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Sample records for alter cellular processes

  1. β-carotene treatment alters the cellular death process in oxidative stress-induced K562 cells.

    Science.gov (United States)

    Akçakaya, Handan; Tok, Sabiha; Dal, Fulya; Cinar, Suzan Adin; Nurten, Rustem

    2017-03-01

    Oxidizing agents (e.g., H2 O2 ) cause structural and functional disruptions of molecules by affecting lipids, proteins, and nucleic acids. As a result, cellular mechanisms related to disrupted macro molecules are affected and cell death is induced. Oxidative damage can be prevented at a certain point by antioxidants or the damage can be reversed. In this work, we studied the cellular response against oxidative stress induced by H2 O2 and antioxidant-oxidant (β-carotene-H2 O2 ) interactions in terms of time, concentration, and treatment method (pre-, co-, and post) in K562 cells. We showed that co- or post-treatment with β-carotene did not protect cells from the damage of oxidative stress furthermore co- and post-β-carotene-treated oxidative stress induced cells showed similar results with only H2 O2 treated cells. However, β-carotene pre-treatment prevented oxidative damage induced by H2 O2 at concentrations lower than 1,000 μM compared with only H2 O2 -treated and co- and post-β-carotene-treated oxidative stress-induced cells in terms of studied cellular parameters (mitochondrial membrane potential [Δψm ], cell cycle and apoptosis). Prevention effect of β-carotene pre-treatment was lost at concentrations higher than 1,000 μM H2 O2 (2-10 mM). These findings suggest that β-carotene pre-treatment alters the effects of oxidative damage induced by H2 O2 and cell death processes in K562 cells.

  2. Cellular hyper-excitability caused by mutations that alter the activation process of voltage-gated sodium channels

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    Mohamed-Yassine eAMAROUCH

    2015-02-01

    Full Text Available Voltage-gated sodium channels (Nav are widely expressed as macro-molecular complexes in both excitable and non-excitable tissues. In excitable tissues, the upstroke of the action potential is the result of the passage of a large and rapid influx of sodium ions through these channels. NaV dysfunction has been associated with an increasingly wide range of neurological, muscular and cardiac disorders. The purpose of this review is to summarize the recently identified sodium channel mutations that are linked to hyper-excitability phenotypes and associated with the alteration of the activation process of voltage gated sodium channels. Indeed, several clinical manifestations that demonstrate an alteration of tissue excitability were recently shown to be strongly associated with the presence of mutations that affect the activation process of the voltage-gated sodium channels. These emerging genotype-phenotype correlations have expanded the clinical spectrum of sodium channelopathies to include disorders which feature a hyper-excitability phenotype that may or may not be associated with a cardiomyopathy. The p.I141V mutation in SCN4A and SCN5A, as well as its homologous p.I136V mutation in SCN9A, are interesting examples of mutations that have been linked to inherited hyperexcitability myotonia, exercise-induced polymorphic ventricular arrhythmias and erythromelalgia, respectively. Regardless of which sodium channel isoform is investigated, the substitution of the isoleucine to valine in the locus 141 induces similar modifications in the biophysical properties of the voltage-gated sodium channels by shifting the voltage-dependence of steady state activation towards more negative potentials.

  3. Cellular Alterations in Shock and Ischemia and Their Correction.

    Science.gov (United States)

    Chaudry, Irshad H.

    1985-01-01

    Reviews recent advances in cellular alterations in shock to help physicians and physiologists keep abreast of current research. Specifically addresses changes occurring as a result of hemorrhagic shock and possible ways such lesions could be corrected. (DH)

  4. 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.

  5. Music and Alterity Processes

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    Josep Martí

    2014-10-01

    Full Text Available The concept of alterity constitutes an important issue in anthropological research and, therefore, in the study of musical practices, as well. Without it, we could hardly understand other kinds of music situated in different spaces and time from the observer. In order to effectively approach these musical practices, we have to develop strategies to help us reduce as much as possible that which distorts the vision of the other. However, beyond the strictly epistemological and methodological issues, the study of music cannot ignore the ethical question related to the manner in which Western thought has understood and treated the other: through a hierarchical and stereotypical type of thinking based on the condition of otherness. Throughout the article, different alterity procedures are presented and discussed, such as synecdochization, exoticization, undervaluation, overvaluation, misunderstanding and exclusion. Taking these different alterity strategies into account may help us to better understand how the musical other is constructed, used and ultimately instrumentalized.

  6. Altered composition of bone as triggered by irradiation facilitates the rapid erosion of the matrix by both cellular and physicochemical processes.

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    Danielle E Green

    Full Text Available Radiation rapidly undermines trabecular architecture, a destructive process which proceeds despite a devastated cell population. In addition to the 'biologically orchestrated' resorption of the matrix by osteoclasts, physicochemical processes enabled by a damaged matrix may contribute to the rapid erosion of bone quality. 8w male C57BL/6 mice exposed to 5 Gy of Cs(137 γ-irradiation were compared to age-matched control at 2d, 10d, or 8w following exposure. By 10d, irradiation had led to significant loss of trabecular bone volume fraction. Assessed by reflection-based Fourier transform infrared imaging (FTIRI, chemical composition of the irradiated matrix indicated that mineralization had diminished at 2d by -4.3±4.8%, and at 10d by -5.8±3.2%. These data suggest that irradiation facilitates the dissolution of the matrix through a change in the material itself, a conclusion supported by a 13.7±4.5% increase in the elastic modulus as measured by nanoindentation. The decline in viable cells within the marrow of irradiated mice at 2d implies that the immediate collapse of bone quality and inherent increased risk of fracture is not solely a result of an overly-active biologic process, but one fostered by alterations in the material matrix that predisposes the material to erosion.

  7. 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...

  8. Manipulation of Cellular Processing Bodies and Their Constituents by Viruses

    OpenAIRE

    Pattnaik, Asit K.; Dinh, Phat X.

    2013-01-01

    The processing bodies (PBs) are a form of cytoplasmic aggregates that house the cellular RNA decay machinery as well as many RNA-binding proteins and mRNAs. The PBs are constitutively present in eukaryotic cells and are involved in maintaining cellular homeostasis by regulating RNA metabolism, cell signaling, and survival. Virus infections result in modification of the PBs and their constituents. Many viruses induce compositionally altered PBs, while many others use specific components of the...

  9. Cellular automata in image processing and geometry

    CERN Document Server

    Adamatzky, Andrew; Sun, Xianfang

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    徐永忠; 谢建平; 李瑶; 乐军; 陈建平; 淳于利娟; 王洪海

    2003-01-01

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

  11. EFFECTIVENESS OF CELLULAR INJECTION MOLDING PROCESS

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    Tomasz Garbacz

    2013-06-01

    Full Text Available In a study of cellular injection, molding process uses polyvinylchloride PVC. Polymers modified with introducing blowing agents into them in the Laboratory of the Department of Technologies and Materiase of Technical University of Kosice. For technological reasons, blowing agents have a form of granules. In the experiment, the content of the blowing agent (0–2,0 % by mass fed into the processed polymer was adopted as a variable factor. In the studies presented in the article, the chemical blowing agents occurring in the granulated form with a diameter of 1.2 to 1.4 mm were used. The view of the technological line for cellular injection molding and injection mold cavity with injection moldings are shown in Figure 1. The results of the determination of selected properties of injection molded parts for various polymeric materials, obtained with different content of blowing agents, are shown in Figures 4-7. Microscopic examination of cross-sectional structure of the moldings were obtained using the author's position image analysis of porous structure. Based on analysis of photographs taken (Figures 7, 8, 9 it was found that the coating containing 1.0% of blowing agents is a clearly visible solid outer layer and uniform distribution of pores and their sizes are similar.

  12. Bronchoalveolar lavage as a tool for evaluation of cellular alteration during Aelurostrongylus abstrusus infection in cats

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    Vitor M. Ribeiro

    2014-10-01

    Full Text Available Bronchoalveolar lavage (BAL is a procedure that retrieves cells and other elements from the lungs for evaluation, which helps in the diagnosis of pulmonary diseases. The aim of this study was to perform this procedure for cellular analysis of BAL fluid alterations during experimental infection with Aelurostrongylus abstrusus in cats. Fourteen cats were individually inoculated with 800 third stage larvae of A. abstrusus and five non-infected cats lined as a control group. The BAL procedure was performed through the use of an endotracheal tube on the nineteen cats with a mean age of 18 months, on 0, 30, 60, 90, 120, 180 and 270 days after infection. Absolute cell counts in the infected cats revealed that alveolar macrophages and eosinophils were the predominant cells following infection. This study shows that the technique allows us to retrieve cells and first stage larvae what provides information about the inflammatory process caused by aelurostrongylosis.

  13. Different Candida parapsilosis clinical isolates and lipase deficient strain trigger an altered cellular immune response

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    Renata eToth

    2015-10-01

    Full Text Available Numerous human diseases can be associated with fungal infections either as potential causative agents or as a result of changed immune status due to a primary disease. Fungal infections caused by Candida species can vary from mild to severe dependent upon the site of infection, length of exposure and past medical history. Patients with impaired immune status are at increased risk for chronic fungal infections. Recent epidemiologic studies have revealed the increasing incidence of candidiasis caused by non-albicans species such as C. parapsilosis. Due to its increasing relevance we chose two distinct C. parapsilosis strains, to describe the cellular innate immune response towards this species. In the first section of our study we compared the interaction of CLIB 214 and GA1 cells with murine and human macrophages. Both strains are commonly used to investigate C. parapsilosis virulence properties. CLIB 214 is a rapidly pseudohyphae-forming strain and GA1 is an isolate that mainly exists in a yeast form. Our results showed, that the phagocyte response was similar in terms of overall uptake, however differences were observed in macrophage migration and engulfment of fungal cells. As C. parapsilosis releases extracellular lipases in order to promote host invasion we further investigated the role of these secreted components during the distinct stages of the phagocytic process. Using a secreted lipase deficient mutant strain and the parental strain GA1 individually and simultaneously, we confirmed that fungal secreted lipases influence the fungi’s virulence by detecting altered innate cellular responses.In this study we report that two isolates of a single species can trigger markedly distinct host responses and that lipase secretion plays a role on the cellular level of host pathogen interactions.

  14. Additional force field in cooling process of cellular Al alloy

    Institute of Scientific and Technical Information of China (English)

    郑明军; 何德坪; 戴戈

    2002-01-01

    The foaming process of Al alloy is similar to that of Al, but there is a solid-liquid state zone in the solidification process of cellular Al alloy which does not exist in the case of Al. In the unidirectional solidification of cellular Al alloy, the proportion of the solid phase gradually reduces from the solid front to the liquid front. This will introduce a force and result in a serious quick shrinkage. By the mathematic and physical mode, the solidification of the cellular Al alloy is studied. The data measured by experiment are close to the result calculated by the mode. This kind of shrinkage can be solved by suitable cooling method in appropriate growth stage. The compressive strength of the cellular Al alloy made by this way is 40% higher than that of cellular Al.

  15. Can bread processing conditions alter glycaemic response?

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    Lau, Evelyn; Soong, Yean Yean; Zhou, Weibiao; Henry, Jeyakumar

    2015-04-15

    Bread is a staple food that is traditionally made from wheat flour. This study aimed to compare the starch digestibility of western baked bread and oriental steamed bread. Four types of bread were prepared: western baked bread (WBB) and oriental steamed bread (OSB), modified baked bread (MBB) made with the OSB recipe and WBB processing, and modified steamed bread (MSB) made with the WBB recipe and OSB processing. MBB showed the highest starch digestibility in vitro, followed by WBB, OSB and MSB. A similar trend was observed for glycaemic response in vivo. MBB, WBB, OSB and MSB had a glycaemic index of 75±4, 71±5, 68±5 and 65±4, respectively. Processing differences had a more pronounced effect on starch digestibility in bread, and steamed bread was healthier in terms of glycaemic response. The manipulation of processing conditions could be an innovative route to alter the glycaemic response of carbohydrate-rich foods.

  16. Minimal model for complex dynamics in cellular processes.

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    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.

  17. Volcanic glasses, their origins and alteration processes

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    Friedman, I.; Long, W.

    1984-01-01

    Natural glass can be formed by volcanic processes, lightning (fulgarites) burning coal, and by meteorite impact. By far the most common process is volcanic - basically the glass is rapidly chilled molten rock. All natural glasses are thermodynamically unstable and tend to alter chemically or to crystallize. The rate of these processes is determined by the chemical composition of the magma. The hot and fluid basaltic melts have a structure that allows for rapid crystal growth, and seldom forms glass selvages greater than a few centimeters thick, even when the melt is rapidly cooled by extrusion in the deep sea. In contrast the cooler and very viscous rhyolitic magmas can yield bodies of glass that are tens of meters thick. These highly polymerized magmas have a high silica content - often 71-77% SiO2. Their high viscosity inhibits diffusive crystal growth. Basalt glass in sea water forms an alteration zone called palagonite whose thickness increases linearly with time. The rate of diffusion of water into rhyolitic glass, which follows the relationship - thickness = k (time) 1 2, has been determined as a function of the glass composition and temperature. Increased SiO2 increases the rate, whereas increased CaO, MgO and H2O decrease the rate. The activation energy of water diffusion varies from about 19 to 22 kcal/mol. for the glasses studied. The diffusion of alkali out of rhyolite glass occurs simultaneously with water diffusion into the glass. The rate of devitrification of rhyolitic glass is a function of the glass viscosity, which in turn is a function of water content and temperature. Although all of the aforementioned processes tend to destroy natural glasses, the slow rates of these processes, particularly for rhyolitic glass, has allowed samples of glass to persist for 60 million years. ?? 1984.

  18. Neisseria gonorrhoeae infection induces altered amphiregulin processing and release.

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    Sonja Löfmark

    Full Text Available Adhesion of the human pathogen Neisseria gonorrhoeae has established effects on the host cell and evokes a variety of cellular events including growth factor activation. In the present study we report that infection with N. gonorrhoeae causes altered amphiregulin processing and release in human epithelial cells. Amphiregulin is a well-studied growth factor with functions in various cell processes and is upregulated in different forms cancer and proliferative diseases. The protein is prototypically cleaved on the cell surface in response to external stimuli. We demonstrate that upon infection, a massive upregulation of amphiregulin mRNA is seen. The protein changes its subcellular distribution and is also alternatively cleaved at the plasma membrane, which results in augmented release of an infection-specific 36 kDa amphiregulin product from the surface of human cervical epithelial cells. Further, using antibodies directed against different domains of the protein we could determine the impact of infection on pro-peptide processing. In summary, we present data showing that the infection of N. gonorrhoeae causes an alternative amphiregulin processing, subcellular distribution and release in human epithelial cervical cells that likely contribute to the predisposition cellular abnormalities and anti-apoptotic features of N. gonorrhoeae infections.

  19. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium.

    Science.gov (United States)

    Walker, Nancy M; Liu, Jinghua; Stein, Sydney R; Stefanski, Casey D; Strubberg, Ashlee M; Clarke, Lane L

    2016-01-15

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl(-) and HCO3 (-) efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3 (-))-loading proteins and upregulation of the basolateral membrane HCO3 (-)-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl(-)/HCO3 (-) exchange with maximized gradients, it also had increased intracellular Cl(-) concentration relative to wild-type. Pharmacological reduction of intracellular Cl(-) concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl(-) and HCO3 (-) efflux, which impairs pHi regulation by Ae2. Retention of Cl(-) and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine.

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

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    McCune, Matthew; Kosztin, Ioan

    2013-03-01

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

  1. MODERNIZATION OF TECHNOLOGICAL LINE FOR CELLULAR EXTRUSION PROCESS

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    Tomasz Garbacz

    2014-06-01

    As part of the modernization of the cellular extrusion technology the extrusion head was designed and made. During the designing and modeling of the head the Auto CAD programe was used. After the prototyping the extrusion head was tested. In the article specification of cellular extrusion process of thermoplastics was presented. In the research, the endothermal chemical blowing agents in amount 1,0% by mass were used. The quantity of used blowing agent has a direct influence on density and structure of the extruded product of modified polymers. However, these properties have further influence on porosity, impact strength, hardness, tensile strength and another.

  2. Piezo proteins: regulators of mechanosensation and other cellular processes.

    Science.gov (United States)

    Bagriantsev, Sviatoslav N; Gracheva, Elena O; Gallagher, Patrick G

    2014-11-14

    Piezo proteins have recently been identified as ion channels mediating mechanosensory transduction in mammalian cells. Characterization of these channels has yielded important insights into mechanisms of somatosensation, as well as other mechano-associated biologic processes such as sensing of shear stress, particularly in the vasculature, and regulation of urine flow and bladder distention. Other roles for Piezo proteins have emerged, some unexpected, including participation in cellular development, volume regulation, cellular migration, proliferation, and elongation. Mutations in human Piezo proteins have been associated with a variety of disorders including hereditary xerocytosis and several syndromes with muscular contracture as a prominent feature.

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

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    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.

  4. Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2

    Energy Technology Data Exchange (ETDEWEB)

    Salaita, Khalid; Nair, Pradeep M; Petit, Rebecca S; Neve, Richard M; Das, Debopriya; Gray, Joe W; Groves, Jay T

    2009-09-09

    Activation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. Receptor-ligand binding, clustering, and subsequent lateral transport within this junction were observed. EphA2 transport can be blocked by physical barriers nanofabricated onto the underlying substrate. This physical reorganization of EphA2 alters the cellular response to ephrin-A1, as observed by changes in cytoskeleton morphology and recruitment of a disintegrin and metalloprotease 10. Quantitative analysis of receptor-ligand spatial organization across a library of 26 mammary epithelial cell lines reveals characteristic differences that strongly correlate with invasion potential. These observations reveal a mechanism for spatio-mechanical regulation of EphA2 signaling pathways.

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

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    Merlin Nanayakkara

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

  6. Multiscale mathematical modeling and simulation of cellular dynamical process.

    Science.gov (United States)

    Nakaoka, Shinji

    2014-01-01

    Epidermal homeostasis is maintained by dynamic interactions among molecules and cells at different spatiotemporal scales. Mathematical modeling and simulation is expected to provide clear understanding and precise description of multiscaleness in tissue homeostasis under systems perspective. We introduce a stochastic process-based description of multiscale dynamics. Agent-based modeling as a framework of multiscale modeling to achieve consistent integration of definitive subsystems is proposed. A newly developed algorithm that particularly aims to perform stochastic simulations of cellular dynamical process is introduced. Finally we review applications of multiscale modeling and quantitative study to important aspects of epidermal and epithelial homeostasis.

  7. Cellular Automaton Simulation of Evacuation Process in Story

    Institute of Scientific and Technical Information of China (English)

    MA Chang-Qun; ZHENG Rong-Sen; GAO Chun-Yuan; QIU Bing; DENG Min-Yi; KONC Ling-Jiang; LIU Mu-Ren

    2008-01-01

    Computer simulations on the evacuation process in a story are launched with cellular automaton in this article. The story is composed of five rooms and one corridor. Influence of various parameters on the evacuation process is investigated. It shows that the width of the door of rooms has little influence but the width of the corridor and themaximum velocity of the pedestrian have great influence on the time for evacuation. The relation between evacuation time and the width of corridor is found as tc ∝ W-.0.84. It is also found that appropriate shape of the room is helpful to evacuation.

  8. Wave dynamic processes in cellular detonation reflection from wedges

    Institute of Scientific and Technical Information of China (English)

    Zongmin Hu; Zonglin Jiang

    2007-01-01

    When the cell width of the incident deto-nation wave (IDW) is comparable to or larger than theMach stem height,self-similarity will fail during IDWreflection from a wedge surface.In this paper,the det-onation reflection from wedges is investigated for thewave dynamic processes occurring in the wave front,including transverse shock motion and detonation cellvariations behind the Mach stem.A detailed reactionmodel is implemented to simulate two-dimensional cel-lular detonations in stoichiometric mixtures of H2/O2diluted by Argon.The numerical results show that thetransverse waves,which cross the triple point trajec-tory of Mach reflection,travel along the Mach stem andreflect back from the wedge surface,control the size ofthe cells in the region swept by the Mach stem.It is theenergy carried by these transverse waves that sustainsthe triple-wave-collision with a higher frequency withinthe over-driven Mach stem.In some cases,local wavedynamic processes and wave structures play a dominantrole in determining the pattern of cellular record,lead-ing to the fact that the cellular patterns after the Machstem exhibit some peculiar modes.

  9. Parallelizing the Cellular Potts Model on graphics processing units

    Science.gov (United States)

    Tapia, José Juan; D'Souza, Roshan M.

    2011-04-01

    The Cellular Potts Model (CPM) is a lattice based modeling technique used for simulating cellular structures in computational biology. The computational complexity of the model means that current serial implementations restrict the size of simulation to a level well below biological relevance. Parallelization on computing clusters enables scaling the size of the simulation but marginally addresses computational speed due to the limited memory bandwidth between nodes. In this paper we present new data-parallel algorithms and data structures for simulating the Cellular Potts Model on graphics processing units. Our implementations handle most terms in the Hamiltonian, including cell-cell adhesion constraint, cell volume constraint, cell surface area constraint, and cell haptotaxis. We use fine level checkerboards with lock mechanisms using atomic operations to enable consistent updates while maintaining a high level of parallelism. A new data-parallel memory allocation algorithm has been developed to handle cell division. Tests show that our implementation enables simulations of >10 cells with lattice sizes of up to 256 3 on a single graphics card. Benchmarks show that our implementation runs ˜80× faster than serial implementations, and ˜5× faster than previous parallel implementations on computing clusters consisting of 25 nodes. The wide availability and economy of graphics cards mean that our techniques will enable simulation of realistically sized models at a fraction of the time and cost of previous implementations and are expected to greatly broaden the scope of CPM applications.

  10. Alterations of Cellular Immune Reactions in Crew Members Overwintering in the Antarctic Research Station Concordia

    Science.gov (United States)

    Crucian, Brian; Feuerecker, Matthias; Moreels, Marjan; Crucian, Brian; Kaufmann, Ines; Salam, Alex Paddy; Rybka, Alex; Ulrike, Thieme; Quintens, Roel; Sams, Clarence F.; Schelling, Gustav; Thiel, Manfred; Baatout, Sarah; Chouker, Alexander

    2012-01-01

    Background: Concordia Station is located inside Antarctica about 1000km from the coast at an altitude of 3200m (Dome C). Hence, individuals living in this harsh environment are exposed to two major conditions: 1.) hypobaric hypoxia and 2.) confinement and extreme isolation. Both hypoxia and confinement can affect human immunity and health, and are likely to be present during exploration class space missions. This study focused on immune alterations measured by a new global immunity test assay, similar to the phased out delayed type hypersensitivity (DTH) skin test. Methods: After informed written consent 14 healthy male subjects were included to the CHOICE-study (Consequences-of-longterm-Confinement-and-Hypobaric-HypOxia-on-Immunity-in-the Antarctic-Concordia-Environment). Data collection occurred during two winter-over periods lasting each one year. During the first campaign 6 healthy male were enrolled followed by a second campaign with 8 healthy males. Blood was drawn monthly and incubated for 48h with various bacterial, viral and fungal antigens followed by an analysis of plasma cytokine levels (TNF-alpha, IL2, IFN-gamma, IL10). As a control, blood was incubated without stimulation ("resting condition"). Goals: The scope of this study was to assess the consequences of hypoxia and confinement on cellular immunity as assessed by a new in vitro DTH-like test. Results: Initial results indicate that under resting conditions the in vitro DTH-like test showed low cytokine levels which remained almost unchanged during the entire observation period. However, cytokine responses to viral, bacterial and fungal antigens were remarkably reduced at the first month after arrival at Concordia when compared to levels measured in Europe prior to departure for Antarctica. With incrementing months of confinement this depressed DTH-like response tended to reverse, and in fact to show an "overshooting" immune reaction after stimulation. Conclusion: The reduced in vitro DTH-like test

  11. Public Evacuation Process Modeling and Simulatiaon Based on Cellular Automata

    Directory of Open Access Journals (Sweden)

    Zhikun Wang

    2013-11-01

    Full Text Available Considering attraction of the nearest exit, repulsive force of the fire, barrier and its display style, effect of fire exit location on escape time in fire hazard, a mathematical model of evacuation process model was build based on cellular automatic theory. The program was developed by JavaScript. The influencing factors of evacuation were obtained through the simulation model by inputting crew size, creating initial positions of crew and fire seat stochastically. The experimental results show that the evacuation simulation model with authenticity and validity, which has guiding significance for people evacuation and public escape system design.  

  12. Cellular Signaling Pathway Alterations and Potential Targeted Therapies for Medullary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Serena Giunti

    2013-01-01

    Full Text Available Parafollicular C-cell-derived medullary thyroid cancer (MTC comprises 3% to 4% of all thyroid cancers. While cytotoxic treatments have been shown to have limited efficacy, targeted molecular therapies that inhibit rearranged during transfection (RET and other tyrosine kinase receptors that are mainly involved in angiogenesis have shown great promise in the treatment of metastatic or locally advanced MTC. Multi-tyrosine kinase inhibitors such as vandetanib, which is already approved for the treatment of progressive MTC, and cabozantinib have shown distinct advantages with regard to rates of disease response and control. However, these types of tyrosine kinase inhibitor compounds are able to concurrently block several types of targets, which limits the understanding of RET as a specific target. Moreover, important resistances to tyrosine kinase inhibitors can occur, which limit the long-term efficacy of these treatments. Deregulated cellular signaling pathways and genetic alterations in MTC, particularly the activation of the RAS/mammalian target of rapamycin (mTOR cascades and RET crosstalk signaling, are now emerging as novel and potentially promising therapeutic treatments for aggressive MTC.

  13. Stanniocalcin 2 alters PERK signalling and reduces cellular injury during cerulein induced pancreatitis in mice

    Directory of Open Access Journals (Sweden)

    DiMattia Gabriel E

    2011-05-01

    Full Text Available Abstract Background Stanniocalcin 2 (STC2 is a secreted protein activated by (PKR-like Endoplasmic Reticulum Kinase (PERK signalling under conditions of ER stress in vitro. Over-expression of STC2 in mice leads to a growth-restricted phenotype; however, the physiological function for STC2 has remained elusive. Given the relationship of STC2 to PERK signalling, the objective of this study was to examine the role of STC2 in PERK signalling in vivo. Results Since PERK signalling has both physiological and pathological roles in the pancreas, STC2 expression was assessed in mouse pancreata before and after induction of injury using a cerulein-induced pancreatitis (CIP model. Increased Stc2 expression was identified within four hours of initiating pancreatic injury and correlated to increased activation of PERK signalling. To determine the effect of STC2 over-expression on PERK, mice systemically expressing human STC2 (STC2Tg were examined. STC2Tg pancreatic tissue exhibited normal pancreatic morphology, but altered activation of PERK signalling, including increases in Activating Transcription Factor (ATF 4 accumulation and autophagy. Upon induction of pancreatic injury, STC2Tg mice exhibited limited increases in circulating amylase levels and increased maintenance of cellular junctions. Conclusions This study links STC2 to the pathological activation of PERK in vivo, and suggests involvement of STC2 in responding to pancreatic acinar cell injury.

  14. Alterations in phosphate metabolism during cellular recovery of radiation damage in yeast

    Energy Technology Data Exchange (ETDEWEB)

    Holahan, P.K.; Knizner, S.A.; Gabriel, C.M.; Swenberg, C.E.

    1988-10-01

    The authors examined alterations in phosphate pools during cellular recovery from radiation damage in intact, wild-type diploid yeast cells using /sup 31/P nuclear magnetic resonance (NMR) spectroscopy. Concurrent cell survival analysis was determined following exposure to /sup 60/Co ..gamma..-irradiation. Cells held in citrate-buffered saline (CBS) showed increased survival with increasing time after irradiation (liquid holding recovery, LHR) with no further recovery beyond 48 h. Addition of 100 mmol dm/sup -3/ glucose to the recovery medium resulted in greater recovery. In the presence of 5 mmol dm/sup /-/sup 3/ 2-deoxyglucose (2-DG), LHR was completely inhibited. NMR analyses were done on cells perfused in agarose threads and maintained under conditions similar to those in the survival studies. ATP was observable by NMR only when glucose was present in the recovery medium. In control cells, ATP concentrations increased and plateaued with increasing recovery time. With increasing radiation dose the increase in ATP was of lesser magnitude, and after 2000 Gy no increase was observed.

  15. Alterations in phosphate metabolism during cellular recovery of radiation damage in yeast

    Energy Technology Data Exchange (ETDEWEB)

    Holahan, P.K.; Knizner, S.A.; Gabriel, C.M.; Swenberg, C.E.

    1988-01-01

    Alterations were examined in phosphate pools during cellular recovery from radiation damage in intact, wild-type diploid yeast cells using phosphorus 31 nuclear magnetic resonance (NMR) spectroscopy. Concurrent cell survival analysis was determined following exposure to cobalt 60 gamma radiation. Cells held in citrate-buffered saline (CBS) showed increased survival with increasing time after irradiation (liquid holding recovery, LHR) with no further recovery beyond 48 h. Addition of 100 mmol/cu. dm glucose to the recovery medium resulted in greater recovery. In the presence of 5 mmol/cu. dm 2-deoxyglucose (2-DG), LHR was completely inhibited. ATP was observable by NMR only when glucose was present in the recovery medium. In control cells, ATP concentrations increased and plateaued with increasing recovery time. With increasing radiation dose, the increase in ATP was of lesser magnitude, and after 2000 Gy no increase was observed. The observations suggest that either the production of ATP in irradiated cells is suppressed, or there is enhanced ATP utilization for repair of radiation damage. In CBS with 100 mmol/cu. dm glucose, a dose-dependent decrease in polyphosphate (polyP) was detectable with no concurrent increase in inorganic phosphate (p sub i). When 2-DG was present in the recovery medium, polyP decreased, but there was a simultaneous increase in p sub i with increasing radiation dose and recovery time. This suggests that the polyP are hydrolyzed as a source of phosphates for repair of radiation damage.

  16. Comprehensive analysis of temporal alterations in cellular proteome of Bacillus subtilis under curcumin treatment.

    Directory of Open Access Journals (Sweden)

    Panga Jaipal Reddy

    Full Text Available Curcumin is a natural dietary compound with antimicrobial activity against various gram positive and negative bacteria. This study aims to investigate the proteome level alterations in Bacillus subtilis due to curcumin treatment and identification of its molecular/cellular targets to understand the mechanism of action. We have performed a comprehensive proteomic analysis of B. subtilis AH75 strain at different time intervals of curcumin treatment (20, 60 and 120 min after the drug exposure, three replicates to compare the protein expression profiles using two complementary quantitative proteomic techniques, 2D-DIGE and iTRAQ. To the best of our knowledge, this is the first comprehensive longitudinal investigation describing the effect of curcumin treatment on B. subtilis proteome. The proteomics analysis revealed several interesting targets such UDP-N-acetylglucosamine 1-carboxyvinyltransferase 1, putative septation protein SpoVG and ATP-dependent Clp protease proteolytic subunit. Further, in silico pathway analysis using DAVID and KOBAS has revealed modulation of pathways related to the fatty acid metabolism and cell wall synthesis, which are crucial for cell viability. Our findings revealed that curcumin treatment lead to inhibition of the cell wall and fatty acid synthesis in addition to differential expression of many crucial proteins involved in modulation of bacterial metabolism. Findings obtained from proteomics analysis were further validated using 5-cyano-2,3-ditolyl tetrazolium chloride (CTC assay for respiratory activity, resazurin assay for metabolic activity and membrane integrity assay by potassium and inorganic phosphate leakage measurement. The gene expression analysis of selected cell wall biosynthesis enzymes has strengthened the proteomics findings and indicated the major effect of curcumin on cell division.

  17. Estradiol-induced promotion of hepatocarcinogenesis in medaka: Relationship of foci of cellular alteration to neoplasia

    Energy Technology Data Exchange (ETDEWEB)

    Cooke, J.B.; Hinton, D.E. [Univ. of California, Davis, CA (United States)

    1995-12-31

    In some laboratory and field studies, female fish have higher prevalences of liver tumors than do males. The authors hypothesize gender and site-specific differences in prevalence are due to variable exposures of previously initiated fish to tumor modulating compounds. Estradiol, a growth promoter, increases incidences of hepatic tumors in carcinogen-treated rainbow trout and medaka (Oryzias latipes). Estradiol also increases incidences of hepatic foci of cellular alteration (FCA) in medaka. FCA are found in subadults of tumor-bearing feral populations. Lack of knowledge about the relationship of various phenotypes of FCA to eventual tumors, however, has prevented use of FCA as a biomarker. The authors examined fate and growth of liver FCA using a 2-step, initiation-promotion protocol. Three week old medaka were exposed to 200 ppm diethylnitrosamine (DEN) for 24 hr. and then fed 0.1 ppm 17-{beta}-estradiol (E2) continuously through sampling at weeks 4--26. Percent volume of FCA and morphometric characteristics of normal and focal hepatocytes, including numerical density and average hepatocyte volume were quantified using computer-assisted stereology. E2 increased percentage of liver occupied by DEN-initiated amphophilic, basophilic and eosinophilic FCA in both sexes. Focal parameters of young, DEN-initiated and estradiol-treated medaka were not reached until much later in fish given only DEN. Non-focal hepatocytes in estradiol-treated medaka were smaller and more numerous than in DEN-only counterparts. Morphometric analysis is quantitatively tracking the fate of specific phenotypes of FCA to determine their role in progression to cancer.

  18. Cellular phosphatases facilitate combinatorial processing of receptor-activated signals

    Directory of Open Access Journals (Sweden)

    Siddiqui Zaved

    2008-09-01

    Full Text Available Abstract Background Although reciprocal regulation of protein phosphorylation represents a key aspect of signal transduction, a larger perspective on how these various interactions integrate to contribute towards signal processing is presently unclear. For example, a key unanswered question is that of how phosphatase-mediated regulation of phosphorylation at the individual nodes of the signaling network translates into modulation of the net signal output and, thereby, the cellular phenotypic response. Results To address the above question we, in the present study, examined the dynamics of signaling from the B cell antigen receptor (BCR under conditions where individual cellular phosphatases were selectively depleted by siRNA. Results from such experiments revealed a highly enmeshed structure for the signaling network where each signaling node was linked to multiple phosphatases on the one hand, and each phosphatase to several nodes on the other. This resulted in a configuration where individual signaling intermediates could be influenced by a spectrum of regulatory phosphatases, but with the composition of the spectrum differing from one intermediate to another. Consequently, each node differentially experienced perturbations in phosphatase activity, yielding a unique fingerprint of nodal signals characteristic to that perturbation. This heterogeneity in nodal experiences, to a given perturbation, led to combinatorial manipulation of the corresponding signaling axes for the downstream transcription factors. Conclusion Our cumulative results reveal that it is the tight integration of phosphatases into the signaling network that provides the plasticity by which perturbation-specific information can be transmitted in the form of a multivariate output to the downstream transcription factor network. This output in turn specifies a context-defined response, when translated into the resulting gene expression profile.

  19. BRCA1 haploinsufficiency leads to altered expression of genes involved in cellular proliferation and development.

    Directory of Open Access Journals (Sweden)

    Harriet E Feilotter

    Full Text Available The assessment of BRCA1 and BRCA2 coding sequences to identify pathogenic mutations associated with inherited breast/ovarian cancer syndrome has provided a method to identify high-risk individuals, allowing them to seek preventative treatments and strategies. However, the current test is expensive, and cannot differentiate between pathogenic variants and those that may be benign. Focusing only on one of the two BRCA partners, we have developed a biological assay for haploinsufficiency of BRCA1. Using a series of EBV-transformed cell lines, we explored gene expression patterns in cells that were BRCA1 wildtype compared to those that carried (heterozygous BRCA1 pathogenic mutations. We identified a subset of 43 genes whose combined expression pattern is a sensitive predictor of BRCA1 status. The gene set was disproportionately made up of genes involved in cellular differentiation, lending credence to the hypothesis that single copy loss of BRCA1 function may impact differentiation, rendering cells more susceptible to undergoing malignant processes.

  20. IN ABSENCE OF THE CELLULAR PRION PROTEIN, ALTERATIONS IN COPPER METABOLISM AND COPPER-DEPENDENT OXIDASE ACTIVITY AFFECT IRON DISTRIBUTION

    OpenAIRE

    Lisa Gasperini; Elisa Meneghetti; Giuseppe Legname; Federico Benetti

    2016-01-01

    Essential elements as copper and iron modulate a wide range of physiological functions. Their metabolism is strictly regulated by cellular pathways, since dysregulation of metal homeostasis is responsible for many detrimental effects. Neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and prion diseases are characterized by alterations of metal ions. These neurodegenerative maladies involve proteins that bind metals and mediate their metabolism through not well-defin...

  1. In Absence of the Cellular Prion Protein, Alterations in Copper Metabolism and Copper-Dependent Oxidase Activity Affect Iron Distribution

    OpenAIRE

    Gasperini, Lisa; Meneghetti, Elisa; Legname, Giuseppe; Benetti, Federico

    2016-01-01

    Essential elements as copper and iron modulate a wide range of physiological functions. Their metabolism is strictly regulated by cellular pathways, since dysregulation of metal homeostasis is responsible for many detrimental effects. Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and prion diseases are characterized by alterations of metal ions. These neurodegenerative maladies involve proteins that bind metals and mediate their metabolism through not well-defin...

  2. Cellular modelling using P systems and process algebra

    Institute of Scientific and Technical Information of China (English)

    Francisco J.Romero-Campero; Marian Gheorghe; Gabriel Ciobanu; John M. Auld; Mario J. Pérez-Jiménez

    2007-01-01

    In this paper various molecular chemical interactions are modelled under different computational paradigms. P systems and π-calculus are used to describe intra-cellular reactions like protein-protein interactions and gene regulation control.

  3. In Absence of the Cellular Prion Protein, Alterations in Copper Metabolism and Copper-Dependent Oxidase Activity Affect Iron Distribution.

    Science.gov (United States)

    Gasperini, Lisa; Meneghetti, Elisa; Legname, Giuseppe; Benetti, Federico

    2016-01-01

    Essential elements as copper and iron modulate a wide range of physiological functions. Their metabolism is strictly regulated by cellular pathways, since dysregulation of metal homeostasis is responsible for many detrimental effects. Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and prion diseases are characterized by alterations of metal ions. These neurodegenerative maladies involve proteins that bind metals and mediate their metabolism through not well-defined mechanisms. Prion protein, for instance, interacts with divalent cations via multiple metal-binding sites and it modulates several metal-dependent physiological functions, such as S-nitrosylation of NMDA receptors. In this work we focused on the effect of prion protein absence on copper and iron metabolism during development and adulthood. In particular, we investigated copper and iron functional values in serum and several organs such as liver, spleen, total brain and isolated hippocampus. Our results show that iron content is diminished in prion protein-null mouse serum, while it accumulates in liver and spleen. Our data suggest that these alterations can be due to impairments in copper-dependent cerulopalsmin activity which is known to affect iron mobilization. In prion protein-null mouse total brain and hippocampus, metal ion content shows a fluctuating trend, suggesting the presence of homeostatic compensatory mechanisms. However, copper and iron functional values are likely altered also in these two organs, as indicated by the modulation of metal-binding protein expression levels. Altogether, these results reveal that the absence of the cellular prion protein impairs copper metabolism and copper-dependent oxidase activity, with ensuing alteration of iron mobilization from cellular storage compartments.

  4. In Absence of the Cellular Prion Protein, Alterations in Copper Metabolism and Copper-Dependent Oxidase Activity Affect Iron Distribution

    Science.gov (United States)

    Gasperini, Lisa; Meneghetti, Elisa; Legname, Giuseppe; Benetti, Federico

    2016-01-01

    Essential elements as copper and iron modulate a wide range of physiological functions. Their metabolism is strictly regulated by cellular pathways, since dysregulation of metal homeostasis is responsible for many detrimental effects. Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and prion diseases are characterized by alterations of metal ions. These neurodegenerative maladies involve proteins that bind metals and mediate their metabolism through not well-defined mechanisms. Prion protein, for instance, interacts with divalent cations via multiple metal-binding sites and it modulates several metal-dependent physiological functions, such as S-nitrosylation of NMDA receptors. In this work we focused on the effect of prion protein absence on copper and iron metabolism during development and adulthood. In particular, we investigated copper and iron functional values in serum and several organs such as liver, spleen, total brain and isolated hippocampus. Our results show that iron content is diminished in prion protein-null mouse serum, while it accumulates in liver and spleen. Our data suggest that these alterations can be due to impairments in copper-dependent cerulopalsmin activity which is known to affect iron mobilization. In prion protein-null mouse total brain and hippocampus, metal ion content shows a fluctuating trend, suggesting the presence of homeostatic compensatory mechanisms. However, copper and iron functional values are likely altered also in these two organs, as indicated by the modulation of metal-binding protein expression levels. Altogether, these results reveal that the absence of the cellular prion protein impairs copper metabolism and copper-dependent oxidase activity, with ensuing alteration of iron mobilization from cellular storage compartments. PMID:27729845

  5. Alteration of cellular lipids and lipid metabolism markers in RTL-W1 cells exposed to model endocrine disrupters.

    Science.gov (United States)

    Dimastrogiovanni, Giorgio; Córdoba, Marlon; Navarro, Isabel; Jáuregui, Olga; Porte, Cinta

    2015-08-01

    This work investigates the suitability of the rainbow trout liver cell line (RTL-W1) as an in-vitro model to study the ability of model endocrine disrupters, namely TBT, TPT, 4-NP, BPA and DEHP, to act as metabolic disrupters by altering cellular lipids and markers of lipid metabolism. Among the tested compounds, BPA and DEHP significantly increased the intracellular accumulation of triacylglycerols (TAGs), while all the compounds -apart from TPT-, altered membrane lipids - phosphatidylcholines (PCs) and plasmalogen PCs - indicating a strong interaction of the toxicants with cell membranes and cell signaling. RTL-W1 expressed a number of genes involved in lipid metabolism that were modulated by exposure to BPA, TBT and TPT (up-regulation of FATP1 and FAS) and 4-NP and DEHP (down-regulation of FAS and LPL). Multiple and complex modes of action of these chemicals were observed in RTL-W1 cells, both in terms of expression of genes related to lipid metabolism and alteration of cellular lipids. Although further characterization is needed, this might be a useful model for the detection of chemicals leading to steatosis or other diseases associated with lipid metabolism in fish.

  6. Non-heme induction of heme oxygenase-1 does not alter cellular iron metabolism.

    Science.gov (United States)

    Sheftel, Alex D; Kim, Sangwon F; Ponka, Prem

    2007-04-06

    The catabolism of heme is carried out by members of the heme oxygenase (HO) family. The products of heme catabolism by HO-1 are ferrous iron, biliverdin (subsequently converted to bilirubin), and carbon monoxide. In addition to its function in the recycling of hemoglobin iron, this microsomal enzyme has been shown to protect cells in various stress models. Implicit in the reports of HO-1 cytoprotection to date are its effects on the cellular handling of heme/iron. However, the limited amount of uncommitted heme in non-erythroid cells brings to question the source of substrate for this enzyme in non-hemolytic circumstances. In the present study, HO-1 was induced by either sodium arsenite (reactive oxygen species producer) or hemin or overexpressed in the murine macrophage-like cell line, RAW 264.7. Both of the inducers elicited an increase in active HO-1; however, only hemin exposure caused an increase in the synthesis rate of the iron storage protein, ferritin. This effect of hemin was the direct result of the liberation of iron from heme by HO. Cells stably overexpressing HO-1, although protected from oxidative stress, did not display elevated basal ferritin synthesis. However, these cells did exhibit an increase in ferritin synthesis, compared with untransfected controls, in response to hemin treatment, suggesting that heme levels, and not HO-1, limit cellular heme catabolism. Our results suggest that the protection of cells from oxidative insult afforded by HO-1 is not due to the catabolism of significant amounts of cellular heme as thought previously.

  7. Opt2 mediates the exposure of phospholipids during cellular adaptation to altered lipid asymmetry.

    Science.gov (United States)

    Yamauchi, Saori; Obara, Keisuke; Uchibori, Kenya; Kamimura, Akiko; Azumi, Kaoru; Kihara, Akio

    2015-01-01

    Plasma membrane lipid asymmetry is important for various membrane-associated functions and is regulated by membrane proteins termed flippases and floppases. The Rim101 pathway senses altered lipid asymmetry in the yeast plasma membrane. The mutant lem3Δ cells, in which lipid asymmetry is disturbed owing to the inactivation of the plasma membrane flippases, showed a severe growth defect when the Rim101 pathway was impaired. To identify factors involved in the Rim101-pathway-dependent adaptation to altered lipid asymmetry, we performed DNA microarray analysis and found that Opt2 induced by the Rim101 pathway plays an important role in the adaptation to altered lipid asymmetry. Biochemical investigation of Opt2 revealed its localization to the plasma membrane and the Golgi, and provided several lines of evidence for the Opt2-mediated exposure of phospholipids. In addition, Opt2 was found to be required for the maintenance of vacuolar morphology and polarized cell growth. These results suggest that Opt2 is a novel factor involved in cell homeostasis by regulating lipid asymmetry.

  8. Alteration of the Cyclin D1/p16-pRB Pathway, Cellular Proliferation and Apoptosis in Glioma

    Institute of Scientific and Technical Information of China (English)

    WANGCun-zu; FUZhen; ZHAOZhu.qing

    2004-01-01

    To study the alteration of cyclin D1, p16 and pRB in glioma, analyze proliferation and apoptosis of tmnor cells, and discuss the pathogenesis of glioma, Methods : Thirty-seven glioma specimens were classified as astrocytoma(25 cases, including 7 fibrillary cases; 6 protoplasmic cases; 12 anaplastic cases), and glioblastoma( 12 cases, including 4 GBM cases). Ten normal brain tissues were taken as controls. The expression of cyclin D1, p16 and pRB were detected by imrnunohistochemical method, Cellular proliferation was assessed by Ki-67 label index( Ki-67 LI). Cellular apoptosis was detected by TUNEL and apoptotic indices(AI) was calculated. Resu/ts: The alterations of three proteins were cyclin D1 overexpression( 28/37,75.7% ), p16 and pRB deletion( 20/37.54.1% and 12/37,32.4% ), which were closely related to tumor types, particularly in malignant glioma. Ki-67 LI and AI were higher when pRB pathway was abnormal. Apoptosis was minor in astrocytic tumors( astrocytomas, 0.010±0.002; glioblastomas, 0.057±0.016). Condusion:The abnormalities of cyclin DI/pl6-pRB pathway correlated closely with pathogenesis of glioma.

  9. Identification of an mtDNA mutation hot spot in UV-induced mouse skin tumors producing altered cellular biochemistry.

    Science.gov (United States)

    Jandova, Jana; Eshaghian, Alex; Shi, Mingjian; Li, Meiling; King, Lloyd E; Janda, Jaroslav; Sligh, James E

    2012-02-01

    There is increasing awareness of the role of mtDNA alterations in the development of cancer, as mtDNA point mutations are found at high frequency in a variety of human tumors. To determine the biological effects of mtDNA mutations in UV-induced skin tumors, hairless mice were irradiated to produce tumors, and the tumor mtDNAs were screened for single-nucleotide changes using temperature gradient capillary electrophoresis (TGCE), followed by direct sequencing. A mutation hot spot (9821insA) in the mitochondrially encoded tRNA arginine (mt-Tr) locus (tRNA(Arg)) was discovered in approximately one-third of premalignant and malignant skin tumors. To determine the functional relevance of this particular mutation in vitro, cybrid cell lines containing different mt-Tr (tRNA(Arg)) alleles were generated. The resulting cybrid cell lines contained the same nuclear genotype and differed only in their mtDNAs. The biochemical analysis of the cybrids revealed that the mutant haplotype is associated with diminished levels of complex I protein (CI), resulting in lower levels of baseline oxygen consumption and lower cellular adenosine triphosphate (ATP) production. We hypothesize that this specific mtDNA mutation alters cellular biochemistry, supporting the development of keratinocyte neoplasia.

  10. HIV-1 TAR miRNA protects against apoptosis by altering cellular gene expression

    Directory of Open Access Journals (Sweden)

    Meiri Eti

    2009-02-01

    Full Text Available Abstract Background RNA interference is a gene regulatory mechanism that employs small RNA molecules such as microRNA. Previous work has shown that HIV-1 produces TAR viral microRNA. Here we describe the effects of the HIV-1 TAR derived microRNA on cellular gene expression. Results Using a variation of standard techniques we have cloned and sequenced both the 5' and 3' arms of the TAR miRNA. We show that expression of the TAR microRNA protects infected cells from apoptosis and acts by down-regulating cellular genes involved in apoptosis. Specifically, the microRNA down-regulates ERCC1 and IER3, protecting the cell from apoptosis. Comparison to our cloned sequence reveals possible target sites for the TAR miRNA as well. Conclusion The TAR microRNA is expressed in all stages of the viral life cycle, can be detected in latently infected cells, and represents a mechanism wherein the virus extends the life of the infected cell for the purpose of increasing viral replication.

  11. Impaired information processing triggers altered states of consciousness.

    Science.gov (United States)

    Fritzsche, M

    2002-04-01

    Schizophrenia, intoxication with tetrahydrocannabinol (Delta-THC), and cannabis psychosis induce characteristic time and space distortions suggesting a common psychotic dysfunction. Since genetic research into schizophrenia has led into disappointing dead ends, the present study is focusing on this phenotype. It is shown that information theory can account for the dynamical basis of higher sensorimotor information processing and consciousness under physiologic as well as pathologic conditions. If Kolmogorov entropy (inherent in the processing of action and time) breaks down in acute psychosis, it is predicted that Shannon entropy (inherent in the processing of higher dimensional perception) will increase, provoking positive symptoms and altered states of consciousness. In the search for candidate genes and the protection of vulnerable individuals from cannabis abuse, non-linear EEG analysis of Kolmogorov information could thus present us with a novel diagnostic tool to directly assess the breakdown of information processing in schizophrenia.

  12. Lymphocyte maintenance during healthy aging requires no substantial alterations in cellular turnover.

    Science.gov (United States)

    Westera, Liset; van Hoeven, Vera; Drylewicz, Julia; Spierenburg, Gerrit; van Velzen, Jeroen F; de Boer, Rob J; Tesselaar, Kiki; Borghans, José A M

    2015-04-01

    In healthy humans, lymphocyte populations are maintained at a relatively constant size throughout life, reflecting a balance between lymphocyte production and loss. Given the profound immunological changes that occur during healthy aging, including a significant decline in T-cell production by the thymus, lymphocyte maintenance in the elderly is generally thought to require homeostatic alterations in lymphocyte dynamics. Surprisingly, using in vivo (2) H2 O labeling, we find similar dynamics of most lymphocyte subsets between young adult and elderly healthy individuals. As the contribution of thymic output to T-cell production is only minor from young adulthood onward, compensatory increases in peripheral T-cell division rates are not required to maintain the T-cell pool, despite a tenfold decline in thymic output. These fundamental insights will aid the interpretation of further research into aging and clinical conditions related to disturbed lymphocyte dynamics.

  13. Modulating cellular recombination potential through alterations in RecA structure and regulation.

    Science.gov (United States)

    Bakhlanova, Irina V; Dudkina, Alexandra V; Baitin, Dima M; Knight, Kendall L; Cox, Michael M; Lanzov, Vladislav A

    2010-12-01

    The wild-type Escherichia coli RecA protein is a recombinase platform with unrealized recombination potential. We have explored the factors affecting recombination during conjugation with a quantitative assay. Regulatory proteins that affect RecA function have the capacity to increase or decrease recombination frequencies by factors up to sixfold. Autoinhibition by the RecA C-terminus can affect recombination frequency by factors up to fourfold. The greatest changes in recombination frequency measured here are brought about by point mutations in the recA gene. RecA variants can increase recombination frequencies by more than 50-fold. The RecA protein thus possesses an inherently broad functional range. The RecA protein of E. coli (EcRecA) is not optimized for recombination function. Instead, much of the recombination potential of EcRecA is structurally suppressed, probably reflecting cellular requirements. One point mutation in EcRecA with a particularly dramatic effect on recombination frequency, D112R, exhibits an enhanced capacity to load onto SSB-coated ssDNA, overcome the effects of regulatory proteins such as PsiB and RecX, and to pair homologous DNAs. Comparisons of key RecA protein mutants reveal two components to RecA recombination function - filament formation and the inherent DNA pairing activity of the formed filaments.

  14. Cellular and molecular alterations in human epithelial cells transformed by high let radiation

    Science.gov (United States)

    Hei, T. K.; Piao, C. Q.; Sutter, T.; Willey, J. C.; Suzuki, K.

    An understanding of the radiobiological effects of high LET radiation is essential for human risk estimation and radiation protection. In the present study, we show that a single, 30 cGy dose of 150 keV/mum ^4He ions can malignantly transform human papillomavirus immortalized human bronchial epithelial [BEP2D] cells. Transformed cells produce progressively growing tumors in nude mice. The transformation frequency by the single dose of alpha particles is estimated to be approximately 4 x 10^-7. Based on the average cross-sectional area of BEP2D cells, it can be calculated that a mean traversal of 1.4 particles per cell is sufficient to induce tumorigenic conversion of these cells 3 to 4 months post-irradiation. Tumorigenic BEP2D cells overexpress mutated p53 tumor suppressor oncoproteins in addition to the cell cycle control gene cyclin D1 and D2. This model provides an opportunity to study the cellular and molecular changes at the various stages in radiation carcinogenesis involving human cells.

  15. Mobile Phone Service Process Hiccups at Cellular Inc.

    Science.gov (United States)

    Edgington, Theresa M.

    2010-01-01

    This teaching case documents an actual case of process execution and failure. The case is useful in MIS introductory courses seeking to demonstrate the interdependencies within a business process, and the concept of cascading failure at the process level. This case demonstrates benefits and potential problems with information technology systems,…

  16. Alterations in cellular metabolome after pharmacological inhibition of Notch in glioblastoma cells.

    Science.gov (United States)

    Kahlert, Ulf D; Cheng, Menglin; Koch, Katharina; Marchionni, Luigi; Fan, Xing; Raabe, Eric H; Maciaczyk, Jarek; Glunde, Kristine; Eberhart, Charles G

    2016-03-01

    Notch signaling can promote tumorigenesis in the nervous system and plays important roles in stem-like cancer cells. However, little is known about how Notch inhibition might alter tumor metabolism, particularly in lesions arising in the brain. The gamma-secretase inhibitor MRK003 was used to treat glioblastoma neurospheres, and they were subdivided into sensitive and insensitive groups in terms of canonical Notch target response. Global metabolomes were then examined using proton magnetic resonance spectroscopy, and changes in intracellular concentration of various metabolites identified which correlate with Notch inhibition. Reductions in glutamate were verified by oxidation-based colorimetric assays. Interestingly, the alkylating chemotherapeutic agent temozolomide, the mTOR-inhibitor MLN0128, and the WNT inhibitor LGK974 did not reduce glutamate levels, suggesting that changes to this metabolite might reflect specific downstream effects of Notch blockade in gliomas rather than general sequelae of tumor growth inhibition. Global and targeted expression analyses revealed that multiple genes important in glutamate homeostasis, including glutaminase, are dysregulated after Notch inhibition. Treatment with an allosteric inhibitor of glutaminase, compound 968, could slow glioblastoma growth, and Notch inhibition may act at least in part by regulating glutaminase and glutamate.

  17. Sustainability and the anthropogenic alteration of evolutionary processes

    Directory of Open Access Journals (Sweden)

    John Cairns, Jr.

    2004-08-01

    Full Text Available Persuasive evidence indicates that Earth is now experiencing a major biotic crisis. Even if humankind ceases severe stress on natural systems, the crisis will probably disrupt the basic evolutionary processes that characterized the period preceding the agricultural and industrial revolutions.Proliferation of drug and pesticide resistant species and opportunistic species that thrive in human-dominated ecosystems will become increasingly common. The effect on humankind of altering basic evolutionary processes is uncertain because the understanding of these processes is not robust. The probable result will not be an environment as favorable to humans as the one that has existed for most of human history. Humans probably have altered the environment since Homo sapiens first appeared. However, only in the last two centuries has the degree and rate of change reached levels now considered by many people to be ‘normal’, even though the record shows they are not.Greatly improved technology has facilitated increased exploitation of natural resources to unsustainablelevels. This exploitation, in turn, has led to exponential human population growth, which has depleted natural capital (living systems and the services they provide. Economic globalization has ensured that ecosystems far distant from consumers can be and are profitably exploited. Economicgrowth has become a universal mantra that is coupled with a conviction that such growth can continue indefinitely on a finite planet. A major paradigm shift is essential if sustainable use of the planet is to become a reality.

  18. Myocardial perfusion alterations observed months after radiotherapy are related to the cellular damage

    Energy Technology Data Exchange (ETDEWEB)

    Dogan, I.; Sonmez, B. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Nuclear Medicine; Sezen, O.; Zengin, A.Y.; Bahat, Z. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Radiation Oncology; Yenilmez, E.; Yulug, E. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Histology and Embryology; Abidin, I. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Biophysics

    2010-07-01

    Myocardial perfusion scintigraphy (MPS) is one of the widely used tools to follow developing radiation-induced heart disease (RIHD). But the clinical significance of MPS defects has not been fully understood. We have investigated the biodistribution alterations related to perfusion defects following radiotherapy (RT) and showed coexisting morphological changes. Animals, methods: A total of 18 Wistar rats were divided into three groups (1 control and 2 irradiated groups). A single cardiac 20 Gy radiation dose was used to induce long term cardiac defects. Biodistribution studies with technetium ({sup 99m}Tc) sestamibi and histological evaluations were performed 4 and 6 months after irradiation. The percent radioactivity (%ID/g) was calculated for each heart. For determination of the myocardial damage, positive apoptotic cardiomyocytes, myocardial cell degeneration, myocardial fibrosis, vascular damage and ultrastructural structures were evaluated. Results: Six months after treatment, a significant drop of myocardial uptake was observed (p < 0.05). Irradiation-induced apoptosis rose within the first 4 months after radiation treatment and were stayed elevated until the end of the observation period (p < 0.05). Also, the irradiation has induced myocardial degeneration, perivascular and interstitial fibrosis in the heart at the end of six and four months (p < 0.01). The severity and extent of myocardial injury has became more evident at the end of six month (p < 0.05). At ultrastructural level, prominent changes have been observed in the capillary endothelial and myocardial cells. Conclusion: Our findings suggest that the reduced rest myocardial perfusion, occuring months after the radiation, indicates a serious myocard tissue damage which is characterized by myocardial degeneration and fibrosis. (orig.)

  19. Prenatal IV Cocaine: Alterations in Auditory Information Processing

    Directory of Open Access Journals (Sweden)

    Charles F. Mactutus

    2011-06-01

    Full Text Available One clue regarding the basis of cocaine-induced deficits in attentional processing is provided by the clinical findings of changes in the infants’ startle response; observations buttressed by neurophysiological evidence of alterations in brainstem transmission time. Using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, the present study examined the effects of prenatal cocaine on auditory information processing via tests of the acoustic startle response (ASR, habituation, and prepulse inhibition (PPI in the offspring. Nulliparous Long-Evans female rats, implanted with an IV access port prior to breeding, were administered saline, 0.5, 1.0, or 3.0 mg/kg/injection of cocaine HCL (COC from gestation day (GD8-20 (1x/day-GD8-14, 2x/day-GD15-20. COC had no significant effects on maternal/litter parameters or growth of the offspring. At 18-20 days of age, one male and one female, randomly selected from each litter displayed an increased ASR (>30% for males at 1.0 mg/kg and >30% for females at 3.0 mg/kg. When reassessed in adulthood (D90-100, a linear dose-response increase was noted on response amplitude. At both test ages, within-session habituation was retarded by prenatal cocaine treatment. Testing the females in diestrus vs. estrus did not alter the results. Prenatal cocaine altered the PPI response function across interstimulus interval (ISI and induced significant sex-dependent changes in response latency. Idazoxan, an alpha2-adrenergic receptor antagonist, significantly enhanced the ASR, but less enhancement was noted with increasing doses of prenatal cocaine. Thus, in utero exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, causes persistent, if not permanent, alterations in auditory information processing, and suggests dysfunction of the central noradrenergic circuitry modulating, if not mediating, these responses.

  20. A distinct role for interleukin-6 as a major mediator of cellular adjustment to an altered culture condition.

    Science.gov (United States)

    Son, Hwa-Kyung; Park, Iha; Kim, Jue Young; Kim, Do Kyeong; Illeperuma, Rasika P; Bae, Jung Yoon; Lee, Doo Young; Oh, Eun-Sang; Jung, Da-Woon; Williams, Darren R; Kim, Jin

    2015-11-01

    Tissue microenvironment adjusts biological properties of different cells by modulating signaling pathways and cell to cell interactions. This study showed that epithelial-mesenchymal transition (EMT)/ mesenchymal-epithelial transition (MET) can be modulated by altering culture conditions. HPV E6/E7-transfected immortalized oral keratinocytes (IHOK) cultured in different media displayed reversible EMT/MET accompanied by changes in cell phenotype, proliferation, gene expression at transcriptional, and translational level, and migratory and invasive activities. Cholera toxin, a major supplement to culture medium, was responsible for inducing the morphological and biological changes of IHOK. Cholera toxin per se induced EMT by triggering the secretion of interleukin 6 (IL-6) from IHOK. We found IL-6 to be a central molecule that modulates the reversibility of EMT based not only on the mRNA level but also on the level of secretion. Taken together, our results demonstrate that IL-6, a cytokine whose transcription is activated by alterations in culture conditions, is a key molecule for regulating reversible EMT/MET. This study will contribute to understand one way of cellular adjustment for surviving in unfamiliar conditions.

  1. Betaine suppressed Aβ generation by altering amyloid precursor protein processing.

    Science.gov (United States)

    Liu, Xiu-Ping; Qian, Xiang; Xie, Yue; Qi, Yan; Peng, Min-Feng; Zhan, Bi-Cui; Lou, Zheng-Qing

    2014-07-01

    Betaine was an endogenous catabolite of choline, which could be isolated from vegetables and marine products. Betaine could promote the metabolism of homocysteine in healthy subjects and was used for hyperlipidemia, coronary atherosclerosis, and fatty liver in clinic. Recent findings shown that Betaine rescued neuronal damage due to homocysteine induced Alzheimer's disease (AD) like pathological cascade, including tau hyperphosphorylation and amyloid-β (Aβ) deposition. Aβ was derived from amyloid precursor protein (APP) processing, and was a triggering factor for AD pathological onset. Here, we demonstrated that Betaine reduced Aβ levels by altering APP processing in N2a cells stably expressing Swedish mutant of APP. Betaine increased α-secretase activity, but decreased β-secretase activity. Our data indicate that Betaine might play a protective role in Aβ production.

  2. Active Cellular Mechanics and Information Processing in the Living Cell

    Science.gov (United States)

    Rao, M.

    2014-07-01

    I will present our recent work on the organization of signaling molecules on the surface of living cells. Using novel experimental and theoretical approaches we have found that many cell surface receptors are organized as dynamic clusters driven by active currents and stresses generated by the cortical cytoskeleton adjoining the cell surface. We have shown that this organization is optimal for both information processing and computation. In connecting active mechanics in the cell with information processing and computation, we bring together two of the seminal works of Alan Turing.

  3. Altered lateralisation of emotional prosody processing in schizophrenia.

    Science.gov (United States)

    Bach, Dominik R; Herdener, Marcus; Grandjean, Didier; Sander, David; Seifritz, Erich; Strik, Werner K

    2009-05-01

    Alterations of cerebral lateralisation in schizophrenia have been reported consistently, and a reduced left-lateralisation has been suggested for language functions. Speech contains non-verbal information, e.g. prosody, and on a behavioural level, the extraction of emotional information from prosody is often impaired in schizophrenia. A previous functional magnetic resonance imaging study suggests increased left-lateralisation in schizophrenia during prosody processing, but did not disentangle effects of speech processing as such and emotional prosody processing. Here, we used meaningless syllables spoken with neutral, angry or fearful speech melody and measured blood oxygen level-dependent (BOLD) responses in 15 in-patients with schizophrenia and 15 healthy control participants matched for age and gender. Lateralisation indices were calculated for responses to emotional versus neutral prosody, and for all types of prosody versus baseline. Compared to control participants, patients with schizophrenia showed an increased right-lateralisation of emotional and non-emotional prosody processing in the temporal and parietal cortex. This right-lateralisation was increased in patients with reduced right-handedness and decreased in patients with stronger negative symptoms, particularly affective blunting, and with longer hospitalisation. Although patients with schizophrenia performed worse in emotion identification, this deficit was not related to lateralisation indices. Enhanced right-lateralisation to prosody resembles previous findings on laterality changes in speech processing and might suggest a common underlying cause in the organization of language functions.

  4. Cryotherapy Reduces Inflammatory Response Without Altering Muscle Regeneration Process and Extracellular Matrix Remodeling of Rat Muscle.

    Science.gov (United States)

    Vieira Ramos, Gracielle; Pinheiro, Clara Maria; Messa, Sabrina Peviani; Delfino, Gabriel Borges; Marqueti, Rita de Cássia; Salvini, Tania de Fátima; Durigan, Joao Luiz Quagliotti

    2016-01-04

    The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling.

  5. Association with emotional information alters subsequent processing of neutral faces.

    Science.gov (United States)

    Riggs, Lily; Fujioka, Takako; Chan, Jessica; McQuiggan, Douglas A; Anderson, Adam K; Ryan, Jennifer D

    2014-01-01

    The processing of emotional as compared to neutral information is associated with different patterns in eye movement and neural activity. However, the 'emotionality' of a stimulus can be conveyed not only by its physical properties, but also by the information that is presented with it. There is very limited work examining the how emotional information may influence the immediate perceptual processing of otherwise neutral information. We examined how presenting an emotion label for a neutral face may influence subsequent processing by using eye movement monitoring (EMM) and magnetoencephalography (MEG) simultaneously. Participants viewed a series of faces with neutral expressions. Each face was followed by a unique negative or neutral sentence to describe that person, and then the same face was presented in isolation again. Viewing of faces paired with a negative sentence was associated with increased early viewing of the eye region and increased neural activity between 600 and 1200 ms in emotion processing regions such as the cingulate, medial prefrontal cortex, and amygdala, as well as posterior regions such as the precuneus and occipital cortex. Viewing of faces paired with a neutral sentence was associated with increased activity in the parahippocampal gyrus during the same time window. By monitoring behavior and neural activity within the same paradigm, these findings demonstrate that emotional information alters subsequent visual scanning and the neural systems that are presumably invoked to maintain a representation of the neutral information along with its emotional details.

  6. Altering automatic verbal processes with transcranial direct current stimulation

    Directory of Open Access Journals (Sweden)

    Tracy D Vannorsdall

    2012-08-01

    Full Text Available AbstractBackground: Word retrieval during verbal fluency tasks utilizes both automatic and controlled cognitive processes. A distinction has been made between the generation of clusters and switches on verbal fluency tasks. Clusters, or the reporting of contiguous words within semantic or phonemic subcategories, are thought to reflect a relatively automatic processes In contrast, switching from one subcategory to another is thought to represent more controlled, effortful form of cognitive processing. Objective: In this single-blind experiment, we investigated whether tDCS can modify qualitative aspects of verbal fluency, such as clustering and switching, in healthy adults. Methods: Participants were randomly assigned to receive 1mA of either anodal/excitatory or cathodal/inhibitory active tDCS over the left prefrontal cortex in addition to sham stimulation. In the last segment of each 30-minute session, participants completed letter- and category-cued fluency tasks.Results: Anodal tDCS increased both overall productivity and the number and proportion of words in clusters during category-guided verbal fluency, whereas cathodal stimulation produced the opposite effect. Conclusions: tDCS can selectively alter automatic aspects of speeded lexical retrieval in a polarity-dependent fashion during a category-guided fluency task.  

  7. Tensegrity II. How structural networks influence cellular information processing networks

    Science.gov (United States)

    Ingber, Donald E.

    2003-01-01

    The major challenge in biology today is biocomplexity: the need to explain how cell and tissue behaviors emerge from collective interactions within complex molecular networks. Part I of this two-part article, described a mechanical model of cell structure based on tensegrity architecture that explains how the mechanical behavior of the cell emerges from physical interactions among the different molecular filament systems that form the cytoskeleton. Recent work shows that the cytoskeleton also orients much of the cell's metabolic and signal transduction machinery and that mechanical distortion of cells and the cytoskeleton through cell surface integrin receptors can profoundly affect cell behavior. In particular, gradual variations in this single physical control parameter (cell shape distortion) can switch cells between distinct gene programs (e.g. growth, differentiation and apoptosis), and this process can be viewed as a biological phase transition. Part II of this article covers how combined use of tensegrity and solid-state mechanochemistry by cells may mediate mechanotransduction and facilitate integration of chemical and physical signals that are responsible for control of cell behavior. In addition, it examines how cell structural networks affect gene and protein signaling networks to produce characteristic phenotypes and cell fate transitions during tissue development.

  8. Altered Auditory and Multisensory Temporal Processing in Autism Spectrum Disorders

    Science.gov (United States)

    Kwakye, Leslie D.; Foss-Feig, Jennifer H.; Cascio, Carissa J.; Stone, Wendy L.; Wallace, Mark T.

    2011-01-01

    Autism spectrum disorders (ASD) are characterized by deficits in social reciprocity and communication, as well as by repetitive behaviors and restricted interests. Unusual responses to sensory input and disruptions in the processing of both unisensory and multisensory stimuli also have been reported frequently. However, the specific aspects of sensory processing that are disrupted in ASD have yet to be fully elucidated. Recent published work has shown that children with ASD can integrate low-level audiovisual stimuli, but do so over an extended range of time when compared with typically developing (TD) children. However, the possible contributions of altered unisensory temporal processes to the demonstrated changes in multisensory function are yet unknown. In the current study, unisensory temporal acuity was measured by determining individual thresholds on visual and auditory temporal order judgment (TOJ) tasks, and multisensory temporal function was assessed through a cross-modal version of the TOJ task. Whereas no differences in thresholds for the visual TOJ task were seen between children with ASD and TD, thresholds were higher in ASD on the auditory TOJ task, providing preliminary evidence for impairment in auditory temporal processing. On the multisensory TOJ task, children with ASD showed performance improvements over a wider range of temporal intervals than TD children, reinforcing prior work showing an extended temporal window of multisensory integration in ASD. These findings contribute to a better understanding of basic sensory processing differences, which may be critical for understanding more complex social and cognitive deficits in ASD, and ultimately may contribute to more effective diagnostic and interventional strategies. PMID:21258617

  9. Altered auditory and multisensory temporal processing in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Leslie D Kwakye

    2011-01-01

    Full Text Available Autism spectrum disorders (ASD are characterized by deficits in social reciprocity and communication, as well as repetitive behaviors and restricted interests. Unusual responses to sensory input and disruptions in the processing of both unisensory and multisensory stimuli have also frequently been reported. However, the specific aspects of sensory processing that are disrupted in ASD have yet to be fully elucidated. Recent published work has shown that children with ASD can integrate low-level audiovisual stimuli, but do so over an extended range of time when compared with typically-developing (TD children. However, the possible contributions of altered unisensory temporal processes to the demonstrated changes in multisensory function are yet unknown. In the current study, unisensory temporal acuity was measured by determining individual thresholds on visual and auditory temporal order judgment (TOJ tasks, and multisensory temporal function was assessed through a cross-modal version of the TOJ task. Whereas no differences in thresholds for the visual TOJ task were seen between children with ASD and TD, thresholds were higher in ASD on the auditory TOJ task, providing preliminary evidence for impairment in auditory temporal processing. On the multisensory TOJ task, children with ASD showed performance improvements over a wider range of temporal intervals than TD children, reinforcing prior work showing an extended temporal window of multisensory integration in ASD. These findings contribute to a better understanding of basic sensory processing differences, which may be critical for understanding more complex social and cognitive deficits in ASD, and ultimately may contribute to more effective diagnostic and interventional strategies.

  10. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    Energy Technology Data Exchange (ETDEWEB)

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Casas, Josefina [Department of Biomedicinal Chemistry, IQAC–CSIC, 08034 Barcelona, Catalonia (Spain); Lacorte, Sílvia, E-mail: slbqam@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Porte, Cinta, E-mail: cinta.porte@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain)

    2014-06-01

    The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

  11. 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...

  12. Bovine spongiform encephalopathy induces misfolding of alleged prion-resistant species cellular prion protein without altering its pathobiological features.

    Science.gov (United States)

    Vidal, Enric; Fernández-Borges, Natalia; Pintado, Belén; Ordóñez, Montserrat; Márquez, Mercedes; Fondevila, Dolors; Torres, Juan María; Pumarola, Martí; Castilla, Joaquín

    2013-05-01

    Bovine spongiform encephalopathy (BSE) prions were responsible for an unforeseen epizootic in cattle which had a vast social, economic, and public health impact. This was primarily because BSE prions were found to be transmissible to humans. Other species were also susceptible to BSE either by natural infection (e.g., felids, caprids) or in experimental settings (e.g., sheep, mice). However, certain species closely related to humans, such as canids and leporids, were apparently resistant to BSE. In vitro prion amplification techniques (saPMCA) were used to successfully misfold the cellular prion protein (PrP(c)) of these allegedly resistant species into a BSE-type prion protein. The biochemical and biological properties of the new prions generated in vitro after seeding rabbit and dog brain homogenates with classical BSE were studied. Pathobiological features of the resultant prion strains were determined after their inoculation into transgenic mice expressing bovine and human PrP(C). Strain characteristics of the in vitro-adapted rabbit and dog BSE agent remained invariable with respect to the original cattle BSE prion, suggesting that the naturally low susceptibility of rabbits and dogs to prion infections should not alter their zoonotic potential if these animals became infected with BSE. This study provides a sound basis for risk assessment regarding prion diseases in purportedly resistant species.

  13. A cellular automata model for simulating fed-batch penicillin fermentation process

    Institute of Scientific and Technical Information of China (English)

    Yu Naigong; Ruan Xiaogang

    2006-01-01

    A cellular automata model to simulate penicillin fed-batch fermentation process(CAPFM)was established in this study,based on a morphologically structured dynamic penicillin production model,that is in turn based on the growth mechanism of penicillin producing microorganisms and the characteristics of penicillin fed-batch fermentation.CAPFM uses the three-dimensional cellular automata as a growth space,and a Moore-type neighborhood as the cellular neighborhood.The transition roles of CAPFM are designed based on mechanical and structural kinetic models of penicillin batch-fed fermentation processes.Every cell of CAPFM represents a single or specific number of penicillin producing microorganisms,and has various state.The simulation experimental results show that CAPFM replicates the evolutionary behavior of penicillin batch-fed fermentation processes described by the structured penicillin production kinetic model accordingly.

  14. Identification of genes that regulate multiple cellular processes/responses in the context of lipotoxicity to hepatoma cells

    Directory of Open Access Journals (Sweden)

    Yedwabnick Matthew

    2007-10-01

    Full Text Available Abstract Background In order to devise efficient treatments for complex, multi-factorial diseases, it is important to identify the genes which regulate multiple cellular processes. Exposure to elevated levels of free fatty acids (FFAs and tumor necrosis factor alpha (TNF-α alters multiple cellular processes, causing lipotoxicity. Intracellular lipid accumulation has been shown to reduce the lipotoxicity of saturated FFA. We hypothesized that the genes which simultaneously regulate lipid accumulation as well as cytotoxicity may provide better targets to counter lipotoxicity of saturated FFA. Results As a model system to test this hypothesis, human hepatoblastoma cells (HepG2 were exposed to elevated physiological levels of FFAs and TNF-α. Triglyceride (TG accumulation, toxicity and the genomic responses to the treatments were measured. Here, we present a framework to identify such genes in the context of lipotoxicity. The aim of the current study is to identify the genes that could be altered to treat or ameliorate the cellular responses affected by a complex disease rather than to identify the causal genes. Genes that regulate the TG accumulation, cytotoxicity or both were identified by a modified genetic algorithm partial least squares (GA/PLS analysis. The analyses identified NADH dehydrogenase and mitogen activated protein kinases (MAPKs as important regulators of both cytotoxicity and lipid accumulation in response to FFA and TNF-α exposure. In agreement with the predictions, inhibiting NADH dehydrogenase and c-Jun N-terminal kinase (JNK reduced cytotoxicity significantly and increased intracellular TG accumulation. Inhibiting another MAPK pathway, the extracellular signal regulated kinase (ERK, on the other hand, improved the cytotoxicity without changing TG accumulation. Much greater reduction in the toxicity was observed upon inhibiting the NADH dehydrogenase and MAPK (which were identified by the dual-response analysis, than for the

  15. Transposon mutagenesis identifies genes and cellular processes driving epithelial-mesenchymal transition in hepatocellular carcinoma

    Science.gov (United States)

    Kodama, Takahiro; Newberg, Justin Y.; Kodama, Michiko; Rangel, Roberto; Yoshihara, Kosuke; Tien, Jean C.; Parsons, Pamela H.; Wu, Hao; Finegold, Milton J.; Copeland, Neal G.; Jenkins, Nancy A.

    2016-01-01

    Epithelial-mesenchymal transition (EMT) is thought to contribute to metastasis and chemoresistance in patients with hepatocellular carcinoma (HCC), leading to their poor prognosis. The genes driving EMT in HCC are not yet fully understood, however. Here, we show that mobilization of Sleeping Beauty (SB) transposons in immortalized mouse hepatoblasts induces mesenchymal liver tumors on transplantation to nude mice. These tumors show significant down-regulation of epithelial markers, along with up-regulation of mesenchymal markers and EMT-related transcription factors (EMT-TFs). Sequencing of transposon insertion sites from tumors identified 233 candidate cancer genes (CCGs) that were enriched for genes and cellular processes driving EMT. Subsequent trunk driver analysis identified 23 CCGs that are predicted to function early in tumorigenesis and whose mutation or alteration in patients with HCC is correlated with poor patient survival. Validation of the top trunk drivers identified in the screen, including MET (MET proto-oncogene, receptor tyrosine kinase), GRB2-associated binding protein 1 (GAB1), HECT, UBA, and WWE domain containing 1 (HUWE1), lysine-specific demethylase 6A (KDM6A), and protein-tyrosine phosphatase, nonreceptor-type 12 (PTPN12), showed that deregulation of these genes activates an EMT program in human HCC cells that enhances tumor cell migration. Finally, deregulation of these genes in human HCC was found to confer sorafenib resistance through apoptotic tolerance and reduced proliferation, consistent with recent studies showing that EMT contributes to the chemoresistance of tumor cells. Our unique cell-based transposon mutagenesis screen appears to be an excellent resource for discovering genes involved in EMT in human HCC and potentially for identifying new drug targets. PMID:27247392

  16. A priming dose of protons alters the early cardiac cellular and molecular response to 56Fe irradiation

    Science.gov (United States)

    Ramadan, Samy S.; Sridharan, Vijayalakshmi; Koturbash, Igor; Miousse, Isabelle R.; Hauer-Jensen, Martin; Nelson, Gregory A.; Boerma, Marjan

    2016-02-01

    Purpose: Recent evidence suggests that the heart may be injured by ionizing radiation at lower doses than was previously thought. This raises concerns about the cardiovascular risks from exposure to radiation during space travel. Since space travel is associated with exposure to both protons from solar particle events and heavy ions from galactic cosmic rays, we here examined the effects of a "priming" dose of protons on the cardiac cellular and molecular response to a "challenge" dose of 56Fe in a mouse model. Methods: Male C57BL/6 mice at 10 weeks of age were exposed to sham-irradiation, 0.1 Gy of protons (150 MeV), 0.5 Gy of 56Fe (600 MeV/n), or 0.1 Gy of protons 24 hours prior to 0.5 Gy of 56Fe. Hearts were obtained at 7 days post-irradiation and western-blots were used to determine protein markers of cardiac remodeling, inflammatory infiltration, and cell death. Results: Exposure to 56Fe caused an increase in expression of α-smooth muscle cell actin, collagen type III, the inflammatory cell markers mast cell tryptase, CD2 and CD68, the endothelial glycoprotein thrombomodulin, and cleaved caspase 3. Of all proteins investigated, protons at a dose of 0.1 Gy induced a small increase only in cleaved caspase 3 levels. On the other hand, exposure to protons 24 hours before 56Fe prevented all of the responses to 56Fe. Conclusions: This study shows that a low dose of protons may prime the heart to respond differently to a subsequent challenge dose of heavy ions. Further investigation is required to identify responses at additional time points, consequences for cardiac function, threshold dose levels, and mechanisms by which a proton priming dose may alter the response to heavy ions.

  17. A simple yeast-based strategy to identify host cellular processes targeted by bacterial effector proteins.

    Directory of Open Access Journals (Sweden)

    Eran Bosis

    Full Text Available Bacterial effector proteins, which are delivered into the host cell via the type III secretion system, play a key role in the pathogenicity of gram-negative bacteria by modulating various host cellular processes to the benefit of the pathogen. To identify cellular processes targeted by bacterial effectors, we developed a simple strategy that uses an array of yeast deletion strains fitted into a single 96-well plate. The array is unique in that it was optimized computationally such that despite the small number of deletion strains, it covers the majority of genes in the yeast synthetic lethal interaction network. The deletion strains in the array are screened for hypersensitivity to the expression of a bacterial effector of interest. The hypersensitive deletion strains are then analyzed for their synthetic lethal interactions to identify potential targets of the bacterial effector. We describe the identification, using this approach, of a cellular process targeted by the Xanthomonas campestris type III effector XopE2. Interestingly, we discover that XopE2 affects the yeast cell wall and the endoplasmic reticulum stress response. More generally, the use of a single 96-well plate makes the screening process accessible to any laboratory and facilitates the analysis of a large number of bacterial effectors in a short period of time. It therefore provides a promising platform for studying the functions and cellular targets of bacterial effectors and other virulence proteins.

  18. Wnt Signaling Alteration in the Spinal Cord of Amyotrophic Lateral Sclerosis Transgenic Mice: Special Focus on Frizzled-5 Cellular Expression Pattern.

    Directory of Open Access Journals (Sweden)

    Carlos González-Fernández

    Full Text Available Amyotrophic lateral sclerosis is a chronic neurodegenerative disease characterized by progressive paralysis due to degeneration of motor neurons by unknown causes. Recent evidence shows that Wnt signaling is involved in neurodegenerative processes, including Amyotrophic Lateral Sclerosis. However, to date, little is known regarding the expression of Wnt signaling components in this fatal condition. In the present study we used transgenic SOD1G93A mice to evaluate the expression of several Wnt signaling components, with special focus on Frizzled-5 cellular expression alteration along disease progression.Based on previous studies demonstrating the expression of Wnts and their transcriptional regulation during Amyotrophic lateral sclerosis development, we have analyzed the mRNA expression of several Wnt signaling components in the spinal cord of SOD1G93A transgenic mice at different stages of the disease by using real time quantitative PCR analysis. Strikingly, one of the molecules that seemed not to be altered at mRNA level, Frizzled-5, showed a clear up-regulation at late stages in neurons, as evidenced by immunofluorescence assays. Moreover, increased Frizzled-5 appears to correlate with a decrease in NeuN signal in these cells, suggesting a correlation between neuronal affectation and the increased expression of this receptor.Our data suggest the involvement of Wnt signaling pathways in the pathophysiology of Amyotrophic Lateral Sclerosis and, more specifically, the implication of Frizzled-5 receptor in the response of neuronal cells against neurodegeneration. Nevertheless, further experimental studies are needed to shed light on the specific role of Frizzled-5 and the emerging but increasing Wnt family of proteins research field as a potential target for this neuropathology.

  19. Divalent metals stabilize cellular prion proteins and alter the rate of proteinase-K dependent limited proteolysis

    Science.gov (United States)

    Background: The key biochemical event in the pathogenesis of prion diseases is the conversion of normal cellular prion proteins (PrP**c) to the proteinase K (PK) resistant, abnormal form (PrP**sc); however, the cellular mechanisms underlying the conversion remain enigmatic. Binding of divalent ca...

  20. Cellular compartments cause multistability and allow cells to process more information

    DEFF Research Database (Denmark)

    Harrington, Heather A; Feliu, Elisenda; Wiuf, Carsten;

    2013-01-01

    recent developments from dynamical systems and chemical reaction network theory to identify and characterize the key-role of the spatial organization of eukaryotic cells in cellular information processing. In particular, the existence of distinct compartments plays a pivotal role in whether a system...... outcomes for cellular-decision making. We combine different mathematical techniques to provide a heuristic procedure to determine if a system has the capacity for multiple steady states, and find conditions that ensure that multiple steady states cannot occur. Notably, we find that introducing species......Many biological, physical, and social interactions have a particular dependence on where they take place; e.g., in living cells, protein movement between the nucleus and cytoplasm affects cellular responses (i.e., proteins must be present in the nucleus to regulate their target genes). Here we use...

  1. Cellular scanning strategy for selective laser melting: Generating reliable, optimized scanning paths and processing parameters

    DEFF Research Database (Denmark)

    Mohanty, Sankhya; Hattel, Jesper Henri

    2015-01-01

    to generate optimized cellular scanning strategies and processing parameters, with an objective of reducing thermal asymmetries and mechanical deformations. The optimized scanning strategies are used for selective laser melting of the standard samples, and experimental and numerical results are compared....... gradients that occur during the process. While process monitoring and control of selective laser melting is an active area of research, establishing the reliability and robustness of the process still remains a challenge.In this paper, a methodology for generating reliable, optimized scanning paths...

  2. A new cellular nonlinear network emulation on FPGA for EEG signal processing in epilepsy

    Science.gov (United States)

    Müller, Jens; Müller, Jan; Tetzlaff, Ronald

    2011-05-01

    For processing of EEG signals, we propose a new architecture for the hardware emulation of discrete-time Cellular Nonlinear Networks (DT-CNN). Our results show the importance of a high computational accuracy in EEG signal prediction that cannot be achieved with existing analogue VLSI circuits. The refined architecture of the processing elements and its resource schedule, the cellular network structure with local couplings, the FPGA-based embedded system containing the DT-CNN, and the data flow in the entire system will be discussed in detail. The proposed DT-CNN design has been implemented and tested on an Xilinx FPGA development platform. The embedded co-processor with a multi-threading kernel is utilised for control and pre-processing tasks and data exchange to the host via Ethernet. The performance of the implemented DT-CNN has been determined for a popular example and compared to that of a conventional computer.

  3. The effect of oxidant and the non-oxidant alteration of cellular thiol concentration on the formation of protein mixed-disulfides in HEK 293 cells.

    Directory of Open Access Journals (Sweden)

    Jasen Lee Gilge

    Full Text Available Cellular molecules possess various mechanisms in responding to oxidant stress. In terms of protein responses, protein S-glutathionylation is a unique post-translational modification of protein reactive cysteines forming disulfides with glutathione molecules. This modification has been proposed to play roles in antioxidant, regulatory and signaling in cells under oxidant stress. Recently, the increased level of protein S-glutathionylation has been linked with the development of diseases. In this report, specific S-glutathionylated proteins were demonstrated in human embryonic kidney 293 cells treated with two different oxidative reagents: diamide and hydrogen peroxide. Diamide is a chemical oxidizing agent whereas hydrogen peroxide is a physiological oxidant. Under the experimental conditions, these two oxidants decreased glutathione concentration without toxicity. S-glutathionylated proteins were detected by immunoblotting and glutathione concentrations were determined by high performance liquid chromatography. We further show the effect of alteration of the cellular thiol pool on the amount of protein S-glutathionylation in oxidant-treated cells. Cellular thiol concentrations were altered either by a specific way using buthionine sulfoximine, a specific inhibitor of glutathione biosynthesis or by a non-specific way, incubating cells in cystine-methionine deficient media. Cells only treated with either buthionine sulfoximine or cystine-methionine deficient media did not induce protein S-glutathionylation, even though both conditions decreased 65% of cellular glutathione. Moreover, the amount of protein S-glutathionylation under both conditions in the presence of oxidants was not altered when compared to the amount observed in regular media with oxidants present. Protein S-glutathionylation is a dynamic reaction which depends on the rate of adding and removing glutathione. Phenylarsine oxide, which specifically forms a covalent adduct with

  4. Reorganization of microtubular cytoskeleton and formation of cellular processes during post-telophase in haemanthus endosperm.

    Science.gov (United States)

    Bajer, A S; Smirnova, E A

    1999-10-01

    We followed time-dependent post-telophase reorganization of the microtubule cytoskeleton on immunostained preparations of endosperm of the higher plant Haemanthus. After completion of mitosis, the phragmoplast continued to reorganize for several hours. This prompted the formation of phragmoplast-like derivatives (secondary and accessory phragmoplasts and peripheral microtubular ring). Next, elongated cellular protrusions (processes) appeared at the cell periphery. These processes contained long microtubule bundles and disorderly arranged actin filaments. Microtubule converging centers or accessory phragmoplasts were often present at the tips of the processes. Observation in vivo demonstrated that processes were formed at the cell periphery as extensions of lammelipodia or filopodia-type protrusions that commonly terminated with cytoplasmic blobs. We suggest that processes are derivatives of a peripheral microtubular ring that reorganizes gradually into cellular protrusions. Endosperm processes have several features of neuronal cells, or animal somatic cells with overexpressed MAPs. Since microtubule-containing processes were never detected shortly after extrusion of the cells from the embryo sac, this course of events might be restricted specifically to extruded endosperm and triggered either by removal of cells, their placement in monolayer on agar substrate, or both. Thus, post telophase behavior of endosperm cells offers a novel experimental system for studies of cytoskeleton in higher plants.

  5. Improving cellularity and quality of liquid-based cytology slides processed from pancreatobiliary tract brushings.

    Science.gov (United States)

    Campion, Michael B; Kipp, Benjamin R; Humphrey, Sandra K; Zhang, Jun; Clayton, Amy C; Henry, Michael R

    2010-09-01

    Cytology has been reported to have suboptimal sensitivity for detecting pancreatobiliary tract cancer in biliary tract specimens partly as a result of low specimen cellularity and obscuring noncellular components. The goal of this study was to determine if the use of a glacial acetic acid wash prior to processing would increase the cellularity and improve the quality of ThinPrep slides when compared to standard non-gyn ThinPrep processing. Fifty consecutive pancreatobiliary tract specimens containing 20 ml of sample/PreservCyt were divided equally for standard non-gyn ThinPrep (STP) and glacial acetic acid ThinPrep processing (GATP). A manual drop preparation was also performed on residual STP specimen to determine the number of cells left in the vial during STP processing. Twenty-six (52%) specimens had more epithelial cell groupings with the GATP methodology while 19 (38%) had equivalent cellularity with both methods. The STP method produced more epithelial cell groupings in 5 (10%) of the specimens. Of the 26 specimens that had less cells with the STP method, 14 (54%) had > or = 50 cell groupings on the manual drop slide processed from the residual STP specimen suggesting that many cells remain in the vial after STP processing. The GATP method was preferred in 25 (50%) of the specimens, the STP method in 5 (10%), while both methodologies provided similar findings in the remaining 20 (40%) of specimens. The data from this study suggests that the GATP method results in more cells being placed on the slide and was preferred over the STP method in a majority of specimens.

  6. Characterization of Deciliation-Regeneration Process of Tetrahymena Pyriformis for Cellular Robot Fabrication

    Institute of Scientific and Technical Information of China (English)

    Dal Hyung Kim; Sean E. Brigandi; Paul Kim; Doyoung Byun; Min Jun Kim

    2011-01-01

    Artificial magnetotactic Tetrahymena pyriformis GL (T. pyriformis) cells were created by the internalization of iron oxide nano particles and became controllable with a time-varying external magnetic field. Thus, T. pyriformis can be utilized as a cellular robot to conduct micro-scale tasks such as transportation and manipulation. To complete these tasks, loading inorganic or organic materials onto the cell body is essential, but functionalization of the cell membrane is obstructed by their motile organelles, cilia. Dibucaine HCl, a local anesthetic, removes the cilia from the cell body, and the functional group would be absorbed more efficiently during cilia regeneration. In this paper, we characterize the recovery of artificial magnetotactic T.pyriformis after the deciliation process to optimize a cellular robot fabrication process. After sufficient time to recover, the motility rate and the average velocity of the deciliated cells were six and ten percent lower than that of non-deciliated cells, respectively. We showed that the motile cells after recovery can still be controlled using magnetotaxis, making T. pyriformis a good candidate to be used as a cellular robot.

  7. Early leaf senescence is associated with an altered cellular redox balance in Arabidopsis cpr5/old1 mutants

    NARCIS (Netherlands)

    Jing, H. -C.; Hebeler, R.; Oeljeklaus, S.; Sitek, B.; Stuehler, K.; Meyer, H. E.; Sturre, M. J. G.; Hille, J.; Warscheid, B.; Dijkwel, P. P.; Stühler, K.

    2008-01-01

    Reactive oxygen species (ROS) are the inevitable by-products of essential cellular metabolic and physiological activities. Plants have developed sophisticated gene networks of ROS generation and scavenging systems. However, ROS regulation is still poorly understood. Here, we report that mutations in

  8. Sediment contaminated with the Azo Dye disperse yellow 7 alters cellular stress- and androgen-related transcription in Silurana tropicalis larvae.

    Science.gov (United States)

    Mathieu-Denoncourt, Justine; Martyniuk, Christopher J; de Solla, Shane R; Balakrishnan, Vimal K; Langlois, Valérie S

    2014-01-01

    Azo dyes are the most commonly used type of dye, accounting for 60-70% of all organic dye production worldwide. They are used as direct dyes in the textile, leather, printing ink, and cosmetic industries. The aim of this study was to assess the lethal and sublethal effects of the disazo dye Disperse Yellow 7 (DY7) in frogs to address a knowledge gap regarding mechanisms of toxicity and the potential for endocrine disrupting properties. Larvae of Silurana tropicalis (Western clawed frog) were exposed to DY7-contaminated water (0 to 22 μg/L) and sediment (0 to 209 μg/g) during early larval development. The concentrations used included the range of similar azo dyes found in surface waters in Canada. A significant decrease in tadpole survivorship was observed at 209 μg/g while there was a significant increase in malformations at the two highest concentrations tested in sediment. In the 209 μg/g treatment, DY7 significantly induced hsp70 (2.5-fold) and hsp90 (2.4-fold) mRNA levels, suggesting that cells required oxidative protection. The same treatment also altered the expression of two androgen-related genes: decreased ar (2-fold) and increased srd5a2 (2.6-fold). Furthermore, transcriptomics generated new hypotheses regarding the mechanisms of toxic action of DY7. Gene network analysis revealed that high concentrations of DY7 in sediment induced cellular stress-related gene transcription and affected genes associated with necrotic cell death, chromosome condensation, and mRNA processing. This study is the first to report on sublethal end points for azo dyes in amphibians, a growing environmental pollutant of concern for aquatic species.

  9. Phase matching alters spatial multiphoton processes in dense atomic ensembles

    CERN Document Server

    Leszczyński, Adam; Wasilewski, Wojciech

    2016-01-01

    Multiphoton processes in dense atomic vapors such as four-wave mixing or coherent blue light generation are typically viewed from single-atom perspective. Here we study the surprisingly important effect of phase matching near two-photon resonances that arises due to spatial extent of the atomic medium within which the multiphoton process occurs. The non-unit refractive index of the atomic vapor may inhibit generation of light in nonlinear processes, significantly shift the efficiency maxima in frequencies and redirect emitted beam. We present these effects on an example of four-wave mixing in dense rubidium vapors in a double-ladder configuration. By deriving a simple theory that takes into account essential spatial properties of the process, we give precise predictions and confirm their validity in the experiment. The model allows us to improve on the geometry of the experiment and engineer more efficient four-wave mixing.

  10. Phase matching alters spatial multiphoton processes in dense atomic ensembles.

    Science.gov (United States)

    Leszczyński, Adam; Parniak, Michał; Wasilewski, Wojciech

    2017-01-09

    Multiphoton processes in dense atomic vapors such as four-wave mixing or coherent blue light generation are typically viewed from single-atom perspective. Here we study the surprisingly important effect of phase matching near two-photon resonances that arises due to spatial extent of the atomic medium within which the multiphoton process occurs. The non-unit refractive index of the atomic vapor may inhibit generation of light in nonlinear processes, significantly shift the efficiency maxima in frequencies and redirect emitted beam. We present these effects on an example of four-wave mixing in dense rubidium vapors in a double-ladder configuration. By deriving a simple theory that takes into account essential spatial properties of the process, we give precise predictions and confirm their validity in the experiment. The model allows us to improve on the geometry of the experiment and engineer more efficient four-wave mixing.

  11. Early Visual Deprivation Alters Multisensory Processing in Peripersonal Space

    Science.gov (United States)

    Collignon, Olivier; Charbonneau, Genevieve; Lassonde, Maryse; Lepore, Franco

    2009-01-01

    Multisensory peripersonal space develops in a maturational process that is thought to be influenced by early sensory experience. We investigated the role of vision in the effective development of audiotactile interactions in peripersonal space. Early blind (EB), late blind (LB) and sighted control (SC) participants were asked to lateralize…

  12. Fluorescence-Based Codetection with Protein Markers Reveals Distinct Cellular Compartments for Altered MicroRNA Expression in Solid Tumors

    DEFF Research Database (Denmark)

    Sempere, Lorenzo F.; Preis, Meir; Yezefski, Todd;

    2010-01-01

    Purpose: High-throughput profiling experiments have linked altered expression of microRNAs (miRNA) to different types of cancer. Tumor tissues are a heterogeneous mixture of not only cancer cells, but also supportive and reactive tumor microenvironment elements. To clarify the clinical significan...

  13. Herpes Simplex Virus 1 Infection Alters the mRNA Translation Processing in L-02 Cells

    Institute of Scientific and Technical Information of China (English)

    Min HONG; Yan-chun CHE; Gui-zhen TANG; Wei CUN; Xue-mei ZHANG; Long-ding LIU; Qi-han LI

    2008-01-01

    HSV-1 infection-mediated regulation of mRNA translation in host cells is a systematic and complicated process. Investigation of the details of this mechanism will facilitate understanding of biological variations in the viral replication process and host cells. In this study, a comparative proteomics technology platform was applied by two-dimension electrophoresis of HSV-1 infected normal human L-02 cell and control cell lysates. The observed protein spots were analyzed qualitatively and quantitatively by the PDQuest software package. A number of the different observed protein spots closely associated with cellular protein synthesis were identified by matrix-assisted laser-desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS). The expression levels of the RPLP1 protein, which is required for mRNA translation, and KHSRP protein, which is involved in rapid decay of mRNA, were up-regulated, whereas the expression level of RNP H2, which is involved in positive regulation on the mRNA splicing process, was down-regulated. All of these results suggest that HSV-1 infection can influence cellular protein synthesis via modulation of cellular regulatory proteins involved in RNA splicing, translation and decay, resulting in optimisation of viral protein synthesis when cellular protein synthesis is shut off. Although there is need for further investigations regarding the detailed mechanisms of cellular protein control, our studies provide new insight into the targeting of varied virus signaling pathways involved in host cellular protein synthesis.

  14. Alterations of Cloud Microphysics Due to Cloud Processed CCN

    Science.gov (United States)

    Hudson, J. G.; Tabor, S. S.; Noble, S. R., Jr.

    2015-12-01

    High-resolution CCN spectra have revealed bimodality (Hudson et al. 2015) similar to aerosol size spectra (e.g., Hoppel et al. 1985). Bimodality is caused by chemical and physical cloud processes that increase mass or hygroscopicity of only CCN that produced activated cloud droplets. Bimodality is categorized by relative CCN concentrations (NCCN) within the two modes, Nu-Np; i.e., NCCN within the higher critical supersaturation, Sc, mode that did not undergo cloud processing minus NCCN within the lower Sc mode that was cloud processed. Lower, especially negative, Nu-Np designates greater processing. The table shows regressions between Nu-Np and characteristics of clouds nearest the CCN measurements. ICE-T MASE parameter R SL R SL Nc 0.17 93.24 -0.26 98.65 MD -0.31 99.69 0.33 99.78 σ -0.27 99.04 0.48 100.00 Ld -0.31 99.61 0.38 99.96 Table. Correlation coefficients, R, and one-tailed significance levels in percent, SL, for Nu-Np with microphysics of the clouds closest to each CCN measurement, 75 ICE-T and 74 MASE cases. Nc is cloud droplet concentration, MD is cloud droplet mean diameter, σ is standard deviation of cloud droplet spectra, Ldis drizzle drop LWC. Two aircraft field campaigns, Ice in Clouds Experiment-Tropical (ICE-T) and Marine Stratus/Stratocumulus Experiment (MASE) show opposite R signs because coalescence dominated cloud processing in low altitude ICE-T cumuli whereas chemical transformations predominated in MASE low altitude polluted stratus. Coalescence reduces Nc and NCCN, which thus increases MD, and σ, which promote Ld. Chemical transformations, e.g., SO2 to SO4, increase CCN hygroscopicity, thus reducing Sc, but not affecting Nc or NCCN. Lower Sc CCN are capable of producing greater Nc in subsequent cloud cycles, which leads to lower MD and σ which reduce Ld (figure). These observations are consistent with cloud droplet growth models for the higher vertical wind (W) of cumuli and lower W of stratus. Coalescence thus reduces the indirect

  15. Inhomogeneous Poisson point process nucleation: comparison of analytical solution with cellular automata simulation

    Directory of Open Access Journals (Sweden)

    Paulo Rangel Rios

    2009-06-01

    Full Text Available Microstructural evolution in three dimensions of nucleation and growth transformations is simulated by means of cellular automata (CA. In the simulation, nuclei are located in space according to a heterogeneous Poisson point processes. The simulation is compared with exact analytical solution recently obtained by Rios and Villa supposing that the intensity is a harmonic function of the spatial coordinate. The simulated data gives very good agreement with the analytical solution provided that the correct shape factor for the growing CA grains is used. This good agreement is auspicious because the analytical expressions were derived and thus are exact only if the shape of the growing regions is spherical.

  16. Numerical study on photoresist etching processes based on a cellular automata model

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    For the three-dimensional (3-D) numerical study of photoresist etching processes, the 2-D dynamic cellular automata (CA) model has been successfully extended to a 3-D dynamic CA model. Only the boundary cells will be processed in the 3-D dy-namic CA model and the structure of “if-else” description in the simulation pro-gram is avoided to speed up the simulation. The 3-D dynamic CA model has found to be stable, fast and accurate for the numerical study of photoresist etching processes. The exposure simulation, post-exposure bake (PEB) simulation and etching simulation are integrated together to further investigate the performances of the CA model. Simulation results have been compared with the available ex-perimental results and the simulations show good agreement with the available experiments.

  17. Numerical study on photoresist etching processes based on a cellular automata model

    Institute of Scientific and Technical Information of China (English)

    ZHOU ZaiFa; HUANG QingAn; LI WeiHua; LU Wei

    2007-01-01

    For the three-dimensional (3-D) numerical study of photoresist etching processes, the 2-D dynamic cellular automata (CA) model has been successfully extended to a 3-D dynamic CA model. Only the boundary cells will be processed in the 3-D dynamic CA model and the structure of "if-else" description in the simulation program is avoided to speed up the simulation. The 3-D dynamic CA model has found to be stable, fast and accurate for the numerical study of photoresist etching processes. The exposure simulation, post-exposure bake (PEB) simulation and etching simulation are integrated together to further investigate the performances of the CA model. Simulation results have been compared with the available experimental results and the simulations show good agreement with the available experiments.

  18. Phenylpyrazole insecticides induce cytotoxicity by altering mechanisms involved in cellular energy supply in the human epithelial cell model Caco-2.

    Science.gov (United States)

    Vidau, Cyril; Brunet, Jean-Luc; Badiou, Alexandra; Belzunces, Luc P

    2009-06-01

    Phenylpyrazoles are relatively new insecticides designed to manage problematic insect resistance and public health hazards encountered with older pesticide families. In vitro cytotoxicity induced by the phenylpyrazole insecticides, Ethiprol and Fipronil, and Fipronil metabolites, sulfone and sulfide, was studied in Caco-2 cells. This cellular model was chosen because it made possible to mimic the primary site of oral exposure to xenobiotics, the intestinal epithelium. Assessment of the barrier function of Caco-2 epithelium was assessed by TEER measurement and showed a major loss of barrier integrity after exposure to Fipronil and its metabolites, but not to Ethiprol. The disruption of the epithelial barrier was attributed to severe ATP depletion independent of cell viability, as revealed by LDH release. The origin of energetic metabolism failure was investigated and revealed a transient enhancement of tetrazolium salt reduction and an increase in lactate production by Caco-2 cells, suggesting an increase in glucose metabolism by pesticides. Cellular symptoms observed in these experiments lead us to hypothesize that phenylpyrazole insecticides interacted with mitochondria.

  19. Alterations in cellular energy metabolism associated with the antiproliferative effects of the ATM inhibitor KU-55933 and with metformin.

    Directory of Open Access Journals (Sweden)

    Mahvash Zakikhani

    Full Text Available KU-55933 is a specific inhibitor of the kinase activity of the protein encoded by Ataxia telangiectasia mutated (ATM, an important tumor suppressor gene with key roles in DNA repair. Unexpectedly for an inhibitor of a tumor suppressor gene, KU-55933 reduces proliferation. In view of prior preliminary evidence suggesting defective mitochondrial function in cells of patients with Ataxia Telangiectasia (AT, we examined energy metabolism of cells treated with KU-55933. The compound increased AMPK activation, glucose uptake and lactate production while reducing mitochondrial membrane potential and coupled respiration. The stimulation of glycolysis by KU-55933 did not fully compensate for the reduction in mitochondrial functions, leading to decreased cellular ATP levels and energy stress. These actions are similar to those previously described for the biguanide metformin, a partial inhibitor of respiratory complex I. Both compounds decreased mitochondrial coupled respiration and reduced cellular concentrations of fumarate, malate, citrate, and alpha-ketogluterate. Succinate levels were increased by KU-55933 levels and decreased by metformin, indicating that the effects of ATM inhibition and metformin are not identical. These observations suggest a role for ATM in mitochondrial function and show that both KU-55933 and metformin perturb the TCA cycle as well as oxidative phosphorylation.

  20. Proteomic characterization of cellular and molecular processes that enable the Nanoarchaeum equitans--Ignicoccus hospitalis relationship.

    Directory of Open Access Journals (Sweden)

    Richard J Giannone

    Full Text Available Nanoarchaeum equitans, the only cultured representative of the Nanoarchaeota, is dependent on direct physical contact with its host, the hyperthermophile Ignicoccus hospitalis. The molecular mechanisms that enable this relationship are unknown. Using whole-cell proteomics, differences in the relative abundance of >75% of predicted protein-coding genes from both Archaea were measured to identify the specific response of I. hospitalis to the presence of N. equitans on its surface. A purified N. equitans sample was also analyzed for evidence of interspecies protein transfer. The depth of cellular proteome coverage achieved here is amongst the highest reported for any organism. Based on changes in the proteome under the specific conditions of this study, I. hospitalis reacts to N. equitans by curtailing genetic information processing (replication, transcription in lieu of intensifying its energetic, protein processing and cellular membrane functions. We found no evidence of significant Ignicoccus biosynthetic enzymes being transported to N. equitans. These results suggest that, under laboratory conditions, N. equitans diverts some of its host's metabolism and cell cycle control to compensate for its own metabolic shortcomings, thus appearing to be entirely dependent on small, transferable metabolites and energetic precursors from I. hospitalis.

  1. Proteomic characterization of cellular and molecular processes that enable the Nanoarchaeum equitans--Ignicoccus hospitalis relationship.

    Science.gov (United States)

    Giannone, Richard J; Huber, Harald; Karpinets, Tatiana; Heimerl, Thomas; Küper, Ulf; Rachel, Reinhard; Keller, Martin; Hettich, Robert L; Podar, Mircea

    2011-01-01

    Nanoarchaeum equitans, the only cultured representative of the Nanoarchaeota, is dependent on direct physical contact with its host, the hyperthermophile Ignicoccus hospitalis. The molecular mechanisms that enable this relationship are unknown. Using whole-cell proteomics, differences in the relative abundance of >75% of predicted protein-coding genes from both Archaea were measured to identify the specific response of I. hospitalis to the presence of N. equitans on its surface. A purified N. equitans sample was also analyzed for evidence of interspecies protein transfer. The depth of cellular proteome coverage achieved here is amongst the highest reported for any organism. Based on changes in the proteome under the specific conditions of this study, I. hospitalis reacts to N. equitans by curtailing genetic information processing (replication, transcription) in lieu of intensifying its energetic, protein processing and cellular membrane functions. We found no evidence of significant Ignicoccus biosynthetic enzymes being transported to N. equitans. These results suggest that, under laboratory conditions, N. equitans diverts some of its host's metabolism and cell cycle control to compensate for its own metabolic shortcomings, thus appearing to be entirely dependent on small, transferable metabolites and energetic precursors from I. hospitalis.

  2. Altering adsorbed proteins or cellular gene expression in bone-metastatic cancer cells affects PTHrP and Gli2 without altering cell growth

    Directory of Open Access Journals (Sweden)

    Jonathan M. Page

    2015-09-01

    Full Text Available The contents of this data in brief are related to the article titled “Matrix Rigidity Regulates the Transition of Tumor Cells to a Bone-Destructive Phenotype through Integrin β3 and TGF-β Receptor Type II”. In this DIB we will present our supplemental data investigating Integrin expression, attachment of cells to various adhesion molecules, and changes in gene expression in multiple cancer cell lines. Since the interactions of Integrins with adsorbed matrix proteins are thought to affect the ability of cancer cells to interact with their underlying substrates, we examined the expression of Integrin β1, β3, and β5 in response to matrix rigidity. We found that only Iβ3 increased with increasing substrate modulus. While it was shown that fibronectin greatly affects the expression of tumor-produced factors associated with bone destruction (parathyroid hormone-related protein, PTHrP, and Gli2, poly-l-lysine, vitronectin and type I collagen were also analyzed as potential matrix proteins. Each of the proteins was independently adsorbed on both rigid and compliant polyurethane films which were subsequently used to culture cancer cells. Poly-l-lysine, vitronectin and type I collagen all had negligible effects on PTHrP or Gli2 expression, but fibronectin was shown to have a dose dependent effect. Finally, altering the expression of Iβ3 demonstrated that it is required for tumor cells to respond to the rigidity of the matrix, but does not affect other cell growth or viability. Together these data support the data presented in our manuscript to show that the rigidity of bone drives Integrinβ3/TGF-β crosstalk, leading to increased expression of Gli2 and PTHrP.

  3. Signal processing for molecular and cellular biological physics: an emerging field

    Science.gov (United States)

    Little, Max A.; Jones, Nick S.

    2013-01-01

    Recent advances in our ability to watch the molecular and cellular processes of life in action—such as atomic force microscopy, optical tweezers and Forster fluorescence resonance energy transfer—raise challenges for digital signal processing (DSP) of the resulting experimental data. This article explores the unique properties of such biophysical time series that set them apart from other signals, such as the prevalence of abrupt jumps and steps, multi-modal distributions and autocorrelated noise. It exposes the problems with classical linear DSP algorithms applied to this kind of data, and describes new nonlinear and non-Gaussian algorithms that are able to extract information that is of direct relevance to biological physicists. It is argued that these new methods applied in this context typify the nascent field of biophysical DSP. Practical experimental examples are supplied. PMID:23277603

  4. Simulation of abrasive water jet cutting process: Part 2. Cellular automata approach

    Science.gov (United States)

    Orbanic, Henri; Junkar, Mihael

    2004-11-01

    A new two-dimensional cellular automata (CA) model for the simulation of the abrasive water jet (AWJ) cutting process is presented. The CA calculates the shape of the cutting front, which can be used as an estimation of the surface quality. The cutting front is formed based on material removal rules and AWJ propagation rules. The material removal rule calculates when a particular part of the material will be removed with regard to the energy of AWJ. The AWJ propagation rule calculates the distribution of AWJ energy through CA by using a weighted average. The modelling with CA also provides a visual narrative of the moving of the cutting front, which is hard to observe in real process. The algorithm is fast and has been successfully tested in comparison to cutting fronts obtained with cutting experiments of aluminium alloy.

  5. Antisense expression of a rice cellular apoptosis susceptibility gene (OsCAS) alters the height of transgenic rice

    Institute of Scientific and Technical Information of China (English)

    XU Chunxiao; HE Chaozu

    2007-01-01

    Cellular apoptosis susceptibility (CAS) gene plays important roles in mitosis, development and export of importin αfrom the nucleus, but its function in plant is unknown. In this study, a rice CAS ortholog (OsCAS), which encodes a predicted protein of 983 amino acids with 62% similarity to human CAS, was identified. DNA gel blot analysis revealed a single copy of OsCAS in the rice genome. A 973 bp fragment at the 3' end of OsCAS cDNA was cloned from rice cDNA library and transferred into rice in the antisense direction under the control of CaMV 35S promoter via Agrobacterium-mediated transformation method, 105 transgenic lines were obtained. Expression of OsCAS was suppressed in the antisense transgenic lines as revealed by semi-quantitative RT-PCR. The antisense transgenic lines showed dwarf phenotypes. The results indicated that OsCAS was involved in culm development of rice.

  6. Alteration of cellular behavior and response to PI3K pathway inhibition by culture in 3D collagen gels.

    Directory of Open Access Journals (Sweden)

    Brian Fallica

    Full Text Available Most investigations into cancer cell drug response are performed with cells cultured on flat (2D tissue culture plastic. Emerging research has shown that the presence of a three-dimensional (3D extracellular matrix (ECM is critical for normal cell behavior including migration, adhesion, signaling, proliferation and apoptosis. In this study we investigate differences between cancer cell signaling in 2D culture and a 3D ECM, employing real-time, live cell tracking to directly observe U2OS human osteosarcoma and MCF7 human breast cancer cells embedded in type 1 collagen gels. The activation of the important PI3K signaling pathway under these different growth conditions is studied, and the response to inhibition of both PI3K and mTOR with PI103 investigated. Cells grown in 3D gels show reduced proliferation and migration as well as reduced PI3K pathway activation when compared to cells grown in 2D. Our results quantitatively demonstrate that a collagen ECM can protect U2OS cells from PI103. Overall, our data suggests that 3D gels may provide a better medium for investigation of anti-cancer drugs than 2D monolayers, therefore allowing better understanding of cellular response and behavior in native like environments.

  7. Hierarchical random cellular neural networks for system-level brain-like signal processing.

    Science.gov (United States)

    Kozma, Robert; Puljic, Marko

    2013-09-01

    Sensory information processing and cognition in brains are modeled using dynamic systems theory. The brain's dynamic state is described by a trajectory evolving in a high-dimensional state space. We introduce a hierarchy of random cellular automata as the mathematical tools to describe the spatio-temporal dynamics of the cortex. The corresponding brain model is called neuropercolation which has distinct advantages compared to traditional models using differential equations, especially in describing spatio-temporal discontinuities in the form of phase transitions. Phase transitions demarcate singularities in brain operations at critical conditions, which are viewed as hallmarks of higher cognition and awareness experience. The introduced Monte-Carlo simulations obtained by parallel computing point to the importance of computer implementations using very large-scale integration (VLSI) and analog platforms.

  8. Cellular Automata Modelling of Photo-Induced Oxidation Processes in Molecularly Doped Polymers

    Directory of Open Access Journals (Sweden)

    David M. Goldie

    2016-11-01

    Full Text Available The possibility of employing cellular automata (CA to model photo-induced oxidation processes in molecularly doped polymers is explored. It is demonstrated that the oxidation dynamics generated using CA models exhibit stretched-exponential behavior. This dynamical characteristic is in general agreement with an alternative analysis conducted using standard rate equations provided the molecular doping levels are sufficiently low to prohibit the presence of safe-sites which are impenetrable to dissolved oxygen. The CA models therefore offer the advantage of exploring the effect of dopant agglomeration which is difficult to assess from standard rate equation solutions. The influence of UV-induced bleaching or darkening upon the resulting oxidation dynamics may also be easily incorporated into the CA models and these optical effects are investigated for various photo-oxidation product scenarios. Output from the CA models is evaluated for experimental photo-oxidation data obtained from a series of hydrazone-doped polymers.

  9. Altered Competitive Fitness, Antimicrobial Susceptibility, and Cellular Morphology in a Triclosan-Induced Small-Colony Variant of Staphylococcus aureus.

    Science.gov (United States)

    Forbes, Sarah; Latimer, Joe; Bazaid, Abdulrahman; McBain, Andrew J

    2015-08-01

    Staphylococcus aureus can produce small-colony variants (SCVs) that express various phenotypes. While their significance is unclear, SCV propagation may be influenced by relative fitness, antimicrobial susceptibility, and the underlying mechanism. We have investigated triclosan-induced generation of SCVs in six S. aureus strains, including methicillin-resistant S. aureus (MRSA). Parent strains (P0) were repeatedly passaged on concentration gradients of triclosan using a solid-state exposure system to generate P10. P10 was subsequently passaged without triclosan to generate X10. Susceptibility to triclosan and 7 antibiotics was assessed at all stages. For S. aureus ATCC 6538, SCVs were further characterized by determining microbicide susceptibility and competitive fitness. Cellular morphology was examined using electron microscopy, and protein expression was evaluated through proteomics. Triclosan susceptibility in all SCVs (which could be generated from 4/6 strains) was markedly decreased, while antibiotic susceptibility was significantly increased in the majority of cases. An SCV of S. aureus ATCC 6538 exhibited significantly increased susceptibility to all tested microbicides. Cross-wall formation was impaired in this bacterium, while expression of FabI, a target of triclosan, and IsaA, a lytic transglycosylase involved in cell division, was increased. The P10 SCV was 49% less fit than P0. In summary, triclosan exposure of S. aureus produced SCVs in 4/6 test bacteria, with decreased triclosan susceptibility but with generally increased antibiotic susceptibility. An SCV derived from S. aureus ATCC 6538 showed reduced competitive fitness, potentially due to impaired cell division. In this SCV, increased FabI expression could account for reduced triclosan susceptibility, while IsaA may be upregulated in response to cell division defects.

  10. Effects of Rhythmic and Melodic Alterations and Selected Musical Experiences on Rhythmic Processing.

    Science.gov (United States)

    Sink, Patricia E.

    1984-01-01

    Study showed that music listening habits and preferences and instrument training may affect ways an individual processes the multiple dimensions of rhythm. Apparent alterations in tempo, duration and pitch characteristics, rhythmic and melodic phrase patterning, and monotony may serve as organizers of rhythmic processing. (Author/RM)

  11. Floodplain geomorphic processes and environmental impacts of human alteration along coastal plain rivers, USA

    Science.gov (United States)

    Hupp, C.R.; Pierce, A.R.; Noe, G.B.

    2009-01-01

    Human alterations along stream channels and within catchments have affected fluvial geomorphic processes worldwide. Typically these alterations reduce the ecosystem services that functioning floodplains provide; in this paper we are concerned with the sediment and associated material trapping service. Similarly, these alterations may negatively impact the natural ecology of floodplains through reductions in suitable habitats, biodiversity, and nutrient cycling. Dams, stream channelization, and levee/canal construction are common human alterations along Coastal Plain fluvial systems. We use three case studies to illustrate these alterations and their impacts on floodplain geomorphic and ecological processes. They include: 1) dams along the lower Roanoke River, North Carolina, 2) stream channelization in west Tennessee, and 3) multiple impacts including canal and artificial levee construction in the central Atchafalaya Basin, Louisiana. Human alterations typically shift affected streams away from natural dynamic equilibrium where net sediment deposition is, approximately, in balance with net erosion. Identification and understanding of critical fluvial parameters (e.g., stream gradient, grain-size, and hydrography) and spatial and temporal sediment deposition/erosion process trajectories should facilitate management efforts to retain and/or regain important ecosystem services. ?? 2009, The Society of Wetland Scientists.

  12. Persistent Morbillivirus Infection Leads to Altered Cortactin Distribution in Histiocytic Sarcoma Cells with Decreased Cellular Migration Capacity

    Science.gov (United States)

    Pfankuche, Vanessa Maria; Sayed-Ahmed, Mohamed; Contioso, Vanessa Bono; Spitzbarth, Ingo; Rohn, Karl; Ulrich, Reiner; Deschl, Ulrich; Kalkuhl, Arno; Baumgärtner, Wolfgang; Puff, Christina

    2016-01-01

    Histiocytic sarcomas represent rare but fatal neoplasms in humans. Based on the absence of a commercially available human histiocytic sarcoma cell line the frequently affected dog displays a suitable translational model. Canine distemper virus, closely related to measles virus, is a highly promising candidate for oncolytic virotherapy. Therapeutic failures in patients are mostly associated with tumour invasion and metastasis often induced by misdirected cytoskeletal protein activities. Thus, the impact of persistent canine distemper virus infection on the cytoskeletal protein cortactin, which is frequently overexpressed in human cancers with poor prognosis, was investigated in vitro in a canine histiocytic sarcoma cell line (DH82). Though phagocytic activity, proliferation and apoptotic rate were unaltered, a significantly reduced migration activity compared to controls (6 hours and 1 day after seeding) accompanied by a decreased number of cortactin mRNA transcripts (1 day) was detected. Furthermore, persistently canine distemper virus infected DH82 cells showed a predominant diffuse intracytoplasmic cortactin distribution at 6 hours and 1 day compared to controls with a prominent membranous expression pattern (p ≤ 0.05). Summarized, persistent canine distemper virus infection induces reduced tumour cell migration associated with an altered intracellular cortactin distribution, indicating cytoskeletal changes as one of the major pathways of virus-associated inhibition of tumour spread. PMID:27911942

  13. Tribulus terrestris (Linn.) Attenuates Cellular Alterations Induced by Ischemia in H9c2 Cells Via Antioxidant Potential.

    Science.gov (United States)

    Reshma, P L; Lekshmi, V S; Sankar, Vandana; Raghu, K G

    2015-06-01

    Tribulus terrestris L. was evaluated for its cardioprotective property against myocardial ischemia in a cell line model. Initially, methanolic extract was prepared and subjected to sequential extraction with various solvents. The extract with high phenolic content (T. terrestris L. ethyl acetate extract-TTME) was further characterized for its chemical constituents and taken forward for evaluation against cardiac ischemia. HPLC analysis revealed the presence of phenolic compounds like caffeic acid (12.41 ± 0.22 mg g(-1)), chlorogenic acid (0.52 ± 0.06 mg g(-1)) and 4-hydroxybenzoic acid (0.60 ± 0.08 mg g(-1)). H9c2 cells were pretreated with TTME (10, 25, 50 and 100 µg/ml) for 24 h before the induction of ischemia. Then ischemia was induced by exposing cells to ischemia buffer, in a hypoxic chamber, maintained at 0.1% O2, 95% N2 and 5% CO2, for 1 h. A significant (p ≤ 0.05) increase in reactive oxygen species generation (56%), superoxide production (18%), loss of plasma membrane integrity, dissipation of transmembrane potential, permeability transition pore opening and apoptosis had been observed during ischemia. However, pretreatment with TTME was found to significantly (p ≤ 0.05) attenuate the alterations caused by ischemia. The overall results of this study partially reveal the scientific basis of the use of T. terrestris L. in the traditional system of medicine for heart diseases.

  14. Alterations in cellular pharmacokinetics and pharmacodynamics of elvitegravir in response to ethanol exposure in HIV-1 infected monocytic (U1) cells

    Science.gov (United States)

    Midde, Narasimha M.; Sinha, Namita; Lukka, Pradeep B.; Meibohm, Bernd

    2017-01-01

    Ethanol consumption is negatively associated with antiretroviral therapy (ART) adherence and general health in HIV positive individuals. Previously, we demonstrated ethanol-mediated alterations to metabolism of elvitegravir (EVG) in human liver microsomes. In the current study, we investigated ethanol influence on the pharmacokinetic and pharmacodynamic interactions of EVG in HIV infected monocytic (U1) cells. U1 cells were treated with 5 μM EVG, 2 μM Cobicistat (COBI), a booster drug, and 20 mM ethanol for up to 24 hours. EVG, HIV p24 levels, alterations in cytochrome P450 (CYP) 3A4, MRP1, and MDR1 protein expressions were measured. Presence of ethanol demonstrated a significant effect on the total exposures of both EVG and EVG in combination with COBI. Ethanol also increased the HIV replication despite the presence of drugs and this elevated HIV replication was reduced in the presence of MRP1 and MDR1 inhibitors. Consequently, a slight increase in EVG concentration was observed in the presence of MRP1 inhibitor but not with MDR1 inhibitor. Furthermore, CYP3A4, MRP1 and MDR1 protein levels were significantly induced in treatment groups which included ethanol compared to those with no treatment. In summary, these findings suggest that Ethanol reduces intra cellular EVG exposure by modifying drug metabolism and transporter protein expression. This study provides valuable evidence for further investigation of ethanol effects on the intracellular concentration of EVG in ex vivo or in vivo studies. PMID:28231276

  15. Multi-scale continuum modeling of biological processes: from molecular electro-diffusion to sub-cellular signaling transduction

    Science.gov (United States)

    Cheng, Y.; Kekenes-Huskey, P.; Hake, J. E.; Holst, M. J.; McCammon, J. A.; Michailova, A. P.

    2012-01-01

    This paper presents a brief review of multi-scale modeling at the molecular to cellular scale, with new results for heart muscle cells. A finite element-based simulation package (SMOL) was used to investigate the signaling transduction at molecular and sub-cellular scales (http://mccammon.ucsd.edu/smol/, http://FETK.org) by numerical solution of the time-dependent Smoluchowski equations and a reaction-diffusion system. At the molecular scale, SMOL has yielded experimentally validated estimates of the diffusion-limited association rates for the binding of acetylcholine to mouse acetylcholinesterase using crystallographic structural data. The predicted rate constants exhibit increasingly delayed steady-state times, with increasing ionic strength, and demonstrate the role of an enzyme's electrostatic potential in influencing ligand binding. At the sub-cellular scale, an extension of SMOL solves a nonlinear, reaction-diffusion system describing Ca2+ ligand buffering and diffusion in experimentally derived rodent ventricular myocyte geometries. Results reveal the important role of mobile and stationary Ca2+ buffers, including Ca2+ indicator dye. We found that alterations in Ca2+-binding and dissociation rates of troponin C (TnC) and total TnC concentration modulate sub-cellular Ca2+ signals. The model predicts that reduced off-rate in the whole troponin complex (TnC, TnI, TnT) versus reconstructed thin filaments (Tn, Tm, actin) alters cytosolic Ca2+ dynamics under control conditions or in disease-linked TnC mutations. The ultimate goal of these studies is to develop scalable methods and theories for the integration of molecular-scale information into simulations of cellular-scale systems.

  16. Manufacturing processes of cellular metals. Part II. Solid route, metals deposition, other processes; Procesos de fabricacion de metales celulares. Parte II: Via solida, deposicion de metales otros procesos

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, P.; Cruz, L. J.; Coleto, J.

    2009-07-01

    At the first part of this paper review a description about cellular metal processes by liquid route, was made. In this second part, solid processes and metals deposition are described. In similar way, the different kind of processes in each case are reviewed; making a short description about the main parameters involved and the advantages and drawbacks in each of them. (Author) 147 refs.

  17. Cellular cholesterol delivery, intracellular processing and utilization for biosynthesis of steroid hormones

    Directory of Open Access Journals (Sweden)

    Azhar Salman

    2010-06-01

    Full Text Available Abstract Steroid hormones regulate diverse physiological functions such as reproduction, blood salt balance, maintenance of secondary sexual characteristics, response to stress, neuronal function and various metabolic processes. They are synthesized from cholesterol mainly in the adrenal gland and gonads in response to tissue-specific tropic hormones. These steroidogenic tissues are unique in that they require cholesterol not only for membrane biogenesis, maintenance of membrane fluidity and cell signaling, but also as the starting material for the biosynthesis of steroid hormones. It is not surprising, then, that cells of steroidogenic tissues have evolved with multiple pathways to assure the constant supply of cholesterol needed to maintain optimum steroid synthesis. The cholesterol utilized for steroidogenesis is derived from a combination of sources: 1 de novo synthesis in the endoplasmic reticulum (ER; 2 the mobilization of cholesteryl esters (CEs stored in lipid droplets through cholesteryl ester hydrolase; 3 plasma lipoprotein-derived CEs obtained by either LDL receptor-mediated endocytic and/or SR-BI-mediated selective uptake; and 4 in some cultured cell systems from plasma membrane-associated free cholesterol. Here, we focus on recent insights into the molecules and cellular processes that mediate the uptake of plasma lipoprotein-derived cholesterol, events connected with the intracellular cholesterol processing and the role of crucial proteins that mediate cholesterol transport to mitochondria for its utilization for steroid hormone production. In particular, we discuss the structure and function of SR-BI, the importance of the selective cholesterol transport pathway in providing cholesterol substrate for steroid biosynthesis and the role of two key proteins, StAR and PBR/TSO in facilitating cholesterol delivery to inner mitochondrial membrane sites, where P450scc (CYP11A is localized and where the conversion of cholesterol to

  18. Rutin as a Mediator of Lipid Metabolism and Cellular Signaling Pathways Interactions in Fibroblasts Altered by UVA and UVB Radiation

    Science.gov (United States)

    Rybałtowska-Kawałko, Paula

    2017-01-01

    Background. Rutin is a natural nutraceutical that is a promising compound for the prevention of UV-induced metabolic changes in skin cells. The aim of this study was to examine the effects of rutin on redox and endocannabinoid systems, as well as proinflammatory and proapoptotic processes, in UV-irradiated fibroblasts. Methods. Fibroblasts exposed to UVA and UVB radiation were treated with rutin. The activities and levels of oxidants/antioxidants and endocannabinoid system components, as well as lipid, DNA, and protein oxidation products, and the proinflammatory and pro/antiapoptotic proteins expression were measured. Results. Rutin reduced UV-induced proinflammatory response and ROS generation and enhanced the activity/levels of antioxidants (SOD, GSH-Px, vitamin E, GSH, and Trx). Rutin also normalized UV-induced Nrf2 expression. Its biological activity prevented changes in the levels of the lipid mediators: MDA, 4-HNE, and endocannabinoids, as well as the endocannabinoid receptors CB1/2, VR1, and GPR55 expression. Furthermore, rutin prevented the protein modifications (tyrosine derivatives formation in particular) and decreased the levels of the proapoptotic markers—caspase-3 and cytochrome c. Conclusion. Rutin prevents UV-induced inflammation and redox imbalance at protein and transcriptional level which favors lipid, protein, and DNA protection. In consequence rutin regulates endocannabinoid system and apoptotic balance. PMID:28168010

  19. Rutin as a Mediator of Lipid Metabolism and Cellular Signaling Pathways Interactions in Fibroblasts Altered by UVA and UVB Radiation

    Directory of Open Access Journals (Sweden)

    Agnieszka Gęgotek

    2017-01-01

    Full Text Available Background. Rutin is a natural nutraceutical that is a promising compound for the prevention of UV-induced metabolic changes in skin cells. The aim of this study was to examine the effects of rutin on redox and endocannabinoid systems, as well as proinflammatory and proapoptotic processes, in UV-irradiated fibroblasts. Methods. Fibroblasts exposed to UVA and UVB radiation were treated with rutin. The activities and levels of oxidants/antioxidants and endocannabinoid system components, as well as lipid, DNA, and protein oxidation products, and the proinflammatory and pro/antiapoptotic proteins expression were measured. Results. Rutin reduced UV-induced proinflammatory response and ROS generation and enhanced the activity/levels of antioxidants (SOD, GSH-Px, vitamin E, GSH, and Trx. Rutin also normalized UV-induced Nrf2 expression. Its biological activity prevented changes in the levels of the lipid mediators: MDA, 4-HNE, and endocannabinoids, as well as the endocannabinoid receptors CB1/2, VR1, and GPR55 expression. Furthermore, rutin prevented the protein modifications (tyrosine derivatives formation in particular and decreased the levels of the proapoptotic markers—caspase-3 and cytochrome c. Conclusion. Rutin prevents UV-induced inflammation and redox imbalance at protein and transcriptional level which favors lipid, protein, and DNA protection. In consequence rutin regulates endocannabinoid system and apoptotic balance.

  20. Large-scale analysis of expression signatures reveals hidden links among diverse cellular processes

    Directory of Open Access Journals (Sweden)

    Ge Steven X

    2011-05-01

    Full Text Available Abstract Background Cells must respond to various perturbations using their limited available gene repertoires. In order to study how cells coordinate various responses, we conducted a comprehensive comparison of 1,186 gene expression signatures (gene lists associated with various genetic and chemical perturbations. Results We identified 7,419 statistically significant overlaps between various published gene lists. Most (80% of the overlaps can be represented by a highly connected network, a "molecular signature map," that highlights the correlation of various expression signatures. By dissecting this network, we identified sub-networks that define clusters of gene sets related to common biological processes (cell cycle, immune response, etc. Examination of these sub-networks has confirmed relationships among various pathways and also generated new hypotheses. For example, our result suggests that glutamine deficiency might suppress cellular growth by inhibiting the MYC pathway. Interestingly, we also observed 1,369 significant overlaps between a set of genes upregulated by factor X and a set of genes downregulated by factor Y, suggesting a repressive interaction between X and Y factors. Conclusions Our results suggest that molecular-level responses to diverse chemical and genetic perturbations are heavily interconnected in a modular fashion. Also, shared molecular pathways can be identified by comparing newly defined gene expression signatures with databases of previously published gene expression signatures.

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

    Science.gov (United States)

    2008-01-01

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

  2. Near infrared probes for biochemical, cellular, and whole animal analysis of disease processes

    Science.gov (United States)

    Kovar, Joy; Boveia, Vince; Chen, Huaxian; Peng, Xinzhan; Skopp, Rose; Little, Garrick; Draney, Dan; Olive, D. M.

    2009-02-01

    The study of disease processes requires a number of tools for detection of proteins and biomarkers in cell and animal based assays. Near infrared (NIR) technologies offer the advantage of high signal without interference from background producing factors such as tissues, blood, or plastics. NIR fluorescence quenching biochemical assays employing a novel NIR quencher are homogeneous and sensitive. NIR-based immunocytochemical assays offer a means of quantitatively evaluating cell signaling pathways. The technology can be extended to the development of targeted molecular imaging agents for disease analysis in animal models. We describe here model assays for each of these categories. A fluorescence quenching caspase-3 assay was developed employing a novel, broadly applicable quencher dye suitable for use with both visible and NIR dye chemistries. An NIR cell based assay is described for assessment of phosphorylation of p53 in response to a cellular stimulus. Finally, we describe the development and application of a targeted NIR optical imaging agent for monitoring tumor growth in whole animals. The NIR biochemical and cell based assays are robust with Z' factors greater than 0.7. The use of an IRDye (R)800CW-labeled cyclic RGD peptide is presented as a model for development and application of targeted imaging agents. NIR technologies are compatible with the complete spectrum of assay needs for disease analysis and therapeutic development.

  3. Selected papers from the Fourth Annual q-bio Conference on Cellular Information Processing.

    Science.gov (United States)

    Nemenman, Ilya; Faeder, James R; Hlavacek, William S; Jiang, Yi; Wall, Michael E; Zilman, Anton

    2011-10-01

    This special issue consists of 11 original papers that elaborate on work presented at the Fourth Annual q-bio Conference on Cellular Information Processing, which was held on the campus of St John's College in Santa Fe, New Mexico, USA, 11-14 August 2010. Now in its fourth year, the q-bio conference has changed considerably over time. It is now well established and a major event in systems biology. The 2010 conference saw attendees from all continents (except Antarctica!) sharing novel results and participating in lively discussions at both the oral and poster sessions. The conference was oversubscribed and grew to 27 contributed talks, 16 poster spotlights and 137 contributed posters. We deliberately decreased the number of invited speakers to 21 to leave more space for contributed presentations, and the attendee feedback confirmed that the choice was a success. Although the q-bio conference has grown and matured, it has remained true to the original goal of being an intimate and dynamic event that brings together modeling, theory and quantitative experimentation for the study of cell regulation and information processing. Funded in part by a grant from NIGMS and by DOE funds through the Los Alamos National Laboratory Directed Research and Development program, the conference has continued to exhibit youth and vigor by attracting (and partially supporting) over 100 undergraduate, graduate and postdoctoral researchers. The associated q-bio summer school, which precedes the conference each year, further emphasizes the development of junior scientists and makes q-bio a singular event in its impact on the future of quantitative biology. In addition to an increased international presence, the conference has notably diversified its demographic representation within the USA, including increased participation from the southeastern corner of the country. One big change in the conference this year is our new publication partner, Physical Biology. Although we are very

  4. Biochemical aspects of overtraining in endurance sports : the metabolism alteration process syndrome.

    Science.gov (United States)

    Petibois, Cyril; Cazorla, Georges; Poortmans, Jacques-Rémi; Déléris, Gérard

    2003-01-01

    Recent studies have shown that endurance overtraining could result from successive and cumulative alterations in metabolism, which become chronic during training. The onset of this process is a biochemical alteration in carbohydrate (saccharide) metabolism. During endurance exercises, the amount of saccharide chains from two blood glycoproteins (alpha(2)-macroglobulin and alpha(1)-acid glycoprotein) was found to have decreased, i.e. concentrations of these proteins remained unchanged but their quality changed. These saccharide chains were probably used for burning liver glycogen stores during exercise. This step was followed by alterations in lipid metabolism. The most relevant aspect of this step was that the mean chain length of blood fatty acids decreased, i.e. the same amount of fatty acids were found within the blood, but overtrained individuals presented shorter fatty acids than well-trained individuals. This suggests that alterations appeared in the liver synthesis of long-chain fatty acids or that higher peroxidation of blood lipoparticles occurred. For the final step of this overtraining process, it was found that these dysfunctions in carbohydrate/lipid metabolism led to the higher use of amino acids, which probably resulted from protein catabolism. The evolution of three protein concentrations (alpha(1)-acid glycoprotein, alpha(2)-macroglobulin and IgG(3)) correlated with this amino acid concentration increase, suggesting a specific catabolism of these proteins. At this time only, overtraining was clinically diagnosed through conventional symptoms. Therefore, this process described successive alterations in exercise metabolism that shifted from the main energetic stores of exercise (carbohydrates and lipids) towards molecular pools (proteins) normally not substantially used for the energetic supply of skeletal muscles. Now, a general biochemical model of the overtraining process may be proposed which includes most of the previously identified metabolic

  5. Altered BOLD response during inhibitory and error processing in adolescents with anorexia nervosa.

    Directory of Open Access Journals (Sweden)

    Christina Wierenga

    Full Text Available BACKGROUND: Individuals with anorexia nervosa (AN are often cognitively rigid and behaviorally over-controlled. We previously showed that adult females recovered from AN relative to healthy comparison females had less prefrontal activation during an inhibition task, which suggested a functional brain correlate of altered inhibitory processing in individuals recovered from AN. However, the degree to which these functional brain alterations are related to disease state and whether error processing is altered in AN individuals is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In the current study, ill adolescent AN females (n = 11 and matched healthy comparison adolescents (CA with no history of an eating disorder (n = 12 performed a validated stop signal task (SST during functional magnetic resonance imaging (fMRI to explore differences in error and inhibitory processing. The groups did not differ on sociodemographic variables or on SST performance. During inhibitory processing, a significant group x difficulty (hard, easy interaction was detected in the right dorsal anterior cingulate cortex (ACC, right middle frontal gyrus (MFG, and left posterior cingulate cortex (PCC, which was characterized by less activation in AN compared to CA participants during hard trials. During error processing, a significant group x accuracy (successful inhibit, failed inhibit interaction in bilateral MFG and right PCC was observed, which was characterized by less activation in AN compared to CA participants during error (i.e., failed inhibit trials. CONCLUSION/SIGNIFICANCE: Consistent with our prior findings in recovered AN, ill AN adolescents, relative to CA, showed less inhibition-related activation within the dorsal ACC, MFG and PCC as inhibitory demand increased. In addition, ill AN adolescents, relative to CA, also showed reduced activation to errors in the bilateral MFG and left PCC. These findings suggest that altered prefrontal and cingulate activation during

  6. Altered BOLD Response during Inhibitory and Error Processing in Adolescents with Anorexia Nervosa

    Science.gov (United States)

    Wierenga, Christina; Bischoff-Grethe, Amanda; Melrose, A. James; Grenesko-Stevens, Emily; Irvine, Zoë; Wagner, Angela; Simmons, Alan; Matthews, Scott; Yau, Wai-Ying Wendy; Fennema-Notestine, Christine; Kaye, Walter H.

    2014-01-01

    Background Individuals with anorexia nervosa (AN) are often cognitively rigid and behaviorally over-controlled. We previously showed that adult females recovered from AN relative to healthy comparison females had less prefrontal activation during an inhibition task, which suggested a functional brain correlate of altered inhibitory processing in individuals recovered from AN. However, the degree to which these functional brain alterations are related to disease state and whether error processing is altered in AN individuals is unknown. Methodology/Principal Findings In the current study, ill adolescent AN females (n = 11) and matched healthy comparison adolescents (CA) with no history of an eating disorder (n = 12) performed a validated stop signal task (SST) during functional magnetic resonance imaging (fMRI) to explore differences in error and inhibitory processing. The groups did not differ on sociodemographic variables or on SST performance. During inhibitory processing, a significant group x difficulty (hard, easy) interaction was detected in the right dorsal anterior cingulate cortex (ACC), right middle frontal gyrus (MFG), and left posterior cingulate cortex (PCC), which was characterized by less activation in AN compared to CA participants during hard trials. During error processing, a significant group x accuracy (successful inhibit, failed inhibit) interaction in bilateral MFG and right PCC was observed, which was characterized by less activation in AN compared to CA participants during error (i.e., failed inhibit) trials. Conclusion/Significance Consistent with our prior findings in recovered AN, ill AN adolescents, relative to CA, showed less inhibition-related activation within the dorsal ACC, MFG and PCC as inhibitory demand increased. In addition, ill AN adolescents, relative to CA, also showed reduced activation to errors in the bilateral MFG and left PCC. These findings suggest that altered prefrontal and cingulate activation during

  7. Chronic loss of noradrenergic tone produces β-arrestin2-mediated cocaine hypersensitivity and alters cellular D2 responses in the nucleus accumbens.

    Science.gov (United States)

    Gaval-Cruz, Meriem; Goertz, Richard B; Puttick, Daniel J; Bowles, Dawn E; Meyer, Rebecca C; Hall, Randy A; Ko, Daijin; Paladini, Carlos A; Weinshenker, David

    2016-01-01

    Cocaine blocks plasma membrane monoamine transporters and increases extracellular levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT). The addictive properties of cocaine are mediated primarily by DA, while NE and 5-HT play modulatory roles. Chronic inhibition of dopamine β-hydroxylase (DBH), which converts DA to NE, increases the aversive effects of cocaine and reduces cocaine use in humans, and produces behavioral hypersensitivity to cocaine and D2 agonism in rodents, but the underlying mechanism is unknown. We found a decrease in β-arrestin2 (βArr2) in the nucleus accumbens (NAc) following chronic genetic or pharmacological DBH inhibition, and overexpression of βArr2 in the NAc normalized cocaine-induced locomotion in DBH knockout (Dbh -/-) mice. The D2/3 agonist quinpirole decreased excitability in NAc medium spiny neurons (MSNs) from control, but not Dbh -/- animals, where instead there was a trend for an excitatory effect. The Gαi inhibitor NF023 abolished the quinpirole-induced decrease in excitability in control MSNs, but had no effect in Dbh -/- MSNs, whereas the Gαs inhibitor NF449 restored the ability of quinpirole to decrease excitability in Dbh -/- MSNs, but had no effect in control MSNs. These results suggest that chronic loss of noradrenergic tone alters behavioral responses to cocaine via decreases in βArr2 and cellular responses to D2/D3 activation, potentially via changes in D2-like receptor G-protein coupling in NAc MSNs.

  8. Сalculation theory for shrinkage stresses in cellular concrete wall panels in carbonation processes with account of creep

    Directory of Open Access Journals (Sweden)

    Chepurnenko Anton Sergeevich

    2016-12-01

    Full Text Available The task of comprehensive analysis presented in this article is a development of theory of calculation of shrinkage stresses in cellular concrete wall panels; such stresses occur due to carbonation of concrete because of the creep of material. Analytical dependences characterizing the influence of carbonation on the modulus of elasticity, shrinkage and creep of autoclaved cellular concrete, as well as the regularity of variation of carbonation degree as per thickness of the wall panels depending on time, were obtained. The proposed theory of calculation of shrinkage stresses in cellular concrete wall panels, with account of concrete creep, makes it possible to predict the influence of carbonation processes on crack resistance thereof, and thus to develop measures of technological and structural nature, in order to improve their operational reliability and durability.

  9. Pump Linewidth Requirements for Processing Dispersion-Altered DQPSK Signals using FWM

    CERN Document Server

    Dúill, Séan Ó; Barry, Liam P

    2015-01-01

    We report on a potentially deleterious issue regarding the four-wave mixing based processing of dispersion-altered signals. We estimate the baudrate-dependent pump linewidth tolerances by calculating the extra optical signal to noise ratio (OSNR) penalty with respect to the propagation distance. We find that the issue is not important for 10 Gbaud differential quadrature phase shift keying (DQPSK) signals, though for 28 Gbaud (and 56 Gbaud) DQPSK signals we find that the pump linewidth requirements to implement FWM based optical signal processing needs to be in the sub-MHz range in order to avoid excessive OSNR penalties for the case of dispersion-altered signals. These results are pertinent for systems employing FWM, which could be all-optical wavelength converters for packet switching or mid-span spectral inversion techniques.

  10. Induction and reversion process of molecular and cytological alterations after highly irradiated food ingestion in mice

    Energy Technology Data Exchange (ETDEWEB)

    Rojo M, M.I. (Comision Chilena de Energia Nuclear, Santiago. Dept. de Aplicaciones de los Isotopos y Radiaciones); Fernandez C, M. (Chile Univ., Santiago. Dept. de Fisica)

    1984-04-01

    The molecular and cytological alterations induced in a mammal (Mus musculus) fed ad libitum with a balanced pellet diet irradiated with 50 KGy gamma radiation from weaning, for different periods, are analyzed. The transient chromosomal changes that recall tumor-like phenomena could be the expression of the damage and repair processes induced by changed molecules present in irradiated food. The reversible alterations of DNA structure and cytoplasmatic soluble proteins observed in mice fed with irradiated pellet diet could be interpreted as a result of the enhancement of the repair processes which could also explain the significant increase of the radioresistance of DNA found at 200 days after irradiated food ingestion. Finally, our results would suggest an induction of a pseudo-neoplasia due to a prolongated and exclusive ingestion of food irradiated with sterilizing gamma dose. Moreover, the maintenance of the irradiated diet induce the reversion of the observed phenomena by an eventual activation of the repair mechanisms.

  11. Influence of hydrothermal alteration on phreatic eruption processes in Solfatara (Campi Flegrei)

    Science.gov (United States)

    Mayer, K.; Scheu, B.; Montanaro, C.; Isaia, R.; Dingwell, D. B.

    2014-12-01

    The strong hydrothermal activity exhibited at Campi Flegrei by the Solfatara and Pisciarelli fumaroles points to a significant risk for phreatic eruptions in this densely populated area. Phreatic eruptions, triggered by various processes are hardly predictable in occurrence time and size. Despite their hazard potential, these eruptions, as well as the influence of hydrothermal alteration on their likelihood, magnitude and style, have so far been largely overlooked in experimental volcanology. The physical properties and the mechanical behavior of volcanic rocks are highly dependent on their original magmatic microstructure and on any eventual alteration of those microstructures due to hydrothermal reactions. We have therefore investigated the potential effects of hydrothermal alteration on rock microstructure and, as a consequence, on fragmentation dynamics. Rock samples from the vicinity of the Solfatara fumaroles have been characterized 1) geochemically (X-ray fluorescence, X-ray diffraction), 2) physically (density, porosity, permeability and elastic wave velocity) and 3) mechanically (uniaxial compressive strength, tensile strength). We have investigated the effects of hydrothermal alteration on fragmentation processes using a shock-tube apparatus, operating with Argon gas, water vapor and superheated water at temperatures up to 400°C and maximum pressures of 20 MPa. The three different energy sources within the pores initiating fragmentation, have been investigated: overpressure by 1) Argon gas; or 2) water vapor and due to 3) steam flashing of water. Fragmentation speed, fragmentation efficiency and fragmented particle ejection velocity were measured. Our results indicate, that steam flashing provides the highest energy - resulting in increased particle ejection velocity and higher fragmentation efficiency. Based on our results, we aim to constrain the influence of hydrothermal alteration on the dynamics of phreatic explosions and the effect on the amount of

  12. Intra- and Extra-Cellular Events Related to Altered Glycosylation of MUC1 Promote Chronic Inflammation, Tumor Progression, Invasion, and Metastasis

    Directory of Open Access Journals (Sweden)

    Sandra Cascio

    2016-10-01

    Full Text Available Altered glycosylation of mucin 1 (MUC1 on tumor cells compared to normal epithelial cells was previously identified as an important antigenic modification recognized by the immune system in the process of tumor immunosurveillance. This tumor form of MUC1 is considered a viable target for cancer immunotherapy. The importance of altered MUC1 glycosylation extends also to its role as a promoter of chronic inflammatory conditions that lead to malignant transformation and cancer progression. We review here what is known about the role of specific cancer-associated glycans on MUC1 in protein-protein interactions and intracellular signaling in cancer cells and in their adhesion to each other and the tumor stroma. The tumor form of MUC1 also creates a different landscape of inflammatory cells in the tumor microenvironment by controlling the recruitment of inflammatory cells, establishing specific interactions with dendritic cells (DCs and macrophages, and facilitating tumor escape from the immune system. Through multiple types of short glycans simultaneously present in tumors, MUC1 acquires multiple oncogenic properties that control tumor development, progression, and metastasis at different steps of the process of carcinogenesis.

  13. Cellular Automata as a learning process in Architecture and Urban design

    DEFF Research Database (Denmark)

    Jensen, Mads Brath; Foged, Isak Worre

    2014-01-01

    . An architectural methodological response to this situation is presented through the development of a conceptual computational design system that allows these dynamics to unfold and to be observed for architectural design decision taking. Reflecting on the development and implementation of a cellular automata based...

  14. Alteration of bioelectrically-controlled processes in the embryo: a teratogenic mechanism for anticonvulsants.

    Science.gov (United States)

    Hernández-Díaz, Sonia; Levin, Michael

    2014-08-01

    Maternal use of anticonvulsants during the first trimester of pregnancy has been associated with an elevated risk of major congenital malformations in the offspring. Whether the increased risk is caused by the specific pharmacological mechanisms of certain anticonvulsants, the underlying epilepsy, or common genetic or environmental risk factors shared by epilepsy and malformations has been controversial. We hypothesize that anticonvulsant therapies during pregnancy that attain more successful inhibition of neurotransmission might lead to both better seizure control in the mother and stronger alteration of bioelectrically-controlled processes in the embryo that result in structural malformations. We propose that development of pharmaceuticals that do not alter cell resting transmembrane voltage levels could result in safer drugs.

  15. TGF-β and iron differently alter HBV replication in human hepatocytes through TGF-β/BMP signaling and cellular microRNA expression.

    Directory of Open Access Journals (Sweden)

    Sun O Park

    Full Text Available The nature of host-virus interactions in hepatitis B virus infection is incompletely understood. Since soluble factors, e.g., cytokines and metals, may exacerbate liver injury in chronic hepatitis, we considered that defining the effects of receptor-mediated signaling upon viral replication will be significant. Consequently, we studied effects of iron or TGF-β-induced TGF-β/BMP signaling in the HepG2 2.2.15 cell model of hepatitis B virus replication. We found iron and TGF-β increased hepcidin mRNA expression or TGF-β receptor kinase activity, respectively, which indicated that 2.2.15 cells responded appropriately to these substances. However, iron increased but TGF-β decreased hepatitis B virus mRNA and DNA expression. TGF-β induced expression at the mRNA level of multiple TGF-β/BMP pathway genes. This change was not observed in iron-treated cells. On the other hand, presence of SMAD proteins in iron or TGF-β-treated cells, including of SMAD4, did confirm convergence of TGF-β/BMP signaling pathways under these conditions. Since transcription factors in TGF-β/BMP signaling pathways could not have directly targeted hepatitis B virus itself, we studied whether iron or TGF-β exerted their effects through alternative mechanisms, such as by involvement of antiviral cellular microRNAs. We discovered cellular microRNA expression profiles were significantly different in iron or TGF-β-treated cells compared with untreated control cells. In many cases, exposure to iron or TGF-β changed microRNA expression in opposite directions. Introduction in cells of sequences representing such differentially expressed microRNAs, e.g., hsa-miR-125a-5p and -151-5p, even reproduced effects on virus replication of iron- or TGF-β. We surmised that TGF-β/BMP pathway members, i.e., SMADs, likely governed iron or TGF-β-induced microRNA expression. Iron may have mediated Drosha/DGCR8/heme-mediated processing of microRNAs. In turn, cellular microRNAs regulated

  16. Alterations of monetary reward and punishment processing in chronic cannabis users: an FMRI study.

    Science.gov (United States)

    Enzi, Björn; Lissek, Silke; Edel, Marc-Andreas; Tegenthoff, Martin; Nicolas, Volkmar; Scherbaum, Norbert; Juckel, Georg; Roser, Patrik

    2015-01-01

    Alterations in reward and punishment processing have been reported in adults suffering from long-term cannabis use. However, previous findings regarding the chronic effects of cannabis on reward and punishment processing have been inconsistent. In the present study, we used functional magnetic resonance imaging (fMRI) to reveal the neural correlates of reward and punishment processing in long-term cannabis users (n = 15) and in healthy control subjects (n = 15) with no history of drug abuse. For this purpose, we used the well-established Monetary Incentive Delay (MID) task, a reliable experimental paradigm that allows the differentiation between anticipatory and consummatory aspects of reward and punishment processing. Regarding the gain anticipation period, no significant group differences were observed. In the left caudate and the left inferior frontal gyrus, cannabis users were - in contrast to healthy controls - not able to differentiate between the conditions feedback of reward and control. In addition, cannabis users showed stronger activations in the left caudate and the bilateral inferior frontal gyrus following feedback of no punishment as compared to healthy controls. We interpreted these deficits in dorsal striatal functioning as altered stimulus-reward or action-contingent learning in cannabis users. In addition, the enhanced lateral prefrontal activation in cannabis users that is related to non-punishing feedback may reflect a deficit in emotion regulation or cognitive reappraisal in these subjects.

  17. Modulation of ROS levels in fibroblasts by altering mitochondria regulates the process of wound healing.

    Science.gov (United States)

    Janda, Jaroslav; Nfonsam, Valentine; Calienes, Fernanda; Sligh, James E; Jandova, Jana

    2016-05-01

    Mitochondria are the major source of reactive oxygen species (ROS) in fibroblasts which are thought to be crucial regulators of wound healing with a potential to affect the expression of nuclear genes involved in this process. ROS generated by mitochondria are involved in all stages of tissue repair process but the regulation of ROS-generating system in fibroblasts still remains poorly understood. The purpose of this study was to better understand molecular mechanisms of how the regulation of ROS levels generated by mitochondria may influence the process of wound repair. Cybrid model system of mtDNA variations was used to study the functional consequences of altered ROS levels on wound healing responses in a uniform nuclear background of cultured ρ(0) fibroblasts. Mitochondrial ROS in cybrids were modulated by antioxidants that quench ROS to examine their ability to close the wound. Real-time PCR arrays were used to investigate whether ROS generated by specific mtDNA variants have the ability to alter expression of some key nuclear-encoded genes central to the wound healing response and oxidative stress. Our data suggest levels of mitochondrial ROS affect expression of some nuclear encoded genes central to wound healing response and oxidative stress and modulation of mitochondrial ROS by antioxidants positively affects in vitro process of wound closure. Thus, regulation of mitochondrial ROS-generating system in fibroblasts can be used as effective natural redox-based strategy to help treat non-healing wounds.

  18. A new model for anaerobic processes of up-flow anaerobic sludge blanket reactors based on cellular automata

    DEFF Research Database (Denmark)

    Skiadas, Ioannis V.; Ahring, Birgitte Kiær

    2002-01-01

    characteristics and lead to different reactor behaviour. A dynamic mathematical model has been developed for the anaerobic digestion of a glucose based synthetic wastewater in UASB reactors. Cellular automata (CA) theory has been applied to simulate the granule development process. The model takes...... into consideration that granule diameter and granule microbial composition are functions of the reactor operational parameters and is capable of predicting the UASB performance and the layer structure of the granules....

  19. Macro-cellular silica foams: synthesis during the natural creaming process of an oil-in-water emulsion.

    Science.gov (United States)

    Sen, T; Tiddy, G J T; Casci, J L; Anderson, M W

    2003-09-01

    The room-temperature synthesis of a macro-mesoporous silica material during the natural creaming process of an oil-in-water emulsion is reported. The material has 3-dimensional interconnected macropores with a strut-like structure similar to meso-cellular silica foams with mesoporous walls of worm-hole structure. The material has very high surface area (approximately 800 m2 g(-1)) with narrow mesopore size distribution.

  20. Mindfulness meditation associated with alterations in bottom-up processing: psychophysiological evidence for reduced reactivity.

    Science.gov (United States)

    van den Hurk, Paul A M; Janssen, Barbara H; Giommi, Fabio; Barendregt, Henk P; Gielen, Stan C

    2010-11-01

    Mental training by meditation has been related to changes in high-level cognitive functions that involve top-down processing. The aim of this study was to investigate whether the practice of meditation is also related to alterations in low-level, bottom-up processing. Therefore, intersensory facilitation (IF) effects in a group of mindfulness meditators (MM) were compared to IF effects in an age- and gender-matched control group. Smaller and even absent IF effects were found in the MM group, which suggests that changes in bottom-up processing are associated with MM. Furthermore, reduced interference of a visual warning stimulus with the IF effects was found, which suggests an improved allocation of attentional resources in mindfulness meditators, even across modalities.

  1. Effects of a hypnotically altered state of consciousness on intensification of semantic processing.

    Science.gov (United States)

    Szendi, István; Kovács, Zoltán Ambrus; Szekeres, György; Galsi, Gabriella; Boda, Krisztina; Boncz, István; Janka, Zoltán

    2009-10-01

    In a study of the linguistic processes involved in hypnosis, 22 volunteer medical students performed semantic and phonologic fluency tasks and then associative priming tests with 2 delay-lengths in waking alert and hypnotic conditions as well. The participants performed better during semantic than phonological fluency tests in alert and also in hypnotic states, and this difference was significantly greater in hypnosis. The increased semantic performance in hypnosis was accompanied by a decrease of the rule-offending errors. Significant semantic priming effects were detected in both states of consciousness in direct and indirect relations as well as in the automatic, intralexical level, and also when the extralexical control processes were activated. Overall, the results appear to show that the hypnotically altered state of consciousness produces significantly better performance in semantic information processing than can be elicited in alert waking conditions.

  2. Carbon dioxide enrichment alleviates heat stress by improving cellular redox homeostasis through an ABA-independent process in tomato plants.

    Science.gov (United States)

    Li, X; Ahammed, G J; Zhang, Y Q; Zhang, G Q; Sun, Z H; Zhou, J; Zhou, Y H; Xia, X J; Yu, J Q; Shi, K

    2015-01-01

    Plant responses to elevated CO₂ and high temperature are critically regulated through a complex network of phytohormones and redox homeostasis. However, the involvement of abscisic acid (ABA) in plant adaptation to heat stress under elevated CO₂ conditions has not been thoroughly studied. This study investigated the interactive effects of elevated CO₂ (800 μmol·mol(-1) ) and heat stress (42 °C for 24 h) on the endogenous level of ABA and the cellular redox state of two genotypes of tomato with different ABA biosynthesis capacities. Heat stress significantly decreased maximum photochemical efficiency of PSII (Fv/Fm) and leaf water potential, but also increased levels of malondialdehyde (MDA) and electrolyte leakage (EL) in both genotypes. Heat-induced damage was more severe in the ABA-deficient mutant notabilis (not) than in its parental cultivar Ailsa Craig (Ailsa), suggesting that a certain level of endogenous ABA is required to minimise the heat-induced oxidative damage to the photosynthetic apparatus. Irrespective of genotype, the enrichment of CO₂ remarkably stimulated Fv/Fm, MDA and EL in heat-stressed plants towards enhanced tolerance. In addition, elevated CO₂ significantly strengthened the antioxidant capacity of heat-stressed tomato seedlings towards a reduced cellular redox state for a prolonged period, thereby mitigating oxidative stress. However, elevated CO₂ and heat stress did not alter the endogenous level of ABA or the expression of its biosynthetic gene NCED2 in either genotype, indicating that ABA is not involved in elevated CO₂ -induced heat stress alleviation. The results of this study suggest that elevated CO₂ alleviated heat stress through efficient regulation of the cellular redox poise in an ABA-independent manner in tomato plants.

  3. Distinct roles of specific fatty acids in cellular processes: implications for interpreting and reporting experiments

    OpenAIRE

    Watt, Matthew J.; Hoy, Andrew J.; Muoio, Deborah M.; Coleman, Rosalind A.

    2011-01-01

    Plasma contains a variety of long-chain fatty acids (FAs), such that about 35% are saturated and 65% are unsaturated. There are countless examples that show how different FAs impart specific and unique effects, or even opposing actions, on cellular function. Despite these differing effects, palmitate (C16:0) is regularly used to represent “FAs” in cell based experiments. Although palmitate can be useful to induce and study stress effects in cultured cells, these effects in isolation are not p...

  4. Evolution and regulation of cellular periodic processes: a role for paralogues

    DEFF Research Database (Denmark)

    Trachana, Kalliopi; Jensen, Lars Juhl; Bork, Peer

    2010-01-01

    paralogues. Thus, diverged temporal expression of paralogues seems to facilitate cellular orchestration under different periodic stimuli. Lineage-specific functional repertoires of periodic-associated paralogues imply that this mode of regulation might have evolved independently in several organisms....... performed the first systematic comparison in three organisms (Homo sapiens, Arabidopsis thaliana and Saccharomyces cerevisiae) by using public microarray data. We observed that although diurnal-regulated and ultradian-regulated genes are not generally cell-cycle-regulated, they tend to have cell-cycle-regulated...

  5. Altered processing of sweet taste in the brain of diet soda drinkers.

    Science.gov (United States)

    Green, Erin; Murphy, Claire

    2012-11-05

    Artificially sweetened beverage consumption has been linked to obesity, and it has been hypothesized that considerable exposure to nonnutritive sweeteners may be associated with impaired energy regulation. The reward system plays an integral role in modulating energy intake, but little is known about whether habitual use of artificial sweetener (i.e., diet soda consumption) may be related to altered reward processing of sweet taste in the brain. To investigate this, we examined fMRI response after a 12-hour fast to sucrose (a nutritive sweetener) and saccharin (a nonnutritive sweetener) during hedonic evaluation in young adult diet soda drinkers and non-diet soda drinkers. Diet soda drinkers demonstrated greater activation to sweet taste in the dopaminergic midbrain (including ventral tegmental area) and right amygdala. Saccharin elicited a greater response in the right orbitofrontal cortex (Brodmann Area 47) relative to sucrose in non-diet soda drinkers. There was no difference in fMRI response to the nutritive or nonnutritive sweetener for diet soda drinkers. Within the diet soda drinkers, fMRI activation of the right caudate head in response to saccharin was negatively associated with the amount of diet sodas consumed per week; individuals who consumed a greater number of diet sodas had reduced caudate head activation. These findings suggest that there are alterations in reward processing of sweet taste in individuals who regularly consume diet soda, and this is associated with the degree of consumption. These findings may provide some insight into the link between diet soda consumption and obesity.

  6. 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

  7. Differentiation of cellular processes involved in the induction and maintenance of stimulated neutrophil adherence.

    Science.gov (United States)

    English, D; Gabig, T G

    1986-05-01

    Neutrophil adherence stimulated by phorbol myristate acetate (PMA) was investigated by quantitating the attachment of 51Cr-labeled neutrophils to plastic surfaces and to the endothelium of umbilical veins mounted in compartmentalized Lucite chambers. PMA-induced adherence could be functionally separated into an induction phase requiring cellular metabolism and a Mg++ dependent maintenance phase that was independent of cellular metabolism. Thus, metabolic inhibitors (N-ethylmaleimide, 2-deoxyglucose) blocked adherence when added to neutrophils prior to PMA, but did not cause detachment of cells adhering as a consequence of prior exposure to PMA. PMA failed to induce adherence of neutrophils incubated at low (0.4 degree C) temperature, but temperature reduction, even for prolonged periods, did not cause detachment of adherent cells. Thus, the attractive forces that mediate stimulated adherence persist independently of any sustained metabolic response to the inducing stimulus. However, removal of Mg++ from the media above adherent cells resulted in immediate detachment, indicating that the cation was required for the persistent expression or maintenance of the attractive forces involved. The extent of stimulated adherence correlated well with the extent of degranulation when rates were varied by limiting the incubation time or stimulus concentration. This correlation was not absolute; in the absence of Mg++, PMA induced degranulation normally but failed to enhance adherence. To explain these findings, we investigated the possibility that PMA-stimulated adherence was maintained by Mg++-dependent cellular adherence molecules released during exocytosis. Supernatants of stimulated neutrophils were devoid of adherence-promoting activity, and only weak activity was recovered in supernatants of mechanically disrupted neutrophils. PMA effectively stimulated the tight adherence of degranulated neutrophil cytoplasts to plastic surfaces and did so in the absence of stimulated

  8. Beta Cell Formation in vivo Through Cellular Networking, Integration and Processing (CNIP) in Wild Type Adult Mice.

    Science.gov (United States)

    Doiron, Bruno; Hu, Wenchao; DeFronzo, Ralph A

    2016-01-01

    Insulin replacement therapy is essential in type 1 diabetic individuals and is required in ~40- 50% of type 2 diabetics during their lifetime. Prior attempts at beta cell regeneration have relied upon pancreatic injury to induce beta cell proliferation, dedifferentiation and activation of the embryonic pathway, or stem cell replacement. We report an alternative method to transform adult non-stem (somatic) cells into pancreatic beta cells. The Cellular Networking, Integration and Processing (CNIP) approach targets cellular mechanisms involved in pancreatic function in the organ's adult state and utilizes a synergistic mechanism that integrates three important levels of cellular regulation to induce beta cell formation: (i) glucose metabolism, (ii) membrane receptor function, and (iii) gene transcription. The aim of the present study was to induce pancreatic beta cell formation in vivo in adult animals without stem cells and without dedifferentiating cells to recapitulate the embryonic pathway as previously published (1-3). Our results employing CNIP demonstrate that: (i) insulin secreting cells can be generated in adult pancreatic tissue in vivo and circumvent the problem of generating endocrine (glucagon and somatostatin) cells that exert deleterious effects on glucose homeostasis, and (ii) longterm normalization of glucose tolerance and insulin secretion can be achieved in a wild type diabetic mouse model. The CNIP cocktail has the potential to be used as a preventative or therapeutic treatment or cure for both type 1 and type 2 diabetes.

  9. 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...

  10. Cellular scanning strategy for selective laser melting: Generating reliable, optimized scanning paths and processing parameters

    DEFF Research Database (Denmark)

    Mohanty, Sankhya; Hattel, Jesper Henri

    2015-01-01

    Selective laser melting is yet to become a standardized industrial manufacturing technique. The process continues to suffer from defects such as distortions, residual stresses, localized deformations and warpage caused primarily due to the localized heating, rapid cooling and high temperature...... gradients that occur during the process. While process monitoring and control of selective laser melting is an active area of research, establishing the reliability and robustness of the process still remains a challenge.In this paper, a methodology for generating reliable, optimized scanning paths...... and process parameters for selective laser melting of a standard sample is introduced. The processing of the sample is simulated by sequentially coupling a calibrated 3D pseudo-analytical thermal model with a 3D finite element mechanical model.The optimized processing parameters are subjected to a Monte Carlo...

  11. Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration

    Directory of Open Access Journals (Sweden)

    Wendell Q Sun

    2013-09-01

    Full Text Available Extracellular matrices derived from animal tissues for human tissue repairs are processed by various methods of physical, chemical, or enzymatic decellularization, viral inactivation, and terminal sterilization. The mechanisms of action in tissue repair vary among bioscaffolds and are suggested to be associated with process-induced extracellular matrix modifications. We compared three non-cross-linked, commercially available extracellular matrix scaffolds (Strattice, Veritas, and XenMatrix, and correlated extracellular matrix alterations to in vivo biological responses upon implantation in non-human primates. Structural evaluation showed significant differences in retaining native tissue extracellular matrix histology and ultrastructural features among bioscaffolds. Tissue processing may cause both the condensation of collagen fibers and fragmentation or separation of collagen bundles. Calorimetric analysis showed significant differences in the stability of bioscaffolds. The intrinsic denaturation temperature was measured to be 51°C, 38°C, and 44°C for Strattice, Veritas, and XenMatrix, respectively, demonstrating more extracellular matrix modifications in the Veritas and XenMatrix scaffolds. Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues. Using a non-human primate model, three bioscaffolds were found to elicit different biological responses, have distinct mechanisms of action, and yield various outcomes of tissue repair. Strattice permitted cell repopulation and was remodeled over 6 months. Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation. XenMatrix caused severe inflammation and sustained immune reactions. This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration. The data offer useful insights into the

  12. Altered visual information processing systems in bipolar disorder: evidence from visual MMN and P3

    Directory of Open Access Journals (Sweden)

    Toshihiko eMaekawa

    2013-07-01

    Full Text Available Objective: Mismatch negativity (MMN and P3 are unique ERP components that provide objective indices of human cognitive functions such as short-term memory and prediction. Bipolar disorder (BD is an endogenous psychiatric disorder characterized by extreme shifts in mood, energy, and ability to function socially. BD patients usually show cognitive dysfunction, and the goal of this study was to access their altered visual information processing via visual MMN (vMMN and P3 using windmill pattern stimuli.Methods: Twenty patients with BD and 20 healthy controls matched for age, gender, and handedness participated in this study. Subjects were seated in front of a monitor and listened to a story via earphones. Two types of windmill patterns (standard and deviant and white circle (target stimuli were randomly presented on the monitor. All stimuli were presented in random order at 200-ms durations with an 800-ms inter-stimulus interval. Stimuli were presented at 80% (standard, 10% (deviant, and 10% (target probabilities. The participants were instructed to attend to the story and press a button as soon as possible when the target stimuli were presented. Event-related potentials were recorded throughout the experiment using 128-channel EEG equipment. vMMN was obtained by subtracting standard from deviant stimuli responses, and P3 was evoked from the target stimulus.Results: Mean reaction times for target stimuli in the BD group were significantly higher than those in the control group. Additionally, mean vMMN-amplitudes and peak P3-amplitudes were significantly lower in the BD group than in controls.Conclusions: Abnormal vMMN and P3 in patients indicate a deficit of visual information processing in bipolar disorder, which is consistent with their increased reaction time to visual target stimuli.Significance: Both bottom-up and top-down visual information processing are likely altered in BD.

  13. Cognitive alterations in motor imagery process after left hemispheric ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Jing Yan

    Full Text Available BACKGROUND: Motor imagery training is a promising rehabilitation strategy for stroke patients. However, few studies had focused on the neural mechanisms in time course of its cognitive process. This study investigated the cognitive alterations after left hemispheric ischemic stroke during motor imagery task. METHODOLOGY/PRINCIPAL FINDINGS: Eleven patients with ischemic stroke in left hemisphere and eleven age-matched control subjects participated in mental rotation task (MRT of hand pictures. Behavior performance, event-related potential (ERP and event-related (desynchronization (ERD/ERS in beta band were analyzed to investigate the cortical activation. We found that: (1 The response time increased with orientation angles in both groups, called "angle effect", however, stoke patients' responses were impaired with significantly longer response time and lower accuracy rate; (2 In early visual perceptual cognitive process, stroke patients showed hypo-activations in frontal and central brain areas in aspects of both P200 and ERD; (3 During mental rotation process, P300 amplitude in control subjects decreased while angle increased, called "amplitude modulation effect", which was not observed in stroke patients. Spatially, patients showed significant lateralization of P300 with activation only in contralesional (right parietal cortex while control subjects showed P300 in both parietal lobes. Stroke patients also showed an overall cortical hypo-activation of ERD during this sub-stage; (4 In the response sub-stage, control subjects showed higher ERD values with more activated cortical areas particularly in the right hemisphere while angle increased, named "angle effect", which was not observed in stroke patients. In addition, stroke patients showed significant lower ERD for affected hand (right response than that for unaffected hand. CONCLUSIONS/SIGNIFICANCE: Cortical activation was altered differently in each cognitive sub-stage of motor imagery after

  14. Cellular differentiation in the process of generation of the eukaryotic cell

    Science.gov (United States)

    Nakamura, Hakobu; Hase, Atsushi

    1990-11-01

    Primitive atmosphere of the earth did not contain oxygen gas (O2) when the proto-cells were generated successfully as the resut of chemical evolution and then evolved. Therefore, they first had acquired anaerobic energy metabolism, fermentation. The cellular metabolisms have often been formed by reorganizing to combine or recombinate between pre-existing metabolisms and newly born bioreactions. Photosynthetic metabolism in eukaryotic chloroplast consists of an electron-transfer photosystem and a fermentative reductive pentose phosphate cycle. On the other hand, O2-respiration of eukaryotic mitochondrion is made of Embden-Meyerhof (EM) pathway and tricarboxylic acid cycle, which originate from a connection of fermentative metabolisms, and an electron-transfer respiratory chain, which has been derived from the photosystem. These metabolisms already are completed in some evolved prokaryotes, for example the cyanobacteriumChlorogloea fritschii and aerobic photosynthetic bacteriaRhodospirillum rubrum andErythrobacter sp. Therefore, it can be reasonably presumed that the eukaryotic chloroplast and mitochondrion have once been formed as the result of metabolic (and genetic) differentiations in most evolved cyanobacterium. Symbiotic theory has explained the origin of eukaryotic cell as that in which the mitochondrion and chloroplast have been derived from endosymbionts of aerobic bacterium and cyanobacterium, respectively, and has mentioned as one of the most potent supportive evidences that amino acid sequences of the photosynthetic and O2 -respiratory enzymes show similarities to corresponding prokaryotic enzymes. However, as will be shown in this discussion, many examples have shown currently that prokaryotic sequences of informative molecules are conserved well not only in those of the mitochondrial and chloroplast molecules but also in the nuclear molecules. In fact, the similarities in sequence of informative molecules are preserved well among the organisms not only

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

    Directory of Open Access Journals (Sweden)

    Ling Yang

    2016-01-01

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

  16. Cellular and molecular processes of regeneration, with special emphasis on fish fins.

    Science.gov (United States)

    Nakatani, Yuki; Kawakami, Atsushi; Kudo, Akira

    2007-02-01

    The phenomenon of 'epimorphic regeneration', a complete reformation of lost tissues and organs from adult differentiated cells, has been fascinating many biologists for many years. While most vertebrate species including humans do not have a remarkable ability for regeneration, the lower vertebrates such as urodeles and fish have exceptionally high regeneration abilities. In particular, the teleost fish has a high ability to regenerate a variety of tissues and organs including scales, muscles, spinal cord and heart among vertebrate species. Hence, an understanding of the regeneration mechanism in teleosts will provide an essential knowledge base for rational approaches to tissue and organ regeneration in mammals. In the last decade, small teleost fish such as the zebrafish and medaka have emerged as powerful animal models in which a variety of developmental, genetic and molecular approaches are applicable. In addition, rapid progress in the development of genome resources such as expressed sequence tags and genome sequences has accelerated the speed of the molecular analysis of regeneration. This review summarizes the current status of our understanding of the cellular and molecular basis of regeneration, particularly that regarding fish fins.

  17. From Hills to Holes: How Climate Change and Mining are Altering Runoff Processes in Canada

    Science.gov (United States)

    Carey, S. K.

    2015-12-01

    Canadian environments are under considerable pressure from both climate and land-use change. While warming temperatures are widespread and amplified in the north, surface mining has resulted in large-scale landscape disturbance. How these changes affect catchment response is profound, fundamentally altering the cycling and delivery of water and geochemicals to the drainage network. In permafrost-underlain environments, coupled mass and energy processes control runoff response, and as ground thaw increases, new subsurface pathways become accessible while changing overall catchment storage. With surface mining, watersheds are altered such that they bare little resemblance to what existed prior to mining. In this presentation, data will be presented from long-term experiments exploring the impact of climate and mining on runoff processes in cold catchments using stable isotopes of water and associated hydrometric measurements. In southern Yukon, results from the Wolf Creek Research Basin highlights the influence of surface energy balances on controlling the timing and magnitude of flow response, with inter-annual variability largely driven by how atmospheric forcing interacts with permafrost-underlain areas of the catchment. In mountainous areas of southern British Columbia, surface mining reconfigures landscapes as valleys are filled with waste-rock. Mine-influenced catchments exhibit attenuated flows with delays in spring freshet and a more muted to precipitation. Stable isotopes in stream water suggests that both waste-rock and reference catchments are well mixed, however reference catchments are more responsive to enrichment and depletion events and that mine-influenced catchments had a heavier isotope signature than reference watersheds, suggesting enhanced influence of rainfall on recharge. In both cases, snow storage and release exerts considerable control on streamflow responses, and future changes in streamflow regimes will reflect both a changes in the snow

  18. Diurnal Regulation of Cellular Processes in the Cyanobacterium Synechocystis sp. Strain PCC 6803: Insights from Transcriptomic, Fluxomic, and Physiological Analyses

    Directory of Open Access Journals (Sweden)

    Rajib Saha

    2016-05-01

    Full Text Available Synechocystis sp. strain PCC 6803 is the most widely studied model cyanobacterium, with a well-developed omics level knowledgebase. Like the lifestyles of other cyanobacteria, that of Synechocystis PCC 6803 is tuned to diurnal changes in light intensity. In this study, we analyzed the expression patterns of all of the genes of this cyanobacterium over two consecutive diurnal periods. Using stringent criteria, we determined that the transcript levels of nearly 40% of the genes in Synechocystis PCC 6803 show robust diurnal oscillating behavior, with a majority of the transcripts being upregulated during the early light period. Such transcripts corresponded to a wide array of cellular processes, such as light harvesting, photosynthetic light and dark reactions, and central carbon metabolism. In contrast, transcripts of membrane transporters for transition metals involved in the photosynthetic electron transport chain (e.g., iron, manganese, and copper were significantly upregulated during the late dark period. Thus, the pattern of global gene expression led to the development of two distinct transcriptional networks of coregulated oscillatory genes. These networks help describe how Synechocystis PCC 6803 regulates its metabolism toward the end of the dark period in anticipation of efficient photosynthesis during the early light period. Furthermore, in silico flux prediction of important cellular processes and experimental measurements of cellular ATP, NADP(H, and glycogen levels showed how this diurnal behavior influences its metabolic characteristics. In particular, NADPH/NADP+ showed a strong correlation with the majority of the genes whose expression peaks in the light. We conclude that this ratio is a key endogenous determinant of the diurnal behavior of this cyanobacterium.

  19. Anatomical alterations of the visual motion processing network in migraine with and without aura.

    Directory of Open Access Journals (Sweden)

    Cristina Granziera

    2006-10-01

    Full Text Available BACKGROUND: Patients suffering from migraine with aura (MWA and migraine without aura (MWoA show abnormalities in visual motion perception during and between attacks. Whether this represents the consequences of structural changes in motion-processing networks in migraineurs is unknown. Moreover, the diagnosis of migraine relies on patient's history, and finding differences in the brain of migraineurs might help to contribute to basic research aimed at better understanding the pathophysiology of migraine. METHODS AND FINDINGS: To investigate a common potential anatomical basis for these disturbances, we used high-resolution cortical thickness measurement and diffusion tensor imaging (DTI to examine the motion-processing network in 24 migraine patients (12 with MWA and 12 MWoA and 15 age-matched healthy controls (HCs. We found increased cortical thickness of motion-processing visual areas MT+ and V3A in migraineurs compared to HCs. Cortical thickness increases were accompanied by abnormalities of the subjacent white matter. In addition, DTI revealed that migraineurs have alterations in superior colliculus and the lateral geniculate nucleus, which are also involved in visual processing. CONCLUSIONS: A structural abnormality in the network of motion-processing areas could account for, or be the result of, the cortical hyperexcitability observed in migraineurs. The finding in patients with both MWA and MWoA of thickness abnormalities in area V3A, previously described as a source in spreading changes involved in visual aura, raises the question as to whether a "silent" cortical spreading depression develops as well in MWoA. In addition, these experimental data may provide clinicians and researchers with a noninvasively acquirable migraine biomarker.

  20. A model for Intelligent Random Access Memory architecture (IRAM) cellular automata algorithms on the Associative String Processing machine (ASTRA)

    CERN Document Server

    Rohrbach, F; Vesztergombi, G

    1997-01-01

    In the near future, the computer performance will be completely determined by how long it takes to access memory. There are bottle-necks in memory latency and memory-to processor interface bandwidth. The IRAM initiative could be the answer by putting Processor-In-Memory (PIM). Starting from the massively parallel processing concept, one reached a similar conclusion. The MPPC (Massively Parallel Processing Collaboration) project and the 8K processor ASTRA machine (Associative String Test bench for Research \\& Applications) developed at CERN \\cite{kuala} can be regarded as a forerunner of the IRAM concept. The computing power of the ASTRA machine, regarded as an IRAM with 64 one-bit processors on a 64$\\times$64 bit-matrix memory chip machine, has been demonstrated by running statistical physics algorithms: one-dimensional stochastic cellular automata, as a simple model for dynamical phase transitions. As a relevant result for physics, the damage spreading of this model has been investigated.

  1. NMDA-R inhibition affects cellular process formation in Tilapia melanocytes; a model for pigmented adrenergic neurons in process formation and retraction.

    Science.gov (United States)

    Ogundele, Olalekan Michael; Okunnuga, Adetokunbo Adedotun; Fabiyi, Temitope Deborah; Olajide, Olayemi Joseph; Akinrinade, Ibukun Dorcas; Adeniyi, Philip Adeyemi; Ojo, Abiodun Ayodele

    2014-06-01

    Parkinson's disease has long been described to be a product of dopamine and (or) melanin loss in the substanstia nigra (SN). Although most studies have focused on dopaminergic neurons, it is important to consider the role of pigment cells in the etiology of the disease and to create an in vitro live cell model for studies involving pigmented adrenergic cells of the SN in Parkinsonism. The Melanocytes share specific features with the pigmented adrenergic neurons as both cells are pigmented, contain adrenergic receptors and have cellular processes. Although the melanocyte cellular processes are relatively short and observable only when stimulated appropriately by epinephrine and other factors or molecules. This study employs the manipulation of N-Methyl-D-Aspartate Receptor (NMDA-R), a major receptor in neuronal development, in the process formation pattern of the melanocyte in order to create a suitable model to depict cellular process elongation and shortening in pigmented adrenergic cells. NMDA-R is an important glutamate receptor implicated in neurogenesis, neuronal migration, maturation and cell death, thus we investigated the role of NMDA-R potentiation by glutamate/KCN and its inhibition by ketamine in the behavior of fish scale melanocytes in vitro. This is aimed at establishing the regulatory role of NMDA-R in this cell type (melanocytes isolated form Tilapia) in a similar manner to what is observable in the mammalian neurons. In vitro live cell culture was prepared in modified Ringer's solution following which the cells were treated as follows; Control, Glutamate, Ketamine, Glutamate + Ketamine, KCN + Ketamine and KCN. The culture was maintained for 10 min and the changes were captured in 3D-Time frame at 0, 5 and 10 min for the control and 5, 7 and 10 min for each of the treatment category. Glutamate treatment caused formation of short cellular processes localized directly on the cell body while ketamine treatment (inhibition of NMDA-R) facilitated

  2. Cellular processing of the amyloidogenic cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Merz, G S; Schwenk, V

    1999-01-01

    of an amyloidogenic mutation on the intracellular processing of its protein product. The protein, a mutant of the cysteine protease inhibitor cystatin C, is the amyloid precursor protein in Hereditary Cerebral Hemorrhage with Amyloidosis--Icelandic type (HCHWA-I). The amyloid fibers are composed of mutant cystatin C...

  3. Assessment of alteration processes on circumstellar and interstellar grains in Queen Alexandra Range 97416

    Science.gov (United States)

    Bose, Maitrayee; Zega, Thomas J.; Williams, Peter

    2014-08-01

    Insight into the presolar and interstellar grain inventory of the CO3 chondrite Queen Alexandra Range (QUE) 97416 is gained through correlated secondary ion mass spectrometry (SIMS), transmission electron microscopy (TEM), and synchrotron-based X-ray absorption near-edge structure spectroscopy (XANES). Only one presolar silicate grain [O17/O16=(9.96±0.75)×10-4; O18/O16=(19.49±0.96)×10-4] that may have formed in a low-mass Red Giant or Asymptotic Giant Branch star occurs in the coarse-grained matrix of QUE 97416. No other presolar grains were identified. Although presolar grains are rare in QUE 97416, numerous (898±259 ppm) 15N-rich domains (δN15∼+1447‰ to +3069‰) occur in the thin section. Based on TEM of an extracted section, two 15N-rich domains are amorphous, C-bearing, and texturally uniform, and they are embedded in a ferromagnesian silicate matrix with varied grain sizes. The individual 15N-rich organic regions with high δN15 (+2942±107‰ and +2341±140‰) exhibit diverse carbon functional groups, such as aromatic, vinyl-keto, amidyl, and carboxylic functionality, while the nitrogen XANES reveals traces of nitrile functionality. QUE 97416 appears to have escaped aqueous alteration based on the absence of hydrated minerals but is thermally altered, which could have resulted in the destruction of presolar grains. However, this process at >400 °C metamorphic temperatures was inefficient in destroying the carriers of N isotope anomalies, which may indicate the resistant nature of the organic carriers and/or the limited extent of thermal metamorphism on the QUE 97416 parent body.

  4. PDGF supplementation alters oxidative events in wound healing process: a time course study.

    Science.gov (United States)

    Kaltalioglu, Kaan; Coskun-Cevher, Sule; Tugcu-Demiroz, Fatmanur; Celebi, Nevin

    2013-07-01

    Platelet-derived growth factor (PDGF), an important stimulant, plays a role in almost all stages of wound healing process. In various studies, it has been shown that PDGF has healing effects in this process. In the present study, we especially focused on investigating the effects of exogenous PDGF administration on oxidative events during cutaneous wound healing process. Experiments were performed on 42 female Wistar-albino rats. Animals were divided into four groups: control, untreated, chitosan-treated and chitosan + PDGF-treated. Two uniform full-thickness excisional skin wounds were made under anesthesia in all animals except control group. In the chitosan + PDGF-treated groups, the wounds were treated topically with a single daily dose PDGF-BB (7 ng/ml) after wounding. In the chitosan-treated groups, the wounds were treated topically with equal amount of blank chitosan gel. After that, on the 3rd and 7th days of wound healing, the animals were killed. Thiobarbituric acid-reactive substances (TBARS), nitric oxide (NOx), ascorbic acid (AA), glutathione (GSH) levels and superoxide dismutase (SOD) activity were measured spectrophotometrically in the wound tissues. PDGF significantly increased TBARS levels in early phase of wound healing. In contrast, it significantly decreased TBARS levels in later phase of healing. In the chitosan + PDGF-treated group, NOx levels decreased on days 3 and 7 when compared with the chitosan-treated groups. Non-enzymatic antioxidant levels were increased by PDGF administration and this may have contributed to increase in wound tissue antioxidant capacity. In the light of these findings, PDGF supplementation may have altering effects on oxidative events depending on the time in wound healing process.

  5. A differential genome-wide transcriptome analysis: impact of cellular copper on complex biological processes like aging and development.

    Directory of Open Access Journals (Sweden)

    Jörg Servos

    Full Text Available The regulation of cellular copper homeostasis is crucial in biology. Impairments lead to severe dysfunctions and are known to affect aging and development. Previously, a loss-of-function mutation in the gene encoding the copper-sensing and copper-regulated transcription factor GRISEA of the filamentous fungus Podospora anserina was reported to lead to cellular copper depletion and a pleiotropic phenotype with hypopigmentation of the mycelium and the ascospores, affected fertility and increased lifespan by approximately 60% when compared to the wild type. This phenotype is linked to a switch from a copper-dependent standard to an alternative respiration leading to both a reduced generation of reactive oxygen species (ROS and of adenosine triphosphate (ATP. We performed a genome-wide comparative transcriptome analysis of a wild-type strain and the copper-depleted grisea mutant. We unambiguously assigned 9,700 sequences of the transcriptome in both strains to the more than 10,600 predicted and annotated open reading frames of the P. anserina genome indicating 90% coverage of the transcriptome. 4,752 of the transcripts differed significantly in abundance with 1,156 transcripts differing at least 3-fold. Selected genes were investigated by qRT-PCR analyses. Apart from this general characterization we analyzed the data with special emphasis on molecular pathways related to the grisea mutation taking advantage of the available complete genomic sequence of P. anserina. This analysis verified but also corrected conclusions from earlier data obtained by single gene analysis, identified new candidates of factors as part of the cellular copper homeostasis system including target genes of transcription factor GRISEA, and provides a rich reference source of quantitative data for further in detail investigations. Overall, the present study demonstrates the importance of systems biology approaches also in cases were mutations in single genes are analyzed to

  6. HIV Protease Inhibitor-Induced Cathepsin Modulation Alters Antigen Processing and Cross-Presentation.

    Science.gov (United States)

    Kourjian, Georgio; Rucevic, Marijana; Berberich, Matthew J; Dinter, Jens; Wambua, Daniel; Boucau, Julie; Le Gall, Sylvie

    2016-05-01

    Immune recognition by T cells relies on the presentation of pathogen-derived peptides by infected cells, but the persistence of chronic infections calls for new approaches to modulate immune recognition. Ag cross-presentation, the process by which pathogen Ags are internalized, degraded, and presented by MHC class I, is crucial to prime CD8 T cell responses. The original degradation of Ags is performed by pH-dependent endolysosomal cathepsins. In this article, we show that HIV protease inhibitors (PIs) prescribed to HIV-infected persons variably modulate cathepsin activities in human APCs, dendritic cells and macrophages, and CD4 T cells, three cell subsets infected by HIV. Two HIV PIs acted in two complementary ways on cathepsin hydrolytic activities: directly on cathepsins and indirectly on their regulators by inhibiting Akt kinase activities, reducing NADPH oxidase 2 activation, and lowering phagolysosomal reactive oxygen species production and pH, which led to enhanced cathepsin activities. HIV PIs modified endolysosomal degradation and epitope production of proteins from HIV and other pathogens in a sequence-dependent manner. They altered cross-presentation of Ags by dendritic cells to epitope-specific T cells and T cell-mediated killing. HIV PI-induced modulation of Ag processing partly changed the MHC self-peptidome displayed by primary human cells. This first identification, to our knowledge, of prescription drugs modifying the regulation of cathepsin activities and the MHC-peptidome may provide an alternate therapeutic approach to modulate immune recognition in immune disease beyond HIV.

  7. In vitro cellular responses to silicon carbide particles manufactured through the Acheson process: impact of physico-chemical features on pro-inflammatory and pro-oxidative effects.

    Science.gov (United States)

    Boudard, Delphine; Forest, Valérie; Pourchez, Jérémie; Boumahdi, Najih; Tomatis, Maura; Fubini, Bice; Guilhot, Bernard; Cottier, Michèle; Grosseau, Philippe

    2014-08-01

    Silicon carbide (SiC) an industrial-scale product manufactured through the Acheson process, is largely employed in various applications. Its toxicity has been poorly investigated. Our study aims at characterizing the physico-chemical features and the in vitro impact on biological activity of five manufactured SiC powders: two coarse powders (SiC C1/C2), two fine powders (SiC F1/F2) and a powder rich in iron impurities (SiC I). RAW 264.7 macrophages were exposed to the different SiC particles and the cellular responses were evaluated. Contrary to what happens with silica, no SiC cytotoxicity was observed but pro-oxidative and pro-inflammatory responses of variable intensity were evidenced. Oxidative stress (H₂O₂ production) appeared related to SiC particle size, while iron level regulated pro-inflammatory response (TNFα production). To investigate the impact of surface reactivity on the biological responses, coarse SiC C1 and fine SiC F1 powders were submitted to different thermal treatments (650-1400 °C) in order to alter the oxidation state of the particle surface. At 1400 °C a decrease in TNFα production and an increase in HO·, COO(·-) radicals production were observed in correlation with the formation of a surface layer of crystalline silica. Finally, a strong correlation was observed between surface oxidation state and in vitro toxicity.

  8. Evaluation of dynamic behavior forecasting parameters in the process of transition rule induction of unidimensional cellular automata.

    Science.gov (United States)

    Weinert, Wagner Rodrigo; Lopes, Heitor Silvério

    2010-01-01

    The simulation of the dynamics of a cellular systems based on cellular automata (CA) can be computationally expensive. This is particularly true when such simulation is part of a procedure of rule induction to find suitable transition rules for the CA. Several efforts have been described in the literature to make this problem more treatable. This work presents a study about the efficiency of dynamic behavior forecasting parameters (DBFPs) used for the induction of transition rules of CA for a specific problem: the classification by the majority rule. A total of 8 DBFPs were analyzed for the 31 best-performing rules found in the literature. Some of these DBFPs were highly correlated each other, meaning they yield the same information. Also, most rules presented values of the DBFPs very close each other. An evolutionary algorithm, based on gene expression programming, was developed for finding transition rules according a given preestablished behavior. The simulation of the dynamic behavior of the CA is not used to evaluate candidate transition rules. Instead, the average values for the DBFPs were used as reference. Experiments were done using the DBFPs separately and together. In both cases, the best induced transition rules were not acceptable solutions for the desired behavior of the CA. We conclude that, although the DBFPs represent interesting aspects of the dynamic behavior of CAs, the transition rule induction process still requires the simulation of the dynamics and cannot rely only on the DBFPs.

  9. Cellular and molecular mechanisms activating the cell death processes by chalcones: Critical structural effects.

    Science.gov (United States)

    Champelovier, Pierre; Chauchet, Xavier; Hazane-Puch, Florence; Vergnaud, Sabrina; Garrel, Catherine; Laporte, François; Boutonnat, Jean; Boumendjel, Ahcène

    2013-12-01

    Chalcones are naturally occurring compounds with diverse pharmacological activities. Chalcones derive from the common structure: 1,3-diphenylpropenone. The present study aims to better understand the mechanistic pathways triggering chalcones anticancer effects and providing evidences that minor structural difference could lead to important difference in mechanistic effect. We selected two recently investigated chalcones (A and B) and investigated them on glioblastoma cell lines. It was found that chalcone A induced an apoptotic process (type I PCD), via the activation of caspase-3, -8 and -9. Chalcone A also increased CDK1/cyclin B ratios and decreased the mitochondrial transmembrane potential (ΔΨm). Chalcone B induced an autophagic cell death process (type II PCD), ROS-related but independent of both caspases and protein synthesis. Both chalcones increased Bax/Bcl2 ratios and decreased Ki67 and CD71 antigen expressions. The present investigation reveals that despite the close structure of chalcones A and B, significant differences in mechanism of effect were found.

  10. Quantification of diagenetic overprint processes deduced from fossil carbonate shells and laboratory-based hydrothermal alteration experiments

    Science.gov (United States)

    Griesshaber, Erika; Casella, Laura; Mavromatis, Vasileios; Dietzel, Martin; Immenhauser, Adrian; Schmahl, Wolfgang

    2016-04-01

    Benthic and nektonic marine biogenic carbonate archives represent the foundation of numerous studies aiming at reconstructions of past climate dynamics and environmental change. However, living organisms are not in thermodynamic equilibrium and create local chemical environments where physiologic processes such as biomineralization takes place. After the death of the organism the former physiologic disequilibrium conditions are not sustained any more and all biological tissues are altered by equilibration according to the surrounding environment: diagenesis. With increasing diagenetic alteration, the biogenic structure and fingerprint fades away and is replaced by inorganic features. Thus, recrystallization of organism-specific microstructure is a clear indicator for diagenetic overprint. Microstructural data, which mirror recrystallization, are of great value for interpreting geochemical proxies for paleo-environment reconstruction. Despite more than a century of research dealing with carbonate diagenesis, many of the controlling processes and factors are only understood in a qualitative manner. One of the main issues is that diagenetically altered carbonates are usually present as the product of a complex preceding diagenetic pathway with an unknown number of intermediate steps. In this contribution we present and discuss laboratory based alteration experiments with the aim to investigate time-series data sets in a controlled manner. We conducted hydrothermal alteration experiments with modern Arctica islandica (bivalvia) and Notosaria nigricans (brachiopoda) in order to mimic diagenetic overprint. We explore first the potential of electron backscattered diffraction (EBSD) measurements together with statistical data evaluation as a tool to quantify diagenetic alteration of carbonate skeletons. Subsequently, we compare microstructural patterns obtained from experimentally altered shell material with those of fossil specimens that have undergone variable degrees of

  11. Cellular Aspects of Shigella Pathogenesis: Focus on the Manipulation of Host Cell Processes.

    Science.gov (United States)

    Killackey, Samuel A; Sorbara, Matthew T; Girardin, Stephen E

    2016-01-01

    Shigella is a Gram-negative bacterium that is responsible for shigellosis. Over the years, the study of Shigella has provided a greater understanding of how the host responds to bacterial infection, and how bacteria have evolved to effectively counter the host defenses. In this review, we provide an update on some of the most recent advances in our understanding of pivotal processes associated with Shigella infection, including the invasion into host cells, the metabolic changes that occur within the bacterium and the infected cell, cell-to-cell spread mechanisms, autophagy and membrane trafficking, inflammatory signaling and cell death. This recent progress sheds a new light into the mechanisms underlying Shigella pathogenesis, and also more generally provides deeper understanding of the complex interplay between host cells and bacterial pathogens in general.

  12. Altered food-cue processing in chronically ill and recovered women with anorexia nervosa.

    Science.gov (United States)

    Sanders, Nicole; Smeets, Paul A M; van Elburg, Annemarie A; Danner, Unna N; van Meer, Floor; Hoek, Hans W; Adan, Roger A H

    2015-01-01

    Anorexia nervosa (AN) is a severe mental disorder characterized by food restriction and weight loss. This study aimed to test the model posed by Brooks et al. (2012a,b) that women suffering from chronic AN show decreased food-cue processing activity in brain regions associated with energy balance and food reward (bottom-up; BU) and increased activity in brain regions associated with cognitive control (top-down; TD) when compared with long-term recovered AN (REC) and healthy controls (HC). Three groups of women, 15 AN (mean illness duration 7.8 ± 4.1 years), 14 REC (mean duration of recovery 4.7 ± 2.7 years) and 15 HC viewed alternating blocks of food and non-food images preceded by a short instruction during functional magnetic resonance imaging (fMRI), after fasting overnight. Functional region of interests (fROIs) were defined in BU (e.g., striatum, hippocampus, amygdala, hypothalamus, and cerebellum), TD (e.g., medial and lateral prefrontal cortex, and anterior cingulate), the insula, and visual processing areas (VPA). Food-cue processing activation was extracted from all fROIs and compared between the groups. In addition, functional connectivity between the fROIs was examined by modular partitioning of the correlation matrix of all fROIs. We could not confirm the hypothesis that BU areas are activated to a lesser extent in AN upon visual processing of food images. Among the BU areas the caudate showed higher activation in both patient groups compared to HC. In accordance with Brooks et al.'s model, we did find evidence for increased TD control in AN and REC. The functional connectivity analysis yielded two clusters in HC and REC, but three clusters in AN. In HC, fROIs across BU, TD, and VPA areas clustered; in AN, one cluster span across BU, TD, and insula; one across BU, TD, and VPA areas; and one was confined to the VPA network. In REC, BU, TD, and VPA or VPA and insula clustered. In conclusion, despite weight recovery, neural processing of food

  13. Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

    Directory of Open Access Journals (Sweden)

    Borini Paulo

    1999-01-01

    Full Text Available Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehydrogenase, altered in 16% of the cases; alpha-1 globulin, 24%; alpha-2 globulin, 88%; leucocyte counts, 28% was correlated with alterations of bilirubin or liver enzymes. Lactic dehydrogenase was poorly sensitive for detection of hepatocytic or muscular damage. Alterations of alpha-globulins seemed to have been due more to alcohol metabolism-induced increase of lipoproteins than to inflammation. Among indicators of cell damage, serum iron, increased in 40% of the cases, seemed to be related to liver damage while creatine phosphokinase, increased in 84% of the cases, related to muscle damage. Hyperamylasemia was found in 20% of the cases and significantly correlated with levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase. It was indicated that injuries of liver, pancreas, salivary glands, and muscle occurred in asymptomatic or oligosymptomatic chronic alcoholics.

  14. Processing and characterization of multi-cellular monolithic bioceramics for bone regenerative scaffolds

    Science.gov (United States)

    Ari-Wahjoedi, Bambang; Ginta, Turnad Lenggo; Parman, Setyamartana; Abustaman, Mohd Zikri Ahmad

    2014-10-01

    Multicellular monolithic ceramic body is a ceramic material which has many gas or liquid passages partitioned by thin walls throughout the bulk material. There are many currently known advanced industrial applications of multicellular ceramics structures i.e. as supports for various catalysts, electrode support structure for solid oxide fuel cells, refractories, electric/electronic materials, aerospace vehicle re-entry heat shields and biomaterials for dental as well as orthopaedic implants by naming only a few. Multicellular ceramic bodies are usually made of ceramic phases such as mullite, cordierite, aluminum titanate or pure oxides such as silica, zirconia and alumina. What make alumina ceramics is excellent for the above functions are the intrinsic properties of alumina which are hard, wear resistant, excellent dielectric properties, resists strong acid and alkali attacks at elevated temperatures, good thermal conductivities, high strength and stiffness as well as biocompatible. In this work the processing technology leading to truly multicellular monolithic alumina ceramic bodies and their characterization are reported. Ceramic slip with 66 wt.% solid loading was found to be optimum as impregnant to the polyurethane foam template. Mullitic ceramic composite of alumina-sodium alumino disilicate-Leucite-like phases with bulk and true densities of 0.852 and 1.241 g cm-3 respectively, pore linear density of ±35 cm-1, linear and bulk volume shrinkages of 7-16% and 32 vol.% were obtained. The compressive strength and elastic modulus of the bioceramics are ≈0.5-1.0 and ≈20 MPa respectively.

  15. Cellular lipid production of a heterotrophic bacterium isolated from poultry processing wastewater

    Directory of Open Access Journals (Sweden)

    Rattiya Ongmali

    2014-06-01

    Full Text Available Cell growth and lipid production of a heterotrophic bacterium, R4.4 which accumulated the highest lipid content among 12 bacterial colonies being isolated from wastewater of a poultry processing plant in Thailand, were evaluated in this study. The culture was identified as Aeromonas sp. by 16S ribosomal DNA sequencing analysis.The highest lipid content was obtained when the cells were in the early stationary growth phase compared to the cells in the exponential and the late stationary phase. Over 50% of the fatty acid production by Aeromonas sp. KMITL-R4.4 were unsaturated fatty acids, including linoleic acid (C18:2, 43.2%, oleic acid (C18:1, 19.0%, and palmitoleic acid (C16:1, 8.2%. The culture had a preference for glucose and fructose as seen from the maximum biomass and lipid contents that were obtained. Among volatile fatty acid (VFA species tested, acetic acid was the preferred substrate for lipid production but not favorable for cell growth. In addition, ammonium sulfate was found to be the best among nitrogen sources tested. The C/N ratio exerts significant impact on lipid production as seen from an increase of the lipid content from 10.8% to 18.2% by exposing the bacterial cells to a medium with lower nitrogen concentration (0.1g/l and higher level of glucose (28 g/l.

  16. Correlation between altered central pain processing and concentration of peritoneal fluid inflammatory cytokines in endometriosis patients with chronic pelvic pain.

    Science.gov (United States)

    Neziri, Alban Y; Bersinger, Nick A; Andersen, Ole K; Arendt-Nielsen, Lars; Mueller, Michael D; Curatolo, Michele

    2014-01-01

    Translational research has not yet elucidated whether alterations in central pain processes are related to peripheral inflammatory processes in chronic pain patients. We tested the hypothesis that the concentration of cytokines in the peritoneal fluid of endometriosis patients with chronic pain correlate with parameters of hyperexcitability of the nociceptive system. The concentrations of 15 peritoneal fluid cytokines were measured in 11 patients with chronic pelvic pain and a diagnosis of endometriosis. Six parameters assessing central pain processes were recorded. Positive correlations between concentration of some cytokines in the peritoneal fluid and amplification of central pain processing were found. The results suggest that inflammatory mechanisms may be important in the pathophysiology of altered central pain processes and that cytokines produced in the environment of endometriosis could act as mediators between the peripheral lesion and changes in central nociceptive processes.

  17. Thermal nociceptive threshold testing detects altered sensory processing in broiler chickens with spontaneous lameness.

    Directory of Open Access Journals (Sweden)

    Becky Hothersall

    Full Text Available Lameness is common in commercially reared broiler chickens but relationships between lameness and pain (and thus bird welfare have proved complex, partly because lameness is often partially confounded with factors such as bodyweight, sex and pathology. Thermal nociceptive threshold (TNT testing explores the neural processing of noxious stimuli, and so can contribute to our understanding of pain. Using an acute model of experimentally induced articular pain, we recently demonstrated that TNT was reduced in lame broiler chickens, and was subsequently attenuated by administration of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs. This study extended these findings to a large sample of commercial broilers. It examined factors affecting thermal threshold (Part 1 and the effect of an NSAID drug (meloxicam, 5 mg/kg and of an opioid (butorphanol; 4 mg/kg (Part 2. Spontaneously lame and matched non-lame birds (n=167 from commercial farms were exposed to ramped thermal stimulations via a probe attached to the lateral aspect of the tarsometatarsus. Baseline skin temperature and temperature at which a behavioural avoidance response occurred (threshold were recorded. In Part 1 bird characteristics influencing threshold were modelled; In Part 2 the effect of subcutaneous administration of meloxicam or butorphanol was investigated. Unexpectedly, after accounting for other influences, lameness increased threshold significantly (Part 1. In Part 2, meloxicam affected threshold differentially: it increased further in lame birds and decreased in non-lame birds. No effect of butorphanol was detected. Baseline skin temperature was also consistently a significant predictor of threshold. Overall, lameness significantly influenced threshold after other bird characteristics were taken into account. This, and a differential effect of meloxicam on lame birds, suggests that nociceptive processing may be altered in lame birds, though mechanisms for this require further

  18. Altered frontocingulate activation during aversive interoceptive processing in young adults transitioning to problem stimulant use

    Directory of Open Access Journals (Sweden)

    Jennifer Lorraine Stewart

    2013-11-01

    Full Text Available Problems associated with stimulant use have been linked to frontocingulate, insular, and thalamic dysfunction during decision-making and alterations in interoceptive processing. However, little is known about how interoception and decision-making interact and contribute to dysfunctions that promote the transition from recreational drug use to abuse or dependence. Here, we investigate brain activation in response to reward, punishment, and uncertainty during an aversive interoceptive challenge in current and former stimulant (cocaine and amphetamine users using functional magnetic resonance imaging (fMRI. Young adults previously identified as recreational users (n=184 were followed up three years later. Of these, 18 individuals progressed to problem stimulant use (PSU, whereas 15 desisted stimulant use (DSU. PSU, DSU, and 14 healthy comparison subjects (CTL performed a two-choice prediction task at three fixed error rates (20%=reward, 50%=uncertainty, 80%=punishment during which they anticipated and experienced episodes of inspiratory breathing load. Although groups did not differ in insula activation or subjective breathing load ratings, PSU exhibited lower right inferior frontal gyrus (IFG and bilateral anterior cingulate (ACC activation than DSU and CTL during aversive interoceptive processing as well as lower right IFG in response to decision making involving uncertainty. However, PSU exhibited greater bilateral IFG activation than DSU and CTL while making choices within the context of punishing feedback, and both PSU and DSU showed lower thalamic activation during breathing load than CTL. Findings suggest that frontocingulate attenuation, reflecting reduced resources devoted to goal maintenance and action selection in the presence of uncertainty and interoceptive perturbations, may be a biomarker for susceptibility to problem stimulant use.

  19. Role of neurotrophic factor alterations in the neurodegenerative process in HIV associated neurocognitive disorders.

    Science.gov (United States)

    Fields, Jerel; Dumaop, Wilmar; Langford, T D; Rockenstein, Edward; Masliah, E

    2014-03-01

    Migration of HIV infected cells into the CNS is associated with a spectrum of neurological disorders, ranging from milder forms of HIV-associated neurocognitive disorders (HAND) to HIV-associated dementia (HAD). These neuro-psychiatric syndromes are related to the neurodegenerative pathology triggered by the release of HIV proteins and cytokine/chemokines from monocytes/macrophages into the CNS -a condition known as HIV encephalitis (HIVE). As a result of more effective combined anti-retroviral therapy patients with HIV are living longer and thus the frequency of HAND has increased considerably, resulting in an overlap between the neurodegenerative pathology associated with HIV and that related to aging. In fact, HIV infection is believed to hasten the aging process. The mechanisms through which HIV and aging lead to neurodegeneration include: abnormal calcium flux, excitotoxicity, signaling abnormalities, oxidative stress and autophagy defects. Moreover, recent studies have shown that defects in the processing and transport of neurotrophic factors such as fibroblast growth factors (FGFs), neural growth factor (NGF) and brain-derived growth factor (BDNF) might also play a role. Recent evidence implicates alterations in neurotrophins in the pathogenesis of neurodegeneration associated with HAND in the context of aging. Here, we report FGF overexpression curtails gp120-induced neurotoxicity in a double transgenic mouse model. Furthermore, our data show disparities in brain neurotrophic factor levels may be exacerbated in HIV patients over 50 years of age. In this review, we discuss the most recent findings on neurotrophins and HAND in the context of developing new therapies to combat HIV infection in the aging population.

  20. Thermal nociceptive threshold testing detects altered sensory processing in broiler chickens with spontaneous lameness.

    Science.gov (United States)

    Hothersall, Becky; Caplen, Gina; Parker, Richard M A; Nicol, Christine J; Waterman-Pearson, Avril E; Weeks, Claire A; Murrell, Joanna C

    2014-01-01

    Lameness is common in commercially reared broiler chickens but relationships between lameness and pain (and thus bird welfare) have proved complex, partly because lameness is often partially confounded with factors such as bodyweight, sex and pathology. Thermal nociceptive threshold (TNT) testing explores the neural processing of noxious stimuli, and so can contribute to our understanding of pain. Using an acute model of experimentally induced articular pain, we recently demonstrated that TNT was reduced in lame broiler chickens, and was subsequently attenuated by administration of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). This study extended these findings to a large sample of commercial broilers. It examined factors affecting thermal threshold (Part 1) and the effect of an NSAID drug (meloxicam, 5 mg/kg) and of an opioid (butorphanol; 4 mg/kg) (Part 2). Spontaneously lame and matched non-lame birds (n=167) from commercial farms were exposed to ramped thermal stimulations via a probe attached to the lateral aspect of the tarsometatarsus. Baseline skin temperature and temperature at which a behavioural avoidance response occurred (threshold) were recorded. In Part 1 bird characteristics influencing threshold were modelled; In Part 2 the effect of subcutaneous administration of meloxicam or butorphanol was investigated. Unexpectedly, after accounting for other influences, lameness increased threshold significantly (Part 1). In Part 2, meloxicam affected threshold differentially: it increased further in lame birds and decreased in non-lame birds. No effect of butorphanol was detected. Baseline skin temperature was also consistently a significant predictor of threshold. Overall, lameness significantly influenced threshold after other bird characteristics were taken into account. This, and a differential effect of meloxicam on lame birds, suggests that nociceptive processing may be altered in lame birds, though mechanisms for this require further investigation.

  1. Processing and characterization of multi-cellular monolithic bioceramics for bone regenerative scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Ari-Wahjoedi, Bambang, E-mail: bambang-ariwahjoedi@petronas.com.my [Department of Fundamental and Applied Sciences, Universiti Teknologi PETRONAS, Bandar Seri Iskandar, 31750 Tronoh, Perak Darul Ridzuan (Malaysia); Centre for Intelligent Signal and Imaging Research, Universiti Teknologi PETRONAS, Bandar Seri Iskandar (Malaysia); Ginta, Turnad Lenggo [Department of Mechanical Engineering, Universiti Teknologi PETRONAS, Bandar Seri Iskandar, 31750 Tronoh, Perak Darul Ridzuan (Malaysia); Centre for Intelligent Signal and Imaging Research, Universiti Teknologi PETRONAS, Bandar Seri Iskandar, 31750 Tro (Malaysia); Parman, Setyamartana [Department of Mechanical Engineering, Universiti Teknologi PETRONAS, Bandar Seri Iskandar, 31750 Tronoh, Perak Darul Ridzuan (Malaysia); Abustaman, Mohd Zikri Ahmad [Kebabangan Petroleum Operating Company Sdn Bhd, Lvl. 52, Tower 2, PETRONAS Twin Towers, KLCC, 50088 Kuala Lumpur (Malaysia)

    2014-10-24

    Multicellular monolithic ceramic body is a ceramic material which has many gas or liquid passages partitioned by thin walls throughout the bulk material. There are many currently known advanced industrial applications of multicellular ceramics structures i.e. as supports for various catalysts, electrode support structure for solid oxide fuel cells, refractories, electric/electronic materials, aerospace vehicle re-entry heat shields and biomaterials for dental as well as orthopaedic implants by naming only a few. Multicellular ceramic bodies are usually made of ceramic phases such as mullite, cordierite, aluminum titanate or pure oxides such as silica, zirconia and alumina. What make alumina ceramics is excellent for the above functions are the intrinsic properties of alumina which are hard, wear resistant, excellent dielectric properties, resists strong acid and alkali attacks at elevated temperatures, good thermal conductivities, high strength and stiffness as well as biocompatible. In this work the processing technology leading to truly multicellular monolithic alumina ceramic bodies and their characterization are reported. Ceramic slip with 66 wt.% solid loading was found to be optimum as impregnant to the polyurethane foam template. Mullitic ceramic composite of alumina-sodium alumino disilicate-Leucite-like phases with bulk and true densities of 0.852 and 1.241 g cm{sup −3} respectively, pore linear density of ±35 cm{sup −1}, linear and bulk volume shrinkages of 7-16% and 32 vol.% were obtained. The compressive strength and elastic modulus of the bioceramics are ≈0.5-1.0 and ≈20 MPa respectively.

  2. Cell surface glycan alterations in epithelial mesenchymal transition process of Huh7 hepatocellular carcinoma cell.

    Directory of Open Access Journals (Sweden)

    Shan Li

    Full Text Available BACKGROUND AND OBJECTIVE: Due to recurrence and metastasis, the mortality of Hepatocellular carcinoma (HCC is high. It is well known that the epithelial mesenchymal transition (EMT and glycan of cell surface glycoproteins play pivotal roles in tumor metastasis. The goal of this study was to identify HCC metastasis related differential glycan pattern and their enzymatic basis using a HGF induced EMT model. METHODOLOGY: HGF was used to induce HCC EMT model. Lectin microarray was used to detect the expression of cell surface glycan and the difference was validated by lectin blot and fluorescence cell lectin-immunochemistry. The mRNA expression levels of glycotransferases were determined by qRT-PCR. RESULTS: After HGF treatment, the Huh7 cell lost epithelial characteristics and obtained mesenchymal markers. These changes demonstrated that HGF could induce a typical cell model of EMT. Lectin microarray analysis identified a decreased affinity in seven lectins ACL, BPL, JAC, MPL, PHA-E, SNA, and SBA to the glycan of cell surface glycoproteins. This implied that glycan containing T/Tn-antigen, NA2 and bisecting GlcNAc, Siaα2-6Gal/GalNAc, terminal α or βGalNAc structures were reduced. The binding ability of thirteen lectins, AAL, LCA, LTL, ConA, NML, NPL, DBA, HAL, PTL II, WFL, ECL, GSL II and PHA-L to glycan were elevated, and a definite indication that glycan containing terminal αFuc and ± Sia-Le, core fucose, α-man, gal-β(α GalNAc, β1,6 GlcNAc branching and tetraantennary complex oligosaccharides structures were increased. These results were further validated by lectin blot and fluorescence cell lectin-immunochemistry. Furthermore, the mRNA expression level of Mgat3 decreased while that of Mgat5, FucT8 and β3GalT5 increased. Therefore, cell surface glycan alterations in the EMT process may coincide with the expression of glycosyltransferase. CONCLUSIONS: The findings of this study systematically clarify the alterations of cell surface

  3. Influence of processing conditions on strut structure and compressive properties of cellular lattice structures fabricated by selective laser melting

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Chunlei, E-mail: c.qiu@bham.ac.uk [School of Metallurgy and Materials, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); Yue, Sheng [School of Materials, University of Manchester, Manchester M13 9PL (United Kingdom); Research Complex at Harwell, Rutherford Appleton Laboratory, Didcot, Oxfordshire OX11 0FA (United Kingdom); Adkins, Nicholas J.E.; Ward, Mark; Hassanin, Hany [School of Metallurgy and Materials, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); Lee, Peter D., E-mail: peter.lee@manchester.ac.uk [School of Materials, University of Manchester, Manchester M13 9PL (United Kingdom); Research Complex at Harwell, Rutherford Appleton Laboratory, Didcot, Oxfordshire OX11 0FA (United Kingdom); Withers, Philip J., E-mail: p.j.withers@manchester.ac.uk [School of Materials, University of Manchester, Manchester M13 9PL (United Kingdom); Research Complex at Harwell, Rutherford Appleton Laboratory, Didcot, Oxfordshire OX11 0FA (United Kingdom); Attallah, Moataz M., E-mail: m.m.attallah@bham.ac.uk [School of Metallurgy and Materials, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom)

    2015-03-25

    AlSi10Mg cellular lattice structures have been fabricated by selective laser melting (SLM) using a range of laser scanning speeds and powers. The as-fabricated strut size, morphology and internal porosity were investigated using optical microscopy (OM), scanning electron microscopy (SEM) and X-ray microtomography (micro-CT) and correlated to the compressive properties of the structure. Strut diameter was found to increase monotonically with laser power while the porosity was largest at intermediate powers. Laser scanning speed was found to thicken the struts only at slow rates while the porosity was largest at intermediate speeds. High speed imaging showed the melt pool to be larger at high laser powers. Further the melt pool shape was found to vary cyclically over time, steadily growing before becoming increasingly instable and irregularly shaped before abruptly falling in size due to splashing of molten materials and the process repeating. Upon compressive loading, lattice deformation was homogeneous prior to the peak stress before falling sharply due to the creation of a (one strut wide) shear band at around 45° to the compression axis. The specific yield strength expressed as the yield stress/(yield stress of the aluminium × relative density) is not independent of processing conditions, suggesting that further improvements in properties can be achieved by process optimisation. Lattice struts failed near nodes by a mixture of ductile and brittle fracture.

  4. A multi-faceted approach to characterize acid-sulfate alteration processes in volcanic hydrothermal systems on Earth and Mars

    Science.gov (United States)

    Marcucci, Emma Cordts

    Acid-sulfate alteration is a dominant weathering process in high temperature, low pH, sulfur-rich volcanic environments. Additionally, hydrothermal environments have been proposed as locations where life could have originated on Earth. Based on the extensive evidence of flowing surface water and persistent volcanism, similar locations and processes could have existed on early Mars. Globally observed alteration mineral assemblages likely represent relic Martian hydrothermal settings. Yet the limited understanding of environmental controls, limits the confidence of interpreting the paleoconditions of these hydrothermal systems and assessing their habitability to support microbial life. This thesis presents a series of laboratory experiments, geochemical models, analog fieldwork, and Martian remote sensing to characterize distinguishing features and controls of acid-sulfate alteration. The experiments and models were designed to replicate alteration is a highly acidic, sulfurous, and hot field sites. The basaltic minerals were individually reacted in both experimental and model simulations with varying initial parameters to infer the geochemical pathways of acid-sulfate alteration on Earth and Mars. It was found that for a specific starting material, secondary mineralogies were consistent. Variations in pH, temperature and duration affected the abundance, shape, and size of mineral products. Additionally evaporation played a key role in secondary deposits; therefore, both alteration and evaporitic processes need to be taken into consideration. Analog volcanic sites in Nicaragua were used to supplement this work and highlight differences between natural and simulated alteration. In situ visible near-infrared spectroscopy demonstrated that primary lithology and gas chemistry were dominant controls of alteration, with secondary effects from environmental controls, such as temperature and pH. The spectroscopic research from the field was directly related to Mars

  5. Igneous Hydrothermal Alteration and Ore-Forming Processes in the Land's End Granite, Nanjizal

    OpenAIRE

    Eik, Marte

    2015-01-01

    This study addresses the hydrothermal alteration and mineralization related to a system of tourmaline-quartz veins intersecting biotite-granite in Nanjizal, in the Land s End granites of the cornubian batholith. Nanjizal is an important site as it is one of the few locations in the southern segment of the Land s End Granite where magmatic-hydrothermal tin mineralizations have been mined. The aim is to identify the alteration-patterns and their correlation with hydrothermal ore-forming events ...

  6. Alteration of immature sedimentary rocks on Earth and Mars. Recording Aqueous and Surface-atmosphere Processes

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, Kenneth M. [Brown Univ., Providence, RI (United States); Mustard, John F. [Brown Univ., Providence, RI (United States); Salvatore, Mark R. [Arizona State Univ., Mesa, AZ (United States)

    2015-03-05

    The rock alteration and rind formation in analog environments like Antarctica may provide clues to rock alteration and therefore paleoclimates on Mars. Clastic sedimentary rocks derived from basaltic sources have been studied in situ by martian rovers and are likely abundant on the surface of Mars. Moreover, how such rock types undergo alteration when exposed to different environmental conditions is poorly understood compared with alteration of intact basaltic flows. Here we characterize alteration in the chemically immature Carapace Sandstone from Antarctica, a terrestrial analog for martian sedimentary rocks. We employ a variety of measurements similar to those used on previous and current Mars missions. Laboratory techniques included bulk chemistry, powder X-ray diffraction (XRD), hyperspectral imaging and X-ray absorption spectroscopy. Through these methods we find that primary basaltic material in the Carapace Sandstone is pervasively altered to hydrated clay minerals and palagonite as a result of water–rock interaction. A thick orange rind is forming in current Antarctic conditions, superimposing this previous aqueous alteration signature. The rind exhibits a higher reflectance at visible-near infrared wavelengths than the rock interior, with an enhanced ferric absorption edge likely due to an increase in Fe3+ of existing phases or the formation of minor iron (oxy)hydroxides. This alteration sequence in the Carapace Sandstone results from decreased water–rock interaction over time, and weathering in a cold, dry environment, mimicking a similar transition early in martian history. This transition may be recorded in sedimentary rocks on Mars through a similar superimposition mechanism, capturing past climate changes at the hand sample scale. These results also suggest that basalt-derived sediments could have sourced significant volumes of hydrated minerals on early Mars due to their greater permeability compared with intact igneous rocks.

  7. The Cellular Processing Capacity Limits the Amounts of Chimeric U7 snRNA Available for Antisense Delivery.

    Science.gov (United States)

    Eckenfelder, Agathe; Tordo, Julie; Babbs, Arran; Davies, Kay E; Goyenvalle, Aurélie; Danos, Olivier

    2012-06-26

    Many genetic diseases are induced by mutations disturbing the maturation of pre-mRNAs, often affecting splicing. Antisense oligoribonucleotides (AONs) have been used to modulate splicing thereby circumventing the deleterious effects of mutations. Stable delivery of antisense sequences is achieved by linking them to small nuclear RNA (snRNAs) delivered by viral vectors, as illustrated by studies where therapeutic exon skipping was obtained in animal models of Duchenne muscular dystrophy (DMD). Yet, clinical translation of these approaches is limited by the amounts of vector to be administered. In this respect, maximizing the amount of snRNA antisense shuttle delivered by the vector is essential. Here, we have used a muscle- and heart-specific enhancer (MHCK) to drive the expression of U7 snRNA shuttles carrying antisense sequences against the human or murine DMD pre-mRNAs. Although antisense delivery and subsequent exon skipping were improved both in tissue culture and in vivo, we observed the formation of additional U7 snRNA by-products following gene transfer. These included aberrantly 3' processed as well as unprocessed species that may arise because of the saturation of the cellular processing capacity. Future efforts to increase the amounts of functional U7 shuttles delivered into a cell will have to take this limitation into account.

  8. Brain morphological alterations and cellular metabolic changes in patients with generalized anxiety disorder: A combined DARTEL-based VBM and (1)H-MRS study.

    Science.gov (United States)

    Moon, Chung-Man; Jeong, Gwang-Woo

    2016-05-01

    Generalized anxiety disorder (GAD) is characterized by emotional dysregulation and cognitive deficit in conjunction with brain morphometric and metabolic alterations. This study assessed the combined neural morphological deficits and metabolic abnormality in patients with GAD. Thirteen patients with GAD and 13 healthy controls matched for age, sex, and education level underwent high-resolution T1-weighted MRI and proton magnetic resonance spectroscopy ((1)H-MRS) at 3Tesla. In this study, the combination of voxel-based morphometry (VBM) and (1)H-MRS was used to assess the brain morphometric and metabolic alterations in GAD. The patients showed significantly reduced white matter (WM) volumes in the midbrain (MB), precentral gyrus (PrG), dorsolateral prefrontal cortex (DLPFC) and anterior limb of the internal capsule (ALIC) compared to the controls. In MRS study, the choline/creatine (Cho/Cr) and choline/N-acetylaspartate (Cho/NAA) ratios in the DLPFC were significantly lower in the patients. Particularly, the WM volume variation of the DLPFC was positively correlated with both of the Cho/Cr and Cho/NAA ratios in patients with GAD. This study provides an evidence for the association between the morphometric deficit and metabolic changes in GAD. This finding would be helpful to understand the neural dysfunction and pathogenesis in connection with cognitive impairments in GAD.

  9. 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

  10. Determination of Cellular Processing Rates for a Trastuzumab-Maytansinoid Antibody-Drug Conjugate (ADC) Highlights Key Parameters for ADC Design

    OpenAIRE

    Maass, Katie F.; Kulkarni, Chethana; Betts, Alison M.; Wittrup, K. Dane

    2016-01-01

    Antibody-drug conjugates (ADCs) are a promising class of cancer therapeutics that combine the specificity of antibodies with the cytotoxic effects of payload drugs. A quantitative understanding of how ADCs are processed intracellularly can illustrate which processing steps most influence payload delivery, thus aiding the design of more effective ADCs. In this work, we develop a kinetic model for ADC cellular processing as well as generalizable methods based on flow cytometry and fluorescence ...

  11. Determination of Cellular Processing Rates for a Trastuzumab-Maytansinoid Antibody-Drug Conjugate (ADC) Highlights Key Parameters for ADC Design

    OpenAIRE

    Kulkarni, Chethana; Maass, Katie F.; Betts, Alison M.; Wittrup, Karl Dane

    2015-01-01

    Antibody-drug conjugates (ADCs) are a promising class of cancer therapeutics that combine the specificity of antibodies with the cytotoxic effects of payload drugs. A quantitative understanding of how ADCs are processed intracellularly can illustrate which processing steps most influence payload delivery, thus aiding the design of more effective ADCs. In this work, we develop a kinetic model for ADC cellular processing as well as generalizable methods based on flow cytometry and fluorescence ...

  12. Alteration processes in igneous rocks of the michilla mining area, coastal range, northern chile, and their relation with copper mineralisation

    Science.gov (United States)

    Oliveros, V.; Aguirre, L.; Townley, B.

    2003-04-01

    A 10 km thick homoclinal sequence of intermediate volcanic and sedimentary Jurassic rocks crops out in the Michilla mining area, Coastal Range, northern Chile (22-22°45S, 70-70°15W). Cretaceous plutons, intermediate to acid in composition, intrude this sequence together with numerous small basic to acid dykes and stocks. Main deposits are stratabound Cu-(Ag) with the ore minerals emplaced at the porous tops of the volcanic flows. However, some discordant orebodies, e.g. hydrothermal breccias, exist within the manto-type deposits. The volcanic sequence, and a minor part of the plutonic rocks, have been affected by three different alteration processes, each of them with their distinct mineral assemblages reflecting that every process was developed under different physicochemical conditions. The volcanic rocks far from the mining area are affected by a regional scale alteration process, basically isochemical. Its products are typical of a low-grade event: chl + ep +qtz + ttn (+- ab +- cal) with no ore minerals associated. The temperature interval, estimated by the chlorite geothermometer, ranges between 250 and 350°C. This alteration is either due to very low grade burial metamorphism or to hydrothermalism related to the Late Jurassic - Cretaceous plutonism. Inside the mining district the volcanic rocks are affected by a local scale alteration process originated by the intrusion of small stocks and dykes. This event is characterized by strong sodic metasomatism and minor Mg mobility. Two stages probably occurred as suggested by the two main mineral assemblages present, a propylitic (ab + ep + chl + act + ttn + qtz) and a quartz-sericitic one (ab + ser + qtz + tnn). They would reflect the changes in temperature, water/rock ratio and pH conditions during the whole process. Ore minerals related to this alteration are chalcopyrite, chalcocite and minor bornite and native silver. A temperature interval of 200-300°C is indicated by the chlorite geothermometer for the

  13. Caspase-9 inhibitor Z-LEHD-FMK enhances the yield of in vitro produced buffalo (Bubalus bubalis) pre-implantation embryos and alters cellular stress response.

    Science.gov (United States)

    Mullani, N; Singh, M K; Sharma, A; Rameshbabu, K; Manik, R S; Palta, P; Singla, S K; Chauhan, M S

    2016-02-01

    The present investigation was done to study the effect of caspase-9 inhibitor Z-LEHD-FMK, on in vitro produced buffalo embryos. Z-LEHD-FMK is a cell-permeable, competitive and irreversible inhibitor of enzyme caspase-9, which helps in cell survival. Buffalo ovaries were collected from slaughterhouse and the oocytes were subjected to in vitro maturation (IVM), in vitro fertilization (IVF) and in vitro culture (IVC). The culture medium was supplemented with Z-LEHD-FMK at different concentrations i.e. 0 μM (control), 10 μM, 20 μM, 30 μM and 50 μM during IVM and IVC respectively. After day-2 post-insemination, the cleavage rate was significantly higher (74.20 ± 5.87% at PZ-LEHD-FMK than at any other concentration. Same trend was observed in the blastocyst production rate which was higher at 20 μM (27.42 ± 2.94% at PZ-LEHD-FMK which showed apoptotic index significantly lower (1.88 ± 0.87 at PZ-LEHD-FMK treated blastocysts. The quantitative gene expression of CHOP and HSP10 genes showed significant increase (PZ-LEHD-FMK, while, HSP40 showed significant increase (PZ-LEHD-FMK concentrations. From the afore mentioned results we conclude that, Z-LEHD-FMK at 20 μM increased the cleavage and blastocyst rate of buffalo pre-implantation embryos also affecting the rate of apoptosis and cellular stress at various concentrations.

  14. New role of lupeol in reticence of angiogenesis, the cellular parameter of neoplastic progression in tumorigenesis models through altered gene expression.

    Science.gov (United States)

    Vijay Avin, B R; Prabhu, T; Ramesh, C K; Vigneshwaran, V; Riaz, Mahmood; Jayashree, K; Prabhakar, B T

    2014-05-30

    There is a major unmet medical need for effective and well tolerated treatment options for cancer. The search now seeks to identify active biomolecules with multiple targets. Lupeol, an important dietary triterpenoid known as anticarcinogen by inducing apoptosis. But it is still more to reveal the potency of lupeol in the inhibition of neovascularization in cancer context. The study aimed to explore the efficacy of the lupeol in targeting angiogenesis. In this study, the inhibition of neovessel formation was assessed by preliminary antiangiogenesis assays like chorio allontoic membrane (CAM) and rat corneal micro pocket models. Further, validated for the micro vessel density (MVD) in histological sections of peritoneum, solid tumor and xenograft tumor by immunostaining with anti CD31 antibody. Antitumor potency was verified in ascites carcinoma, solid lymphoma and human nueroblastoma xenograft in CAM. Altered angiogenic gene expression by RT-PCR, ELISA and gelatin zymography. Lupeol significantly inhibits the neovessel formation in CAM and in the rat cornea. The similar effect was ascertained in mice and human xenograft tumor models with the regressed growth. Eventually reflecting on the differential transcription of angiogenic genes like MMP-2 & 9, HIF-1α, VEGFa and Flt-1 was noteworthy. It is now evident from our studies that, a new avenue of dietary triterpenoid lupeol by targeting angiogenesis, potentially inferring the multimode action in cancer prevention.

  15. Immunoendocrine alterations following Marine Corps Martial Arts training are associated with changes in moral cognitive processes.

    Science.gov (United States)

    Siedlik, Jacob A; Deckert, Jake A; Clopton, Aaron W; Gigliotti, Nicole; Chan, Marcia A; Benedict, Stephen H; Herda, Trent J; Gallagher, Philip M; Vardiman, John P

    2016-02-01

    Combined physical and psychological stress events have been associated with exacerbated endocrine responses and increased alterations in immune cell trafficking when compared to exercise stress alone. Military training programs are rigorous in nature and often purposefully delivered in environments combining high levels of both physical and mental stress. The objective of this study was to assess physiological and cognitive changes following U.S. Marine Corps Martial Arts training. Seven active-duty, male Marines were observed during a typical Marine Corps Martial Arts training session. Immune parameters, including immunomodulatory cytokines, and hormone concentrations were determined from blood samples obtained at baseline, immediately post training (IP) and at 15min intervals post-training to 1h (R15, R30, R45, R60). Assessments of cognitive moral functioning (moral judgment and intent) were recorded at intervals during recovery. There were significant fluctuations in immunoendocrine parameters. Peak endocrine measures were observed within the IP-R15 time interval. Distributions of circulating immune cells were significantly altered with neutrophils and all lymphocyte subsets elevated at IP. IFN-γ and IL-17a exhibited small, non-significant, parallel increases over the recovery period. Moral functioning was informed by different social identities during the recovery resulting in changes in moral decision-making. These data demonstrate that the Marine Corps Martial Arts Program induces significant alterations in lymphocyte and leukocyte distributions, but does not shift the balance of Th1/Th2 cytokines or induce a systemic inflammatory response. The program does, however, induce alterations in moral decision-making ability associated with the observed endocrine responses, even suggesting a potential interaction between one's social identities and endocrine responses upon moral decision-making.

  16. Aqueous alteration in CR chondrites: Meteorite parent body processes as analogue for long-term corrosion processes relevant for nuclear waste disposal

    Science.gov (United States)

    Morlok, Andreas; Libourel, Guy

    2013-02-01

    Aqueous alteration of carbonaceous chondrites is one of the fundamental processes on accreting planetesimals that changes pristine materials from the formation of the Solar System. The study of mineralogical, petrological and chemical changes resulting from this alteration provides insight into the physical and chemical setting of forming planetesimals. CR chondrites provide samples for all stages of aqueous alteration, from type 3 to 1 (entirely hydrated), and are thus suited to study the alteration of pristine materials in a coherent sequence. Vitrification is a common way to store and stabilize fission products and minor actinides resulting from the reprocessing of nuclear spent fuel in a nuclear boro-silica glass in steel containers. The waste material has to be stored safely for a period of at least 105-106 years in a clay-rich geological repository. Laboratory experiments being too short to follow the long-term evolution of these materials, we analyzed the mineralogical, petrological and chemical changes in a series of CR chondrites (Renazzo CR2, Al Rais CR2, and GRO 95577 CR1) to serve as analogues. Rims of secondary materials around metal grains in contact to the fine-grained matrix serve as analogue to the interface between steel containment and the surrounding clay-rich geological layer, while chondrule glassy mesostasis is used as a proxy of the nuclear glass. With increasing degree of aqueous alteration in the sequence, Renazzo → Al Rais → GRO 95577, the size of the rims increase. Fe-rich alteration rims are ˜10 μm in thickness around metal grains in the fine-grained matrix in Renazzo. In Al Rais, multi-layered structures of interchanging Fe, S and P/Ca-rich layers appear, with a thickness of up to ˜30 μm. In the highly altered GRO 95577, extensive inner and external rims of secondary phases reach up to ˜200 μm into the surrounding matrix. In chondrules, metal in contact with the altered mesostasis shows similar trends, but with thinner

  17. Microglia in the mouse retina alter the structure and function of retinal pigmented epithelial cells: a potential cellular interaction relevant to AMD.

    Directory of Open Access Journals (Sweden)

    Wenxin Ma

    Full Text Available BACKGROUND: Age-related macular degeneration (AMD is a leading cause of legal blindness in the elderly in the industrialized word. While the immune system in the retina is likely to be important in AMD pathogenesis, the cell biology underlying the disease is incompletely understood. Clinical and basic science studies have implicated alterations in the retinal pigment epithelium (RPE layer as a locus of early change. Also, retinal microglia, the resident immune cells of the retina, have been observed to translocate from their normal position in the inner retina to accumulate in the subretinal space close to the RPE layer in AMD eyes and in animal models of AMD. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we examined the effects of retinal microglia on RPE cells using 1 an in vitro model where activated retinal microglia are co-cultured with primary RPE cells, and 2 an in vivo mouse model where retinal microglia are transplanted into the subretinal space. We found that retinal microglia induced in RPE cells 1 changes in RPE structure and distribution, 2 increased expression and secretion of pro-inflammatory, chemotactic, and pro-angiogenic molecules, and 3 increased extent of in vivo choroidal neovascularization in the subretinal space. CONCLUSIONS/SIGNIFICANCE: These findings share similarities with important pathological features found in AMD and suggest the relevance of microglia-RPE interactions in AMD pathogenesis. We speculate that the migration of retinal microglia into the subretinal space in early stages of the disease induces significant changes in RPE cells that perpetuate further microglial accumulation, increase inflammation in the outer retina, and fosters an environment conducive for the formation of neovascular changes responsible for much of vision loss in advanced AMD.

  18. PREFACE: Selected papers from the Fourth Annual q-bio Conference on Cellular Information Processing Selected papers from the Fourth Annual q-bio Conference on Cellular Information Processing

    Science.gov (United States)

    Nemenman, Ilya; Faeder, James R.; Hlavacek, William S.; Jiang, Yi; Wall, Michael E.; Zilman, Anton

    2011-10-01

    Summary This special issue consists of 11 original papers that elaborate on work presented at the Fourth Annual q-bio Conference on Cellular Information Processing, which was held on the campus of St John's College in Santa Fe, New Mexico, USA, 11-14 August 2010. Now in its fourth year, the q-bio conference has changed considerably over time. It is now well established and a major event in systems biology. The 2010 conference saw attendees from all continents (except Antarctica!) sharing novel results and participating in lively discussions at both the oral and poster sessions. The conference was oversubscribed and grew to 27 contributed talks, 16 poster spotlights and 137 contributed posters. We deliberately decreased the number of invited speakers to 21 to leave more space for contributed presentations, and the attendee feedback confirmed that the choice was a success. Although the q-bio conference has grown and matured, it has remained true to the original goal of being an intimate and dynamic event that brings together modeling, theory and quantitative experimentation for the study of cell regulation and information processing. Funded in part by a grant from NIGMS and by DOE funds through the Los Alamos National Laboratory Directed Research and Development program, the conference has continued to exhibit youth and vigor by attracting (and partially supporting) over 100 undergraduate, graduate and postdoctoral researchers. The associated q-bio summer school, which precedes the conference each year, further emphasizes the development of junior scientists and makes q-bio a singular event in its impact on the future of quantitative biology. In addition to an increased international presence, the conference has notably diversified its demographic representation within the USA, including increased participation from the southeastern corner of the country. One big change in the conference this year is our new publication partner, Physical Biology. Although we are very

  19. Altered cellular infiltration and cytokine levels during early Mycobacterium tuberculosis sigC mutant infection are associated with late-stage disease attenuation and milder immunopathology in mice

    Directory of Open Access Journals (Sweden)

    McMurray David N

    2008-09-01

    Full Text Available Abstract Background Mouse virulence assessments of certain Mycobacterium tuberculosis mutants have revealed an immunopathology defect in which high tissue CFU counts are observed but the tissue pathology and lethality are reduced. M. tuberculosis mutants which grow and persist in the mouse lungs, but have attenuated disease progression, have the immunopathology (imp phenotype. The antigenic properties of these strains may alter the progression of disease due to a reduction in host immune cell recruitment to the lungs resulting in disease attenuation and prolonged host survival. Results In this study we focused on the mouse immune response to one such mutant; the M. tuberculosis ΔsigC mutant. Aerosol infection of DBA/2 and SCID mice with the M. tuberculosis ΔsigC mutant, complemented mutant and wild type strain showed proliferation of mutant bacilli in mouse lungs, but with decreased inflammation and mortality in DBA/2 mice. SCID mice shared the same phenotype as the DBA/2 mice in response to the ΔsigC mutant, however, they succumbed to the infection faster. Bronchoalveolar lavage (BAL fluid analysis revealed elevated numbers of infiltrating neutrophils in the lungs of mice infected with wild type and complemented ΔsigC mutant strains but not in mice infected with the ΔsigC mutant. In addition, DBA/2 mice infected with the ΔsigC mutant had reduced levels of TNF-α, IL-1β, IL-6 and IFN-γ in the lungs. Similarly, there was a reduction in proinflammatory cytokines in the lungs of SCID mice. In contrast to the mouse model, the ΔsigC mutant had reduced initial growth in guinea pig lungs. A possible mechanism of attenuation in the ΔsigC mutant may be a reduction in neutrophilic-influx in the alveolar spaces of the lungs, and decreased proinflammatory cytokine secretion. In contrast to mouse data, the M. tuberculosis ΔsigC mutant proliferates slowly in guinea pig lungs, a setting characterized by caseating necrosis. Conclusion Our

  20. Insight into the impact of dietary saturated fat on tissue-specific cellular processes underlying obesity-related diseases.

    Science.gov (United States)

    Enos, Reilly T; Velázquez, Kandy T; Murphy, E Angela

    2014-06-01

    This study investigated the influence of three high-fat diets (HFDs), differing in the percentage of total calories from saturated fat (SF) (6%, 12%, 24%) but identical in total fat (40%), for a 16-week period in mice on a variety of tissue-specific cellular processes believed to be at the root of obesity-related diseases. Specifically, we examined ectopic lipid accumulation, oxidative capacity [peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) mRNA and protein; mtDNA; Cox IV and cytochrome C protein; citrate synthase activity; and gene expression of fission 1, mitofusin (Mfn) 1 and Mfn2], oxidative stress (4-hydroxy-2-nonenal), endoplasmic reticulum (ER) stress (binding immunoglobulin protein, activating transcription factor 6-p50, p-eukaryotic initiation factor 2 alpha and x-box binding protein 1 spliced protein), inflammatory [p-c-Jun N-terminal kinase (JNK), p-nuclear factor kappa-B, p-p38 mitogen-activated protein kinase) and insulin signaling (p-Akt), and inflammation [tumor necrosis factor-alpha, monocyte chemotactic protein-1, interleukin-6, F4/80, toll-like receptor (TLR)2 and TLR4 gene expression] in various tissues, including the adipose tissue, liver, skeletal muscle and heart. In general, adipose and hepatic tissues were the only tissues which displayed evidence of dysfunction. All HFDs down-regulated adipose, cardiac and hepatic PGC-1α mRNA and hepatic citrate synthase activity, and induced adipose tissue oxidative stress, whereas only the 6%-SF and 12%-SF diet produced hepatic steatosis. However, compared to the 6%-SF and 24%-SF diets, consumption of the 12%-SF diet resulted in the greatest degree of dysregulation (hepatic ER and oxidative stress, JNK activation, increased F4/80 gene expression and down-regulation of adipose tissue Akt signaling). These findings suggest that the saturated fatty acid composition of an HFD can greatly influence the processes responsible for obesity-related diseases - nonalcoholic fatty

  1. A two years simulation using a real data cellular automaton: A predictive case study with the schistosomiasis expansion process along the coastline of Brazil

    OpenAIRE

    Albuquerque,Jones O.; Bocanegra,Silvana; Ferrer-Savall, Jordi; López Codina, Daniel; Souza, Marco Antônio de; Souza Santos, Reinaldo; Barbosa, Constança

    2013-01-01

    This work presents a Cellular Automata model to characterize the social and environmental factors which contribute for the analysis of the expansion process of Schistosoma mansoni infection in Pernambuco - Brazil. The model has been experimented with a set of two years real data from a study area at North Coast of Pernambuco – Brazil. The main constraint equations, the modelling process and the results obtained until now with the simulating scenarios generated are presented here. The results ...

  2. Alteration of Fractured Rocks Due to Coupled Chemical and Mechanical Processes: High-Resolution Simulations and Experimental Observations

    Science.gov (United States)

    Ameli, Pasha

    Engineering activities such as enhanced geothermal energy production and improved oil recovery techniques are heavily dependent on the permeability of the subsurface, while others such as CO2 sequestration and nuclear waste disposal rely on the efficiency of rock formations as transport barriers. In either case fractures provide the main pathways for fluid flow and transport, especially in rocks with lower matrix porosity. Laboratory experiments aimed at quantifying the chemo-mechanical responses of fractures have shown a range of results, some of which contradict simple conceptual models. For example, under conditions favoring mineral dissolution, where one would expect an overall increase in permeability, experiments show that permeability increases under some conditions and decreases under others. Recent experiments have attempted to link these core-scale observations to the relevant small-scale processes occurring within fractures. Results suggest that the loss of mechanical strength in asperities due to chemical alteration may cause non-uniform deformation and alteration of fracture apertures. However, due to the lack of direct micro-scale measurements of the coupled chemical and mechanical processes that lead to alteration of contacting fracture surfaces, our ability to predict the long-term evolution of fractures is still limited. To explore the processes that control permeability evolution, I developed a computational model that uses micro-scale surface roughness and explicitly couples dissolution and elastic deformation to calculate local alterations in fracture aperture under chemical and mechanical stresses. A depth-averaged algorithm of fracture flow is used to model reactive transport and chemical alteration of the fracture surfaces. Then, I deform the resulting altered fracture-surfaces using an algorithm that calculates the elastic deformation. The results of the model are compared with flow-through experiments conducted on fractured limestone. The

  3. A meta-analysis to evaluate the cellular processes regulated by the interactome of endogenous and over-expressed estrogen receptor alpha.

    Science.gov (United States)

    Simões, Joana; Amado, Francisco M; Vitorino, Rui; Helguero, Luisa A

    2015-01-01

    The nature of the proteins complexes that regulate ERα subcellular localization and activity is still an open question in breast cancer biology. Identification of such complexes will help understand development of endocrine resistance in ER+ breast cancer. Mass spectrometry (MS) has allowed comprehensive analysis of the ERα interactome. We have compared six published works analyzing the ERα interactome of MCF-7 and HeLa cells in order to identify a shared or different pathway-related fingerprint. Overall, 806 ERα interacting proteins were identified. The cellular processes were differentially represented according to the ERα purification methodology, indicating that the methodologies used are complementary. While in MCF-7 cells, the interactome of endogenous and over-expressed ERα essentially represents the same biological processes and cellular components, the proteins identified were not over-lapping; thus, suggesting that the biological response may differ as the regulatory/participating proteins in these complexes are different. Interestingly, biological processes uniquely associated to ERα over-expressed in HeLa cell line included L-serine biosynthetic process, cellular amino acid biosynthetic process and cell redox homeostasis. In summary, all the approaches analyzed in this meta-analysis are valid and complementary; in particular, for those cases where the processes occur at low frequency with normal ERα levels, and can be identified when the receptor is over-expressed. However special effort should be put into validating these findings in cells expressing physiological ERα levels.

  4. Cellular automata

    CERN Document Server

    Codd, E F

    1968-01-01

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

  5. Suitability of the cellular viability technique as a control tool of the chlorine dosage on the activated sludge of a biological process affected by bulking; Empleo de la viabilidad celular como herramienta para el control de la dosificacion de cloro sobre un fango activado con problemas de bulking

    Energy Technology Data Exchange (ETDEWEB)

    Montaya Martinez, T.; Zornoza Zornoza, A.; Granell Munoz, P.; Fayos, G.; Fajarddo, V.; Zorrilla, F.; Alonso Molina, J. L.; Morenilla Martinez, J. J.; Bernacer Bonora, I.; Martinez Francisco, F. J.

    2009-07-01

    This work demonstrates the suitability of the cellular viability technique as a control tool of the chlorine dosage on the activated sludge of a biological process affected by the overabundance of the filamentous bacteria (Thiothrix-021N). This technique was used to establish the chlorine dosage according to the observed damages on cellular membranes of both, floc-forming bacteria as well as filamentous bacteria. To identify the filamentous bacteria responsible for the macro-structural alteration of the flocs, several criteria were, met, including morphologic characteristics as well as conventional microbiological stains: Gram, Neisser and polyhydroxy alkanoates. FISH was used to confirm the obtained results, providing a definitive identification of the filamentous bacteria responsible for the alteration. (Author) 11 refs.

  6. Personal exploration: Serendipity and intentionality as altering positions in a creative process

    Directory of Open Access Journals (Sweden)

    Maarit Mäkelä

    2016-06-01

    Full Text Available Artists and designers have recently begun to take an active role in contextualising the creative process in relation to their practice. Thus, understanding how the creative mind proceeds has been supplemented with knowledge obtained inside the creative process. In this way, the spheres of knowledge, material thinking and experience that are fostered through creative work have become entangled and embedded as elemental parts of the research process. This article is based on documentation and reflection of the author’s creative practice in contemporary ceramic art at the beginning of 2015. The article discusses how the creative process proceeds by alternating between two positions: serendipity and intentionality. By describing the different phases of the process, it reveals the interplay between the diverse range of activities and how these gradually construct the creative process

  7. Carbon nanotubes affect the toxicity of CuO nanoparticles to denitrification in marine sediments by altering cellular internalization of nanoparticle

    Science.gov (United States)

    Zheng, Xiong; Su, Yinglong; Chen, Yinguang; Wan, Rui; Li, Mu; Huang, Haining; Li, Xu

    2016-06-01

    Denitrification is an important pathway for nitrate transformation in marine sediments, and this process has been observed to be negatively affected by engineered nanomaterials. However, previous studies only focused on the potential effect of a certain type of nanomaterial on microbial denitrification. Here we show that the toxicity of CuO nanoparticles (NPs) to denitrification in marine sediments is highly affected by the presence of carbon nanotubes (CNTs). It was found that the removal efficiency of total NOX‑-N (NO3‑-N and NO2‑-N) in the presence of CuO NPs was only 62.3%, but it increased to 81.1% when CNTs appeared in this circumstance. Our data revealed that CuO NPs were more easily attached to CNTs rather than cell surface because of the lower energy barrier (3.5 versus 36.2 kT). Further studies confirmed that the presence of CNTs caused the formation of large, incompact, non-uniform dispersed, and more negatively charged CuO-CNTs heteroaggregates, and thus reduced the nanoparticle internalization by cells, leading to less toxicity to metabolism of carbon source, generation of reduction equivalent, and activities of nitrate reductase and nitrite reductase. These results indicate that assessing nanomaterial-induced risks in real circumstances needs to consider the “mixed” effects of nanomaterials.

  8. Binding of EBP50 to Nox organizing subunit p47phox is pivotal to cellular reactive species generation and altered vascular phenotype.

    Science.gov (United States)

    Al Ghouleh, Imad; Meijles, Daniel N; Mutchler, Stephanie; Zhang, Qiangmin; Sahoo, Sanghamitra; Gorelova, Anastasia; Henrich Amaral, Jefferson; Rodríguez, Andrés I; Mamonova, Tatyana; Song, Gyun Jee; Bisello, Alessandro; Friedman, Peter A; Cifuentes-Pagano, M Eugenia; Pagano, Patrick J

    2016-09-06

    Despite numerous reports implicating NADPH oxidases (Nox) in the pathogenesis of many diseases, precise regulation of this family of professional reactive oxygen species (ROS) producers remains unclear. A unique member of this family, Nox1 oxidase, functions as either a canonical or hybrid system using Nox organizing subunit 1 (NoxO1) or p47(phox), respectively, the latter of which is functional in vascular smooth muscle cells (VSMC). In this manuscript, we identify critical requirement of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50; aka NHERF1) for Nox1 activation and downstream responses. Superoxide (O2 (•-)) production induced by angiotensin II (AngII) was absent in mouse EBP50 KO VSMC vs. WT. Moreover, ex vivo incubation of aortas with AngII showed a significant increase in O2 (•-) in WT but not EBP50 or Nox1 nulls. Similarly, lipopolysaccharide (LPS)-induced oxidative stress was attenuated in femoral arteries from EBP50 KO vs. WT. In silico analyses confirmed by confocal microscopy, immunoprecipitation, proximity ligation assay, FRET, and gain-/loss-of-function mutagenesis revealed binding of EBP50, via its PDZ domains, to a specific motif in p47(phox) Functional studies revealed AngII-induced hypertrophy was absent in EBP50 KOs, and in VSMC overexpressing EBP50, Nox1 gene silencing abolished VSMC hypertrophy. Finally, ex vivo measurement of lumen diameter in mouse resistance arteries exhibited attenuated AngII-induced vasoconstriction in EBP50 KO vs. WT. Taken together, our data identify EBP50 as a previously unidentified regulator of Nox1 and support that it promotes Nox1 activity by binding p47(phox) This interaction is pivotal for agonist-induced smooth muscle ROS, hypertrophy, and vasoconstriction and has implications for ROS-mediated physiological and pathophysiological processes.

  9. 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

  10. Expertise in folk music alters the brain processing of Western harmony.

    Science.gov (United States)

    Tervaniemi, M; Tupala, T; Brattico, E

    2012-04-01

    In various paradigms of modern neurosciences of music, experts of Western classical music have displayed superior brain architecture when compared with individuals without explicit training in music. In this paper, we show that chord violations embedded in musical cadences were neurally processed in a facilitated manner also by musicians trained in Finnish folk music. This result, obtained by using early right anterior negativity (ERAN) as an index of harmony processing, suggests that tonal processing is advanced in folk musicians by their long-term exposure to both Western and non-Western music.

  11. Intracellular insulin processing is altered in monocytes from patients with type II diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Trischitta, V.; Benzi, L.; Brunetti, A.; Cecchetti, P.; Marchetti, P.; Vigneri, R.; Navalesi, R.

    1987-05-01

    We studied total cell-associated A14-(/sup 125/I)insulin radioactivity (including surface-bound and internalized radioactivity), insulin internalization, and its intracellular degradation at 37 C in monocytes from nonobese type II untreated diabetic patients (n = 9) and normal subjects (n = 7). Total cell-associated radioactivity was decreased in diabetic patients (2.65 +/- 1.21% (+/- SD) vs. 4.47 +/- 1.04% of total radioactivity. Insulin internalization was also reduced in diabetic patients (34.0 +/- 6.8% vs. 59.0 +/- 11.3% of cell-associated radioactivity. Using high performance liquid chromatography six intracellular forms of radioactivity derived from A14-(/sup 125/I) insulin were identified; 10-20% of intracellular radioactivity had approximately 300,000 mol wt and was identified as radioactivity bound to the insulin receptor, and the remaining intracellular radioactivity included intact A14-(/sup 125/I)insulin, (/sup 125/I)iodide, or (/sup 125/I)tyrosine, and three intermediate compounds. A progressive reduction of intact insulin and a corresponding increase in iodine were found when the incubation time was prolonged. Intracellular insulin degradation was reduced in monocytes from diabetic patients; intracellular intact insulin was 65.6 +/- 18.1% vs. 37.4 +/- 18.0% of intracellular radioactivity after 2 min and 23.6 +/- 22.3% vs. 3.9 +/- 2.3% after 60 min in diabetic patients vs. normal subjects, respectively. In conclusion, 1) human monocytes internalize and degrade insulin in the intracellular compartment in a stepwise time-dependent manner; and 2) in monocytes from type II diabetic patients total cell-associated radioactivity, insulin internalization, and insulin degradation are significantly reduced. These defects may be related to the cellular insulin resistance present in these patients.

  12. Climate-induced changes in bottom-up and top-down processes independently alter a marine ecosystem.

    Science.gov (United States)

    Jochum, Malte; Schneider, Florian D; Crowe, Tasman P; Brose, Ulrich; O'Gorman, Eoin J

    2012-11-05

    Climate change has complex structural impacts on coastal ecosystems. Global warming is linked to a widespread decline in body size, whereas increased flood frequency can amplify nutrient enrichment through enhanced run-off. Altered population body-size structure represents a disruption in top-down control, whereas eutrophication embodies a change in bottom-up forcing. These processes are typically studied in isolation and little is known about their potential interactive effects. Here, we present the results of an in situ experiment examining the combined effects of top-down and bottom-up forces on the structure of a coastal marine community. Reduced average body mass of the top predator (the shore crab, Carcinus maenas) and nutrient enrichment combined additively to alter mean community body mass. Nutrient enrichment increased species richness and overall density of organisms. Reduced top-predator body mass increased community biomass. Additionally, we found evidence for an allometrically induced trophic cascade. Here, the reduction in top-predator body mass enabled greater biomass of intermediate fish predators within the mesocosms. This, in turn, suppressed key micrograzers, which led to an overall increase in microalgal biomass. This response highlights the possibility for climate-induced trophic cascades, driven by altered size structure of populations, rather than species extinction.

  13. Alterations in welding process voltage affect the generation of ultrafine particles, fume composition, and pulmonary toxicity.

    Science.gov (United States)

    Antonini, James M; Keane, Michael; Chen, Bean T; Stone, Samuel; Roberts, Jenny R; Schwegler-Berry, Diane; Andrews, Ronnee N; Frazer, David G; Sriram, Krishnan

    2011-12-01

    The goal was to determine if increasing welding voltage changes the physico-chemical properties of the fume and influences lung responses. Rats inhaled 40 mg/m³ (3 h/day × 3 days) of stainless steel (SS) welding fume generated at a standard voltage setting of 25 V (regular SS) or at a higher voltage (high voltage SS) of 30 V. Particle morphology, size and composition were characterized. Bronchoalveolar lavage was performed at different times after exposures to assess lung injury. Fumes collected from either of the welding conditions appeared as chain-like agglomerates of nanometer-sized primary particles. High voltage SS welding produced a greater number of ultrafine-sized particles. Fume generated by high voltage SS welding was higher in manganese. Pulmonary toxicity was more substantial and persisted longer after exposure to the regular SS fume. In summary, a modest raise in welding voltage affected fume size and elemental composition and altered the temporal lung toxicity profile.

  14. 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.

  15. Altered Topology in Information Processing of a Narrated Story in Older Adults with Mild Cognitive Impairment.

    Science.gov (United States)

    Yogev-Seligmann, Galit; Oren, Noga; Ash, Elissa L; Hendler, Talma; Giladi, Nir; Lerner, Yulia

    2016-05-03

    The ability to store, integrate, and manipulate information declines with aging. These changes occur earlier, faster, and to a greater degree as a result of neurodegeneration. One of the most common and early characteristics of cognitive decline is difficulty with comprehension of information. The neural mechanisms underlying this breakdown of information processing are poorly understood. Using functional MRI and natural stimuli (e.g., stories), we mapped the neural mechanisms by which the human brain accumulates and processes information with increasing duration and complexity in participants with amnestic mild cognitive impairment (aMCI) and healthy older adults. To explore the mechanisms of information processing, we measured the reliability of brain responses elicited by listening to different versions of a narrated story created by segmenting the story into words, sentences, and paragraphs and then scrambling the segments. Comparing healthy older adults and participants with aMCI revealed that in both groups, all types of stimuli similarly recruited primary auditory areas. However, prominent differences between groups were found at the level of processing long and complex stimuli. In healthy older adults, parietal and frontal regions demonstrated highly synchronized responses in both the paragraph and full story conditions, as has been previously reported in young adults. Participants with aMCI, however, exhibited a robust functional shift of long time scale processing to the pre- and post-central sulci. Our results suggest that participants with aMCI experienced a functional shift of higher order auditory information processing, possibly reflecting a functional response to concurrent or impending neuronal or synaptic loss. This observation might assist in understanding mechanisms of cognitive decline in aMCI.

  16. Hydrothermal Alteration Zoning and Kinetic Process of Mineral-Water Interactions

    Institute of Scientific and Technical Information of China (English)

    张荣华; 胡书敏; 苏艳丰

    2002-01-01

    This study reports the kinetic experimental results of albite in water and in KCl solution at 22 MPa in the temperature range of 25 to 400(C. Kinetic experiments have been carried out in an open flow-through reaction system (packed bed reactor). Albite dissolution is always incongruent in water at most temperatures, but becomes congruent at 300(C (close to the critical point 374(C). At temperatures from 25 to 300(C, the incongruent dissolution of albite is reflected by the fact that sodium and aluminum are easily dissolved into water; from 300 to 400(C it is reflected by silicon being more easily dissolved in water than Al and Na. Maximum albite dissolution rates in the flow hydrothermal systems have been repeatedly observed at 300(C, independent of flow rates.The kinetic experiments of albite dissolution in a KCl aqueous solution (0.1 mol KCl) indicate that the dissolution rate of albite increases with increasing temperature. Maximum silicon release rates of albite have been observed at 400(C, while maximum aluminum release rates of albite at 374(C. The reaction rates of albite also depend on the potassium concentration in the aqueous solution.These results can be used to interpret the mechanism for forming hydrothermal alteration. The kinetic experiments of mineral-aqueous solutions interactions in the hydrothermal system from 25 to 400(C and at 22 MPa indicate that the formation of the feldspar-mica-kaolinite zoning occurring in some ore deposits may depend not only on the mineral stability but also on the kinetics of feldspar hydration, which is affected by the water property variation when crossing the critical point.

  17. Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy.

    Science.gov (United States)

    Mori, Marcelo A; Thomou, Thomas; Boucher, Jeremie; Lee, Kevin Y; Lallukka, Susanna; Kim, Jason K; Torriani, Martin; Yki-Järvinen, Hannele; Grinspoon, Steven K; Cypess, Aaron M; Kahn, C Ronald

    2014-08-01

    miRNAs are important regulators of biological processes in many tissues, including the differentiation and function of brown and white adipocytes. The endoribonuclease dicer is a major component of the miRNA-processing pathway, and in adipose tissue, levels of dicer have been shown to decrease with age, increase with caloric restriction, and influence stress resistance. Here, we demonstrated that mice with a fat-specific KO of dicer develop a form of lipodystrophy that is characterized by loss of intra-abdominal and subcutaneous white fat, severe insulin resistance, and enlargement and "whitening" of interscapular brown fat. Additionally, KO of dicer in cultured brown preadipocytes promoted a white adipocyte-like phenotype and reduced expression of several miRNAs. Brown preadipocyte whitening was partially reversed by expression of miR-365, a miRNA known to promote brown fat differentiation; however, introduction of other miRNAs, including miR-346 and miR-362, also contributed to reversal of the loss of the dicer phenotype. Interestingly, fat samples from patients with HIV-related lipodystrophy exhibited a substantial downregulation of dicer mRNA expression. Together, these findings indicate the importance of miRNA processing in white and brown adipose tissue determination and provide a potential link between this process and HIV-related lipodystrophy.

  18. Diets of differentially processed wheat alter ruminal fermentation parameters and microbial populations in beef cattle.

    Science.gov (United States)

    Jiang, S Z; Yang, Z B; Yang, W R; Li, Z; Zhang, C Y; Liu, X M; Wan, F C

    2015-11-01

    The influences of differently processed wheat products on rumen fermentation, microbial populations, and serum biochemistry profiles in beef cattle were studied. Four ruminally cannulated Limousin × Luxi beef cattle (400 ± 10 kg) were used in the experiment with a 4 × 4 Latin square design. The experimental diets contained (on a DM basis) 60% corn silage as a forage source and 40% concentrate with 4 differently processed wheat products (extruded, pulverized, crushed, and rolled wheat). Concentrations of ruminal NH-N and microbial protein (MCP) in cattle fed crushed and rolled wheat were greater ( cattle fed pulverized and extruded wheat. Ruminal concentrations of total VFA and acetate and the ratio of acetate to propionate decreased ( cattle fed extruded wheat had the lowest concentrations of total VFA and acetate among all treatments. The relative abundance of , , ciliated protozoa, and was lower in cattle fed the pulverized wheat diet than in the other 3 diets ( cattle fed extruded wheat compared with cattle fed crushed and rolled wheat ( 0.05). Our findings suggest that the method of wheat processing could have a significant effect on ruminal fermentation parameters and microbial populations in beef cattle and that crushed and rolled processing is better in terms of ruminal NH-N and MCP content, acetate-to-propionate ratio, and relative abundance of rumen microorganisms.

  19. Mount St. Augustine volcano fumarole wall rock alteration: Mineralogy, zoning, composition and numerical models of its formation process

    Science.gov (United States)

    Getahun, A.; Reed, M.H.; Symonds, R.

    1996-01-01

    ), sulfates (anhydrite) and halides (halite). The cooling calculations produce: (a) anhydrite, halite, sylvite; (b) Cu, Mo, Fe and Zn sulfides; (c) Mg fluoride at high temperature (> 370??C); (d) chlorides, fluorides and sulfates of Mn, Fe, Zn, Cu and Al at intermediate temperature (170-370??C); and (e) hydrated sulfates, liquid sulfur, crystalline sulfur, hydrated sulfuric acid and water at low temperature ( 0.41 (> 628??C). This is followed by precipitation of sulfates of Fe, Cu, Pb, Zn and Al at lg/a ratios between 0.41 and -0.4 (628-178??C). At a lg/r ratio of low g/a ratios, hydrated sulfuric acid becomes the dominant phase in the system. Comparison of the thermochemical modeling results with the natural samples suggests that the alteration assemblages include: (1) minerals that precipitate from direct cooling of the volcanic gas; (2) phases that form by volcanic gases mixing with air; and (3) phases that form by volcanic gas-air-rock reaction. A complex interplay of the three processes produces the observed mineral zoning. Another implication of the numerical simulation results is that most of the observed incrustation and sublimate minerals apparently formed below 700??C.

  20. Alteration of the interconversion of pyruvate and malate in the plastid or cytosol of ripening tomato fruit invokes diverse consequences on sugar but similar effects on cellular organic acid, metabolism, and transitory starch accumulation.

    Science.gov (United States)

    Osorio, Sonia; Vallarino, José G; Szecowka, Marek; Ufaz, Shai; Tzin, Vered; Angelovici, Ruthie; Galili, Gad; Fernie, Alisdair R

    2013-02-01

    The aim of this work was to investigate the effect of decreased cytosolic phosphoenolpyruvate carboxykinase (PEPCK) and plastidic NADP-dependent malic enzyme (ME) on tomato (Solanum lycopersicum) ripening. Transgenic tomato plants with strongly reduced levels of PEPCK and plastidic NADP-ME were generated by RNA interference gene silencing under the control of a ripening-specific E8 promoter. While these genetic modifications had relatively little effect on the total fruit yield and size, they had strong effects on fruit metabolism. Both transformants were characterized by lower levels of starch at breaker stage. Analysis of the activation state of ADP-glucose pyrophosphorylase correlated with the decrease of starch in both transformants, which suggests that it is due to an altered cellular redox status. Moreover, metabolic profiling and feeding experiments involving positionally labeled glucoses of fruits lacking in plastidic NADP-ME and cytosolic PEPCK activities revealed differential changes in overall respiration rates and tricarboxylic acid (TCA) cycle flux. Inactivation of cytosolic PEPCK affected the respiration rate, which suggests that an excess of oxaloacetate is converted to aspartate and reintroduced in the TCA cycle via 2-oxoglutarate/glutamate. On the other hand, the plastidic NADP-ME antisense lines were characterized by no changes in respiration rates and TCA cycle flux, which together with increases of pyruvate kinase and phosphoenolpyruvate carboxylase activities indicate that pyruvate is supplied through these enzymes to the TCA cycle. These results are discussed in the context of current models of the importance of malate during tomato fruit ripening.

  1. Alpha-band oscillations reflect altered multisensory processing of the McGurk illusion in schizophrenia

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    Yadira eRoa Romero

    2016-02-01

    Full Text Available The formation of coherent multisensory percepts requires integration of stimuli across the multiple senses. Patients with schizophrenia (ScZ often experience a loss of coherent perception and hence, they might also show dysfunctional multisensory processing. In this high-density electroencephalography study we investigated the neural signatures of the McGurk illusion, as a phenomenon of speech-specific multisensory processing. In the McGurk illusion lip movements are paired with incongruent auditory syllables, which can induce a fused percept. In ScZ patients and healthy controls we compared neural oscillations and event-related potentials (ERPs to congruent audiovisual speech stimuli and McGurk illusion trials, where a visual /ga/ and an auditory /pa/ was often perceived as /ka/. There were no significant group differences in illusion rates. However, we found larger short latency ERPs to McGurk illusion compared with congruent trials in controls, whereas they were reduced in ScZ patients, indicating an early audiovisual processing deficit. Moreover, we observed stronger suppression of medio-central alpha-band power (8-10 Hz, 550-700 ms in response to McGurk illusion compared with control trials in the control group. The reversed pattern was found in SCZ patients. Within groups, alpha-band suppression was negatively correlated with the McGurk illusion rate in ScZ patients, while the correlation tended to be positive in controls. The topography of alpha-band effects suggests an involvement of auditory and/or frontal structures. Our study suggests that early ERPs and later alpha-band oscillations reflect abnormal multisensory processing of the McGurk illusion in schizophrenia.

  2. Acoustic Noise Alters Selective Attention Processes as Indicated by Direct Current (DC Brain Potential Changes

    Directory of Open Access Journals (Sweden)

    Karin Trimmel

    2014-09-01

    Full Text Available Acoustic environmental noise, even of low to moderate intensity, is known to adversely affect information processing in animals and humans via attention mechanisms. In particular, facilitation and inhibition of information processing are basic functions of selective attention. Such mechanisms can be investigated by analyzing brain potentials under conditions of externally directed attention (intake of environmental information versus internally directed attention (rejection of environmental stimuli and focusing on memory/planning processes. This study investigated brain direct current (DC potential shifts—which are discussed to represent different states of cortical activation—of tasks that require intake and rejection of environmental information under noise. It was hypothesized that without background noise rejection tasks would show more positive DC potential changes compared to intake tasks and that under noise both kinds of tasks would show positive DC shifts as an expression of cortical inhibition caused by noise. DC potential shifts during intake and rejection tasks were analyzed at 16 standard locations in 45 persons during irrelevant speech or white noise vs. control condition. Without noise, rejection tasks were associated with more positive DC potential changes compared to intake tasks. During background noise, however, this difference disappeared and both kinds of tasks led to positive DC shifts. Results suggest—besides some limitations—that noise modulates selective attention mechanisms by switching to an environmental information processing and noise rejection mode, which could represent a suggested “attention shift”. Implications for fMRI studies as well as for public health in learning and performance environments including susceptible persons are discussed.

  3. Alteration assemblages in Martian meteorites: implications for near-surface processes

    OpenAIRE

    Bridges, J.C.; Catling, D.C.; Saxton, J M; Swindle, T. D.; Lyon, I C; Grady, M.M

    2001-01-01

    The SNC (Shergotty-Nakhla-Chassigny) meteorites have recorded interactions between martian crustal fluids and the parent igneous rocks. The resultant secondary minerals – which comprise up to 1 vol.% of the meteorites – provide information about the timing and nature of hydrous activity and atmospheric processes on Mars. We suggest that the most plausible models for secondary mineral formation involve the evaporation of low temperature (25 – 150 °C) brines. This is consistent with the simple ...

  4. Acoustic noise alters selective attention processes as indicated by direct current (DC) brain potential changes.

    Science.gov (United States)

    Trimmel, Karin; Schätzer, Julia; Trimmel, Michael

    2014-09-26

    Acoustic environmental noise, even of low to moderate intensity, is known to adversely affect information processing in animals and humans via attention mechanisms. In particular, facilitation and inhibition of information processing are basic functions of selective attention. Such mechanisms can be investigated by analyzing brain potentials under conditions of externally directed attention (intake of environmental information) versus internally directed attention (rejection of environmental stimuli and focusing on memory/planning processes). This study investigated brain direct current (DC) potential shifts-which are discussed to represent different states of cortical activation-of tasks that require intake and rejection of environmental information under noise. It was hypothesized that without background noise rejection tasks would show more positive DC potential changes compared to intake tasks and that under noise both kinds of tasks would show positive DC shifts as an expression of cortical inhibition caused by noise. DC potential shifts during intake and rejection tasks were analyzed at 16 standard locations in 45 persons during irrelevant speech or white noise vs. control condition. Without noise, rejection tasks were associated with more positive DC potential changes compared to intake tasks. During background noise, however, this difference disappeared and both kinds of tasks led to positive DC shifts. Results suggest-besides some limitations-that noise modulates selective attention mechanisms by switching to an environmental information processing and noise rejection mode, which could represent a suggested "attention shift". Implications for fMRI studies as well as for public health in learning and performance environments including susceptible persons are discussed.

  5. Amphetamine Sensitization Alters Reward Processing in the Human Striatum and Amygdala

    Science.gov (United States)

    O’Daly, Owen G.; Joyce, Daniel; Tracy, Derek K.; Azim, Adnan; Stephan, Klaas E.; Murray, Robin M.; Shergill, Sukhwinder S.

    2014-01-01

    Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS) has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD) signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders. PMID:24717936

  6. Amphetamine sensitization alters reward processing in the human striatum and amygdala.

    Directory of Open Access Journals (Sweden)

    Owen G O'Daly

    Full Text Available Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders.

  7. From symptom to process: how the PDM alters goals and strategies in psychological assessment.

    Science.gov (United States)

    Bornstein, Robert F

    2011-03-01

    In many respects the Psychodynamic Diagnostic Manual (PDM) P and M Axes represent psychoanalytic versions of Diagnostic and Statistical Manual of Mental Disorders (DSM) Axes II and V: Whereas the DSM axes focus on surface behaviors and their associated mental states (e.g., thought patterns, affective responses), the PDM axes emphasize underlying psychodynamic processes (e.g., implicit motives, conflicts, defenses), with more modest attention to expressed behavior. The paradigmatic shift envisioned by the PDM creates tremendous opportunities for clinicians and researchers, and significant assessment challenges as well. This article discusses those opportunities and challenges. After briefly contrasting the DSM and PDM conceptualizations of personality pathology and global psychological functioning, I discuss the implications of these contrasting perspectives for diagnosis and psychological assessment, outline strategies for documenting the construct validity of DSM and PDM symptom criteria using symptom-focused and process-focused methods, and offer suggestions for how DSM symptom-focused data can be integrated with PDM process-focused data to facilitate case conceptualization and treatment planning.

  8. Altered joint tribology in osteoarthritis: Reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches.

    Science.gov (United States)

    Szychlinska, M A; Leonardi, R; Al-Qahtani, M; Mobasheri, A; Musumeci, G

    2016-06-01

    Osteoarthritis (OA) is the most common form of joint disease. This review aimed to consolidate the current evidence that implicates the inflammatory process in the attenuation of synovial lubrication and joint tissue homeostasis in OA. Moreover, with these findings, we propose some evidence for novel therapeutic strategies for preventing and/or treating this complex disorder. The studies reviewed support that inflammatory mediators participate in the onset and progression of OA after joint injury. The flow of pro-inflammatory cytokines following an acute injury seems to be directly associated with altered lubricating ability in the joint tissue. The latter is associated with reduced level of lubricin, one of the major joint lubricants. Future research should focus on the development of new therapies that attenuate the inflammatory process and restore lubricin synthesis and function. This approach could support joint tribology and synovial lubrication leading to improved joint function and pain relief.

  9. Altered processing of self-related emotional stimuli in mindfulness meditators.

    Science.gov (United States)

    Lutz, J; Brühl, A B; Doerig, N; Scheerer, H; Achermann, R; Weibel, A; Jäncke, L; Herwig, U

    2016-01-01

    Mental health benefits of mindfulness techniques are thought to involve changes in self-processing, such as decreased attachment to the self, higher self-compassion and lower emotional reactivity to inner experience. However, self-related emotion processing in regular mindfulness practitioners is not extensively studied. In the current work we investigate differential neural and behavioral correlates of self-criticism and self-praise in 22 mid-to-long-term mindfulness meditators (LTM) compared to 22 matched meditation-naïve participants (MNP). In an fMRI experiment, participants were presented with blocks of individually selected positive (self-praise, SP), negative (self-critical, SC), negative but not-self-critical (NNSC), and general, neutral (NT) adjectives, and reported their affective state after the blocks. On the neural level, both SP and SC yielded more activation in the dorso-medial prefrontal cortex (DMPFC) in LTM compared to MNP. Activation in this region correlated positively with non-react scores of the Five Facets Mindfulness Questionnaire (FFMQ) and showed decreased functional connectivity to posterior midline and parietal regions in LTM compared to MNP during both self-related appraisals. Further, we found evidence for emotional reactivity in LTM on the neural level, particularly during SP. On the behavioral level, a mixed effects analysis revealed significantly higher differences in affective ratings after blocks of SC compared to SP in MNP compared to LTM. Differences in DMPFC activation and affective ratings point towards increased awareness, potentially mindful regulation of SC and SP in LTM, while decreased connectivity to other regions of the default mode network could reflect a decreased self-focus in this group. As such, our results illustrate differences in self-related emotional processes in meditators and offer clinically relevant insights into mechanisms of mindful emotion regulation when facing self-criticism and self-praise.

  10. Cesium Toxicity Alters MicroRNA Processing and AGO1 Expressions in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Il Lae Jung

    Full Text Available MicroRNAs (miRNAs are short RNA fragments that play important roles in controlled gene silencing, thus regulating many biological processes in plants. Recent studies have indicated that plants modulate miRNAs to sustain their survival in response to a variety of environmental stimuli, such as biotic stresses, cold, drought, nutritional starvation, and toxic heavy metals. Cesium and radio-cesium contaminations have arisen as serious problems that both impede plant growth and enter the food chain through contaminated plants. Many studies have been performed to define plant responses against cesium intoxication. However, the complete profile of miRNAs in plants during cesium intoxication has not been established. Here we show the differential expression of the miRNAs that are mostly down-regulated during cesium intoxication. Furthermore, we found that cesium toxicity disrupts both the processing of pri-miRNAs and AGONOUTE 1 (AGO1-mediated gene silencing. AGO 1 seems to be especially destabilized by cesium toxicity, possibly through a proteolytic regulatory pathway. Our study presents a comprehensive profile of cesium-responsive miRNAs, which is distinct from that of potassium, and suggests two possible mechanisms underlying the cesium toxicity on miRNA metabolism.

  11. Perturbations of amino acid metabolism associated with glyphosate-dependent inhibition of shikimic acid metabolism affect cellular redox homeostasis and alter the abundance of proteins involved in photosynthesis and photorespiration.

    Science.gov (United States)

    Vivancos, Pedro Diaz; Driscoll, Simon P; Bulman, Christopher A; Ying, Liu; Emami, Kaveh; Treumann, Achim; Mauve, Caroline; Noctor, Graham; Foyer, Christine H

    2011-09-01

    The herbicide glyphosate inhibits the shikimate pathway of the synthesis of amino acids such as phenylalanine, tyrosine, and tryptophan. However, much uncertainty remains concerning precisely how glyphosate kills plants or affects cellular redox homeostasis and related processes in glyphosate-sensitive and glyphosate-resistant crop plants. To address this issue, we performed an integrated study of photosynthesis, leaf proteomes, amino acid profiles, and redox profiles in the glyphosate-sensitive soybean (Glycine max) genotype PAN809 and glyphosate-resistant Roundup Ready Soybean (RRS). RRS leaves accumulated much more glyphosate than the sensitive line but showed relatively few changes in amino acid metabolism. Photosynthesis was unaffected by glyphosate in RRS leaves, but decreased abundance of photosynthesis/photorespiratory pathway proteins was observed together with oxidation of major redox pools. While treatment of a sensitive genotype with glyphosate rapidly inhibited photosynthesis and triggered the appearance of a nitrogen-rich amino acid profile, there was no evidence of oxidation of the redox pools. There was, however, an increase in starvation-associated and defense proteins. We conclude that glyphosate-dependent inhibition of soybean leaf metabolism leads to the induction of defense proteins without sustained oxidation. Conversely, the accumulation of high levels of glyphosate in RRS enhances cellular oxidation, possibly through mechanisms involving stimulation of the photorespiratory pathway.

  12. Biomedical implications of altered product composition in advanced coal liquefaction processes

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, B.W.; Mahlum, D.D.; Pelroy, R.A.

    1986-04-01

    Chemical and toxicologic characteristics of direct coal liquefaction materials are highly dependent upon the specific process operations by which the coal liquids were produced, including, in particular, those that affect boiling point range and degree of hydrogen incorporation. Recent advances in direct coal liquefaction technology, such as the use of catalytic hydrogenation, reduced liquefaction severity and lowering the upper temperature cut point for the distillation of fuels, have resulted in products with higher hydrogen-to-carbon ratios and lower heteroatom content. These higher-quality fuels tend to be less mutagenic and carcinogenic in laboratory assays than earlier coal liquefaction products. It is likely that application of postproduction hydrotreatment, as well as restriction of upper distillation temperature, for coal-based fuel products could result in materials that exhibit mutagenic or carcinogenic activity which is no greater than that of their petroleum-derived counterparts. 2 figs., 3 tabs., 46 refs.

  13. EXTERIOR PRESSURE OF THE GASEOUS MEDIUM AS AN ADDITIONAL TECHNOLOGICAL FACTOR FOR OPTIMIZING THE VAPORIZATION PROCESS IN THE PRODUCTION OF CELLULAR SILICATE CONCRETE

    Directory of Open Access Journals (Sweden)

    A. A. Rezanov

    2012-11-01

    Full Text Available Statement of the problem. The quality of silicate porous concrete is largely determined by vapor-ization processes at the stage of the formation of the macrostructure of the obtained material. In the production of cellular concrete with the use of injection molding, the existing manufacturing technologies do not enable the expeditious handling of the vaporization process. This is why there is a growing need to develop additional efficient methods of handling the vaporization process thus improving cellular silicate concrete.Results. Based on modelling and detailed examination of the balance of pressure affecting devel-oping gas pores, mechanisms and factors governing a defect-free structure are found. An additional governing factor, which is a pressure of the external gaseous medium, was discovered. The approaches to handling the vaporization process have been developed and a plant fitted with a system of automatic control of vaporization process by conscious operative pressuring effect from the external gaseous phase on a poring mixture has been designed.Conclusions. Theoretical validation along with the results of the experimental study help to arrive at the conclusion about the efficiency of the suggested system in controlling vaporization that could provide a good addition to the traditional injection molding and make it more susceptible against varying characteristics of raw materials.

  14. Disturbances of visual information processing in early states of psychosis and experimental delta-9-tetrahydrocannabinol altered states of consciousness.

    Science.gov (United States)

    Koethe, Dagmar; Gerth, Christoph W; Neatby, Miriam A; Haensel, Anita; Thies, Martin; Schneider, Udo; Emrich, Hinderk M; Klosterkötter, Joachim; Schultze-Lutter, Frauke; Leweke, F Markus

    2006-12-01

    Recent data on alterations of the endogenous cannabinoid system in schizophrenia have raised the question of its functional role in this disease. The psychoactive compound of Cannabis sativa, delta-9-tetrahydrocannabinol (Delta9-THC), has been shown to induce psychotic symptoms, but it is unknown to what extend prodromal states of psychoses are reflected by these experimental approaches. This study compares four groups of subjects: antipsychotic-naïve patients suffering from acute paranoid schizophrenic or schizophreniform psychosis (SZ), patients in the prodromal state (IPS), healthy controls without any pharmacological intervention (HC) and a second group of healthy volunteers who were orally administered synthetic Delta9-THC (Dronabinol) (HC-THC). Neither SZ and IPS nor HC received the experimental drug. All subjects were assessed using the Brief Psychiatric Rating Scale (BPRS) and the Binocular Depth Inversion Illusion Test (BDII). The latter represents a sensitive measure of impaired visual information processing that manifests in various experimental and naturally occurring psychotic states. BDII values were well comparable in SZ, IPS and HC-THC, and all groups differed significantly to HC. The BPRS revealed no significant difference between HC-THC and IPS while both were significantly different from SZ and HC, respectively. Our results suggest that Delta9-THC-induced altered states of consciousness may serve as a useful tool for modeling psychotic disorders, particularly their prodromal states. Furthermore, they provide insight into the perceptual and psychopathological alterations induced by Delta9-THC, which is essential for the understanding of the pro-psychotic effects of herbal cannabis preparations with highly enriched Delta9-THC content.

  15. Acute stress alters transcript expression pattern and reduces processing of proBDNF to mature BDNF in Dicentrarchus labrax

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    Saroglia Marco

    2010-01-01

    Full Text Available Abstract Background Stress involves alterations of brain functioning that may precipitate to mood disorders. The neurotrophin Brain Derived Neurotrophic Factor (BDNF has recently been involved in stress-induced adaptation. BDNF is a key regulator of neuronal plasticity and adaptive processes. Regulation of BDNF is complex and may reflect not only stress-specific mechanisms but also hormonal and emotional responses. For this reason we used, as an animal model of stress, a fish whose brain organization is very similar to that of higher vertebrates, but is generally considered free of emotional reactions. Results We provide a comprehensive characterization of BDNF gene in the Dicentrarchus labrax and its transcriptional, translational and post-translational regulation following acute stress. While total BDNF mRNA levels are unchanged, BDNF transcripts 1c and 1d resulted down regulated after acute stress. Acute stress induces also a significant increase in proBDNF levels and reduction in mature BDNF suggesting altered regulation of proBDNF proteolytic processing. Notably, we provide here the first evidence that fishes possess a simplified proteolytic regulation of BDNF since the pro28Kda form, generated by the SKI-1 protease in mammals, is absent in fishes because the cleavage site has first emerged in reptilians. Finally, we show that the proBDNF/totBDNF ratio is a highly predictive novel quantitative biomarker to detect stress in fishes with sensitivity = 100%, specificity = 87%, and Negative Predictive Value = 100%. Conclusion The high predictivity of proBDNF/totBDNF ratio for stress in lower vertebrates indicates that processing of BDNF is a central mechanism in adaptation to stress and predicts that a similar regulation of pro/mature BDNF has likely been conserved throughout evolution of vertebrates from fish to man.

  16. Altered Onset Response Dynamics in Somatosensory Processing in Autism Spectrum Disorder.

    Science.gov (United States)

    Khan, Sheraz; Hashmi, Javeria A; Mamashli, Fahimeh; Bharadwaj, Hari M; Ganesan, Santosh; Michmizos, Konstantinos P; Kitzbichler, Manfred G; Zetino, Manuel; Garel, Keri-Lee A; Hämäläinen, Matti S; Kenet, Tal

    2016-01-01

    Abnormalities in cortical connectivity and evoked responses have been extensively documented in autism spectrum disorder (ASD). However, specific signatures of these cortical abnormalities remain elusive, with data pointing toward abnormal patterns of both increased and reduced response amplitudes and functional connectivity. We have previously proposed, using magnetoencephalography (MEG) data, that apparent inconsistencies in prior studies could be reconciled if functional connectivity in ASD was reduced in the feedback (top-down) direction, but increased in the feedforward (bottom-up) direction. Here, we continue this line of investigation by assessing abnormalities restricted to the onset, feedforward inputs driven, component of the response to vibrotactile stimuli in somatosensory cortex in ASD. Using a novel method that measures the spatio-temporal divergence of cortical activation, we found that relative to typically developing participants, the ASD group was characterized by an increase in the initial onset component of the cortical response, and a faster spread of local activity. Given the early time window, the results could be interpreted as increased thalamocortical feedforward connectivity in ASD, and offer a plausible mechanism for the previously observed increased response variability in ASD, as well as for the commonly observed behaviorally measured tactile processing abnormalities associated with the disorder.

  17. Suppression of savanna ants alters invertebrate composition and influences key ecosystem processes.

    Science.gov (United States)

    Parr, C L; Eggleton, P; Davies, A B; Evans, T A; Holdsworth, S

    2016-06-01

    In almost every ecosystem, ants (Hymenoptera: Formicidae) are the dominant terrestrial invertebrate group. Their functional value was highlighted by Wilson (1987) who famously declared that invertebrates are the "little things that run the world." However, while it is generally accepted that ants fulfil important functions, few studies have tested these assumptions and demonstrated what happens in their absence. We report on a novel large-scale field experiment in undisturbed savanna habitat where we examined how ants influence the abundance of other invertebrate taxa in the system, and affect the key processes of decomposition and herbivory. Our experiment demonstrated that ants suppressed the abundance and activity of beetles, millipedes, and termites, and also influenced decomposition rates and levels of herbivory. Our study is the first to show that top-down control of termites by ants can have important ecosystem consequences. Further studies are needed to elucidate the effects ant communities have on other aspects of the ecosystem (e.g., soils, nutrient cycling, the microbial community) and how their relative importance for ecosystem function varies among ecosystem types (e.g., savanna vs. forest).

  18. Saltwater intrusion into tidal freshwater marshes alters the biogeochemical processing of organic carbon

    Directory of Open Access Journals (Sweden)

    S. C. Neubauer

    2013-07-01

    Full Text Available Environmental perturbations in wetlands affect the integrated plant-microbial-soil system, causing biogeochemical responses that can manifest at local to global scales. The objective of this study was to determine how saltwater intrusion affects carbon mineralization and greenhouse gas production in coastal wetlands. Working with tidal freshwater marsh soils that had experienced roughly 3.5 yr of in situ saltwater additions, we quantified changes in soil properties, measured extracellular enzyme activity associated with organic matter breakdown, and determined potential rates of anaerobic carbon dioxide (CO2 and methane (CH4 production. Soils from the field plots treated with brackish water had lower carbon content and higher C : N ratios than soils from freshwater plots, indicating that saltwater intrusion reduced carbon availability and increased organic matter recalcitrance. This was reflected in reduced activities of enzymes associated with the hydrolysis of cellulose and the oxidation of lignin, leading to reduced rates of soil CO2 and CH4 production. The effects of long-term saltwater additions contrasted with the effects of short-term exposure to brackish water during three-day laboratory incubations, which increased rates of CO2 production but lowered rates of CH4 production. Collectively, our data suggest that the long-term effect of saltwater intrusion on soil CO2 production is indirect, mediated through the effects of elevated salinity on the quantity and quality of autochthonous organic matter inputs to the soil. In contrast, salinity, organic matter content, and enzyme activities directly influence CH4 production. Our analyses demonstrate that saltwater intrusion into tidal freshwater marshes affects the entire process of carbon mineralization, from the availability of organic carbon through its terminal metabolism to CO2 and/or CH4, and illustrate that long-term shifts in biogeochemical functioning are not necessarily consistent

  19. Alteration processes of medieval stained glass windows. Study and protection treatments

    Directory of Open Access Journals (Sweden)

    Fernández Navarro, J. María

    1996-06-01

    Full Text Available The anxiety caused by the fast growing decay of historical stained glass windows as a consequence of increasing environmental pollution, encouraged institutions of several countries to sponsor a series of scientific works aimed both to slow down this fast forwarding deterioration and to develop repair and preservation methods. After an initial review of the chemical composition of the stained glass windows and of the differences depending on historical epochs and origins, a discussion about chemical attack mechanisms, degradation processes and formation of superficial crusts opens up. Finally, the methodology used in their cleaning and restoration is briefly exposed and some criteria on the still polemic quest.

    La inquietud creada por la creciente alteración que, como consecuencia del aumento de la contaminación atmosférica, están sufriendo las vidrieras históricas, ha movido a las instituciones de varios países a patrocinar la realización de una serie de trabajos científicos dirigidos, por una parte, a detener el avance de este deterioro y, por otra, a desarrollar métodos para su restauración y conservación. Tras una revisión inicial sobre la composición química de las vidrieras y sus diferencias según las distintas épocas y lugares de procedencia, se discuten los mecanismos de ataque químico, los procesos de degradación y la formación de costras superficiales. Finalmente se expone brevemente la metodología seguida para su limpieza y restauración y se comentan algunos de los criterios sobre la todavía polémica cuestión de los tratamientos de protección.

  20. Cellular photobiology.

    OpenAIRE

    2005-01-01

    The various cell lines of the epidermis and dermis can be activated or conversely altered by actinic irradiations. Keratinocytes, melanocytes, Langerhans cells and connective tissue cells are the main targets. Peer reviewed

  1. Sleep, Plasticity and the Pathophysiology of Neurodevelopmental Disorders: The Potential Roles of Protein Synthesis and Other Cellular Processes

    Directory of Open Access Journals (Sweden)

    Dante Picchioni

    2014-03-01

    Full Text Available Sleep is important for neural plasticity, and plasticity underlies sleep-dependent memory consolidation. It is widely appreciated that protein synthesis plays an essential role in neural plasticity. Studies of sleep-dependent memory and sleep-dependent plasticity have begun to examine alterations in these functions in populations with neurological and psychiatric disorders. Such an approach acknowledges that disordered sleep may have functional consequences during wakefulness. Although neurodevelopmental disorders are not considered to be sleep disorders per se, recent data has revealed that sleep abnormalities are among the most prevalent and common symptoms and may contribute to the progression of these disorders. The main goal of this review is to highlight the role of disordered sleep in the pathology of neurodevelopmental disorders and to examine some potential mechanisms by which sleep-dependent plasticity may be altered. We will also briefly attempt to extend the same logic to the other end of the developmental spectrum and describe a potential role of disordered sleep in the pathology of neurodegenerative diseases. We conclude by discussing ongoing studies that might provide a more integrative approach to the study of sleep, plasticity, and neurodevelopmental disorders.

  2. Biochemical Alterations during the Obese-Aging Process in Female and Male Monosodium Glutamate (MSG-Treated Mice

    Directory of Open Access Journals (Sweden)

    René J. Hernández-Bautista

    2014-06-01

    Full Text Available Obesity, from children to the elderly, has increased in the world at an alarming rate over the past three decades, implying long-term detrimental consequences for individual’s health. Obesity and aging are known to be risk factors for metabolic disorder development, insulin resistance and inflammation, but their relationship is not fully understood. Prevention and appropriate therapies for metabolic disorders and physical disabilities in older adults have become a major public health challenge. Hence, the aim of this study was to evaluate inflammation markers, biochemical parameters and glucose homeostasis during the obese-aging process, to understand the relationship between obesity and health span during the lifetime. In order to do this, the monosodium glutamate (MSG obesity mice model was used, and data were evaluated at 4, 8, 12, 16 and 20 months in both female and male mice. Our results showed that obesity was a major factor contributing to premature alterations in MSG-treated mice metabolism; however, at older ages, obesity effects were attenuated and MSG-mice became more similar to normal mice. At a younger age (four months old, the Lee index, triglycerides, total cholesterol, TNF-α and transaminases levels increased; while adiponectin decreased and glucose tolerance and insulin sensitivity levels were remarkably altered. However, from 16 months old-on, the Lee index and TNF-α levels diminished significantly, while adiponectin increased, and glucose and insulin homeostasis was recovered. In summary, MSG-treated obese mice showed metabolic changes and differential susceptibility by gender throughout life and during the aging process. Understanding metabolic differences between genders during the lifespan will allow the discovery of specific preventive treatment strategies for chronic diseases and functional decline.

  3. Retinal aging in the diurnal Chilean rodent (Octodon degus: histological, ultrastructural and neurochemical alterations of the vertical information processing pathway

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    Krisztina eSzabadfi

    2015-04-01

    Full Text Available The retina is sensitive to age-dependent degeneration. To find suitable animal models to understand and map this process has particular importance. The degu (Octodon degus is a diurnal rodent with dichromatic color vision. Its retinal structure is similar to that in humans in many respects, therefore, it is well suited to study retinal aging. Histological, cell type-specific and ultrastructural alterations were examined in 6, 12 and 36 months old degus. The characteristic layers of the retina were present at all ages, but slightly loosened tissue structure could be observed in 36-month-old animals both at light and electron microscopic levels. Elevated glial fibrillary acidic protein expression was observed in Müller glial cells in aging retinas. The number of rod bipolar cells and the ganglion cells was reduced in the aging specimens, while that of cone bipolar cells remained unchanged. Other age-related differences were detected at ultrastructural level: alteration of the retinal pigment epithelium and degenerated photoreceptor cells were evident. Ribbon synapses were sparse and often differed in morphology from those in the young animals. These results support our hypothesis that (i the rod pathway seems to be more sensitive than the cone pathway to age-related cell loss; (ii structural changes in the basement membrane of pigment epithelial cells can be one of the early signs of degenerative processes; (iii the loss of synaptic proteins especially from those of the ribbon synapses are characteristic and (iv the degu retina may be a suitable model for studying retinal aging.

  4. Biochemical Alterations during the Obese-Aging Process in Female and Male Monosodium Glutamate (MSG)-Treated Mice

    Science.gov (United States)

    Hernández-Bautista, René J.; Alarcón-Aguilar, Francisco J.; Escobar-Villanueva, María Del C.; Almanza-Pérez, Julio C.; Merino-Aguilar, Héctor; Konigsberg Fainstein, Mina; López-Diazguerrero, Norma E.

    2014-01-01

    Obesity, from children to the elderly, has increased in the world at an alarming rate over the past three decades, implying long-term detrimental consequences for individual’s health. Obesity and aging are known to be risk factors for metabolic disorder development, insulin resistance and inflammation, but their relationship is not fully understood. Prevention and appropriate therapies for metabolic disorders and physical disabilities in older adults have become a major public health challenge. Hence, the aim of this study was to evaluate inflammation markers, biochemical parameters and glucose homeostasis during the obese-aging process, to understand the relationship between obesity and health span during the lifetime. In order to do this, the monosodium glutamate (MSG) obesity mice model was used, and data were evaluated at 4, 8, 12, 16 and 20 months in both female and male mice. Our results showed that obesity was a major factor contributing to premature alterations in MSG-treated mice metabolism; however, at older ages, obesity effects were attenuated and MSG-mice became more similar to normal mice. At a younger age (four months old), the Lee index, triglycerides, total cholesterol, TNF-α and transaminases levels increased; while adiponectin decreased and glucose tolerance and insulin sensitivity levels were remarkably altered. However, from 16 months old-on, the Lee index and TNF-α levels diminished significantly, while adiponectin increased, and glucose and insulin homeostasis was recovered. In summary, MSG-treated obese mice showed metabolic changes and differential susceptibility by gender throughout life and during the aging process. Understanding metabolic differences between genders during the lifespan will allow the discovery of specific preventive treatment strategies for chronic diseases and functional decline. PMID:24979131

  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. Novel TiC/Ti Open Cellular Foams Prepared by a Modified Sponge-coating Method Using High Frequency Induction Heating Process

    Institute of Scientific and Technical Information of China (English)

    Yong Gao; Xingxiang Xu; Zhenming Yang; Junqi Zhang; Chunhai Jiang; Jinsong Zhang

    2013-01-01

    A new kind of open cellular foam material with three dimensionally interconnected TiC/Ti struts was prepared by a two-step sponge-coating and high frequency induction heating process.The microstructure,composition and compression strength of the prepared TiC/Ti foam materials were characterized.It was confirmed that the incorporation of Ti into TiC resulted in an inter-bonded Ti-TiC-Ti layered structure in the struts,which enhanced the plasticity of the composite foam materials.

  7. Mindfulness training alters emotional memory recall compared to active controls: support for an emotional information processing model of mindfulness

    Directory of Open Access Journals (Sweden)

    Doug eRoberts-Wolfe

    2012-02-01

    Full Text Available Objectives: While mindfulness-based interventions have received widespread application in both clinical and non-clinical populations, the mechanism by which mindfulness meditation improves well-being remains elusive. One possibility is that mindfulness training alters the processing of emotional information, similar to prevailing cognitive models of depression and anxiety. The aim of this study was to investigating the effects of mindfulness training on emotional information processing (i.e. memory biases in relation to both clinical symptomatology and well-being in comparison to active control conditions.Methods: Fifty-eight university students (28 female, age = 20.1 ± 2.7 years participated in either a 12-week course containing a "meditation laboratory" or an active control course with similar content or experiential practice laboratory format (music. Participants completed an emotional word recall task and self-report questionnaires of well-being and clinical symptoms before and after the 12-week course.Results: Meditators showed greater increases in positive word recall compared to controls F(1, 56 = 6.6, p = .02. The meditation group increased significantly more on measures of well-being [F(1, 56 = 6.6, p = .01], with a marginal decrease in depression and anxiety [(F(1, 56 = 3.0, p = .09] compared to controls. Increased positive word recall was associated with increased psychological well-being [r = 0.31, p = .02] and decreased clinical symptoms [r = -0.29, p = .03].Conclusion: Mindfulness training was associated with greater improvements in processing efficiency for positively valenced stimuli than active control conditions. This change in emotional information processing was associated with improvements in psychological well-being and less depression and anxiety. These data suggest that mindfulness training may improve well-being via changes in emotional information processing.

  8. 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

  9. Proteasome-Mediated Processing of Def1, a Critical Step in the Cellular Response to Transcription Stress

    OpenAIRE

    Wilson, Marcus D.; Harreman, Michelle; Taschner, Michael; Reid, James; Walker, Jane; Erdjument-Bromage, Hediye; Tempst, Paul; Svejstrup, Jesper Q.

    2013-01-01

    Summary DNA damage triggers polyubiquitylation and degradation of the largest subunit of RNA polymerase II (RNAPII), a “mechanism of last resort” employed during transcription stress. In yeast, this process is dependent on Def1 through a previously unresolved mechanism. Here, we report that Def1 becomes activated through ubiquitylation- and proteasome-dependent processing. Def1 processing results in the removal of a domain promoting cytoplasmic localization, resulting in nuclear accumulation ...

  10. Perlecan/Hspg2 deficiency alters the pericellular space of the lacunocanalicular system surrounding osteocytic processes in cortical bone.

    Science.gov (United States)

    Thompson, William R; Modla, Shannon; Grindel, Brian J; Czymmek, Kirk J; Kirn-Safran, Catherine B; Wang, Liyun; Duncan, Randall L; Farach-Carson, Mary C

    2011-03-01

    Osteocytes project long, slender processes throughout the mineralized matrix of bone, where they connect and communicate with effector cells. The interconnected cellular projections form the functional lacunocanalicular system, allowing fluid to pass for cell-to-cell communication and nutrient and waste exchange. Prevention of mineralization in the pericellular space of the lacunocanalicular pericellular space is crucial for uninhibited interstitial fluid movement. Factors contributing to the ability of the pericellular space of the lacunocanalicular system to remain open and unmineralized are unclear. Immunofluorescence and immunogold localization by transmission electron microscopy demonstrated perlecan/Hspg2 signal localized to the osteocyte lacunocanalicular system of cortical bone, and this proteoglycan was found in the pericellular space of the lacunocanalicular system. In this study we examined osteocyte lacunocanalicular morphology in mice deficient in the large heparan sulfate proteoglycan perlecan/Hspg2 in this tissue. Ultrastructural measurements with electron microscopy of perlecan/Hspg2-deficient mice demonstrated diminished osteocyte canalicular pericellular area, resulting from a reduction in the total canalicular area. Additionally, perlecan/Hspg2-deficient mice showed decreased canalicular density and a reduced number of transverse tethering elements per canaliculus. These data indicated that perlecan/Hspg2 contributed to the integrity of the osteocyte lacunocanalicular system by maintaining the size of the pericellular space, an essential task to promote uninhibited interstitial fluid movement in this mechanosensitive environment. This work thus identified a new barrier function for perlecan/Hspg2 in murine cortical bone.

  11. Effect of compositional alteration of food matrices and processing on availability of selected nutrients and bioactive components in rice products.

    Science.gov (United States)

    Oghbaei, Morteza; Prakash, Jamuna

    2011-05-01

    The aim was to determine the influence of compositional alteration and processing on the digestibility/availability of nutrients and bioactive components [protein (IVPD), starch (IVSD), iron, calcium, polyphenols, flavonoids] in rice products. The compositional changes representing fortified foods in 'wafers' and 'noodles' were addition of iron, rice bran, onion and cabbage. The moisture content of wafer and noodles ranged from 4.1 to 4.8% and from 73.3 to 82.1%, respectively. Wafer control (73.9-75.9%) and noodle with iron and control (85.4-87.0%) showed the highest IVPD and IVSD. Addition of rice bran decreased nutrient digestibility. The control and iron-added products exhibited least and highest available iron (2.50-2.69% and 5.99-7.07%). Total and available bioactive components increased in proportion to added external source. Overall availability of all components was better in noodles than in wafers, indicating high moisture supported higher availability. In conclusion, it can be said that both composition of the food matrix and processing influenced the availability of analyzed components.

  12. Determination of Cellular Processing Rates for a Trastuzumab-Maytansinoid Antibody-Drug Conjugate (ADC) Highlights Key Parameters for ADC Design.

    Science.gov (United States)

    Maass, Katie F; Kulkarni, Chethana; Betts, Alison M; Wittrup, K Dane

    2016-05-01

    Antibody-drug conjugates (ADCs) are a promising class of cancer therapeutics that combine the specificity of antibodies with the cytotoxic effects of payload drugs. A quantitative understanding of how ADCs are processed intracellularly can illustrate which processing steps most influence payload delivery, thus aiding the design of more effective ADCs. In this work, we develop a kinetic model for ADC cellular processing as well as generalizable methods based on flow cytometry and fluorescence imaging to parameterize this model. A number of key processing steps are included in the model: ADC binding to its target antigen, internalization via receptor-mediated endocytosis, proteolytic degradation of the ADC, efflux of the payload out of the cell, and payload binding to its intracellular target. The model was developed with a trastuzumab-maytansinoid ADC (TM-ADC) similar to trastuzumab-emtansine (T-DM1), which is used in the clinical treatment of HER2+ breast cancer. In three high-HER2-expressing cell lines (BT-474, NCI-N87, and SK-BR-3), we report for TM-ADC half-lives for internalization of 6-14 h, degradation of 18-25 h, and efflux rate of 44-73 h. Sensitivity analysis indicates that the internalization rate and efflux rate are key parameters for determining how much payload is delivered to a cell with TM-ADC. In addition, this model describing the cellular processing of ADCs can be incorporated into larger pharmacokinetics/pharmacodynamics models, as demonstrated in the associated companion paper.

  13. Identification of microbes from the surfaces of food-processing lines based on the flow cytometric evaluation of cellular metabolic activity combined with cell sorting.

    Science.gov (United States)

    Juzwa, W; Duber, A; Myszka, K; Białas, W; Czaczyk, K

    2016-09-01

    In this study the design of a flow cytometry-based procedure to facilitate the detection of adherent bacteria from food-processing surfaces was evaluated. The measurement of the cellular redox potential (CRP) of microbial cells was combined with cell sorting for the identification of microorganisms. The procedure enhanced live/dead cell discrimination owing to the measurement of the cell physiology. The microbial contamination of the surface of a stainless steel conveyor used to process button mushrooms was evaluated in three independent experiments. The flow cytometry procedure provided a step towards monitoring of contamination and enabled the assessment of microbial food safety hazards by the discrimination of active, mid-active and non-active bacterial sub-populations based on determination of their cellular vitality and subsequently single cell sorting to isolate microbial strains from discriminated sub-populations. There was a significant correlation (r = 0.97; p flow cytometry, despite there being differences in the absolute number of cells detected. The combined approach of flow cytometric CRP measurement and cell sorting allowed an in situ analysis of microbial cell vitality and the identification of species from defined sub-populations, although the identified microbes were limited to culturable cells.

  14. Matrix density alters zyxin phosphorylation, which limits peripheral process formation and extension in endothelial cells invading 3D collagen matrices.

    Science.gov (United States)

    Abbey, Colette A; Bayless, Kayla J

    2014-09-01

    integrate signals from multiple exogenous factors, including changes in matrix density, to accomplish successful sprouting responses. We show here for the first time that zyxin limited the formation and extension of fine peripheral processes used by ECs for matrix interrogation, providing a molecular explanation for altered EC responses to high and low density collagen matrices.

  15. Systematic genetic array analysis links the Saccharomyces cerevisiae SAGA/SLIK and NuA4 component Tra1 to multiple cellular processes

    Directory of Open Access Journals (Sweden)

    Andrews Brenda

    2008-07-01

    Full Text Available Abstract Background Tra1 is an essential 437-kDa component of the Saccharomyces cerevisiae SAGA/SLIK and NuA4 histone acetyltransferase complexes. It is a member of a group of key signaling molecules that share a carboxyl-terminal domain related to phosphatidylinositol-3-kinase but unlike many family members, it lacks kinase activity. To identify genetic interactions for TRA1 and provide insight into its function we have performed a systematic genetic array analysis (SGA on tra1SRR3413, an allele that is defective in transcriptional regulation. Results The SGA analysis revealed 114 synthetic slow growth/lethal (SSL interactions for tra1SRR3413. The interacting genes are involved in a range of cellular processes including gene expression, mitochondrial function, and membrane sorting/protein trafficking. In addition many of the genes have roles in the cellular response to stress. A hierarchal cluster analysis revealed that the pattern of SSL interactions for tra1SRR3413 most closely resembles deletions of a group of regulatory GTPases required for membrane sorting/protein trafficking. Consistent with a role for Tra1 in cellular stress, the tra1SRR3413 strain was sensitive to rapamycin. In addition, calcofluor white sensitivity of the strain was enhanced by the protein kinase inhibitor staurosporine, a phenotype shared with the Ada components of the SAGA/SLIK complex. Through analysis of a GFP-Tra1 fusion we show that Tra1 is principally localized to the nucleus. Conclusion We have demonstrated a genetic association of Tra1 with nuclear, mitochondrial and membrane processes. The identity of the SSL genes also connects Tra1 with cellular stress, a result confirmed by the sensitivity of the tra1SRR3413 strain to a variety of stress conditions. Based upon the nuclear localization of GFP-Tra1 and the finding that deletion of the Ada components of the SAGA complex result in similar phenotypes as tra1SRR3413, we suggest that the effects of tra1SRR3413

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

    Institute of Scientific and Technical Information of China (English)

    M.Kalpana; P.Balasubramaniam

    2013-01-01

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

  17. E-cadherin acts as a regulator of transcripts associated with a wide range of cellular processes in mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Francesca Soncin

    Full Text Available BACKGROUND: We have recently shown that expression of the cell adhesion molecule E-cadherin is required for LIF-dependent pluripotency of mouse embryonic stem (ES cells. METHODOLOGY: In this study, we have assessed global transcript expression in E-cadherin null (Ecad-/- ES cells cultured in either the presence or absence of LIF and compared these to the parental cell line wtD3. RESULTS: We show that LIF has little effect on the transcript profile of Ecad-/- ES cells, with statistically significant transcript alterations observed only for Sp8 and Stat3. Comparison of Ecad-/- and wtD3 ES cells cultured in LIF demonstrated significant alterations in the transcript profile, with effects not only confined to cell adhesion and motility but also affecting, for example, primary metabolic processes, catabolism and genes associated with apoptosis. Ecad-/- ES cells share similar, although not identical, gene expression profiles to epiblast-derived pluripotent stem cells, suggesting that E-cadherin expression may inhibit inner cell mass to epiblast transition. We further show that Ecad-/- ES cells maintain a functional β-catenin pool that is able to induce β-catenin/TCF-mediated transactivation but, contrary to previous findings, do not display endogenous β-catenin/TCF-mediated transactivation. We conclude that loss of E-cadherin in mouse ES cells leads to significant transcript alterations independently of β-catenin/TCF transactivation.

  18. Photoinhibition induced alterations in energy transfer process in phycobilisomes of PS II in the cyanobacterium, Spirulina platensis.

    Science.gov (United States)

    Kumar, Duvvuri Prasanna; Murthy, Sistla D S

    2007-09-30

    Exposure of algae or plants to irradiance from above the light saturation point of photosynthesis is known as high light stress. This high light stress induces various responses including photoinhibition of the photosynthetic apparatus. The degree of photoinhibition could be clearly determined by measuring the parameters such as absorption and fluorescence of chromoproteins. In cyanobacteria and red algae, most of the photosystem (PS) II associated light harvesting is performed by a membrane attached complex called the phycobilisome (PBS). The effects of high intensity light (1000-4000 micromol photons m(-2) s(-1)) on excitation energy transfer from PBSs to PS II in a cyanobacterium Spirulina platensis were studied by measuring room temperature PC fluorescence emission spectra. High light (3000 micromol photons m(-2) s(-1)) stress had a significant effect on PC fluorescence emission spectra. On the other hand, light stress induced an increase in the ratio of PC fluorescence intensity of PBS indicating that light stress inhibits excitation energy transfer from PBS to PS II. The high light treatment to 3000 micromol photons m(-2) s(-1) caused disappearance of 31.5 kDa linker polypeptide which is known to link PC discs together. In addition we observed the similar decrease in the other polypeptide contents. Our data concludes that the Spirulina cells upon light treatment causes alterations in the phycobiliproteins (PBPs) and affects the energy transfer process within the PBSs.

  19. Inactivation of a single copy of Crebbp selectively alters pre-mRNA processing in mouse hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Madeleine E Lemieux

    Full Text Available Global expression analysis of fetal liver hematopoietic stem cells (FL HSCs revealed the presence of unspliced pre-mRNA for a number of genes in normal FL HSCs. In a subset of these genes, Crebbp+/- FL HSCs had less unprocessed pre-mRNA without a corresponding reduction in total mRNA levels. Among the genes thus identified were the key regulators of HSC function Itga4, Msi2 and Tcf4. A similar but much weaker effect was apparent in Ep300+/- FL HSCs, indicating that, in this context as in others, the two paralogs are not interchangeable. As a group, the down-regulated intronic probe sets could discriminate adult HSCs from more mature cell types, suggesting that the underlying mechanism is regulated with differentiation stage and is active in both fetal and adult hematopoiesis. Consistent with increased myelopoiesis in Crebbp hemizygous mice, targeted reduction of CREBBP abundance by shRNA in the multipotent EML cell line triggered spontaneous myeloid differentiation in the absence of the normally required inductive signals. In addition, differences in protein levels between phenotypically distinct EML subpopulations were better predicted by taking into account not only the total mRNA signal but also the amount of unspliced message present. CREBBP thus appears to selectively influence the timing and degree of pre-mRNA processing of genes essential for HSC regulation and thereby has the potential to alter subsequent cell fate decisions in HSCs.

  20. Alteration causes and processes in the stone material from the pavement in Baelo Claudia archeological site, Cadiz/Spain

    Directory of Open Access Journals (Sweden)

    Hoyos, M.

    1999-09-01

    Full Text Available A detailed study of the alteration causes in the stone material used in buildings and pavements from the ancient roman town of Baelo Claudia (Cádiz, South Spain was carried out to establish their degree of conservation. Slabs from the pavement of the Forum showed in general a high and irreversible degree of degradation. In order to palliate the action of processes of degradation in subaerial conditions, in this work some measures are proposed to try to preserve the slabs in better conditions.

    En este trabajo se muestran los resultados de un estudio detallado sobre el estado de conservación de los materiales pétreos usados en construcciones y pavimentos de la antigua ciudad romana de Baelo Claudia (Cádiz, Sur de España. En especial, las losas del pavimento del Foro romano mostraron, en general, un alto e irreversible grado de alteración. En este estudio, se proponen medidas correctoras para una mejor preservación de las losas, amortiguando la acción de los procesos de degradación propios de condiciones subaéreas.

  1. Guinea-pig interpubic joint (symphysis pubica relaxation at parturition: Underlying cellular processes that resemble an inflammatory response

    Directory of Open Access Journals (Sweden)

    Muñoz-de-Toro Mónica

    2003-11-01

    Full Text Available Abstract Background At term, cervical ripening in coordination with uterine contractions becomes a prerequisite for a normal vaginal delivery. Currently, cervical ripening is considered to occur independently from uterine contractions. Many evidences suggest that cervical ripening resembles an inflammatory process. Comparatively little attention has been paid to the increased flexibility of the pelvic symphysis that occurs in many species to enable safe delivery. The aim of this study was to investigate whether the guinea-pig interpubic joint relaxation process observed during late pregnancy and parturition resembles an inflammatory process. Methods Samples of pubic symphysis were taken from pregnant guinea-pigs sacrificed along gestation, parturition and postpartum. Serial sections of paraffin-embedded tissues were used to measure the interpubic distance on digitalized images, stained with Giemsa to quantify leukocyte infiltration and to describe the vascular area changes, or studied by the picrosirius-polarization method to evaluate collagen remodeling. P4 and E2 serum levels were measured by a sequential immunometric assay. Results Data showed that the pubic relaxation is associated with an increase in collagen remodeling. In addition, a positive correlation between E2 serum levels and the increase in the interpubic distance was found. On the other hand, a leukocyte infiltration in the interpubic tissue around parturition was described, with the presence of almost all inflammatory cells types. At the same time, histological images show an increase in vascular area (angiogenesis. Eosinophils reached their highest level immediately before parturition; whereas for the neutrophilic and mononuclear infiltration higher values were recorded one day after parturition. Correlation analysis showed that eosinophils and mononuclear cells were positively correlated with E2 levels, but only eosinophilic infiltration was associated with collagen remodeling

  2. Evidence for mechanical and chemical alteration of iron-nickel meteorites on Mars: Process insights for Meridiani Planum

    Science.gov (United States)

    Ashley, James W.; Golombek, M.P.; Christensen, P.R.; Squyres, S. W.; McCoy, T.J.; Schroder, C.; Fleischer, I.; Johnson, J. R.; Herkenhoff, K. E.; Parker, T.J.

    2011-01-01

    The weathering of meteorites found on Mars involves chemical and physical processes that can provide clues to climate conditions at the location of their discovery. Beginning on sol 1961, the Opportunity rover encountered three large iron meteorites within a few hundred meters of each other. In order of discovery, these rocks have been assigned the unofficial names Block Island, Shelter Island, and Mackinac Island. Each rock presents a unique but complimentary set of features that increase our understanding of weathering processes at Meridiani Planum. Significant morphologic characteristics interpretable as weathering features include (1) a large pit in Block Island, lined with delicate iron protrusions suggestive of inclusion removal by corrosive interaction; (2) differentially eroded kamacite and taenite lamellae in Block Island and Shelter Island, providing relative timing through crosscutting relationships with deposition of (3) an iron oxide-rich dark coating; (4) regmaglypted surfaces testifying to regions of minimal surface modification, with other regions in the same meteorites exhibiting (5) large-scale, cavernous weathering (in Shelter Island and Mackinac Island). We conclude that the current size of the rocks is approximate to their original postfall contours. Their morphology thus likely results from a combination of atmospheric interaction and postfall weathering effects. Among our specific findings is evidence supporting (1) at least one possible episode of aqueous acidic exposure for Block Island; (2) ripple migration over portions of the meteorites; (3) a minimum of two separate episodes of wind abrasion; alternating with (4) at least one episode of coating-forming chemical alteration, most likely at subzero temperatures. Copyright 2011 by the American Geophysical Union.

  3. Altered olfactory processing of stress-related body odors and artificial odors in patients with panic disorder.

    Directory of Open Access Journals (Sweden)

    Gloria-Beatrice Wintermann

    Full Text Available BACKGROUND: Patients with Panic Disorder (PD direct their attention towards potential threat, followed by panic attacks, and increased sweat production. Onés own anxiety sweat odor influences the attentional focus, and discrimination of threat or non-threat. Since olfactory projection areas overlap with neuronal areas of a panic-specific fear network, the present study investigated the neuronal processing of odors in general and of stress-related sweat odors in particular in patients with PD. METHODS: A sample of 13 patients with PD with/ without agoraphobia and 13 age- and gender-matched healthy controls underwent an fMRI investigation during olfactory stimulation with their stress-related sweat odors (TSST, ergometry as well as artificial odors (peach, artificial sweat as non-fearful non-body odors. PRINCIPAL FINDINGS: The two groups did not differ with respect to their olfactory identification ability. Independent of the kind of odor, the patients with PD showed activations in fronto-cortical areas in contrast to the healthy controls who showed activations in olfaction-related areas such as the amygdalae and the hippocampus. For artificial odors, the patients with PD showed a decreased neuronal activation of the thalamus, the posterior cingulate cortex and the anterior cingulate cortex. Under the presentation of sweat odor caused by ergometric exercise, the patients with PD showed an increased activation in the superior temporal gyrus, the supramarginal gyrus, and the cingulate cortex which was positively correlated with the severity of the psychopathology. For the sweat odor from the anxiety condition, the patients with PD showed an increased activation in the gyrus frontalis inferior, which was positively correlated with the severity of the psychopathology. CONCLUSIONS: The results suggest altered neuronal processing of olfactory stimuli in PD. Both artificial odors and stress-related body odors activate specific parts of a fear

  4. Altered brain processing of decision-making in healthy first-degree biological relatives of suicide completers.

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    Ding, Y; Pereira, F; Hoehne, A; Beaulieu, M-M; Lepage, M; Turecki, G; Jollant, F

    2016-12-13

    Suicidal behavior is heritable, with the transmission of risk being related to the transmission of vulnerability traits. Previous studies suggest that risky decision-making may be an endophenotype of suicide. Here, we aimed at investigating brain processing of decision-making in relatives of suicide completers in order to shed light on heritable mechanisms of suicidal vulnerability. Seventeen healthy first-degree biological relatives of suicide completers with no personal history of suicidal behavior, 16 relatives of depressed patients without any personal or family history of suicidal behavior, and 19 healthy controls were recruited. Functional 3 T magnetic resonance imaging scans were acquired while participants underwent the Iowa Gambling Task, an economic decision-making test. Whole-brain analyses contrasting activations during risky vs safe choices were conducted with AFNI and FSL. Individuals with a family history of suicide in comparison to control groups showed altered contrasts in left medial orbitofrontal cortex, and right dorsomedial prefrontal cortex. This pattern was different from the neural basis of familial depression. Moreover, controls in comparison to relatives showed increased contrast in several regions including the post-central gyrus, posterior cingulate and parietal cortices, and cerebellum (culmen) in familial suicide; and inferior parietal, temporal, occipital, anteromedial and dorsolateral prefrontal cortices, and cerebellum (vermis) in familial depression. These findings most likely represent a complex combination of vulnerability and protective mechanisms in relatives. They also support a significant role for deficient risk processing, and ventral and dorsal prefrontal cortex functioning in the suicidal diathesis.Molecular Psychiatry advance online publication, 13 December 2016; doi:10.1038/mp.2016.221.

  5. 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.

  6. Effects of chlorate on the sulfation process of Trypanosoma cruzi glycoconjugates. Implication of parasite sulfates in cellular invasion.

    Science.gov (United States)

    Ferrero, Maximiliano R; Soprano, Luciana L; Acosta, Diana M; García, Gabriela A; Esteva, Mónica I; Couto, Alicia S; Duschak, Vilma G

    2014-09-01

    Sulfation, a post-translational modification which plays a key role in various biological processes, is inhibited by competition with chlorate. In Trypanosoma cruzi, the agent of Chagas' disease, sulfated structures have been described as part of glycolipids and we have reported sulfated high-mannose type oligosaccharides in the C-T domain of the cruzipain (Cz) glycoprotein. However, sulfation pathways have not been described yet in this parasite. Herein, we studied the effect of chlorate treatment on T. cruzi with the aim to gain some knowledge about sulfation metabolism and the role of sulfated molecules in this parasite. In chlorate-treated epimastigotes, immunoblotting with anti-sulfates enriched Cz IgGs (AS-enriched IgGs) showed Cz undersulfation. Accordingly, a Cz mobility shift toward higher isoelectric points was observed in 2D-PAGE probed with anti-Cz antibodies. Ultrastructural membrane abnormalities and a significant decrease of dark lipid reservosomes were shown by electron microscopy and a significant decrease in sulfatide levels was confirmed by TLC/UV-MALDI-TOF-MS analysis. Altogether, these results suggest T. cruzi sulfation occurs via PAPS. Sulfated epitopes in trypomastigote and amastigote forms were evidenced using AS-enriched IgGs by immunoblotting. Their presence on trypomastigotes surface was demonstrated by flow cytometry and IF with Cz/dCz specific antibodies. Interestingly, the percentage of infected cardiac HL-1 cells decreased 40% when using chlorate-treated trypomastigotes, suggesting sulfates are involved in the invasion process. The same effect was observed when cells were pre-incubated with dCz, dC-T or an anti-high mannose receptor (HMR) antibody, suggesting Cz sulfates and HMR are also involved in the infection process by T. cruzi.

  7. Genomic alterations in pancreatic cancer and their relevance to therapy

    Institute of Scientific and Technical Information of China (English)

    Erina; Takai; Shinichi; Yachida

    2015-01-01

    Pancreatic cancer is a highly lethal cancer type, for which there are few viable therapeutic options. But, with the advance of sequencing technologies for global genomic analysis, the landscape of genomic alterations in pancreatic cancer is becoming increasingly well understood. In this review, we summarize current knowledge of genomic alterations in 12 core signaling pathways or cellular processes in pancreatic ductal adenocarcinoma, which is the most common type of malignancy in the pancreas, including four commonly mutated genes and many other genes that are mutated at low frequencies. We also describe the potential implications of these genomic alterations for development of novel therapeutic approaches in the context of personalized medicine.

  8. 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 decreased testosterone secretion. The results suggested that graded doses of ecstasy elicit depletion of antioxidant defence system and induce oxidative stress in testis of rats. In conclusion: the adverse effect of ecstasy on male reproduction may be due to induction of oxidative stress

  9. Biological soil crust as a bio-mediator alters hydrological processes in stabilized dune system of the Tengger Desert, China

    Science.gov (United States)

    Li, Xinrong

    2016-04-01

    Biological soil crust (BSC) is a vital component in the stabilized sand dunes with a living cover up to more than 70% of the total, which has been considered as a bio-mediator that directly influences and regulates the sand dune ecosystem processes. However, its influences on soil hydrological processes have been long neglected in Chinese deserts. In this study, BSCs of different successional stages were chose to test their influence on the hydrological processes of stabilized dune, where the groundwater deep exceeds 30m, further to explore why occur the sand-binding vegetation replacement between shrubs and herbs. Our long-term observation (60 years) shows that cyanobacteria crust has been colonized and developed after 3 years since the sand-binding vegetation has been established and dune fixation using planted xerophytic shrubs and made sand barrier (straw-checkerboard) on shifting dune surface, lichen and moss crust occurred after 20 years, and the cover of moss dominated crust could reach 70 % after 50 years. The colonization and development of BSC altered the initial soil water balance of revegetated areas by influencing rainfall infiltration, soil evaporation and dew water entrapment. The results show that BSC obviously reduced the infiltration that occurred during most rainfall events (80%), when rainfall was greater than 5 mm or less than 20 mm. The presence of BSC reduced evaporation of topsoil after small rainfall (BSC. Moreover, the effect of the later successional BSC to dew entrapment, rainfall infiltration and evaporation was more obvious than the early successional BSC on stabilized dunes. In general, BSC reduced the amount of rainfall water that reached deeper soil (0.4-3m), which is where the roots of shrubs are primarily distributed. These changes in the soil moisture pattern induced shifting of sand-binding vegetation from initial planted xerophytic shrub communities with higher coverage (35%) to complex communities dominated by shallow

  10. Sulfur and carbon geochemistry of the Santa Elena peridotites: Comparing oceanic and continental processes during peridotite alteration

    Science.gov (United States)

    Schwarzenbach, Esther M.; Gill, Benjamin C.; Gazel, Esteban; Madrigal, Pilar

    2016-05-01

    Ultramafic rocks exposed on the continent serve as a window into oceanic and continental processes of water-peridotite interaction, so called serpentinization. In both environments there are active carbon and sulfur cycles that contain abiogenic and biogenic processes, which are eventually imprinted in the geochemical signatures of the basement rocks and the calcite and magnesite deposits associated with fluids that issue from these systems. Here, we present the carbon and sulfur geochemistry of ultramafic rocks and carbonate deposits from the Santa Elena ophiolite in Costa Rica. The aim of this study is to leverage the geochemistry of the ultramafic sequence and associated deposits to distinguish between processes that were dominant during ocean floor alteration and those dominant during low-temperature, continental water-peridotite interaction. The peridotites are variably serpentinized with total sulfur concentrations up to 877 ppm that is typically dominated by sulfide over sulfate. With the exception of one sample the ultramafic rocks are characterized by positive δ34Ssulfide (up to + 23.1‰) and δ34Ssulfate values (up to + 35.0‰). Carbon contents in the peridotites are low and are isotopically distinct from typical oceanic serpentinites. In particular, δ13C of the inorganic carbon suggests that the carbon is not derived from seawater, but rather the product of the interaction of meteoric water with the ultramafic rocks. In contrast, the sulfur isotope data from sulfide minerals in the peridotites preserve evidence for interaction with a hydrothermal fluid. Specifically, they indicate closed system abiogenic sulfate reduction suggesting that oceanic serpentinization occurred with limited input of seawater. Overall, the geochemical signatures preserve evidence for both oceanic and continental water-rock interaction with the majority of carbon (and possibly sulfate) being incorporated during continental water-rock interaction. Furthermore, there is

  11. [General and ethical considerations for the informed consent process: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

    Science.gov (United States)

    Thibert, Jean-Baptiste; Polomeni, Alice; Yakoub-Agha, Ibrahim; Bordessoule, Dominique

    2016-11-01

    Informed consent is not restricted to clinical research and must be applied to high-risk care such as hematopoietic stem cell transplantation. If standardized informed consent might improve inequalities in medical practices between different transplantation centers, it is strongly recommended that it be adapted with an honest dialogue between physicians and patients and physicians and donors. In an attempt to harmonize clinical practices among French hematopoietic stem cell transplantation centers, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held its sixth annual workshop series in September 2015 in Lille. This event brought together practitioners from across the country. The purpose of this paper is to highlight the French law concerning patients' rights and ethical practices for an informed consent process to be applied to care or research.

  12. 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

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

    LENUS (Irish Health Repository)

    Duncan, H F

    2011-12-01

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

  14. Root gravitropism: an experimental tool to investigate basic cellular and molecular processes underlying mechanosensing and signal transmission in plants

    Science.gov (United States)

    Boonsirichai, K.; Guan, C.; Chen, R.; Masson, P. H.

    2002-01-01

    The ability of plant organs to use gravity as a guide for growth, named gravitropism, has been recognized for over two centuries. This growth response to the environment contributes significantly to the upward growth of shoots and the downward growth of roots commonly observed throughout the plant kingdom. Root gravitropism has received a great deal of attention because there is a physical separation between the primary site for gravity sensing, located in the root cap, and the site of differential growth response, located in the elongation zones (EZs). Hence, this system allows identification and characterization of different phases of gravitropism, including gravity perception, signal transduction, signal transmission, and curvature response. Recent studies support some aspects of an old model for gravity sensing, which postulates that root-cap columellar amyloplasts constitute the susceptors for gravity perception. Such studies have also allowed the identification of several molecules that appear to function as second messengers in gravity signal transduction and of potential signal transducers. Auxin has been implicated as a probable component of the signal that carries the gravitropic information between the gravity-sensing cap and the gravity-responding EZs. This has allowed the identification and characterization of important molecular processes underlying auxin transport and response in plants. New molecular models can be elaborated to explain how the gravity signal transduction pathway might regulate the polarity of auxin transport in roots. Further studies are required to test these models, as well as to study the molecular mechanisms underlying a poorly characterized phase of gravitropism that is independent of an auxin gradient.

  15. Hydrothermal alteration of surficial rocks at Solfatara (Campi Flegrei): Petrophysical properties and implications for phreatic eruption processes

    Science.gov (United States)

    Mayer, Klaus; Scheu, Bettina; Montanaro, Cristian; Yilmaz, Tim I.; Isaia, Roberto; Aßbichler, Donjá; Dingwell, Donald B.

    2016-06-01

    Solfatara crater is located within the Campi Flegrei caldera to the west of Naples (Italy). It is one of the largest fumarolic manifestations known, and the rocks hosting the hydrothermal system are affected by intense hydrothermal alteration. Alteration can result in changes of degassing behavior, and in the formation of a cap rock thereby increasing the probability of phreatic eruptions. Here, we investigate the effects of alunitic (solfataric) alteration on the mineralogy, the physical properties (porosity, density, permeability) and the mechanical properties (strength) of the rocks involved, as well as its influence on fragmentation and ejection behavior. Our results show that the pristine mineralogy of deposits from the vicinity of the Solfatara cryptodome and from Pisciarelli is almost completely replaced by amorphous silica and alunite. The differences in the degree of alteration among the samples series are reflected in the investigated properties and behavior as well as in the analysis of the experimentally generated particles. Alunitic alteration increases porosity and permeability, whereas it reduces density, elastic wave velocity and strength leading to higher fragmentation and ejection speeds for the sample series examined in this study. Our results also show that alteration results in the generation of a high fraction of fines (particle sizes < 10 μm) during fragmentation, mainly composed of alunite crystals. Due to their potential for inducing chronic disease, dispersion of such material should represent a serious health hazard on a local scale and the evaluation of precautions should be considered.

  16. 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

  17. Alteration Information Extraction by Applying Synthesis Processing Techniques to Landsat ETM+Data: Case Study of Zhaoyuan Gold Mines,Shandong Province, China

    Institute of Scientific and Technical Information of China (English)

    Liu Fujiang; Wu Xincai; Sun Huashan; Guo Yan

    2007-01-01

    Satellite remote sensing data are usually used to analyze the spatial distribution pattern of geological structures and generally serve as a significant means for the identification of alteration zones. Based on the Landsat Enhanced Thematic Mapper (ETM+) data, which have better spectral resolution (8 bands) and spatial resolution (15 m in PAN band), the synthesis processing techniques were presented to fulfill alteration information extraction: data preparation, vegetation indices and band ratios, and expert classifier-based classification. These techniques have been implemented in the MapGIS-RSP software (version 1.0), developed by the Wuhan Zondy Cyber Technology Co., Ltd,China. In the study area application of extracting alteration information in the Zhaoyuan (招远) gold mines, Shandong (山东) Province, China, several hydorthermally altered zones (included two new sites) were found after satellite imagery interpretation coupled with field surveys. It is concluded that these synthesis processing techniques are useful approaches and are applicable to a wide range of gold-mineralized alteration information extraction.

  18. Partial sleep deprivation does not alter processes involved in semantic word priming: event-related potential evidence.

    Science.gov (United States)

    Tavakoli, Paniz; Muller-Gass, Alexandra; Campbell, Kenneth

    2015-03-01

    Sleep deprivation has generally been observed to have a detrimental effect on tasks that require sustained attention for successful performance. It might however be possible to counter these effects by altering cognitive strategies. A recent semantic word priming study indicated that subjects used an effortful predictive-expectancy search of semantic memory following normal sleep, but changed to an automatic, effortless strategy following total sleep deprivation. Partial sleep deprivation occurs much more frequently than total sleep deprivation. The present study therefore employed a similar priming task following either 4h of sleep or following normal sleep. The purpose of the study was to determine whether partial sleep deprivation would also lead to a shift in cognitive strategy to compensate for an inability to sustain attention and effortful processing necessary for using the predicative expectancy strategy. Sixteen subjects were presented with word pairs, a prime and a target that were either strongly semantically associated (cat...dog), weakly associated (cow...barn) or not associated (apple...road). The subject's task was to determine if the target word was semantically associated to the prime. A strong priming effect was observed in both conditions. RTs were slower, accuracy lower, and N400 larger to unassociated targets, independent of the amount of sleep. The overall N400 did not differ as a function of sleep. The scalp distribution of the N400 was also similar following both normal sleep and sleep loss. There was thus little evidence of a difference in the processing of the target stimulus as a function of the amount sleep. Similarly, ERPs in the period between the onset of the prime and the subsequent target also did not differ between the normal sleep and sleep loss conditions. In contrast to total sleep deprivation, subjects therefore appeared to use a common predictive expectancy strategy in both conditions. This strategy does however require an

  19. CLMP is essential for intestinal development, but does not play a key role in cellular processes involved in intestinal epithelial development.

    Directory of Open Access Journals (Sweden)

    Christine S van der Werf

    Full Text Available Loss-of-function mutations in CLMP have been found in patients with Congenital Short Bowel Syndrome (CSBS, suggesting that its encoded protein plays a major role in intestinal development. CLMP is a membrane protein that co-localizes with tight junction proteins, but its function is largely unknown. We expressed wild-type (WT-CLMP and a mutant-CLMP (associated with CSBS in human intestinal epithelial T84 cells that, as we show here, do not produce endogenous CLMP. We investigated the effects of WT-CLMP and mutant-CLMP proteins on key cellular processes that are important for intestinal epithelial development, including migration, proliferation, viability and transepithelial resistance. Our data showed that expression of WT-CLMP or mutant-CLMP does not affect any of these processes. Moreover, our aggregation assays in CHO cells show that CLMP does not act as a strong adhesion molecule. Thus, our data suggest that, in the in vitro model systems we used, the key processes involved in intestinal epithelial development appear to be unaffected by WT-CLMP or mutant-CLMP. Further research is needed to determine the role of CLMP in the development of the intestine.

  20. 1,4-Naphthoquinones: From Oxidative Damage to Cellular and Inter-Cellular Signaling

    Directory of Open Access Journals (Sweden)

    Lars-Oliver Klotz

    2014-09-01

    Full Text Available Naphthoquinones may cause oxidative stress in exposed cells and, therefore, affect redox signaling. Here, contributions of redox cycling and alkylating properties of quinones (both natural and synthetic, such as plumbagin, juglone, lawsone, menadione, methoxy-naphthoquinones, and others to cellular and inter-cellular signaling processes are discussed: (i naphthoquinone-induced Nrf2-dependent modulation of gene expression and its potentially beneficial outcome; (ii the modulation of receptor tyrosine kinases, such as the epidermal growth factor receptor by naphthoquinones, resulting in altered gap junctional intercellular communication. Generation of reactive oxygen species and modulation of redox signaling are properties of naphthoquinones that render them interesting leads for the development of novel compounds of potential use in various therapeutic settings.

  1. Characterization and detection of cellular and proteomic alterations in stable stathmin-overexpressing, taxol-resistant BT549 breast cancer cells using offgel IEF/PAGE difference gel electrophoresis.

    Science.gov (United States)

    Balasubramani, Manimalha; Nakao, Chitose; Uechi, Guy T; Cardamone, John; Kamath, Kathy; Leslie, Kristen L; Balachandran, Raghavan; Wilson, Leslie; Day, Billy W; Jordan, Mary Ann

    2011-06-17

    Stathmin/oncoprotein 18, a protein that regulates microtubule dynamics, is highly expressed in a number of tumors including leukemia, lymphoma, neuroblastoma, breast, ovarian, and prostate cancers. High stathmin levels have been associated with the development of resistance to the widely used anti-cancer drug taxol ((®)Taxol, paclitaxel). The mechanisms of stathmin-mediated taxol resistance are not well-understood at the molecular level. To better understand the role of stathmin in taxol resistance, we stably overexpressed stathmin twofold in BT549 human breast cancer cells and characterized several cell processes involved in the mechanism of action of taxol. After stable overexpression of stathmin, neither the cell doubling time nor the mitotic index was altered and the microtubule polymer mass was reduced only modestly (by 18%). Unexpectedly, microtubule dynamicity was reduced by 29% after stathmin overexpression, resulting primarily from reduction in the catastrophe frequency. Sensitivity to taxol was reduced significantly (by 44%) in a clonogenic assay, and stathmin appeared to protect the cells from the spindle-damaging effects of taxol. The results suggest that in the stably stathmin-overexpressing clones, compensatory gene expression occurred that resulted in normal rates of cell proliferation and prevented the increase in catastrophe frequency expected in response to stathmin. Stathmin overexpression protected the cells from taxol-induced abnormal mitoses, and thus induced taxol resistance. Using offgel IEF/PAGE difference gel electrophoresis, we identified a number of proteins whose expression is reduced in the taxol-resistant stathmin-overexpressing cell lines, including proteins involved in the cytoskeleton and cell structure, the stress response, protein folding, glycolysis, and catalysis.

  2. The Extracellular Environment's Effect on Cellular Processes: An In Vitro Study of Mechanical and Chemical Cues on Human Mesenchymal Stem Cells and C17.2 Neural Stem Cells

    Science.gov (United States)

    Casey, Meghan E.

    Stem cells are widely used in the area of tissue engineering. The ability of cells to interact with materials on the nano- and micro- level is important in the success of the biomaterial. It is well-known that cells respond to their micro- and nano-environments through a process termed chemo-mechanotransduction. It is important to establish standard protocols for cellular experiments, as chemical modifications to maintenance environments can alter long-term research results. In this work, the effects of different media compositions on human mesenchymal stem cells (hMSCs) throughout normal in vitro maintenance are investigated. Changes in RNA regulation, protein expression and proliferation are studied via quantitative polymerase chain reaction (qPCR), immunocytochemistry (ICC) and cell counts, respectively. Morphological differences are also observed throughout the experiment. Results of this study illustrate the dynamic response of hMSC maintenance to differences in growth medium and passage number. These experiments highlight the effect growth medium has on in vitro experiments and the need of consistent protocols in hMSC research. A substantial opportunity exists in neuronal research to develop a material platform that allows for both the proliferation and differentiation of stem cells into neurons and the ability to quantify the secretome of neuronal cells. Anodic aluminum oxide (AAO) membranes are fabricated in a two-step anodization procedure where voltage is varied to control the pore size and morphology of the membranes. C17.2 neural stem cells are differentiated on the membranes via serum-withdrawal. Cellular growth is characterized by scanning electron microscopy (SEM), ICC and qPCR. ImageJ software is used to obtain phenotypic cell counts and neurite outgrowth lengths. Results indicate a highly tunable correlation between AAO nanopore sizes and differentiated cell populations. By selecting AAO membranes with specific pore size ranges, control of neuronal

  3. Enhanced protein adsorption and cellular adhesion using transparent titanate nanotube thin films made by a simple and inexpensive room temperature process: application to optical biochips.

    Science.gov (United States)

    Nador, Judit; Orgovan, Norbert; Fried, Miklos; Petrik, Peter; Sulyok, Attila; Ramsden, Jeremy J; Korosi, Laszlo; Horvath, Robert

    2014-10-01

    A new type of titanate nanotube (TNT) coating is investigated for exploitation in biosensor applications. The TNT layers were prepared from stable but additive-free sols without applying any binding compounds. The simple, fast spin-coating process was carried out at room temperature, and resulted in well-formed films around 10nm thick. The films are highly transparent as expected from their nanostructure and may, therefore, be useful as coatings for surface-sensitive optical biosensors to enhance the specific surface area. In addition, these novel coatings could be applied to medical implant surfaces to control cellular adhesion. Their morphology and structure was characterized by spectroscopic ellipsometry (SE) and atomic force microscopy (AFM), and their chemical state by X-ray photoelectron spectroscopy (XPS). For quantitative surface adhesion studies, the films were prepared on optical waveguides. The coated waveguides were shown to still guide light; thus, their sensing capability remains. Protein adsorption and cell adhesion studies on the titanate nanotube films and on smooth control surfaces revealed that the nanostructured titanate enhanced the adsorption of albumin; furthermore, the coatings considerably enhanced the adhesion of living mammalian cells (human embryonic kidney and preosteoblast).

  4. Comparative genomic analysis of a neurotoxigenic Clostridium species using partial genome sequence: Phylogenetic analysis of a few conserved proteins involved in cellular processes and metabolism.

    Science.gov (United States)

    Alam, Syed Imteyaz; Dixit, Aparna; Tomar, Arvind; Singh, Lokendra

    2010-04-01

    Clostridial organisms produce neurotoxins, which are generally regarded as the most potent toxic substances of biological origin and potential biological warfare agents. Clostridium tetani produces tetanus neurotoxin and is responsible for the fatal tetanus disease. In spite of the extensive immunization regimen, the disease is an important cause of death especially among neonates. Strains of C. tetani have not been genetically characterized except the complete genome sequencing of strain E88. The present study reports the genetic makeup and phylogenetic affiliations of an environmental strain of this bacterium with respect to C. tetani E88 and other clostridia. A shot gun library was constructed from the genomic DNA of C. tetani drde, isolated from decaying fish sample. Unique clones were sequenced and sequences compared with its closest relative C. tetani E88. A total of 275 clones were obtained and 32,457 bases of non-redundant sequence were generated. A total of 150 base changes were observed over the entire length of sequence obtained, including, additions, deletions and base substitutions. Of the total 120 ORFs detected, 48 exhibited closest similarity to E88 proteins of which three are hypothetical proteins. Eight of the ORFs exhibited similarity with hypothetical proteins from other organisms and 10 aligned with other proteins from unrelated organisms. There is an overall conservation of protein sequences among the two strains of C. tetani and. Selected ORFs involved in cellular processes and metabolism were subjected to phylogenetic analysis.

  5. Processing the Bouguer anomaly map of Biga and the surrounding area by the cellular neural network: application to the southwestern Marmara region

    Science.gov (United States)

    Aydogan, D.

    2007-04-01

    An image processing technique called the cellular neural network (CNN) approach is used in this study to locate geological features giving rise to gravity anomalies such as faults or the boundary of two geologic zones. CNN is a stochastic image processing technique based on template optimization using the neighborhood relationships of cells. These cells can be characterized by a functional block diagram that is typical of neural network theory. The functionality of CNN is described in its entirety by a number of small matrices (A, B and I) called the cloning template. CNN can also be considered to be a nonlinear convolution of these matrices. This template describes the strength of the nearest neighbor interconnections in the network. The recurrent perceptron learning algorithm (RPLA) is used in optimization of cloning template. The CNN and standard Canny algorithms were first tested on two sets of synthetic gravity data with the aim of checking the reliability of the proposed approach. The CNN method was compared with classical derivative techniques by applying the cross-correlation method (CC) to the same anomaly map as this latter approach can detect some features that are difficult to identify on the Bouguer anomaly maps. This approach was then applied to the Bouguer anomaly map of Biga and its surrounding area, in Turkey. Structural features in the area between Bandirma, Biga, Yenice and Gonen in the southwest Marmara region are investigated by applying the CNN and CC to the Bouguer anomaly map. Faults identified by these algorithms are generally in accordance with previously mapped surface faults. These examples show that the geologic boundaries can be detected from Bouguer anomaly maps using the cloning template approach. A visual evaluation of the outputs of the CNN and CC approaches is carried out, and the results are compared with each other. This approach provides quantitative solutions based on just a few assumptions, which makes the method more

  6. The pig as a model for excisional skin wound healing: characterization of the molecular and cellular biology, and bacteriology of the healing process.

    Science.gov (United States)

    Wang, J F; Olson, M E; Reno, C R; Wright, J B; Hart, D A

    2001-08-01

    A pig model of wound healing was developed by excision of 2-cm-diameter full thickness skin in young Yorkshire pigs. The results indicated that wound re-epithelialization in this animal model took an average of 20 days. Analysis of cellular change was assessed by use of DNA quantification and determination of apoptotic cells in tissue sections. The results indicate that RNA and DNA contents paralleled each other throughout the healing process, and observed changes in the pattern of RNA and DNA content of the scar tissues were consistent with cell loss due to apoptosis in this model. Expression of mRNA for relevant genes was assessed by use of semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis, using porcine specific primer sets and RNA isolated from normal skin and specimens obtained at various times after wounding. The mRNA values for tumor necrosis factor-alpha (TNF-alpha), connective tissue growth factor (CTGF), insulin-like growth factor II (IGF-II), and decorin were significantly high at specific times after wounding, but mRNA values for the transcription factors (c-fos and c-jun) were significantly decreased. Quantitative bacteriologic results indicated that the total bacterial count in this animal model reached 10(9) colony-forming units (CFU)/g, with the highest value at post-wounding day 7, and Pseudomonas aeruginosa and Staphylocococci aureus were the most common bacteria detected in this model. Further definition of this model should identify unique points in the healing process, and such information could lead to development of therapeutic interventions to improve skin wound healing.

  7. The GH/IGF-1 axis in a critical period early in life determines cellular DNA repair capacity by altering transcriptional regulation of DNA repair-related genes: implications for the developmental origins of cancer.

    Science.gov (United States)

    Podlutsky, Andrej; Valcarcel-Ares, Marta Noa; Yancey, Krysta; Podlutskaya, Viktorija; Nagykaldi, Eszter; Gautam, Tripti; Miller, Richard A; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2017-02-23

    Experimental, clinical, and epidemiological findings support the concept of developmental origins of health and disease (DOHAD), suggesting that early-life hormonal influences during a sensitive period around adolescence have a powerful impact on cancer morbidity later in life. The endocrine changes that occur during puberty are highly conserved across mammalian species and include dramatic increases in circulating GH and IGF-1 levels. Importantly, patients with developmental IGF-1 deficiency due to GH insensitivity (Laron syndrome) do not develop cancer during aging. Rodents with developmental GH/IGF-1 deficiency also exhibit significantly decreased cancer incidence at old age, marked resistance to chemically induced carcinogenesis, and cellular resistance to genotoxic stressors. Early-life treatment of GH/IGF-1-deficient mice and rats with GH reverses the cancer resistance phenotype; however, the underlying molecular mechanisms remain elusive. The present study was designed to test the hypothesis that developmental GH/IGF-1 status impacts cellular DNA repair mechanisms. To achieve that goal, we assessed repair of γ-irradiation-induced DNA damage (single-cell gel electrophoresis/comet assay) and basal and post-irradiation expression of DNA repair-related genes (qPCR) in primary fibroblasts derived from control rats, Lewis dwarf rats (a model of developmental GH/IGF-1 deficiency), and GH-replete dwarf rats (GH administered beginning at 5 weeks of age, for 30 days). We found that developmental GH/IGF-1 deficiency resulted in persisting increases in cellular DNA repair capacity and upregulation of several DNA repair-related genes (e.g., Gadd45a, Bbc3). Peripubertal GH treatment reversed the radiation resistance phenotype. Fibroblasts of GH/IGF-1-deficient Snell dwarf mice also exhibited improved DNA repair capacity, showing that the persisting influence of peripubertal GH/IGF-1 status is not species-dependent. Collectively, GH/IGF-1 levels during a critical period

  8. Growth hormone and melatonin prevent age-related alteration in apoptosis processes in the dentate gyrus of male rats

    OpenAIRE

    R A Kireev; Vara, E. (E.); Tresguerres, J. A. F.

    2013-01-01

    It has been suggested that the age-related decrease in the number of neurons in the hippocampus that leads to alterations in brain function, may be associated with an increase in apoptosis due to the reduced secretion of growth hormone (GH) and/or melatonin in old animals. In order to investigate this possibility, male Wistar rats of 22 months of age were divided into three groups. One group remained untreated and acted as the control group. The second was treated with growth hormone (hGH) fo...

  9. 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.

  10. Developmental changes in reading do not alter the development of visual processing skills: An application of explanatory item response models in grades K-2

    Directory of Open Access Journals (Sweden)

    Kristi L Santi

    2015-02-01

    Full Text Available Visual processing has been widely studied in regard to its impact on a students’ ability to read. A less researched area is the role of reading in the development of visual processing skills. A cohort-sequential, accelerated-longitudinal design was utilized with 932 kindergarten, first, and second grade students to examine the impact of reading acquisition on the processing of various types of visual discrimination and visual motor test items. Students were assessed four times per year on a variety of reading measures and reading precursors and two popular measures of visual processing over a three-year period. Explanatory item response models were used to examine the roles of person and item characteristics on changes in visual processing abilities and changes in item difficulties over time. Results showed different developmental patterns for five types of visual processing test items, but most importantly failed to show consistent effects of learning to read on changes in item difficulty. Thus, the present study failed to find support for the hypothesis that learning to read alters performance on measures of visual processing. Rather, visual processing and reading ability improved together over time with no evidence to suggest cross-domain influences from reading to visual processing. Results are discussed in the context of developmental theories of visual processing and brain-based research on the role of visual skills in learning to read.

  11. 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.

  12. Raman-Mössbauer-XRD studies of selected samples from "Los Azulejos" outcrop: A possible analogue for assessing the alteration processes on Mars

    Science.gov (United States)

    Lalla, E. A.; Sanz-Arranz, A.; Lopez-Reyes, G.; Sansano, A.; Medina, J.; Schmanke, D.; Klingelhoefer, G.; Rodríguez-Losada, J. A.; Martínez-Frías, J.; Rull, F.

    2016-06-01

    The outcrop of "Los Azulejos" is visible at the interior of the Cañadas Caldera in Tenerife Island (Spain). It exhibits a great variety of alteration processes that could be considered as terrestrial analogue for several geological processes on Mars. This outcrop is particularly interesting due to the content of clays, zeolite, iron oxides, and sulfates corresponding to a hydrothermal alteration catalogued as "Azulejos" type alteration. A detailed analysis by portable and laboratory Raman systems as well as other different techniques such as X-ray diffraction (XRD) and Mössbauer spectroscopy has been carried out (using twin-instruments from Martian lander missions: Mössbauer spectrometer MIMOS-II from the NASA-MER mission of 2001 and the XRD diffractometer from the NASA-MSL Curiosity mission of 2012). The mineral identification presents the following mineral species: magnetite, goethite, hematite, anatase, rutile, quartz, gregoryite, sulfate (thenardite and hexahydrite), diopside, feldspar, analcime, kaolinite and muscovite. Moreover, the in-situ Raman and Micro-Raman measurements have been performed in order to compare the capabilities of the portable system specially focused for the next ESA Exo-Mars mission. The mineral detection confirms the sub-aerial alteration on the surface and the hydrothermal processes by the volcanic fluid circulations in the fresh part. Therefore, the secondary more abundant mineralization acts as the color agent of the rocks. Thus, the zeolite-illite group is the responsible for the bluish coloration, as well as the feldspars and carbonates for the whitish and the iron oxide for the redish parts. The XRD system was capable to detect a minor proportion of pyroxene, which is not visible by Raman and Mössbauer spectroscopy due to the "Azulejos" alteration of the parent material on the outcrop. On the other hand, Mössbauer spectroscopy was capable of detecting different types of iron-oxides (Fe3+/2+-oxide phases). These analyses

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

    Directory of Open Access Journals (Sweden)

    Yu Lingfeng

    2006-03-01

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

  14. Altered Neural Correlates of Emotion Associated Pain Processing in Persistent Somatoform Pain Disorder: An fMRI Study.

    Science.gov (United States)

    Luo, Yanli; Yan, Chao; Huang, Tianming; Fan, Mingxia; Liu, Liang; Zhao, Zhiyong; Ni, Kaiji; Jiang, Hong; Huang, Xiao; Lu, Zheng; Wu, Wenyuan; Zhang, Mingyuan; Fan, Xiaoduo

    2016-09-19

    Patients with persistent somatoform pain disorder (PSPD) suffer from long-term pain and emotional conflicts. Recently, accumulating evidence indicated that emotion has a significant role in pain perception of somatoform pain disorder. To further understand the association between emotion and pain-related brain activities, functional activities of patients with PSPD fulfilling ICD-10 criteria and healthy controls were assessed using functional magnetic resonance imaging technology, while participants viewed a series of positive, neutral, or negative pictures with or without pinprick pain stimulation. Results showed that patients with PSPD had altered brain activities in the parietal gyrus, temporal gyrus, posterior cingulate cortex, prefrontal cortex, and parahippocampus in response to pinprick pain stimuli during different emotions compared with the healthy control group. Moreover, patients with PSPD consistently showed hyperactivities in the prefrontal, the fusiform gyrus and the insula in response to negative stimuli under pinprick pain vs. non-pain condition. The current findings provide some insights into the underlying relationship between emotion and pain-related brain activity in patients with PSPD, which is of both theoretical and clinical importance.

  15. Elephant Moraine 96029, a very mildly aqueously altered and heated CM carbonaceous chondrite: Implications for the drivers of parent body processing

    Science.gov (United States)

    Lee, Martin R.; Lindgren, Paula; King, Ashley J.; Greenwood, Richard C.; Franchi, Ian A.; Sparkes, Robert

    2016-08-01

    Elephant Moraine (EET) 96029 is a CM carbonaceous chondrite regolith breccia with evidence for unusually mild aqueous alteration, a later phase of heating and terrestrial weathering. The presence of phyllosilicates and carbonates within chondrules and the fine-grained matrix indicates that this meteorite was aqueously altered in its parent body. Features showing that water-mediated processing was arrested at a very early stage include a matrix with a low magnesium/iron ratio, chondrules whose mesostasis contains glass and/or quench crystallites, and a gehlenite-bearing calcium- and aluminium-rich inclusion. EET 96029 is also rich in Fe,Ni metal relative to other CM chondrites, and more was present prior to its partial replacement by goethite during Antarctic weathering. In combination, these properties indicate that EET 96029 is one of the least aqueously altered CMs yet described (CM2.7) and so provides new insights into the original composition of its parent body. Following aqueous alteration, and whilst still in the parent body regolith, the meteorite was heated to ∼400-600 °C by impacts or solar radiation. Heating led to the amorphisation and dehydroxylation of serpentine, replacement of tochilinite by magnetite, loss of sulphur from the matrix, and modification to the structure of organic matter that includes organic nanoglobules. Significant differences between samples in oxygen isotope compositions, and water/hydroxyl contents, suggests that the meteorite contains lithologies that have undergone different intensities of heating. EET 96029 may be more representative of the true nature of parent body regoliths than many other CM meteorites, and as such can help interpret results from the forthcoming missions to study and return samples from C-complex asteroids.

  16. Insights into magmatic processes and hydrothermal alteration of in situ superfast spreading ocean crust at ODP/IODP site 1256 from a cluster analysis of rock magnetic properties

    Science.gov (United States)

    Dekkers, Mark J.; Heslop, David; Herrero-Bervera, Emilio; Acton, Gary; Krasa, David

    2014-08-01

    analyze magnetic properties from Ocean Drilling Program (ODP)/Integrated ODP (IODP) Hole 1256D (6°44.1' N, 91°56.1' W) on the Cocos Plate in ˜15.2 Ma oceanic crust generated by superfast seafloor spreading, the only drill hole that has sampled all three oceanic crust layers in a tectonically undisturbed setting. Fuzzy c-means cluster analysis and nonlinear mapping are utilized to study down-hole trends in the ratio of the saturation remanent magnetization and the saturation magnetization, the coercive force, the ratio of the remanent coercive force and coercive force, the low-field magnetic susceptibility, and the Curie temperature, to evaluate the effects of magmatic and hydrothermal processes on magnetic properties. A statistically robust five cluster solution separates the data predominantly into three clusters that express increasing hydrothermal alteration of the lavas, which differ from two distinct clusters mainly representing the dikes and gabbros. Extensive alteration can obliterate magnetic property differences between lavas, dikes, and gabbros. The imprint of thermochemical alteration on the iron-titanium oxides is only partially related to the porosity of the rocks. Thus, the analysis complements interpretation based on electrofacies analysis. All clusters display rock magnetic characteristics compatible with an ability to retain a stable natural remanent magnetization suggesting that the entire sampled sequence of ocean crust can contribute to marine magnetic anomalies. Paleointensity determination is difficult because of the propensity of oxyexsolution during laboratory heating and/or the presence of intergrowths. The upper part of the extrusive sequence, the granoblastic dikes, and moderately altered gabbros may contain a comparatively uncontaminated thermoremanent magnetization.

  17. Processing strawberries to different products alters contents of vitamin C, total phenolics, total anthocyanins, and antioxidant capacity.

    Science.gov (United States)

    Klopotek, Yvonne; Otto, Konrad; Böhm, Volker

    2005-07-13

    Strawberries were processed to juice, nectar, wine, and puree. For investigation of the antioxidant capacity as well as the contents of ascorbic acid, total phenolics and total anthocyanins, samples were taken after different stages of production to determine the effects of processing. The content of vitamin C was measured spectrophotometrically. The total phenolic content was analyzed by using the Folin-Ciocalteu method, and the amount of total anthocyanins was determined by using the pH-differential method. Two different methods-the trolox equivalent antioxidant capacity assay and the ferric reducing antioxidant power test-were used to determine the hydrophilic antioxidant capacity. This study showed the decrease of all investigated parameters within processing strawberries to different products. The content of ascorbic acid decreased with production time and processing steps, especially during heat treatment. The investigations on total phenolics in strawberry products proved fining to be a mild method to clarify berry juices and wines without removing high amounts of total phenolics. Fermentation did not lead to heavy losses of total phenolics, probably due to polymerization and condensation of monomer phenolics such as anthocyanins. Total anthocyanins and the hydrophilic antioxidant capacity decreased while using high temperatures. Anthocyanins also decreased considerably during the processing of wines, mainly caused by fermentation and pasteurization.

  18. Alterations in neural processing of emotional faces in adolescent anorexia nervosa patients - an event-related potential study.

    Science.gov (United States)

    Sfärlea, Anca; Greimel, Ellen; Platt, Belinda; Bartling, Jürgen; Schulte-Körne, Gerd; Dieler, Alica C

    2016-09-01

    The present study explored the neurophysiological correlates of perception and recognition of emotional facial expressions in adolescent anorexia nervosa (AN) patients using event-related potentials (ERPs). We included 20 adolescent girls with AN and 24 healthy girls and recorded ERPs during a passive viewing task and three active tasks requiring processing of emotional faces in varying processing depths; one of the tasks also assessed emotion recognition abilities behaviourally. Despite the absence of behavioural differences, we found that across all tasks AN patients exhibited a less pronounced early posterior negativity (EPN) in response to all facial expressions compared to controls. The EPN is an ERP component reflecting an automatic, perceptual processing stage which is modulated by the intrinsic salience of a stimulus. Hence, the less pronounced EPN in anorexic girls suggests that they might perceive other people's faces as less intrinsically relevant, i.e. as less "important" than do healthy girls.

  19. Growth hormone and melatonin prevent age-related alteration in apoptosis processes in the dentate gyrus of male rats.

    Science.gov (United States)

    Kireev, R A; Vara, E; Tresguerres, J A F

    2013-08-01

    It has been suggested that the age-related decrease in the number of neurons in the hippocampus that leads to alterations in brain function, may be associated with an increase in apoptosis due to the reduced secretion of growth hormone (GH) and/or melatonin in old animals. In order to investigate this possibility, male Wistar rats of 22 months of age were divided into three groups. One group remained untreated and acted as the control group. The second was treated with growth hormone (hGH) for 10 weeks (2 mg/kg/d sc) and the third was subjected to melatonin treatment (1 mg/kg/d) in the drinking water for the same time. A group of 2-months-old male rats was used as young controls. All rats were killed by decapitation at more than 24 month of age and dentate gyri of the hippocampi were collected. Aging in the dentate gyrus was associated with an increase in apoptosis promoting markers (Bax, Bad and AIF) and with the reduction of some anti-apoptotic ones (XIAP, NIAP, Mcl-1). Expressions of sirtuin 1 and 2 (SIRT1 and 2) as well as levels of HSP 70 were decreased in the dentate gyrus of old rats. GH treatment was able to reduce the pro/anti-apoptotic ratio to levels observed in young animals and also to increase SIRT2. Melatonin reduced also expression of pro-apoptotic genes and proteins (Bax, Bad and AIF), and increased levels of myeloid cell leukemia-1 proteins and SIRT1. Both treatments were able to reduce apoptosis and to enhance survival markers in this part of the hippocampus.

  20. Matching plant and animal processes to alter nutrient supply in strip-grazed cattle: timing of herbage and fasting allocation.

    Science.gov (United States)

    Gregorini, P; Gunter, S A; Beck, P A

    2008-04-01

    This work aimed to assess the impact of timing of herbage allocation and fasting on patterns of ingestive behavior, herbage intake, ruminal fermentation, nutrient flow to the duodenum, and site and extent of digestion. Treatments were daily herbage allocation in the afternoon (1500 h, AHA), morning (0800 h, MHA), AHA after 20 h of fasting (AHAF), and MHA after 20 h of fasting (MHAF). Four ruminally and duodenally fistulated heifers (279 +/- 99 kg of BW) individually strip-grazed wheat pastures in a Latin-square design. Eating, rumination, and idling behavior were recorded every 2 min, and bite and eating step rates were measured hourly while the heifers were grazing (11 h MHA and AHA; 4 h MHAF and AHAF). Ruminal DM pools were measured 4 times daily (0800, 1200, 1500, and 1900 h) to estimate daily herbage DMI and its pattern. Ruminal fluid was sampled at these same times and also at 2300 h. Duodenal digesta was sampled over 2 d to determine the site of herbage digestibility. Treatments did not affect daily herbage DMI (16.5 g/ kg of BW, SE = 0.0025; P > 0.05). However, they altered the eating pattern; the evening grazing bout of AHA and AHAF was greater (P 0.05) among MHA, MHAF, and AHAF; however, it averaged 970, 40, 300, and 540 g/d, respectively, greater (P 0.05) for MHA, AHA, and AHAF, but was lower for MHAF (P 0.05) within fasted and nonfasted treatments; however, it was greater (P 0.05) among MHA, MHAF, and AHAF, but was greater (P nutrient supply. At the same amount of resource allocation, nutrient supply to grazing cattle can be modified through strategic grazing management.

  1. 苜蓿中华根瘤菌nifA基因突变影响多种细胞学过程%Disruption of nifA Gene Influences Multiple Cellular Processes in Sinorhizobium meliloti

    Institute of Scientific and Technical Information of China (English)

    巩子英; 朱家璧; 俞冠翘; 邹华松

    2007-01-01

    Sinorhizobium meliloti nifA is important in fixing nitrogen during symbiosis. A nifA null mutant induces small white invalid nodules in the roots of host plant. The additional phenotypic alterations associated with the disruption of the nifA gene are reported in this study. Under a free-living state, S. meliloti nifA mutant reduces its ability to swarm on a half-solid plate. Interestingly, the AHL (Acylhomoserine lactones) contents in the nifA mutant are lower than that of the wild type during the lag phase,whereas it is reversed in the logarithmic and stationary phases. Quantitative spectrophotometric assays reveal that the total amount of extracellular proteins of the nifA mutant are lower than that of the wild type. In addition, the mutant abolishes its nodulation competitive ability during symbiosis. These findings indicate that NifA plays a regulatory role in multiple cellular processes in S.meliloti.%苜蓿中华根瘤菌nifA基因在共生固氮过程中担负着调控功能,nifA突变株Rm1354在宿主植物的根部诱导白色无效根瘤.本文报道Rm1354在自生状态下的表型变化.nifA的突变导致根瘤菌在半固体培养基上泳动变慢,胞外蛋白含量降低.有趣的是,Rm1354在延宕期间高丝氨酸内酯含量比野生型低,在指数期和静止期却比野生型高.另外,突变株Rm1354的竞争结瘤能力也大大减弱.这些结果揭示了苜蓿中华根瘤菌nifA基因对许多细胞学过程都有调控作用.

  2. Genetic and epigenetic alterations in pancreatic carcinogenesis.

    Science.gov (United States)

    Delpu, Yannick; Hanoun, Naïma; Lulka, Hubert; Sicard, Flavie; Selves, Janick; Buscail, Louis; Torrisani, Jérôme; Cordelier, Pierre

    2011-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Despite significant progresses in the last decades, the origin of this cancer remains unclear and no efficient therapy exists. PDAC does not arise de novo: three remarkable different types of pancreatic lesions can evolve towards pancreatic cancer. These precursor lesions include: Pancreatic intraepithelial neoplasia (PanIN) that are microscopic lesions of the pancreas, Intraductal Papillary Mucinous Neoplasms (IPMN) and Mucinous Cystic Neoplasms (MCN) that are both macroscopic lesions. However, the cellular origin of these lesions is still a matter of debate. Classically, neoplasm initiation or progression is driven by several genetic and epigenetic alterations. The aim of this review is to assemble the current information on genetic mutations and epigenetic disorders that affect genes during pancreatic carcinogenesis. We will further discuss the interest of the genetic and epigenetic alterations for the diagnosis and prognosis of PDAC. Large genetic alterations (chromosomal deletion/amplification) and single point mutations are well described for carcinogenesis inducers. Mutations classically occur within key regions of the genome. Consequences are various and include activation of mitogenic pathways or silencing of apoptotic processes. Alterations of K-RAS, P16 and DPC4 genes are frequently observed in PDAC samples and have been described to arise gradually during carcinogenesis. DNA methylation is an epigenetic process involved in imprinting and X chromosome inactivation. Alteration of DNA methylation patterns leads to deregulation of gene expression, in the absence of mutation. Both genetic and epigenetic events influence genes and non-coding RNA expression, with dramatic effects on proliferation, survival and invasion. Besides improvement in our fundamental understanding of PDAC development, highlighting the molecular alterations that occur in pancreatic carcinogenesis could

  3. Prism adaptation does not alter configural processing of faces [v1; ref status: indexed, http://f1000r.es/1wk

    Directory of Open Access Journals (Sweden)

    Janet H. Bultitude

    2013-10-01

    Full Text Available Patients with hemispatial neglect (‘neglect’ following a brain lesion show difficulty responding or orienting to objects and events on the left side of space. Substantial evidence supports the use of a sensorimotor training technique called prism adaptation as a treatment for neglect. Reaching for visual targets viewed through prismatic lenses that induce a rightward shift in the visual image results in a leftward recalibration of reaching movements that is accompanied by a reduction of symptoms in patients with neglect. The understanding of prism adaptation has also been advanced through studies of healthy participants, in whom adaptation to leftward prismatic shifts results in temporary neglect-like performance. Interestingly, prism adaptation can also alter aspects of non-lateralised spatial attention. We previously demonstrated that prism adaptation alters the extent to which neglect patients and healthy participants process local features versus global configurations of visual stimuli. Since deficits in non-lateralised spatial attention are thought to contribute to the severity of neglect symptoms, it is possible that the effect of prism adaptation on these deficits contributes to its efficacy. This study examines the pervasiveness of the effects of prism adaptation on perception by examining the effect of prism adaptation on configural face processing using a composite face task. The composite face task is a persuasive demonstration of the automatic global-level processing of faces: the top and bottom halves of two familiar faces form a seemingly new, unknown face when viewed together. Participants identified the top or bottom halves of composite faces before and after prism adaptation. Sensorimotor adaptation was confirmed by significant pointing aftereffect, however there was no significant change in the extent to which the irrelevant face half interfered with processing. The results support the proposal that the therapeutic effects

  4. Ultrastructural alterations of the hepatopancreas in Porcellio scaber under stress.

    Science.gov (United States)

    Znidaršič, Nada; Strus, Jasna; Drobne, Damjana

    2003-04-01

    Cellular ultrastructure varies in accordance with physiological processes, also reflecting responses to environmental stress factors. Ultrastructural changes of the hepatopancreatic cells in the terrestrial isopod Porcellio scaber exposed to sublethal concentrations of zinc or cadmium in their food were identified by transmission electron microscopy. The exclusive structural characteristic of the hepatopancreas of animals exposed to metal-dosed food was grain-like electrondense deposits (EDD) observed in the intercellular spaces and in vesicles of B cells. In addition, hepatopancreatic cells of metal-exposed animals displayed non-specific, stress-indicating alterations such as cellular disintegration, the reduction of energetic reserves (lipid droplets, glycogen), electron dense cytoplasm, ultrastructural alterations of granular endoplasmic reticulum (GER), the Golgi complex and mitochondria.

  5. A computational account of altered error processing in older age: Dopamine and the error-related negativity

    NARCIS (Netherlands)

    Nieuwenhuis, Sander; Ridderinkhof, K. Richard; Talsma, Durk; Coles, Michael G.H.; Holroyd, Clay B.; Kok, Albert; Molen, van der Maurits W.

    2002-01-01

    When participants commit errors or receive feedback signaling that they have made an error, a negative brain potential is elicited. According to Holroyd and Coles’s (in press) neurocomputational model of error processing, this error-related negativity (ERN) is elicited when the brain first detects t

  6. A computational account of altered error processing in older age: Dopamine and the error-related negativity

    NARCIS (Netherlands)

    Nieuwenhuis, S.; Ridderinkhof, K.R.; Talsma, D.; Coles, M.G.; Holroyd, C.B.; Kok, A.

    2002-01-01

    When participants commit errors or receive feedback signaling that they have made an error, a negative brain potential is elicited. According to Holroyd and Coles's (in press) neurocomputational model of error processing, this error-related negativity (ERN) is elicited when the brain first detects t

  7. Acute serotonin 2A receptor blocking alters the processing of fearful faces in the orbitofrontal cortex and amygdala

    DEFF Research Database (Denmark)

    Hornboll, Bettina; Macoveanu, Julian; Rowe, James;

    2013-01-01

    blockade reduced the neural response to fearful faces in the medial orbitofrontal cortex (OFC), independently of 5-HT2A receptor occupancy or neocortical 5-HT2A receptor BPp . The medial OFC also showed increased functional coupling with the left amygdala during processing of fearful faces depending...

  8. Altered Cell Mechanics from the Inside: Dispersed Single Wall Carbon Nanotubes Integrate with and Restructure Actin

    Directory of Open Access Journals (Sweden)

    Mohammad F. Islam

    2012-05-01

    Full Text Available With a range of desirable mechanical and optical properties, single wall carbon nanotubes (SWCNTs are a promising material for nanobiotechnologies. SWCNTs also have potential as biomaterials for modulation of cellular structures. Previously, we showed that highly purified, dispersed SWCNTs grossly alter F-actin inside cells. F-actin plays critical roles in the maintenance of cell structure, force transduction, transport and cytokinesis. Thus, quantification of SWCNT-actin interactions ranging from molecular, sub-cellular and cellular levels with both structure and function is critical for developing SWCNT-based biotechnologies. Further, this interaction can be exploited, using SWCNTs as a unique actin-altering material. Here, we utilized molecular dynamics simulations to explore the interactions of SWCNTs with actin filaments. Fluorescence lifetime imaging microscopy confirmed that SWCNTs were located within ~5 nm of F-actin in cells but did not interact with G-actin. SWCNTs did not alter myosin II sub-cellular localization, and SWCNT treatment in cells led to significantly shorter actin filaments. Functionally, cells with internalized SWCNTs had greatly reduced cell traction force. Combined, these results demonstrate direct, specific SWCNT alteration of F-actin structures which can be exploited for SWCNT-based biotechnologies and utilized as a new method to probe fundamental actin-related cellular processes and biophysics.

  9. Massive bowel resection upregulates the intestinal mRNA expression levels of cellular retinol-binding protein II and apolipoprotein A-IV and alters the intestinal vitamin A status in rats.

    Science.gov (United States)

    Hebiguchi, Taku; Mezaki, Yoshihiro; Morii, Mayako; Watanabe, Ryo; Yoshikawa, Kiwamu; Miura, Mitsutaka; Imai, Katsuyuki; Senoo, Haruki; Yoshino, Hiroaki

    2015-03-01

    Short bowel (SB) syndrome causes the malabsorption of various nutrients. Among these, vitamin A is important for a number of physiological activities. Vitamin A is absorbed by epithelial cells of the small intestine and is discharged into the lymphatic vessels as a component of chylomicrons and is delivered to the liver. In the present study, we used a rat model of SB syndrome in order to assess its effects on the expression of genes associated with the absorption, transport and metabolism of vitamin A. In the rats with SB, the intestinal mRNA expression levels of cellular retinol-binding protein II (CRBP II, gene symbol Rbp2) and apolipoprotein A-IV (gene symbol Apoa4) were higher than those in the sham-operated rats, as shown by RT-qPCR. Immunohistochemical analysis revealed that absorptive epithelial cells stained positive for both CRBP II and lecithin retinol acyltransferase, which are both required for the effective esterification of vitamin A. In the rats with SB, the retinol content in the ileum and the retinyl ester content in the jejunum were lower than those in the sham-operated rats, as shown by quantitative analysis of retinol and retinyl esters by high performance liquid chromatography. These results suggest that the elevated mRNA expression levels of Rbp2 and Apoa4 in the rats with SB contribute to the effective esterification and transport of vitamin A.

  10. DIFFERENTIAL KINETICS IN ALTERATION AND RECOVERY OF COGNITIVE PROCESSES FROM A CHRONIC SLEEP RESTRICTION IN YOUNG HEALTHY MEN.

    Directory of Open Access Journals (Sweden)

    Arnaud Alexandre Rabat

    2016-05-01

    Full Text Available Chronic sleep restriction (CSR induces neurobehavioral deficits in young and healthy people with a morning failure of sustained attention process. Testing both the kinetic of failure and recovery of different cognitive processes (i.e. attention, executive under CSR and their potential links with subject’s capacities (stay awake, baseline performance, age and with some biological markers of stress and anabolism would be useful in order to understand the role of sleep debt on human behavior. Twelve healthy subjects spent 14 days in laboratory with 2 baseline days (B1 and B2, 8h TIB followed by 7 days of sleep restriction (SR1-SR7, 4h TIB, 3 sleep recovery days (R1-R3, 8h TIB and 2 more ones 8 days later (R12-R13. Subjective sleepiness (KSS, maintenance of wakefulness latencies (MWT were evaluated 4 times a day (10:00, 12:00 a.m. and 2:00, 4:00 p.m. and cognitive tests were realized at morning (8:30 a.m. and evening (6:30 p.m. sessions during B2, SR1, SR4, SR7, R2, R3 and R13. Saliva (B2, SR7, R2, R13 and blood (B1, SR6, R1, R12 samples were collected in the morning. Cognitive processes were differently impaired and recovered with a more rapid kinetic for sustained attention process. Besides, a significant time of day effect was only evidenced for sustained attention failures that seemed to be related to subject’s age and their morning capacity to stay awake. Executive processes were equally disturbed/recovered during the day and this failure/recovery process seemed to be mainly related to baseline subject’s performance and to their capacity to stay awake. Morning concentrations of testosterone, cortisol and α-amylase were significantly decreased at SR6-SR7, but were either and respectively early (R1, tardily (after R2 and no recovered (R13. All these results suggest a differential deleterious and restorative effect of CSR on cognition through biological changes of the stress pathway and subject’s capacity (ClinicalTrials-NCT01989741.

  11. Differential Kinetics in Alteration and Recovery of Cognitive Processes from a Chronic Sleep Restriction in Young Healthy Men.

    Science.gov (United States)

    Rabat, Arnaud; Gomez-Merino, Danielle; Roca-Paixao, Laura; Bougard, Clément; Van Beers, Pascal; Dispersyn, Garance; Guillard, Mathias; Bourrilhon, Cyprien; Drogou, Catherine; Arnal, Pierrick J; Sauvet, Fabien; Leger, Damien; Chennaoui, Mounir

    2016-01-01

    Chronic sleep restriction (CSR) induces neurobehavioral deficits in young and healthy people with a morning failure of sustained attention process. Testing both the kinetic of failure and recovery of different cognitive processes (i.e., attention, executive) under CSR and their potential links with subject's capacities (stay awake, baseline performance, age) and with some biological markers of stress and anabolism would be useful in order to understand the role of sleep debt on human behavior. Twelve healthy subjects spent 14 days in laboratory with 2 baseline days (B1 and B2, 8 h TIB) followed by 7 days of sleep restriction (SR1-SR7, 4 h TIB), 3 sleep recovery days (R1-R3, 8 h TIB) and two more ones 8 days later (R12-R13). Subjective sleepiness (KSS), maintenance of wakefulness latencies (MWT) were evaluated four times a day (10:00, 12:00 a.m. and 2:00, 4:00 p.m.) and cognitive tests were realized at morning (8:30 a.m.) and evening (6:30 p.m.) sessions during B2, SR1, SR4, SR7, R2, R3 and R13. Saliva (B2, SR7, R2, R13) and blood (B1, SR6, R1, R12) samples were collected in the morning. Cognitive processes were differently impaired and recovered with a more rapid kinetic for sustained attention process. Besides, a significant time of day effect was only evidenced for sustained attention failures that seemed to be related to subject's age and their morning capacity to stay awake. Executive processes were equally disturbed/recovered during the day and this failure/recovery process seemed to be mainly related to baseline subject's performance and to their capacity to stay awake. Morning concentrations of testosterone, cortisol and α-amylase were significantly decreased at SR6-SR7, but were either and respectively early (R1), tardily (after R2) and not at all (R13) recovered. All these results suggest a differential deleterious and restorative effect of CSR on cognition through biological changes of the stress pathway and subject's capacity (ClinicalTrials-NCT01989741).

  12. 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.

  13. Balancing bilateral sensory activity: callosal processing modulates sensory transmission through the contralateral thalamus by altering the response threshold.

    Science.gov (United States)

    Li, Lu; Ebner, Ford F

    2006-07-01

    Rats tactually explore a nearly spherical space field around their heads with their whiskers. The information sampled by the two sets of whiskers is integrated bilaterally at the cortical level in an activity dependent manner via the corpus callosum. We have recently shown that sensory activity in one barrel field cortex (BFC) modulates the processing of incoming sensory information to the other BFC. Whether interhemispheric integration is dynamically linked with corticothalamic modulation of incoming sensory activity is an important hypothesis to test, since subcortical relay neurons are directly modulated by cortical neurons through top-down processes. In the present study, we compared the direct sensory responses of single thalamic relay neurons under urethane anesthesia before and after inactivating the BFC contralateral to a thalamic neuron. The data show that silencing one BFC reduces response magnitude in contralateral thalamic relay neurons, significantly and reversibly, in response to test stimuli applied to the principal whisker at two times response threshold (2T) intensity for each unit. Neurons in the ventral posterior medial (VPM) nucleus and the medial division of the posterior nucleus (POm) react in a similar manner, although POm neurons are more profoundly depressed by inactivation of the contralateral BFC than VPM neurons. The results support the novel idea that the subcortical relay of sensory information to one hemisphere is strongly modulated by activity levels in the contralateral as well as in the ipsilateral SI cortex. The mechanism of the modulation appears to be based on shifting the stimulus-response curves of thalamic neurons, thereby rendering them more or less sensitive to sensory stimuli. We conclude that global sensory processing is created by combining activity in each cerebral hemisphere and continually balancing the flow of information to cortex by adjusting the responsiveness of ascending sensory pathways.

  14. Biological effects of the electrostatic field: red blood cell-related alterations of oxidative processes in blood

    Science.gov (United States)

    Harutyunyan, Hayk A.; Sahakyan, Gohar V.

    2016-01-01

    The aim of this study was to determine activities of pro-/antioxidant enzymes, reactive oxygen species (ROS) content, and oxidative modification of proteins and lipids in red blood cells (RBCs) and blood plasma of rats exposed to electrostatic field (200 kV/m) during the short (1 h) and the long periods (6 day, 6 h daily). Short-term exposure was characterized by the increase of oxidatively damaged proteins in blood of rats. This was strongly expressed in RBC membranes. After long-term action, RBC content in peripheral blood was higher than in control ( P < 0.01) and the attenuation of prooxidant processes was shown.

  15. Reactive biomolecular divergence in genetically altered yeast cells and isolated mitochondria as measured by biocavity laser spectroscopy : a rapid diagnostic method for studying cellular responses to stress and disease.

    Energy Technology Data Exchange (ETDEWEB)

    Yaffe, Michael P. (University of California, San Diego, CA); Gourley, Paul Lee; Copeland, Robert Guild; McDonald, Anthony Eugene; Hendricks, Judy K.; Naviaux, Robert K. (Univesity of California, San Diego, CA)

    2006-12-01

    We report an analysis of four strains of baker's yeast (Saccharomyces cerevisiae) using biocavity laser spectroscopy. The four strains are grouped in two pairs (wild type and altered), in which one strain differs genetically at a single locus, affecting mitochondrial function. In one pair, the wild-type rho+ and a rho0 strain differ by complete removal of mitochondrial DNA (mtDNA). In the second pair, the wild-type rho+ and a rho- strain differ by knock-out of the nuclear gene encoding Cox4, an essential subunit of cytochrome c oxidase. The biocavity laser is used to measure the biophysical optic parameter Deltalambda, a laser wavelength shift relating to the optical density of cell or mitochondria that uniquely reflects its size and biomolecular composition. As such, Deltalambda is a powerful parameter that rapidly interrogates the biomolecular state of single cells and mitochondria. Wild-type cells and mitochondria produce Gaussian-like distributions with a single peak. In contrast, mutant cells and mitochondria produce leptokurtotic distributions that are asymmetric and highly skewed to the right. These distribution changes could be self-consistently modeled with a single, log-normal distribution undergoing a thousand-fold increase in variance of biomolecular composition. These features reflect a new state of stressed or diseased cells that we call a reactive biomolecular divergence (RBD) that reflects the vital interdependence of mitochondria and the nucleus.

  16. Adults with high social anhedonia have altered neural connectivity with ventral lateral prefrontal cortex when processing positive social signals

    Directory of Open Access Journals (Sweden)

    Hong eYin

    2015-08-01

    Full Text Available Social anhedonia (SA is a debilitating characteristic of schizophrenia and a vulnerability for developing schizophrenia among people at risk. Prior work (Hooker et al, 2014 has revealed neural deficits in ventral lateral prefrontal cortex (VLPFC during processing of positive emotion in a community sample of people with high social anhedonia. Deficits in VLPFC neural activity are related to worse self-reported schizophrenia-spectrum symptoms and worse mood and behavior after social stress. In the current study, psychophysiological interaction (PPI analysis was applied to investigate the neural mechanisms mediated by VLPFC during emotion processing. PPI analysis revealed that, compared to low SA controls, participants with high SA displayed reduced VLPFC integration, specifically reduced connectivity between VLPFC and premotor cortex, inferior parietal and posterior temporal regions when viewing positive relative to neutral emotion. Across all participants, connectivity between VLPFC and inferior parietal region when viewing positive (versus neutral emotion was significantly correlated with measures of emotion management and attentional control. Additionally connectivity between VLPFC and superior temporal sulcus was related to reward and pleasure anticipation, and connectivity between VLPFC and inferior temporal sulcus correlated with attentional control measure. Our results suggest that impairments to VLPFC mediated neural circuitry underlie the cognitive and emotional deficits.

  17. Altered threat and safety neural processing linked to persecutory delusions in schizophrenia: a two-task fMRI study

    Science.gov (United States)

    Perez, David L.; Pan, Hong; Weisholtz, Daniel S.; Root, James C.; Tuescher, Oliver; Fischer, David B.; Butler, Tracy; Vago, David R.; Isenberg, Nancy; Epstein, Jane; Landa, Yulia; Smith, Thomas E.; Savitz, Adam J.; Silbersweig, David A.; Stern, Emily

    2016-01-01

    Persecutory delusions are a clinically important symptom in schizophrenia associated with social avoidance and increased violence. Few studies have investigated the neurobiology of persecutory delusions, which is a prerequisite for developing novel treatments. The aim of this two-paradigm functional magnetic resonance imaging (fMRI) study is to characterize social “real world” and linguistic threat brain activations linked to persecutory delusions in schizophrenia (n=26) using instructed-fear/safety and emotional word paradigms. Instructed-fear/safety activations correlated to persecutory delusion severity demonstrated significant increased lateral orbitofrontal cortex and visual association cortex activations for the instructed-fear vs. safety and instructed-fear vs. baseline contrasts; decreased lateral orbitofrontal cortex and ventral occipital-temporal cortex activations were observed for the instructed-safety stimuli vs. baseline contrast. The salience network also showed divergent fear and safety cued activations correlated to persecutory delusions. Emotional word paradigm analyses showed positive correlations between persecutory delusion severity and left-lateralized linguistic and hippocampal-parahippocampal activations for the threat vs. neutral word contrast. Visual word form area activations correlated positively with persecutory delusions for both threat and neutral word vs. baseline contrasts. This study links persecutory delusions to enhanced neural processing of threatening stimuli and decreased processing of safety cues, and helps elucidate systems-level activations associated with persecutory delusions in schizophrenia. PMID:26208746

  18. The beta-receptor blocker metoprolol alters detoxification processes in the non-target organism Dreissena polymorpha

    Energy Technology Data Exchange (ETDEWEB)

    Contardo-Jara, Valeska, E-mail: contardo@igb-berlin.d [Dpt. Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Pflugmacher, Stephan, E-mail: pflugmacher@igb-berlin.d [Dpt. Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Nuetzmann, Gunnar, E-mail: nuetzmann@igb-berlin.d [Dpt. Ecohydrology, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Kloas, Werner, E-mail: werner.kloas@igb-berlin.d [Dpt. Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Wiegand, Claudia, E-mail: wiegand@biology.sdu.d [University of Southern Denmark Institute of Biology, Campusvej 55, 5230 Odense M (Denmark)

    2010-06-15

    Due to increasing amounts of pharmaceutically active compounds (PhACs) in the aquatic environment, their largely unknown effects to non-target organisms need to be assessed. This study examined physiological changes in the freshwater mussel Dreissena polymorpha exposed to increasing concentrations (0.534, 5.34, 53.4 and 534 mug L{sup -1}) of the beta-blocker metoprolol in a flow-through system for seven days. The two lower concentrations represent the environmentally relevant range. Surprisingly, metallothionein mRNA was immediately up-regulated in all treatments. For the two higher concentrations mRNA up-regulation in gills was found for P-glycoprotein after one day, and after four days for pi class glutathione S-transferase, demonstrating elimination and biotransformation processes, respectively. Additionally, catalase and superoxide dismutase were up-regulated in the digestive gland indicating oxidative stress. In all treated mussels a significant up-regulation of heat shock protein mRNA was observed in gills after four days, which suggests protein damage and the requirement for repair processes. Metoprolol was 20-fold bioaccumulated for environmentally relevant concentrations. - Evidence for significant physiological changes in an aquatic mollusc due to exposure to a pharmaceutically active compound detected by real-time PCR.

  19. 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.

  20. Altered reward processing in the orbitofrontal cortex and hippocampus in healthy first-degree relatives of patients with depression

    DEFF Research Database (Denmark)

    Macoveanu, J; Knorr, U; Skimminge, A

    2014-01-01

    BACKGROUND: Healthy first-degree relatives of patients with major depression (rMD+) show brain structure and functional response anomalies and have elevated risk for developing depression, a disorder linked to abnormal serotonergic neurotransmission and reward processing. METHOD: In a two...... in rMD+ but not in rMD- individuals. The orbitofrontal cortex (OFC) displayed a stronger neural response when subjects missed a large reward after a low-risk choice in the rMD+ group compared to the rMD- group. The enhanced orbitofrontal response to negative outcomes was reversed following escitalopram...... intervention compared to placebo. Conversely, for positive outcomes, the left hippocampus showed attenuated response to high wins in the rMD+ compared to the rMD- group. The SSRI intervention reinforced the hippocampal response to large wins. A subsequent structural analysis revealed that the abnormal neural...

  1. 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

  2. Alterations in soil microbial activity and N-transformation processes due to sulfadiazine loads in pig-manure

    Energy Technology Data Exchange (ETDEWEB)

    Kotzerke, Anja [Berlin University of Technology, Institute of Ecology, Franklinstrasse 29, 10587 Berlin (Germany)], E-mail: anja.kotzerke@tu-berlin.de; Sharma, Shilpi [GSF-National Research Center for Environment and Health, Institute of Soil Ecology, Ingolstaedter Landstrasse 1, 85764 Neuherberg (Germany)], E-mail: shilpi.sharma@gsf.de; Schauss, Kristina [GSF-National Research Center for Environment and Health, Institute of Soil Ecology, Ingolstaedter Landstrasse 1, 85764 Neuherberg (Germany)], E-mail: kristina.schauss@gsf.de; Heuer, Holger [Federal Biological Research Centre for Agriculture and Forestry (BBA), Messeweg 11-12, 38104 Braunschweig (Germany)], E-mail: h.heuer@bba.de; Thiele-Bruhn, Soeren [Trier University, Soil Science, Behringstrasse 21, 54286 Trier (Germany)], E-mail: thiele@uni-trier.de; Smalla, Kornelia [Federal Biological Research Centre for Agriculture and Forestry (BBA), Messeweg 11-12, 38104 Braunschweig (Germany)], E-mail: k.smalla@bba.de; Wilke, Berndt-Michael [Berlin University of Technology, Institute of Ecology, Franklinstrasse 29, 10587 Berlin (Germany)], E-mail: bmwilke@tu-berlin.de; Schloter, Michael [GSF-National Research Center for Environment and Health, Institute of Soil Ecology, Ingolstaedter Landstrasse 1, 85764 Neuherberg (Germany)], E-mail: michael.schloter@gsf.de

    2008-05-15

    Most veterinary drugs enter the environment via manure application. However, it is unclear how these substances interact with soil biota. Therefore, it was the aim of the present study to investigate the effects of manure containing different concentrations of the antibiotic sulfadiazine (SDZ) on the soil microbial communities. It was shown that manure alone has a stimulating effect on microbial activity. Only potential nitrification was negatively influenced by manure application. The addition of SDZ to the manure reduced microbial activity. Depending on the SDZ concentration, levels of activity were in the range of the control soil without manure application. Also, selected processes in nitrogen turnover were negatively influenced by the addition of SDZ to the manure, with nitrification being the only exception. The effects were visible for up to 4 days after application of the manure with or without SDZ and were correlated with the bioavailability of the antibiotic. - This study gives first insights into the effects of manure containing the antibiotic sulfadiazine on microbial activity and nitrogen transformation potentials in soil.

  3. Modulating the RNA processing and decay by the exosome: altering Rrp44/Dis3 activity and end-product.

    Directory of Open Access Journals (Sweden)

    Filipa P Reis

    Full Text Available In eukaryotes, the exosome plays a central role in RNA maturation, turnover, and quality control. In Saccharomyces cerevisiae, the core exosome is composed of nine catalytically inactive subunits constituting a ring structure and the active nuclease Rrp44, also known as Dis3. Rrp44 is a member of the ribonuclease II superfamily of exoribonucleases which include RNase R, Dis3L1 and Dis3L2. In this work we have functionally characterized three residues located in the highly conserved RNB catalytic domain of Rrp44: Y595, Q892 and G895. To address their precise role in Rrp44 activity, we have constructed Rrp44 mutants and compared their activity to the wild-type Rrp44. When we mutated residue Q892 and tested its activity in vitro, the enzyme became slightly more active. We also showed that when we mutated Y595, the final degradation product of Rrp44 changed from 4 to 5 nucleotides. This result confirms that this residue is responsible for the stacking of the RNA substrate in the catalytic cavity, as was predicted from the structure of Rrp44. Furthermore, we also show that a strain with a mutation in this residue has a growth defect and affects RNA processing and degradation. These results lead us to hypothesize that this residue has an important biological role. Molecular dynamics modeling of these Rrp44 mutants and the wild-type enzyme showed changes that extended beyond the mutated residues and helped to explain these results.

  4. Age-related alterations of relaxation processes and non-Markov effects in stochastic dynamics of R-R intervals variability from human ECGs

    CERN Document Server

    Yulmetyev, R M; Panischev, O Y; Hänggi, P; Yulmetyev, Renat M.; Demin, Sergey A.; Panischev, Oleg Yu.; H\\"anggi, Peter

    2005-01-01

    In this paper we consider the age-related alterations of heart rate variability on the basis of the study of non-Markovian effects. The age dynamics of relaxation processes is quantitatively described by means of local relaxation parameters, calculated by the specific localization procedure. We offer a quantitative informational measure of non-Markovity to evaluate the change of statistical effects of memory. Local relaxation parameters for young and elderly people differ by 3.3 times, and quantitative measures of non-Markovity differ by 4.2 times. The comparison of quantitative parameters allows to draw conclusions about the reduction of relaxation rate with ageing and the higher degree of the Markovity of heart rate variability of elderly people.

  5. Experimental study of gold activation-transportation in the process of potash metasomatism-alteration ——North China platform gold deposit taken as an example

    Institute of Scientific and Technical Information of China (English)

    WANG; Yurong; HU; Shouxi

    2001-01-01

    Chemical reactions of plagioclase, biotite and their single minerals, as well as a mineral mixture of (plagioclase +biotite+quartz), with KCl and (KCl+KHCO3) solutions were carried out at 150400℃ and 5080 MPa. Experiments show that alkaline fluid promotes plagioclase’s changing into potash feldspar, while acid fluid helps plagioclase, potash feldspar and biotite alteration form chlorite and sericite. After chemical reaction the acidity-alkalinity of solutions often changes reversely. It was observed that gold dissolved from the tube wall and recrystallized on the surfaces of biotite and pyrite. Therefore the transportation and enrichment of gold are related to the elementary effect of the fluid-mineral interfaces. Fe3+-Fe2+, as an oxidition-reduction agent, and volatile components Cl? and CO2 play important roles in the reaction process.

  6. 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.

  7. 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.

  8. Altered attentional and perceptual processes as indexed by N170 during gaze perception in schizophrenia: Relationship with perceived threat and paranoid delusions.

    Science.gov (United States)

    Tso, Ivy F; Calwas, Anita M; Chun, Jinsoo; Mueller, Savanna A; Taylor, Stephan F; Deldin, Patricia J

    2015-08-01

    Using gaze information to orient attention and guide behavior is critical to social adaptation. Previous studies have suggested that abnormal gaze perception in schizophrenia (SCZ) may originate in abnormal early attentional and perceptual processes and may be related to paranoid symptoms. Using event-related brain potentials (ERPs), this study investigated altered early attentional and perceptual processes during gaze perception and their relationship to paranoid delusions in SCZ. Twenty-eight individuals with SCZ or schizoaffective disorder and 32 demographically matched healthy controls (HCs) completed a gaze-discrimination task with face stimuli varying in gaze direction (direct, averted), head orientation (forward, deviated), and emotion (neutral, fearful). ERPs were recorded during the task. Participants rated experienced threat from each face after the task. Participants with SCZ were as accurate as, though slower than, HCs on the task. Participants with SCZ displayed enlarged N170 responses over the left hemisphere to averted gaze presented in fearful relative to neutral faces, indicating a heightened encoding sensitivity to faces signaling external threat. This abnormality was correlated with increased perceived threat and paranoid delusions. Participants with SCZ also showed a reduction of N170 modulation by head orientation (normally increased amplitude to deviated faces relative to forward faces), suggesting less integration of contextual cues of head orientation in gaze perception. The psychophysiological deviations observed during gaze discrimination in SCZ underscore the role of early attentional and perceptual abnormalities in social information processing and paranoid symptoms of SCZ.

  9. Altered processing of rewarding and aversive basic taste stimuli in symptomatic women with anorexia nervosa and bulimia nervosa: An fMRI study.

    Science.gov (United States)

    Monteleone, Alessio Maria; Monteleone, Palmiero; Esposito, Fabrizio; Prinster, Anna; Volpe, Umberto; Cantone, Elena; Pellegrino, Francesca; Canna, Antonietta; Milano, Walter; Aiello, Marco; Di Salle, Francesco; Maj, Mario

    2017-02-21

    Functional magnetic resonance imaging (fMRI) studies have displayed a dysregulation in the way in which the brain processes pleasant taste stimuli in patients with anorexia nervosa (AN) and bulimia nervosa (BN). However, exactly how the brain processes disgusting basic taste stimuli has never been investigated, even though disgust plays a role in food intake modulation and AN and BN patients exhibit high disgust sensitivity. Therefore, we investigated the activation of brain areas following the administration of pleasant and aversive basic taste stimuli in symptomatic AN and BN patients compared to healthy subjects. Twenty underweight AN women, 20 symptomatic BN women and 20 healthy women underwent fMRI while tasting 0.292 M sucrose solution (sweet taste), 0.5 mM quinine hydrochloride solution (bitter taste) and water as a reference taste. In symptomatic AN and BN patients the pleasant sweet stimulus induced a higher activation in several brain areas than that induced by the aversive bitter taste. The opposite occurred in healthy controls. Moreover, compared to healthy controls, AN patients showed a decreased response to the bitter stimulus in the right amygdala and left anterior cingulate cortex, while BN patients showed a decreased response to the bitter stimulus in the right amygdala and left insula. These results show an altered processing of rewarding and aversive taste stimuli in ED patients, which may be relevant for understanding the pathophysiology of AN and BN.

  10. Mobile Technologies Altering All Processes

    Science.gov (United States)

    2012-01-01

    Android and Apple devices. The third source for apps iden- tified by the CSDA project is from the users themselves. The Army hosted the “Apps for...instruction were converted into digital media on a variety of devices ranging from iPods , readers, tablets and phones. The eighth pilot focused on

  11. 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

  12. 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.

  13. The CK1 family: contribution to cellular stress response and its role in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Uwe eKnippschild

    2014-05-01

    Full Text Available Members of the highly conserved and ubiquitously expressed pleiotropic CK1 family play major regulatory roles in many cellular processes including DNA-processing and repair, proliferation, cytoskeleton dynamics, vesicular trafficking, apoptosis, and cell differentiation. As a consequence of cellular stress conditions, interaction of CK1 with the mitotic spindle is manifold increased pointing to regulatory functions at the mitotic checkpoint. Furthermore, CK1 is able to alter the activity of key regulatory proteins and signal integration molecules and is tightly connected to the regulation of β-catenin, p53- and MDM2-specific functions and degradation. Considering the importance of CK1 for accurate cell division and regulation of tumor suppressor functions it is not surprising that mutations and alterations in the expression and/or activity of CK1 isoforms are often detected in various tumor entities including cancer of the kidney, choriocarcinomas, breast carcinomas, oral cancer, adenocarcinomas of the pancreas, and ovarian cancer. Therefore, effort has enormously increased (i to understand the regulation of CK1 and its involvement in tumorigenesis- and tumor progression-related signal transduction pathways and (ii to develop CK1-specific inhibitors for the use in personalized therapy concepts. In this review we summarize the current knowledge regarding the regulation, functions, and interactions of CK1 family members with cellular proteins playing central roles in cellular stress-responses and carcinogenesis.

  14. Sequestration of DROSHA and DGCR8 by Expanded CGG RNA Repeats Alters MicroRNA Processing in Fragile X-Associated Tremor/Ataxia Syndrome

    Directory of Open Access Journals (Sweden)

    Chantal Sellier

    2013-03-01

    Full Text Available Fragile X-associated tremor/ataxia syndrome (FXTAS is an inherited neurodegenerative disorder caused by the expansion of 55–200 CGG repeats in the 5′ UTR of FMR1. These expanded CGG repeats are transcribed and accumulate in nuclear RNA aggregates that sequester one or more RNA-binding proteins, thus impairing their functions. Here, we have identified that the double-stranded RNA-binding protein DGCR8 binds to expanded CGG repeats, resulting in the partial sequestration of DGCR8 and its partner, DROSHA, within CGG RNA aggregates. Consequently, the processing of microRNAs (miRNAs is reduced, resulting in decreased levels of mature miRNAs in neuronal cells expressing expanded CGG repeats and in brain tissue from patients with FXTAS. Finally, overexpression of DGCR8 rescues the neuronal cell death induced by expression of expanded CGG repeats. These results support a model in which a human neurodegenerative disease originates from the alteration, in trans, of the miRNA-processing machinery.

  15. Sequestration of DROSHA and DGCR8 by expanded CGG RNA repeats alters microRNA processing in fragile X-associated tremor/ataxia syndrome.

    Science.gov (United States)

    Sellier, Chantal; Freyermuth, Fernande; Tabet, Ricardos; Tran, Tuan; He, Fang; Ruffenach, Frank; Alunni, Violaine; Moine, Herve; Thibault, Christelle; Page, Adeline; Tassone, Flora; Willemsen, Rob; Disney, Matthew D; Hagerman, Paul J; Todd, Peter K; Charlet-Berguerand, Nicolas

    2013-03-28

    Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited neurodegenerative disorder caused by the expansion of 55-200 CGG repeats in the 5' UTR of FMR1. These expanded CGG repeats are transcribed and accumulate in nuclear RNA aggregates that sequester one or more RNA-binding proteins, thus impairing their functions. Here, we have identified that the double-stranded RNA-binding protein DGCR8 binds to expanded CGG repeats, resulting in the partial sequestration of DGCR8 and its partner, DROSHA, within CGG RNA aggregates. Consequently, the processing of microRNAs (miRNAs) is reduced, resulting in decreased levels of mature miRNAs in neuronal cells expressing expanded CGG repeats and in brain tissue from patients with FXTAS. Finally, overexpression of DGCR8 rescues the neuronal cell death induced by expression of expanded CGG repeats. These results support a model in which a human neurodegenerative disease originates from the alteration, in trans, of the miRNA-processing machinery.

  16. Cellular and molecular aspects of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Malcolm G Smith; Georgina L Hold; Eiichi Tahara; Emad M El-Omar

    2006-01-01

    Gastric cancer remains a global killer with a shifting burden from the developed to the developing world.The cancer develops along a multistage process that is defined by distinct histological and pathophysiological phases. Several genetic and epigenetic alterations mediate the transition from one stage to another and these include mutations in oncogenes, tumour suppressor genes and cell cycle and mismatch repair genes. The most significant advance in the fight against gastric caner came with the recognition of the role of Helicobacter pylori (H pylori) as the most important acquired aetiological agent for this cancer. Recent work has focussed on elucidating the complex host/microbial interactions that underlie the neoplastic process. There is now considerable insight into the pathogenesis of this cancer and the prospect of preventing and eradicating the disease has become a reality. Perhaps more importantly, the study of H pylori-induced gastric carcinogenesis offers a paradigm for understanding more complex human cancers. In this review, we examine the molecular and cellular events that underlie H pyloriinduced gastric cancer.

  17. IGF-I enhances cellular senescence via the reactive oxygen species-p53 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Takahashi, Yutaka, E-mail: takahash@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Cellular senescence plays an important role in tumorigenesis and aging process. Black-Right-Pointing-Pointer We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. Black-Right-Pointing-Pointer IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. Black-Right-Pointing-Pointer These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated {beta}-galactosidase (SA-{beta}-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, {gamma}H2AX, the increased levels of p53 and p21 proteins, and activated SA-{beta}-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-{beta}-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

  18. Combinatorial Contextualization of Peptidic Epitopes for Enhanced Cellular Immunity

    Science.gov (United States)

    Ito, Masaki; Hayashi, Kazumi; Adachi, Eru; Minamisawa, Tamiko; Homma, Sadamu; Koido, Shigeo; Shiba, Kiyotaka

    2014-01-01

    Invocation of cellular immunity by epitopic peptides remains largely dependent on empirically developed protocols, such as interfusion of aluminum salts or emulsification using terpenoids and surfactants. To explore novel vaccine formulation, epitopic peptide motifs were co-programmed with structural motifs to produce artificial antigens using our “motif-programming” approach. As a proof of concept, we used an ovalbumin (OVA) system and prepared an artificial protein library by combinatorially polymerizing MHC class I and II sequences from OVA along with a sequence that tends to form secondary structures. The purified endotoxin-free proteins were then examined for their ability to activate OVA-specific T-cell hybridoma cells after being processed within dendritic cells. One clone, F37A (containing three MHC I and two MHC II OVA epitopes), possessed a greater ability to evoke cellular immunity than the native OVA or the other artificial antigens. The sensitivity profiles of drugs that interfered with the F37A uptake differed from those of the other artificial proteins and OVA, suggesting that alteration of the cross-presentation pathway is responsible for the enhanced immunogenicity. Moreover, F37A, but not an epitopic peptide, invoked cellular immunity when injected together with monophosphoryl lipid A (MPL), and retarded tumor growth in mice. Thus, an artificially synthesized protein antigen induced cellular immunity in vivo in the absence of incomplete Freund's adjuvant or aluminum salts. The method described here could be potentially used for developing vaccines for such intractable ailments as AIDS, malaria and cancer, ailments in which cellular immunity likely play a crucial role in prevention and treatment. PMID:25343355

  19. Order of amino acids in C-terminal cysteine-containing peptide-based chelators influences cellular processing and biodistribution of 99mTc-labeled recombinant Affibody molecules.

    Science.gov (United States)

    Altai, Mohamed; Wållberg, Helena; Orlova, Anna; Rosestedt, Maria; Hosseinimehr, Seyed Jalal; Tolmachev, Vladimir; Ståhl, Stefan

    2012-05-01

    Affibody molecules constitute a novel class of molecular display selected affinity proteins based on non-immunoglobulin scaffold. Preclinical investigations and pilot clinical data have demonstrated that Affibody molecules provide high contrast imaging of tumor-associated molecular targets shortly after injection. The use of cysteine-containing peptide-based chelators at the C-terminus of recombinant Affibody molecules enabled site-specific labeling with the radionuclide 99mTc. Earlier studies have demonstrated that position, composition and the order of amino acids in peptide-based chelators influence labeling stability, cellular processing and biodistribution of Affibody molecules. To investigate the influence of the amino acid order, a series of anti-HER2 Affibody molecules, containing GSGC, GEGC and GKGC chelators have been prepared and characterized. The affinity to HER2, cellular processing of 99mTc-labeled Affibody molecules and their biodistribution were investigated. These properties were compared with that of the previously studied 99mTc-labeled Affibody molecules containing GGSC, GGEC and GGKC chelators. All variants displayed picomolar affinities to HER2. The substitution of a single amino acid in the chelator had an appreciable influence on the cellular processing of 99mTc. The biodistribution of all 99mTc-labeled Affibody molecules was in general comparable, with the main difference in uptake and retention of radioactivity in excretory organs. The hepatic accumulation of radioactivity was higher for the lysine-containing chelators and the renal retention of 99mTc was significantly affected by the amino acid composition of chelators. The order of amino acids influenced renal uptake of some conjugates at 1 h after injection, but the difference decreased at later time points. Such information can be helpful for the development of other scaffold protein-based imaging and therapeutic radiolabeled conjugates.

  20. HIV-1 viral infectivity factor (Vif) alters processive single-stranded DNA scanning of the retroviral restriction factor APOBEC3G.

    Science.gov (United States)

    Feng, Yuqing; Love, Robin P; Chelico, Linda

    2013-03-01

    APOBEC3G is a retroviral restriction factor that can inhibit the replication of human immunodeficiency virus, type 1 (HIV-1) in the absence of the viral infectivity factor (Vif) protein. Virion-encapsidated APOBEC3G can deaminate cytosine to uracil in viral (-)DNA, which leads to hypermutation and inactivation of the provirus. APOBEC3G catalyzes these deaminations processively on single-stranded DNA using sliding and jumping movements. Vif is thought to primarily overcome APOBEC3G through an interaction that mediates APOBEC3G ubiquitination and results in its proteasomal degradation. However, Vif may also inhibit APOBEC3G mRNA translation, virion encapsidation, and deamination activity. Here we investigated the molecular mechanism of VifIIIB- and VifHXB2-mediated inhibition of APOBEC3G deamination activity. Biochemical assays using a model HIV-1 replication assay and synthetic single-stranded or partially double-stranded DNA substrates demonstrated that APOBEC3G has an altered processive mechanism in the presence of Vif. Specifically, VifHXB2 inhibited the jumping and VifIIIB inhibited the sliding movements of APOBEC3G. The absence of such an effect by Vif on degradation-resistant APOBEC3G D128K indicates that a Vif-APOBEC3G interaction mediates this effect. That the partially processive APOBEC3G was less effective at inducing mutagenesis in a model HIV-1 replication assay suggests that Vif co-encapsidation with APOBEC3G can promote sublethal mutagenesis of HIV-1 proviral DNA.

  1. Nucleolar proteins change in altered gravity

    Science.gov (United States)

    Sobol, M. A.; Kordyum, E. L.; Gonzalez-Camacho, F.; Medina, F. J.

    Discovery of gravisensitivity of cells no specified to gravity perception focused continuous attention on an elucidation of mechanisms involved in altered gravity effects at the different levels of cellular organization A nucleolus is the nuclear domain in which the major portion of ribosome biogenesis takes place This is a basic process for cell vitality beginning with the transcription of rDNA followed by processing newly synthesized pre-rRNA molecules A wide range of nucleolar proteins plays a highly significant role in all stages of biosynthesis of ribosomes Different steps of ribosome biogenesis should respond to various external factors affecting generally the cell metabolism Nevertheless a nucleolus remains not enough studied under the influence of altered environmental conditions For this reason we studied root apices from 2-day old Lepidium sativum seedlings germinated and grown under slow horizontal clinorotation and stationary conditions in darkness The extraction of cell nuclei followed by sequential fractionation of nuclear proteins according to their solubility in buffers of increasing ionic strength was carried out This procedure gave rise to 5 distinct fractions We analyzed nuclear subproteomes of the most soluble fraction called S2 It is actually a functionally significant fraction consisting of ribonucleoproteins actively engaged in pre-rRNA synthesis and processing 2D-electrophoresis of S2 fraction proteins was carried out The gels were silver stained and stained gels were scanned and analyzed

  2. 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...

  3. Altered effects of perspective-taking on functional connectivity during self- and other-referential processing in adults with autism spectrum disorder.

    Science.gov (United States)

    Hashimoto, Ryu-Ichiro; Itahashi, Takashi; Ohta, Haruhisa; Yamada, Takashi; Kanai, Chieko; Nakamura, Motoaki; Watanabe, Hiromi; Kato, Nobumasa

    2016-08-30

    In interactive social situations, it is often crucial to be able to take another person's perspective when evaluating one's own or another person's specific trait; individuals with autism spectrum disorder (ASD) critically lack this social skill. To examine how perspective-dependent self- and other-evaluation processes modulate functional connectivity in ASD, we conducted a functional magnetic resonance imaging study in which 26 high-functioning adults with ASD and 24 typically developed (TD) controls were asked to decide whether an adjective describing a personality trait correctly described the participant himself/herself ("self") or the participant's mother ("other") by taking either the first (1P) or third person (3P) perspective. We observed that functional connectivity between the left sensorimotor cortex and the left middle cingulate cortex was enhanced in TD control individuals taking the 3P perspective, this enhancement was significantly reduced in ASD, and the degree of reduction was significantly correlated with the severity of autistic traits. Furthermore, the self-reference effect on functional connectivity between the left inferior frontal cortex and frontopolar cortices was significantly enhanced in TD control individuals taking the 3P perspective, whereas such effect was reversed in ASD. These findings indicate altered effects of perspective on the functional connectivity, which may underlie the deficits in social interaction and communication observed in individuals with ASD.

  4. 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

  5. Attention Alters Perceived Attractiveness.

    Science.gov (United States)

    Störmer, Viola S; Alvarez, George A

    2016-04-01

    Can attention alter the impression of a face? Previous studies showed that attention modulates the appearance of lower-level visual features. For instance, attention can make a simple stimulus appear to have higher contrast than it actually does. We tested whether attention can also alter the perception of a higher-order property-namely, facial attractiveness. We asked participants to judge the relative attractiveness of two faces after summoning their attention to one of the faces using a briefly presented visual cue. Across trials, participants judged the attended face to be more attractive than the same face when it was unattended. This effect was not due to decision or response biases, but rather was due to changes in perceptual processing of the faces. These results show that attention alters perceived facial attractiveness, and broadly demonstrate that attention can influence higher-level perception and may affect people's initial impressions of one another.

  6. 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.

  7. 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.

  8. Research of the Production Process of a Company Based on Cellular Automata%基于元胞自动机的企业生产过程的研究

    Institute of Scientific and Technical Information of China (English)

    罗丽珍; 吴瑞明

    2012-01-01

    To reduce and prevent the accidents in the production process of a company, the theory of cellular automata is applied to the research of this, a cellular automata model for the executing system of the workers in the processing plant is formulated. Through the simulation in different states of personal factors and environmental factors , the analysis shows that the extend that the works comply with the regulations is one of the key factors that affect the degree of safety in the production process. The advices are helpful that the company must pay more attention to how the regulations can be executed carefully to reduce the gaps between actual behaviors and standard behaviors according to the regulations. This is meaningful for the research of safe production of a company.%为减少和预防企业生产中意外事故的发生,将元胞自动机理论应用于企业生产过程的研究,建立了某企业生产中基层-员工执行系统的元胞自动机模型.通过对安全生产的个人因素和环境因素在不同状态下的模拟和分析,认为员工遵守规章规程的程度是影响企业安全生产的关键因素之一;并在此基础上,建议企业多关注于如何保证政策法规被规范执行,以缩小实际操作与规则规程之间的差距.这为企业安全生产的研究提供了一种新的思路.

  9. Effects of Silica Aerogel Content on Microstructural and Mechanical Properties of Poly(methyl methacry-late)/Silica Aerogel Dual-scale Cellular Foams Processed in Supercritical Carbon Dioxide

    Institute of Scientific and Technical Information of China (English)

    GU Xiaoli; LUO Guoqiang; ZHANG Ruizhi; ZHANG Jian; LI Meijuan; SHEN Qiang; WANG Jin; ZHANG Lianmeng

    2016-01-01

    A novel poly(methyl-methacrylate)/silica aerogel (PMMA/SA) dual-scale cellular foam was synthesized with internal mixing followed by the supercritical carbon dioxide foaming process. The effects of silica aerogel content on the microstructural and mechanical performance of the foams were investigated by SEM, TEM analysis, and mechanical tests. The experimental results suggest that the employment of silica aerogel granule as addictive can distinctly improve the morphological feature as well as the mechanical performance in comparison to neat PMMA foam by uniformizing cell size distribution, decreasing cell size and increasing cell density. And dual-scale cells including micrometric cells of 3-10 μm and nanometric cells of about 50nm existed in the structure of foams resulting from the retained original framework structure of silica aerogel, which has not been described in other studies with the addition of various fillers. Furthermore, the mechanical strength was signiifcantly elevated even with a small amount of silica aerogel resulting from the unique microstructure, decreased cell size and enhanced cell walls. The compressive strength was 18.12 MPa and the lfexural strength was 18.90 MPa by adding 5wt% and 2wt% silica aerogel, respectively. These results demonstrate the potential to synthesize PMMA/SA dual-scale cellular foams to be used as structural materials with the advantages of low density and high strength.

  10. 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.

  11. Effects of extra-cellular polymeric substances on organic pollutants biodegradation kinetics for A-step of adsorption-biodegradation process

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The features of organic pollutants degradation mainly characterized by bio-flocculation for step-A of adsorption-biodegredation(AB) process were studied. By investigating the relationship of extracellular polymeric substances(EPS) with bioflocculation and introducing kinetic model of organic pollutant degradation into EPS, the kinetic model of organic pollutant degradation for step-A bioflocculation was deducted. And through the experiments,the kinetic constants were calculated as follows: k1 =0. 005 3; kc1 =1710.7 and vmax1=10 min-1.

  12. 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

  13. Alterations in the mir-15a/16-1 Loci Impairs Its Processing and Augments B-1 Expansion in De Novo Mouse Model of Chronic Lymphocytic Leukemia (CLL.

    Directory of Open Access Journals (Sweden)

    Siddha Kasar

    Full Text Available New Zealand Black (NZB mice, a de novo model of CLL, share multiple characteristics with CLL patients, including decreased expression of miR-15a/16-1. We previously discovered a point mutation and deletion in the 3' flanking region of mir-16-1 of NZB and a similar mutation has been found in a small number of CLL patients. However, it was unknown whether the mutation is the cause for the reduced miR-15a/16-1 expression and CLL development. Using PCR and in vitro microRNA processing assays, we found that the NZB sequence alterations in the mir-15a/16-1 loci result in deficient processing of the precursor forms of miR-15a/16-1, in particular, we observe impaired conversion of pri-miR-15a/16-1 to pre-miR-15a/16-1. The in vitro data was further supported by derivation of congenic strains with replaced mir-15a/16-1 loci at one or both alleles: NZB congenic mice (NmiR+/- and DBA congenic mice (DmiR-/-. The level of miR-15a/16-1 reflected the configuration of the mir-15a/16-1 loci with DBA congenic mice (DmiR-/- showing reduced miR-15a levels compared to homozygous wild-type allele, while the NZB congenic mice (NmiR+/- showed an increase in miR-15a levels relative to homozygous mutant allele. Similar to Monoclonal B-cell Lymphocytosis (MBL, the precursor stage of the human disease, an overall expansion of the B-1 population was observed in DBA congenic mice (DmiR-/- relative to wild-type (DmiR+/+. These studies support our hypothesis that the mutations in the mir-15a/16-1 loci are responsible for decreased expression of this regulatory microRNA leading to B-1 expansion and CLL development.

  14. Alteration of the digestive motility linked with radiation-induced inflammatory processes in rats; Alterations de la motricite digestive associees aux processus inflammatoires induits par les rayonnements ionisants chez le rat

    Energy Technology Data Exchange (ETDEWEB)

    Picard, C

    2000-12-01

    Exposure to ionizing radiation, whether accidental or for medical reasons, may lead to gastro-intestinal injury, characterized by nausea, vomiting, diarrhea and abdominal cramps. The aetiology of radiation-induced diarrhea remains to date unclear. In this study, we have investigated the acute effects of a 10 Gy abdominal irradiation on rat digestive functions. The objective of the first study was to evaluate the role of sensory afferent neurons, capsaicin-sensitive, on morphological changes and the inflammatory response following exposure. Three days after irradiation, we observed an inflammatory response characterized by neutrophils infiltration and mast cells de-granulation. No effect of capsaicin pre-treatment was seen on these parameters. However, neutrophils infiltration was increased as early as one day after irradiation in capsaicin-treated rats. No difference in severity of diarrhea was observed after denervation nor in morphological changes. These data demonstrate that abdominal irradiation results in diarrhea concomitant with an inflammatory response, and that sensory innervation does not play a major protective role. The objective of the rest of the work was in the first instance to characterize radiation-induced alterations of intestinal and colonic motility leading to diarrhea and secondly to evaluate the role of serotonin in such disorders. Perturbations in intestinal (MMC) and colonic (LSB) motor profiles were observed from the first day onwards. Migrating motor complexes (MMC) were completely disrupted at three days at the same time as the onset of diarrhea. In addition to inhibition of LSB, colonic fluid absorptive capacity was decreased and serotonin colonic tissue levels were increased three days after irradiation. Radiation-induced diarrhea was reduced by treatment with an antagonist of 5-HT{sub 3} receptors, granisetron, as were alterations of colonic motility and serotonin tissue levels. However, this treatment did not significantly ameliorate

  15. Multiplex assay for live-cell monitoring of cellular fates of amyloid-β precursor protein (APP.

    Directory of Open Access Journals (Sweden)

    Maria Merezhko

    Full Text Available Amyloid-β precursor protein (APP plays a central role in pathogenesis of Alzheimer's disease. APP has a short half-life and undergoes complex proteolytic processing that is highly responsive to various stimuli such as changes in cellular lipid or energy homeostasis. Cellular trafficking of APP is controlled by its large protein interactome, including dozens of cytosolic adaptor proteins, and also by interactions with lipids. Currently, cellular regulation of APP is mostly studied based on appearance of APP-derived proteolytic fragments to conditioned media and cellular extracts. Here, we have developed a novel live-cell assay system based on several indirect measures that reflect altered APP trafficking and processing in cells. Protein-fragment complementation assay technology for detection of APP-BACE1 protein-protein interaction forms the core of the new assay. In a multiplex form, the assay can measure four endpoints: total cellular APP level, total secreted sAPP level in media, APP-BACE1 interaction in cells and in exosomes released by the cells. Functional validation of the assay with pharmacological and genetic tools revealed distinct patterns of cellular fates of APP, with immediate mechanistic implications. This new technology will facilitate functional genomics studies of late-onset Alzheimer's disease, drug discovery efforts targeting APP and characterization of the physiological functions of APP and its proteolytic fragments.

  16. Alteration of the Cyclin D1/p16-pRB Pathway,Cellular Proliferation and Apoptosis in Glioma%人脑胶质瘤中cyclin D1/p16-pRB路径异常以及细胞增殖和凋亡的变化

    Institute of Scientific and Technical Information of China (English)

    王存祖; 傅震; 赵竹

    2004-01-01

    Objective: To study the alteration of cyclin D1, p16 and pRB in glioma, analyze proliferation and apoptosis of tumor cells, and discuss the pathogenesis of glioma. Methods:Thirty-seven glioma specimens were classified as astrocytoma(25 cases, including 7 fibrillary cases; 6 protoplasmic cases; 12 anaplasfic cases), and glioblastoma( 12 cases,including 4 GBM cases). Ten normal brain tissues were taken as controls. The expression of cyclin D1, p16 and pRB were detected by immunohistochemical method. Cellular proliferation was assessed by Ki-67 label index(Ki-67 LI). Cellular apoptosis was detected by TUNEL and apoptotic indices(Al) was calculated. Results: The alterations of three proteins were cyclin D1 overexpression( 28/37,75.7% ), p16 and pRB deletion(20/37,54.1% and 12/37,32.4% ), which were closely related to tumor types, particularly in malignant glioma. Ki-67 LI and AI were higher when pRB pathway was abnormal. Apoptosis was minor in astrocytic tumors(astrocytomas,0.010 ± 0.002;glioblastomas,0.057 + 0.016). Conclusion: The abnormalities of cyclin D1/p16-pRB pathway correlated closely with pathogenesis of glioma.%目的:研究Gl→S调控点中cyclin Dl、p16及pRB基因在胶质瘤中表达情况,分析与细胞增殖和凋亡的关系,探讨肿瘤发生的原因.方法:37例人脑胶质瘤标本按WHO分类标准(1990)分为:星形细胞瘤(25例,纤维型7例,原浆型6例,间变型12例),胶质母细胞瘤(12例,包括GBM4例).正常对照脑组织10例.cyclin Dl、p16和Ki-67的表达用免疫组化的方法,凋亡细胞通过TUNEL进行检测,细胞增殖和凋亡的评估分别用Ki-67LI和凋亡指数(AI).结果:3种因子在胶质瘤中都存在着异常,其中cyclin Dl表现为过度表达(28/37,75.7%),p16、pRB表现为缺失(20/37,56.8%和12/37,32.4%),且都与肿瘤分型有关,在恶性肿瘤中更加明显;pRB路径的异常在胶质瘤中更是频发事件,与肿瘤恶化有关;pRB路径异常时,Ki-67LI和AI均明显增高;凋讯发

  17. Data for mitochondrial proteomic alterations in the aging mouse brain

    Directory of Open Access Journals (Sweden)

    Kelly L. Stauch

    2015-09-01

    Full Text Available Mitochondria are dynamic organelles critical for many cellular processes, including energy generation. Thus, mitochondrial dysfunction likely plays a role in the observed alterations in brain glucose metabolism during aging. Despite implications of mitochondrial alterations during brain aging, comprehensive quantitative proteomic studies remain limited. Therefore, to characterize the global age-associated mitochondrial proteomic changes in the brain, we analyzed mitochondria isolated from the brain of 5-, 12-, and 24-month old mice using quantitative mass spectrometry. We identified changes in the expression of proteins important for biological processes involved in the generation of precursor metabolites and energy through the breakdown of carbohydrates, lipids, and proteins. These results are significant because we identified age-associated proteomic changes suggestive of altered mitochondrial catabolic reactions during brain aging. The proteomic data described here can be found in the PRIDE Archive using the reference number PXD001370. A more comprehensive analysis of this data may be obtained from the article “Proteomic analysis and functional characterization of mouse brain mitochondria during aging reveal alterations in energy metabolism” in PROTEOMICS.

  18. Cellular membrane collapse by atmospheric-pressure plasma jet

    Science.gov (United States)

    Kim, Kangil; Jun Ahn, Hak; Lee, Jae-Hyeok; Kim, Jae-Ho; Sik Yang, Sang; Lee, Jong-Soo

    2014-01-01

    Cellular membrane dysfunction caused by air plasma in cancer cells has been studied to exploit atmospheric-pressure plasma jets for cancer therapy. Here, we report that plasma jet treatment of cervical cancer HeLa cells increased electrical conductivity across the cellular lipid membrane and caused simultaneous lipid oxidation and cellular membrane collapse. We made this finding by employing a self-manufactured microelectrode chip. Furthermore, increased roughness of the cellular lipid membrane and sequential collapse of the membrane were observed by atomic force microscopy following plasma jet treatment. These results suggest that the cellular membrane catastrophe occurs via coincident altered electrical conductivity, lipid oxidation, and membrane roughening caused by an atmospheric-pressure plasma jet, possibly resulting in cellular vulnerability to reactive species generated from the plasma as well as cytotoxicity to cancer cells.

  19. Cellular membrane collapse by atmospheric-pressure plasma jet

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kangil; Sik Yang, Sang, E-mail: jsjlee@ajou.ac.kr, E-mail: ssyang@ajou.ac.kr [Department of Electrical and Computer Engineering, Ajou University, Suwon 443-749 (Korea, Republic of); Jun Ahn, Hak; Lee, Jong-Soo, E-mail: jsjlee@ajou.ac.kr, E-mail: ssyang@ajou.ac.kr [Department of Biological Sciences, Ajou University, Suwon 443-749 (Korea, Republic of); Lee, Jae-Hyeok; Kim, Jae-Ho [Department of Molecular Science and Technology, Ajou University, Suwon 443-749 (Korea, Republic of)

    2014-01-06

    Cellular membrane dysfunction caused by air plasma in cancer cells has been studied to exploit atmospheric-pressure plasma jets for cancer therapy. Here, we report that plasma jet treatment of cervical cancer HeLa cells increased electrical conductivity across the cellular lipid membrane and caused simultaneous lipid oxidation and cellular membrane collapse. We made this finding by employing a self-manufactured microelectrode chip. Furthermore, increased roughness of the cellular lipid membrane and sequential collapse of the membrane were observed by atomic force microscopy following plasma jet treatment. These results suggest that the cellular membrane catastrophe occurs via coincident altered electrical conductivity, lipid oxidation, and membrane roughening caused by an atmospheric-pressure plasma jet, possibly resulting in cellular vulnerability to reactive species generated from the plasma as well as cytotoxicity to cancer cells.

  20. MicroRNA Profiling of the Effect of the Heptapeptide Angiotensin-(1-7) in A549 Lung Tumor Cells Reveals a Role for miRNA149-3p in Cellular Migration Processes

    Science.gov (United States)

    da Silva, Brenda de Oliveira; Lima, Kelvin Furtado; Gonçalves, Letícia Rocha; da Silveira, Marina Bonfogo; Moraes, Karen C. M.

    2016-01-01

    Lung cancer is one of the most frequent types of cancer in humans and a leading cause of death worldwide. The high mortality rates are correlated with late diagnosis, which leads to high rates of metastasis found in patients. Thus, despite all the improvement in therapeutic approaches, the development of new drugs that control cancer cell migration and metastasis are required. The heptapeptide angiotensin-(1–7) [ang-(1–7)] has demonstrated the ability to control the growth rates of human lung cancer cells in vitro and in vivo, and the elucidation of central elements that control the fine-tuning of cancer cells migration in the presence of the ang-(1–7), will support the development of new therapeutic approaches. Ang-(1–7) is a peptide hormone of the renin-angiotensin system (RAS) and this study investigates the modulatory effect of the heptapeptide on the expression pattern of microRNAs (miRNAs) in lung tumor cells, to elucidate mechanistic concerns about the effect of the peptide in the control of tumor migratory processes. Our primary aim was to compare the miRNA profiling between treated and untreated-heptapeptide cells to characterize the relevant molecule that modulates cellular migration rates. The analyses selected twenty one miRNAs, which are differentially expressed between the groups; however, statistical analyses indicated miRNA-149-3p as a relevant molecule. Once functional analyses were performed, we demonstrated that miRNA-149-3p plays a role in the cellular migration processes. This information could be useful for future investigations on drug development. PMID:27598578

  1. Effect of PD 128763, a new potent inhibitor of poly(ADP-ribose) polymerase, on X-ray-induced cellular recovery processes in Chinese hamster V79 cells

    Energy Technology Data Exchange (ETDEWEB)

    Arundel-Suto, C.M.; Scavone, S.V.; Turner, W.R.; Suto, M.J.; Sebolt-Leopold, J.S. (Warner-Lambert Company, Ann Arbor, MI (USA))

    1991-06-01

    The modifying effects of PD 128763 (3,4-dihydro-5-methyl-1(2H)-isoquinolinone), a potent inhibitor of poly(adenosine-diphosphate (ADP)-ribose) polymerase, on radiation-induced cell killing were examined in Chinese hamster V79 cells. This compound has an IC50 value against the purified enzyme approximately 50X lower than 3-aminobenzamide (3-AB), a widely used specific inhibitor of the enzyme. Exposure of exponentially growing cells to a noncytotoxic concentration (0.5 mM) of PD 128763 for 2 h immediately following X irradiation increased their radiation sensitivity, modifying both the shoulder and the slope of the survival curve. When recovery from sublethal damage and potentially lethal damage was examined in exponential and plateau-phase cells, respectively, postirradiation incubation with 0.5 mM PD 128763 was found not only to inhibit both these processes fully, but also to enhance further the level of radiation-induced cell killing. This is in contrast to the slight effect seen with the less potent inhibitor, 3-AB. The results presented suggest that the mechanism of radiosensitization by PD 128763 is related to the potent inhibition of poly(ADP-ribose) polymerase by this compound.

  2. 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

  3. 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.

  4. Planar optical waveguide based sandwich assay sensors and processes for the detection of biological targets including protein markers, pathogens and cellular debris

    Science.gov (United States)

    Martinez, Jennifer S.; Swanson, Basil I.; Grace, Karen M.; Grace, Wynne K.; Shreve, Andrew P.

    2009-06-02

    An assay element is described including recognition ligands bound to a film on a single mode planar optical waveguide, the film from the group of a membrane, a polymerized bilayer membrane, and a self-assembled monolayer containing polyethylene glycol or polypropylene glycol groups therein and an assay process for detecting the presence of a biological target is described including injecting a biological target-containing sample into a sensor cell including the assay element, with the recognition ligands adapted for binding to selected biological targets, maintaining the sample within the sensor cell for time sufficient for binding to occur between selected biological targets within the sample and the recognition ligands, injecting a solution including a reporter ligand into the sensor cell; and, interrogating the sample within the sensor cell with excitation light from the waveguide, the excitation light provided by an evanescent field of the single mode penetrating into the biological target-containing sample to a distance of less than about 200 nanometers from the waveguide thereby exciting the fluorescent-label in any bound reporter ligand within a distance of less than about 200 nanometers from the waveguide and resulting in a detectable signal.

  5. 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.

  6. Hypergravity-induced altered behavior in Drosophila

    Science.gov (United States)

    Hosamani, Ravikumar; Wan, Judy; Marcu, Oana; Bhattacharya, Sharmila

    2012-07-01

    Microgravity and mechanical stress are important factors of the spaceflight environment, and affect astronaut health and behavior. Structural, functional, and behavioral mechanisms of all cells and organisms are adapted to Earth's gravitational force, 1G, while altered gravity can pose challenges to their adaptability to this new environment. On ground, hypergravity paradigms have been used to predict and complement studies on microgravity. Even small changes that take place at a molecular and genetic level during altered gravity may result in changes in phenotypic behavior. Drosophila provides a robust and simple, yet very reliable model system to understand the complexity of hypergravity-induced altered behavior, due to availability of a plethora of genetic tools. Locomotor behavior is a sensitive parameter that reflects the array of molecular adaptive mechanisms recruited during exposure to altered gravity. Thus, understanding the genetic basis of this behavior in a hypergravity environment could potentially extend our understanding of mechanisms of adaptation in microgravity. In our laboratory we are trying to dissect out the cellular and molecular mechanisms underlying hypergravity-induced oxidative stress, and its potential consequences on behavioral alterations by using Drosophila as a model system. In the present study, we employed pan-neuronal and mushroom body specific knock-down adult flies by using Gal4/UAS system to express inverted repeat transgenes (RNAi) to monitor and quantify the hypergravity-induced behavior in Drosophila. We established that acute hypergravity (3G for 60 min) causes a significant and robust decrease in the locomotor behavior in adult Drosophila, and that this change is dependent on genes related to Parkinson's disease, such as DJ-1α , DJ-1β , and parkin. In addition, we also showed that anatomically the control of this behavior is significantly processed in the mushroom body region of the fly brain. This work links a molecular

  7. 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.

  8. A study of the alterability of terminal residues stabilized by a mineral-binder-based solidification/stabilization process; Etude de l`alterabilite de residus ultimes stabilises par un procede de solidification, stabilisation a base de liants mineraux

    Energy Technology Data Exchange (ETDEWEB)

    Humez, N.; Prost, R. [Institut National de Recherches Agronomiques (INRA), 78 - Versailles (France). Unite de Science du Sol; Piketty, L.; Schnuriger, B.; Benchara, A.; Pichat, P. [Centre de Solidification, Stabilisation et Stockage, Sarp Industries, 78 - Limay (France)

    1997-12-31

    A new laboratory approach has been developed for the study of the long term behaviour of stabilized terminal residues, and is based on the experimental method for the study of rock alteration. The method consists in examining the migration of elements that are present in the solution contained in the pores, and studying the structural modifications which result from the dissolution of certain constituents, the transformation and the neo-formation of other ones in the material. The method allows for the evaluation, in a short time, of the alterability and perenniality of stabilized terminal wastes. Results show that the long term alterability of solidified/stabilized samples that have been processed using the ECOFIX method, is low

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. RNA assemblages orchestrate complex cellular processes

    DEFF Research Database (Denmark)

    Nielsen, Finn Cilius; Hansen, Heidi Theil; Christiansen, Jan

    2016-01-01

    Eukaryotic mRNAs are monocistronic, and therefore mechanisms exist that coordinate the synthesis of multiprotein complexes in order to obtain proper stoichiometry at the appropriate intracellular locations. RNA-binding proteins containing low-complexity sequences are prone to generate liquid...... droplets via liquid-liquid phase separation, and in this way create cytoplasmic assemblages of functionally related mRNAs. In a recent iCLIP study, we showed that the Drosophila RNA-binding protein Imp, which exhibits a C-terminal low-complexity sequence, increases the formation of F-actin by binding to 3......' untranslated regions of mRNAs encoding components participating in F-actin biogenesis. We hypothesize that phase transition is a mechanism the cell employs to increase the local mRNA concentration considerably, and in this way synchronize protein production in cytoplasmic territories, as discussed...

  14. Cardiac troponin and tropomyosin: structural and cellular perspectives to unveil the Hypertrophic Cardiomyopathy phenotype

    Directory of Open Access Journals (Sweden)

    Mayra de A. Marques

    2016-09-01

    Full Text Available Inherited myopathies affect both skeletal and cardiac muscle and are commonly associated with genetic dysfunctions, leading to the production of anomalous proteins. In cardiomyopathies, mutations frequently occur in sarcomeric genes, but the cause-effect scenario between genetic alterations and pathological processes remains elusive. Hypertrophic cardiomyopathy (HCM was the first cardiac disease associated with a genetic background. Since the discovery of the first mutation in the β-myosin heavy chain, more than 1,400 new mutations in 11 sarcomeric genes have been reported, awarding HCM the title of the disease of the sarcomere. The most common macroscopic phenotypes are left ventricle and interventricular septal thickening, but because the clinical profile of this disease is quite heterogeneous, these phenotypes are not suitable for an accurate diagnosis. The development of genomic approaches for clinical investigation allows for diagnostic progress and understanding at the molecular level. Meanwhile, the lack of accurate in vivo models to better comprehend the cellular events triggered by this pathology has become a challenge. Notwithstanding, the imbalance of Ca2+ concentrations, altered signaling pathways, induction of apoptotic factors, and heart remodeling leading to abnormal anatomy have already been reported. Of note, a misbalance of signaling biomolecules, such as kinases and tumor suppressors (e.g., Akt and p53, seems to participate in apoptotic and fibrotic events. In HCM, structural and cellular information about defective sarcomeric proteins and their altered interactome is emerging but still represents a bottleneck for developing new concepts in basic research and for future therapeutic interventions. This review focuses on the structural and cellular alterations triggered by HCM-causing mutations in troponin and tropomyosin proteins and how structural biology can aid in the discovery of new platforms for therapeutics. We

  15. Monocyte Activation in Immunopathology: Cellular Test for Development of Diagnostics and Therapy

    Directory of Open Access Journals (Sweden)

    Ekaterina A. Ivanova

    2016-01-01

    Full Text Available Several highly prevalent human diseases are associated with immunopathology. Alterations in the immune system are found in such life-threatening disorders as cancer and atherosclerosis. Monocyte activation followed by macrophage polarization is an important step in normal immune response to pathogens and other relevant stimuli. Depending on the nature of the activation signal, macrophages can acquire pro- or anti-inflammatory phenotypes that are characterized by the expression of distinct patterns of secreted cytokines and surface antigens. This process is disturbed in immunopathologies resulting in abnormal monocyte activation and/or bias of macrophage polarization towards one or the other phenotype. Such alterations could be used as important diagnostic markers and also as possible targets for the development of immunomodulating therapy. Recently developed cellular tests are designed to analyze the phenotype and activity of living cells circulating in patient’s bloodstream. Monocyte/macrophage activation test is a successful example of cellular test relevant for atherosclerosis and oncopathology. This test demonstrated changes in macrophage activation in subclinical atherosclerosis and breast cancer and could also be used for screening a panel of natural agents with immunomodulatory activity. Further development of cellular tests will allow broadening the scope of their clinical implication. Such tests may become useful tools for drug research and therapy optimization.

  16. 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 ...

  17. Targeting cellular mRNAs translation by CRISPR-Cas9.

    Science.gov (United States)

    Liu, Yuchen; Chen, Zhicong; He, Anbang; Zhan, Yonghao; Li, Jianfa; Liu, Li; Wu, Hanwei; Zhuang, Chengle; Lin, Junhao; Zhang, Qiaoxia; Huang, Weiren

    2016-07-13

    Recently CRISPR-Cas9 system has been reported to be capable of targeting a viral RNA, and this phenomenon thus raises an interesting question of whether Cas9 can also influence translation of cellular mRNAs. Here, we show that both natural and catalytically dead Cas9 can repress mRNA translation of cellular genes, and that only the first 14 nt in the 5' end of sgRNA is essential for this process. CRISPR-Cas9 can suppress the protein expression of an unintended target gene without affecting its DNA sequence and causes unexpected phenotypic changes. Using the designed RNA aptamer-ligand complexes which physically obstruct translation machinery, we indicate that roadblock mechanism is responsible for this phenomenon. Our work suggests that studies on Cas9 should avoid the potential off-target effects by detecting the alteration of genes at both the DNA and protein levels.

  18. The cellular decision between apoptosis and autophagy

    Institute of Scientific and Technical Information of China (English)

    Yong-Jun Fan; Wei-Xing Zong

    2013-01-01

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

  19. 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

  20. Disturbance Distance: Using a process based ecosystem model to estimate and map potential thresholds in disturbance rates that would give rise to fundamentally altered ecosystems

    Science.gov (United States)

    Dolan, K. A.; Hurtt, G. C.; Fisk, J.; Flanagan, S.; LePage, Y.; Sahajpal, R.

    2014-12-01

    Disturbance plays a critical role in shaping the structure and function of forested ecosystems as well as the ecosystem services they provide, including but not limited to: carbon storage, biodiversity habitat, water quality and flow, and land atmosphere exchanges of energy and water. As recent studies highlight novel disturbance regimes resulting from pollution, invasive pests and climate change, there is a need to include these alterations in predictions of future forest function and structure. The Ecosystem Demography (ED) model is a mechanistic model of forest ecosystem dynamics in which individual-based forest dynamics can be efficiently implemented over regional to global scales due to advanced scaling methods. We utilize ED to characterize the sensitivity of potential vegetation structure and function to changes in rates of density independent mortality. Disturbance rate within ED can either be altered directly or through the development of sub-models. Disturbance sub-models in ED currently include fire, land use and hurricanes. We use a tiered approach to understand the sensitivity of North American ecosystems to changes in background density independent mortality. Our first analyses were conducted at half-degree spatial resolution with a constant rate of disturbance in space and time, which was altered between runs. Annual climate was held constant at the site level and the land use and fire sub-models were turned off. Results showed an ~ 30% increase in non-forest area across the US when disturbance rates were changed from 0.6% a year to 1.2% a year and a more than 3.5 fold increase in non-forest area when disturbance rates doubled again from 1.2% to 2.4%. Continued runs altered natural background disturbance rates with the existing fire and hurricane sub models turned on as well as historic and future land use. By quantify differences between model outputs that characterize ecosystem structure and function related to the carbon cycle across the US, we

  1. Sinorhizobium meliloti mutants lacking phosphotransferase system enzyme HPr or EIIA are altered in diverse processes, including carbon metabolism, cobalt requirements, and succinoglycan production.

    Science.gov (United States)

    Pinedo, Catalina Arango; Bringhurst, Ryan M; Gage, Daniel J

    2008-04-01

    Sinorhizobium meliloti is a member of the Alphaproteobacteria that fixes nitrogen when it is in a symbiotic relationship. Genes for an incomplete phosphotransferase system (PTS) have been found in the genome of S. meliloti. The genes present code for Hpr and ManX (an EIIA(Man)-type enzyme). HPr and EIIA regulate carbon utilization in other bacteria. hpr and manX in-frame deletion mutants exhibited altered carbon metabolism and other phenotypes. Loss of HPr resulted in partial relief of succinate-mediated catabolite repression, extreme sensitivity to cobalt limitation, rapid die-off during stationary phase, and altered succinoglycan production. Loss of ManX decreased expression of melA-agp and lac, the operons needed for utilization of alpha- and beta-galactosides, slowed growth on diverse carbon sources, and enhanced accumulation of high-molecular-weight succinoglycan. A strain with both hpr and manX deletions exhibited phenotypes similar to those of the strain with a single hpr deletion. Despite these strong phenotypes, deletion mutants exhibited wild-type nodulation and nitrogen fixation when they were inoculated onto Medicago sativa. The results show that HPr and ManX (EIIA(Man)) are involved in more than carbon regulation in S. meliloti and suggest that the phenotypes observed occur due to activity of HPr or one of its phosphorylated forms.

  2. Mitochondrial Morphology and Fundamental Parameters of the Mitochondrial Respiratory Chain Are Altered in Caenorhabditis elegans Strains Deficient in Mitochondrial Dynamics and Homeostasis Processes.

    Science.gov (United States)

    Luz, Anthony L; Rooney, John P; Kubik, Laura L; Gonzalez, Claudia P; Song, Dong Hoon; Meyer, Joel N

    2015-01-01

    Mitochondrial dysfunction has been linked to myriad human diseases and toxicant exposures, highlighting the need for assays capable of rapidly assessing mitochondrial health in vivo. Here, using the Seahorse XFe24 Analyzer and the pharmacological inhibitors dicyclohexylcarbodiimide and oligomycin (ATP-synthase inhibitors), carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (mitochondrial uncoupler) and sodium azide (cytochrome c oxidase inhibitor), we measured the fundamental parameters of mitochondrial respiratory chain function: basal oxygen consumption, ATP-linked respiration, maximal respiratory capacity, spare respiratory capacity and proton leak in the model organism Caenhorhabditis elegans. Since mutations in mitochondrial homeostasis genes cause mitochondrial dysfunction and have been linked to human disease, we measured mitochondrial respiratory function in mitochondrial fission (drp-1)-, fusion (fzo-1)-, mitophagy (pdr-1, pink-1)-, and electron transport chain complex III (isp-1)-deficient C. elegans. All showed altered function, but the nature of the alterations varied between the tested strains. We report increased basal oxygen consumption in drp-1; reduced maximal respiration in drp-1, fzo-1, and isp-1; reduced spare respiratory capacity in drp-1 and fzo-1; reduced proton leak in fzo-1 and isp-1; and increased proton leak in pink-1 nematodes. As mitochondrial morphology can play a role in mitochondrial energetics, we also quantified the mitochondrial aspect ratio for each mutant strain using a novel method, and for the first time report increased aspect ratios in pdr-1- and pink-1-deficient nematodes.

  3. Cellular network entropy as the energy potential in Waddington's differentiation landscape.

    Science.gov (United States)

    Banerji, Christopher R S; Miranda-Saavedra, Diego; Severini, Simone; Widschwendter, Martin; Enver, Tariq; Zhou, Joseph X; Teschendorff, Andrew E

    2013-10-24

    Differentiation is a key cellular process in normal tissue development that is significantly altered in cancer. Although molecular signatures characterising pluripotency and multipotency exist, there is, as yet, no single quantitative mark of a cellular sample's position in the global differentiation hierarchy. Here we adopt a systems view and consider the sample's network entropy, a measure of signaling pathway promiscuity, computable from a sample's genome-wide expression profile. We demonstrate that network entropy provides a quantitative, in-silico, readout of the average undifferentiated state of the profiled cells, recapitulating the known hierarchy of pluripotent, multipotent and differentiated cell types. Network entropy further exhibits dynamic changes in time course differentiation data, and in line with a sample's differentiation stage. In disease, network entropy predicts a higher level of cellular plasticity in cancer stem cell populations compared to ordinary cancer cells. Importantly, network entropy also allows identification of key differentiation pathways. Our results are consistent with the view that pluripotency is a statistical property defined at the cellular population level, correlating with intra-sample heterogeneity, and driven by the degree of signaling promiscuity in cells. In summary, network entropy provides a quantitative measure of a cell's undifferentiated state, defining its elevation in Waddington's landscape.

  4. Cellular network entropy as the energy potential in Waddington's differentiation landscape

    Science.gov (United States)

    Banerji, Christopher R. S.; Miranda-Saavedra, Diego; Severini, Simone; Widschwendter, Martin; Enver, Tariq; Zhou, Joseph X.; Teschendorff, Andrew E.

    2013-10-01

    Differentiation is a key cellular process in normal tissue development that is significantly altered in cancer. Although molecular signatures characterising pluripotency and multipotency exist, there is, as yet, no single quantitative mark of a cellular sample's position in the global differentiation hierarchy. Here we adopt a systems view and consider the sample's network entropy, a measure of signaling pathway promiscuity, computable from a sample's genome-wide expression profile. We demonstrate that network entropy provides a quantitative, in-silico, readout of the average undifferentiated state of the profiled cells, recapitulating the known hierarchy of pluripotent, multipotent and differentiated cell types. Network entropy further exhibits dynamic changes in time course differentiation data, and in line with a sample's differentiation stage. In disease, network entropy predicts a higher level of cellular plasticity in cancer stem cell populations compared to ordinary cancer cells. Importantly, network entropy also allows identification of key differentiation pathways. Our results are consistent with the view that pluripotency is a statistical property defined at the cellular population level, correlating with intra-sample heterogeneity, and driven by the degree of signaling promiscuity in cells. In summary, network entropy provides a quantitative measure of a cell's undifferentiated state, defining its elevation in Waddington's landscape.

  5. Analysis of genes differentially expressed during initial cellular dedifferentiation in cotton

    Institute of Scientific and Technical Information of China (English)

    ZHU HuaGuo; TU LiLi; JIN ShuangXia; XU Li; TAN JiaFu; DENG FengLin; ZHANG XianLong

    2008-01-01

    The early phase of phytohormone induction is a vital stage of somatic embryogenesis. This phase includes a key process for acquiring cellular totipotency through cellular dedifferentiation. To unravel the molecular mechanism of cellular dedifferentiation in cotton, we constructed a cDNA library using the suppression subtractive hybridization method. A total of 286 differential cDNA clones were sequenced and identified. Among these clones, 112 unique ESTs were significantly up-regulated during the early phase of phytohormone induction, and 40.2% of the ESTs were first identified. GST was highly expressed from 6 to 24 h after induction with phytohormone treatment. PRPs were predominantly expressed and exhibited distinct expression patterns in different treatments, suggesting that they are closely related to cellular dedifferentiation in cotton. Putative GhSAMS, GhSAMDC, GhSAHH and GhACO3 involvement in SAM metabolism was identified in this library. The analysis of qRT-PCR showed that two remarkable increased expressions of the four SAM-related genes happened during the early phase of phytohormone induction, and that a highly positive correlation existed between GhSAMS and GhSAHH. The highest expression level of GhSAMS might be associated with its reentry into the cell cycle. The histological observations further showed that some cells accomplished cellular dedifferentiation and division within 72 h in 2,4-D treatment, and that cellular dedifferentiation might be regulated through two alterations in SAM-dependent transmethylation activity in cotton. In addition, the expression patterns of differential genes in different treatments disclosed the complicated interaction between 2, 4-D and kinetin.

  6. 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.

  7. 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 ...

  8. 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....

  9. 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.

  10. Systems biology analysis merging phenotype, metabolomic and genomic data identifies Non-SMC Condensin I Complex, Subunit G (NCAPG and cellular maintenance processes as major contributors to genetic variability in bovine feed efficiency.

    Directory of Open Access Journals (Sweden)

    Philipp Widmann

    Full Text Available Feed efficiency is a paramount factor for livestock economy. Previous studies had indicated a substantial heritability of several feed efficiency traits. In our study, we investigated the genetic background of residual feed intake, a commonly used parameter of feed efficiency, in a cattle resource population generated from crossing dairy and beef cattle. Starting from a whole genome association analysis, we subsequently performed combined phenotype-metabolome-genome analysis taking a systems biology approach by inferring gene networks based on partial correlation and information theory approaches. Our data about biological processes enriched with genes from the feed efficiency network suggest that genetic variation in feed efficiency is driven by genetic modulation of basic processes relevant to general cellular functions. When looking at the predicted upstream regulators from the feed efficiency network, the Tumor Protein P53 (TP53 and Transforming Growth Factor beta 1 (TGFB1 genes stood out regarding significance of overlap and number of target molecules in the data set. These results further support the hypothesis that TP53 is a major upstream regulator for genetic variation of feed efficiency. Furthermore, our data revealed a significant effect of both, the Non-SMC Condensin I Complex, Subunit G (NCAPG I442M (rs109570900 and the Growth /differentiation factor 8 (GDF8 Q204X (rs110344317 loci, on residual feed intake and feed conversion. For both loci, the growth promoting allele at the onset of puberty was associated with a negative, but favorable effect on residual feed intake. The elevated energy demand for increased growth triggered by the NCAPG 442M allele is obviously not fully compensated for by an increased efficiency in converting feed into body tissue. As a consequence, the individuals carrying the NCAPG 442M allele had an additional demand for energy uptake that is reflected by the association of the allele with increased daily

  11. Plant growth conditions alter phytolith carbon

    Directory of Open Access Journals (Sweden)

    Kimberley L Gallagher

    2015-09-01

    Full Text Available Many plants, including grasses and some important human food sources, accumulate and precipitate silica in their cells to form opaline phytoliths. These phytoliths contain small amounts of organic matter (OM that are trapped during the process of silicification. Previous work has suggested that plant silica is associated with compounds such as proteins, lipids, lignin and carbohydrate complexes. It is not known whether these compounds are cellular components passively encapsulated as the cell silicifies, polymers actively involved in the precipitation process or random compounds assimilated by the plant and discarded into a glass wastebasket. Here, we used Raman spectroscopy to map the distribution of OM in phytoliths, and to analyze individual phytoliths isolated from Sorghum bicolor plants grown under different laboratory treatments. Using mapping, we showed that OM in phytoliths is distributed throughout the silica and is not related to dark spots visible in light microscopy, previously assumed to be the repository for phytolith OM. The Raman spectra exhibited common bands indicative of C-H stretching modes of general OM, and further more diagnostic bands consistent with carbohydrates, lignins and other OM. These Raman spectra exhibited variability of spectral signatures and of relative intensities between sample treatments indicating that differing growth conditions altered the phytolith carbon. This may have strong implications for understanding the mechanism of phytolith formation, and for use of phytolith carbon isotope values in dating or paleoclimate reconstruction.

  12. Complexity, dynamic cellular network, and tumorigenesis.

    Science.gov (United States)

    Waliszewski, P

    1997-01-01

    A holistic approach to tumorigenesis is proposed. The main element of the model is the existence of dynamic cellular network. This network comprises a molecular and an energetistic structure of a cell connected through the multidirectional flow of information. The interactions within dynamic cellular network are complex, stochastic, nonlinear, and also involve quantum effects. From this non-reductionist perspective, neither tumorigenesis can be limited to the genetic aspect, nor the initial event must be of molecular nature, nor mutations and epigenetic factors are mutually exclusive, nor a link between cause and effect can be established. Due to complexity, an unstable stationary state of dynamic cellular network rather than a group of unrelated genes determines the phenotype of normal and transformed cells. This implies relativity of tumor suppressor genes and oncogenes. A bifurcation point is defined as an unstable state of dynamic cellular network leading to the other phenotype-stationary state. In particular, the bifurcation point may be determined by a change of expression of a single gene. Then, the gene is called bifurcation point gene. The unstable stationary state facilitates the chaotic dynamics. This may result in a fractal dimension of both normal and tumor tissues. The co-existence of chaotic dynamics and complexity is the essence of cellular processes and shapes differentiation, morphogenesis, and tumorigenesis. In consequence, tumorigenesis is a complex, unpredictable process driven by the interplay between self-organisation and selection.

  13. Corneal cellular proliferation and wound healing

    OpenAIRE

    Gan, Lisha

    2000-01-01

    Background. Cellular proliferation plays an important role in both physiological and pathological processes. Epithelial hyperplasia in the epithelium, excessive scar formation in retrocorneal membrane formation and neovascularization are examples of excessive proliferation of cornea cells. Lack of proliferative ability causes corneal degeneration. The degree of proliferative and metabolic activity will directly influence corneal transparency and very evidently refractive res...

  14. 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.

  15. Biological Effects of Electromagnetic Fields on Cellular Growth

    Science.gov (United States)

    Eftekhari, Beheshte; Wilson, James; Masood, Samina

    2012-10-01

    The interaction of organisms with environmental magnetic fields at the cellular level is well documented, yet not fully understood. We review the existing experimental results to understand the physics behind the effects of ambient magnetic fields on the growth, metabolism, and proliferation of in vitro cell cultures. Emphasis is placed on identifying the underlying physical principles responsible for alterations to cell structure and behavior.

  16. Prevalência de alteração morfológica do processo estilóide em pacientes com desordem temporomandibular Prevalence of morphological alterations of the styloid process in patients with temporomandibular joint disorder

    Directory of Open Access Journals (Sweden)

    Simone Maria Ragone Guimarães

    2006-12-01

    Full Text Available OBJETIVO: Avaliar, radiograficamente, a prevalência de alterações morfológicas do processo estilóide em pacientes com desordens temporomandibulares. MATERIAIS E MÉTODOS: Foram analisadas 1.500 radiografias panorâmicas da articulação temporomandibular de pacientes de ambos os sexos e sem limitação de idade, que foram atendidos pelo Serviço de Desordem Temporomandibular da Faculdade de Odontologia da Universidade Federal de Juiz de Fora, MG, no período de 1997 a 2003. RESULTADOS: Oitenta e três (5,53% dos pacientes da amostra apresentaram pelo menos um dos lados da articulação com alteração morfológica do processo estilóide, sendo 74 do sexo feminino e 9 do sexo masculino, concentrados na faixa dos 41 a 50 anos de idade (32,5%. Com relação ao tipo morfológico do processo estilóide, verificaram-se 113 alongados, 21 pseudo-articulados e 19 segmentados. Constatou-se, também, que as alterações morfológicas do processo estilóide desenvolvem-se de forma simétrica. CONCLUSÃO: Em pacientes com desordem temporomandibular as alterações do processo estilóide ocorrem de forma diferenciada e de maneira simétrica em cada paciente, independentemente do sexo e da idade.OBJECTIVE: To assess radiographically the prevalence of morphological alterations of the styloid process in patients with temporomandibular joint disorders. MATERIALS AND METHODS: We have analyzed 1,500 panoramic x-ray films of temporomandibular joint from both male and female patients with no age limit, who were attended in the Service of Temporomandibular Joint Disorder of Faculty of Odontology at Universidade Federal de Juiz de Fora, MG, Brazil, in the period between 1997 and 2003. RESULTS: Eighty-three (5.53% of the analyzed patients (74 female and 9 male, predominantly in the age range between 41 and 50 years (32.5%, presented with, at least, one of the joint sides with morphological alteration of the styloid process. As far as the type of styloid process in

  17. Cellular basis of Alzheimer′s disease

    Directory of Open Access Journals (Sweden)

    Bali Jitin

    2010-10-01

    Full Text Available 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.

  18. Cellular basis of Alzheimer’s disease

    Science.gov (United States)

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

    2010-01-01

    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. PMID:21369424

  19. 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...

  20. 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....

  1. 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.

  2. Real time kinetic flow cytometry measurements of cellular parameter changes evoked by nanosecond pulsed electric field.

    Science.gov (United States)

    Orbán, Csaba; Pérez-García, Esther; Bajnok, Anna; McBean, Gethin; Toldi, Gergely; Blanco-Fernandez, Alfonso

    2016-05-01

    Nanosecond pulsed electric field (nsPEF) is a novel method to increase cell proliferation rate. The phenomenon is based on the microporation of cellular organelles and membranes. However, we have limited information on the effects of nsPEF on cell physiology. Several studies have attempted to describe the effects of this process, however no real time measurements have been conducted to date. In this study we designed a model system which allows the measurement of cellular processes before, during and after nsPEF treatment in real time. The system employs a Vabrema Mitoplicator(TM) nsPEF field generating instrument connected to a BD Accuri C6 cytometer with a silicon tube led through a peristaltic pump. This model system was applied to observe the effects of nsPEF in mammalian C6 glioblastoma (C6 glioma) and HEK-293 cell lines. Viability (using DRAQ7 dye), intracellular calcium levels (using Fluo-4 dye) and scatter characteristics were measured in a kinetic manner. Data were analyzed using the FACSKin software. The viability and morphology of the investigated cells was not altered upon nsPEF treatment. The response of HEK-293 cells to ionomycin as positive control was significantly lower in the nsPEF treated samples compared to non-treated cells. This difference was not observed in C6 cells. FSC and SSC values were not altered significantly by the nsPEF treatment. Our results indicate that this model system is capable of reliably investigating the effects of nsPEF on cellular processes in real time. © 2016 International Society for Advancement of Cytometry.

  3. pna - assisted cellular migration on patterned surfaces

    OpenAIRE

    2013-01-01

    ABSTRACT - The ability to control the cellular microenvironment, such as cell-substrate and cell-cell interactions at the micro- and nanoscale, is important for advances in several fields such as medicine and immunology, biochemistry, biomaterials, and tissue engineering. In order to undergo fundamental biological processes, most mammalian cells must adhere to the underlying extracellular matrix (ECM), eliciting cell adhesion and migration processes that are critical to embryogenesis, angioge...

  4. A methodological report from the Malmö Diet and Cancer study: development and evaluation of altered routines in dietary data processing

    Directory of Open Access Journals (Sweden)

    Wallström Peter

    2002-11-01

    Full Text Available Abstract Background In the Malmö Diet and Cancer study, information on dietary habits was obtained through a modified diet history method, combining a 7-day menu book for cooked meals and a diet questionnaire for foods with low day-to-day variation. Half way through the baseline data collection, a change of interview routines was implemented in order to reduce interview time. Methods Changes concentrated on portion-size estimation and recipe coding of mixed dishes reported in the menu book. All method development and tests were carefully monitored, based on experiential knowledge, and supplemented with empirical data. A post hoc evaluation study using "real world" data compared observed means of selected dietary variables before and after the alteration of routines handling dietary data, controlling for potential confounders. Results These tests suggested that simplified coding rules and standard portion-sizes could be used on a limited number of foods, without distortions of the group mean nutrient intakes, or the participants' ranking. The post hoc evaluation suggested that mean intakes of energy-adjusted fat were higher after the change in routines. The impact appeared greater in women than in men. Conclusions Future descriptive studies should consider selecting subsets assessed with either method version to avoid distortion of observed mean intakes. The impact in analytical studies may be small, because method version and diet assistant explained less than 1 percent of total variation. The distribution of cases and non-cases across method versions should be monitored.

  5. Online isolation of defects in cellular nanocomputers

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  6. Cellular and molecular drivers of differential organ growth: insights from the limbs of Monodelphis domestica.

    Science.gov (United States)

    Dowling, Anna; Doroba, Carolyn; Maier, Jennifer A; Cohen, Lorna; VandeBerg, John; Sears, Karen E

    2016-06-01

    A fundamental question in biology is "how is growth differentially regulated during development to produce organs of particular sizes?" We used a new model system for the study of differential organ growth, the limbs of the opossum (Monodelphis domestica), to investigate the cellular and molecular basis of differential organ growth in mammals. Opossum forelimbs grow much faster than hindlimbs, making opossum limbs an exceptional system with which to study differential growth. We first used the great differences in opossum forelimb and hindlimb growth to identify cellular processes and molecular signals that underlie differential limb growth. We then used organ culture and pharmacological addition of FGF ligands and inhibitors to test the role of the Fgf/Mitogen-activated protein kinases (MAPK) signaling pathway in driving these cellular processes. We found that molecular signals from within the limb drive differences in cell proliferation that contribute to the differential growth of the forelimb and hindlimbs of opossums. We also found that alterations in the Fgf/MAPK pathway can generate differences in cell proliferation that mirror those observed between wild-type forelimb and hindlimbs of opossums and that manipulation of Fgf/MAPK signaling affects downstream focal adhesion-extracellular matrix (FA-ECM) and Wnt signaling in opossum limbs. Taken together, these findings suggest that evolutionary changes in the Fgf/MAPK pathway could help drive the observed differences in cell behaviors and growth in opossum forelimb and hindlimbs.

  7. Modern 'junk food' and minimally-processed 'natural food' cafeteria diets alter the response to sweet taste but do not impair flavor-nutrient learning in rats.

    Science.gov (United States)

    Palframan, Kristen M; Myers, Kevin P

    2016-04-01

    Animals learn to prefer and increase consumption of flavors paired with postingestive nutrient sensing. Analogous effects have been difficult to observe in human studies. One possibility is experience with the modern, processed diet impairs learning. Food processing manipulates flavor, texture, sweetness, and nutrition, obscuring ordinary correspondences between sensory cues and postingestive consequences. Over time, a diet of these processed 'junk' foods may impair flavor-nutrient learning. This 'flavor-confusion' hypothesis was tested by providing rats long-term exposure to cafeteria diets of unusual breadth (2 or 3 foods per day, 96 different foods over 3 months, plus ad libitum chow). One group was fed processed foods (PF) with added sugars/fats and manipulated flavors, to mimic the sensory-nutrient properties of the modern processed diet. Another group was fed only 'natural' foods (NF) meaning minimally-processed foods without manipulated flavors or added sugars/fats (e.g., fresh fruits, vegetables, whole grains) ostensibly preserving the ordinary correspondence between flavors and nutrition. A CON group was fed chow only. In subsequent tests of flavor-nutrient learning, PF and NF rats consistently acquired strong preferences for novel nutrient-paired flavors and PF rats exhibited enhanced learned acceptance, contradicting the 'flavor-confusion' hypothesis. An unexpected finding was PF and NF diets both caused lasting reduction in ad lib sweet solution intake. Groups did not differ in reinforcing value of sugar in a progressive ratio task. In lick microstructure analysis the NF group paradoxically showed increased sucrose palatability relative to PF and CON, suggesting the diets have different effects on sweet taste evaluation.

  8. 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

  9. Enhanced neuropeptide Y synthesis during intermittent hypoxia in the rat adrenal medulla: role of reactive oxygen species-dependent alterations in precursor peptide processing.

    Science.gov (United States)

    Raghuraman, Gayatri; Kalari, Apeksha; Dhingra, Rishi; Prabhakar, Nanduri R; Kumar, Ganesh K

    2011-04-01

    Intermittent hypoxia (IH) associated with recurrent apneas often leads to cardiovascular abnormalities. Previously, we showed that IH treatment elevates blood pressure and increases plasma catecholamines (CAs) in rats via reactive oxygen species (ROS)-dependent enhanced synthesis and secretion from the adrenal medulla (AM). Neuropeptide Y (NPY), a sympathetic neurotransmitter that colocalizes with CA in the AM, has been implicated in blood pressure regulation during persistent stress. Here, we investigated whether IH facilitates NPY synthesis in the rat AM and assessed the role of ROS signaling. IH increased NPY-like immunoreactivity in many dopamine-β-hydroxylase-expressing chromaffin cells with a parallel increase in preproNPY mRNA and protein. IH increased the activities of proNPY-processing enzymes, which were due, in part, to elevated protein expression and increased proteolytic processing. IH increased ROS generation, and antioxidants reversed IH-induced increases in ROS, preproNPY, and its processing to bioactive NPY in the AM. IH treatment increased blood pressure and antioxidants and inhibition of NPY amidation prevented this response. These findings suggest that IH-induced elevation in NPY expression in the rat AM is mediated by ROS-dependent augmentation of preproNPY mRNA expression and proNPY-processing enzyme activities and contributes to IH-induced elevation of blood pressure.

  10. Music alters visual perception.

    Directory of Open Access Journals (Sweden)

    Jacob Jolij

    Full Text Available BACKGROUND: Visual perception is not a passive process: in order to efficiently process visual input, the brain actively uses previous knowledge (e.g., memory and expectations about what the world should look like. However, perception is not only influenced by previous knowledge. Especially the perception of emotional stimuli is influenced by the emotional state of the observer. In other words, how we perceive the world does not only depend on what we know of the world, but also by how we feel. In this study, we further investigated the relation between mood and perception. METHODS AND FINDINGS: We let observers do a difficult stimulus detection task, in which they had to detect schematic happy and sad faces embedded in noise. Mood was manipulated by means of music. We found that observers were more accurate in detecting faces congruent with their mood, corroborating earlier research. However, in trials in which no actual face was presented, observers made a significant number of false alarms. The content of these false alarms, or illusory percepts, was strongly influenced by the observers' mood. CONCLUSIONS: As illusory percepts are believed to reflect the content of internal representations that are employed by the brain during top-down processing of visual input, we conclude that top-down modulation of visual processing is not purely predictive in nature: mood, in this case manipulated by music, may also directly alter the way we perceive the world.

  11. Hypogene and supergene alteration of the zeolite-bearing pyroclastic deposits at Tell Rimah, Jordan, and rift-related processes along the Dead-Sea-Transform Fault System during the Quaternary

    Science.gov (United States)

    Dill, H. G.; Techmer, A.; Botz, R.; Dohrmann, R.; Kaufhold, S.

    2012-09-01

    The boundary between the Arabian and African plates, is marked in the Middle East by one of the most prominent deep-seated lineamentary structures, called the Dead-Sea-Transform Fault System (DSTFS). Structural and mineralogical processes related to the DSTFS were correlated with equivalent processes leading to the alteration of pyroclastic deposits of alkali-olivine basaltic to nepheline basaltic composition which formed during a time span of less than 0.5 Ma. The large deposit of Tell Rimah, Jordan, is operated for the exploitation of zeolites, tuffs, and as pozzolana raw material. Four discrete stages of mineralizations have been distinguished from each other within these volcanic-hosted mineral deposits. (1) Hypogene syneruptive alteration of pyroclastic rocks produced siliceous gels ("allophane"), smectite, analcime, and phillipsite in vesicles when the groundwater level was low in the rift basin of the DSTFS. The lake-level lowstand caused the fluid system in the pyroclastic cone to become self-sufficient and it has been considered as a closed hydrothermal system. (2) Periods of tectonic and magmatic quiescence grinded the detrital sedimentation in the rift basin to a halt, while triggering a supergene alteration in the eruptive cones on the adjacent Arabian Plate. (3) Epigenetic alteration affected the pyroclastic rocks in the distal part of the DSTFS as a result of a rising water level. The water gradually filled the pore space of the permeable pyroclastic deposits almost to completeness and caused meniscus and blocky cements of calcite, phillipsite and chabazite to develop. In the rift basin, contemporaneously with the alteration of the pyroclastic rocks, freshwater limestones formed on calcareous bedrocks. Ba and Mn minerals in these freshwater limestones were supplied by subaquatic brines. Subsequently, a drastic lowering of the lake water level in the DSTFS converted the system of subaquatic freshwater limestones into subaerial tufa and travertine. As

  12. 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.

  13. 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.

  14. Implications of TGFβ on transcriptome and cellular biofunctions of palatal mesenchyme

    Directory of Open Access Journals (Sweden)

    Xiujuan eZhu

    2012-04-01

    Full Text Available Development of the palate comprises sequential stages of growth, elevation and fusion of the palatal shelves. The mesenchymal component of palates plays a major role in early phases of palatogenesis, such as growth and elevation. Failure in these steps may result in cleft palate, the second most common birth defect in the world. These early stages of palatogenesis require precise and chronological orchestration of key physiological processes, such as growth, proliferation, differentiation, migration, and apoptosis. There is compelling evidence for the vital role of TGFβ-mediated regulation of palate development. We hypothesized that the isoforms of TGFβ regulate different cellular biofunctions of the palatal mesenchyme to various extents. Human embryonic palatal mesenchyme (HEPM cells were treated with TGFβ1, β2, and β3 for microarray-based gene expression studies in order to identify the roles of TGFβ in the transcriptome of the palatal mesenchyme. Following normalization and modeling of 28,869 human genes, 566 transcripts were detected as differentially expressed in TGFβ-treated HEPM cells. Out of these altered transcripts, 234 of them were clustered in cellular biofunctions, including growth and proliferation, development, morphology, movement, cell cycle, and apoptosis. Biological interpretation and network analysis of the genes active in cellular biofunctions were performed using IPA. Among the differentially expressed genes, 11 of them were previously identified as being crucial for palatogenesis (EDN1, INHBA, LHX8, PDGFC, PIGA, RUNX1, SNAI1, SMAD3, TGFβ1, TGFβ2, and TGFβR1. These genes were used for a merged interaction network with cellular behaviors. Overall, we have determined that more than 2% of human transcripts were differentially expressed in response to TGFβ treatment in HEPM cells. Our results suggest that both TGFβ1 and TGFβ2 orchestrate major cellular biofunctions within the palatal mesenchyme in vitro by

  15. Mutations altering a structurally conserved loop-helix-loop region of a viral packaging motor change DNA translocation velocity and processivity.

    Science.gov (United States)

    Tsay, James M; Sippy, Jean; DelToro, Damian; Andrews, Benjamin T; Draper, Bonnie; Rao, Venigalla; Catalano, Carlos E; Feiss, Michael; Smith, Douglas E

    2010-07-30

    Many double-stranded DNA viruses employ ATP-driven motors to translocate their genomes into small, preformed viral capsids against large forces resisting confinement. Here, we show via direct single-molecule measurements that a mutation T194M downstream of the Walker B motif in the phage lambda gpA packaging motor causes an 8-fold reduction in translocation velocity without substantially changing processivity or force dependence, whereas the mutation G212S in the putative C (coupling) motif causes a 3-fold reduction in velocity and a 6-fold reduction in processivity. Meanwhile a T194M pseudorevertant (T194V) showed a near restoration of the wild-type dynamics. Structural comparisons and modeling show that these mutations are in a loop-helix-loop region that positions the key residues of the catalytic motifs, Walker B and C, in the ATPase center and is structurally homologous with analogous regions in chromosome transporters and SF2 RNA helicases. Together with recently published studies of SpoIIIE chromosome transporter and Ded1 RNA helicase mutants, these findings suggest the presence of a structurally conserved region that may be a part of the mechanism that determines motor velocity and processivity in several different types of nucleic acid translocases.

  16. The interconnection of wet and dry deposition and the alteration of deposition budgets due to incorporation of new process understanding in regional models

    Science.gov (United States)

    Dennis, R. L.; Bash, J. O.; Foley, K. M.; Gilliam, R.; Pinder, R. W.

    2013-12-01

    Deposition is affected by the chemical and physical processes represented in the regional models as well as source strength. The overall production and loss budget (wet and dry deposition) is dynamically connected and adjusts internally to changes in process representation. In addition, the scrubbing of pollutants from the atmosphere by precipitation is one of several processes that remove pollutants, creating a coupling with the atmospheric aqueous and gas phase chemistry that can influence wet deposition rates in a nonlinear manner. We explore through model sensitivities with the regional Community Multiscale Air Quality (CMAQ) model the influence on wet and dry deposition, and the overall continental nitrogen budget, of changes in three process representations in the model: (1) incorporation of lightning generated NO, (2) improved representation of convective precipitation, and (3) replacement of the typical unidirectional dry deposition of NH3 with a state of the science representation of NH3 bi-directional air-surface exchange. Results of the sensitivity studies will be presented. (1) Incorporation of lightning generated NO significantly reduces a negative bias in summer wet nitrate deposition, but is sensitive to the choice of convective parameterization. (2) Use of a less active trigger of convective precipitation in the WRF meteorological model to reduce summertime precipitation over prediction bias reduces the generation of NO from lightning. It also reduces the wet deposition of nitrate and increases the dry deposition of oxidized nitrogen, as well as changing (reducing) the surface level exposure to ozone. Improvements in the convective precipitation processes also result in more non-precipitating clouds leading to an increase in SO4 production through the aqueous pathway resulting in improvements in summertime SO4 ambient aerosol estimates.(3) Incorporation of state of the science ammonia bi-directional air surface exchange affects both the dry

  17. [Altered states of consciousness].

    Science.gov (United States)

    Gora, E P

    2005-01-01

    The review of modern ideas concerning the altered states of consciousness is presented in this article. Various methods of entry into the altered states of consciousness are looked over. It is shown that the altered states of consciousness are insufficiently known, but important aspects of human being existence. The role of investigation of the altered states of consciousness for the creation of integrative scientific conception base is discussed.

  18. Liver Fibrosis and Altered Matrix Synthesis

    Directory of Open Access Journals (Sweden)

    Katrin Neubauer

    2001-01-01

    Full Text Available Liver fibrosis represents the uniform response of liver to toxic, infectious or metabolic agents. The process leading to liver fibrosis resembles the process of wound healing, including the three phases following tissue injury: inflammation, synthesis of collagenous and noncollagenous extracellular matrix components, and tissue remodelling (scar formation. While a single liver tissue injury can be followed by an almost complete restitution ad integrum, the persistence of the original damaging noxa results in tissue damage. During the establishment of liver fibrosis, the basement membrane components collagen type IV, entactin and laminin increase and form a basement membrane-like structure within the space of Disse. The number of endothelial fenestrae of the sinusoids decreases. These changes of the sinusoids are called 'capillarization' because the altered structure of the sinusoids resembles that of capillaries. At the cellular level, origin of liver fibrogenesis is initiated by the damage of hepatocytes, resulting in the recruitment of inflammatory cells and platelets, and activation of Kupffer cells, with subsequent release of cytokines and growth factors. The hepatic stellate cells seem to be the primary target cells for these inflammatory stimuli, because during fibrogenesis, they undergo an activation process to a myofibroblast-like cell, which represents the major matrix-producing cell. Based on this pathophysiological mechanism, therapeutic methods are developed to inhibit matrix synthesis or stimulate matrix degradation. A number of substances are currently being tested that either neutralize fibrogenic stimuli and prevent the activation of hepatic stellate cells, or directly modulate the matrix metabolism. However, until now, the elimination of the hepatotoxins has been the sole therapeutic concept available for the treatment of liver fibrogenesis in humans.

  19. 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.

  20. 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.

  1. 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.

  2. Molecular and cellular mechanisms of muscle aging and sarcopenia and effects of electrical stimulation in seniors

    Directory of Open Access Journals (Sweden)

    Laura Barberi

    2015-08-01

    Full Text Available The prolongation of skeletal muscle strength in aging and neuromuscular disease has been the objective of numerous studies employing a variety of approaches. It is generally accepted that cumulative failure to repair damage related to an overall decrease in anabolic processes is a primary cause of functional impairment in muscle. The functional performance of skeletal muscle tissues declines during post- natal life and it is compromised in different diseases, due to an alteration in muscle fiber composition and an overall decrease in muscle integrity as fibrotic invasions replace functional contractile tissue. Characteristics of skeletal muscle aging and diseases include a conspicuous reduction in myofiber plasticity (due to the progressive loss of muscle mass and in particular of the most powerful fast fibers, alteration in muscle-specific transcriptional mechanisms, and muscle atrophy. An early decrease in protein synthetic rates is followed by a later increase in protein degradation, to affect biochemical, physiological, and morphological parameters of muscle fibers during the aging process. Alterations in regenerative pathways also compromise the functionality of muscle tissues. In this review we will give an overview of the work on molecular and cellular mechanisms of aging and sarcopenia and the effects of electrical stimulation in seniors.

  3. Altered Pathway Analyzer: A gene expression dataset analysis tool for identification and prioritization of differentially regulated and network rewired pathways

    Science.gov (United States)

    Kaushik, Abhinav; Ali, Shakir; Gupta, Dinesh

    2017-01-01

    Gene connection rewiring is an essential feature of gene network dynamics. Apart from its normal functional role, it may also lead to dysregulated functional states by disturbing pathway homeostasis. Very few computational tools measure rewiring within gene co-expression and its corresponding regulatory networks in order to identify and prioritize altered pathways which may or may not be differentially regulated. We have developed Altered Pathway Analyzer (APA), a microarray dataset analysis tool for identification and prioritization of altered pathways, including those which are differentially regulated by TFs, by quantifying rewired sub-network topology. Moreover, APA also helps in re-prioritization of APA shortlisted altered pathways enriched with context-specific genes. We performed APA analysis of simulated datasets and p53 status NCI-60 cell line microarray data to demonstrate potential of APA for identification of several case-specific altered pathways. APA analysis reveals several altered pathways not detected by other tools evaluated by us. APA analysis of unrelated prostate cancer datasets identifies sample-specific as well as conserved altered biological processes, mainly associated with lipid metabolism, cellular differentiation and proliferation. APA is designed as a cross platform tool which may be transparently customized to perform pathway analysis in different gene expression datasets. APA is freely available at http://bioinfo.icgeb.res.in/APA. PMID:28084397

  4. MIMO Communication for Cellular Networks

    CERN Document Server

    Huang, Howard; Venkatesan, Sivarama

    2012-01-01

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

  5. Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Payne CM

    2011-05-01

    Full Text Available Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated with DNA repair, spindle checkpoint function, apoptosis, multiple microRNAs, the Wnt signaling pathway, tumor suppression, antioxidant activities, and defense against environmental toxins. Loss of 1p is dangerous since it would likely contribute to genomic instability leading to tumorigenesis. The 1p deletion-associated colon carcinogenesis pathways are reviewed at the molecular and cellular levels. Sporadic colon cancer is strongly linked to a high-fat/low-vegetable/low-micronutrient, Western-style diet. We also consider how selected dietary-related compounds (eg, excess hydrophobic bile acids, and low levels of folic acid, niacin, plant-derived antioxidants, and other modulatory compounds might affect processes leading to chromosomal deletions, and to the molecular and cellular pathways specifically altered by chromosome 1p loss.Keywords: chromosome 1p, colon carcinogenesis, molecular pathways, cellular pathways

  6. Vector-averaged gravity does not alter acetylcholine receptor single channel properties

    Science.gov (United States)

    Reitstetter, R.; Gruener, R.

    1994-01-01

    To examine the physiological sensitivity of membrane receptors to altered gravity, we examined the single channel properties of the acetylcholine receptor (AChR), in co-cultures of Xenopus myocytes and neurons, to vector-averaged gravity in the clinostat. This experimental paradigm produces an environment in which, from the cell's perspective, the gravitational vector is "nulled" by continuous averaging. In that respect, the clinostat simulates one aspect of space microgravity where the gravity force is greatly reduced. After clinorotation, the AChR channel mean open-time and conductance were statistically not different from control values but showed a rotation-dependent trend that suggests a process of cellular adaptation to clinorotation. These findings therefore suggest that the ACHR channel function may not be affected in the microgravity of space despite changes in the receptor's cellular organization.

  7. Cellular modifications and interventions for the damaged heart

    NARCIS (Netherlands)

    Engels, M.C.

    2016-01-01

    The aim of this thesis was to explore cellular modification processes associated with heart disease, as well as harnessing its potential for treatment and prevention of detrimental electrophysiological consequences of heart disease. For regenerative cell replacement therapies, optimal differentiatio

  8. Thermal Processing Alters the Chemical Quality and Sensory Characteristics of Sweetsop (Annona squamosa L.) and Soursop (Annona muricata L.) Pulp and Nectar.

    Science.gov (United States)

    Baskaran, Revathy; Ravi, Ramasamy; Rajarathnam, Somasundaram

    2016-01-01

    The objective of this study was to investigate the effect of thermal processing on the chemical quality and sensory characteristics of Annona squamosa L. and Annona muricata L. fruit pulps and nectar. The fruit pulps were pasteurized at 85 °C for 20 min and nectar prepared as per Food Safety and Standards Authority of India (FSSAI) specifications. The chemical composition of fresh and heated pulps of A. squamosa and A. muricata showed that compared to fresh, the chemical profile and sensory profile changed in heated samples and nectar. The free and bound phenolics of A. squamosa increased in heated pulp (127.61 to 217.22 mg/100 g and 150.34 to 239.74 mg/100 g, respectively), while in A. muricata, free phenolics increased very marginally from 31.73 to 33.74 mg/100 g and bound phenolics decreased from 111.11 to 86.91 mg/100 g. This increase in phenolic content may be attributed to the perception of bitterness and astringency in A. squamosa pulp on heating. In electronic tongue studies, principal component analysis (PCA) confirmed that the fresh and heated pulps had different scores, as indicated by sensory analysis using qualitative descriptive analysis (QDA). E-tongue analysis of samples discriminated the volatile compounds released from the heated A. squamosa and A. muricata fruit pulps and nectar in their respective PCA plots by forming different clusters.

  9. Modification, adsorption, and geochemistry processes on altered minerals and amorphous phases on the nanometer scale: examples from copper mining refuse, Touro, Spain.

    Science.gov (United States)

    Civeira, Matheus; Oliveira, Marcos L S; Hower, James C; Agudelo-Castañeda, Dayana M; Taffarel, Silvio R; Ramos, Claudete G; Kautzmann, Rubens M; Silva, Luis F O

    2016-04-01

    The sulfide oxidation and precipitation of Al-Fe-secondary minerals associated with abandoned acid mine drainage (AMD) from the abandoned copper mine waste pile at Touro, Spain, has been studied by sequential extraction (SE) combined with several techniques with the intent of understanding the role of these processes play in the natural attenuation of hazardous element contaminants in the AMD. In addition, the fragile nature of nanominerals and ultrafine particle (UFP) assemblages from contaminated sediment systems from the abandoned copper mine required novel techniques and experimental approaches. The investigation of the geochemistry of complex nanominerals and UFP assemblages was a prerequisite to accurately assess the environmental and human health risks of contaminants and cost-effective chemical and biogeological remediation strategies. Particular emphasis was placed on the study and characterization of the complex mixed nanominerals and UFP containing potentially toxic elements. Nanometer-sized phases in sediments were characterized using energy-dispersive X-ray spectrometer (EDS), field-emission scanning electron microscope (FE-SEM), and high-resolution transmission electron microscopy (HR-TEM) images. The identification of the geochemical and mineralogical composition of AMD in Touro, as well as the different formation mechanisms proposed, complement the existing literature on secondary mineral assemblages and provide new emphasis to increase the understanding of extreme environments. The results also demonstrated that variations in the geochemical fractionation of hazardous elements in AMD were more influenced by the secondary mineral proportion and by AMD pH.

  10. [Effect of acute hypoxia on the intensity of free radical processes in the basal nuclei of the brain, and the rat behaviour in the open field test under conditions of altered photoperiod].

    Science.gov (United States)

    Sopova, I Iu; Zamorskiĭ, I I

    2011-03-01

    The effect of acute hypoxia on the intensity of free radical processes in the basal nuclei (the nucleus caudatus, globus pallidus. nucleus accumbens. amygdaloid complex) of the brain, and the rat behaviour in the open field test has been studied under conditions of altered photoperiod. It has been shown that constant darkness levels the effect of acute hypoxia on the intensity of lipid peroxidation, preserves the activity of superoxide dismutase and catalase at a higher level, lowers the activity of glutathione peroxidase. Under light, the sensitivity of basal nuclei neurons to acute hypoxia is enhanced, the latter being reflected in intensification of lipid peroxidation at the expense of increased formation of dien conjugates. The activity of catalase at that considerably exceeds the level of even intact rats in all the structures. It has been established that an altered photoperiod modulates the effect of acute hypoxia on the parameters of rat's activity in the open field, the character of their change depending on the nature of a photophase change.

  11. Untangling Magmatic Processes and Hydrothermal Alteration of in situ Superfast Spreading Ocean Crust at ODP/IODP Site 1256 with Fuzzy c-means Cluster Analysis of Rock Magnetic Properties

    Science.gov (United States)

    Dekkers, M. J.; Heslop, D.; Herrero-Bervera, E.; Acton, G.; Krasa, D.

    2014-12-01

    Ocean Drilling Program (ODP)/Integrated ODP (IODP) Hole 1256D (6.44.1' N, 91.56.1' W) on the Cocos Plate occurs in 15.2 Ma oceanic crust generated by superfast seafloor spreading. Presently, it is the only drill hole that has sampled all three oceanic crust layers in a tectonically undisturbed setting. Here we interpret down-hole trends in several rock-magnetic parameters with fuzzy c-means cluster analysis, a multivariate statistical technique. The parameters include the magnetization ratio, the coercivity ratio, the coercive force, the low-field susceptibility, and the Curie temperature. By their combined, multivariate, analysis the effects of magmatic and hydrothermal processes can be evaluated. The optimal number of clusters - a key point in the analysis because there is no a priori information on this - was determined through a combination of approaches: by calculation of several cluster validity indices, by testing for coherent cluster distributions on non-linear-map plots, and importantly by testing for stability of the cluster solution from all possible starting points. Here, we consider a solution robust if the cluster allocation is independent of the starting configuration. The five-cluster solution appeared to be robust. Three clusters are distinguished in the extrusive segment of the Hole that express increasing hydrothermal alteration of the lavas. The sheeted dike and gabbro portions are characterized by two clusters, both with higher coercivities than in lava samples. Extensive alteration, however, can obliterate magnetic property differences between lavas, dikes, and gabbros. The imprint of thermochemical alteration on the iron-titanium oxides is only partially related to the porosity of the rocks. All clusters display rock magnetic characteristics in line with a stable NRM. This implies that the entire sampled sequence of ocean crust can contribute to marine magnetic anomalies. Determination of the absolute paleointensity with thermal techniques is

  12. Toxicokinetics and toxicodynamics of chlorpyrifos is altered in embryos of Japanese medaka exposed to oil sands process-affected water: evidence for inhibition of P-glycoprotein.

    Science.gov (United States)

    Alharbi, Hattan A; Alcorn, Jane; Al-Mousa, Ahmed; Giesy, John P; Wiseman, Steve B

    2016-10-24

    Oil sands process-affected water (OSPW) is generated during extraction of bitumen in the surface mining oil sands industry in Alberta, Canada. Studies were performed in vitro by use of Caco-2 cells, and in vivo with larvae of Japanese medaka (Oryzias latipes) to determine if organic compounds from the aqueous phase of OSPW inhibit ATP binding cassette protein ABCB1 (permeability-glycoprotein, P-gp). Neutral and basic fractions of OSPW inhibited activity of P-gp in Caco-2 cells by 1.9- and 2.0-fold, respectively, while the acidic fraction had the least effect. The organophosphate pesticides chlorpyrifos (a substrate of P-gp) and malathion (not a substrate of P-gp), were used as model chemicals to investigate inhibition of P-gp in larvae. Co-exposure to chlorpyrifos and an extract of OSPW containing basic and neutral compounds reduced survival of larvae to 26.5% compared to survival of larvae exposed only to chlorpyrifos, which was 93.7%. However, co-exposure to malathion and the extract of OSPW did not cause acute lethality compared to exposure only to malathion. Accumulation and bioconcentration of chlorpyrifos, but not malathion, was greater in larvae co-exposed with the extract of OSPW. The terminal elimination half-life of chlorpyrifos in larvae exposed to chlorpyrifos in freshwater was 5 days compared with 11.3 days in larvae exposed to chlorpyrifos in OSPW. Results suggest that in non-acute exposures, basic and neutral organic compounds in the water-soluble fraction of OSPW inhibit activity of P-gp, which suggests that OSPW has the potential to cause adverse effects by chemosensitization. Copyright © 2016 John Wiley & Sons, Ltd.

  13. EEG Theta Dynamics within Frontal and Parietal Cortices for Error Processing during Reaching Movements in a Prism Adaptation Study Altering Visuo-Motor Predictive Planning.

    Science.gov (United States)

    Arrighi, Pieranna; Bonfiglio, Luca; Minichilli, Fabrizio; Cantore, Nicoletta; Carboncini, Maria Chiara; Piccotti, Emily; Rossi, Bruno; Andre, Paolo

    2016-01-01

    Modulation of frontal midline theta (fmθ) is observed during error commission, but little is known about the role of theta oscillations in correcting motor behaviours. We investigate EEG activity of healthy partipants executing a reaching task under variable degrees of prism-induced visuo-motor distortion and visual occlusion of the initial arm trajectory. This task introduces directional errors of different magnitudes. The discrepancy between predicted and actual movement directions (i.e. the error), at the time when visual feedback (hand appearance) became available, elicits a signal that triggers on-line movement correction. Analysis were performed on 25 EEG channels. For each participant, the median value of the angular error of all reaching trials was used to partition the EEG epochs into high- and low-error conditions. We computed event-related spectral perturbations (ERSP) time-locked either to visual feedback or to the onset of movement correction. ERSP time-locked to the onset of visual feedback showed that fmθ increased in the high- but not in the low-error condition with an approximate time lag of 200 ms. Moreover, when single epochs were sorted by the degree of motor error, fmθ started to increase when a certain level of error was exceeded and, then, scaled with error magnitude. When ERSP were time-locked to the onset of movement correction, the fmθ increase anticipated this event with an approximate time lead of 50 ms. During successive trials, an error reduction was observed which was associated with indices of adaptations (i.e., aftereffects) suggesting the need to explore if theta oscillations may facilitate learning. To our knowledge this is the first study where the EEG signal recorded during reaching movements was time-locked to the onset of the error visual feedback. This allowed us to conclude that theta oscillations putatively generated by anterior cingulate cortex activation are implicated in error processing in semi-naturalistic motor

  14. 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.

  15. EEG Theta Dynamics within Frontal and Parietal Cortices for Error Processing during Reaching Movements in a Prism Adaptation Study Altering Visuo-Motor Predictive Planning.

    Directory of Open Access Journals (Sweden)

    Pieranna Arrighi

    Full Text Available Modulation of frontal midline theta (fmθ is observed during error commission, but little is known about the role of theta oscillations in correcting motor behaviours. We investigate EEG activity of healthy partipants executing a reaching task under variable degrees of prism-induced visuo-motor distortion and visual occlusion of the initial arm trajectory. This task introduces directional errors of different magnitudes. The discrepancy between predicted and actual movement directions (i.e. the error, at the time when visual feedback (hand appearance became available, elicits a signal that triggers on-line movement correction. Analysis were performed on 25 EEG channels. For each participant, the median value of the angular error of all reaching trials was used to partition the EEG epochs into high- and low-error conditions. We computed event-related spectral perturbations (ERSP time-locked either to visual feedback or to the onset of movement correction. ERSP time-locked to the onset of visual feedback showed that fmθ increased in the high- but not in the low-error condition with an approximate time lag of 200 ms. Moreover, when single epochs were sorted by the degree of motor error, fmθ started to increase when a certain level of error was exceeded and, then, scaled with error magnitude. When ERSP were time-locked to the onset of movement correction, the fmθ increase anticipated this event with an approximate time lead of 50 ms. During successive trials, an error reduction was observed which was associated with indices of adaptations (i.e., aftereffects suggesting the need to explore if theta oscillations may facilitate learning. To our knowledge this is the first study where the EEG signal recorded during reaching movements was time-locked to the onset of the error visual feedback. This allowed us to conclude that theta oscillations putatively generated by anterior cingulate cortex activation are implicated in error processing in semi

  16. Biophysical responses upon the interaction of nanomaterials with cellular interfaces.

    Science.gov (United States)

    Wu, Yun-Long; Putcha, Nirupama; Ng, Kee Woei; Leong, David Tai; Lim, Chwee Teck; Loo, Say Chye Joachim; Chen, Xiaodong

    2013-03-19

    The explosion of study of nanomaterials in biological applications (the nano-bio interface) can be ascribed to nanomaterials' growing importance in diagnostics, therapeutics, theranostics (therapeutic diagnostics), and targeted modulation of cellular processes. However, a growing number of critics have raised concerns over the potential risks of nanomaterials to human health and safety. It is essential to understand nanomaterials' potential toxicity before they are tested in humans. These risks are complicated to unravel, however, because of the complexity of cells and their nanoscale macromolecular components, which enable cells to sense and respond to environmental cues, including nanomaterials. In this Account, we explore these risks from the perspective of the biophysical interactions between nanomaterials and cells. Biophysical responses to the uptake of nanomaterials can include conformational changes in biomolecules like DNA and proteins, and changes to the cellular membrane and the cytoskeleton. Changes to the latter two, in particular, can induce changes in cell elasticity, morphology, motility, adhesion, and invasion. This Account reviews what is known about cells' biophysical responses to the uptake of the most widely studied and used nanoparticles, such as carbon-based, metal, metal-oxide, and semiconductor nanomaterials. We postulate that the biophysical structure impairment induced by nanomaterials is one of the key causes of nanotoxicity. The disruption of cellular structures is affected by the size, shape, and chemical composition of nanomaterials, which are also determining factors of nanotoxicity. Currently, popular nanotoxicity characterizations, such as the MTT and lactate dehydrogenase (LDH) assays, only provide end-point results through chemical reactions. Focusing on biophysical structural changes induced by nanomaterials, possibly in real-time, could deepen our understanding of the normal and altered states of subcellular structures and

  17. Computer simulation of cellular patterning within the Drosophila pupal eye.

    Directory of Open Access Journals (Sweden)

    David E Larson

    Full Text Available We present a computer simulation and associated experimental validation of assembly of glial-like support cells into the interweaving hexagonal lattice that spans the Drosophila pupal eye. This process of cell movements organizes the ommatidial array into a functional pattern. Unlike earlier simulations that focused on the arrangements of cells within individual ommatidia, here we examine the local movements that lead to large-scale organization of the emerging eye field. Simulations based on our experimental observations of cell adhesion, cell death, and cell movement successfully patterned a tracing of an emerging wild-type pupal eye. Surprisingly, altering cell adhesion had only a mild effect on patterning, contradicting our previous hypothesis that the patterning was primarily the result of preferential adhesion between IRM-class surface proteins. Instead, our simulations highlighted the importance of programmed cell death (PCD as well as a previously unappreciated variable: the expansion of cells' apical surface areas, which promoted rearrangement of neighboring cells. We tested this prediction experimentally by preventing expansion in the apical area of individual cells: patterning was disrupted in a manner predicted by our simulations. Our work demonstrates the value of combining computer simulation with in vivo experiments to uncover novel mechanisms that are perpetuated throughout the eye field. It also demonstrates the utility of the Glazier-Graner-Hogeweg model (GGH for modeling the links between local cellular interactions and emergent properties of developing epithelia as well as predicting unanticipated results in vivo.

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

    Directory of Open Access Journals (Sweden)

    Savino W.

    2003-01-01

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

  19. Proteomic analysis of cellular response induced by multi-walled carbon nanotubes exposure in A549 cells.

    Directory of Open Access Journals (Sweden)

    Li Ju

    Full Text Available The wide application of multi-walled carbon nanotubes (MWCNT has raised serious concerns about their safety on human health and the environment. However, the potential harmful effects of MWCNT remain unclear and contradictory. To clarify the potentially toxic effects of MWCNT and to elucidate the associated underlying mechanisms, the effects of MWCNT on human lung adenocarcinoma A549 cells were examined at both the cellular and the protein level. Cytotoxicity and genotoxicity were examined, followed by a proteomic analysis (2-DE coupled with LC-MS/MS of the cellular response to MWCNT. Our results demonstrate that MWCNT induces cytotoxicity in A549 cells only at relatively high concentrations and longer exposure time. Within a relatively low dosage range (30 µg/ml and short time period (24 h, MWCNT treatment does not induce significant cytotoxicity, cell cycle changes, apoptosis, or DNA damage. However, at these low doses and times, MWCNT treatment causes significant changes in protein expression. A total of 106 proteins show altered expression at various time points and dosages, and of these, 52 proteins were further identified by MS. Identified proteins are involved in several cellular processes including proliferation, stress, and cellular skeleton organization. In particular, MWCNT treatment causes increases in actin expression. This increase has the potential to contribute to increased migration capacity and may be mediated by reactive oxygen species (ROS.

  20. Radiation induces acute alterations in neuronal function.

    Directory of Open Access Journals (Sweden)

    Peter H Wu

    Full Text Available Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation damage. In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. Moreover, because radiation-induced brain dysfunction is believed to evolve over months to years, most studies have focused on late changes in brain parenchyma. However, clinically, acute changes in cognition are also observed. Because neurons are fully differentiated post-mitotic cells, little information exists on the acute effects of radiation on synaptic function. The purpose of our study was to assess the potential acute effects of radiation on neuronal function utilizing ex vivo hippocampal brain slices. The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. Electrophysiological recordings were obtained both for populations of neuronal cells and individual neurons. In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABA(ARs. These alterations in cellular localization corresponded with altered synaptic responses and inhibition of long-term potentiation. The non-competitive NMDAR antagonist memantine blocked these radiation-induced alterations in cellular distribution. These findings demonstrate acute effects of radiation on neuronal cells within isolated brain slices and open new avenues for study.

  1. 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.

  2. On Cellular Darwinism: Mitochondria.

    Science.gov (United States)

    Bull, Larry

    2016-01-01

    The significant role of mitochondria within cells is becoming increasingly clear. This letter uses the NKCS model of coupled fitness landscapes to explore aspects of organelle-nucleus coevolution. The phenomenon of mitochondrial diversity is allowed to emerge under a simple intracellular evolutionary process, including varying the relative rate of evolution by the organelle. It is shown how the conditions for the maintenance of more than one genetic variant of mitochondria are similar to those previously suggested as needed for the original symbiotic origins of the relationship using the NKCS model.

  3. Quantitative proteomics reveals cellular targets of celastrol.

    Directory of Open Access Journals (Sweden)

    Jakob Hansen

    Full Text Available Celastrol, a natural substance isolated from plant extracts used in traditional Chinese medicine, has been extensively investigated as a possible drug for treatment of cancer, autoimmune diseases, and protein misfolding disorders. Although studies focusing on celastrol's effects in specific cellular pathways have revealed a considerable number of targets in a diverse array of in vitro models there is an essential need for investigations that can provide a global view of its effects. To assess cellular effects of celastrol and to identify target proteins as biomarkers for monitoring treatment regimes, we performed large-scale quantitative proteomics in cultured human lymphoblastoid cells, a cell type that can be readily prepared from human blood samples. Celastrol substantially modified the proteome composition and 158 of the close to 1800 proteins with robust quantitation showed at least a 1.5 fold change in protein levels. Up-regulated proteins play key roles in cytoprotection with a prominent group involved in quality control and processing of proteins traversing the endoplasmic reticulum. Increased levels of proteins essential for the cellular protection against oxidative stress including heme oxygenase 1, several peroxiredoxins and thioredoxins as well as proteins involved in the control of iron homeostasis were also observed. Specific analysis of the mitochondrial proteome strongly indicated that the mitochondrial association of certain antioxidant defense and apoptosis-regulating proteins increased in cells exposed to celastrol. Analysis of selected mRNA transcripts showed that celastrol activated several different stress response pathways and dose response studies furthermore showed that continuous exposure to sub-micromolar concentrations of celastrol is associated with reduced cellular viability and proliferation. The extensive catalog of regulated proteins presented here identifies numerous cellular effects of celastrol and constitutes

  4. Rhabdomyosarcoma: Advances in Molecular and Cellular Biology

    Directory of Open Access Journals (Sweden)

    Xin Sun

    2015-01-01

    Full Text Available Rhabdomyosarcoma (RMS is the most common soft tissue malignancy in childhood and adolescence. The two major histological subtypes of RMS are alveolar RMS, driven by the fusion protein PAX3-FKHR or PAX7-FKHR, and embryonic RMS, which is usually genetically heterogeneous. The prognosis of RMS has improved in the past several decades due to multidisciplinary care. However, in recent years, the treatment of patients with metastatic or refractory RMS has reached a plateau. Thus, to improve the survival rate of RMS patients and their overall well-being, further understanding of the molecular and cellular biology of RMS and identification of novel therapeutic targets are imperative. In this review, we describe the most recent discoveries in the molecular and cellular biology of RMS, including alterations in oncogenic pathways, miRNA (miR, in vivo models, stem cells, and important signal transduction cascades implicated in the development and progression of RMS. Furthermore, we discuss novel potential targeted therapies that may improve the current treatment of RMS.

  5. 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)

  6. Pyrogenic organic matter can alter microbial communication

    Science.gov (United States)

    Masiello, Caroline; Gao, Xiaodong; Cheng, Hsiao-Ying; Silberg, Jonathan

    2016-04-01

    Soil microbes communicate with each other to manage a large range of processes that occur more efficiently when microbes are able to act simultaneously. This coordination occurs through the continuous production of signaling compounds that are easily diffused into and out of cells. As the number of microbes in a localized environment increases, the internal cellular concentration of these signaling compounds increases, and when a threshold concentration is reached, gene expression shifts, leading to altered (and coordinated) microbial behaviors. Many of these coordinated behaviors have biogeochemically important outcomes. For example, methanogenesis, denitrification, biofilm formation, and the development of plant-rhizobial symbioses are all regulated by a simple class of cell-cell signaling molecules known as acyl homoserine lactones (AHLs). Pyrogenic organic matter in soils can act to disrupt microbial communication through multiple pathways. In the case of AHLs, charcoal's very high surface area can sorb these signaling compounds, preventing microbes from detecting each others' presence (Masiello et al., 2014). In addition, the lactone ring in AHLs is vulnerable to pH increases accompanying PyOM inputs, with soil pH values higher than 7-8 leading to ring opening and compound destabilization. Different microbes use different classes of signaling compounds, and not all microbial signaling compounds are pH-vulnerable. This implies that PyOM-driven pH increases may trigger differential outcomes for Gram negative bacteria vs fungi, for example. A charcoal-driven reduction in microbes' ability to detect cell-cell communication compounds may lead to a shift in the ability of microbes to participate in key steps of C and N cycling. For example, an increase in an archaeon-specific AHL has been shown to lead to a cascade of metabolic processes that eventually results in the upregulation of CH4 production (Zhang et al., 2012). Alterations in similar AHL compounds leads to

  7. Genetic alterations in Krebs cycle and its impact on cancer pathogenesis.

    Science.gov (United States)

    Sajnani, Karishma; Islam, Farhadul; Smith, Robert Anthony; Gopalan, Vinod; Lam, Alfred King-Yin

    2017-04-01

    Cancer cells exhibit alterations in many cellular processes, including oxygen sensing and energy metabolism. Glycolysis in non-oxygen condition is the main energy production process in cancer rather than mitochondrial respiration as in benign cells. Genetic and epigenetic alterations of Krebs cycle enzymes favour the shift of cancer cells from oxidative phosphorylation to anaerobic glycolysis. Mutations in genes encoding aconitase, isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydratase, and citrate synthase are noted in many cancers. Abnormalities of Krebs cycle enzymes cause ectopic production of Krebs cycle intermediates (oncometabolites) such as 2-hydroxyglutarate, and citrate. These oncometabolites stabilize hypoxia inducible factor 1 (HIF1), nuclear factor like 2 (Nrf2), inhibit p53 and prolyl hydroxylase 3 (PDH3) activities as well as regulate DNA/histone methylation, which in turn activate cell growth signalling. They also stimulate increased glutaminolysis, glycolysis and production of reactive oxygen species (ROS). Additionally, genetic alterations in Krebs cycle enzymes are involved with increased fatty acid β-oxidations and epithelial mesenchymal transition (EMT) induction. These altered phenomena in cancer could in turn promote carcinogenesis by stimulating cell proliferation and survival. Overall, epigenetic and genetic changes of Krebs cycle enzymes lead to the production of oncometabolite intermediates, which are important driving forces of cancer pathogenesis and progression. Understanding and applying the knowledge of these mechanisms opens new therapeutic options for patients with cancer.

  8. 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.

  9. Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis.

    Science.gov (United States)

    Jafari, Abbas; Qanie, Diyako; Andersen, Thomas L; Zhang, Yuxi; Chen, Li; Postert, Benno; Parsons, Stuart; Ditzel, Nicholas; Khosla, Sundeep; Johansen, Harald Thidemann; Kjærsgaard-Andersen, Per; Delaisse, Jean-Marie; Abdallah, Basem M; Hesselson, Daniel; Solberg, Rigmor; Kassem, Moustapha

    2017-02-14

    Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.

  10. 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.

  11. A Real Space Cellular Automaton Laboratory

    Science.gov (United States)

    Rozier, O.; Narteau, C.

    2013-12-01

    Investigations in geomorphology may benefit from computer modelling approaches that rely entirely on self-organization principles. In the vast majority of numerical models, instead, points in space are characterised by a variety of physical variables (e.g. sediment transport rate, velocity, temperature) recalculated over time according to some predetermined set of laws. However, there is not always a satisfactory theoretical framework from which we can quantify the overall dynamics of the system. For these reasons, we prefer to concentrate on interaction patterns using a basic cellular automaton modelling framework, the Real Space Cellular Automaton Laboratory (ReSCAL), a powerful and versatile generator of 3D stochastic models. The objective of this software suite released under a GNU license is to develop interdisciplinary research collaboration to investigate the dynamics of complex systems. The models in ReSCAL are essentially constructed from a small number of discrete states distributed on a cellular grid. An elementary cell is a real-space representation of the physical environment and pairs of nearest neighbour cells are called doublets. Each individual physical process is associated with a set of doublet transitions and characteristic transition rates. Using a modular approach, we can simulate and combine a wide range of physical, chemical and/or anthropological processes. Here, we present different ingredients of ReSCAL leading to applications in geomorphology: dune morphodynamics and landscape evolution. We also discuss how ReSCAL can be applied and developed across many disciplines in natural and human sciences.

  12. 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...

  13. 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.

  14. 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, and arachidonate metabolism. Scientific report

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-01-01

    Changes in total number, differentials, cell protein, adherence properties, acetyltransferase and acetylhydrolase activities, prostaglandin E2 and leukotriene C4 production, as well as calcium (2+) ionophore A23187 stimulation were examined in resident peritoneal cells isolated from mice 2h 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-vitro irradiation also elevated the activities of acetyltransferase and acetylhydrolase (catalyzing 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 acetylhydrolase activity. Prostaglandin E2 and leukotriene C4 synthesis were elevated postexposure, suggesting increased substrate (arachidonate) availability and increased cyclooxygenase and lipoxygenase activities. Ionospheric stimulation of enzyme activities and eicosanoid release also differed in irradiated peritoneal cells. While the properties of adherence, platelet-activating factor synthesis/inactivation-associated enzyme activities, and eicosanoid production are generally characterized as those of macrophages, lymphocytes or their products may influence or contribute to the observed radiation-induced changes.

  15. 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.

  16. Prodrug Approach for Increasing Cellular Glutathione Levels

    Directory of Open Access Journals (Sweden)

    Ivana Cacciatore

    2010-03-01

    Full Text Available Reduced glutathione (GSH is the most abundant non-protein thiol in mammalian cells and the preferred substrate for several enzymes in xenobiotic metabolism and antioxidant defense. It plays an important role in many cellular processes, such as cell differentiation, proliferation and apoptosis. GSH deficiency has been observed in aging and in a wide range of pathologies, including neurodegenerative disorders and cystic fibrosis (CF, as well as in several viral infections. Use of GSH as a therapeutic agent is limited because of its unfavorable biochemical and pharmacokinetic properties. Several reports have provided evidence for the use of GSH prodrugs able to replenish intracellular GSH levels. This review discusses different strategies for increasing GSH levels by supplying reversible bioconjugates able to cross the cellular membrane more easily than GSH and to provide a source of thiols for GSH synthesis.

  17. 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.

  18. Cellular Dynamics Revealed by Digital Holographic Microscopy☆

    KAUST Repository

    Marquet, P.

    2016-11-22

    Digital holographic microscopy (DHM) is a new optical method that provides, without the use of any contrast agent, real-time, three-dimensional images of transparent living cells, with an axial sensitivity of a few tens of nanometers. They result from the hologram numerical reconstruction process, which permits a sub wavelength calculation of the phase shift, produced on the transmitted wave front, by the optically probed cells, namely the quantitative phase signal (QPS). Specifically, in addition to measurements of cellular surface morphometry and intracellular refractive index (RI), various biophysical cellular parameters including dry mass, absolute volume, membrane fluctuations at the nanoscale and biomechanical properties, transmembrane water permeability as swell as current, can be derived from the QPS. This article presents how quantitative phase DHM (QP-DHM) can explored cell dynamics at the nanoscale with a special attention to both the study of neuronal dynamics and the optical resolution of local neuronal network.

  19. Strategies To Modulate Heritable Epigenetic Defects in Cellular Machinery: Lessons from Nature

    Directory of Open Access Journals (Sweden)

    Ganesh N. Pandian

    2012-12-01

    Full Text Available Natural epigenetic processes precisely orchestrate the intricate gene network by expressing and suppressing genes at the right place and time, thereby playing an essential role in maintaining the cellular homeostasis. Environment-mediated alteration of this natural epigenomic pattern causes abnormal cell behavior and shifts the cell from the normal to a diseased state, leading to certain cancers and neurodegenerative disorders. Unlike heritable diseases that are caused by the irreversible mutations in DNA, epigenetic errors can be reversed. Inheritance of epigenetic memory is also a major concern in the clinical translation of the Nobel Prize-winning discovery of induced pluripotent stem cell technology. Consequently, there is an increasing interest in the development of novel epigenetic switch-based therapeutic strategies that could potentially restore the heritable changes in epigenetically inherited disorders. Here we give a comprehensive overview of epigenetic inheritance and suggest the prospects of therapeutic gene modulation using epigenetic-based drugs, in particular histone deacetylase inhibitors. This review suggests that there is a need to develop therapeutic strategies that effectively mimic the natural environment and include the ways to modulate the gene expression at both the genetic and epigenetic levels. The development of tailor-made small molecules that could epigenetically alter DNA in a sequence-specific manner is a promising approach for restoring defects in an altered epigenome and may offer a sustainable solution to some unresolved clinical issues.

  20. Strategies to modulate heritable epigenetic defects in cellular machinery: lessons from nature.

    Science.gov (United States)

    Pandian, Ganesh N; Sugiyama, Hiroshi

    2012-12-27

    Natural epigenetic processes precisely orchestrate the intricate gene network by expressing and suppressing genes at the right place and time, thereby playing an essential role in maintaining the cellular homeostasis. Environment-mediated alteration of this natural epigenomic pattern causes abnormal cell behavior and shifts the cell from the normal to a diseased state, leading to certain cancers and neurodegenerative disorders. Unlike heritable diseases that are caused by the irreversible mutations in DNA, epigenetic errors can be reversed. Inheritance of epigenetic memory is also a major concern in the clinical translation of the Nobel Prize-winning discovery of induced pluripotent stem cell technology. Consequently, there is an increasing interest in the development of novel epigenetic switch-based therapeutic strategies that could potentially restore the heritable changes in epigenetically inherited disorders. Here we give a comprehensive overview of epigenetic inheritance and suggest the prospects of therapeutic gene modulation using epigenetic-based drugs, in particular histone deacetylase inhibitors. This review suggests that there is a need to develop therapeutic strategies that effectively mimic the natural environment and include the ways to modulate the gene expression at both the genetic and epigenetic levels. The development of tailor-made small molecules that could epigenetically alter DNA in a sequence-specific manner is a promising approach for restoring defects in an altered epigenome and may offer a sustainable solution to some unresolved clinical issues.

  1. The effect of ion implantation on cellular adhesion.

    Science.gov (United States)

    Howlett, C R; Evans, M D; Wildish, K L; Kelly, J C; Fisher, L R; Francis, G W; Best, D J

    1993-01-01

    As there are only a finite number of materials suitable for orthopaedic reconstruction, considerable effort has been devoted recently to investigating ways of altering the surface chemistry of prosthetic materials without altering their bulk properties. Ion beam implantation is one such technique which is appropriate for orthopaedic reconstructive materials. This paper investigates the early effect of ion beam modification on cellular attachment of bone derived cells using a prototype device which measures the strength of attachment of individual cells to a silicon substratum. The results point to several conclusions. (1) There is no evidence that ion beam implantation with nitrogen, phosphorus, manganese or magnesium produces increased adhesion of human bone derived cells. (2) Surface etching with hydrofluoric acid, electron bombardment and thermal oxidation increases the strength of attachment between cells and substrata. (3) There is a correlation between wettability and rate of cellular attachment to oxygen implanted substrata during the first 2 h after cellular seeding. However, the increase in cellular attachment cannot be entirely explained by the change in critical surface tension or via increased fibronectin attachment to the substrata.

  2. Intrinsic and extrinsic negative regulators of nuclear protein transport processes

    OpenAIRE

    Sekimoto, Toshihiro; Yoneda, Yoshihiro

    2012-01-01

    The nuclear–cytoplasmic protein transport is a critical process in cellular events. The identification of transport signals (nuclear localization signal and nuclear export signal) and their receptors has facilitated our understanding of this expanding field. Nuclear transport must be appropriately regulated to deliver proteins through the nuclear pore when their functions are required in the nucleus, and to export them into the cytoplasm when they are not needed in the nucleus. Altered nuclea...

  3. Huntingtin processing in pathogenesis of Huntington disease

    Institute of Scientific and Technical Information of China (English)

    Zhenghong QIN; Zhenlun GU

    2004-01-01

    Huntington's disease (HD) is caused by an expansion of the polyglutamine tract in the protein named huntingtin.The expansion of polyglutamine tract induces selective degeneration of striatal projection neurons and cortical pyramidal neurons. The bio-hallmark of HD is the formation of intranuclear inclusions and cytoplasmic aggregates in association with other cellular proteins in vulnerable neurons. Accumulation of N-terminal mutant huntingtin in HD brains is prominent. These pathological features are related to protein misfolding and impairments in protein processing and degradation in neurons. This review focused on the role of proteases in huntingtin cleavage and degradation and the contribution of altered processing of mutant huntingtin to HD pathogenesis.

  4. 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.

  5. 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

  6. Effect of lysosomotropic molecules on cellular homeostasis.

    Science.gov (United States)

    Kuzu, Omer F; Toprak, Mesut; Noory, M Anwar; Robertson, Gavin P

    2017-03-01

    Weak bases that readily penetrate through the lipid bilayer and accumulate inside the acidic organelles are known as lysosomotropic molecules. Many lysosomotropic compounds exhibit therapeutic activity and are commonly used as antidepressant, antipsychotic, antihistamine, or antimalarial agents. Interestingly, studies also have shown increased sensitivity of cancer cells to certain lysosomotropic agents and suggested their mechanism of action as a promising approach for selective destruction of cancer cells. However, their chemotherapeutic utility may be limited due to various side effects. Hence, understanding the homeostatic alterations mediated by lysosomotropic compounds has significant importance for revealing their true therapeutic potential as well as toxicity. In this review, after briefly introducing the concept of lysosomotropism and classifying the lysosomotropic compounds into two major groups according to their cytotoxicity on cancer cells, we focused on the subcellular alterations mediated by class-II lysosomotropic compounds. Briefly, their effect on intracellular cholesterol homeostasis, autophagy and lysosomal sphingolipid metabolism was discussed. Accordingly, class-II lysosomotropic molecules inhibit intracellular cholesterol transport, leading to the accumulation of cholesterol inside the late endosomal-lysosomal cell compartments. However, the accumulated lysosomal cholesterol is invisible to the cellular homeostatic circuits, hence class-II lysosomotropic molecules also upregulate cholesterol synthesis pathway as a downstream event. Considering the fact that Niemann-Pick disease, a lysosomal cholesterol storage disorder, also triggers similar pathologic abnormalities, this review combines the knowledge obtained from the Niemann-Pick studies and lysosomotropic compounds. Taken together, this review is aimed at allowing readers a better understanding of subcellular alterations mediated by lysosomotropic drugs, as well as their potential

  7. Comparative analysis of Salmonella susceptibility and tolerance to the biocide chlorhexidine identifies a complex cellular defence network

    Directory of Open Access Journals (Sweden)

    Orla eCondell

    2014-08-01

    Full Text Available Chlorhexidine is one of the most widely used biocides in health and agricultural settings as well as in the modern food industry. It is a cationic biocide of the biguanide class. Details of its mechanism of action are largely unknown. The frequent use of chlorhexidine has been questioned recently, amidst concerns that an overuse of this compound may select for bacteria displaying an altered susceptibility to antimicrobials, including clinically important anti-bacterial agents.We generated a Salmonella enterica serovar Typhimurium isolate (ST24CHX that exhibited a high-level tolerant phenotype to chlorhexidine, following several rounds of in vitro selection, using sub-lethal concentrations of the biocide. This mutant showed altered suceptibility to a panel of clinically important antimicrobial compounds. Here we describe a genomic, transcriptomic, proteomic, and phenotypic analysis of the chlorhexidine tolerant S. Typhimurium compared with its isogenic sensitive progenitor. Results from this study describe a chlorhexidine defence network that functions in both the reference chlorhexidine sensitive isolate and the tolerant mutant. The defence network involved multiple cell targets including those associated with the synthesis and modification of the cell wall, the SOS response, virulence, and a shift in cellular metabolism towards anoxic pathways, some of which were regulated by CreB and Fur. In addition, results indicated that chlorhexidine tolerance was associated with more extensi