell-material interfaces driven by nanotechnology and its tools and techniques. This tutorial review begins by providing a brief introduction to nanostructured materials, followed by an overview of the wealth of nanoscale fabrication and analysis tools available for their development. This background serves as the basis for a discussion of early breakthroughs and recent key developments in the endeavour to develop nanostructured materials as smart interfaces for fundamental cellular studies, tissue engineering and regenerative medicine. The review covers three major aspects of nanostructured interfaces - nanotopographical control, dynamic behaviour and intracellular manipulation and sensing - where efforts are continuously being made to further understand cell function and provide new ways to control cell behaviour. A critical reflection of the current status and future challenges are discussed as a conclusion to the review.

  3. Statistical physical models of cellular motility

    Science.gov (United States)

    Banigan, Edward J.

    Cellular motility is required for a wide range of biological behaviors and functions, and the topic poses a number of interesting physical questions. In this work, we construct and analyze models of various aspects of cellular motility using tools and ideas from statistical physics. We begin with a Brownian dynamics model for actin-polymerization-driven motility, which is responsible for cell crawling and "rocketing" motility of pathogens. Within this model, we explore the robustness of self-diffusiophoresis, which is a general mechanism of motility. Using this mechanism, an object such as a cell catalyzes a reaction that generates a steady-state concentration gradient that propels the object in a particular direction. We then apply these ideas to a model for depolymerization-driven motility during bacterial chromosome segregation. We find that depolymerization and protein-protein binding interactions alone are sufficient to robustly pull a chromosome, even against large loads. Next, we investigate how forces and kinetics interact during eukaryotic mitosis with a many-microtubule model. Microtubules exert forces on chromosomes, but since individual microtubules grow and shrink in a force-dependent way, these forces lead to bistable collective microtubule dynamics, which provides a mechanism for chromosome oscillations and microtubule-based tension sensing. Finally, we explore kinematic aspects of cell motility in the context of the immune system. We develop quantitative methods for analyzing cell migration statistics collected during imaging experiments. We find that during chronic infection in the brain, T cells run and pause stochastically, following the statistics of a generalized Levy walk. These statistics may contribute to immune function by mimicking an evolutionarily conserved efficient search strategy. Additionally, we find that naive T cells migrating in lymph nodes also obey non-Gaussian statistics. Altogether, our work demonstrates how physical

  4. Melanoma screening with cellular phones.

    Directory of Open Access Journals (Sweden)

    Cesare Massone

    Full Text Available BACKGROUND: Mobile teledermatology has recently been shown to be suitable for teledermatology despite limitations in image definition in preliminary studies. The unique aspect of mobile teledermatology is that this system represents a filtering or triage system, allowing a sensitive approach for the management of patients with emergent skin diseases. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigated the feasibility of teleconsultation using a new generation of cellular phones in pigmented skin lesions. 18 patients were selected consecutively in the Pigmented Skin Lesions Clinic of the Department of Dermatology, Medical University of Graz, Graz (Austria. Clinical and dermoscopic images were acquired using a Sony Ericsson with a built-in two-megapixel camera. Two teleconsultants reviewed the images on a specific web application (http://www.dermahandy.net/default.asp where images had been uploaded in JPEG format. Compared to the face-to-face diagnoses, the two teleconsultants obtained a score of correct telediagnoses of 89% and of 91.5% reporting the clinical and dermoscopic images, respectively. CONCLUSIONS/SIGNIFICANCE: The present work is the first study performing mobile teledermoscopy using cellular phones. Mobile teledermatology has the potential to become an easy applicable tool for everyone and a new approach for enhanced self-monitoring for skin cancer screening in the spirit of the eHealth program of the European Commission Information for Society and Media.

  5. Cellular automata modelling of SEIRS

    Institute of Scientific and Technical Information of China (English)

    Liu Quan-Xing; Jin Zhen

    2005-01-01

    In this paper the SEIRS epidemic spread is analysed, and a two-dimensional probability cellular automata model for SEIRS is presented. Each cellular automation cell represents a part of the population that may be found in one of five states of individuals: susceptible, exposed (or latency), infected, immunized (or recovered) and death. Here studied are the effects of two cases on the epidemic spread. i.e. the effects of non-segregation and segregation on the latency and the infected of population. The conclusion is reached that the epidemic will persist in the case of non-segregation but it will decrease in the case of segregation. The proposed model can serve as a basis for the development of algorithms to simulate real epidemics based on real data. Last we find the density series of the exposed and the infected will fluctuate near a positive equilibrium point, when the constant for the immunized is less than its corresponding constant τ0. Our theoretical results are verified by numerical simulations.

  6. REACTIVE OXYGEN SPECIES, CELLULAR REDOX SYSTEMS AND APOPTOSIS

    OpenAIRE

    2010-01-01

    Reactive oxygen species (ROS) are products of normal metabolism and xenobiotic exposure, and depending on concentrations, ROS can be beneficial or harmful to cells and tissues. At physiological low levels, ROS function as “redox messengers” in intracellular signaling and regulation while excess ROS induce oxidative modification of cellular macromolecules, inhibit protein function and promote cell death. Additionally, various redox systems, such as the glutathione, thioredoxin, and pyridine nu...

  7. 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.

  8. Divergent synthesis and identification of the cellular targets of deoxyelephantopins

    Science.gov (United States)

    Lagoutte, Roman; Serba, Christelle; Abegg, Daniel; Hoch, Dominic G.; Adibekian, Alexander; Winssinger, Nicolas

    2016-08-01

    Herbal extracts containing sesquiterpene lactones have been extensively used in traditional medicine and are known to be rich in α,β-unsaturated functionalities that can covalently engage target proteins. Here we report synthetic methodologies to access analogues of deoxyelephantopin, a sesquiterpene lactone with anticancer properties. Using alkyne-tagged cellular probes and quantitative proteomics analysis, we identified several cellular targets of deoxyelephantopin. We further demonstrate that deoxyelephantopin antagonizes PPARγ activity in situ via covalent engagement of a cysteine residue in the zinc-finger motif of this nuclear receptor.

  9. Selfish cellular networks and the evolution of complex organisms.

    Science.gov (United States)

    Kourilsky, Philippe

    2012-03-01

    Human gametogenesis takes years and involves many cellular divisions, particularly in males. Consequently, gametogenesis provides the opportunity to acquire multiple de novo mutations. A significant portion of these is likely to impact the cellular networks linking genes, proteins, RNA and metabolites, which constitute the functional units of cells. A wealth of literature shows that these individual cellular networks are complex, robust and evolvable. To some extent, they are able to monitor their own performance, and display sufficient autonomy to be termed "selfish". Their robustness is linked to quality control mechanisms which are embedded in and act upon the individual networks, thereby providing a basis for selection during gametogenesis. These selective processes are equally likely to affect cellular functions that are not gamete-specific, and the evolution of the most complex organisms, including man, is therefore likely to occur via two pathways: essential housekeeping functions would be regulated and evolve during gametogenesis within the parents before being transmitted to their progeny, while classical selection would operate on other traits of the organisms that shape their fitness with respect to the environment.

  10. Cellular identity at the single-cell level.

    Science.gov (United States)

    Coskun, Ahmet F; Eser, Umut; Islam, Saiful

    2016-10-20

    A single cell creates surprising heterogeneity in a multicellular organism. While every organismal cell shares almost an identical genome, molecular interactions in cells alter the use of DNA sequences to modulate the gene of interest for specialization of cellular functions. Each cell gains a unique identity through molecular coding across the DNA, RNA, and protein conversions. On the other hand, loss of cellular identity leads to critical diseases such as cancer. Most cell identity dissection studies are based on bulk molecular assays that mask differences in individual cells. To probe cell-to-cell variability in a population, we discuss single cell approaches to decode the genetic, epigenetic, transcriptional, and translational mechanisms for cell identity formation. In combination with molecular instructions, the physical principles behind cell identity determination are examined. Deciphering and reprogramming cellular types impact biology and medicine.

  11. Cellular uptake of metallated cobalamins

    DEFF Research Database (Denmark)

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry

    2016-01-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN...... including [Cbl-OH2](+), [{Co}-CN-{cis-PtCl(NH3)2}](+), [{Re}-{Co}-CN-{cis-PtCl(NH3)2}](+), and [{Co}-CN-{trans-Pt(Cyt)(NH3)2}](2+) (Cyt = cytarabin) was high compared to neutral B12, which implied the existence of an additional internalization pathway for charged B12 vitamin analogs. The affinities...

  12. Thermomechanical characterisation of cellular rubber

    Science.gov (United States)

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

    2016-09-01

    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.

  13. Bioinspired Cellular Structures: Additive Manufacturing and Mechanical Properties

    Science.gov (United States)

    Stampfl, J.; Pettermann, H. E.; Liska, R.

    Biological materials (e.g., wood, trabecular bone, marine skeletons) rely heavily on the use of cellular architecture, which provides several advantages. (1) The resulting structures can bear the variety of "real life" load spectra using a minimum of a given bulk material, featuring engineering lightweight design principles. (2) The inside of the structures is accessible to body fluids which deliver the required nutrients. (3) Furthermore, cellular architectures can grow organically by adding or removing individual struts or by changing the shape of the constituting elements. All these facts make the use of cellular architectures a reasonable choice for nature. Using additive manufacturing technologies (AMT), it is now possible to fabricate such structures for applications in engineering and biomedicine. In this chapter, we present methods that allow the 3D computational analysis of the mechanical properties of cellular structures with open porosity. Various different cellular architectures including disorder are studied. In order to quantify the influence of architecture, the apparent density is always kept constant. Furthermore, it is shown that how new advanced photopolymers can be used to tailor the mechanical and functional properties of the fabricated structures.

  14. 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.

  15. Fundamental Limits to Cellular Sensing

    Science.gov (United States)

    ten Wolde, Pieter Rein; Becker, Nils B.; Ouldridge, Thomas E.; Mugler, Andrew

    2016-03-01

    In recent years experiments have demonstrated that living cells can measure low chemical concentrations with high precision, and much progress has been made in understanding what sets the fundamental limit to the precision of chemical sensing. Chemical concentration measurements start with the binding of ligand molecules to receptor proteins, which is an inherently noisy process, especially at low concentrations. The signaling networks that transmit the information on the ligand concentration from the receptors into the cell have to filter this receptor input noise as much as possible. These networks, however, are also intrinsically stochastic in nature, which means that they will also add noise to the transmitted signal. In this review, we will first discuss how the diffusive transport and binding of ligand to the receptor sets the receptor correlation time, which is the timescale over which fluctuations in the state of the receptor, arising from the stochastic receptor-ligand binding, decay. We then describe how downstream signaling pathways integrate these receptor-state fluctuations, and how the number of receptors, the receptor correlation time, and the effective integration time set by the downstream network, together impose a fundamental limit on the precision of sensing. We then discuss how cells can remove the receptor input noise while simultaneously suppressing the intrinsic noise in the signaling network. We describe why this mechanism of time integration requires three classes (groups) of resources—receptors and their integration time, readout molecules, energy—and how each resource class sets a fundamental sensing limit. We also briefly discuss the scheme of maximum-likelihood estimation, the role of receptor cooperativity, and how cellular copy protocols differ from canonical copy protocols typically considered in the computational literature, explaining why cellular sensing systems can never reach the Landauer limit on the optimal trade

  16. 78 FR 15726 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-03-12

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and recommendations...

  17. 77 FR 63840 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-10-17

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee..., Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and..., Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, and...

  18. 76 FR 18768 - Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-04-05

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue, and Gene Therapies Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Cellular, Tissue, and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and recommendations...

  19. 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

  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 signaling by fibroblast growth factor receptors.

    Science.gov (United States)

    Eswarakumar, V P; Lax, I; Schlessinger, J

    2005-04-01

    The 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosine kinases (RTKs) designated FGFR1, FGFR2, FGFR3 and FGFR4. Unlike other growth factors, FGFs act in concert with heparin or heparan sulfate proteoglycan (HSPG) to activate FGFRs and to induce the pleiotropic responses that lead to the variety of cellular responses induced by this large family of growth factors. A variety of human skeletal dysplasias have been linked to specific point mutations in FGFR1, FGFR2 and FGFR3 leading to severe impairment in cranial, digital and skeletal development. Gain of function mutations in FGFRs were also identified in a variety of human cancers such as myeloproliferative syndromes, lymphomas, prostate and breast cancers as well as other malignant diseases. The binding of FGF and HSPG to the extracellular ligand domain of FGFR induces receptor dimerization, activation and autophosphorylation of multiple tyrosine residues in the cytoplasmic domain of the receptor molecule. A variety of signaling proteins are phosphorylated in response to FGF stimulation including Shc, phospholipase-Cgamma, STAT1, Gab1 and FRS2alpha leading to stimulation of intracellular signaling pathways that control cell proliferation, cell differentiation, cell migration, cell survival and cell shape. The docking proteins FRS2alpha and FRS2beta are major mediators of the Ras/MAPK and PI-3 kinase/Akt signaling pathways as well as negative feedback mechanisms that fine-tune the signal that is initiated at the cell surface following FGFR stimulation.

  2. Cellular-level surgery using nano robots.

    Science.gov (United States)

    Song, Bo; Yang, Ruiguo; Xi, Ning; Patterson, Kevin Charles; Qu, Chengeng; Lai, King Wai Chiu

    2012-12-01

    The atomic force microscope (AFM) is a popular instrument for studying the nano world. AFM is naturally suitable for imaging living samples and measuring mechanical properties. In this article, we propose a new concept of an AFM-based nano robot that can be applied for cellular-level surgery on living samples. The nano robot has multiple functions of imaging, manipulation, characterizing mechanical properties, and tracking. In addition, the technique of tip functionalization allows the nano robot the ability for precisely delivering a drug locally. Therefore, the nano robot can be used for conducting complicated nano surgery on living samples, such as cells and bacteria. Moreover, to provide a user-friendly interface, the software in this nano robot provides a "videolized" visual feedback for monitoring the dynamic changes on the sample surface. Both the operation of nano surgery and observation of the surgery results can be simultaneously achieved. This nano robot can be easily integrated with extra modules that have the potential applications of characterizing other properties of samples such as local conductance and capacitance.

  3. Biophysical Tools to Study Cellular Mechanotransduction

    Directory of Open Access Journals (Sweden)

    Ismaeel Muhamed

    2017-02-01

    Full Text Available The cell membrane is the interface that volumetrically isolates cellular components from the cell’s environment. Proteins embedded within and on the membrane have varied biological functions: reception of external biochemical signals, as membrane channels, amplification and regulation of chemical signals through secondary messenger molecules, controlled exocytosis, endocytosis, phagocytosis, organized recruitment and sequestration of cytosolic complex proteins, cell division processes, organization of the cytoskeleton and more. The membrane’s bioelectrical role is enabled by the physiologically controlled release and accumulation of electrochemical potential modulating molecules across the membrane through specialized ion channels (e.g., Na+, Ca2+, K+ channels. The membrane’s biomechanical functions include sensing external forces and/or the rigidity of the external environment through force transmission, specific conformational changes and/or signaling through mechanoreceptors (e.g., platelet endothelial cell adhesion molecule (PECAM, vascular endothelial (VE-cadherin, epithelial (E-cadherin, integrin embedded in the membrane. Certain mechanical stimulations through specific receptor complexes induce electrical and/or chemical impulses in cells and propagate across cells and tissues. These biomechanical sensory and biochemical responses have profound implications in normal physiology and disease. Here, we discuss the tools that facilitate the understanding of mechanosensitive adhesion receptors. This article is structured to provide a broad biochemical and mechanobiology background to introduce a freshman mechano-biologist to the field of mechanotransduction, with deeper study enabled by many of the references cited herein.

  4. Myoblast fusion: Experimental systems and cellular mechanisms.

    Science.gov (United States)

    Schejter, Eyal D

    2016-12-01

    Fusion of myoblasts gives rise to the large, multi-nucleated muscle fibers that power and support organism motion and form. The mechanisms underlying this prominent form of cell-cell fusion have been investigated by a variety of experimental approaches, in several model systems. The purpose of this review is to describe and discuss recent progress in the field, as well as point out issues currently unresolved and worthy of further investigation. Following a description of several new experimental settings employed in the study of myoblast fusion, a series of topics relevant to the current understanding of the process are presented. These pertain to elements of three major cellular machineries- cell-adhesion, the actin-based cytoskeleton and membrane-associated elements- all of which play key roles in mediating myoblast fusion. Among the issues raised are the diversity of functions ascribed to different adhesion proteins (e.g. external cell apposition and internal recruitment of cytoskeleton regulators); functional significance of fusion-associated actin structures; and discussion of alternative mechanisms employing single or multiple fusion pore formation as the basis for muscle cell fusion.

  5. Systems and photosystems: cellular limits of autotrophic productivity in cyanobacteria.

    Science.gov (United States)

    Burnap, Robert L

    2015-01-01

    Recent advances in the modeling of microbial growth and metabolism have shown that growth rate critically depends upon the optimal allocation of finite proteomic resources among different cellular functions and that modeling growth rates becomes more realistic with the explicit accounting for the costs of macromolecular synthesis, most importantly, protein expression. The "proteomic constraint" is considered together with its application to understanding photosynthetic microbial growth. The central hypothesis is that physical limits of cellular space (and corresponding solvation capacity) in conjunction with cell surface-to-volume ratios represent the underlying constraints on the maximal rate of autotrophic microbial growth. The limitation of cellular space thus constrains the size the total complement of macromolecules, dissolved ions, and metabolites. To a first approximation, the upper limit in the cellular amount of the total proteome is bounded this space limit. This predicts that adaptation to osmotic stress will result in lower maximal growth rates due to decreased cellular concentrations of core metabolic proteins necessary for cell growth owing the accumulation of compatible osmolytes, as surmised previously. The finite capacity of membrane and cytoplasmic space also leads to the hypothesis that the species-specific differences in maximal growth rates likely reflect differences in the allocation of space to niche-specific proteins with the corresponding diminution of space devoted to other functions including proteins of core autotrophic metabolism, which drive cell reproduction. An optimization model for autotrophic microbial growth, the autotrophic replicator model, was developed based upon previous work investigating heterotrophic growth. The present model describes autotrophic growth in terms of the allocation protein resources among core functional groups including the photosynthetic electron transport chain, light-harvesting antennae, and the

  6. Systems and Photosystems: Cellular Limits of Autotrophic Productivity in Cyanobacteria

    Directory of Open Access Journals (Sweden)

    Robert L Burnap

    2015-01-01

    Full Text Available Recent advances in the modeling of microbial growth and metabolism have shown that growth rate critically depends upon the optimal allocation of finite proteomic resources among different cellular functions and that modeling growth rates becomes more realistic with the explicit accounting for the costs of macromolecular, most importantly, protein expression. The ‘proteomic constraint’ is considered together with its application to understanding photosynthetic microbial growth. The central hypothesis is that physical limits of cellular space (and corresponding solvation capacity and cell surface to volume ratios represent the underlying constraints on the maximal rate of autotrophic microbial growth. The limitation of cellular space thus constrains the size the total complement of macromolecules, dissolved ions, and metabolites. To a first approximation, the upper limit in the cellular amount of the total proteome is bounded the space limit. This predicts that adaptation to osmotic stress will result in lower maximal growth rates due to decreased cellular concentrations of core metabolic proteins necessary for cell growth owing the accumulation of compatible osmolytes, as surmised previously. The finite capacity of membrane and cytoplasmic space also leads to the hypothesis that the species-specific differences in maximal growth rates likely reflect differences in the allocation of space to niche-specific proteins with the corresponding diminution of space devoted to other functions including proteins of core autotrophic metabolism, which drive cell reproduction. An optimization model for autotrophic microbial growth, the autotrophic replicator model (ARM, was developed based upon previous work investigating heterotrophic growth. The present model describes autotrophic growth in terms of the allocation protein resources among core functional groups including the photosynthetic electron transport chain, light harvesting antennae, and the

  7. 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

  8. Intrinsic Simulations between Stochastic Cellular Automata

    Directory of Open Access Journals (Sweden)

    Pablo Arrighi

    2012-08-01

    Full Text Available The paper proposes a simple formalism for dealing with deterministic, non-deterministic and stochastic cellular automata in a unifying and composable manner. Armed with this formalism, we extend the notion of intrinsic simulation between deterministic cellular automata, to the non-deterministic and stochastic settings. We then provide explicit tools to prove or disprove the existence of such a simulation between two stochastic cellular automata, even though the intrinsic simulation relation is shown to be undecidable in dimension two and higher. The key result behind this is the caracterization of equality of stochastic global maps by the existence of a coupling between the random sources. We then prove that there is a universal non-deterministic cellular automaton, but no universal stochastic cellular automaton. Yet we provide stochastic cellular automata achieving optimal partial universality.

  9. THE RELATIONSHIPS OF THREE ELEMENTARY CELLULAR AUTOMATA

    Institute of Scientific and Technical Information of China (English)

    Zhisong JIANG

    2006-01-01

    Limit language complexity of cellular automata which is first posed by S. Wolfram has become a new branch of cellular automata. In this paper, we obtain two interesting relationships between elementary cellular automata of rules 126, 146(182) and 18, and prove that if the limit language of rule 18 is not regular, nor are the limit languages of rules 126 and 146(182).

  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. Cellular interactions with tissue-engineered microenvironments and nanoparticles

    Science.gov (United States)

    Pan, Zhi

    Tissue-engineered hydrogels composed of intermolecularlly crosslinked hyaluronan (HA-DTPH) and fibronectin functional domains (FNfds) were applied as a physiological relevant ECM mimic with controlled mechanical and biochemical properties. Cellular interactions with this tissue-engineered environment, especially physical interactions (cellular traction forces), were quantitatively measured by using the digital image speckle correlation (DISC) technique and finite element method (FEM). By correlating with other cell functions such as cell morphology and migration, a comprehensive structure-function relationship between cells and their environments was identified. Furthermore, spatiotemporal redistribution of cellular traction stresses was time-lapse measured during cell migration to better understand the dynamics of cell mobility. The results suggest that the reinforcement of the traction stresses around the nucleus, as well as the relaxation of nuclear deformation, are critical steps during cell migration, serving as a speed regulator, which must be considered in any dynamic molecular reconstruction model of tissue cell migration. Besides single cell migration, en masse cell migration was studied by using agarose droplet migration assay. Cell density was demonstrated to be another important parameter to influence cell behaviors besides substrate properties. Findings from these studies will provide fundamental design criteria to develop novel and effective tissue-engineered constructs. Cellular interactions with rutile and anatase TiO2 nanoparticles were also studied. These particles can penetrate easily through the cell membrane and impair cell function, with the latter being more damaging. The exposure to nanoparticles was found to decrease cell area, cell proliferation, motility, and contractility. To prevent this, a dense grafted polymer brush coating was applied onto the nanoparticle surface. These modified nanoparticles failed to adhere to and penetrate

  12. Paramagnetic Liposome Nanoparticles for Cellular and Tumour Imaging

    Directory of Open Access Journals (Sweden)

    Nazila Kamaly

    2010-04-01

    Full Text Available In this review we discuss the development of paramagnetic liposomes incorporating MRI contrast agents and show how these are utilized in cellular imaging in vitro. Bi-functional, bi-modal imaging paramagnetic liposome systems are also described. Next we discuss the upgrading of paramagnetic liposomes into bi-modal imaging neutral nanoparticles for in vivo imaging applications. We discuss the development of such systems and show how paramagnetic liposomes and imaging nanoparticles could be developed as platforms for future multi-functional, multi-modal imaging theranostic nanodevices tailor-made for the combined imaging of early stage disease pathology and functional drug delivery.

  13. 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...

  14. Integration of mobile satellite and cellular systems

    Science.gov (United States)

    Drucker, Elliott H.; Estabrook, Polly; Pinck, Deborah; Ekroot, Laura

    1993-01-01

    By integrating the ground based infrastructure component of a mobile satellite system with the infrastructure systems of terrestrial 800 MHz cellular service providers, a seamless network of universal coverage can be established. Users equipped for both cellular and satellite service can take advantage of a number of features made possible by such integration, including seamless handoff and universal roaming. To provide maximum benefit at lowest posible cost, the means by which these systems are integrated must be carefully considered. Mobile satellite hub stations must be configured to efficiently interface with cellular Mobile Telephone Switching Offices (MTSO's), and cost effective mobile units that provide both cellular and satellite capability must be developed.

  15. Optimized Cellular Core for Rotorcraft Project

    Data.gov (United States)

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

  16. A multiscale theoretical model for diffusive mass transfer in cellular biological media.

    Science.gov (United States)

    Kapellos, George E; Alexiou, Terpsichori S; Payatakes, Alkiviades C

    2007-11-01

    An integrated methodology is developed for the theoretical analysis of solute transport and reaction in cellular biological media, such as tissues, microbial flocs, and biofilms. First, the method of local spatial averaging with a weight function is used to establish the equation which describes solute conservation at the cellular biological medium scale, starting with a continuum-based formulation of solute transport at finer spatial scales. Second, an effective-medium model is developed for the self-consistent calculation of the local diffusion coefficient in the cellular biological medium, including the effects of the structural heterogeneity of the extra-cellular space and the reversible adsorption to extra-cellular polymers. The final expression for the local effective diffusion coefficient is: D(Abeta)=lambda(beta)D(Aupsilon), where D(Aupsilon) is the diffusion coefficient in water, and lambda(beta) is a function of the composition and fundamental geometric and physicochemical system properties, including the size of solute molecules, the size of extra-cellular polymer fibers, and the mass permeability of the cell membrane. Furthermore, the analysis sheds some light on the function of the extra-cellular hydrogel as a diffusive barrier to solute molecules approaching the cell membrane, and its implications on the transport of chemotherapeutic agents within a cellular biological medium. Finally, the model predicts the qualitative trend as well as the quantitative variability of a large number of published experimental data on the diffusion coefficient of oxygen in cell-entrapping gels, microbial flocs, biofilms, and mammalian tissues.

  17. Transient expression and cellular localization of recombinant proteins in cultured insect cells

    Science.gov (United States)

    Heterologous protein expression systems are used for production of recombinant proteins, interpretation of cellular trafficking/localization, and for the determination of biochemical function of proteins at the sub-organismal level. Although baculovirus expression systems are increasingly used for ...

  18. A new cellular stress response that triggers centriolar satellite reorganization and ciliogenesis

    DEFF Research Database (Denmark)

    Villumsen, Bine H; Danielsen, Jannie R; Povlsen, Lou;

    2013-01-01

    Centriolar satellites are small, granular structures that cluster around centrosomes, but whose biological function and regulation are poorly understood. We show that centriolar satellites undergo striking reorganization in response to cellular stresses such as UV radiation, heat shock...

  19. 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...

  20. 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.

  1. Cellular Deconstruction: Finding Meaning in Individual Cell Variation.

    Science.gov (United States)

    Eberwine, James; Kim, Junhyong

    2015-10-01

    The advent of single cell transcriptome analysis has permitted the discovery of cell-to-cell variation in transcriptome expression of even presumptively identical cells. We hypothesize that this variability reflects a many-to-one relation between transcriptome states and the phenotype of a cell. In this relation, the molecular ratios of the subsets of RNA are determined by the stoichiometric constraints of the cell systems, which underdetermine the transcriptome state. Furthermore, the variability is, in part, induced by the tissue context and is important for system-level function. This theory is analogous to theories of literary deconstruction, where multiple 'signifiers' work in opposition to one another to create meaning. By analogy, transcriptome phenotypes should be defined as subsets of RNAs comprising selected RNA systems where the system-associated RNAs are balanced with each other to produce the associated cellular function. This idea provides a framework for understanding cellular heterogeneity in phenotypic responses to variant conditions, such as disease challenge.

  2. Complement-Mediated Regulation of Metabolism and Basic Cellular Processes.

    Science.gov (United States)

    Hess, Christoph; Kemper, Claudia

    2016-08-16

    Complement is well appreciated as a critical arm of innate immunity. It is required for the removal of invading pathogens and works by directly destroying them through the activation of innate and adaptive immune cells. However, complement activation and function is not confined to the extracellular space but also occurs within cells. Recent work indicates that complement activation regulates key metabolic pathways and thus can impact fundamental cellular processes, such as survival, proliferation, and autophagy. Newly identified functions of complement include a key role in shaping metabolic reprogramming, which underlies T cell effector differentiation, and a role as a nexus for interactions with other effector systems, in particular the inflammasome and Notch transcription-factor networks. This review focuses on the contributions of complement to basic processes of the cell, in particular the integration of complement with cellular metabolism and the potential implications in infection and other disease settings.

  3. Regulation and quantification of cellular mitochondrial morphology and content.

    Science.gov (United States)

    Tronstad, Karl J; Nooteboom, Marco; Nilsson, Linn I H; Nikolaisen, Julie; Sokolewicz, Maciek; Grefte, Sander; Pettersen, Ina K N; Dyrstad, Sissel; Hoel, Fredrik; Willems, Peter H G M; Koopman, Werner J H

    2014-01-01

    Mitochondria play a key role in signal transduction, redox homeostasis and cell survival, which extends far beyond their classical functioning in ATP production and energy metabolism. In living cells, mitochondrial content ("mitochondrial mass") depends on the cell-controlled balance between mitochondrial biogenesis and degradation. These processes are intricately linked to changes in net mitochondrial morphology and spatiotemporal positioning ("mitochondrial dynamics"), which are governed by mitochondrial fusion, fission and motility. It is becoming increasingly clear that mitochondrial mass and dynamics, as well as its ultrastructure and volume, are mechanistically linked to mitochondrial function and the cell. This means that proper quantification of mitochondrial morphology and content is of prime importance in understanding mitochondrial and cellular physiology in health and disease. This review first presents how cellular mitochondrial content is regulated at the level of mitochondrial biogenesis, degradation and dynamics. Next we discuss how mitochondrial dynamics and content can be analyzed with a special emphasis on quantitative live-cell microscopy strategies.

  4. 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.

  5. 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

  6. Identification of a novel Rev-interacting cellular protein

    Directory of Open Access Journals (Sweden)

    Werner Thomas

    2005-04-01

    Full Text Available Abstract Background Human cell types respond differently to infection by human immunodeficiency virus (HIV. Defining specific interactions between host cells and viral proteins is essential in understanding how viruses exploit cellular functions and the innate strategies underlying cellular control of HIV replication. The HIV Rev protein is a post-transcriptional inducer of HIV gene expression and an important target for interaction with cellular proteins. Identification of Rev-modulating cellular factors may eventually contribute to the design of novel antiviral therapies. Results Yeast-two hybrid screening of a T-cell cDNA library with Rev as bait led to isolation of a novel human cDNA product (16.4.1. 16.4.1-containing fusion proteins showed predominant cytoplasmic localization, which was dependent on CRM1-mediated export from the nucleus. Nuclear export activity of 16.4.1 was mapped to a 60 amino acid region and a novel transport signal identified. Interaction of 16.4.1 with Rev in human cells was shown in a mammalian two-hybrid assay and by colocalization of Rev and 16.4.1 in nucleoli, indicating that Rev can recruit 16.4.1 to the nucleus/nucleoli. Rev-dependent reporter expression was inhibited by overexpressing 16.4.1 and stimulated by siRNAs targeted to 16.4.1 sequences, demonstrating that 16.4.1 expression influences the transactivation function of Rev. Conclusion These results suggest that 16.4.1 may act as a modulator of Rev activity. The experimental strategies outlined in this study are applicable to the identification and biological characterization of further novel Rev-interacting cellular factors.

  7. Digital implementation of shunting-inhibitory cellular neural network

    Science.gov (United States)

    Hammadou, Tarik; Bouzerdoum, Abdesselam; Bermak, Amine

    2000-05-01

    Shunting inhibition is a model of early visual processing which can provide contrast and edge enhancement, and dynamic range compression. An architecture of digital Shunting Inhibitory Cellular Neural Network for real time image processing is presented. The proposed architecture is intended to be used in a complete vision system for edge detection and image enhancement. The present hardware architecture, is modeled and simulated in VHDL. Simulation results show the functional validity of the proposed architecture.

  8. Novel intracellular proteins associated with cellular vitamin D action.

    Science.gov (United States)

    Angelo, Giana; Wood, Richard J; Mayer, Jean

    2002-07-01

    Work with vitamin D-resistant New World primates has revealed novel cellular proteins involved in vitamin D action. An "intracellular vitamin D-binding protein" functions to bind vitamin D metabolites in the cell and enhances vitamin D action. By contrast, a "vitamin D response element-binding protein" inhibits vitamin D receptor binding to the DNA and is responsible for vitamin D resistance in New World primates.

  9. 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...

  10. Behavior of impulsive fuzzy cellular neural networks with distributed delays

    Directory of Open Access Journals (Sweden)

    Kelin Li

    2007-04-01

    Full Text Available In this paper, we investigate a generalized model of fuzzy cellular neural networks with distributed delays and impulses. By employing the theory of topological degree, M-matrix and Lypunov functional, we find sufficient conditions for the existence, uniqueness and global exponential stability of both the equilibrium point and the periodic solution. Two examples are given to illustrate the results obtained here.

  11. Effect of Gold Nanorod Surface Chemistry on Cellular Response

    Science.gov (United States)

    2011-03-15

    Recombi - nation DNA Repair Network for Targeted Cancer Therapy. World J. Clin. Oncol. 2011, 2, 73–79. 36. Higashi, H.; Vallb€ohmer, D.; Warnecke-Eberz, U...cellular morphology, mitochondrial function, mitochondrial membrane potential (MMP), intracellular calcium levels, DNA damage-related gene expression, and of...observed in the MMP and Ca++ levels, up or down regulation of DNA damage related gene expression suggested a differential cell death mechanism based on

  12. Flexible substrata for the detection of cellular traction forces

    Science.gov (United States)

    Beningo, Karen A.; Wang, Yu-Li

    2002-01-01

    By modulating adhesion signaling and cytoskeletal organization, mechanical forces play an important role in various cellular functions, from propelling cell migration to mediating communication between cells. Recent developments have resulted in several new approaches for the detection, analysis and visualization of mechanical forces generated by cultured cells. Combining these methods with other approaches, such as green-fluorescent protein (GFP) imaging and gene manipulation, proves to be particularly powerful for analyzing the interplay between extracellular physical forces and intracellular chemical events.

  13. 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.

  14. Functionalization and cellular uptake of boron carbide nanoparticles

    DEFF Research Database (Denmark)

    Mortensen, M. W.; Björkdahl, O.; Sørensen, P. G.;

    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....

  15. Cellular functions of gamma-secretase-related proteins

    OpenAIRE

    Haffner, Christof; Haass, Christian

    2006-01-01

    Amyloid-beta pepticle (A beta) is generated by gamma-secretase, a membrane protein complex with an unusual aspartyl protease activity consisting of the four components presenilin, nicastrin, APH-1 and PEN-2. Presenilin is considered the catalytic subunit of this complex since it represents the prototype of the new family of intramembrane-cleaving GxGD-type aspartyl proteases. Recently, five novel members of this family and a nicastrin-like protein were identified. Whereas one of the GxGD-type...

  16. Functional and cellular adaptation to weightlessness in primates

    Science.gov (United States)

    Bodine-Fowler, Sue C.; Pierotti, David J.; Talmadge, Robert J.

    1995-01-01

    Considerable data has been collected on the response of hindlimb muscles to unloading due to both spaceflight and hindlimb suspension. One generalized response to a reduction in load is muscle fiber atrophy, although not all muscles respond the same. Our understanding of how muscles respond to microgravity, however, has come primarily from the examination of hindlimb muscles in the unrestrained rate in space. The non-human primate spaceflight paradigm differs considerably from the rodent paradigm in that the monkeys are restrained, usually in a sitting position, while in space. Recently, we examined the effects of microgravity on muscles of the Rhesus monkey by taking biopsies of selected hindlimb muscles prior to and following spaceflights of 14 and 12 day durations (Cosmos 2044 and 2229). Our results revealed that the monkey's response to microgravity differs from that of the rat. The apparent differences in the atrophic response of the hindlimb muscles of the monkey and rat to spaceflight may be attributed to the following: (1) a species difference; (2) a difference in the manner in which the animals were maintained during the flight (i.e., chair restraint or 'free-floating'); and/or (3) an ability of the monkeys to counteract the effects of spaceflight with resistive exercise.

  17. 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.

  18. 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.

  19. Cellular encoding for interactive evolutionary robotics

    NARCIS (Netherlands)

    Gruau, F.C.; Quatramaran, K.

    1996-01-01

    This work reports experiments in interactive evolutionary robotics. The goal is to evolve an Artificial Neural Network (ANN) to control the locomotion of an 8-legged robot. The ANNs are encoded using a cellular developmental process called cellular encoding. In a previous work similar experiments ha

  20. LMS filters for cellular CDMA overlay

    OpenAIRE

    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.

  1. 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.

  2. On noise limited cellular networks

    CERN Document Server

    Decreusefond, Laurent; Vu, Thanh-Tung

    2010-01-01

    This paper introduces a general theoretical framework to analyze noise limited networks. More precisely, we consider two homogenous Poisson point processes of base stations and users. General model of radio signal propagation and effect of fading are also considered. The main difference of our model with respect to other existing models is that a user connects to his best servers but not necessarily the closest one. We provide general formula for the outage probability. We study functionals related to the SNR as well as the sum of these functionals over all users per cell. For the latter, the expectation and bounds on the variance are obtained.

  3. 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.

  4. 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.

  5. 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.

  6. The Universe as a Cellular System

    CERN Document Server

    Aragón-Calvo, Miguel A

    2014-01-01

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

  7. The mammary cellular hierarchy and breast cancer.

    Science.gov (United States)

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

    2014-11-01

    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 regulation of the mammary cellular hierarchy and we describe the development of the concepts that have guided our investigations. We outline recent advances in in vivo lineage tracing that is now challenging many of our assumptions regarding the behavior of mammary stem cells, and we show how understanding these cellular lineages has altered our view of breast cancer.

  8. Seeing cellular sialidase transform sugars

    OpenAIRE

    Fukuda, Minoru; Bao, Xingfeng

    2008-01-01

    Cell-surface carbohydrates are synthesized in a step-wise fashion, yielding products with unique capping structures. A recent study has shown that carbohydrates at the cell surface can be further remodeled by an endogenous glycosidase to alter the carbohydrate structure, thus generating a new function.

  9. Endothelial Cellular Responses to Biodegradable Metal Zinc.

    Science.gov (United States)

    Ma, Jun; Zhao, Nan; Zhu, Donghui

    Biodegradable zinc (Zn) metals, a new generation of biomaterials, have attracted much attention due to their excellent biodegradability, bioabsorbability, and adaptability to tissue regeneration. Compared with magnesium (Mg) and iron (Fe), Zn exhibits better corrosion and mechanical behaviors in orthopedic and stent applications. After implantation, Zn containing material will slowly degrade, and Zn ions (Zn(2+)) will be released to the surrounding tissue. For stent applications, the local Zn(2+)concentration near endothelial tissue/cells could be high. However, it is unclear how endothelia will respond to such high concentrations of Zn(2+), which is pivotal to vascular remodeling and regeneration. Here, we evaluated the short-term cellular behaviors of primary human coronary artery endothelial cells (HCECs) exposed to a concentration gradient (0-140 μM) of extracellular Zn(2+). Zn(2+) had an interesting biphasic effect on cell viability, proliferation, spreading, and migration. Generally, low concentrations of Zn(2+) promoted viability, proliferation, adhesion, and migration, while high concentrations of Zn(2+) had opposite effects. For gene expression profiles, the most affected functional genes were related to cell adhesion, cell injury, cell growth, angiogenesis, inflammation, vessel tone, and coagulation. These results provide helpful information and guidance for Zn-based alloy design as well as the controlled release of Zn(2+)in stent and other related medical applications.

  10. Cellular effector mechanisms against Plasmodium liver stages.

    Science.gov (United States)

    Frevert, Ute; Nardin, Elizabeth

    2008-10-01

    Advances in our understanding of the molecular and cell biology of the malaria parasite have led to new vaccine development efforts resulting in a pipeline of over 40 candidates undergoing clinical phase I-III trials. Vaccine-induced CD4+ and CD8+ T cells specific for pre-erythrocytic stage antigens have been found to express cytolytic and multi-cytokine effector functions that support a key role for these T cells within the hepatic environment. However, little is known of the cellular interactions that occur during the effector phase in which the intracellular hepatic stage of the parasite is targeted and destroyed. This review focuses on cell biological aspects of the interaction between malaria-specific effector cells and the various antigen-presenting cells that are known to exist within the liver, including hepatocytes, dendritic cells, Kupffer cells, stellate cells and sinusoidal endothelia. Considering the unique immune properties of the liver, it is conceivable that these different hepatic antigen-presenting cells fulfil distinct but complementary roles during the effector phase against Plasmodium liver stages.

  11. Inhibitory role of peroxiredoxin II (Prx II) on cellular senescence.

    Science.gov (United States)

    Han, Ying-Hao; Kim, Hyun-Sun; Kim, Jin-Man; Kim, Sang-Keun; Yu, Dae-Yeul; Moon, Eun-Yi

    2005-08-29

    Reactive oxygen species (ROS) were generated in all oxygen-utilizing organisms. Peroxiredoxin II (Prx II) as one of antioxidant enzymes may play a protective role against the oxidative damage caused by ROS. In order to define the role of Prx II in organismal aging, we evaluated cellular senescence in Prx II(-/-) mouse embryonic fibroblast (MEF). As compared to wild type MEF, cellular senescence was accelerated in Prx II(-/-) MEF. Senescence-associated (SA)-beta-galactosidase (Gal)-positive cell formation was about 30% higher in Prx II(-/-) MEF. N-Acetyl-l-cysteine (NAC) treatment attenuated SA-beta-Gal-positive cell formation. Prx II(-/-) MEF exhibited the higher G2/M (41%) and lower S (1.6%) phase cells as compared to 24% and 7.3% [corrected] in wild type MEF, respectively. A high increase in the p16 and a slight increase in the p21 and p53 levels were detected in PrxII(-/-) MEF cells. The cellular senescence of Prx II(-/-) MEF was correlated with the organismal aging of Prx II(-/-) mouse skin. While extracellular signal-regulated kinase (ERK) and p38 activation was detected in Prx II(-/-) MEF, ERK and c-Jun N-terminal kinase (JNK) activation was detected in Prx II(-/-) skin. These results suggest that Prx II may function as an enzymatic antioxidant to prevent cellular senescence and skin aging.

  12. 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.

  13. 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.

  14. Optimal Band Allocation for Cognitive Cellular Networks

    CERN Document Server

    Liu, Tingting

    2011-01-01

    FCC new regulation for cognitive use of the TV white space spectrum provides a new means for improving traditional cellular network performance. But it also introduces a number of technical challenges. This letter studies one of the challenges, that is, given the significant differences in the propagation property and the transmit power limitations between the cellular band and the TV white space, how to jointly utilize both bands such that the benefit from the TV white space for improving cellular network performance is maximized. Both analytical and simulation results are provided.

  15. Cryptographic primitives based on cellular transformations

    Directory of Open Access Journals (Sweden)

    B.V. Izotov

    2003-11-01

    Full Text Available Design of cryptographic primitives based on the concept of cellular automata (CA is likely to be a promising trend in cryptography. In this paper, the improved method performing data transformations by using invertible cyclic CAs (CCA is considered. Besides, the cellular operations (CO as a novel CAs application in the block ciphers are introduced. Proposed CCAs and COs, integrated under the name of cellular transformations (CT, suit well to be used in cryptographic algorithms oriented to fast software and cheap hardware implementation.

  16. 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

  17. On-Chip Detection of Cellular Activity

    Science.gov (United States)

    Almog, R.; Daniel, R.; Vernick, S.; Ron, A.; Ben-Yoav, H.; Shacham-Diamand, Y.

    The use of on-chip cellular activity monitoring for biological/chemical sensing is promising for environmental, medical and pharmaceutical applications. The miniaturization revolution in microelectronics is harnessed to provide on-chip detection of cellular activity, opening new horizons for miniature, fast, low cost and portable screening and monitoring devices. In this chapter we survey different on-chip cellular activity detection technologies based on electrochemical, bio-impedance and optical detection. Both prokaryotic and eukaryotic cell-on-chip technologies are mentioned and reviewed.

  18. Cellular Factors Required for Lassa Virus Budding

    OpenAIRE

    Urata, Shuzo; Noda, Takeshi; Kawaoka, Yoshihiro; Yokosawa, Hideyoshi; Yasuda, Jiro

    2006-01-01

    It is known that Lassa virus Z protein is sufficient for the release of virus-like particles (VLPs) and that it has two L domains, PTAP and PPPY, in its C terminus. However, little is known about the cellular factor for Lassa virus budding. We examined which cellular factors are used in Lassa virus Z budding. We demonstrated that Lassa Z protein efficiently produces VLPs and uses cellular factors, Vps4A, Vps4B, and Tsg101, in budding, suggesting that Lassa virus budding uses the multivesicula...

  19. Modeling Integrated Cellular Machinery Using Hybrid Petri-Boolean Networks

    Science.gov (United States)

    Berestovsky, Natalie; Zhou, Wanding; Nagrath, Deepak; Nakhleh, Luay

    2013-01-01

    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 using such more

  20. 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

  1. 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.

  2. 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'.

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

    Science.gov (United States)

    Howarth, Clare; Kurth-Nelson, Zebulun; Mishra, Anusha

    2016-01-01

    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

  4. Cellular and molecular neuronal plasticity.

    Science.gov (United States)

    Griesbach, Grace S; Hovda, David A

    2015-01-01

    The brain has the capability to adapt to function when tissue is compromised. This capability of adaptation paves the road to recovery and allows for rehabilitation after a traumatic brain injury (TBI). This chapter addresses neuroplasticity within the context of TBI. Here neuroplasticity is defined as changes in neuronal structure and function, including synaptic changes as well as modifications in neural pathways. First, the influence of TBI pathology on neuroplasticity is addressed. Here, proteins that are important in neuroplasticity are introduced and a description given of how these are affected in a temporal and severity-dependent manner. Secondly, given that we are becoming increasingly aware that the brain's response to injury is highly influenced by the environmental milieu, the manner in which behavioral manipulations have an effect on TBI-associated neuroplasticity is addressed. A description is given of how specific environmental qualities may facilitate or hinder neuroplasticity. Finally, the long-term effects of neuroplasticity and the relevance it has to rehabilitation are described.

  5. High-throughput microcavitation bubble induced cellular mechanotransduction

    Science.gov (United States)

    Compton, Jonathan Lee

    Focused pulsed laser irradiation allows for the deposition of energy with high spatial and temporal resolution. These attributes provide an optimal tool for non-contact manipulation in cellular biology such as laser microsurgery, cell membrane permeabilization, as well as targeted cell death. In this thesis we investigate the direct physical effects produced by laser- generated microcavitation bubbles in adherent cell cultures. We examine how variation in pulse durations (180 ps - 6ns) and pulse energy (0.5 - 40 mu;J) affect microcavitation bubble (mu;CB) generated cell lysis, necrosis, and molecular delivery. To compare the effects of pulse duration we employ classical fluid dynamics modeling to quantify the perturbation caused on cell populations from mu;CB generated microTsunamis (a transient microscale burst of hydrodynamic shear stress). Through time-resolved imaging we capture the mu;CB dynamics at various energies and pulse durations. Moreover, the mathematical modeling provides information regarding the cellular exposure to time varying shear stress and impulse as a function of radial location from the mu;CB center. We demonstrate that the resultant cellular effect can be predicted based on the total impulse across a two order of magnitude span of pulse duration and pulse energy. We also examine the region of cells beyond the zone of molecular delivery to investigate possible cellular reactions to mu;Tsunami exposure. Our studies have shown that cellular mechanotransduction occurs within cell populations spanning an area of up to 1 mm2 surrounding the mu;CB. Visualization of mechanotransduction is achieved through the visualization of intracellular calcium signaling via fluorescence microscopy that occurs due to the ability of the muTsunami generated shear stresses to stimulate G-protein coupled receptors at the apical cell surface. Moreover, we have shown that the observed signaling can be attenuated in a dose-dependent manner using 2-APB which is a known

  6. Stress testing at the cellular and molecular level to unravel cellular dysfunction and growth factor signal transduction defects: what Molecular Cell Biology can learn from Cardiology.

    Science.gov (United States)

    Waltenberger, Johannes

    2007-11-01

    Clinical medicine has been revolutionized by the impact of cellular and molecular biology in the past 30 years. This article focuses on a novel approach, whereby the clinically proven and important concept of patient or organ stress testing is being applied to cellular models, thereby developing and validating novel quantitative molecular and cellular stress tests. One example is monocyte chemotaxis analysis, whereby circulating monocytes freshly isolated from peripheral blood are being tested for their migratory responsiveness towards relevant biological stimuli such as growth factors or chemokines. These stimuli are relevant for recruiting monocytes to sites of local inflammation such as during wound healing or arteriogenesis, i.e. growth of collateral arteries. Initial clinical studies to validate "ligand-induced monocyte chemotaxis" indicate that this parameter is impaired in the presence of various cardiovascular risk factors including diabetes mellitus, hypercholesterolemia or smoking. In addition, there is proof of concept that impaired monocyte chemotaxis is reversible as shown for anti-oxidants in smokers. Moreover, the parameter "ligand-induced monocyte chemotaxis" is of great relevance for basic science (including Molecular Cell Biology) as unravelling the underlying molecular mechanisms of cellular dysfunction will certainly stimulate our understanding of the molecular basis of cellular function. This article highlights the concept of stress testing in modern medicine. Cellular stress testing is introduced as a novel and intriguing approach, which was developed as bedside-to-bench. Future prospective clinical trials will have to validate the predictive value of cellular stress testing.

  7. Effects of freque ncy radiation of 900MHz cellular phone on the liver structure and function of rats at different time points%不同时间900 MHz 手机频率辐射对 SD 雄鼠肝组织形态和功能的影响

    Institute of Scientific and Technical Information of China (English)

    罗亚萍; 李春香; 马惠荣; 栗晶晶; 李媛媛; 马雪莲; 宫志强

    2013-01-01

    Objective To investigate the influence of frequency radiation of 900 MHz cellular phone on the liver structure and function of rats at different time points .Methods Thirty adult male SD rats were randomly divided into three groups,control group,12-day radiation group and 18-day radiation group.The rats in control group did not receive radiation , the rats in radiation groups received frequency radiation from 900 MHz cellular phone for 12 days and 18 days (4h/d),respectively.Finally the serum levels of ALT and AST were detected and the changes of liver structure were observed by HE staining .Results As compared with those in control group,the serum levels of ALT and AST were not obviously changed in 12-day radiation group and 18-day radiation group .HE staining results showed that as compared with that in control group , hepatic lobules was clear , hepatocyte nuclear was partly atrophy or disappeared in 12-day radiation group ,and hepatic lobules structure was basically complete , hepatocyte was swelling and vacuolar degeneration appeared in part of cytoplasm in 18-day radiation group.Con-lc usion The frequency radiation of 900 MHz cellular phone can result in hepatic injury of rats ,with hepatocyte nu-clear atrophy , swelling and vacuolar degeneration , however , serum levels of ALT and AST are not obviously changed .%目的观察900 MHz手机频率辐射12 d、18 d对雄性SD大鼠肝组织形态和功能的影响。方法选育龄期SD雄鼠30只。将雄性大鼠按体重均衡的原则随机分为3组,正常组、12 d、18 d辐射组。正常组不接受辐射,辐射组分别接受900 MHz手机频率辐射连续12 d、18 d4 h/d,于辐射结束次晨处死。观察比较3组大鼠血清丙氨酸转氨酶( ALT)、门冬氨酸氨基转移酶( AST)及二者比值,雄鼠肝脏HE染色。结果与正常组比较,12 d和18 d辐射组血清ALT、AST无显著性改变;肝的HE染色结果显示:与正常组比较,12 d辐射组肝小叶结构基

  8. Influence of infection of Mycobacterium tuberculosis in peripheral blood mononuclear cells on the function of cellular immunity%结核杆菌感染外周血单个核细胞对细胞免疫功能的影响

    Institute of Scientific and Technical Information of China (English)

    王健; 赵尔君; 孙琳; 吴传良; 段建明

    2001-01-01

    Objective:To investigate the influence of Mycobacteriumtuberculosis(Mtb) infection in peripheral blood mononuclear cells(PBMC) on the function of cellular immunity and its effects on the transformation of tuberculosis.Methods:The Mtb DNA in PBMC was detected by polymerase chain reaction(PCR),and phenotypes of T cell subsets and the expressing level of membrane interleukin-2 receptor(mIL-2R) with or without PHA inducement were detected by biotin-streptavidin(BSA) technique.Results:Both the proportion of T cell subsets and the level of mIL-2R were decreased in patients with tuberculosis than those in normal controls(P<0.05~P<0.01).While the proportion of CD3+ and CD4+ cells in PBMC,the ratio of CD4+/CD8+ cells,and the level of mIL-2R in PBMC were significantly lower in Mtb-DNA(+) group than those in Mtb-DNA(-) group(P<0.01),the proportion of CD8+ cells in PBMC was higher in Mtb-DNA(+) group than that in Mtb-DNA(-) group(P<0.05).Conclusions:The results in this study showed that the cellular immunity was obviously lower in patients with tuberculosis.The disorder of cellular immunity in patients with tuberculosis was further aggravated and the level of mIL-2R was restrained by infection of Mtb in PBMC.%目的:探讨结核杆菌感染外周血单个核细胞(PBMC)对细胞免疫功能的影响及在结核病转归中的作用。方法:用PCR检测结核病患者PBMC中结核杆菌DNA(TB-DNA),用生物素-链霉亲和素(BSA)系统同步检测其T细胞亚群及经植物血凝素(PHA)诱导前后膜白介素-2受体(mIL-2R)水平。结果:结核病患者T细胞亚群及mIL-2R水平与对照组相比均显著降低(P<0.05~P<0.01)。其中PBMC内TB-DNA(+)组与TB-DNA(-)组相比,CD3+、CD4+百分率及CD4+/CD8+比值降低,CD8+百分率增高(P<0.05);PHA诱导前后mIL-2R水平较对照组相比均低下,差异均有显著性(P<0.01)。结论:结核病患者体内细胞免疫功能低下,结核杆菌感染PBMC后可加重患者细胞

  9. Cellular compatibility of improved scaffold material with deproteinized heterogeneous bone

    Institute of Scientific and Technical Information of China (English)

    LIU Lei; PEI Fu-xing; ZHOU Zong-ke; LI Qi-hong

    2007-01-01

    Objective:To study cellular compatibility of improved scaffold material with deproteinized heterogeneous bone and provide experimental basis on choosing the scaffold material in bone tissue engineering.Methods: Bone marrow stromal cells (BMSC) were co-cultured with heterogeneous deproteinized bone in vitro. The contrast phase microscope, scanning electron microscope, MTT assay, flow cytometry were performed and the BGP content and ALP activities were detected in order to observe the cell growth, adhesion in the material, cell cycle and cell viability.Results: The scaffold material of deproteinized heterogeneous bone had no inhibitory effect on cellular proliferation, differentiation and secretion function of BMSCs.Conclusions: The established heterogeneous deproteinized bone has good biocompatibility with BMSCs and is a potentially ideal scaffold material for bone tissue engineering.

  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. Schema Redescription in Cellular Automata: Revisiting Emergence in Complex Systems

    CERN Document Server

    Marques-Pita, Manuel

    2011-01-01

    We present a method to eliminate redundancy in the transition tables of Boolean automata: schema redescription with two symbols. One symbol is used to capture redundancy of individual input variables, and another to capture permutability in sets of input variables: fully characterizing the canalization present in Boolean functions. Two-symbol schemata explain aspects of the behaviour of automata networks that the characterization of their emergent patterns does not capture. We use our method to compare two well-known cellular automata for the density classification task: the human engineered CA GKL, and another obtained via genetic programming. We show that despite having very different collective behaviour, these rules are very similar. Indeed, GKL is a special case of GP. Therefore, we demonstrate that it is more feasible to compare cellular automata via schema redescriptions of their rules, than by looking at their emergent behaviour, leading us to question the tendency in complexity research to pay much m...

  12. 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...

  13. Micro/Nanoscale Thermometry for Cellular Thermal Sensing.

    Science.gov (United States)

    Bai, Tingting; Gu, Ning

    2016-09-01

    Temperature is a key parameter to regulate cell function, and biochemical reactions inside a cell in turn affect the intracellular temperature. It's vitally necessary to measure cellular temperature to provide sufficient information to fully understand life science, while the conventional methods are incompetent. Over the last decade, many ingenious thermometers have been developed with the help of nanotechnology, and real-time intracellular temperature measurement at the micro/nanoscale has been realized with high temporal-spatial resolution. With the help of these techniques, several mechanisms of thermogenesis inside cells have been investigated, even in subcellular organelles. Here, current developments in cellular thermometers are highlighted, and a picture of their applications in cell biology is presented. In particular, temperature measurement principle, thermometer design and latest achievements are also introduced. Finally, the existing opportunities and challenges in this ongoing field are discussed.

  14. Virus-encapsulated DNA origami nanostructures for cellular delivery.

    Science.gov (United States)

    Mikkilä, Joona; Eskelinen, Antti-Pekka; Niemelä, Elina H; Linko, Veikko; Frilander, Mikko J; Törmä, Päivi; Kostiainen, Mauri A

    2014-01-01

    DNA origami structures can be programmed into arbitrary shapes with nanometer scale precision, which opens up numerous attractive opportunities to engineer novel functional materials. One intriguing possibility is to use DNA origamis for fully tunable, targeted, and triggered drug delivery. In this work, we demonstrate the coating of DNA origami nanostructures with virus capsid proteins for enhancing cellular delivery. Our approach utilizes purified cowpea chlorotic mottle virus capsid proteins that can bind and self-assemble on the origami surface through electrostatic interactions and further pack the origami nanostructures inside the viral capsid. Confocal microscopy imaging and transfection studies with a human HEK293 cell line indicate that protein coating improves cellular attachment and delivery of origamis into the cells by 13-fold compared to bare DNA origamis. The presented method could readily find applications not only in sophisticated drug delivery applications but also in organizing intracellular reactions by origami-based templates.

  15. A cellular automata model with probability infection and spatial dispersion

    Institute of Scientific and Technical Information of China (English)

    Jin Zhen; Liu Quan-Xing; Mainul Haque

    2007-01-01

    In this article, we have proposed an epidemic model based on the probability cellular automata theory. The essential mathematical features are analysed with the help of stability theory. We have given an alternative modelling approach for the spatiotemporal system which is more realistic from the practical point of view. A discrete and spatiotemporal approach is shown by using cellular automata theory. It is interesting to note that both the size of the endemic equilibrium and the density of the individuals increase with the increase of the neighbourhood size and infection rate, but the infections decrease with the increase of the recovery rate. The stability of the system around the positive interior equilibrium has been shown by using a suitable Lyapunov function. Finally, experimental data simulation for SARS disease in China in 2003 and a brief discussion are given.

  16. 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.

  17. Cellular Defect May Be Linked to Parkinson's

    Science.gov (United States)

    ... 160862.html Cellular Defect May Be Linked to Parkinson's: Study Abnormality might apply to all forms of ... that may be common to all forms of Parkinson's disease. The defect plays a major role in ...

  18. Integration of Mobil Satellite and Cellular Systems

    Science.gov (United States)

    Drucker, E. H.; Estabrook, P.; Pinck, D.; Ekroot, L.

    1993-01-01

    By integrating the ground based infrastructure component of a mobile satellite system with the infrastructure systems of terrestrial 800 MHz cellular service providers, a seamless network of universal coverage can be established.

  19. Cellular Automaton Modeling of Pattern Formation

    NARCIS (Netherlands)

    Boerlijst, M.C.

    2006-01-01

    Book review Andreas Deutsch and Sabine Dormann, Cellular Automaton Modeling of Biological Pattern Formation, Characterization, Applications, and Analysis, Birkhäuser (2005) ISBN 0-8176-4281-1 331pp..

  20. 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 Core,...

  1. Densities and entropies in cellular automata

    CERN Document Server

    Guillon, Pierre

    2012-01-01

    Following work by Hochman and Meyerovitch on multidimensional SFT, we give computability-theoretic characterizations of the real numbers that can appear as the topological entropies of one-dimensional and two-dimensional cellular automata.

  2. The origin of cellular life

    Science.gov (United States)

    Ingber, D. E.

    2000-01-01

    This essay presents a scenario of the origin of life that is based on analysis of biological architecture and mechanical design at the microstructural level. My thesis is that the same architectural and energetic constraints that shape cells today also guided the evolution of the first cells and that the molecular scaffolds that support solid-phase biochemistry in modern cells represent living microfossils of past life forms. This concept emerged from the discovery that cells mechanically stabilize themselves using tensegrity architecture and that these same building rules guide hierarchical self-assembly at all size scales (Sci. Amer 278:48-57;1998). When combined with other fundamental design principles (e.g., energy minimization, topological constraints, structural hierarchies, autocatalytic sets, solid-state biochemistry), tensegrity provides a physical basis to explain how atomic and molecular elements progressively self-assembled to create hierarchical structures with increasingly complex functions, including living cells that can self-reproduce.

  3. 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.

  4. Sponging of Cellular Proteins by Viral RNAs

    OpenAIRE

    Charley, Phillida A.; Wilusz, Jeffrey

    2014-01-01

    Viral RNAs accumulate to high levels during infection and interact with a variety of cellular factors including miRNAs and RNA-binding proteins. Although many of these interactions exist to directly modulate replication, translation and decay of viral transcripts, evidence is emerging that abundant viral RNAs may in certain cases serve as a sponge to sequester host non coding RNAs and proteins. By effectively reducing the ability of cellular RNA binding proteins to regulate host cell gene exp...

  5. Polymersomes containing quantum dots for cellular imaging

    Directory of Open Access Journals (Sweden)

    Camblin M

    2014-05-01

    Full Text Available Marine Camblin,1 Pascal Detampel,1 Helene Kettiger,1 Dalin Wu,2 Vimalkumar Balasubramanian,1,* Jörg Huwyler1,*1Division of Pharmaceutical Technology, 2Department of Chemistry, University of Basel, Basel, Switzerland*These authors contributed equally to this workAbstract: Quantum dots (QDs are highly fluorescent and stable probes for cellular and molecular imaging. However, poor intracellular delivery, stability, and toxicity of QDs in biological compartments hamper their use in cellular imaging. To overcome these limitations, we developed a simple and effective method to load QDs into polymersomes (Ps made of poly(dimethylsiloxane-poly(2-methyloxazoline (PDMS-PMOXA diblock copolymers without compromising the characteristics of the QDs. These Ps showed no cellular toxicity and QDs were successfully incorporated into the aqueous compartment of the Ps as confirmed by transmission electron microscopy, fluorescence spectroscopy, and fluorescence correlation spectroscopy. Ps containing QDs showed colloidal stability over a period of 6 weeks if stored in phosphate-buffered saline (PBS at physiological pH (7.4. Efficient intracellular delivery of Ps containing QDs was achieved in human liver carcinoma cells (HepG2 and was visualized by confocal laser scanning microscopy (CLSM. Ps containing QDs showed a time- and concentration-dependent uptake in HepG2 cells and exhibited better intracellular stability than liposomes. Our results suggest that Ps containing QDs can be used as nanoprobes for cellular imaging.Keywords: quantum dots, polymersomes, cellular imaging, cellular uptake

  6. Global stability analysis on a class of cellular neural networks

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Yi

    2001-01-01

    [1]Chua, L. O., Yang, L., Cellular neural networks: Theory, IEEE Trans. CAS, 1988, (10): 1257.[2]Chua, L. O., Yang, L., Cellular neural networks: Applications, IEEE Trans. CAS, 1988, (10): 1273.[3]Chua, L. O., Roska, T., The CNN paradigm, IEEE Trans. CAS-I, 1993, (3): 147.[4]Matsumoto, T. Chua, L. O., Suzuki, H., CNN cloning template: Connected component detector, IEEE Trans. CAS, 1990, (8): 633.[5]Cao, L, Sun, Y, Yu, J., A CNN-based signature verification system,Proc. ICONIP′95, Beijing, 1995, 913—916.[6]Roska, T., Chua, L. O., The CNN universal machine: An analogic array computer, IEEE Trans. CAS Ⅱ, 1993, (3): 163.[7]Chua, L. O., Roska, T., Stability of a class of nonreciprocal cellular neural networks, IEEE Trans. CAS, 1990, (3): 1520.[8]Roska, T., Wu, C. W., Balsi, M. Et al., Stability and dynamics of delay type general and cellular neural networks, IEEE Trans. CAS, 1992, (6): 487.[9]Roska, T., Wu, C. W., Chua, L. O., Stability of cellular neural networks with dominant nonlinear and delaytype templates, IEEE Trans. CAS, 1993, (4): 270.[10]Civalleri, P. P., On stability of cellular neural networks with delay, IEEE Trans. CAS-I, 1993, (3): 157.[11]Gilli, G., Stability of cellular neural network and delayed cellular neural networks with nonpositive templates and nonmonotonic output functions, IEEE Trans CAS-I, 1994, (8): 518.[12]Baldi, P., Atiya, A. F., How delays affect neural dynamics and learning, IEEE Trans. On Neural Networks, 1994, (4): 612.[13]Liao, X. X., Mathematic foundation of cellular neural networks (Ⅰ), Science in China, Ser. A, 1994, 37(9): 902.[14]Liao, X. X., Mathematic foundation of cellular neural networks (Ⅱ), Science in China, Ser. A, 1994, 37(9): 1037.[15]Zhang, Y., Global exponential stability and periodic solutions of delay Hopfild neural networks, International J. Sys. Sci., 1996, (2): 227.[16]Zhang Yi, Zhong, S. M., Li, Z. L., Periodic solutions and global

  7. Amplitude metrics for cellular circadian bioluminescence reporters.

    Science.gov (United States)

    St John, Peter C; Taylor, Stephanie R; Abel, John H; Doyle, Francis J

    2014-12-01

    Bioluminescence rhythms from cellular reporters have become the most common method used to quantify oscillations in circadian gene expression. These experimental systems can reveal phase and amplitude change resulting from circadian disturbances, and can be used in conjunction with mathematical models to lend further insight into the mechanistic basis of clock amplitude regulation. However, bioluminescence experiments track the mean output from thousands of noisy, uncoupled oscillators, obscuring the direct effect of a given stimulus on the genetic regulatory network. In many cases, it is unclear whether changes in amplitude are due to individual changes in gene expression level or to a change in coherence of the population. Although such systems can be modeled using explicit stochastic simulations, these models are computationally cumbersome and limit analytical insight into the mechanisms of amplitude change. We therefore develop theoretical and computational tools to approximate the mean expression level in large populations of noninteracting oscillators, and further define computationally efficient amplitude response calculations to describe phase-dependent amplitude change. At the single-cell level, a mechanistic nonlinear ordinary differential equation model is used to calculate the transient response of each cell to a perturbation, whereas population-level dynamics are captured by coupling this detailed model to a phase density function. Our analysis reveals that amplitude changes mediated at either the individual-cell or the population level can be distinguished in tissue-level bioluminescence data without the need for single-cell measurements. We demonstrate the effectiveness of the method by modeling experimental bioluminescence profiles of light-sensitive fibroblasts, reconciling the conclusions of two seemingly contradictory studies. This modeling framework allows a direct comparison between in vitro bioluminescence experiments and in silico ordinary

  8. Cysteinyl-Leukotriene Receptors and Cellular Signals

    Directory of Open Access Journals (Sweden)

    G. Enrico Rovati

    2007-01-01

    Full Text Available Cysteinyl-leukotrienes (cysteinyl-LTs exert a range of proinflammatory effects, such as constriction of airways and vascular smooth muscle, increase of endothelial cell permeability leading to plasma exudation and edema, and enhanced mucus secretion. They have proved to be important mediators in asthma, allergic rhinitis, and other inflammatory conditions, including cardiovascular diseases, cancer, atopic dermatitis, and urticaria. The classification into subtypes of the cysteinyl-LT receptors (CysLTRs was based initially on binding and functional data, obtained using the natural agonists and a wide range of antagonists. CysLTRs have proved remarkably resistant to cloning. However, in 1999 and 2000, the CysLT1R and CysLT2R were successfully cloned and both shown to be members of the G-protein coupled receptors (GPCRs superfamily. Molecular cloning has confirmed most of the previous pharmacological characterization and identified distinct expression patterns only partially overlapping. Recombinant CysLTRs couple to the Gq/11 pathway that modulates inositol phospholipids hydrolysis and calcium mobilization, whereas in native systems, they often activate a pertussis toxin-insensitive Gi/o-protein, or are coupled promiscuously to both G-proteins. Interestingly, recent data provide evidence for the existence of an additional receptor subtype that seems to respond to both cysteinyl-LTs and uracil nucleosides, and of an intracellular pool of CysLTRs that may have roles different from those of plasma membrane receptors. Finally, a cross-talk between the cysteinyl-LT and the purine systems is being delineated. This review will summarize recent data derived from studies on the molecular and cellular pharmacology of CysLTRs.

  9. 维生素D治疗对2型糖尿病合并呼吸道感染患者细胞免疫功能的影响研究%Influence of Vitamin D Therapy on Cellular Immune Function of Type 2 Diabetes Mellitus Patients Complicated with Respiratory Tract Infection

    Institute of Scientific and Technical Information of China (English)

    么焕新; 柴颖; 张永敬

    2015-01-01

    Objective To investigate the influence of vitamin D therapy on cellular immune function of type 2 diabetes mellitus patients complicated with respiratory tract infection. Methods A total of 60 type 2 diabetes mellitus patients complicated with respiratory tract infection were selected in Xiehe Hospital of Tangshan from January to March in 2013,and they were randomly divided into control group and observation group,each of 30 cases. Both groups given routine treatment,and control group given extra placebo, while observation group given extra calcitriol soft capsules;both groups treated for 4 weeks. Before and after treatment,bone metabolic markers including serum levels of calcium,phosphorus,alkaline phosphatase and 25 hydroxy vitamin D3 , index of cellular immunity including CD3+, CD4+, CD8+ percentage and CD4+ /CD8+ ratio were compared between the two groups. Results No significant differences of bone metabolic markers including serum levels of calcium,phosphorus,alkaline phosphatase and 25 hydroxy vitamin D3 or index of cellular immunity including CD3+, CD4+, CD8+ percentage and CD4+ /CD8+ ratio was found between the two groups before treatment(P﹥0. 05);after treatment,serum levels of calcium and 25 hydroxy vitamin D3 ,CD3+ percentage and CD4+ /CD8+ ratio of observation group were higher than those of control group(P﹤0. 05),but no significant differences of serum phosphorus and alkaline phosphatase levels or CD4+,CD8+percentage was found between the two groups ( P﹥0. 05 ). Conclusion Vitamin D therapy can improve the cellular immune function of type 2 diabetes mellitus patients complicated with respiratory tract infection,and is safe.%目的:探讨维生素D治疗对2型糖尿病合并呼吸道感染患者细胞免疫功能的影响。方法选取唐山市协和医院2013年1—3月收治的2型糖尿病合并呼吸道感染患者60例,随机分为对照组和观察组,每组30例。对照组患者在常规治疗基础上给予安慰剂,观察组

  10. Lymphatic Regulation of Cellular Trafficking

    Science.gov (United States)

    Jackson, David G.

    2016-01-01

    Lymphatic vessels play vital roles in immune surveillance and immune regulation by conveying antigen loaded dendritic cells, memory T cells, macrophages and neutrophils from the peripheral tissues to draining lymph nodes where they initiate as well as modify immune responses. Until relatively recently however, there was little understanding of how entry and migration through lymphatic vessels is organized or the specific molecular mechanisms that might be involved. Within the last decade, the situation has been transformed by an explosion of knowledge generated largely through the application of microscopic imaging, transgenic animals, specific markers and function blocking mAbs that is beginning to provide a rational conceptual framework. This article provides a critical review of the recent literature, highlighting seminal discoveries that have revealed the fascinating ultrastructure of leucocyte entry sites in lymphatic vessels, as well as generating controversies over the involvement of integrin adhesion, chemotactic and haptotactic mechanisms in DC entry under normal and inflamed conditions. It also discusses the major changes in lymphatic architecture that occur during inflammation and the different modes of leucocyte entry and trafficking within inflamed lymphatic vessels, as well as presenting a timely update on the likely role of hyaluronan and the major lymphatic endothelial hyaluronan receptor LYVE-1 in leucocyte transit.

  11. 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.

  12. 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.

  13. The virtual cell animation collection: tools for teaching molecular and cellular biology.

    Science.gov (United States)

    Reindl, Katie M; White, Alan R; Johnson, Christina; Vender, Bradley; Slator, Brian M; McClean, Phillip

    2015-04-01

    A cell is a minifactory in which structures and molecules are assembled, rearranged, disassembled, packaged, sorted, and transported. Because cellular structures and molecules are invisible to the human eye, students often have difficulty conceptualizing the dynamic nature of cells that function at multiple scales across time and space. To represent these dynamic cellular processes, the Virtual Cell Productions team at North Dakota State University develops freely available multimedia materials to support molecular and cellular biology learning inside and outside the high school and university classroom.

  14. The Virtual Cell Animation Collection: Tools for Teaching Molecular and Cellular Biology

    Science.gov (United States)

    Reindl, Katie M.; White, Alan R.; Johnson, Christina; Vender, Bradley; Slator, Brian M.; McClean, Phillip

    2015-01-01

    A cell is a minifactory in which structures and molecules are assembled, rearranged, disassembled, packaged, sorted, and transported. Because cellular structures and molecules are invisible to the human eye, students often have difficulty conceptualizing the dynamic nature of cells that function at multiple scales across time and space. To represent these dynamic cellular processes, the Virtual Cell Productions team at North Dakota State University develops freely available multimedia materials to support molecular and cellular biology learning inside and outside the high school and university classroom. PMID:25856580

  15. 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.

  16. p53-Mediated Cellular Response to DNA Damage in Cells with Replicative Hepatitis B Virus

    Science.gov (United States)

    Puisieux, Alain; Ji, Jingwei; Guillot, Celine; Legros, Yann; Soussi, Thierry; Isselbacher, Kurt; Ozturk, Mehmet

    1995-02-01

    Wild-type p53 acts as a tumor suppressor gene by protecting cells from deleterious effects of genotoxic agents through the induction of a G_1/S arrest or apoptosis as a response to DNA damage. Transforming proteins of several oncogenic DNA viruses inactivate tumor suppressor activity of p53 by blocking this cellular response. To test whether hepatitis B virus displays a similar effect, we studied the p53-mediated cellular response to DNA damage in 2215 hepatoma cells with replicative hepatitis B virus. We demonstrate that hepatitis B virus replication does not interfere with known cellular functions of p53 protein.

  17. 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.

  18. Cellular Metabolic Rate Is Influenced by Life-History Traits in Tropical and Temperate Birds

    OpenAIRE

    Ana Gabriela Jimenez; James Van Brocklyn; Matthew Wortman; Williams, Joseph B.

    2014-01-01

    In general, tropical birds have a "slow pace of life," lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cel...

  19. 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.

  20. 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.