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Sample records for 4g cellular systems

  1. Radio Resource Allocation on Complex 4G Wireless Cellular Networks

    NASA Astrophysics Data System (ADS)

    Psannis, Kostas E.

    2015-09-01

    In this article we consider the heuristic algorithm which improves step by step wireless data delivery over LTE cellular networks by using the total transmit power with the constraint on users’ data rates, and the total throughput with the constraints on the total transmit power as well as users’ data rates, which are jointly integrated into a hybrid-layer design framework to perform radio resource allocation for multiple users, and to effectively decide the optimal system parameter such as modulation and coding scheme (MCS) in order to adapt to the varying channel quality. We propose new heuristic algorithm which balances the accessible data rate, the initial data rates of each user allocated by LTE scheduler, the priority indicator which signals delay- throughput- packet loss awareness of the user, and the buffer fullness by achieving maximization of radio resource allocation for multiple users. It is noted that the overall performance is improved with the increase in the number of users, due to multiuser diversity. Experimental results illustrate and validate the accuracy of the proposed methodology.

  2. Non-telephone healthcare: the role of 4G and emerging mobile systems for future m-health systems.

    PubMed

    Istepanian, R; Philip, N; Wang, X H; Laxminarayan, S

    2004-01-01

    The next generation of "m-health technologies" is a new and evolving topic in the areas of telemedical and telecare systems. These technologies involve the exploitation of mobile telecommunication and multimedia technologies to provide better access to healthcare personnel on the move, by removing the key disadvantage of trailing wires in current systems. These technologies provide equal access to medical information and expert care by overcoming the boundaries of separation that exist today between different users of such medical information. A great benefit to all users will be a more efficient use of resources and far greater location independence. In this paper we will address some notes and future trends in these emerging areas and their applications for m-health systems. Especially we will discuss the role of 4G and emerging mobile systems for future m-health systems. The new technologies can make the remote medical monitoring, consulting, and health care more flexible and convenient. But, there are challenges for successful wireless telemedicine, which are addressed in this paper. PMID:15747957

  3. VizieR Online Data Catalog: S4G galaxy morphologies in the CVRHS system (Buta+, 2015)

    NASA Astrophysics Data System (ADS)

    Buta, R. J.; Sheth, K.; Athanassoula, E.; Bosma, A.; Knapen, J. H.; Laurikainen, E.; Salo, H.; Elmegreen, D.; Ho, L. C.; Zaritsky, D.; Courtois, H.; Hinz, J. L.; Munoz-Mateos, J.-C.; Kim, T.; Regan, M. W.; Gadotti, D. A.; Gil de, Paz A.; Laine, J.; Menendez-Delmestre, K.; Comeron, S.; Erroz-Ferrer, S.; Seibert, M.; Mizusawa, T.; Holwerda, B.; Madore, B. F.

    2015-05-01

    Our final list has 2412 galaxies, 60 more than the extended S4< sample. All of the additional galaxies are companions or in the same area as an S4G sample galaxy. Of the selected galaxies, ~600 had already been observed by Spitzer for other projects, and thus images were already available. New data were collected for the ~1750 remaining sample galaxies. The CVRHS system is a modified version of the de Vaucouleurs (1959HDP....53..275D) revised Hubble-Sandage (VRHS) system that is described in the de Vaucouleurs Atlas of Galaxies (dVA, Buta et al. 2007dvag.book.....B). (4 data files).

  4. Application of 4G wireless network-based system for remote diagnosis and nursing of stomal complications

    PubMed Central

    Xu, Xiulian; Cao, Yingjuan; Luan, Xiaorong

    2014-01-01

    Background: This study aims to apply 4G wireless network in the remote diagnosis of stoma complications for the first time. Background: Remote diagnosis and nursing care for a variety of illnesses are urgently needed in clinical settings. Objectives: Combining with relevant clinical manifestations, an Android phone-based intelligent diagnosis system was designed to construct a universe, easy access to exploitation and human-computer interaction database and exploitation environment for applications and programs. Methods: “Production rule” and forward reasoning method were utilized to design arborescence structures and logic reasoner associated with stoma complications. Stoma physicians were responsible for delivering evaluation scores on patients’ health status using analytic hierarchy process. The emphasis of this study is to exploit an “Android phone-based system for remote diagnosis of stoma”, which is of certain universe usage. Results: Such system was tested in the Medicine Information Center of Qilu Hospital of Shandong University and initially applied in the city of De Zhou, Shandong province, China. Conclusions: These results collectively demonstrated that the system is easy to carry, of high utility and free from the limitations of wire network environment, etc. It provides clinical evidence for establishing a novel type model for the exchange between patients and physicians. PMID:25550986

  5. Cellular-based preemption system

    NASA Technical Reports Server (NTRS)

    Bachelder, Aaron D. (Inventor)

    2011-01-01

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

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

    PubMed

    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.

  7. Integration of mobile satellite and cellular systems

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  8. Integration of mobile satellite and cellular systems

    NASA Astrophysics Data System (ADS)

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

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

  9. Cellular Manufacturing Internet Performance Support System

    SciTech Connect

    Bohley, M.C.; Schwartz, M.E.

    1998-03-04

    The objective of this project was to develop an Internet-based electronic performance support system (EPSS) for cellular manufacturing providing hardware/software specifications, process descriptions, estimated cost savings, manufacturing simulations, training information, and service resources for government and industry users of Cincinnati Milacron machine tools and products. AlliedSignal Federal Manufacturing and Technologies (ASFM and T) used expertise in the areas of Internet design and multimedia creation to develop a performance support system (PSS) for the Internet with assistance from CM's subject matter experts from engineering, manufacturing, and technical support. Reference information was both created and re-purposed from other existing formats, then made available on the Internet. On-line references on cellular manufacturing operations include: definitions of cells and cellular manufacturing; illustrations on how cellular manufacturing improves part throughput, resource utilization, part quality, and manufacturing flexibility; illustrations on how cellular manufacturing reduces labor and overhead costs; identification of critical factors driving decisions toward cellular manufacturing; a method for identifying process improvement areas using cellular manufacturing; a method for customizing the size of cells for a specific site; a simulation for making a part using cellular manufacturing technology; and a glossary of terms and concepts.

  10. Remote Energy Monitoring System via Cellular Network

    NASA Astrophysics Data System (ADS)

    Yunoki, Shoji; Tamaki, Satoshi; Takada, May; Iwaki, Takashi

    Recently, improvement on power saving and cost efficiency by monitoring the operation status of various facilities over the network has gained attention. Wireless network, especially cellular network, has advantage in mobility, coverage, and scalability. On the other hand, it has disadvantage of low reliability, due to rapid changes in the available bandwidth. We propose a transmission control scheme based on data priority and instantaneous available bandwidth to realize a highly reliable remote monitoring system via cellular network. We have developed our proposed monitoring system and evaluated the effectiveness of our scheme, and proved it reduces the maximum transmission delay of sensor status to 1/10 compared to best effort transmission.

  11. Dynamical Systems Perspective of Wolfram's Cellular Automata

    NASA Astrophysics Data System (ADS)

    Courbage, M.; Kamiński, B.

    2013-01-01

    Leon Chua, following Wolfram, devoted a big effort to understand deeply the wealth of complexity of the rules of all elementary one-dimensional cellular automata from the point of view of the nonlinear dynamicist. Here we complete this point of view by a dynamical system perspective, extending them to the limit of infinite number of sites.

  12. Cellular Automata Generalized To An Inferential System

    NASA Astrophysics Data System (ADS)

    Blower, David J.

    2007-11-01

    Stephen Wolfram popularized elementary one-dimensional cellular automata in his book, A New Kind of Science. Among many remarkable things, he proved that one of these cellular automata was a Universal Turing Machine. Such cellular automata can be interpreted in a different way by viewing them within the context of the formal manipulation rules from probability theory. Bayes's Theorem is the most famous of such formal rules. As a prelude, we recapitulate Jaynes's presentation of how probability theory generalizes classical logic using modus ponens as the canonical example. We emphasize the important conceptual standing of Boolean Algebra for the formal rules of probability manipulation and give an alternative demonstration augmenting and complementing Jaynes's derivation. We show the complementary roles played in arguments of this kind by Bayes's Theorem and joint probability tables. A good explanation for all of this is afforded by the expansion of any particular logic function via the disjunctive normal form (DNF). The DNF expansion is a useful heuristic emphasized in this exposition because such expansions point out where relevant 0s should be placed in the joint probability tables for logic functions involving any number of variables. It then becomes a straightforward exercise to rely on Boolean Algebra, Bayes's Theorem, and joint probability tables in extrapolating to Wolfram's cellular automata. Cellular automata are seen as purely deductive systems, just like classical logic, which probability theory is then able to generalize. Thus, any uncertainties which we might like to introduce into the discussion about cellular automata are handled with ease via the familiar inferential path. Most importantly, the difficult problem of predicting what cellular automata will do in the far future is treated like any inferential prediction problem.

  13. System and method for monitoring cellular activity

    NASA Technical Reports Server (NTRS)

    Bearman, Gregory H. (Inventor); Fraser, Scott E. (Inventor); Lansford, Russell D. (Inventor)

    2004-01-01

    A system and method for monitoring cellular activity in a cellular specimen. According to one embodiment, a plurality of excitable markers are applied to the specimen. A multi-photon laser microscope is provided to excite a region of the specimen and cause fluorescence to be radiated from the region. The radiating fluorescence is processed by a spectral analyzer to separate the fluorescence into respective wavelength bands. The respective bands of fluorescence are then collected by an array of detectors, with each detector receiving a corresponding one of the wavelength bands.

  14. System and method for monitoring cellular activity

    NASA Technical Reports Server (NTRS)

    Bearman, Gregory H. (Inventor); Fraser, Scott E. (Inventor); Lansford, Russell D. (Inventor)

    2002-01-01

    A system and method for monitoring cellular activity in a cellular specimen. According to one embodiment, a plurality of excitable markers are applied to the specimen. A multi-photon laser microscope is provided to excite a region of the specimen and cause fluorescence to be radiated from the region. The radiating fluorescence is processed by a spectral analyzer to separate the fluorescence into respective wavelength bands. The respective bands of fluorescence are then collected by an array of detectors, with each detector receiving a corresponding one of the wavelength bands.

  15. Literature Review on Dynamic Cellular Manufacturing System

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

  16. Mediator-free direct Z-scheme photocatalytic system: BiVO4/g-C3N4 organic-inorganic hybrid photocatalyst with highly efficient visible-light-induced photocatalytic activity.

    PubMed

    Tian, Na; Huang, Hongwei; He, Ying; Guo, Yuxi; Zhang, Tierui; Zhang, Yihe

    2015-03-01

    We disclose the fabrication of a mediator-free direct Z-scheme photocatalyst system BiVO4/g-C3N4 using a mixed-calcination method based on the more reliable interfacial interaction. The facet coupling occurred between the g-C3N4 (002) and BiVO4 (121), and it was revealed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and transmission electron microscope (TEM). The crystal structure and optical properties of the as-prepared samples have also been characterized by Fourier-transform infrared (FTIR), scanning electron microscopy (SEM) and UV-vis diffuse reflectance spectra (DRS) in details. The photocatalytic experiments indicated that the BiVO4/g-C3N4 composite photocatalysts display a significantly enhanced photocatalytic activity pertaining to RhB degradation and photocurrent generation (PC) compared to the pristine BiVO4 and g-C3N4. This remarkably improved photocatalytic performance should be attributed to the fabrication of a direct Z-scheme system of BiVO4/g-C3N4, which can result in a more efficient separation of photoinduced charge carriers than band-band transfer, thus endowing it with the much more powerful oxidation and reduction capability, as confirmed by the photoluminescence (PL) spectra and electrochemical impedance spectra (EIS). The Z-scheme mechanism of BiVO4/g-C3N4 heterostructure was verified by a series of combined techniques, including the active species trapping experiments, NBT transformation and terephthalic acid photoluminescence probing technique (TA-PL) over BiVO4/g-C3N4 composites and the pristine samples. The present work not only furthered the understanding of mediator-free Z-scheme photocatalysis, but also shed new light on the design of heterostructural photocatalysts with high-performance. PMID:25635354

  17. Mediator-free direct Z-scheme photocatalytic system: BiVO4/g-C3N4 organic-inorganic hybrid photocatalyst with highly efficient visible-light-induced photocatalytic activity.

    PubMed

    Tian, Na; Huang, Hongwei; He, Ying; Guo, Yuxi; Zhang, Tierui; Zhang, Yihe

    2015-03-01

    We disclose the fabrication of a mediator-free direct Z-scheme photocatalyst system BiVO4/g-C3N4 using a mixed-calcination method based on the more reliable interfacial interaction. The facet coupling occurred between the g-C3N4 (002) and BiVO4 (121), and it was revealed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and transmission electron microscope (TEM). The crystal structure and optical properties of the as-prepared samples have also been characterized by Fourier-transform infrared (FTIR), scanning electron microscopy (SEM) and UV-vis diffuse reflectance spectra (DRS) in details. The photocatalytic experiments indicated that the BiVO4/g-C3N4 composite photocatalysts display a significantly enhanced photocatalytic activity pertaining to RhB degradation and photocurrent generation (PC) compared to the pristine BiVO4 and g-C3N4. This remarkably improved photocatalytic performance should be attributed to the fabrication of a direct Z-scheme system of BiVO4/g-C3N4, which can result in a more efficient separation of photoinduced charge carriers than band-band transfer, thus endowing it with the much more powerful oxidation and reduction capability, as confirmed by the photoluminescence (PL) spectra and electrochemical impedance spectra (EIS). The Z-scheme mechanism of BiVO4/g-C3N4 heterostructure was verified by a series of combined techniques, including the active species trapping experiments, NBT transformation and terephthalic acid photoluminescence probing technique (TA-PL) over BiVO4/g-C3N4 composites and the pristine samples. The present work not only furthered the understanding of mediator-free Z-scheme photocatalysis, but also shed new light on the design of heterostructural photocatalysts with high-performance.

  18. Fluorescent Sensing of Fluoride in Cellular System

    PubMed Central

    Jiao, Yang; Zhu, Baocun; Chen, Jihua; Duan, Xiaohong

    2015-01-01

    Fluoride ions have the important roles in a lot of physiological activities related with biological and medical system, such as water fluoridation, caries treatment, and bone disease treatment. Great efforts have been made to develop new methods and strategies for F- detection in the past decades. Traditional methods for the detection of F- including ion chromatography, ion-selective electrodes, and spectroscopic techniques have the limitations in the biomedicine research. The fluorescent probes for F- are very promising that overcome some drawbacks of traditional fluoride detection methods. These probes exhibit high selectivity, high sensitivity as well as quick response to the detection of fluoride anions. The review commences with a brief description of photophysical mechanisms for fluorescent probes for fluoride, including photo induced electron transfer (PET), intramolecular charge transfer (ICT), fluorescence resonance energy transfer (FRET), and excited-state intramolecular proton transfer (ESIPT). Followed by a discussion about common dyes for fluorescent fluoride probes, such as anthracene, naphalimide, pyrene, BODIPY, fluorescein, rhodamine, resorufin, coumarin, cyanine, and near-infrared (NIR) dyes. We divide the fluorescent probes for fluoride in cellular application systems into nine groups, for example, type of hydrogen bonds, type of cleavage of Si-O bonds, type of Si-O bond cleavage and cylization reactions, etc. We also review the recent reported carriers in the delivery of fluorescent fluoride probes. Seventy-four typical fluorescent fluoride probes are listed and compared in detail, including quantum yield, reaction medium, excitation and emission wavelengths, linear detection range, selectivity for F-, mechanism, and analytical applications. Finally, we discuss the future challenges of the application of fluorescent fluoride probes in cellular system and in vivo. We wish that more and more excellent fluorescent fluoride probes will be developed

  19. Multichamber Multipotentiostat System for Cellular Microphysiometry

    PubMed Central

    Lima, Eduardo A.; Snider, Rachel M.; Reiserer, Ronald S.; McKenzie, Jennifer R.; Kimmel, Danielle W.; Eklund, Sven E.; Wikswo, John P.

    2014-01-01

    Multianalyte microphysiometry is a powerful technique for studying cellular metabolic flux in real time. Monitoring several analytes concurrently in a number of individual chambers, however, requires specific instrumentation that is not available commercially in a single, compact, benchtop form at an affordable cost. We developed a multipotentiostat system capable of performing simultaneous amperometric and potentiometric measurements in up to eight individual chambers. The modular design and custom LabVIEW™ control software provide flexibility and allow for expansion and modification to suit different experimental conditions. Superior accuracy is achieved when operating the instrument in a standalone configuration; however, measurements performed in conjunction with a previously developed multianalyte microphysiometer have shown low levels of crosstalk as well. Calibrations and experiments with primary and immortalized cell cultures demonstrate the performance of the instrument and its capabilities. PMID:25242863

  20. Cellular solidification in a monotectic system

    NASA Technical Reports Server (NTRS)

    Kaukler, W. F.; Curreri, P. A.

    1987-01-01

    Succinonitrile-glycerol, SN-G, transparent organic monotectic alloy is studied with particular attention to cellular growth. The phase diagram is determined, near the monotectic composition, with greater accuracy than previous studies. A solidification interface stability diagram is determined for planar growth. The planar-to-cellular transition is compared to predictions from the Burton, Primm, Schlichter theory. A new technique to determine the solute segregation by Fourier transform infrared spectroscopy is developed. Proposed models that involve the cellular interface for alignment of monotectic second-phase spheres or rods are compared with observations.

  1. Immunoisolation Patch System for Cellular Transplantation

    NASA Technical Reports Server (NTRS)

    Wang, Taylor G. (Inventor)

    2014-01-01

    An immunoisolation patch system, and particularly a patch system comprising multiple immunoisolation microcapsules, each encapsulating biological material such as cells for transplantation, which can be used in the prophylactic and therapeutic treatment of disease in large animals and humans without the need for immunosuppression.

  2. Microchip-based electrochemical detection for monitoring cellular systems.

    PubMed

    Johnson, Alicia S; Selimovic, Asmira; Martin, R Scott

    2013-04-01

    The use of microchip devices to study cellular systems is a rapidly growing research area. There are numerous advantages of using on-chip integrated electrodes to monitor various cellular processes. The purpose of this review is to give examples of advancements in microchip-based cellular analysis, specifically where electrochemistry is used for the detection scheme. These examples include on-chip detection of single-cell quantal exocytosis, electrochemical analysis of intracellular contents, the ability to integrate cell culture/immobilization with electrochemistry, and the use of integrated electrodes to ensure cell confluency in longer-term cell culture experiments. A perspective on future trends in this area is also given.

  3. A high-efficiency cellular extraction system for biological proteomics

    PubMed Central

    Dhabaria, Avantika; Cifani, Paolo; Reed, Casie; Steen, Hanno; Kentsis, Alex

    2015-01-01

    Recent developments in quantitative high-resolution mass spectrometry have led to significant improvements in the sensitivity and specificity of biochemical analyses of cellular reactions, protein-protein interactions, and small molecule drug discovery. These approaches depend on cellular proteome extraction that preserves native protein activities. Here, we systematically analyzed mechanical methods of cell lysis and physical protein extraction to identify those that maximize the extraction of cellular proteins while minimizing their denaturation. Cells were mechanically disrupted using Potter-Elvehjem homogenization, probe or adaptive focused acoustic sonication, and in the presence of various detergents, including polyoxyethylene ethers and esters, glycosides, and zwitterions. Using fluorescence spectroscopy, biochemical assays, and mass spectrometry proteomics, we identified the combination of adaptive focused acoustic (AFA) sonication in the presence of binary poloxamer-based mixture of octyl-β-glucoside and Pluronic F-127 to maximize the depth and yield of proteome extraction while maintaining native protein activity. This binary poloxamer extraction system allowed native proteome extraction, comparable in coverage to proteomes extracted using denaturing SDS or guanidine containing buffers, including efficient extraction of all major cellular organelles. This high-efficiency cellular extraction system should prove useful for a variety of cell biochemical studies, including structural and functional proteomics. PMID:26153614

  4. Cellular Phone Face Recognition System Based on Optical Phase Correlation

    NASA Astrophysics Data System (ADS)

    Watanabe, Eriko; Ishikawa, Sayuri; Ohta, Maiko; Kodate, Kashiko

    We propose a high security facial recognition system using a cellular phone on the mobile network. This system is composed of a face recognition engine based on optical phase correlation which uses phase information with emphasis on a Fourier domain, a control sever and the cellular phone with a compact camera for taking pictures, as a portable terminal. Compared with various correlation methods, our face recognition engine revealed the most accurate EER of less than 1%. By using the JAVA interface on this system, we implemented the stable system taking pictures, providing functions to prevent spoofing while transferring images. This recognition system was tested on 300 women students and the results proved this system effective.

  5. Modulation of cellular redox homeostasis by the endocannabinoid system

    PubMed Central

    2016-01-01

    The endocannabinoid system (ECS) and reactive oxygen species (ROS) constitute two key cellular signalling systems that participate in the modulation of diverse cellular functions. Importantly, growing evidence suggests that cross-talk between these two prominent signalling systems acts to modulate functionality of the ECS as well as redox homeostasis in different cell types. Herein, we review and discuss evidence pertaining to ECS-induced regulation of ROS generating and scavenging mechanisms, as well as highlighting emerging work that supports redox modulation of ECS function. Functionally, the studies outlined reveal that interactions between the ECS and ROS signalling systems can be both stimulatory and inhibitory in nature, depending on cell stimulus, the source of ROS species and cell context. Importantly, such cross-talk may act to maintain cell function, whereas abnormalities in either system may propagate and undermine the stability of both systems, thereby contributing to various pathologies associated with their dysregulation. PMID:27248801

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

    NASA Astrophysics Data System (ADS)

    Newman, Timothy

    2003-10-01

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

  7. Microchip-based electrochemical detection for monitoring cellular systems

    PubMed Central

    Johnson, Alicia S.; Selimovic, Asmira; Martin, R. Scott

    2013-01-01

    The use of microchip devices to study cellular systems is a rapidly growing research area. There are numerous advantages of using on-chip integrated electrodes to monitor various cellular processes. The purpose of this review article is to give examples of advancements in microchip-based cellular analysis, specifically where electrochemistry is used for the detection scheme. These examples include on-chip detection of single cell quantal exocytosis, electrochemical analysis of intracellular contents, the ability to integrate cell culture/immobilization with electrochemistry, and the use of integrated electrodes to ensure cell confluency in longer term cell culture experiments. A perspective on future trends in this area is also given. PMID:23340999

  8. Neuroendocrine system response modulates oxidative cellular damage in burn patients.

    PubMed

    Xie, Xiao-Qi; Shinozawa, Yotaro; Sasaki, Junichi; Takuma, Kiyotsugu; Akaishi, Satoshi; Yamanouchi, Satoshi; Endo, Tomoyuki; Nomura, Ryosuke; Kobayashi, Michio; Kudo, Daisuke; Hojo, Nobuko

    2007-02-01

    Oxygen-derived free radicals play important roles in pathophysiological processes in critically ill patients, but the data characterizing relationships between radicals and neuroendocrine system response are sparse. To search the cue to reduce the oxidative cellular damage from the point of view of neuroendocrine system response, we studied the indicators of neuroendocrine and inflammatory responses excreted in urine in 14 burn patients (42.3 +/- 31.4 years old, and 32.3 +/- 27.6% burn of total body surface area [%TBSA]) during the first seven days post burn. The daily mean amounts of urinary excretion of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a marker of oxidative cellular damage, were above the upper limit of the standard value during the studied period. The total amount of urinary excretion of 8-OHdG in the first day post burn correlated with burn severity indices: %TBSA (r = 0.63, p = 0.021) and burn index (r = 0.70, p = 0.008). The daily urinary excretion of 8-OHdG correlated with the daily urinary excretion of norepinephrine and nitrite plus nitrate (NOx) during the studied period except day 2 post burn, and correlated with the daily urinary excretion of 17-hydroxycorticosteriod (17-OHCS) in days 2, 3, and 7 post burn. These data suggest that oxidative cellular damage correlates with burn severity and neuroendocrine system response modulates inflammation and oxidative cellular damage. Modulation of neuroendocrine system response and inflammation in the treatment in the early phase of burn may be useful to reduce the oxidative cellular damage and to prevent multiple organ failures in patients with extensive burn.

  9. Modeling a Nonlinear Liquid Level System by Cellular Neural Networks

    NASA Astrophysics Data System (ADS)

    Hernandez-Romero, Norberto; Seck-Tuoh-Mora, Juan Carlos; Gonzalez-Hernandez, Manuel; Medina-Marin, Joselito; Flores-Romero, Juan Jose

    This paper presents the analogue simulation of a nonlinear liquid level system composed by two tanks; the system is controlled using the methodology of exact linearization via state feedback by cellular neural networks (CNNs). The relevance of this manuscript is to show how a block diagram representing the analogue modeling and control of a nonlinear dynamical system, can be implemented and regulated by CNNs, whose cells may contain numerical values or arithmetic and control operations. In this way the dynamical system is modeled by a set of local-interacting elements without need of a central supervisor.

  10. Application System Architecture for Cellular Phones by Dividing Interaction Logics

    NASA Astrophysics Data System (ADS)

    Kitamura, Misayo; Todoroki, Nobutoshi; Akiyoshi, Masanori; Kojima, Taizo

    This paper describes application system architecture using cellular phones as user interface devices, which enables users to interact with the system by graphic symbols on a client screen. Our approach has the following features: (i) divided interaction logics running on a server and a Java phone client; both interaction logics cooperate to accomplish a user's operation using a simplified script, (ii) local interaction which enables users to handle figures on a client screen without connecting to a server, and (iii) device-independent script which hides the differences of API sets among various cellular phones. By using this architecture, complicated figures including lots of graphic symbols can be displayed in spite of program-size limitation on a client device, and application programs including same interaction logics are just described once for various cellular phones. Our experiments show the advantage of the local interaction. A client program can respond immediately when handling complicated figures. The ratio of requests to the server is reduced to 23%. It takes less than 9 seconds to display typical contents, which is good enough for practical use. This method also reduces development costs at the second development or later.

  11. Cellular structure of detonation utilized in propulsion system

    NASA Astrophysics Data System (ADS)

    Zhang, XuDong; Fan, BaoChun; Gui, MingYue; Pan, ZhenHua

    2012-10-01

    How to confine a detonation in a combustor is a key issue of detonation applications in propulsion systems. Based on achieving schemes, detonations applied in the combustor, including pulse detonation wave (PDW), oblique detonation wave (ODW) and rotating detonation wave (RDW), are different from that described by the classic CJ theory in fine structures and its self-sustaining mechanisms. In this work, the cellular structures and flow fields of ODW and RDW were obtained numerically, and the fundamental characteristics and self-sustaining mechanisms of the detonations were analyzed and discussed. ODW front consists of three parts: the ZND-like front, the single-headed triple point front and the dual-headed triple point front. Cellular structures of RDW are heterogeneous, and the cell size near the outer wall is smaller than that near the inner wall.

  12. Cellular Biotechnology Operations Support System Fluid Dynamics Investigation

    NASA Technical Reports Server (NTRS)

    2003-01-01

    Aboard the International Space Station (ISS), the Tissue Culture Medium (TCM) is the bioreactor vessel in which cell cultures are grown. With its two syringe ports, it is much like a bag used to administer intravenous fluid, except it allows gas exchange needed for life. The TCM contains cell culture medium, and when frozen cells are flown to the ISS, they are thawed and introduced to the TCM through the syringe ports. In the Cellular Biotechnology Operations Support System-Fluid Dynamics Investigation (CBOSS-FDI) experiment, several mixing procedures are being assessed to determine which method achieves the most uniform mixing of growing cells and culture medium.

  13. Cellular phenotype database: a repository for systems microscopy data

    PubMed Central

    Kirsanova, Catherine; Brazma, Alvis; Rustici, Gabriella; Sarkans, Ugis

    2015-01-01

    Motivation: The Cellular Phenotype Database (CPD) is a repository for data derived from high-throughput systems microscopy studies. The aims of this resource are: (i) to provide easy access to cellular phenotype and molecular localization data for the broader research community; (ii) to facilitate integration of independent phenotypic studies by means of data aggregation techniques, including use of an ontology and (iii) to facilitate development of analytical methods in this field. Results: In this article we present CPD, its data structure and user interface, propose a minimal set of information describing RNA interference experiments, and suggest a generic schema for management and aggregation of outputs from phenotypic or molecular localization experiments. The database has a flexible structure for management of data from heterogeneous sources of systems microscopy experimental outputs generated by a variety of protocols and technologies and can be queried by gene, reagent, gene attribute, study keywords, phenotype or ontology terms. Availability and implementation: CPD is developed as part of the Systems Microscopy Network of Excellence and is accessible at http://www.ebi.ac.uk/fg/sym. Contact: jes@ebi.ac.uk or ugis@ebi.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25861964

  14. A unified theory for systems and cellular memory consolidation.

    PubMed

    Dash, Pramod K; Hebert, April E; Runyan, Jason D

    2004-04-01

    The time-limited role of the hippocampus for explicit memory storage has been referred to as systems consolidation where learning-related changes occur first in the hippocampus followed by the gradual development of a more distributed memory trace in the neocortex. Recent experiments are beginning to show that learning induces plasticity-related molecular changes in the neocortex as well as in the hippocampus and with a similar time course. Present memory consolidation theories do not account for these findings. In this report, we present a theory (the C theory) that incorporates these new findings, provides an explanation for the length of time for hippocampal dependency, and that can account for the apparent longer consolidation periods in species with larger brains. This theory proposes that a process of cellular consolidation occurs in the hippocampus and in areas of the neocortex during and shortly after learning resulting in long-term memory storage in both areas. For a limited time, the hippocampus is necessary for memory retrieval, a process involving the coordinated reactivation of these areas. This reactivation is later mediated by longer extrahippocampal connectivity between areas. The delay in hippocampal-independent memory retrieval is the time it takes for gene products in these longer extrahippocampal projections to be transported from the soma to tagged synapses by slow axonal transport. This cellular transport event defines the period of hippocampal dependency and, thus, the duration of memory consolidation. The theoretical description for memory consolidation presented in this review provides alternative explanations for several experimental observations and presents a unification of the concepts of systems and cellular memory consolidation.

  15. Network modeling of membrane-based artificial cellular systems

    NASA Astrophysics Data System (ADS)

    Freeman, Eric C.; Philen, Michael K.; Leo, Donald J.

    2013-04-01

    Computational models are derived for predicting the behavior of artificial cellular networks for engineering applications. The systems simulated involve the use of a biomolecular unit cell, a multiphase material that incorporates a lipid bilayer between two hydrophilic compartments. These unit cells may be considered building blocks that enable the fabrication of complex electrochemical networks. These networks can incorporate a variety of stimuli-responsive biomolecules to enable a diverse range of multifunctional behavior. Through the collective properties of these biomolecules, the system demonstrates abilities that recreate natural cellular phenomena such as mechanotransduction, optoelectronic response, and response to chemical gradients. A crucial step to increase the utility of these biomolecular networks is to develop mathematical models of their stimuli-responsive behavior. While models have been constructed deriving from the classical Hodgkin-Huxley model focusing on describing the system as a combination of traditional electrical components (capacitors and resistors), these electrical elements do not sufficiently describe the phenomena seen in experiment as they are not linked to the molecular scale processes. From this realization an advanced model is proposed that links the traditional unit cell parameters such as conductance and capacitance to the molecular structure of the system. Rather than approaching the membrane as an isolated parallel plate capacitor, the model seeks to link the electrical properties to the underlying chemical characteristics. This model is then applied towards experimental cases in order that a more complete picture of the underlying phenomena responsible for the desired sensing mechanisms may be constructed. In this way the stimuli-responsive characteristics may be understood and optimized.

  16. Traffic Dimensioning and Performance Modeling of 4G LTE Networks

    ERIC Educational Resources Information Center

    Ouyang, Ye

    2011-01-01

    Rapid changes in mobile techniques have always been evolutionary, and the deployment of 4G Long Term Evolution (LTE) networks will be the same. It will be another transition from Third Generation (3G) to Fourth Generation (4G) over a period of several years, as is the case still with the transition from Second Generation (2G) to 3G. As a result,…

  17. Regulation of System xc(-) by Pharmacological Manipulation of Cellular Thiols.

    PubMed

    Albano, Rebecca; Raddatz, Nicholas J; Hjelmhaug, Julie; Baker, David A; Lobner, Doug

    2015-01-01

    The cystine/glutamate exchanger (system xc (-)) mediates the transport of cystine into the cell in exchange for glutamate. By releasing glutamate, system xc (-) can potentially cause excitotoxicity. However, through providing cystine to the cell, it regulates the levels of cellular glutathione (GSH), the main endogenous intracellular antioxidant, and may protect cells against oxidative stress. We tested two different compounds that deplete primary cortical cultures containing both neurons and astrocytes of intracellular GSH, L-buthionine-sulfoximine (L-BSO), and diethyl maleate (DEM). Both compounds caused significant concentration and time dependent decreases in intracellular GSH levels. However; DEM caused an increase in radiolabeled cystine uptake through system xc (-), while unexpectedly BSO caused a decrease in uptake. The compounds caused similar low levels of neurotoxicity, while only BSO caused an increase in oxidative stress. The mechanism of GSH depletion by these two compounds is different, DEM directly conjugates to GSH, while BSO inhibits γ-glutamylcysteine synthetase, a key enzyme in GSH synthesis. As would be expected from these mechanisms of action, DEM caused a decrease in intracellular cysteine, while BSO increased cysteine levels. The results suggest that negative feedback by intracellular cysteine is an important regulator of system xc (-) in this culture system.

  18. Cellular Manufacturing System with Dynamic Lot Size Material Handling

    NASA Astrophysics Data System (ADS)

    Khannan, M. S. A.; Maruf, A.; Wangsaputra, R.; Sutrisno, S.; Wibawa, T.

    2016-02-01

    Material Handling take as important role in Cellular Manufacturing System (CMS) design. In several study at CMS design material handling was assumed per pieces or with constant lot size. In real industrial practice, lot size may change during rolling period to cope with demand changes. This study develops CMS Model with Dynamic Lot Size Material Handling. Integer Linear Programming is used to solve the problem. Objective function of this model is minimizing total expected cost consisting machinery depreciation cost, operating costs, inter-cell material handling cost, intra-cell material handling cost, machine relocation costs, setup costs, and production planning cost. This model determines optimum cell formation and optimum lot size. Numerical examples are elaborated in the paper to ilustrate the characterictic of the model.

  19. An opportunistic theory of cellular and systems consolidation

    PubMed Central

    Mednick, Sara C.; Cai, Denise J.; Shuman, Tristan; Anagnostaras, Stephan; Wixted, John

    2011-01-01

    Memories are often classified as hippocampus-dependent or –independent, and sleep has been found to facilitate both, but in different ways. In this Opinion article, we explore the optimal neural state for cellular and systems consolidation of hippocampus-dependent memories that benefit from sleep. We suggest that these two kinds of consolidation, which are ordinarily treated separately, may overlap in time and jointly benefit from a period of reduced interference (during which no new memories are formed). Conditions that result in reduced interference include slow wave sleep (SWS), NMDA receptor antagonists, benzodiazepines, alcohol, and acetylcholine antagonists. We hypothesize that the consolidation of hippocampal-dependent memories may not depend on SWS per se. Instead, the brain opportunistically consolidates previously encoded memories whenever the hippocampus is not otherwise occupied by the task of encoding new memories. PMID:21742389

  20. Cellular mechanisms underlying the interaction between cannabinoid and opioid system.

    PubMed

    Parolaro, D; Rubino, T; Viganò, D; Massi, P; Guidali, C; Realini, N

    2010-04-01

    Recently, the presence of functional interaction between the opioid and cannabinoid system has been shown in various pharmacological responses. Although there is an increasing interest for the feasible therapeutic application of a co-administration of cannabinoids and opioids in some disorders (i.e. to manage pain, to modulate immune system and emotions) and the combined use of the two drugs by drug abusers is becoming largely diffuse, only few papers focused on cellular and molecular mechanisms underlying this interaction. This review updates the biochemical and molecular underpinnings of opioid and cannabinoid interaction, both within the central nervous system and periphery. The most convincing theory for the explanation of this reciprocal interaction involves (i) the release of opioid peptides by cannabinoids or endocannabinoids by opioids, (ii) the existence of a direct receptor-receptor interaction when the receptors are co-expressed in the same cells, and (iii) the interaction of their intracellular pathways. Finally, the cannabinoid/opioid interaction might be different in the brain rewarding networks and in those accounting for other pharmacological effects (antinociception, modulation of emotionality and cognitive behavior), as well as between the central nervous system and periphery. Further insights about the cannabinoid/opioid interaction could pave the way for new and promising therapeutic approaches.

  1. Cellular barcoding tool for clonal analysis in the hematopoietic system.

    PubMed

    Gerrits, Alice; Dykstra, Brad; Kalmykowa, Olga J; Klauke, Karin; Verovskaya, Evgenia; Broekhuis, Mathilde J C; de Haan, Gerald; Bystrykh, Leonid V

    2010-04-01

    Clonal analysis is important for many areas of hematopoietic stem cell research, including in vitro cell expansion, gene therapy, and cancer progression and treatment. A common approach to measure clonality of retrovirally transduced cells is to perform integration site analysis using Southern blotting or polymerase chain reaction-based methods. Although these methods are useful in principle, they generally provide a low-resolution, biased, and incomplete assessment of clonality. To overcome those limitations, we labeled retroviral vectors with random sequence tags or "barcodes." On integration, each vector introduces a unique, identifiable, and heritable mark into the host cell genome, allowing the clonal progeny of each cell to be tracked over time. By coupling the barcoding method to a sequencing-based detection system, we could identify major and minor clones in 2 distinct cell culture systems in vitro and in a long-term transplantation setting. In addition, we demonstrate how clonal analysis can be complemented with transgene expression and integration site analysis. This cellular barcoding tool permits a simple, sensitive assessment of clonality and holds great promise for future gene therapy protocols in humans, and any other applications when clonal tracking is important.

  2. T-4G Methodology: Undergraduate Pilot Training T-37 Phase.

    ERIC Educational Resources Information Center

    Woodruff, Robert R.; And Others

    The report's brief introduction describes the application of T-4G methodology to the T-37 instrument phase of undergraduate pilot training. The methodology is characterized by instruction in trainers, proficiency advancement, a highly structured syllabus, the training manager concept, early exposure to instrument training, and hands-on training.…

  3. Perturbation Biology: Inferring Signaling Networks in Cellular Systems

    PubMed Central

    Miller, Martin L.; Gauthier, Nicholas P.; Jing, Xiaohong; Kaushik, Poorvi; He, Qin; Mills, Gordon; Solit, David B.; Pratilas, Christine A.; Weigt, Martin; Braunstein, Alfredo; Pagnani, Andrea; Zecchina, Riccardo; Sander, Chris

    2013-01-01

    We present a powerful experimental-computational technology for inferring network models that predict the response of cells to perturbations, and that may be useful in the design of combinatorial therapy against cancer. The experiments are systematic series of perturbations of cancer cell lines by targeted drugs, singly or in combination. The response to perturbation is quantified in terms of relative changes in the measured levels of proteins, phospho-proteins and cellular phenotypes such as viability. Computational network models are derived de novo, i.e., without prior knowledge of signaling pathways, and are based on simple non-linear differential equations. The prohibitively large solution space of all possible network models is explored efficiently using a probabilistic algorithm, Belief Propagation (BP), which is three orders of magnitude faster than standard Monte Carlo methods. Explicit executable models are derived for a set of perturbation experiments in SKMEL-133 melanoma cell lines, which are resistant to the therapeutically important inhibitor of RAF kinase. The resulting network models reproduce and extend known pathway biology. They empower potential discoveries of new molecular interactions and predict efficacious novel drug perturbations, such as the inhibition of PLK1, which is verified experimentally. This technology is suitable for application to larger systems in diverse areas of molecular biology. PMID:24367245

  4. Stochastic simulations of minimal self-reproducing cellular systems.

    PubMed

    Mavelli, Fabio; Ruiz-Mirazo, Kepa

    2007-10-29

    This paper is a theoretical attempt to gain insight into the problem of how self-assembling vesicles (closed bilayer structures) could progressively turn into minimal self-producing and self-reproducing cells, i.e. into interesting candidates for (proto)biological systems. With this aim, we make use of a recently developed object-oriented platform to carry out stochastic simulations of chemical reaction networks that take place in dynamic cellular compartments. We apply this new tool to study the behaviour of different minimal cell models, making realistic assumptions about the physico-chemical processes and conditions involved (e.g. thermodynamic equilibrium/non-equilibrium, variable volume-to-surface relationship, osmotic pressure, solute diffusion across the membrane due to concentration gradients, buffering effect). The new programming platform has been designed to analyse not only how a single protometabolic cell could maintain itself, grow or divide, but also how a collection of these cells could 'evolve' as a result of their mutual interactions in a common environment. PMID:17510021

  5. Challenges in Characterizing and Controlling Complex Cellular Systems

    NASA Astrophysics Data System (ADS)

    Wikswo, John

    2011-03-01

    Multicellular dynamic biological processes such as developmental differentiation, wound repair, disease, aging, and even homeostasis can be represented by trajectories through a phase space whose extent reflects the genetic, post-translational, and metabolic complexity of the process - easily extending to tens of thousands of dimensions. Intra- and inter-cellular sensing and regulatory systems and their nested, redundant, and non-linear feed-forward and feed-back controls create high-dimensioned attractors in this phase space. Metabolism provides free energy to drive non-equilibrium processes and dynamically reconfigure attractors. Studies of single molecules and cells provide only minimalist projections onto a small number of axes. It may be difficult to infer larger-scale emergent behavior from linearized experiments that perform only small amplitude perturbations on a limited number of the dimensions. Complete characterization may succeed for bounded component problems, such as an individual cell cycle or signaling cascade, but larger systems problems will require a coarse-grained approach. Hence a new experimental and analytical framework is needed. Possibly one could utilize high-amplitude, multi-variable driving of the system to infer coarse-grained, effective models, which in turn can be tested by their ability to control systems behavior. Navigation at will between attractors in a high-dimensioned dynamical system will provide not only detailed knowledge of the shape of attractor basins, but also measures of underlying stochastic events such as noise in gene expression or receptor binding and how both affect system stability and robustness. Needed for this are wide-bandwidth methods to sense and actuate large numbers of intracellular and extracellular variables and automatically and rapidly infer dynamic control models. The success of this approach may be determined by how broadly the sensors and actuators can span the full dimensionality of the phase space

  6. Peptide-Mediated Interference of PB2-eIF4G1 Interaction Inhibits Influenza A Viruses' Replication in Vitro and in Vivo.

    PubMed

    Yuan, Shuofeng; Chu, Hin; Ye, Jiahui; Hu, Meng; Singh, Kailash; Chow, Billy K C; Zhou, Jie; Zheng, Bo-Jian

    2016-07-01

    Influenza viruses are obligate parasites that hijack the host cellular system. Previous results have shown that the influenza virus PB2 subunit confers a dependence of host eukaryotic translation initiation factor 4-γ 1 (eIF4G1) for viral mRNA translation. Here, we demonstrated that peptide-mediated interference of the PB2-eIF4G1 interaction inhibited virus replication in vitro and in vivo. Remarkably, intranasal administration of the peptide provided 100% protection against lethal challenges of influenza A viruses in BALB/c mice, including H1N1, H5N1, and H7N9 influenza virus subtypes. Mapping of the PB2 protein indicated that the eIF4G1 binding sites resided within the PB2 cap-binding domain. Virtual docking analysis suggested that the inhibitory peptide associated with the conserved amino acid residues that were essential to PB2 cap-binding activity. Overall, our results identified the PB2-eIF4G1 interactive site as a druggable target for influenza therapeutics. PMID:27626099

  7. The similia principle: results obtained in a cellular model system.

    PubMed

    Wiegant, Fred; Van Wijk, Roeland

    2010-01-01

    This paper describes the results of a research program focused on the beneficial effect of low dose stress conditions that were applied according to the similia principle to cells previously disturbed by more severe stress conditions. In first instance, we discuss criteria for research on the similia principle at the cellular level. Then, the homologous ('isopathic') approach is reviewed, in which the initial (high dose) stress used to disturb cellular physiology and the subsequent (low dose) stress are identical. Beneficial effects of low dose stress are described in terms of increased cellular survival capacity and at the molecular level as an increase in the synthesis of heat shock proteins (hsps). Both phenomena reflect a stimulation of the endogenous cellular self-recovery capacity. Low dose stress conditions applied in a homologous approach stimulate the synthesis of hsps and enhance survival in comparison with stressed cells that were incubated in the absence of low dose stress conditions. Thirdly, the specificity of the low dose stress condition is described where the initial (high dose) stress is different in nature from the subsequently applied (low dose) stress; the heterologous or 'heteropathic' approach. The results support the similia principle at the cellular level and add to understanding of how low dose stress conditions influence the regulatory processes underlying self-recovery. In addition, the phenomenon of 'symptom aggravation' which is also observed at the cellular level, is discussed in the context of self-recovery. Finally, the difference in efficiency between the homologous and the heterologous approach is discussed; a perspective is indicated for further research; and the relationship between studies on the similia principle and the recently introduced concept of 'postconditioning hormesis' is emphasized.

  8. Whole-Organism Cellular Pathology: A Systems Approach to Phenomics.

    PubMed

    Cheng, K C; Katz, S R; Lin, A Y; Xin, X; Ding, Y

    2016-01-01

    Phenotype is defined as the state of an organism resulting from interactions between genes, environment, disease, molecular mechanisms, and chance. The purpose of the emerging field of phenomics is to systematically determine and measure phenotypes across biology for the sake of understanding. Phenotypes can affect more than one cell type and life stage, so ideal phenotyping would include the state of every cell type within the context of both tissue architecture and the whole organism at each life stage. In medicine, high-resolution anatomic assessment of phenotype is obtained from histology. Histology's interpretative power, codified by Virchow as cellular pathology, is derived from its ability to discern diagnostic and characteristic cellular changes in diseased tissues. Cellular pathology is observed in every major human disease and relies on the ability of histology to detect cellular change in any cell type due to unbiased pan-cellular staining, even in optically opaque tissues. Our laboratory has shown that histology is far more sensitive than stereomicroscopy for detecting phenotypes in zebrafish mutants. Those studies have also shown that more complete sampling, greater consistency in sample orientation, and the inclusion of phenotypes extending over longer length scales would provide greater coverage of common phenotypes. We are developing technical approaches to achieve an ideal detection of cellular pathology using an improved form of X-ray microtomography that retains the strengths and addresses the weaknesses of histology as a screening tool. We are using zebrafish as a vertebrate model based on the overlaps between zebrafish and mammalian tissue architecture, and a body size small enough to allow whole-organism, volumetric imaging at cellular resolution. Automation of whole-organism phenotyping would greatly increase the value of phenomics. Potential societal benefits would include reduction in the cost of drug development, a reduction in the

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

    PubMed Central

    Burnap, Robert L.

    2014-01-01

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

  10. [Cellular immune system of surgical maggots Lucilia sericata (Diptera, Calliphoridae)].

    PubMed

    Kind, T V

    2014-01-01

    In the hemolymph of surgical maggots Lucilia sericata seven types of hemocytes were revealed. These are prohemocytes, stable and unstable hyaline cells, thrombocytoids, spindle cells, larval plasmatocytes and plasmatocytes I-IV, which represent sequential stages of one cell line differentiation. In contrast to Calliphora hyaline cells, this type of hemocytes in cropemptying larvae of Lucilia is elongated or vermiform in shape. Hyaline cells may be transformed to both prothrombocytoids and unstable prophenoloxydase-producing cells. Appearance and differentiation of each hemocyte type is rigidly linked with a definite stage of development. In cellular defense the main role play juvenile plasmatocytes, plasmatocytes II and III and trombocytoides. Juvenile plasmatocytes are the most active ones. After charcoal particles injection they were instantly surrounded by the thick envelope of adhered alien particles and form uniform morules aggregations or conglomerates together with thrombocytoidal agglutinates. Plasmatocytes II and III during the early stages of differentiation may be involved in adhesion and phagocytosis of alien particles and during the last stages in the engulfing of apoptose desintegrated tissues. Thus the cellular defense reaction is assisted by 4 hemocyte types--prophenoloxydase-unstable hyaline cells, thrombocytoids, juvenile plasmatocytes and plasmatocytes I-IV.

  11. A Cellular System for Spatial Signal Decoding in Chemical Gradients.

    PubMed

    Hegemann, Björn; Unger, Michael; Lee, Sung Sik; Stoffel-Studer, Ingrid; van den Heuvel, Jasmin; Pelet, Serge; Koeppl, Heinz; Peter, Matthias

    2015-11-23

    Directional cell growth requires that cells read and interpret shallow chemical gradients, but how the gradient directional information is identified remains elusive. We use single-cell analysis and mathematical modeling to define the cellular gradient decoding network in yeast. Our results demonstrate that the spatial information of the gradient signal is read locally within the polarity site complex using double-positive feedback between the GTPase Cdc42 and trafficking of the receptor Ste2. Spatial decoding critically depends on low Cdc42 activity, which is maintained by the MAPK Fus3 through sequestration of the Cdc42 activator Cdc24. Deregulated Cdc42 or Ste2 trafficking prevents gradient decoding and leads to mis-oriented growth. Our work discovers how a conserved set of components assembles a network integrating signal intensity and directionality to decode the spatial information contained in chemical gradients.

  12. Integration of peroxisomes into an endomembrane system that governs cellular aging

    PubMed Central

    Beach, Adam; Burstein, Michelle T.; Richard, Vincent R.; Leonov, Anna; Levy, Sean; Titorenko, Vladimir I.

    2012-01-01

    The peroxisome is an organelle that has long been known for its essential roles in oxidation of fatty acids, maintenance of reactive oxygen species (ROS) homeostasis and anaplerotic replenishment of tricarboxylic acid (TCA) cycle intermediates destined for mitochondria. Growing evidence supports the view that these peroxisome-confined metabolic processes play an essential role in defining the replicative and chronological age of a eukaryotic cell. Much progress has recently been made in defining molecular mechanisms that link cellular aging to fatty acid oxidation, ROS turnover, and anaplerotic metabolism in peroxisomes. Emergent studies have revealed that these organelles not only house longevity-defining metabolic reactions but can also regulate cellular aging via their dynamic communication with other cellular compartments. Peroxisomes communicate with other organelles by establishing extensive physical contact with lipid bodies, maintaining an endoplasmic reticulum (ER) to peroxisome connectivity system, exchanging certain metabolites, and being involved in the bidirectional flow of some of their protein and lipid constituents. The scope of this review is to summarize the evidence that peroxisomes are dynamically integrated into an endomembrane system that governs cellular aging. We discuss recent progress in understanding how communications between peroxisomes and other cellular compartments within this system influence the development of a pro- or anti-aging cellular pattern. We also propose a model for the integration of peroxisomes into the endomembrane system governing cellular aging and critically evaluate several molecular mechanisms underlying such integration. PMID:22936916

  13. Recognition of eIF4G by rotavirus NSP3 reveals a basis for mRNA circularization.

    PubMed

    Groft, Caroline M; Burley, Stephen K

    2002-06-01

    Rotaviruses, segmented double-stranded RNA viruses, co-opt the eukaryotic translation machinery with the aid of nonstructural protein 3 (NSP3), a rotaviral functional homolog of the cellular poly(A) binding protein (PABP). NSP3 binds to viral mRNA 3' consensus sequences and circularizes mRNA via interactions with eIF4G. Here, we present the X-ray structure of the C-terminal domain of NSP3 (NSP3-C) recognizing a fragment of eIF4GI. Homodimerization of NSP3-C yields a symmetric, elongated, largely alpha-helical structure with two hydrophobic eIF4G binding pockets at the dimer interface. Site-directed mutagenesis and isothermal titration calorimetry documented that NSP3 and PABP use analogous eIF4G recognition strategies, despite marked differences in tertiary structure.

  14. Tensegrity, cellular biophysics, and the mechanics of living systems

    PubMed Central

    Ingber, Donald E.; Wang, Ning; Stamenović, Dimitrije

    2014-01-01

    The recent convergence between physics and biology has led many physicists to enter the fields of cell and developmental biology. One of the most exciting areas of interest has been the emerging field of mechanobiology that centers on how cells control their mechanical properties, and how physical forces regulate cellular biochemical responses, a process that is known as mechanotransduction. In this article, we review the central role that tensegrity (tensional integrity) architecture, which depends on tensile prestress for its mechanical stability, plays in biology. We describe how tensional prestress is a critical governor of cell mechanics and function, and how use of tensegrity by cells contributes to mechanotransduction. Theoretical tensegrity models are also described that predict both quantitative and qualitative behaviors of living cells, and these theoretical descriptions are placed in context of other physical models of the cell. In addition, we describe how tensegrity is used at multiple size scales in the hierarchy of life — from individual molecules to whole living organisms — to both stabilize three-dimensional form and to channel forces from the macroscale to the nanoscale, thereby facilitating mechanochemical conversion at the molecular level. PMID:24695087

  15. Tensegrity, cellular biophysics, and the mechanics of living systems.

    PubMed

    Ingber, Donald E; Wang, Ning; Stamenovic, Dimitrije

    2014-04-01

    The recent convergence between physics and biology has led many physicists to enter the fields of cell and developmental biology. One of the most exciting areas of interest has been the emerging field of mechanobiology that centers on how cells control their mechanical properties, and how physical forces regulate cellular biochemical responses, a process that is known as mechanotransduction. In this article, we review the central role that tensegrity (tensional integrity) architecture, which depends on tensile prestress for its mechanical stability, plays in biology. We describe how tensional prestress is a critical governor of cell mechanics and function, and how use of tensegrity by cells contributes to mechanotransduction. Theoretical tensegrity models are also described that predict both quantitative and qualitative behaviors of living cells, and these theoretical descriptions are placed in context of other physical models of the cell. In addition, we describe how tensegrity is used at multiple size scales in the hierarchy of life—from individual molecules to whole living organisms—to both stabilize three-dimensional form and to channel forces from the macroscale to the nanoscale, thereby facilitating mechanochemical conversion at the molecular level. PMID:24695087

  16. Tensegrity, cellular biophysics, and the mechanics of living systems

    NASA Astrophysics Data System (ADS)

    Ingber, Donald E.; Wang, Ning; Stamenović, Dimitrije

    2014-04-01

    The recent convergence between physics and biology has led many physicists to enter the fields of cell and developmental biology. One of the most exciting areas of interest has been the emerging field of mechanobiology that centers on how cells control their mechanical properties, and how physical forces regulate cellular biochemical responses, a process that is known as mechanotransduction. In this article, we review the central role that tensegrity (tensional integrity) architecture, which depends on tensile prestress for its mechanical stability, plays in biology. We describe how tensional prestress is a critical governor of cell mechanics and function, and how use of tensegrity by cells contributes to mechanotransduction. Theoretical tensegrity models are also described that predict both quantitative and qualitative behaviors of living cells, and these theoretical descriptions are placed in context of other physical models of the cell. In addition, we describe how tensegrity is used at multiple size scales in the hierarchy of life—from individual molecules to whole living organisms—to both stabilize three-dimensional form and to channel forces from the macroscale to the nanoscale, thereby facilitating mechanochemical conversion at the molecular level.

  17. Eukaryotic Translation Initiation Factor 4G Is Targeted for Proteolytic Cleavage by Caspase 3 during Inhibition of Translation in Apoptotic Cells

    PubMed Central

    Marissen, Wilfred E.; Lloyd, Richard E.

    1998-01-01

    Although much is known about the multiple mechanisms which induce apoptosis, comparatively little is understood concerning the execution phase of apoptosis and the mechanism(s) of cell killing. Several reports have demonstrated that cellular translation is shut off during apoptosis; however, details of the mechanism of translation inhibition are lacking. Translation initiation factor 4G (eIF4G) is a crucial protein required for binding cellular mRNA to ribosomes and is known to be cleaved as the central part of the mechanism of host translation shutoff exerted by several animal viruses. Treatment of HeLa cells with the apoptosis inducers cisplatin and etoposide resulted in cleavage of eIF4G, and the extent of its cleavage correlated with the onset and extent of observed inhibition of cellular translation. The eIF4G-specific cleavage activity could be measured in cell lysates in vitro and was inhibited by the caspase inhibitor Ac-DEVD-CHO at nanomolar concentrations. A combination of in vivo and in vitro inhibitor studies suggest the involvement of one or more caspases in the activation and execution of eIF4G cleavage. Furthermore recombinant human caspase 3 was expressed in bacteria, and when incubated with HeLa cell lysates, was shown to produce the same eIF4G cleavage products as those observed in apoptotic cells. In addition, purified caspase 3 caused cleavage of purified eIF4G, demonstrating that eIF4G could serve as a substrate for caspase 3. Taken together, these data suggest that cellular translation is specifically inhibited during apoptosis by a mechanism involving cleavage of eIF4G, an event dependent on caspase activity. PMID:9819442

  18. Eukaryotic Initiation Factor eIFiso4G1 and eIFiso4G2 Are Isoforms Exhibiting Distinct Functional Differences in Supporting Translation in Arabidopsis.

    PubMed

    Gallie, Daniel R

    2016-01-15

    The eukaryotic translation initiation factor (eIF) 4G is required during protein synthesis to promote the assembly of several factors involved in the recruitment of a 40S ribosomal subunit to an mRNA. Although many eukaryotes express two eIF4G isoforms that are highly similar, the eIF4G isoforms in plants, referred to as eIF4G and eIFiso4G, are highly divergent in size, sequence, and domain organization but both can interact with eIF4A, eIF4B, eIF4E isoforms, and the poly(A)-binding protein. Nevertheless, eIF4G and eIFiso4G from wheat exhibit preferences in the mRNAs they translate optimally. For example, mRNA containing the 5'-leader (called Ω) of tobacco mosaic virus preferentially uses eIF4G in wheat germ lysate. In this study, the eIF4G isoform specificity of Ω was used to examine functional differences of the eIF4G isoforms in Arabidopsis. As in wheat, Ω-mediated translation was reduced in an eif4g null mutant. Loss of the eIFiso4G1 isoform, which is similar in sequence to wheat eIFiso4G, did not substantially affect Ω-mediated translation. However, loss of the eIFiso4G2 isoform substantially reduced Ω-mediated translation. eIFiso4G2 is substantially divergent from eIFiso4G1 and is present only in the Brassicaceae, suggesting a recent evolution. eIFiso4G2 isoforms exhibit sequence-specific differences in regions representing partner protein and RNA binding sites. Loss of any eIF4G isoform also resulted in a substantial reduction in reporter transcript level. These results suggest that eIFiso4G2 appeared late in plant evolution and exhibits more functional similarity with eIF4G than with eIFiso4G1 during Ω-mediated translation.

  19. Eukaryotic Initiation Factor eIFiso4G1 and eIFiso4G2 Are Isoforms Exhibiting Distinct Functional Differences in Supporting Translation in Arabidopsis.

    PubMed

    Gallie, Daniel R

    2016-01-15

    The eukaryotic translation initiation factor (eIF) 4G is required during protein synthesis to promote the assembly of several factors involved in the recruitment of a 40S ribosomal subunit to an mRNA. Although many eukaryotes express two eIF4G isoforms that are highly similar, the eIF4G isoforms in plants, referred to as eIF4G and eIFiso4G, are highly divergent in size, sequence, and domain organization but both can interact with eIF4A, eIF4B, eIF4E isoforms, and the poly(A)-binding protein. Nevertheless, eIF4G and eIFiso4G from wheat exhibit preferences in the mRNAs they translate optimally. For example, mRNA containing the 5'-leader (called Ω) of tobacco mosaic virus preferentially uses eIF4G in wheat germ lysate. In this study, the eIF4G isoform specificity of Ω was used to examine functional differences of the eIF4G isoforms in Arabidopsis. As in wheat, Ω-mediated translation was reduced in an eif4g null mutant. Loss of the eIFiso4G1 isoform, which is similar in sequence to wheat eIFiso4G, did not substantially affect Ω-mediated translation. However, loss of the eIFiso4G2 isoform substantially reduced Ω-mediated translation. eIFiso4G2 is substantially divergent from eIFiso4G1 and is present only in the Brassicaceae, suggesting a recent evolution. eIFiso4G2 isoforms exhibit sequence-specific differences in regions representing partner protein and RNA binding sites. Loss of any eIF4G isoform also resulted in a substantial reduction in reporter transcript level. These results suggest that eIFiso4G2 appeared late in plant evolution and exhibits more functional similarity with eIF4G than with eIFiso4G1 during Ω-mediated translation. PMID:26578519

  20. [Cellular immunotherapy: complexity of immune system and industrial development].

    PubMed

    Abastado, J-P

    2003-01-01

    Cell immunotherapy aims at treating patients by stimulating their own immune system using appropriate cells. This approach is one of the most promising therapeutic strategy against cancer. The use of cells, the mobilization of a system, the targeting of interactions between the immune system and the tumor constitute the hallmarks of complexity, an area of intense academic and industrial research during the past twenty years. The present article reviews some unique characteristics of the industrial development of these cell drugs.

  1. The eIF4G-eIF4E complex is the target for direct cleavage by the rhinovirus 2A proteinase.

    PubMed Central

    Haghighat, A; Svitkin, Y; Novoa, I; Kuechler, E; Skern, T; Sonenberg, N

    1996-01-01

    The 2A proteinases (2Apro) of certain picornaviruses induce the cleavage of the eIF4G subunit of the cap-binding protein complex, eIF4F. Several reports have demonstrated that 2Apro of rhinovirus and coxsackievirus B4 cleave eIF4G directly. However, it was suggested that in poliovirus infection, the 2Apro induces the activation of a cellular proteinase which in turn cleaves eIF4G. Furthermore, it is not clear whether eIF4G is cleaved as part of the eIF4F complex or as an individual polypeptide. To address these issues, recombinant eIF4G was purified from Sf9 insect cells and tested for cleavage by purified rhinovirus 2Apro. Here we report that eIF4G alone is a relatively poor substrate for cleavage by the rhinovirus 2Apro. However, an eIF4G-eIF4E complex is cleaved efficiently by the 2Apro, suggesting that eIF4F is a preferred substrate for cleavage by rhinovirus 2Apro. Furthermore, 2Apr drastically reduced the translation of a capped mRNA. An eIF4G-eIF4E complex, but not eIF4G alone, was required to restore translation. PMID:8970966

  2. Development of Cellular Absorptive Tracers (CATs) for a Quantitative Characterization of Microbial Mass in Flow Systems

    SciTech Connect

    Saripalli, Prasad; Brown, Christopher F.; Lindberg, Michael J.

    2005-03-16

    We report on a new Cellular Absorptive Tracers (CATs) method, for a simple, non-destructive characterization of bacterial mass in flow systems. Results show that adsorption of a CAT molecule into the cellular mass results in its retardation during flow, which is a good, quantitative measure of the biomass quantity and distribution. No such methods are currently available for a quantitative characterization of cell mass.

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

    PubMed

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

    2011-01-01

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

  4. GLOBULAR CLUSTER POPULATIONS: FIRST RESULTS FROM S{sup 4}G EARLY-TYPE GALAXIES

    SciTech Connect

    Zaritsky, Dennis; Aravena, Manuel; Athanassoula, E.; Bosma, Albert; Comerón, Sébastien; Laine, Jarkko; Laurikainen, Eija; Salo, Heikki; Elmegreen, Bruce G.; Erroz-Ferrer, Santiago; Knapen, Johan H.; Gadotti, Dimitri A.; Muñoz-Mateos, Juan Carlos; Hinz, Joannah L.; Ho, Luis C.; Holwerda, Benne; Sheth, Kartik

    2015-02-01

    Using 3.6 μm images of 97 early-type galaxies, we develop and verify methodology to measure globular cluster populations from the S{sup 4}G survey images. We find that (1) the ratio, T {sub N}, of the number of clusters, N {sub CL}, to parent galaxy stellar mass, M {sub *}, rises weakly with M {sub *} for early-type galaxies with M {sub *} > 10{sup 10} M {sub ☉} when we calculate galaxy masses using a universal stellar initial mass function (IMF) but that the dependence of T {sub N} on M {sub *} is removed entirely once we correct for the recently uncovered systematic variation of IMF with M {sub *}; and (2) for M {sub *} < 10{sup 10} M {sub ☉}, there is no trend between N {sub CL} and M {sub *}, the scatter in T {sub N} is significantly larger (approaching two orders of magnitude), and there is evidence to support a previous, independent suggestion of two families of galaxies. The behavior of N {sub CL} in the lower-mass systems is more difficult to measure because these systems are inherently cluster-poor, but our results may add to previous evidence that large variations in cluster formation and destruction efficiencies are to be found among low-mass galaxies. The average fraction of stellar mass in clusters is ∼0.0014 for M {sub *} > 10{sup 10} M {sub ☉} and can be as large as ∼0.02 for less massive galaxies. These are the first results from the S{sup 4}G sample of galaxies and will be enhanced by the sample of early-type galaxies now being added to S{sup 4}G and complemented by the study of later-type galaxies within S{sup 4}G.

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

    PubMed Central

    Garcia-Perez, Josselyn E.; Lagou, Vasiliki; Lee, James C.; Wouters, Carine; Meyts, Isabelle; Goris, An; Boeckxstaens, Guy

    2015-01-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2016-04-01

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

  8. Method for analyzing signaling networks in complex cellular systems.

    PubMed

    Plavec, Ivan; Sirenko, Oksana; Privat, Sylvie; Wang, Yuker; Dajee, Maya; Melrose, Jennifer; Nakao, Brian; Hytopoulos, Evangelos; Berg, Ellen L; Butcher, Eugene C

    2004-02-01

    Now that the human genome has been sequenced, the challenge of assigning function to human genes has become acute. Existing approaches using microarrays or proteomics frequently generate very large volumes of data not directly related to biological function, making interpretation difficult. Here, we describe a technique for integrative systems biology in which: (i) primary cells are cultured under biologically meaningful conditions; (ii) a limited number of biologically meaningful readouts are measured; and (iii) the results obtained under several different conditions are combined for analysis. Studies of human endothelial cells overexpressing different signaling molecules under multiple inflammatory conditions show that this system can capture a remarkable range of functions by a relatively small number of simple measurements. In particular, measurement of seven different protein levels by ELISA under four different conditions is capable of reconstructing pathway associations of 25 different proteins representing four known signaling pathways, implicating additional participants in the NF-kappaBorRAS/mitogen-activated protein kinase pathways and defining additional interactions between these pathways. PMID:14745015

  9. Method for analyzing signaling networks in complex cellular systems

    PubMed Central

    Plavec, Ivan; Sirenko, Oksana; Privat, Sylvie; Wang, Yuker; Dajee, Maya; Melrose, Jennifer; Nakao, Brian; Hytopoulos, Evangelos; Berg, Ellen L.; Butcher, Eugene C.

    2004-01-01

    Now that the human genome has been sequenced, the challenge of assigning function to human genes has become acute. Existing approaches using microarrays or proteomics frequently generate very large volumes of data not directly related to biological function, making interpretation difficult. Here, we describe a technique for integrative systems biology in which: (i) primary cells are cultured under biologically meaningful conditions; (ii) a limited number of biologically meaningful readouts are measured; and (iii) the results obtained under several different conditions are combined for analysis. Studies of human endothelial cells overexpressing different signaling molecules under multiple inflammatory conditions show that this system can capture a remarkable range of functions by a relatively small number of simple measurements. In particular, measurement of seven different protein levels by ELISA under four different conditions is capable of reconstructing pathway associations of 25 different proteins representing four known signaling pathways, implicating additional participants in the NF-κBorRAS/mitogen-activated protein kinase pathways and defining additional interactions between these pathways. PMID:14745015

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

    PubMed

    Marguet, Maïté; Bonduelle, Colin; Lecommandoux, Sébastien

    2013-01-21

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

  11. Design mobile satellite system architecture as an integral part of the cellular access digital network

    NASA Technical Reports Server (NTRS)

    Chien, E. S. K.; Marinho, J. A.; Russell, J. E., Sr.

    1988-01-01

    The Cellular Access Digital Network (CADN) is the access vehicle through which cellular technology is brought into the mainstream of the evolving integrated telecommunications network. Beyond the integrated end-to-end digital access and per call network services provisioning of the Integrated Services Digital Network (ISDN), the CADN engenders the added capability of mobility freedom via wireless access. One key element of the CADN network architecture is the standard user to network interface that is independent of RF transmission technology. Since the Mobile Satellite System (MSS) is envisioned to not only complement but also enhance the capabilities of the terrestrial cellular telecommunications network, compatibility and interoperability between terrestrial cellular and mobile satellite systems are vitally important to provide an integrated moving telecommunications network of the future. From a network standpoint, there exist very strong commonalities between the terrestrial cellular system and the mobile satellite system. Therefore, the MSS architecture should be designed as an integral part of the CADN. This paper describes the concept of the CADN, the functional architecture of the MSS, and the user-network interface signaling protocols.

  12. Paramecium--a model system for studying cellular graviperception.

    PubMed

    Hemmersbach, R; Bromeis, B; Block, I; Braucker, R; Krause, M; Freiberger, N; Stieber, C; Wilczek, M

    2001-01-01

    Experiments under varied gravitational accelerations as well as in density-adjusted media showed that sensation of gravity in protists may be linked to the known principles of mechanosensation. Paramecium, a ciliate with clear graviresponses (gravitaxis and gravikinesis) is an ideal model system to prove this hypothesis since the ciliary activity and thus the swimming behaviour is controlled by the membrane potential. It has also been assumed that the cytoplasmic mass causes a distinct stimulation of the bipolarly distributed mechano-sensitive K+ and Ca2+ ion channels in the plasma membrane in dependence of the spatial orientation of the cell. In order to prove this hypothesis, different channel blockers are currently under investigation. Gadolinium did not inhibit gravitaxis in Paramecium, showing that it does not specifically block gravireceptors. Further studies concentrated on the question of whether second messengers are involved in the gravity signal transduction chain. Exposure to 5 g for up to 10 min led to a significant increase in cAMP.

  13. Interactions of the interferon system with cellular metabolism

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1986-01-01

    The results of studies concerning the interaction of the interferon (Inf) system with the activities of carcinogens, tumor promoters, and cytochrome P-450 are presented. The results show that the addition of a tumor promoter (TPA or 4-O-methyl-TPA) to a tissue culture enhances virus-induced Inf-gamma production, suggesting a potential value of tumor promoters in the biosynthesis of commercial Inf. On the other hand, the carcinogens were reported to inhibit the induction of Inf-alpha/beta in cultured cells and in intact animals (with no effect on the administered or preformed Inf). The demonstration of a correlation between the carcinogenic potential of a compound and its inhibitive effect on Inf production suggests a possible use of the Inf production assay in the evaluation of the carcinogenicity of chemicals. In addition, it was shown that the induction of Inf-alpha/beta as well as the administration of this Inf depresses the levels of rat liver cytochrome P-450 which is responsible for binding lipophilic drugs, steroids, and carcinogens, thus increasing the toxicity of the respective chemical.

  14. An Intergenic Region Shared by At4g35985 and At4g35987 in Arabidopsis thaliana Is a Tissue Specific and Stress Inducible Bidirectional Promoter Analyzed in Transgenic Arabidopsis and Tobacco Plants

    PubMed Central

    Banerjee, Joydeep; Sahoo, Dipak Kumar; Dey, Nrisingha; Houtz, Robert L.; Maiti, Indu Bhushan

    2013-01-01

    On chromosome 4 in the Arabidopsis genome, two neighboring genes (calmodulin methyl transferase At4g35987 and senescence associated gene At4g35985) are located in a head-to-head divergent orientation sharing a putative bidirectional promoter. This 1258 bp intergenic region contains a number of environmental stress responsive and tissue specific cis-regulatory elements. Transcript analysis of At4g35985 and At4g35987 genes by quantitative real time PCR showed tissue specific and stress inducible expression profiles. We tested the bidirectional promoter-function of the intergenic region shared by the divergent genes At4g35985 and At4g35987 using two reporter genes (GFP and GUS) in both orientations in transient tobacco protoplast and Agro-infiltration assays, as well as in stably transformed transgenic Arabidopsis and tobacco plants. In transient assays with GFP and GUS reporter genes the At4g35985 promoter (P85) showed stronger expression (about 3.5 fold) compared to the At4g35987 promoter (P87). The tissue specific as well as stress responsive functional nature of the bidirectional promoter was evaluated in independent transgenic Arabidopsis and tobacco lines. Expression of P85 activity was detected in the midrib of leaves, leaf trichomes, apical meristemic regions, throughout the root, lateral roots and flowers. The expression of P87 was observed in leaf-tip, hydathodes, apical meristem, root tips, emerging lateral root tips, root stele region and in floral tissues. The bidirectional promoter in both orientations shows differential up-regulation (2.5 to 3 fold) under salt stress. Use of such regulatory elements of bidirectional promoters showing spatial and stress inducible promoter-functions in heterologous system might be an important tool for plant biotechnology and gene stacking applications. PMID:24260266

  15. Application of spectral hole burning to the study of in vitro cellular systems

    SciTech Connect

    Milanovich, Nebojsa

    1999-11-08

    Chapter 1 of this thesis describes the various stages of tumor development and a multitude of diagnostic techniques used to detect cancer. Chapter 2 gives an overview of the aspects of hole burning spectroscopy important for its application to the study of cellular systems. Chapter 3 gives general descriptions of cellular organelles, structures, and physical properties that can serve as possible markers for the differentiation of normal and cancerous cells. Also described in Chapter 3 are the principles of cryobiology important for low temperature spectroscopy of cells, characterization of MCF-10F (normal) and MCF-7 (cancer) cells lines which will serve as model systems, and cellular characteristics of aluminum phthalocyanine tetrasulfonate (APT), which was used as the test probe. Chapters 4 and 5 are previously published papers by the author pertaining to the results obtained from the application of hole burning to the study of cellular systems. Chapter 4 presents the first results obtained by spectral hole burning of cellular systems and Chapter 5 gives results for the differentiation of MCF-10F and MCF-7 cells stained with APT by an external applied electric (Stark) field. A general conclusion is presented in Chapter 6. Appendices A and B provide additional characterization of the cell/probe model systems. Appendix A describes the uptake and subcellular distribution of APT in MCF-10F and MCF-7 cells and Appendix B compares the hole burning characteristics of APT in cells when the cells are in suspension and when they are examined while adhering to a glass coverslip. Appendix C presents preliminary results for a novel probe molecule, referred to as a molecular thumbtack, designed by the authors for use in future hole burning applications to cellular systems.

  16. Influence of hydrodynamic conditions on quantitative cellular assays in microfluidic systems.

    PubMed

    Yin, Huabing; Zhang, Xunli; Pattrick, Nicola; Klauke, Norbert; Cordingley, Hayley C; Haswell, Stephen J; Cooper, Jonathan M

    2007-09-15

    This study demonstrates the importance of the hydrodynamic environment in microfluidic systems in quantitative cellular assays using live cells. Commonly applied flow conditions used in microfluidics were evaluated using the quantitative intracellular Ca2+ analysis of Chinese hamster ovary (CHO) cells as a model system. Above certain thresholds of shear stress, hydrodynamically induced intracellular Ca2+ fluxes were observed which mimic the responses induced by chemical stimuli, such as the agonist uridine 5'-triphosphate tris salt (UTP). This effect is of significance given the increasing application of microfluidic devices in high-throughput cellular analysis for biophysical applications and pharmacological screening.

  17. Influenza A virus interacts extensively with the cellular SUMOylation system during infection.

    PubMed

    Pal, Sangita; Santos, Andres; Rosas, Juan M; Ortiz-Guzman, Joshua; Rosas-Acosta, Germán

    2011-06-01

    SUMOylation, the post-translational conjugation of the Small Ubiquitin-like MOdifier (SUMO) to a target protein, regulates a wide array of cellular processes and plays important roles for numerous viruses during infection. However, the relevance of the cellular SUMOylation system for influenza virus infection remains mostly unexplored. We previously reported that the non-structural protein of influenza A virus NS1 is a bona fide SUMO target. Here we determine that at least four additional influenza virus proteins, namely PB1, NP, M1, and NS2, are also authentic SUMO targets, and provide data supporting that PB1, NP, and M1 are SUMOylated during viral infection. The functional relevance of SUMOylation for these proteins is supported by the observation that, despite no apparent changes in the cellular levels of the E1 and E2 SUMO enzymes, influenza viral infection leads to a global increase in cellular SUMOylation. This increase, characterized by the appearance of two new SUMOylated proteins of ∼70kDa and ∼52kDa of molecular weight, is dependent upon viral replication and cannot be recreated by interferon stimulation alone. Altogether, these observations indicate that influenza A virus interacts extensively with the cellular SUMOylation system during infection and suggest that SUMOylation plays an important role during influenza virus infection, potentially contributing to the functional diversity exhibited by influenza viral proteins.

  18. Circulating Levels of PAI-1 and SERPINE1 4G/4G Polymorphism Are Predictive of Poor Prognosis in HCC Patients Undergoing TACE1

    PubMed Central

    Divella, Rosa; Daniele, Antonella; Abbate, Ines; Savino, Eufemia; Casamassima, Porzia; Sciortino, Giancarlo; Simone, Giovanni; Gadaleta-Caldarola, Gennaro; Fazio, Vito; Gadaleta, Cosimo Damiano; Sabbà, Carlo; Mazzocca, Antonio

    2015-01-01

    Although several molecular markers have been proposed as prognostic of disease progression in Hepatocellular carcinoma (HCC), predictive markers of response to treatment are still unsatisfactory. Here, we propose a genetic polymorphism as a potential predictive factor of poor prognosis in HCC patients treated with transcatheter arterial chemoembolization (TACE). In particular, we show that the guanosine insertion/deletion polymorphism in the promoter region of SERPINE1 gene at the − 675 bp position, named 4G/4G, predicts poor prognosis in a cohort of 75 patients with HCC undergoing TACE. By a combination of ELISA and SERPINE1 promoter study, we found that the presence of elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) in patients with 4G/4G genotype is significantly associated with reduced overall survival compared to patients with 5G/5G or 4G/5G genotype in HCC patients after TACE. Our analysis provided evidence that variation in SERPINE1 gene plays a role in defining the outcome in patients treated with TACE. In addition to a poor disease outcome, the 4G/4G variant represents an unfavorable predictive factor for response to chemotherapy as well. PMID:26310373

  19. REVIEWS OF TOPICAL PROBLEMS: Study of spatially extended dynamical systems using probabilistic cellular automata

    NASA Astrophysics Data System (ADS)

    Vanag, Vladimir K.

    1999-05-01

    Spatially extended dynamical systems are ubiquitous and include such things as insect and animal populations; complex chemical, technological, and geochemical processes; humanity itself, and much more. It is clearly desirable to have a certain universal tool with which the highly complex behaviour of nonlinear dynamical systems can be analyzed and modelled. For this purpose, cellular automata seem to be good candidates. In the present review, emphasis is placed on the possibilities that various types of probabilistic cellular automata (PCA), such as DSMC (direct simulation Monte Carlo) and LGCA (lattice-gas cellular automata), offer. The methods are primarily designed for modelling spatially extended dynamical systems with inner fluctuations accounted for. For the Willamowskii-Roessler and Oregonator models, PCA applications to the following problems are illustrated: the effect of fluctuations on the dynamics of nonlinear systems; Turing structure formation; the effect of hydrodynamic modes on the behaviour of nonlinear chemical systems (stirring effects); bifurcation changes in the dynamical regimes of complex systems with restricted geometry or low spatial dimension; and the description of chemical systems in microemulsions.

  20. PAI-1 4G-4G and MTHFR 677TT in non-hepatitis C virus/hepatitis B virus-related liver cirrhosis

    PubMed Central

    Pasta, Linda; Pasta, Francesca

    2015-01-01

    AIM: To evaluate the different roles of thrombophilia in patients with and without viral etiology. The thrombophilic genetic factors (THRGFs), PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q and prothrombin 20210A, were studied as risk factors in 1079 patients with liver cirrhosis (LC), enrolled from January 2000 to January 2014. METHODS: All Caucasian LC patients consecutively observed in a fourteen-year period were included; the presence of portal vein thrombosis (PVT) and Budd Chiari syndrome (BCS) was registered. The differences between the proportions of each THRGF with regard to the presence or absence of viral etiology and the frequencies of the THRGF genotypes with those predicted in a population by the Hardy-Weinberg equilibrium were registered. RESULTS: Four hundred and seventeen/one thousand and seventy-six patients (38.6%) showed thrombophilia: 217 PAI-1 4G-4G, 176 MTHFR C677TT, 71 V Leiden factor and 41 prothrombin G20210 A, 84 with more than 1 THRGF; 350 presented with no viral liver cirrhosis (NVLC) and 729 with, called viral liver cirrhosis (VLC), of whom 56 patients were hepatitis C virus + hepatitis B virus. PAI-1 4G-4G, MTHFR C677TT, the presence of at least one TRHGF and the presence of > 1 THRGF, were statistically more frequent in patients with NVLC vs patients with VLC: All χ2 > 3.85 and P < 0.05. Patients with PVT and/or BCS with at least one TRHGF were 189/352 (53.7%). The Hardy-Weinberg of PAI-1 and MTHFR 677 genotypes deviated from that expected from a population in equilibrium in patients with NVLC (respectively χ2 = 39.3; P < 0.000 and χ2 = 27.94; P < 0.05), whereas the equilibrium was respected in VLC. CONCLUSION: MTHFR 677TT was nearly twofold and PAI-1 4G-4G more than threefold more frequently found in NVLC vs patients with VLC; the Hardy-Weinberg equilibrium of these two polymorphisms confirms this data in NVLC. We suggest that PAI-1 4G-4G and MTHFR 677TT could be considered as factors of fibrosis and thrombosis mechanisms, increasing

  1. Cellular and molecular mechanisms of sexual differentiation in the mammalian nervous system.

    PubMed

    Forger, Nancy G; Strahan, J Alex; Castillo-Ruiz, Alexandra

    2016-01-01

    Neuroscientists are likely to discover new sex differences in the coming years, spurred by the National Institutes of Health initiative to include both sexes in preclinical studies. This review summarizes the current state of knowledge of the cellular and molecular mechanisms underlying sex differences in the mammalian nervous system, based primarily on work in rodents. Cellular mechanisms examined include neurogenesis, migration, the differentiation of neurochemical and morphological cell phenotype, and cell death. At the molecular level we discuss evolving roles for epigenetics, sex chromosome complement, the immune system, and newly identified cell signaling pathways. We review recent findings on the role of the environment, as well as genome-wide studies with some surprising results, causing us to re-think often-used models of sexual differentiation. We end by pointing to future directions, including an increased awareness of the important contributions of tissues outside of the nervous system to sexual differentiation of the brain. PMID:26790970

  2. Stochastic extension of cellular manufacturing systems: a queuing-based analysis

    NASA Astrophysics Data System (ADS)

    Fardis, Fatemeh; Zandi, Afagh; Ghezavati, Vahidreza

    2013-07-01

    Clustering parts and machines into part families and machine cells is a major decision in the design of cellular manufacturing systems which is defined as cell formation. This paper presents a non-linear mixed integer programming model to design cellular manufacturing systems which assumes that the arrival rate of parts into cells and machine service rate are stochastic parameters and described by exponential distribution. Uncertain situations may create a queue behind each machine; therefore, we will consider the average waiting time of parts behind each machine in order to have an efficient system. The objective function will minimize summation of idleness cost of machines, sub-contracting cost for exceptional parts, non-utilizing machine cost, and holding cost of parts in the cells. Finally, the linearized model will be solved by the Cplex solver of GAMS, and sensitivity analysis will be performed to illustrate the effectiveness of the parameters.

  3. Interactive effect of PAI-1 4G/5G genotype and salt intake on PAI-1 antigen.

    PubMed

    Brown, N J; Murphey, L J; Srikuma, N; Koschachuhanan, N; Williams, G H; Vaughan, D E

    2001-06-01

    Activation of the renin-angiotensin-aldosterone system (RAAS) is associated with increased circulating PAI-1 antigen and increased risk of thrombotic cardiovascular events. A 4G/5G polymorphism located 675 bp upstream from the transcription start site of the PAI-1 gene affects PAI-1 antigen concentrations. To test the hypothesis that PAI-1 4G/5G genotype influences the effect of activation of the RAAS on PAI-1 expression, we measured morning PAI-1 antigen concentrations in 76 subjects with essential hypertension during low (10 mmol/d) and high (200 mmol/d) salt intake. Low salt intake was associated with activation of the RAAS as measured by plasma renin activity (2.3+/-0.2 versus 0.5+/-0.0 ng angiotensin I. mL(-1). h(-1), P<0.001) and aldosterone (529+/-40 versus 145+/-12 pmol/L). PAI-1 antigen concentrations were 17.9+/-2.7, 19.2+/-2.5, and 27.8+/-4.0 ng/mL during high salt intake and 19.2+/-2.7, 21.6+/-2.9, and 38.9+/-7.2 ng/mL during low salt intake in the 5G/5G (n=14), 4G/5G (n=40), and 4G/4G (n=22) groups, respectively. There was a significant effect of both salt intake (F=6.0, P=0.017) and PAI-1 4G/5G genotype (F=7.6, P=0.001) on PAI-1 antigen. More importantly, there was a significant interactive effect (F=7.8, P=0.001) of salt intake and PAI-1 4G/5G genotype on PAI-1 antigen. PAI-1 4G/5G genotype influenced the relationship between serum triglycerides and PAI-1 antigen such that the relationship was significant only in 4G homozygotes during either high (R(2)=0.31, P=0.014) or low (R(2)=0.37, P=0.006) salt intake. This study identifies an important gene-by-environment interaction that may influence cardiovascular morbidity and the response to pharmacological therapies that interrupt the RAAS.

  4. A single-cell bioluminescence imaging system for monitoring cellular gene expression in a plant body.

    PubMed

    Muranaka, Tomoaki; Kubota, Saya; Oyama, Tokitaka

    2013-12-01

    Gene expression is a fundamental cellular process and expression dynamics are of great interest in life science. We succeeded in monitoring cellular gene expression in a duckweed plant, Lemna gibba, using bioluminescent reporters. Using particle bombardment, epidermal and mesophyll cells were transfected with the luciferase gene (luc+) under the control of a constitutive [Cauliflower mosaic virus 35S (CaMV35S)] and a rhythmic [Arabidopsis thaliana CIRCADIAN CLOCK ASSOCIATED 1 (AtCCA1)] promoter. Bioluminescence images were captured using an EM-CCD (electron multiply charged couple device) camera. Luminescent spots of the transfected cells in the plant body were quantitatively measured at the single-cell level. Luminescence intensities varied over a 1,000-fold range among CaMV35S::luc+-transfected cells in the same plant body and showed a log-normal-like frequency distribution. We monitored cellular gene expression under light-dark conditions by capturing bioluminescence images every hour. Luminescence traces of ≥50 individual cells in a frond were successfully obtained in each monitoring procedure. Rhythmic and constitutive luminescence behaviors were observed in cells transfected with AtCCA1::luc+ and CaMV35S::luc+, respectively. Diurnal rhythms were observed in every AtCCA1::luc+-introduced cell with traceable luminescence, and slight differences were detected in their rhythmic waveforms. Thus the single-cell bioluminescence monitoring system was useful for the characterization of cellular gene expression in a plant body. PMID:24058151

  5. A single-cell bioluminescence imaging system for monitoring cellular gene expression in a plant body.

    PubMed

    Muranaka, Tomoaki; Kubota, Saya; Oyama, Tokitaka

    2013-12-01

    Gene expression is a fundamental cellular process and expression dynamics are of great interest in life science. We succeeded in monitoring cellular gene expression in a duckweed plant, Lemna gibba, using bioluminescent reporters. Using particle bombardment, epidermal and mesophyll cells were transfected with the luciferase gene (luc+) under the control of a constitutive [Cauliflower mosaic virus 35S (CaMV35S)] and a rhythmic [Arabidopsis thaliana CIRCADIAN CLOCK ASSOCIATED 1 (AtCCA1)] promoter. Bioluminescence images were captured using an EM-CCD (electron multiply charged couple device) camera. Luminescent spots of the transfected cells in the plant body were quantitatively measured at the single-cell level. Luminescence intensities varied over a 1,000-fold range among CaMV35S::luc+-transfected cells in the same plant body and showed a log-normal-like frequency distribution. We monitored cellular gene expression under light-dark conditions by capturing bioluminescence images every hour. Luminescence traces of ≥50 individual cells in a frond were successfully obtained in each monitoring procedure. Rhythmic and constitutive luminescence behaviors were observed in cells transfected with AtCCA1::luc+ and CaMV35S::luc+, respectively. Diurnal rhythms were observed in every AtCCA1::luc+-introduced cell with traceable luminescence, and slight differences were detected in their rhythmic waveforms. Thus the single-cell bioluminescence monitoring system was useful for the characterization of cellular gene expression in a plant body.

  6. Characterization of the Expression of the RNA Binding Protein eIF4G1 and Its Clinicopathological Correlation with Serous Ovarian Cancer

    PubMed Central

    Xie, Zhe; Li, Guiqin; Mao, Chengyi; Liu, Yi; Wen, Xin; Yin, Na; Cao, Jianzhong; Wang, Jing; Li, Li; Yu, Jianhua; Wang, Fang; Yi, Ping

    2016-01-01

    Background Ovarian cancer is the most lethal type of malignant tumor in gynecological cancers and is associated with a high percentage of late diagnosis and chemotherapy resistance. Thus, it is urgent to identify a tumor marker or a molecular target that allows early detection and effective treatment. RNA-binding proteins (RBPs) are crucial in various cellular processes at the post-transcriptional level. The eukaryotic translation initiation factor 4 gamma, 1(eIF4G1), an RNA-binding protein, facilitates the recruitment of mRNA to the ribosome, which is a rate-limiting step during the initiation phase of protein synthesis. However, little is known regarding the characteristics of eIF4G1 expression and its clinical significance in ovarian cancer. Therefore, we propose to investigate the expression and clinicopathological significance of eIF4G1 in ovarian cancer patients. Methods We performed Real-time PCR in 40 fresh serous ovarian cancer tissues and 27 normal ovarian surface epithelial cell specimens to assess eIF4G1mRNA expression. Immunohistochemistry (IHC) was used to examine the expression of eIF4G1 at the protein level in 134 patients with serous ovarian cancer and 18 normal ovarian tissues. Statistical analysis was conducted to determine the correlation of the eIF4G1 protein levels with the clinicopathological characteristics and prognosis in ovarian cancer. Results The expression of eIF4G1 was upregulated in serous ovarian cancer tissues at both the mRNA (P = 0.0375) and the protein (P = 0.0007) levels. The eIF4G1 expression was significantly correlated with the clinical tumor stage (P = 0.0004) and omentum metastasis (P = 0.024). Moreover, patients with low eIF4G1 protein expression had a longer overall survival time (P = 0.026). Conclusions These data revealed that eIF4G1 is markedly expressed in serous ovarian cancer and that upregulation of the eIF4G1 protein expression is significantly associated with an advanced tumor stage. Besides, the patients with

  7. Green light radiation effects on free radicals inhibition in cellular and chemical systems.

    PubMed

    Comorosan, Sorin; Polosan, Silviu; Jipa, Silviu; Popescu, Irinel; Marton, George; Ionescu, Elena; Cristache, Ligia; Badila, Dumitru; Mitrica, Radu

    2011-01-10

    Free radicals generation is inhibited through green light (GL) irradiation in cellular systems and in chemical reactions. Standard melanocyte cultures were UV-irradiated and the induced cellular reactive oxygen species (ROS) were quantified by the fluorescence technique. The same cell cultures, previously protected by a 24h GL exposure, displayed a significantly lower ROS production. A simple chemical reaction is subsequently chosen, in which the production of free radicals is well defined. Paraffin wax and mineral oil were GL irradiated during thermal degradation and the oxidation products checked by chemiluminescence [CL] and Fourier transform infrared spectra [FT-IR]. The same clear inhibition of the radical oxidation of alkanes is recorded. A quantum chemistry modeling of these results is performed and a mechanism involving a new type of Rydberg macromolecular systems with implications for biology and medicine is suggested. PMID:20934350

  8. Efficient Inference of Parsimonious Phenomenological Models of Cellular Dynamics Using S-Systems and Alternating Regression

    PubMed Central

    Daniels, Bryan C.; Nemenman, Ilya

    2015-01-01

    The nonlinearity of dynamics in systems biology makes it hard to infer them from experimental data. Simple linear models are computationally efficient, but cannot incorporate these important nonlinearities. An adaptive method based on the S-system formalism, which is a sensible representation of nonlinear mass-action kinetics typically found in cellular dynamics, maintains the efficiency of linear regression. We combine this approach with adaptive model selection to obtain efficient and parsimonious representations of cellular dynamics. The approach is tested by inferring the dynamics of yeast glycolysis from simulated data. With little computing time, it produces dynamical models with high predictive power and with structural complexity adapted to the difficulty of the inference problem. PMID:25806510

  9. Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy.

    PubMed

    Marengo, Barbara; Nitti, Mariapaola; Furfaro, Anna Lisa; Colla, Renata; Ciucis, Chiara De; Marinari, Umberto Maria; Pronzato, Maria Adelaide; Traverso, Nicola; Domenicotti, Cinzia

    2016-01-01

    Reactive oxygen species (ROS) and their products are components of cell signaling pathways and play important roles in cellular physiology and pathophysiology. Under physiological conditions, cells control ROS levels by the use of scavenging systems such as superoxide dismutases, peroxiredoxins, and glutathione that balance ROS generation and elimination. Under oxidative stress conditions, excessive ROS can damage cellular proteins, lipids, and DNA, leading to cell damage that may contribute to carcinogenesis. Several studies have shown that cancer cells display an adaptive response to oxidative stress by increasing expression of antioxidant enzymes and molecules. As a double-edged sword, ROS influence signaling pathways determining beneficial or detrimental outcomes in cancer therapy. In this review, we address the role of redox homeostasis in cancer growth and therapy and examine the current literature regarding the redox regulatory systems that become upregulated in cancer and their role in promoting tumor progression and resistance to chemotherapy. PMID:27418953

  10. Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy.

    PubMed

    Marengo, Barbara; Nitti, Mariapaola; Furfaro, Anna Lisa; Colla, Renata; Ciucis, Chiara De; Marinari, Umberto Maria; Pronzato, Maria Adelaide; Traverso, Nicola; Domenicotti, Cinzia

    2016-01-01

    Reactive oxygen species (ROS) and their products are components of cell signaling pathways and play important roles in cellular physiology and pathophysiology. Under physiological conditions, cells control ROS levels by the use of scavenging systems such as superoxide dismutases, peroxiredoxins, and glutathione that balance ROS generation and elimination. Under oxidative stress conditions, excessive ROS can damage cellular proteins, lipids, and DNA, leading to cell damage that may contribute to carcinogenesis. Several studies have shown that cancer cells display an adaptive response to oxidative stress by increasing expression of antioxidant enzymes and molecules. As a double-edged sword, ROS influence signaling pathways determining beneficial or detrimental outcomes in cancer therapy. In this review, we address the role of redox homeostasis in cancer growth and therapy and examine the current literature regarding the redox regulatory systems that become upregulated in cancer and their role in promoting tumor progression and resistance to chemotherapy.

  11. Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy

    PubMed Central

    Ciucis, Chiara De

    2016-01-01

    Reactive oxygen species (ROS) and their products are components of cell signaling pathways and play important roles in cellular physiology and pathophysiology. Under physiological conditions, cells control ROS levels by the use of scavenging systems such as superoxide dismutases, peroxiredoxins, and glutathione that balance ROS generation and elimination. Under oxidative stress conditions, excessive ROS can damage cellular proteins, lipids, and DNA, leading to cell damage that may contribute to carcinogenesis. Several studies have shown that cancer cells display an adaptive response to oxidative stress by increasing expression of antioxidant enzymes and molecules. As a double-edged sword, ROS influence signaling pathways determining beneficial or detrimental outcomes in cancer therapy. In this review, we address the role of redox homeostasis in cancer growth and therapy and examine the current literature regarding the redox regulatory systems that become upregulated in cancer and their role in promoting tumor progression and resistance to chemotherapy. PMID:27418953

  12. Encapsulated cellular implants for recombinant protein delivery and therapeutic modulation of the immune system.

    PubMed

    Lathuilière, Aurélien; Mach, Nicolas; Schneider, Bernard L

    2015-05-08

    Ex vivo gene therapy using retrievable encapsulated cellular implants is an effective strategy for the local and/or chronic delivery of therapeutic proteins. In particular, it is considered an innovative approach to modulate the activity of the immune system. Two recently proposed therapeutic schemes using genetically engineered encapsulated cells are discussed here: the chronic administration of monoclonal antibodies for passive immunization against neurodegenerative diseases and the local delivery of a cytokine as an adjuvant for anti-cancer vaccines.

  13. Encapsulated Cellular Implants for Recombinant Protein Delivery and Therapeutic Modulation of the Immune System

    PubMed Central

    Lathuilière, Aurélien; Mach, Nicolas; Schneider, Bernard L.

    2015-01-01

    Ex vivo gene therapy using retrievable encapsulated cellular implants is an effective strategy for the local and/or chronic delivery of therapeutic proteins. In particular, it is considered an innovative approach to modulate the activity of the immune system. Two recently proposed therapeutic schemes using genetically engineered encapsulated cells are discussed here: the chronic administration of monoclonal antibodies for passive immunization against neurodegenerative diseases and the local delivery of a cytokine as an adjuvant for anti-cancer vaccines. PMID:26006227

  14. Fiber optics as an rf transmission medium in cellular telephone systems

    NASA Astrophysics Data System (ADS)

    Jakubowski, Ronald J.

    1996-01-01

    Fiber optics has become an important medium in the development of worldwide cellular system microcell and remote antenna applications. Several products are available which take advantage of single mode 1310 and 1550 nm fiber optic transmission and its low loss and relative ease of installation. This paper presents a brief history of RF transmission technology, summarizes the technical aspects of the RF to light conversion, and describes the Allen Telecom fiber-based microcell and active antenna products while presenting examples of applications.

  15. Efficient Preamble Design Technique for Millimeter-Wave Cellular Systems with Beamforming.

    PubMed

    Han, Dae Geun; Kim, Yeong Jun; Cho, Yong Soo

    2016-01-01

    The processing time for beam training in millimeter-wave (mmWave) cellular systems can be significantly reduced by a code division multiplexing (CDM)-based technique, where multiple beams are transmitted simultaneously with their corresponding Tx beam IDs (BIDs) in the preamble. However, mmWave cellular systems with CDM-based preambles require a large number of cell IDs (CIDs) and BIDs, and a high computational complexity for CID and BID (CBID) searches. In this paper, a new preamble design technique that can increase the number of CBIDs significantly is proposed, using a preamble sequence constructed by a combination of two Zadoff-Chu (ZC) sequences. An efficient technique for the CBID detection is also described for the proposed preamble. It is shown by simulations using a simple model of an mmWave cellular system that the proposed technique can obtain a significant reduction in the complexity of the CBID detection without a noticeable performance degradation, compared to the previous technique.

  16. Efficient Preamble Design Technique for Millimeter-Wave Cellular Systems with Beamforming

    PubMed Central

    Han, Dae Geun; Kim, Yeong Jun; Cho, Yong Soo

    2016-01-01

    The processing time for beam training in millimeter-wave (mmWave) cellular systems can be significantly reduced by a code division multiplexing (CDM)-based technique, where multiple beams are transmitted simultaneously with their corresponding Tx beam IDs (BIDs) in the preamble. However, mmWave cellular systems with CDM-based preambles require a large number of cell IDs (CIDs) and BIDs, and a high computational complexity for CID and BID (CBID) searches. In this paper, a new preamble design technique that can increase the number of CBIDs significantly is proposed, using a preamble sequence constructed by a combination of two Zadoff-Chu (ZC) sequences. An efficient technique for the CBID detection is also described for the proposed preamble. It is shown by simulations using a simple model of an mmWave cellular system that the proposed technique can obtain a significant reduction in the complexity of the CBID detection without a noticeable performance degradation, compared to the previous technique. PMID:27455260

  17. Measuring information flow in cellular networks by the systems biology method through microarray data.

    PubMed

    Chen, Bor-Sen; Li, Cheng-Wei

    2015-01-01

    In general, it is very difficult to measure the information flow in a cellular network directly. In this study, based on an information flow model and microarray data, we measured the information flow in cellular networks indirectly by using a systems biology method. First, we used a recursive least square parameter estimation algorithm to identify the system parameters of coupling signal transduction pathways and the cellular gene regulatory network (GRN). Then, based on the identified parameters and systems theory, we estimated the signal transductivities of the coupling signal transduction pathways from the extracellular signals to each downstream protein and the information transductivities of the GRN between transcription factors in response to environmental events. According to the proposed method, the information flow, which is characterized by signal transductivity in coupling signaling pathways and information transductivity in the GRN, can be estimated by microarray temporal data or microarray sample data. It can also be estimated by other high-throughput data such as next-generation sequencing or proteomic data. Finally, the information flows of the signal transduction pathways and the GRN in leukemia cancer cells and non-leukemia normal cells were also measured to analyze the systematic dysfunction in this cancer from microarray sample data. The results show that the signal transductivities of signal transduction pathways change substantially from normal cells to leukemia cancer cells.

  18. 49 CFR 173.65 - Exceptions for Division 1.4G consumer fireworks.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Exceptions for Division 1.4G consumer fireworks... Class 1 § 173.65 Exceptions for Division 1.4G consumer fireworks. (a) Notwithstanding the requirements of §§ 173.56(b), 173.56(f), 173.56(i), and 173.64, Division 1.4G consumer fireworks may be...

  19. 49 CFR 173.65 - Exceptions for Division 1.4G consumer fireworks.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Exceptions for Division 1.4G consumer fireworks... Class 1 § 173.65 Exceptions for Division 1.4G consumer fireworks. (a) Notwithstanding the requirements of §§ 173.56(b), 173.56(f), 173.56(i), and 173.64, Division 1.4G consumer fireworks may be...

  20. An analysis of cellular telephone and INMARSAT systems for providing radio data link computer communications for US Navy vessels

    NASA Astrophysics Data System (ADS)

    Cooper, David L., Jr.

    1993-12-01

    This thesis examines radio frequency data link computer communications systems with emphasis on their potential application to ship/shore communications. Covered are two systems that experts believe hold the most promise for DOD application, International Maritime Satellite (INMARSAT) and cellular radiotelephones. An analysis of system capabilities, cost, and future potential is performed for each, and then the two systems are compared. In addition, a thorough discussion of the security issues for each system and final conclusions/recommendations are presented. The conclusions suggest that increased cellular radiotelephone usage vice INMARSAT by fleet units would optimize fleet readiness and improve supply system performance. Based on these conclusions, this author's recommendation is that all Navy ships be equipped with a cellular telephone system, while all aircraft carriers and amphibious aircraft carriers be equipped with both cellular and INMARSAT systems.

  1. Cognitive Cellular Systems: A New Challenge on the RF Analog Frontend

    NASA Astrophysics Data System (ADS)

    Varga, Gabor; Schrey, Moritz; Subbiah, Iyappan; Ashok, Arun; Heinen, Stefan

    2016-07-01

    Cognitive Cellular Systems are seen today as one of the most promising ways of moving forward solving or at least easing the still worsening situation of congested spectrum caused by the growing number of users and the expectation of higher data transfer rates. As the intelligence of a Cognitive Radio system is located in the digital domain - the Cognitive Engine and associated layers - extensive research has been ongoing in that domain since Mitola published his idea in 1999. Since, a big progress has been made in the domain of architectures and algorithms making systems more efficient and highly flexible. The pace of this progress, however, is going to be impeded by hard requirements on the received and transmitted signal quality, introducing ultimate challenges on the performance of the RF analog frontend, such as in-band local oscillator harmonics, ultra low sensitivity and ultra high linearity. The RF frontend is thus likely to become the limiting technical factor in the true realization of a Cognitive Cellular System. Based on short recapitulations of the most crucial issues in RF analog design for Cognitive Systems, this article will point out why those mechanisms become responsible for the limitation of the overall performance particularly in a broadband Cognitive Cellular System. Furthermore, as part of a possible solution to ease the situation, system design of a high intermediate frequency (IF) to UHF frequency converter for cognitive radios is discussed and the performance of such a converter analyzed as a proof of concept. In addition to successfully tackling some of the challenges, such a high-IF converter enables white space operation for existing commercial devices by acting as frequency converter. From detailed measurements, the capabilities in both physical layer and application layer performance of a high-IF frontend developed out of off-the-shelf components is explained and is shown to provide negligible degradation to the commercial device

  2. Functional role of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) in NSCLC

    PubMed Central

    Cao, Yueyu; Wei, Mengdan; Li, Bing; Liu, Yali; Lu, Ying; Tang, Zhipeng; Lu, Tianbao; Yin, Yujiao; Qin, Zhiqiang; Xu, Zengguang

    2016-01-01

    Eukaryotic translation initiation factor 4 gamma 1(EIF4G1) is related to tumorigenesis and tumor progression. However, its role and the underlying mechanisms in the regulation of tumor development in non–small cell lung cancers (NSCLC) remain largely unknown. Here we report that the levels of EIF4G1 expression are much higher in NSCLC cell lines and tumor tissues than those in the normal lung cells and adjacent normal tissues from the same patients. Using shRNA to knock down EIF4G1 expression stably, we found EIF4G1 required for NSCLC cell proliferation, anchorage-independent growth, migration and invasion. Furthermore, silencing of EIF4G1 induces NSCLC cell apoptosis and causes G0/G1 cell cycle arrest. To identify the partner protein network of EIF4G1 in NSCLC cells, we found that Ubiquitin-specific protease 10 (USP10) can directly interacts with EIF4G1, while acting as a negative regulator for EIF4G1-mediated functions. Together, our results indicate that EIF4G1 functions as an oncoprotein during NSCLC development, which may represent a novel and promising therapeutic target in lung cancer. PMID:27003362

  3. Functional role of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) in NSCLC.

    PubMed

    Cao, Yueyu; Wei, Mengdan; Li, Bing; Liu, Yali; Lu, Ying; Tang, Zhipeng; Lu, Tianbao; Yin, Yujiao; Qin, Zhiqiang; Xu, Zengguang

    2016-04-26

    Eukaryotic translation initiation factor 4 gamma 1(EIF4G1) is related to tumorigenesis and tumor progression. However, its role and the underlying mechanisms in the regulation of tumor development in non-small cell lung cancers (NSCLC) remain largely unknown. Here we report that the levels of EIF4G1 expression are much higher in NSCLC cell lines and tumor tissues than those in the normal lung cells and adjacent normal tissues from the same patients. Using shRNA to knock down EIF4G1 expression stably, we found EIF4G1 required for NSCLC cell proliferation, anchorage-independent growth, migration and invasion. Furthermore, silencing of EIF4G1 induces NSCLC cell apoptosis and causes G0/G1 cell cycle arrest. To identify the partner protein network of EIF4G1 in NSCLC cells, we found that Ubiquitin-specific protease 10 (USP10) can directly interacts with EIF4G1, while acting as a negative regulator for EIF4G1-mediated functions. Together, our results indicate that EIF4G1 functions as an oncoprotein during NSCLC development, which may represent a novel and promising therapeutic target in lung cancer.

  4. BioXyce : an engineering platform for the study of cellular systems.

    SciTech Connect

    May, Elebeoba Eni; Schiek, Richard Louis

    2008-11-01

    Researchers use constructs from the field of electrical engineering for the modeling and analysis of biological systems, but few exploit parallels between electrical and biological circuits for simulation purposes. The authors discuss the development of BioXyce, a circuit-based biological simulation platform that uses Xyce, a large-scale electrical circuit simulator, as its simulation engine. BioXyce is capable of simulating whole-cell and multicellular systems. Simulation results for the central metabolism in Escherichia coli K12 and cellular differentiation in Drosophila sp. are presented.

  5. Cytosolic Iron-Sulfur Cluster Assembly (CIA) System: Factors, Mechanism, and Relevance to Cellular Iron Regulation*

    PubMed Central

    Sharma, Anil K.; Pallesen, Leif J.; Spang, Robert J.; Walden, William E.

    2010-01-01

    FeS cluster biogenesis is an essential process in virtually all forms of life. Complex protein machineries that are conserved from bacteria through higher eukaryotes facilitate assembly of the FeS cofactor in proteins. In the last several years, significant strides have been made in our understanding of FeS cluster assembly and the functional overlap of this process with cellular iron homeostasis. This minireview summarizes the present understanding of the cytosolic iron-sulfur cluster assembly (CIA) system in eukaryotes, with a focus on information gained from studies in budding yeast and mammalian systems. PMID:20522543

  6. Cytosolic iron-sulfur cluster assembly (CIA) system: factors, mechanism, and relevance to cellular iron regulation.

    PubMed

    Sharma, Anil K; Pallesen, Leif J; Spang, Robert J; Walden, William E

    2010-08-27

    FeS cluster biogenesis is an essential process in virtually all forms of life. Complex protein machineries that are conserved from bacteria through higher eukaryotes facilitate assembly of the FeS cofactor in proteins. In the last several years, significant strides have been made in our understanding of FeS cluster assembly and the functional overlap of this process with cellular iron homeostasis. This minireview summarizes the present understanding of the cytosolic iron-sulfur cluster assembly (CIA) system in eukaryotes, with a focus on information gained from studies in budding yeast and mammalian systems.

  7. The evolution of early cellular systems viewed through the lens of biological interactions

    PubMed Central

    Poole, Anthony M.; Lundin, Daniel; Rytkönen, Kalle T.

    2015-01-01

    The minimal cell concept represents a pragmatic approach to the question of how few genes are required to run a cell. This is a helpful way to build a parts-list, and has been more successful than attempts to deduce a minimal gene set for life by inferring the gene repertoire of the last universal common ancestor, as few genes trace back to this hypothetical ancestral state. However, the study of minimal cellular systems is the study of biological outliers where, by practical necessity, coevolutionary interactions are minimized or ignored. In this paper, we consider the biological context from which minimal genomes have been removed. For instance, some of the most reduced genomes are from endosymbionts and are the result of coevolutionary interactions with a host; few such organisms are “free-living.” As few, if any, biological systems exist in complete isolation, we expect that, as with modern life, early biological systems were part of an ecosystem, replete with organismal interactions. We favor refocusing discussions of the evolution of cellular systems on processes rather than gene counts. We therefore draw a distinction between a pragmatic minimal cell (an interesting engineering problem), a distributed genome (a system resulting from an evolutionary transition involving more than one cell) and the looser coevolutionary interactions that are ubiquitous in ecosystems. Finally, we consider the distributed genome and coevolutionary interactions between genomic entities in the context of early evolution. PMID:26539175

  8. Cleavage of Eukaryotic Translation Initiation Factor 4G by Exogenously Added Hybrid Proteins Containing Poliovirus 2Apro in HeLa Cells: Effects on Gene Expression

    PubMed Central

    Novoa, Isabel; Carrasco, Luis

    1999-01-01

    Efficient cleavage of both forms of eukaryotic initiation factor 4G (eIF4G-1 and eIF4G-2) has been achieved in HeLa cells by incubation with hybrid proteins containing poliovirus 2Apro. Entry of these proteins into cells is promoted by adenovirus particles. Substantial levels of ongoing translation on preexisting cellular mRNAs still continue for several hours after eIF4G degradation. Treatment of control HeLa cells with hypertonic medium causes an inhibition of translation that is reversed upon restoration of cells to normal medium. Protein synthesis is not restored in cells lacking intact eIF4G after hypertonic treatment. Notably, induction of synthesis of heat shock proteins still occurs in cells pretreated with poliovirus 2Apro, suggesting that transcription and translation of these mRNAs takes place even in the presence of cleaved eIF4G. Finally, the synthesis of luciferase was examined in a HeLa cell line bearing the luciferase gene under control of a tetracycline-regulated promoter. Transcription of the luciferase gene and transport of the mRNA to the cytoplasm occurs at control levels in eIF4G-deficient cells. However, luciferase synthesis is strongly inhibited in these cells. These findings indicate that intact eIF4G is necessary for the translation of mRNAs not engaged in translation with the exception of heat shock mRNAs but is not necessary for the translation of mRNAs that are being translated. PMID:10082510

  9. Mobile Applications and 4G Wireless Networks: A Framework for Analysis

    ERIC Educational Resources Information Center

    Yang, Samuel C.

    2012-01-01

    Purpose: The use of mobile wireless data services continues to increase worldwide. New fourth-generation (4G) wireless networks can deliver data rates exceeding 2 Mbps. The purpose of this paper is to develop a framework of 4G mobile applications that utilize such high data rates and run on small form-factor devices. Design/methodology/approach:…

  10. Feeding behavior of Aplysia: a model system for comparing cellular mechanisms of classical and operant conditioning.

    PubMed

    Baxter, Douglas A; Byrne, John H

    2006-01-01

    Feeding behavior of Aplysia provides an excellent model system for analyzing and comparing mechanisms underlying appetitive classical conditioning and reward operant conditioning. Behavioral protocols have been developed for both forms of associative learning, both of which increase the occurrence of biting following training. Because the neural circuitry that mediates the behavior is well characterized and amenable to detailed cellular analyses, substantial progress has been made toward a comparative analysis of the cellular mechanisms underlying these two forms of associative learning. Both forms of associative learning use the same reinforcement pathway (the esophageal nerve, En) and the same reinforcement transmitter (dopamine, DA). In addition, at least one cellular locus of plasticity (cell B51) is modified by both forms of associative learning. However, the two forms of associative learning have opposite effects on B51. Classical conditioning decreases the excitability of B51, whereas operant conditioning increases the excitability of B51. Thus, the approach of using two forms of associative learning to modify a single behavior, which is mediated by an analytically tractable neural circuit, is revealing similarities and differences in the mechanisms that underlie classical and operant conditioning.

  11. DNA Mismatch Repair System: Repercussions in Cellular Homeostasis and Relationship with Aging

    PubMed Central

    Conde-Pérezprina, Juan Cristóbal; León-Galván, Miguel Ángel; Konigsberg, Mina

    2012-01-01

    The mechanisms that concern DNA repair have been studied in the last years due to their consequences in cellular homeostasis. The diverse and damaging stimuli that affect DNA integrity, such as changes in the genetic sequence and modifications in gene expression, can disrupt the steady state of the cell and have serious repercussions to pathways that regulate apoptosis, senescence, and cancer. These altered pathways not only modify cellular and organism longevity, but quality of life (“health-span”). The DNA mismatch repair system (MMR) is highly conserved between species; its role is paramount in the preservation of DNA integrity, placing it as a necessary focal point in the study of pathways that prolong lifespan, aging, and disease. Here, we review different insights concerning the malfunction or absence of the DNA-MMR and its impact on cellular homeostasis. In particular, we will focus on DNA-MMR mechanisms regulated by known repair proteins MSH2, MSH6, PMS2, and MHL1, among others. PMID:23213348

  12. Synchronization, TIGoRS, and Information Flow in Complex Systems: Dispositional Cellular Automata.

    PubMed

    Sulis, William H

    2016-04-01

    Synchronization has a long history in physics where it refers to the phase matching of two identical oscillators. This notion has been extensively studied in physics as well as in biology, where it has been applied to such widely varying phenomena as the flashing of fireflies and firing of neurons in the brain. Human behavior, however, may be recurrent but it is not oscillatory even though many physiological systems do exhibit oscillatory tendencies. Moreover, much of human behaviour is collaborative and cooperative, where the individual behaviours may be distinct yet contemporaneous (if not simultaneous) and taken collectively express some functionality. In the context of behaviour, the important aspect is the repeated co-occurrence in time of behaviours that facilitate the propagation of information or of functionality, regardless of whether or not these behaviours are similar or identical. An example of this weaker notion of synchronization is transient induced global response synchronization (TIGoRS). Previous work has shown that TIGoRS is a ubiquitous phenomenon among complex systems, enabling them to stably parse environmental transients into salient units to which they stably respond. This leads to the notion of Sulis machines, which emergently generate a primitive linguistic structure through their dynamics. This article reviews the notion of TIGoRS and its expression in several complex systems models including tempered neural networks, driven cellular automata and cocktail party automata. The emergent linguistics of Sulis machines are discussed. A new class of complex systems model, the dispositional cellular automaton is introduced. A new metric for TIGoRS, the excess synchronization, is introduced and applied to the study of TIGoRS in dispositional cellular automata. It is shown that these automata exhibit a nonlinear synchronization response to certain perturbing transients. PMID:27033136

  13. Synchronization, TIGoRS, and Information Flow in Complex Systems: Dispositional Cellular Automata.

    PubMed

    Sulis, William H

    2016-04-01

    Synchronization has a long history in physics where it refers to the phase matching of two identical oscillators. This notion has been extensively studied in physics as well as in biology, where it has been applied to such widely varying phenomena as the flashing of fireflies and firing of neurons in the brain. Human behavior, however, may be recurrent but it is not oscillatory even though many physiological systems do exhibit oscillatory tendencies. Moreover, much of human behaviour is collaborative and cooperative, where the individual behaviours may be distinct yet contemporaneous (if not simultaneous) and taken collectively express some functionality. In the context of behaviour, the important aspect is the repeated co-occurrence in time of behaviours that facilitate the propagation of information or of functionality, regardless of whether or not these behaviours are similar or identical. An example of this weaker notion of synchronization is transient induced global response synchronization (TIGoRS). Previous work has shown that TIGoRS is a ubiquitous phenomenon among complex systems, enabling them to stably parse environmental transients into salient units to which they stably respond. This leads to the notion of Sulis machines, which emergently generate a primitive linguistic structure through their dynamics. This article reviews the notion of TIGoRS and its expression in several complex systems models including tempered neural networks, driven cellular automata and cocktail party automata. The emergent linguistics of Sulis machines are discussed. A new class of complex systems model, the dispositional cellular automaton is introduced. A new metric for TIGoRS, the excess synchronization, is introduced and applied to the study of TIGoRS in dispositional cellular automata. It is shown that these automata exhibit a nonlinear synchronization response to certain perturbing transients.

  14. Nature and Development of Membrane Systems in Food Vacuoles of Cellular Slime Molds Predatory upon Bacteria.

    PubMed

    Hohl, H R

    1965-09-01

    Hohl, Hans R. (University of Hawaii, Honolulu). Nature and development of membrane systems in food vacuoles of cellular slime molds predatory upon bacteria. J. Bacteriol. 90:755-765. 1965.-During the digestion of bacteria by the myxamoebae of cellular slime molds, systems of concentric lamellae begin to appear within the food vacuoles. Each constituent lamella is a unit membrane of 75 to 85 A thickness. A study of these lamellae in Dictyostelium discoideum and Polysphondylium pallidum reveals that most of them do not represent original membranes of the ingested bacteria but are formed mainly in two ways. (i) After swelling and partial digestion of the bacteria, the first membranes appear adjacent to pre-existing membranes, e.g., the membrane lining the food vacuole and the cytoplasmic membrane surrounding the bacterium. Progressive addition of lamellae leads to the formation of the systems of concentric lamellae. (ii) After digestion of the bacteria has proceeded to a high degree, the concentric lamellae are formed spontaneously from clouds of amorphous material through condensation and orientation of precursor material. The study shows that, in biological systems, unit membranes may be formed from amorphous material through template action of pre-existing membranes, and does not necessarily involve fusion of membrane-bound vesicles.

  15. Propagation experiment of COMETS Ka/Q-band communication link for future satellite cellular system

    NASA Technical Reports Server (NTRS)

    Hase, Yoshihiro

    1995-01-01

    Mobile/Personal Satellite Communication Systems in L/S-bands are going into the operational phase. In the future, they will be operated in much higher frequency bands, for example in Ka-band, because the available bandwidth in L-band is limited. Systems with large on-board antennas in higher frequencies allow the same configuration as terrestrial cellular radio systems, since the on-board antennas will have many small spot beams. This may be true especially in a low earth orbit system such as Teledesic, which will use Ka-band. The most important parameter of Satellite Cellular may be cell size, that is, a diameter of the spot beam. A system designer needs the local correlation data in a cell and the size of the correlative area. On the other hand, the most significant difficulty of Ka and higher band systems is the countermeasure to rain attenuation. Many-cell systems can manage the limited power of on-board transponders by controlling output power of each beam depending on the rain attenuation of each cell. If the cell size is equal to the correlative area, the system can probably achieve the maximum performance. Propagation data of Ka and higher band obtained in the past shows a long term cumulative feature and link availability, but do not indicate the correlative area. The Japanese COMETS satellite, which will be launched in February 1997, has transponders in Ka and Q-band. The CRL is planning to measure the correlative area using 21 GHz and 44 GHz CW transmissions from the COMETS.

  16. [Evaluation of the state of systemic and local cellular immunity using loading tests].

    PubMed

    Stefani, A V; Mikhu, I Ia; Khavkin, A I

    1993-01-01

    Local and systemic cellular immunity parameters of the blood and gastrointestinal mucosa were studied in 165 children suffering from chronic gastritis, duodenitis, celiac, secondary malabsorption syndrome, and phosphate diabetes by spontaneous E-RFC method with a number of loading tests in vitro. Thymalin, theophylline, cold incubation were used. Three types of T lymphocyte response were distinguished: the hypoergic, resistant, and hyperergic. To make the interpretation of the findings easier, coefficients were calculated for each type of response of the blood and gastrointestinal mucosa immunocompetent cells.

  17. In Silico Modeling of the Immune System: Cellular and Molecular Scale Approaches

    PubMed Central

    Belfiore, Mariagrazia; Aricò, Giuseppina; Ronsisvalle, Simone

    2014-01-01

    The revolutions in biotechnology and information technology have produced clinical data, which complement biological data. These data enable detailed descriptions of various healthy and diseased states and responses to therapies. For the investigation of the physiology and pathology of the immune responses, computer and mathematical models have been used in the last decades, enabling the representation of biological processes. In this modeling effort, a major issue is represented by the communication between models that work at cellular and molecular level, that is, multiscale representation. Here we sketch some attempts to model immune system dynamics at both levels. PMID:24804217

  18. Development of a Sox2 reporter system modeling cellular heterogeneity in glioma

    PubMed Central

    Stoltz, Kevin; Sinyuk, Maksim; Hale, James S.; Wu, Qiulian; Otvos, Balint; Walker, Kiera; Vasanji, Amit; Rich, Jeremy N.; Hjelmeland, Anita B.; Lathia, Justin D.

    2015-01-01

    Background Malignant gliomas are complex systems containing a number of factors that drive tumor initiation and progression, including genetic aberrations that lead to extensive cellular heterogeneity within the neoplastic compartment. Mouse models recapitulate these genetic aberrations, but readily observable heterogeneity remains challenging. Methods To interrogate cellular heterogeneity in mouse glioma models, we utilized a replication-competent avian sarcoma-leukosis virus long terminal repeat with splice acceptor/tumor virus A (RCAS-tva) system to generate spontaneous mouse gliomas that contained a Sox2-enhanced green fluorescent protein (EGFP) reporter. Glial fibrillary acidic protein-tva mice were crossed with Sox2–EGFP mice, and tumors were initiated that contained a subpopulation of Sox2–EGFP-high cells enriched for tumor-initiating cell properties such as self-renewal, multilineage differentiation potential, and perivascular localization. Results Following implantation into recipient mice, Sox2–EGFP-high cells generated tumors containing Sox2–EGFP-high and Sox2–EGFP-low cells. Kinomic analysis of Sox2–EGFP-high cells revealed activation of known glioma signaling pathways that are strongly correlated with patient survival including platelet-derived growth factor receptor beta, phosphoinositide-3 kinase, and vascular endothelial growth factor. Our functional analysis identified active feline sarcoma (Fes) signaling in Sox2–EGFP-high cells. Fes negatively correlated with glioma patient survival and was coexpressed with Sox2-positive cells in glioma xenografts and primary patient-derived tissue. Conclusions Our RCAS-tva/Sox2-EGFP model will empower closer examination of cellular heterogeneity and will be useful for identifying novel glioma pathways as well as testing preclinical treatment efficacy. PMID:25416826

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

    PubMed

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

    2016-02-19

    Precise control of biosystems requires development of materials that can dynamically change physicochemical properties. Inspired by the ability of proteins to alter their conformation to mediate function, we explored the use of DNA as molecular keys to assemble and transform colloidal nanoparticle systems. The systems consist of a core nanoparticle surrounded by small satellites, the conformation of which can be transformed in response to DNA via a toe-hold displacement mechanism. The conformational changes can alter the optical properties and biological interactions of the assembled nanosystem. Photoluminescent signal is altered by changes in fluorophore-modified particle distance, whereas cellular targeting efficiency is increased 2.5 times by changing the surface display of targeting ligands. These concepts provide strategies for engineering dynamic nanotechnology systems for navigating complex biological environments. PMID:26912892

  20. New Tools and New Biology: Recent Miniaturized Systems for Molecular and Cellular Biology

    PubMed Central

    Hamon, Morgan; Hong, Jong Wook

    2013-01-01

    Recent advances in applied physics and chemistry have led to the development of novel microfluidic systems. Microfluidic systems allow minute amounts of reagents to be processed using μm-scale channels and offer several advantages over conventional analytical devices for use in biological sciences: faster, more accurate and more reproducible analytical performance, reduced cell and reagent consumption, portability, and integration of functional components in a single chip. In this review, we introduce how microfluidics has been applied to biological sciences. We first present an overview of the fabrication of microfluidic systems and describe the distinct technologies available for biological research. We then present examples of microsystems used in biological sciences, focusing on applications in molecular and cellular biology. PMID:24305843

  1. Effect of optimal Lambertian order for cellular indoor optical wireless communication and positioning systems

    NASA Astrophysics Data System (ADS)

    Wu, Dehao; Ghassemlooy, Zabih; Zhong, Wen-De; Khalighi, Mohammad-Ali; Minh, Hoa Le; Chen, Chen; Zvanovec, Stanislav; Boucouvalas, Anthony C.

    2016-06-01

    We propose and analyze an optimized Lambertian order (OLO) of light-emitting diode for both indoor cellular optical wireless communication and positioning systems. We carry out analysis for the system consisting of a Lambertian source and a tilted optical receiver, and develop an expression for OLO for four-, six-, and nine-cell configurations. We investigate the channel characteristics including the optical path loss, impulse response, transmission bandwidth, and positioning accuracy for the proposed systems with and without OLO, showing that there is a significant improvement in the transmission bandwidth as well as the positioning accuracy when employing OLO. For example, for a four-cell configuration with the optimum Lambertian order, 99% of cumulative distribution function of the estimation errors is within the Cramer-Rao bound (CRB) accuracy of 6.7 to 26.7 cm, compared to the CRB accuracy of 12.8 to 29.7 cm for the Lambertian order of m=1.

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  3. Microfluidics-based in vivo mimetic systems for the study of cellular biology.

    PubMed

    Kim, Donghyuk; Wu, Xiaojie; Young, Ashlyn T; Haynes, Christy L

    2014-04-15

    The human body is a complex network of molecules, organelles, cells, tissues, and organs: an uncountable number of interactions and transformations interconnect all the system's components. In addition to these biochemical components, biophysical components, such as pressure, flow, and morphology, and the location of all of these interactions play an important role in the human body. Technical difficulties have frequently limited researchers from observing cellular biology as it occurs within the human body, but some state-of-the-art analytical techniques have revealed distinct cellular behaviors that occur only in the context of the interactions. These types of findings have inspired bioanalytical chemists to provide new tools to better understand these cellular behaviors and interactions. What blocks us from understanding critical biological interactions in the human body? Conventional approaches are often too naïve to provide realistic data and in vivo whole animal studies give complex results that may or may not be relevant for humans. Microfluidics offers an opportunity to bridge these two extremes: while these studies will not model the complexity of the in vivo human system, they can control the complexity so researchers can examine critical factors of interest carefully and quantitatively. In addition, the use of human cells, such as cells isolated from donated blood, captures human-relevant data and limits the use of animals in research. In addition, researchers can adapt these systems easily and cost-effectively to a variety of high-end signal transduction mechanisms, facilitating high-throughput studies that are also spatially, temporally, or chemically resolved. These strengths should allow microfluidic platforms to reveal critical parameters in the human body and provide insights that will help with the translation of pharmacological advances to clinical trials. In this Account, we describe selected microfluidic innovations within the last 5 years

  4. [Motivation and Emotional States: Structural Systemic, Neurochemical, Molecular and Cellular Mechanisms].

    PubMed

    Bazyan, A S

    2016-01-01

    The structural, systemic, neurochemical, molecular and cellular mechanisms of organization and coding motivation and emotional states are describe. The GABA and glutamatergic synaptic systems of basal ganglia form a neural network and participate in the implementation of voluntary behavior. Neuropeptides, neurohormones and paracrine neuromodulators involved in the organization of motivation and emotional states, integrated with synaptic systems, controlled by neural networks and organizing goal-directed behavior. Structural centers for united and integrated of information in voluntary and goal-directed behavior are globus pallidus. Substantia nigra pars reticulata switches the information from corticobasal networks to thalamocortical networks, induces global dopaminergic (DA) signal and organize interaction of mesolimbic and nigostriatnoy DA systems controlled by prefrontal and motor cortex. Together with the motor cortex, substantia nigra displays information in the brainstem and spinal cord to implementation of behavior. Motivation states are formed in the interaction of neurohormonal and neuropeptide systems by monoaminergic systems of brain. Emotional states are formed by monoaminergic systems of the mid-brain, where the leading role belongs to the mesolimbic DA system. The emotional and motivation state of the encoded specific epigenetic molecular and chemical pattern of neuron. PMID:27149821

  5. [Motivation and Emotional States: Structural Systemic, Neurochemical, Molecular and Cellular Mechanisms].

    PubMed

    Bazyan, A S

    2016-01-01

    The structural, systemic, neurochemical, molecular and cellular mechanisms of organization and coding motivation and emotional states are describe. The GABA and glutamatergic synaptic systems of basal ganglia form a neural network and participate in the implementation of voluntary behavior. Neuropeptides, neurohormones and paracrine neuromodulators involved in the organization of motivation and emotional states, integrated with synaptic systems, controlled by neural networks and organizing goal-directed behavior. Structural centers for united and integrated of information in voluntary and goal-directed behavior are globus pallidus. Substantia nigra pars reticulata switches the information from corticobasal networks to thalamocortical networks, induces global dopaminergic (DA) signal and organize interaction of mesolimbic and nigostriatnoy DA systems controlled by prefrontal and motor cortex. Together with the motor cortex, substantia nigra displays information in the brainstem and spinal cord to implementation of behavior. Motivation states are formed in the interaction of neurohormonal and neuropeptide systems by monoaminergic systems of brain. Emotional states are formed by monoaminergic systems of the mid-brain, where the leading role belongs to the mesolimbic DA system. The emotional and motivation state of the encoded specific epigenetic molecular and chemical pattern of neuron.

  6. Microfluidics-Based in Vivo Mimetic Systems for the Study of Cellular Biology

    PubMed Central

    2015-01-01

    Conspectus The human body is a complex network of molecules, organelles, cells, tissues, and organs: an uncountable number of interactions and transformations interconnect all the system’s components. In addition to these biochemical components, biophysical components, such as pressure, flow, and morphology, and the location of all of these interactions play an important role in the human body. Technical difficulties have frequently limited researchers from observing cellular biology as it occurs within the human body, but some state-of-the-art analytical techniques have revealed distinct cellular behaviors that occur only in the context of the interactions. These types of findings have inspired bioanalytical chemists to provide new tools to better understand these cellular behaviors and interactions. What blocks us from understanding critical biological interactions in the human body? Conventional approaches are often too naïve to provide realistic data and in vivo whole animal studies give complex results that may or may not be relevant for humans. Microfluidics offers an opportunity to bridge these two extremes: while these studies will not model the complexity of the in vivo human system, they can control the complexity so researchers can examine critical factors of interest carefully and quantitatively. In addition, the use of human cells, such as cells isolated from donated blood, captures human-relevant data and limits the use of animals in research. In addition, researchers can adapt these systems easily and cost-effectively to a variety of high-end signal transduction mechanisms, facilitating high-throughput studies that are also spatially, temporally, or chemically resolved. These strengths should allow microfluidic platforms to reveal critical parameters in the human body and provide insights that will help with the translation of pharmacological advances to clinical trials. In this Account, we describe selected microfluidic innovations within the

  7. Development of novel monoclonal antibody 4G8 against swine leukocyte antigen class I alpha chain.

    PubMed

    Tang, Wei-Ran; Kiyokawa, Nobutaka; Eguchi, Tomoko; Matsui, Jun; Takenouchi, Hisami; Honma, Daisuk; Yasue, Hiroshi; Enosawa, Shin; Mimori, Kenichi; Itagaki, Mitsuko; Taguchi, Tomoko; Katagiri, Yohko U; Okita, Hajime; Amemiya, Hiroshi; Fujimoto, Junichiro

    2004-06-01

    A mouse monoclonal antibody (MAb) was generated against swine leukocyte antigen (SLA) class I alpha chain. A newly developed series of MAb clones that react with pan leukocytes were selected and tested by immuno-histochemistry using SLA class I alpha chain expressing Cos-7 cells. Among them, MAb 4G8 was characterized by the following features: (1) 4G8 reacted with Cos-7 cells transfected with SLA class I alpha chain from the d haplotype, (2) 4G8 recognized epitopes that were different from those of commercially available anti-SLA class I MAbs 74-11-10 and PT85A, and (3) 4G8 could be used to immunostain frozen sections of thymus, spleen, lymph node, kidney, and liver tissues with good results.

  8. A rapid microfluidic switching system for analysis at the single cellular level.

    PubMed

    Yamada, Akira; Katanosaka, Yuki; Mohri, Satoshi; Naruse, Keiji

    2009-12-01

    Analysis of cellular responses to chemicals at high spatiotemporal resolution is required for precise understanding of intracellular signal transduction. Here, we demonstrated a novel method for applying different solutions to a part of or all of a cell at high spatiotemporal resolution. We fabricated a microfluidic device using polydimethylsiloxane, and the sharp interface between the two solution streams flowing in the channel was used for the application of different solutions. We constructed a computer-controlled system to control the interface movement precisely, rapidly, and reproducibly during positioning, and spatial and temporal resolutions attained were 1.6 mum and 189 ms, respectively. We then applied the present system to the analysis of intracellular responses to chemicals. We were able to measure [Ca (2+)] (i) increases within 500 ms, when one laminar stream covered a part of the cell. This method can be used as a generic platform to investigate responses against drugs at the single cell level.

  9. Cellular ferroelectrets for electroactive polymer hybrid systems: soft matter integrated devices with advanced functionality

    NASA Astrophysics Data System (ADS)

    Schwödiauer, Reinhard; Graz, Ingrid; Kaltenbrunner, Martin; Keplinger, Christoph; Bartu, Petr; Buchberger, Gerda; Ortwein, Christoph; Bauer, Siegfried

    2008-03-01

    Thin polymer foams with a closed cell void-structure can be internally charged by silent or partial discharges within the voids. The resulting material, which carries positive and negative charges on the internal void surfaces is called a ferroelectret. Ferroelectrets behave like typical ferroelectrics, hence they provide a novel class of ferroic materials. The soft foams are strongly piezoelectric in the 3-direction, but show negligible piezoelectric response in the transverse direction. This, together with a very low pyroelectric coefficient, make ferroelectrets highly suitable for flexible electroactive transducer element which can be integrated in thin bendable organic electronic devices. Here we describe some fundamental characteristics of cellular ferroelectrets and present a number of promising examples for a possible combination with various functional polymer systems. Our examples focus on flexible ferroelectret field-effect transistor systems for large-area sensor skins and microphones, flexible large-array position detectors (touchpad), and stretchable large-array pressure sensors.

  10. Flux-driven cellular precipitation in open system to form porous Cu3Sn

    NASA Astrophysics Data System (ADS)

    Gusak, Andriy M.; Chen, Chih; Tu, K. N.

    2016-05-01

    Recently, a new morphology of porous Cu3Sn with lamellar structure is observed. Several possible explanations of the formation are proposed and compared. The most reasonable one seems to be the one based on a theory of flux-driven cellular precipitation in open system. Outflux of Sn from Cu6Sn5 generates simultaneously supersaturation with vacancies and with copper leading to the eutectoid-like transformation β → α + γ (where γ is void). The transformation is complete due to a complete outflux of Sn from the Cu6Sn5 phase. Simple formulae for prediction of the lamellar structure parameters and the propagation velocity are obtained and compared reasonably with experimental data. The suggested model can be interpreted as one more case of the flux-driven phase transformations in open systems.

  11. TransportDB: a relational database of cellular membrane transport systems.

    PubMed

    Ren, Qinghu; Kang, Katherine H; Paulsen, Ian T

    2004-01-01

    TransportDB (http://www.membranetransport.org) is a relational database designed for describing the predicted cellular membrane transport proteins in organisms whose complete genome sequences are available. For each organism, the complete set of membrane transport systems was identified and classified into different types and families according to putative membrane topology, protein family, bioenergetics and substrate specificities. Web pages were created to provide user-friendly interfaces to easily access, query and download the data. Additional features, such as a BLAST search tool against known transporter protein sequences, comparison of transport systems from different organisms and phylogenetic trees of individual transporter families are also provided. TransportDB will be regularly updated with data obtained from newly sequenced genomes.

  12. Crystal structure of an eIF4G-like protein from Danio rerio

    SciTech Connect

    Bae, Euiyoung; Bitto, Eduard; Bingman, Craig A.; McCoy, Jason G.; Wesenberg, Gary E.; Phillips, Jr., George N.

    2012-04-18

    The gene LOC 91917 Danio rerio (zebrafish) encodes a protein annotated in the UniProt knowledgebase as the middle domain of eukaryotic initiation factor 4G domain containing protein b (MIF4Gdb). Its molecular weight is 25.8 kDa, and it comprises 222 amino acid residues. BLAST searches revealed homologues of D. rerio MIF4Gdb in many eukaryotes including humans. The homologue sand MIF4Gdb were identified as members of the Pfam family, MIF4G (PF2854), which is named after the middle domain of eukaryotic initiation factor 4G (eIF4G). eIF4G is a component of eukaryotic translational initiation complex, and contains binding sites for other initiation factors, suggesting its critical role in translational initiation. The MIF4G domain also occurs in several other proteins involved in RNA metabolism, including the Nonsense-mediated mRNA decay 2 protein (NMD2/UPF2), and the nuclear cap-binding protein 80-kDa subunit (CBP80). Sequence and structure analysis of the MIF4G domains in many proteins indicate that the domain assumes an all helical fold and has tandem repeated motifs. The zebrafish protein described here has homology to domains of other proteins variously referred to as NIC-containing proteins (NMD2, eIF4G, CBP80). The biological function of D. rerio MIF4Gdb has not yet been experimentally characterized, and the annotation is based on amino acid sequence comparison. D. rerio MIF4Gdb did not share more than 25% sequence identity with any protein for which the three-dimensional structure is known and was selected as a target for structure determination by the Center for Eukaryotic Structural Genomics (CESG). Here, they report the crystal structure of D. rerio MIF4Gdb (UniGene code Dr.79360, UniProt code Q5EAQ1, CESG target number GO.79294).

  13. T-4G Simulator and T-4 Ground Training Devices in USAF Undergraduate Pilot Training.

    ERIC Educational Resources Information Center

    Woodruff, Robert R.; Smith, James F.

    The objective of the project was to investigate the utility of using an A/F37A-T4G T-37 flight simulator within the context of Air Force undergraduate pilot training. Twenty-one subjects, selected from three undergraduate pilot training classes, were given contact flight training in a TP4G/EPT simulator before going to T-37 aircraft for further…

  14. Consideration of Remote Support System for Deaf-Blind Persons using Body-Braille and Cellular Phones

    NASA Astrophysics Data System (ADS)

    Ohtsuka, Satoshi; Sasaki, Nobuyuki; Hasegawa, Sadao; Harakawa, Tetsumi

    New type of remote support system for handicapped persons is proposed in this paper. Body-Braille system is consisted of six small vibrators which have been used in cellular phones. And this system is put on the any part of human body. Supports method are similar to usual Braille, and the impaired persons acquire the communication or information about circumferences by reading the vibration patterns on the skin which are consisted of six on-off vibrations of small motors. This paper has shown the remote support system and experiment in which Body-Braille system and cellular phone are connected to realize its functions. The deaf-blind persons have cellular phone with small camera, and remote supporter can get the necessary information by receiving images from the phone, and then send recognition result to subject using Body-Braille. From the results of the experiment, proposed support system has been clarified to be effective.

  15. Lipidomics: a mass spectrometry based, systems level analysis of cellular lipids

    PubMed Central

    Ivanova, Pavlina T.; Milne, Stephen B.; Myers, David S.; Brown, H. Alex

    2009-01-01

    Lipidomics is a logical outcome of the history and traditions of lipid biochemistry and advances in mass spectrometry are at the heart of a renaissance in understanding the roles of lipids in cellular functions. Our desire to understand the complexity of lipids in biology has led to new techniques that allow us to identify over 1000 phospholipids in mammalian cell types and tissues. Improvements in chromatographic separation and mass spectrometry have positioned us to determine not only the lipid composition (i.e., parts list) of cells and tissues, but also address questions regarding lipid substrates and products that previously overwhelmed traditional analytical technologies. In the decade since lipidomics was conceived much of the efforts have been on new methodologies, development of computer programs to decipher the gigabytes of raw data, and struggling with the highly variable nature of biological systems where absolute quantities of a given metabolite may be less important than its relative change in concentration. It is clear that the technology is now sufficiently developed to address fundamental questions about the roles of lipids in cellular signaling and metabolic pathways. PMID:19744877

  16. Adaptive Cellular Stress Pathways as Therapeutic Targets of Dietary Phytochemicals: Focus on the Nervous System

    PubMed Central

    Jo, Dong-Gyu; Park, Daeui; Chung, Hae Young

    2014-01-01

    During the past 5 decades, it has been widely promulgated that the chemicals in plants that are good for health act as direct scavengers of free radicals. Here we review evidence that favors a different hypothesis for the health benefits of plant consumption, namely, that some phytochemicals exert disease-preventive and therapeutic actions by engaging one or more adaptive cellular response pathways in cells. The evolutionary basis for the latter mechanism is grounded in the fact that plants produce natural antifeedant/noxious chemicals that discourage insects and other organisms from eating them. However, in the amounts typically consumed by humans, the phytochemicals activate one or more conserved adaptive cellular stress response pathways and thereby enhance the ability of cells to resist injury and disease. Examplesof such pathways include those involving the transcription factors nuclear factor erythroid 2-related factor 2, nuclear factor-κB, hypoxia-inducible factor 1α, peroxisome proliferator-activated receptor γ, and forkhead box subgroup O, as well as the production and action of trophic factors and hormones. Translational research to develop interventions that target these pathways may lead to new classes of therapeutic agents that act by stimulating adaptive stress response pathways to bolster endogenous defenses against tissue injury and disease. Because neurons are particularly sensitive to potentially noxious phytochemicals, we focus on the nervous system but also include findings from other cell types in which actions of phytochemicals on specific signal transduction pathways have been more thoroughly studied. PMID:24958636

  17. Adaptive cellular stress pathways as therapeutic targets of dietary phytochemicals: focus on the nervous system.

    PubMed

    Lee, Jaewon; Jo, Dong-Gyu; Park, Daeui; Chung, Hae Young; Mattson, Mark P

    2014-07-01

    During the past 5 decades, it has been widely promulgated that the chemicals in plants that are good for health act as direct scavengers of free radicals. Here we review evidence that favors a different hypothesis for the health benefits of plant consumption, namely, that some phytochemicals exert disease-preventive and therapeutic actions by engaging one or more adaptive cellular response pathways in cells. The evolutionary basis for the latter mechanism is grounded in the fact that plants produce natural antifeedant/noxious chemicals that discourage insects and other organisms from eating them. However, in the amounts typically consumed by humans, the phytochemicals activate one or more conserved adaptive cellular stress response pathways and thereby enhance the ability of cells to resist injury and disease. Examplesof such pathways include those involving the transcription factors nuclear factor erythroid 2-related factor 2, nuclear factor-κB, hypoxia-inducible factor 1α, peroxisome proliferator-activated receptor γ, and forkhead box subgroup O, as well as the production and action of trophic factors and hormones. Translational research to develop interventions that target these pathways may lead to new classes of therapeutic agents that act by stimulating adaptive stress response pathways to bolster endogenous defenses against tissue injury and disease. Because neurons are particularly sensitive to potentially noxious phytochemicals, we focus on the nervous system but also include findings from other cell types in which actions of phytochemicals on specific signal transduction pathways have been more thoroughly studied. PMID:24958636

  18. Physiological mechanisms in plant growth models: do we need a supra-cellular systems biology approach?

    PubMed

    Poorter, Hendrik; Anten, Niels P R; Marcelis, Leo F M

    2013-09-01

    In the first part of this paper, we review the extent to which various types of plant growth models incorporate ecophysiological mechanisms. Many growth models have a central role for the process of photosynthesis; and often implicitly assume C-gain to be the rate-limiting step for biomass accumulation. We subsequently explore the extent to which this assumption actually holds and under what condition constraints on growth due to a limited sink strength are likely to occur. By using generalized dose-response curves for growth with respect to light and CO₂, models can be tested against a benchmark for their overall performance. In the final part, a call for a systems approach at the supra-cellular level is made. This will enable a better understanding of feedbacks and trade-offs acting on plant growth and its component processes. Mechanistic growth models form an indispensable element of such an approach and will, in the end, provide the link with the (sub-)cellular approaches that are yet developing. Improved insight will be gained if model output for the various physiological processes and morphological variables ('virtual profiling') is compared with measured correlation networks among these processes and variables. Two examples of these correlation networks are presented.

  19. Genetic controls and cellular behaviors in branching morphogenesis of the renal collecting system

    PubMed Central

    Costantini, Frank

    2012-01-01

    The mammalian kidney, which at maturity contains thousands of nephrons joined to a highly branched collecting duct system, is an important model system for studying the development of a complex organ. Furthermore, congenital anomalies of the kidney and urinary tract, often resulting from defects in ureteric bud branching morphogenesis, are relatively common human birth defects. Kidney development is initiated by interactions between the nephric duct and the metanephric mesenchyme, leading to the outgrowth and repeated branching of the ureteric bud epithelium, which gives rise to the entire renal collecting duct (CD) system. Meanwhile, signals from the ureteric bud induce the mesenchyme cells to form the nephron epithelia. This review focuses on development of the collecting duct system, with emphasis on the mouse as an experimental system. The major topics covered include the origin and development of the nephric duct, formation of the ureteric bud, branching morphogenesis of the ureteric bud and elongation of the collecting ducts. The signals, receptors, transcription factors and other regulatory molecules implicated in these processes are discussed. In addition, our current knowledge of cellular behaviors that are controlled by these genes and underlie development of the collecting system is reviewed. PMID:22942910

  20. Cellular association and assembly of a multi-stage delivery system

    PubMed Central

    Serda, Rita E.; Mack, Aaron; Pulikkathara, Merlyn; Zaske, Ana Maria; Chiappini, Ciro; Fakhoury, Jean; Webb, Douglas; Godin, Biana; Conyers, Jodie L.; Liu, XueWu; Bankson, James A.; Ferrari, Mauro

    2010-01-01

    The realization that blood-borne delivery systems must overcome a multiplicity of biological barriers has led to the fabrication of a multi-stage delivery system (MDS) designed to temporally release successive stages of particles or agents to conquer sequential barriers with a goal of enhancing delivery of therapeutic and diagnostic agents to the target site. In its simplest appearance, the MDS is comprised of stage one porous silicon microparticles that function as carriers of second stage nanoparticles. In this study, cellular uptake of non-targeted discoidal silicon microparticles by macrophages was confirmed by electron and atomic force microscopy (AFM). Using SPIONs as a model of secondary nanoparticles, successful loading of the porous matrix of silicon microparticles was achieved and retention of the nanoparticles was enhanced by aminosilylation of the loaded microparticle with 3-aminopropyltriethoxysilane. The impact of silane concentration and reaction time on the nature of the silane polymer on porous silicon was investigated by AFM and X-ray photoelectron microscopy. Tissue samples from mice intravenously administered the MDS supported co-localization of silicon microparticles and SPIONs across various tissues with enhanced SPION release in spleen, compared to liver and lungs, and enhanced retention of SPIONs following silane capping of the MDS. Phantom models of the SPION-loaded MDS displayed negative contrast in magnetic resonance images. In addition to forming a cap over the silicon pores, the silane polymer provided free amines for antibody conjugation to the microparticles, with both VEGFR-2 and PECAM specific antibodies leading to enhanced endothelial association. This study demonstrates assembly and cellular association of a multi-particle delivery system that is bio-molecularly targeted and has potential for applications in biological imaging. PMID:20517877

  1. On the Use of FOSS4G in Land Cover Fraction Estimation with Unmixing Algorithms

    NASA Astrophysics Data System (ADS)

    Kumar, U.; Milesi, C.; Raja, K.; Ganguly, S.; Wang, W.; Zhang, G.; Nemani, R. R.

    2014-12-01

    The popularity and usage of FOSS4G (FOSS for Geoinformatics) has increased drastically in the last two decades with increasing benefits that facilitate spatial data analysis, image processing, graphics and map production, spatial modeling and visualization. The objective of this paper is to use FOSS4G to implement and perform a quantitative analysis of three different unmixing algorithms: Constraint Least-Square (CLS), Unconstraint Least-Square, and Orthogonal Subspace Projection to estimate land cover (LC) fraction estimates from RS data. The LC fractions obtained by unmixing of mixed pixels represent mixture of more than one class per pixel rendering more accurate LC abundance estimates. The algorithms were implemented in C++ programming language with OpenCV package (http://opencv.org/) and boost C++ libraries (www.boost.org) in the NASA Earth Exchange at the NASA Advanced Supercomputing Facility. GRASS GIS was used for visualization of results and statistical analysis was carried in R in a Linux system environment. A set of global endmembers for substrate, vegetation and dark objects were used to unmix the data using the three algorithms and were compared with Singular Value decomposition unmixed outputs available in ENVI image processing software. First, computer simulated data of different signal to noise ratio were used to evaluate the algorithms. The second set of experiments was carried out in an agricultural set-up with a spectrally diverse collection of 11 Landsat-5 scenes (acquired in 2008) for an agricultural setup in Frenso, California and the ground data were collected on those specific dates when the satellite passed through the site. Finally, in the third set of experiments, a pair of coincident clear sky Landsat and World View 2 data for an urbanized area of San Francisco were used to assess the algorithm. Validation of the results using descriptive statistics, correlation coefficient (cc), RMSE, boxplot and bivariate distribution function

  2. The anatomical and cellular basis of immune surveillance in the central nervous system.

    PubMed

    Ransohoff, Richard M; Engelhardt, Britta

    2012-09-01

    The central nervous system (CNS) comprises the brain, spinal cord, optic nerves and retina, and contains post-mitotic, delicate cells. As the rigid coverings of the CNS render swelling dangerous and destructive, inflammatory reactions must be carefully controlled in CNS tissues. Nevertheless, effector immune responses that protect the host during CNS infection still occur in the CNS. Here, we describe the anatomical and cellular basis of immune surveillance in the CNS, and explain how this shapes the unique immunology of these tissues. The Review focuses principally on insights gained from the study of autoimmune responses in the CNS and to a lesser extent on models of infectious disease. Furthermore, we propose a new model to explain how antigen-specific T cell responses occur in the CNS.

  3. Pathogens penetrating the central nervous system: infection pathways and the cellular and molecular mechanisms of invasion.

    PubMed

    Dando, Samantha J; Mackay-Sim, Alan; Norton, Robert; Currie, Bart J; St John, James A; Ekberg, Jenny A K; Batzloff, Michael; Ulett, Glen C; Beacham, Ifor R

    2014-10-01

    The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis.

  4. Designing a mathematical model for integrating dynamic cellular manufacturing into supply chain system

    NASA Astrophysics Data System (ADS)

    Aalaei, Amin; Davoudpour, Hamid

    2012-11-01

    This article presents designing a new mathematical model for integrating dynamic cellular manufacturing into supply chain system with an extensive coverage of important manufacturing features consideration of multiple plants location, multi-markets allocation, multi-period planning horizons with demand and part mix variation, machine capacity, and the main constraints are demand of markets satisfaction in each period, machine availability, machine time-capacity, worker assignment, available time of worker, production volume for each plant and the amounts allocated to each market. The aim of the proposed model is to minimize holding and outsourcing costs, inter-cell material handling cost, external transportation cost, procurement & maintenance and overhead cost of machines, setup cost, reconfiguration cost of machines installation and removal, hiring, firing and salary worker costs. Aimed to prove the potential benefits of such a design, presented an example is shown using a proposed model.

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

    PubMed

    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.

  6. Cellular Biotechnology Operations Support Systems-Fluid Dynamics Investigation (CBOSS-FDI)

    NASA Technical Reports Server (NTRS)

    2003-01-01

    Aboard the International Space Station (ISS), the Tissue Culture Module (TCM) is the stationary bioreactor vessel in which cell cultures grow. However, for the Cellular Biotechnology Operations Support Systems-Fluid Dynamics Investigation (CBOSS-FDI), color polystyrene beads are used to measure the effectiveness of various mixing procedures. The beads are similar in size and density to human lymphoid cells. Uniform mixing is a crucial component of CBOSS experiments involving the immune response of human lymphoid cell suspensions. The goal is to develop procedures that are both convenient for the flight crew and are optimal in providing uniform and reproducible mixing of all components, including cells. The average bead density in a well mixed TCM will be uniform, with no bubbles, and it will be measured using the absorption of light. In this photograph, beads are trapped in the injection port, with bubbles forming shortly after injection.

  7. Cellular Biotechnology Operations Support Systems-Fluid Dynamics Investigation (CBOSS-FDI)

    NASA Technical Reports Server (NTRS)

    2003-01-01

    Aboard the International Space Station (ISS), the Tissue Culture Module (TCM) is the stationary bioreactor vessel in which cell cultures grow. However, for the Cellular Biotechnology Operations Support Systems-Fluid Dynamics Investigation (CBOSS-FDI), color polystyrene beads are used to measure the effectiveness of various mixing procedures. The beads are similar in size and density to human lymphoid cells. Uniform mixing is a crucial component of CBOSS experiments involving the immune response of human lymphoid cell suspensions. The goal is to develop procedures that are both convenient for the flight crew and are optimal in providing uniform and reproducible mixing of all components, including cells. The average bead density in a well mixed TCM will be uniform, with no bubbles, and it will be measured using the absorption of light. In this photograph, a TCM is shown after mixing protocols, and bubbles of various sizes can be seen.

  8. Cellular and molecular pathways of extremely-low-frequency electromagnetic field interactions with living systems

    SciTech Connect

    Tenforde, T.S.

    1992-06-01

    There is growing evidence that environmental electric and magnetic fields in the extremely-low-frequency (ELF) band below 300 Hz can influence biological functions by mechanisms that are only poorly understood at the present time. The primary objectives of this paper are to review the physical properties of ELF fields, their interactions with living systems at the tissue, cellular, and subcellular levels, and the key role of cell membranes ;in the transduction of signals from imposed ELF fields. Topics of discussion include signal-to-noise ratios for single cells and cell aggregates, resonance phenomena involving a combination of static and ELF magnetic fields, and the possible influence of ELF fields on molecular signaling pathways that involve membrane receptors and cytoplasmic second messengers.

  9. Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

    PubMed Central

    Dando, Samantha J.; Mackay-Sim, Alan; Norton, Robert; Currie, Bart J.; St. John, James A.; Ekberg, Jenny A. K.; Batzloff, Michael

    2014-01-01

    SUMMARY The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis. PMID:25278572

  10. Cellular localization of Na(+), K(+)-ATPase in the mammalian vestibular system

    NASA Technical Reports Server (NTRS)

    Kerr, T. P.

    1984-01-01

    Two different, but complementary, procedures for cellular localization of Na+, K+-ATPase in the guinea pig vestibular system were employed. One of these techniques, devised by Stirling, depends upon the well documented ability of the specific inhibitor ouabain to bind selectively to Na+,K+-ATPase, blocking catalytic activity. Microdisected vestibular tissues are incubated with tritium-labelled (3H-) ouabain, and regions with a high concentration of Na+,K+-ATPase are subsequently identified by light microscope autoradiography. A second method, originated by Ernst, detects inorganic phosphate released from an artificial substrate (nitrophenyl phosphate) by catalytic activity of the enzyme. In the presence of strontium ion, phosphate is precipitated near regions of high activity, then converted to a product which may finally be visualized in the electron microscope. This cytochemical enzymatic reaction is inhibited by ouabain.

  11. The role of time delay in adaptive cellular negative feedback systems.

    PubMed

    Lapytsko, Anastasiya; Schaber, Jörg

    2016-06-01

    Adaptation in cellular systems is often mediated by negative feedbacks, which usually come with certain time delays causing several characteristic response patterns including an overdamped response, damped or sustained oscillations. Here, we analyse generic two-dimensional delay differential equations with delayed negative feedback describing the dynamics of biochemical adaptive signal-response networks. We derive explicit thresholds and boundaries showing how time delay determines characteristic response patterns of these networks. Applying our theoretical analyses to concrete data we show that adaptation to osmotic stress in yeast is optimal in the sense of minimizing adaptation time without causing oscillatory behaviour, i.e., a critically damped response. In addition, our framework demonstrates that a slight increase of time delay in the NF-κB system might induce a switch from damped to sustained oscillatory behaviour. Thus, we demonstrate how delay differential equations can be used to explicitly study the delay in biochemical negative feedback systems. Our analysis also provides insight into how time delay may tune biological signal-response patterns and control the systems behaviour.

  12. Plasminogen activator inhibitor-1 4G/5G polymorphism, factor V Leiden, prothrombin mutations and the risk of VTE recurrence.

    PubMed

    Sundquist, Kristina; Wang, Xiao; Svensson, Peter J; Sundquist, Jan; Hedelius, Anna; Larsson Lönn, Sara; Zöller, Bengt; Memon, Ashfaque A

    2015-11-25

    Plasminogen-activator inhibitor (PAI)-1 is an important inhibitor of the plasminogen/plasmin system. PAI-1 levels are influenced by the 4G/5G polymorphism in the PAI-1 promoter. We investigated the relationship between the PAI-1 polymorphism and VTE recurrence, and its possible modification by factor V Leiden (FVL) and prothrombin (PTM) mutations. Patients (n=1,069) from the Malmö Thrombophilia Study were followed from discontinuation of anticoagulant treatment until diagnosis of VTE recurrence or the end of the study (maximum follow-up 9.8 years). One hundred twenty-seven patients (11.9 %) had VTE recurrence. PAI-1 was genotyped by TaqMan PCR. Cox regression analysis adjusted for age, sex and acquired risk factors of VTE showed no evidence of an association between PAI-1 genotype and risk of VTE recurrence in the study population as a whole. However, by including an interaction term in the analysis we showed that FVL but not PTM modified the effect of PAI-1 genotype: patients with the 4G allele plus FVL had a higher risk of VTE recurrence [hazard ratio (HR) =2.3, 95 % confidence interval (CI) =1.5-3.3] compared to patients with the 4G allele but no FVL (reference group) or FVL irrespective of PAI-1 genotype (HR=1.8, 95 % CI=1.3-2.5). Compared to reference group, 5G allele irrespective of FVL was associated with lower risk of VTE recurrence only when compared with 4G allele together with FVL. In conclusion, FVL has a modifying effect on PAI-1 polymorphism in relation to risk of VTE recurrence. The role of PAI-1 polymorphism as a risk factor of recurrent VTE may be FVL dependent.

  13. Length Scale Correlations of Cellular Microstructures in Directionally Solidified Binary System

    SciTech Connect

    Yunxue Shen

    2002-08-01

    In a cellular array, a range of primary spacing is found to be stable under given growth conditions. Since a strong coupling of solute field exists between the neighboring cells, primary spacing variation should also influence other microstructure features such as cell shape and cell length. The existence of multiple solutions is examined in this study both theoretically as well as experimentally. A theoretical model is developed that identifies and relates four important microstructural lengths, which are found to be primary spacing, tip radius, cell width and cell length. This general microstructural relationship is shown to be valid for different cells in an array as well as for other cellular patterns obtained under different growth conditions. The unique feature of the model is that the microstructure correlation does not depend on composition or growth conditions since these variables scale microstructural lengths to satisfy the relationship obtained in this study. Detailed directional solidification experimental studies have been carried out in the succinonitrile-salol system to characterize and measure these four length scales. Besides the validation of the model, experimental results showed additional scaling laws to be present. In the regime where only a cellular structure is formed, the shape of the cell, the cell tip radius and the length of the cell are all found to scale individually with the local primary spacing. The presence of multiple solutions of primary spacing is also shown to influence the cell-dendrite transition that is controlled not only by the processing variables (growth velocity, thermal gradient and composition) but also by the local cell spacing. The cell-dendrite transition was found not to be sharp, but occurred over a range of processing conditions. Two critical conditions have been identified such that only cells are present below lower critics condition, and only dendrites are formed above the upper critics condition. Between

  14. Length Scale Correlations of Cellular Microstructures in Directionally Solidified Binary System

    SciTech Connect

    Yunxue Shen

    2002-06-27

    In a cellular array, a range of primary spacing is found to be stable under given growth conditions. Since a strong coupling of solute field exists between the neighboring cells, primary spacing variation should also influence other microstructure features such as cell shape and cell length. The existence of multiple solutions is examined in this study both theoretically as well as experimentally. A theoretical model is developed that identifies and relates four important microstructural lengths, which are found to be primary spacing, tip radius, cell width and cell length. This general microstructural relationship is shown to be valid for different cells in an array as well as for other cellular patterns obtained under different growth conditions. The unique feature of the model is that the microstructure correlation does not depend on composition or growth conditions since these variables scale microstructural lengths to satisfy the relationship obtained in this study. Detailed directional solidification experimental studies have been carried out in the succinonitrile-salol system to characterize and measure these four length scales. Besides the validation of the model, experimental results showed additional scaling laws to be present. In the regime where only a cellular structure is formed, the shape of the cell, the cell tip radius and the length of the cell are all found to scale individually with the local primary spacing. The presence of multiple solutions of primary spacing is also shown to influence the cell-dendrite transition that is controlled not only by the processing variables (growth velocity, thermal gradient and composition) but also by the local cell spacing. The cell-dendrite transition was found not to be sharp, but occurred over a range of processing conditions. Two critical conditions have been identified such that only cells are present below lower critics condition, and only dendrites are formed above the upper critics condition. Between

  15. A cellular isolation system for real-time single-cell oxygen consumption monitoring

    PubMed Central

    Dragavon, Joe; Molter, Tim; Young, Cody; Strovas, Tim; McQuaide, Sarah; Holl, Mark; Zhang, Meng; Cookson, Brad; Jen, Alex; Lidstrom, Mary; Meldrum, Deirdre; Burgess, Lloyd

    2008-01-01

    The development of a cellular isolation system (CIS) that enables the monitoring of single-cell oxygen consumption rates in real time is presented. The CIS was developed through a multidisciplinary effort within the Microscale Life Sciences Center (MLSC) at the University of Washington. The system comprises arrays of microwells containing Pt-porphyrin-embedded polystyrene microspheres as the reporter chemistry, a lid actuator system and a gated intensified imaging camera, all mounted on a temperature-stabilized confocal microscope platform. Oxygen consumption determination experiments were performed on RAW264.7 mouse macrophage cells as proof of principle. Repeatable and consistent measurements indicate that the oxygen measurements did not adversely affect the physiological state of the cells measured. The observation of physiological rates in real time allows studies of cell-to-cell heterogeneity in oxygen consumption rate to be performed. Such studies have implications in understanding the role of mitochondrial function in the progression of inflammatory-based diseases, and in diagnosing and treating such diseases. PMID:18522927

  16. Semaphorin 5A mediated cellular navigation: connecting nervous system and cancer

    PubMed Central

    Purohit, Abhilasha; Sadanandam, Anguraj; Myneni, Pavan; Singh, Rakesh K.

    2014-01-01

    The ultraprecise wiring of neurons banks on the instructions provided by guidance cue proteins that steer them to their appropriate target tissue during neuronal development. Semaphorins are one such family of proteins. Semaphorins are known to play major physiological roles during the development of various organs including nervous system, cardiovascular, and immune systems. Their role in different pathologies including cancer remains an intense area of investigation. This review focuses on a novel member of this family of proteins, semaphorin 5A, which is much less explored in comparison to its other affiliates. Recent reports suggest that semaphorins play important roles in the pathology of cancer by affecting angiogenesis, tumor growth and metastasis. We will firstly give a general overview of the semaphorin family and its receptors. Next, we discuss their roles in cellular movements and how that makes them a connecting link between nervous system and cancer. Finally, we focus our discussion on semaphorin 5A to summarize the prevailing knowledge for this molecule in developmental biology and carcinogenesis. PMID:25263940

  17. Identifying the Cellular Targets of Drug Action in the Central Nervous System Following Corticosteroid Therapy

    PubMed Central

    2013-01-01

    Corticosteroid (CS) therapy is used widely in the treatment of a range of pathologies, but can delay production of myelin, the insulating sheath around central nervous system nerve fibers. The cellular targets of CS action are not fully understood, that is, “direct” action on cells involved in myelin genesis [oligodendrocytes and their progenitors the oligodendrocyte precursor cells (OPCs)] versus “indirect” action on other neural cells. We evaluated the effects of the widely used CS dexamethasone (DEX) on purified OPCs and oligodendrocytes, employing complementary histological and transcriptional analyses. Histological assessments showed no DEX effects on OPC proliferation or oligodendrocyte genesis/maturation (key processes underpinning myelin genesis). Immunostaining and RT-PCR analyses show that both cell types express glucocorticoid receptor (GR; the target for DEX action), ruling out receptor expression as a causal factor in the lack of DEX-responsiveness. GRs function as ligand-activated transcription factors, so we simultaneously analyzed DEX-induced transcriptional responses using microarray analyses; these substantiated the histological findings, with limited gene expression changes in DEX-treated OPCs and oligodendrocytes. With identical treatment, microglial cells showed profound and global changes post-DEX addition; an unexpected finding was the identification of the transcription factor Olig1, a master regulator of myelination, as a DEX responsive gene in microglia. Our data indicate that CS-induced myelination delays are unlikely to be due to direct drug action on OPCs or oligodendrocytes, and may occur secondary to alterations in other neural cells, such as the immune component. To the best of our knowledge, this is the first comparative molecular and cellular analysis of CS effects in glial cells, to investigate the targets of this major class of anti-inflammatory drugs as a basis for myelination deficits. PMID:24147833

  18. Investigating the quality of video consultations performed using fourth generation (4G) mobile telecommunications.

    PubMed

    Caffery, Liam J; Smith, Anthony C

    2015-09-01

    The use of fourth-generation (4G) mobile telecommunications to provide real-time video consultations were investigated in this study with the aims of determining if 4G is a suitable telecommunications technology; and secondly, to identify if variation in perceived audio and video quality were due to underlying network performance. Three patient end-points that used 4G Internet connections were evaluated. Consulting clinicians recorded their perception of audio and video quality using the International Telecommunications Union scales during clinics with these patient end-points. These scores were used to calculate a mean opinion score (MOS). The network performance metrics were obtained for each session and the relationships between these metrics and the session's quality scores were tested. Clinicians scored the quality of 50 hours of video consultations, involving 36 clinic sessions. The MOS for audio was 4.1 ± 0.62 and the MOS for video was 4.4 ± 0.22. Image impairment and effort to listen were also rated favourably. There was no correlation between audio or video quality and the network metrics of packet loss or jitter. These findings suggest that 4G networks are an appropriate telecommunication technology to deliver real-time video consultations. Variations in quality scores observed during this study were not explained by the packet loss and jitter in the underlying network. Before establishing a telemedicine service, the performance of the 4G network should be assessed at the location of the proposed service. This is due to known variability in performance of 4G networks.

  19. Cellular defense system gene expression profiling of human whole blood: opportunities to predict health benefits in response to diet.

    PubMed

    Drew, Janice E

    2012-07-01

    Diet is a critical factor in the maintenance of human cellular defense systems, immunity, inflammation, redox regulation, metabolism, and DNA repair that ensure optimal health and reduce disease risk. Assessment of dietary modulation of cellular defense systems in humans has been limited due to difficulties in accessing target tissues. Notably, peripheral blood gene expression profiles associated with nonhematologic disease are detectable. Coupled with recent innovations in gene expression technologies, gene expression profiling of human blood to determine predictive markers associated with health status and dietary modulation is now a feasible prospect for nutrition scientists. This review focuses on cellular defense system gene expression profiling of human whole blood and the opportunities this presents, using recent technological advances, to predict health status and benefits conferred by diet. PMID:22797985

  20. Cellular Decomposition Based Hybrid-Hierarchical Control Systems with Applications to Flight Management Systems

    NASA Technical Reports Server (NTRS)

    Caines, P. E.

    1999-01-01

    The work in this research project has been focused on the construction of a hierarchical hybrid control theory which is applicable to flight management systems. The motivation and underlying philosophical position for this work has been that the scale, inherent complexity and the large number of agents (aircraft) involved in an air traffic system imply that a hierarchical modelling and control methodology is required for its management and real time control. In the current work the complex discrete or continuous state space of a system with a small number of agents is aggregated in such a way that discrete (finite state machine or supervisory automaton) controlled dynamics are abstracted from the system's behaviour. High level control may then be either directly applied at this abstracted level, or, if this is in itself of significant complexity, further layers of abstractions may be created to produce a system with an acceptable degree of complexity at each level. By the nature of this construction, high level commands are necessarily realizable at lower levels in the system.

  1. Feeding Behaviors in Cellular Slime Molds: A Microbial System To Study Competition.

    ERIC Educational Resources Information Center

    Bozzone, Donna M.

    1997-01-01

    Describes a laboratory project for first-year biology students that examines competition among various cellular slime molds. After a brief introduction to the topic of competition and basic life history information about cellular slime molds, students choose a question and design original experiments to seek an answer. (Author/AIM)

  2. Using a Virtual Tissue Culture System to Assist Students in Understanding Life at the Cellular Level

    ERIC Educational Resources Information Center

    McLauglin, Jacqueline S.; Seaquist, Stephen B.

    2008-01-01

    In every biology course ever taught in the nation's classrooms, and in every biology book ever published, students are taught about the "cell." The cell is as fundamental to biology as the atom is to chemistry. Truly, everything an organism does occurs fundamentally at the cellular level. Beyond memorizing the cellular definition, students are not…

  3. Distribution of the cellular prion protein in the central nervous system of the chicken.

    PubMed

    Atoji, Yasuro; Ishiguro, Naotaka

    2009-12-01

    The cellular prion protein (PrP), a cell membrane-bound glycoprotein mainly located in the dendrites and axons of the central nervous system (CNS), is responsible for transmissible spongiform encephalopathies in mammals. PrP genes are widely conserved in vertebrates. In birds, the presence of PrP mRNA has been confirmed in neurons of the chicken brain, but localization of the protein remains to be determined. In the present study, we demonstrated the regional distribution of PrP in the CNS of adult chickens by immunohistochemical staining with a monoclonal antibody that recognizes chicken PrP 161-164. Immunoreactivity was observed in the neuropil, but not in neuronal somata or glial cells. It was preferentially intense in the olfactory bulb, the dorsal thalamus, the hypothalamus, and most regions of the telencephalon. Immunostaining became less intense toward the brainstem, but many nuclei were immunoreactive. Among brainstem nuclei, moderate immunostaining was observed in the nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and substantia gelatinosa Rolandi. The cerebellar cortex was devoid of PrP immunoreactivity. The dorsal horn in the spinal cord was strongly immunoreactive. In situ hybridization with two probes of the C-terminal portion demonstrated localization of PrP mRNA in neurons of the brain and spinal cord. These findings suggest that PrP in the chicken CNS is localized in the dendrites and axons of neurons and that it is associated with certain sensory systems.

  4. Kinetic Monte Carlo and cellular particle dynamics simulations of multicellular systems

    NASA Astrophysics Data System (ADS)

    Flenner, Elijah; Janosi, Lorant; Barz, Bogdan; Neagu, Adrian; Forgacs, Gabor; Kosztin, Ioan

    2012-03-01

    Computer modeling of multicellular systems has been a valuable tool for interpreting and guiding in vitro experiments relevant to embryonic morphogenesis, tumor growth, angiogenesis and, lately, structure formation following the printing of cell aggregates as bioink particles. Here we formulate two computer simulation methods: (1) a kinetic Monte Carlo (KMC) and (2) a cellular particle dynamics (CPD) method, which are capable of describing and predicting the shape evolution in time of three-dimensional multicellular systems during their biomechanical relaxation. Our work is motivated by the need of developing quantitative methods for optimizing postprinting structure formation in bioprinting-assisted tissue engineering. The KMC and CPD model parameters are determined and calibrated by using an original computational-theoretical-experimental framework applied to the fusion of two spherical cell aggregates. The two methods are used to predict the (1) formation of a toroidal structure through fusion of spherical aggregates and (2) cell sorting within an aggregate formed by two types of cells with different adhesivities.

  5. An integrative model of the cardiovascular system coupling heart cellular mechanics with arterial network hemodynamics.

    PubMed

    Kim, Young-Tae; Lee, Jeong Sang; Youn, Chan-Hyun; Choi, Jae-Sung; Shim, Eun Bo

    2013-08-01

    The current study proposes a model of the cardiovascular system that couples heart cell mechanics with arterial hemodynamics to examine the physiological role of arterial blood pressure (BP) in left ventricular hypertrophy (LVH). We developed a comprehensive multiphysics and multiscale cardiovascular model of the cardiovascular system that simulates physiological events, from membrane excitation and the contraction of a cardiac cell to heart mechanics and arterial blood hemodynamics. Using this model, we delineated the relationship between arterial BP or pulse wave velocity and LVH. Computed results were compared with existing clinical and experimental observations. To investigate the relationship between arterial hemodynamics and LVH, we performed a parametric study based on arterial wall stiffness, which was obtained in the model. Peak cellular stress of the left ventricle and systolic blood pressure (SBP) in the brachial and central arteries also increased; however, further increases were limited for higher arterial stiffness values. Interestingly, when we doubled the value of arterial stiffness from the baseline value, the percentage increase of SBP in the central artery was about 6.7% whereas that of the brachial artery was about 3.4%. It is suggested that SBP in the central artery is more critical for predicting LVH as compared with other blood pressure measurements.

  6. A biofidelic 3D culture model to study the development of brain cellular systems

    PubMed Central

    Ren, M.; Du, C.; Herrero Acero, E.; Tang-Schomer, M. D.; Özkucur, N.

    2016-01-01

    Little is known about how cells assemble as systems during corticogenesis to generate collective functions. We built a neurobiology platform that consists of fetal rat cerebral cortical cells grown within 3D silk scaffolds (SF). Ivermectin (Ivm), a glycine receptor (GLR) agonist, was used to modulate cell resting membrane potential (Vmem) according to methods described in a previous work that implicated Ivm in the arrangement and connectivity of cortical cell assemblies. The cells developed into distinct populations of neuroglial stem/progenitor cells, mature neurons or epithelial-mesenchymal cells. Importantly, the synchronized electrical activity in the newly developed cortical assemblies could be recorded as local field potential (LFP) measurements. This study therefore describes the first example of the development of a biologically relevant cortical plate assembly outside of the body. This model provides i) a preclinical basis for engineering cerebral cortex tissue autografts and ii) a biofidelic 3D culture model for investigating biologically relevant processes during the functional development of cerebral cortical cellular systems. PMID:27112667

  7. A CLASSICAL MORPHOLOGICAL ANALYSIS OF GALAXIES IN THE SPITZER SURVEY OF STELLAR STRUCTURE IN GALAXIES (S{sup 4}G)

    SciTech Connect

    Buta, Ronald J.; Sheth, Kartik; Muñoz-Mateos, Juan-Carlos; Kim, Taehyun; Knapen, Johan H.; Laurikainen, Eija; Salo, Heikki; Laine, Jarkko; Comerón, Sébastien; Elmegreen, Debra; Ho, Luis C.; Zaritsky, Dennis; Hinz, Joannah L.; Courtois, Helene; Gadotti, Dimitri A.; Paz, Armando Gil de; Menéndez-Delmestre, Karín; and others

    2015-04-15

    The Spitzer Survey of Stellar Structure in Galaxies (S{sup 4}G) is the largest available database of deep, homogeneous middle-infrared (mid-IR) images of galaxies of all types. The survey, which includes 2352 nearby galaxies, reveals galaxy morphology only minimally affected by interstellar extinction. This paper presents an atlas and classifications of S{sup 4}G galaxies in the Comprehensive de Vaucouleurs revised Hubble-Sandage (CVRHS) system. The CVRHS system follows the precepts of classical de Vaucouleurs morphology, modified to include recognition of other features such as inner, outer, and nuclear lenses, nuclear rings, bars, and disks, spheroidal galaxies, X patterns and box/peanut structures, OLR subclass outer rings and pseudorings, bar ansae and barlenses, parallel sequence late-types, thick disks, and embedded disks in 3D early-type systems. We show that our CVRHS classifications are internally consistent, and that nearly half of the S{sup 4}G sample consists of extreme late-type systems (mostly bulgeless, pure disk galaxies) in the range Scd-Im. The most common family classification for mid-IR types S0/a to Sc is SA while that for types Scd to Sm is SB. The bars in these two type domains are very different in mid-IR structure and morphology. This paper examines the bar, ring, and type classification fractions in the sample, and also includes several montages of images highlighting the various kinds of “stellar structures” seen in mid-IR galaxy morphology.

  8. Development of an Insert Co-culture System of Two Cellular Types in the Absence of Cell-Cell Contact.

    PubMed

    Renaud, Justine; Martinoli, Maria-Grazia

    2016-01-01

    The role of secreted soluble factors in the modification of cellular responses is a recurrent theme in the study of all tissues and systems. In an attempt to make straightforward the very complex relationships between the several cellular subtypes that compose multicellular organisms, in vitro techniques have been developed to help researchers acquire a detailed understanding of single cell populations. One of these techniques uses inserts with a permeable membrane allowing secreted soluble factors to diffuse. Thus, a population of cells grown in inserts can be co-cultured in a well or dish containing a different cell type for evaluating cellular changes following paracrine signaling in the absence of cell-cell contact. Such insert co-culture systems offer various advantages over other co-culture techniques, namely bidirectional signaling, conserved cell polarity and population-specific detection of cellular changes. In addition to being utilized in the field of inflammation, cancer, angiogenesis and differentiation, these co-culture systems are of prime importance in the study of the intricate relationships that exist between the different cellular subtypes present in the central nervous system, particularly in the context of neuroinflammation. This article offers general methodological guidelines in order to set up an experiment in order to evaluating cellular changes mediated by secreted soluble factors using an insert co-culture system. Moreover, a specific protocol to measure the neuroinflammatory effects of cytokines secreted by lipopolysaccharide-activated N9 microglia on neuronal PC12 cells will be detailed, offering a concrete understanding of insert co-culture methodology. PMID:27500972

  9. Hetero-cellular prototyping by synchronized multi-material bioprinting for rotary cell culture system.

    PubMed

    Snyder, Jessica; Son, Ae Rin; Hamid, Qudus; Wu, Honglu; Sun, Wei

    2016-03-01

    Bottom-up tissue engineering requires methodological progress of biofabrication to capture key design facets of anatomical arrangements across micro, meso and macro-scales. The diffusive mass transfer properties necessary to elicit stability and functionality require hetero-typic contact, cell-to-cell signaling and uniform nutrient diffusion. Bioprinting techniques successfully build mathematically defined porous architecture to diminish resistance to mass transfer. Current limitations of bioprinted cell assemblies include poor micro-scale formability of cell-laden soft gels and asymmetrical macro-scale diffusion through 3D volumes. The objective of this work is to engineer a synchronized multi-material bioprinter (SMMB) system which improves the resolution and expands the capability of existing bioprinting systems by packaging multiple cell types in heterotypic arrays prior to deposition. This unit cell approach to arranging multiple cell-laden solutions is integrated with a motion system to print heterogeneous filaments as tissue engineered scaffolds and nanoliter droplets. The set of SMMB process parameters control the geometric arrangement of the combined flow's internal features and constituent material's volume fractions. SMMB printed hepatocyte-endothelial laden 200 nl droplets are cultured in a rotary cell culture system (RCCS) to study the effect of microgravity on an in vitro model of the human hepatic lobule. RCCS conditioning for 48 h increased hepatocyte cytoplasm diameter 2 μm, increased metabolic rate, and decreased drug half-life. SMMB hetero-cellular models present a 10-fold increase in metabolic rate, compared to SMMB mono-culture models. Improved bioprinting resolution due to process control of cell-laden matrix packaging as well as nanoliter droplet printing capability identify SMMB as a viable technique to improve in vitro model efficacy. PMID:26759993

  10. Pb-induced cellular defense system in the root meristematic cells of Allium sativum L

    PubMed Central

    2010-01-01

    Background Electron microscopy (EM) techniques enable identification of the main accumulations of lead (Pb) in cells and cellular organelles and observations of changes in cell ultrastructure. Although there is extensive literature relating to studies on the influence of heavy metals on plants, Pb tolerance strategies of plants have not yet been fully explained. Allium sativum L. is a potential plant for absorption and accumulation of heavy metals. In previous investigations the effects of different concentrations (10-5 to 10-3 M) of Pb were investigated in A. sativum, indicating a significant inhibitory effect on shoot and root growth at 10-3 to 10-4 M Pb. In the present study, we used EM and cytochemistry to investigate ultrastructural alterations, identify the synthesis and distribution of cysteine-rich proteins induced by Pb and explain the possible mechanisms of the Pb-induced cellular defense system in A. sativum. Results After 1 h of Pb treatment, dictyosomes were accompanied by numerous vesicles within cytoplasm. The endoplasm reticulum (ER) with swollen cisternae was arranged along the cell wall after 2 h. Some flattened cisternae were broken up into small closed vesicles and the nuclear envelope was generally more dilated after 4 h. During 24-36 h, phenomena appeared such as high vacuolization of cytoplasm and electron-dense granules in cell walls, vacuoles, cytoplasm and mitochondrial membranes. Other changes included mitochondrial swelling and loss of cristae, and vacuolization of ER and dictyosomes during 48-72 h. In the Pb-treatment groups, silver grains were observed in cell walls and in cytoplasm, suggesting the Gomori-Swift reaction can indirectly evaluate the Pb effects on plant cells. Conclusions Cell walls can immobilize some Pb ions. Cysteine-rich proteins in cell walls were confirmed by the Gomori-Swift reaction. The morphological alterations in plasma membrane, dictyosomes and ER reflect the features of detoxification and tolerance under Pb

  11. Adoption of 4G Mobile Services from the Female Student's Perspective: Case of Princess Nora University

    ERIC Educational Resources Information Center

    Rawashdeh, Awni

    2015-01-01

    The aim this study was to examine the relationship between the perceived usefulness, perceived ease of use, perceived entertainment, attitude and the users' intention toward using the fourth-generation (4G) wireless mobile services. Data of this study were collected by survey with a cross sectional approach. The data were analyzed with factor…

  12. Kinetic approach and estimation of the parameters of cellular interaction between the immunity system and a tumor.

    PubMed

    Kuznetsov, V A; Zhivoglyadov, V P; Stepanova, L A

    1993-01-01

    A method is suggested to estimate multi component dynamic systems, which permits, with the help of the computer-calculated kinetic curves, to obtain information about the possible mechanisms of the system component interaction. The method is based on the structural and parametrical identification of mathematical models presented in the form of a system of nonlinear differential equations, using a multi-criterial approach. Using experimental data of studies on growth kinetics and regression of multicellular tumor EMT6 line spheroids in the mouse allogenic system and the immune system cell accumulation in spheroids a mathematical model has been developed of the cellular interaction process in a spheroid. It has been stated that the rate of macrophage and neutrophil accumulation in a spheroid depends on the amount of tumor cells and is determined by the hyperbolic law (as analogous to the Michaelis-Menthen kinetics), while the accumulation of immune lymphocytes in a tumor is determined besides that by the three-cellular cooperation of lymphocytes, macrophages and tumor cells. According to the model, the inhibition of the process of neutrophil and lymphocyte (but not of macrophages) accumulation is realized through the auto-suppression mechanism. The numerical values of the process parameters, which characterise the rates of accumulation, cellular death in a tumor and of local cellular interactions intensity are obtained. PMID:8239905

  13. Optical system module having zooming function and image quality of mega pixel for a cellular phone camera

    NASA Astrophysics Data System (ADS)

    Park, Seong Jong; Lee, Jong Jin; Chung, Chang Sub

    2009-08-01

    We designed and developed a cellular phone camera like HD digital still camera having zooming function. To design an optical system module having the auto-zooming and the image quality of 2M mega pixel using Code V, we considered 6 lenses which were four aspheric plastic lenses and two glass lenses. The specifications of designed optical system module for a cellular phone camera were the focal length of 4.29mm at wide position to 10.55mm at tele position, fnumber of 3.2 at wide position to 5.3 at tele position, and field of view of 27.4 degree at tele position to 65.8 degree at wide position. Its zoom ratio was 2.5. The values of modulation transfer function (MTF) at 200lp/mm of the designed optical system module were over 21% at zoom position. We applied the design results of optical system module to the fabrication of a cellular phone camera having the zoom ratio of 2.5 and the image quality of 2M mega pixel, and adopted the aspheric glass lens having higher abbe number to compensate chromatic aberration and the VCM (Voice Coil Motor) as sub-miniature motor. We fabricated the optical module system having zoom ratio of 2.5 and image quality of 2M mega pixel in order to apply to a HD cellular phone camera.

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

    PubMed

    Bak, Marek; Zmyślony, Marek

    2010-01-01

    In the opinion of some experts, a growing emission of man-made electromagnetic fields (EMF), also known as electromagnetic is a source of continuously increasing health hazards to the general population. Due to their large number and very close proximity to the user's head, mobile phones deserve special attention. This work is intended to give a systematic review of objective studies, assessing the effects of mobile phone EMF on the functions of the central nervous system (CNS) structures. Our review shows that short exposures to mobile phone EMF, experienced by telephone users during receiving calls, do not affect the cochlear function. Effects of GSM mobile phone EMF on the conduction of neural impulses from the inner car neurons to the brainstem auditory centres have not been detected either. If Picton's principle, saying that P300 amplitude varies with the improbability of the targets and its latency varies with difficulty of discriminating the target stimulus from standard stimuli, is true, EMF changes the improbability of the targets without hindering their discrimination. Experiments with use of indirect methods do not enable unequivocal verification of EMF effects on the cognitive functions due to the CNS anatomical and functional complexity. Thus, it seems advisable to develop a model of EMF effects on the excitable brain structures at the cellular level. PMID:21452571

  15. The effect of an autologous cellular gel-matrix integrated implant system on wound healing

    PubMed Central

    2010-01-01

    Background This manuscript reports the production and preclinical studies to examine the tolerance and efficacy of an autologous cellular gel-matrix integrated implant system (IIS) aimed to treat full-thickness skin lesions. Methods The best concentration of fibrinogen and thrombin was experimentally determined by employing 28 formula ratios of thrombin and fibrinogen and checking clot formation and apparent stability. IIS was formed by integrating skin cells by means of the in situ gelification of fibrin into a porous crosslinked scaffold composed of chitosan, gelatin and hyaluronic acid. The in vitro cell proliferation within the IIS was examined by the MTT assay and PCNA expression. An experimental rabbit model consisting of six circular lesions was utilized to test each of the components of the IIS. Then, the IIS was utilized in an animal model to cover a 35% body surface full thickness lesion. Results The preclinical assays in rabbits demonstrated that the IIS was well tolerated and also that IIS-treated rabbit with lesions of 35% of their body surface, exhibited a better survival rate (p = 0,06). Conclusion IIS should be further studied as a new wound dressing which shows promising properties, being the most remarkable its good biological tolerance and cell growth promotion properties. PMID:20565787

  16. Designing and implementing a regional urban modeling system using the SLEUTH cellular urban model

    USGS Publications Warehouse

    Jantz, C.A.; Goetz, S.J.; Donato, D.; Claggett, P.

    2010-01-01

    This paper presents a fine-scale (30 meter resolution) regional land cover modeling system, based on the SLEUTH cellular automata model, that was developed for a 257000 km2 area comprising the Chesapeake Bay drainage basin in the eastern United States. As part of this effort, we developed a new version of the SLEUTH model (SLEUTH-3r), which introduces new functionality and fit metrics that substantially increase the performance and applicability of the model. In addition, we developed methods that expand the capability of SLEUTH to incorporate economic, cultural and policy information, opening up new avenues for the integration of SLEUTH with other land-change models. SLEUTH-3r is also more computationally efficient (by a factor of 5) and uses less memory (reduced 65%) than the original software. With the new version of SLEUTH, we were able to achieve high accuracies at both the aggregate level of 15 sub-regional modeling units and at finer scales. We present forecasts to 2030 of urban development under a current trends scenario across the entire Chesapeake Bay drainage basin, and three alternative scenarios for a sub-region within the Chesapeake Bay watershed to illustrate the new ability of SLEUTH-3r to generate forecasts across a broad range of conditions. ?? 2009 Elsevier Ltd.

  17. Trans-species learning of cellular signaling systems with bimodal deep belief networks

    PubMed Central

    Chen, Lujia; Cai, Chunhui; Chen, Vicky; Lu, Xinghua

    2015-01-01

    Motivation: Model organisms play critical roles in biomedical research of human diseases and drug development. An imperative task is to translate information/knowledge acquired from model organisms to humans. In this study, we address a trans-species learning problem: predicting human cell responses to diverse stimuli, based on the responses of rat cells treated with the same stimuli. Results: We hypothesized that rat and human cells share a common signal-encoding mechanism but employ different proteins to transmit signals, and we developed a bimodal deep belief network and a semi-restricted bimodal deep belief network to represent the common encoding mechanism and perform trans-species learning. These ‘deep learning’ models include hierarchically organized latent variables capable of capturing the statistical structures in the observed proteomic data in a distributed fashion. The results show that the models significantly outperform two current state-of-the-art classification algorithms. Our study demonstrated the potential of using deep hierarchical models to simulate cellular signaling systems. Availability and implementation: The software is available at the following URL: http://pubreview.dbmi.pitt.edu/TransSpeciesDeepLearning/. The data are available through SBV IMPROVER website, https://www.sbvimprover.com/challenge-2/overview, upon publication of the report by the organizers. Contact: xinghua@pitt.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25995230

  18. Integrating the system dynamic and cellular automata models to predict land use and land cover change

    NASA Astrophysics Data System (ADS)

    Xu, Xiaoming; Du, Ziqiang; Zhang, Hong

    2016-10-01

    Land use and land cover change (LULCC) is a widely researched topic in related studies. A number of models have been established to simulate LULCC patterns. However, the integration of the system dynamic (SD) and the cellular automata (CA) model have been rarely employed in LULCC simulations, although it allows for combining the advantages of each approach and therefore improving the simulation accuracy. In this study, we integrated an SD model and a CA model to predict LULCC under three future development scenarios in Northern Shanxi province of China, a typical agro-pastoral transitional zone. The results indicated that our integrated approach represented the impacts of natural and socioeconomic factors on LULCC well, and could accurately simulate the magnitude and spatial pattern of LULCC. The modeling scenarios illustrated that different development pathways would lead to various LULCC patterns. This study demonstrated the advantages of the integration approach for simulating LULCC and suggests that LULCC is affected to a large degree by natural and socioeconomic factors.

  19. Molecular links between cellular senescence, longevity and age-related diseases - a systems biology perspective.

    PubMed

    Tacutu, Robi; Budovsky, Arie; Yanai, Hagai; Fraifeld, Vadim E

    2011-12-01

    The role of cellular senescence (CS) in age-related diseases (ARDs) is a quickly emerging topic in aging research. Our comprehensive data mining revealed over 250 genes tightly associated with CS. Using systems biology tools, we found that CS is closely interconnected with aging, longevity and ARDs, either by sharing common genes and regulators or by protein-protein interactions and eventually by common signaling pathways. The most enriched pathways across CS, ARDs and aging-associated conditions (oxidative stress and chronic inflammation) are growth-promoting pathways and the pathways responsible for cell-extracellular matrix interactions and stress response. Of note, the patterns of evolutionary conservation of CS and cancer genes showed a high degree of similarity, suggesting the co-evolution of these two phenomena. Moreover, cancer genes and microRNAs seem to stand at the crossroad between CS and ARDs. Our analysis also provides the basis for new predictions: the genes common to both cancer and other ARD(s) are highly likely candidates to be involved in CS and vice versa. Altogether, this study shows that there are multiple links between CS, aging, longevity and ARDs, suggesting a common molecular basis for all these conditions. Modulating CS may represent a potential pro-longevity and anti-ARDs therapeutic strategy. PMID:22184282

  20. A multi-objective model for designing a group layout of a dynamic cellular manufacturing system

    NASA Astrophysics Data System (ADS)

    Kia, Reza; Shirazi, Hossein; Javadian, Nikbakhsh; Tavakkoli-Moghaddam, Reza

    2013-04-01

    This paper presents a multi-objective mixed-integer nonlinear programming model to design a group layout of a cellular manufacturing system in a dynamic environment, in which the number of cells to be formed is variable. Cell formation (CF) and group layout (GL) are concurrently made in a dynamic environment by the integrated model, which incorporates with an extensive coverage of important manufacturing features used in the design of CMSs. Additionally, there are some features that make the presented model different from the previous studies. These features include the following: (1) the variable number of cells, (2) the integrated CF and GL decisions in a dynamic environment by a multi-objective mathematical model, and (3) two conflicting objectives that minimize the total costs (i.e., costs of intra and inter-cell material handling, machine relocation, purchasing new machines, machine overhead, machine processing, and forming cells) and minimize the imbalance of workload among cells. Furthermore, the presented model considers some limitations, such as machine capability, machine capacity, part demands satisfaction, cell size, material flow conservation, and location assignment. Four numerical examples are solved by the GAMS software to illustrate the promising results obtained by the incorporated features.

  1. Cellular Biotechnology Operations Support Systems-Fluid Dynamics Investigation (CBOSS-FDI)

    NASA Technical Reports Server (NTRS)

    2003-01-01

    Aboard the International Space Station (ISS), the Tissue Culture Module (TCM) is the stationary bioreactor vessel in which cell cultures grow. However, for the Cellular Biotechnology Operations Support Systems-Fluid Dynamics Investigation (CBOSS-FDI), color polystyrene beads are used to measure the effectiveness of various mixing procedures. Uniform mixing is a crucial component of CBOSS experiments involving the immune response of human lymphoid cell suspensions. In this picture, the beads are trapped in the injection port shortly after injection. Swirls of beads indicate, event to the naked eye, the contents of the TCM are not fully mixed. The beads are similar in size and density to human lymphoid cells. The goal is to develop procedures that are both convenient for the flight crew and are optimal in providing uniform and reproducible mixing of all components, including cells. The average bead density in a well mixed TCM will be uniform, with no bubbles, and it will be measured using the absorption of light

  2. GC-based dynamic QoS priority handoff scheme in multimedia cellular systems

    NASA Astrophysics Data System (ADS)

    Chen, Huan; Kumar, Sunil; Kuo, C.-C. Jay

    2001-03-01

    A dynamic call admission control (CAC) and its associated resource reservation (RR) schemes are proposed in this research based on the guard channel (GC) concept for a wireless cellular system supporting multiple QoS classes. A comprehensive service model is developed, which includes not only mobile terminals' bandwidth requirements but also their different levels of priorities, rate adaptivity and mobility. The proposed CAC policy selects the resource access thresold according to the estimated number of incoming call requests of different QoS classes. The amount of resources to be reserved is dynamically adjusted by considering neighboring-cell higher-priority calls which are likely to handoff. The handoff interaction between adjacent cells is estimated by using radio propagation in terms of the signal-to-noise ratio (SNR) and the distance of each active call in neighboring cells. Experiments are conducted by using the OPNET simulator to study the performance of the proposed scheme under various traffic conditions. It is shown that better QoS guarantees can be provided by the proposed CAC and RR schemes.

  3. An archived multi-objective simulated annealing for a dynamic cellular manufacturing system

    NASA Astrophysics Data System (ADS)

    Shirazi, Hossein; Kia, Reza; Javadian, Nikbakhsh; Tavakkoli-Moghaddam, Reza

    2014-05-01

    To design a group layout of a cellular manufacturing system (CMS) in a dynamic environment, a multi-objective mixed-integer non-linear programming model is developed. The model integrates cell formation, group layout and production planning (PP) as three interrelated decisions involved in the design of a CMS. This paper provides an extensive coverage of important manufacturing features used in the design of CMSs and enhances the flexibility of an existing model in handling the fluctuations of part demands more economically by adding machine depot and PP decisions. Two conflicting objectives to be minimized are the total costs and the imbalance of workload among cells. As the considered objectives in this model are in conflict with each other, an archived multi-objective simulated annealing (AMOSA) algorithm is designed to find Pareto-optimal solutions. Matrix-based solution representation, a heuristic procedure generating an initial and feasible solution and efficient mutation operators are the advantages of the designed AMOSA. To demonstrate the efficiency of the proposed algorithm, the performance of AMOSA is compared with an exact algorithm (i.e., ∈-constraint method) solved by the GAMS software and a well-known evolutionary algorithm, namely NSGA-II for some randomly generated problems based on some comparison metrics. The obtained results show that the designed AMOSA can obtain satisfactory solutions for the multi-objective model.

  4. Space experiment "Cellular Responses to Radiation in Space (CellRad)": Hardware and biological system tests.

    PubMed

    Hellweg, Christine E; Dilruba, Shahana; Adrian, Astrid; Feles, Sebastian; Schmitz, Claudia; Berger, Thomas; Przybyla, Bartos; Briganti, Luca; Franz, Markus; Segerer, Jürgen; Spitta, Luis F; Henschenmacher, Bernd; Konda, Bikash; Diegeler, Sebastian; Baumstark-Khan, Christa; Panitz, Corinna; Reitz, Günther

    2015-11-01

    One factor contributing to the high uncertainty in radiation risk assessment for long-term space missions is the insufficient knowledge about possible interactions of radiation with other spaceflight environmental factors. Such factors, e.g. microgravity, have to be considered as possibly additive or even synergistic factors in cancerogenesis. Regarding the effects of microgravity on signal transduction, it cannot be excluded that microgravity alters the cellular response to cosmic radiation, which comprises a complex network of signaling pathways. The purpose of the experiment "Cellular Responses to Radiation in Space" (CellRad, formerly CERASP) is to study the effects of combined exposure to microgravity, radiation and general space flight conditions on mammalian cells, in particular Human Embryonic Kidney (HEK) cells that are stably transfected with different plasmids allowing monitoring of proliferation and the Nuclear Factor κB (NF-κB) pathway by means of fluorescent proteins. The cells will be seeded on ground in multiwell plate units (MPUs), transported to the ISS, and irradiated by an artificial radiation source after an adaptation period at 0 × g and 1 × g. After different incubation periods, the cells will be fixed by pumping a formaldehyde solution into the MPUs. Ground control samples will be treated in the same way. For implementation of CellRad in the Biolab on the International Space Station (ISS), tests of the hardware and the biological systems were performed. The sequence of different steps in MPU fabrication (cutting, drilling, cleaning, growth surface coating, and sterilization) was optimized in order to reach full biocompatibility. Different coatings of the foil used as growth surface revealed that coating with 0.1 mg/ml poly-D-lysine supports cell attachment better than collagen type I. The tests of prototype hardware (Science Model) proved its full functionality for automated medium change, irradiation and fixation of cells. Exposure of

  5. Space experiment "Cellular Responses to Radiation in Space (CELLRAD)": Hardware and biological system tests

    NASA Astrophysics Data System (ADS)

    Hellweg, Christine E.; Dilruba, Shahana; Adrian, Astrid; Feles, Sebastian; Schmitz, Claudia; Berger, Thomas; Przybyla, Bartos; Briganti, Luca; Franz, Markus; Segerer, Jürgen; Spitta, Luis F.; Henschenmacher, Bernd; Konda, Bikash; Diegeler, Sebastian; Baumstark-Khan, Christa; Panitz, Corinna; Reitz, Günther

    2015-11-01

    One factor contributing to the high uncertainty in radiation risk assessment for long-term space missions is the insufficient knowledge about possible interactions of radiation with other spaceflight environmental factors. Such factors, e.g. microgravity, have to be considered as possibly additive or even synergistic factors in cancerogenesis. Regarding the effects of microgravity on signal transduction, it cannot be excluded that microgravity alters the cellular response to cosmic radiation, which comprises a complex network of signaling pathways. The purpose of the experiment "Cellular Responses to Radiation in Space" (CELLRAD, formerly CERASP) is to study the effects of combined exposure to microgravity, radiation and general space flight conditions on mammalian cells, in particular Human Embryonic Kidney (HEK) cells that are stably transfected with different plasmids allowing monitoring of proliferation and the Nuclear Factor κB (NF-κB) pathway by means of fluorescent proteins. The cells will be seeded on ground in multiwell plate units (MPUs), transported to the ISS, and irradiated by an artificial radiation source after an adaptation period at 0 × g and 1 × g. After different incubation periods, the cells will be fixed by pumping a formaldehyde solution into the MPUs. Ground control samples will be treated in the same way. For implementation of CELLRAD in the Biolab on the International Space Station (ISS), tests of the hardware and the biological systems were performed. The sequence of different steps in MPU fabrication (cutting, drilling, cleaning, growth surface coating, and sterilization) was optimized in order to reach full biocompatibility. Different coatings of the foil used as growth surface revealed that coating with 0.1 mg/ml poly-D-lysine supports cell attachment better than collagen type I. The tests of prototype hardware (Science Model) proved its full functionality for automated medium change, irradiation and fixation of cells. Exposure of

  6. Space experiment "Cellular Responses to Radiation in Space (CellRad)": Hardware and biological system tests.

    PubMed

    Hellweg, Christine E; Dilruba, Shahana; Adrian, Astrid; Feles, Sebastian; Schmitz, Claudia; Berger, Thomas; Przybyla, Bartos; Briganti, Luca; Franz, Markus; Segerer, Jürgen; Spitta, Luis F; Henschenmacher, Bernd; Konda, Bikash; Diegeler, Sebastian; Baumstark-Khan, Christa; Panitz, Corinna; Reitz, Günther

    2015-11-01

    One factor contributing to the high uncertainty in radiation risk assessment for long-term space missions is the insufficient knowledge about possible interactions of radiation with other spaceflight environmental factors. Such factors, e.g. microgravity, have to be considered as possibly additive or even synergistic factors in cancerogenesis. Regarding the effects of microgravity on signal transduction, it cannot be excluded that microgravity alters the cellular response to cosmic radiation, which comprises a complex network of signaling pathways. The purpose of the experiment "Cellular Responses to Radiation in Space" (CellRad, formerly CERASP) is to study the effects of combined exposure to microgravity, radiation and general space flight conditions on mammalian cells, in particular Human Embryonic Kidney (HEK) cells that are stably transfected with different plasmids allowing monitoring of proliferation and the Nuclear Factor κB (NF-κB) pathway by means of fluorescent proteins. The cells will be seeded on ground in multiwell plate units (MPUs), transported to the ISS, and irradiated by an artificial radiation source after an adaptation period at 0 × g and 1 × g. After different incubation periods, the cells will be fixed by pumping a formaldehyde solution into the MPUs. Ground control samples will be treated in the same way. For implementation of CellRad in the Biolab on the International Space Station (ISS), tests of the hardware and the biological systems were performed. The sequence of different steps in MPU fabrication (cutting, drilling, cleaning, growth surface coating, and sterilization) was optimized in order to reach full biocompatibility. Different coatings of the foil used as growth surface revealed that coating with 0.1 mg/ml poly-D-lysine supports cell attachment better than collagen type I. The tests of prototype hardware (Science Model) proved its full functionality for automated medium change, irradiation and fixation of cells. Exposure of

  7. Geospatial Data Stream Processing in Python Using FOSS4G Components

    NASA Astrophysics Data System (ADS)

    McFerren, G.; van Zyl, T.

    2016-06-01

    One viewpoint of current and future IT systems holds that there is an increase in the scale and velocity at which data are acquired and analysed from heterogeneous, dynamic sources. In the earth observation and geoinformatics domains, this process is driven by the increase in number and types of devices that report location and the proliferation of assorted sensors, from satellite constellations to oceanic buoy arrays. Much of these data will be encountered as self-contained messages on data streams - continuous, infinite flows of data. Spatial analytics over data streams concerns the search for spatial and spatio-temporal relationships within and amongst data "on the move". In spatial databases, queries can assess a store of data to unpack spatial relationships; this is not the case on streams, where spatial relationships need to be established with the incomplete data available. Methods for spatially-based indexing, filtering, joining and transforming of streaming data need to be established and implemented in software components. This article describes the usage patterns and performance metrics of a number of well known FOSS4G Python software libraries within the data stream processing paradigm. In particular, we consider the RTree library for spatial indexing, the Shapely library for geometric processing and transformation and the PyProj library for projection and geodesic calculations over streams of geospatial data. We introduce a message oriented Python-based geospatial data streaming framework called Swordfish, which provides data stream processing primitives, functions, transports and a common data model for describing messages, based on the Open Geospatial Consortium Observations and Measurements (O&M) and Unidata Common Data Model (CDM) standards. We illustrate how the geospatial software components are integrated with the Swordfish framework. Furthermore, we describe the tight temporal constraints under which geospatial functionality can be invoked when

  8. 78 FR 8191 - Certain Wireless Devices With 3G and/or 4G Capabilities and Components Thereof; Institution of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-05

    ... COMMISSION Certain Wireless Devices With 3G and/or 4G Capabilities and Components Thereof; Institution of... certain wireless devices with 3G and/or 4G capabilities and components thereof by reason of infringement... wireless devices with 3G and/or 4G capabilities and components thereof by reason of infringement of one...

  9. Cellular respiration: replicating in vivo systems biology for in vitro exploration of human exposome, microbiome, and disease pathogenesis biomarkers

    EPA Science Inventory

    This editorial develops a philosophy for expanding the scope of Journal of Breath Research (JBR) into the realm of cellular level study, and links certain topics back to more traditional systemic research for understanding human health based on exhaled breath constituents. The ex...

  10. The role of ATP-sensitive potassium channels in cellular function and protection in the cardiovascular system.

    PubMed

    Tinker, Andrew; Aziz, Qadeer; Thomas, Alison

    2014-01-01

    ATP-sensitive potassium channels (K(ATP)) are widely distributed and present in a number of tissues including muscle, pancreatic beta cells and the brain. Their activity is regulated by adenine nucleotides, characteristically being activated by falling ATP and rising ADP levels. Thus, they link cellular metabolism with membrane excitability. Recent studies using genetically modified mice and genomic studies in patients have implicated K(ATP) channels in a number of physiological and pathological processes. In this review, we focus on their role in cellular function and protection particularly in the cardiovascular system.

  11. Cosegregation of the ND4 G11696A mutation with the LHON-associated ND4 G11778A mutation in a four generation Chinese family.

    PubMed

    Qu, Jia; Li, Ronghua; Zhou, Xiangtian; Tong, Yi; Yang, Li; Chen, Jie; Zhao, Fuxing; Lu, Chunjie; Qian, Yaping; Lu, Fan; Guan, Min-Xin

    2007-01-01

    We report here the characterization of a four-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON). This Chinese family exhibited a variable severity and age-at-onset of visual loss. Notably, the average age-at-onset of vision impairment changed from 26 years (generation III) to 14 years (generation IV), with the average of 18 years in this family. In addition, 30% and 50% of matrilineal relatives in generation III and IV of this family developed visual loss with a variability of severity, ranging from blindness to normal vision. Sequence analysis of the complete mitochondrial DNA in this pedigree revealed the presence of the homoplasmic ND4 G11778A mutation and 33 other variants, belonging to the Asian haplogroup D4. Of other variants, the homoplasmic G11696A mutation in the ND4 gene is of special interest as it was implicated to be associated with LHON in a large Dutch family and five Chinese pedigrees with extremely penetrance of visual loss. In fact, the G11696A mutation caused the substitution of an isoleucine for valine at amino acid position 313, located in a predicted transmembrane region of ND4. These imply that the G11696A mutation may act in synergy with the primary LHON-associated G11778A mutation in this Chinese pedigree.

  12. Thermoregulation in unrestrained rats during and after exposure to 1.5-4 G

    NASA Technical Reports Server (NTRS)

    Giacchino, J.; Horwitz, B. A.; Horowitz, J. M.

    1979-01-01

    Unrestrained rats were exposed to cold for 1 h during and immediately after exposure to hypergravic fields (1.5-4 G) to determine if they recover their ability to thermoregulate on reentry to 1-G conditions. In contrast to the decreased body temperatures observed when cold exposure occurred concurrently with acceleration, hypothalamic, carotid, and brown fat temperatures did not fall when rats were exposed to cold immediately after return to 1 G. These results support the hypothesis that the thermoregulatory alterations seen under hypergravic conditions are manifestations of an effect of ongoing exposure to hypergravity and can be reversed on termination of acceleration. The reversibility of the thermoregulatory impairment is apparently unaffected by the magnitude of the acceleration field over a range of 1.5-4 G.

  13. Plasminogen activator inhibitor-1 4G/5G polymorphism and retinopathy risk in type 2 diabetes: a meta-analysis

    PubMed Central

    2013-01-01

    Background Mounting evidence has suggested that plasminogen activator inhibitor-1 (PAI-1) is a candidate for increased risk of diabetic retinopathy. Studies have reported that insertion/deletion polymorphism in the PAI-1 gene may influence the risk of this disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the association of PAI-1 4G/5G polymorphism with diabetic retinopathy in type 2 diabetes. Methods Data were retrieved in a systematic manner and analyzed using Review Manager and STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Results Nine studies with 1, 217 cases and 1, 459 controls were included. Allelic and genotypic comparisons between cases and controls were evaluated. Overall analysis suggests a marginal association of the 4G/5G polymorphism with diabetic retinopathy (for 4G versus 5G: OR 1.13, 95%CI 1.01 to 1.26; for 4G/4G versus 5G/5G: OR 1.30, 95%CI 1.04 to 1.64; for 4G/4G versus 5G/5G + 4G/5G: OR 1.26, 95%CI 1.05 to 1.52). In subgroup analysis by ethnicity, we found an association among the Caucasian population (for 4G versus 5G: OR 1.14, 95% CI 1.00 to 1.30; for 4G/4G versus 5G/5G: OR 1.33, 95%CI 1.02 to 1.74; for 4G/4G versus 5G/5G + 4G/5G: OR 1.41, 95%CI 1.13 to 1.77). When stratified by the average duration of diabetes, patients with diabetes histories longer than 10 years have an elevated susceptibility to diabetic retinopathy than those with shorter histories (for 4G/4G versus 5G/5G: OR 1.47, 95%CI 1.08 to 2.00). We also detected a higher risk in hospital-based studies (for 4G/4G versus 5G/5G+4G/5G: OR 1.27, 95%CI 1.02 to 1.57). Conclusions The present meta-analysis suggested that 4G/5G polymorphism in the PAI-1 gene potentially increased the risk of diabetic retinopathy in type 2 diabetes and showed a discrepancy in different ethnicities. A higher susceptibility in patients with longer duration of diabetes (more than 10

  14. Cellular and genetic regulation of the development of the cerebellar system.

    PubMed

    Sotelo, Constantino

    2004-04-01

    Recent advances in molecular biology have drastically changed our vision on the development of the nervous system, the cerebellum in particular. After a classical descriptive period, we are now in a modern mechanistic epoch as we begin to answer crucial questions in our quest to understand the mechanisms underlying the emergence of brain complexity. This review begins with an analysis of the role of the "isthmic organizer" in the induction and specification of the cerebellar territory and progresses through cerebellar development to the formation of cerebellar maps. It gathers information about the control of the proliferation of granule cell precursors by Purkinje cells and the role of Shh/Gli-patched signaling. The migratory routes for cerebellar and precerebellar neurons, together with the long-range and short-range cues guiding gliophilic and, particularly, neurophilic migrations, are also discussed. Because these cues are similar to those involved in axon guidance, both processes are under the same molecular constraints. Finally, using primarily the olivocerebellar projection as a model, the cellular and molecular mechanisms involved in the formation of cerebellar maps are discussed. During embryonic development, Purkinje cells in the cerebellum and neurons in the inferior olive follow a simultaneous, but independent, process of intrinsic parcellation, giving rise to subsets of biochemically different cortical compartments. The occurrence of positional information shared between olivary axons and their postsynaptic targets, the Purkinje cells, provides a molecular code for the formation of coarse-grained maps. Activity-dependent mechanisms are required for the transition from crude to fine-grained maps. This important refinement, which confers ultimate specificity to the maps, is under the regulation of parallel fiber-Purkinje cell synaptic activity.

  15. Association between plasminogen activator inhibitor-1 4G/5G gene polymorphism and immunoglobulin A nephropathy susceptibility.

    PubMed

    Zhou, Tian-Biao; Jiang, Zong-Pei

    2015-02-01

    The association between plasminogen activator inhibitor-1 (PAI-1) 4 G/5 G gene polymorphism and immunoglobulin A nephropathy (IgAN) risk is still controversial. A meta-analysis was performed to evaluate the association between PAI-1 4 G/5 G gene polymorphism and IgAN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Four articles were identified for the analysis of association between PAI-1 4 G/5 G gene polymorphism and IgAN risk. 4 G allele was not associated with IgAN susceptibility in overall populations and in Asians. Furthermore, 4 G/4 G and 5 G/5 G genotype were not associated with IgAN for overall populations, Asians. In conclusion, PAI-1 4 G/5 G gene polymorphism was not associated with IgAN risk in overall populations and in Asians. However, more studies should be performed in the future.

  16. Structural and functional similarities between the central eukaryotic initiation factor (eIF)4A-binding domain of mammalian eIF4G and the eIF4A-binding domain of yeast eIF4G.

    PubMed Central

    Dominguez, D; Kislig, E; Altmann, M; Trachsel, H

    2001-01-01

    The translation eukaryotic initiation factor (eIF)4G of the yeast Saccharomyces cerevisiae interacts with the RNA helicase eIF4A (a member of the DEAD-box protein family; where DEAD corresponds to Asp-Glu-Ala-Asp) through a C-terminal domain in eIF4G (amino acids 542-883). Mammalian eIF4G has two interaction domains for eIF4A, a central domain and a domain close to the C-terminus. This raises the question of whether eIF4A binding to eIF4G is conserved between yeast and mammalian cells or whether it is different. We isolated eIF4G1 mutants defective in eIF4A binding and showed that these mutants are strongly impaired in translation and growth. Extracts from mutants displaying a temperature-sensitive phenotype for growth have low in vitro translation activity, which can be restored by addition of the purified eIF4G1-eIF4E complex, but not by eIF4E alone. Analysis of mutant eIF4G(542-883) proteins defective in eIF4A binding shows that the interaction of yeast eIF4A with eIF4G1 depends on amino acid motifs that are conserved between the yeast eIF4A-binding site and the central eIF4A-binding domain of mammalian eIF4G. We show that mammalian eIF4A binds tightly to yeast eIF4G1 and, furthermore, that mutant yeast eIF4G(542-883) proteins, which do not bind yeast eIF4A, do not interact with mammalian eIF4A. Despite the conservation of the eIF4A-binding site in eIF4G and the strong sequence conservation between yeast and mammalian eIF4A (66% identity; 82% similarity at the amino acid level) mammalian eIF4A does not substitute for the yeast factor in vivo and is not functional in a yeast in vitro translation system. PMID:11256967

  17. Micro 3D cell culture systems for cellular behavior studies: Culture matrices, devices, substrates, and in-situ sensing methods.

    PubMed

    Choi, Jonghoon; Lee, Eun Kyu; Choo, Jaebum; Yuh, Junhan; Hong, Jong Wook

    2015-09-01

    Microfabricated systems equipped with 3D cell culture devices and in-situ cellular biosensing tools can be a powerful bionanotechnology platform to investigate a variety of biomedical applications. Various construction substrates such as plastics, glass, and paper are used for microstructures. When selecting a construction substrate, a key consideration is a porous microenvironment that allows for spheroid growth and mimics the extracellular matrix (ECM) of cell aggregates. Various bio-functionalized hydrogels are ideal candidates that mimic the natural ECM for 3D cell culture. When selecting an optimal and appropriate microfabrication method, both the intended use of the system and the characteristics and restrictions of the target cells should be carefully considered. For highly sensitive and near-cell surface detection of excreted cellular compounds, SERS-based microsystems capable of dual modal imaging have the potential to be powerful tools; however, the development of optical reporters and nanoprobes remains a key challenge. We expect that the microsystems capable of both 3D cell culture and cellular response monitoring would serve as excellent tools to provide fundamental cellular behavior information for various biomedical applications such as metastasis, wound healing, high throughput screening, tissue engineering, regenerative medicine, and drug discovery and development. PMID:26358782

  18. Modeling step-pool systems in steep streams by a cellular automaton sandpile model

    NASA Astrophysics Data System (ADS)

    Saletti, M.; Molnar, P.; Hassan, M. A.; Zimmermann, A. E.; Fraccarollo, L.

    2013-12-01

    Alluvial step-pool systems in gravel-bed rivers have been widely studied in the last decades in both field and flume experiments. The focus has been on step formation, the geometry of step-pool sequences, the spatial and temporal variation in step properties, and the hydraulics of flow over steps. Scientists have focused on the conditions under which step-pool sequences form, remain stable and eventually collapse (Church and Zimmermann, 2007; Curran 2007). Step-pool systems are usually stable for very long periods, in which the macro-morphology does not change, even if single step-pool units may change during small flood events. Step structures typically collapse during intense flood events, with return times of 20÷50 years. These breakdown events produce an avalanche-like pulse of sediment and a rearrangement in the channel morphology. Despite a rich literature on the processes of step formation and collapse, the modeling thereof is still in its infancy. It has been proposed by Church and Zimmermann (2007) that step formation is ruled mainly by random location of big boulders along the channel--these grains act as keystones which block smaller particles and create a channel-spanning step. The nonlinear threshold-driven processes of jamming and collapse, together with the stochastic nature of bedload transport and the random location of the keystones, makes it impossible to model the step-pool system in a deterministic way. Instead, we hypothesize that step-pool systems during intense sediment transport events behave like open, dynamical and dissipative systems close to a critical state, and we adopt the modeling framework of self-organized criticality (Bak et al., 1988) in this description. To test our hypothesis we developed a cellular automaton model based on ideas of the simple sandpile model in 1-D and 2-D. Grains are added at the top of a channel randomly, they pass through the channel and form bed structures, and ultimately exit the channel at the

  19. Adipose depots differ in cellularity, adipokines produced, gene expression, and cell systems

    PubMed Central

    Dodson, Michael V; Du, Min; Wang, Songbo; Bergen, Werner G; Fernyhough-Culver, Melinda; Basu, Urmila; Poulos, Sylvia P; Hausman, Gary J

    2014-01-01

    The race to manage the health concerns related to excess fat deposition has spawned a proliferation of clinical and basic research efforts to understand variables including dietary uptake, metabolism, and lipid deposition by adipocytes. A full appreciation of these variables must also include a depot-specific understanding of content and location in order to elucidate mechanisms governing cellular development and regulation of fat deposition. Because adipose tissue depots contain various cell types, differences in the cellularity among and within adipose depots are presently being documented to ascertain functional differences. This has led to the possibility of there being, within any one adipose depot, cellular distinctions that essentially result in adipose depots within depots. The papers comprising this issue will underscore numerous differences in cellularity (development, histogenesis, growth, metabolic function, regulation) of different adipose depots. Such information is useful in deciphering adipose depot involvement both in normal physiology and in pathology. Obesity, diabetes, metabolic syndrome, carcass composition of meat animals, performance of elite athletes, physiology/pathophysiology of aging, and numerous other diseases might be altered with a greater understanding of adipose depots and the cells that comprise them—including stem cells—during initial development and subsequent periods of normal/abnormal growth into senescence. Once thought to be dormant and innocuous, the adipocyte is emerging as a dynamic and influential cell and research will continue to identify complex physiologic regulation of processes involved in adipose depot physiology. PMID:26317047

  20. The interaction of yeast hexokinase with Procion Green H-4G.

    PubMed

    Clonis, Y D; Goldfinch, M J; Lowe, C R

    1981-07-01

    1. A number of reactive triazine dyes specifically and irreversibly inactive yeast hexokinase at pH 8.5 and 33 degrees C. Under these conditions, the enzyme is readily inactivated by 100 microM-Procion Green H-4G, Blue H-B, Turquoise H-7G and Turquoise H-A, is less readily inactivated by Procion Brown H-2G. Green HE-4BD, Red HE-3B and Yellow H-5G and is not inactivated at all by Procion Yellow H-A. 2. The inactivation of hexokinase by Procion Green H-4G is competitively inhibited by the adenine nucleotides ATP and ADP and the sugar substrates D-glucose, D-mannose and D-fructose but not by nonsubstrates such as D-arabinose and D-galactose. 3. Quantitatively inhibited hexokinase contains approx. 1 mol of dye per mol of monomer of mol.wt. 51000. The inhibition is irreversible and activity cannot be recovered on incubation with high concentration (20 mM) of ATP or D-glucose. 4. Mg2+ protects the enzyme against inactivation by Procion Green H-4G but enhances the rate of inactivation by all the other Procion dyes tested. In the presence of 10 mM-Mg2+ the apparent dissociation constant between enzyme and dye is reduced from 199.0 microM to 41.6 microM. Binding of the dye to hexokinase is accompanied by characteristic spectral changes in the range 560-700 nm. 5. Mg2+ promotes binding of yeast hexokinase to agarose-immobilized Procion Green H-4G but not to the other dyes tested. Elution could be effected by omission of Mg2+ from the column irrigants or by inclusion of MgATP or D-glucose, but not by D-galactose. These effects can be exploited to purify hexokinase from crude yeast extracts. 6. The specific active-site-directed binding of triazine dyes to yeast hexokinase is interpreted in terms of the crystallographic structure of the hexokinase monomer.

  1. Synthesis and biological activities of pyrazolo[3,4-g]quinoxaline derivatives.

    PubMed

    Gavara, Laurent; Saugues, Emmanuelle; Alves, Georges; Debiton, Eric; Anizon, Fabrice; Moreau, Pascale

    2010-11-01

    The synthesis of new pyrazolo[3,4-g]quinoxaline derivatives, as well as their Pim kinases (Pim-1, Pim-2, Pim-3) inhibitory potencies and in vitro antiproliferative activities toward a human fibroblast primary culture and three human solid cancer cell lines (PA1, PC3 and DU145) are described. The results obtained in this preliminary structure-activity relationship study have pointed out that most of the compounds in this series exhibited interesting in vitro Pim-3 kinase inhibitory potencies. Moreover, some of the tested compounds have demonstrated favorable antiproliferative potencies.

  2. Structure of the foot-and-mouth disease virus leader protease: a papain-like fold adapted for self-processing and eIF4G recognition.

    PubMed Central

    Guarné, A; Tormo, J; Kirchweger, R; Pfistermueller, D; Fita, I; Skern, T

    1998-01-01

    The leader protease of foot-and-mouth disease virus, as well as cleaving itself from the nascent viral polyprotein, disables host cell protein synthesis by specific proteolysis of a cellular protein: the eukaryotic initiation factor 4G (eIF4G). The crystal structure of the leader protease presented here comprises a globular catalytic domain reminiscent of that of cysteine proteases of the papain superfamily, and a flexible C-terminal extension found intruding into the substrate-binding site of an adjacent molecule. Nevertheless, the relative disposition of this extension and the globular domain to each other supports intramolecular self-processing. The different sequences of the two substrates cleaved during viral replication, the viral polyprotein (at LysLeuLys/GlyAlaGly) and eIF4G (at AsnLeuGly/ArgThrThr), appear to be recognized by distinct features in a narrow, negatively charged groove traversing the active centre. The structure illustrates how the prototype papain fold has been adapted to the requirements of an RNA virus. Thus, the protein scaffold has been reduced to a minimum core domain, with the active site being modified to increase specificity. Furthermore, surface features have been developed which enable C-terminal self-processing from the viral polyprotein. PMID:9857201

  3. Overview of cellular CDMA

    NASA Astrophysics Data System (ADS)

    Lee, William C. Y.

    1991-05-01

    A general description of code division multiple access (CDMA) is presented. This overview of CDMA highlights the potential of increasing capacity in future cellular communications. The author describes the mobile radio environment and its impact on narrowband and wideband propagation. The advantage of having CDMA in cellular systems is discussed, and the concept of radio capacity in cellular is introduced. The power control schemes in CDMA are analyzed in detail.

  4. Design and validation of a multi-electrode bioimpedance system for enhancing spatial resolution of cellular impedance studies.

    PubMed

    Alexander, Frank A; Celestin, Michael; Price, Dorielle T; Nanjundan, Meera; Bhansali, Shekhar

    2013-07-01

    This paper reports the design and evaluation of a multi-electrode design that improves upon the statistical significance and spatial resolution of cellular impedance data measured using commercial electric cell-substrate impedance sensing (ECIS) systems. By evaluating cellular impedance using eight independent sensing electrodes, position-dependent impedance measurements can be recorded across the device and compare commonly used equivalent circuit and mathematical models for extraction of cell parameters. Data from the 8-electrode device was compared to data taken from commercial electric cell-substrate impedance sensing (ECIS) system by deriving a relationship between equivalent circuit and mathematically modelled parameters. The impedance systems were evaluated and compared by investigating the effects of arsenic trioxide (As2O3), a well-established chemotherapeutic agent, on ovarian cancer cells. Impedance spectroscopy, a non-destructive, label-free technique, was used to continuously measure the frequency-dependent cellular properties, without adversely affecting the cells. The importance of multiple measurements within a cell culture was demonstrated; and the data illustrated that the non-uniform response of cells within a culture required redundant measurements in order to obtain statistically significant data, especially for drug discovery applications. Also, a correlation between equivalent circuit modelling and mathematically modelled parameters was derived, allowing data to be compared across different modelling techniques.

  5. A new flow-regulating cell type in the Demosponge Tethya wilhelma - functional cellular anatomy of a leuconoid canal system.

    PubMed

    Hammel, Jörg U; Nickel, Michael

    2014-01-01

    Demosponges possess a leucon-type canal system which is characterized by a highly complex network of canal segments and choanocyte chambers. As sponges are sessile filter feeders, their aquiferous system plays an essential role in various fundamental physiological processes. Due to the morphological and architectural complexity of the canal system and the strong interdependence between flow conditions and anatomy, our understanding of fluid dynamics throughout leuconoid systems is patchy. This paper provides comprehensive morphometric data on the general architecture of the canal system, flow measurements and detailed cellular anatomical information to help fill in the gaps. We focus on the functional cellular anatomy of the aquiferous system and discuss all relevant cell types in the context of hydrodynamic and evolutionary constraints. Our analysis is based on the canal system of the tropical demosponge Tethya wilhelma, which we studied using scanning electron microscopy. We found a hitherto undescribed cell type, the reticuloapopylocyte, which is involved in flow regulation in the choanocyte chambers. It has a highly fenestrated, grid-like morphology and covers the apopylar opening. The minute opening of the reticuloapopylocyte occurs in an opened, intermediate and closed state. These states permit a gradual regulation of the total apopylar opening area. In this paper the three states are included in a theoretical study into flow conditions which aims to draw a link between functional cellular anatomy, the hydrodynamic situation and the regular body contractions seen in T. wilhelma. This provides a basis for new hypotheses regarding the function of bypass elements and the role of hydrostatic pressure in body contractions. Our study provides insights into the local and global flow conditions in the sponge canal system and thus enhances current understanding of related physiological processes.

  6. Effects of phthalates on the human corneal endothelial cell line B4G12.

    PubMed

    Krüger, Tanja; Cao, Yi; Kjærgaard, Søren K; Knudsen, Lisbeth E; Bonefeld-Jørgensen, Eva C

    2012-01-01

    Phthalates are industrial chemicals used in many cosmetics. We evaluated an in vitro model for eye irritancy testing using the human corneal endothelial cell line B4G12. Cell proliferation and toxicity were assessed after exposing to di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), di-2-ethylhexyl phthalate (DEHP), diisodecyl phthalate (DIDP), di-n-octyl phthalate (DnOP), and di-isononyl phthalate (DINP). Gene expression and secretion of inflammatory cytokines were evaluated after exposure to DBP. Decreased cell proliferation was observed for the phthalates DBP, BBP, and DEHP, and cell toxicity was observed for DBP and BBP. Upon DBP exposure at nontoxic concentrations, a significant increased gene expression and cytokine cell secretion were observed for interleukin-1β (IL-1β) and IL-8, and also an increased IL-6 secretion was observed. In conclusion, the human corneal endothelial cell line B4G12 may be a potential model for inflammatory eye irritancy testing of phthalates. PMID:22723514

  7. A telemedicine wound care model using 4G with smart phones or smart glasses

    PubMed Central

    Ye, Junna; Zuo, Yanhai; Xie, Ting; Wu, Minjie; Ni, Pengwen; Kang, Yutian; Yu, Xiaoping; Sun, Xiaofang; Huang, Yao; Lu, Shuliang

    2016-01-01

    Abstract To assess the feasibility of a wound care model using 4th-generation mobile communication technology standards (4G) with smart phones or smart glasses for wound management. This wound care model is an interactive, real-time platform for implementing telemedicine changing wound dressings, or doing operations. It was set up in March 2015 between Jinhua in Zhejiang province and Shanghai, China, which are 328 km apart. It comprised of a video application (APP), 4G net, smart phones or smart glasses, and a central server. This model service has been used in 30 patients with wounds on their lower extremities for 109 times in 1 month. Following a short learning curve, the service worked well and was deemed to be user-friendly. Two (6.7%) patients had wounds healed, while others still required wound dressing changes after the study finished. Both local surgeons and patients showed good acceptance of this model (100% and 83.33%, respectively). This telemedicine model is feasible and valuable because it provides an opportunity of medical service about wound healing in remote areas where specialists are scarce. PMID:27495023

  8. Regeneration in Macrostomum lignano (Platyhelminthes): cellular dynamics in the neoblast stem cell system.

    PubMed

    Nimeth, Katharina Theresia; Egger, Bernhard; Rieger, Reinhard; Salvenmoser, Willi; Peter, Roland; Gschwentner, Robert

    2007-03-01

    Neoblasts are potentially totipotent stem cells and the only proliferating cells in adult Platyhelminthes. We have examined the cellular dynamics of neoblasts during the posterior regeneration of Macrostomum lignano. Double-labeling of neoblasts with bromodeoxyuridine and the anti-phospho histone H3 mitosis marker has revealed a complex cellular response in the first 48 h after amputation; this response is different from that known to occur during regeneration in triclad platyhelminths and in starvation/feeding experiments in M. lignano. Mitotic activity is reduced during the first 8 h of regeneration but, at 48 h after amputation, reaches almost twice the value of control animals. The total number of S-phase cells significantly increases after 1 day of regeneration. A subpopulation of fast-cycling neoblasts surprisingly shows the same dynamics during regeneration as those in control animals. Wound healing and regeneration are accompanied by the formation of a distinct blastema. These results present new insights, at the cellular level, into the early regeneration of rhabditophoran Platyhelminthes.

  9. ARRAKIS: atlas of resonance rings as known in the S4G

    NASA Astrophysics Data System (ADS)

    Comerón, S.; Salo, H.; Laurikainen, E.; Knapen, J. H.; Buta, R. J.; Herrera-Endoqui, M.; Laine, J.; Holwerda, B. W.; Sheth, K.; Regan, M. W.; Hinz, J. L.; Muñoz-Mateos, J. C.; Gil de Paz, A.; Menéndez-Delmestre, K.; Seibert, M.; Mizusawa, T.; Kim, T.; Erroz-Ferrer, S.; Gadotti, D. A.; Athanassoula, E.; Bosma, A.; Ho, L. C.

    2014-02-01

    Context. Resonance rings and pseudorings (here collectively called rings) are thought to be related to the gathering of material near dynamical resonances caused by non-axisymmetries in galaxy discs. This means that they are the result of secular evolution processes that redistribute material and angular momentum in discs. Studying them may give clues on the formation and growth of bars and other disc non-axisymmetries. Aims: Our aims are to produce a catalogue and an atlas of the rings detected in the Spitzer Survey of Stellar Structure in Galaxies (S4G) and to conduct a statistical study of the data in the catalogue. Methods: We traced the contours of rings previously identified and fitted them with ellipses. We found the orientation of bars by studying the galaxy ellipse fits from the S4G pipeline 4. We used the galaxy orientation data obtained by the S4G pipeline 4 to obtain intrinsic ellipticities and orientations of rings and the bars. Results: ARRAKIS contains data on 724 ringed galaxies in the S4G. The frequency of resonance rings in the S4G is of 16 ± 1% and 35 ± 1% for outer and inner features, respectively. Outer rings are mostly found in Hubble stages - 1 ≤ T ≤ 4. Inner rings are found in a broad distribution that covers the range - 1 ≤ T ≤ 7. We confirm that outer rings have two preferred orientations, namely parallel and perpendicular to the bar. We confirm a tendency for inner rings to be oriented parallel to the bar, but we report the existence of a significant fraction (maybe as large as 50%) of inner features that have random orientations with respect to the bar. These misaligned inner rings are mostly found in late-type galaxies (T ≥ 4). We find that the fraction of barred galaxies hosting outer (inner) rings is ~1.7 times (~1.3 times) that in unbarred galaxies. Conclusions: We confirm several results from previous surveys as well as predictions from simulations of resonant rings and/or from manifold flux tube theory. We report that a

  10. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets... Services Information, Cellular MSA/RSA Markets and Counties”, dated January 24, 1992, DA 92-109, 7 FCC...

  11. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets... Services Information, Cellular MSA/RSA Markets and Counties”, dated January 24, 1992, DA 92-109, 7 FCC...

  12. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets... Services Information, Cellular MSA/RSA Markets and Counties”, dated January 24, 1992, DA 92-109, 7 FCC...

  13. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets... Services Information, Cellular MSA/RSA Markets and Counties”, dated January 24, 1992, DA 92-109, 7 FCC...

  14. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets... Services Information, Cellular MSA/RSA Markets and Counties”, dated January 24, 1992, DA 92-109, 7 FCC...

  15. The C-terminal domain of eukaryotic protein synthesis initiation factor (eIF) 4G is sufficient to support cap-independent translation in the absence of eIF4E.

    PubMed Central

    Ohlmann, T; Rau, M; Pain, V M; Morley, S J

    1996-01-01

    The foot and mouth disease virus, a picornavirus, encodes two forms of a cysteine proteinase (leader or L protease) that bisects the EIF4G polypeptide of the initiation factor complex eIF4F into N-terminal (Nt) and C-terminal (Ct) domains. Previously we showed that, although in vitro cleavage of the translation initiation factor, eIF4G, with L protease decreases cap-dependent translation, the cleavage products themselves may directly promote cap-dependent protein synthesis. We now demonstrate that translation of uncapped mRNAs normally exhibits a strong requirement for eIF4F. However, this dependence is abolished when eIF4G is cleaved, with the Ct domain capable of supporting translation in the absence of the Nt domain. In contrast, the efficient translation of the second cistron of bicistronic mRNAs, directed by two distinct Internal Ribosome Entry Segments (IRES), exhibits no requirement for eIF4E but is dependent upon either intact eIF4G or the Ct domain. These results demonstrate that: (i) the apparent requirement for eIF4F for internal initiation on IRES-driven mRNAs can be fulfilled by the Ct proteolytic cleavage product; (ii) when eIF4G is cleaved, the Ct domain can also support cap-independent translation of cellular mRNAs not possessing an IRES element, in the absence of eIF4E; and (iii) when eIF4G is intact, translation of cellular mRNAs, whether capped or uncapped, is strictly dependent upon eIF4E. These data complement recent work in other laboratories defining the binding sites for other initiation factors on the eIF4G molecule. Images PMID:8635470

  16. Mitotic phosphorylation of eukaryotic initiation factor 4G1 (eIF4G1) at Ser1232 by Cdk1:cyclin B inhibits eIF4A helicase complex binding with RNA.

    PubMed

    Dobrikov, Mikhail I; Shveygert, Mayya; Brown, Michael C; Gromeier, Matthias

    2014-02-01

    During mitosis, global translation is suppressed, while synthesis of proteins with vital mitotic roles must go on. Prior evidence suggests that the mitotic translation shift involves control of initiation. Yet, no signals specifically targeting translation initiation factors during mitosis have been identified. We used phosphoproteomics to investigate the central translation initiation scaffold and "ribosome adaptor," eukaryotic initiation factor 4G1 (eIF4G1) in interphase or nocodazole-arrested mitotic cells. This approach and kinase inhibition assays, in vitro phosphorylation with recombinant kinase, and kinase depletion-reconstitution experiments revealed that Ser1232 in eIF4G1 is phosphorylated by cyclin-dependent kinase 1 (Cdk1):cyclin B during mitosis. Ser1232 is located in an unstructured region of the C-terminal portion of eIF4G1 that coordinates assembly of the eIF4G/-4A/-4B helicase complex and binding of the mitogen-activated protein kinase (MAPK) signal-integrating kinase, Mnk. Intense phosphorylation of Ser1232 in mitosis strongly enhanced the interactions of eIF4A with HEAT domain 2 of eIF4G and decreased association of eIF4G/-4A with RNA. Our findings implicate phosphorylation of eIF4G1(Ser1232) by Cdk1:cyclin B and its inhibitory effects on eIF4A helicase activity in the mitotic translation initiation shift.

  17. Abnormalities in the cellular phase of blood fibrinolytic activity in systemic lupus erythematosus and in venous thromboembolism

    SciTech Connect

    Moroz, L.A.; MacLean, L.D.; Langleben, D.

    1986-09-15

    Fibrinolytic activities of whole blood and plasma were determined by /sup 125/I-fibrin radiometric assay in 16 normal subjects, and in 11 patients with systemic lupus erythematosus (SLE), 14 with progressive systemic sclerosis (PSS), 23 with venous thromboembolic disease, and 20 patients awaiting elective surgery. Mean whole blood and plasma activities for patients with PSS, and for those awaiting elective surgery, were similar to normal values, as was the mean plasma activity in patients with SLE. However, mean whole blood activity in SLE was significantly decreased compared with normals (p less than 0.05), with mean plasma activity accounting for 44% of mean whole blood activity (compared with 17% in normal subjects), representing a 67% decrease in mean calculated cellular phase activity in SLE, when compared with normals. Since the numbers of cells (neutrophils, monocytes) possibly involved in cellular activity were not decreased, the findings suggest a functional defect in fibrinolytic activity of one or more blood cell types in SLE. An additional finding was the participation of the cellular phase as well as the well-known plasma phase of blood in the fibrinolytic response to thromboembolism.

  18. A tandem regression-outlier analysis of a ligand cellular system for key structural modifications around ligand binding

    PubMed Central

    2013-01-01

    Background A tandem technique of hard equipment is often used for the chemical analysis of a single cell to first isolate and then detect the wanted identities. The first part is the separation of wanted chemicals from the bulk of a cell; the second part is the actual detection of the important identities. To identify the key structural modifications around ligand binding, the present study aims to develop a counterpart of tandem technique for cheminformatics. A statistical regression and its outliers act as a computational technique for separation. Results A PPARγ (peroxisome proliferator-activated receptor gamma) agonist cellular system was subjected to such an investigation. Results show that this tandem regression-outlier analysis, or the prioritization of the context equations tagged with features of the outliers, is an effective regression technique of cheminformatics to detect key structural modifications, as well as their tendency of impact to ligand binding. Conclusions The key structural modifications around ligand binding are effectively extracted or characterized out of cellular reactions. This is because molecular binding is the paramount factor in such ligand cellular system and key structural modifications around ligand binding are expected to create outliers. Therefore, such outliers can be captured by this tandem regression-outlier analysis. PMID:23627990

  19. Characterization of galactic bars from 3.6 μm S4G imaging

    NASA Astrophysics Data System (ADS)

    Díaz-García, S.; Salo, H.; Laurikainen, E.; Herrera-Endoqui, M.

    2016-03-01

    Context. Stellar bars play an essential role in the secular evolution of disk galaxies because they are responsible for the redistribution of matter and angular momentum. Dynamical models predict that bars become stronger and longer in time, while their rotation speed slows down. Aims: We use the Spitzer Survey of Stellar Structure in Galaxies (S4G) 3.6 μm imaging to study the properties (length and strength) and fraction of bars at z = 0 over a wide range of galaxy masses (M∗ ≈ 108-1011 M⊙) and Hubble types (-3 ≤ T ≤ 10). Methods: We calculated gravitational forces from the 3.6 μm images for galaxies with a disk inclination lower than 65°. We used the maximum of the tangential-to-radial force ratio in the bar region (Qb) as a measure of the bar-induced perturbation strength for a sample of ~600 barred galaxies. We also used the maximum of the normalized m = 2 Fourier density amplitude (A2max) to characterize the bar. Bar sizes were estimated i) visually; ii) from ellipse fitting; iii) from the radii of the strongest torque; and iv) from the radii of the largest m = 2 Fourier amplitude in the bar region. By combining our force calculations with the H i kinematics from the literature, we estimated the ratio of the halo-to-stellar mass (Mh/M∗) within the optical disk and by further using the universal rotation curve models, we obtained a first-order model of the rotation curve decomposition of 1128 disk galaxies. Results: We probe possible sources of uncertainty in our Qb measurements: the assumed scale height and its radial variation, the influence of the spiral arms torques, the effect of non-stellar emission in the bar region, and the dilution of the bar forces by the dark matter halo (our models imply that only ~10% of the disks in our sample are maximal). We find that for early- and intermediate-type disks (-3 ≤ T< 5), the relatively modest influence of the dark matter halo leads to a systematic reduction of the mean Qb by about 10-15%, which is

  20. Systems Biology-Based Investigation of Cellular Antiviral Drug Targets Identified by Gene-Trap Insertional Mutagenesis.

    PubMed

    Cheng, Feixiong; Murray, James L; Zhao, Junfei; Sheng, Jinsong; Zhao, Zhongming; Rubin, Donald H

    2016-09-01

    Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap) host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins. We herein reported 712 candidate cellular genes, characterizing distinct topological network and evolutionary signatures, and occupying central hubs in the human interactome. Cell cycle phase-specific network analysis showed that host cell cycle programs played critical roles during viral replication (e.g. MYC and TAF4 regulating G0/1 phase). Moreover, the viral perturbation of host cellular networks reflected disease etiology in that host genes (e.g. CTCF, RHOA, and CDKN1B) identified were frequently essential and significantly associated with Mendelian and orphan diseases, or somatic mutations in cancer. Computational drug repositioning framework via incorporating drug-gene signatures from the Connectivity Map into the virus-host interactome identified 110 putative druggable antiviral targets and prioritized several existing drugs (e.g. ajmaline) that may be potential for antiviral indication (e.g. anti-Ebola). In summary, this work provides a powerful methodology with a tight integration of gene-trap insertional mutagenesis testing and systems biology to identify new antiviral targets and drugs for the development of broadly acting and targeted clinical antiviral therapeutics.

  1. Systems Biology-Based Investigation of Cellular Antiviral Drug Targets Identified by Gene-Trap Insertional Mutagenesis.

    PubMed

    Cheng, Feixiong; Murray, James L; Zhao, Junfei; Sheng, Jinsong; Zhao, Zhongming; Rubin, Donald H

    2016-09-01

    Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap) host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins. We herein reported 712 candidate cellular genes, characterizing distinct topological network and evolutionary signatures, and occupying central hubs in the human interactome. Cell cycle phase-specific network analysis showed that host cell cycle programs played critical roles during viral replication (e.g. MYC and TAF4 regulating G0/1 phase). Moreover, the viral perturbation of host cellular networks reflected disease etiology in that host genes (e.g. CTCF, RHOA, and CDKN1B) identified were frequently essential and significantly associated with Mendelian and orphan diseases, or somatic mutations in cancer. Computational drug repositioning framework via incorporating drug-gene signatures from the Connectivity Map into the virus-host interactome identified 110 putative druggable antiviral targets and prioritized several existing drugs (e.g. ajmaline) that may be potential for antiviral indication (e.g. anti-Ebola). In summary, this work provides a powerful methodology with a tight integration of gene-trap insertional mutagenesis testing and systems biology to identify new antiviral targets and drugs for the development of broadly acting and targeted clinical antiviral therapeutics. PMID:27632082

  2. Systems Biology-Based Investigation of Cellular Antiviral Drug Targets Identified by Gene-Trap Insertional Mutagenesis

    PubMed Central

    Zhao, Junfei; Sheng, Jinsong; Rubin, Donald H.

    2016-01-01

    Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap) host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins. We herein reported 712 candidate cellular genes, characterizing distinct topological network and evolutionary signatures, and occupying central hubs in the human interactome. Cell cycle phase-specific network analysis showed that host cell cycle programs played critical roles during viral replication (e.g. MYC and TAF4 regulating G0/1 phase). Moreover, the viral perturbation of host cellular networks reflected disease etiology in that host genes (e.g. CTCF, RHOA, and CDKN1B) identified were frequently essential and significantly associated with Mendelian and orphan diseases, or somatic mutations in cancer. Computational drug repositioning framework via incorporating drug-gene signatures from the Connectivity Map into the virus-host interactome identified 110 putative druggable antiviral targets and prioritized several existing drugs (e.g. ajmaline) that may be potential for antiviral indication (e.g. anti-Ebola). In summary, this work provides a powerful methodology with a tight integration of gene-trap insertional mutagenesis testing and systems biology to identify new antiviral targets and drugs for the development of broadly acting and targeted clinical antiviral therapeutics. PMID:27632082

  3. Thrombophilic genetic factors PAI-1 4G-4G and MTHFR 677TT as risk factors of alcohol, cryptogenic liver cirrhosis and portal vein thrombosis, in a Caucasian population.

    PubMed

    D'Amico, Mario; Pasta, Francesca; Pasta, Linda

    2015-08-15

    The thrombophilic genetic factors (THRGFs), PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q and Prothrombin 20210A, were studied as risk factors in 865 Caucasian patients with liver cirrhosis, consecutively enrolled from June 2008 to January 2014. A total of 582 HCV, 80 HBV, 94 alcohol, (82 with more than one etiologic factor) and 191 cryptogenic patients with liver cirrhosis had been consecutively enrolled; 243 patients showed portal vein thrombosis (PVT). At least one of the above THRGFs was present in 339/865 patients (39.2%). PAI-1 4G-4G and MTHFR 677TT were the most frequent THRGFs, statistically significant in patients with alcohol, cryptogenic liver cirrhosis, and PVT: respectively 24 and 28, 50 and 73, and 65 and 83 (all chi-square tests>3.84, and p values<0.05). Two logistic regression analysis, using PAI-1 4G-4G and MTHFR 677TT, as dependent variable, confirmed the independent significant relationship of these THRGFs with alcohol, cryptogenic liver cirrhosis and PVT. PAI 1 and MTHFR 677 genotypes, deviated from those expected in populations in Hardy-Weinberg equilibrium (all p values<0.05), in the subgroups of patients with alcohol, cryptogenic liver cirrhosis and presence of PVT. Our study shows the pivotal role of PAI-1 4G-4G and MTHFR 677TT in patients with alcohol, cryptogenic liver cirrhosis, and PVT, in a Caucasian population. In conclusion, thrombo and fibro-genetic mechanisms of PAI-1 4G-4G and MTHFR 677TT, could have a role in the development of liver cirrhosis, mainly in patients without HCV and HBV, and PVT.

  4. Systems Glycobiology: Integrating Glycogenomics, Glycoproteomics, Glycomics, and Other 'Omics Data Sets to Characterize Cellular Glycosylation Processes.

    PubMed

    Bennun, Sandra V; Hizal, Deniz Baycin; Heffner, Kelley; Can, Ozge; Zhang, Hui; Betenbaugh, Michael J

    2016-08-14

    The number of proteins encoded in the human genome has been estimated at between 20,000 and 25,000, despite estimates that the entire proteome contains more than a million proteins. One reason for this difference is due to many post-translational modifications of protein that contribute to proteome complexity. Among these, glycosylation is of particular relevance because it serves to modify a large number of cellular proteins. Glycogenomics, glycoproteomics, glycomics, and glycoinformatics are helping to accelerate our understanding of the cellular events involved in generating the glycoproteome, the variety of glycan structures possible, and the importance of roles that glycans play in therapeutics and disease. Indeed, interest in glycosylation has expanded rapidly over the past decade, as large amounts of experimental 'omics data relevant to glycosylation processing have accumulated. Furthermore, new and more sophisticated glycoinformatics tools and databases are now available for glycan and glycosylation pathway analysis. Here, we summarize some of the recent advances in both experimental profiling and analytical methods involving N- and O-linked glycosylation processing for biotechnological and medically relevant cells together with the unique opportunities and challenges associated with interrogating and assimilating multiple, disparate high-throughput glycosylation data sets. This emerging era of advanced glycomics will lead to the discovery of key glycan biomarkers linked to diseases and help establish a better understanding of physiology and improved control of glycosylation processing in diverse cells and tissues important to disease and production of recombinant therapeutics. Furthermore, methodologies that facilitate the integration of glycomics measurements together with other 'omics data sets will lead to a deeper understanding and greater insights into the nature of glycosylation as a complex cellular process.

  5. A Novel Cell Traction Force Microscopy to Study Multi-Cellular System

    PubMed Central

    Anand, Sandeep V.; Saif, Taher A.

    2014-01-01

    Traction forces exerted by adherent cells on their microenvironment can mediate many critical cellular functions. Accurate quantification of these forces is essential for mechanistic understanding of mechanotransduction. However, most existing methods of quantifying cellular forces are limited to single cells in isolation, whereas most physiological processes are inherently multi-cellular in nature where cell-cell and cell-microenvironment interactions determine the emergent properties of cell clusters. In the present study, a robust finite-element-method-based cell traction force microscopy technique is developed to estimate the traction forces produced by multiple isolated cells as well as cell clusters on soft substrates. The method accounts for the finite thickness of the substrate. Hence, cell cluster size can be larger than substrate thickness. The method allows computing the traction field from the substrate displacements within the cells' and clusters' boundaries. The displacement data outside these boundaries are not necessary. The utility of the method is demonstrated by computing the traction generated by multiple monkey kidney fibroblasts (MKF) and human colon cancerous (HCT-8) cells in close proximity, as well as by large clusters. It is found that cells act as individual contractile groups within clusters for generating traction. There may be multiple of such groups in the cluster, or the entire cluster may behave a single group. Individual cells do not form dipoles, but serve as a conduit of force (transmission lines) over long distances in the cluster. The cell-cell force can be either tensile or compressive depending on the cell-microenvironment interactions. PMID:24901766

  6. Microbial Consortia Engineering for Cellular Factories: in vitro to in silico systems

    PubMed Central

    Bernstein, Hans C; Carlson, Ross P

    2012-01-01

    This mini-review discusses the current state of experimental and computational microbial consortia engineering with a focus on cellular factories. A discussion of promising ecological theories central to community resource usage is presented to facilitate interpretation of consortial designs. Recent case studies exemplifying different resource usage motifs and consortial assembly templates are presented. The review also highlights in silico approaches to design and to analyze consortia with an emphasis on stoichiometric modeling methods. The discipline of microbial consortia engineering possesses a widely accepted potential to generate highly novel and effective bio-catalysts for applications from biofuels to specialty chemicals to enhanced mineral recovery. PMID:24688677

  7. Depression correlated with cellular immunity in systemic immunodeficient Epstein-Barr virus syndrome (SIDES).

    PubMed

    Allen, A D; Tilkian, S M

    1986-03-01

    We conducted studies on the peripheral blood of 12 depressed patients with previous diagnoses of mood and/or personality disorders. These patients, and other depressives we observed informally, were resistant to infectious mononucleosis during an epidemic of that illness. All 12 had serologic evidence of a chronic or recrudescent viremia caused by the Epstein-Barr virus (EBV), the infectious agent in infectious mononucleosis. Additional evidence that EBV viremia may be causally related to depression was provided by a strong correlation between the intensity of depressive symptoms and the cellular immune response to the EBV infection. PMID:3005245

  8. In vitro characterization of EHV-4 gG-deleted mutant.

    PubMed

    Azab, Walid; El-Sheikh, Abuelyazeed; Abdel-Gawad, Azza

    2012-02-01

    Equine herpesvirus 4 (EHV-4) is an important pathogen that causes respiratory tract disease in horse populations worldwide. Glycoprotein G (gG) homologs have been identified in several alphaherpesviruses as minor non-essential membrane-anchored glycoproteins. In this study, EHV-4 gG deletion mutant has been generated by using bacterial artificial chromosome technology to investigate the role of gG in viral pathogenesis. Our findings reported here revealed no significant difference between parental EHV-4 and gG-negative strain in their replication cycle in cell culture. Furthermore, virus titers and plaque formation were comparable in both viruses. It is noteworthy that these findings disagree with the previously published study describing gG deletion in another EHV-4 strain.

  9. `Inorganics-in-Organics': recent developments and outlook for 4G polymer solar cells

    NASA Astrophysics Data System (ADS)

    Jayawardena, K. D. G. Imalka; Rozanski, Lynn J.; Mills, Chris A.; Beliatis, Michail J.; Nismy, N. Aamina; Silva, S. Ravi P.

    2013-08-01

    Recent developments in solution processable single junction polymer solar cells have led to a significant improvement in power conversion efficiencies from ~5% to beyond 9%. While much of the initial efficiency improvements were driven through judicious design of donor polymers, it is the engineering of device architectures through the incorporation of inorganic nanostructures and better processing that has continued the efficiency gains. Inorganic nano-components such as carbon nanotubes, graphene and its derivatives, metal nanoparticles and metal oxides have played a central role in improving device performance and longevity beyond those achieved by conventional 3G polymer solar cells. The present work aims to summarise the diverse roles played by the nanosystems and features in state of the art next generation (4G) polymer solar cells. The challenges associated with the engineering of such devices for future deployment are also discussed.

  10. Complete genome sequence of Cupriavidus basilensis 4G11, isolated from the Oak Ridge Field Research Center site

    DOE PAGES

    Ray, Jayashree; Waters, R. Jordan; Skerker, Jeffrey M.; Kuehl, Jennifer V.; Price, Morgan N.; Huang, Jiawen; Chakraborty, Romy; Arkin, Adam P.; Deutschbauer, Adam

    2015-05-14

    Cupriavidus basilensis 4G11 was isolated from groundwater at the Oak Ridge Field Research Center (FRC) site. Here, we report the complete genome sequence and annotation of Cupriavidus basilensis 4G11. The genome contains 8,421,483 bp, 7,661 predicted protein-coding genes, and a total GC content of 64.4%.

  11. Draft Genome Sequence of Lewinella sp. Strain 4G2 Isolated from the Coastal Sea Surface Microlayer.

    PubMed

    Wong, Shu-Kuan; Yoshizawa, Susumu; Nakajima, Yu; Ogura, Yoshitoshi; Hayashi, Tetsuya; Hamasaki, Koji

    2016-01-01

    We report here the draft genome of Lewinella sp. strain 4G2, isolated from the sea surface microlayer (SML) of a coastal marine inlet. The genome sequence of strain 4G2 should contribute to understanding the lifestyles of bacteria living in the SML. PMID:27469943

  12. The Effect of PAI-1 4G/5G Polymorphism and Clinical Factors on Coronary Artery Occlusion in Myocardial Infarction

    PubMed Central

    Parpugga, Tajinder Kumar; Tatarunas, Vacis; Skipskis, Vilius; Kupstyte, Nora; Zaliaduonyte-Peksiene, Diana; Lesauskaite, Vaiva

    2015-01-01

    Objective. Data on the impact of PAI-1-675 4G/5G genotype for fibrinolysis during myocardial infarction are inconsistent. The aim of our study was to evaluate the association of clinical and genetic (PAI-1-675 4G/5G polymorphism) factors with coronary artery occlusion in patients with myocardial infarction. Materials and Methods. PAI-1-675 4G/5G detection was achieved by using Sanger sequencing in a sample of patients hospitalized for stent implantation due to myocardial infarction. We categorized the patients into two groups: patients with coronary artery occlusion and patients without coronary artery occlusion according to angiographic evaluation. Results. We identified n = 122 (32.4%) 4G/4G, n = 186 (49.5%) 4G/5G, and n = 68 (18.1%) 5G/5G PAI-1 genotype carriers. Univariate and multivariate analysis showed that only the 4G/5G genotype was associated with coronary artery occlusion (OR: 1.656 and 95% CI: 1.009–2.718, p = 0.046). Conclusions. Our results showed that carriers of PAI-1 4G/5G genotype with myocardial infarction have increased odds of coronary artery occlusion more than 1.6 times in comparison to the carriers of homozygous genotypes. PMID:26273123

  13. Cellular Biology in Terms of Stochastic Nonlinear Biochemical Dynamics: Emergent Properties, Isogenetic Variations and Chemical System Inheritability

    NASA Astrophysics Data System (ADS)

    Qian, Hong

    2010-12-01

    Based on a stochastic, nonlinear, open biochemical reaction system perspective, we present an analytical theory for cellular biochemical processes. The chemical master equation (CME) approach provides a unifying mathematical framework for cellular modeling. We apply this theory to both self-regulating gene networks and phosphorylation-dephosphorylation signaling modules with feedbacks. Two types of bistability are illustrated in mesoscopic biochemical systems: one that has a macroscopic, deterministic counterpart and another that does not. In certain cases, the latter stochastic bistability is shown to be a "ghost" of the extinction phenomenon. We argue the thermal fluctuations inherent in molecular processes do not disappear in mesoscopic cell-sized nonlinear systems; rather they manifest themselves as isogenetic variations on a different time scale. Isogenetic biochemical variations in terms of the stochastic attractors can have extremely long lifetime. Transitions among discrete stochastic attractors spend most of the time in "waiting", exhibit punctuated equilibria. It can be naturally passed to "daughter cells" via a simple growth and division process. The CME system follows a set of nonequilibrium thermodynamic laws that include non-increasing free energy F( t) with external energy drive Q hk ≥0, and total entropy production rate e p =- dF/ dt+ Q hk ≥0. In the thermodynamic limit, with a system's size being infinitely large, the nonlinear bistability in the CME exhibits many of the characteristics of macroscopic equilibrium phase transition.

  14. High resolution light-sheet based high-throughput imaging cytometry system enables visualization of intra-cellular organelles

    NASA Astrophysics Data System (ADS)

    Regmi, Raju; Mohan, Kavya; Mondal, Partha Pratim

    2014-09-01

    Visualization of intracellular organelles is achieved using a newly developed high throughput imaging cytometry system. This system interrogates the microfluidic channel using a sheet of light rather than the existing point-based scanning techniques. The advantages of the developed system are many, including, single-shot scanning of specimens flowing through the microfluidic channel at flow rate ranging from micro- to nano- lit./min. Moreover, this opens-up in-vivo imaging of sub-cellular structures and simultaneous cell counting in an imaging cytometry system. We recorded a maximum count of 2400 cells/min at a flow-rate of 700 nl/min, and simultaneous visualization of fluorescently-labeled mitochondrial network in HeLa cells during flow. The developed imaging cytometry system may find immediate application in biotechnology, fluorescence microscopy and nano-medicine.

  15. Cellular activation in limbic brain systems during social play behaviour in rats

    PubMed Central

    van Kerkhof, Linda W.M.; Trezza, Viviana; Mulder, Tessa; Gao, Ping; Voorn, Pieter; Vanderschuren, Louk J.M.J.

    2013-01-01

    Positive social interactions during the juvenile and adolescent phases of life are essential for proper social and cognitive development in mammals, including humans. During this developmental period, there is a marked increase in peer-peer interactions, signified by the abundance of social play behaviour. Despite its importance for behavioural development, our knowledge of the neural underpinnings of social play behaviour is limited. Therefore, the purpose of this study was to map the neural circuits involved in social play behaviour in rats. This was achieved by examining cellular activity after social play using the immediate early gene c-fos as a marker. After a session of social play behaviour, pronounced increases in c-fos expression were observed in the medial prefrontal cortex, medial and ventral orbitofrontal cortex, dorsal striatum, nucleus accumbens core and shell, lateral amygdala, several thalamic nuclei, dorsal raphe and the pedunculopontine tegmental nucleus. Importantly, the cellular activity patterns after social play were topographically organised in this network, as indicated by play-specific correlations in c-fos activity between regions with known direct connections. These correlations suggest involvement in social play behaviour of the projections from the medial prefrontal cortex to the striatum, and of amygdala and monoaminergic inputs to frontal cortex and striatum. The analyses presented here outline a topographically organised neural network implicated in processes such as reward, motivation and cognitive control over behaviour, which mediates social play behaviour in rats. PMID:23670540

  16. Cellular activation in limbic brain systems during social play behaviour in rats.

    PubMed

    van Kerkhof, Linda W M; Trezza, Viviana; Mulder, Tessa; Gao, Ping; Voorn, Pieter; Vanderschuren, Louk J M J

    2014-07-01

    Positive social interactions during the juvenile and adolescent phases of life are essential for proper social and cognitive development in mammals, including humans. During this developmental period, there is a marked increase in peer-peer interactions, signified by the abundance of social play behaviour. Despite its importance for behavioural development, our knowledge of the neural underpinnings of social play behaviour is limited. Therefore, the purpose of this study was to map the neural circuits involved in social play behaviour in rats. This was achieved by examining cellular activity after social play using the immediate early gene c-Fos as a marker. After a session of social play behaviour, pronounced increases in c-Fos expression were observed in the medial prefrontal cortex, medial and ventral orbitofrontal cortex, dorsal striatum, nucleus accumbens core and shell, lateral amygdala, several thalamic nuclei, dorsal raphe and the pedunculopontine tegmental nucleus. Importantly, the cellular activity patterns after social play were topographically organized in this network, as indicated by play-specific correlations in c-Fos activity between regions with known direct connections. These correlations suggest involvement in social play behaviour of the projections from the medial prefrontal cortex to the striatum, and of amygdala and monoaminergic inputs to frontal cortex and striatum. The analyses presented here outline a topographically organized neural network implicated in processes such as reward, motivation and cognitive control over behaviour, which mediates social play behaviour in rats. PMID:23670540

  17. Cellular activation in limbic brain systems during social play behaviour in rats.

    PubMed

    van Kerkhof, Linda W M; Trezza, Viviana; Mulder, Tessa; Gao, Ping; Voorn, Pieter; Vanderschuren, Louk J M J

    2014-07-01

    Positive social interactions during the juvenile and adolescent phases of life are essential for proper social and cognitive development in mammals, including humans. During this developmental period, there is a marked increase in peer-peer interactions, signified by the abundance of social play behaviour. Despite its importance for behavioural development, our knowledge of the neural underpinnings of social play behaviour is limited. Therefore, the purpose of this study was to map the neural circuits involved in social play behaviour in rats. This was achieved by examining cellular activity after social play using the immediate early gene c-Fos as a marker. After a session of social play behaviour, pronounced increases in c-Fos expression were observed in the medial prefrontal cortex, medial and ventral orbitofrontal cortex, dorsal striatum, nucleus accumbens core and shell, lateral amygdala, several thalamic nuclei, dorsal raphe and the pedunculopontine tegmental nucleus. Importantly, the cellular activity patterns after social play were topographically organized in this network, as indicated by play-specific correlations in c-Fos activity between regions with known direct connections. These correlations suggest involvement in social play behaviour of the projections from the medial prefrontal cortex to the striatum, and of amygdala and monoaminergic inputs to frontal cortex and striatum. The analyses presented here outline a topographically organized neural network implicated in processes such as reward, motivation and cognitive control over behaviour, which mediates social play behaviour in rats.

  18. Far-field 2.45 GHz irradiation system for cellular monolayers in vitro.

    PubMed

    Harrison, G H; McCulloch, D; Balcer-Kubiczek, E K; Robinson, J E

    1985-01-01

    A 2.45-GHz microwave exposure facility was developed for long-term TEM irradiation of cellular monolayers. Culture flasks with cells attached to the inside bottom surface were filled with medium, submerged in a 60 X 60 X 12-cm water bath on the field central axis, and exposed in the far-field 2 m below the ceiling-mounted antenna. A quarter-wave transformer plate increased the power transmitted into the water bath, and treatment temperatures were maintained by closed circulation with an external temperature control reservoir. Power density mapped below the quarter-wave plate indicated uniform TEM fields in the 25 X 25-cm region where flasks were located. With 1 kW of forward power to the antenna, the SAR [W/kg] = 45 exp(-0.607d) where d [cm] is the depth in water at any point within this area.

  19. Protozoa as model systems for the study of cellular responses to altered gravity conditions.

    PubMed

    Hemmersbach-Krause, R; Briegleb, W; Häder D-P; Vogel, K; Klein, S; Mulisch, M

    1994-01-01

    The orientation behavior of Paramecium changed in a similar way after transition to conditions of free-fall in a sounding rocket and after transition to conditions of simulated weightlessness on a fast rotating clinostat. After a period of residual orientation, Paramecium cells distributed themselves randomly 80 s (120 s) after onset of free-fall (simulated weightlessness). Swimming velocity increased significantly; however, the increase was transient and subsided after 3 min in the rocket experiments, while the velocity remained enhanced even during 2 h of rotation on a fast clinostat. Trichocysts were present and without morphological changes in Paramecium cells which had been exposed to a rocket flight, as well as to fast or slow rotation on a clinostat. Regeneration of the oral apparatus of Stentor and morphogenesis of Eufolliculina proceeded normally on the clinostat. The results demonstrate that the clinostat is a useful tool to simulate the conditions of weightlessness on earth and to detect gravisensitive cellular functions. PMID:11537958

  20. Protozoa as model systems for the study of cellular responses to altered gravity conditions

    NASA Astrophysics Data System (ADS)

    Hemmersbach-Krause, R.; Briegleb, W.; Häder, D.-P.; Vogel, K.; Klein, S.; Mulisch, M.

    1994-08-01

    The orientation behavior of Paramecium changed in a similar way after transition to conditions of free-fall in a sounding rocket and after transition to conditions of simulated weightlessness on a fast rotating clinostat. After a period of residual orientation, Paramecium cells distributed themselves randomly 80 s (120 s) after onset of free-fall (simulated weightlessness). Swimming velocity increased significantly; however, the increase was transient and subsided after 3 min in the rocket experiments, while the velocity remained enhanced even during 2 h of rotation on a fast clinostat. Trichocysts were present and without morphological changes in Paramecium cells which had been exposed to a rocket flight, as well as to fast or slow rotation on a clinostat. Regeneration of the oral apparatus of Stentor and morphogenesis of Eufolliculina proceeded normally on the clinostat. The results demonstrate that the clinostat is a useful tool to stimulate the conditions of weightlessness on earth and to detect gravisensitive cellular functions.

  1. Multiscale Systems Analysis of Root Growth and Development: Modeling Beyond the Network and Cellular Scales

    PubMed Central

    Band, Leah R.; Fozard, John A.; Godin, Christophe; Jensen, Oliver E.; Pridmore, Tony; Bennett, Malcolm J.; King, John R.

    2012-01-01

    Over recent decades, we have gained detailed knowledge of many processes involved in root growth and development. However, with this knowledge come increasing complexity and an increasing need for mechanistic modeling to understand how those individual processes interact. One major challenge is in relating genotypes to phenotypes, requiring us to move beyond the network and cellular scales, to use multiscale modeling to predict emergent dynamics at the tissue and organ levels. In this review, we highlight recent developments in multiscale modeling, illustrating how these are generating new mechanistic insights into the regulation of root growth and development. We consider how these models are motivating new biological data analysis and explore directions for future research. This modeling progress will be crucial as we move from a qualitative to an increasingly quantitative understanding of root biology, generating predictive tools that accelerate the development of improved crop varieties. PMID:23110897

  2. Protozoa as model systems for the study of cellular responses to altered gravity conditions.

    PubMed

    Hemmersbach-Krause, R; Briegleb, W; Häder D-P; Vogel, K; Klein, S; Mulisch, M

    1994-01-01

    The orientation behavior of Paramecium changed in a similar way after transition to conditions of free-fall in a sounding rocket and after transition to conditions of simulated weightlessness on a fast rotating clinostat. After a period of residual orientation, Paramecium cells distributed themselves randomly 80 s (120 s) after onset of free-fall (simulated weightlessness). Swimming velocity increased significantly; however, the increase was transient and subsided after 3 min in the rocket experiments, while the velocity remained enhanced even during 2 h of rotation on a fast clinostat. Trichocysts were present and without morphological changes in Paramecium cells which had been exposed to a rocket flight, as well as to fast or slow rotation on a clinostat. Regeneration of the oral apparatus of Stentor and morphogenesis of Eufolliculina proceeded normally on the clinostat. The results demonstrate that the clinostat is a useful tool to simulate the conditions of weightlessness on earth and to detect gravisensitive cellular functions.

  3. Multiscale systems analysis of root growth and development: modeling beyond the network and cellular scales.

    PubMed

    Band, Leah R; Fozard, John A; Godin, Christophe; Jensen, Oliver E; Pridmore, Tony; Bennett, Malcolm J; King, John R

    2012-10-01

    Over recent decades, we have gained detailed knowledge of many processes involved in root growth and development. However, with this knowledge come increasing complexity and an increasing need for mechanistic modeling to understand how those individual processes interact. One major challenge is in relating genotypes to phenotypes, requiring us to move beyond the network and cellular scales, to use multiscale modeling to predict emergent dynamics at the tissue and organ levels. In this review, we highlight recent developments in multiscale modeling, illustrating how these are generating new mechanistic insights into the regulation of root growth and development. We consider how these models are motivating new biological data analysis and explore directions for future research. This modeling progress will be crucial as we move from a qualitative to an increasingly quantitative understanding of root biology, generating predictive tools that accelerate the development of improved crop varieties.

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

    PubMed

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

    2015-12-01

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

  5. Hit to lead studies on (hetero)arylpyrimidines--agonists of the canonical Wnt-beta-catenin cellular messaging system.

    PubMed

    Gilbert, Adam M; Bursavich, Matthew G; Alon, Nippa; Bhat, Bheem M; Bex, Frederick J; Cain, Michael; Coleburn, Valerie; Gironda, Virginia; Green, Paula; Hauze, Diane B; Kharode, Yogendra; Krishnamurthy, Girija; Kirisits, Matthew; Lam, Ho-Sun; Liu, Yao-Bin; Lombardi, Sabrina; Matteo, Jeanne; Murrills, Richard; Robinson, John A; Selim, Sally; Sharp, Michael; Unwalla, Raymond; Varadarajan, Usha; Zhao, Weiguang; Yaworsky, Paul J

    2010-01-01

    A series of (hetero)arylpyrimidines agonists of the Wnt-beta-catenin cellular messaging system have been prepared. These compounds show activity in U2OS cells transfected with Wnt-3a, TCF-luciferase, Dkk-1 and tk-Renilla. Selected compounds show minimal GSK-3beta inhibition indicating that the Wnt-beta-catenin agonism activity most likely comes from interaction at Wnt-3a/Dkk-1. Two examples 1 and 25 show in vivo osteogenic activity in a mouse calvaria model. One example 1 is shown to activate non-phosphorylated beta-catenin formation in bone. PMID:19897365

  6. WRF4G project: Adaptation of WRF Model to Distributed Computing Infrastructures

    NASA Astrophysics Data System (ADS)

    Cofino, Antonio S.; Fernández Quiruelas, Valvanuz; García Díez, Markel; Blanco Real, Jose C.; Fernández, Jesús

    2013-04-01

    Nowadays Grid Computing is powerful computational tool which is ready to be used for scientific community in different areas (such as biomedicine, astrophysics, climate, etc.). However, the use of this distributed computing infrastructures (DCI) is not yet common practice in climate research, and only a few teams and applications in this area take advantage of this infrastructure. Thus, the first objective of this project is to popularize the use of this technology in the atmospheric sciences area. In order to achieve this objective, one of the most used applications has been taken (WRF; a limited- area model, successor of the MM5 model), that has a user community formed by more than 8000 researchers worldwide. This community develop its research activity on different areas and could benefit from the advantages of Grid resources (case study simulations, regional hind-cast/forecast, sensitivity studies, etc.). The WRF model is been used as input by many energy and natural hazards community, therefore those community will also benefit. However, Grid infrastructures have some drawbacks for the execution of applications that make an intensive use of CPU and memory for a long period of time. This makes necessary to develop a specific framework (middleware). This middleware encapsulates the application and provides appropriate services for the monitoring and management of the jobs and the data. Thus, the second objective of the project consists on the development of a generic adaptation of WRF for Grid (WRF4G), to be distributed as open-source and to be integrated in the official WRF development cycle. The use of this WRF adaptation should be transparent and useful to face any of the previously described studies, and avoid any of the problems of the Grid infrastructure. Moreover it should simplify the access to the Grid infrastructures for the research teams, and also to free them from the technical and computational aspects of the use of the Grid. Finally, in order to

  7. A Retroviral CRISPR-Cas9 System for Cellular Autism-Associated Phenotype Discovery in Developing Neurons

    PubMed Central

    Williams, Michael R.; Fricano-Kugler, Catherine J.; Getz, Stephanie A.; Skelton, Patrick D.; Lee, Jeonghoon; Rizzuto, Christian P.; Geller, Joseph S.; Li, Meijie; Luikart, Bryan W.

    2016-01-01

    Retroviruses expressing a fluorescent protein, Cas9, and a small guide RNA are used to mimic nonsense PTEN mutations from autism patients in developing mouse neurons. We compare the cellular phenotype elicited by CRISPR-Cas9 to those elicited using shRNA or Cre/Lox technologies and find that knockdown or knockout (KO) produced a corresponding moderate or severe neuronal hypertrophy in all cells. In contrast, the Cas9 approach produced missense and nonsense Pten mutations, resulting in a mix of KO-equivalent hypertrophic and wild type-like phenotypes. Importantly, despite this mixed phenotype, the neuronal hypertrophy resulting from Pten loss was evident on average in the population of manipulated cells. Having reproduced the known Pten KO phenotype using the CRISPR-Cas9 system we design viruses to target a gene that has recently been associated with autism, KATNAL2. Katnal2 deletion in the mouse results in decreased dendritic arborization of developing neurons. We conclude that retroviral implementation of the CRISPR-Cas9 system is an efficient system for cellular phenotype discovery in wild-type animals. PMID:27161796

  8. A Retroviral CRISPR-Cas9 System for Cellular Autism-Associated Phenotype Discovery in Developing Neurons.

    PubMed

    Williams, Michael R; Fricano-Kugler, Catherine J; Getz, Stephanie A; Skelton, Patrick D; Lee, Jeonghoon; Rizzuto, Christian P; Geller, Joseph S; Li, Meijie; Luikart, Bryan W

    2016-05-10

    Retroviruses expressing a fluorescent protein, Cas9, and a small guide RNA are used to mimic nonsense PTEN mutations from autism patients in developing mouse neurons. We compare the cellular phenotype elicited by CRISPR-Cas9 to those elicited using shRNA or Cre/Lox technologies and find that knockdown or knockout (KO) produced a corresponding moderate or severe neuronal hypertrophy in all cells. In contrast, the Cas9 approach produced missense and nonsense Pten mutations, resulting in a mix of KO-equivalent hypertrophic and wild type-like phenotypes. Importantly, despite this mixed phenotype, the neuronal hypertrophy resulting from Pten loss was evident on average in the population of manipulated cells. Having reproduced the known Pten KO phenotype using the CRISPR-Cas9 system we design viruses to target a gene that has recently been associated with autism, KATNAL2. Katnal2 deletion in the mouse results in decreased dendritic arborization of developing neurons. We conclude that retroviral implementation of the CRISPR-Cas9 system is an efficient system for cellular phenotype discovery in wild-type animals.

  9. The nucleotide sequence of the equine herpesvirus 4 gC gene homologue.

    PubMed

    Nicolson, L; Onions, D E

    1990-11-01

    The genomic position of an equine herpesvirus 4 (EHV-4) gene homologue of the herpes simplex virus 1 (HSV-1) gC gene was determined by Southern analysis and DNA sequencing. The gene lies within a 2-kbp Bg/II-EcoRI fragment mapping between 0.15 and 0.17 within the long unique component of the EHV-4 genome and is transcribed from right to left. Putative promoter elements were identified upstream of the 1455-bp open reading frame which encodes a 485-amino-acid protein of unglycosylated molecular weight 52,513. Computer-assisted analysis of the primary sequence predicts the protein possesses a domain structure characteristic of a type 1 integral membrane glycoprotein. Four domains were distinguished--(i) an N-terminal signal sequence, (ii) a large extracellular domain containing 11 putative N-linked glycosylation sites, (iii) a hydrophobic transmembrane domain, and (iv) a C-terminal charged domain. Comparison of the predicted amino acid sequence to that of other herpesvirus glycoproteins indicated identities of between 22 and 29% with HSV-1 gC, HSV-2 gC, VZV gpV, PRV gIII, BHV-1 gIII, and MDV A antigen and of 79% with EHV-1 gp13. A gene with no apparent homologue in HSV-1 or VZV maps immediately downstream of the EHV-4 gC gene homologue. PMID:2171212

  10. Human eukaryotic initiation factor 4G (eIF4G) protein binds to eIF3c, -d, and -e to promote mRNA recruitment to the ribosome.

    PubMed

    Villa, Nancy; Do, Angelie; Hershey, John W B; Fraser, Christopher S

    2013-11-15

    Recruitment of mRNA to the 40S ribosomal subunit requires the coordinated interaction of a large number of translation initiation factors. In mammals, the direct interaction between eukaryotic initiation factor 4G (eIF4G) and eIF3 is thought to act as the molecular bridge between the mRNA cap-binding complex and the 40S subunit. A discrete ∼90 amino acid domain in eIF4G is responsible for binding to eIF3, but the identity of the eIF3 subunit(s) involved is less clear. The eIF3e subunit has been shown to directly bind eIF4G, but the potential role of other eIF3 subunits in stabilizing this interaction has not been investigated. It is also not clear if the eIF4A helicase plays a role in stabilizing the interaction between eIF4G and eIF3. Here, we have used a fluorescence anisotropy assay to demonstrate that eIF4G binds to eIF3 independently of eIF4A binding to the middle region of eIF4G. By using a site-specific cross-linking approach, we unexpectedly show that the eIF4G-binding surface in eIF3 is comprised of the -c, -d and -e subunits. Screening multiple cross-linker positions reveals that eIF4G contains two distinct eIF3-binding subdomains within the previously identified eIF3-binding domain. Finally, by employing an eIF4G-dependent translation assay, we establish that both of these subdomains are required for efficient mRNA recruitment to the ribosome and stimulate translation. Our study reveals unexpected complexity to the eIF3-eIF4G interaction that provides new insight into the regulation of mRNA recruitment to the human ribosome.

  11. Targeted delivery of photosensitizers: efficacy and selectivity issues revealed by multifunctional ORMOSIL nanovectors in cellular systems

    NASA Astrophysics Data System (ADS)

    Selvestrel, Francesco; Moret, Francesca; Segat, Daniela; Woodhams, Josephine H.; Fracasso, Giulio; Echevarria, Iria M. Rio; Baù, Luca; Rastrelli, Federico; Compagnin, Chiara; Reddi, Elena; Fedeli, Chiara; Papini, Emanuele; Tavano, Regina; MacKenzie, Alexandra; Bovis, Melissa; Yaghini, Elnaz; MacRobert, Alexander J.; Zanini, Silvia; Boscaini, Anita; Colombatti, Marco; Mancin, Fabrizio

    2013-06-01

    PEGylated and non-PEGylated ORMOSIL nanoparticles prepared by microemulsion condensation of vinyltriethoxy-silane (VTES) were investigated in detail for their micro-structure and ability to deliver photoactive agents. With respect to pure silica nanoparticles, organic modification substantially changes the microstructure and the surface properties. This in turn leads to a modulation of both the photophysical properties of embedded photosensitizers and the interaction of the nanoparticles with biological entities such as serum proteins. The flexibility of the synthetic procedure allows the rapid preparation and screening of multifunctional nanosystems for photodynamic therapy (PDT). Selective targeting of model cancer cells was tested by using folate, an integrin specific RGD peptide and anti-EGFR antibodies. Data suggest the interference of the stealth-conferring layer (PEG) with small targeting agents, but not with bulky antibodies. Moreover, we showed that selective photokilling of tumour cells may be limited even in the case of efficient targeting because of intrinsic transport limitations of active cellular uptake mechanisms or suboptimum localization.PEGylated and non-PEGylated ORMOSIL nanoparticles prepared by microemulsion condensation of vinyltriethoxy-silane (VTES) were investigated in detail for their micro-structure and ability to deliver photoactive agents. With respect to pure silica nanoparticles, organic modification substantially changes the microstructure and the surface properties. This in turn leads to a modulation of both the photophysical properties of embedded photosensitizers and the interaction of the nanoparticles with biological entities such as serum proteins. The flexibility of the synthetic procedure allows the rapid preparation and screening of multifunctional nanosystems for photodynamic therapy (PDT). Selective targeting of model cancer cells was tested by using folate, an integrin specific RGD peptide and anti-EGFR antibodies. Data

  12. Enhanced Handoff Scheme for Downlink-Uplink Asymmetric Channels in Cellular Systems

    PubMed Central

    2013-01-01

    In the latest cellular networks, data services like SNS and UCC can create asymmetric packet generation rates over the downlink and uplink channels. This asymmetry can lead to a downlink-uplink asymmetric channel condition being experienced by cell edge users. This paper proposes a handoff scheme to cope effectively with downlink-uplink asymmetric channels. The proposed handoff scheme exploits the uplink channel quality as well as the downlink channel quality to determine the appropriate timing and direction of handoff. We first introduce downlink and uplink channel models that consider the intercell interference, to verify the downlink-uplink channel asymmetry. Based on these results, we propose an enhanced handoff scheme that exploits both the uplink and downlink channel qualities to reduce the handoff-call dropping probability and the service interruption time. The simulation results show that the proposed handoff scheme reduces the handoff-call dropping probability about 30% and increases the satisfaction of the service interruption time requirement about 7% under high-offered load, compared to conventional mobile-assisted handoff. Especially, the proposed handoff scheme is more efficient when the uplink QoS requirement is much stricter than the downlink QoS requirement or uplink channel quality is worse than downlink channel quality. PMID:24501576

  13. Tetanus toxoid-loaded layer-by-layer nanoassemblies for efficient systemic, mucosal, and cellular immunostimulatory response following oral administration.

    PubMed

    Harde, Harshad; Agrawal, Ashish Kumar; Jain, Sanyog

    2015-10-01

    The present study reports the tetanus toxoid (TT)-loaded layer-by-layer nanoassemblies (layersomes) with enhanced protection, permeation, and presentation for comprehensive oral immunization. The stable and lyophilized TT-loaded layersomes were prepared by a thin-film hydration method followed by alternate layer-by-layer coating of an electrolyte. The developed system was assessed for in vitro stability of antigen and formulation, cellular uptake, ex vivo intestinal uptake, and immunostimulatory response using a suitable experimental protocol. Layersomes improved the stability in simulated biological media as well as protected the integrity/conformation and native 3D structure of TT as confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism (CD), and fluorescence spectroscopy, respectively. The cell culture studies demonstrated a 3.8-fold higher permeation of layersomes in Caco-2 cells and an 8.5-fold higher uptake by antigen-presenting cells (RAW 264.7). The TT-loaded layersomes elicited a complete immunostimulatory profile consisting of higher systemic (serum IgG titer), mucosal (sIgA titer), and cellular (interleukin-2 (IL-2) and interferon-γ (IFN-γ) levels) immune response after peroral administration in mice. The modified TT inhibition assay further confirmed the elicitation of complete protective levels of anti-TT antibody (>0.1 IU/mL) by layersomes. In conclusion, the proposed strategy is expected to contribute significantly in the field of stable liposome technology for mass immunization through the oral route.

  14. Cellular systems for toxicity testing. Final report 1 Sep 82-31 Aug 83

    SciTech Connect

    Williams, G.M.; Dunkel, V.C.; Ray, V.A.

    1983-06-01

    Metabolism and End Points of In Vitro Systems, Cytotoxicity, DNA Damage, Chromosome Effects, Mutagenicity Systems, Mammalian Mutagenesis, Transformation Systems, Effects of Tumor Promoters, Mechanistic Significance and Relevance of Short-Term Tests, Application of Short-Term Tests to Chemical Safety Evaluation, and Poster Papers.

  15. Circulating histones are major mediators of systemic inflammation and cellular injury in patients with acute liver failure

    PubMed Central

    Wen, Zongmei; Lei, Zhen; Yao, Lu; Jiang, Ping; Gu, Tao; Ren, Feng; Liu, Yan; Gou, Chunyan; Li, Xiuhui; Wen, Tao

    2016-01-01

    Acute liver failure (ALF) is a life-threatening systemic disorder. Here we investigated the impact of circulating histones, recently identified inflammatory mediators, on systemic inflammation and liver injury in murine models and patients with ALF. We analyzed histone levels in blood samples from 62 patients with ALF, 60 patients with chronic liver disease, and 30 healthy volunteers. We incubated patients' sera with human L02 hepatocytes and monocytic U937 cells to assess cellular damage and cytokine production. d-galactosamine plus lipopolysaccharide (GalN/LPS), concanavalin A (ConA), and acetaminophen (APAP) were given to C57BL/6N mice to induce liver injury, respectively, and the pathogenic role of circulating histones was studied. Besides, the protective effect of nonanticoagulant heparin, which can bind histones, was evaluated with in vivo and ex vivo investigations. We observed that circulating histones were significantly increased in patients with ALF, and correlated with disease severity and mortality. Significant systemic inflammation was also pronounced in ALF patients, which were associated with histone levels. ALF patients' sera induced significant L02 cell death and stimulated U937 cells to produce cytokines, which were abrogated by nonanticoagulant heparin. Furthermore, circulating histones were all released remarkably in GalN/LPS, ConA, and APAP-treated mice, and associated with high levels of inflammatory cytokines. Heparin reduced systemic inflammation and liver damage in mice, suggesting that it could interfere with histone-associated liver injury. Collectively, these findings demonstrate that circulating histones are critical mediators of systemic inflammation and cellular damage in ALF, which may be potentially translatable for clinical use. PMID:27685635

  16. Cytochrome P450 gene, CYP4G51, modulates hydrocarbon production in the pea aphid, Acyrthosiphon pisum.

    PubMed

    Chen, Nan; Fan, Yong-Liang; Bai, Yu; Li, Xiang-Dong; Zhang, Zhan-Feng; Liu, Tong-Xian

    2016-09-01

    Terrestrial insects deposit a layer of hydrocarbons (HCs) as waterproofing agents on their epicuticle. The insect-specific CYP4G genes, subfamily members of P450, have been found in all insects with sequenced genomes to date. They are critical for HC biosynthesis in Drosophila; however, their functional roles in other insects including the piercing-sucking hemipterous aphids remain unknown. In this study, we presented the molecular characterization and a functional study of the CYP4G51 gene in the pea aphid, Acyrthosiphon pisum (Harris). CYP4G51 transcript was detectable across the whole life cycle of A. pisum, and was prominently expressed in the aphid head and abdominal cuticle. Up-regulation of CYP4G51 under desiccation stress was more significant in the third instar nymphs compared with the adults. Also, up-regulation of CYP4G51 was observed when the aphids fed on an artificial diet compared with those fed on the broad bean plant, and was positively correlated with a high level of cuticular HCs (CHCs). RNAi knockdown of CYP4G51 significantly reduced its expression and caused reductions in both internal and external HCs. A deficiency in CHCs resulted in aphids being more susceptible to desiccation, with increased mortality under desiccation stress. The current results confirm that CYP4G51 modulates HC biosynthesis to protect aphids from desiccation. Moreover, our data also indicate that saturated and straight-chain HCs play a major role in cuticular waterproofing in the pea aphid. A. pisum CYP4G51 could be considered as a novel RNAi target in the field of insect pest management. PMID:27425674

  17. Peptide-MHC Cellular Microarray with Innovative Data Analysis System for Simultaneously Detecting Multiple CD4 T-Cell Responses

    PubMed Central

    Ge, Xinhui; Gebe, John A.; Bollyky, Paul L.; James, Eddie A.; Yang, Junbao; Stern, Lawrence J.; Kwok, William W.

    2010-01-01

    Background Peptide:MHC cellular microarrays have been proposed to simultaneously characterize multiple Ag-specific populations of T cells. The practice of studying immune responses to complicated pathogens with this tool demands extensive knowledge of T cell epitopes and the availability of peptide:MHC complexes for array fabrication as well as a specialized data analysis approach for result interpretation. Methodology/Principal Findings We co-immobilized peptide:DR0401 complexes, anti-CD28, anti-CD11a and cytokine capture antibodies on the surface of chamber slides to generate a functional array that was able to detect rare Ag-specific T cell populations from previously primed in vitro T cell cultures. A novel statistical methodology was also developed to facilitate batch processing of raw array-like data into standardized endpoint scores, which linearly correlated with total Ag-specific T cell inputs. Applying these methods to analyze Influenza A viral antigen-specific T cell responses, we not only revealed the most prominent viral epitopes, but also demonstrated the heterogeneity of anti-viral cellular responses in healthy individuals. Applying these methods to examine the insulin producing beta-cell autoantigen specific T cell responses, we observed little difference between autoimmune diabetic patients and healthy individuals, suggesting a more subtle association between diabetes status and peripheral autoreactive T cells. Conclusions/Significance The data analysis system is reliable for T cell specificity and functional testing. Peptide:MHC cellular microarrays can be used to obtain multi-parametric results using limited blood samples in a variety of translational settings. PMID:20634998

  18. Temporal order of evolution of DNA replication systems inferred by comparison of cellular and viral DNA polymerases

    PubMed Central

    Koonin, Eugene V

    2006-01-01

    Background The core enzymes of the DNA replication systems show striking diversity among cellular life forms and more so among viruses. In particular, and counter-intuitively, given the central role of DNA in all cells and the mechanistic uniformity of replication, the core enzymes of the replication systems of bacteria and archaea (as well as eukaryotes) are unrelated or extremely distantly related. Viruses and plasmids, in addition, possess at least two unique DNA replication systems, namely, the protein-primed and rolling circle modalities of replication. This unexpected diversity makes the origin and evolution of DNA replication systems a particularly challenging and intriguing problem in evolutionary biology. Results I propose a specific succession for the emergence of different DNA replication systems, drawing argument from the differences in their representation among viruses and other selfish replicating elements. In a striking pattern, the DNA replication systems of viruses infecting bacteria and eukaryotes are dominated by the archaeal-type B-family DNA polymerase (PolB) whereas the bacterial replicative DNA polymerase (PolC) is present only in a handful of bacteriophage genomes. There is no apparent mechanistic impediment to the involvement of the bacterial-type replication machinery in viral DNA replication. Therefore, I hypothesize that the observed, markedly unequal distribution of the replicative DNA polymerases among the known cellular and viral replication systems has a historical explanation. I propose that, among the two types of DNA replication machineries that are found in extant life forms, the archaeal-type, PolB-based system evolved first and had already given rise to a variety of diverse viruses and other selfish elements before the advent of the bacterial, PolC-based machinery. Conceivably, at that stage of evolution, the niches for DNA-viral reproduction have been already filled with viruses replicating with the help of the archaeal

  19. Structure-activity relationship study of 4EGI-1, small molecule eIF4E/eIF4G protein-protein interaction inhibitors

    PubMed Central

    Takrouri, Khuloud; Chen, Ting; Papadopoulos, Evangelos; Sahoo, Rupam; Kabha, Eihab; Chen, Han; Cantel, Sonia; Wagner, Gerhard; Halperin, Jose A; Aktas, Bertal H; Chorev, Michael

    2014-01-01

    Protein-protein interactions are critical for regulating the activity of translation initiation factors and multitude of other cellular process, and form the largest block of untapped albeit most challenging targets for drug development. 4EGI-1, (E/Z)-2-(2-(4-(3,4-dichlorophenyl)thiazol-2-yl)hydrazono)-3-(2-nitrophenyl)propanoic acid, is a hit compound discovered in a screening campaign of small molecule libraries as an inhibitor of translation initiation factors eIF4E and eIF4G protein-protein interaction; it inhibits translation initiation in vitro and in vivo. A series of 4EGI-1-derived thiazol-2-yl hydrazones have been designed and synthesized in order to delineate the structural latitude and improve its binding affinity to eIF4E, and increase its potency in inhibiting the eIF4E/eIF4G interaction. Probing a wide range of substituents on both phenyl rings comprising the 3-phenylpropionic acid and 4-phenylthiazolidine moieties in the context of both E- and Z-isomers of 4EGI-1 led to analogs with enhanced binding affinity and translation initiation inhibitory activities. PMID:24675136

  20. Microbial Protein-Protein Interactions (MiPPI) Data from the Genomics: GTL Center for Molecular and Cellular Systems (CMCS)

    DOE Data Explorer

    The Genomic Science Center for Molecular and Cellular Systems (CMCS), established in 2002, seeks to identify and characterize the complete set of protein complexes within a cell to provide a mechanistic basis for the understanding of biochemical functions. The CMCS is anchored at ORNL and PNNL. CMCS initially focused on the identification and characterization of protein complexes in two microbial systems,Rhodopseudomonas palustris (R. palustris) and Shewanella oneidensis (S. oneidensis). These two organisms have also been the focus of major DOE Genomic Science/Microbial Cell Program (MCP) projects. To develop an approach for identifying the diverse types of complexes present in microbial organisms, CMCS incorporates a number of molecular biology, microbiology, analytical and computational tools in an integrated pipeline.

  1. Identification of cellular genes critical to recombinant protein production using a Gaussia luciferase-based siRNA screening system.

    PubMed

    Lwa, Teng Rhui; Tan, Chuan Hao; Lew, Qiao Jing; Chu, Kai Ling; Tan, Janice; Lee, Yih Yean; Chao, Sheng-Hao

    2010-04-15

    Development of high-throughput functional genomic screening, including siRNA screening, provides a novel approach for quick identification of critical factors involved in biological processes. Here, we apply this strategy to search for cellular genes involved in recombinant protein production. Since most of biopharmaceutical proteins are secreted proteins, we develop a cell-based reporter assay using a secreted luciferase, Gaussia luciferase (Gluc), as the reporter. Human embryonic kidney 293 (HEK293) cells transiently transfected with the Gluc reporter plasmid are used to screen our siRNA panel. Three cellular genes, CCAAT/enhancer binding protein gamma (CEBPG), potassium channel tetramerisation domain containing 2 (KCTD2), transmembrane protein 183A (TMEM183A), were isolated from the screening. Production of erythropoietin (EPO) was significantly inhibited when CEBPG, KCTD2, and TMEM183A were knocked down. Furthermore, overexpression of CEBPG is shown to significantly improve production of recombinant EPO, interferon gamma, and monoclonal antibody in HEK293 and Chinese hamster ovary cells. Collectively, this novel Gluc-based siRNA screening system is proven to be a useful tool for investigation of secreted protein production in mammalian cells. PMID:20188772

  2. Catalogue of the morphological features in the Spitzer Survey of Stellar Structure in Galaxies (S4G)

    NASA Astrophysics Data System (ADS)

    Herrera-Endoqui, M.; Díaz-García, S.; Laurikainen, E.; Salo, H.

    2015-10-01

    Context. A catalogue of the features for the complete Spitzer Survey of Stellar Structure in Galaxies (S4G), including 2352 nearby galaxies, is presented. The measurements are made using 3.6 μm images, largely tracing the old stellar population; at this wavelength the effects of dust are also minimal. The measured features are the sizes, ellipticities, and orientations of bars, rings, ringlenses, and lenses. Measured in a similar manner are also barlenses (lens-like structures embedded in the bars), which are not lenses in the usual sense, being rather the more face-on counterparts of the boxy/peanut structures in the edge-on view. In addition, pitch angles of spiral arm segments are measured for those galaxies where they can be reliably traced. More than one pitch angle may appear for a single galaxy. All measurements are made in a human-supervised manner so that attention is paid to each galaxy. Aims: We create a catalogue of morphological features in the complete S4G. Methods: We used isophotal analysis, unsharp masking, and fitting ellipses to measured structures. Results: We find that the sizes of the inner rings and lenses normalized to barlength correlate with the galaxy mass: the normalized sizes increase toward the less massive galaxies; it has been suggested that this is related to the larger dark matter content in the bar region in these systems. Bars in the low mass galaxies are also less concentrated, likely to be connected to the mass cut-off in the appearance of the nuclear rings and lenses. We also show observational evidence that barlenses indeed form part of the bar, and that a large fraction of the inner lenses in the non-barred galaxies could be former barlenses in which the thin outer bar component has dissolved. Full Tables 2 and 3 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/582/A86

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

    PubMed

    Mayer, M P; Bukau, B

    1998-03-01

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

  4. Effect of the Route of Administration and PEGylation of Poly(amidoamine) Dendrimers on Their Systemic and Lung Cellular Biodistribution.

    PubMed

    Zhong, Qian; Merkel, Olivia M; Reineke, Joshua J; da Rocha, Sandro R P

    2016-06-01

    There are many opportunities in the development of oral inhalation (oi) formulations for the delivery of small molecule therapeutics and biologics to and through the lungs. Nanocarriers have the potential to play a key role in advancing oi technologies and pushing the boundary of the pulmonary delivery market. In this work we investigate the effect of the route of administration and PEGylation on the systemic and lung cellular biodistribution of generation 3, amino-terminated poly(amidoamine) (PAMAM) dendrimers (G3NH2). Pharmacokinetic profiles show that the dendrimers reach their peak concentration in systemic circulation within a few hours after pulmonary delivery, independent of their chemistry (PEGylated or not), charge (+24 mV for G3NH2 vs -3.7 mV for G3NH2-24PEG1000), or size (5.1 nm for G3NH2 and 9.9 nm for G3NH2-24PEG1000). However, high density of surface modification with PEG enhances pulmonary absorption and the peak plasma concentration upon pulmonary delivery. The route of administration and PEGylation also significantly impact the whole body and local (lung cellular) distribution of the dendrimers. While ca. 83% of G3NH2 is found in the lungs upon pulmonary delivery at 6.5 h post administration, only 2% reached the lungs upon intravenous (iv) delivery. Moreover, no measurable concentration of either G3NH2 or G3NH2-24PEG1000 is found in the lymph nodes upon iv administration, while these are the tissues with the second highest mass distribution of dendrimers post pulmonary delivery. Dendrimer chemistry also significantly impacts the (cellular) distribution of the nanocarriers in the lung tissue. Upon pulmonary delivery, approximately 20% of the lung endothelial cells are seen to internalize G3NH2-24PEG1000, compared to only 6% for G3NH2. Conversely, G3NH2 is more readily taken up by lung epithelial cells (35%) when compared to its PEGylated counterpart (24%). The results shown here suggest that both the pulmonary route of administration and dendrimer

  5. On the definition of adapted audio/video profiles for high-quality video calling services over LTE/4G

    NASA Astrophysics Data System (ADS)

    Ndiaye, Maty; Quinquis, Catherine; Larabi, Mohamed Chaker; Le Lay, Gwenael; Saadane, Hakim; Perrine, Clency

    2014-01-01

    During the last decade, the important advances and widespread availability of mobile technology (operating systems, GPUs, terminal resolution and so on) have encouraged a fast development of voice and video services like video-calling. While multimedia services have largely grown on mobile devices, the generated increase of data consumption is leading to the saturation of mobile networks. In order to provide data with high bit-rates and maintain performance as close as possible to traditional networks, the 3GPP (The 3rd Generation Partnership Project) worked on a high performance standard for mobile called Long Term Evolution (LTE). In this paper, we aim at expressing recommendations related to audio and video media profiles (selection of audio and video codecs, bit-rates, frame-rates, audio and video formats) for a typical video-calling services held over LTE/4G mobile networks. These profiles are defined according to targeted devices (smartphones, tablets), so as to ensure the best possible quality of experience (QoE). Obtained results indicate that for a CIF format (352 x 288 pixels) which is usually used for smartphones, the VP8 codec provides a better image quality than the H.264 codec for low bitrates (from 128 to 384 kbps). However sequences with high motion, H.264 in slow mode is preferred. Regarding audio, better results are globally achieved using wideband codecs offering good quality except for opus codec (at 12.2 kbps).

  6. Identification of IAA transport inhibitors including compounds affecting cellular PIN trafficking by two chemical screening approaches using maize coleoptile systems.

    PubMed

    Nishimura, Takeshi; Matano, Naoyuki; Morishima, Taichi; Kakinuma, Chieko; Hayashi, Ken-Ichiro; Komano, Teruya; Kubo, Minoru; Hasebe, Mitsuyasu; Kasahara, Hiroyuki; Kamiya, Yuji; Koshiba, Tomokazu

    2012-10-01

    The monocot coleoptile tip region has been generally supposed to be the source of IAA to supply IAA to basal parts by the polar IAA transport system, which results in gravi- and phototropic curvature of coleoptiles. Based on this IAA transport system and gravitropism of maize coleoptiles, we have developed two screening methods to identify small molecules from a large chemical library that inhibit IAA transport. The methods detect molecules that affect (i) gravitropic curvature of coleoptiles; and (ii) the amount of IAA transported from the tip. From 10,000 chemicals, eight compounds were identified and categorized into two groups. Four chemicals in group A decreased IAA transport from the tip, and increased endogenous IAA levels in the tip. The structures of two compounds resembled that of 1-N-naphthylphthalamic acid (NPA), but those of the other two differed from structures of known IAA transport inhibitors. Four chemicals in group B strongly inhibited IAA transport from the tip, but IAA levels at the tip were only slightly affected. At higher concentrations, group B compounds inhibited germination of Arabidopsis, similarly to brefeldin A (BFA). Analysis of the cellular distribution of PIN2-green fluorescent protein (GFP) and PIN1-GFP in Arabidopsis revealed that one of the four chemicals in group B induced internalization of PIN1 and PIN2 proteins into vesicles smaller than BFA bodies, suggesting that this compound affects cellular vesicle trafficking systems related to PIN trafficking. The eight chemicals identified here will be a useful tool for understanding the mechanisms of IAA transport in plants. PMID:22875609

  7. Characterization of a novel bioreactor system for 3D cellular mechanobiology studies.

    PubMed

    Cook, Colin A; Huri, Pinar Y; Ginn, Brian P; Gilbert-Honick, Jordana; Somers, Sarah M; Temple, Joshua P; Mao, Hai-Quan; Grayson, Warren L

    2016-08-01

    In vitro engineering systems can be powerful tools for studying tissue development in response to biophysical stimuli as well as for evaluating the functionality of engineered tissue grafts. It has been challenging, however, to develop systems that adequately integrate the application of biomimetic mechanical strain to engineered tissue with the ability to assess functional outcomes in real time. The aim of this study was to design a bioreactor system capable of real-time conditioning (dynamic, uniaxial strain, and electrical stimulation) of centimeter-long 3D tissue engineered constructs simultaneously with the capacity to monitor local strains. The system addresses key limitations of uniform sample loading and real-time imaging capabilities. Our system features an electrospun fibrin scaffold, which exhibits physiologically relevant stiffness and uniaxial alignment that facilitates cell adhesion, alignment, and proliferation. We have demonstrated the capacity for directly incorporating human adipose-derived stromal/stem cells into the fibers during the electrospinning process and subsequent culture of the cell-seeded constructs in the bioreactor. The bioreactor facilitates accurate pre-straining of the 3D constructs as well as the application of dynamic and static uniaxial strains while monitoring bulk construct tensions. The incorporation of fluorescent nanoparticles throughout the scaffolds enables in situ monitoring of local strain fields using fluorescent digital image correlation techniques, since the bioreactor is imaging compatible, and allows the assessment of local sample stiffness and stresses when coupled with force sensor measurements. In addition, the system is capable of measuring the electromechanical coupling of skeletal muscle explants by applying an electrical stimulus and simultaneously measuring the force of contraction. The packaging of these technologies, biomaterials, and analytical methods into a single bioreactor system has produced a

  8. Cellular and molecular pathogenesis of systemic lupus erythematosus: lessons from animal models.

    PubMed

    Pathak, Simanta; Mohan, Chandra

    2011-01-01

    Systemic lupus erythematosus (SLE) is a complex disease characterized by the appearance of autoantibodies against nuclear antigens and the involvement of multiple organ systems, including the kidneys. The precise immunological events that trigger the onset of clinical manifestations of SLE are not yet well understood. However, research using various mouse strains of spontaneous and inducible lupus in the last two decades has provided insights into the role of the immune system in the pathogenesis of this disease. According to our present understanding, the immunological defects resulting in the development of SLE can be categorized into two phases: (a) systemic autoimmunity resulting in increased serum antinuclear and antiglomerular autoantibodies and (b) immunological events that occur within the target organ and result in end organ damage. Aberrations in the innate as well as adaptive arms of the immune system both play an important role in the genesis and progression of lupus. Here, we will review the present understanding--as garnered from studying mouse models--about the roles of various immune cells in lupus pathogenesis.

  9. Eukaryotic Initiation Factor 4G Suppresses Nonsense-Mediated mRNA Decay by Two Genetically Separable Mechanisms

    PubMed Central

    Joncourt, Raphael; Eberle, Andrea B.; Rufener, Simone C.; Mühlemann, Oliver

    2014-01-01

    Nonsense-mediated mRNA decay (NMD), which is best known for degrading mRNAs with premature termination codons (PTCs), is thought to be triggered by aberrant translation termination at stop codons located in an environment of the mRNP that is devoid of signals necessary for proper termination. In mammals, the cytoplasmic poly(A)-binding protein 1 (PABPC1) has been reported to promote correct termination and therewith antagonize NMD by interacting with the eukaryotic release factors 1 (eRF1) and 3 (eRF3). Using tethering assays in which proteins of interest are recruited as MS2 fusions to a NMD reporter transcript, we show that the three N-terminal RNA recognition motifs (RRMs) of PABPC1 are sufficient to antagonize NMD, while the eRF3-interacting C-terminal domain is dispensable. The RRM1-3 portion of PABPC1 interacts with eukaryotic initiation factor 4G (eIF4G) and tethering of eIF4G to the NMD reporter also suppresses NMD. We identified the interactions of the eIF4G N-terminus with PABPC1 and the eIF4G core domain with eIF3 as two genetically separable features that independently enable tethered eIF4G to inhibit NMD. Collectively, our results reveal a function of PABPC1, eIF4G and eIF3 in translation termination and NMD suppression, and they provide additional evidence for a tight coupling between translation termination and initiation. PMID:25148142

  10. A cellular and regulatory map of the cholinergic nervous system of C. elegans

    PubMed Central

    Pereira, Laura; Kratsios, Paschalis; Serrano-Saiz, Esther; Sheftel, Hila; Mayo, Avi E; Hall, David H; White, John G; LeBoeuf, Brigitte; Garcia, L Rene; Alon, Uri; Hobert, Oliver

    2015-01-01

    Nervous system maps are of critical importance for understanding how nervous systems develop and function. We systematically map here all cholinergic neuron types in the male and hermaphrodite C. elegans nervous system. We find that acetylcholine (ACh) is the most broadly used neurotransmitter and we analyze its usage relative to other neurotransmitters within the context of the entire connectome and within specific network motifs embedded in the connectome. We reveal several dynamic aspects of cholinergic neurotransmitter identity, including a sexually dimorphic glutamatergic to cholinergic neurotransmitter switch in a sex-shared interneuron. An expression pattern analysis of ACh-gated anion channels furthermore suggests that ACh may also operate very broadly as an inhibitory neurotransmitter. As a first application of this comprehensive neurotransmitter map, we identify transcriptional regulatory mechanisms that control cholinergic neurotransmitter identity and cholinergic circuit assembly. DOI: http://dx.doi.org/10.7554/eLife.12432.001 PMID:26705699

  11. Comparison of two in vitro systems to assess cellular effects of nanoparticles-containing aerosols

    PubMed Central

    Fröhlich, Eleonore; Bonstingl, Gudrun; Höfler, Anita; Meindl, Claudia; Leitinger, Gerd; Pieber, Thomas R.; Roblegg, Eva

    2013-01-01

    Inhalation treatment with nanoparticle containing aerosols appears a promising new therapeutic option but new formulations have to be assessed for efficacy and toxicity. We evaluated the utility of a VITROCELL®6 PT-CF + PARI LC SPRINT® Baby Nebulizer (PARI BOY) system compared with a conventional MicroSprayer. A549 cells were cultured in the air–liquid interface, exposed to nanoparticle aerosols and characterized by measurement of transepithelial electrical resistance and staining for tight junction proteins. Deposition and distribution rates of polystyrene particles and of carbon nanotubes on the cells were assessed. In addition, cytotoxicity of aerosols containing polystyrene particles was compared with cytotoxicity of polystyrene particles in suspension tested in submersed cultures. Exposure by itself in both exposure systems did not damage the cells. Deposition rates of aerosolized polystyrene particles were about 700 times and that of carbon nanotubes about 4 times higher in the MicroSprayer than in the VITROCELL®6 PT-CF system. Cytotoxicity of amine-functionalized polystyrene nanoparticles was significantly higher when applied as an aerosol on cell cultured in air–liquid interface culture compared with nanoparticle suspensions tested in submersed culture. The higher cytotoxicity of aerosolized nanoparticles underscores the importance of relevant exposure systems. PMID:22906573

  12. Feeding Behavior of Aplysia: A Model System for Comparing Cellular Mechanisms of Classical and Operant Conditioning

    ERIC Educational Resources Information Center

    Baxter, Douglas A.; Byrne, John H.

    2006-01-01

    Feeding behavior of Aplysia provides an excellent model system for analyzing and comparing mechanisms underlying appetitive classical conditioning and reward operant conditioning. Behavioral protocols have been developed for both forms of associative learning, both of which increase the occurrence of biting following training. Because the neural…

  13. GIS Based System for Post-Earthquake Crisis Managment Using Cellular Network

    NASA Astrophysics Data System (ADS)

    Raeesi, M.; Sadeghi-Niaraki, A.

    2013-09-01

    Earthquakes are among the most destructive natural disasters. Earthquakes happen mainly near the edges of tectonic plates, but they may happen just about anywhere. Earthquakes cannot be predicted. Quick response after disasters, like earthquake, decreases loss of life and costs. Massive earthquakes often cause structures to collapse, trapping victims under dense rubble for long periods of time. After the earthquake and destroyed some areas, several teams are sent to find the location of the destroyed areas. The search and rescue phase usually is maintained for many days. Time reduction for surviving people is very important. A Geographical Information System (GIS) can be used for decreasing response time and management in critical situations. Position estimation in short period of time time is important. This paper proposes a GIS based system for post-earthquake disaster management solution. This system relies on several mobile positioning methods such as cell-ID and TA method, signal strength method, angel of arrival method, time of arrival method and time difference of arrival method. For quick positioning, the system can be helped by any person who has a mobile device. After positioning and specifying the critical points, the points are sent to a central site for managing the procedure of quick response for helping. This solution establishes a quick way to manage the post-earthquake crisis.

  14. Nano-jewels in biology. Gold and platinum on diamond nanoparticles as antioxidant systems against cellular oxidative stress.

    PubMed

    Martín, Roberto; Menchón, Cristina; Apostolova, Nadezda; Victor, Victor M; Alvaro, Mercedes; Herance, José Raúl; García, Hermenegildo

    2010-11-23

    Diamond nanoparticles (DNPs) obtained by explosive detonation have become commercially available. These commercial DNPs can be treated under Fenton conditions (FeSO(4) and H(2)O(2) at acidic pH) to obtain purer DNP samples with a small average particle size (4 nm) and a large population of surface OH groups (HO-DNPs). These Fenton-treated HO-DNPs have been used as a support of gold and platinum nanoparticles (≤2 nm average size). The resulting materials (Au/HO-DNP and Pt/HO-DNP) exhibit a high antioxidant activity against reactive oxygen species induced in a hepatoma cell line. In addition to presenting good biocompatibility, Au/HO- and Pt/HO-DNP exhibit about a two-fold higher antioxidant activity than glutathione, one of the reference antioxidant systems. The most active material against cellular oxidative stress was Au/HO-DNP. PMID:20939514

  15. The regeneration of epidermal cells of Saintpaulia leaves as a new plant-tissue system for cellular radiation biology.

    PubMed

    Engels, F M; van der Laan, F M; Leenhouts, H P; Chadwick, K H

    1980-09-01

    Investigation of the nucleus of epidermal cells of the petioles of Saintpaulia leaves by cytofluorimetry revealed that all cells are in a non-cycling pre DNA synthesis phase. Cultivation of dissected leaves results in a synchronous regeneration process of a defined number of cells. Five days after onset of cultivation the cells reach the first mitosis. The nuclear development during the regeneration process is described. Irradiation of the leaves results in a directly visible inhibition of this regenerating capability which is used to quantify cell survival in a tissue. The data show that the radiation response has a similar shape to that of the survival of single cells in culture. This response can be observed before the first mitosis of the cells and its application as a new plant tissue system for cellular radiation research is discussed. PMID:7012060

  16. The activation sequence of cellular protein handling systems after proteasomal inhibition in dopaminergic cells

    PubMed Central

    Xiong, Rui; Siegel, David; Ross, David

    2013-01-01

    Dysfunction of protein handling has been implicated in many neurodegenerative diseases and inhibition of the ubiquitin-proteasome system (UPS) has been linked to the formation of protein aggregates and proteinopathies in such diseases. While proteasomal inhibition could trigger an array of downstream protein handling changes including up-regulation of heat shock proteins (HSPs), induction of molecular chaperones, activation of the ER stress/unfolded protein response (UPR), autophagy and aggresome formation, little is known of the relationship of proteasomal inhibition to the sequence of activation of these diverse protein handling systems. In this study we utilized the reversible proteasome inhibitor MG132 and examined the activity of several major protein handling systems in the immortalized dopaminergic neuronal N27 cell line. In the early phase (up to 6 hours after proteasomal inhibition), MG132 induced time-dependent proteasomal inhibition which resulted in stimulation of the UPR, increased autophagic flux and stimulated heat shock protein response as determined by increased levels of phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2α), C/EBP homologous protein (CHOP)/GADD153, turnover of autophagy related microtubule-associated protein 1 light chain 3 (LC3) and increased levels of Hsp70 respectively. After prolonged proteasomal inhibition induced by MG132, we observed the formation of vimentin-caged aggresome-like inclusion bodies. A recovery study after MG132-induced proteasomal inhibition indicated that the autophagy-lysosomal pathway participated in the clearance of aggresomes. Our data characterizes the relationship between proteasome inhibition and activation of other protein handling systems. These data also indicated that the induction of alternate protein handling systems and their temporal relationships may be important factors that determine the extent of accumulation of misfolded proteins in cells as a result of

  17. Early Systemic Cellular Immune Response in Children and Young Adults Receiving Decellularized Fresh Allografts for Pulmonary Valve Replacement

    PubMed Central

    Neumann, Anneke; Breymann, Thomas; Cebotari, Serghei; Boethig, Dietmar; Horke, Alexander; Beerbaum, Philipp; Westhoff-Bleck, Mechthild; Bertram, Harald; Ono, Masamichi; Tudorache, Igor; Haverich, Axel; Beutel, Gernot

    2014-01-01

    Objectives: The longevity of homografts is determined by the activation of the recipients' immune system resulting from allogenic antigen exposition. Fresh decellularized pulmonary homografts (DPH) have shown promising early results in pulmonary valve replacement in children and young adults and could potentially avoid significant activation of the immune system, as more than 99% of the donor DNA is removed during the decellularization process. While the humoral immune response to decellularized allografts has been studied, detailed information on the more significant cellular immune response is currently lacking. Methods and Results: Peripheral blood samples were obtained from patients undergoing pulmonary valve replacement with DPH before, after, and for approximately 3 years after implantation. Absolute counts and percentages of mature T- (CD3+), B- (CD19+), and natural killer- (CD16+/CD56+) cells, as well as T helper- (CD4+) and cytotoxic T-cell- (CD8+) subsets, were determined by fluorescence-activated cell sorting (FACS). Between May 2009 and September 2013, 199 blood samples taken from 47 patients with a mean age at DPH implantation of 16.6±10.8 years were analyzed. The hemodynamic performance of DPH was excellent in all but one patient, and no valve-related deaths or conduit explantations were observed. The short-term follow up revealed a significant postoperative decrease in cell counts of most subtypes with reconstitution after 3 months. Continued assessment did not show any significant deviations in cell counts from their baseline values. Conclusion: The absence of cellular immune response in patients receiving DPH supports the concept that decellularization can provide a basis for autologous regeneration. PMID:24138470

  18. Immunohistochemical Expression of Matrix Metalloproteinase-7 in Human Colorectal Adenomas Using Specified Automated Cellular Image Analysis System: A Clinicopathological Study

    PubMed Central

    Qasim, Ban J.; Ali, Hussam H.; Hussein, Alaa G.

    2013-01-01

    Background/Aim: To evaluate the immunohistochemical expression of matrix metalloproteinase-7 (MMP-7) in colorectal adenomas, and to correlate this expression with different clinicopathological parameters. Patients and Methods: The study was retrospectively designed. Thirty three paraffin blocks from patients with colorectal adenoma and 20 samples of non-tumerous colonic tissue taken as control group were included in the study. MMP-7 expression was assessed by immunohistochemistry method. The scoring of immunohistochemical staining was conducted utilizing a specified automated cellular image analysis system (Digimizer). Results: The frequency of positive immunohistochemical expression of MMP-7 was significantly higher in adenoma than control group (45.45% versus 10%) (P value < 0.001). Strong MMP-7 staining was mainly seen in adenoma cases (30.30%) in comparison with control (0%) the difference is significant (P < 0.001). The three digital parameters of MMP-7 immunohistochemical expression (Area (A), Number of objects (N), and intensity (I)) were significantly higher in adenoma than control. Mean (A and I) of MMP-7 showed a significant correlation with large sized adenoma (≥ 1cm) (P < 0.05), also a significant positive correlation of the three digital parameters (A, N, and I) of MMP-7 expression with villous configuration and severe dysplasia in colorectal adenoma had been identified (P < 0.05). Conclusion: MMP-7 plays an important role in the growth and malignant conversion of colorectal adenomas as it is more likely to be expressed in advanced colorectal adenomatous polyps with large size, severe dysplasia and villous histology. The use of automated cellular image analysis system (Digmizer) to quantify immunohistochemical staining yields more consistent assay results, converts semi-quantitative assay to a truly quantitative assay, and improves assay objectivity and reproducibility. PMID:23319034

  19. The p53 network: Cellular and systemic DNA damage responses in aging and cancer

    PubMed Central

    Reinhardt, H. Christian; Schumacher, Björn

    2014-01-01

    Genome instability contributes to cancer development and accelerates age-related pathologies as evidenced by a variety of congenital cancer susceptibility and progeroid syndromes that are caused by defects in genome maintenance mechanisms. DNA damage response pathways that are mediated through the tumor suppressor p53 play an important role in the cell intrinsic responses to genome instability, including a transient cell cycle arrest, senescence and apoptosis. Both senescence and apoptosis are powerful tumor suppressive pathways preventing the uncontrolled proliferation of transformed cells. However, both pathways can potentially deplete stem and progenitor cell pools, thus promoting tissue degeneration and organ failure, which are both hallmarks of aging. p53 signaling is also involved in mediating non-cell autonomous interactions with the innate immune system and in the systemic adjustments during the aging process. The network of p53 target genes thus functions as an important regulator of cancer prevention and the physiology of aging. PMID:22265392

  20. Dynamic regulation of the translation initiation helicase complex by mitogenic signal transduction to eukaryotic translation initiation factor 4G.

    PubMed

    Dobrikov, Mikhail I; Dobrikova, Elena Y; Gromeier, Matthias

    2013-03-01

    Eukaryotic translation initiation factor 4F (eIF4F), comprising the cap-binding protein eIF4E, the helicase eIF4A, and the central scaffold eIF4G, is a convergence node for a complex signaling network that controls protein synthesis. Together with eIF3 and eIF4A/4B, eIF4G recruits ribosomal subunits to mRNAs and facilitates 5' untranslated region unwinding. Mammalian eIF4G contains three HEAT domains and unstructured regions involved in protein-protein interactions. Despite detailed eIF4G structure data, the mechanisms controlling initiation scaffold formation remain obscure. We found a new, highly regulated eIF4B/-3 binding site within the HEAT-1/-2 interdomain linker, harboring two phosphorylation sites that we identified as substrates for Erk1/2 and casein kinase 2. Phorbol ester-induced sequential phosphorylation of both sites detached HEAT-2 from the complex with eIF4A/-4B/-3 and stimulated the association of HEAT-3 with the mitogen-activated protein kinase signal integrating kinase Mnk1. Our results provide a mechanistic link between intracellular signal transduction and dynamic initiation complex formation coordinated by flexible eIF4G structure.

  1. New approaches in cellular radio systems using dynamic radio channel management

    NASA Astrophysics Data System (ADS)

    Yilmaz, Nusret; Ergul, F. R.

    2004-09-01

    New approaches are presented to facilitate dynamic radio bandwidth management for mobile communication systems. The aim is achieve an overall high level of QoS for both handoff calls and new calls. At the same time, the utilization of wireless network resources, i.e. the revenues earned by the operator. The simultaneous satisfaction of these two conflicting interests, under varying mobility and network traffic conditions, will be difficult. However, a balanced operation could be obtained by applying two novel approaches in system management. First, apriori information about possible handoffs, in the form of cell transition probabilities could be provided by the mobile, which is based on data collected by the mobile itself. This information is used to make handoff reservation requests in neighboring cells. Second, simultaneously controlling the radio resource reservation and new call admission to the system. This approach controls both the amount of reserved channels and the number of new calls admitted in a dynamic way. A theoretical analysis and a simulation have been used to study these approaches and it has been demonstrated that these approaches perform better then other reported approaches in the literature.

  2. Model Systems of Precursor Cellular Membranes: Long-Chain Alcohols Stabilize Spontaneously Formed Oleic Acid Vesicles

    PubMed Central

    Rendón, Adela; Carton, David Gil; Sot, Jesús; García-Pacios, Marcos; Montes, Ruth; Valle, Mikel; Arrondo, José-Luis R.; Goñi, Felix M.; Ruiz-Mirazo, Kepa

    2012-01-01

    Oleic acid vesicles have been used as model systems to study the properties of membranes that could be the evolutionary precursors of more complex, stable, and impermeable phospholipid biomembranes. Pure fatty acid vesicles in general show high sensitivity to ionic strength and pH variation, but there is growing evidence that this lack of stability can be counterbalanced through mixtures with other amphiphilic or surfactant compounds. Here, we present a systematic experimental analysis of the oleic acid system and explore the spontaneous formation of vesicles under different conditions, as well as the effects that alcohols and alkanes may have in the process. Our results support the hypothesis that alcohols (in particular 10- to 14-C-atom alcohols) contribute to the stability of oleic acid vesicles under a wider range of experimental conditions. Moreover, studies of mixed oleic-acid-alkane and oleic-acid-alcohol systems using infrared spectroscopy and Langmuir trough measurements indicate that precisely those alcohols that increased vesicle stability also decreased the mobility of oleic acid polar headgroups, as well as the area/molecule of lipid. PMID:22339864

  3. Differences in cytokinin control on cellular dynamics of zucchini cotyledons cultivated in two experimental systems.

    PubMed

    Stoynova-Bakalova, E; Petrov, P; Gigova, L; Ivanova, N

    2011-01-01

    The effect of endogenous cytokinins on the pattern of palisade cell division post-germination does not depend on the conditions of cotyledon development -in planta (attached to seedlings) or in vitro (isolated from dry zucchini seeds and cultured on water). In cotyledons originating from 4-day-old seedlings (experimental system 1), exogenous cytokinin temporarily (in the first 2 day of cultivation) enhanced post-mitotic cell enlargement of palisade cells, mainly due to enhanced water uptake and use of cell storage compounds, all of which lead to cotyledon senescence. Cytokinin is not able to resume the completed palisade cell division on day 5. As a result, the number of cells and the final areas of treated and control cotyledons are quite similar. By contrast, the effects of cytokinin on cotyledons isolated from dry seeds (experimental system 2) are better expressed, promoting an increase in number of palisade cells accompanied by additional cotyledon area enlargement. However, the prolonged post-mitotic cell expansion in control cotyledons compensates for the reduced speed of cell growth and division activity and decreases differences in final cotyledon area between treatments. The results define cell division as the primary target of cytokinin stimulation in cotyledon tissues competent for division, and determine the temporal patterns of palisade cell cycling related to cotyledon age. This knowledge permits a better choice of experimental system to study effects on cell proliferation and cell growth, as well as cell enlargement and senescence-related events using physiologically homogeneous material.

  4. Radiating Fröhlich system as a model of cellular electromagnetism.

    PubMed

    Šrobár, Fedor

    2015-01-01

    Oscillating polar entities inside the biological cells, most notably microtubules, are bound to emit electromagnetic radiation. This phenomenon is described by Fröhlich kinetic equations expressing, in terms of quantum occupancy numbers of each discrete collective oscillatory mode, the balance between incoming metabolic energy flow and losses due to linear and non-linear interactions with the thermal environs of the oscillators. Hitherto, radiation losses have not been introduced as part of the balance; it was assumed that they were proportional to the modal occupation numbers. It is demonstrated that this formulation is incorrect and the radiation losses must be taken into account in the kinetic equations explicitly. Results of a numerical study of kinetic equations, enlarged in this sense, are presented for the case of three coupled oscillators which was shown to evince the essential attributes of the Fröhlich systems. Oscillator eigenfrequencies were chosen, alternatively, to fall into the MHz and the THz frequency domains. It was found that large radiation levels destroy the main hallmark of the Fröhlich systems, the energy condensation in the lowest frequency mode. The system then functions as a convertor of metabolic energy into radiation. At more moderate radiation levels, both energy condensation and significant radiation can coexist. Possible consequences for the cell physiology are suggested.

  5. A cellular and regulatory map of the GABAergic nervous system of C. elegans

    PubMed Central

    Gendrel, Marie; Atlas, Emily G; Hobert, Oliver

    2016-01-01

    Neurotransmitter maps are important complements to anatomical maps and represent an invaluable resource to understand nervous system function and development. We report here a comprehensive map of neurons in the C. elegans nervous system that contain the neurotransmitter GABA, revealing twice as many GABA-positive neuron classes as previously reported. We define previously unknown glia-like cells that take up GABA, as well as 'GABA uptake neurons' which do not synthesize GABA but take it up from the extracellular environment, and we map the expression of previously uncharacterized ionotropic GABA receptors. We use the map of GABA-positive neurons for a comprehensive analysis of transcriptional regulators that define the GABA phenotype. We synthesize our findings of specification of GABAergic neurons with previous reports on the specification of glutamatergic and cholinergic neurons into a nervous system-wide regulatory map which defines neurotransmitter specification mechanisms for more than half of all neuron classes in C. elegans. DOI: http://dx.doi.org/10.7554/eLife.17686.001 PMID:27740909

  6. Simultaneous model discrimination and parameter estimation in dynamic models of cellular systems

    PubMed Central

    2013-01-01

    Background Model development is a key task in systems biology, which typically starts from an initial model candidate and, involving an iterative cycle of hypotheses-driven model modifications, leads to new experimentation and subsequent model identification steps. The final product of this cycle is a satisfactory refined model of the biological phenomena under study. During such iterative model development, researchers frequently propose a set of model candidates from which the best alternative must be selected. Here we consider this problem of model selection and formulate it as a simultaneous model selection and parameter identification problem. More precisely, we consider a general mixed-integer nonlinear programming (MINLP) formulation for model selection and identification, with emphasis on dynamic models consisting of sets of either ODEs (ordinary differential equations) or DAEs (differential algebraic equations). Results We solved the MINLP formulation for model selection and identification using an algorithm based on Scatter Search (SS). We illustrate the capabilities and efficiency of the proposed strategy with a case study considering the KdpD/KdpE system regulating potassium homeostasis in Escherichia coli. The proposed approach resulted in a final model that presents a better fit to the in silico generated experimental data. Conclusions The presented MINLP-based optimization approach for nested-model selection and identification is a powerful methodology for model development in systems biology. This strategy can be used to perform model selection and parameter estimation in one single step, thus greatly reducing the number of experiments and computations of traditional modeling approaches. PMID:23938131

  7. Microscale screening systems for 3D cellular microenvironments: platforms, advances, and challenges

    PubMed Central

    Montanez-Sauri, Sara I.; Beebe, David J.; Sung, Kyung Eun

    2015-01-01

    The increasing interest in studying cells using more in vivo-like three-dimensional (3D) microenvironments has created a need for advanced 3D screening platforms with enhanced functionalities and increased throughput. 3D screening platforms that better mimic in vivo microenvironments with enhanced throughput would provide more in-depth understanding of the complexity and heterogeneity of microenvironments. The platforms would also better predict the toxicity and efficacy of potential drugs in physiologically relevant conditions. Traditional 3D culture models (e.g. spinner flasks, gyratory rotation devices, non-adhesive surfaces, polymers) were developed to create 3D multicellular structures. However, these traditional systems require large volumes of reagents and cells, and are not compatible with high throughput screening (HTS) systems. Microscale technology offers the miniaturization of 3D cultures and allows efficient screening of various conditions. This review will discuss the development, most influential works, and current advantages and challenges of microscale culture systems for screening cells in 3D microenvironments. PMID:25274061

  8. Tinnitus: pathology of synaptic plasticity at the cellular and system levels

    PubMed Central

    Guitton, Matthieu J.

    2012-01-01

    Despite being more and more common, and having a high impact on the quality of life of sufferers, tinnitus does not yet have a cure. This has been mostly the result of limited knowledge of the biological mechanisms underlying this adverse pathology. However, the last decade has witnessed tremendous progress in our understanding on the pathophysiology of tinnitus. Animal models have demonstrated that tinnitus is a pathology of neural plasticity, and has two main components: a molecular, peripheral component related to the initiation phase of tinnitus; and a system-level, central component-related to the long-term maintenance of tinnitus. Using the most recent experimental data and the molecular/system dichotomy as a framework, we describe here the biological basis of tinnitus. We then discuss these mechanisms from an evolutionary perspective, highlighting similarities with memory. Finally, we consider how these discoveries can translate into therapies, and we suggest operative strategies to design new and effective combined therapeutic solutions using both pharmacological (local and systemic) and behavioral tools (e.g., using tele-medicine and virtual reality settings). PMID:22408611

  9. In Vitro Testing of Biomaterials for Neural Repair: Focus on Cellular Systems and High-Content Analysis.

    PubMed

    Baldassarro, Vito Antonio; Dolci, Luisa Stella; Mangano, Chiara; Giardino, Luciana; Gualandi, Chiara; Focarete, Maria Letizia; Calzà, Laura

    2016-01-01

    Biomimetic materials are designed to stimulate specific cellular responses at the molecular level. To improve the soundness of in vitro testing of the biological impact of new materials, appropriate cell systems and technologies must be standardized also taking regulatory issues into consideration. In this study, the biological and molecular effects of different scaffolds on three neural systems, that is, the neural cell line SH-SY5Y, primary cortical neurons, and neural stem cells, were compared. The effect of poly(L-lactic acid) scaffolds having different surface geometry (conventional two-dimensional seeding flat surface, random or aligned fibers as semi3D structure) and chemical functionalization (laminin or ECM extract) were studied. The endpoints were defined for efficacy (i.e., neural differentiation and neurite elongation) and for safety (i.e., cell death/survival) using high-content analysis. It is demonstrated that (i) the definition of the biological properties of biomaterials is profoundly influenced by the test system used; (ii) the definition of the in vitro safety profile of biomaterials for neural repair is also influenced by the test system; (iii) cell-based high-content screening may well be successfully used to characterize both the efficacy and safety of novel biomaterials, thus speeding up and improving the soundness of this critical step in material science having medical applications. PMID:27588220

  10. In Vitro Testing of Biomaterials for Neural Repair: Focus on Cellular Systems and High-Content Analysis

    PubMed Central

    Baldassarro, Vito Antonio; Dolci, Luisa Stella; Mangano, Chiara; Giardino, Luciana; Gualandi, Chiara; Focarete, Maria Letizia; Calzà, Laura

    2016-01-01

    Abstract Biomimetic materials are designed to stimulate specific cellular responses at the molecular level. To improve the soundness of in vitro testing of the biological impact of new materials, appropriate cell systems and technologies must be standardized also taking regulatory issues into consideration. In this study, the biological and molecular effects of different scaffolds on three neural systems, that is, the neural cell line SH-SY5Y, primary cortical neurons, and neural stem cells, were compared. The effect of poly(L-lactic acid) scaffolds having different surface geometry (conventional two-dimensional seeding flat surface, random or aligned fibers as semi3D structure) and chemical functionalization (laminin or ECM extract) were studied. The endpoints were defined for efficacy (i.e., neural differentiation and neurite elongation) and for safety (i.e., cell death/survival) using high-content analysis. It is demonstrated that (i) the definition of the biological properties of biomaterials is profoundly influenced by the test system used; (ii) the definition of the in vitro safety profile of biomaterials for neural repair is also influenced by the test system; (iii) cell-based high-content screening may well be successfully used to characterize both the efficacy and safety of novel biomaterials, thus speeding up and improving the soundness of this critical step in material science having medical applications. PMID:27588220

  11. Cellular automata model simulating traffic car accidents in the on-ramp system

    NASA Astrophysics Data System (ADS)

    Echab, H.; Lakouari, N.; Ez-Zahraouy, H.; Benyoussef, A.

    2015-01-01

    In this paper, using Nagel-Schreckenberg model we study the on-ramp system under the expanded open boundary condition. The phase diagram of the two-lane on-ramp system is computed. It is found that the expanded left boundary insertion strategy enhances the flow in the on-ramp lane. Furthermore, we have studied the probability of the occurrence of car accidents. We distinguish two types of car accidents: the accident at the on-ramp site (Prc) and the rear-end accident in the main road (Pac). It is shown that car accidents at the on-ramp site are more likely to occur when traffic is free on road A. However, the rear-end accidents begin to occur above a critical injecting rate αc1. The influence of the on-ramp length (LB) and position (xC0) on the car accidents probabilities is studied. We found that large LB or xC0 causes an important decrease of the probability Prc. However, only large xC0 provokes an increase of the probability Pac. The effect of the stochastic randomization is also computed.

  12. Consideration of the cellular microenvironment: physiologically relevant co-culture systems in drug discovery.

    PubMed

    L Berg, Ellen; Hsu, Yu-Chih; Lee, Jonathan A

    2014-04-01

    There is renewed interest in phenotypic approaches to drug discovery, using cell-based assays to select new drugs, with the goal of improving pharmaceutical success. Assays that are more predictive of human biology can help researchers achieve this goal. Primary cells are more physiologically relevant to human biology and advances are being made in methods to expand the available cell types and improve the potential clinical translation of these assays through the use of co-cultures or three-dimensional (3D) technologies. Of particular interest are assays that may be suitable for industrial scale drug discovery. Here we review the use of primary human cells and co-cultures in drug discovery and describe the characteristics of co-culture models for inflammation biology (BioMAP systems), neo-vascularization and tumor microenvironments. Finally we briefly describe technical trends that may enable and impact the development of physiologically relevant co-culture assays in the near future. PMID:24524933

  13. Cellular Dose of Partly Soluble Cu Particle Aerosols at the Air–Liquid Interface Using an In Vitro Lung Cell Exposure System

    PubMed Central

    Cronholm, Pontus; Karlsson, Hanna L.; Midander, Klara; Odnevall Wallinder, Inger; Möller, Lennart

    2013-01-01

    Abstract Background There is currently a need to develop and test in vitro systems for predicting the toxicity of nanoparticles. One challenge is to determine the actual cellular dose of nanoparticles after exposure. Methods In this study, human epithelial lung cells (A549) were exposed to airborne Cu particles at the air–liquid interface (ALI). The cellular dose was determined for two different particle sizes at different deposition conditions, including constant and pulsed Cu aerosol flow. Results Airborne polydisperse particles with a geometric mean diameter (GMD) of 180 nm [geometric standard deviation (GSD) 1.5, concentration 105 particles/mL] deposited at the ALI yielded a cellular dose of 0.4–2.6 μg/cm2 at pulsed flow and 1.6–7.6 μg/cm2 at constant flow. Smaller polydisperse particles in the nanoregime (GMD 80 nm, GSD 1.5, concentration 107 particles/mL) resulted in a lower cellular dose of 0.01–0.05 μg/cm2 at pulsed flow, whereas no deposition was observed at constant flow. Exposure experiments with and without cells showed that the Cu particles were partly dissolved upon deposition on cells and in contact with medium. Conclusions Different cellular doses were obtained for the different Cu particle sizes (generated with different methods). Furthermore, the cellular doses were affected by the flow conditions in the cell exposure system and the solubility of Cu. The cellular doses of Cu presented here are the amount of Cu that remained on the cells after completion of an experiment. As Cu particles were partly dissolved, Cu (a nonnegligible contribution) was, in addition, present and analyzed in the nourishing medium present beneath the cells. This study presents cellular doses induced by Cu particles and demonstrates difficulties with deposition of nanoparticles at the ALI and of partially soluble particles. PMID:22889118

  14. In vivo and in vitro studies of the cellular defense system of the human lung.

    PubMed

    Stahlhofen, W; Möller, W

    1994-06-01

    Magnetic microparticles were used to investigate the defence system of the human lungs against foreign material. About 0.5 mg of spherical monodisperse magnetite particles were deposited in the alveolar region of the human lung by voluntary inhalation. After primary magnetization a remanent magnetic field (RMF) of the lung can be measured that allows estimation of the amount of dust retained in the lung. The decay of this RMF, called relaxation, results from a misalignment of the dipole particles due to the activity of pulmonary macrophages. This macrophage activity was characterized by a cell energy Ez. With a secondary magnetization the lung can be remagnetized by rotation of the dipole particles. This allows estimation of the intracellular viscosity and the motility of the alveolar macrophages in vivo. The macrophage cell-line J774 was used to verify the dynamic processes of the magnetic particles within the cells in vitro. In vitro and in vivo relaxation curves of polydisperse and of spherical monodisperse magnetite particles are presented. Thermal relaxation of mono-disperse and polydisperse particles within a viscous standard could be verified with the Brownian rotary diffusion model. Relaxation with monodisperse particles was double exponential in vivo as well as in vitro, suggesting that 2 different viscous compartments of the cytoplasm should be considered. Relaxation in the macrophage cell-line J774 was particle-size-dependent.

  15. Extralysosomal turnover of cellular proteins: Targeting substrates in the ubiquitin, ATP-dependent degradation system

    SciTech Connect

    Marriott, D.

    1988-01-01

    Calmodulin derived from a cloned chicken gene can be ubiquitinated and degraded by an in vitro reticulocyte lysate system. The chemical reactivity and the surface accessibility of the {epsilon}-amino group on lysine 115 in the calmodulin polypeptide chain were studied by trace labeling with acetic anhydride and with a ubiquitin derivative containing an azido group at the C-terminal glycine residue. Fractionation of reticulocyte lysate proteins separated the activity which degrades the calmodulin moiety of ubiquitin-calmodulin conjugates from that which acts on the isopeptide linkage. Neither of these two activities act on a synthetic isopeptide, which mimics the junction of ubiquitin-calmodulin, indicating the importance of the folding of ubiquitin for recognition. Based on recent findings that the ubiquitin moieties linked to {beta}galactosidase exist as a single multiubiquitin chain, studies were carried out to determine the structure of the ubiquitin-ubiquitin linkage. Ubiquitin was in vivo labeled with ({sup 3}H) and conjugated to {beta}galactosidase. Individual conjugates were isolated and subjected to peptide mapping by trypsin digestion, and tryptic fragments were analyzed of HPLC. The results indicated that the ubiquitin-ubiquitin linkage involves lysine residue 48 in the ubiquitin sequence.

  16. Laser micromanipulation systems as universal tools in cellular and molecular biology and in medicine.

    PubMed

    Schütze, K; Pösl, H; Lahr, G

    1998-07-01

    The UV-laser microbeam has been established as a valuable tool in a wide area of molecular biology as well as in medical research and applications. This system allows to cut or fuse microscopically small specimen. An important application of the cutting laser is laser microbeam microdissection (LMM) combined with laser pressure catapulting (LPC), which allows to procure single cells or small homogeneous cell areas for subsequent molecular analysis in an entirely "non-contact" manner. With LMM minute tissue areas, single cells or chromosomes are microdissected and separated from their surroundings. Subsequently, LPC ejects the dissectates directly into the cap of a sample tube without any mechanical contact. This enables the rapid procurement of homogeneous specimen from less than one up to several hundreds of micrometers in diameter without encroachment of the adjacent region. The mRNA information of the selected specimen as well as of the remaining probe are well preserved, as demonstrated with laser isolated samples from a routinely prepared tissue section of a differentiated colorectal adenocarcinoma. Reverse transcription of specific mRNA coding for cytoplasmic beta-actin and subsequent hemi-nested PCR amplification was not impaired. Any kind of tissue, as well as single cells from different sources and even subcellular structures can be captured using this laser method. Wherever homogeneous samples are required to analyze cell or chromosome-specific genetic alterations such as in cancer research or prenatal diagnosis this unique and rapid laser micropreparation method will become a key technology of great value.

  17. Cellular aging and cancer

    PubMed Central

    Hornsby, Peter J.

    2010-01-01

    Aging is manifest in a variety of changes over time, including changes at the cellular level. Cellular aging acts primarily as a tumor suppressor mechanism, but also may enhance cancer development under certain circumstances. One important process of cellular aging is oncogene-induced senescence, which acts as an important anti-cancer mechanism. Cellular senescence resulting from damage caused by activated oncogenes prevents the growth or potentially neoplastic cells. Moreover, cells that have entered senescence appear to be targets for elimination by the innnate immune system. In another aspect of cellular aging, the absence of telomerase activity in normal tissues results in such cells lacking a telomere maintenance mechanism. One consequence is that in aging there is an increase in cells with shortened telomeres. In the presence of active oncogenes that cause expansion of a neoplastic clone, shortening of telomeres leading to telomere dysfunction prevents the indefinite expansion of the clone because the cells enter crisis. Crisis results from fusions and other defects caused by dysfunctional telomeres and is a terminal state of the neoplastic clone. In this way the absence of telomerase in human cells, while one cause of cellular aging, also acts as an anti-cancer mechanism. PMID:20705476

  18. Study of the rat adrenal renin-angiotensin system at a cellular level.

    PubMed Central

    Chiou, C Y; Williams, G H; Kifor, I

    1995-01-01

    To address the question as to how zona glomerulosa (ZG) cell angiotensin II (Ang II) secretion is regulated, we developed an immuno-cell blot assay to measure its secretion from single cells. We compared these results with those obtained from population studies using a superfusion system. Modulation of Ang II secretion was investigated acutely (by administrating potassium [K+] or captopril) and chronically (by feeding the animals low or high sodium diets). The area of secretory cells, halo areas, and halo intensities varied widely but were highly significantly correlated (P < 0.001) with each other. A disproportionate amount of Ang II was secreted by a small number of large cells. When K+ concentration was increased from 3.6 to 0 mM, superfused ZG cells increased their Ang II secretion 2.32 +/- 0.59-fold. Administration of captopril reduced the K(+)-stimulated Ang II secretion 1.24 +/- 0.07 fold. These findings were reflected in the cell blot assay as a change in the frequency distribution of halo area by K+ and captopril in the same direction as in the population study. In both conditions, the percentage of secretory cells did not change significantly from control. Superfused ZG cells from rats on a low sodium diet secreted 1.85 +/- 0.58-fold more Ang II than cells from sodium-loaded rats (p < 0.05, n = 6). The cell blot assay confirmed these findings with sodium restriction significantly increasing (P < 0.001) both the halo area and its frequency distribution to a larger portion of high secreting cells. However, in contrast to acute treatment with K+ or captopril, the number of secretory cells also doubled. Thus, the individual ZG cell uses two mechanisms to modify Ang II production. In response to acute stimulation and suppression, the amount of Ang II secreted per cell is modified without changing the number of secretary cells. With chronic stimulation, both the amount of Ang II secreted per cell and the number of secretary cells increase. Images PMID:7657812

  19. Plasma membrane calcium ATPases: From generic Ca(2+) sump pumps to versatile systems for fine-tuning cellular Ca(2.).

    PubMed

    Strehler, Emanuel E

    2015-04-24

    The plasma membrane calcium ATPases (PMCAs) are ATP-driven primary ion pumps found in all eukaryotic cells. They are the major high-affinity calcium extrusion system for expulsion of Ca(2+) ions from the cytosol and help restore the low resting levels of intracellular [Ca(2+)] following the temporary elevation of Ca(2+) generated during Ca(2+) signaling. Due to their essential role in the maintenance of cellular Ca(2+) homeostasis they were initially thought to be "sump pumps" for Ca(2+) removal needed by all cells to avoid eventual calcium overload. The discovery of multiple PMCA isoforms and alternatively spliced variants cast doubt on this simplistic assumption, and revealed instead that PMCAs are integral components of highly regulated multi-protein complexes fulfilling specific roles in calcium-dependent signaling originating at the plasma membrane. Biochemical, genetic, and physiological studies in gene-manipulated and mutant animals demonstrate the important role played by specific PMCAs in distinct diseases including those affecting the peripheral and central nervous system, cardiovascular disease, and osteoporosis. Human PMCA gene mutations and allelic variants associated with specific disorders continue to be discovered and underline the crucial role of different PMCAs in particular cells, tissues and organs.

  20. Genomes to Life''Center for Molecular and Cellular Systems'': A research program for identification and characterization of protein complexes.

    SciTech Connect

    Buchanan, M V.; Larimer, Frank; Wiley, H S.; Kennel, S J.; Squier, Thomas C.; Ramsey, John M.; Rodland, Karin D.; Hurst, G B.; Smith, Richard D.; Xu, Ying; Dixon, David A.; Doktycz, M J.; Colson, Steve D.; Gesteland, R; Giometti, Carol S.; Young, Mark E.; Giddings, Ralph M.

    2002-02-01

    Goal 1 of Department of Energy's Genomes to Life (GTL) program seeks to identify and characterize the complete set of protein complexes within a cell. Goal 1 forms the foundation necessary to accomplish the other objectives of the GTL program, which focus on gene regulatory networks and molecular level characterization of interactions in microbial communities. Together this information would allow cells and their components to be understood in sufficient detail to predict, test, and understand the responses of a biological system to its environment. The Center for Molecular and Cellular Systems has been established to identify and characterize protein complexes using high through-put analytical technologies. A dynamic research program is being developed that supports the goals of the Center by focusing on the development of new capabilities for sample preparation and complex separations, molecular level identification of the protein complexes by mass spectrometry, characterization of the complexes in living cells by imaging techniques, and bioinformatics and computational tools for the collection and interpretation of data and formation of databases and tools to allow the data to be shared by the biological community.

  1. Development of an on-line exposure system to determine freshly produced diesel engine emission-induced cellular effects.

    PubMed

    Oostingh, Gertie J; Papaioannou, Eleni; Chasapidis, Leonidas; Akritidis, Theofylaktos; Konstandopoulos, Athanasios G; Duschl, Albert

    2013-09-01

    Diesel engine emission particle filters are often placed at exhaust outlets to remove particles from the exhaust. The use of filters results in the exposure to a reduced number of nanometer-sized particles, which might be more harmful than the exposure to a larger number of micrometer-sized particles. An in vitro exposure system was established to expose human alveolar epithelial cells to freshly generated exhaust. Computer simulations were used to determine the optimal flow characteristics and ensure equal exposure conditions for each well of a 6-well plate. A selective particle size sampler was used to continuously deliver diesel soot particles with different particle size distributions to cells in culture. To determine, whether the system could be used for cellular assays, alterations in cytokine production and cell viability of human alveolar A549 cells were determined after 3h on-line exposure followed by a 21-h conventional incubation period. Data indicated that complete diesel engine emission slightly affected pre-stimulated cells, but naive cells were not affected. The fractions containing large or small particles never affected the cells. The experimental set-up allowed a reliable exposure of the cells to the complete exhaust fraction or to the fractions containing either large or small diesel engine emission particles.

  2. Pseudo-epidermis: A model system for investigating molecular and cellular pathways of cutaneous epidermal toxicity from sulfur mustard

    SciTech Connect

    Bernstein, I.A.; Bernstam, L.I.; Yang, Y.H.; Lin, P.P.; Vaughan, F.L.

    1993-05-13

    Damage to DNA, Inhibition of DNA replication and mitosis, appearance of abnormal keratin peptide and large differentiated cells and, finally, death of cells occur dose- and time-responsively in submerged cultures of keratinocytes exposed to bis-(b-chloroethyl)sulfide (BCES). However, the relevance of these parameters to vesication in human skin exposed to mustard in vivo has yet to be established. The pseudo-epidermis cultured from human cutaneous keratinocytes offers a system in which the pathogenic importance of each of these parameters can be evaluated. To establish the validity of the system, it is necessary to show that the pseudo-epidermis undergoes similar dose- and time-dependent cytotoxicity from BCES as is observed in the human skin after topical exposure to the mustard. This report includes data which demonstrate a dose- and time-dependent destruction of the germinative layer in human pseudo-epidermis after topical application of BCES. In addition, data are included to show that DNA is a primary target for BCES in pseudo-epidermis as it is in vivo. Also included in this report is a proposed sequence of molecular and cellular events to account for cytotoxicity in the germinative population of the pseudo-epidermis after exposure to BCES.

  3. Remodelling of cellular excitation (reaction) and intercellular coupling (diffusion) by chronic atrial fibrillation represented by a reaction-diffusion system

    NASA Astrophysics Data System (ADS)

    Zhang, Henggui; Garratt, Clifford J.; Kharche, Sanjay; Holden, Arun V.

    2009-06-01

    Human atrial tissue is an excitable system, in which myocytes are excitable elements, and cell-to-cell electrotonic interactions are via diffusive interactions of cell membrane potentials. We developed a family of excitable system models for human atrium at cellular, tissue and anatomical levels for both normal and chronic atrial fibrillation (AF) conditions. The effects of AF-induced remodelling of cell membrane ionic channels (reaction kinetics) and intercellular gap junctional coupling (diffusion) on atrial excitability, conduction of excitation waves and dynamics of re-entrant excitation waves are quantified. Both ionic channel and gap junctional coupling remodelling have rate dependent effects on atrial propagation. Membrane channel conductance remodelling allows the propagation of activity at higher rates than those sustained in normal tissue or in tissue with gap junctional remodelling alone. Membrane channel conductance remodelling is essential for the propagation of activity at rates higher than 300/min as seen in AF. Spatially heterogeneous gap junction coupling remodelling increased the risk of conduction block, an essential factor for the genesis of re-entry. In 2D and 3D anatomical models, the dynamical behaviours of re-entrant excitation waves are also altered by membrane channel modelling. This study provides insights to understand the pro-arrhythmic effects of AF-induced reaction and diffusion remodelling in atrial tissue.

  4. Temporal and Spatial Properties of a Yeast Multi-Cellular Amplification System Based on Signal Molecule Diffusion

    PubMed Central

    Jahn, Michael; Mölle, Annett; Rödel, Gerhard; Ostermann, Kai

    2013-01-01

    We report on the spatial and temporal signaling properties of a yeast pheromone-based cell communication and amplifier system. It utilizes the Saccharomyces cerevisiae mating response pathway and relies on diffusion of the pheromone α–factor as key signaling molecule between two cell types. One cell type represents the α–factor secreting sensor part and the other the reporter part emitting fluorescence upon activation. Although multi-cellular signaling systems promise higher specificity and modularity, the complex interaction of the cells makes prediction of sensor performance difficult. To test the maximum distance and response time between sensor and reporter cells, the two cell types were spatially separated in defined compartments of agarose hydrogel (5 × 5 mm) and reconnected by diffusion of the yeast pheromone. Different ratios of sensor to reporter cells were tested to evaluate the minimum amount of sensor cells required for signal transduction. Even the smallest ratio, one α–factor-secreting cell to twenty reporter cells, generated a distinct fluorescence signal. When using a 1:1 ratio, the secreted pheromone induced fluorescence in a distance of up to four millimeters after six hours. We conclude from both our experimental results and a mathematical diffusion model that in our approach: (1) the maximum dimension of separated compartments should not exceed five millimeters in gradient direction; and (2) the time-limiting step is not diffusion of the signaling molecule but production of the reporter protein. PMID:24233076

  5. Whole exome sequencing of rare variants in EIF4G1 and VPS35 in Parkinson disease

    PubMed Central

    Nuytemans, Karen; Bademci, Guney; Inchausti, Vanessa; Dressen, Amy; Kinnamon, Daniel D.; Mehta, Arpit; Wang, Liyong; Züchner, Stephan; Beecham, Gary W.; Martin, Eden R.; Scott, William K.

    2013-01-01

    Objective: Recently, vacuolar protein sorting 35 (VPS35) and eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) have been identified as 2 causal Parkinson disease (PD) genes. We used whole exome sequencing for rapid, parallel analysis of variations in these 2 genes. Methods: We performed whole exome sequencing in 213 patients with PD and 272 control individuals. Those rare variants (RVs) with <5% frequency in the exome variant server database and our own control data were considered for analysis. We performed joint gene-based tests for association using RVASSOC and SKAT (Sequence Kernel Association Test) as well as single-variant test statistics. Results: We identified 3 novel VPS35 variations that changed the coded amino acid (nonsynonymous) in 3 cases. Two variations were in multiplex families and neither segregated with PD. In EIF4G1, we identified 11 (9 nonsynonymous and 2 small indels) RVs including the reported pathogenic mutation p.R1205H, which segregated in all affected members of a large family, but also in 1 unaffected 86-year-old family member. Two additional RVs were found in isolated patients only. Whereas initial association studies suggested an association (p = 0.04) with all RVs in EIF4G1, subsequent testing in a second dataset for the driving variant (p.F1461) suggested no association between RVs in the gene and PD. Conclusions: We confirm that the specific EIF4G1 variation p.R1205H seems to be a strong PD risk factor, but is nonpenetrant in at least one 86-year-old. A few other select RVs in both genes could not be ruled out as causal. However, there was no evidence for an overall contribution of genetic variability in VPS35 or EIF4G1 to PD development in our dataset. PMID:23408866

  6. 47 CFR 22.901 - Cellular service requirements and limitations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... limitations. The licensee of each cellular system is responsible for ensuring that its cellular system operates in compliance with this section. (a) Each cellular system must provide either mobile service... cellular services, each cellular system may incorporate any technology that meets all applicable...

  7. 47 CFR 22.901 - Cellular service requirements and limitations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... limitations. The licensee of each cellular system is responsible for ensuring that its cellular system operates in compliance with this section. (a) Each cellular system must provide either mobile service... cellular services, each cellular system may incorporate any technology that meets all applicable...

  8. 47 CFR 22.901 - Cellular service requirements and limitations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... limitations. The licensee of each cellular system is responsible for ensuring that its cellular system operates in compliance with this section. (a) Each cellular system must provide either mobile service... cellular services, each cellular system may incorporate any technology that meets all applicable...

  9. 47 CFR 22.901 - Cellular service requirements and limitations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... limitations. The licensee of each cellular system is responsible for ensuring that its cellular system operates in compliance with this section. (a) Each cellular system must provide either mobile service... cellular services, each cellular system may incorporate any technology that meets all applicable...

  10. Simulating the conversion of rural settlements to town land based on multi-agent systems and cellular automata.

    PubMed

    Liu, Yaolin; Kong, Xuesong; Liu, Yanfang; Chen, Yiyun

    2013-01-01

    Rapid urbanization in China has triggered the conversion of land from rural to urban use, particularly the conversion of rural settlements to town land. This conversion is the result of the joint effects of the geographic environment and agents involving the government, investors, and farmers. To understand the dynamic interaction dominated by agents and to predict the future landscape of town expansion, a small town land-planning model is proposed based on the integration of multi-agent systems (MAS) and cellular automata (CA). The MAS-CA model links the decision-making behaviors of agents with the neighbor effect of CA. The interaction rules are projected by analyzing the preference conflicts among agents. To better illustrate the effects of the geographic environment, neighborhood, and agent behavior, a comparative analysis between the CA and MAS-CA models in three different towns is presented, revealing interesting patterns in terms of quantity, spatial characteristics, and the coordinating process. The simulation of rural settlements conversion to town land through modeling agent decision and human-environment interaction is very useful for understanding the mechanisms of rural-urban land-use change in developing countries. This process can assist town planners in formulating appropriate development plans. PMID:24244472

  11. Simulating the Conversion of Rural Settlements to Town Land Based on Multi-Agent Systems and Cellular Automata

    PubMed Central

    Liu, Yaolin; Kong, Xuesong; Liu, Yanfang; Chen, Yiyun

    2013-01-01

    Rapid urbanization in China has triggered the conversion of land from rural to urban use, particularly the conversion of rural settlements to town land. This conversion is the result of the joint effects of the geographic environment and agents involving the government, investors, and farmers. To understand the dynamic interaction dominated by agents and to predict the future landscape of town expansion, a small town land-planning model is proposed based on the integration of multi-agent systems (MAS) and cellular automata (CA). The MAS-CA model links the decision-making behaviors of agents with the neighbor effect of CA. The interaction rules are projected by analyzing the preference conflicts among agents. To better illustrate the effects of the geographic environment, neighborhood, and agent behavior, a comparative analysis between the CA and MAS-CA models in three different towns is presented, revealing interesting patterns in terms of quantity, spatial characteristics, and the coordinating process. The simulation of rural settlements conversion to town land through modeling agent decision and human-environment interaction is very useful for understanding the mechanisms of rural-urban land-use change in developing countries. This process can assist town planners in formulating appropriate development plans. PMID:24244472

  12. Simulating the conversion of rural settlements to town land based on multi-agent systems and cellular automata.

    PubMed

    Liu, Yaolin; Kong, Xuesong; Liu, Yanfang; Chen, Yiyun

    2013-01-01

    Rapid urbanization in China has triggered the conversion of land from rural to urban use, particularly the conversion of rural settlements to town land. This conversion is the result of the joint effects of the geographic environment and agents involving the government, investors, and farmers. To understand the dynamic interaction dominated by agents and to predict the future landscape of town expansion, a small town land-planning model is proposed based on the integration of multi-agent systems (MAS) and cellular automata (CA). The MAS-CA model links the decision-making behaviors of agents with the neighbor effect of CA. The interaction rules are projected by analyzing the preference conflicts among agents. To better illustrate the effects of the geographic environment, neighborhood, and agent behavior, a comparative analysis between the CA and MAS-CA models in three different towns is presented, revealing interesting patterns in terms of quantity, spatial characteristics, and the coordinating process. The simulation of rural settlements conversion to town land through modeling agent decision and human-environment interaction is very useful for understanding the mechanisms of rural-urban land-use change in developing countries. This process can assist town planners in formulating appropriate development plans.

  13. Cleavage of eIF4G by HIV-1 protease: effects on translation.

    PubMed

    Perales, Celia; Carrasco, Luis; Ventoso, Iván

    2003-01-01

    We have recently reported that HIV-1 protease (PR) cleaves the initiation factor of translation eIF4GI [Ventoso et al., Proc. Natl. Acad. Sci. USA 98 (2001) 12966-12971]. Here, we analyze the proteolytic activity of HIV-1 PR on eIF4GI and eIF4GII and its implications for the translation of mRNAs. HIV-1 PR efficiently cleaves eIF4GI, but not eIF4GII, in cell-free systems as well as in transfected mammalian cells. This specific proteolytic activity of the retroviral protease on eIF4GI was more selective than that observed with poliovirus 2A(pro). Despite the presence of an intact endogenous eIF4GII, cleavage of eIF4GI by HIV-1 PR was sufficient to impair drastically the translation of capped and uncapped mRNAs. In contrast, poliovirus IRES-driven translation was unaffected or even enhanced by HIV-1 PR after cleavage of eIF4GI. Further support for these in vitro results has been provided by the expression of HIV-1 PR in COS cells from a Gag-PR precursor. Our present findings suggest that eIF4GI intactness is necessary to maintain cap-dependent translation, not only in cell-free systems but also in mammalian cells.

  14. Molecular and cellular neuroinflammatory status of mouse brain after systemic lipopolysaccharide challenge: importance of CCR2/CCL2 signaling

    PubMed Central

    2014-01-01

    , associated with overproduction of pro-inflammatory cytokines and chemokines, especially CCL2. LPS also induced a marked and selective increase of CCR2+ inflammatory monocytes within the brain. Finally, we showed that CCL2 hyperpolarized serotonergic raphe neurons in mouse midbrain slices, thus probably reducing the serotonin tone in projection areas. Conclusion Together, we provide a detailed characterization of the molecular and cellular players involved in the establishment of neuroinflammation after systemic injection of LPS. This highlights the importance of the CCL2/CCR2 signaling and suggests a possible link with depressive disorders. PMID:25065370

  15. Cellular Contraction and Polarization Drive Collective Cellular Motion.

    PubMed

    Notbohm, Jacob; Banerjee, Shiladitya; Utuje, Kazage J C; Gweon, Bomi; Jang, Hwanseok; Park, Yongdoo; Shin, Jennifer; Butler, James P; Fredberg, Jeffrey J; Marchetti, M Cristina

    2016-06-21

    Coordinated motions of close-packed multicellular systems typically generate cooperative packs, swirls, and clusters. These cooperative motions are driven by active cellular forces, but the physical nature of these forces and how they generate collective cellular motion remain poorly understood. Here, we study forces and motions in a confined epithelial monolayer and make two experimental observations: 1) the direction of local cellular motion deviates systematically from the direction of the local traction exerted by each cell upon its substrate; and 2) oscillating waves of cellular motion arise spontaneously. Based on these observations, we propose a theory that connects forces and motions using two internal state variables, one of which generates an effective cellular polarization, and the other, through contractile forces, an effective cellular inertia. In agreement with theoretical predictions, drugs that inhibit contractility reduce both the cellular effective elastic modulus and the frequency of oscillations. Together, theory and experiment provide evidence suggesting that collective cellular motion is driven by at least two internal variables that serve to sustain waves and to polarize local cellular traction in a direction that deviates systematically from local cellular velocity. PMID:27332131

  16. Epigenetics and Cellular Metabolism

    PubMed Central

    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

  17. Epigenetics and Cellular Metabolism

    PubMed Central

    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.

  18. Hα kinematics of S4G spiral galaxies - II. Data description and non-circular motions

    NASA Astrophysics Data System (ADS)

    Erroz-Ferrer, Santiago; Knapen, Johan H.; Leaman, Ryan; Cisternas, Mauricio; Font, Joan; Beckman, John E.; Sheth, Kartik; Muñoz-Mateos, Juan Carlos; Díaz-García, Simón; Bosma, Albert; Athanassoula, E.; Elmegreen, Bruce G.; Ho, Luis C.; Kim, Taehyun; Laurikainen, Eija; Martinez-Valpuesta, Inma; Meidt, Sharon E.; Salo, Heikki

    2015-07-01

    We present a kinematical study of 29 spiral galaxies included in the Spitzer Survey of Stellar Structure in Galaxies, using Hα Fabry-Perot (FP) data obtained with the Galaxy Hα Fabry-Perot System instrument at the William Herschel Telescope in La Palma, complemented with images in the R band and in Hα. The primary goal is to study the evolution and properties of the main structural components of galaxies through the kinematical analysis of the FP data, complemented with studies of morphology, star formation and mass distribution. In this paper we describe how the FP data have been obtained, processed and analysed. We present the resulting moment maps, rotation curves, velocity model maps and residual maps. Images are available in FITS format through the NASA/IPAC Extragalactic Database and the Centre de Données Stellaires. With these data products we study the non-circular motions, in particular those found along the bars and spiral arms. The data indicate that the amplitude of the non-circular motions created by the bar does not correlate with the bar strength indicators. The amplitude of those non-circular motions in the spiral arms does not correlate with either arm class or star formation rate along the spiral arms. This implies that the presence and the magnitude of the streaming motions in the arms is a local phenomenon.

  19. Synthesis and preliminary in vitro kinase inhibition evaluation of new diversely substituted pyrido[3,4-g]quinazoline derivatives.

    PubMed

    Zeinyeh, Wael; Esvan, Yannick J; Nauton, Lionel; Loaëc, Nadège; Meijer, Laurent; Théry, Vincent; Anizon, Fabrice; Giraud, Francis; Moreau, Pascale

    2016-09-01

    The synthesis of new diversely substituted pyrido[3,4-g]quinazolines is described. The inhibitory potencies of prepared compounds toward a panel of five CMGC protein kinases (CDK5, CLK1, DYRK1A, CK1, GSK3), that are known to play a potential role in Alzheimer's disease, were evaluated. The best overall kinase inhibition profile was found for nitro compound 4 bearing an ethyl group at the 5-position. PMID:27469128

  20. Synthesis and preliminary in vitro kinase inhibition evaluation of new diversely substituted pyrido[3,4-g]quinazoline derivatives.

    PubMed

    Zeinyeh, Wael; Esvan, Yannick J; Nauton, Lionel; Loaëc, Nadège; Meijer, Laurent; Théry, Vincent; Anizon, Fabrice; Giraud, Francis; Moreau, Pascale

    2016-09-01

    The synthesis of new diversely substituted pyrido[3,4-g]quinazolines is described. The inhibitory potencies of prepared compounds toward a panel of five CMGC protein kinases (CDK5, CLK1, DYRK1A, CK1, GSK3), that are known to play a potential role in Alzheimer's disease, were evaluated. The best overall kinase inhibition profile was found for nitro compound 4 bearing an ethyl group at the 5-position.

  1. Novel mucus-penetrating liposomes as a potential oral drug delivery system: preparation, in vitro characterization, and enhanced cellular uptake

    PubMed Central

    Li, Xiuying; Chen, Dan; Le, Chaoyi; Zhu, Chunliu; Gan, Yong; Hovgaard, Lars; Yang, Mingshi

    2011-01-01

    Background The aim of this study was to investigate the intestinal mucus-penetrating properties and intestinal cellular uptake of two types of liposomes modified by Pluronic F127 (PF127). Methods The two types of liposomes, ie, PF127-inlaid liposomes and PF127-adsorbed liposomes, were prepared by a thin-film hydration method followed by extrusion, in which coumarin 6 was loaded as a fluorescence marker. A modified Franz diffusion cell mounted with the intestinal mucus of rats was used to study the diffusion characteristics of the two types of PF127 liposomes. Cell uptake studies were conducted in Caco-2 cells and analyzed using confocal laser scanning microcopy as well as flow cytometry. Results The diffusion efficiency of the two types of PF127-modified liposomes through intestinal rat mucus was 5–7-fold higher than that of unmodified liposomes. Compared with unmodified liposomes, PF127-inlaid liposomes showed significantly higher cellular uptake of courmarin 6. PF127-adsorbed liposomes showed a lower cellular uptake. Moreover, and interestingly, the two types of PF127-modified liposomes showed different cellular uptake mechanisms in Caco-2 cells. Conclusion PF127-inlaid liposomes with improved intestinal mucus-penetrating ability and enhanced cellular uptake might be a potential carrier candidate for oral drug delivery. PMID:22163166

  2. Autoantibodies to angiotensin and endothelin receptors in systemic sclerosis induce cellular and systemic events associated with disease pathogenesis

    PubMed Central

    2014-01-01

    Introduction Vasculopathy, inflammatory fibrosis and functional autoantibodies (Abs) are major manifestations of systemic sclerosis (SSc). Abs directed against the angiotensin II type 1 receptor (AT1R) and endothelin-1 type A receptor (ETAR) are associated with characteristic disease features including vascular, inflammatory, and fibrotic complications indicating their role in SSc pathogenesis. Therefore, the impact of anti-AT1R and anti-ETAR Abs on initiation of inflammation and fibrosis was analyzed. Methods Anti-AT1R and anti-ETAR Ab-positive immunoglobulin G (IgG) from SSc patients (SSc-IgG) was used for experiments. Healthy donor IgG served as a normal control, and AT1R and ETAR activation was inhibited by antagonists. Protein expression was measured with ELISA, mRNA expression with real time-PCR, endothelial repair with a scratch assay, and collagen expression with immunocytochemistry. Transendothelial neutrophil migration was measured with a culture insert system, and neutrophil ROS activation with immunofluorescence. Neutrophils in bronchoalveolar lavage fluids (BALFs) were analyzed microscopically after passive transfer of SSc-IgG or NC-IgG into naïve C57BL/6J mice. KC plasma levels were quantified by a suspension array system. Histologic analyses were performed by using light microscopy. Results Anti-AT1R and anti-ETAR Ab-positive SSc-IgG induced activation of human microvascular endothelial cells (HMEC-1). Elevated protein and mRNA levels of the proinflammatory chemokine interleukin-8 (IL-8, CXCL8) and elevated mRNA levels of the vascular cell adhesion molecule-1 (VCAM-1) were induced in HMEC-1. Furthermore, activation of HMEC-1 with SSc-IgG increased neutrophil migration through an endothelial cell layer and activation of reactive oxygen species (ROS). SSc-IgG decreased HMEC-1 wound repair and induced type I collagen production in healthy donor skin fibroblasts. Effects of migration, wound repair, and collagen expression were dependent on the Ab

  3. Cellular automata to understand the behaviour of beach-dune systems: Application to El Fangar Spit active dune system (Ebro delta, Spain)

    NASA Astrophysics Data System (ADS)

    Barrio-Parra, Fernando; Rodríguez-Santalla, Inmaculada

    2016-08-01

    Coastal dunes are sedimentary environments characterized by their high dynamism. Their evolution is determined by sedimentary exchanges between the beach-dune subsystems and the dune dynamics itself. Knowledge about these exchanges is important to prioritize management and conservation strategies of these environments. The aim of this work is the inclusion of the aeolian transport rates obtained using a calibrated cellular automaton to estimate the beach-dune sediment exchange rates in a real active dune field at El Fangar Spit (Ebro Delta, Spain). The dune dynamics model is able to estimate average aeolian sediment fluxes. These are used in combination with the observed net sediment budget to obtain a quantitative characterization of the sediment exchange interactions. The methods produce a substantial improvement in the understanding of coastal sedimentary systems that could have major implications in areas where the management and conservation of dune fields are of concern.

  4. The Perilipins: Major Cytosolic Lipid Droplet-Associated Proteins and Their Roles in Cellular Lipid Storage, Mobilization, and Systemic Homeostasis.

    PubMed

    Kimmel, Alan R; Sztalryd, Carole

    2016-07-17

    The discovery by Dr. Constantine Londos of perilipin 1, the major scaffold protein at the surface of cytosolic lipid droplets in adipocytes, marked a fundamental conceptual change in the understanding of lipolytic regulation. Focus then shifted from the enzymatic activation of lipases to substrate accessibility, mediated by perilipin-dependent protein sequestration and recruitment. Consequently, the lipid droplet became recognized as a unique, metabolically active cellular organelle and its surface as the active site for novel protein-protein interactions. A new area of investigation emerged, centered on lipid droplets' biology and their role in energy homeostasis. The perilipin family is of ancient origin and has expanded to include five mammalian genes and a growing list of evolutionarily conserved members. Universally, the perilipins modulate cellular lipid storage. This review provides a summary that connects the perilipins to both cellular and whole-body homeostasis. PMID:27431369

  5. Alternative Oxidase Pathway Optimizes Photosynthesis During Osmotic and Temperature Stress by Regulating Cellular ROS, Malate Valve and Antioxidative Systems

    PubMed Central

    Vishwakarma, Abhaypratap; Raghavendra, Agepati S.; Padmasree, Kollipara

    2016-01-01

    The present study reveals the importance of alternative oxidase (AOX) pathway in optimizing photosynthesis under osmotic and temperature stress conditions in the mesophyll protoplasts of Pisum sativum. The responses of photosynthesis and respiration were monitored at saturating light intensity of 1000 μmoles m–2 s–1 at 25°C under a range of sorbitol concentrations from 0.4 to 1.0 M to induce hyper-osmotic stress and by varying the temperature of the thermo-jacketed pre-incubation chamber from 25 to 10°C to impose sub-optimal temperature stress. Compared to controls (0.4 M sorbitol and 25°C), the mesophyll protoplasts showed remarkable decrease in NaHCO3-dependent O2 evolution (indicator of photosynthetic carbon assimilation), under both hyper-osmotic (1.0 M sorbitol) and sub-optimal temperature stress conditions (10°C), while the decrease in rates of respiratory O2 uptake were marginal. The capacity of AOX pathway increased significantly in parallel to increase in intracellular pyruvate and reactive oxygen species (ROS) levels under both hyper-osmotic stress and sub-optimal temperature stress under the background of saturating light. The ratio of redox couple (Malate/OAA) related to malate valve increased in contrast to the ratio of redox couple (GSH/GSSG) related to antioxidative system during hyper-osmotic stress. Further, the ratio of GSH/GSSG decreased in the presence of sub-optimal temperature, while the ratio of Malate/OAA showed no visible changes. Also, the redox ratios of pyridine nucleotides increased under hyper-osmotic (NADH/NAD) and sub-optimal temperature (NADPH/NADP) stresses, respectively. However, upon restriction of AOX pathway by using salicylhydroxamic acid (SHAM), the observed changes in NaHCO3-dependent O2 evolution, cellular ROS, redox ratios of Malate/OAA, NAD(P)H/NAD(P) and GSH/GSSG were further aggravated under stress conditions with concomitant modulations in NADP-MDH and antioxidant enzymes. Taken together, the results indicated

  6. MSAT and cellular hybrid networking

    NASA Technical Reports Server (NTRS)

    Baranowsky, Patrick W., II

    1993-01-01

    Westinghouse Electric Corporation is developing both the Communications Ground Segment and the Series 1000 Mobile Phone for American Mobile Satellite Corporation's (AMSC's) Mobile Satellite (MSAT) system. The success of the voice services portion of this system depends, to some extent, upon the interoperability of the cellular network and the satellite communication circuit switched communication channels. This paper will describe the set of user-selectable cellular interoperable modes (cellular first/satellite second, etc.) provided by the Mobile Phone and described how they are implemented with the ground segment. Topics including roaming registration and cellular-to-satellite 'seamless' call handoff will be discussed, along with the relevant Interim Standard IS-41 Revision B Cellular Radiotelecommunications Intersystem Operations and IOS-553 Mobile Station - Land Station Compatibility Specification.

  7. miR-139-5p controls translation in myeloid leukemia through EIF4G2.

    PubMed

    Emmrich, S; Engeland, F; El-Khatib, M; Henke, K; Obulkasim, A; Schöning, J; Katsman-Kuipers, J E; Michel Zwaan, C; Pich, A; Stary, J; Baruchel, A; de Haas, V; Reinhardt, D; Fornerod, M; van den Heuvel-Eibrink, M M; Klusmann, J H

    2016-04-01

    MicroRNAs (miRNAs) are crucial components of homeostatic and developmental gene regulation. In turn, dysregulation of miRNA expression is a common feature of different types of cancer, which can be harnessed therapeutically. Here we identify miR-139-5p suppression across several cytogenetically defined acute myeloid leukemia (AML) subgroups. The promoter of mir-139 was transcriptionally silenced and could be reactivated by histone deacetylase inhibitors in a dose-dependent manner. Restoration of mir-139 expression in cell lines representing the major AML subgroups (t[8;21], inv[16], mixed lineage leukemia-rearranged and complex karyotype AML) caused cell cycle arrest and apoptosis in vitro and in xenograft mouse models in vivo. During normal hematopoiesis, mir-139 is exclusively expressed in terminally differentiated neutrophils and macrophages. Ectopic expression of mir-139 repressed proliferation of normal CD34(+)-hematopoietic stem and progenitor cells and perturbed myelomonocytic in vitro differentiation. Mechanistically, mir-139 exerts its effects by repressing the translation initiation factor EIF4G2, thereby reducing overall protein synthesis while specifically inducing the translation of cell cycle inhibitor p27(Kip1). Knockdown of EIF4G2 recapitulated the effects of mir-139, whereas restoring EIF4G2 expression rescued the mir-139 phenotype. Moreover, elevated miR-139-5p expression is associated with a favorable outcome in a cohort of 165 pediatric patients with AML. Thus, mir-139 acts as a global tumor suppressor-miR in AML by controlling protein translation. As AML cells are dependent on high protein synthesis rates controlling the expression of mir-139 constitutes a novel path for the treatment of AML. PMID:26165837

  8. Downscaling seasonal to centennial simulations on distributed computing infrastructures using WRF model. The WRF4G project

    NASA Astrophysics Data System (ADS)

    Cofino, A. S.; Fernández Quiruelas, V.; Blanco Real, J. C.; García Díez, M.; Fernández, J.

    2013-12-01

    Nowadays Grid Computing is powerful computational tool which is ready to be used for scientific community in different areas (such as biomedicine, astrophysics, climate, etc.). However, the use of this distributed computing infrastructures (DCI) is not yet common practice in climate research, and only a few teams and applications in this area take advantage of this infrastructure. Thus, the WRF4G project objective is to popularize the use of this technology in the atmospheric sciences area. In order to achieve this objective, one of the most used applications has been taken (WRF; a limited- area model, successor of the MM5 model), that has a user community formed by more than 8000 researchers worldwide. This community develop its research activity on different areas and could benefit from the advantages of Grid resources (case study simulations, regional hind-cast/forecast, sensitivity studies, etc.). The WRF model is used by many groups, in the climate research community, to carry on downscaling simulations. Therefore this community will also benefit. However, Grid infrastructures have some drawbacks for the execution of applications that make an intensive use of CPU and memory for a long period of time. This makes necessary to develop a specific framework (middleware). This middleware encapsulates the application and provides appropriate services for the monitoring and management of the simulations and the data. Thus,another objective of theWRF4G project consists on the development of a generic adaptation of WRF to DCIs. It should simplify the access to the DCIs for the researchers, and also to free them from the technical and computational aspects of the use of theses DCI. Finally, in order to demonstrate the ability of WRF4G solving actual scientific challenges with interest and relevance on the climate science (implying a high computational cost) we will shown results from different kind of downscaling experiments, like ERA-Interim re-analysis, CMIP5 models

  9. The signal to noise and distortion ratio for sigma delta ADC for SDR 3G/4G mobile receivers

    NASA Astrophysics Data System (ADS)

    Trivedi, Preeti; Verma, Ajay

    2013-01-01

    In this paper, we propose a Simulation for the test of SNDR (Signal to noise and Distortion ratio) in Sigma Delta ADC for SDR 3G and 4G mobile Receivers. Now a days, SNDR is one of the most important parameter which directly effects the performance of ADC. Simulation results show the Capability of the simulink to obtain SNDR for a 8 bit and 10 bit audio Sigma delta ADC. SNDR of ADC will always be less than SNR. The simulation model of second order Sigma Delta ADC is given in the paper. The SNR and SNDR have been taken into account.

  10. A telemedicine wound care model using 4G with smart phones or smart glasses: A pilot study.

    PubMed

    Ye, Junna; Zuo, Yanhai; Xie, Ting; Wu, Minjie; Ni, Pengwen; Kang, Yutian; Yu, Xiaoping; Sun, Xiaofang; Huang, Yao; Lu, Shuliang

    2016-08-01

    To assess the feasibility of a wound care model using 4th-generation mobile communication technology standards (4G) with smart phones or smart glasses for wound management.This wound care model is an interactive, real-time platform for implementing telemedicine changing wound dressings, or doing operations. It was set up in March 2015 between Jinhua in Zhejiang province and Shanghai, China, which are 328 km apart. It comprised of a video application (APP), 4G net, smart phones or smart glasses, and a central server.This model service has been used in 30 patients with wounds on their lower extremities for 109 times in 1 month. Following a short learning curve, the service worked well and was deemed to be user-friendly. Two (6.7%) patients had wounds healed, while others still required wound dressing changes after the study finished. Both local surgeons and patients showed good acceptance of this model (100% and 83.33%, respectively).This telemedicine model is feasible and valuable because it provides an opportunity of medical service about wound healing in remote areas where specialists are scarce. PMID:27495023

  11. An accurately preorganized IRES RNA structure enables eIF4G capture for initiation of viral translation.

    PubMed

    Imai, Shunsuke; Kumar, Parimal; Hellen, Christopher U T; D'Souza, Victoria M; Wagner, Gerhard

    2016-09-01

    Many viruses bypass canonical cap-dependent translation in host cells by using internal ribosomal entry sites (IRESs) in their transcripts; IRESs hijack initiation factors for the assembly of initiation complexes. However, it is currently unknown how IRES RNAs recognize initiation factors that have no endogenous RNA binding partners; in a prominent example, the IRES of encephalomyocarditis virus (EMCV) interacts with the HEAT-1 domain of eukaryotic initiation factor 4G (eIF4G). Here we report the solution structure of the J-K region of this IRES and show that its stems are precisely organized to position protein-recognition bulges. This multisite interaction mechanism operates on an all-or-nothing principle in which all domains are required. This preorganization is accomplished by an 'adjuster module': a pentaloop motif that acts as a dual-sided docking station for base-pair receptors. Because subtle changes in the orientation abrogate protein capture, our study highlights how a viral RNA acquires affinity for a target protein. PMID:27525590

  12. Deletion of the eIFiso4G subunit of the Arabidopsis eIFiso4F translation initiation complex impairs health and viability.

    PubMed

    Lellis, Andrew D; Allen, M Leah; Aertker, Alice W; Tran, Jonathan K; Hillis, David M; Harbin, Courtney R; Caldwell, Christian; Gallie, Daniel R; Browning, Karen S

    2010-10-01

    Arabidopsis thaliana knockout lines for the plant-specific eukaryotic translation initiation factors eIFiso4G1 (i4g1) and eIFiso4G2 (i4g2) genes have been obtained. To address the potential for functional redundancy of these genes, homozygous double mutant lines were generated by crossing individual knockout lines. Both single and double mutant plants were analyzed for changes in gross morphology, development, and responses to selected environmental stressors. Single gene knockouts appear to have minimal effect on morphology, germination rate, growth rate, flowering time, or fertility. However, double mutant i4g1/i4g2 knockout plants show reduced germination rates, slow growth rates, moderate chlorosis, impaired fertility and reduced long term seed viability. Double mutant plants also exhibit altered responses to dehydration, salinity, and heat stress. The i4g2 and i4g1/i4g2 double mutant has reduced amounts of chlorophyll a and b suggesting a role in the expression of chloroplast proteins. General protein synthesis did not appear to be affected as the levels of gross protein expression did not appear to change in the mutants. The lack of a phenotype for either of the single mutants suggests there is considerable functional overlap. However, the strong phenotypes observed for the double mutant indicates that the individual gene products may have specialized roles in the expression of proteins involved in plant growth and development.

  13. A New Flow-Regulating Cell Type in the Demosponge Tethya wilhelma – Functional Cellular Anatomy of a Leuconoid Canal System

    PubMed Central

    Hammel, Jörg U.; Nickel, Michael

    2014-01-01

    Demosponges possess a leucon-type canal system which is characterized by a highly complex network of canal segments and choanocyte chambers. As sponges are sessile filter feeders, their aquiferous system plays an essential role in various fundamental physiological processes. Due to the morphological and architectural complexity of the canal system and the strong interdependence between flow conditions and anatomy, our understanding of fluid dynamics throughout leuconoid systems is patchy. This paper provides comprehensive morphometric data on the general architecture of the canal system, flow measurements and detailed cellular anatomical information to help fill in the gaps. We focus on the functional cellular anatomy of the aquiferous system and discuss all relevant cell types in the context of hydrodynamic and evolutionary constraints. Our analysis is based on the canal system of the tropical demosponge Tethya wilhelma, which we studied using scanning electron microscopy. We found a hitherto undescribed cell type, the reticuloapopylocyte, which is involved in flow regulation in the choanocyte chambers. It has a highly fenestrated, grid-like morphology and covers the apopylar opening. The minute opening of the reticuloapopylocyte occurs in an opened, intermediate and closed state. These states permit a gradual regulation of the total apopylar opening area. In this paper the three states are included in a theoretical study into flow conditions which aims to draw a link between functional cellular anatomy, the hydrodynamic situation and the regular body contractions seen in T. wilhelma. This provides a basis for new hypotheses regarding the function of bypass elements and the role of hydrostatic pressure in body contractions. Our study provides insights into the local and global flow conditions in the sponge canal system and thus enhances current understanding of related physiological processes. PMID:25409176

  14. A cardiac electrical activity model based on a cellular automata system in comparison with neural network model.

    PubMed

    Khan, Muhammad Sadiq Ali; Yousuf, Sidrah

    2016-03-01

    Cardiac Electrical Activity is commonly distributed into three dimensions of Cardiac Tissue (Myocardium) and evolves with duration of time. The indicator of heart diseases can occur randomly at any time of a day. Heart rate, conduction and each electrical activity during cardiac cycle should be monitor non-invasively for the assessment of "Action Potential" (regular) and "Arrhythmia" (irregular) rhythms. Many heart diseases can easily be examined through Automata model like Cellular Automata concepts. This paper deals with the different states of cardiac rhythms using cellular automata with the comparison of neural network also provides fast and highly effective stimulation for the contraction of cardiac muscles on the Atria in the result of genesis of electrical spark or wave. The specific formulated model named as "States of automaton Proposed Model for CEA (Cardiac Electrical Activity)" by using Cellular Automata Methodology is commonly shows the three states of cardiac tissues conduction phenomena (i) Resting (Relax and Excitable state), (ii) ARP (Excited but Absolutely refractory Phase i.e. Excited but not able to excite neighboring cells) (iii) RRP (Excited but Relatively Refractory Phase i.e. Excited and able to excite neighboring cells). The result indicates most efficient modeling with few burden of computation and it is Action Potential during the pumping of blood in cardiac cycle.

  15. A cardiac electrical activity model based on a cellular automata system in comparison with neural network model.

    PubMed

    Khan, Muhammad Sadiq Ali; Yousuf, Sidrah

    2016-03-01

    Cardiac Electrical Activity is commonly distributed into three dimensions of Cardiac Tissue (Myocardium) and evolves with duration of time. The indicator of heart diseases can occur randomly at any time of a day. Heart rate, conduction and each electrical activity during cardiac cycle should be monitor non-invasively for the assessment of "Action Potential" (regular) and "Arrhythmia" (irregular) rhythms. Many heart diseases can easily be examined through Automata model like Cellular Automata concepts. This paper deals with the different states of cardiac rhythms using cellular automata with the comparison of neural network also provides fast and highly effective stimulation for the contraction of cardiac muscles on the Atria in the result of genesis of electrical spark or wave. The specific formulated model named as "States of automaton Proposed Model for CEA (Cardiac Electrical Activity)" by using Cellular Automata Methodology is commonly shows the three states of cardiac tissues conduction phenomena (i) Resting (Relax and Excitable state), (ii) ARP (Excited but Absolutely refractory Phase i.e. Excited but not able to excite neighboring cells) (iii) RRP (Excited but Relatively Refractory Phase i.e. Excited and able to excite neighboring cells). The result indicates most efficient modeling with few burden of computation and it is Action Potential during the pumping of blood in cardiac cycle. PMID:27087101

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

    PubMed

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

    2014-01-01

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

  17. Kinematical evidence for secular evolution in Spitzer Survey of Stellar Structure in Galaxies (S4G) spirals

    NASA Astrophysics Data System (ADS)

    Erroz-Ferrer, Santiago; Knapen, Johan H.; Font, Joan; Beckman, John E.

    2015-03-01

    We present a study of the kinematics of a sample of isolated spiral galaxies in the Spitzer Survey of Stellar Structure in Galaxies (S4G). We use Hα Fabry-Perot data from the GHαFaS instrument at the William Herschel Telescope (WHT) in La Palma, complemented with images at 3.6 microns, in the R band and in the Hα filter. The resulting data cubes and velocity field maps allow a complete study of the kinematics of a galaxy, including in-depth investigations of the rotation curve, velocity moment maps, velocity residual maps, gradient maps and position-velocity (PV) diagrams. We find clear evidence of the secular evolution processes going on in these galaxies, such as asymmetries in the velocity field in the bar zone, and non-circular motions, probably in response to the potential of the structural components of the galaxies, or to past or present interactions.

  18. Metallicities of Low Mass Inefficient Star Forming Dwarfs in S4G: Testing the Closed Box Paradigm

    NASA Astrophysics Data System (ADS)

    McKay, Myles; Stirewalt, Sabrina; Sheth, Kartik; de Swardt, Bonita; Walter, Donald

    2015-03-01

    Low mass dwarf galaxies are the most numerous extragalactic population in the Local Universe. Many gas-rich dwarfs appear to be forming stars less efficiently than normal, massive disk galaxies and are therefore important laboratories for the study of star formation. Here we present new observations using the Palomar Double Spectrograph for 19 dwarf galaxies from the S4G Survey with the lowest stellar to HI mass ratios. Preliminary analysis of the data indicate a wide range of metallicities which vary by as much as 0.5 dex in a single galaxy in different star forming regions. Such a dispersion in metallicities favors an open box model and the results suggest a varied star formation history, possibly induced via minor mergers and accretion. The National Radio Astronomy Observatory(NRAO), National Science Foundation(NSF), and the National Astronomy Consortium (NAC) Cville Cohort. Additional support was provided by NSF Awards AST-0750814 and AST-1358913 to South Carolina State University.

  19. VizieR Online Data Catalog: S4G pipeline 4: multi-component decompositions (Salo+, 2015)

    NASA Astrophysics Data System (ADS)

    Salo, H.; Laurikainen, E.; Laine, J.; Comeron, S.; Gadotti, D. A.; Buta, R.; Sheth, K.; Zaritsky, D.; Ho, L.; Knapen, J.; Athanassoula, E.; Bosma, A.; Laine, S.; Cisternas, M.; Kim, T.; Munoz-Mateos, J. C.; Regan, M.; Hinz, J. L.; Gil de, Paz A.; Menendez-Delmestre, K.; Mizusawa, T.; Erroz-Ferrer, S.; Meidt, S. E.; Querejeta, M.

    2015-09-01

    The Spitzer Survey of Stellar Structure in Galaxies (S4G, Sheth et al. 2010, J/PASP/122/1397) is a survey of 2352 galaxies observed in the mid-infrared (mid-IR) at 3.6 and 4.5um, wavelengths that are largely unaffected by internal extinction. The data have been processed through Pipeline 1 (Munoz-Mateos et al. 2015ApJS..219....3M; MM15) which makes mosaics of the observed individual frames, Pipeline 2 (MM15) which makes masks of the foreground stars and image defects, and Pipeline 3 (MM15) which measures the basic photometric parameters like the galaxy magnitudes and concentration indices. In Pipeline 4 (P4), described in this study, we decompose the two-dimensional flux distributions of the images into several structural components using GALFIT (Peng et al. 2010AJ....139.2097P). (3 data files).

  20. VizieR Online Data Catalog: Catalogue of features in the S4G (Herrera-Endoqui+, 2015)

    NASA Astrophysics Data System (ADS)

    Herrera-Endoqui, M.; Diaz-Garcia, S.; Laurikainen, E.; Salo, H.

    2015-08-01

    Table 2 contains the properties of bars, ring- and lens-structures in the S4G. Data for bars contains the visual estimated barlength, the maximum ellipticity in the bar region, the visual estimated position angle, and the barlength obtained from the ellipticity maximum. They are given in both the sky plane and the disk plane, the conversion is made using P4 orientation parameters (Salo et al., 2015ApJS..219....4S; Table 1). For bars the disk plane values are given only when a reliable ellipticity maximum was found and the galaxy inclination i<65 deg. For other features the parameters are obtained from fitting ellipses to points tracing the structure. A quality flag for our measurement is also given: 1 indicates a good fit and unambiguously identified feature, 2 indicates a hard to trace feature, 3 indicates an uncertain feature identification (due to high inclination of host galaxy or incomplete feature). Table 3 contains the properties of spiral arms in the S4G. Type of spiral arms, the pitch angle, the inner and the outer radius are given for every spiral segment (see the catalogue web page). The type of spiral arms are taken from Buta et al. (2015ApJS..217...32B, Cat. J/ApJS/217/32): G for grand design, M for multiple, and F for flocculent spiral arms. Our estimation of the quality of the fit is also given (1.0 = good; 2.0 = acceptable). (2 data files).

  1. Complete genome sequence of Cupriavidus basilensis 4G11, isolated from the Oak Ridge Field Research Center site

    SciTech Connect

    Ray, Jayashree; Waters, R. Jordan; Skerker, Jeffrey M.; Kuehl, Jennifer V.; Price, Morgan N.; Huang, Jiawen; Chakraborty, Romy; Arkin, Adam P.; Deutschbauer, Adam

    2015-05-14

    Cupriavidus basilensis 4G11 was isolated from groundwater at the Oak Ridge Field Research Center (FRC) site. Here, we report the complete genome sequence and annotation of Cupriavidus basilensis 4G11. The genome contains 8,421,483 bp, 7,661 predicted protein-coding genes, and a total GC content of 64.4%.

  2. Fabrication of cellular materials

    NASA Astrophysics Data System (ADS)

    Prud'homme, Robert K.; Aksay, Ilhan A.; Garg, Rajeev

    1996-02-01

    Nature uses cellular materials in applications requiring strength while, simultaneously, minimizing raw materials requirements. Minimizing raw materials is efficient both in terms of the energy expended by the organism to synthesize the structure and in terms of the strength- to-weight ratio of the structure. Wood is the most obvious example of cellular bio-materials, and it is the focus of other presentations in this symposium. The lightweight bone structure of birds is another excellent example where weight is a key criterion. The anchoring foot of the common muscle [Mytilus edulis] whereby it attaches itself to objects is a further example of a biological system that uses a foam to fill space and yet conserve on raw materials. In the case of the muscle the foam is water filled and the foot structure distributes stress over a larger area so that the strength of the byssal thread from which it is suspended is matched to the strength of interfacial attachment of the foot to a substrate. In these examples the synthesis and fabrication of the cellular material is directed by intercellular, genetically coded, biochemical reactions. The resulting cell sizes are microns in scale. Cellular materials at the next larger scale are created by organisms at the next higher level of integration. For example an African tree frog lays her eggs in a gas/fluid foam sack she builds on a branch overhanging a pond. The outside of the foam sack hardens in the sun and prevents water evaporation. The foam structure minimizes the amount of fluid that needs to be incorporated into the sack and minimizes its weight. However, as far as the developing eggs are concerned, they are in an aqueous medium, i.e. the continuous fluid phase of the foam. After precisely six days the eggs hatch, and the solidified outer wall re-liquefies and dumps the emerging tadpoles into the pond below. The bee honeycomb is an example of a cellular material with exquisite periodicity at millimeter length scales. The

  3. Probabilistic Cellular Automata

    PubMed Central

    Agapie, Alexandru; Giuclea, Marius

    2014-01-01

    Abstract Cellular automata are binary lattices used for modeling complex dynamical systems. The automaton evolves iteratively from one configuration to another, using some local transition rule based on the number of ones in the neighborhood of each cell. With respect to the number of cells allowed to change per iteration, we speak of either synchronous or asynchronous automata. If randomness is involved to some degree in the transition rule, we speak of probabilistic automata, otherwise they are called deterministic. With either type of cellular automaton we are dealing with, the main theoretical challenge stays the same: starting from an arbitrary initial configuration, predict (with highest accuracy) the end configuration. If the automaton is deterministic, the outcome simplifies to one of two configurations, all zeros or all ones. If the automaton is probabilistic, the whole process is modeled by a finite homogeneous Markov chain, and the outcome is the corresponding stationary distribution. Based on our previous results for the asynchronous case—connecting the probability of a configuration in the stationary distribution to its number of zero-one borders—the article offers both numerical and theoretical insight into the long-term behavior of synchronous cellular automata. PMID:24999557

  4. A systemic approach to explore the flexibility of energy stores at the cellular scale: Examples from muscle cells.

    PubMed

    Taghipoor, Masoomeh; van Milgen, Jaap; Gondret, Florence

    2016-09-01

    Variations in energy storage and expenditure are key elements for animals adaptation to rapidly changing environments. Because of the multiplicity of metabolic pathways, metabolic crossroads and interactions between anabolic and catabolic processes within and between different cells, the flexibility of energy stores in animal cells is difficult to describe by simple verbal, textual or graphic terms. We propose a mathematical model to study the influence of internal and external challenges on the dynamic behavior of energy stores and its consequence on cell energy status. The role of the flexibility of energy stores on the energy equilibrium at the cellular level is illustrated through three case studies: variation in eating frequency (i.e., glucose input), level of physical activity (i.e., ATP requirement), and changes in cell characteristics (i.e., maximum capacity of glycogen storage). Sensitivity analysis has been performed to highlight the most relevant parameters of the model; model simulations have then been performed to illustrate how variation in these key parameters affects cellular energy balance. According to this analysis, glycogen maximum accumulation capacity and homeostatic energy demand are among the most important parameters regulating muscle cell metabolism to ensure its energy equilibrium.

  5. A systemic approach to explore the flexibility of energy stores at the cellular scale: Examples from muscle cells.

    PubMed

    Taghipoor, Masoomeh; van Milgen, Jaap; Gondret, Florence

    2016-09-01

    Variations in energy storage and expenditure are key elements for animals adaptation to rapidly changing environments. Because of the multiplicity of metabolic pathways, metabolic crossroads and interactions between anabolic and catabolic processes within and between different cells, the flexibility of energy stores in animal cells is difficult to describe by simple verbal, textual or graphic terms. We propose a mathematical model to study the influence of internal and external challenges on the dynamic behavior of energy stores and its consequence on cell energy status. The role of the flexibility of energy stores on the energy equilibrium at the cellular level is illustrated through three case studies: variation in eating frequency (i.e., glucose input), level of physical activity (i.e., ATP requirement), and changes in cell characteristics (i.e., maximum capacity of glycogen storage). Sensitivity analysis has been performed to highlight the most relevant parameters of the model; model simulations have then been performed to illustrate how variation in these key parameters affects cellular energy balance. According to this analysis, glycogen maximum accumulation capacity and homeostatic energy demand are among the most important parameters regulating muscle cell metabolism to ensure its energy equilibrium. PMID:27338303

  6. Cellular: Toward personal communications

    NASA Astrophysics Data System (ADS)

    Heffernan, Stuart

    1991-09-01

    The cellular industry is one of the fastest growing segment of the telecommunications industry. With an estimated penetration rate of 20 percent in the near future, cellular is becoming an ubiquitous telecommunications service in the U.S. In this paper we will examine the major advancements in the cellular industry: customer equipment, cellular networks, engineering tools, customer support, and nationwide seamless service.

  7. Genome-wide assessment of the carriers involved in the cellular uptake of drugs: a model system in yeast

    PubMed Central

    2011-01-01

    Background The uptake of drugs into cells has traditionally been considered to be predominantly via passive diffusion through the bilayer portion of the cell membrane. The recent recognition that drug uptake is mostly carrier-mediated raises the question of which drugs use which carriers. Results To answer this, we have constructed a chemical genomics platform built upon the yeast gene deletion collection, using competition experiments in batch fermenters and robotic automation of cytotoxicity screens, including protection by 'natural' substrates. Using these, we tested 26 different drugs and identified the carriers required for 18 of the drugs to gain entry into yeast cells. Conclusions As well as providing a useful platform technology, these results further substantiate the notion that the cellular uptake of pharmaceutical drugs normally occurs via carrier-mediated transport and indicates that establishing the identity and tissue distribution of such carriers should be a major consideration in the design of safe and effective drugs. PMID:22023736

  8. Meta-analysis of expression of hepatic organic anion-transporting polypeptide (OATP) transporters in cellular systems relative to human liver tissue.

    PubMed

    Badée, Justine; Achour, Brahim; Rostami-Hodjegan, Amin; Galetin, Aleksandra

    2015-04-01

    Organic anion-transporting polypeptide (OATP)1B1, OATP1B3, and OATP2B1 transporters play an important role in hepatic drug disposition. Recently, an increasing number of studies have reported proteomic expression data for OATP transporters. However, systematic analysis and understanding of the actual differences in OATP expression between liver tissue and commonly used cellular systems is lacking. In the current study, meta-analysis was performed to assess the protein expression of OATP transporters reported in hepatocytes relative to liver tissue and to identify any potential correlations in transporter expression levels in the same individual. OATP1B1 was identified as the most abundant uptake transporter at 5.9 ± 8.3, 5.8 ± 3.3, and 4.2 ± 1.7 fmol/μg protein in liver tissue, sandwich-cultured human hepatocytes (SCHH), and cryopreserved suspended hepatocytes, respectively. The rank order in average expression in liver tissue and cellular systems was OATP1B1 > OATP1B3 ≈ OATP2B1. Abundance levels of the OATP transporters investigated were not significantly different between liver and cellular systems, with the exception of OATP2B1 expression in SCHH relative to liver tissue. Analysis of OATP1B1, OATP1B3, and OATP2B1 liver expression data in the same individuals (n = 86) identified weak (OATP1B1-OATP2B1) to moderately (OATP1B3-OATP2B1) significant correlations. A significant weak correlation was noted between OATP1B1 abundance and age of human donors, whereas expression of the OATPs investigated was independent of sex. Implications of the current analysis on the in vitro-in vivo extrapolation of transporter-mediated drug disposition using physiologically based pharmacokinetic models are discussed.

  9. Pharmacokinetics of amoxicillin and flucloxacillin following the simultaneous intravenous administration of 4 g and 1 g, respectively.

    PubMed

    Adam, D; Koeppe, P; Heilmann, H D

    1983-01-01

    The combination of amoxicillin and flucloxacillin not only widens the spectrum of pathogenic organisms covered by either of the substances alone; synergy has also been observed, particularly against beta-lactamase-producing organisms. For this reason, the possible interaction of these two penicillins regarding their pharmacokinetics was investigated with respect to therapeutic application. The parameters were calculated on the basis of an open two-compartment model. The highest serum levels of amoxicillin from 551 to 1074 mg/l when 4 g were administered alone, and from 403 to 1133 mg/l when administered together with 1 g flucloxacillin. Flucloxacillin concentrations ranged from 118 to 357 mg/l when administered alone, and from 151 to 226 mg/l in the presence of amoxicillin. Thus, there is no significant difference in the peak levels of either substance when given alone or in combination. The pharmacokinetic parameters of both substances basically do not depend on the presence of the other. A slight decrease was observed in the distribution rate of amoxicillin from the central to the peripheral compartment in the presence of flucloxacillin. Its relevance is questionable, however, since the effect was only minor.

  10. Leber's hereditary optic neuropathy is associated with the mitochondrial ND4 G11696A mutation in five Chinese families

    SciTech Connect

    Zhou Xiangtian |; Wei Qiping; Yang Li; Tong Yi |; Zhao Fuxin; Lu Chunjie; Qian Yaping; Sun Yanghong; Lu Fan; Qu Jia |. E-mail: jqu@wzmc.net; Guan Minxin ||. E-mail: min-xin.guan@cchmc.org

    2006-02-03

    We report here the clinical, genetic, and molecular characterization of five Chinese families with Leber's hereditary optic neuropathy (LHON). Clinical and genetic evaluations revealed the variable severity and age-of-onset in visual impairment in these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the distinct sets of mtDNA polymorphism, in addition to the identical ND4 G11696A mutation associated with LHON. Indeed, this mutation is present in homoplasmy only in the maternal lineage of those pedigrees but not other members of these families. In fact, the occurrence of the G11696A mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. Furthermore, the N405D in the ND5 and G5820A in the tRNA{sup Cys}, showing high evolutional conservation, may contribute to the phenotypic expression of G11696A mutation in the WZ10 pedigree. However, there was the absence of functionally significant mtDNA mutations in other four Chinese pedigrees carrying the G11696A mutation. Therefore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic expression of the LHON-associated G11696A mutation in these Chinese pedigrees.

  11. GRAND DESIGN AND FLOCCULENT SPIRALS IN THE SPITZER SURVEY OF STELLAR STRUCTURE IN GALAXIES (S{sup 4}G)

    SciTech Connect

    Elmegreen, Debra Meloy; Yau, Andrew; Elmegreen, Bruce G.; Athanassoula, E.; Bosma, Albert; Helou, George; Sheth, Kartik; Ho, Luis C.; Madore, Barry F.; Menendez-Delmestre, KarIn; Gadotti, Dimitri A.; Knapen, Johan H.; Laurikainen, Eija; Salo, Heikki; Meidt, Sharon E.; Regan, Michael W.; Zaritsky, Dennis; Aravena, Manuel

    2011-08-10

    Spiral arm properties of 46 galaxies in the Spitzer Survey of Stellar Structure in Galaxies (S{sup 4}G) were measured at 3.6 {mu}m, where extinction is small and the old stars dominate. The sample includes flocculent, multiple arm, and grand design types with a wide range of Hubble and bar types. We find that most optically flocculent galaxies are also flocculent in the mid-IR because of star formation uncorrelated with stellar density waves, whereas multiple arm and grand design galaxies have underlying stellar waves. Arm-interarm contrasts increase from flocculent to multiple arm to grand design galaxies and with later Hubble types. Structure can be traced further out in the disk than in previous surveys. Some spirals peak at mid-radius while others continuously rise or fall, depending on Hubble and bar type. We find evidence for regular and symmetric modulations of the arm strength in NGC 4321. Bars tend to be long, high amplitude, and flat-profiled in early-type spirals, with arm contrasts that decrease with radius beyond the end of the bar, and they tend to be short, low amplitude, and exponential-profiled in late Hubble types, with arm contrasts that are constant or increase with radius. Longer bars tend to have larger amplitudes and stronger arms.

  12. Gender-dependent cellular and biochemical effects of maternal deprivation on the hippocampus of neonatal rats: a possible role for the endocannabinoid system.

    PubMed

    Llorente, Ricardo; Llorente-Berzal, Alvaro; Petrosino, Stefania; Marco, Eva-María; Guaza, Carmen; Prada, Carmen; López-Gallardo, Meritxell; Di Marzo, Vincenzo; Viveros, María-Paz

    2008-09-15

    Adult animals submitted to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal days (PND) 9-10] show behavioral alterations that resemble specific symptoms of schizophrenia. These behavioral impairments may be related to neuronal loss in the hippocampus triggered by elevated glucocorticoids. Furthermore, our previous data suggested functional relationships between MD stress and the endocannabinoid system. In this study, we addressed the effects of MD on hippocampal glial cells and the possible relationship with changes in plasma corticosterone (CORT) levels. In addition, we investigated the putative involvement of the endocannabinoid system by evaluating (a) the effects of MD on hippocampal levels of endocannabinoids (b) The modulation of MD effects by two inhibitors of endocannabinoids inactivation, the fatty acid amide hydrolase inhibitor N-arachidonoyl-serotonin (AA-5-HT), and the endocannabinoid reuptake inhibitor, OMDM-2. Drug treatments were administered once daily from PND 7 to PND 12 at a dose of 5 mg/kg, and the animals were sacrificed at PND 13. MD induced increased CORT levels in both genders. MD males also showed an increased number of astrocytes in CA1 and CA3 areas and a significant increase in hippocampal 2-arachidonoylglycerol. The cannabinoid compounds reversed the endocrine and cellular effects of maternal deprivation. We provide direct evidence for gender-dependent cellular and biochemical effects of MD on developmental hippocampus, including changes in the endocannabinoid system.

  13. Healthy aging: regulation of the metabolome by cellular redox modulation and prooxidant signaling systems: the essential roles of superoxide anion and hydrogen peroxide.

    PubMed

    Linnane, Anthony William; Kios, Michael; Vitetta, Luis

    2007-10-01

    The production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) has long been proposed as leading to random deleterious modification of macromolecules with an associated progressive development of age associated systemic disease. ROS and RNS formation has been posited as a major contributor to the aging process. On the contrary, this review presents evidence that superoxide anion (and hydrogen peroxide) and nitric oxide (and peroxynitrite) constitute regulated prooxidant second messenger systems, with specific sub-cellular locales of production and are essential for normal metabolome and physiological function. The role of these second messengers in the regulation of the metabolome is discussed in terms of radical formation as an essential contributor to the physiologically normal regulation of sub-cellular bioenergy systems; proteolysis regulation; transcription activation; enzyme activation; mitochondrial DNA changes; redox regulation of metabolism and cell differentiation; the concept that orally administered small molecule antioxidant therapy is a chimera. The formation of superoxide anion/hydrogen peroxide and nitric oxide do not conditionally lead to random macromolecular damage; under normal physiological conditions their production is actually regulated consistent with their second messenger roles.

  14. The Role of Dynamics and Allostery in the Inhibition of the eIF4E/eIF4G Translation Initiation Factor Complex

    PubMed Central

    Papadopoulos, Evangelos; Blackledge, Martin

    2016-01-01

    Lack of regulation of the eIF4E/eIF4G interaction is a hallmark of cancer. 4EGI-1 binds to eIF4E preventing association to eIF4G via an allosteric mechanism. We use NMR spectroscopy and MD simulations to obtain a mechanistic description of the role of correlated dynamics in this allosteric regulation. We show that binding of 4EGI-1 perturbs native correlated motions and increases correlated fluctuations in part of the eIF4G binding site. PMID:27162083

  15. Influence of drought stress on cellular ultrastructure and antioxidant system in tea cultivars with different drought sensitivities.

    PubMed

    Das, Akan; Mukhopadhyay, Mainaak; Sarkar, Bipasa; Saha, Dipanwita; Mondal, Tapan K

    2015-07-01

    Drought is the major yield-limiting abiotic factor of tea cultivation. In the present study, influence of drought stress on cellular ultrastructure and antioxidants was studied drought-tolerant (TV-23) and -sensitive (S.3/A3) tea cultivars by imposing drought stress for 21 days. Drought stress led to considerable structural alterations in mitochondria, chloroplast and vacuole. Lesser membrane integrity and higher structural damage was observed in S.3/A3. Chlorophyll a, chl-b and carotenoids content in leaves decreased in each cultivar; however, the decrement was more brisk in S.3/A3. Proline, total soluble sugar, ascorbic acid and abscisic acid were elevated in TV-23 whereas hydrogen peroxide, superoxide anion, lipid peroxidation and electrolyte leakage increased rapidly in S.3/A3. Starch content decreased both in leaves and roots of each cultivar and was more pronounced in roots of TV-23. Under drought, enhanced activities of ascorbate peroxidase, catalase, peroxidase and superoxide dismutase were recorded in both roots and leaves of each cultivar, but the rate of enhancement was more in TV-23. This indicated that tolerant cultivar exhibited higher antioxidant capacity and a stronger protective mechanism such that their ultrastructural integrity was better maintained during exposure to drought stress. PMID:26364464

  16. Cellular mechanics and motility

    NASA Astrophysics Data System (ADS)

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

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

  17. Cellular Phone Towers

    MedlinePlus

    ... the call. How are people exposed to the energy from cellular phone towers? As people use cell ... where people can be exposed to them. The energy from a cellular phone tower antenna, like that ...

  18. LmCYP4G102: An oenocyte-specific cytochrome P450 gene required for cuticular waterproofing in the migratory locust, Locusta migratoria.

    PubMed

    Yu, Zhitao; Zhang, Xueyao; Wang, Yiwen; Moussian, Bernard; Zhu, Kun Yan; Li, Sheng; Ma, Enbo; Zhang, Jianzhen

    2016-01-01

    Cytochrome P450 superfamily proteins play important roles in detoxification of xenobiotics and during physiological and developmental processes. To contribute to our understanding of this large gene family in insects, we have investigated the function of the cytochrome P450 gene LmCYP4G102 in the migratory locust Locusta migratoria. Suppression of LmCYP4G102 expression by RNA interference (RNAi) does not interfere with moulting but causes rapid loss of body weight - probably due to massive loss of water, and death soon after moulting. Accordingly, maintaining these animals at 90% relative humidity prevented lethality. Consistently, RNAi against LmCYP4G102 provoked a decrease in the content of cuticular alkanes, which as an important fraction of cuticular hydrocarbons have been shown to confer desiccation resistance. In addition, the cuticle of LmCYP4G102-knockdown locusts was fragile and easier deformable than in control animals. Presumably, this phenotype is due to decreased amounts of cuticular water that is reported to modulate cuticle mechanics. Interestingly, LmCYP4G102 was not expressed in the epidermis that produces the cuticle but in the sub-epdiermal hepatocyte-like oenocytes. Together, our results suggest that the oenocyte-specific LmCYP4G102 plays a critical role in the synthesis of cuticular hydrocarbons, which are important for cuticle waterproofing and mechanical stability in L. migratoria. PMID:27444410

  19. LmCYP4G102: An oenocyte-specific cytochrome P450 gene required for cuticular waterproofing in the migratory locust, Locusta migratoria

    PubMed Central

    Yu, Zhitao; Zhang, Xueyao; Wang, Yiwen; Moussian, Bernard; Zhu, Kun Yan; Li, Sheng; Ma, Enbo; Zhang, Jianzhen

    2016-01-01

    Cytochrome P450 superfamily proteins play important roles in detoxification of xenobiotics and during physiological and developmental processes. To contribute to our understanding of this large gene family in insects, we have investigated the function of the cytochrome P450 gene LmCYP4G102 in the migratory locust Locusta migratoria. Suppression of LmCYP4G102 expression by RNA interference (RNAi) does not interfere with moulting but causes rapid loss of body weight - probably due to massive loss of water, and death soon after moulting. Accordingly, maintaining these animals at 90% relative humidity prevented lethality. Consistently, RNAi against LmCYP4G102 provoked a decrease in the content of cuticular alkanes, which as an important fraction of cuticular hydrocarbons have been shown to confer desiccation resistance. In addition, the cuticle of LmCYP4G102-knockdown locusts was fragile and easier deformable than in control animals. Presumably, this phenotype is due to decreased amounts of cuticular water that is reported to modulate cuticle mechanics. Interestingly, LmCYP4G102 was not expressed in the epidermis that produces the cuticle but in the sub-epdiermal hepatocyte-like oenocytes. Together, our results suggest that the oenocyte-specific LmCYP4G102 plays a critical role in the synthesis of cuticular hydrocarbons, which are important for cuticle waterproofing and mechanical stability in L. migratoria PMID:27444410

  20. Cellular stress response, redox status, and vitagenes in glaucoma: a systemic oxidant disorder linked to Alzheimer’s disease

    PubMed Central

    Trovato Salinaro, Angela; Cornelius, Carolin; Koverech, Guido; Koverech, Angela; Scuto, Maria; Lodato, Francesca; Fronte, Vincenzo; Muccilli, Vera; Reibaldi, Michele; Longo, Antonio; Uva, Maurizio G.; Calabrese, Vittorio

    2014-01-01

    Amyloid deposits, constituted of amyloid beta (Aβ) aggregates, are a characteristic feature of several neurodegenerative diseases, such as Alzheimer’s, mild cognitive impairment and Parkinson’s disease. They also have been recently implicated in the pathogenesis of retinal damage, as well as age-related macular degeneration and glaucoma. Glaucoma is a progressive optic neuropathy characterized by gradual degeneration of neuronal tissue due to retinal ganglion cell loss, associated to visual field loss over time resulting in irreversible blindness. Accumulation of Aβ characterizes glaucoma as a protein misfolding disease, suggesting a pathogenic role for oxidative stress in the pathogenesis of retinal degenerative damage associated to glaucoma. There is a growing body of evidence demonstrating a link between Alzheimer’s disease and glaucoma. Further, several heat shock proteins (HSPs) members have been implicated both in neurodegenerative diseases and glaucomatous apoptosis. To maintain redox homeostasis vitagenes, as integrated mechanisms, operate actively to preserve cell survival under condition of stress. Vitagenes encode for sirtuin, thioredoxin and HSPs. The present study was designed to investigate cellular stress response mechanisms in the blood of patients with glaucoma, compared to control subjects. Levels of vitagenes HSP-72, heme oxygenase-1, as well as F2-isoprostanes were significantly higher in the blood of patients with glaucoma than in controls. Furthermore, in the same experimental group increased expression of Trx and sirtuin 1 were measured. Our results sustain the importance of redox homeostasis disruption in the pathogenesis of glaucoma and highlights the opportunity that new therapies that prevents neurodegeneration through non-immunomodulatory mechanisms might be synergistically associated with current glaucoma therapies, thus unraveling important targets for novel cytoprotective strategies. PMID:24936186

  1. Perinatal Exposure to a Low Dose of Bisphenol A Impaired Systemic Cellular Immune Response and Predisposes Young Rats to Intestinal Parasitic Infection

    PubMed Central

    Ménard, Sandrine; Guzylack-Piriou, Laurence; Lencina, Corinne; Leveque, Mathilde; Naturel, Manon; Sekkal, Soraya; Harkat, Cherryl; Gaultier, Eric; Olier, Maïwenn; Garcia-Villar, Raphael; Theodorou, Vassilia; Houdeau, Eric

    2014-01-01

    Perinatal exposure to the food contaminant bisphenol A (BPA) in rats induces long lasting adverse effects on intestinal immune homeostasis. This study was aimed at examining the immune response to dietary antigens and the clearance of parasites in young rats at the end of perinatal exposure to a low dose of BPA. Female rats were fed with BPA [5 µg/kg of body weight/day] or vehicle from gestational day 15 to pup weaning. Juvenile female offspring (day (D)25) were used to analyze immune cell populations, humoral and cellular responses after oral tolerance or immunization protocol to ovalbumin (OVA), and susceptibility to infection by the intestinal nematode Nippostrongylus brasiliensis (N. brasiliensis). Anti-OVA IgG titers following either oral tolerance or immunization were not affected after BPA perinatal exposure, while a sharp decrease in OVA-induced IFNγ secretion occurred in spleen and mesenteric lymph nodes (MLN) of OVA-immunized rats. These results are consistent with a decreased number of helper T cells, regulatory T cells and dendritic cells in spleen and MLN of BPA-exposed rats. The lack of cellular response to antigens questioned the ability of BPA-exposed rats to clear intestinal infections. A 1.5-fold increase in N. brasiliensis living larvae was observed in the intestine of BPA-exposed rats compared to controls due to an inappropriate Th1/Th2 cytokine production in infected jejunal tissues. These results show that perinatal BPA exposure impairs cellular response to food antigens, and increases susceptibility to intestinal parasitic infection in the juveniles. This emphasized the maturing immune system during perinatal period highly sensitive to low dose exposure to BPA, altering innate and adaptative immune response capacities in early life. PMID:25415191

  2. Hierarchical cellular materials

    SciTech Connect

    Gibson, L.J.

    1991-12-31

    In this paper a method for estimating the contributions of both the composite and the cellular microstructures to the overall material properties and the mechanical efficiency of natural cellular solids will be described. The method will be demonstrated by focusing on the Young`s modulus; similar techniques can be used for other material properties. The results suggest efficient microstructures for engineered cellular materials.

  3. Hierarchical cellular materials

    SciTech Connect

    Gibson, L.J.

    1991-01-01

    In this paper a method for estimating the contributions of both the composite and the cellular microstructures to the overall material properties and the mechanical efficiency of natural cellular solids will be described. The method will be demonstrated by focusing on the Young's modulus; similar techniques can be used for other material properties. The results suggest efficient microstructures for engineered cellular materials.

  4. Adaptive stochastic cellular automata: Applications

    NASA Astrophysics Data System (ADS)

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

    1990-09-01

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

  5. Synthesis of Rigidified eIF4E/eIF4G Inhibitor-1 (4EGI-1) Mimetic and Their in Vitro Characterization as Inhibitors of Protein–Protein Interaction

    PubMed Central

    2015-01-01

    The 4EGI-1 is the prototypic inhibitor of eIF4E/eIF4G interaction, a potent inhibitor of translation initiation in vitro and in vivo and an efficacious anticancer agent in animal models of human cancers. We report on the design, synthesis, and in vitro characterization of a series of rigidified mimetic of this prototypic inhibitor in which the phenyl in the 2-(4-(3,4-dichlorophenyl)thiazol-2-yl) moiety was bridged into a tricyclic system. The bridge consisted one of the following: ethylene, methylene oxide, methylenesulfide, methylenesulfoxide, and methylenesulfone. Numerous analogues in this series were found to be markedly more potent than the parent prototypic inhibitor in the inhibition of eIF4E/eIF4G interaction, thus preventing the eIF4F complex formation, a rate limiting step in the translation initiation cascade in eukaryotes, and in inhibition of human cancer cell proliferation. PMID:24827861

  6. From cells to embryos: the application of femtosecond laser pulses for altering cellular material in complex biological systems

    NASA Astrophysics Data System (ADS)

    Kohli, V.; Elezzabi, A. Y.

    2008-02-01

    We report the application of high-intensity femtosecond laser pulses as a novel tool for manipulating biological specimens. When femtosecond laser pulses were focused to a near diffraction-limited focal spot, cellular material within the laser focal volume was surgically ablated. Several dissection cuts were made in the membrane of live mammalian cells, and membrane surgery was accomplished without inducing cell collapse or disassociation. By altering how the laser pulses were applied, focal adhesions joining live epithelial cells were surgically removed, resulting in single cell isolation. To further examine the versatility of this reported tool, cells were transiently permeabilized for introducing foreign material into the cytoplasm of live mammalian cells. Localizing focused femtosecond laser pulses on the biological membrane resulted in the formation of transient pores, which were harnessed as a pathway for the delivery of exogenous material. Individual mammalian cells were permeabilized in the presence of a hyperosmotic cryoprotective disaccharide. Material delivery was confirmed by measuring the volumetric response of cells permeabilized in 0.2, 0.3, 0.4 and 0.5 M cryoprotective sugar. The survival of permeabilized cells in increasing osmolarity of sugar was assessed using a membrane integrity assay. Further demonstrating the novelty of this reported tool, laser surgery of an aquatic embryo, the zebrafish (Danio rerio), was also performed. Utilizing the transient pores that were formed in the embryonic cells of the zebrafish embryo, an exogenous fluorescent probe FITC, Streptavidin-conjugated quantum dots or plasmid DNA (sCMV) encoding EGFP was introduced into the developing embryonic cells. To determine if the laser induced any short- or long-term effects on development, laser-manipulated embryos were reared to 2 and 7 days post-fertilization and compared to control embryos at the same developmental stages. Light microscopy and scanning electron microscopy

  7. Application of AirCell Cellular AMPS Network and Iridium Satellite System Dual Mode Service to Air Traffic Management

    NASA Technical Reports Server (NTRS)

    Shamma, Mohammed A.

    2004-01-01

    The AirCell/Iridium dual mode service is evaluated for potential applications to Air Traffic Management (ATM) communication needs. The AirCell system which is largely based on the Advanced Mobile Phone System (AMPS) technology, and the Iridium FDMA/TDMA system largely based on the Global System for Mobile Communications(GSM) technology, can both provide communication relief for existing or future aeronautical communication links. Both have a potential to serve as experimental platforms for future technologies via a cost effective approach. The two systems are well established in the entire CONUS and globally hence making it feasible to utilize in all regions, for all altitudes, and all classes of aircraft. Both systems have been certified for air usage. The paper summarizes the specifications of the AirCell/Iridium system, as well as the ATM current and future links, and application specifications. the paper highlights the scenarios, applications, and conditions under which the AirCell/Iridium technology can be suited for ATM Communication.

  8. Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1

    PubMed Central

    Sekiyama, Naotaka; Arthanari, Haribabu; Papadopoulos, Evangelos; Rodriguez-Mias, Ricard A.; Wagner, Gerhard; Léger-Abraham, Mélissa

    2015-01-01

    The eIF4E-binding protein (4E-BP) is a phosphorylation-dependent regulator of protein synthesis. The nonphosphorylated or minimally phosphorylated form binds translation initiation factor 4E (eIF4E), preventing binding of eIF4G and the recruitment of the small ribosomal subunit. Signaling events stimulate serial phosphorylation of 4E-BP, primarily by mammalian target of rapamycin complex 1 (mTORC1) at residues T37/T46, followed by T70 and S65. Hyperphosphorylated 4E-BP dissociates from eIF4E, allowing eIF4E to interact with eIF4G and translation initiation to resume. Because overexpression of eIF4E is linked to cellular transformation, 4E-BP is a tumor suppressor, and up-regulation of its activity is a goal of interest for cancer therapy. A recently discovered small molecule, eIF4E/eIF4G interaction inhibitor 1 (4EGI-1), disrupts the eIF4E/eIF4G interaction and promotes binding of 4E-BP1 to eIF4E. Structures of 14- to 16-residue 4E-BP fragments bound to eIF4E contain the eIF4E consensus binding motif, 54YXXXXLΦ60 (motif 1) but lack known phosphorylation sites. We report here a 2.1-Å crystal structure of mouse eIF4E in complex with m7GTP and with a fragment of human 4E-BP1, extended C-terminally from the consensus-binding motif (4E-BP150–84). The extension, which includes a proline-turn-helix segment (motif 2) followed by a loop of irregular structure, reveals the location of two phosphorylation sites (S65 and T70). Our major finding is that the C-terminal extension (motif 3) is critical to 4E-BP1–mediated cell cycle arrest and that it partially overlaps with the binding site of 4EGI-1. The binding of 4E-BP1 and 4EGI-1 to eIF4E is therefore not mutually exclusive, and both ligands contribute to shift the equilibrium toward the inhibition of translation initiation. PMID:26170285

  9. Enhanced visible-light photocatalytic decomposition of 2,4-dichlorophenoxyacetic acid over ZnIn2S4/g-C3N4 photocatalyst.

    PubMed

    Qiu, Pengxiang; Yao, Jinhua; Chen, Huan; Jiang, Fang; Xie, Xianchuan

    2016-11-01

    ZnIn2S4/g-C3N4 heterojunction photocatalyst was successfully synthesized via a simple hydrothermal method and applied to visible-light photocatalytic decomposition of 2,4-dichlorophenoxyacetic acid (2,4-D) from aqueous phase. The flower-like ZnIn2S4 particles were dispersed on the surface of g-C3N4 nanosheets in the ZnIn2S4/g-C3N4 composite. The composite showed higher separation rate of electron-hole pairs as compared to ZnIn2S4 and g-C3N4. Consequently, the ZnIn2S4/g-C3N4 composite exhibited enhanced visible light photocatalytic decomposition efficiency of 2,4-D, within 20% ZnIn2S4/g-C3N4 composite owning the highest photocatalytic efficiency and initial rate. The initial rates of 2,4-D degradation on g-C3N4, ZnIn2S4, and 20% ZnIn2S4/g-C3N4 were 1.23, 0.57 and 3.69mmol/(gcath), respectively. The h(+) and O2(-) were found to be the dominant active species for 2,4-D decomposition. The photocatalytic degradation pathways of 2,4-D by ZnIn2S4/g-C3N4 under visible light irradiation were explored. The ZnIn2S4/g-C3N4 composite displayed high photostability in recycling tests, reflecting its promising potential as an effective visible light photocatalyst for 2,4-D treatment.

  10. Enhanced visible-light photocatalytic decomposition of 2,4-dichlorophenoxyacetic acid over ZnIn2S4/g-C3N4 photocatalyst.

    PubMed

    Qiu, Pengxiang; Yao, Jinhua; Chen, Huan; Jiang, Fang; Xie, Xianchuan

    2016-11-01

    ZnIn2S4/g-C3N4 heterojunction photocatalyst was successfully synthesized via a simple hydrothermal method and applied to visible-light photocatalytic decomposition of 2,4-dichlorophenoxyacetic acid (2,4-D) from aqueous phase. The flower-like ZnIn2S4 particles were dispersed on the surface of g-C3N4 nanosheets in the ZnIn2S4/g-C3N4 composite. The composite showed higher separation rate of electron-hole pairs as compared to ZnIn2S4 and g-C3N4. Consequently, the ZnIn2S4/g-C3N4 composite exhibited enhanced visible light photocatalytic decomposition efficiency of 2,4-D, within 20% ZnIn2S4/g-C3N4 composite owning the highest photocatalytic efficiency and initial rate. The initial rates of 2,4-D degradation on g-C3N4, ZnIn2S4, and 20% ZnIn2S4/g-C3N4 were 1.23, 0.57 and 3.69mmol/(gcath), respectively. The h(+) and O2(-) were found to be the dominant active species for 2,4-D decomposition. The photocatalytic degradation pathways of 2,4-D by ZnIn2S4/g-C3N4 under visible light irradiation were explored. The ZnIn2S4/g-C3N4 composite displayed high photostability in recycling tests, reflecting its promising potential as an effective visible light photocatalyst for 2,4-D treatment. PMID:27267690

  11. Yeast eukaryotic initiation factor 4B (eIF4B) enhances complex assembly between eIF4A and eIF4G in vivo.

    PubMed

    Park, Eun-Hee; Walker, Sarah E; Zhou, Fujun; Lee, Joseph M; Rajagopal, Vaishnavi; Lorsch, Jon R; Hinnebusch, Alan G

    2013-01-25

    Translation initiation factor eIF4F (eukaryotic initiation factor 4F), composed of eIF4E, eIF4G, and eIF4A, binds to the m(7)G cap structure of mRNA and stimulates recruitment of the 43S preinitiation complex and subsequent scanning to the initiation codon. The HEAT domain of eIF4G stabilizes the active conformation of eIF4A required for its RNA helicase activity. Mammalian eIF4B also stimulates eIF4A activity, but this function appears to be lacking in yeast, making it unclear how yeast eIF4B (yeIF4B/Tif3) stimulates translation. We identified Ts(-) mutations in the HEAT domains of yeast eIF4G1 and eIF4G2 that are suppressed by overexpressing either yeIF4B or eIF4A, whereas others are suppressed only by eIF4A overexpression. Importantly, suppression of HEAT domain substitutions by yeIF4B overexpression was correlated with the restoration of native eIF4A·eIF4G complexes in vivo, and the rescue of specific mutant eIF4A·eIF4G complexes by yeIF4B was reconstituted in vitro. Association of eIF4A with WT eIF4G in vivo also was enhanced by yeIF4B overexpression and was impaired in cells lacking yeIF4B. Furthermore, we detected native complexes containing eIF4G and yeIF4B but lacking eIF4A. These and other findings lead us to propose that yeIF4B acts in vivo to promote eIF4F assembly by enhancing a conformation of the HEAT domain of yeast eIF4G conducive for stable binding to eIF4A.

  12. A Conserved Interaction between a C-Terminal Motif in Norovirus VPg and the HEAT-1 Domain of eIF4G Is Essential for Translation Initiation.

    PubMed

    Leen, Eoin N; Sorgeloos, Frédéric; Correia, Samantha; Chaudhry, Yasmin; Cannac, Fabien; Pastore, Chiara; Xu, Yingqi; Graham, Stephen C; Matthews, Stephen J; Goodfellow, Ian G; Curry, Stephen

    2016-01-01

    Translation initiation is a critical early step in the replication cycle of the positive-sense, single-stranded RNA genome of noroviruses, a major cause of gastroenteritis in humans. Norovirus RNA, which has neither a 5´ m7G cap nor an internal ribosome entry site (IRES), adopts an unusual mechanism to initiate protein synthesis that relies on interactions between the VPg protein covalently attached to the 5´-end of the viral RNA and eukaryotic initiation factors (eIFs) in the host cell. For murine norovirus (MNV) we previously showed that VPg binds to the middle fragment of eIF4G (4GM; residues 652-1132). Here we have used pull-down assays, fluorescence anisotropy, and isothermal titration calorimetry (ITC) to demonstrate that a stretch of ~20 amino acids at the C terminus of MNV VPg mediates direct and specific binding to the HEAT-1 domain within the 4GM fragment of eIF4G. Our analysis further reveals that the MNV C terminus binds to eIF4G HEAT-1 via a motif that is conserved in all known noroviruses. Fine mutagenic mapping suggests that the MNV VPg C terminus may interact with eIF4G in a helical conformation. NMR spectroscopy was used to define the VPg binding site on eIF4G HEAT-1, which was confirmed by mutagenesis and binding assays. We have found that this site is non-overlapping with the binding site for eIF4A on eIF4G HEAT-1 by demonstrating that norovirus VPg can form ternary VPg-eIF4G-eIF4A complexes. The functional significance of the VPg-eIF4G interaction was shown by the ability of fusion proteins containing the C-terminal peptide of MNV VPg to inhibit in vitro translation of norovirus RNA but not cap- or IRES-dependent translation. These observations define important structural details of a functional interaction between norovirus VPg and eIF4G and reveal a binding interface that might be exploited as a target for antiviral therapy.

  13. A Conserved Interaction between a C-Terminal Motif in Norovirus VPg and the HEAT-1 Domain of eIF4G Is Essential for Translation Initiation

    PubMed Central

    Leen, Eoin N.; Sorgeloos, Frédéric; Correia, Samantha; Chaudhry, Yasmin; Cannac, Fabien; Pastore, Chiara; Xu, Yingqi; Graham, Stephen C.; Matthews, Stephen J.; Goodfellow, Ian G.; Curry, Stephen

    2016-01-01

    Translation initiation is a critical early step in the replication cycle of the positive-sense, single-stranded RNA genome of noroviruses, a major cause of gastroenteritis in humans. Norovirus RNA, which has neither a 5´ m7G cap nor an internal ribosome entry site (IRES), adopts an unusual mechanism to initiate protein synthesis that relies on interactions between the VPg protein covalently attached to the 5´-end of the viral RNA and eukaryotic initiation factors (eIFs) in the host cell. For murine norovirus (MNV) we previously showed that VPg binds to the middle fragment of eIF4G (4GM; residues 652–1132). Here we have used pull-down assays, fluorescence anisotropy, and isothermal titration calorimetry (ITC) to demonstrate that a stretch of ~20 amino acids at the C terminus of MNV VPg mediates direct and specific binding to the HEAT-1 domain within the 4GM fragment of eIF4G. Our analysis further reveals that the MNV C terminus binds to eIF4G HEAT-1 via a motif that is conserved in all known noroviruses. Fine mutagenic mapping suggests that the MNV VPg C terminus may interact with eIF4G in a helical conformation. NMR spectroscopy was used to define the VPg binding site on eIF4G HEAT-1, which was confirmed by mutagenesis and binding assays. We have found that this site is non-overlapping with the binding site for eIF4A on eIF4G HEAT-1 by demonstrating that norovirus VPg can form ternary VPg-eIF4G-eIF4A complexes. The functional significance of the VPg-eIF4G interaction was shown by the ability of fusion proteins containing the C-terminal peptide of MNV VPg to inhibit in vitro translation of norovirus RNA but not cap- or IRES-dependent translation. These observations define important structural details of a functional interaction between norovirus VPg and eIF4G and reveal a binding interface that might be exploited as a target for antiviral therapy. PMID:26734730

  14. Human Translation Initiation Factor eIF4G1 Possesses a Low-Affinity ATP Binding Site Facing the ATP-Binding Cleft of eIF4A in the eIF4G/eIF4A Complex

    PubMed Central

    2015-01-01

    Eukaryotic translation initiation factor 4G (eIF4G) plays a crucial role in translation initiation, serving as a scaffolding protein binding several other initiation factors, other proteins, and RNA. Binding of eIF4G to the ATP-dependent RNA helicase eukaryotic translation initiation factor 4A (eIF4A) enhances the activity of eIF4A in solution and in crowded environments. Previously, this activity enhancement was solely attributed to eIF4G, conferring a closed, active conformation upon eIF4A. Here we show that eIF4G contains a low-affinity binding site at the entrance to the ATP-binding cleft on eIF4A, suggesting that regulation of the local ATP concentration may be an additional reason for the enhancement in activity. PMID:25255371

  15. 47 CFR 22.901 - Cellular service requirements and limitations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular service requirements and limitations... SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.901 Cellular service requirements and... operates in compliance with this section. (a) Each cellular system must provide either mobile...

  16. Identification of a porcine DC-SIGN-related C-type lectin, porcine CLEC4G (LSECtin), and its order of intron removal during splicing: comparative genomic analyses of the cluster of genes CD23/CLEC4G/DC-SIGN among mammalian species.

    PubMed

    Huang, Y W; Meng, X J

    2009-06-01

    Human CLEC4G (previously named LSECtin), DC-SIGN, and L-SIGN are three important C-type lectins capable of mediating viral and bacterial pathogen recognitions. These three genes, together with CD23, form a lectin gene cluster at chromosome 19p13.3. In this study, we have experimentally identified the cDNA and the gene encoding porcine CLEC4G (pCLEC4G). Full-length pCLEC4G cDNA encodes a type II transmembrane protein of 290 amino acids. pCLEC4G gene has the same gene structure as the human and the predicted bovine, canis, mouse and rat CLEC4G genes with nine exons. A multi-species-conserved site at the extreme 3'-untranslated region of CLEC4G mRNAs was predicted to be targeted by microRNA miR-350 in domesticated animals and by miR-145 in primates, respectively. We detected pCLEC4G mRNA expression in liver, lymph node and spleen tissues. We also identified a series of sequential intermediate products of pCLEC4G pre-mRNA during splicing from pig liver. The previously unidentified porcine CD23 cDNA containing the complete coding region was subsequently cloned and found to express in spleen, thymus and lymph node. Furthermore, we compared the chromosomal regions syntenic to the human cluster of genes CD23/CLEC4G/DC-SIGN/L-SIGN in representative mammalian species including primates, domesticated animal, rodents and opossum. The L-SIGN homologues do not exist in non-primates mammals. The evolutionary processes of the gene cluster, from marsupials to primates, were proposed based upon their genomic structures and phylogenetic relationships.

  17. Cellular automaton for chimera states

    NASA Astrophysics Data System (ADS)

    García-Morales, Vladimir

    2016-04-01

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

  18. Synthetic biology in cellular immunotherapy

    PubMed Central

    Chakravarti, Deboki; Wong, Wilson W.

    2015-01-01

    The adoptive transfer of genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. This form of cellular immunotherapy presents a unique opportunity to incorporate advanced systems and synthetic biology approaches to create cancer therapeutics with novel functions. Here, we first review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. In addition, we discuss the cellular engineering and genome editing of host cells (or the chassis) to improve the efficacy of cell-based cancer therapeutics, and to reduce the time and cost of manufacturing. PMID:26088008

  19. Cellular senescence in aging primates.

    PubMed

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

    2006-03-01

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

  20. miR-34a Inhibits Proliferation and Invasion of Bladder Cancer Cells by Targeting Orphan Nuclear Receptor HNF4G

    PubMed Central

    Sun, Huaibin; Tian, Jun; Xian, Wanhua; Xie, Tingting; Yang, Xiangdong

    2015-01-01

    miR-34a is a member of the miR-34 family and acts as a tumor suppressor in bladder cancer. This study explored the regulative role of miR-34a on an orphan nuclear receptor HNF4G, which has a well-confirmed role in bladder tumor growth and invasion. qRT-PCR analysis was applied to measure miR-34a expression in two tumorigenic bladder cancer cell lines 5637 and T24 and one normal human urothelial cell line SV-HUC-1. Luciferase assay was performed to verify the putative binding between miR-34a and HNF4G. The influence of miR-34a-HNF4G axis on cell viability, colony formation, and invasion was assessed with loss- and gain-of-function analysis. This study observed that the miR-34a expressions in 5637 and T24 cells were significantly lower than in SV-HUC-1, while the muscle invasive cell sublines 5637-M and T24-M had even lower miR-34a expression than in the nonmuscle invasive sublines. HNF4G has a 3′-UTR binding site with miR-34a and is a direct downstream target of miR-34a. miR-34a can directly downregulate the expression of HNF4G and thus inhibit tumor cell viability, colony formation, and invasion. Therefore, miR-34a-HNF4G axis is an important pathway modulating cell viability, proliferation, and invasion of bladder cancer cells. PMID:25878394

  1. The soy isoflavone equol may increase cancer malignancy via up-regulation of eukaryotic protein synthesis initiation factor eIF4G.

    PubMed

    de la Parra, Columba; Otero-Franqui, Elisa; Martinez-Montemayor, Michelle; Dharmawardhane, Suranganie

    2012-12-01

    Dietary soy is thought to be cancer-preventive; however, the beneficial effects of soy on established breast cancer is controversial. We recently demonstrated that dietary daidzein or combined soy isoflavones (genistein, daidzein, and glycitein) increased primary mammary tumor growth and metastasis. Cancer-promoting molecules, including eukaryotic protein synthesis initiation factors (eIF) eIF4G and eIF4E, were up-regulated in mammary tumors from mice that received dietary daidzein. Herein, we show that increased eIF expression in tumor extracts of mice after daidzein diets is associated with protein expression of mRNAs with internal ribosome entry sites (IRES) that are sensitive to eIF4E and eIF4G levels. Results with metastatic cancer cell lines show that some of the effects of daidzein in vivo can be recapitulated by the daidzein metabolite equol. In vitro, equol, but not daidzein, up-regulated eIF4G without affecting eIF4E or its regulator, 4E-binding protein (4E-BP), levels. Equol also increased metastatic cancer cell viability. Equol specifically increased the protein expression of IRES containing cell survival and proliferation-promoting molecules and up-regulated gene and protein expression of the transcription factor c-Myc. Moreover, equol increased the polysomal association of mRNAs for p 120 catenin and eIF4G. The elevated eIF4G in response to equol was not associated with eIF4E or 4E-binding protein in 5' cap co-capture assays or co-immunoprecipitations. In dual luciferase assays, IRES-dependent protein synthesis was increased by equol. Therefore, up-regulation of eIF4G by equol may result in increased translation of pro-cancer mRNAs with IRESs and, thus, promote cancer malignancy.

  2. miR-34a inhibits proliferation and invasion of bladder cancer cells by targeting orphan nuclear receptor HNF4G.

    PubMed

    Sun, Huaibin; Tian, Jun; Xian, Wanhua; Xie, Tingting; Yang, Xiangdong

    2015-01-01

    miR-34a is a member of the miR-34 family and acts as a tumor suppressor in bladder cancer. This study explored the regulative role of miR-34a on an orphan nuclear receptor HNF4G, which has a well-confirmed role in bladder tumor growth and invasion. qRT-PCR analysis was applied to measure miR-34a expression in two tumorigenic bladder cancer cell lines 5637 and T24 and one normal human urothelial cell line SV-HUC-1. Luciferase assay was performed to verify the putative binding between miR-34a and HNF4G. The influence of miR-34a-HNF4G axis on cell viability, colony formation, and invasion was assessed with loss- and gain-of-function analysis. This study observed that the miR-34a expressions in 5637 and T24 cells were significantly lower than in SV-HUC-1, while the muscle invasive cell sublines 5637-M and T24-M had even lower miR-34a expression than in the nonmuscle invasive sublines. HNF4G has a 3'-UTR binding site with miR-34a and is a direct downstream target of miR-34a. miR-34a can directly downregulate the expression of HNF4G and thus inhibit tumor cell viability, colony formation, and invasion. Therefore, miR-34a-HNF4G axis is an important pathway modulating cell viability, proliferation, and invasion of bladder cancer cells.

  3. Cellular manufacturing for clinical applications.

    PubMed

    Sheu, Jonathan; Klassen, Henry; Bauer, Gerhard

    2014-01-01

    Rapid progress has been made in the development of novel cell-based approaches for the potential treatment of retinal degenerative diseases. As a result, one must consider carefully the conditions under which these therapeutics are manufactured if they are to be used in clinical studies or, ultimately, be approved as licensed cellular therapeutics. Here, we describe the principles behind the manufacturing of clinical-grade cellular products, as well as potential methods for large-scale expansion and processing according to Good Manufacturing Practice (GMP) standards sets by the United States Food and Drug Administration. Standards for personnel, materials, procedures, and facilities required for such manufacturing processes are reviewed. We also discuss current and future scale-up methods for the manufacturing of large doses of cellular therapeutics under GMP conditions and compare the use of conventional culture methods such as tissue culture flasks and multi-layered cell factories with novel systems such as closed system hollow-fiber bioreactors. Incorporation of these novel bioreactor systems into GMP facilities may enable us to provide adequate cell numbers for multi-center clinical trials and paves the way for development of cellular therapeutics with the potential to treat very large numbers of patients.

  4. Effects of Lipids on in Vitro Release and Cellular Uptake of β-Carotene in Nanoemulsion-Based Delivery Systems.

    PubMed

    Yi, Jiang; Zhong, Fang; Zhang, Yuzhu; Yokoyama, Wallace; Zhao, Liqing

    2015-12-23

    β-Carotene (BC) nanoemulsions were successfully prepared by microfluidization. BC micellarization was significantly affected by bile salts and pancreatin concentration. Positive and linear correlation was observed between BC release and bile salts concentration. Pancreatin facilitated BC's release in simulated digestion. Compared to the control (bulk oil) (4.6%), nanoemulsion delivery systems significantly improved the micellarization of BC (70.9%). The amount of BC partitioned into micelles was positively proportional to the length of carrier oils. Unsaturated fatty acid (UFA)-rich oils were better than saturated fatty acid (SFA)-rich oils in transferring BC (p < 0.05). No significant difference was observed between monounsaturated fatty acid (MUFA)-rich oils and polyunsaturated fatty acid (PUFA)-rich oils (p > 0.05). A positive and linear relationship between the degree of lipolysis and the release of BC in vitro digestion was observed. Bile salts showed cytotoxicity to Caco-2 cells below 20 times dilution. BC uptake by Caco-2 cells was not affected by fatty acid (FA) compositions in micelles, but BC uptake was proportional to its concentration in the diluted micelle fraction. The results obtained are beneficial to encapsulate and deliver BC or other bioactive lipophilic carotenoids in a wide range of commercial products. PMID:26629789

  5. Cellular damages in the Allium cepa test system, caused by BTEX mixture prior and after biodegradation process.

    PubMed

    Mazzeo, Dânia Elisa Christofoletti; Fernandes, Thaís Cristina Casimiro; Marin-Morales, Maria Aparecida

    2011-09-01

    Petroleum and derivatives have been considered one of the main environmental contaminants. Among petroleum derivatives, the volatile organic compounds benzene, toluene, ethylbenzene and xylene (BTEX) represent a major concern due to their toxicity and easy accumulation in groundwater. Biodegradation methods seem to be suitable tools for the clean-up of BTEX contaminants from groundwater. Genotoxic and mutagenic potential of BTEX prior and after biodegradation process was evaluated through analyses of chromosomal aberrations and MN test in meristematic and F(1) root cells using the Allium cepa test system. Seeds of A. cepa were germinated into five concentrations of BTEX, non-biodegraded and biodegraded, in ultra-pure water (negative control), in MMS 4×10(-4)M (positive control) and in culture medium used in the biodegradation (blank biodegradation control). Results showed a significant frequency of both chromosomal and nuclear aberrations. The micronucleus (MN) frequency in meristematic cells was significant for most of tested samples. However, MN was not present in significant levels in the F(1) cells, suggesting that there was no permanent damage for the meristematic cell. The BTEX effects were significantly reduced in the biodegraded samples when compared to the respective non-biodegraded concentrations. Therefore, in this study, the biodegradation process showed to be a reliable and effective alternative to treat BTEX-contaminated waters. Based on our results and available data, the BTEX toxicity could also be related to a synergistic effect of its compounds. PMID:21741065

  6. Cellular responses induced in vitro by iron (Fe) in a central nervous system cell line (U343MGa).

    PubMed

    Alcântara, D D F A; Ribeiro, H F; Matos, L A; Sousa, J M C; Burbano, R R; Bahia, M O

    2013-01-01

    Iron is the most important metallic chemical element on Earth. Poisoning caused by excessive iron in humans has been associated with pulmonary diseases including neoplasms caused by inhalation of iron oxides. The involvement of iron in neurodegenerative processes has already been described. DNA alterations are induced by iron and other chemical compounds containing this metal; however, the data are controversial and the mechanism by which iron induces mutagenesis remains unknown. This study assessed in vitro iron-induced cytotoxic and genotoxic responses in an astrocytic cell line. Short- and long-term cytotoxicity and genotoxicity were evaluated with the Cell Proliferation Kit II and micronucleus test, respectively. Results indicated that the highest concentration of iron sulfate tested was cytotoxic in long-term cytotoxic assays and increased micronucleus frequency in comparison to controls. The significant cytotoxicity observed here might be due to the intrinsic ability of iron to induce apoptosis and possible changes in cell cycle kinetics; the genotoxic effects are probably due to the oxidant properties of iron itself. This was the first study to investigate the induction of micronuclei by iron in central nervous system cells. PMID:23765962

  7. Smokeless tobacco consumption impedes metabolic, cellular, apoptotic and systemic stress pattern: A study on Government employees in Kolkata, India

    PubMed Central

    Biswas, Sushobhan; Manna, Krishnendu; Das, Ujjal; Khan, Amitava; Pradhan, Anirban; Sengupta, Aaveri; Bose, Surajit; Ghosh, Saurabh; Dey, Sanjit

    2015-01-01

    Smokeless tobacco (SLT) remains a threat amongst a large population across the globe and particularly in India. The oral use of tobacco has been implicated to cause physiological stress leading to extreme toxicological challenge. The study included 47 SLT-users and 44 non-users providing a spectrum of pathophysiological, clinico-biochemical, antioxidant parameters, cell cycle progression study of PBMC and morphological changes of red blood cells (RBC). The expressions of p53, p21, Bax, Bcl-2, IL-6, TNF- α, Cox-2, iNOS were analyzed from thirteen representative SLT-users and twelve non-users. Difference in CRP, random glucose, serum cholesterol, TG, HLDL-C, LDL-C, VLDL-C, neutrophil count, monocyte count, ESR, SOD (PBMC) and TBARS (RBC membrane) were found to be statistically significant (p < 0.05) between the studied groups. The current study confers crucial insight into SLT mediated effects on systemic toxicity and stress. This has challenged the metabolic condition leading to a rise in the inflammatory status, increased apoptosis and RBC membrane damage. The above findings were substantiated with metabolic, clinical and biochemical parameters. This is possibly the first ever in-depth report and remains an invaluable document on the fatal effects of SLT. PMID:26669667

  8. A comparative systems analysis of polysaccharide-elicited responses in Neurospora crassa reveals carbon source-specific cellular adaptations

    PubMed Central

    Benz, J. Philipp; Chau, Bryant H.; Zheng, Diana; Bauer, Stefan; Glass, N. Louise; Somerville, Chris R.

    2014-01-01

    Summary Filamentous fungi are powerful producers of hydrolytic enzymes for the deconstruction of plant cell wall polysaccharides. However, the central question of how these sugars are perceived in the context of the complex cell wall matrix remains largely elusive. To address this question in a systematic fashion we performed an extensive comparative systems analysis of how the model filamentous fungus Neurospora crassa responds to the three main cell wall polysaccharides: pectin, hemicellulose and cellulose. We found the pectic response to be largely independent of the cellulolytic one with some overlap to hemicellulose, and in its extent surprisingly high, suggesting advantages for the fungus beyond being a mere carbon source. Our approach furthermore allowed us to identify carbon source-specific adaptations, such as the induction of the unfolded protein response on cellulose, and a commonly induced set of 29 genes likely involved in carbon scouting. Moreover, by hierarchical clustering we generated a co-expression matrix useful for the discovery of new components involved in polysaccharide utilization. This is exemplified by the identification of lat-1, which we demonstrate to encode for the physiologically relevant arabinose transporter in Neurospora. The analyses presented here are an important step towards understanding fungal degradation processes of complex biomass. PMID:24224966

  9. Expansion and concatenation of nonmuscle myosin IIA filaments drive cellular contractile system formation during interphase and mitosis

    PubMed Central

    Fenix, Aidan M.; Taneja, Nilay; Buttler, Carmen A.; Lewis, John; Van Engelenburg, Schuyler B.; Ohi, Ryoma; Burnette, Dylan T.

    2016-01-01

    Cell movement and cytokinesis are facilitated by contractile forces generated by the molecular motor, nonmuscle myosin II (NMII). NMII molecules form a filament (NMII-F) through interactions of their C-terminal rod domains, positioning groups of N-terminal motor domains on opposite sides. The NMII motors then bind and pull actin filaments toward the NMII-F, thus driving contraction. Inside of crawling cells, NMIIA-Fs form large macromolecular ensembles (i.e., NMIIA-F stacks), but how this occurs is unknown. Here we show NMIIA-F stacks are formed through two non–mutually exclusive mechanisms: expansion and concatenation. During expansion, NMIIA molecules within the NMIIA-F spread out concurrent with addition of new NMIIA molecules. Concatenation occurs when multiple NMIIA-Fs/NMIIA-F stacks move together and align. We found that NMIIA-F stack formation was regulated by both motor activity and the availability of surrounding actin filaments. Furthermore, our data showed expansion and concatenation also formed the contractile ring in dividing cells. Thus interphase and mitotic cells share similar mechanisms for creating large contractile units, and these are likely to underlie how other myosin II–based contractile systems are assembled. PMID:26960797

  10. Hijacking cellular garbage cans.

    PubMed

    Welsch, Sonja; Locker, Jacomine Krijnse

    2010-06-25

    Viruses are perfect opportunists that have evolved to modify numerous cellular processes in order to complete their replication cycle in the host cell. An article by Reggiori and coworkers in this issue of Cell Host & Microbe reveals how coronaviruses can divert a cellular quality control pathway that normally functions in degradation of mis-folded proteins to replicate the viral genome. PMID:20542246

  11. Dualband microstrip antennas for cellular telephone

    NASA Astrophysics Data System (ADS)

    Wnuk, Marian

    2004-04-01

    Intensive development of cellular personal communications system has been observed lately. Thus, protection of a man, and especially protection of his head against non-ionizing electromagnetic radiation generated by cellular telephones is becoming one of the most important problems. The results of elaborated microstrip antennas which have minimized radiation towards the user's head are presented in this paper.

  12. 3-Substituted Indazoles as Configurationally Locked 4EGI-1 Mimetic and Inhibitors of eIF4E/eIF4G Interaction

    PubMed Central

    Yefidoff-Freedman, Revital; Chen, Ting; Sahoo, Rupam; Chen, Limo; Wagner, Gerhard; Halperin, Jose A.; Aktas, Bertal H.; Chorev, Michael

    2014-01-01

    4EGI-1, the prototypic inhibitor of eIF4E/eIF4G interaction, was identified in a high-throughput screening of small molecule libraries using a fluorescence polarization assay that measures inhibition of binding of an eIF4G-derived peptide to recombinant eIF4E. As such, the molecular probe 4EGI-1 holds a potential for studying molecular mechanisms involved in human disorders characterized by loss of physiologic restrains on translation initiation. A hit-to-lead optimization campaign was carried out to overcome the liability of the configurational instability in 4EGI-1, which stems from the (E)-to-(Z) isomerization of the hydrazone function. We identified compound 1a, in which the labile hydrazone was incorporated into a rigid indazole scaffold as a promising rigidified 4EGI-1 mimetic lead. In a structure-activity relationship study aimed at probing the structural latitude of this new chemotype as an inhibitor of eIF4E/eIF4G interaction and translation initiation we identified 1d, an indazole-based 4EGI-1 mimetic, as a new and improved lead inhibitor of eIF4E/eIF4G interaction and a promising molecular probe candidate for elucidating the role of cap-dependent translation initiation in a host of pathophysiological states. PMID:24458973

  13. 16 CFR 1615.32 - Method for establishment and use of alternate laundering procedures under section 4(g)(4)(ii) of...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...-6X (16 CFR 1615.4(g)(4)(ii)) requires that all fabrics and certain garments subject to the standard... American Association of Textile Chemists and Colorists, P.O. Box 12215, Research Triangle Park, North...(a) and 1 CFR part 51. (2) This rule provides the procedures to be followed by persons...

  14. Chromosomal assignment of six genes (EIF4G3, HSP90, RBBP6, IL8, TERT, and TERC) in four species of the genus Equus.

    PubMed

    Vidale, Pamela; Piras, Francesca M; Nergadze, Solomon G; Bertoni, Livia; Verini-Supplizi, Andrea; Adelson, David; Guérin, Gérard; Giulotto, Elena

    2011-01-01

    We mapped six genes (EIF4G3, HSP90, RBBP6, IL8, TERT, and TERC) on the chromosomes of Equus caballus, Equus asinus, Equus grevyi, and Equus burchelli by fluorescence in situ hybridization. Our results add six type I markers to the cytogenetic map of these species and provide new information on the comparative genomics of the genus Equus.

  15. 16 CFR 1615.32 - Method for establishment and use of alternate laundering procedures under section 4(g)(4)(ii) of...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...-6X (16 CFR 1615.4(g)(4)(ii)) requires that all fabrics and certain garments subject to the standard...: http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. This...(a) and 1 CFR part 51. (2) This rule provides the procedures to be followed by persons...

  16. 78 FR 958 - Certain Wireless Devices With 3G and/or 4G Capabilities and Components Thereof Notice of Receipt...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-07

    ... filed on behalf of InterDigital Communications, Inc., InterDigital Technology Corporation, IPR Licensing.../or 4g capabilities and components thereof. The complaint names as respondents Samsung Electronics Co., Ltd. of Korea; Samsung Electronics America, Inc. of NJ; Samsung Telecommunications America, LLC of...

  17. 16 CFR 1615.32 - Method for establishment and use of alternate laundering procedures under section 4(g)(4)(ii) of...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...-6X (16 CFR 1615.4(g)(4)(ii)) requires that all fabrics and certain garments subject to the standard...(a) and 1 CFR part 51. (2) This rule provides the procedures to be followed by persons seeking... FLAMMABILITY OF CHILDREN'S SLEEPWEAR: SIZES 0 THROUGH 6X (FF 3-71) Rules and Regulations § 1615.32 Method...

  18. Effects of temperature, CO2/O2 concentrations and light intensity on cellular prolification of microalgae, eugrena gracilis, in aquatic food production of bioregenerative life support systems

    NASA Astrophysics Data System (ADS)

    Kitaya, Y.; Azuma, H.; Kiyota, M.

    Microalgae are likely to play an important role in aquatic food production modules in bioregenerative systems for producing feeds for fish, converting CO_2 to O_2 and remedying water quality as well as aquatic higher plants. In the present study, the effects of culture conditions on the cellular proliferation of microalgae, Eugrena gracilis, was investigated to determine the optimum culture conditions for microalgae production in aquatic food production modules including both microalgae culture and fish culture systems. E. gracilis was cultured under conditions with five levels of temperature (25-33°C), three levels of CO_2 concentration (2-6%), four levels of O_2 concentration (10-25%), and three levels of photosynthetic photon flux density (50-120 μmol m-2 s-1). The number of Eugrena cells in a certain volume of solution was monitored with a microscope under each environment. The multiplication rate of the cells was highest at temperatures of 29°C, 4% CO_2, 20% O_2 and 90 μmol m-2 s-1 PPFD. The results demonstrate that E. gracilis could efficiently produce biomass and convert CO_2 to O_2 under relatively low light intensities in aquatic food production modules.

  19. The cellular immune system in myelomagenesis: NK cells and T cells in the development of MM and their uses in immunotherapies

    PubMed Central

    Dosani, T; Carlsten, M; Maric, I; Landgren, O

    2015-01-01

    As vast strides are being made in the management and treatment of multiple myeloma (MM), recent interests are increasingly focusing on understanding the development of the disease. The knowledge that MM develops exclusively from a protracted phase of monoclonal gammopathy of undetermined significance provides an opportunity to study tumor evolution in this process. Although the immune system has been implicated in the development of MM, the scientific literature on the role and status of various immune components in this process is broad and sometimes contradictory. Accordingly, we present a review of cellular immune subsets in myelomagenesis. We summarize the current literature on the quantitative and functional profiles of natural killer cells and T-cells, including conventional T-cells, natural killer T-cells, γδ T-cells and regulatory T-cells, in myelomagenesis. Our goal is to provide an overview of the status and function of these immune cells in both the peripheral blood and the bone marrow during myelomagenesis. This provides a better understanding of the nature of the immune system in tumor evolution, the knowledge of which is especially significant considering that immunotherapies are increasingly being explored in the treatment of both MM and its precursor conditions. PMID:25885426

  20. The cellular immune system in myelomagenesis: NK cells and T cells in the development of myeloma [corrected] and their uses in immunotherapies.

    PubMed

    Dosani, T; Carlsten, M; Maric, I; Landgren, O

    2015-01-01

    As vast strides are being made in the management and treatment of multiple myeloma (MM), recent interests are increasingly focusing on understanding the development of the disease. The knowledge that MM develops exclusively from a protracted phase of monoclonal gammopathy of undetermined significance provides an opportunity to study tumor evolution in this process. Although the immune system has been implicated in the development of MM, the scientific literature on the role and status of various immune components in this process is broad and sometimes contradictory. Accordingly, we present a review of cellular immune subsets in myelomagenesis. We summarize the current literature on the quantitative and functional profiles of natural killer cells and T-cells, including conventional T-cells, natural killer T-cells, γδ T-cells and regulatory T-cells, in myelomagenesis. Our goal is to provide an overview of the status and function of these immune cells in both the peripheral blood and the bone marrow during myelomagenesis. This provides a better understanding of the nature of the immune system in tumor evolution, the knowledge of which is especially significant considering that immunotherapies are increasingly being explored in the treatment of both MM and its precursor conditions.

  1. Time course and cellular localization of interleukin-10 mRNA and protein expression in autoimmune inflammation of the rat central nervous system.

    PubMed Central

    Jander, S.; Pohl, J.; D'Urso, D.; Gillen, C.; Stoll, G.

    1998-01-01

    Experimental autoimmune encephalomyelitis of the Lewis rat is a T-cell-mediated autoimmune disease of the central nervous system characterized by a self-limiting monophasic course. In this study, we analyzed the expression of the anti-inflammatory cytokine interleukin (IL)-10 at the mRNA and protein level in experimental autoimmune encephalomyelitis actively induced with the encephalitogenic 68-86 peptide of guinea pig myelin basic protein. Semiquantitative reverse transcriptase-polymerase chain reaction revealed that IL-10 mRNA expression peaked during the acute phase of the disease at days 11 and 13. IL-10 mRNA was synchronously induced with mRNA for the proinflammatory cytokine interferon-gamma. Immunocytochemistry with a monoclonal antibody against rat IL-10 showed that the peak of IL-10 mRNA was accompanied by an abundant expression of IL-10 protein during the acute stage of the disease. Both in situ hybridization and double labeling immunocytochemistry in combination with confocal microscopy identified T cells, macrophages/microglia, and astrocytes as major cellular sources of IL-10 in vivo. The early peak of IL-10 production was unexpected in light of its well-documented anti-inflammatory properties. Additional studies are required to determine whether endogenous IL-10 contributes to rapid clinical remission typical for Lewis rat experimental autoimmune encephalomyelitis or if it plays other, yet undefined, roles in central nervous system autoimmunity. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9546358

  2. In black South Africans from rural and urban communities, the 4G/5G PAI-1 polymorphism influences PAI-1 activity, but not plasma clot lysis time.

    PubMed

    de Lange, Zelda; Rijken, Dingeman C; Hoekstra, Tiny; Conradie, Karin R; Jerling, Johann C; Pieters, Marlien

    2013-01-01

    Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT). We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009) but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1act variance. (Central) obesity was the biggest contributor to PAI-1act variance (12.5%). Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT. PMID:24386152

  3. In Black South Africans from Rural and Urban Communities, the 4G/5G PAI-1 Polymorphism Influences PAI-1 Activity, but Not Plasma Clot Lysis Time

    PubMed Central

    de Lange, Zelda; Rijken, Dingeman C.; Hoekstra, Tiny; Conradie, Karin R.; Jerling, Johann C.; Pieters, Marlien

    2013-01-01

    Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT). We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009) but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1act variance. (Central) obesity was the biggest contributor to PAI-1act variance (12.5%). Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT. PMID:24386152

  4. PAI-1 -675 4G/5G Polymorphism in Association with Diabetes and Diabetic Complications Susceptibility: a Meta-Analysis Study

    PubMed Central

    Yang, Fan; Cui, Dai; Shi, Yun; Shen, Chong; Tang, Wei; Yang, Tao

    2013-01-01

    A meta-analysis was performed to assess the association between the PAI-1 -675 4G/5G polymorphism and susceptibility to diabetes mellitus (DM), diabetic nephropathy (DN), diabetic retinopathy (DR) and diabetic coronary artery disease (CAD). A literature-based search was conducted to identify all relevant studies. The fixed or random effect pooled measure was calculated mainly at the allele level to determine heterogeneity bias among studies. Further stratified analyses and sensitivity analyses were also performed. Publication bias was examined by the modified Begg’s and Egger’s test. Twenty published articles with twenty-seven outcomes were included in the meta-analysis: 6 studies with a total of 1,333 cases and 3,011 controls were analyzed for the PAI-1 -675 4G/5G polymorphism with diabetes risk, 7 studies with 1,060 cases and 1,139 controls for DN risk, 10 studies with 1,327 cases and 1,557 controls for DR and 4 studies with 610 cases and 1,042 controls for diabetic CAD risk respectively. Using allelic comparison (4G vs. 5G), the PAI-1 -675 4G/5G polymorphism was observed to have no significant association with diabetes (REM OR 1.07, 95% CI 0.96, 1.20), DN (REM OR 1.10, 95% CI 0.98, 1.25), DR (REM OR 1.09, 95% CI 0.97, 1.22) or diabetic CAD risk (REM OR 1.07, 95% CI 0.81, 1.42), and similar results were obtained in the dominant, recessive and co-dominant models. Our meta-analyses suggest that the PAI-1 -675 4G/5G polymorphism might not be a risk factor for DM, DN, DR or diabetic CAD risk in the populations investigated. This conclusion warrants confirmation by further studies. PMID:24223897

  5. Evolving gene regulation networks into cellular networks guiding adaptive behavior: an outline how single cells could have evolved into a centralized neurosensory system

    PubMed Central

    Fritzsch, Bernd; Jahan, Israt; Pan, Ning; Elliott, Karen L.

    2014-01-01

    Understanding the evolution of the neurosensory system of man, able to reflect on its own origin, is one of the major goals of comparative neurobiology. Details of the origin of neurosensory cells, their aggregation into central nervous systems and associated sensory organs, their localized patterning into remarkably different cell types aggregated into variably sized parts of the central nervous system begin to emerge. Insights at the cellular and molecular level begin to shed some light on the evolution of neurosensory cells, partially covered in this review. Molecular evidence suggests that high mobility group (HMG) proteins of pre-metazoans evolved into the definitive Sox [SRY (sex determining region Y)-box] genes used for neurosensory precursor specification in metazoans. Likewise, pre-metazoan basic helix-loop-helix (bHLH) genes evolved in metazoans into the group A bHLH genes dedicated to neurosensory differentiation in bilaterians. Available evidence suggests that the Sox and bHLH genes evolved a cross-regulatory network able to synchronize expansion of precursor populations and their subsequent differentiation into novel parts of the brain or sensory organs. Molecular evidence suggests metazoans evolved patterning gene networks early and not dedicated to neuronal development. Only later in evolution were these patterning gene networks tied into the increasing complexity of diffusible factors, many of which were already present in pre-metazoans, to drive local patterning events. It appears that the evolving molecular basis of neurosensory cell development may have led, in interaction with differentially expressed patterning genes, to local network modifications guiding unique specializations of neurosensory cells into sensory organs and various areas of the central nervous system. PMID:25416504

  6. Cellular Reflectarray Antenna

    NASA Technical Reports Server (NTRS)

    Romanofsky, Robert R.

    2010-01-01

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

  7. Active Cellular Nematics

    NASA Astrophysics Data System (ADS)

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

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

  8. Effects of Methanol Extract of Breadfruit (Artocarpus altilis) on Atherogenic Indices and Redox Status of Cellular System of Hypercholesterolemic Male Rats.

    PubMed

    Adaramoye, Oluwatosin Adekunle; Akanni, Olubukola Oyebimpe

    2014-01-01

    We investigated the effects of methanol extract of Artocarpus altilis (AA) on atherogenic indices and redox status of cellular system of rats fed with dietary cholesterol while Questran (QUE) served as standard. Biochemical indices such as total cholesterol (TC), triglycerides (TG), low- and high-density lipoproteins-cholesterol (LDL-C and HDL-C), aspartate and alanine aminotransferases (AST and ALT), lactate dehydrogenase (LDH), reduced glutathione, glutathione-s-transferase, glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and lipid peroxidation (LPO) were assessed. Hypercholesterolemic (HC) rats had significantly increased relative weight of liver and heart. Dietary cholesterol caused a significant increase (P < 0.05) in the levels of serum, hepatic, and cardiac TC by 110%, 70%, and 85%, LDL-C by 79%, 82%, and 176%, and TG by 68%, 96%, and 62%, respectively. Treatment with AA significantly reduced the relative weight of the organs and lipid parameters. There were beneficial increases in serum and cardiac HDL-C levels in HC rats treated with AA. In HC rats, serum LDH, ALT, and AST activities and levels of LPO were increased, whereas hepatic and cardiac SOD, CAT, and GPx were reduced. All biochemical and histological alterations were ameliorated upon treatment with AA. Extract of AA had protective effects against dietary cholesterol-induced hypercholesterolemia.

  9. BDMC33, A Curcumin Derivative Suppresses Inflammatory Responses in Macrophage-Like Cellular System: Role of Inhibition in NF-κB and MAPK Signaling Pathways

    PubMed Central

    Lee, Ka-Heng; Chow, Yuh-Lit; Sharmili, Vidyadaran; Abas, Faridah; Alitheen, Noorjahan Banu Mohamed; Shaari, Khozirah; Israf, Daud Ahmad; Lajis, Nordin Haji; Syahida, Ahmad

    2012-01-01

    Our preliminary screening has shown that curcumin derivative BDMC33 [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] exerted promising nitric oxide inhibitory activity in activated macrophages. However, the molecular basis and mechanism for its pharmacological action is yet to be elucidated. The aim of this study was to investigate the anti-inflammatory properties of BDMC33 and elucidate its underlying mechanism action in macrophage cells. Our current study demonstrated that BDMC33 inhibits the secretion of major pro-inflammatory mediators in stimulated macrophages, and includes NO, TNF-α and IL-1β through interference in both nuclear factor kappaB (NF-κB) and mitogen activator protein kinase (MAPK) signaling cascade in IFN-γ/LPS-stimulated macrophages. Moreover, BDMC33 also interrupted LPS signaling through inhibiting the surface expression of CD-14 accessory molecules. In addition, the inhibitory action of BDMC33 not only restricted the macrophages cell (RAW264.7), but also inhibited the secretion of NO and TNF-α in IFN-γ/LPS-challenged microglial cells (BV-2). The experimental data suggests the inflammatory action of BDMC33 on activated macrophage-like cellular systems, which could be used as a future therapeutic agent in the management of chronic inflammatory diseases. PMID:22489138

  10. Solving a mathematical model integrating unequal-area facilities layout and part scheduling in a cellular manufacturing system by a genetic algorithm.

    PubMed

    Ebrahimi, Ahmad; Kia, Reza; Komijan, Alireza Rashidi

    2016-01-01

    In this article, a novel integrated mixed-integer nonlinear programming model is presented for designing a cellular manufacturing system (CMS) considering machine layout and part scheduling problems simultaneously as interrelated decisions. The integrated CMS model is formulated to incorporate several design features including part due date, material handling time, operation sequence, processing time, an intra-cell layout of unequal-area facilities, and part scheduling. The objective function is to minimize makespan, tardiness penalties, and material handling costs of inter-cell and intra-cell movements. Two numerical examples are solved by the Lingo software to illustrate the results obtained by the incorporated features. In order to assess the effects and importance of integration of machine layout and part scheduling in designing a CMS, two approaches, sequentially and concurrent are investigated and the improvement resulted from a concurrent approach is revealed. Also, due to the NP-hardness of the integrated model, an efficient genetic algorithm is designed. As a consequence, computational results of this study indicate that the best solutions found by GA are better than the solutions found by B&B in much less time for both sequential and concurrent approaches. Moreover, the comparisons between the objective function values (OFVs) obtained by sequential and concurrent approaches demonstrate that the OFV improvement is averagely around 17 % by GA and 14 % by B&B. PMID:27536537

  11. Effects of Methanol Extract of Breadfruit (Artocarpus altilis) on Atherogenic Indices and Redox Status of Cellular System of Hypercholesterolemic Male Rats.

    PubMed

    Adaramoye, Oluwatosin Adekunle; Akanni, Olubukola Oyebimpe

    2014-01-01

    We investigated the effects of methanol extract of Artocarpus altilis (AA) on atherogenic indices and redox status of cellular system of rats fed with dietary cholesterol while Questran (QUE) served as standard. Biochemical indices such as total cholesterol (TC), triglycerides (TG), low- and high-density lipoproteins-cholesterol (LDL-C and HDL-C), aspartate and alanine aminotransferases (AST and ALT), lactate dehydrogenase (LDH), reduced glutathione, glutathione-s-transferase, glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and lipid peroxidation (LPO) were assessed. Hypercholesterolemic (HC) rats had significantly increased relative weight of liver and heart. Dietary cholesterol caused a significant increase (P < 0.05) in the levels of serum, hepatic, and cardiac TC by 110%, 70%, and 85%, LDL-C by 79%, 82%, and 176%, and TG by 68%, 96%, and 62%, respectively. Treatment with AA significantly reduced the relative weight of the organs and lipid parameters. There were beneficial increases in serum and cardiac HDL-C levels in HC rats treated with AA. In HC rats, serum LDH, ALT, and AST activities and levels of LPO were increased, whereas hepatic and cardiac SOD, CAT, and GPx were reduced. All biochemical and histological alterations were ameliorated upon treatment with AA. Extract of AA had protective effects against dietary cholesterol-induced hypercholesterolemia. PMID:24592277

  12. Effects of Methanol Extract of Breadfruit (Artocarpus altilis) on Atherogenic Indices and Redox Status of Cellular System of Hypercholesterolemic Male Rats

    PubMed Central

    Adaramoye, Oluwatosin Adekunle; Akanni, Olubukola Oyebimpe

    2014-01-01

    We investigated the effects of methanol extract of Artocarpus altilis (AA) on atherogenic indices and redox status of cellular system of rats fed with dietary cholesterol while Questran (QUE) served as standard. Biochemical indices such as total cholesterol (TC), triglycerides (TG), low- and high-density lipoproteins-cholesterol (LDL-C and HDL-C), aspartate and alanine aminotransferases (AST and ALT), lactate dehydrogenase (LDH), reduced glutathione, glutathione-s-transferase, glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and lipid peroxidation (LPO) were assessed. Hypercholesterolemic (HC) rats had significantly increased relative weight of liver and heart. Dietary cholesterol caused a significant increase (P < 0.05) in the levels of serum, hepatic, and cardiac TC by 110%, 70%, and 85%, LDL-C by 79%, 82%, and 176%, and TG by 68%, 96%, and 62%, respectively. Treatment with AA significantly reduced the relative weight of the organs and lipid parameters. There were beneficial increases in serum and cardiac HDL-C levels in HC rats treated with AA. In HC rats, serum LDH, ALT, and AST activities and levels of LPO were increased, whereas hepatic and cardiac SOD, CAT, and GPx were reduced. All biochemical and histological alterations were ameliorated upon treatment with AA. Extract of AA had protective effects against dietary cholesterol-induced hypercholesterolemia. PMID:24592277

  13. [Main Cellular Redox Couples].

    PubMed

    Bilan, D S; Shokhina, A G; Lukyanov, S A; Belousov, V V

    2015-01-01

    Most of the living cells maintain the continuous flow of electrons, which provides them by energy. Many of the compounds are presented in a cell at the same time in the oxidized and reduced states, forming the active redox couples. Some of the redox couples, such as NAD+/NADH, NADP+/NADPH, oxidized/reduced glutathione (GSSG/GSH), are universal, as they participate in adjusting of many cellular reactions. Ratios of the oxidized and reduced forms of these compounds are important cellular redox parameters. Modern research approaches allow setting the new functions of the main redox couples in the complex organization of cellular processes. The following information is about the main cellular redox couples and their participation in various biological processes.

  14. Effect of systemic injection of heterogenous and homogenous opioids on peripheral cellular immune response in rats with bone cancer pain: A comparative study

    PubMed Central

    Du, Jun-Ying; Liang, Yi; Fang, Jun-Fan; Jiang, Yong-Liang; Shao, Xiao-Mei; He, Xiao-Fen; Fang, Jian-Qiao

    2016-01-01

    Exogenous and endogenous opioids have been shown to modulate the immune system. Morphine-induced immunosuppression has been investigated extensively. However, the immune-regulating function of endogenous opioid peptides is unclear. The present study aimed to evaluate the difference in effects on cellular immune function between recombinant rat β-endorphin (β-EP; 50 µg/kg) and plant source morphine (10 mg/kg) via intraperitoneal injection treatment in a rat model of bone cancer pain. Walker 256 cells were injected into a tibial cavity injection to establish the bone cancer pain model. The paw withdrawal thresholds and body weights were measured prior to surgery, at 6 days after surgery, and following 1, 3,6 and 8 treatments. The spleen cells were harvested for detection of T cell proliferation, natural killer (NK) cell cytotoxicity, and the relative quantities of T cell subtypes (CD3+, CD4+ and CD8+ cells). Plasma levels of interleukin-2 (IL-2) were also determined. It was found that single or multiple treatments with β-EP (a homogenous opioid peptide) and morphine (a heterogenous opioid) had good analgesic effects on bone cancer pain, while the analgesia provided by morphine was stronger than that of β-EP. Treatment with β-EP 3, 6 and 8 times increased the body weight gain in the rat model of bone cancer pain, while morphine treatment had on effect on it. With regard to immunomodulatory functions, β-EP treatment increased T cell proliferation and NK cell cytotoxicity, and increased the relative quantities of T cell subtypes, but no effect on T cell secretion. However, morphine treatment decreased T cell proliferation and the levels of T cell subtypes. These data indicate that opioids from different sources have different effects on cellular immune function in vivo. A small dose of homogenous opioid peptide exhibited positive effects (analgesia and immune enhancement) on cancer pain. These results provide experimental evidence supporting the exploitation of

  15. Nanostructured cellular networks.

    PubMed

    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.

  16. The effect of plasminogen activator inhibitor-1 -675 4G/5G polymorphism on PAI-1 gene expression and adipocyte differentiation.

    PubMed

    Ozel Demiralp, Duygu; Aktas, Huseyin; Akar, Nejat

    2008-10-01

    Obesity is a complex, multifactorial chronic disease frequently associated with cardiovascular risks, hypertriglyceridemia, low high-density lipoprotein-cholesterol, high blood pressure, and the insulin resistance that appears to be central to the pathogenesis of Type II diabetes. Plasminogen activator inhibitor-1 expression induced in differentiating adipose tissue, but its role in adipogenesis and obesity is poorly understood. Circulating plasminogen activator inhibitor-1 levels are elevated at an early stage of impaired glucose tolerance, resulting in diabetes and metabolic syndrome. Plasminogen activator inhibitor-1 levels are also significantly elevated in the plasma of obese individuals and in adipose tissues of obese mice and humans. Some investigators proposed that the -675 4G/5G polymorphism in plasminogen activator inhibitor-1 promoter caused overexpression of this gene and predisposed carriers to obesity. In this study, we investigated the role of -675 4G/5G polymorphism in plasminogen activator inhibitor-1 promoter in the expression of this gene and the contribution of plasminogen activator inhibitor-1 to adipogenesis. Using a dual-luciferase promoter assay, we determined that the -675 4G/5G polymorphism contributes significantly to overexpression of plasminogen activator inhibitor-1 in the course of adipogenesis. The antidiabetic agents troglitazone and ciglitazone inhibited reporter gene expression driven by wild-type and -675 4G/5G mutant promoter, as well as the expression of endogenous plasminogen activator inhibitor-1, indicating that suppression of plasminogen activator inhibitor-1 expression may contribute to antidiabetic effects of these agents. The results indicate that absence of plasminogen activator inhibitor-1 in adipocytes may protect the cells against insulin resistance by promoting glucose uptake and adipocyte differentiation via a decrease in the peroxisome proliferator activated receptor-gamma expression that modulates the adipocyte

  17. Characterization of a cytochrome P450 gene (CYP4G) and modulation under different exposures to xenobiotics (tributyltin, nonylphenol, bisphenol A) in Chironomus riparius aquatic larvae.

    PubMed

    Martínez-Paz, Pedro; Morales, Mónica; Martínez-Guitarte, José Luis; Morcillo, Gloria

    2012-03-01

    Cytochrome P450 family members participate in xenobiotic transformation as a detoxification mechanism. We have characterized a CYP gene, assigned to the 4G family, in Chironomus riparius, a reference organism in aquatic toxicology. Due to the potential interest of CYP genes and P450 proteins for monitoring pollution effects at the molecular level, the alterations in the pattern of expression of this gene, induced by different xenobiotics, were analyzed. Different compounds, such as the biocide tributyltin (TBTO) and two other well-known endocrine disruptors, nonylphenol (NP) and bisphenol A (BPA), were tested at different concentrations and acute exposures. Upregulation of the CrCYP4G gene was found after exposures to TBTO (1 ng/L 24h-0.1 ng/L 96 h) and, as measured by RT-PCR mRNA quantification, its level was up to twofold that of controls. However, in contrast, NP (1, 10, 100 μg/L, 24h) and BPA (0.5mg/L 24h-3mg/L 96 h) downregulated the gene (by around a half of the control level) suggesting that this gene responds specifically to particular chemicals in the environment. Glutathione-S-transferase (GST) enzymatic activity was also evaluated for each condition. A fairly good correlation was found with CYP4G gene behavior, as it was activated by TBTO (96 h), but inhibited by NP and BPA (24h). Only the higher concentration of BPA tested activated GST, whereas it inhibited CYP4G activity. The results show that different xenobiotics can induce distinct responses in the detoxification pathway, suggesting multiple xenobiotic transduction mechanisms. This work confirms that specific P450 codifying genes, as well as GST enzyme activities, could be suitable biomarkers for ecotoxicological studies.

  18. Intra-articular glenohumeral injections of HYADD®4-G for the treatment of painful shoulder osteoarthritis: a prospective multicenter, open-label trial

    PubMed Central

    PORCELLINI, GIUSEPPE; MEROLLA, GIOVANNI; GIORDAN, NICOLA; PALADINI, PAOLO; BURINI, ANDREA; CESARI, EUGENIO; CASTAGNA, ALESSANDRO

    2015-01-01

    Purpose numerous experimental and clinical studies in osteoarthritis (OA) have demonstrated that intra-articular (IA) administration of hyaluronic acid can improve the altered rheological properties of the synovial fluid and exert protective and reparative effects on the joint structure. The objective of this study was to evaluate the safety and performance of HYADD®4-G (Hymovis®) in patients with glenohumeral joint OA. Methods forty-one patients with shoulder pain and limited shoulder function resulting from concentric glenohumeral joint OA were enrolled in a multicenter clinical trial. Patients received two HYADD®4-G injections administered one week apart. The main outcome measure was improvement in shoulder pain on movement at six months as assessed through a 100-mm visual analog scale (VAS), range of motion (ROM) values, and Constant-Murley Shoulder Outcome Score (CS). Results two IA injections of HYADD®4-G (Hymovis®) significantly decreased pain and improved shoulder function for up to six months from the first injection. The VAS score decreased (from 66.1 mm to 37.7 mm at six months) and improvements were recorded in the total CS and in the ROM values ( rotation decreased from a mean value of 54.2° at baseline to 63.2° at six months and internal rotation from a mean value of 44.0° at baseline to 45.7° at 26 weeks). No serious adverse events occurred. Conclusions the study results demonstrated that two IA injections of HYADD®4-G (Hymovis®) may be a safe and effective treatment option for shoulder pain associated with glenohumeral OA and that the effects of the injections are still present for up to six months after the treatment. Level of evidence Level IV, therapeutic case series. PMID:26889467

  19. Equol, an isoflavone metabolite, regulates cancer cell viability and protein synthesis initiation via c-Myc and eIF4G.

    PubMed

    de la Parra, Columba; Borrero-Garcia, Luis D; Cruz-Collazo, Ailed; Schneider, Robert J; Dharmawardhane, Suranganie

    2015-03-01

    Epidemiological studies implicate dietary soy isoflavones as breast cancer preventives, especially due to their anti-estrogenic properties. However, soy isoflavones may also have a role in promoting breast cancer, which has yet to be clarified. We previously reported that equol, a metabolite of the soy isoflavone daidzein, may advance breast cancer potential via up-regulation of the eukaryotic initiation factor 4GI (eIF4GI). In estrogen receptor negative (ER-) metastatic breast cancer cells, equol induced elevated levels of eIF4G, which were associated with increased cell viability and the selective translation of mRNAs that use non-canonical means of initiation, including internal ribosome entry site (IRES), ribosome shunting, and eIF4G enhancers. These mRNAs typically code for oncogenic, survival, and cell stress molecules. Among those mRNAs translationally increased by equol was the oncogene and eIF4G enhancer, c-Myc. Here we report that siRNA-mediated knockdown of c-Myc abrogates the increase in cancer cell viability and mammosphere formation by equol, and results in a significant down-regulation of eIF4GI (the major eIF4G isoform), as well as reduces levels of some, but not all, proteins encoded by mRNAs that are translationally stimulated by equol treatment. Knockdown of eIF4GI also markedly reduces an equol-mediated increase in IRES-dependent mRNA translation and the expression of specific oncogenic proteins. However, eIF4GI knockdown did not reciprocally affect c-Myc levels or cell viability. This study therefore implicates c-Myc as a potential regulator of the cancer-promoting effects of equol via up-regulation of eIF4GI and selective initiation of translation on mRNAs that utilize non-canonical initiation, including certain oncogenes. PMID:25593313

  20. Parkinson’s disease genes VPS35 and EIF4G1 interact genetically and converge on α–synuclein

    PubMed Central

    Dhungel, Nripesh; Eleuteri, Simona; Li, Ling-bo; Kramer, Nicholas J.; Chartron, Justin; Spencer, Brian; Kosberg, Kori; Fields, Jerel Adam; Klodjan, Stafa; Adame, Anthony; Lashuel, Hilal; Frydman, Judith; Shen, Kang; Masliah, Eliezer; Gitler, Aaron D.

    2014-01-01

    Summary Parkinson’s disease (PD) is a common neurodegenerative disorder. Functional interactions between some PD genes, like PINK1 and parkin, have been identified, but whether other ones interact remains elusive. Here we report an unexpected genetic interaction between two PD genes, VPS35 and EIF4G1. We provide evidence that EIF4G1 upregulation causes defects associated with protein misfolding. Expression of a sortilin protein rescues these defects, downstream of VPS35, suggesting a potential role for sortilins in PD. We also show interactions between VPS35, EIF4G1 and α–synuclein, a protein with a key role in PD. We extend our findings from yeast to an animal model and show these interactions are conserved in neurons and in transgenic mice. Our studies reveal unexpected genetic and functional interactions between two seemingly unrelated PD genes and functionally connect them to α–synuclein pathobiology in yeast, worms, and mouse. Finally, we provide a resource of candidate PD genes for future interrogation. PMID:25533483

  1. Activation of a GPCR leads to eIF4G phosphorylation at the 5' cap and to IRES-dependent translation.

    PubMed

    León, Kelly; Boulo, Thomas; Musnier, Astrid; Morales, Julia; Gauthier, Christophe; Dupuy, Laurence; Heyne, Steffen; Backofen, Rolf; Poupon, Anne; Cormier, Patrick; Reiter, Eric; Crepieux, Pascale

    2014-06-01

    The control of mRNA translation has been mainly explored in response to activated tyrosine kinase receptors. In contrast, mechanistic details on the translational machinery are far less available in the case of ligand-bound G protein-coupled receptors (GPCRs). In this study, using the FSH receptor (FSH-R) as a model receptor, we demonstrate that part of the translational regulations occurs by phosphorylation of the translation pre-initiation complex scaffold protein, eukaryotic initiation factor 4G (eIF4G), in HEK293 cells stably expressing the FSH-R. This phosphorylation event occurred when eIF4G was bound to the mRNA 5' cap, and probably involves mammalian target of rapamycin. This regulation might contribute to cap-dependent translation in response to FSH. The cap-binding protein eIF4E also had its phosphorylation level enhanced upon FSH stimulation. We also show that FSH-induced signaling not only led to cap-dependent translation but also to internal ribosome entry site (IRES)-dependent translation of some mRNA. These data add detailed information on the molecular bases underlying the regulation of selective mRNA translation by a GPCR, and a topological model recapitulating these mechanisms is proposed.

  2. The mammary cellular hierarchy and breast cancer.

    PubMed

    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.

  3. Cellular solidification of transparent monotectics

    NASA Technical Reports Server (NTRS)

    Kaulker, W. F.

    1986-01-01

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

  4. The Central Nervous System (CNS)-independent Anti-bone-resorptive Activity of Muscle Contraction and the Underlying Molecular and Cellular Signatures*

    PubMed Central

    Qin, Weiping; Sun, Li; Cao, Jay; Peng, Yuanzhen; Collier, Lauren; Wu, Yong; Creasey, Graham; Li, Jianhua; Qin, Yiwen; Jarvis, Jonathan; Bauman, William A.; Zaidi, Mone; Cardozo, Christopher

    2013-01-01

    Muscle and bone work as a functional unit. Cellular and molecular mechanisms underlying effects of muscle activity on bone mass are largely unknown. Spinal cord injury (SCI) causes muscle paralysis and extensive sublesional bone loss and disrupts neural connections between the central nervous system (CNS) and bone. Muscle contraction elicited by electrical stimulation (ES) of nerves partially protects against SCI-related bone loss. Thus, application of ES after SCI provides an opportunity to study the effects of muscle activity on bone and roles of the CNS in this interaction, as well as the underlying mechanisms. Using a rat model of SCI, the effects on bone of ES-induced muscle contraction were characterized. The SCI-mediated increase in serum C-terminal telopeptide of type I collagen (CTX) was completely reversed by ES. In ex vivo bone marrow cell cultures, SCI increased the number of osteoclasts and their expression of mRNA for several osteoclast differentiation markers, whereas ES significantly reduced these changes; SCI decreased osteoblast numbers, but increased expression in these cells of receptor activator of NF-κB ligand (RANKL) mRNA, whereas ES increased expression of osteoprotegerin (OPG) and the OPG/RANKL ratio. A microarray analysis revealed that ES partially reversed SCI-induced alterations in expression of genes involved in signaling through Wnt, FSH, parathyroid hormone (PTH), oxytocin, and calcineurin/nuclear factor of activated T-cells (NFAT) pathways. ES mitigated SCI-mediated increases in mRNA levels for the Wnt inhibitors DKK1, sFRP2, and sclerostin in ex vivo cultured osteoblasts. Our results demonstrate an anti-bone-resorptive activity of muscle contraction by ES that develops rapidly and is independent of the CNS. The pathways involved, particularly Wnt signaling, suggest future strategies to minimize bone loss after immobilization. PMID:23530032

  5. Immunohistochemical Expression of PCNA and CD34 in Colorectal Adenomas and Carcinomas Using Specified Automated Cellular Image Analysis System: A Clinicopathologic Study

    PubMed Central

    Qasim, Ban J.; Ali, Hussam H.; Hussein, Alaa G.

    2012-01-01

    Background/Aim: To evaluate the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) and CD34 in colorectal adenomas and carcinomas, and to correlate this expression with different clinicopathologic parameters. Materials and Methods: The study was retrospectively designed. A total of 86 tissue samples, including 33 paraffin blocks from patients with colorectal adenomas, 33 paraffin blocks from patients with colorectal adenocarcinomas, and a control group of 20 samples of nontumerous colonic tissue, were included in the study. From each block, 3 sections of 5 ΅m thickness were taken, 1 section was stained with hematoxylin and eosin (H and E) and the other 2 sections were stained immunohistochemically for PCNA and CD34. Scoring of the immunohistochemical staining was performed using a specified automated cellular image analysis system (Digimizer). Results: PCNA expression was significantly increased in a sequence of normal mucosa–adenoma–carcinoma. It was significantly higher in adenomas ≥ 1 cm and those with severe dysplasia, and it showed a significant positive correlation with grade and lymph node involvement in colorectal carcinoma. CD34 showed significantly higher expression in carcinoma than adenoma and in adenoma than in the control group. CD34 expression showed a significant correlation with adenomas carrying severe dysplasia and large-sized adenomas (≥1cm). It was significantly correlated with tumor grade, lymphovascular invasion, and lymph node involvement in colorectal carcinoma. Conclusion: PCNA plays an important role in colorectal neoplastic progression and can be utilized as ancillary marker for the risk of malignant transformation in colorectal adenomas as it correlates with high grade dysplasia and size. Intratumoral quantification of the mean (A and N) of CD34 in colorectal carcinoma reflects the grade of tumors and can predict lymph node involvement and lymphovascular invasion, to make a useful additional prognostic

  6. Temperature effects on biomass, geosmin, and 2-methylisoborneol production and cellular activity by Nocardia spp. and Streptomyces spp. isolated from rainbow trout recirculating aquaculture systems.

    PubMed

    Schrader, Kevin K; Harries, Marcuslene D; Page, Phaedra N

    2015-05-01

    Isolates of Nocardia cummidelens, Nocard ia fluminea, Streptomyces albidoflavus, and Streptomyces luridiscabiei attributed as the cause of "earthy-musty" off-flavor in rainbow trout (Oncorhynchus mykiss) raised in recirculating aquaculture systems (RAS) were evaluated for the effect of temperature (10-30 °C) on biomass, geosmin, and 2-methylisoborneol (MIB) production and cellular activity. Cultures of these isolates were monitored over 7 days by measuring culture dry weight, geosmin, and MIB production using solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS), and ATP production via a luminometer. Compared to the other isolates, S. luridiscabiei had significantly (P < 0.05) higher biomass (8.17 ± 0.35 mg/mL) at 15 °C (water temperature in the RAS) after 7 days incubation. In addition, S. luridiscabiei produced significantly (P < 0.05) higher geosmin (69,976 ± 15,733 ng/L) at 15 °C. At 25 °C and 30 °C, S. albidoflavus produced significantly (P < 0.05) higher geosmin (182,074 ± 60,272 ng/L and 399,991 ± 102,262 ng/L, respectively). All isolates produced MIB at 15 °C, but S. luridiscabiei produced significantly (P < 0.05) higher MIB (97,143 ± 28,972 ng/L) and ATP after 7 days. Therefore, S. luridiscabiei appears to be a likely contributor of geosmin and MIB in the RAS.

  7. Origins of cellular geometry

    PubMed Central

    2011-01-01

    Cells are highly complex and orderly machines, with defined shapes and a startling variety of internal organizations. Complex geometry is a feature of both free-living unicellular organisms and cells inside multicellular animals. Where does the geometry of a cell come from? Many of the same questions that arise in developmental biology can also be asked of cells, but in most cases we do not know the answers. How much of cellular organization is dictated by global cell polarity cues as opposed to local interactions between cellular components? Does cellular structure persist across cell generations? What is the relationship between cell geometry and tissue organization? What ensures that intracellular structures are scaled to the overall size of the cell? Cell biology is only now beginning to come to grips with these questions. PMID:21880160

  8. Architected Cellular Materials

    NASA Astrophysics Data System (ADS)

    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.

  9. 47 CFR 32.5003 - Cellular mobile revenue.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  10. Integrating mitochondrial translation into the cellular context.

    PubMed

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

    2015-10-01

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

  11. Genetic Dominance & Cellular Processes

    ERIC Educational Resources Information Center

    Seager, Robert D.

    2014-01-01

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

  12. The New Cellular Immunology

    ERIC Educational Resources Information Center

    Claman, Henry N.

    1973-01-01

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

  13. Trypanosoma brucei translation initiation factor homolog EIF4E6 forms a tripartite cytosolic complex with EIF4G5 and a capping enzyme homolog.

    PubMed

    Freire, Eden R; Malvezzi, Amaranta M; Vashisht, Ajay A; Zuberek, Joanna; Saada, Edwin A; Langousis, Gerasimos; Nascimento, Janaína D F; Moura, Danielle; Darzynkiewicz, Edward; Hill, Kent; de Melo Neto, Osvaldo P; Wohlschlegel, James A; Sturm, Nancy R; Campbell, David A

    2014-07-01

    Trypanosomes lack the transcriptional control characteristic of the majority of eukaryotes that is mediated by gene-specific promoters in a one-gene-one-promoter arrangement. Rather, their genomes are transcribed in large polycistrons with no obvious functional linkage. Posttranscriptional regulation of gene expression must thus play a larger role in these organisms. The eIF4E homolog TbEIF4E6 binds mRNA cap analogs in vitro and is part of a complex in vivo that may fulfill such a role. Knockdown of TbEIF4E6 tagged with protein A-tobacco etch virus protease cleavage site-protein C to approximately 15% of the normal expression level resulted in viable cells that displayed a set of phenotypes linked to detachment of the flagellum from the length of the cell body, if not outright flagellum loss. While these cells appeared and behaved as normal under stationary liquid culture conditions, standard centrifugation resulted in a marked increase in flagellar detachment. Furthermore, the ability of TbEIF4E6-depleted cells to engage in social motility was reduced. The TbEIF4E6 protein forms a cytosolic complex containing a triad of proteins, including the eIF4G homolog TbEIF4G5 and a hypothetical protein of 70.3 kDa, referred to as TbG5-IP. The TbG5-IP analysis revealed two domains with predicted secondary structures conserved in mRNA capping enzymes: nucleoside triphosphate hydrolase and guanylyltransferase. These complex members have the potential for RNA interaction, either via the 5' cap structure for TbEIF4E6 and TbG5-IP or through RNA-binding domains in TbEIF4G5. The associated proteins provide a signpost for future studies to determine how this complex affects capped RNA molecules. PMID:24839125

  14. Trypanosoma brucei translation initiation factor homolog EIF4E6 forms a tripartite cytosolic complex with EIF4G5 and a capping enzyme homolog.

    PubMed

    Freire, Eden R; Malvezzi, Amaranta M; Vashisht, Ajay A; Zuberek, Joanna; Saada, Edwin A; Langousis, Gerasimos; Nascimento, Janaína D F; Moura, Danielle; Darzynkiewicz, Edward; Hill, Kent; de Melo Neto, Osvaldo P; Wohlschlegel, James A; Sturm, Nancy R; Campbell, David A

    2014-07-01

    Trypanosomes lack the transcriptional control characteristic of the majority of eukaryotes that is mediated by gene-specific promoters in a one-gene-one-promoter arrangement. Rather, their genomes are transcribed in large polycistrons with no obvious functional linkage. Posttranscriptional regulation of gene expression must thus play a larger role in these organisms. The eIF4E homolog TbEIF4E6 binds mRNA cap analogs in vitro and is part of a complex in vivo that may fulfill such a role. Knockdown of TbEIF4E6 tagged with protein A-tobacco etch virus protease cleavage site-protein C to approximately 15% of the normal expression level resulted in viable cells that displayed a set of phenotypes linked to detachment of the flagellum from the length of the cell body, if not outright flagellum loss. While these cells appeared and behaved as normal under stationary liquid culture conditions, standard centrifugation resulted in a marked increase in flagellar detachment. Furthermore, the ability of TbEIF4E6-depleted cells to engage in social motility was reduced. The TbEIF4E6 protein forms a cytosolic complex containing a triad of proteins, including the eIF4G homolog TbEIF4G5 and a hypothetical protein of 70.3 kDa, referred to as TbG5-IP. The TbG5-IP analysis revealed two domains with predicted secondary structures conserved in mRNA capping enzymes: nucleoside triphosphate hydrolase and guanylyltransferase. These complex members have the potential for RNA interaction, either via the 5' cap structure for TbEIF4E6 and TbG5-IP or through RNA-binding domains in TbEIF4G5. The associated proteins provide a signpost for future studies to determine how this complex affects capped RNA molecules.

  15. THE SPITZER SURVEY OF STELLAR STRUCTURE IN GALAXIES (S{sup 4}G): MULTI-COMPONENT DECOMPOSITION STRATEGIES AND DATA RELEASE

    SciTech Connect

    Salo, Heikki; Laurikainen, Eija; Laine, Jarkko; Comerón, Sebastien; Gadotti, Dimitri A.; Kim, Taehyun; Buta, Ron; Sheth, Kartik; Muñoz-Mateos, Juan Carlos; Ho, Luis; Knapen, Johan; Cisternas, Mauricio; Athanassoula, E.; Bosma, Albert; Laine, Seppo; Regan, Michael; De Paz, Armando Gil; Menendez-Delmestre, Karin; and others

    2015-07-20

    The Spitzer Survey of Stellar Structure in Galaxies (S{sup 4}G) is a deep 3.6 and 4.5 μm imaging survey of 2352 nearby (<40 Mpc) galaxies. We describe the S{sup 4}G data analysis pipeline 4, which is dedicated to two-dimensional structural surface brightness decompositions of 3.6 μm images, using GALFIT3.0. Besides automatic 1-component Sérsic fits, and 2-component Sérsic bulge + exponential disk fits, we present human-supervised multi-component decompositions, which include, when judged appropriate, a central point source, bulge, disk, and bar components. Comparison of the fitted parameters indicates that multi-component models are needed to obtain reliable estimates for the bulge Sérsic index and bulge-to-total light ratio (B/T), confirming earlier results. Here, we describe the preparations of input data done for decompositions, give examples of our decomposition strategy, and describe the data products released via IRSA and via our web page (www.oulu.fi/astronomy/S4G-PIPELINE4/MAIN). These products include all the input data and decomposition files in electronic form, making it easy to extend the decompositions to suit specific science purposes. We also provide our IDL-based visualization tools (GALFIDL) developed for displaying/running GALFIT-decompositions, as well as our mask editing procedure (MASK-EDIT) used in data preparation. A detailed analysis of the bulge, disk, and bar parameters derived from multi-component decompositions will be published separately.

  16. Trypanosoma brucei Translation Initiation Factor Homolog EIF4E6 Forms a Tripartite Cytosolic Complex with EIF4G5 and a Capping Enzyme Homolog

    PubMed Central

    Freire, Eden R.; Malvezzi, Amaranta M.; Vashisht, Ajay A.; Zuberek, Joanna; Saada, Edwin A.; Langousis, Gerasimos; Nascimento, Janaína D. F.; Moura, Danielle; Darzynkiewicz, Edward; Hill, Kent; de Melo Neto, Osvaldo P.; Wohlschlegel, James A.; Sturm, Nancy R.

    2014-01-01

    Trypanosomes lack the transcriptional control characteristic of the majority of eukaryotes that is mediated by gene-specific promoters in a one-gene–one-promoter arrangement. Rather, their genomes are transcribed in large polycistrons with no obvious functional linkage. Posttranscriptional regulation of gene expression must thus play a larger role in these organisms. The eIF4E homolog TbEIF4E6 binds mRNA cap analogs in vitro and is part of a complex in vivo that may fulfill such a role. Knockdown of TbEIF4E6 tagged with protein A-tobacco etch virus protease cleavage site-protein C to approximately 15% of the normal expression level resulted in viable cells that displayed a set of phenotypes linked to detachment of the flagellum from the length of the cell body, if not outright flagellum loss. While these cells appeared and behaved as normal under stationary liquid culture conditions, standard centrifugation resulted in a marked increase in flagellar detachment. Furthermore, the ability of TbEIF4E6-depleted cells to engage in social motility was reduced. The TbEIF4E6 protein forms a cytosolic complex containing a triad of proteins, including the eIF4G homolog TbEIF4G5 and a hypothetical protein of 70.3 kDa, referred to as TbG5-IP. The TbG5-IP analysis revealed two domains with predicted secondary structures conserved in mRNA capping enzymes: nucleoside triphosphate hydrolase and guanylyltransferase. These complex members have the potential for RNA interaction, either via the 5′ cap structure for TbEIF4E6 and TbG5-IP or through RNA-binding domains in TbEIF4G5. The associated proteins provide a signpost for future studies to determine how this complex affects capped RNA molecules. PMID:24839125

  17. Discovery of pyrido[3,4-g]quinazoline derivatives as CMGC family protein kinase inhibitors: Design, synthesis, inhibitory potency and X-ray co-crystal structure.

    PubMed

    Esvan, Yannick J; Zeinyeh, Wael; Boibessot, Thibaut; Nauton, Lionel; Théry, Vincent; Knapp, Stefan; Chaikuad, Apirat; Loaëc, Nadège; Meijer, Laurent; Anizon, Fabrice; Giraud, Francis; Moreau, Pascale

    2016-08-01

    The design and synthesis of new pyrido[3,4-g]quinazoline derivatives is described as well as their protein kinase inhibitory potencies toward five CMGC family members (CDK5, CK1, GSK3, CLK1 and DYRK1A). The interest for this original tricyclic heteroaromatic scaffold as modulators of CLK1/DYRK1A activity was validated by nanomolar potencies (compounds 12 and 13). CLK1 co-crystal structures with two inhibitors revealed the binding mode of these compounds within the ATP-binding pocket. PMID:27128181

  18. Bioorthogonal Catalysis: A General Method To Evaluate Metal-Catalyzed Reactions in Real Time in Living Systems Using a Cellular Luciferase Reporter System.

    PubMed

    Hsu, Hsiao-Tieh; Trantow, Brian M; Waymouth, Robert M; Wender, Paul A

    2016-02-17

    The development of abiological catalysts that can function in biological systems is an emerging subject of importance with significant ramifications in synthetic chemistry and the life sciences. Herein we report a biocompatible ruthenium complex [Cp(MQA)Ru(C3H5)](+)PF6(-) 2 (Cp = cyclopentadienyl, MQA = 4-methoxyquinoline-2-carboxylate) and a general analytical method for evaluating its performance in real time based on a luciferase reporter system amenable to high throughput screening in cells and by extension to evaluation in luciferase transgenic animals. Precatalyst 2 activates alloc-protected aminoluciferin 4b, a bioluminescence pro-probe, and releases the active luminophore, aminoluciferin (4a), in the presence of luciferase-transfected cells. The formation and enzymatic turnover of 4a, an overall process selected because it emulates pro-drug activation and drug turnover by an intracellular target, is evaluated in real time by photon counting as 4a is converted by intracellular luciferase to oxyaminoluciferin and light. Interestingly, while the catalytic conversion (activation) of 4b to 4a in water produces multiple products, the presence of biological nucleophiles such as thiols prevents byproduct formation and provides almost exclusively luminophore 4a. Our studies show that precatalyst 2 activates 4b extracellularly, exhibits low toxicity at concentrations relevant to catalysis, and is comparably effective in two different cell lines. This proof of concept study shows that precatalyst 2 is a promising lead for bioorthogonal catalytic activation of pro-probes and, by analogy, similarly activatable pro-drugs. More generally, this study provides an analytical method to measure abiological catalytic activation of pro-probes and, by analogy with our earlier studies on pro-Taxol, similarly activatable pro-drugs in real time using a coupled biological catalyst that mediates a bioluminescent readout, providing tools for the study of imaging signal amplification

  19. Bioorthogonal Catalysis: A General Method To Evaluate Metal-Catalyzed Reactions in Real Time in Living Systems Using a Cellular Luciferase Reporter System

    PubMed Central

    2015-01-01

    The development of abiological catalysts that can function in biological systems is an emerging subject of importance with significant ramifications in synthetic chemistry and the life sciences. Herein we report a biocompatible ruthenium complex [Cp(MQA)Ru(C3H5)]+PF6–2 (Cp = cyclopentadienyl, MQA = 4-methoxyquinoline-2-carboxylate) and a general analytical method for evaluating its performance in real time based on a luciferase reporter system amenable to high throughput screening in cells and by extension to evaluation in luciferase transgenic animals. Precatalyst 2 activates alloc-protected aminoluciferin 4b, a bioluminescence pro-probe, and releases the active luminophore, aminoluciferin (4a), in the presence of luciferase-transfected cells. The formation and enzymatic turnover of 4a, an overall process selected because it emulates pro-drug activation and drug turnover by an intracellular target, is evaluated in real time by photon counting as 4a is converted by intracellular luciferase to oxyaminoluciferin and light. Interestingly, while the catalytic conversion (activation) of 4b to 4a in water produces multiple products, the presence of biological nucleophiles such as thiols prevents byproduct formation and provides almost exclusively luminophore 4a. Our studies show that precatalyst 2 activates 4b extracellularly, exhibits low toxicity at concentrations relevant to catalysis, and is comparably effective in two different cell lines. This proof of concept study shows that precatalyst 2 is a promising lead for bioorthogonal catalytic activation of pro-probes and, by analogy, similarly activatable pro-drugs. More generally, this study provides an analytical method to measure abiological catalytic activation of pro-probes and, by analogy with our earlier studies on pro-Taxol, similarly activatable pro-drugs in real time using a coupled biological catalyst that mediates a bioluminescent readout, providing tools for the study of imaging signal amplification and

  20. Cellular immune responses to HIV

    NASA Astrophysics Data System (ADS)

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

    2001-04-01

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

  1. Pharmacodynamic analysis of time-variant cellular disposition: reticulocyte disposition changes in phlebotomized sheep

    PubMed Central

    Freise, Kevin J.; Widness, John A.; Schmidt, Robert L.

    2010-01-01

    Most pharmacodynamic (PD) models of cellular response assume a time-invariant (i.e., constant) cellular disposition despite known changes in the disposition with time, such as the reticulocyte residence time in the systemic circulation during stress erythropoiesis. To account for changes in cellular disposition, a comprehensive PD model that involves endogenous erythropoietin (Epo), reticulocytes, and hemoglobin responses was developed in phlebotomized sheep that considers a time-variant reticulocyte residence time and allows for the simultaneous determination of changes in the cellular disposition and cellular production. Five sheep were phlebotomized to hemoglobin concentrations of approximately 4 g/dl. Epo concentrations, reticulocytes, and hemoglobin concentrations were frequently sampled for 5–7 days prior to and 25–30 days following the phlebotomy. Initial steady-state conditions were assumed and the time-variant reticulocyte residence time in the systemic circulation was semiparametrically represented using a constrained spline function. Hemoglobin production was modeled using a Hill function via an effect site compartment. The initial steady state reticulocyte residence time in the systemic circulation was estimated as 0.477 (0.100) (mean (SD)) days, which maximally increased 2.01- to 2.64-fold higher than the initial steady-state residence time 5.95 (0.899) days post-phlebotomy (P < 0.01). On average, the residence time returned to steady-state values 15.4 (2.36) days post-phlebotomy, which was not significantly different from the initial steady-state value (P > 0.05). The baseline hemoglobin production rate was estimated at 0.0929 (0.0472) g/kg/day and the maximum production rate under stress phlebotomy was estimated at 0.504 (0.0422) g/kg/day. These data indicate that endogenously released Epo under acute anemic conditions can increase hemoglobin production approximately 5-fold. The determined increase in reticulocyte residence time produced under

  2. Cellular therapy in tuberculosis.

    PubMed

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

    2015-03-01

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

  3. Expression of Cellular Oncogenes in Human Malignancies

    NASA Astrophysics Data System (ADS)

    Slamon, Dennis J.; Dekernion, Jean B.; Verma, Inder M.; Cline, Martin J.

    1984-04-01

    Cellular oncogenes have been implicated in the induction of malignant transformation in some model systems in vitro and may be related to malignancies in vivo in some vertebrate species. This article describes a study of the expression of 15 cellular oncogenes in fresh human tumors from 54 patients, representing 20 different tumor types. More than one cellular oncogene was transcriptionally active in all of the tumors examined. In 14 patients it was possible to study normal and malignant tissue from the same organ. In many of these patients, the transcriptional activity of certain oncogenes was greater in the malignant than the normal tissue. The cellular fes (feline sarcoma) oncogene, not previously known to be transcribed in mammalian tissue, was found to be active in lung and hematopoietic malignancies.

  4. Correlation between plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G polymorphism and metabolic/proinflammatory factors in polycystic ovary syndrome.

    PubMed

    Sales, M F; Sóter, M O; Candido, A L; Fernandes, A P; Oliveira, F R; Ferreira, A C S; Sousa, M O; Ferreira, C N; Gomes, K B

    2013-10-01

    Polycystic Ovary Syndrome (PCOS) is the most common cause of subfertility associated to metabolic disorders. The aim of this study was to correlate metabolic and proinflammatory factors in women with PCOS. The frequency of Plasminogen Activator Inhibitor-1 (PAI-1) promoter 4 G/5 G polymorphism was also compared to healthy controls. We evaluated 79 PCOS and 79 healthy women. PAI-1 levels are positively correlated with proinflammatory factors in PCOS group. 4 G allele in PAI-1 gene was more frequent in PCOS and the 4G/4 G genotype was associated with increased PAI-1 levels. A correlation between insulin resistance and proinflammatory and overweight was also observed. C-reactive protein, serum levels of vascular cell adhesion molecule-1 (sVCAM-1), Lipid Accumulation Product (LAP) and vitamin D are good tools to evaluated factors associated to cardiovascular risk in women with PCOS.

  5. Characterization of pokeweed antiviral protein binding to mRNA cap analogs: competition with nucleotides and enhancement by translation initiation factor iso4G.

    PubMed

    Baldwin, Amy E; Khan, Mateen A; Tumer, Nilgun E; Goss, Dixie J; Friedland, Diana E

    2009-02-01

    Pokeweed antiviral protein (PAP) is a type I ribosomal inactivating protein (RIP). PAP binds to and depurinates the sarcin/ricin loop (SRL) of ribosomal RNA resulting in the cessation of protein synthesis. PAP has also been shown to bind to mRNA cap analogs and depurinate mRNA downstream of the cap structure. The biological role of cap binding and its possible role in PAP activity are not known. Here we show the first direct quantitative evidence for PAP binding to the cap analog m(7)GTP. We report a binding affinity of 43.3+/-0.1 nM at 25 degrees C as determined by fluorescence quenching experiments. This is similar to the values reported for wheat cap-binding proteins eIFiso4E and eIFiso4F. van't Hoff analysis of m(7)GTP-PAP equilibrium reveals a binding reaction that is enthalpy driven and entropy favored with TDeltaS degrees contributing 15% to the overall value of DeltaG degrees . This is in contrast to the wheat cap-binding proteins which are enthalpically driven in the DeltaG degrees for binding. Competition experiments indicate that ATP and GTP compete for the cap-binding site on PAP with slightly different affinities. Fluorescence studies of PAP-eIFiso4G binding reveal a protein-protein interaction with a K(d) of 108.4+/-0.3 nM. eIFiso4G was shown to enhance the interaction of PAP with m(7)GTP cap analog by 2.4-fold. These results suggest the involvement of PAP-translation initiation factor complexes in RNA selection and depurination.

  6. cDNA cloning, expression analysis, and chromosomal localization of a gene with high homology to wheat eIF-(iso)4F and mammalian eIF-4G

    SciTech Connect

    Shaughnessy, J.D. Jr.; Jenkins, N.A.; Copeland, N.G.

    1997-01-15

    A novel mammalian gene, Eif4g2, with a high degree of homology to the p82 subunit of the wheat germ eukaryotic translation initiation factor eIF-(iso)4F and mammalian eIF-4G has been isolated. Zoo blot analysis indicates that Eif4g2 is a single-copy gene that is highly conserved among vertebrates. Northern blot analysis shows that Eif4g2 is ubiquitously expressed at high levels in all human and mouse tissues examined. The 3810-nucleotide Eif4g2 cDNA contains a 907-amino-acid open reading frame that codes for a polypeptide with a predicted molecular mass of 102 kDa. The Eif4g2 polypeptide exhibits an overall similarity to wheat p82 of 52%. A 248-amino-acid segment at the amino-terminal end of both peptides exhibits 63% similarity and contains conserved potential RNA binding domains and a phosphorylation site. The Eif4g2 polypeptide contains multiple potential N-linked glycosylation sites as well as protein kinase C and casein kinase II phosphorylation sites. Southern blot analysis of DNA from interspecific backcross mice shows that Eif4g2 is localized to distal mouse chromosome 7 in a region syntenic with human chromosome 11p15. 25 refs., 5 figs.

  7. Formin’ cellular structures

    PubMed Central

    Bogdan, Sven; Schultz, Jörg; Grosshans, Jörg

    2014-01-01

    Members of the Diaphanous (Dia) protein family are key regulators of fundamental actin driven cellular processes, which are conserved from yeast to humans. Researchers have uncovered diverse physiological roles in cell morphology, cell motility, cell polarity, and cell division, which are involved in shaping cells into tissues and organs. The identification of numerous binding partners led to substantial progress in our understanding of the differential functions of Dia proteins. Genetic approaches and new microscopy techniques allow important new insights into their localization, activity, and molecular principles of regulation. PMID:24719676

  8. Cellular signalling: the role of the peroxisome.

    PubMed

    Masters, C J

    1996-03-01

    This article reviews the role of the peroxisome in cellular signalling, with particular emphasis on the unique contributions of this organelle to the complex regulatory inter-relationships of cellular processes within the mammalian organism. Among the topics covered are the close alignments between the signalling systems governing peroxisome proliferation and those of the steroid hormone/thyroid hormone/vitamin D nuclear-receptor superfamily; the regulation of the permeability of the peroxisomal membrane; the involvements of lysophosphatidic acid as an intra- and inter-cellular messenger; the special role of the phosphatidylcholine cycle and its derivative messengers in relation to peroxisomal metabolism; peroxisomal contributions to the regulation of oxygen free radical levels in tissues and the significance of these radicals as second messengers; the evidence of peroxisomal influences on inter-cellular signalling from metabolic turnover studies; modifications of the regulatory significance of fatty acids by the peroxisome; the commonalities in metabolic relationships between the peroxisome and other cellular organelles; and regulatory shuttles associated with peroxisomal function. It is concluded that the peroxisome displays several significant interconnections with the cellular-signalling apparatus, that it is capable of imprinting a characteristic influence on the regulatory network in the cell, and that the contributions of this organelle deserve greater consideration in future investigations of cell-signalling phenomena.

  9. Understanding the cellular mechanism of recovery from freeze-thaw injury in spinach: possible role of aquaporins, heat shock proteins, dehydrin and antioxidant system.

    PubMed

    Chen, Keting; Arora, Rajeev

    2014-03-01

    Recovery from reversible freeze-thaw injury in plants is a critical component of ultimate frost survival. However, little is known about this aspect at the cellular level. To explore possible cellular mechanism(s) for post-thaw recovery (REC), we used Spinacia oleracea L. cv. Bloomsdale leaves to first determine the reversible freeze-thaw injury point. Freeze (-4.5°C)-thaw-injured tissues (32% injury vs <3% in unfrozen control) fully recovered during post-thaw, as assessed by an ion leakage-based method. Our data indicate that photosystem II efficiency (Fv/Fm) was compromised in injured tissues but recovered during post-thaw. Similarly, the reactive oxygen species (O2 (•-) and H2 O2 ) accumulated in injured tissues but dissipated during recovery, paralleled by the repression and restoration, respectively, of activities of antioxidant enzymes, superoxide dismutase (SOD) (EC. 1.14.1.1), and catalase (CAT) (EC.1.11.1.6) and ascorbate peroxidase (APX) (EC.1.11.1.11). Restoration of CAT and APX activities during recovery was slower than SOD, concomitant with a slower depletion of H2 O2 compared to O2 (•-) . A hypothesis was also tested that the REC is accompanied by changes in the expression of water channels [aquaporines (AQPs)] likely needed for re-absorption of thawed extracellular water. Indeed, the expression of two spinach AQPs, SoPIP2;1 and SoδTIP, was downregulated in injured tissues and restored during recovery. Additionally, a notion that molecular chaperones [heat shock protein of 70 kDa (HSP70s)] and putative membrane stabilizers [dehydrins (DHNs)] are recruited during recovery to restore cellular homeostasis was also tested. We noted that, after an initial repression in injured tissues, the expression of three HSP70s (cytosolic, endoplasmic reticulum and mitochondrial) and a spinach DHN (CAP85) was significantly restored during the REC. PMID:23981077

  10. Understanding the cellular mechanism of recovery from freeze-thaw injury in spinach: possible role of aquaporins, heat shock proteins, dehydrin and antioxidant system.

    PubMed

    Chen, Keting; Arora, Rajeev

    2014-03-01

    Recovery from reversible freeze-thaw injury in plants is a critical component of ultimate frost survival. However, little is known about this aspect at the cellular level. To explore possible cellular mechanism(s) for post-thaw recovery (REC), we used Spinacia oleracea L. cv. Bloomsdale leaves to first determine the reversible freeze-thaw injury point. Freeze (-4.5°C)-thaw-injured tissues (32% injury vs <3% in unfrozen control) fully recovered during post-thaw, as assessed by an ion leakage-based method. Our data indicate that photosystem II efficiency (Fv/Fm) was compromised in injured tissues but recovered during post-thaw. Similarly, the reactive oxygen species (O2 (•-) and H2 O2 ) accumulated in injured tissues but dissipated during recovery, paralleled by the repression and restoration, respectively, of activities of antioxidant enzymes, superoxide dismutase (SOD) (EC. 1.14.1.1), and catalase (CAT) (EC.1.11.1.6) and ascorbate peroxidase (APX) (EC.1.11.1.11). Restoration of CAT and APX activities during recovery was slower than SOD, concomitant with a slower depletion of H2 O2 compared to O2 (•-) . A hypothesis was also tested that the REC is accompanied by changes in the expression of water channels [aquaporines (AQPs)] likely needed for re-absorption of thawed extracellular water. Indeed, the expression of two spinach AQPs, SoPIP2;1 and SoδTIP, was downregulated in injured tissues and restored during recovery. Additionally, a notion that molecular chaperones [heat shock protein of 70 kDa (HSP70s)] and putative membrane stabilizers [dehydrins (DHNs)] are recruited during recovery to restore cellular homeostasis was also tested. We noted that, after an initial repression in injured tissues, the expression of three HSP70s (cytosolic, endoplasmic reticulum and mitochondrial) and a spinach DHN (CAP85) was significantly restored during the REC.

  11. Modelling mammalian cellular quiescence

    PubMed Central

    Yao, Guang

    2014-01-01

    Cellular quiescence is a reversible non-proliferating state. The reactivation of ‘sleep-like’ quiescent cells (e.g. fibroblasts, lymphocytes and stem cells) into proliferation is crucial for tissue repair and regeneration and a key to the growth, development and health of higher multicellular organisms, such as mammals. Quiescence has been a primarily phenotypic description (i.e. non-permanent cell cycle arrest) and poorly studied. However, contrary to the earlier thinking that quiescence is simply a passive and dormant state lacking proliferating activities, recent studies have revealed that cellular quiescence is actively maintained in the cell and that it corresponds to a collection of heterogeneous states. Recent modelling and experimental work have suggested that an Rb-E2F bistable switch plays a pivotal role in controlling the quiescence–proliferation balance and the heterogeneous quiescent states. Other quiescence regulatory activities may crosstalk with and impinge upon the Rb-E2F bistable switch, forming a gene network that controls the cells’ quiescent states and their dynamic transitions to proliferation in response to noisy environmental signals. Elucidating the dynamic control mechanisms underlying quiescence may lead to novel therapeutic strategies that re-establish normal quiescent states, in a variety of hyper- and hypo-proliferative diseases, including cancer and ageing. PMID:24904737

  12. Improvement of Cellular Uptake and Transfection Ability of pDNA Using α-Cyclodextrin-Polyamidoamine Conjugates as Gene Delivery System.

    PubMed

    Qin, Linghao; Cao, Duanwen; Huang, Huan; Ji, Gangjian; Feng, Min; Chen, Jianhai; Pan, Shirong

    2016-02-01

    Polyamidoamine (PAMAM) dendrimers are a class of unique nanomaterials which attracted attention because of their extraordinary properties, such as highly branched structure and types of terminal primary groups. In addition, development in PAMAM chemical modification has broadened its biological application especially for drug and gene delivery. In this study, PAMAMs are covalently conjugated onto α-Cyclodextrin (α-CD) via amide bonds obtaining the starburst cationic polymers (CD-PG2). The chemical structure and composition of CD-PG2 was characterized by IH NMR. Physicochemical and biological properties of CD-PG2/pDNA polyplex were evaluated by agarose gel retardation, stability test against DNasecñ, MTT assay, DLS measurement, CLSM observation, LDH leakage test, cellular uptake route analysis and in-vitro cell transfection. Results showed that CD-PG2 can efficiently condense pDNA into nanoscale particles with a narrow size distribution, and protect pDNA form DNase I degradation. Compared with free PEI-25K and commercial product Lipofectamine2000, CD-PG2 shows excellent gene transfection efficiency without serum interference as well as relatively low cytotoxicity. Cellular uptake of CD-PG2/pDNA polyplex is mainly through CME and CvME route and further investigations demonstrate that α-CD can regulate CvME pathway to improve polyplex transfection behavior. In conclusion, CD-PG2 can be considered as a versatile tool for gene delivery, especially for gene transfer in-vivo. PMID:27305760

  13. Cellular cardiomyoplasty A preliminary clinical report

    SciTech Connect

    Zhang Fumin; Gao Xiang; Yiang Zhijian; Ma Wenzhu; Li Chuanfu; Kao, Race L

    2003-03-01

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

  14. Prevalence of the CYP2D6*10 (C100T), *4 (G1846A), and *14 (G1758A) alleles among Iranians of different ethnicities.

    PubMed

    Bagheri, Ali; Kamalidehghan, Behnam; Haghshenas, Maryam; Azadfar, Parisa; Akbari, Leila; Sangtarash, Mohammad Hossein; Vejdandoust, Faramarz; Ahmadipour, Fatemeh; Meng, Goh Yong; Houshmand, Massoud

    2015-01-01

    The presence of polymorphisms in the CYP2D6 gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatment. Here, we compared the prevalence of the CYP2D6*10, *4, and 14* alleles in an Iranian population of different ethnicities with those of other populations. Allele and genotype frequency distributions of CYP2D6*10 variants and predicted phenotypes including extensive metabolizers, intermediate metabolizers, and poor metabolizers were analysed in blood samples of 300 unrelated healthy individuals in an Iranian population using polymerase chain reaction (PCR)-restriction fragment length polymorphism, PCR-single-strand conformation polymorphism, and direct genomic DNA sequencing. The CYP2D6*4 (G1846A) and *14 (G1758A) allelic frequencies were not detected in different ethnicities, demonstrating the absence of a significant contribution of these alleles in Iranian populations. However, the T/T, C/T, and C/C genotype frequencies of the CYP2D6*10 allele were significantly different (P<0.01) in all Iranian ethnic groups. Additionally, the frequency of the homozygous T/T variant of the CYP2D6*10 allele was significantly high in the Lure (P<0.017) and low in the Kurd (P<0.002) ethnicities. The frequency of the T/T variant of the CYP2D6*10 allele in central Iran was the highest (P<0.001), while the south of Iran had the lowest frequency (P<0.001). The frequency of the C/T variant of the CYP2D6*10 allele was significantly a bit high (P<0.001) in females compare to males, while the frequencies of the T/T variant in females is similar to males, which are 24.4% and 24.3%, respectively. In contrast to absence of the CYP2D6*4 (G1846A) and *14 (G1758A) alleles in Iranian populations of different ethnicities, the prediction of the CYP2D6*10 allele is required in drug research and routine treatment, where the information would be helpful for clinicians to optimize therapy or identify persons at risk of adverse drug reactions before

  15. The effects of consuming a high protein diet (4.4 g/kg/d) on body composition in resistance-trained individuals

    PubMed Central

    2014-01-01

    Background The consumption of dietary protein is important for resistance-trained individuals. It has been posited that intakes of 1.4 to 2.0 g/kg/day are needed for physically active individuals. Thus, the purpose of this investigation was to determine the effects of a very high protein diet (4.4 g/kg/d) on body composition in resistance-trained men and women. Methods Thirty healthy resistance-trained individuals participated in this study (mean ± SD; age: 24.1 ± 5.6 yr; height: 171.4 ± 8.8 cm; weight: 73.3 ± 11.5 kg). Subjects were randomly assigned to one of the following groups: Control (CON) or high protein (HP). The CON group was instructed to maintain the same training and dietary habits over the course of the 8 week study. The HP group was instructed to consume 4.4 grams of protein per kg body weight daily. They were also instructed to maintain the same training and dietary habits (e.g. maintain the same fat and carbohydrate intake). Body composition (Bod Pod®), training volume (i.e. volume load), and food intake were determined at baseline and over the 8 week treatment period. Results The HP group consumed significantly more protein and calories pre vs post (p < 0.05). Furthermore, the HP group consumed significantly more protein and calories than the CON (p < 0.05). The HP group consumed on average 307 ± 69 grams of protein compared to 138 ± 42 in the CON. When expressed per unit body weight, the HP group consumed 4.4 ± 0.8 g/kg/d of protein versus 1.8 ± 0.4 g/kg/d in the CON. There were no changes in training volume for either group. Moreover, there were no significant changes over time or between groups for body weight, fat mass, fat free mass, or percent body fat. Conclusions Consuming 5.5 times the recommended daily allowance of protein has no effect on body composition in resistance-trained individuals who otherwise maintain the same training regimen. This is the first interventional study to demonstrate that consuming a hypercaloric high

  16. Cellular Morphogenesis In Silico

    PubMed Central

    Shinbrot, Troy; Chun, Young; Caicedo-Carvajal, Carlos; Foty, Ramsey

    2009-01-01

    Abstract We describe a model that simulates spherical cells of different types that can migrate and interact either attractively or repulsively. We find that both expected morphologies and previously unreported patterns spontaneously self-assemble. Among the newly discovered patterns are a segmented state of alternating discs, and a “shish-kebab” state, in which one cell type forms a ring around a second type. We show that these unique states result from cellular attraction that increases with distance (e.g., as membranes stretch viscoelastically), and would not be seen in traditional, e.g., molecular, potentials that diminish with distance. Most of the states found computationally have been observed in vitro, and it remains to be established what role these self-assembled states may play in in vivo morphogenesis. PMID:19686642

  17. Investigation of a calcium-responsive contrast agent in cellular model systems: feasibility for use as a smart molecular probe in functional MRI.

    PubMed

    Angelovski, Goran; Gottschalk, Sven; Milošević, Milena; Engelmann, Jörn; Hagberg, Gisela E; Kadjane, Pascal; Andjus, Pavle; Logothetis, Nikos K

    2014-05-21

    Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca(2+) may allow tracking neuronal activity independent of brain vasculature, thus avoiding the characteristic limitations of current fMRI techniques. Here we report an in vitro proof-of-principle study with a Ca(2+)-sensitive, Gd(3+)-based SCA in an attempt to validate its potential use as a functional in vivo marker. First, we quantified its relaxometric response in a complex 3D cell culture model. Subsequently, we examined potential changes in the functionality of primary glial cells following administration of this SCA. Monitoring intracellular Ca(2+) showed that, despite a reduction in the Ca(2+) level, transport of Ca(2+) through the plasma membrane remained unaffected, while stimulation with ATP induced Ca(2+)-transients suggested normal cellular signaling in the presence of low millimolar SCA concentrations. SCAs merely lowered the intracellular Ca(2+) level. Finally, we estimated the longitudinal relaxation times (T1) for an idealized in vivo fMRI experiment with SCA, for extracellular Ca(2+) concentration level changes expected during intense neuronal activity which takes place upon repetitive stimulation. The values we obtained indicate changes in T1 of around 1-6%, sufficient to be robustly detectable using modern MRI methods in high field scanners. Our results encourage further attempts to develop even more potent SCAs and appropriate fMRI protocols. This would result in novel methods that allow monitoring of essential physiological processes at the cellular and molecular level. PMID:24712900

  18. Investigation of a Calcium-Responsive Contrast Agent in Cellular Model Systems: Feasibility for Use as a Smart Molecular Probe in Functional MRI

    PubMed Central

    2014-01-01

    Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca2+ may allow tracking neuronal activity independent of brain vasculature, thus avoiding the characteristic limitations of current fMRI techniques. Here we report an in vitro proof-of-principle study with a Ca2+-sensitive, Gd3+-based SCA in an attempt to validate its potential use as a functional in vivo marker. First, we quantified its relaxometric response in a complex 3D cell culture model. Subsequently, we examined potential changes in the functionality of primary glial cells following administration of this SCA. Monitoring intracellular Ca2+ showed that, despite a reduction in the Ca2+ level, transport of Ca2+ through the plasma membrane remained unaffected, while stimulation with ATP induced Ca2+-transients suggested normal cellular signaling in the presence of low millimolar SCA concentrations. SCAs merely lowered the intracellular Ca2+ level. Finally, we estimated the longitudinal relaxation times (T1) for an idealized in vivo fMRI experiment with SCA, for extracellular Ca2+ concentration level changes expected during intense neuronal activity which takes place upon repetitive stimulation. The values we obtained indicate changes in T1 of around 1–6%, sufficient to be robustly detectable using modern MRI methods in high field scanners. Our results encourage further attempts to develop even more potent SCAs and appropriate fMRI protocols. This would result in novel methods that allow monitoring of essential physiological processes at the cellular and molecular level. PMID:24712900

  19. Saturable absorption and two-photon absorption of 1,2,5-thiadiazolo[3,4-g]quinoxaline based derivatives with near-infrared fluorescence

    NASA Astrophysics Data System (ADS)

    Du, Yabing; Lin, Xiaodong; Jia, Tingjian; Dong, Jun

    2015-03-01

    Organic molecules with near-infrared (NIR) fluorescence are extremely interesting for the applications in nonlinear optical devices and bioimaging. However, such kind of materials have been relatively rarely studied. In this work, the nonlinear optical properties of 1,2,5-thiadiazolo[3,4-g]quinoxaline based derivatives with NIR fluorescence emission have been investigated for the first time. Under the excitation of femtosecond pulses at 532 nm, the chromophore with dithienyl as donor (TQ2) presents saturable absorption (SA) behavior, while no SA has been observed in the derivative with biphenyl (TQ1) as donor. Moreover, TQ2 exhibits much larger two-photon absorption (TPA) cross-sections with strong NIR fluorescence in the second biological window. The larger nonlinear optical properties of TQ2 is due to the introduction of stronger electron-donating group (dithienyl) and the resultant enhanced intramolecular charge transfer properties. At the end, TPA based optical limiting behaviors of the molecules are demonstrated in THF solutions, thanks to their large solubility and strong TPA.

  20. Facile synthesis of novel CaFe2O4/g-C3N4 nanocomposites for degradation of methylene blue under visible-light irradiation.

    PubMed

    Vadivel, S; Maruthamani, D; Habibi-Yangjeh, A; Paul, Bappi; Dhar, Siddhartha Sankar; Selvam, Kaliyamoorthy

    2016-10-15

    Hybrid organic/inorganic nanocomposites comprised of calcium ferrite (CaFe2O4) and graphitic carbon nitride (g-C3N4) were prepared via a simple two-step process. The hybridized CaFe2O4/g-C3N4 heterostructure was characterized by a variety of techniques, including X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FT-IR), UV-vis diffuse reflectance spectroscopy (UV-vis DRS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive analysis of X-rays (EDS), X-ray photoelectron spectroscopy (XPS), photoluminescence spectroscopy, electrochemical impedance spectroscopy (EIS), and photoelectrochemical studies. Photocatalytic activity of the prepared samples was evaluated against degradation of methylene blue (MB) under visible-light irradiation. The photocatalytic activity of CaFe2O4 30%/g-C3N4 nanocomposite, as optimum photocatalyst, for degradation of MB was superior to the pure CaFe2O4 and g-C3N4 samples. It was demonstrated that the photogenerated holes and superoxide ion radicals were the two main reactive species towards the photocatalytic degradation of MB over the nanocomposite. Based on the experimental results, a possible photocatalytic mechanism for the MB degradation over the nanocomposite was proposed. This work may provide some inspiration for the fabrication of spinel ferrites with efficient photocatalytic performance. PMID:27421115

  1. Very high penetrance and occurrence of Leber's hereditary optic neuropathy in a large Han Chinese pedigree carrying the ND4 G11778A mutation.

    PubMed

    Zhou, Xiangtian; Zhang, Hongxing; Zhao, Fuxin; Ji, Yanchun; Tong, Yi; Zhang, Juanjuan; Zhang, Yu; Yang, Li; Qian, Yaping; Lu, Fan; Qu, Jia; Guan, Min-Xin

    2010-08-01

    We report here the clinical, genetics and molecular characterization of a five-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON). Strikingly, this family exhibits very high penetrance and occurrence of optic neuropathy. In particular, 25 (10 males/15 females) of 30 matrilineal relatives exhibited the variable severity, ranging from profound to mild of visual impairment. This penetrance of optic neuropathy in this Chinese family is much higher than those in many families with LHON worldwide. The age-at-onset for visual impairment in matrilineal relatives in this Chinese family varied from 7 to 24years old, with the average of 15 years old. Furthermore, the ratio between affected male and female matrilineal relatives is 1:1.5 in the Chinese family. This observation is in contrast with the typical features in LHON pedigrees that there was predominance of affected males in LHON in many families from different ethnic origins. Molecular analysis of mitochondrial genome identified the known ND4 G11778A mutation and 51 variants, belonging to Asian haplogroup C4a1. The absence of other known secondary LHON-associated and functionally significant mtDNA mutations in this Chinese family suggested that mitochondrial variants may not play an important role in the phenotypic manifestation of the G11778A mutation in this Chinese family. Therefore, nuclear modifier gene(s) may be responsible for very high penetrance and occurrence of optic neuropathy in this Chinese pedigree.

  2. Cellular Automata Simulation for Wealth Distribution

    NASA Astrophysics Data System (ADS)

    Lo, Shih-Ching

    2009-08-01

    Wealth distribution of a country is a complicate system. A model, which is based on the Epstein & Axtell's "Sugars cape" model, is presented in Netlogo. The model considers the income, age, working opportunity and salary as control variables. There are still other variables should be considered while an artificial society is established. In this study, a more complicate cellular automata model for wealth distribution model is proposed. The effects of social welfare, tax, economical investment and inheritance are considered and simulated. According to the cellular automata simulation for wealth distribution, we will have a deep insight of financial policy of the government.

  3. Analysis of blocking rate and bandwidth usage of mobile IPTV services in wireless cellular networks.

    PubMed

    Li, Mingfu

    2014-01-01

    Mobile IPTV services over wireless cellular networks become more and more popular, owing to the significant growth in access bandwidth of wireless cellular networks such as 3G/4G and WiMAX. However, the spectrum resources of wireless cellular networks is rare. How to enhance the spectral efficiency of mobile networks becomes an important issue. Unicast, broadcast, and multicast are the most important transport schemes for offering mobile IPTV services over wireless cellular networks. Therefore, bandwidth usages and blocking rates of unicast, broadcast, and multicast IPTV services were analyzed and compared in this paper. Simulations were also conducted to validate the analytical results. Numerical results demonstrate that the presented analysis is correct, and multicast scheme achieves the best bandwidth usage and blocking rate performance, relative to the other two schemes. PMID:25379521

  4. Analysis of Blocking Rate and Bandwidth Usage of Mobile IPTV Services in Wireless Cellular Networks

    PubMed Central

    Li, Mingfu

    2014-01-01

    Mobile IPTV services over wireless cellular networks become more and more popular, owing to the significant growth in access bandwidth of wireless cellular networks such as 3G/4G and WiMAX. However, the spectrum resources of wireless cellular networks is rare. How to enhance the spectral efficiency of mobile networks becomes an important issue. Unicast, broadcast, and multicast are the most important transport schemes for offering mobile IPTV services over wireless cellular networks. Therefore, bandwidth usages and blocking rates of unicast, broadcast, and multicast IPTV services were analyzed and compared in this paper. Simulations were also conducted to validate the analytical results. Numerical results demonstrate that the presented analysis is correct, and multicast scheme achieves the best bandwidth usage and blocking rate performance, relative to the other two schemes. PMID:25379521

  5. Analysis of blocking rate and bandwidth usage of mobile IPTV services in wireless cellular networks.

    PubMed

    Li, Mingfu

    2014-01-01

    Mobile IPTV services over wireless cellular networks become more and more popular, owing to the significant growth in access bandwidth of wireless cellular networks such as 3G/4G and WiMAX. However, the spectrum resources of wireless cellular networks is rare. How to enhance the spectral efficiency of mobile networks becomes an important issue. Unicast, broadcast, and multicast are the most important transport schemes for offering mobile IPTV services over wireless cellular networks. Therefore, bandwidth usages and blocking rates of unicast, broadcast, and multicast IPTV services were analyzed and compared in this paper. Simulations were also conducted to validate the analytical results. Numerical results demonstrate that the presented analysis is correct, and multicast scheme achieves the best bandwidth usage and blocking rate performance, relative to the other two schemes.

  6. Coordination of autophagy with other cellular activities

    PubMed Central

    Wang, Yan; Qin, Zheng-hong

    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. PMID:23474706

  7. Cellular bioluminescence imaging.

    PubMed

    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.

  8. Molecular and cellular targets.

    PubMed

    Bode, Ann M; Dong, Zigang

    2006-06-01

    Carcinogenesis is a multistage process consisting of initiation, promotion, and progression stages and each stage may be a possible target for chemopreventive agents. A significant outcome of these investigations on the elucidation of molecular and cellular mechanisms is the explication of signal transduction pathways induced by tumor promoters in cancer development. The current belief today is that cancer may be prevented or treated by targeting specific cancer genes, signaling proteins, and transcription factors. The molecular mechanisms explaining how normal cells undergo neoplastic transformation induced by tumor promoters are rapidly being clarified. Accumulating research evidence suggests that many of dietary factors, including tea compounds, may be used alone or in combination with traditional chemotherapeutic agents to prevent or treat cancer. The potential advantage of many natural or dietary compounds seems to focus on their potent anticancer activity combined with low toxicity and very few adverse side effects. This review summarizes some of our recent work regarding the effects of the various tea components on signal transduction pathways involved in neoplastic cell transformation and carcinogenesis. PMID:16688728

  9. Molecular and Cellular Targets

    PubMed Central

    Bode, Ann M.; Dong, Zigang

    2008-01-01

    Carcinogenesis is a multistage process consisting of initiation, promotion and progression stages and each stage may be a possible target for chemopreventive agents. A significant outcome of these investigations on the elucidation of molecular and cellular mechanisms is the explication of signal transduction pathways induced by tumor promoters in cancer development. The current belief today is that cancer may be prevented or treated by targeting specific cancer genes, signaling proteins and transcription factors. The molecular mechanisms explaining how normal cells undergo neoplastic transformation induced by tumor promoters are rapidly being clarified. Accumulating research evidence suggests that many of dietary factors, including tea compounds, may be used alone or in combination with traditional chemotherapeutic agents to prevent or treat cancer. The potential advantage of many natural or dietary compounds seems to focus on their potent anticancer activity combined with low toxicity and very few adverse side effects. This review summarizes some of our recent work regarding the effects of the various tea components on signal transduction pathways involved in neoplastic cell transformation and carcinogenesis. PMID:16688728

  10. Cellular energy metabolism

    SciTech Connect

    Glaser, M.

    1991-06-01

    Studies have been carried out on adenylate kinase which is an important enzyme in determining the concentrations of the adenine nucleotides. An efficient method has been developed to clone mutant adenylate kinase genes in E. coli. Site-specific mutagenesis of the wild type gene also has been used to obtain forms of adenylate kinase with altered amino acids. The wild type and mutant forms of adenylate kinase have been overexpressed and large quantities were readily isolated. The kinetic and fluorescence properties of the different forms of adenylate kinase were characterized. This has led to a new model for the location of the AMP and ATP bindings sites on the enzyme and a proposal for the mechanism of substrate inhibition. Crystals of the wild type enzyme were obtained that diffract to at least 2.3 {angstrom} resolution. Experiments were also initiated to determine the function of adenylate kinase in vivo. In one set of experiments, E. coli strains with mutations in adenylate kinase showed large changes in cellular nucleotides after reaching the stationary phase in a low phosphate medium. This was caused by selective proteolytic degradation of the mutant adenylate kinase caused by phosphate starvation.

  11. Fundamental Limits to Cellular Sensing

    NASA Astrophysics Data System (ADS)

    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

  12. THICK DISKS OF EDGE-ON GALAXIES SEEN THROUGH THE SPITZER SURVEY OF STELLAR STRUCTURE IN GALAXIES (S{sup 4}G): LAIR OF MISSING BARYONS?

    SciTech Connect

    Comeron, Sebastien; Elmegreen, Bruce G.; Knapen, Johan H.; Salo, Heikki; Laine, Jarkko; Laurikainen, Eija; Athanassoula, E.; Bosma, Albert; Hinz, Joannah L.; De Paz, Armando Gil; Menendez-Delmestre, KarIn; Seibert, Mark; Ho, Luis C.; Elmegreen, Debra M.; Gadotti, Dimitri A.

    2011-11-01

    Most, if not all, disk galaxies have a thin (classical) disk and a thick disk. In most models thick disks are thought to be a necessary consequence of the disk formation and/or evolution of the galaxy. We present the results of a study of the thick disk properties in a sample of carefully selected edge-on galaxies with types ranging from T = 3 to T = 8. We fitted one-dimensional luminosity profiles with physically motivated functions-the solutions of two stellar and one gaseous isothermal coupled disks in equilibrium-which are likely to yield more accurate results than other functions used in previous studies. The images used for the fits come from the Spitzer Survey of Stellar Structure in Galaxies (S{sup 4}G). We found that thick disks are on average more massive than previously reported, mostly due to the selected fitting function. Typically, the thin and thick disks have similar masses. We also found that thick disks do not flare significantly within the observed range in galactocentric radii and that the ratio of thick-to-thin disk scale heights is higher for galaxies of earlier types. Our results tend to favor an in situ origin for most of the stars in the thick disk. In addition, the thick disk may contain a significant amount of stars coming from satellites accreted after the initial buildup of the galaxy and an extra fraction of stars coming from the secular heating of the thin disk by its own overdensities. Assigning thick disk light to the thin disk component may lead to an underestimate of the overall stellar mass in galaxies because of different mass-to-light ratios in the two disk components. On the basis of our new results, we estimate that disk stellar masses are between 10% and 50% higher than previously thought and we suggest that thick disks are a reservoir of 'local missing baryons'.

  13. A marker-derived gene network reveals the regulatory role of PPARGC1A, HNF4G, and FOXP3 in intramuscular fat deposition of beef cattle.

    PubMed

    Ramayo-Caldas, Y; Fortes, M R S; Hudson, N J; Porto-Neto, L R; Bolormaa, S; Barendse, W; Kelly, M; Moore, S S; Goddard, M E; Lehnert, S A; Reverter, A

    2014-07-01

    High intramuscular fat (IMF) awards price premiums to beef producers and is associated with meat quality and flavor. Studying gene interactions and pathways that affect IMF might unveil causative physiological mechanisms and inform genomic selection, leading to increased accuracy of predictions of breeding value. To study gene interactions and pathways, a gene network was derived from genetic markers associated with direct measures of IMF, other fat phenotypes, feedlot performance, and a number of meat quality traits relating to body conformation, development, and metabolism that might be plausibly expected to interact with IMF biology. Marker associations were inferred from genomewide association studies (GWAS) based on high density genotypes and 29 traits measured on 10,181 beef cattle animals from 3 breed types. For the network inference, SNP pairs were assessed according to the strength of the correlation between their additive association effects across the 29 traits. The co-association inferred network was formed by 2,434 genes connected by 28,283 edges. Topological network parameters suggested a highly cohesive network, in which the genes are strongly functionally interconnected. Pathway and network analyses pointed towards a trio of transcription factors (TF) as key regulators of carcass IMF: PPARGC1A, HNF4G, and FOXP3. Importantly, none of these genes would have been deemed as significantly associated with IMF from the GWAS. Instead, a total of 313 network genes show significant co-association with the 3 TF. These genes belong to a wide variety of biological functions, canonical pathways, and genetic networks linked to IMF-related phenotypes. In summary, our GWAS and network predictions are supported by the current literature and suggest a cooperative role for the 3 TF and other interacting genes including CAPN6, STC2, MAP2K4, EYA1, COPS5, XKR4, NR2E1, TOX, ATF1, ASPH, TGS1, and TTPA as modulators of carcass and meat quality traits in beef cattle.

  14. THE GALEX/S{sup 4}G UV–IR COLOR–COLOR DIAGRAM: CATCHING SPIRAL GALAXIES AWAY FROM THE BLUE SEQUENCE

    SciTech Connect

    Bouquin, Alexandre Y. K.; Gil de Paz, Armando; Gallego, Jesús; Boissier, Samuel; Muñoz-Mateos, Juan-Carlos; Sheth, Kartik; Laine, Jarkko; Peletier, Reynier F.; Röck, Benjamin R.; Knapen, Johan H.

    2015-02-10

    We obtained GALEX FUV, NUV, and Spitzer/IRAC 3.6 μm photometry for >2000 galaxies, available for 90% of the S{sup 4}G sample. We find a very tight GALEX blue sequence (GBS) in the (FUV–NUV) versus (NUV–[3.6]) color–color diagram, which is populated by irregular and spiral galaxies, and is mainly driven by changes in the formation timescale (τ) and a degeneracy between τ and dust reddening. The tightness of the GBS provides an unprecedented way of identifying star-forming galaxies and objects that are just evolving to (or from) what we call the GALEX green valley (GGV). At the red end of the GBS, at (NUV–[3.6]) > 5, we find a wider GALEX red sequence (GRS) mostly populated by E/S0 galaxies that has a perpendicular slope to that of the GBS and of the optical red sequence. We find no such dichotomy in terms of stellar mass (measured by M{sub [3.6]}) since both massive (M{sub ⋆}>10{sup 11}M{sub ⊙}) blue- and red-sequence galaxies are identified. The type that is proportionally more often found in the GGV is the S0-Sa’s, and most of these are located in high-density environments. We discuss evolutionary models of galaxies that show a rapid transition from the blue to the red sequence on a timescale of 10{sup 8} yr.

  15. Identification of Vibrio vulnificus by cellular fatty acid composition using the Hewlett-Packard 5898A Microbial Identification System: collaborative study.

    PubMed

    Landry, W L

    1994-01-01

    A gas chromatographic method using a capillary column for rapid identification of Vibrio vulnificus was examined in a collaborative study. Identifications were performed by analysis of cellular fatty acid profiles which were automatically searched against reference profiles stored in a computer-generated library. Each of the 13 collaborators was sent 15 unknown isolates, which included 10 V. vulnificus isolates and 5 negative control isolates. Each collaborator was furnished with a computer-generated library, developed by the Dallas U.S. Food and Drug Administration laboratory, which contained entries for V. vulnificus, V. cholerae, V. fluvialis, V. parahaemolyticus, V. mimicus, and Aeromonas hydrophila. Of the 195 isolates sent to the collaborators, results for 190 isolates were received. The other 5 isolates were nonviable before analyses began. Of the 126 V. vulnificus isolates analyzed, 118 (93.7%) were correctly identified. Of the 65 negative control isolates sent, one was nonviable, one was misidentified as V. vulnificus, and 2 were misidentified as V. parahaemolyticus. Of the 64 negative controls analyzed, 95.3% were correctly identified. Statistical analysis shows a sensitivity rate of 0.872, specificity rate of 0.982, false positive rate of 0.010, and false negative rate of 0.206. The gas chromatographic method for identification of Vibrio vulnificus by microbial fatty acid profile has been adopted first action by AOAC INTERNATIONAL.

  16. A cellular system for quantitation of vitamin K cycle activity: structure-activity effects on vitamin K antagonism by warfarin metabolites

    PubMed Central

    Haque, Jamil A.; McDonald, Matthew G.; Kulman, John D.

    2014-01-01

    Warfarin and other 4-hydroxycoumarins inhibit vitamin K epoxide reductase (VKOR) by depleting reduced vitamin K that is required for posttranslational modification of vitamin K–dependent clotting factors. In vitro prediction of the in vivo potency of vitamin K antagonists is complicated by the complex multicomponent nature of the vitamin K cycle. Here we describe a sensitive assay that enables quantitative analysis of γ-glutamyl carboxylation and its antagonism in live cells. We engineered a human embryonic kidney (HEK) 293–derived cell line (HEK 293-C3) to express a chimeric protein (F9CH) comprising the Gla domain of factor IX fused to the transmembrane and cytoplasmic regions of proline-rich Gla protein 2. Maximal γ-glutamyl carboxylation of F9CH required vitamin K supplementation, and was dose-dependently inhibited by racemic warfarin at a physiologically relevant concentration. Cellular γ-glutamyl carboxylation also exhibited differential VKOR inhibition by warfarin enantiomers (S > R) consistent with their in vivo potencies. We further analyzed the structure-activity relationship for inhibition of γ-glutamyl carboxylation by warfarin metabolites, observing tolerance to phenolic substitution at the C-5 and especially C-6, but not C-7 or C-8, positions on the 4-hydroxycoumarin nucleus. After correction for in vivo concentration and protein binding, 10-hydroxywarfarin and warfarin alcohols were predicted to be the most potent inhibitory metabolites in vivo. PMID:24297869

  17. Cellular iron metabolism.

    PubMed

    Ponka, P

    1999-03-01

    Iron is essential for oxidation-reduction catalysis and bioenergetics, but unless appropriately shielded, iron plays a key role in the formation of toxic oxygen radicals that can attack all biological molecules. Hence, specialized molecules for the acquisition, transport (transferrin), and storage (ferritin) of iron in a soluble nontoxic form have evolved. Delivery of iron to most cells, probably including those of the kidney, occurs following the binding of transferrin to transferrin receptors on the cell membrane. The transferrin-receptor complexes are then internalized by endocytosis, and iron is released from transferrin by a process involving endosomal acidification. Cellular iron storage and uptake are coordinately regulated post-transcriptionally by cytoplasmic factors, iron-regulatory proteins 1 and 2 (IRP-1 and IRP-2). Under conditions of limited iron supply, IRP binding to iron-responsive elements (present in 5' untranslated region of ferritin mRNA and 3' untranslated region of transferrin receptor mRNA) blocks ferritin mRNA translation and stabilizes transferrin receptor mRNA. The opposite scenario develops when iron in the transit pool is plentiful. Moreover, IRP activities/levels can be affected by various forms of "oxidative stress" and nitric oxide. The kidney also requires iron for metabolic processes, and it is likely that iron deficiency or excess can cause disturbed function of kidney cells. Transferrin receptors are not evenly distributed throughout the kidney, and there is a cortical-to-medullary gradient in heme biosynthesis, with greatest activity in the cortex and least in the medulla. This suggests that there are unique iron/heme metabolism features in some kidney cells, but the specific aspects of iron and heme metabolism in the kidney are yet to be explained.

  18. Primary intranodal cellular angiolipoma.

    PubMed

    Kazakov, Dmitry V; Hes, Ondrej; Hora, Milan; Sima, Radek; Michal, Michal

    2005-01-01

    Angiolipoma is a distinct, benign soft tissue tumor that most commonly occurs in young males as multiple small, subcutaneous, tender to painful nodules with predilection for the forearms. We report a case of angiolipoma that developed within a lymph node. The patient was a 67-year-old man who underwent radical retropubic prostatectomy with diagnostic pelvic lymphadenectomy because of adenocarcinoma of the prostate. The prostate and 3 lymph nodes located in the obturator fossa were removed. On gross examination, the cut surface of 1 of the lymph nodes revealed an 8 x 5 mm, ovoid, sharply demarcated, nonencapsulated, gray lesion being suspicious for adenocarcinoma metastasis. Microscopically, the major portion of the lymph node was replaced by mature metaplastic adipose tissue. The angiolipoma was seen as a well-demarcated, nonencapsulated lesion composed of numerous small blood vessels lined by monomorphous flattened or spindled endothelial cells. Many vascular lumina were filled with fibrin thrombi. There were scanty mature adipocytes. Focally, areas with increased cellularity and a suggestion of solid growth of the endothelial cells were seen. Lymph nodes are known to be a rare primary site of various tumors usually occurring in other organs. The knowledge of these tumors is important in order not to interpret them as metastatic lesions. The most recognized examples are pigmented nevi, palisading myofibroblastoma, various benign epithelial inclusions, serous cystic tumors of borderline malignancy, and hyperplastic mesothelial inclusions. As we present in this report, angiolipoma is another neoplasm whose primary occurrence in the lymph node should not be misinterpreted as a metastatic tumor or malignant vascular tumor.

  19. Cellular mechanisms in the actions of antiglaucoma drugs.

    PubMed

    Yorio, T

    1985-01-01

    There are several classes of drugs currently in use for the therapeutic management of the glaucomas. Although the ocular hypotensive effects of these agents have been well characterized and described, little is known of their site of action and cellular mechanism. This review attempts to describe those cellular mechanisms that may be linked to the actions of several classes of antiglaucoma drugs. Special emphasis was placed on drug actions and 1) the adenylate cyclase system; 2) receptor-coupled phosphoinositide turnover; 3) prostaglandins and 4) ion transport processes. Models are presented depicting proposed cellular sites of the interaction of the antiglaucoma drugs with these cellular processes.

  20. Phase separation and the formation of cellular bodies

    NASA Astrophysics Data System (ADS)

    Xu, Bin; Broedersz, Chase P.; Meir, Yigal; Wingreen, Ned S.

    Cellular bodies in eukaryotic cells spontaneously assemble to form cellular compartments. Among other functions, these bodies carry out essential biochemical reactions. Cellular bodies form micron-sized structures, which, unlike canonical cell organelles, are not surrounded by membranes. A recent in vitro experiment has shown that phase separation of polymers in solution can explain the formation of cellular bodies. We constructed a lattice-polymer model to capture the essential mechanism leading to this phase separation. We used both analytical and numerical tools to predict the phase diagram of a system of two interacting polymers, including the concentration of each polymer type in the condensed and dilute phase.

  1. Cellular noise and information transmission.

    PubMed

    Levchenko, Andre; Nemenman, Ilya

    2014-08-01

    The technological revolution in biological research, and in particular the use of molecular fluorescent labels, has allowed investigation of heterogeneity of cellular responses to stimuli on the single cell level. Computational, theoretical, and synthetic biology advances have allowed predicting and manipulating this heterogeneity with an exquisite precision previously reserved only for physical sciences. Functionally, this cell-to-cell variability can compromise cellular responses to environmental signals, and it can also enlarge the repertoire of possible cellular responses and hence increase the adaptive nature of cellular behaviors. And yet quantification of the functional importance of this response heterogeneity remained elusive. Recently the mathematical language of information theory has been proposed to address this problem. This opinion reviews the recent advances and discusses the broader implications of using information-theoretic tools to characterize heterogeneity of cellular behaviors.

  2. Cellular lifespan and senescence: a complex balance between multiple cellular pathways.

    PubMed

    Dolivo, David; Hernandez, Sarah; Dominko, Tanja

    2016-07-01

    The study of cellular senescence and proliferative lifespan is becoming increasingly important because of the promises of autologous cell therapy, the need for model systems for tissue disease and the implication of senescent cell phenotypes in organismal disease states such as sarcopenia, diabetes and various cancers, among others. Here, we explain the concepts of proliferative cellular lifespan and cellular senescence, and we present factors that have been shown to mediate cellular lifespan positively or negatively. We review much recent literature and present potential molecular mechanisms by which lifespan mediation occurs, drawing from the fields of telomere biology, metabolism, NAD(+) and sirtuin biology, growth factor signaling and oxygen and antioxidants. We conclude that cellular lifespan and senescence are complex concepts that are governed by multiple independent and interdependent pathways, and that greater understanding of these pathways, their interactions and their convergence upon specific cellular phenotypes may lead to viable therapies for tissue regeneration and treatment of age-related pathologies, which are caused by or exacerbated by senescent cells in vivo.

  3. Cellular lifespan and senescence: a complex balance between multiple cellular pathways.

    PubMed

    Dolivo, David; Hernandez, Sarah; Dominko, Tanja

    2016-07-01

    The study of cellular senescence and proliferative lifespan is becoming increasingly important because of the promises of autologous cell therapy, the need for model systems for tissue disease and the implication of senescent cell phenotypes in organismal disease states such as sarcopenia, diabetes and various cancers, among others. Here, we explain the concepts of proliferative cellular lifespan and cellular senescence, and we present factors that have been shown to mediate cellular lifespan positively or negatively. We review much recent literature and present potential molecular mechanisms by which lifespan mediation occurs, drawing from the fields of telomere biology, metabolism, NAD(+) and sirtuin biology, growth factor signaling and oxygen and antioxidants. We conclude that cellular lifespan and senescence are complex concepts that are governed by multiple independent and interdependent pathways, and that greater understanding of these pathways, their interactions and their convergence upon specific cellular phenotypes may lead to viable therapies for tissue regeneration and treatment of age-related pathologies, which are caused by or exacerbated by senescent cells in vivo. PMID:27417120

  4. SELF-ORGANIZED CRITICALITY AND CELLULAR AUTOMATA

    SciTech Connect

    CREUTZ,M.

    2007-01-01

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

  5. Long-term administration of 4G-beta-D-galactosylsucrose (lactosucrose) enhances intestinal calcium absorption in young women: a randomized, placebo-controlled 96-wk study.

    PubMed

    Teramoto, Fusako; Rokutan, Kazuhito; Sugano, Yasuko; Oku, Kazuyuki; Kishino, Eriko; Fujita, Koki; Hara, Kozo; Kishi, Kyouichi; Fukunaga, Masao; Morita, Tetsuro

    2006-10-01

    This study determined the effect of long-term administration of 4(G)-beta-D-galactosylsucrose (lactosucrose; LS) on intestinal calcium absorption. In a randomized, single-blind, parallel-group study, LS (n=9, 6.0 g twice daily) or a placebo (maltose; n=8, 6.0 g twice daily) was administered to healthy young women for 92 wk: the study also included a 4-wk post-administration period. All participants completed the study. Dietary nutrient intake; fecal weight, pH, and moisture content; fecal concentrations of short-chain fatty acids (SCFA), putrefactive products, ammonia, and minerals (calcium, magnesium, phosphorus, and iron); and serum calcium and osteocalcin concentrations were measured every 24 wk. Urinary pyridinoline (PYR) and deoxypyridinoline (DPD), and urinary calcium excretion were measured every 12 wk. Significant effects of oligosaccharide treatment, time, and the interaction between oligosaccharide treatment and time were observed for fecal pH, SCFA, ammonia, and putrefactive product values (p<0.05). Fecal pH, ammonia, and putrefactive product values decreased in the LS group, and the fecal SCFA concentration significantly increased during the administration period; these changes were not observed 4 wk post-administration. To examine the mineral balance of calcium, magnesium, and phosphorus in detail, all the participants completed a 6-d mineral balance study, sometime between week 56 and 60 of the longer study. During the mineral balance study, the daily calcium intake was set at 400 mg; all feces and urine were collected each day for 6 d after an 8-d acclimation period. In the balance study, fecal calcium excretion was significantly lower in the LS group than in the placebo group (p<0.05), and apparent calcium absorption and retention, apparent magnesium and phosphorus absorption, and magnesium retention were significantly higher in the LS group than in the placebo group (p<0.05). Our results suggest that the administration of LS produces a long

  6. Cellular adhesion, proliferation and viability on conducting polymer substrates.

    PubMed

    del Valle, Luis J; Estrany, Francesc; Armelin, Elaine; Oliver, Ramón; Alemán, Carlos

    2008-12-01

    This work reports a comprehensive study about cell adhesion and proliferation on the surface of different electroactive substrates formed by pi-conjugated polymers. Biological assays were performed considering four different cellular lines: two epithelial and two fibroblasts. On the other hand, the electroactivity of the three conducting systems was determined in physiological conditions. Results indicate that the three substrates behave as a cellular matrix, even though compatibility with cells is larger for PPy and the 3-layered system. Furthermore, the three polymeric systems are electro-compatible with the cellular monolayers. PMID:18683167

  7. Peptide-mediated cellular delivery of semiconductor quantum dots

    NASA Astrophysics Data System (ADS)

    Gemmill, Kelly Boeneman; Muttenthaler, Markus; Delehanty, James; Deschamps, Jeff; Susumu, Kimihiro; Stewart, Michael; Dawson, Philip; Huston, Alan; Medintz, Igor

    2013-05-01

    CdSe/ZnS semiconductor quantum dots (QDs) are ideal materials for biological sensing and cellular imaging applications due to their superior photophysical properties in comparison to fluorescent proteins or dyes and their ease of conjugation to biological materials. We have previously developed a number of in vitro FRET based biosensors in the laboratory for detection of proteases and biological and chemical agents. We would like to expand these biosensing capabilities into cellular systems, requiring development of QD cellular delivery techniques. Peptide mediated cellular delivery of QDs is ideal as peptides are small, easily conjugated to QDs, easily manipulated and synthesized, and can be designed with "handles" for further chemical conjugation with other cargo. Here we discuss four cell delivery peptides that facilitate QD uptake in live cells. Understanding these peptides will help us design better nanoparticle cellular delivery systems and advance our capabilities for in vivo biosensing.

  8. Integrated adaptive optics optical coherence tomography and adaptive optics scanning laser ophthalmoscope system for simultaneous cellular resolution in vivo retinal imaging.

    PubMed

    Zawadzki, Robert J; Jones, Steven M; Pilli, Suman; Balderas-Mata, Sandra; Kim, Dae Yu; Olivier, Scot S; Werner, John S

    2011-06-01

    We describe an ultrahigh-resolution (UHR) retinal imaging system that combines adaptive optics Fourier-domain optical coherence tomography (AO-OCT) with an adaptive optics scanning laser ophthalmoscope (AO-SLO) to allow simultaneous data acquisition by the two modalities. The AO-SLO subsystem was integrated into the previously described AO-UHR OCT instrument with minimal changes to the latter. This was done in order to ensure optimal performance and image quality of the AO- UHR OCT. In this design both imaging modalities share most of the optical components including a common AO-subsystem and vertical scanner. One of the benefits of combining Fd-OCT with SLO includes automatic co-registration between two acquisition channels for direct comparison between retinal structures imaged by both modalities (e.g., photoreceptor mosaics or microvasculature maps). Because of differences in the detection scheme of the two systems, this dual imaging modality instrument can provide insight into retinal morphology and potentially function, that could not be accessed easily by a single system. In this paper we describe details of the components and parameters of the combined instrument, including incorporation of a novel membrane magnetic deformable mirror with increased stroke and actuator count used as a single wavefront corrector. We also discuss laser safety calculations for this multimodal system. Finally, retinal images acquired in vivo with this system are presented.

  9. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension

    PubMed Central

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A.; Castillo, Andrés E.; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E.; Kalergis, Alexis M.

    2016-01-01

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage. PMID:27347925

  10. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension.

    PubMed

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A; Castillo, Andrés E; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E; Kalergis, Alexis M

    2016-06-23

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage.

  11. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension.

    PubMed

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A; Castillo, Andrés E; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E; Kalergis, Alexis M

    2016-01-01

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage. PMID:27347925

  12. Survey of cellular radiosensitivity parameters.

    PubMed

    Katz, R; Zachariah, R; Cucinotta, F A; Zhang, C

    1994-12-01

    A model of the formation of particle tracks in emulsion has been extended through the use of biological target theory to formulate a theory of the response of biological cells and molecules of biological importance to irradiation with energetic heavy ions. For this purpose the response to gamma rays is represented by the single-hit, multitarget model with parameters m and D0, while additional parameters kappa (or a0) and sigma 0 are required to represent the size of internal cellular targets and the effective cross-sectional area of the cell nucleus, respectively, for heavy-ion bombardments. For one-or-more-hit detectors, only the first three of these parameters are required and m = 1. For cells m is typically 2 or more. The model is developed from the concept that response to secondary electrons follows the same functional form for gamma rays and for the gamma rays surrounding an ion's path. Originally applied to dry enzymes and viruses in 1967, the model of the one-hit detector has been extended to emulsions, to other physical and chemical detectors, to single- and double-strand breaks in DNA in EO buffer and to three E. coli strains. The two-hit response has been observed for "track core" effects in radiation chemistry, for supralinearity in thermoluminescent dosimeters and for desensitized nuclear emulsions, where hit numbers up to 6 have been observed. In its extension to biological cells, additional concepts are required relating to the character of the track, namely the grain-count and track-width regimes, and to the ability o