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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. [PAL-1 5G/4G polymorphism in patients with systemic lupus erythematosus].

    PubMed

    Savov, A; Andonova, S; Tanev, D; Robeva, R; Marincheva, Ts; Tomova, A; Kumanov, Ph; Rashkov, R; Kolarov, Zl

    2014-01-01

    Systemic lupus erythematosus (SLE) is a connective tissue disease affecting predominantly women that has been widely associated with obstetric complications. Inherited thrombophilias are significant risk factors for pregnancy loss, but their role in patients with SLE, and especially in those without concomitant secondary antiphospholipid syndrome (APS) has not been clarified. The aim of the present study was to study PAI-1 5G/4G polymorphism in women with lupus. A total of 103 SLE patients as well as 69 healthy volunteers were genotyped for PAI-1 5G/4G (rs1799889). No significant differences in the PAI-1 5G/4G genotype prevalence between patients and controls were found. After exclusion of the women with secondary APS, the frequency of pregnancies and spontaneous abortions, as well as the number of live births were similar in the studied patients with different PAI-1 genotype (p> 0.05). PAI-1 5G/4G polymorphism was not significantly related to any of the lupus ACR criteria or disease activity (p > 0.05), but it could influence the platelet number in the studied patients (263.52 ± 91.10 [5G/5G genotype] versus 210.12 ± 71.79 [4G/4G genotype], p = 0.023). In conclusion, our results showed that PAI-1 4G/5G polymorphism did not worsen the reproductive outcome in SLE women without secondary APS.

  3. 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

  4. RoXaN, a Novel Cellular Protein Containing TPR, LD, and Zinc Finger Motifs, Forms a Ternary Complex with Eukaryotic Initiation Factor 4G and Rotavirus NSP3

    PubMed Central

    Vitour, Damien; Lindenbaum, Pierre; Vende, Patrice; Becker, Michelle M.; Poncet, Didier

    2004-01-01

    Rotavirus mRNAs are capped but not polyadenylated, and viral proteins are translated by the cellular translation machinery. This is accomplished through the action of the viral nonstructural protein NSP3, which specifically binds the 3′ consensus sequence of viral mRNAs and interacts with the eukaryotic translation initiation factor eIF4G I. To further our understanding of the role of NSP3 in rotavirus replication, we looked for other cellular proteins capable of interacting with this viral protein. Using the yeast two-hybrid assay, we identified a novel cellular protein-binding partner for rotavirus NSP3. This 110-kDa cellular protein, named RoXaN (rotavirus X protein associated with NSP3), contains a minimum of three regions predicted to be involved in protein-protein or nucleic acid-protein interactions. A tetratricopeptide repeat region, a protein-protein interaction domain most often found in multiprotein complexes, is present in the amino-terminal region. In the carboxy terminus, at least five zinc finger motifs are observed, further suggesting the capacity of RoXaN to bind other proteins or nucleic acids. Between these two regions exists a paxillin leucine-aspartate repeat (LD) motif which is involved in protein-protein interactions. RoXaN is capable of interacting with NSP3 in vivo and during rotavirus infection. Domains of interaction were mapped and correspond to the dimerization domain of NSP3 (amino acids 163 to 237) and the LD domain of RoXaN (amino acids 244 to 341). The interaction between NSP3 and RoXaN does not impair the interaction between NSP3 and eIF4G I, and a ternary complex made of NSP3, RoXaN, and eIF4G I can be detected in rotavirus-infected cells, implicating RoXaN in translation regulation. PMID:15047801

  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. 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.

  7. Integrating 4G Optics (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Tabiryan, Nelson V.; Hwang, Jeoungyeon; Steeves, Diane M.; Kimball, Brian R.; Bunning, Timothy J.; White, Timothy J.

    2016-09-01

    The thickness of functional layers in liquid crystal photonics devices is negligibly small compared to the substrates. New opportunities provided by multilayer 4G optical systems require minimizing the thickness of each layer. We report about our progress made by developing technology of thin flexible substrates, functional polymer films, solid electro-optical layers, and graphene oxide based electro-conductive coatings.

  8. 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.

  9. Cellular systems for epithelial invagination

    PubMed Central

    2017-01-01

    Epithelial invagination is a fundamental module of morphogenesis that iteratively occurs to generate the architecture of many parts of a developing organism. By changing the physical properties such as the shape and/or position of a population of cells, invagination drives processes ranging from reconfiguring the entire body axis during gastrulation, to forming the primordia of the eyes, ears and multiple ducts and glands, during organogenesis. The epithelial bending required for invagination is achieved through a variety of mechanisms involving systems of cells. Here we provide an overview of the different mechanisms, some of which can work in combination, and outline the circumstances in which they apply. This article is part of the themed issue ‘Systems morphodynamics: understanding the development of tissue hardware’. PMID:28348256

  10. 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.

  11. 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.

  12. 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.

  13. [Division of regulatory cellular systems (Lvov)].

    PubMed

    Kusen', S I

    1995-01-01

    Two departments of the A. V. Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine were founded in 1969 in Lviv. These were: the Department of Biochemistry of Cell Differentiation headed by Professor S. I. Kusen and Department of Regulation of Cellular Synthesis of Low Molecular Weight Compounds headed by Professor G. M. Shavlovsky. The Lviv Division of the A. V. Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine with Professor S. I. Kusen as its chief, was founded in 1974 on the basis of these departments and the Laboratory of Modelling of Regulatory Cellular Systems headed by Professor M. P. Derkach. The above mentioned laboratory which was not the structural unit obtained the status of Structural Laboratory of Cellular Biophysics in 1982 and was headed by O. A. Goida, Candidate of biological sciences. From 1983 the Laboratory of Correcting Therapy of Malignant Tumors and Hemoblastoses at the Institute of Molecular Biology and Genetics, Academy of Sciences of Ukraine (Chief--S. V. Ivasivka, Candidate of medical sciences) was included in the structure of the Division. That Laboratory was soon transformed into the Department of Carbohydrate Metabolism Regulation headed by Professor I. D. Holovatsky. In 1988 this Department was renamed into the Department of Glycoprotein Biochemistry and headed by M. D. Lutsik, Doctor of biological sciences. In 1982 one more Laboratory of Biochemical Genetics was founded at the Department of Regulation of Cellular Synthesis of Low Molecular Weight Compounds, in 1988 it was transformed into the Department of Biochemical Genetics (Chief--Professor A. A. Sibirny). In 1989 the Laboratory of Anion Transport was taken from A. V. Palladin Institute of Biochemistry, Academy of Sciences of Ukraine to Lviv Division of this Institute. This laboratory was headed by Professor M. M. Veliky. One more reorganization in the Division structure took place in 1994. The Department of

  14. Fluorescent sensing of fluoride in cellular system.

    PubMed

    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

  15. 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

  16. 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

  17. 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.

  18. Myoblast fusion: Experimental systems and cellular mechanisms.

    PubMed

    Schejter, Eyal D

    2016-12-01

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

  19. Modems for emerging digital cellular-mobile radio system

    NASA Technical Reports Server (NTRS)

    Feher, Kamilo

    1991-01-01

    Digital modem techniques for emerging digital cellular telecommunications-mobile radio system applications are described and analyzed. In particular, theoretical performance, experimental results, principles of operation, and various architectures of pi/4-QPSK (pi/4-shifted coherent or differential QPSK) modems for second-generation US digital cellular radio system applications are presented. The spectral/power efficiency and performance of the pi/4-QPSK modems (American and Japanese digital cellular emerging standards) are studied and briefly compared to GMSK (Gaussian minimum-shift keying) modems (proposed for European DECT and GSM cellular standards). Improved filtering strategies and digital pilot-aided (digital channel sounding) techniques are also considered for pi/4-QPSK and other digital modems. These techniques could significantly improve the performance of digital cellular and other digital land mobile and satellite mobile radio systems. More spectrally efficient modem trends for future cellular/mobile (land mobile) and satellite communication systems applications are also highlighted.

  20. Modems for emerging digital cellular-mobile radio system

    NASA Astrophysics Data System (ADS)

    Feher, Kamilo

    1991-05-01

    Digital modem techniques for emerging digital cellular telecommunications-mobile radio system applications are described and analyzed. In particular, theoretical performance, experimental results, principles of operation, and various architectures of pi/4-QPSK (pi/4-shifted coherent or differential QPSK) modems for second-generation US digital cellular radio system applications are presented. The spectral/power efficiency and performance of the pi/4-QPSK modems (American and Japanese digital cellular emerging standards) are studied and briefly compared to GMSK (Gaussian minimum-shift keying) modems (proposed for European DECT and GSM cellular standards). Improved filtering strategies and digital pilot-aided (digital channel sounding) techniques are also considered for pi/4-QPSK and other digital modems. These techniques could significantly improve the performance of digital cellular and other digital land mobile and satellite mobile radio systems. More spectrally efficient modem trends for future cellular/mobile (land mobile) and satellite communication systems applications are also highlighted.

  1. Loss-of-function analysis reveals distinct requirements of the translation initiation factors eIF4E, eIF4E-3, eIF4G and eIF4G2 in Drosophila spermatogenesis.

    PubMed

    Ghosh, Sanjay; Lasko, Paul

    2015-01-01

    In eukaryotes, post-transcriptional regulation of gene expression has a key role in many cellular and developmental processes. Spermatogenesis involves a complex developmental program that includes changes in cell cycle dynamics and dramatic cellular remodeling. Translational control is critical for spermatogenesis in Drosophila as many mRNAs synthesized in the spermatocytes are translated only much later during spermatid differentiation. Testes-specific translation initiation factors eIF4E-3 and eIF4G2 are essential specifically for male fertility. However, details of their roles during different stages of spermatogenesis are unknown, and the role of canonical translation initiation factors in spermatogenesis remains unexplored. In this study, we addressed the functional role of eIF4E-1, eIF4E-3, eIF4G and eIF4G2 in testes development and formation of mature sperm. Using the UAS-Gal4 system and RNA interference, we systematically knocked down these four genes in different stages of germ cell development, and in the somatic cells. Our results show that eIF4E-1 function in early germ cells and the surrounding somatic cells is critical for spermatogenesis. Both eIF4E-1 and eIF4E-3 are required in spermatocytes for chromosome condensation and cytokinesis during the meiotic stages. Interestingly, we find that eIF4G knockdown did not affect male fertility while eIF4G2 has distinct functions during spermatogenesis; it is required in early germ cells for proper meiotic divisions and spermatid elongation while its abrogation in spermatocytes caused meiotic arrest. Double knockdown of eIF4G and eIF4G2 shows that these proteins act redundantly during the early stages of spermatogenesis. Taken together, our analysis reveals spatio-temporal roles of the canonical and testes-specific translation initiation factors in coordinating developmental programs during spermatogenesis.

  2. Bio-inspired self-organizing cellular systems.

    PubMed

    Stauffer, André; Mange, Daniel; Rossier, Joël; Vannel, Fabien

    2008-01-01

    Bio-inspiration borrows three properties characteristic of living organisms: multicellular architecture, cellular division, and cellular differentiation. Implemented in silicon according to these properties, our self-organizing systems are able to grow, to self-replicate, and to self-repair. The growth and branching processes, performed by the so-called Tom Thumb algorithm, lead thus to the configuration and cloning mechanisms of the systems. The repair processes allow its cicatrization and regeneration mechanisms. The cellular design and hardware implementation of these mechanisms constitute the core of this paper.

  3. Development of a Disaster Information Collection System using Cellular Phone

    NASA Astrophysics Data System (ADS)

    Jeong, Byeong-Pyo; Zama, Shinsaku; Takizawa, Osamu; Endo, Makoto; Shibayama, Akihiro

    We have developed a prototype of Disaster Information Collection System using Cellular Phone that can be used under the communication congestion after a large earthquake. The person in charge of responses can easily store disaster information such as image, characters and location in a memory card of a cellular phone. We performed the field experiment on usability and simulating disaster information collection with ordinary citizen in Takamastu city, Kagawa Prefecture. Using the system using Cellular Phone, people could easily input such as public telephones, banks, mailboxes searched on their ways.

  4. 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.

  5. Cellular monitoring systems for the assessment of space environmental factors

    NASA Astrophysics Data System (ADS)

    Hellweg, C. E.; Arenz, A.; Meier, M. M.; Baumstark-Khan, C.

    Harmful environmental factors - namely ionizing radiation - will continue to influence future manned space missions. The Cellular Biodiagnostic group at the German Aerospace Center (DLR) develops cellular monitoring systems, which include bacterial and mammalian cell systems capable of recognizing DNA damage as a consequence of the presence of genotoxic conditions. Such bioassay or biosensor systems will complement the physical detector systems used in space, insofar as they yield intrinsically biologically weighted measures of cellular responses. Furthermore, synergistic mutagenic and cancerogenic impacts of the radiation environment together with other potentially genotoxic constituents of the space habitat can be quantified using such systems, whose signals are especially relevant for the molecular damage to the DNA or the chromosomes. The experiment Cellular Responses to Radiation in Space (CERASP) has been selected by NASA to be performed on the International Space Station. It will supply basic information on the cellular response to radiation applied in microgravity. One of the biological end-points under investigation will be survival reflected by radiation-dependent reduction of constitutive expression of the enhanced variant of green fluorescent protein (EGFP), originally isolated from the bioluminescent jellyfish Aequorea victoria. A second end-point will be gene activation by space flight conditions in mammalian cells, based on fluorescent promoter reporter systems using the destabilized EGFP variant (d2EGFP). The promoter element to be investigated will reflect the activity of the NF-kB stress response pathway as an anti-apoptotic radiation response. DNA damage will be measured by fluorescent analysis of DNA unwinding (FADU). The systems have worked properly for terrestrial applications during the first experiments. Experiments using accelerated particles produced at the French heavy ion accelerator GANIL have given insights into cellular mechanisms

  6. 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

  7. Miniaturized holographic imaging system for real-time cellular detection

    NASA Astrophysics Data System (ADS)

    Song, Jun; Im, Hyungsoon; Liong, Monty; Fexon, Lioubov; Pivovarov, Misha; Weissleder, Ralph; Lee, Hakho

    2013-03-01

    We herein present a miniaturized holographic imaging system for high throughput cellular detection. The system consists of an imager chip with a microfluidic channel built on top. Clinical samples (e.g., blood) are introduced into the fluidic channel, and holographic images of cells are recorded by the imager chip. We then perform computational reconstruction of original cell images, retrieving both the intensity and phase information. For fast image reconstruction, we have implemented parallel computing software and utilized multicore GPU (graphics processing unit) chips. The resulting imaging system enabled high throughput cellular detection; up to 1000 cells/ μL could be imaged over a wide detection area (20 mm2), and cellular images could be reconstructed in real time (20 frames/sec). Furthermore, assays can be performed without extra dilution and washing steps, which significantly simplifies the diagnosis process. This cost-effective, real-time holographic imaging system can be used for target cell detection in point-of-care applications.

  8. 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.

  9. 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.

  10. Decisions on the fly in cellular sensory systems

    PubMed Central

    Siggia, Eric D.; Vergassola, Massimo

    2013-01-01

    Cells send and receive signals through pathways that have been defined in great detail biochemically, and it is often presumed that the signals convey only level information. Cell signaling in the presence of noise is extensively studied but only rarely is the speed required to make a decision considered. However, in the immune system, rapidly developing embryos, and cellular response to stress, fast and accurate actions are required. Statistical theory under the rubric of “exploit–explore” quantifies trade-offs between decision speed and accuracy and supplies rigorous performance bounds and algorithms that realize them. We show that common protein phosphorylation networks can implement optimal decision theory algorithms and speculate that the ubiquitous chemical modifications to receptors during signaling actually perform analog computations. We quantify performance trade-offs when the cellular system has incomplete knowledge of the data model. For the problem of sensing the time when the composition of a ligand mixture changes, we find a nonanalytic dependence on relative concentrations and specify the number of parameters needed for near-optimal performance and how to adjust them. The algorithms specify the minimal computation that has to take place on a single receptor before the information is pooled across the cell. PMID:24019464

  11. Cellular behavior in micropatterned hydrogels by bioprinting system depended on the cell types and cellular interaction.

    PubMed

    Hong, Soyoung; Song, Seung-Joon; Lee, Jae Yeon; Jang, Hwanseok; Choi, Jaesoon; Sun, Kyung; Park, Yongdoo

    2013-08-01

    The fabrication of patterned microstructures within three-dimensional (3D) matrices is a challenging subject in tissue engineering and regenerative medicine. A 3D, free-moving bioprinting system was developed and hydrogels were patterned by varying the process parameters of z-axis moving velocity and ejection velocity. The patterning of hydrogel based microfibers in a 3D matrigel was achieved with dimensions of 4.5 mm length and widths from 79 to 200 μm. Hyaluronan-based hydrogels mixed with fibroblasts (L929), mouse endothelial cells (MS1), or human mesenchymal stem cells (hMSCs) were patterned using a 3D moving axis bioprinter and cell behavior was monitored in culture for up to 16 days. L929 and MS1 cells and hMSCs in patterned hydrogel revealed cell-cell interactions and a morphological dependency on cell types. HMSCs formed spheres through cell aggregation, while L929 cells increased in cellular mass without cell aggregation and MS1 dispersed into the matrix instead of aggregating. The aggregation of hMSCs was attenuated by treatment with Rho kinase (ROCK) inhibitor and cadherin antibody. This reflected the close relationship between cell aggregation and migration with RhoA and cell-cell adhesion molecules. Angiogenic-specific gene expression profiles showed that expression of CD105 decreased to 22% in the ROCK inhibitor group compared to control group. These results showed that cell-based patterns in a 3D matrix are highly dependent on both cell aggregation and migration over time.

  12. 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,…

  13. Cellular defense mechanisms against lead toxicity in the vascular system.

    PubMed

    Shinkai, Yasuhiro; Kaji, Toshiyuki

    2012-01-01

    Lead is a toxic heavy metal that can cause a range of health problems. In this context, the vascular system is a particular target of the deleterious effects of lead. Lead exerts its toxicity through substitution of other divalent cations such as calcium and zinc, resulting in disruption of homeostasis. Based on the evidence that lead up-regulates endoplasmic reticulum (ER) chaperone glucose-regulated protein 78 (GRP78) and/or antioxidant proteins such as hemeoxygenase-1, it is believed that the heavy metal is able to induce ER and/or oxidative stress in cells. These events also suggest that the unfolded protein response (UPR) system and the antioxidant defense system Kelch-like ECH-associated protein 1-nuclear factor (NF)-E2-related factor 2 (Keap1-Nrf2) play a critical role in adaptive response to lead. In this review, we summarize recent progress in lead toxicity in terms of cellular defense systems, including stress proteins and transcription factors involved in the vascular system.

  14. 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.

  15. The stellar mass distribution of S4G disk galaxies

    NASA Astrophysics Data System (ADS)

    Díaz-García, Simón; Salo, Heikki; Laurikainen, Eija

    2017-03-01

    We use 3.6 μm imaging from the S4G survey to characterize the typical stellar density profiles (Σ*) and bars as a function of fundamental galaxy parameters (e.g. the total stellar mass M *), providing observational constraints for galaxy simulation models to be compared with. We rescale galaxy images to a common frame determined by the size in physical units, by their disk scalelength, or by their bar size and orientation. We stack the resized images to obtain statistically representative average stellar disks and bars. For a given M * bin (>= 109 M ⊙), we find a significant difference in the stellar density profiles of barred and non-barred systems that gives evidence for bar-induced secular evolution of disk galaxies: (i) disks in barred galaxies show larger scalelengths and fainter extrapolated central surface brightnesses, (ii) the mean surface brightness profiles of barred and non-barred galaxies intersect each other slightly beyond the mean bar length, most likely at the bar corotation, and (iii) the central mass concentration of barred galaxies is larger (by almost a factor 2 when T < 5) than in their non-barred counterparts. We also show that early- and intermediate-type spirals (0 <= T < 5) host intrinsically narrower bars than the later types and S0s, whose bars are oval-shaped. We show a clear correlation between galaxy family and bar ellipticity.

  16. Cellular and System Biology of Memory: Timing, Molecules, and Beyond.

    PubMed

    Korte, Martin; Schmitz, Dietmar

    2016-04-01

    The storage of information in the mammalian nervous systems is dependent on a delicate balance between change and stability of neuronal networks. The induction and maintenance of processes that lead to changes in synaptic strength to a multistep process which can lead to long-lasting changes, which starts and ends with a highly choreographed and perfectly timed dance of molecules in different cell types of the central nervous system. This is accompanied by synchronization of specific networks, resulting in the generation of characteristic "macroscopic" rhythmic electrical fields, whose characteristic frequencies correspond to certain activity and information-processing states of the brain. Molecular events and macroscopic fields influence each other reciprocally. We review here cellular processes of synaptic plasticity, particularly functional and structural changes, and focus on timing events that are important for the initial memory acquisition, as well as mechanisms of short- and long-term memory storage. Then, we cover the importance of epigenetic events on the long-time range. Furthermore, we consider how brain rhythms at the network level participate in processes of information storage and by what means they participating in it. Finally, we examine memory consolidation at the system level during processes of sleep.

  17. The Tumorigenic Roles of the Cellular REDOX Regulatory Systems

    PubMed Central

    Castaldo, Stéphanie Anaís; Freitas, Joana Raquel; Conchinha, Nadine Vasconcelos; Madureira, Patrícia Alexandra

    2016-01-01

    The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, survival, and proliferation. To date, a substantial amount of data has demonstrated that cancer cells typically undergo increasing oxidative stress as the tumor develops, upregulating these important antioxidant systems in order to survive, proliferate, and metastasize under these extreme oxidative stress conditions. Since a large number of chemotherapeutic agents currently used in the clinic rely on the induction of ROS overload or change of ROS quality to kill the tumor, the cancer cell REDOX adaptation represents a significant obstacle to conventional chemotherapy. In this review we will first examine the different factors that contribute to the enhanced oxidative stress generally observed within the tumor microenvironment. We will then make a comprehensive assessment of the current literature regarding the main antioxidant proteins and systems that have been shown to be positively associated with tumor progression and chemoresistance. Finally we will make an analysis of commonly used chemotherapeutic drugs that induce ROS. The current knowledge of cancer cell REDOX adaptation raises the issue of developing novel and more effective therapies for these tumors that are usually resistant to conventional ROS inducing chemotherapy. PMID:26682014

  18. Chemical Model Systems for Cellular Nitros(yl)ation Reactions

    PubMed Central

    Daiber, Andreas; Schildknecht, Stefan; Müller, Johanna; Bachschmid, Markus M.; Ullrich, Volker

    2014-01-01

    S-nitros(yl)ation belongs to the redox-based posttranslational modifications of proteins but the underlying chemistry is controversial. In contrast to current concepts involving the autoxidation of nitric oxide (•NO, nitrogen monoxide), we and others have proposed the formation of peroxynitrite (oxoperoxonitrate(1-)) as an essential intermediate. This requires low cellular fluxes of •NO and superoxide (•O2−), for which model systems have been introduced. We here propose two new systems for nitros(yl)ation that avoid the shortcomings of previous models. Based on the thermal decomposition of 3-morpholinosydnonimine, equal fluxes of •NO and •O2− were generated and modulated by the addition of •NO donors or Cu,Zn-superoxide dismutase. As reactants for S-nitros(yl)ation, NADP+-dependent isocitrate dehydrogenase and glutathione were employed, for which optimal S-nitros(yl)ation was observed at nanomolar fluxes of •NO and •O2− at a ratio of about 3:1. The previously used reactants phenol and diaminonaphthalene, (C- and N-nitrosation) demonstrated potential participation of multiple pathways for nitros(yl)ation. According to our data, neither peroxynitrite nor autoxidation of •NO was as efficient as the 3•NO/1•O2− system in mediating S-nitros(yl)ation. In theory this could lead to an elusive nitrosonium (nitrosyl cation)-like species in the first step and to N2O3 in the subsequent reaction. Which of these two species or whether both together will participate in biological S-nitros(yl)ation remains to be elucidated. Finally, we developed several hypothetical scenarios to which the described U flux model could apply, providing conditions that allow either direct electrophilic substitution at a thiolate or S-nitros(yl)ation via transnitrosation from S-nitrosoglutathione. PMID:19477267

  19. Cellular respiration: replicating in vivo systems biology for in ...

    EPA Pesticide Factsheets

    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 express purpose is to provide a publication outlet for novel breath related research that includes in vitro studies, especially those that explore the biological origin and expression of compounds that may ultimately influence the constituents of exhaled breath. The new topics include all manner of methods and instrumentations for making in vivo and in vitro measurements, the use of different biological media (blood, urine saliva, swabs) including human and microbial cell-lines, in vitro kinetic studies of metabolism, and advances in ex vivo methods for maintaining metabolic competency and viability of biological samples. Traditionally, JBR has published articles on human breath analysis for diagnosing disease, tracking health state, assessing the dose and effect of exogenous chemicals, and contributions of malodorous compounds from the oral/nasal cavity. These have also included research describing novel sampling and analytical technologies, most notably those implementing mass spectrometry, chemical sensors and optical measurement instrumentation (Amann and Smith 2013). The journal’s original scope has also embraced animal models as surrogates for human sampling, new mathematical and

  20. Perturbation biology: inferring signaling networks in cellular systems.

    PubMed

    Molinelli, Evan J; Korkut, Anil; Wang, Weiqing; 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.

  1. 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

  2. Satellite augmentation of cellular type mobile radio telephone systems

    NASA Astrophysics Data System (ADS)

    Anderson, Roy E.

    NASA's ATS-6 satellite relayed voice bandwidth communications between five trucks and the trucking company dispatchers as the trucks traveled throughout the north-eastern quarter of the contiguous United States. The experiment, conducted over a seven month period, demonstrated that propagation characteristics are much different for the satellite-mobile links than for terrestrial-mobile links. A properly designed satellite system can provide high quality, reliable voice and data communications except where the vehicle-satellite path is shadowed by a structure or terrain feature. Mobile equipment in the experiment was adapted from commercial mobile radios. The vehicle antennas were 75 cm tall, 2 cm diam. Another experiment proved the feasibility of vehicle position surveillance using active two-way tone-code ranging through ATS-6 to provide one line of position and passive one-way ranging by measuring the time-of-arrival of a signal from an independent satellite. A position fix was printed out at an earth station 1 sec after it sent the interrogation signal to the distant vehicle, a towboat on the Mississippi River. The line of position from ATS-6 was accurate to 0.1 nautical mile using a voice bandwidth ranging signal. The line of position from the NOAA GOES satellite was accurate to 2 miles, using 100 Hz signal bandwidth. If the signal from the independent satellite had the same bandwidth and signal-to-noise ratio as ATS-6, the fixes would have been accurate to about 0.1 nautical mile. A concept study concluded that satellites might be a cost effective augmentation of terrestrial cellular type mobile radio telephone systems. The satellites would serve thinly populated areas where terrestrial systems are not cost effective. In the United States, the satellites would serve about 90% of the land area where 20% of the population resides. A multibeam satellite with many channels in each beam would be compatible with the urban terrestrial systems and together they would

  3. Review of pre-FFT equalization techniques and their application to 4G

    NASA Astrophysics Data System (ADS)

    Armour, Simon; Doufexi, Angela; Nix, Andrew; Beach, Mark; McGeehan, J.

    2001-11-01

    In this paper a review of the Pre-FFT Equalization technique is presented with a particular focus on 4G applications. The essential concepts and motivations for the use of this technique are first presented. Subsequently, previous research of the topic both by the authors and others is reviewed. In particular, methods for implementing the Pre-FFT Equalizer itself and for adapting it are reviewed in detail. The issue of noise amplification and the use of Channel State Information in the COFDM system to mitigate this phenomenon are also discussed. Application of a Pre-FFT Equalizer to a possible, COFDM based, 4G standard is then discussed and software simulations used to demonstrate the benefits that can be achieved by a Pre-FFT Equalizer in a 4G system.

  4. Structural analysis of the DAP5 MIF4G domain and its interaction with eIF4A

    PubMed Central

    Virgili, Geneviève; Frank, Filipp; Feoktistova, Kateryna; Sawicki, Maxime; Sonenberg, Nahum; Fraser, Christopher S.; Nagar, Bhushan

    2013-01-01

    Summary Death-associated protein 5 (DAP5/p97) is a homolog of the eukaryotic initiation factor 4G (eIF4G) that promotes the IRES-driven translation of multiple cellular mRNAs. Central to its function is the middle domain (MIF4G), which recruits the RNA helicase eIF4A. The middle domain of eIF4G consists of tandem HEAT repeats that coalesce to form a solenoid-type structure. Here, we report the crystal structure of the DAP5 MIF4G domain. Its overall fold is very similar to that of eIF4G, however, significant conformational variations impart distinct surface properties that could explain the observed differences in IRES binding between the two proteins. Interestingly, quantitative analysis of the DAP5-eIF4A interaction using isothermal titration calorimetry reveals a 10-fold lower affinity than with the eIF4G-eIF4A interaction that appears to affect their ability to stimulate eIF4A RNA unwinding activity in vitro. This difference in stability of the complex may have functional implications in selecting the mode of translation initiation. PMID:23478064

  5. 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

  6. 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

  7. PAI-1 promoter 4G/5G polymorphism (rs1799768) contributes to tumor susceptibility: Evidence from meta-analysis.

    PubMed

    Xu, Xin; Xie, Yanqi; Lin, Yiwei; Xu, Xianglai; Zhu, Yi; Mao, Yeqing; Hu, Zhenghui; Wu, Jian; Chen, Hong; Zheng, Xiangyi; Qin, Jie; Xie, Liping

    2012-12-01

    Plasminogen activator inhibitor-1 (PAI-1), belonging to the urokinase plasminogen activation (uPA) system, is involved in cancer development and progression. The PAI-1 promoter 4G/5G polymorphism was shown to contribute to genetic susceptibility to cancer, although the results were inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The electronic databases PubMed, Scopus, Web of Science and Chinese National Knowledge Infrastructure (CNKI) were searched; data were extracted and analyzed independently by two reviewers. Ultimately, 21 eligible case-control studies with a total of 8,415 cancer cases and 9,208 controls were included. The overall odds ratio (OR) with its 95% confidence interval (CI) showed a statistically significant association between the PAI-1 promoter 4G/5G polymorphism and cancer risk (4G/4G vs. 5G/5G: OR=1.25, 95% CI=1.07-1.47, P(heterogeneity)=0.001; 4G/4G vs. 4G/5G+5G/5G: OR=1.10, 95% CI=1.03-1.17, P(heterogeneity)=0.194; 4G/4G+4G/5G vs. 5G/5G: OR=1.17, 95% CI=1.01-1.35, P(heterogeneity)=0.041). In further subgroup analyses, the increased risk of cancer was observed in a subgroup of Caucasians with regards to endometrial cancer. Our meta-analysis suggests that the PAI-1 4G/5G polymorphism most likely contributes to susceptibility to cancer, particularly in Caucasians. Furthermore, the 4G allele may be associated with an increased risk of endometrial cancer.

  8. Cellular aggregation and trauma in cardiotomy suction systems.

    PubMed Central

    Wright, G; Sanderson, J M

    1979-01-01

    Experiments in dogs showed that the high levels of cellular aggregation and trauma caused by cariodtomy suction can be considerably reduced by the avoidance of air aspiration. A hypothesis is proposed to explain this on the basis of shear stresses in the inlet cannula. Roller pump suction was also found to be slightly more traumatic than vaccum suction, but contact of the blood with the pericardium had no effect so long as the pericardium and epicardium had been previously washed with saline. PMID:515984

  9. A unique cellular scaling rule in the avian auditory system.

    PubMed

    Corfield, Jeremy R; Long, Brendan; Krilow, Justin M; Wylie, Douglas R; Iwaniuk, Andrew N

    2016-06-01

    Although it is clear that neural structures scale with body size, the mechanisms of this relationship are not well understood. Several recent studies have shown that the relationship between neuron numbers and brain (or brain region) size are not only different across mammalian orders, but also across auditory and visual regions within the same brains. Among birds, similar cellular scaling rules have not been examined in any detail. Here, we examine the scaling of auditory structures in birds and show that the scaling rules that have been established in the mammalian auditory pathway do not necessarily apply to birds. In galliforms, neuronal densities decrease with increasing brain size, suggesting that auditory brainstem structures increase in size faster than neurons are added; smaller brains have relatively more neurons than larger brains. The cellular scaling rules that apply to auditory brainstem structures in galliforms are, therefore, different to that found in primate auditory pathway. It is likely that the factors driving this difference are associated with the anatomical specializations required for sound perception in birds, although there is a decoupling of neuron numbers in brain structures and hair cell numbers in the basilar papilla. This study provides significant insight into the allometric scaling of neural structures in birds and improves our understanding of the rules that govern neural scaling across vertebrates.

  10. PAI-1 -675 4G/5G polymorphism as a prognostic biomarker in breast cancer.

    PubMed

    Lei, Haixin; Hemminki, Kari; Johansson, Robert; Altieri, Andrea; Enquist, Kerstin; Henriksson, Roger; Lenner, Per; Försti, Asta

    2008-05-01

    Extracellular matrix degradation, mediated by the urokinase plasminogen activation (uPA) system, is a critical step in tumor invasion and metastasis. High tumor levels of uPA and its inhibitor PAI-1 have been correlated with poor prognosis in breast cancer. We examined whether genetic variation in the genes of the uPA system affect breast cancer susceptibility and prognosis. We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) in six genes of the uPA system in 959 Swedish breast cancer patients with detailed clinical data and up to 15 years of follow-up together with 952 matched controls. We used the unconditional logistic regression models to evaluate the associations between genotypes and breast cancer risk and tumor characteristics. The Kaplan-Meier method was used to estimate the survival probabilities; the log-rank test was used to test differences between subgroups. None of the SNPs conferred an increased breast cancer risk, but correlation with some traditional prognostic factors was observed for several SNPs. Most importantly, we identified the -675 4G/5G SNP in the PAI-1 gene as a promising prognostic biomarker for breast cancer. Compared to the 4G/4G and 4G/5G genotypes 5G/5G homozygosity correlated significantly with worse survival (RR 2.04, 95% CI 1.45-2.86, P<0.001), especially in patients with more aggressive tumors. 5G/5G homozygotes were also the group with worse survival among lymph node negative cases. Our finding suggests that genotyping PAI-1 -675 4G/5G may help in clinical prognosis of breast cancer.

  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. Clinical impact of PAI 1 4G/5G gene polymorphism in colorectal carcinoma patients.

    PubMed

    Halamkova, J; Kiss, I; Pavlovsky, Z; Tomasek, J; Jarkovsky, J; Cech, Z; Bednarova, D; Tucek, S; Hanakova, L; Moulis, M; Zavrelova, J; Man, M; Benda, P; Robek, O; Kala, Z; Penka, M

    2013-01-01

    Plasminogen activator ihnibitor (PAI 1) belongs to the plasminogen activator system, which is part of the metastatic cascade and significantly contributes to invasive growth and angiogenesis of malignant tumors. Its plasma level is normally low but 4G/4G homozygotes have higher concentrations of PAI 1. This genotype may be associated with worse prognosis and proximal location of colorectal cancer than 5G/5G homozygotes. In our prospective evaluation we examined plasma level PAI 1 (using photometric microplate method ELISA) pre-surgery and, subsequently, 6-8 weeks later, from 80 patients. For the PAI 1 rs1799889 -675 4G/5G polymorphism test the PCR amplification was used.Analysis of collected data was confirmed that significantly higher plasma levels of PAI 1 were found in patients before starting therapy, which decreased (p=0.004) after initiation of treatment. Patients with higher plasma level PAI 1 before (p=0.013) and after therapy (p=0.004) had significantly shorter survival. We found no relationship between polymorphisms of PAI 1 (-675 4G/5G) in relation to stage, survival or tumor location. PAI 1 is useful as a negative marker of prognosis and could be advantageous when planning adjuvant treatment of patients with colorectal carcinoma. Although opinions on the importance of polymorphisms of PAI 1 in relation to the prognosis are not uniform, it does seem that their role in the prognosis of patients with colorectal cancer is not essential.

  13. 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

  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

    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.

  16. Digital polarization holography advancing 4G optics (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    De Sio, Luciano; Roberts, David E.; Tabiryan, Nelson V.; Steeves, Diane M.; Kimball, Brian R.

    2016-09-01

    The fourth generation optics (4G optics) enables the realization of novel optical components (lenses, gratings, vector vortices, etc.) by patterning the optical axis orientation in the plane of an anisotropic film. Such components exhibit near 100% diffraction efficiency for wavelengths meeting half-wave retardation condition. In this framework, we have advanced a step-forward by realizing different diffractive waveplates (DWs) with arbitrary spatial patterns of the optical axis orientation by exploiting the capability of a Digital Spatial Light Polarization Converter (DSLPC). The DSLPC is based on a reflective, high resolution Spatial Light Modulator (SLM) combined with an "ad hoc" optical setup. The most attractive feature of the use of a DSLPC for photoalignment is that the orientation of the alignment layer, and therefore of the fabricated liquid crystal (LC) or liquid crystal polymer (LCP) DWs, can be specified on a pixel-by-pixel basis. By varying the optical magnification or de-magnification between the SLM and the alignment layer, the spatial resolution of the photoaligned layer can be adjusted to be optimal for each application. We show that with a simple "click" it is possible to record different high resolution optical components as well as arbitrary patterns ranging from lenses to invisible and even dual labels.

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

    PubMed Central

    Gallie, Daniel R.

    2016-01-01

    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

  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 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  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. Cellular changes in the enteric nervous system during ageing.

    PubMed

    Saffrey, M Jill

    2013-10-01

    The intrinsic neurons of the gut, enteric neurons, have an essential role in gastrointestinal functions. The enteric nervous system is plastic and continues to undergo changes throughout life, as the gut grows and responds to dietary and other environmental changes. Detailed analysis of changes in the ENS during ageing suggests that enteric neurons are more vulnerable to age-related degeneration and cell death than neurons in other parts of the nervous system, although there is considerable variation in the extent and time course of age-related enteric neuronal loss reported in different studies. Specific neuronal subpopulations, particularly cholinergic myenteric neurons, may be more vulnerable than others to age-associated loss or damage. Enteric degeneration and other age-related neuronal changes may contribute to gastrointestinal dysfunction that is common in the elderly population. Evidence suggests that caloric restriction protects against age-associated loss of enteric neurons, but recent advances in the understanding of the effects of the microbiota and the complex interactions between enteric ganglion cells, mucosal immune system and intestinal epithelium indicate that other factors may well influence ageing of enteric neurons. Much remains to be understood about the mechanisms of neuronal loss and damage in the gut, although there is evidence that reactive oxygen species, neurotrophic factor dysregulation and/or activation of a senescence associated phenotype may be involved. To date, there is no evidence for ongoing neurogenesis that might replace dying neurons in the ageing gut, although small local sites of neurogenesis would be difficult to detect. Finally, despite the considerable evidence for enteric neurodegeneration during ageing, and evidence for some physiological changes in animal models, the ageing gut appears to maintain its function remarkably well in animals that exhibit major neuronal loss, indicating that the ENS has considerable

  7. Design of mobile telemedicine systems using GSM and IS-54 cellular telephone standards.

    PubMed

    Istepanian, R H; Woodward, B; Gorilas, E; Balos, P A

    1998-01-01

    This paper presents an overview of the design of mobile telemedical systems using cellular telephone channels. A mobile telemedicine communication system was studied using both the GSM and the IS-54 standards, which are the most widely used commercial cellular telephone systems in Europe and North America, respectively. A simulation using a photoplethesmography signal showed successful transmission of data with bit error rates of less than 10(-7) at the receiver for the IS-54 standard and less than 10(-5) for the GSM standard, depending on the mobile channel conditions used.

  8. 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.

  9. 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.

  10. Sensitive Optical and Microfluidic Systems for Cellular Analyses

    NASA Astrophysics Data System (ADS)

    Schiro, Perry G.

    Investigating rare cells and heterogeneous subpopulations is challenging for a myriad reasons. This dissertation describes novel techniques to analyze single molecules, synaptic vesicles, and rare circulating tumor cells. The eDAR platform for isolating rare cells in fluids provides a new method to monitor breast cancer status in patients as well as to guide research for personalized treatment and efficacy. In a side-by-side comparison with CellSearch, eDAR detected CTCs in all 20 Stage IV metastatic breast cancer patients while the CellSearch system found CTCs in just 8 patients. The single-molecule capillary electrophoresis technology is a method to characterize an entire sample one molecule at a time, providing detailed information about the absolute number and nature of molecules present in a sample. The nFASS platform has the potential to apply the advantages that currently exist in flow cytometry to the study of items on a much smaller scale such as subcellular organelles and nanometer-sized objects. For example, the isolation of subpopulations of synaptic vesicles will allow for detailed protein quantification and identification in the study of neurological diseases. These tools facilitate fundamental investigation of objects ranging from single molecules to single cells.

  11. 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.

  12. Cellular systems for studying human oral squamous cell carcinomas.

    PubMed

    Patel, Vyomesh; Iglesias-Bartolome, Ramiro; Siegele, Bradford; Marsh, Christina A; Leelahavanichkul, Kantima; Molinolo, Alfredo A; Gutkind, J Silvio

    2011-01-01

    The human oral squamous epithelium plays an important role in maintaining a barrier function against mechanical, physical, and pathological injury. However, the self-renewing cells residing on the basement membrane of the epithelium can give rise to oral squamous cell carcinomas (OSCC), now the sixth most common cancer in the developed world, which is still associated with poor prognosis. This is due, in part, to the limited availability of well-defined culture systems for studying oral epithelial cell biology, which could advance our understanding of the molecular basis of OSCC. Here, we describe methods to successfully isolate large cultures of human oral epithelial cells and fibroblasts from small pieces of donor tissues for use in techniques such as three-dimensional cultures and animal grafts to validate genes suspected of playing a role in OSCC development and progression. Finally, the use of isolated oral epithelial cells in generating iPS cells is discussed which holds promise in the field of oral regenerative medicine.

  13. 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.

  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. Capacity of a spread spectrum CDMA system for cellular mobile radio with consideration of system imperfections

    NASA Astrophysics Data System (ADS)

    Newson, Paul; Heath, Mark R.

    1994-05-01

    There has been much interest in the use of spread spectrum code division multiple access (CDMA) techniques for cellular mobile radio. To date, spread spectrum has been used mainly for military applications, in which the inherent transmission security and immunity to deliberate jamming are important. Spread spectrum systems, however, possess various other features such as multiple access and multipath rejection capability, which make their use attractive within the mobile radio environment. However, the current interest has been principally motivated by recent work in which it is claimed that the CDMA option may offer capacity improvement over more conventional frequency and time division multiple access (FDMA) (TDMA) techniques. Within this paper, the relative capacities of a basic FDMA and CDMA system are examined. It is shown that, in the absence of capacity-enhancing features such as voice activity detection and cell sectorization, the capacity of each system is comparable. The paper then assesses the sensitivity of the CDMA system to typical propagation conditions, power control errors, and realistic antenna patterns and shows that the capacity of a CDMA system may be significantly reduced under nonideal conditions.

  16. 4G/5G polymorphism modulates PAI-1 circulating levels in obese women.

    PubMed

    Fernandes, Karla S; Sandrim, Valéria C

    2012-05-01

    The increase in plasminogen activator inhibitor type 1 (PAI-1) has been described as a risk factor to thrombosis-related diseases. In addition, it has been demonstrated that the variant 4G of polymorphism 4G/5G located in promoter region of PAI-1 gene is associated with higher PAI-1 levels. We investigate the role of this polymorphism on circulating PAI-1 concentration in a population of 57 obese women (23%, 4G/4G; 49%, 4G/5G and 28%, 5G/5G genotypes). Our results demonstrate a genotype-specific modulation on PAI-1 levels in obese women, thus 5G/5G genotype presented significantly lower levels of plasma PAI-1 when compared to 4G/4G group (46 ± 19 ng/mL vs. 63 ± 13 ng/mL, respectively). Our findings indicate that obese carriers of 4G/4G genotype may have increased risk to develop thrombotic diseases.

  17. Reduced carriership of 4G allele of plasminogen activator inhibitor-1 4G/5G polymorphism in very young survivors of myocardial infarction.

    PubMed

    Rallidis, Loukianos S; Gialeraki, Argyri; Merkouri, Efrosyni; Liakos, George; Dagres, Nikolaos; Sionis, Dimitrios; Travlou, Anthi; Lekakis, John; Kremastinos, Dimitrios T

    2010-05-01

    There are limited and controversial data regarding the impact of 4G/5G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene in the pathogenesis of premature myocardial infarction (MI). We explored whether 4G/5G polymorphism of the PAI-1 gene is associated with the development of MI 4G/5G polymorphism of PAI-1 was tested with polymerase chain reaction and reverse hybridization. 4G allele carriers (4G/4G and 4G/5G genotypes) of PAI-1 were less frequent in patients than in controls (69.6 vs. 83.6%, P = 0.007). 4G carriership of the polymorphism of PAI-1 was associated with lower risk for acute MI (odds ratio 0.45, 95% confidence interval 0.23-0.88, P = 0.02) after adjusting for major cardiovascular risk factors. Patients possessing the 4G allele had higher PAI-1 plasma levels (32.2 +/- 25 vs. 22.2 +/- 11.3 ng/ml, P = 0.006) but lower lipoprotein(a) levels (10.1 [2.1-29.9] vs. 15.3 [8.2-57.1] mg/dl, P = 0.03) compared to 5G/5G homozygotes. Our data indicate that the 4G allele of the PAI-1 4G/5G polymorphism is less frequent among survivors of MI at very young age compared with matched controls.

  18. [Cellular radio systems. Problems faced in assessing exposure to electromagnetic fields].

    PubMed

    Zmyślony, M

    2000-01-01

    Over twenty years of its existence, cellular radio systems have become one of the major sources of human exposure to electromagnetic field (EMF) of high frequency. With the increasing number of cellular phones, the interest in health effects of exposure to EMF emitted by them continues to grow. At present, there is a general opinion that thermal effect (change of electromagnetic energy into thermal energy) is an essential mechanism of possible biological effects. The majority of world standards for exposure to EMF are based on this effect. The author presents Polish standards and those of the International Commission on Nonionizing Radiation Protection (ICNIRP) for EMF of frequencies used in cellular radio systems, both basic that limits SAR (Specific Absorption Rate), and derived that limits the power density, as well as intensity of electric and magnetic fields. Attention was also turned to the problems concerning the application of cellular phones and those resulting from the character of the field emitted by them to which their users are exposed. Bearing in mind the results of the laboratory analyses of SAR values occurring in the user's head, and measurements of power density in the vicinity of the base station antennas, it can be stated that, in view of binding and recommended standards, cellular phones do not present any hazard to their users (private or professional). However, it should be stressed that standards adopted protect the user's head against the thermal effect, whereas the question on whether they also protect against non-thermal effects still remains without answer.

  19. WRF4G: enabling ensemble operational weather forecasting on the GRID

    NASA Astrophysics Data System (ADS)

    Fernández, J.; Fernández-Quiruelas, V.; Cofino, As; Fita, L.; Gutierrez, Jm

    2009-09-01

    The GRID provides transparent access to geographically distributed computational and storage resources. Several applications areas as high energy physics or bio-applications have been proven to benefit from this computational paradigm. Applications from the Earth Science community are starting to take advantage of this technology (see e.g. www.eu-degree.eu). The port of already existing Earth Science applications and, in particular, a numerical atmospheric model to the GRID poses a challenge in terms of the CPU and storage requirements. These applications are organized around communities known as virtual organizations (VO). The limited area models require a large amount of input data to build the boundary conditions. Currently the heterogenous GRID infrastructure is subject to common failures and intermittent availability of resources the numerical weather models are not prepared for. For those reasons, in this contribution we present a new execution framework providing a software wrapper for a numerical prediction model. A wrapper for the WRF Modeling System has been developed to enable limited area model simulations on the GRID. This WRF for the GRID wrapper (WRF4G) is "gridifying" a complex workflow application as the WRF System. The WRF4G framework has been adapted for the middleware developed in the leading european project on GRID computing known as EGEE (http://eu-egee.org/), also used in other GRID european projects (EELA2, ...) and National GRID Initiatives (NGI) like the Spanish NGI (ES-NGI). This GRID environment provides a High Productive Computing allowing to run multiple independent jobs with no high demanding on CPU and memory resources. As an application of the WRF4G framework we present a multi-physics ensemble experiment of precipitation forecast over Spain, which is run daily at a 10km resolution by the Santander Meteorology Group (www.meteo.unican.es). Two parameterizations of the ensemble are run in the local cluster, whereas 15 additional

  20. Functional overlap between eIF4G isoforms in Saccharomyces cerevisiae.

    PubMed

    Clarkson, Bryan K; Gilbert, Wendy V; Doudna, Jennifer A

    2010-02-09

    Initiation factor eIF4G is a key regulator of eukaryotic protein synthesis, recognizing proteins bound at both ends of an mRNA to help recruit messages to the small (40S) ribosomal subunit. Notably, the genomes of a wide variety of eukaryotes encode multiple distinct variants of eIF4G. We found that deletion of eIF4G1, but not eIF4G2, impairs growth and global translation initiation rates in budding yeast under standard laboratory conditions. Not all mRNAs are equally sensitive to loss of eIF4G1; genes that encode messages with longer poly(A) tails are preferentially affected. However, eIF4G1-deletion strains contain significantly lower levels of total eIF4G, relative to eIF4G2-delete or wild type strains. Homogenic strains, which encode two copies of either eIF4G1 or eIF4G2 under native promoter control, express a single isoform at levels similar to the total amount of eIF4G in a wild type cell and have a similar capacity to support normal translation initiation rates. Polysome microarray analysis of these strains and the wild type parent showed that translationally active mRNAs are similar. These results suggest that total eIF4G levels, but not isoform-specific functions, determine mRNA-specific translational efficiency.

  1. Diverse Functions of Restriction-Modification Systems in Addition to Cellular Defense

    PubMed Central

    Vasu, Kommireddy

    2013-01-01

    SUMMARY Restriction-modification (R-M) systems are ubiquitous and are often considered primitive immune systems in bacteria. Their diversity and prevalence across the prokaryotic kingdom are an indication of their success as a defense mechanism against invading genomes. However, their cellular defense function does not adequately explain the basis for their immaculate specificity in sequence recognition and nonuniform distribution, ranging from none to too many, in diverse species. The present review deals with new developments which provide insights into the roles of these enzymes in other aspects of cellular function. In this review, emphasis is placed on novel hypotheses and various findings that have not yet been dealt with in a critical review. Emerging studies indicate their role in various cellular processes other than host defense, virulence, and even controlling the rate of evolution of the organism. We also discuss how R-M systems could have successfully evolved and be involved in additional cellular portfolios, thereby increasing the relative fitness of their hosts in the population. PMID:23471617

  2. Edge detection algorithms implemented on Bi-i cellular vision system

    NASA Astrophysics Data System (ADS)

    Karabiber, Fethullah; Arik, Sabri

    2009-02-01

    Bi-i (Bio-inspired) Cellular Vision system is built mainly on Cellular Neural /Nonlinear Networks (CNNs) type (ACE16k) and Digital Signal Processing (DSP) type microprocessors. CNN theory proposed by Chua has advanced properties for image processing applications. In this study, the edge detection algorithms are implemented on the Bi-i Cellular Vision System. Extracting the edge of an image to be processed correctly and fast is of crucial importance for image processing applications. Threshold Gradient based edge detection algorithm is implemented using ACE16k microprocessor. In addition, pre-processing operation is realized by using an image enhancement technique based on Laplacian operator. Finally, morphologic operations are performed as post processing operations. Sobel edge detection algorithm is performed by convolving sobel operators with the image in the DSP. The performances of the edge detection algorithms are compared using visual inspection and timing analysis. Experimental results show that the ACE16k has great computational power and Bi-i Cellular Vision System is very qualified to apply image processing algorithms in real time.

  3. SIR-based call admission control for DS-CDMA cellular systems

    NASA Astrophysics Data System (ADS)

    Liu, Zhao; Elzarki, Magda

    1994-05-01

    Signal-to-interference ratio (SIR)-based call admission control (CAC) algorithms are proposed and studied in a DS-CDMA cellular system. Residual capacity is introduced as the additional number of initial calls a base station can accept such that system-wide outage probability will be guaranteed to remain below a certain level. The residual capacity at each cell is updated dynamically according to the reverse-link SIR measurements at the base station. A 2(sup k) factorial experimental design and analysis via computer simulations is used to study the impact of the parameters used in the algorithms. The influence of these parameters on system performance, namely blocking probability and outage probability, is then examined via simulation. The performance of the algorithms is compared together with that of a fixed call admission control scheme (fixed CAC) under both homogeneous and hot spot traffic loadings. The results show that SIR-based CAC always outperforms fixed CAC even under overload situations, which is not the case in FDMA/TDMA cellular systems. The primary benefit of SIR-based CAC in DS-CDMA cellular systems, however, lies in improving the system performance under hot spot traffics.

  4. Path loss analysis in millimeter wave cellular systems for urban mobile communications

    NASA Astrophysics Data System (ADS)

    Rajagopalan, Ramesh; Hoffman, Mitchell

    2016-09-01

    The proliferation in the number of mobile devices and developments in cellular technology has led to an ever increasing demand for mobile data. The global bandwidth shortage facing wireless carriers today has motivated research for fifth generation (5G) cellular systems. In recent years, millimeter wave (mmW) frequencies between 30 and 300 GHz are being considered as a promising technology for 5G systems. Such systems can offer superior user experience by providing data rates that exceed one Gigabit per second and latencies lower than a millisecond. However, there is little research about cellular mmW propagation in densely populated urban environments. Understanding the radio channel is a primary requirement for optimal design of mmW systems. Radio propagation in mmW systems faces significant challenges due to rapidly varying channel conditions and intermittent connectivity. In this paper, we study the propagation of mmW spectrum in an urban environment. We use a statistical model to simulate an urban environment with diverse building distributions. We perform extensive simulations to analyze the path loss behavior for both line of sight (LOS) and non line of sight (NLOS) conditions for 28 GHZ and 73 GHZ mmW frequencies. We observe that the path loss approximates a logarithmic fit for both LOS and NLOS environments. Our simulations show that the omnidirectional free space path loss is approximately 30 dB higher for mmW systems compared to current 3G PP cellular systems. To address this challenge, we propose using highly directional horn antennas with beam forming for reducing the path loss.

  5. 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.

  6. Cellular and Molecular Mechanisms of Sexual Differentiation in the Mammalian Nervous System

    PubMed Central

    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 rethink 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

  7. Procion Green H-4G immobilized poly(hydroxyethylmethacrylate/chitosan) composite membranes for heavy metal removal.

    PubMed

    Genç, O; Soysal, L; Bayramoğlu, G; Arica, M Y; Bektaş, S

    2003-02-28

    The effective removal of toxic heavy metals from environmental samples still remains a major topic of present research. Metal-chelating membranes are very promising materials as adsorbents when compared with conventional beads because they are not compressible, and they eliminate internal diffusion limitations. The purpose of this study was to evaluate the performance of a novel adsorbent, Procion Green H-4G immobilized poly(hydroxyethylmethacrylate (HEMA)/chitosan) composite membranes, for the removal of three toxic heavy metal ions, namely, Cd(II), Pb(II) and Hg(II) from aquatic systems. The Procion Green H-4G immobilized poly(hydroxyethylmethacrylate/chitosan) composite membranes were characterized by elemental analysis, scanning electron microscopy and Fourier transform infrared (FTIR) spectroscopy. The immobilized amount of the Procion Green H-4G was calculated as 0.018+/-0.003 micromol/cm(2) from the nitrogen and sulphur stoichiometry. The adsorption capacity of Procion Green H-4G immobilized poly(hydroxyethylmethacrylate/chitosan) composite membranes for selected heavy metal ions from aqueous media containing different amounts of these ions (30-400mg/l) and at different pH values (2.0-6.0) was investigated. The amount of Cd(II), Pb(II) and Hg(II) adsorbed onto the membranes measured at equilibrium, increased with time during the first 45 min and then remained unchanged toward the equilibrium adsorption. The maximum amounts of heavy metal ions adsorbed were 43.60+/-1.74, 68.81+/-2.75 and 48.22+/-1.92 mg/g for Cd(II), Pb(II) and Hg(II), respectively. The heavy metal ion adsorption on the pHEMA/chitosan membranes (carrying no dye) were relatively low, 6.31+/-0.13 mg/g for Cd(II), 18.73+/-0.37 mg/g for Pb(II) and 18.82+/-0.38 mg/g for Hg(II). Competitive adsorption of the metal ions was also studied. When the metal ions competed with each other, the adsorbed amounts were 12.74+/-0.38 mg Cd(II)/g, 28.80+/-0.86 mg Pb(II)/g and 18.41+/-0.54 mg Hg(II)/g. Procion

  8. 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.

  9. A general formalism for tissue morphogenesis based on cellular dynamics and control system interactions.

    PubMed

    Forest, Loïc; Demongeot, Jacques

    2008-06-01

    Morphogenesis is a key process in developmental biology. An important issue is the understanding of the generation of shape and cellular organisation in tissues. Despite of their great diversity, morphogenetic processes share common features. This work is an attempt to describe this diversity using the same formalism based on a cellular description. Tissue is seen as a multi-cellular system whose behaviour is the result of all constitutive cells dynamics. Morphogenesis is then considered as a spatiotemporal organization of cells activities. We show how this formalism relies on Reaction-Diffusion/Positional Information approach and how it permits to generalize its modelling possibilities. Three quite different applications for concrete morphogenetic processes are presented. The first one is a model for epithelial invagination, the second is a model of cellular differentiation by local cell-cell signalling. The last example is the secondary radial growth of conifer trees. From the mathematical point of view, different modelling tools are used according to the specificity of each process.

  10. 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

  11. 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

  12. Effects of 60-Hz electric fields on specific humoral and cellular components of the immune system

    SciTech Connect

    Morris, J.E.; Phillips, R.D.

    1982-01-01

    Humoral and cellular functions of the immune system of Swiss-Webster mice were evaluated after exposure to 60-Hz electric fields at 100 kV/m. No significant differences were observed in primary antibody response to keyhole limpet hemocyanin (precipitating antibody levels) between exposed (30 or 60 days) and control mice, nor were there significant changes in mitogen-stimulation response of spleen cells from mice similarly exposed for 90 or 150 days when compared to sham-exposed animals.

  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. 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.

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

    PubMed Central

    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. PMID:26082788

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

    PubMed

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

    2016-07-21

    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.

  18. 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

  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. 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...

  1. Queuine promotes antioxidant defence system by activating cellular antioxidant enzyme activities in cancer.

    PubMed

    Pathak, Chandramani; Jaiswal, Yogesh K; Vinayak, Manjula

    2008-04-01

    Constant generation of Reactive oxygen species (ROS) during normal cellular metabolism of an organism is generally balanced by similar rate of consumption by antioxidants. Imbalance between ROS production and antioxidant defense results in increased level of ROS causing oxidative stress which leads to promotion of malignancy. Queuine is a hyper modified base analogue of guanine, found at first anti-codon position of Q- family of tRNAs. These tRNAs are completely modified with respect to queuosine in terminally differentiated somatic cells, however hypomodification of Q-tRNAs is close association with cell proliferation. Q-tRNA modification is essential for normal development, differentiation and cellular functions. Queuine is a nutrient factor to eukaryotes. It is found to promote cellular antioxidant defense system and inhibit tumorigenesis. The activities of antioxidant enzymes like catalase, SOD, glutathione peroxidase and glutathione reductase are found to be low in Dalton's lymphoma ascites transplanted (DLAT) mouse liver compared to normal. However, exogenous administration of queuine to DLAT mouse improves the activities of antioxidant enzymes. The results suggest that queuine promotes antioxidant defense system by increasing antioxidant enzyme activities and in turn inhibits oxidative stress and tumorigenesis.

  2. Plasminogen activator inhibitor I 4G/5G polymorphism in neonatal respiratory distress syndrome.

    PubMed

    Armangil, Didem; Yurdakök, Murat; Okur, Hamza; Gürgey, Aytemiz

    2011-08-01

    Fibrin monomers inhibit surfactant function. 4G/5G insertion/deletion polymorphism plays an important role in the regulation of plasminogen activator inhibitor 1 (PAI-1) gene expression. To examine the genotype distribution of PAI-1 polymorphism in 60 infants with respiratory distress syndrome (RDS) and 53 controls, an allele-specific polymerase chain reaction (PCR) was used. The proportion of 4G/4G, 4G/5G, and 5G/5G genotypes did not differ statistically between the RDS and control groups (P > .05). Having PAI-1 4G/4G genotype polymorphism appears to increase the risk of RDS (odds ratio [OR] =1.5; 95% confidence interval [CI], 0.5-4.3), although it was not statistically significant. No relation was found between the PAI-1 4G/5G polymorphisms and RDS, but there was an increased risk associated with the 4G variant of the PAI-1 gene. We believe that our findings of increased 4G allele of the PAI-1 gene in infants with RDS would also help to clarify the pathogenesis of RDS.

  3. The Cellular and Molecular Landscapes of the Developing Human Central Nervous System

    PubMed Central

    Silbereis, John C.; Pochareddy, Sirisha; Zhu, Ying; Li, Mingfeng; Sestan, Nenad

    2016-01-01

    Summary The human central nervous system follows a pattern of development typical of all mammals, but certain neurodevelopmental features are highly derived. Building the human CNS requires the precise orchestration and coordination of myriad molecular and cellular processes across a staggering array of cell types and over a long period of time. Dysregulation of these processes affects the structure and function of the CNS and can lead to neurological or psychiatric disorders. Recent technological advances and increased focus on human neurodevelopment have enabled a more comprehensive characterization of the human CNS and its development in both health and disease. The aim of this review is to highlight recent advancements in our understanding of the molecular and cellular landscapes of the developing human CNS, with focus on the cerebral neocortex, and the insights these findings provide into human neural evolution, function, and dysfunction. PMID:26796689

  4. 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.

  5. Bacterial Filament Systems: Toward Understanding Their Emergent Behavior and Cellular Functions*

    PubMed Central

    Eun, Ye-Jin; Kapoor, Mrinal; Hussain, Saman; Garner, Ethan C.

    2015-01-01

    Bacteria use homologs of eukaryotic cytoskeletal filaments to conduct many different tasks, controlling cell shape, division, and DNA segregation. These filaments, combined with factors that regulate their polymerization, create emergent self-organizing machines. Here, we summarize the current understanding of the assembly of these polymers and their spatial regulation by accessory factors, framing them in the context of being dynamical systems. We highlight how comparing the in vivo dynamics of the filaments with those measured in vitro has provided insight into the regulation, emergent behavior, and cellular functions of these polymeric systems. PMID:25957405

  6. 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.

  7. A spectrum- and power-efficient EHF mobile satellite system to be integrated with terrestrial cellular systems

    NASA Astrophysics Data System (ADS)

    Caini, Carlo; Corazza, Giovanni E.; Falciasecca, Gabriele; Ruggieri, Marina; Vatalaro, Francesco

    1992-10-01

    An EHF satellite system for land-mobile applications to be integrated with a terrestrial cellular system is described in the paper. An approach to evaluate the carrier-to-cochannel interference occurring in a multispot satellite coverage adopting frequency reuse is introduced and results from the analysis are shown. Criteria for spectrum efficiency evaluation are also outlined along with traffic and link budget estimates. Possible options for payload implementation and mobile terminal design are presented.

  8. 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

  9. Characterization of the role of eIF4G in stimulating cap- and IRES-dependent translation in aplysia neurons.

    PubMed

    Dyer, John; Sossin, Wayne S

    2013-01-01

    The rate-limiting step(s) of translation in the nervous system have not been clearly identified. We have been examining this question in the cell body of the Aplysia sensory neuron, where translational regulation is important for the regulation of synaptic strength. In the present study, we examined the role of the adaptor protein eIF4G. We cloned Aplysia eIF4G (Ap4G) and Ap4G contains all the standard metazoan eIF4G protein-protein interaction domains. Overexpressing Ap4G in Aplysia sensory neurons caused an increase in both cap-dependent and internal ribosome entry site (IRES)-dependent translation using a previously characterized bicistronic fluorescent reporter. Unexpectedly, measurement of overall translation using the methionine analog, L-azidohomoalanine, revealed that overexpression of Ap4G did not lead to an increase in overall translation rates. Indeed, the effect of Ap4G on the bicistronic reporter depended on the presence of an upstream open reading frame (uORF) in the 5' UTR encoded by the vector. We have previously shown that Mnk strongly decreased cap-dependent translation and this depended on a putative 4G binding domain. Here we extend these results showing that even in the absence of the uORF, overexpression of Mnk strongly decreases cap-dependent translation and this depends on the Mnk binding site in eIF4G. Similarly, an increase in cap-dependent translation seen with overexpression of elongation factor 2 kinase did not depend on the uORF. Overall, we show that eIF4G is rate limiting for translation of an mRNA encoding an uORF, but is not generally a rate-limiting step for translation.

  10. An integrated systems approach for understanding cellular responses to gamma radiation.

    PubMed

    Whitehead, Kenia; Kish, Adrienne; Pan, Min; Kaur, Amardeep; Reiss, David J; King, Nichole; Hohmann, Laura; DiRuggiero, Jocelyne; Baliga, Nitin S

    2006-01-01

    Cellular response to stress entails complex mRNA and protein abundance changes, which translate into physiological adjustments to maintain homeostasis as well as to repair and minimize damage to cellular components. We have characterized the response of the halophilic archaeon Halobacterium salinarum NRC-1 to (60)Co ionizing gamma radiation in an effort to understand the correlation between genetic information processing and physiological change. The physiological response model we have constructed is based on integrated analysis of temporal changes in global mRNA and protein abundance along with protein-DNA interactions and evolutionarily conserved functional associations. This systems view reveals cooperation among several cellular processes including DNA repair, increased protein turnover, apparent shifts in metabolism to favor nucleotide biosynthesis and an overall effort to repair oxidative damage. Further, we demonstrate the importance of time dimension while correlating mRNA and protein levels and suggest that steady-state comparisons may be misleading while assessing dynamics of genetic information processing across transcription and translation.

  11. Microchip-based cellular biochemical systems for practical applications and fundamental research: from microfluidics to nanofluidics.

    PubMed

    Xu, Yan; Jang, Kihoon; Yamashita, Tadahiro; Tanaka, Yo; Mawatari, Kazuma; Kitamori, Takehiko

    2012-01-01

    By combining cell technology and microchip technology, innovative cellular biochemical tools can be created from the microscale to the nanoscale for both practical applications and fundamental research. On the microscale level, novel practical applications taking advantage of the unique capabilities of microfluidics have been accelerated in clinical diagnosis, food safety, environmental monitoring, and drug discovery. On the other hand, one important trend of this field is further downscaling of feature size to the 10(1)-10(3) nm scale, which we call extended-nano space. Extended-nano space technology is leading to the creation of innovative nanofluidic cellular and biochemical tools for analysis of single cells at the single-molecule level. As a pioneering group in this field, we focus not only on the development of practical applications of cellular microchip devices but also on fundamental research to initiate new possibilities in the field. In this paper, we review our recent progress on tissue reconstruction, routine cell-based assays on microchip systems, and preliminary fundamental method for single-cell analysis at the single-molecule level with integration of the burgeoning technologies of extended-nano space.

  12. 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

  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. 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:…

  15. Development of the hyperspectral cellular imaging system to apply to regenerative medicine

    NASA Astrophysics Data System (ADS)

    Ishihara, Miya; Sato, Masato; Matsumura, Kouji; Mochida, Joji; Kikuchi, Makoto

    2010-02-01

    Regenerative medicine by the transplantation of differentiated cells or tissue stem cells has been clinically performed, particularly in the form of cell sheets. To ensure the safety and effectiveness of cell therapy, the efficient selection of desired cells with high quality is a critical issue, which requires the development of a new evaluation method to discriminate cells non-invasively with high throughput. There were many ways to characterize cells and their components, among which the optical spectral analysis has a powerful potential for this purpose. We developed a cellular hyperspectral imaging system, which captured both spatial and spectral information in a single pixel. Hyperspectral data are composed of continual spectral bands, whereas multispectral data are usually composed of about 5 to 10 discrete bands of large bandwidths. The hyperspectral imaging system which we developed was set up by a commonly-used inverted light microscope for cell culture experiments, and the time-lapse imaging system with automatic focus correction. Spectral line imaging device with EMCCD was employed for spectral imaging. The system finally enabled to acquire 5 dimensional (x, y, z, time, wavelength) data sets and cell-by-cell evaluation. In this study, we optimized the protocol for the creation of cellular spectral database under biological understanding. We enabled to confirm spectrum of autofluorescence of collagen, absorption of specific molecules in the cultural sample and increase of scattering signal due to cell components although detail spectral analyses have not been performed.

  16. 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

  17. Towards local electromechanical probing of cellular and biomolecular systems in a liquid environment.

    PubMed

    Kalinin, Sergei V; Rodriguez, Brian J; Jesse, Stephen; Seal, Katyayani; Proksch, Roger; Hohlbauch, Sophia; Revenko, Irene; Thompson, Gary Lee; Vertegel, Alexey A

    2007-10-24

    Electromechanical coupling is ubiquitous in biological systems, with examples ranging from simple piezoelectricity in calcified and connective tissues to voltage-gated ion channels, energy storage in mitochondria, and electromechanical activity in cardiac myocytes and outer hair cell stereocilia. Piezoresponse force microscopy (PFM) originally emerged as a technique to study electromechanical phenomena in ferroelectric materials, and in recent years has been employed to study a broad range of non-ferroelectric polar materials, including piezoelectric biomaterials. At the same time, the technique has been extended from ambient to liquid imaging on model ferroelectric systems. Here, we present results on local electromechanical probing of several model cellular and biomolecular systems, including insulin and lysozyme amyloid fibrils, breast adenocarcinoma cells, and bacteriorhodopsin in a liquid environment. The specific features of PFM operation in liquid are delineated and bottlenecks on the route towards nanometre-resolution electromechanical imaging of biological systems are identified.

  18. 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

  19. In silico modeling of the immune system: cellular and molecular scale approaches.

    PubMed

    Belfiore, Mariagrazia; Pennisi, Marzio; Aricò, Giuseppina; Ronsisvalle, Simone; Pappalardo, Francesco

    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.

  20. The Triticum Mosaic Virus 5’ Leader Binds to Both eIF4G and eIFiso4G for Translation

    PubMed Central

    Roberts, Robyn; Mayberry, Laura K.; Browning, Karen S.; Rakotondrafara, Aurélie M.

    2017-01-01

    We recently identified a remarkably strong (739 nt-long) IRES-like element in the 5’ untranslated region (UTR) of Triticum mosaic virus (TriMV, Potyviridae). Here, we define the components of the cap-binding translation initiation complex that are required for TriMV translation. Using bio-layer interferometry and affinity capture of the native translation apparatus, we reveal that the viral translation element has a ten-fold greater affinity for the large subunit eIF4G/eIFiso4G than to the cap binding protein eIF4E/eIFiso4E. This data supports a translation mechanism that is largely dependent on eIF4G and its isoform. The binding of both scaffold isoforms requires an eight base-pair-long hairpin structure located 270 nucleotides upstream of the translation initiation site, which we have previously shown to be crucial for IRES activity. Despite a weak binding affinity to the mRNA, eIFiso4G alone or in combination with eIFiso4E supports TriMV translation in a cap-binding factor-depleted wheat germ extract. Notably, TriMV 5’ UTR-mediated translation is dependent upon eIF4A helicase activity, as the addition of the eIF4A inhibitor hippuristanol inhibits 5’ UTR-mediated translation. This inhibition is reversible with the addition of recombinant wheat eIF4A. These results and previous observations demonstrate a key role of eIF4G and eIF4A in this unique mechanism of cap-independent-translation. This work provides new insights into the lesser studied translation mechanisms of plant virus-mediated internal translation initiation. PMID:28046134

  1. The Triticum Mosaic Virus 5' Leader Binds to Both eIF4G and eIFiso4G for Translation.

    PubMed

    Roberts, Robyn; Mayberry, Laura K; Browning, Karen S; Rakotondrafara, Aurélie M

    2017-01-01

    We recently identified a remarkably strong (739 nt-long) IRES-like element in the 5' untranslated region (UTR) of Triticum mosaic virus (TriMV, Potyviridae). Here, we define the components of the cap-binding translation initiation complex that are required for TriMV translation. Using bio-layer interferometry and affinity capture of the native translation apparatus, we reveal that the viral translation element has a ten-fold greater affinity for the large subunit eIF4G/eIFiso4G than to the cap binding protein eIF4E/eIFiso4E. This data supports a translation mechanism that is largely dependent on eIF4G and its isoform. The binding of both scaffold isoforms requires an eight base-pair-long hairpin structure located 270 nucleotides upstream of the translation initiation site, which we have previously shown to be crucial for IRES activity. Despite a weak binding affinity to the mRNA, eIFiso4G alone or in combination with eIFiso4E supports TriMV translation in a cap-binding factor-depleted wheat germ extract. Notably, TriMV 5' UTR-mediated translation is dependent upon eIF4A helicase activity, as the addition of the eIF4A inhibitor hippuristanol inhibits 5' UTR-mediated translation. This inhibition is reversible with the addition of recombinant wheat eIF4A. These results and previous observations demonstrate a key role of eIF4G and eIF4A in this unique mechanism of cap-independent-translation. This work provides new insights into the lesser studied translation mechanisms of plant virus-mediated internal translation initiation.

  2. Efficient Analysis of Systems Biology Markup Language Models of Cellular Populations Using Arrays.

    PubMed

    Watanabe, Leandro; Myers, Chris J

    2016-08-19

    The Systems Biology Markup Language (SBML) has been widely used for modeling biological systems. Although SBML has been successful in representing a wide variety of biochemical models, the core standard lacks the structure for representing large complex regular systems in a standard way, such as whole-cell and cellular population models. These models require a large number of variables to represent certain aspects of these types of models, such as the chromosome in the whole-cell model and the many identical cell models in a cellular population. While SBML core is not designed to handle these types of models efficiently, the proposed SBML arrays package can represent such regular structures more easily. However, in order to take full advantage of the package, analysis needs to be aware of the arrays structure. When expanding the array constructs within a model, some of the advantages of using arrays are lost. This paper describes a more efficient way to simulate arrayed models. To illustrate the proposed method, this paper uses a population of repressilator and genetic toggle switch circuits as examples. Results show that there are memory benefits using this approach with a modest cost in runtime.

  3. A study of the effects of cellular telephone microwave radiation on the auditory system in healthy men.

    PubMed

    Mora, Renzo; Crippa, Barbara; Mora, Francesco; Dellepiane, Massimo

    2006-03-01

    We conducted a study of the effects of mobile cellular telephone microwave radiation on the auditory system in 20 healthy men. After the subjects underwent baseline measurements of transient evoked otoacoustic emission (TEOAE) and auditory brainstem response (ABR), they participated in three sessions of exposure to an electromagnetic field of 900 to 1,800 MHz produced by a cellular phone. Sessions ranged from 15 to 30 minutes in length. TEOAE and ABR were again measured after or during each exposure. Throughout the study, no significant changes in either measurement were noted. We conclude that the use of cellular phones does not alter the auditory system in the short-term.

  4. 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

  5. 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

  6. Cross-talk between the cellular redox state and the circadian system in Neurospora.

    PubMed

    Yoshida, Yusuke; Iigusa, Hideo; Wang, Niyan; Hasunuma, Kohji

    2011-01-01

    The circadian system is composed of a number of feedback loops, and multiple feedback loops in the form of oscillators help to maintain stable rhythms. The filamentous fungus Neurospora crassa exhibits a circadian rhythm during asexual spore formation (conidiation banding) and has a major feedback loop that includes the FREQUENCY (FRQ)/WHITE COLLAR (WC) -1 and -2 oscillator (FWO). A mutation in superoxide dismutase (sod)-1, an antioxidant gene, causes a robust and stable circadian rhythm compared with that of wild-type (Wt). However, the mechanisms underlying the functions of reactive oxygen species (ROS) remain unknown. Here, we show that cellular ROS concentrations change in a circadian manner (ROS oscillation), and the amplitudes of ROS oscillation increase with each cycle and then become steady (ROS homeostasis). The ROS oscillation and homeostasis are produced by the ROS-destroying catalases (CATs) and ROS-generating NADPH oxidase (NOX). cat-1 is also induced by illumination, and it reduces ROS levels. Although ROS oscillation persists in the absence of frq, wc-1 or wc-2, its homeostasis is altered. Furthermore, genetic and biochemical evidence reveals that ROS concentration regulates the transcriptional function of WCC and a higher ROS concentration enhances conidiation banding. These findings suggest that the circadian system engages in cross-talk with the cellular redox state via ROS-regulatory factors.

  7. [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.

  8. 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

  9. Antibody-dependent cellular cytotoxicity of vascular endothelium: characterization and pathogenic associations in systemic sclerosis.

    PubMed Central

    Holt, C M; Lindsey, N; Moult, J; Malia, R G; Greaves, M; Hume, A; Rowell, N R; Hughes, P

    1989-01-01

    Ten sera from 48 patients with systemic sclerosis were found to be capable of producing cytotoxicity of human umbilical venous and arterial endothelium when co-cultured with peripheral blood mononuclear cells. Fractionation of sera on Ultrogel and the preparation of monomeric IgG by ion exchange and affinity chromatography suggested that the cytotoxicity was mediated by anti-endothelial antibodies capable of pre-sensitizing target cells in a mechanism that resembled antibody-dependent cellular cytotoxicity. These anti-endothelial antibodies together with C1q-binding immune complexes and anti-cardiolipin antibodies were found in 18 of 28 patients so investigated, suggesting that multiple immunological mechanisms may be involved in the pathogenesis of the vascular lesion of systemic sclerosis. PMID:2612050

  10. A putative Arabidopsis thaliana glycosyltransferase, At4g01220, which is closely related to three plant cell wall-specific xylosyltransferases, is differentially expressed spatially and temporally.

    PubMed

    Fangel, Jonatan U; Petersen, Bent L; Jensen, Niels B; Willats, William G T; Bacic, Antony; Egelund, Jack

    2011-03-01

    Plant cell wall polysaccharides are amongst the most complex, heterogeneous and abundant bio-molecules on earth. This makes the biosynthetic enzymes, namely the glycosyltransferases and polysaccharide synthases, important research targets in plant science and biotechnology. As an initial step to characterize At4g01220, a putative Arabidopsis thaliana encoding glycosyltransferases in CAZy GT-family-77 that is similar to three known xylosyltransferases involved in the biosynthesis of the pectic polysaccharide, rhamnogalacturonan II, we conducted an expression analysis. In transgenic Arabidopsis thaliana plants containing a fusion between the At4g01220 promoter and the gusA reporter gene we found the expression to be spatially and developmentally regulated. Analysis of Nicotiana benthamiana transfected with the At2g01220::YFP fusion protein revealed that the fusion protein resided in a Brefeldin A-sensitive compartment consistent with a sub-cellular location in the Golgi apparatus. In addition, in silico expression analysis from the Genevestigator database revealed that At4g01220 was up-regulated upon treatment with isoxaben, an inhibitor of cellulose synthesis, which, together with a co-expression analysis that identified a number of plant cell wall co-related biosynthetic genes, suggests involvement in cell wall biosynthesis with pectin being a prime candidate. The data presented provide insights into the expression, sub-cellular location and regulation of At4g01220 under various conditions and may help elucidate its specific function.

  11. Level of CYP4G19 Expression Is Associated with Pyrethroid Resistance in Blattella germanica.

    PubMed

    Guo, Guang-Zhou; Geng, Yi-Jie; Huang, Da-Na; Xue, Cai-Fang; Zhang, Ren-Li

    2010-01-01

    German cockroaches have become a large problem in the Shenzhen area because of their pesticide resistance, especially to pyrethroid. A pyrethroid called "Jia Chong Qing" to prevent pests for a long time were found to be resistant to "Jia Chong Qing" with resistance index of 3.88 measured using RT-PCR and immunohistochemistry analysis showed that both CYP4G19 mRNA and CYP4G19 protein expression levels in the wild strain were substantially higher than that of a sensitive strain. dsRNA segments derived from the target gene CYP4G19 were prepared using in vitro transcription and were microinjected into abdomens of the wild strain. Two to eight days after injection, the result showed that CYP4G19 mRNA expressions were significantly reduced in the groups injected with dsRNAs.

  12. Minimum-noise production of translation factor eIF4G maps to a mechanistically determined optimal rate control window for protein synthesis

    PubMed Central

    Meng, Xiang; Firczuk, Helena; Pietroni, Paola; Westbrook, Richard; Dacheux, Estelle; Mendes, Pedro; McCarthy, John E.G.

    2017-01-01

    Gene expression noise influences organism evolution and fitness. The mechanisms determining the relationship between stochasticity and the functional role of translation machinery components are critical to viability. eIF4G is an essential translation factor that exerts strong control over protein synthesis. We observe an asymmetric, approximately bell-shaped, relationship between the average intracellular abundance of eIF4G and rates of cell population growth and global mRNA translation, with peak rates occurring at normal physiological abundance. This relationship fits a computational model in which eIF4G is at the core of a multi-component–complex assembly pathway. This model also correctly predicts a plateau-like response of translation to super-physiological increases in abundance of the other cap-complex factors, eIF4E and eIF4A. Engineered changes in eIF4G abundance amplify noise, demonstrating that minimum stochasticity coincides with physiological abundance of this factor. Noise is not increased when eIF4E is overproduced. Plasmid-mediated synthesis of eIF4G imposes increased global gene expression stochasticity and reduced viability because the intrinsic noise for this factor influences total cellular gene noise. The naturally evolved eIF4G gene expression noise minimum maps within the optimal activity zone dictated by eIF4G's mechanistic role. Rate control and noise are therefore interdependent and have co-evolved to share an optimal physiological abundance point. PMID:27928055

  13. 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).

  14. 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…

  15. 4G/5G polymorphism and haplotypes of SERPINE1 in atherosclerotic diseases of coronary arteries.

    PubMed

    Koch, Werner; Schrempf, Matthias; Erl, Anna; Mueller, Jakob C; Hoppmann, Petra; Schömig, Albert; Kastrati, Adnan

    2010-06-01

    We assessed the association between common variation at the SERPINE1 (PAI1) locus and myocardial infarction (MI). Haplotype-tagging polymorphisms, including the 4G/5G deletion/insertion polymorphism and seven single nucleotide polymorphisms, were analysed in a German sample containing 3,657 cases with MI and 1,211 controls. The association between the 4G/5G polymorphism and MI was examined in a meta-analysis of data extracted from 32 studies (13,267 cases/14,716 controls). In addition, the relation between the 4G/5G polymorphism and coronary diseases, comprising MI, coronary artery disease, coronary heart disease, or the acute coronary syndrome, was assessed in a combined analysis enclosing 43 studies (17,278 cases/18,039 controls). None of the tagging polymorphisms was associated with MI in the present sample (p 4G allele carriers was 1.02 (95% confidence interval [CI] 0.87-1.19) compared to the 5G5G genotype. None of 13 common (frequency >1.0%) 8-marker haplotypes was related to the risk of MI. In a meta-analysis specifically addressing the association with MI, no elevated risk was found in the carriers of the 4G allele (OR 1.07, 95% CI 0.99-1.16; p = 0.11). A more general combined analysis of coronary diseases showed a marginally increased risk in 4G allele carriers (OR 1.08, 95% CI 1.00-1.16; p = 0.044). In essence, tagging polymorphisms, including the 4G/5G polymorphism, and common haplotypes of the SERPINE1 gene region were not associated with MI in a German sample, and no compelling evidence was obtained for a relationship of the 4G/5G polymorphism to MI and coronary atherosclerosis in a meta-analysis.

  16. Cellular bases of behavioral plasticity: establishing and modifying synaptic circuits in the Drosophila genetic system.

    PubMed

    Rohrbough, Jeffrey; O'Dowd, Diane K; Baines, Richard A; Broadie, Kendal

    2003-01-01

    Genetic malleability and amenability to behavioral assays make Drosophila an attractive model for dissecting the molecular mechanisms of complex behaviors, such as learning and memory. At a cellular level, Drosophila has contributed a wealth of information on the mechanisms regulating membrane excitability and synapse formation, function, and plasticity. Until recently, however, these studies have relied almost exclusively on analyses of the peripheral neuromuscular junction, with a smaller body of work on neurons grown in primary culture. These experimental systems are, by themselves, clearly inadequate for assessing neuronal function at the many levels necessary for an understanding of behavioral regulation. The pressing need is for access to physiologically relevant neuronal circuits as they develop and are modified throughout life. In the past few years, progress has been made in developing experimental approaches to examine functional properties of identified populations of Drosophila central neurons, both in cell culture and in vivo. This review focuses on these exciting developments, which promise to rapidly expand the frontiers of functional cellular neurobiology studies in Drosophila. We discuss here the technical advances that have begun to reveal the excitability and synaptic transmission properties of central neurons in flies, and discuss how these studies promise to substantially increase our understanding of neuronal mechanisms underlying behavioral plasticity.

  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.

  18. Cellular and Molecular Actions of Methylene Blue in the Nervous System

    PubMed Central

    Oz, Murat; Lorke, Dietrich E.; Hasan, Mohammed; Petroianu, George A.

    2010-01-01

    Methylene Blue (MB), following its introduction to biology in the 19th century by Ehrlich, has found uses in various areas of medicine and biology. At present, MB is the first line of treatment in methemoglobinemias, is used frequently in the treatment of ifosfamide-induced encephalopathy, and is routinely employed as a diagnostic tool in surgical procedures. Furthermore, recent studies suggest that MB has beneficial effects in Alzheimer's disease and memory improvement. Although the modulation of the cGMP pathway is considered the most significant effect of MB, mediating its pharmacological actions, recent studies indicate that it has multiple cellular and molecular targets. In the majority of cases, biological effects and clinical applications of MB are dictated by its unique physicochemical properties including its planar structure, redox chemistry, ionic charges, and light spectrum characteristics. In this review article, these physicochemical features and the actions of MB on multiple cellular and molecular targets are discussed with regard to their relevance to the nervous system. PMID:19760660

  19. A Real Space Cellular Automaton Laboratory (ReSCAL) to analyze complex geophysical systems

    NASA Astrophysics Data System (ADS)

    Rozier, O.; Narteau, C.

    2012-04-01

    The Real Space Cellular Automaton Laboratory (ReSCAL) is a generator of 3D multiphysics, markovian and stochastic cellular automata with continuous time. The objective of this new software released under a GNU licence is to develop interdisciplinary research collaboration to investigate the dynamics of complex geophysical systems. In a vast majority of cases, a numerical model is a set of physical variables (temperature, pressure, velocity, etc...) that are recalculated over time according to some predetermined rules or equations. Then, any point in space is entirely characterized by a local set of parameters. This is not the case in ReSCAL where the only local variable is a state-parameter that represent the different phases involved in the problem. An elementary cell represent a given volume of real-space. Pairs of nearest neighbour cells are called doublet. For each individual physical process that we take into account, there is a set of doublet transitions. Using this approach we can model a wide range of physical-chemical or anthropological processes. Here, we present different ingredients of ReSCAL using published applications in geosciences (Narteau et al. 2001 and 2009). We also show how ReSCAL can be developped and used across many displines in geophysics and physical geography. Supplementary informations: Sources files of ReSCAL can be download on http://www.ipgp.fr/~rozier/ReSCAL/rescal-en.html

  20. 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

  1. Molecular and cellular organization of the taste system in the Drosophila larva.

    PubMed

    Kwon, Jae Young; Dahanukar, Anupama; Weiss, Linnea A; Carlson, John R

    2011-10-26

    We examine the molecular and cellular basis of taste perception in the Drosophila larva through a comprehensive analysis of the expression patterns of all 68 Gustatory receptors (Grs). Gr-GAL4 lines representing each Gr are examined, and 39 show expression in taste organs of the larval head, including the terminal organ (TO), the dorsal organ (DO), and the pharyngeal organs. A receptor-to-neuron map is constructed. The map defines 10 neurons of the TO and DO, and it identifies 28 receptors that map to them. Each of these neurons expresses a unique subset of Gr-GAL4 drivers, except for two neurons that express the same complement. All of these neurons express at least two drivers, and one neuron expresses 17. Many of the receptors map to only one of these cells, but some map to as many as six. Conspicuously absent from the roster of Gr-GAL4 drivers expressed in larvae are those of the sugar receptor subfamily. Coexpression analysis suggests that most larval Grs act in bitter response and that there are distinct bitter-sensing neurons. A comprehensive analysis of central projections confirms that sensory information collected from different regions (e.g., the tip of the head vs the pharynx) is processed in different regions of the suboesophageal ganglion, the primary taste center of the CNS. Together, the results provide an extensive view of the molecular and cellular organization of the larval taste system.

  2. Cellular changes, molecular pathways and the immune system following photodynamic treatment.

    PubMed

    Skupin-Mrugalska, P; Sobotta, L; Kucinska, M; Murias, M; Mielcarek, J; Düzgüneş, N

    2014-01-01

    Photodynamic therapy (PDT) is a novel medical technique involving three key components: light, a photosensitizer molecule and molecular oxygen, which are essential to achieve the therapeutic effect. There has been great interest in the use of PDT in the treatment of many cancers and skin disorders. Upon irradiation with light of a specific wavelength, the photosensitizer undergoes several reactions resulting in the production of reactive oxygen species (ROS). ROS may react with different biomolecules, causing defects in many cellular structures and biochemical pathways. PDT-mediated tumor destruction in vivo involves cellular mechanisms with photodamage of mitochondria, lysosomes, nuclei, and cell membranes that activate apoptotic, necrotic and autophagic signals, leading to cell death. PDT is capable of changing the tumor microenvironment, thereby diminishing the supply of oxygen, which explains the antiangiogenic effect of PDT. Finally, inflammatory and immune responses play a crucial role in the long-lasting consequences of PDT treatment. This review is focused on the biochemical effects exerted by photodynamic treatment on cell death signaling pathways, destruction of the vasculature, and the activation of the immune system.

  3. 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

  4. PAI-1 mRNA expression and plasma level in rheumatoid arthritis: relationship with 4G/5G PAI-1 polymorphism.

    PubMed

    Muñoz-Valle, José Francisco; Ruiz-Quezada, Sandra Luz; Oregón-Romero, Edith; Navarro-Hernández, Rosa Elena; Castañeda-Saucedo, Eduardo; De la Cruz-Mosso, Ulises; Illades-Aguiar, Berenice; Leyva-Vázquez, Marco Antonio; Castro-Alarcón, Natividad; Parra-Rojas, Isela

    2012-12-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane, cartilage and bone. PAI-1 is a key regulator of the fibrinolytic system through which plasminogen is converted to plasmin. The plasmin activates the matrix metalloproteinase system, which is closely related with the joint damage and bone destruction in RA. The aim of this study was to investigate the relationship between 4G/5G PAI-1 polymorphism with mRNA expression and PAI-1 plasma protein levels in RA patients. 113 RA patients and 123 healthy subjects (HS) were included in the study. The 4G/5G PAI-1 polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism method; the PAI-1 mRNA expression was determined by real-time PCR; and the soluble PAI-1 (sPAI-1) levels were quantified using an ELISA kit. No significant differences in the genotype and allele frequencies of 4G/5G PAI-1 polymorphism were found between RA patients and HS. However, the 5G/5G genotype was the most frequent in both studied groups: RA (42%) and HS (44%). PAI-1 mRNA expression was slightly increased (0.67 fold) in RA patients with respect to HS (P = 0.0001). In addition, in RA patients, the 4G/4G genotype carriers showed increased PAI-1 mRNA expression (3.82 fold) versus 4G/5G and 5G/5G genotypes (P = 0.0001), whereas the sPAI-1 plasma levels did not show significant differences. Our results indicate that the 4G/5G PAI-1 polymorphism is not a marker of susceptibility in the Western Mexico. However, the 4G/4G genotype is associated with high PAI-1 mRNA expression but not with the sPAI-1 levels in RA patients.

  5. 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

  6. VizieR Online Data Catalog: Morphologies of S4G galaxies (Laine+, 2014)

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

    The sample we used is the full S4G sample (Sheth et al., 2010PASP..122.1397S, Cat. J/PASP/122/1397), consisting of 2352 galaxies (10 of the 2331 galaxies specified in Sheth et al. 2010 were not observed, mostly because they were close to a very bright star, and 31 galaxies were added) with systemic velocity Vsys,radio< 3000km/s, corresponding to a distance d<45Mpc for a Planck-mission-based Hubble constant (Ade et al., 2014A&A...566A..54P) of 67km/s/Mpc and a distance d<41Mpc for a Hubble constant of 71km/s/Mpc, total corrected blue magnitude mBcorr<15.5, blue light isophotal angular diameter D25>1.0-arcmin, and a Galactic latitude |b|>30° (Sheth et al. 2010). All the galaxies in this sample were imaged with the Spitzer Space Telescope's IRAC. We used the channel 1 (3.6um) mosaics made of eight 30-s frames per spatial position. (1 data file).

  7. 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.

  8. 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.

  9. 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.

  10. Cellular computational networks--a scalable architecture for learning the dynamics of large networked systems.

    PubMed

    Luitel, Bipul; Venayagamoorthy, Ganesh Kumar

    2014-02-01

    Neural networks for implementing large networked systems such as smart electric power grids consist of multiple inputs and outputs. Many outputs lead to a greater number of parameters to be adapted. Each additional variable increases the dimensionality of the problem and hence learning becomes a challenge. Cellular computational networks (CCNs) are a class of sparsely connected dynamic recurrent networks (DRNs). By proper selection of a set of input elements for each output variable in a given application, a DRN can be modified into a CCN which significantly reduces the complexity of the neural network and allows use of simple training methods for independent learning in each cell thus making it scalable. This article demonstrates this concept of developing a CCN using dimensionality reduction in a DRN for scalability and better performance. The concept has been analytically explained and empirically verified through application.

  11. 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

  12. 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.

  13. Global stability and exact solution of an arbitrary-solute nonlinear cellular mass transport system.

    PubMed

    Benson, James D

    2014-12-01

    The prediction of the cellular state as a function of extracellular concentrations and temperatures has been of interest to physiologists for nearly a century. One of the most widely used models in the field is one where mass flux is linearly proportional to the concentration difference across the membrane. These fluxes define a nonlinear differential equation system for the intracellular state, which when coupled with appropriate initial conditions, define the intracellular state as a function of the extracellular concentrations of both permeating and nonpermeating solutes. Here we take advantage of a reparametrization scheme to extend existing stability results to a more general setting and to a develop analytical solutions to this model for an arbitrary number of extracellular solutes.

  14. 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.

  15. Cellular and circuit properties supporting different sensory coding strategies in electric fish and other systems.

    PubMed

    Marsat, Gary; Longtin, André; Maler, Leonard

    2012-08-01

    Neural codes often seem tailored to the type of information they must carry. Here we contrast the encoding strategies for two different communication signals in electric fish and describe the underlying cellular and network properties that implement them. We compare an aggressive signal that needs to be quickly detected, to a courtship signal whose quality needs to be evaluated. The aggressive signal is encoded by synchronized bursts and a predictive feedback input is crucial in separating background noise from the communication signal. The courtship signal is accurately encoded through a heterogenous population response allowing the discrimination of signal differences. Most importantly we show that the same strategies are used in other systems arguing that they evolved similar solutions because they faced similar tasks.

  16. 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.

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

    SciTech Connect

    Shen, Yunxue

    2002-01-01

    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

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

    SciTech Connect

    Shen, Yunxue

    2001-01-01

    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

  19. 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

  20. 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

  1. Cellular Defense System Gene Expression Profiling of Human Whole Blood: Opportunities to Predict Health Benefits in Response to Diet12

    PubMed Central

    Drew, Janice E.

    2012-01-01

    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

  2. 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.

  3. Bone remodeling in the context of cellular and systemic regulation: the role of osteocytes and the nervous system.

    PubMed

    Niedźwiedzki, Tadeusz; Filipowska, Joanna

    2015-10-01

    Bone is a dynamic tissue that undergoes constant remodeling. The appropriate course of this process determines development and regeneration of the skeleton. Tight molecular control of bone remodeling is vital for the maintenance of appropriate physiology and microarchitecture of the bone, providing homeostasis, also at the systemic level. The process of remodeling is regulated by a rich innervation of the skeleton, being the source of various growth factors, neurotransmitters, and hormones regulating function of the bone. Although the course of bone remodeling at the cellular level is mainly associated with the activity of osteoclasts and osteoblasts, recently also osteocytes have gained a growing interest as the principal regulators of bone turnover. Osteocytes play a significant role in the regulation of osteogenesis, releasing sclerostin (SOST), an inhibitor of bone formation. The process of bone turnover, especially osteogenesis, is also modulated by extra-skeletal molecules. Proliferation and differentiation of osteoblasts are promoted by the brain-derived serotonin and hypothetically inhibited by its intestinal equivalent. The activity of SOST and serotonin is either directly or indirectly associated with the canonical Wnt/β-catenin signaling pathway, the main regulatory pathway of osteoblasts function. The impairment of bone remodeling may lead to many skeletal diseases, such as high bone mass syndrome or osteoporosis. In this paper, we review the most recent data on the cellular and molecular mechanisms of bone remodeling control, with particular emphasis on the role of osteocytes and the nervous system in this process.

  4. 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.

  5. Isolated renal vein thrombosis associated with MTHFR-1298 and PAI-1 4G gene mutations.

    PubMed

    Cinemre, Hakan; Bilir, Cemil; Akdemir, Nermin

    2010-12-01

    Isolated renal vein thrombosis is very rare without the presence of nephrotic syndrome. It is more common in the newborns and infants. Whereas major risk factors in adults are the procoagulant states such as protein C or S deficiency, factor V Leiden mutation, primary or secondary antiphospholipid syndrome, severe hypothyroidism, and trauma. Here, we report a case of isolated renal vein thrombosis associated with MTHFR-1298 and PAI-1 4G gene mutations. It should be noted that the presence of MTHFR-1298 and PAI-1 4G gene mutations together might be one of the examples of genetic mutation combinations that increase the likelihood of a thrombotic event.

  6. 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…

  7. An Integrative Model of the Cardiovascular System Coupling Heart Cellular Mechanics with Arterial Network Hemodynamics

    PubMed Central

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

    2013-01-01

    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. PMID:23960442

  8. Induced Pluripotent Stem Cell Derived Macrophages as a Cellular System to Study Salmonella and Other Pathogens

    PubMed Central

    Hale, Christine; Yeung, Amy; Goulding, David; Pickard, Derek; Alasoo, Kaur; Powrie, Fiona; Dougan, Gordon; Mukhopadhyay, Subhankar

    2015-01-01

    A number of pathogens, including several human-restricted organisms, persist and replicate within macrophages (Mφs) as a key step in pathogenesis. The mechanisms underpinning such host-restricted intracellular adaptations are poorly understood, in part, due to a lack of appropriate model systems. Here we explore the potential of human induced pluripotent stem cell derived macrophages (iPSDMs) to study such pathogen interactions. We show iPSDMs express a panel of established Mφ-specific markers, produce cytokines, and polarise into classical and alternative activation states in response to IFN-γ and IL-4 stimulation, respectively. iPSDMs also efficiently phagocytosed inactivated bacterial particles as well as live Salmonella Typhi and S. Typhimurium and were able to kill these pathogens. We conclude that iPSDMs can support productive Salmonella infection and propose this as a flexible system to study host/pathogen interactions. Furthermore, iPSDMs can provide a flexible and practical cellular platform for assessing host responses in multiple genetic backgrounds. PMID:25946027

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

    PubMed

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

    2014-12-01

    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 the nervous, 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 the 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.

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

    PubMed

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

    2016-04-26

    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.

  11. A new in vitro cellular system for the analysis of mineral fiber biopersistence.

    PubMed

    Dika Nguea, Hermine; de Reydellet, Aymon; Lehuédé, Patrice; de Méringo, Alain; Robé, Anne; Le Faou, Alain; Rihn, Bertrand H

    2008-07-01

    The toxicity of mineral fibers, whether they are natural or man made (MMMF), is usually evaluated in vivo using biopersistence tests in rodents. Development of an in vitro cellular model would be worthwhile in order to reduce, refine and finally replace animal models. For this purpose, we developed an in vitro assay using human monocytic cell line (U-937) to evaluate a new manufactured rock wool fiber (HDN) biodegradation. Experiments on earlier known mineral fibers asbestos (crocidolite) and glass wool fibers (CM44) were also performed. U-937 responded to HDN and CM44 only if they were activated. Among the different activators we used, Escherichia coli living cells as well as FS were the most efficient as evidenced by alterations of HDN and CM44 surface, detected by scanning electron microscopy, and by the measure of silicon released from the rock wool fibers. Asbestos fibers were not degraded when incubated in the presence of living bacteria. The MMMF modifications were function of the fiber composition, the time of exposure to activated cells and the concentration of activators. The pattern of MMMF degradation by our in vitro system was in accordance with those observed in an in vivo study, thus indicating that the fiber degradation by macrophage cells activated by E. coli living cells as well as FS is a valuable system to assess mineral fibers' biopersistence.

  12. 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

  13. 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.

  14. 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

    2016-01-13

    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.

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

    PubMed

    Renaud, Justine; Martinoli, Maria-Grazia

    2016-07-17

    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.

  16. 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.

  17. Implementation of a cellular neural network-based segmentation algorithm on the bio-inspired vision system

    NASA Astrophysics Data System (ADS)

    Karabiber, Fethullah; Grassi, Giuseppe; Vecchio, Pietro; Arik, Sabri; Yalcin, M. Erhan

    2011-01-01

    Based on the cellular neural network (CNN) paradigm, the bio-inspired (bi-i) cellular vision system is a computing platform consisting of state-of-the-art sensing, cellular sensing-processing and digital signal processing. This paper presents the implementation of a novel CNN-based segmentation algorithm onto the bi-i system. The experimental results, carried out for different benchmark video sequences, highlight the feasibility of the approach, which provides a frame rate of about 26 frame/sec. Comparisons with existing CNN-based methods show that, even though these methods are from two to six times faster than the proposed one, the conceived approach is more accurate and, consequently, represents a satisfying trade-off between real-time requirements and accuracy.

  18. 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…

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. Effects of some iridoids from plant origin on arachidonic acid metabolism in cellular systems.

    PubMed

    Bermejo Benito, P; Díaz Lanza, A M; Silván Sen, A M; De Santos Galindez, J; Fernandez Matellano, L; Sanz Gómez, A; Abad Martínez, M J

    2000-05-01

    Seven iridoid glycosides isolated from different extracts of Scrophularia scorodonia L., namely bartsioside, aucubin, harpagide, harpagoside, 8-acetylharpagide, scorodioside and scropolioside B, had been evaluated for their in vitro anti-inflammatory activity in cellular systems generating COX and LOX metabolites. Structure-activity relationships obtained from in vitro screening results were discussed. Most compounds assayed did not exhibit any significant effect on PGE2- and LTC4-release from calcium ionophore-stimulated mouse peritoneal macrophages. In the LTC4-assay, only aucubin showed a significant effect, with an IC50 value of 72 microM. Harpagoside and harpagide also inhibited release of LTC4, but neither effect reached statistical significance. The release of PGE2 by mouse peritoneal macrophages stimulated with calcium ionophore was inhibited by harpagoside and 8-acetylharpagide, but this effect is not statistically significant. However, most iridoids assayed showed a significant effect on TXB2-release from calcium ionophorestimulated human platelets, with inhibition percentages slightly lower than the reference drug ibuprofen. Only harpagide, scorodioside and scropolioside B had no significant effect on TXB2-release. Our results indicate that selective inhibition of the TX-synthase enzyme may be the primary target of action of most of these iridoids, and one of the mechanisms through which they exert their anti-inflammatory effects.

  4. [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.

  5. Low levels of graphene and graphene oxide inhibit cellular xenobiotic defense system mediated by efflux transporters.

    PubMed

    Liu, Su; Jiang, Wei; Wu, Bing; Yu, Jing; Yu, Haiyan; Zhang, Xu-Xiang; Torres-Duarte, Cristina; Cherr, Gary N

    2016-01-01

    Low levels of graphene and graphene oxide (GO) are considered to be environmentally safe. In this study, we analyzed the potential effects of graphene and GO at relatively low concentrations on cellular xenobiotic defense system mediated by efflux transporters. The results showed that graphene (<0.5 μg/mL) and GO (<20 μg/mL) did not decrease cell viability, generate reactive oxygen species, or disrupt mitochondrial function. However, graphene and GO at the nontoxic concentrations could increase calcein-AM (CAM, an indicator of membrane ATP-binding cassette (ABC) transporter) activity) accumulation, indicating inhibition of ABC transporters' efflux capabilities. This inhibition was observed even at 0.005 μg/mL graphene and 0.05 μg/mL GO, which are 100 times and 400 times lower than their lowest toxic concentration from cytotoxicity experiments, respectively. The inhibition of ABC transporters significantly increased the toxicity of paraquat and arsenic, known substrates of ABC transporters. The inhibition of ABC transporters was found to be based on graphene and GO damaging the plasma membrane structure and fluidity, thus altering functions of transmembrane ABC transporters. This study demonstrates that low levels of graphene and GO are not environmentally safe since they can significantly make cell more susceptible to other xenobiotics, and this chemosensitizing activity should be considered in the risk assessment of graphene and GO.

  6. 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

  7. Computer simulation of a cellular automata model for the immune response in a retrovirus system

    NASA Astrophysics Data System (ADS)

    Pandey, R. B.

    1989-02-01

    Immune response in a retrovirus system is modeled by a network of three binary cell elements to take into account some of the main functional features of T4 cells, T8 cells, and viruses. Two different intercell interactions are introduced, one of which leads to three fixed points while the other yields bistable fixed points oscillating between a healthy state and a sick state in a mean field treatment. Evolution of these cells is studied for quenched and annealed random interactions on a simple cubic lattice with a nearest neighbor interaction using inhomogenous cellular automata. Populations of T4 cells and viral cells oscillate together with damping (with constant amplitude) for annealed (quenched) interaction on increasing the value of mixing probability B from zero to a characteristic value B ca ( B cq). For higher B, the average number of T4 cells increases while that of the viral infected cells decreases monotonically on increasing B, suggesting a phase transition at B ca ( B cq).

  8. Computer simulation of a cellular automata model for the immune response in a retrovirus system

    SciTech Connect

    Pandey, R.B.

    1989-02-01

    Immune response in a retrovirus system is modeled by a network of three binary cell elements to take into account some of the main functional features of T4 cells, T8 cells, and viruses. Two different intercell interactions are introduced, one of which leads to three fixed points while the other yields bistable fixed points oscillating between a healthy state and a sick state in a mean field treatment. Evolution of these cells is studied for quenched and annealed random interactions on a simple cubic lattice with a nearest neighbor interaction using inhomogenous cellular automata. Populations of T4 cells and viral cells oscillate together with damping (with constant amplitude) for annealed (quenched) interaction on increasing the value of mixing probability B from zero to a characteristic value B/sub ca/ (B/sub cq/). For higher B, the average number of T4 cells increases while that of the viral infected cells decreases monotonically on increasing B, suggesting a phase transition at B/sub ca/ (B/sub cq/).

  9. 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

  10. 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

  11. 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

  12. 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...

  13. 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

  14. Randomized Controlled Trial of a Personalized Cellular Phone Reminder System to Enhance Adherence to Antiretroviral Therapy

    PubMed Central

    Kumar, Vikram; Doros, Gheorghe; Farmer, Eric; Drainoni, Mari-Lynn; Rybin, Denis; Myung, Dan; Jackson, Jonathan; Backman, Elke; Stanic, Anela; Skolnik, Paul R.

    2011-01-01

    Abstract Adherence to antiretroviral therapy (ART) represents one of the strongest predictors of progression to AIDS, yet it is difficult for most patients to sustain high levels of adherence. This study compares the efficacy of a personalized cell phone reminder system (ARemind) in enhancing adherence to ART versus a beeper. Twenty-three HIV-infected subjects on ART with self-reported adherence less than 85% were randomized to a cellular phone (CP) or beeper (BP). CP subjects received personalized text messages daily; in contrast, BP subjects received a reminder beep at the time of dosing. Interviews were scheduled at weeks 3 and 6. Adherence to ART was measured by self-report (SR, 7-day recall), pill count (PC, past 30 days at baseline, then past 3 weeks), Medication Event Monitoring System (MEMS; cumulatively at 3 and 6 weeks), and via a composite adherence score constructed by combining MEMS, pill count, and self report. A mixed effects model adjusting for baseline adherence was used to compare adherence rates between the intervention groups at 3 and 6 weeks. Nineteen subjects completed all visits, 10 men and 9 females. The mean age was 42.7 ± 6.5 years, 37% of subjects were Caucasian and 89% acquired HIV heterosexually. The average adherence to ART was 79% by SR and 65% by PC at baseline in both arms; over 6 weeks adherence increased and remained significantly higher in the ARemind group using multiple measures of adherence. A larger and longer prospective study is needed to confirm these findings and to better understand optimal reminder messages and user fatigue. PMID:21323532

  15. 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.

  16. Hybrid-modified poly(D,L-lactide-co-glycolide) nanospheres for a novel cellular drug delivery system.

    PubMed

    Tahara, Kohei; Furukawa, Sahori; Yamamoto, Hiromitsu; Kawashima, Yoshiaki

    2010-06-15

    We prepared surface-modified poly(D,L-lactide-co-glycolide) (PLGA) nanospheres (NS) for use as cellular drug and gene delivery systems using an emulsion solvent diffusion method. In this study, we screened for an appropriate surface modifier to improve NS cellular uptake. Poly-L-lysine (PLL)-modified PLGA NS were taken up by A549 cells in significantly higher amounts (17-fold) than unmodified NS. In order to provide a novel function, PLGA NS were hybrid-modified using both; a cationic polymer, PLL, and a nonionic surfactant, polysorbate 80, to improve cellular uptake in serum-containing medium (SCM). Hybrid modification abrogated the decreased PLGA NS cellular uptake in SCM as a result of better dispersion in serum compared to PLL-PLGA NS, which aggregated in SCM. Luciferase activity of Hybrid-NS/pCMV-Luc complexes in A549 cells in SCM was 122-fold higher than PLL-NS. Hybrid-PLGA NS were not cytotoxic for A549 cells. In conclusion, Hybrid-PLGA NS have great potential as effective cellular drug delivery carriers.

  17. Practical demonstration of spectrally efficient FDM millimeter-wave radio over fiber systems for 5G cellular networking

    NASA Astrophysics Data System (ADS)

    Mikroulis, Spiros; Xu, Tongyang; Darwazeh, Izzat

    2016-02-01

    This work reports the first demonstration of spectrally efficient frequency division multiplexed (SEFDM) signal transmission based on mm-wave radio over fiber (RoF) technology. Such systems aim to satisfy the beyond 4G (5G) demands of low cost, low energy, millimeter-wave carrier frequencies and high spectral efficiency. The proposed radio over fiber topology, using passive optical network (PON) infrastructure and low-cost multimode fiber (MMF), is analyzed and a proof-of-concept SEFDM radio over 250m OM-1 MMF transmission with a 3m 60GHz wireless link is successfully demonstrated. Different systems are demonstrated, at raw data rates up to 3.7 Gb/s, showing SEFDM spectrum saving up to 40% relative to OFDM.

  18. Impact of the 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene on primary nephrotic syndrome.

    PubMed

    Luo, Yuezhong; Wang, Chao; Tu, Haitao

    2014-03-01

    The aim of the present study was to investigate whether the four guanosines (4G)/five guanosines (5G) polymorphism in the gene coding for plasminogen activator inhibitor-1 (PAI-1) affects the clinical features of primary nephrotic syndrome (PNS). A cohort of 200 biopsy-diagnosed PNS patients was studied, with 40 healthy subjects as controls. The PAI-1 gene polymorphism was detected by polymerase chain reaction and DNA sequencing. Associations between the PAI-1 4G/5G polymorphism and clinical features and pathological types of PNS were analyzed. The results indicated that the PAI-1 genotype distribution is significantly different between patients with PNS and healthy controls, with significantly higher numbers of the 4G/4G genotype and lower numbers of the 5G5G genotype detected in PNS patients compared to controls (both P<0.05). The frequency of the 4G allele was also significantly higher in PNS patients compared to healthy controls (P<0.01). Among the different pathological types of PNS, IgA nephropathy (IgAN) and membranous nephropathy (MN) were associated with significantly increased frequencies of the 4G/4G and 4G/5G genotypes, as well as of the 4G allele. The increased 4G frequency was also detected in patients with minimal change disease (MCD). Significantly increased international normalized ratio (INR) and prolonged activated partial thromboplastin time (APTT) were observed in 4G/4G compared to 5G/5G PNS subjects. The response to steroids was not significantly different among the three genotypes. In conclusion, the 4G allele of the PAI-1 gene appears to be associated with PNS, especially in MN and IgAN patients. These findings suggest that specific targeting may be required for the treatment of PNS patients with the 4G/4G genotype.

  19. A preparative suspension culture system permitting quantitation of anchorage-independent growth by direct radiolabeling of cellular DNA.

    PubMed

    Assoian, R K; Boardman, L A; Drosinos, S

    1989-02-15

    We have developed a hybrid methylcellulose/agar suspension culture system which permits long-term colony formation of transformed mesenchymal cells. In contrast to traditional agar suspensions, our system allows for recovery of cells and direct biochemical analysis of anchorage-independent growth. The ability to readily radiolabel cellular macromolecules in these preparative cultures permits a quantitative and objective analysis of colony formation by incorporation of [3H]thymidine into newly synthesized DNA.

  20. 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

  1. 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.

  2. 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

  3. 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

  4. Color image encryption based on hybrid hyper-chaotic system and cellular automata

    NASA Astrophysics Data System (ADS)

    Yaghouti Niyat, Abolfazl; Moattar, Mohammad Hossein; Niazi Torshiz, Masood

    2017-03-01

    This paper proposes an image encryption scheme based on Cellular Automata (CA). CA is a self-organizing structure with a set of cells in which each cell is updated by certain rules that are dependent on a limited number of neighboring cells. The major disadvantages of cellular automata in cryptography include limited number of reversal rules and inability to produce long sequences of states by these rules. In this paper, a non-uniform cellular automata framework is proposed to solve this problem. This proposed scheme consists of confusion and diffusion steps. In confusion step, the positions of the original image pixels are replaced by chaos mapping. Key image is created using non-uniform cellular automata and then the hyper-chaotic mapping is used to select random numbers from the image key for encryption. The main contribution of the paper is the application of hyper chaotic functions and non-uniform CA for robust key image generation. Security analysis and experimental results show that the proposed method has a very large key space and is resistive against noise and attacks. The correlation between adjacent pixels in the encrypted image is reduced and the amount of entropy is equal to 7.9991 which is very close to 8 which is ideal.

  5. Plasminogen Activator Inhibitor-1 (PAI-1) gene 4G/5G alleles frequency distribution in the Lebanese population.

    PubMed

    Shammaa, Dina M R; Sabbagh, Amira S; Taher, Ali T; Zaatari, Ghazi S; Mahfouz, Rami A R

    2008-09-01

    Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of fibrinolysis. Increased plasma PAI-1 levels play an essential role in the pathogenesis of cardiovascular risk and other diseases associated with thrombosis. The 4G/5G polymorphism of the PAI-1 promoter region has been extensively studied in different populations. We studied 160 healthy unrelated Lebanese individuals using a reverse hybridization PCR assay to detect the 5G/5G, 4G/5G and, 4G/4G genotypes of the PAI-1 gene and the frequencies of the 4G and 5G alleles. We found that 4G/5G genotype was the most prevalent (45.6%) followed by 5G/5G (36.9%) and 4G/4G (17.5%). The frequencies of the 4G and 5G alleles were calculated to be 0.403 and 0.597, respectively. Compared to other ethnic communities, the Lebanese population was found to harbour a relatively high prevalence of the rare 4G allele. This, in turn, may predispose this population to develop cardiovascular diseases and other thrombotic clinical conditions. This study aids to enhance our understanding of the genetic features of the Lebanese population.

  6. Study of the genetic variability in a Parkinson's Disease gene: EIF4G1.

    PubMed

    Tucci, Arianna; Charlesworth, Gavin; Sheerin, Una-Marie; Plagnol, Vincent; Wood, Nicholas W; Hardy, John

    2012-06-14

    Chartier-Harlin and colleagues [2] recently reported mutations in the eukaryotic translation initiation factor 4-gamma (EIF4G1) gene in families with parkinsonism. Large-scale screening found two mutations (p.R1205H and p.A502V) only in affected individuals, although their relative frequency was very low. The aim of this study was to investigate EIF4G1 parkinsonism-related variants in two separate cohorts and study coding variability across the gene. We first screened a series of familial Parkinson's Disease (PD) patients in an attempt to confirm previous results by showing segregation. Then, to determine the extent of coding variation in the gene, we first screened a cohort of sub-Saharan African individuals from the Centre d'Etude du Polymorphisme Humain - Human Genome Diversity Cell Line Panel (HGDP) [1] and then analyzed data from 5350 individuals National Heart, Lung, and Blood Institute (NHLBI) exome sequencing project. We failed to identify any PD-related mutations in the familial samples. Conversely we found the p.A502V variant in the NHLBI population. We observed a high number of coding polymorphism in the exons where the two PD variants have been previously reported. We conclude that either EIF4G1 variants are an extremely rare cause of familial PD in Caucasian cohorts, or that A502V is in fact a rare benign variant not involved in PD aetiology. Our data also suggests that the protein can tolerate some extent of variability particularly at this point of the gene.

  7. 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.

  8. 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

  9. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  10. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  11. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  12. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  13. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  14. 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.

  15. Adaptive Cellular Interactions in the Immune System: The Tunable Activation Threshold and the Significance of Subthreshold Responses

    NASA Astrophysics Data System (ADS)

    Grossman, Zvi; Paul, William E.

    1992-11-01

    A major challenge for immunologists is to explain how the immune system adjusts its responses to the microenvironmental context in which antigens are recognized. We propose that lymphocytes achieve this by tuning and updating their responsiveness to recurrent signals. In particular, cellular anergy in vivo is a dynamic state in which the threshold for a stereotypic mode of activation has been elevated. Anergy is associated with other forms of cellular activity, not paralysis. Cells engaged in such subthreshold interactions mediate functions such as maintenance of immunological memory and control of infections. In such interactions, patterns of signals are recognized and classified and evoke selective responses. The robust mechanism proposed for segregation of suprathreshold and subthreshold immune responses allows lymphocytes to use recognition of self-antigens in executing physiological functions. Autoreactivity is allowed where it is dissociated from uncontrolled aggression.

  16. 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

  17. 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

  18. Prognostic value of the PAI-1 4G/5G polymorphism in invasive ductal carcinoma of the breast.

    PubMed

    Yagmurdur, M C; Atac, F B; Tutar, N U; Verdi, H; Isiklar, I; Ozdemir, B H; Ozbek, N; Karakayali, H; Haberal, M

    2008-01-01

    The study group was derived from the archive materials of 55 invasive ductal breast cancer (IDC) patients who had undergone breast-preserving surgery (partial mastectomy/ axillary dissection). All patients included in the study had clinically T(1)-2, N0-M0 invasive ductal carcinoma. Genomic DNA species were extracted from paraffin-embedded blocks, and plasminogen activator inhibitor type-1 (PAI-1) gene 4G/5G genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Patient demographics, axillary metastasis status, metastatic lymph nodi/total dissected lymph nodes from axilla, histopathologic characteristics of tumors, local recurrences, and survival ratio were assessed. PAI-1 4G/5G genotype frequencies were 4G/4G (64%), 4G/5G (31%), and 5G/5G (5%) in the patient group. According to the results based on frequencies, the demographics were not different. Five-year local recurrence rate of 4G/5G patients was the lowest (2/17, 12%) (P = 0.02). Also five-year distant metastases ratio of 4G/5G patients was the highest (18%) (P = 0.01). Five- and 10-year disease-free survival rates for the 4G/4G, 4G/5G, and 5G/5G groups were 97% and 94%, 82% and 77%, and 100% and 94%, respectively (P = 0.004). The results of this study indicate that the 4G allele in the PAI 1 gene had a negative impact on local recurrence and disease-free survival of patients with clinical T(1)-2N0M0 IDC.

  19. 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.

  20. The halo-to-stellar mass ratio in the S4G

    NASA Astrophysics Data System (ADS)

    Díaz-García, Simón; Salo, Heikki; Laurikainen, Eija

    2017-03-01

    We use 3.6 μm photometry for 1154 disk galaxies (i < 65°) in the S4G (Sheth et al. 2010). We obtain the average stellar component of the circular velocity (V disk) and the mean (dark matter) halo-to-stellar mass ratio (M halo/M *) inside the optical radius (R opt) in bins of total stellar mass (M *, from Muñoz-Mateos et al. 2015), providing observational constraints for galaxy formation models to be tested against. We find the M halo/M * - M * relation in good agreement with the best-fit model at z ~ 0 in ΛCDM cosmological simulations (e.g. Moster 2010), assuming that the dark matter halo within R opt comprises a constant fraction (~ 4%) of its total mass.

  1. `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.

  2. PAI-1 4G/5G polymorphism and coronary artery disease risk: a meta-analysis

    PubMed Central

    Liang, Zhongshu; Jiang, Weihong; Ouyang, Mao; Yang, Kan

    2015-01-01

    Many epidemiologic studies have investigated the plasminogen activator inhibitor-1 (PAI-1) gene 4G/5G polymorphism and this association with coronary artery disease (CAD). But definite conclusions can not be drawn. Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) till 10 August 2014. Pooled ORs and 95% CIs were used to assess the strength of the associations. A total of 53 studies including 20921 CAD cases and 18434 controls were included. Significantly elevated CAD risk was found in overall analysis (OR = 1.13, 95% CI: 1.05-1.21, P = 0.0009). In the subgroup analysis by races, significantly increased risk was found in Caucasians (OR = 1.11, 95% CI: 1.03-1.20, P = 0.005) and Asians (OR = 1.20, 95% CI: 1.01-1.42, P = 0.04). In the subgroup analysis by gender, significant association was found in males (OR = 1.15, 95% CI: 1.06-1.25, P = 0.0008), but was not found in females (OR = 1.05, 95% CI: 0.92-1.20, P = 0.47). In the subgroup analysis by age, young populations showed increased CAD risk (OR = 1.19, 95% CI: 1.02-1.37, P = 0.02), but old populations did not show this association (OR = 1.01, 95% CI: 0.82-1.24, P = 0.93). This meta-analysis provides the evidence that PAI-1 4G/5G polymorphism may contribute to the CAD development. PMID:25932140

  3. The endothelin system and endothelin-converting enzyme in the brain: molecular and cellular studies.

    PubMed

    Barnes, K; Turner, A J

    1997-08-01

    The biologically active vasoactive peptides, the endothelins (ETs), are generated from inactive intermediates, the big endothelins, by a unique processing event catalysed by the zinc metalloprotease, endothelin converting enzyme (ECE). In this overview we examine the actions of endothelins in the brain, and focus on the structure and cellular locations of ECE. The heterogeneous distribution in the brain of ET-1, ET-2, and ET-3 is discussed in relation to their hemodynamic, mitogenic and proliferative properties as well as their possible roles as neurotransmitters. The cellular and subcellular localization of ECE in neuronal and in glial cells is compared with that of other brain membrane metalloproteases, neutral endopeptidase-24.11 (neprilysin), angiotensin converting enzyme and aminopeptidase N, which all function in neuropeptide processing and metabolism Unlike these ectoenzymes, ECE exhibits a dual localisation in the cell, being present on the plasma membrane and also, in some instances, being concentrated in a perinuclear region. This differential localization may reflect distinct targeting of different ECE isoforms, ECE-1 alpha, ECE-1 beta, and ECE-2.

  4. 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.; ...

    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%.

  5. Complete Genome Sequence of Cupriavidus basilensis 4G11, Isolated from the Oak Ridge Field Research Center Site.

    PubMed

    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%.

  6. Complete Genome Sequence of Cupriavidus basilensis 4G11, Isolated from the Oak Ridge Field Research Center Site

    PubMed Central

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

    2015-01-01

    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%. PMID:25977418

  7. Endogenous stimuli-sensitive multistage polymeric micelleplex anticancer drug delivery system for efficient tumor penetration and cellular internalization.

    PubMed

    Li, Junjie; Ke, Wendong; Li, Hui; Zha, Zengshi; Han, Yu; Ge, Zhishen

    2015-10-28

    To efficiently deliver anticancer drugs to the entire tumor tissue and cancer cells, an endogenous stimuli-sensitive multistage polymeric micelleplex drug delivery system is developed via electrostatic complexation between poly(ethylene glycol)-block-poly[(N'-dimethylmaleoyl-2-aminoethyl)aspartamide]-block-poly(ε-caprolactone) (PEG-b-PAsp(EDA-DM)-b-PCL) triblock copolymer micelles and cisplatin prodrug (Pt(IV))-conjugated cationic poly(amidoamine) dendrimers (PAMAM-Pt(IV)). The micelleplexes maintain structural stability at pH 7.4 ensuring long blood circulation and high tumor accumulation level, while they exhibit triggered release of secondary PAMAM-Pt(IV) dendrimer nanocarriers at tumoral acidity (≈pH 6.8) due to acid-labile charge-reversal properties of PAsp(EDA-DM) component under mildly acidic condition. The released PAMAM delivery nanocarriers with small size and slightly positive charges exhibit significantly deep tumor tissue penetration and efficient cellular internalization, followed by release of active cisplatin anticancer drug in intracellular reducing medium. In vivo investigation reveals that the Pt(IV)-loading micelleplexes significantly suppress tumor growth via intravenous injection due to synergistic effect of long circulation in bloodstream, high tumor accumulation, deep tumor tissue penetration, and efficient cellular internalization. Thus, the micelleplexes with stimuli-responsive multistage release feature show great potentials for better therapeutic efficacy of cancer especially through enhanced tumor penetration and cellular internalization.

  8. Performance of an adaptive coding scheme in a fixed wireless cellular system working in millimeter-wave bands

    NASA Astrophysics Data System (ADS)

    Farahvash, Shayan; Akhavan, Koorosh; Kavehrad, Mohsen

    1999-12-01

    This paper presents a solution to problem of providing bit- error rate performance guarantees in a fixed millimeter-wave wireless system, such as local multi-point distribution system in line-of-sight or nearly line-of-sight applications. The basic concept is to take advantage of slow-fading behavior of fixed wireless channel by changing the transmission code rate. Rate compatible punctured convolutional codes are used to implement adaptive coding. Cochannel interference analysis is carried out for downlink direction; from base station to subscriber premises. Cochannel interference is treated as a noise-like random process with a power equal to the sum of the power from finite number of interfering base stations. Two different cellular architectures based on using single or dual polarizations are investigated. Average spectral efficiency of the proposed adaptive rate system is found to be at least 3 times larger than a fixed rate system with similar outage requirements.

  9. An asymmetric image cryptosystem based on the adaptive synchronization of an uncertain unified chaotic system and a cellular neural network

    NASA Astrophysics Data System (ADS)

    Cheng, Chao-Jung; Cheng, Chi-Bin

    2013-10-01

    Chaotic dynamics provide a fast and simple means to create an excellent image cryptosystem, because it is extremely sensitive to initial conditions and system parameters, pseudorandomness, and non-periodicity. However, most chaos-based image encryption schemes are symmetric cryptographic techniques, which have been proven to be more vulnerable, compared to an asymmetric cryptosystem. This paper develops an asymmetric image cryptosystem, based on the adaptive synchronization of two different chaotic systems, namely a unified chaotic system and a cellular neural network. An adaptive controller with parameter update laws is formulated, using the Lyapunov stability theory, to asymptotically synchronize the two chaotic systems. The synchronization controller is embedded in the image cryptosystem and generates a pair of asymmetric keys, for image encryption and decryption. Using numerical simulations, three sets of experiments are conducted to evaluate the feasibility and reliability of the proposed chaos-based image cryptosystem.

  10. 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.

  11. 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

  12. 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

  13. Plasminogen activator inhibitor-1 gene 4G/5G polymorphism in Turkish children with asthma and allergic rhinitis.

    PubMed

    Ozbek, Ozlem Yilmaz; Ataç, F Belgin; Ogus, Ersin; Ozbek, Namik

    2009-01-01

    Plasminogen activator inhibitor (PAI-1) has an essential role in tissue remodeling after inflammation. Recent literature revealed only one study evaluating PAI-1 4G/5G gene polymorphism in children with asthma and none in children with allergic rhinitis. We aimed to investigate distribution of PAI-1 4G/5G polymorphism in a group of Turkish children with asthma and allergic rhinitis and compare these findings with those obtained in normal peers. Patients with physician-diagnosed asthma (n = 106) and allergic rhinitis (n = 99) and 83 healthy peers were included in this study. We evaluated PAI-1 4G/5G polymorphism genotype as well as the possible association between PAI-1 4G/5G polymorphism and pulmonary function tests, serum total immunoglobulin E (IgE), total eosinophil count, and skin-prick test positivity in our study. The prevalence of the 4G allele significantly exceeded the values found in the controls both in patients with asthma (p = 0.001) and in patients with allergic rhinitis (p = 0.002). Interestingly, comparison of asthmatic patients revealed that mean baseline percent forced expiratory volume in 1 second and forced vital capacity were significantly higher in patients who bear 5G/5G genotype than in those who have 4G/4G or 4G/5G genotypes. No statistically significant relationship were found between PAI-1 polymorphism and total serum IgE levels, total eosinophil count, or selected skin test responses to aeroallergens. Our study suggests that Turkish children with asthma or allergic rhinitis have a higher prevalence of PAI-1 4G allele compared with their healthy peers.

  14. 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

  15. EphB4 cellular kinase activity assayed using an enzymatic protein interaction system.

    PubMed

    Wehrman, Tom; Nguyen, Mimi; Feng, Wei; Bader, Benjamin

    2013-05-01

    Receptor tyrosine kinases (RTKs) are important players in various cellular processes, including proliferation, migration, metabolism, and neuronal development. EphB4 RTK is essential for the development of a functional arterial-venous network in embryonic and adult neoangiogenesis. To develop novel inhibitors of EphB4 that might have applications in severe diseases like cancer and retinopathies, assays need to be in place that resemble, in a most physiological fashion, the activation and downstream function of the kinase. In addition, such assays need to be amenable to high-throughput screening to serve efficiently the modern drug discovery processes in the pharmaceutical industry. The authors have developed an enzyme fragment complementation assay that measures the interaction of a downstream docking protein to the activated and phosphorylated full-length EphB4 kinase in cells. The assay is specific, robust, and amenable to miniaturization and high-throughput screening. It covers most steps in the activation process of EphB4, including ligand binding, autophosphorylation, and docking of a downstream interactor. This assay format can be transferred to other RTKs and adds an important cell-based kinase assay option to researchers in the field.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. Globular Cluster Populations: Results Including S4G Late-type Galaxies

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

    Using 3.6 and 4.5 μm images of 73 late-type, edge-on galaxies from the S4G survey, we compare the richness of the globular cluster populations of these galaxies to those of early-type galaxies that we measured previously. In general, the galaxies presented here fill in the distribution for galaxies with lower stellar mass, M*, specifically {log}({M}*/{M}⊙ )\\lt 10, overlap the results for early-type galaxies of similar masses, and, by doing so, strengthen the case for a dependence of the number of globular clusters per 109M⊙ of galaxy stellar mass, TN, on M*. For 8.5\\lt {log}({M}*/{M}⊙ )\\lt 10.5 we find the relationship can be satisfactorily described as {T}{{N}}={({M}*/{10}6.7)}-0.56 when M* is expressed in solar masses. The functional form of the relationship is only weakly constrained, and extrapolation outside this range is not advised. Our late-type galaxies, in contrast to our early types, do not show the tendency for low-mass galaxies to split into two TN families. Using these results and a galaxy stellar mass function from the literature, we calculate that, in a volume-limited, local universe sample, clusters are most likely to be found around fairly massive galaxies (M* ˜ 1010.8M⊙) and present a fitting function for the volume number density of clusters as a function of parent-galaxy stellar mass. We find no correlation between TN and large-scale environment, but we do find a tendency for galaxies of fixed M* to have larger TN if they have converted a larger proportion of their baryons into stars.

  2. 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.

  3. 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.

  4. A high-linearity SiGe RF power amplifier for 3 G and 4 G small basestations

    NASA Astrophysics Data System (ADS)

    Johansson, Ted; Solati, Noora; Fritzin, Jonas

    2012-08-01

    This article presents the design and evaluation of a linear 3.3 V SiGe power amplifier for 3 G and 4 G femtocells with 18 dBm modulated output power at 2140 MHz. Different biasing schemes to achieve high linearity with low standby current were studied. The adjacent channel power ratio linearity performance with wide-band code division multiple access (3 G) and long term evolution (4 G) downlink signals were compared and differences analysed and explained.

  5. The cellular and molecular pathology of the motor system in hereditary spastic paraparesis due to mutation of the spastin gene.

    PubMed

    Wharton, Stephen B; McDermott, Christopher J; Grierson, Andrew J; Wood, Jonathan D; Gelsthorpe, Catherine; Ince, Paul G; Shaw, Pamela J

    2003-11-01

    Hereditary spastic paraparesis (HSP) is a genetically heterogeneous disorder, the most common cause of which is mutation of the spastin gene. Recent evidence suggests a role for spastin in microtubule dynamics, but the distribution of the protein within the CNS is unknown. The core neuropathology of HSP is distal degeneration of the lateral corticospinal tract and of fasciculus gracilis, but there are few neuropathological studies of cases with a defined mutation. We aimed to determine the distribution of spastin expression in the human CNS and to investigate the cellular pathology of the motor system in HSP due to mutation of the spastin gene. Using an antibody to spastin, we have carried out immunohistochemistry on postmortem brain. We have demonstrated that spastin is a neuronal protein. It is widely expressed in the CNS so that the selectivity of the degeneration in HSP is not due to the normal cellular distribution of the protein. We have identified mutation of the spastin gene in 3 autopsy cases of HSP. Distal degeneration of long tracts in the spinal cord, consistent with a dying back axonopathy, was accompanied by a microglial reaction. The presence of novel hyaline inclusions in anterior horn cells and an alteration in immunostaining for cytoskeletal proteins and mitochondria indicates that long tract degeneration is accompanied by cytopathology in the motor system and may support a role for derangement of cytoskeletal function. All 3 cases also demonstrated evidence of tau pathology outside the motor system, suggesting that the neuropathology is not confined to the motor system in spastin-related HSP.

  6. (The physics of cellular automata and coherence and chaos in classical many-body systems)

    SciTech Connect

    Not Available

    1992-06-24

    This report contains short discussions on the following topics: non-variational effects in a Ginzburg-Landau equation; algebraic correlations in conserved chaotic systems; chaotic interface models of turbulence; algebraic correlations in coupled order parameter systems; and dynamics of Josephson Junction arrays. (LSP)

  7. Norovirus translation requires an interaction between the C Terminus of the genome-linked viral protein VPg and eukaryotic translation initiation factor 4G.

    PubMed

    Chung, Liliane; Bailey, Dalan; Leen, Eoin N; Emmott, Edward P; Chaudhry, Yasmin; Roberts, Lisa O; Curry, Stephen; Locker, Nicolas; Goodfellow, Ian G

    2014-08-01

    Viruses have evolved a variety of mechanisms to usurp the host cell translation machinery to enable translation of the viral genome in the presence of high levels of cellular mRNAs. Noroviruses, a major cause of gastroenteritis in man, have evolved a mechanism that relies on the interaction of translation initiation factors with the virus-encoded VPg protein covalently linked to the 5' end of the viral RNA. To further characterize this novel mechanism of translation initiation, we have used proteomics to identify the components of the norovirus translation initiation factor complex. This approach revealed that VPg binds directly to the eIF4F complex, with a high affinity interaction occurring between VPg and eIF4G. Mutational analyses indicated that the C-terminal region of VPg is important for the VPg-eIF4G interaction; viruses with mutations that alter or disrupt this interaction are debilitated or non-viable. Our results shed new light on the unusual mechanisms of protein-directed translation initiation.

  8. Plasminogen activator inhibitor-1 4G/5G polymorphism is associated with metabolic syndrome parameters in Malaysian subjects.

    PubMed

    Al-Hamodi, Zaid H; Saif-Ali, Riyadh; Ismail, Ikram S; Ahmed, Khaled A; Muniandy, Sekaran

    2012-05-01

    The plasminogen activator inhibitor-1 4G/5G and tissue plasminogen activator Alu-repeat insertion/deletion polymorphisms might be genetic determinations of increased or decreased of their plasma activities. The aim of this study was to investigate the association of plasminogen activator inhibitor-1 4G/5G and tissue plasminogen activator Alu-repeat I/D polymorphisms with metabolic syndrome parameters in normal Malaysian subjects and to assess the impact of these polymorphisms on their plasma activities and antigens. The genetic polymorphisms were genotyped in 130 normal subjects. In addition, the plasma activities and antigens of plasminogen activator inhibitor-1 and tissue plasminogen activator as well as levels of insulin, glucose, and lipid profile at fasting state were investigated. The subjects with homozygous 4G/4G showed association with an increased triglyceride (p = 0.007), body mass index (p = 0.01) and diastolic blood pressure (p = 0.03). In addition, the plasminogen activator inhibitor-1 4G/5G polymorphism modulates plasma plasminogen activator inhibitor-1 activity and antigen and tissue plasminogen activator activity (p = 0.002, 0.014, 0.003) respectively. These results showed that, the plasminogen activator inhibitor-1 4G/5G polymorphism is associated with metabolic syndrome parameters, plasminogen activator inhibitor-1 and tissue plasminogen activator activities in Malaysian subjects, and may serve to increase the risk of type 2 diabetes and cardiovascular disease in Malaysian subjects.

  9. 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

  10. 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).

  11. 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

  12. Optimization of the Design of Pre-Signal System Using Improved Cellular Automaton

    PubMed Central

    Li, Yan; Li, Ke; Tao, Siran; Chen, Kuanmin

    2014-01-01

    The pre-signal system can improve the efficiency of intersection approach under rational design. One of the main obstacles in optimizing the design of pre-signal system is that driving behaviors in the sorting area cannot be well evaluated. The NaSch model was modified by considering slow probability, turning-deceleration rules, and lane changing rules. It was calibrated with field observed data to explore the interactions among design parameters. The simulation results of the proposed model indicate that the length of sorting area, traffic demand, signal timing, and lane allocation are the most important influence factors. The recommendations of these design parameters are demonstrated. The findings of this paper can be foundations for the design of pre-signal system and show promising improvement in traffic mobility. PMID:25435871

  13. Optimization of the design of pre-signal system using improved cellular automaton.

    PubMed

    Li, Yan; Li, Ke; Tao, Siran; Wan, Xia; Chen, Kuanmin

    2014-01-01

    The pre-signal system can improve the efficiency of intersection approach under rational design. One of the main obstacles in optimizing the design of pre-signal system is that driving behaviors in the sorting area cannot be well evaluated. The NaSch model was modified by considering slow probability, turning-deceleration rules, and lane changing rules. It was calibrated with field observed data to explore the interactions among design parameters. The simulation results of the proposed model indicate that the length of sorting area, traffic demand, signal timing, and lane allocation are the most important influence factors. The recommendations of these design parameters are demonstrated. The findings of this paper can be foundations for the design of pre-signal system and show promising improvement in traffic mobility.

  14. 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…

  15. 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.

  16. Stellar mass distribution of S4G disk galaxies and signatures of bar-induced secular evolution

    NASA Astrophysics Data System (ADS)

    Díaz-García, S.; Salo, H.; Laurikainen, E.

    2016-12-01

    obtain the tangential-to-radial force ratio (QT) and A2 profiles in the different bins. We also apply ellipse fitting to quantitatively characterize the shape of the bar stacks. Results: For M∗ ≥ 109M⊙, we find a significant difference in the stellar density profiles of barred and non-barred systems: (i) disks in barred galaxies show larger scalelengths (hR) and fainter extrapolated central surface brightnesses (Σ°); (ii) the mean surface brightness profiles (Σ∗) of barred and non-barred galaxies intersect each other slightly beyond the mean bar length, most likely at the bar corotation; and (iii) the central mass concentration of barred galaxies is higher (by almost a factor 2 when T ≤ 5) than in their non-barred counterparts. The averaged Σ∗ profiles follow an exponential slope down to at least 10 M⊙ pc-2, which is the typical depth beyond which the sample coverage in the radial direction starts to drop. Central mass concentrations in massive systems (≥1010M⊙) are substantially larger than in fainter galaxies, and their prominence scales with T. This segregation also manifests in the inner slope of the mean stellar component of the circular velocity: lenticular (S0) galaxies present the most sharply rising V3.6 μm. Based on the analysis of bar stacks, we show that early- and intermediate-type spirals (0 ≤ T< 5) have intrinsically narrower bars than later types and S0s, whose bars are oval-shaped. We show a clear agreement between galaxy family and quantitative estimates of bar strength. In early- and intermediate-type spirals, A2 is larger within and beyond the typical bar region among barred galaxies than in the non-barred subsample. Strongly barred systems also tend to have larger A2 amplitudes at all radii than their weakly barred counterparts. Conclusions: Using near-IR wavelengths (S4G 3.6 μm), we provide observational constraints that galaxy formation models can be checked against. In particular, we calculate the mean stellar density

  17. Plasmonic Nanostructured Cellular Automata

    NASA Astrophysics Data System (ADS)

    Alkhazraji, Emad; Ghalib, A.; Manzoor, K.; Alsunaidi, M. A.

    2017-03-01

    In this work, we have investigated the scattering plasmonic resonance characteristics of silver nanospheres with a geometrical distribution that is modelled by Cellular Automata using time-domain numerical analysis. Cellular Automata are discrete mathematical structures that model different natural phenomena. Two binary one-dimensional Cellular Automata rules are considered to model the nanostructure, namely rule 30 and rule 33. The analysis produces three-dimensional scattering profiles of the entire plasmonic nanostructure. For the Cellular Automaton rule 33, the introduction of more Cellular Automata generations resulted only in slight red and blue shifts in the plasmonic modes with respect to the first generation. On the other hand, while rule 30 introduced significant red shifts in the resonance peaks at early generations, at later generations however, a peculiar effect is witnessed in the scattering profile as new peaks emerge as a feature of the overall Cellular Automata structure rather than the sum of the smaller parts that compose it. We strongly believe that these features that emerge as a result adopting the different 256 Cellular Automata rules as configuration models of nanostructures in different applications and systems might possess a great potential in enhancing their capability, sensitivity, efficiency, and power utilization.

  18. The comparative performance of mobile telemedical systems based on the IS-54 and GSM cellular telephone standards.

    PubMed

    Istepanian, R H; Woodward, B; Balos, P A; Chen, S; Luk, B

    1999-01-01

    The performance of mobile telemedical communications links based on the IS-54 and GSM cellular telephone standards (the most widely used commercial systems in North America and Europe, respectively) was studied by computer simulations. A photoplethysmography signal was used to investigate the transmission of medical data over simulated mobile phone channels. Various conditions were simulated in the communications path between a mobile transmitter and receiver, from perfect to distorted conditions. The results showed successful transmission, with bit error rates of better than 10(-7) at the receiver for the IS-54 standard. The performance of the IS-54 standard was superior to that of GSM in terms of minimum path delay variations, especially in built-up (urban) areas.

  19. An integrated microcomputer system using immobilized cellular electrodes for drug screening.

    PubMed

    Li, X M; Schwartz, R M; Cesar, E Y; Wang, H Y

    1988-01-01

    Biosensors based on immobilized microbial cells were developed for drug screening in our laboratory. Compared with the conventional methods such as diffusion and dilution tests, biosensors have been demonstrated to be superior in sensitivity and require much shorter screening time. An integrated microcomputer system has been developed for data acquisition, database management, and mode of action estimation, which automates the screening processes and reduces the labor requirements significantly.

  20. 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.

  1. 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.

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

    PubMed

    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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. Stimulatory and possible antioxidant effects of High Density Green Photons (HDGP) on cellular systems.

    PubMed

    Paslaru, L; Nastase, A; Stefan, L; Florea, R; Sorop, A; Ionescu, E; Popescu, I; Comorasan, S

    2014-01-01

    The interactions between the electromagnetic field and the biological systems were extensively investigated, with remarkable results and advanced technologies. Nevertheless, the visible domain of the spectrum has been rather neglected, since the classic physics did not allow electronic transitions induced by visible light. Recently, the interaction of light with the matter has generated a new scientific domain known in Physics as optical manipulation, with the new concepts of optical matter and optical force. This article presents the results of our work concerning in vitro effects of High Density Green Photons (HDGP) irradiation on cell cultures: stimulation of cell proliferation and migration and a possible antioxidant action.

  10. Cellular and Network Mechanisms Underlying Information Processing in a Simple Sensory System

    NASA Technical Reports Server (NTRS)

    Jacobs, Gwen; Henze, Chris; Biegel, Bryan (Technical Monitor)

    2002-01-01

    Realistic, biophysically-based compartmental models were constructed of several primary sensory interneurons in the cricket cercal sensory system. A dynamic atlas of the afferent input to these cells was used to set spatio-temporal parameters for the simulated stimulus-dependent synaptic inputs. We examined the roles of dendritic morphology, passive membrane properties, and active conductances on the frequency tuning of the neurons. The sensitivity of narrow-band low pass interneurons could be explained entirely by the electronic structure of the dendritic arbors and the dynamic sensitivity of the SIZ. The dynamic characteristics of interneurons with higher frequency sensitivity required models with voltage-dependent dendritic conductances.

  11. Characterization of the emergent properties of a synthetic quasi-cellular system

    PubMed Central

    2012-01-01

    Background The process of solutes entrapment during liposomes formation is interesting for the investigation of the relationship between the formation of compartments and the distribution of molecules inside them; a relevant issue in the studies of the origin of life. Theoretically, when no interactions are supposed among the chemical species to be entrapped, the entrapment is described by a standard Poisson process. But very recent experimental findings show that, for small liposomes (100 nm diameter), the distribution of entrapped molecules is best described by a power-law function. This is of a great importance, as the two random processes give rise to two completely different scenarios. Here we present an in silico stochastic simulation of the encapsulation of a cell-free molecular translation system (the PURE system), obtained following two different entrapment models: a pure Poisson process, and a power-law. The protein synthesis inside the liposomes has been studied in both cases, with the aim to highlight experimental observables that could be measured to assess which model gives a better representation of the real process. Results Firstly, a minimal model for in vitro protein synthesis, based on the PURE system molecular composition, has been formalized. Then, we have designed a reliable experimental simulation where stochastic factors affect the reaction course inside the compartment. To this end, 24 solutes, which represent the PURE system components, have been stochastically distributed among vesicles by following either a Poisson or a power-law distribution. The course of the protein synthesis within each vesicle has been consequently calculated, as a function of vesicle size. Our study can predict translation yield in a population of small liposomes down to the attoliter (10-18 L) range. Our results show that the efficiency of protein synthesis peaks at approximately 3·10-16 L (840 nm diam.) with a Poisson distribution of solutes, while a relative

  12. Human Neurospheres as Three-Dimensional Cellular Systems for Developmental Neurotoxicity Testing

    PubMed Central

    Moors, Michaela; Rockel, Thomas Dino; Abel, Josef; Cline, Jason E.; Gassmann, Kathrin; Schreiber, Timm; Schuwald, Janette; Weinmann, Nicole; Fritsche, Ellen

    2009-01-01

    Background Developmental neurotoxicity (DNT) of environmental chemicals is a serious threat to human health. Current DNT testing guidelines propose investigations in rodents, which require large numbers of animals. With regard to the “3 Rs” (reduction, replacement, and refinement) of animal testing and the European regulation of chemicals [Registration, Evaluation, and Authorisation of Chemicals (REACH)], alternative testing strategies are needed in order to refine and reduce animal experiments and allow faster and less expensive screening. Objectives The goal of this study was to establish a three-dimensional test system for DNT screening based on human fetal brain cells. Methods We established assays suitable for detecting disturbances in basic processes of brain development by employing human neural progenitor cells (hNPCs), which grow as neurospheres. Furthermore, we assessed effects of mercury and oxidative stress on these cells. Results We found that human neurospheres imitate proliferation, differentiation, and migration in vitro. Exposure to the proapoptotic agent staurosporine further suggests that human neurospheres possess functioning apoptosis machinery. The developmental neurotoxicants methylmercury chloride and mercury chloride decreased migration distance and number of neuronal-like cells in differentiated hNPCs. Furthermore, hNPCs undergo caspase-independent apoptosis when exposed toward high amounts of oxidative stress. Conclusions Human neurospheres are likely to imitate basic processes of brain development, and these processes can be modulated by developmental neurotoxicants. Thus, this three-dimensional cell system is a promising approach for DNT testing. PMID:19654924

  13. 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.

  14. The cellular immune system in the post-myocardial infarction repair process.

    PubMed

    Latet, Sam C; Hoymans, Vicky Y; Van Herck, Paul L; Vrints, Christiaan J

    2015-01-20

    Growing evidence indicates that overactivation and prolongation of the inflammatory response after acute myocardial infarction (AMI) result in worse left ventricular remodelling, dysfunction and progression to heart failure. This post-AMI inflammatory response is characterised by the critical involvement of cells from both the innate and adaptive immune systems. In this review paper, we aim to summarise and discuss the emergence of immune cells in the bloodstream and myocardium after AMI in men and mice. Subset composition, phenotypes, and kinetics of immune cells are considered. In addition, the relation with post-MI cardiac remodelling, function and outcome is reported. Increased knowledge of immune components, the mechanisms and interactions by which these cells contribute to myocardial damage and repair following AMI may help to close the gaps that limit improvement of treatments of those who survive the acute infarction.

  15. Antioxidant activity of rosmarinic acid and its principal metabolites in chemical and cellular systems: Importance of physico-chemical characteristics.

    PubMed

    Adomako-Bonsu, Amma G; Chan, Sue Lf; Pratten, Margaret; Fry, Jeffrey R

    2017-04-01

    Persistent accumulation of reactive oxygen species causes cellular oxidative stress which contributes strongly towards the induction and progression of various diseases. Therapeutic focus has therefore shifted towards the use of antioxidants, with recent interest in those of plant origin. In the current study, rosmarinic acid (RA) and its key metabolites were evaluated in non-cellular and cellular antioxidant assays, using quercetin (Q) as a positive control. The non-cellular assay was performed as scavenging of DPPH radical, whilst the cellular assay was performed as protection from an oxidant stress. Radical-scavenging activity of RA and two of its primary metabolites, CA and DHPLA, were comparable to that of Q, whilst FA was of lower potency and m-CoA was inactive. In the cellular assay, RA and CA were markedly less potent than Q, with DHPLA, FA and m-CoA being inactive, this being true in short-term (5-h) or long-term (20-h) exposure conditions. However, antioxidant potency of Q and methyl rosmarinate, a non-ionisable ester of RA, was similar in the non-cellular and short-term cellular assays. It is proposed that marked ionisation of organic acids such as RA and its metabolites at physiological pH greatly limits their intracellular accumulation, and so attenuates intrinsic antioxidant ability demonstrated in the non-cellular assay. This study demonstrates some of the factors that prevent well-known phytochemicals from progressing further along the drug discovery chain.

  16. Immune system - part I. Fundamentals of innate immunity with emphasis on molecular and cellular mechanisms of inflammatory response.

    PubMed

    Cruvinel, Wilson de Melo; Mesquita, Danilo; Araújo, Júlio Antônio Pereira; Catelan, Tânia Tieko Takao; de Souza, Alexandre Wagner Silva; da Silva, Neusa Pereira; Andrade, Luís Eduardo Coelho

    2010-01-01

    The immune system consists of an intricate network of organs, cells, and molecules responsible for maintaining the body's homeostasis and responding to aggression in general. Innate immunity operates in conjunction with adaptive immunity and is characterized by rapid response to aggression, regardless of previous stimulus, being the organism first line of defense. Its mechanisms include physical, chemical and biological barriers, cellular components, as well as soluble molecules. The organism first line of defense against tissue damage involves several steps closely integrated and constituted by different components of this system. The aim of this review is to restore the foundations of this response, which has high complexity and consists of several components that converge to articulate the development of adaptive immune response. We selected some of the following steps to review: perception and molecular recognition of aggressive agents; activation of intracellular pathways, which result in vascular and tissue changes; production of a myriad of mediators with local and systemic effects on cell activation and proliferation, synthesis of new products involved in the chemoattraction and migration of cells specialized in destruction and removal of offending agent; and finally, tissue recovery with restoration of functional tissue or organ.

  17. Identification of multiple cellular uptake pathways of polystyrene nanoparticles and factors affecting the uptake: relevance for drug delivery systems.

    PubMed

    Firdessa, Rebuma; Oelschlaeger, Tobias A; Moll, Heidrun

    2014-01-01

    Nanoparticles may address challenges by human diseases through improving diagnosis, vaccination and treatment. The uptake mechanism regulates the type of threat a particle poses on the host cells and how a cell responds to it. Hence, understanding the uptake mechanisms and cellular interactions of nanoparticles at the cellular and subcellular level is a prerequisite for their effective biomedical applications. The present study shows the uptake mechanisms of polystyrene nanoparticles and factors affecting their uptake in bone marrow-derived macrophages, 293T kidney epithelial cells and L929 fibroblasts. Labeling with the endocytic marker FM4-64 and transmission electron microscopy studies show that the nanoparticles were internalized rapidly via endocytosis and accumulated in intracellular vesicles. Soon after their internalizations, nanoparticles trafficked to organelles with acidic pH. Analysis of the ultrastructural morphology of the plasma membrane invaginations or extravasations provides clear evidence for the involvement of several uptake routes in parallel to internalize a given type of nanoparticles by mammalian cells, highlighting the complexity of the nanoparticle-cell interactions. Blocking the specific endocytic pathways by different pharmacological inhibitors shows similar outcomes. The potential to take up nanoparticles varies highly among different cell types in a particle sizes-, time- and energy-dependent manner. Furthermore, infection and the activation status of bone marrow-derived macrophages significantly affect the uptake potential of the cells, indicating the need to understand the diseases' pathogenesis to establish effective and rational drug-delivery systems. This study enhances our understanding of the application of nanotechnology in biomedical sciences.

  18. Systems biology approaches for understanding cellular mechanisms of immunity in lymph nodes during infection

    PubMed Central

    Mirsky, Henry Philip; Miller, Mark J.; Linderman, Jennifer J.; Kirschner, Denise E.

    2015-01-01

    Adaptive immunity is initiated in secondary lymphoid tissues when naive T cells recognize foreign antigen presented as MHC-bound peptide on the surface of dendritic cells. Only a small fraction of T cells in the naive repertoire will express T cell receptors specific for a given epitope, but antigen recognition triggers T cell activation and proliferation, thus greatly expanding antigen-specific clones. Expanded T cells can serve a helper function for B cell responses or traffic to sites of infection to secrete cytokines or kill infected cells. Over the past decade, two- photon microscopy of lymphoid tissues has shed important light on T cell development, antigen recognition, cell trafficking and effector functions. These data have enabled the development of sophisticated quantitative and computational models that, in turn, have been used to test hypotheses in silico that would otherwise be impossible or difficult to explore experimentally. Here, we review these models and their principal findings and highlight remaining questions where modeling approaches are poised to advance our understanding of complex immunological systems. PMID:21798267

  19. Bone and cellular immune system of multiparous sows are insensitive to ovariectomy and nutritive calcium shortage.

    PubMed

    Sipos, W; Kralicek, E; Rauner, M; Duvigneau, C J; Worliczek, H L; Schamall, D; Hartl, R T; Sommerfeld-Stur, I; Dall'Ara, E; Varga, P; Resch, H; Schwendenwein, I; Zysset, P; Pietschmann, P

    2011-06-01

    Research in osteoporosis, which is a complex systemic disease, demands suitable large animal models. In pigs, most research has been done in growing minipigs, which probably are not ideal models for postmenopausal osteoporosis. Therefore, our aim was to analyze the effects of ovariectomy (OVX) and nutritive calcium shortage on multiparous Large White sows. 32 animals were randomly assigned to 4 groups in a cross design with OVX vs. sham and physiological calcium supplementation (0.75% calcium) vs. dietary calcium shortage (0.3% calcium). The observation period was 10 months with blood sampling every 2 months for hematological, immunological, and biochemical bone marker measurements. At the termination of the experiment, animals were sacrificed. Samples of trabecular bone of distal radius, proximal tibia, and sixth lumbar vertebra were subjected to micro-computed tomography imaging and ashed afterwards. Dual X-ray absorptiometry scans of the proximal femora were performed with prepared bones being placed in a water bath for mimicking soft tissue. Analyses of bone marker and cytokine profile kinetics, distribution of leukocyte subpopulations, and morphometrical and densitometrical analyses showed no evidence of any impact of OVX or calcium shortage. In conclusion, the skeleton of adult sows of a conventional breed is seemingly protected from effects of OVX and calcium shortage.

  20. Cellular and molecular phenotypes depending upon the RNA repair system RtcAB of Escherichia coli

    PubMed Central

    Engl, Christoph; Schaefer, Jorrit; Kotta-Loizou, Ioly; Buck, Martin

    2016-01-01

    RNA ligases function pervasively across the three kingdoms of life for RNA repair, splicing and can be stress induced. The RtcB protein (also HSPC117, C22orf28, FAAP and D10Wsu52e) is one such conserved ligase, involved in tRNA and mRNA splicing. However, its physiological role is poorly described, especially in bacteria. We now show in Escherichia coli bacteria that the RtcR activated rtcAB genes function for ribosome homeostasis involving rRNA stability. Expression of rtcAB is activated by agents and genetic lesions which impair the translation apparatus or may cause oxidative damage in the cell. Rtc helps the cell to survive challenges to the translation apparatus, including ribosome targeting antibiotics. Further, loss of Rtc causes profound changes in chemotaxis and motility. Together, our data suggest that the Rtc system is part of a previously unrecognized adaptive response linking ribosome homeostasis with basic cell physiology and behaviour. PMID:27402162

  1. Effect of subclinical levels of T-2 toxin on the bovine cellular immune system.

    PubMed Central

    Mann, D D; Buening, G M; Osweiler, G D; Hook, B S

    1984-01-01

    The effect of subclinical levels of mycotoxin T-2 on the cells of the bovine immune system was investigated in two in vivo experiments. In experiment 1, five calves were orally dosed with 0.3 mg/kg/day of T-2 toxin for 56 days and five calves were pair fed controls. The neutrophil function as measured by nitroblue tetrazolium reduction was reduced in the mycotoxin treated calves. The cutaneous reaction to intradermally injected phytohemagglutinin was reduced in the T-2 toxin treated calves. B-cell (SIg+) numbers increased slightly, but T-cell (PNA+) numbers were not affected during the experimental period. In the second experiment, six calves were given 0.5 mg/kg/day T-2 toxin orally for 28 days and six calves were pair fed controls. B-cell numbers and the response of a B-cell enriched fraction to phytohemagglutinin increased after toxin administration. T-cell numbers and the response of a T-cell enriched fraction and the whole mononuclear cell population to phytohemagglutinin was reduced only on day 19 posttoxin administration. The in vitro (T-2 toxin) exposure of the mononuclear cell population, B-cell enriched, or T-cell enriched fraction reduced their lymphoblastic response to mitogens. A 50% reduction was induced by as little as 1.4 ng/mL of T-2 toxin. PMID:6332662

  2. Cellular and molecular interactions of thymus with endocrine organs and nervous system.

    PubMed

    Kinoshita, Y; Hato, F

    2001-02-01

    T-cell ontogenesis has been disclosed to depend on the interactions of thymus with endocrine glands and nervous system as follows: i/ Thymic deprivation not only impaired the immunological development but also brought about the dysgenesis of pituitary anterior lobe. Conversely, hypophysectomy resulted in thymus atrophy with the disturbed immune responses. ii/ Binding of pituitary acidophilic cell hormones to their receptors on thymus epithelial cells (TECs) augmented the release of thymic hormonal peptides (THPs) in vitro. iii/ Elevation of blood glucocorticoid level after stress caused atrophy of thymus cortex through double positive thymocyte apoptosis. Morpho-molecular alterations of cytoplasm preceded nuclear damage in the apoptotic thymocytes. iv/ Administration of thymosin to the streptozotocin-induced diabetic mice repressed mononuclear cell infiltration to the pancreatic islets. v/ Autonomic nerve fibers innervate thymic parenchyma. Binding of acetylcholines (Achs) to Ach receptors on TECs enhanced protein synthetic activity which seemed to connect with THP production. vi/ Thymectomy not only depressed the immune responses but also accelerated the reduction of leaming and memory ability with aging. The operation appears to disturb the brain adrenoceptor functions and to suppress the regulatory roles of hypothalamus to other nervous tissues. vii/ Several kinds of THPs, separated from the culture supernatant of TEC line by high performance liquid chromatography, showed a favorable effect on the thymocytes at different stage of differentiation and maturation. viii/ Thymosin, thymulin and THPs were capable of proliferating and differentiating thymocytes in vitro. However, the administration of each thymic product to the thymus-deprived animals could not restore from their "wasting disease". Since TECs are composed of a heterogeneous population, it would be one of essential ways for isolating "true thymus hormone" (TTH) to use the material which consists of

  3. Histopathological findings in systemic sclerosis-related myopathy: fibrosis and microangiopathy with lack of cellular inflammation

    PubMed Central

    Corallo, Claudio; Cutolo, Maurizio; Volpi, Nila; Franci, Daniela; Aglianò, Margherita; Montella, Antonio; Chirico, Chiara; Gonnelli, Stefano; Nuti, Ranuccio; Giordano, Nicola

    2016-01-01

    Objectives: The objective of this study was to identify specific histopathological features of skeletal muscle involvement in systemic sclerosis (SSc) patients. Methods: A total of 35 out of 112 SSc-patients (32%, including 81% female and 68% diffuse scleroderma) presenting clinical, biological and electromyographic (EMG) features of muscle weakness, were included. Patients underwent vastus lateralis biopsy, assessed for individual pathologic features including fibrosis [type I collagen (Coll-I), transforming growth factor β (TGF-β)], microangiopathy [cluster of differentiation 31 (CD31), pro-angiogenic vascular endothelial growth factor A (VEGF-A), anti-angiogenic VEGF-A165b], immune/ inflammatory response [CD4, CD8, CD20, human leucocyte antigens ABC (HLA-ABC)], and membranolytic attack complex (MAC). SSc biopsies were compared with biopsies of (n = 35) idiopathic inflammatory myopathies (IIMs) and to (n = 35) noninflammatory myopathies (NIMs). Ultrastructural abnormalities of SSc myopathy were also analyzed by transmission electron microscopy (TEM). Results: Fibrosis in SSc myopathy (81%) is higher compared with IIM (32%, p < 0.05) and with NIM (18%, p < 0.05). Vascular involvement is dominant in SSc muscle (92%), and in IIM (78%) compared with NIM (21%, p < 0.05). In particular, CD31 shows loss of endomysial vessels in SSc myopathy compared with IIM (p < 0.05) and with NIM (p < 0.01). VEGF-A is downregulated in SSc myopathy compared with IIM (p < 0.05) and NIM (p < 0.05). Conversely, VEGF-A165b is upregulated in SSc myopathy. The SSc immune/inflammatory response suggested humoral process with majority (85%) HLA-ABC fibral neoexpression and complement deposits on endomysial capillaries MAC, compared with IIM (p < 0.05), characterized by CD4+/CD8+/B-cell infiltrate, and NIM (p < 0.05). TEM analysis showed SSc vascular alterations consisting of thickening and lamination of basement membrane and endothelial cell ‘swelling’ coupled to endomysial

  4. 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

  5. Cellular distribution of chromogranin A in excitatory, inhibitory, aminergic and peptidergic neurons of the rodent central nervous system

    PubMed Central

    Schafer, M.K.-H.; Mahata, S.K.; Stroth, N.; Eiden, L.E.; Weihe, E.

    2010-01-01

    Immunoreactivity for both processed and unprocessed forms of chromogranin A (CGA) was examined, using an antibody recognizing the WE14 epitope, among terminal fields and cell bodies of anatomically defined GABAergic, glutamatergic, cholinergic, catecholaminergic, and peptidergic cell groups in the rodent central nervous system. CGA is ubiquitous within neuronal cell bodies, with no obvious anatomical or chemically-coded subdivision of the nervous system in which CGA is not expressed in most neurons. CGA expression is essentially absent from catecholaminergic terminal fields in the CNS, suggesting a relative paucity of large dense-core vesicles in CNS compared to peripheral catecholaminergic neurons. Extensive synaptic co-localization with classical transmitter markers is not observed even in areas such as amygdala, where CGA fibers are numerous, suggesting preferential segregation of CGA to peptidergic terminals in CNS. Localization of CGA in dendrites in some areas of CNS may indicate its involvement in regulation of dendritic release mechanisms. Finally, the ubiquitous presence of CGA in neuronal cell somata, especially pronounced in GABAergic neurons, suggests a second non-secretory vesicle-associated function for CGA in CNS. We propose that CGA may function in the CNS as a prohormone and granulogenic factor in some terminal fields, but also possesses as-yet unknown unique cellular functions within neuronal somata and dendrites. PMID:20005907

  6. 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.

  7. 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.

  8. Effect of Nanoparticle Surface Chemistry on Adsorption and Fluid Phase Partitioning in Aqueous/Toluene and Cellular Systems.

    PubMed

    Gambinossi, Filippo; Lapides, Dana; Anderson, Chris; Chanana, Munish; Ferri, James K

    2015-05-01

    Copolymers of di(ethylene glycol) methyl ether methacrylate (x = MeO2MA) and oligo(ethylene glycol) methyl ether methacrylate (y = OEGMA) display lower critical solution phenomena in aqueous systems that are tunable by the copolymer ratio (x:y), ionic strength, and temperature. These properties enable tuning the hydrophobicity of macromolecular systems by variation of (x:y). For nanoparticles stabilized with these macromolecules, this provides a systematic approach to understanding the impact of surface chemistry, specifically hydrophobicity, on the equilibrium and transport properties of nanomaterials in biphasic systems. We synthesized a homologous series of gold nanoparticles capped by these copolymers, Au@(MeO2MA(x)-co-OEGMA(y)). By varying the copolymer 95:5 < (x:y) < 80:20 ratio, we studied the effect of surface hydrophobicity on the nanoparticle equilibrium adsorption isotherm and phase transfer at the aqueous-toluene interface. The increase in hydrophobicity from (x:y) = 80:20 to (x:y) = 95:5 is accompanied by an increase in the fractional coverage of the aqueous-toluene interface from f = 0.3 to f > 1, or multilayer adsorption and an increase in the characteristic adsorption timescale from τ(D) = 31 to τ(D) = 450 seconds. The equilibrium partition coefficient for the aqueous/toluene systems, K(T/W) is also a strong function of (x:y), increasing from K(T/W) (80:20) = 0.7 to K(T/W) (95:5) = 9.8. We also observed an increase in cellular uptake for increasing (x:y) suggesting that surface chemistry alone plays a significant role in intercellular transport processes.

  9. Low probability of intercept-based adaptive radar waveform optimization in signal-dependent clutter for joint radar and cellular communication systems

    NASA Astrophysics Data System (ADS)

    Shi, Chenguang; Salous, Sana; Wang, Fei; Zhou, Jianjiang

    2016-12-01

    In this paper, we investigate the problem of low probability of intercept (LPI)-based adaptive radar waveform optimization in signal-dependent clutter for joint radar and cellular communication systems, where the radar system optimizes the transmitted waveform such that the interference caused to the cellular communication systems is strictly controlled. Assuming that the precise knowledge of the target spectra, the power spectral densities (PSDs) of signal-dependent clutters, the propagation losses of corresponding channels and the communication signals is known by the radar, three different LPI based criteria for radar waveform optimization are proposed to minimize the total transmitted power of the radar system by optimizing the multicarrier radar waveform with a predefined signal-to-interference-plus-noise ratio (SINR) constraint and a minimum required capacity for the cellular communication systems. These criteria differ in the way the communication signals scattered off the target are considered in the radar waveform design: (1) as useful energy, (2) as interference or (3) ignored altogether. The resulting problems are solved analytically and their solutions represent the optimum power allocation for each subcarrier in the multicarrier radar waveform. We show with numerical results that the LPI performance of the radar system can be significantly improved by exploiting the scattered echoes off the target due to cellular communication signals received at the radar receiver.

  10. Low probability of intercept-based adaptive radar waveform optimization in signal-dependent clutter for joint radar and cellular communication systems.

    PubMed

    Shi, Chenguang; Salous, Sana; Wang, Fei; Zhou, Jianjiang

    2016-01-01

    In this paper, we investigate the problem of low probability of intercept (LPI)-based adaptive radar waveform optimization in signal-dependent clutter for joint radar and cellular communication systems, where the radar system optimizes the transmitted waveform such that the interference caused to the cellular communication systems is strictly controlled. Assuming that the precise knowledge of the target spectra, the power spectral densities (PSDs) of signal-dependent clutters, the propagation losses of corresponding channels and the communication signals is known by the radar, three different LPI based criteria for radar waveform optimization are proposed to minimize the total transmitted power of the radar system by optimizing the multicarrier radar waveform with a predefined signal-to-interference-plus-noise ratio (SINR) constraint and a minimum required capacity for the cellular communication systems. These criteria differ in the way the communication signals scattered off the target are considered in the radar waveform design: (1) as useful energy, (2) as interference or (3) ignored altogether. The resulting problems are solved analytically and their solutions represent the optimum power allocation for each subcarrier in the multicarrier radar waveform. We show with numerical results that the LPI performance of the radar system can be significantly improved by exploiting the scattered echoes off the target due to cellular communication signals received at the radar receiver.

  11. Lack of association between plasminogen activator inhibitor type-1 (PAI-1) gene 4G/5G polymorphism and osteoarthritis.

    PubMed

    Bayram, Banu; Sayin, Emrah; Erkasap, Nilüfer; Onlü, Harun; Ozkurt, Mete; Sahin, Fezan; Türkoğlu, Züleyha

    2012-01-01

    This study was conducted in Turkish osteoarthritis patients to determine the frequency of 4G/5G polymorphism genotypes of plasminogen activator inhibitor type-1 gene and to examine the role of this polymorphism in osteoarthritis development. Genomic DNA obtained from 200 persons (140 patients with osteoarthritis and 60 healthy controls) was used in the study. DNA was amplified by polymerase chain reaction using 4G allele- and 5G allele-specific primers. Polymerase chain reaction products were assessed with CCD camera by being exposed to 2% agarose gel electrophoresis. No statistically significant difference between the groups with respect to genotype distribution was found (P > 0.05) in the study. The 4G allele frequency was indicated as 44% and 5G allele was as 56% in patients, whereas this was 45-55% in the control group. This study has established that 4G/5G polymorphism genotypes of plasminogen activator inhibitor type-1 gene do not play a role in the development of osteoarthritis in the Turkish population.

  12. Myocardial infarction occurs with a similar 24 h pattern in the 4G/5G versions of plasminogen activator inhibitor-1.

    PubMed

    Bergheanu, Sandrin C; Pons, Douwe; Jukema, J Wouter; van der Hoeven, Bas L; Liem, Su-San; Vandenbroucke, Jan P; Rosendaal, Frits R; le Cessie, Saskia; Schalij, Martin J; van der Bom, Johanna G

    2009-05-01

    PAI-1 expression is regulated by a 4G/5G promoter polymorphism. The 4G allele is associated with greater circadian variation of PAI-1 levels. We hypothesized that the 24 h variation of cardiac risk is more pronounced among persons with the 4G4G genotype than among ones with 4G5G and 5G5G genotypes. We assessed the time of onset of symptoms in 623 consecutive patients with acute myocardial infarction (AMI) enrolled in the MISSION! Study between February 1, 2004, and October 29, 2006. All of the patients were genotyped for the PAI-1 4G/5G polymorphism. We quantified the amplitude of the 24 h variation of AMI with a generalized linear model with Poisson distribution. A morning peak, between 06:00-11:59 h (n = 197; 32% of all cases), in the onset of symptoms of AMI was observed. The group composed of patients with the 4G4G genotype did not have a more pronounced morning peak than the groups composed of other genotypes; the 24 h variation was 38% (95% confidence interval 12-70%) in the group of 4G4G patients and 34% (14-58%) and 56% (20-100%) in the 4G5G and 5G5G groups of patients, respectively. Our findings show that 24 h variation of cardiac risk is not more pronounced among the 4G4G genotype of PAI-1.

  13. 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.

  14. 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

  15. Development of the Cellular Immune System of Drosophila Requires the Membrane Attack Complex/Perforin-Like Protein Torso-Like.

    PubMed

    Forbes-Beadle, Lauren; Crossman, Tova; Johnson, Travis K; Burke, Richard; Warr, Coral G; Whisstock, James C

    2016-10-01

    Pore-forming members of the membrane attack complex/perforin-like (MACPF) protein superfamily perform well-characterized roles as mammalian immune effectors. For example, complement component 9 and perforin function to directly form pores in the membrane of Gram-negative pathogens or virally infected/transformed cells, respectively. In contrast, the only known MACPF protein in Drosophila melanogaster, Torso-like, plays crucial roles during development in embryo patterning and larval growth. Here, we report that in addition to these functions, Torso-like plays an important role in Drosophila immunity. However, in contrast to a hypothesized effector function in, for example, elimination of Gram-negative pathogens, we find that torso-like null mutants instead show increased susceptibility to certain Gram-positive pathogens such as Staphylococcus aureus and Enterococcus faecalis We further show that this deficit is due to a severely reduced number of circulating immune cells and, as a consequence, an impaired ability to phagocytose bacterial particles. Together these data suggest that Torso-like plays an important role in controlling the development of the Drosophila cellular immune system.

  16. Increased plasma ammonia may inhibit cellular release of branched-chain amino acids in systemic portal encephalopathy.

    PubMed

    Jahn, H A; Schohn, D C; Koehl, C; Schmitt, R L

    1983-12-01

    Plasma amino acid patterns were determined before and after hemofiltration (HF) and hemodialysis (HD) in 6 patients with portal systemic encephalopathy (PSE) and compared with the plasma AA patterns of 16 patients with chronic renal failure (CRF) treated either by HF or HD. The branched-chain amino acids (BCAA) increased paradoxically in PSE patients during HF but not with HD. There were no differences in BCAA's with HF as compared to HD in the CRF patients. The amount of amino acids lost was the same with both treatment modalities and in both patient groups. Much of the amino acids lost were released from the intracellular space. The BCAA release was significantly higher in PSE patients during HF. No correlation was found between plasma insulin, glucagon, and cortisol levels and BCAA release. An inverse correlation was found between the amount of BCAA's released from the intracellular space and the plasma ammonia levels. It is suggested that a selective cellular transport mechanism for BCAA exists which is inhibited by high plasma ammonia levels in PSE.

  17. Cellular localization, expression and functional implications of the utero-placental endothelin system during maintenance and termination of canine gestation.

    PubMed

    Gram, Aykut; Boos, Alois; Kowalewski, Mariusz P

    2017-02-20

    Utero-placental (Ut-Pl) angiogenesis and blood flow are fundamental for successful outcome of pregnancy. They are controlled by numerous vasodilator and vasoconstrictor systems such as endothelins (EDNs) and the renin angiotensin system. Dogs possess an invasive type of placentation, classified as endotheliochorial. Despite increasing knowledge regarding canine Ut-Pl function, little information exists on uterine and placental vascular activity during initiation, maintenance and termination of pregnancy in this species. The current study investigated expression of EDNs and their receptors (EDNRA and EDNRB) in the pre-implantation uterus and Ut-Pl compartments during gestation and at normal parturition, as well as in mid-pregnant dogs treated with the antigestagen aglepristone. The Ut-Pl mRNA expression of EDN1 and EDNRA was constant until mid-gestation and increased significantly during prepartum luteolysis. In contrast, EDN2 was highest pre-implantation and decreased following placentation, remaining low thereafter. Expression of the EDN-activating enzyme ECE1 and mRNA of EDNRB increased towards mid-gestation and was further elevated at prepartum luteolysis. Antigestagen treatment resulted in increased levels of EDN1 and EDNRA. At the cellular level, the uterine expression of EDN1, ECE1 and EDNRB was found predominantly in the endometrial surface and glandular epithelial cells; uterine signals for EDNRA were weak. In Ut-Pl all targets were mainly localized in the placenta fetalis, with syncytiotrophoblast staining stronger for ECE1 and EDNRB. In contrast, EDNRA stained strongly at the base of the placental labyrinth. Expression and localization of EDNs (EDN-1, -2), EDN receptors and ECE1 in the placenta fetalis suggests their involvement in the trophoblast invasion and proliferation.

  18. 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

  19. Arginine methylation promotes translation repression activity of eIF4G-binding protein, Scd6

    PubMed Central

    Poornima, Gopalakrishna; Shah, Shanaya; Vignesh, Venkadasubramanian; Parker, Roy; Rajyaguru, Purusharth I.

    2016-01-01

    Regulation of translation plays a critical role in determining mRNA fate. A new role was recently reported for a subset of RGG-motif proteins in repressing translation initiation by binding eIF4G1. However the signaling mechanism(s) that leads to spatial and temporal regulation of repression activity of RGG-motif proteins remains unknown. Here we report the role of arginine methylation in regulation of repression activity of Scd6, a conserved RGG-motif protein. We demonstrate that Scd6 gets arginine methylated at its RGG-motif and Hmt1 plays an important role in its methylation. We identify specific methylated arginine residues in the Scd6 RGG-motif in vivo. We provide evidence that methylation augments Scd6 repression activity. Arginine methylation defective (AMD) mutant of Scd6 rescues the growth defect caused by overexpression of Scd6, a feature of translation repressors in general. Live-cell imaging of the AMD mutant revealed that it is defective in inducing formation of stress granules. Live-cell imaging and pull-down results indicate that it fails to bind eIF4G1 efficiently. Consistent with these results, a strain lacking Hmt1 is also defective in Scd6-eIF4G1 interaction. Our results establish that arginine methylation augments Scd6 repression activity by promoting eIF4G1-binding. We propose that arginine methylation of translation repressors with RGG-motif could be a general modulator of their repression activity. PMID:27613419

  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. The FGFR4-G388R polymorphism promotes mitochondrial STAT3 serine phosphorylation to facilitate pituitary growth hormone cell tumorigenesis.

    PubMed

    Tateno, Toru; Asa, Sylvia L; Zheng, Lei; Mayr, Thomas; Ullrich, Axel; Ezzat, Shereen

    2011-12-01

    Pituitary tumors are common intracranial neoplasms, yet few germline abnormalities have been implicated in their pathogenesis. Here we show that a single nucleotide germline polymorphism (SNP) substituting an arginine (R) for glycine (G) in the FGFR4 transmembrane domain can alter pituitary cell growth and hormone production. Compared with FGFR4-G388 mammosomatotroph cells that support prolactin (PRL) production, FGFR4-R388 cells express predominantly growth hormone (GH). Growth promoting effects of FGFR4-R388 as evidenced by enhanced colony formation was ascribed to Src activation and mitochondrial serine phosphorylation of STAT3 (pS-STAT3). In contrast, diminished pY-STAT3 mediated by FGFR4-R388 relieved GH inhibition leading to hormone excess. Using a knock-in mouse model, we demonstrate the ability of FGFR4-R385 to promote GH pituitary tumorigenesis. In patients with acromegaly, pituitary tumor size correlated with hormone excess in the presence of the FGFR4-R388 but not the FGFR4-G388 allele. Our findings establish a new role for the FGFR4-G388R polymorphism in pituitary oncogenesis, providing a rationale for targeting Src and STAT3 in the personalized treatment of associated disorders.

  2. Association Between Plasminogen Activator Inhibitor-1-675 4G/5G Insertion/Deletion Polymorphism and Chronic Obstructive Pulmonary Disease.

    PubMed

    Essa, Enas S; El Wahsh, Rabab A

    2016-12-01

    Molecular pathology of chronic obstructive pulmonary disease (COPD) is still being investigated to discover relationships with disease pathogenesis. Evidence of plasminogen activator inhibitor-1 (PAI-1) overexpression in the sputum and the blood of COPD patients is growing. We aimed to investigate the potential relation between PAI-1 promoter 4G/5G insertion/deletion polymorphism and COPD development. In a case-control study, we genotyped 117 COPD patients and 160 control subjects for PAI-1 promoter 4G/5G polymorphism by an allele-specific polymerase chain reaction analysis. All subjects were male smokers. In the co-dominant model, there was a significant difference in the distribution of 5G/5G, 4G/5G and 4G/4G genotypes between COPD patients and controls (p = 0.002). In the recessive model, carriers of 4G/4G genotype were significantly higher in COPD patients than controls (p = 0.01). Carriers of 4G/4G genotype were at higher risk to develop COPD than those carrying 5G/5G or 4G/5G genotypes (crude odds ratio (OR) = 2.10, 95% confidence interval (CI) = 1.19-3.73, adjusted OR = 2.5, 95% CI = 1.22-3.99). In conclusion, PAI-1 4G/5G genetic variations are associated with COPD development in males.

  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. Integrated Cellular and Plasma Proteomics of Contrasting B-cell Cancers Reveals Common, Unique and Systemic Signatures.

    PubMed

    Johnston, Harvey E; Carter, Matthew J; Cox, Kerry L; Dunscombe, Melanie; Manousopoulou, Antigoni; Townsend, Paul A; Garbis, Spiros D; Cragg, Mark S

    2017-03-01

    Approximately 800,000 leukemia and lymphoma cases are diagnosed worldwide each year. Burkitt's lymphoma (BL) and chronic lymphocytic leukemia (CLL) are examples of contrasting B-cell cancers; BL is a highly aggressive lymphoid tumor, frequently affecting children, whereas CLL typically presents as an indolent, slow-progressing leukemia affecting the elderly. The B-cell-specific overexpression of the myc and TCL1 oncogenes in mice induce spontaneous malignancies modeling BL and CLL, respectively. Quantitative mass spectrometry proteomics and isobaric labeling were employed to examine the biology underpinning contrasting Eμ-myc and Eμ-TCL1 B-cell tumors. Additionally, the plasma proteome was evaluated using subproteome enrichment to interrogate biomarker emergence and the systemic effects of tumor burden. Over 10,000 proteins were identified (q<0.01) of which 8270 cellular and 2095 plasma proteins were quantitatively profiled. A common B-cell tumor signature of 695 overexpressed proteins highlighted ribosome biogenesis, cell-cycle promotion and chromosome segregation. Eμ-myc tumors overexpressed several methylating enzymes and underexpressed many cytoskeletal components. Eμ-TCL1 tumors specifically overexpressed ER stress response proteins and signaling components in addition to both subunits of the interleukin-5 (IL5) receptor. IL5 treatment promoted Eμ-TCL1 tumor proliferation, suggesting an amplification of IL5-induced AKT signaling by TCL1. Tumor plasma contained a substantial tumor lysis signature, most prominent in Eμ-myc plasma, whereas Eμ-TCL1 plasma contained signatures of immune-response, inflammation and microenvironment interactions, with putative biomarkers in early-stage cancer. These findings provide a detailed characterization of contrasting B-cell tumor models, identifying common and specific tumor mechanisms. Integrated plasma proteomics allowed the dissection of a systemic response and a tumor lysis signature present in early- and late

  5. Prospective Elementary Science Teachers' Understanding of Photosynthesis and Cellular Respiration in the Context of Multiple Biological Levels as Nested Systems

    ERIC Educational Resources Information Center

    Akçay, Süleyman

    2017-01-01

    In this study, Turkish prospective elementary science teachers' understanding of photosynthesis and cellular respiration has been analysed within the contexts of ecosystem knowledge, organism knowledge and interconnection knowledge (IK). In the analysis, concept maps developed by 74 prospective teachers were used. The study was carried out with…

  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. The Spitzer Survey of Stellar Structure in Galaxies (S4G): Multi-component Decomposition Strategies and Data Release

    NASA Astrophysics Data System (ADS)

    Salo, Heikki; Laurikainen, Eija; Laine, Jarkko; Comerón, Sebastien; Gadotti, Dimitri A.; Buta, Ron; Sheth, Kartik; Zaritsky, Dennis; Ho, Luis; Knapen, Johan; Athanassoula, E.; Bosma, Albert; Laine, Seppo; Cisternas, Mauricio; Kim, Taehyun; Muñoz-Mateos, Juan Carlos; Regan, Michael; Hinz, Joannah L.; Gil de Paz, Armando; Menendez-Delmestre, Karin; Mizusawa, Trisha; Erroz-Ferrer, Santiago; Meidt, Sharon E.; Querejeta, Miguel

    2015-07-01

    The Spitzer Survey of Stellar Structure in Galaxies (S4G) is a deep 3.6 and 4.5 μm imaging survey of 2352 nearby (<40 Mpc) galaxies. We describe the S4G 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.

  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. Cellular cation transport studied by 6/7Li and 23Na NMR in a porous Mo132 Keplerate type nano-capsule as model system.

    PubMed

    Rehder, Dieter; Haupt, Erhard T K; Müller, Achim

    2008-01-01

    Li+ ions can interplay with other cations intrinsically present in the intra- and extra-cellular space (i.e. Na+, K+, Mg2+ and Ca2+) have therapeutic effects (e.g. in the treatment of bipolar disorder) or toxic effects (at higher doses), likely because Li+ interferes with the intra-/extra-cellular concentration gradients of the mentioned physiologically relevant cations. The cellular transmembrane transport can be modelled by molybdenum-oxide-based Keplerates, i.e. nano-sized porous capsules containing 132 Mo centres, monitored through 6/7Li as well as 23Na NMR spectroscopy. The effects on the transport of Li+ cations through the 'ion channels' of these model cells, caused by variations in water amount, temperature, and by the addition of organic cationic 'plugs' and the shift reagent [Dy(PPP)2](7-) are reported. In the investigated solvent systems, water acts as a transport mediator for Li+. Likewise, the counter-transport (Li+/Na+, Li+/K+, Li+/Cs+ and Li+/Ca2+) has been investigated by 7Li NMR and, in the case of Li+/Na+ exchange, by 23Na NMR, and it has been shown that most (in the case of Na+ and K+, all (Ca2+) or almost none (Cs+) of the Li cations is extruded from the internal sites of the artificial cell to the extra-cellular medium, while Na+, K+ and Ca2+ are partially incorporated.

  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.

  11. Influence of plasminogen activator inhibitor-1 (SERPINE1) 4G/5G polymorphism on circulating SERPINE-1 antigen expression in HCC associated with viral infection.

    PubMed

    Divella, Rosa; Mazzocca, Antonio; Gadaleta, Cosimo; Simone, Giovanni; Paradiso, Angelo; Quaranta, Michele; Daniele, Antonella

    2012-01-01

    Hepatocarcinogenesis is heavily influenced by chronic hepatitis B (HBV) and C (HCV) infection. Elevated levels of plasminogen activator inhibitor-1 (SERPINE1/PAI-1) have been reported in patients with hepatocellular carcinoma (HCC) associated with viral infection. The gene encoding SERPINE1 is highly polymorphic and the frequently associated 4/5 guanosine (4G/5G) polymorphism in the gene promoter may influence its expression. Here, we investigated the distribution of genotypes and the frequency of alleles of the 4G/5G polymorphism in patients with HCC, the influence of the 4G/5G polymorphism on plasma SERPINE1 levels and its association with viral infection. A total of 75 patients with HCC were enrolled: 32 (42.6%) were HBV(+)/HCV(+), 11 (14.6%) were only HCV(+), and 32 (42.6%) were negative for both viruses. A control group of healthy donors was also enrolled (n=50). SERPINE1 plasma concentrations were determined by ELISA and the detection of the promoter 4G/5G polymorphism was performed by an allele-specific PCR analysis. We found that the frequency of both the 4G/4G genotype (p=0.02) and the 4G allele (p=0.006) were significantly higher in patients with HCC compared to the control group, and particularly higher in patients with HCC co-infected with HBV(+)/HCV(+) than in those with no viral infection. We also found that patients with the 4G/4G genotype had significantly higher plasma SERPINE1 protein levels when compared with patients with the 4G/5G or 5G/5G genotype (p<0.001). Differences in frequency of 4G allele and genetic variability of 4G/5G SERPINE1 polymorphism with a higher level of SERPINE1 protein in patients with HCC with HBV(+)/HCV(+) than those without infection, suggest the presence of two distinct pathogenic mechanisms in hepatocarcinogenesis, depending on the etiology.

  12. 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.

  13. 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.

  14. 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).

  15. 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%.

  16. 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

    .... (1) Section 1615.4(g)(4)(ii) of the Standard for the Flammability of Children's Sleepwear in sizes 0... alternate laundering procedures under section 4(g)(4)(ii) of the standard. 1615.32 Section 1615.32... FLAMMABILITY OF CHILDREN'S SLEEPWEAR: SIZES 0 THROUGH 6X (FF 3-71) Rules and Regulations § 1615.32 Method...

  17. Probabilistic cellular automata.

    PubMed

    Agapie, Alexandru; Andreica, Anca; Giuclea, Marius

    2014-09-01

    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.

  18. 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

  19. 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.

  20. Histophysiology of cellular immunity reactions in B-cell deprived rabbits. An X-irradiation model for delineation of an 'isolated T-cell system'.

    PubMed

    Veldman, J E; Keuning, F J

    1978-10-16

    Three times sublethal total body X-irradiation with thymus shielding--at 2 weeks' intervals--delineated a temporarily B-cell deprived animal model, only reconstituted with recently thymus-derived cells. The thymusdependent areas of peripheral lymphoid tissue-repleted with T-cells--are described. The cellular immune capacity of these animals with an "isolated T-cell system" was analyzed by means of skin allografting. Histological and autoradiographic studies were performed in draining lymph nodes after a variety of antigenic stimuli: skin allografts, S. java vaccin, horse-gamma-globulin, horse spleen ferritin and a contact sensitizer (Oxazolone).

  1. Cation-dependent folding of 3' cap-independent translation elements facilitates interaction of a 17-nucleotide conserved sequence with eIF4G.

    PubMed

    Kraft, Jelena J; Treder, Krzysztof; Peterson, Mariko S; Miller, W Allen

    2013-03-01

    The 3'-untranslated regions of many plant viral RNAs contain cap-independent translation elements (CITEs) that drive translation initiation at the 5'-end of the mRNA. The barley yellow dwarf virus-like CITE (BTE) stimulates translation by binding the eIF4G subunit of translation initiation factor eIF4F with high affinity. To understand this interaction, we characterized the dynamic structural properties of the BTE, mapped the eIF4G-binding sites on the BTE and identified a region of eIF4G that is crucial for BTE binding. BTE folding involves cooperative uptake of magnesium ions and is driven primarily by charge neutralization. Footprinting experiments revealed that functional eIF4G fragments protect the highly conserved stem-loop I and a downstream bulge. The BTE forms a functional structure in the absence of protein, and the loop that base pairs the 5'-untranslated region (5'-UTR) remains solvent-accessible at high eIF4G concentrations. The region in eIF4G between the eIF4E-binding site and the MIF4G region is required for BTE binding and translation. The data support the model in which the eIF4F complex binds directly to the BTE which base pairs simultaneously to the 5'-UTR, allowing eIF4F to recruit the 40S ribosomal subunit to the 5'-end.

  2. Spitzer/Infrared Array Camera near-infrared features in the outer parts of S4G galaxies

    NASA Astrophysics Data System (ADS)

    Laine, Seppo; Knapen, Johan H.; Muñoz-Mateos, Juan-Carlos; Kim, Taehyun; Comerón, Sébastien; Martig, Marie; Holwerda, Benne W.; Athanassoula, E.; Bosma, Albert; Johansson, Peter H.; Erroz-Ferrer, Santiago; Gadotti, Dimitri A.; Gil de Paz, Armando; Hinz, Joannah; Laine, Jarkko; Laurikainen, Eija; Menéndez-Delmestre, Karín; Mizusawa, Trisha; Regan, Michael W.; Salo, Heikki; Sheth, Kartik; Seibert, Mark; Buta, Ronald J.; Cisternas, Mauricio; Elmegreen, Bruce G.; Elmegreen, Debra M.; Ho, Luis C.; Madore, Barry F.; Zaritsky, Dennis

    2014-11-01

    We present a catalogue and images of visually detected features, such as asymmetries, extensions, warps, shells, tidal tails, polar rings, and obvious signs of mergers or interactions, in the faint outer regions (at and outside of R25) of nearby galaxies. This catalogue can be used in future quantitative studies that examine galaxy evolution due to internal and external factors. We are able to reliably detect outer region features down to a brightness level of 0.03 MJy sr-1 pixel-1 at 3.6 μm in the Spitzer Survey of Stellar Structure in Galaxies (S4G). We also tabulate companion galaxies. We find asymmetries in the outer isophotes in 22 ± 1 per cent of the sample. The asymmetry fraction does not correlate with galaxy classification as an interacting galaxy or merger remnant, or with the presence of companions. We also compare the detected features to similar features in galaxies taken from cosmological zoom re-simulations. The simulated images have a higher fraction (33 per cent) of outer disc asymmetries, which may be due to selection effects and an uncertain star formation threshold in the models. The asymmetries may have either an internal (e.g. lopsidedness due to dark halo asymmetry) or external origin.

  3. UV-IR color profiles of the outer regions of 2K nearby S4G galaxies

    NASA Astrophysics Data System (ADS)

    Bouquin, Alexandre Y. K.; Gil de Paz, Armando

    2017-03-01

    We present our new, spatially-resolved, photometry in FUV and NUV from images obtained by GALEX, and IRAC1 (3.6 μm) photometry obtained by the Spitzer Space Telescope. We analyzed the surface brightness profiles μFUV, μNUV, μ[3.6], as well as the radial evolution of the (FUV-NUV), (FUV - [3.6]), and (NUV - [3.6]) colors in the Spitzer Survey of Stellar Structures in Galaxies (S4G) galaxies (d < 40 Mpc) sample. We defined the GALEX Blue Sequence (GBS) and GALEX Red Sequence (GBR) from the (FUV - NUV) versus (NUV - [3.6]) color-color diagram, populated by late-type star forming galaxies and quiescent early-type galaxies respectively. While most disk becomes radially bluer for GBS galaxies, and stay constant for GRS galaxies, a large fraction ( > 50%) of intermediary GALEX Green Valley (GGV) galaxies' outer disks are becoming redder. An outside-in quenching mechanism such as environmentally-related mechanisms such as starvation or ram-pressure-stripping could explain our results.

  4. 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.

  5. Divalent toxoids loaded stable chitosan-glucomannan nanoassemblies for efficient systemic, mucosal and cellular immunostimulatory response following oral administration.

    PubMed

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

    2015-06-20

    The present study reports dual tetanus and diphtheria toxoids loaded stable chitosan-glucomannan nanoassemblies (sCh-GM-NAs) formulated using tandem ionic gelation technique for oral mucosal immunization. The stable, lyophilized sCh-GM-NAs exhibited ~152 nm particle size and ~85% EE of both the toxoids. The lyophilized sCh-GM-NAs displayed excellent stability in biomimetic media and preserved chemical, conformation and biological stability of encapsulated toxoids. The higher intracellular APCs uptake of sCh-GM-NAs was concentration and time dependent which may be attributed to the receptor mediated endocytosis via mannose and glucose receptor. The higher Caco-2 uptake of sCh-GM-NAs was further confirmed by ex vivo intestinal uptake studies. The in vivo evaluation revealed that sCh-GM-NAs posed significantly (p<0.001) higher humoral, mucosal and cellular immune response than other counterparts by eliciting complete protective levels of anti-TT and anti-DT (~0.1 IU/mL) antibodies. Importantly, commercial 'Dual antigen' vaccine administered through oral or intramuscular route was unable to elicit all type of immune response. Conclusively, sCh-GM-NAs could be considered as promising vaccine adjuvant for oral mucosal immunization.

  6. 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

  7. Impact of the -675 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene on childhood IgA nephropathy.

    PubMed

    Han, Su-Ryun; Kim, Cheon-Jong; Lee, Byung-Cheol

    2012-04-01

    Plasminogen activator inhibitor-1 (PAI-1) is an important regulator of the fibrinolytic pathway and extracellular matrix (ECM) turnover. The -675 4G/5G polymorphism in the PAI-1 promoter is associated with altered PAI-1 transcription, suggesting that this polymorphism may be a candidate risk factor for diseases characterized by ECM accumulation, such as immunoglobulin A nephropathy (IgAN) and mesangial proliferative glomerulonephritis (MesPGN). We genotyped childhood patients with biopsy-confirmed IgAN (n=111) and MesPGN (n=47), and healthy control subjects (n=230) for the -675 4G/5G PAI-1 polymorphism by polymerase chain reaction-restriction fragment length polymorphism methods. The distribution of the 4G/4G (27.9%), 4G/5G (45.1%) and 5G/5G (27.0%) genotypes in IgAN patients was significantly different from the healthy controls (32.2, 54.3 and 13.5%, respectively) (p=0.0092). There was no significant difference in the genotype distributions of the 4G/5G polymorphism between MesPGN patients and the healthy controls. Regarding the impact of the polymorphism on IgAN, the 4G/4G genotype was markedly increased in patients with proteinuria (≥1,000 mg/day) and/or hypertension when compared to patients without proteinuria and hypertension (OR=5.23, 95% CI 1.34-20.38, P=0.0183). These findings indicate that the PAI-1 gene polymorphism may affect the susceptibility of childhood IgAN.

  8. 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

  9. 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

  10. 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

    2016-07-22

    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.

  11. 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.

  12. 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.

  13. [The physics of cellular automata and coherence and chaos in classical many-body systems]. Progress report, May 1991--present

    SciTech Connect

    Not Available

    1992-06-24

    This report contains short discussions on the following topics: non-variational effects in a Ginzburg-Landau equation; algebraic correlations in conserved chaotic systems; chaotic interface models of turbulence; algebraic correlations in coupled order parameter systems; and dynamics of Josephson Junction arrays. (LSP)

  14. 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.

  15. Cellular Array Processing Simulation

    NASA Astrophysics Data System (ADS)

    Lee, Harry C.; Preston, Earl W.

    1981-11-01

    The Cellular Array Processing Simulation (CAPS) system is a high-level image language that runs on a multiprocessor configuration. CAPS is interpretively decoded on a conventional minicomputer with all image operation instructions executed on an array processor. The synergistic environment that exists between the minicomputer and the array processor gives CAPS its high-speed throughput, while maintaining a convenient conversational user language. CAPS was designed to be both modular and table driven so that it can be easily maintained and modified. CAPS uses the image convolution operator as one of its primitives and performs this cellular operation by decomposing it into parallel image steps that are scheduled to be executed on the array processor. Among its features is the ability to observe the imagery in real time as a user's algorithm is executed. This feature reduces the need for image storage space, since it is feasible to retain only original images and produce resultant images when needed. CAPS also contains a language processor that permits users to develop re-entrant image processing subroutines or algorithms.

  16. 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

  17. A mercury arc lamp-based multi-color confocal real time imaging system for cellular structure and function.

    PubMed

    Saito, Kenta; Kobayashi, Kentaro; Tani, Tomomi; Nagai, Takeharu

    2008-01-01

    Multi-point scanning confocal microscopy using a Nipkow disk enables the acquisition of fluorescent images with high spatial and temporal resolutions. Like other single-point scanning confocal systems that use Galvano meter mirrors, a commercially available Nipkow spinning disk confocal unit, Yokogawa CSU10, requires lasers as the excitation light source. The choice of fluorescent dyes is strongly restricted, however, because only a limited number of laser lines can be introduced into a single confocal system. To overcome this problem, we developed an illumination system in which light from a mercury arc lamp is scrambled to make homogeneous light by passing it through a multi-mode optical fiber. This illumination system provides incoherent light with continuous wavelengths, enabling the observation of a wide range of fluorophores. Using this optical system, we demonstrate both the high-speed imaging (up to 100 Hz) of intracellular Ca(2+) propagation, and the multi-color imaging of Ca(2+) and PKC-gamma dynamics in living cells.

  18. 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

    2016-11-05

    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.

  19. Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1

    SciTech Connect

    Sekiyama, Naotaka; Arthanari, Haribabu; Papadopoulos, Evangelos; Rodriguez-Mias, Ricard A.; Wagner, Gerhard; Léger-Abraham, Mélissa

    2015-07-13

    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 in this paper 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. Finally, 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.

  20. Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1

    DOE PAGES

    Sekiyama, Naotaka; Arthanari, Haribabu; Papadopoulos, Evangelos; ...

    2015-07-13

    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 formore » 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 in this paper 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. Finally, 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.« less

  1. Characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models

    PubMed Central

    Sun, Zhizhi; Yathindranath, Vinith; Worden, Matthew; Thliveris, James A; Chu, Stephanie; Parkinson, Fiona E; Hegmann, Torsten; Miller, Donald W

    2013-01-01

    Background Aminosilane-coated iron oxide nanoparticles (AmS-IONPs) have been widely used in constructing complex and multifunctional drug delivery systems. However, the biocompatibility and uptake characteristics of AmS-IONPs in central nervous system (CNS)-relevant cells are unknown. The purpose of this study was to determine the effect of surface charge and magnetic field on toxicity and uptake of AmS-IONPs in CNS-relevant cell types. Methods The toxicity and uptake profile of positively charged AmS-IONPs and negatively charged COOH-AmS-IONPs of similar size were examined using a mouse brain microvessel endothelial cell line (bEnd.3) and primary cultured mouse astrocytes and neurons. Cell accumulation of IONPs was examined using the ferrozine assay, and cytotoxicity was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results No toxicity was observed in bEnd.3 cells at concentrations up to 200 μg/mL for either AmS-IONPs or COOH-AmS-IONPs. AmS-IONPs at concentrations above 200 μg/mL reduced neuron viability by 50% in the presence or absence of a magnetic field, while only 20% reductions in viability were observed with COOH-AmS-IONPs. Similar concentrations of AmS-IONPs in astrocyte cultures reduced viability to 75% but only in the presence of a magnetic field, while exposure to COOH-AmS-IONPs reduced viability to 65% and 35% in the absence and presence of a magnetic field, respectively. Cellular accumulation of AmS-IONPs was greater in all cell types examined compared to COOH-AmS-IONPs. Rank order of cellular uptake for AmS-IONPs was astrocytes > bEnd.3 > neurons. Accumulation of COOH-AmS-IONPs was minimal and similar in magnitude in different cell types. Magnetic field exposure enhanced cellular accumulation of both AmS- and COOH-AmS-IONPs. Conclusion Both IONP compositions were nontoxic at concentrations below 100 μg/mL in all cell types examined. At doses above 100 μg/mL, neurons were more sensitive to Am

  2. Plasminogen activator inhibitor-1 4G/5G and the MTHFR 677C/T polymorphisms and susceptibility to polycystic ovary syndrome: a meta-analysis.

    PubMed

    Lee, Young Ho; Song, Gwan Gyu

    2014-04-01

    The aim of this study was to explore whether the plasminogen activator inhibitor-1 (PAI-1) 4G/5G and the methylenetetrahydrofolate reductase (MTHFR) 677C/T polymorphisms are associated with susceptibility to polycystic ovary syndrome (PCOS). Meta-analyses were conducted to determine the association between the PAI-1 4G/5G and MTHFR 677C/T polymorphisms and PCOS using: (1) allele contrast (2) homozygote contrast, (3) recessive, and (4) dominant models. For meta-analysis, nine studies of the PAI-1 4G/5G polymorphism with 2384 subjects (PCOS, 1615; controls, 769) and eight studies of the MTHFR 677C/T polymorphism with 1270 study subjects were included. Meta-analysis of all study subjects showed no association between PCOS and the PAI-1 4G allele (OR=0.949, 95% CI=0.671-1.343, p=0.767). Stratification by ethnicity, however, indicated a significant association between the PAI-1 4G allele and PCOS in Turkish and Asian populations (OR=0.776, 95% CI=0.602-0.999, p=0.049; OR=1.749, 95% CI=1.297-2.359, p=2.5×10(-5) respectively). In addition, meta-analysis indicated an association between PCOS and the PAI-1 4G4G+4G5G genotype in Europeans (OR=1.406, 95% CI=1.025-1.928, p=0.035). However, meta-analysis of all study subjects showed no association between PCOS and the MTHFR 677T allele (OR=0.998, 95% CI=0.762-1.307, p=0.989), including Europeans (OR=0.806, 95% CI=0.610-1.063, p=0.126). Meta-analysis showed no association between PCOS and the MTHFR 677C/T polymorphism using homozygote contrast, and recessive and dominant models. In conclusion, meta-analysis suggests the PAI-1 4G/5G polymorphism is associated with susceptibility to PCOS in European, Turkish, and Asian populations, but the MTHFR 677C/T polymorphism is not associated with susceptibility to PCOS in Europeans.

  3. 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

  4. Simulation of a strong ground motion exceeding 4G during the 2008 Iwate-Miyagi Nairiku earthquake, Japan

    NASA Astrophysics Data System (ADS)

    Pulido, N.; Aoi, S.; Suzuki, W.

    2008-12-01

    The Iwate-Miyagi Nairiku earthquake, a powerful reverse fault event that occurred on the southern Iwate prefecture Japan (2008/6/14), produced the largest peak ground acceleration recorded to date (4G), at the West Ichinoseki, KiK-net/NIED strong motion station (IWTH25), which is located immediately above the hypocenter. This KiK-net station which is equipped with surface and borehole accelerometers (GL -260m), also recorded very high peak accelerations up to 1G at the borehole level, despite being located in a rock site (Vs ~ 1800m/s). Preliminary analyses of these waveforms show a very strong content of high frequencies (HF). To understand the generation process of this extreme shaking we simulated the three components of ground motion at the IWTH25 borehole and surface levels, by applying a strong motion simulation methodology based on a dynamic model of fault rupture (Pulido and Dalguer 2008, PD08). Following PD08 we investigated the contribution of rupture velocity changes (Δ Vr) and stress drop (Δσ) across the fault plane to the HF ground motion radiation of the earthquake at the borehole level, and then calculated the non-linear response of the shallow layers to obtain the ground motion at the surface. To calculate the stress drop distribution of the earthquake we apply the methodology of Ripperger and Mai (2004), by using the slip model obtained from an inversion of near-source strong motion recordings (Suzuki et al. 2008), and a 1D velocity model for the Kanto region. The dislocation model of this earthquake is characterized by two patches of large slip, the first one located at the hypocenter and the second at ~7 km south of the hypocenter. Our results for the calculation of stress drop follow a similar pattern, namely a very large stress drop of ~80MPa concentrated at the hypocenter, as well as a large value of ~50MPa for the southern patch. To calculate the HF ground motion we follow PD08 who found that the HF radiation from earthquakes is confined

  5. Reducing translation through eIF4G/IFG-1 improves survival under ER stress that depends on heat shock factor HSF-1 in Caenorhabditis elegans.

    PubMed

    Howard, Amber C; Rollins, Jarod; Snow, Santina; Castor, Sarah; Rogers, Aric N

    2016-08-18

    Although certain methods of lowering and/or altering mRNA translation are associated with increased lifespan, the mechanisms underlying this effect remain largely unknown. We previously showed that the increased lifespan conferred by reducing expression of eukaryotic translation initiation factor 4G (eIF4G/IFG-1) enhances survival under starvation conditions while shifting protein expression toward factors involved with maintaining ER-dependent protein and lipid balance. In this study, we investigated changes in ER homeostasis and found that lower eIF4G/IFG-1 increased survival under conditions of ER stress. Enhanced survival required the ER stress sensor gene ire-1 and the ER calcium ATPase gene sca-1 and corresponded with increased translation of chaperones that mediate the ER unfolded protein response (UPR(ER) ). Surprisingly, the heat-shock transcription factor gene hsf-1 was also required for enhanced survival, despite having little or no influence on the ability of wild-type animals to survive ER stress. The requirement for hsf-1 led us to re-evaluate the role of eIF4G/IFG-1 on thermotolerance. Results show that lowering expression of this translation factor enhanced thermotolerance, but only after prolonged attenuation, the timing of which corresponded to increased transcription of heat-shock factor transcriptional targets. Results indicate that restricting overall translation through eIF4G/IFG-1 enhances ER and cytoplasmic proteostasis through a mechanism that relies heavily on hsf-1.

  6. Facile synthesis of Fe3O4/g-C3N4/HKUST-1 composites as a novel biosensor platform for ochratoxin A.

    PubMed

    Hu, Shuisheng; Ouyang, Wenjun; Guo, Longhua; Lin, Zhenyu; Jiang, Xiaohua; Qiu, Bin; Chen, Guonan

    2017-06-15

    A fluorescent biosensor for ochratoxin A was fabricated on the basis of a new nanocomposite (Fe3O4/g-C3N4/HKUST-1 composites). Fe3O4/g-C3N4/HKUST-1 was synthesized in this work for the first time, which combined HKUST-1 with g-C3N4 to improve its chemical stability. Fe3O4/g-C3N4/HKUST-1 composites have strong adsorption capacity for dye-labeled aptamer and are able to completely quench the fluorescence of the dye through the photoinduced electron transfer (PET) mechanism. In the presence of ochratoxin A (OTA), it can bind with the aptamer with high affinity, causing the releasing of the dye-labeled aptamer from the Fe3O4/g-C3N4/HKUST-1 and therefore results in the recovery of fluorescence. The fluorescence intensity of the biosensor has a linear relationship with the OTA concentration in the range of 5.0-160.0ng/mL. The LOD of sensor is 2.57ng/mL (S/N=3). This fluorescence sensor based on the Fe3O4/g-C3N4/HKUST-1 composites has been applied to detect OTA in corn with satisfying results.

  7. Urinary excretion study following consumption of various poppy seed products and investigation of the new potential street heroin marker ATM4G.

    PubMed

    Maas, Alexandra; Krämer, Michael; Sydow, Konrad; Chen, Pai-Shan; Dame, Torsten; Musshoff, Frank; Diehl, Bernd W K; Madea, Burkhard; Hess, Cornelius

    2017-03-01

    Discrimination between street heroin consumption and poppy seed ingestion represents a major toxicological challenge in daily routine work. Several difficulties associated with conventional street heroin markers originate from their versatile occurrence in various poppy seed products and medications, respectively, as well as to small windows of detection. A novel opportunity to overcome these hindrances is represented by the new potential street heroin marker acetylated-thebaine-4-metabolite glucuronide (ATM4G), originating from thebaine during street heroin synthesis followed by metabolic reactions after administration. In this study, urine samples after consumption of different German poppy seed products and urine samples from subjects with suspicion of preceding heroin consumption were tested for ATM4G, 6-AC (6-acetylcodeine), papaverine, noscapine, 6-MAM (6-monoacetylmorphine), morphine, and codeine. Neither 6-AC and 6-MAM nor ATM4G but morphine and codeine could be detected in urine samples following poppy seed ingestion. As well, neither papaverine nor noscapine could be observed even after consumption of poppy seeds containing up to 37 µg noscapine and up to 9.8 µg papaverine, respectively. Concerning the urine samples with suspicion of preceding heroin consumption, ATM4G could be detected in 9 of 43 cases. By contrast, evidence of 6-AC and 6-MAM, respectively, could only be seen in 7 urine samples. In conclusion, ATM4G should be measured additionally in cases requiring discrimination of street heroin consumption from poppy seed intake. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Single nucleotide polymorphisms in a gene for translation initiation factor (eIF4G) of rice (Oryza sativa) associated with resistance to Rice tungro spherical virus.

    PubMed

    Lee, Jong-Hee; Muhsin, Muhammad; Atienza, Genelou A; Kwak, Do-Yeon; Kim, Suk-Man; De Leon, Teresa B; Angeles, Enrique R; Coloquio, Edgardo; Kondoh, Hiroaki; Satoh, Kouji; Cabunagan, Rogelio C; Cabauatan, Pepito Q; Kikuchi, Shoshi; Leung, Hei; Choi, Il-Ryong

    2010-01-01

    Rice tungro disease (RTD) is a serious constraint to rice production in South and Southeast Asia. RTD is caused by Rice tungro spherical virus (RTSV) and Rice tungro bacilliform virus. Rice cv. Utri Merah is resistant to RTSV. To identify the gene or genes involved in RTSV resistance, the association of genotypic and phenotypic variations for RTSV resistance was examined in backcross populations derived from Utri Merah and rice germplasm with known RTSV resistance. Genetic analysis revealed that resistance to RTSV in Utri Merah was controlled by a single recessive gene (tsv1) mapped within an approximately 200-kb region between 22.05 and 22.25 Mb of chromosome 7. A gene for putative translation initiation factor 4G (eIF4G(tsv1)) was found in the tsv1 region. Comparison of eIF4G(tsv1) gene sequences among susceptible and resistant plants suggested the association of RTSV resistance with one of the single nucleotide polymorphism (SNP) sites found in exon 9 of the gene. Examination of the SNP site in the eIF4G(tsv1) gene among various rice plants resistant and susceptible to RTSV corroborated the association of SNP or deletions in codons for Val(1060-1061) of the predicted eIF4G(tsv1) with RTSV resistance in rice.

  9. Z-scheme mechanism of photogenerated carriers for hybrid photocatalyst Ag3PO4/g-C3N4 in degradation of sulfamethoxazole.

    PubMed

    Zhou, Li; Zhang, Wei; Chen, Ling; Deng, Huiping

    2017-02-01

    Composite or hybrid photocatalysts are gaining increasing interests due to the unique and enhanced photocatalytic activity. In this study, Ag3PO4/g-C3N4 with different ratios of Ag3PO4 and g-C3N4 were synthesized using a facile in situ precipitation method. The photocatalysts were characterized by transmission electron microscopy (TEM), X-ray diffraction pattern (XRD), Fourier transform infrared spectra (FTIR), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET) and ultraviolet-visible diffuse reflectance spectroscopy (UV-vis DRS). The photocatalytic performance was evaluated by the degradation of sulfamethoxazole (SMX), a model antibiotic compound, under visible light irradiation. It was found that the composite photocatalyst Ag3PO4/g-C3N4 with a mass ratio of Ag3PO4:g-C3N4 of 98:2 exhibited a higher photocatalytic activity than Ag3PO4/g-C3N4 with the mass ratio of 2:98 for the degradation of SMX. When Ag3PO4 was the primary part of Ag3PO4/g-C3N4 photocatalyst, the migration of photogenerated electron-hole showed a Z-scheme mechanism with photongenerated holes on the valance band of Ag3PO4 to oxidize pollutants. The separation mechanism was investigated by the photoluminescence technique and the scavengering of reactive oxygen species.

  10. Cellular and network properties in the functioning of the nervous system: from central pattern generators to cognition.

    PubMed

    Arshavsky, Yuri I

    2003-03-01

    The relation between individual neurons and neuronal networks in performing brain functions is one of the central questions in modern neuroscience. Most of the current literature suggests that the role of individual neurons is negligible and neural networks play a dominant role in the functioning of the nervous system. Individual neurons are usually viewed as network elements whose functions are limited to generating electrical signals and releasing neurotransmitters. Here I summarize experimental evidence that challenges this concept and argue that the unique, intrinsic properties of highly specialized individual neurons are as important for the functioning of the brain as the network properties. I first discuss the studies of relatively 'simple' functions of the nervous system, such as the control of rhythmic 'automatic' movements and generation of circadian rhythm, which indicate that individual neurons may continue performing their functions after being separated from corresponding networks. I then argue that the complex cognitive functions, such as declarative memory, language processing, and face recognition, are likely to be underlain by the properties of groups of highly specialized neurons. These neurons appear to be genetically predisposed to perform cognitive functions and their dysfunctions cannot be compensated by other elements of the nervous system. Under this concept, the electrical signals circulating within and between neural networks are considered to be a means of forming coordinated dynamic ensembles of neurons involved in performing specific functions. While still speculative, this hypothesis may provoke new approaches to studies of neural mechanisms underpinning cognitive functions of the brain.

  11. Fine structure and cellular responses at the host-parasite interface in a range of fish-helminth systems.

    PubMed

    Dezfuli, B S; Bo, T; Lorenzoni, M; Shinn, A P; Giari, L

    2015-03-15

    A series of ultrastructural-based studies were conducted on the interface region in different fish-helminth systems: (a) an intestinal infection of the cestode Monobothrium wageneri in tench, Tinca tinca; (b) an extensive intestinal submucosa and mucosal infection in tench by metacercariae of an unidentified digenean trematode; (c) an intestinal infection in brown trout, Salmo trutta, by the acanthocephalan Dentitruncus truttae; (d) an extraintestinal infection by larvae of the acanthocephalan, Pomphorhynchus laevis in three-spined sticklebacks, Gasterosteus aculeatus; and (e) an infection in the livers of Eurasian minnow, Phoxinus phoxinus, by larvae of the nematode Raphidascaris acus. Endoparasitic helminths frequently cause inflammation of the digestive tract and associated organs, inducing the recruitment of various immune cells to the site of infection. In each of the fish-helminth systems that were studied, a massive hyperplastic granulocyte response involving mast cells (MCs) and neutrophils in close proximity to the helminths was documented. The current study presents data on the interface region in each fish-helminth system and documents the penetration of mast cells granules within the tegument of P. laevis larvae. No extracellular vesicles containing tegumental secretions from any of the four different taxa of endoparasitic helminths species at the host-parasite interface region were seen.

  12. 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.

  13. Creep-rupture behavior of a developmental cast-iron-base alloy for use up to 800/sup 0/C. [NASAUT 4G-Al: Fe-15Mn-15Cr-2Mo-1. 5C-1Nb-1Si

    SciTech Connect

    Titran, R.H.; Scheuermann, C.M.

    1987-08-01

    As part of the DOE/NASA Stirling Engine Systems Project, an iron-base cast alloy was developed, designated NASAUT 4G-Al. Its nominal composition, in percent by weight, is Fe-15Mn-15Cr-2Mo-1.5C-1Nb-1Si. This report presents the results of a study of this alloy, 4G-Al, performed to determine its creep-rupture properties. The alloy was studied in the directionally solidified (DS) form with a 650/sup 0/C/100 h anneal recommended by UTRC to optimize properties and in the investment-cast (IC) form with either a 760/sup 0/C/20 h anneal recommended by UTRC to optimize properties, or a solution anneal of 790/sup 0/C/20 h followed by a simulated brazing cycle of 1065/sup 0/C/15 min + a heat treatment of 760/sup 0/C/16 h + 650/sup 0/C/16 h. Alloy 4G-Al exhibited typical 3-stage creep response under all conditions tested. The most creep resistant condition was the DS material. This condition compares very favorably to the prototype (HS-31) and prime candidate (XF-818) alloys for the automotive Stirling engine cylinder/regenerator housing. 14 refs., 7 figs., 6 tabs.

  14. Cellular automata for traffic simulations

    NASA Astrophysics Data System (ADS)

    Wolf, Dietrich E.

    1999-02-01

    Traffic phenomena such as the transition from free to congested flow, lane inversion and platoon formation can be accurately reproduced using cellular automata. Being computationally extremely efficient, they simulate large traffic systems many times faster than real time so that predictions become feasible. A riview of recent results is given. The presence of metastable states at the jamming transition is discussed in detail. A simple new cellular automation is introduced, in which the interaction between cars is Galilei-invariant. It is shown that this type of interaction accounts for metastable states in a very natural way.

  15. 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.

  16. 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

  17. A Cellular Biophysics Textbook

    NASA Astrophysics Data System (ADS)

    Wilder, Alan Joseph

    2011-12-01

    In the past two decades, great advances have been made in understanding of the biophysical mechanisms of the protein machines that carry out the fundamental processes of the cell. It is now known that all major eukaryotic cellular processes require a complicated assemblage of proteins acting via a series of concerted motions. In order to grasp current understanding of cellular mechanisms, the new generation of cell biologists needs to be trained in the general characteristics of these cellular properties and the methods with which to study them. This cellular biophysics textbook, to be used in conjunction with the cellular biophysics course (MCB143) at UC-Davis, provides a great tool in the instruction of the new generation of cellular biologists. It provides a hierarchical view of the cell, from atoms to protein machines and explains in depth the mechanisms of cytoskeletal force generators as an example of these principles.

  18. Radiolabeled novel mAb 4G1 for immunoSPECT imaging of EGFRvIII expression in preclinical glioblastoma xenografts

    PubMed Central

    Liu, Xujie; Dong, Chengyan; Shi, Jiyun; Ma, Teng; Jin, Zhongxia; Jia, Bing; Liu, Zhaofei; Shen, Li; Wang, Fan

    2017-01-01

    Epidermal growth factor receptor mutant III (EGFRvIII) is exclusively expressed in tumors, such as glioblastoma, breast cancer and hepatocellular carcinoma, but never in normal organs. Increasing evidence suggests that EGFRvIII has clinical significance in glioblastoma prognosis due to its enhanced tumorigenicity and chemo/radio resistance, thus the development of an imaging approach to early detect EGFRvIII expression with high specificity is urgently needed. To illustrate this point, we developed a novel anti-EGFRvIII monoclonal antibody 4G1 through mouse immunization, cell fusion and hybridoma screening and then confirmed its specificity and affinity by a serial of assays. Following biodistribution and small animal single-photon emission computed tomography (SPECT/CT) imaging of 125I-4G1 in EGFRvIII positive/negative tumor-bearing mice were performed and evaluated to verify the tumor accumulation of this radiotracer. The biodistribution indicated that 125I-4G1 showed prominent tumor accumulation at 24 h post-injection, which reached maximums of 11.20 ± 0.75% ID/g and 13.98 ± 0.57% ID/g in F98npEGFRvIII and U87vIII xenografts, respectively. In contrast, 125I-4G1 had lower tumor accumulation in F98npEGFR and U87MG xenografts. Small animal SPECT/CT imaging revealed that 125I-4G1 had a higher tumor uptake in EGFRvIII-positive tumors than that in EGFRvIII-negative tumors. This study demonstrates that radiolabeled 4G1 can serve as a valid probe for the imaging of EGFRvIII expression, and would be valuable into the clinical translation for the diagnosis, prognosis, guiding therapy, and therapeutic efficacy evaluation of tumors. PMID:28031526

  19. 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

  20. Systemic delivery of MeCP2 rescues behavioral and cellular deficits in female mouse models of Rett syndrome.

    PubMed

    Garg, Saurabh K; Lioy, Daniel T; Cheval, Hélène; McGann, James C; Bissonnette, John M; Murtha, Matthew J; Foust, Kevin D; Kaspar, Brian K; Bird, Adrian; Mandel, Gail

    2013-08-21

    De novo mutations in the X-linked gene encoding the transcription factor methyl-CpG binding protein 2 (MECP2) are the most frequent cause of the neurological disorder Rett syndrome (RTT). Hemizygous males usually die of neonatal encephalopathy. Heterozygous females survive into adulthood but exhibit severe symptoms including microcephaly, loss of purposeful hand motions and speech, and motor abnormalities, which appear after a period of apparently normal development. Most studies have focused on male mouse models because of the shorter latency to and severity in symptoms, yet how well these mice mimic the disease in affected females is not clear. Very few therapeutic treatments have been proposed for females, the more gender-appropriate model. Here, we show that self-complementary AAV9, bearing MeCP2 cDNA under control of a fragment of its own promoter (scAAV9/MeCP2), is capable of significantly stabilizing or reversing symptoms when administered systemically into female RTT mice. To our knowledge, this is the first potential gene therapy for females afflicted with RTT.

  1. 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

  2. Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers

    PubMed Central

    2013-01-01

    Introduction Early systemic sclerosis (SSc) is characterized by Raynaud's phenomenon together with scleroderma marker autoantibodies and/or a scleroderma pattern at capillaroscopy and no other distinctive feature of SSc. Patients presenting with marker autoantibodies plus a capillaroscopic scleroderma pattern seem to evolve into definite SSc more frequently than patients with either feature. Whether early SSc patients with only marker autoantibodies or capillaroscopic positivity differ in any aspect at presentation is unclear. Methods Seventy-one consecutive early SSc patients were investigated for preclinical cardiopulmonary alterations. Out of these, 44 patients and 25 controls affected by osteoarthritis or primary fibromyalgia syndrome were also investigated for serum markers of fibroblast (carboxyterminal propeptide of collagen I), endothelial (soluble E-selectin) and T-cell (soluble IL-2 receptor alpha) activation. Results Thirty-two of the 71 patients (45.1%) had both a marker autoantibody and a capillaroscopic scleroderma pattern (subset 1), 16 patients (22.5%) had only a marker autoantibody (subset 2), and 23 patients (32.4%) had only a capillaroscopic scleroderma pattern (subset 3). Patients with marker autoantibodies (n = 48, 67.6%) had a higher prevalence of impaired diffusing lung capacity for carbon monoxide (P = 0.0217) and increased serum levels of carboxyterminal propeptide of collagen I (P = 0.0037), regardless of capillaroscopic alterations. Patients with a capillaroscopic scleroderma pattern (n = 55, 77.5%) had a higher prevalence of puffy fingers (P = 0.0001) and increased serum levels of soluble E-selectin (P = 0.0003) regardless of marker autoantibodies. Conclusion These results suggest that the autoantibody and microvascular patterns in early SSc may each be related to different clinical-preclinical features and circulating activation markers at presentation. Longitudinal studies are warranted to investigate whether these subsets undergo a

  3. Enhanced photo-Fenton-like process over Z-scheme CoFe2O4/g-C3N4 Heterostructures under natural indoor light.

    PubMed

    Yao, Yunjin; Wu, Guodong; Lu, Fang; Wang, Shaobin; Hu, Yi; Zhang, Jie; Huang, Wanzheng; Wei, Fengyu

    2016-11-01

    Low-cost catalysts with high activity and stability toward producing strongly oxidative species are extremely desirable, but their development still remains a big challenge. Here, we report a novel strategy for the synthesis of a magnetic CoFe2O4/C3N4 hybrid via a simple self-assembly method. The CoFe2O4/C3N4 was utilized as a photo-Fenton-like catalyst for degradation of organic dyes in the presence of H2O2 under natural indoor light irradiation, a green and energy-saving approach for environmental cleaning. It was found the CoFe2O4/C3N4 hybrid with a CoFe2O4: g-C3N4 mass ratio of 2:1 can completely degrade Rhodamine B nearly 100 % within 210 min under room-light irradiation. The effects of the amount of H2O2 (0.01-0.5 M), initial dye concentration (5-20 mg/L), solution pH (3.08-10.09), fulvic acid concentration (5-50 mg/L), different dyes and catalyst stability on the organic dye degradation were investigated. The introduction of CoFe2O4 on g-C3N4 produced an enhanced separation efficiency of photogenerated electron - hole pairs by a Z-scheme mechanism between the interfaces of g-C3N4 and CoFe2O4, leading to an excellent activity as compared with either g-C3N4 or CoFe2O4 and their mixture. This study demonstrates an efficient way to construct the low-cost magnetic CoFe2O4/C3N4 heterojunction as a typical Z-scheme system in environmental remediation.

  4. 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

    2015-04-17

    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.

  5. 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

  6. Cellular localization and adaptive changes of the cardiac delta opioid receptor system in an experimental model of heart failure in rats.

    PubMed

    Treskatsch, Sascha; Feldheiser, Aarne; Shaqura, Mohammed; Dehe, Lukas; Habazettl, Helmut; Röpke, Torsten K; Shakibaei, Mehdi; Schäfer, Michael; Spies, Claudia D; Mousa, Shaaban A

    2016-02-01

    The role of the cardiac opioid system in congestive heart failure (CHF) is not fully understood. Therefore, this project investigated the cellular localization of delta opioid receptors (DOR) in left ventricle (LV) myocardium and adaptive changes in DOR and its endogenous ligand, the precursor peptide proenkephalin (PENK), during CHF. Following IRB approval, DOR localization was determined by radioligand binding using [H(3)]Naltrindole and by double immunofluorescence confocal analysis in the LV of male Wistar rats. Additionally, 28 days following an infrarenal aortocaval fistula (ACF) the extent of CHF and adaptions in left ventricular DOR and PENK expression were examined by hemodynamic measurements, RT-PCR, and Western blot. DOR specific membrane binding sites were identified in LV myocardium. DOR were colocalized with L-type Ca(2+)-channels (Cav1.2) as well as with intracellular ryanodine receptors (RyR) of the sarcoplasmatic reticulum. Following ACF severe congestive heart failure developed in all rats and was accompanied by up-regulation of DOR and PENK on mRNA as well as receptor proteins representing consecutive adaptations. These findings might suggest that the cardiac delta opioid system possesses the ability to play a regulatory role in the cardiomyocyte calcium homeostasis, especially in response to heart failure.

  7. The association between the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor-1 gene and extension of postsurgical calf vein thrombosis.

    PubMed

    Ferrara, Filippo; Meli, Francesco; Raimondi, Francesco; Montalto, Salvatore; Cospite, Valentina; Novo, Giuseppina; Novo, Salvatore

    2013-04-01

    The objective of this study was to evaluate whether the presence of a plasminogen activator inhibitor type 1 (PAI-1) promoter polymorphism 4G/5G could significantly influence the proximal extension of vein thrombosis in spite of anticoagulant treatment in patients with calf vein thrombosis (CVT) following orthopaedic, urological and abdominal surgery. We studied 168 patients with CVT, who had undergone orthopaedic, urological and abdominal surgery, subdivided as follows: first, 50 patients with thrombosis progression; second, 118 patients without thrombosis progression. The 4G/5G polymorphism of the plasminogen activator inhibitor 1 was evaluated in all patients and in 70 healthy matched controls. We also studied PAI-1 activity in plasma. The presence of 4G/5G genotype was significantly increased in the group of patients with the extension of thrombotic lesions and was associated with an increase in CVT extension risk (odds ratio adjusted for sex 2.692; 95% confidence interval 1.302-4.702). Moreover, we observed a significant increase of PAI-1 plasma activity in patients with extension of thrombotic lesion vs. patients without extension (P=0.0001). Patients with 4G/5G genotype in the promoter of the plasminogen activator inhibitor - 1 gene present a higher risk of extension of thrombotic lesions.

  8. 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, Inc. and InterDigital Holdings, Inc. on January 2, 2013. The complaint alleges violations of section.../or 4g capabilities and components thereof. The complaint names as respondents Samsung Electronics...

  9. 16 CFR 1615.32 - Method for establishment and use of alternate laundering procedures under section 4(g)(4)(ii) of...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... alternate laundering procedures under section 4(g)(4)(ii) of the standard. 1615.32 Section 1615.32 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CHILDREN'S SLEEPWEAR: SIZES 0 THROUGH 6X (FF 3-71) Rules and Regulations § 1615.32 Method...

  10. 16 CFR 1615.32 - Method for establishment and use of alternate laundering procedures under section 4(g)(4)(ii) of...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... alternate laundering procedures under section 4(g)(4)(ii) of the standard. 1615.32 Section 1615.32 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CHILDREN'S SLEEPWEAR: SIZES 0 THROUGH 6X (FF 3-71) Rules and Regulations § 1615.32 Method...

  11. 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

  12. 32 CFR 1630.45 - Class 4-G: Registrant exempted from service because of the death of his parent or sibling while...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... is in a captured or missing in action status. 1630.45 Section 1630.45 National Defense Other... Forces or whose parent or sibling is in a captured or missing in action status. In Class 4-G shall be... missing status as a result of such service in the Armed Forces during any period of time; or (b) The...

  13. 3-substituted indazoles as configurationally locked 4EGI-1 mimetics and inhibitors of the eIF4E/eIF4G interaction.

    PubMed

    Yefidoff-Freedman, Revital; Chen, Ting; Sahoo, Rupam; Chen, Limo; Wagner, Gerhard; Halperin, Jose A; Aktas, Bertal H; Chorev, Michael

    2014-03-03

    4EGI-1, the prototypic inhibitor of eIF4E/eIF4G interaction, was identified in a high-throughput screening of small-molecule libraries with the aid of a fluorescence polarization assay that measures inhibition of binding of an eIF4G-derived peptide to recombinant eIF4E. As such, the molecular probe 4EGI-1 has potential for the study of molecular mechanisms involved in human disorders characterized by loss of physiological restraints on translation initiation. A hit-to-lead optimization campaign was carried out to overcome the configurational instability in 4EGI-1, which stems from the E-to-Z isomerization of the hydrazone function. We identified compound 1 a, 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 directed towards probing the structural latitude of this new chemotype as an inhibitor of eIF4E/eIF4G interaction and translation initiation we identified 1 d, an indazole-based 4EGI-1 mimetic, as a new and improved lead inhibitor of eIF4E/eIF4G interaction and a promising molecular probe candidate for elucidation of the role of cap-dependent translation initiation in a host of pathophysiological states.

  14. Evolving gene regulatory networks into cellular networks guiding adaptive behavior: an outline how single cells could have evolved into a centralized neurosensory system.

    PubMed

    Fritzsch, Bernd; Jahan, Israt; Pan, Ning; Elliott, Karen L

    2015-01-01

    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 and their localized patterning leading to remarkably different cell types aggregated into variably sized parts of the central nervous system have begun to emerge. Insights at the cellular and molecular level have begun 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, which were 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.

  15. 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

  16. PAI-1 -675 4G/5G polymorphism in association with diabetes and diabetic complications susceptibility: a meta-analysis study.

    PubMed

    Xu, Kuanfeng; Liu, Xiaoyun; 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.

  17. Serum PAI-1 and PAI-1 4G/5G Polymorphism in Hepatitis C Virus-Induced Cirrhosis and Hepatitis C Virus-Induced Hepatocellular Carcinoma Patients.

    PubMed

    El Edel, Rawhia H; Essa, Enas Said; Essa, Abdallah S; Hegazy, Sara A; El Rowedy, Dalia I

    2016-11-01

    Association between variable agent-induced hepatocellular carcinoma (HCC) and both PAI-1 4G/5G polymorphism and plasminogen activator inhibitor (PAI-1) levels compared to healthy controls have been reported in earlier studies. We aimed to assess serum PAI-1 and PAI-1 4G/5G polymorphism in hepatitis C virus (HCV)-induced HCC, HCV-induced liver cirrhosis, and viral infection-free apparently healthy control subjects. Forty nine HCC, 52 cirrhosis, and 105 controls were genotyped for PAI-1 4G/5G using an allele-specific polymerase chain reaction analysis. In addition, for 31 HCC, 24 cirrhosis, and 28 controls, serum PAI-1 level was measured by enzyme-linked immunosorbent assay (ELISA). There was no significant difference in PAI-1 4G/5G genotype distribution between cirrhosis and controls (p = 0.33, p = 0.15, and p = 0.38 for the codominant, dominant, and recessive models, respectively) or between HCC and cirrhosis (p = 0.5, p = 0.24, and p = 0.69 for the codominant, dominant, and recessive models, respectively). Serum PAI-1 was significantly higher in cirrhosis than controls and significantly lower in HCC than cirrhosis (p < 0.001 for both). Serum PAI-1 did not differ significantly among the three PAI-1 4G/5G genotypes in controls, cirrhosis, and HCC (p = 0.29, p = 0.28, and p = 0.73 respectively). We documented higher serum PAI-1 in HCV-induced HCC than viral infection-free controls, but interestingly, lower than HCV-induced liver cirrhosis patients. This was not genotype related. Further studies will be needed to clearly elucidate the underlying mechanism.

  18. 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.

  19. 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

  20. 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.

  1. Fibre based cellular transfection.

    PubMed

    Tsampoula, X; Taguchi, K; Cizmár, T; Garces-Chavez, V; Ma, N; Mohanty, S; Mohanty, K; Gunn-Moore, F; Dholakia, K

    2008-10-13

    Optically assisted transfection is emerging as a powerful and versatile method for the delivery of foreign therapeutic agents to cells at will. In particular the use of ultrashort pulse lasers has proved an important route to transiently permeating the cell membrane through a multiphoton process. Though optical transfection has been gaining wider usage to date, all incarnations of this technique have employed free space light beams. In this paper we demonstrate the first system to use fibre delivery for the optical transfection of cells. We engineer a standard optical fibre to generate an axicon tip with an enhanced intensity of the remote output field that delivers ultrashort (~ 800 fs) pulses without requiring the fibre to be placed in very close proximity to the cell sample. A theoretical model is also developed in order to predict the light propagation from axicon tipped and bare fibres, in both air and water environments. The model proves to be in good agreement with the experimental findings and can be used to establish the optimum fibre parameters for successful cellular transfection. We readily obtain efficiencies of up to 57 % which are comparable with free space transfection. This advance paves the way for optical transfection of tissue samples and endoscopic embodiments of this technique.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. Investigation of Doppler Effects on high mobility OFDM-MIMO systems with the support of High Altitude Platforms (HAPs)

    NASA Astrophysics Data System (ADS)

    Mohammed, H. A.; Sibley, M. J. N.; Mather, P. J.

    2012-05-01

    The merging of Orthogonal Frequency Division Multiplexing (OFDM) with Multiple-input multiple-output (MIMO) is a promising mobile air interface solution for next generation wireless local area networks (WLANs) and 4G mobile cellular wireless systems. This paper details the design of a highly robust and efficient OFDM-MIMO system to support permanent accessibility and higher data rates to users moving at high speeds, such as users travelling on trains. It has high relevance for next generation wireless local area networks (WLANs) and 4G mobile cellular wireless systems. The paper begins with a comprehensive literature review focused on both technologies. This is followed by the modelling of the OFDM-MIMO physical layer based on Simulink/Matlab that takes into consideration high vehicular mobility. Then the entire system is simulated and analysed under different encoding and channel estimation algorithms. The use of High Altitude Platform system (HAPs) technology is considered and analysed.

  8. An Overview of Cellular Telecommunications

    DTIC Science & Technology

    1991-03-01

    Standard," Telephony, January 21, 1991. 142 33. Sklar , Bernard , Digital Communications, Prentice Hall, 1988. 34. Jordan, Edward C., Reference Data for...COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP Cellular radio; Digital radio...communications systems, and treats their history, theory and operation, applications, and limitations. Additionally, new experimental digital and micro

  9. Robust vaccine-elicited cellular immune responses in breast milk following systemic simian immunodeficiency virus DNA prime and live virus vector boost vaccination of lactating rhesus monkeys.

    PubMed

    Wilks, Andrew B; Christian, Elizabeth C; Seaman, Michael S; Sircar, Piya; Carville, Angela; Gomez, Carmen E; Esteban, Mariano; Pantaleo, Giuseppe; Barouch, Dan H; Letvin, Norman L; Permar, Sallie R

    2010-12-01

    Breast milk transmission of HIV remains an important mode of infant HIV acquisition. Enhancement of mucosal HIV-specific immune responses in milk of HIV-infected mothers through vaccination may reduce milk virus load or protect against virus transmission in the infant gastrointestinal tract. However, the ability of HIV/SIV strategies to induce virus-specific immune responses in milk has not been studied. In this study, five uninfected, hormone-induced lactating, Mamu A*01(+) female rhesus monkey were systemically primed and boosted with rDNA and the attenuated poxvirus vector, NYVAC, containing the SIVmac239 gag-pol and envelope genes. The monkeys were boosted a second time with a recombinant Adenovirus serotype 5 vector containing matching immunogens. The vaccine-elicited immunodominant epitope-specific CD8(+) T lymphocyte response in milk was of similar or greater magnitude than that in blood and the vaginal tract but higher than that in the colon. Furthermore, the vaccine-elicited SIV Gag-specific CD4(+) and CD8(+) T lymphocyte polyfunctional cytokine responses were more robust in milk than in blood after each virus vector boost. Finally, SIV envelope-specific IgG responses were detected in milk of all monkeys after vaccination, whereas an SIV envelope-specific IgA response was only detected in one vaccinated monkey. Importantly, only limited and transient increases in the proportion of activated or CCR5-expressing CD4(+) T lymphocytes in milk occurred after vaccination. Therefore, systemic DNA prime and virus vector boost of lactating rhesus monkeys elicits potent virus-specific cellular and humoral immune responses in milk and may warrant further investigation as a strategy to impede breast milk transmission of HIV.

  10. Passive Noise Filtering by Cellular Compartmentalization.

    PubMed

    Stoeger, Thomas; Battich, Nico; Pelkmans, Lucas

    2016-03-10

    Chemical reactions contain an inherent element of randomness, which presents itself as noise that interferes with cellular processes and communication. Here we discuss the ability of the spatial partitioning of molecular systems to filter and, thus, remove noise, while preserving regulated and predictable differences between single living cells. In contrast to active noise filtering by network motifs, cellular compartmentalization is highly effective and easily scales to numerous systems without requiring a substantial usage of cellular energy. We will use passive noise filtering by the eukaryotic cell nucleus as an example of how this increases predictability of transcriptional output, with possible implications for the evolution of complex multicellularity.

  11. Equol, an Isoflavone Metabolite, Regulates Cancer Cell Viability and Protein Synthesis Initiation via c-Myc and eIF4G*

    PubMed Central

    de la Parra, Columba; Borrero-Garcia, Luis D.; Cruz-Collazo, Ailed; Schneider, Robert J.; Dharmawardhane, Suranganie

    2015-01-01

    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

  12. 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

  13. 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.

  14. Mixed-calcination synthesis of CdWO4/g-C3N4 heterojunction with enhanced visible-light-driven photocatalytic activity

    NASA Astrophysics Data System (ADS)

    Tian, Na; Huang, Hongwei; Zhang, Yihe

    2015-12-01

    CdWO4/g-C3N4 composite photocatalysts have been successfully synthesized by a simple mixed-calcination method for the first time. X-ray diffraction (XRD), Fourier transforms infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM) and diffuse reflection spectroscopy (DRS) were carried out to analyze the crystal structure, morphology and optical property of the as-prepared samples. The photocatalytic experiments on rhodamine B (RhB) degradation showed that the 1:10 CdWO4/g-C3N4 photocatalyst exhibited the highest efficiency for degradation of RhB under visible light (λ > 420 nm), which was almost 1.6 and 54.6 times as high as those of the pure g-C3N4 and CdWO4, respectively. This enhancement in visible-light photocatalytic activity of CdWO4/g-C3N4 composite should be attributed to the matchable band structures and interfacial interaction between CdWO4 and g-C3N4, resulting in the efficient separation and transfer of photogenerated charge carriers. It was corroborated by the photoluminescence spectroscopy (PL) and active species trapping experiments.

  15. 4G/5G plasminogen activator inhibitor-1 and -308 A/G tumor necrosis factor-α promoter gene polymorphisms in Argentinean lupus patients: focus on lupus nephritis.

    PubMed

    Muñoz, Sebastián Andrés; Aranda, Federico; Allievi, Alberto; Orden, Alberto Omar; Perés Wingeyer, Silvia; Trobo, Rosana; Alvarez, Analía; Eimon, Alicia; Barreira, Juan Carlos; Schneeberger, Emilce; Dal Pra, Fernando; Sarano, Judith; Hofman, Julio; Chamorro, Julián; de Larrañaga, Gabriela

    2014-02-01

    We investigated the relationship between the 4G/5G plasminogen activator inhibitor (PAI-1) and -308 A/G tumor necrosis factor-α (TNF-α) polymorphisms and the clinical and biochemical features of systemic lupus erythematosus (SLE) in an Argentinean patient cohort. A total of 402 patients were studied, including 179 SLE patients and 223 healthy individuals. PCR-RLFP was used to determine the genotypes of the 4G/5G PAI-1 and -308 A/G TNF-α polymorphisms. SLE patients with lupus nephritis (LN) (n = 86) were compared with patients without LN (n = 93). Additionally, LN patients were divided into proliferative LN and non-proliferative LN groups according to the results of the renal biopsies. No significant differences were noted in the genotype distributions or allele frequencies of these TNF-α and PAI-1 polymorphisms between SLE patients and controls. There were higher numbers of criteria for SLE, more lupus flares and higher damage scores in LN patients, but there were similar frequencies of anti-phospholipid antibody (APA) positivity and anti-phospholipid syndrome. No significant difference was noted for any studied variable between the proliferative LN and non-proliferative LN groups except for the presence of APA. We found no significant differences in the TNF-α and PAI-1 genotype distributions or allele frequencies between groups. We found that the -308 A/G TNF-α and 4G/5G PAI-1 polymorphisms are not associated with susceptibility to SLE in an Argentinean population. We also did not find any association between the presence of any specific allele or genotype and the development of LN in SLE patients. Finally, no association was noted between either of the two polymorphisms and the severity of renal disease.

  16. 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.

  17. Rational construction of Z-scheme Ag2CrO4/g-C3N4 composites with enhanced visible-light photocatalytic activity

    NASA Astrophysics Data System (ADS)

    Luo, Jin; Zhou, Xiaosong; Ma, Lin; Xu, Xuyao

    2016-12-01

    Novel visible-light driven Z-scheme Ag2CrO4/g-C3N4 composites with different contents of Ag2CrO4 were fabricated by a facile chemical precipitation method and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectroscopy (UV-vis DRS), photoluminescence (PL) spectroscopy and photoelectrochemical measurements. Compared with individual g-C3N4 and Ag2CrO4, the Ag2CrO4/g-C3N4 composites displayed much larger photocatalytic activities for the photocatalytic degradation of methyl orange (MO) solution at room temperature under visible light irradiation (λ > 420 nm). Importantly, the optimum photodegradation rate constant of the Ag2CrO4/g-C3N4 composite at a theoretical weight content of 8.0% Ag2CrO4 for the photodegradation of MO was 0.0068 min-1, which was 5.7 and 4.3 times higher than that of pure g-C3N4 and Ag2CrO4, respectively. Such enormous enhancement in photocatalytic performance was predominantly ascribed to the efficient separation and transfer of photogenerated electrons and holes at the Ag2CrO4/g-C3N4 interface imparted through the Z-scheme electron transfer. Furthermore, radical trap experiments depicted that both the holes and superoxide radical anions were thought to dominate oxidative species of the Ag2CrO4/g-C3N4 composite for MO degradation under visible light irradiation. Ultimately, a tentative Z-scheme photodegradation mechanism was proposed. This work may be useful for the rational design of new types of Z-scheme photocatalysts and provide some illuminate insights into the Z-scheme transfer mechanism for application in energy conversion and environmental remediation.

  18. 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.

  19. 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

  20. 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.

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

    PubMed

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

    2014-01-01

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

  2. Effects of systemic immunogenic insults and circulating proinflammatory cytokines on the transcription of the inhibitory factor kappaB alpha within specific cellular populations of the rat brain.

    PubMed

    Laflamme, N; Rivest, S

    1999-07-01

    Expression of the inhibitory factor kappaB alpha (IkappaB alpha) reflects the activity of nuclear factor kappaB(NF-kappaB) and is a powerful tool to investigate the regulation of the transcription factor within the CNS. IkappaB alpha mRNA was evaluated in the rat brain by means of in situ hybridization following different immunogenic stimuli; i.e., intraperitoneal (i.p.) and intravenous (i.v.) lipopolysaccharide (LPS), i.v. recombinant rat interleukin (IL) 1beta, IL-6, or tumor necrosis factor-alpha (TNF-alpha), and intramuscular (i.m.) turpentine injection, used here as a model of systemic localized inflammatory insult. Systemic LPS, IL-1beta, and TNF-alpha caused a rapid and transient transcriptional activation of IkappaB alpha along the blood vessels of the entire brain; the signal was very intense 30-60 min after the i.v. injections and returned to undetectable levels from 2 to 12 h depending on the challenge. Double-labeling procedure provided the anatomical evidence that IkappaB alpha-expressing cells within the microvasculature were essentially of the endothelial type, as they were immunoreactive to the von Willebrand factor. Scattered small cells were also found across the brain of LPS-, IL-1beta-, and TNF-alpha-injected rats at time 1-3 h, and microglial (OX-42)-immunoreactive cells were positive for the transcript. Such expression within parenchymal microglia was nevertheless not observed in the brain following a localized and sterile inflammatory insult. Indeed, i.m. turpentine administration stimulated IkappaB alpha transcription quite uniquely within the endothelium of the brain capillaries, an effect that paralleled the swelling of the injection site and lasted up to 24 h after the aggression. In contrast to these immunogenic challenges, i.v. IL-6 injection failed to activate the gene encoding IkappaB alpha in the rat brain. These results indicate that NF-kappaB may play a crucial role in specific cellular populations of the CNS to trigger

  3. Fatigue of cellular materials

    SciTech Connect

    Huang, J.S.; Lin, J.Y.

    1996-01-01

    The fatigue of cellular materials is analyzed using dimensional arguments. When the first unbroken cell wall ahead of the macrocrack tip fails after some cycles of loading, the macrocrack advances one cell diameter, giving the macrocrack growth rate of cellular materials. Paris law for microcrack propagation, Basquin law for high cycle fatigue and Coffin-Manson law for low cycle fatigue are employed in calculating the number of cycles to failure of the first unbroken cell wall ahead of the macrocrack tip. It is found that fatigue of cellular materials depends on cyclic stress intensity range, cell size, relative density and the fatigue parameters of the solid from which they are made. Theoretical modelling of fatigue of foams is compared to data in polymer foams; agreement is good.

  4. Irregular Cellular Learning Automata.

    PubMed

    Esnaashari, Mehdi; Meybodi, Mohammad Reza

    2015-08-01

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

  5. 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

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

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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 service, fixed service, or a combination of mobile and fixed service, subject to the requirements,...

  7. Association between the SERPINE1 (PAI-1) 4G/5G insertion/deletion promoter polymorphism (rs1799889) and pre-eclampsia: a systematic review and meta-analysis.

    PubMed

    Zhao, Linlu; Bracken, Michael B; Dewan, Andrew T; Chen, Suzan

    2013-03-01

    The SERPINE1 -675 4G/5G promoter region insertion/deletion polymorphism (rs1799889) has been implicated in the pathogenesis of pre-eclampsia (PE), but the genetic association has been inconsistently replicated. To derive a more precise estimate of the association, a systematic review and meta-analysis was conducted. This study conformed to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed (MEDLINE), Scopus and HuGE Literature Finder literature databases were systematically searched for relevant studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the allelic comparison (4G versus 5G) and genotypic comparisons following the co-dominant (4G/4G versus 5G/5G and 4G/5G versus 5G/5G), dominant (4G/4G+4G/5G versus 5G/5G) and recessive (4G/4G versus 4G/5G+5G/5G) genetic models. Between-study heterogeneity was quantified by I(2) statistics and publication bias was appraised with funnel plots. Sensitivity analysis was conducted to evaluate the robustness of meta-analysis findings. Meta-analysis of 11 studies involving 1297 PE cases and 1791 controls found a significant association between the SERPINE1 -675 4G/5G polymorphism and PE for the recessive genetic model (OR = 1.36, 95% CI: 1.13-1.64, P = 0.001), a robust finding according to sensitivity analysis. A low level of between-study heterogeneity was detected (I(2) = 20%) in this comparison, which may be explained by ethnic differences. Funnel plot inspection did not reveal evidence of publication bias. In conclusion, this study provides a comprehensive examination of the available literature on the association between SERPINE1 -675 4G/5G and PE. Meta-analysis results support this polymorphism as a likely susceptibility variant for PE.

  8. 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.

  9. 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)

  10. Cellular genetic therapy.

    PubMed

    Del Vecchio, F; Filareto, A; Spitalieri, P; Sangiuolo, F; Novelli, G

    2005-01-01

    Cellular genetic therapy is the ultimate frontier for those pathologies that are consequent to a specific nonfunctional cellular type. A viable cure for there kinds of diseases is the replacement of sick cells with healthy ones, which can be obtained from the same patient or a different donor. In fact, structures can be corrected and strengthened with the introduction of undifferentiated cells within specific target tissues, where they will specialize into the desired cellular types. Furthermore, consequent to the recent results obtained with the transdifferentiation experiments, a process that allows the in vitro differentiation of embryonic and adult stem cells, it has also became clear that many advantages may be obtained from the use of stem cells to produce drugs, vaccines, and therapeutic molecules. Since stem cells can sustain lineage potentials, the capacity for differentiation, and better tolerance for the introduction of exogenous genes, they are also considered as feasible therapeutic vehicles for gene therapy. In fact, it is strongly believed that the combination of cellular genetic and gene therapy approaches will definitely allow the development of new therapeutic strategies as well as the production of totipotent cell lines to be used as experimental models for the cure of genetic disorders.

  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. 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

  13. 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

    2016-08-08

    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.

  14. 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.

  15. The -675 4G/5G polymorphism at the Plasminogen Activator Inhibitor 1 (PAI-1) gene modulates plasma Plasminogen Activator Inhibitor 1 concentrations in response to dietary fat consumption.

    PubMed

    Pérez-Martínez, P; Adarraga-Cansino, M D; Fernández de la Puebla, R A; Blanco-Molina, A; Delgado-Lista, J; Marín, C; Ordovás, J M; López-Miranda, J; Pérez-Jiménez, F

    2008-04-01

    The objective of the study was to determine whether Plasminogen Activator Inhibitor Type 1 (PAI-1) -675 4G/5G polymorphism is associated with the response of functional plasma PAI-1 concentrations to changes in the amount and quality of dietary fat in healthy subjects. PAI-1 is the major inhibitor of fibrinolysis, and a lower level of fibrinolytic activity could be implicated in an increased risk of IHD. Fifty-nine healthy Spanish volunteers (ten 4G/4G homozygotes, twenty-eight heterozygotes 4G/5G and twenty-one 5G/5G homozygotes) consumed three diets for periods of 4 weeks each: a SFA-rich diet (38 % fat, 20 % SFA), followed by a carbohydrate-rich diet (30 % fat, 55 % carbohydrate) and a MUFA-rich diet (38 % fat, 22 % MUFA) according to a randomized crossover design. At the end of each dietary period plasma lipid and functional plasma PAI-1 concentrations were determined. Subjects carrying the 4G allele (4G/4G and 4G/5G) showed a significant decrease in PAI-1 concentrations after the MUFA diet, compared with the SFA-rich and carbohydrate-rich diets (genotype x diet interaction: P = 0.028). 5G/5G homozygotes had the lowest plasma PAI-1 concentrations compared with 4G/4G and 4G/5G subjects (genotype: P = 0.002), without any changes as a result of the amount and the quality of the dietary fat. In summary, no differences in plasma PAI-1 concentration response were found after changes in dietary fat intake in 5G/5G homozygotes, although these subjects displayed the lowest concentrations of PAI-1. On the other hand, carriers of the 4G allele are more likely to hyper-respond to the presence of MUFA in the diet because of a greater decrease in PAI-1 concentrations.

  16. The plasminogen activator inhibitor-1 (PAI-1) gene -844 A/G and -675 4G/5G promoter polymorphism significantly influences plasma PAI-1 levels in women with polycystic ovary syndrome.

    PubMed

    Lin, Sun; Huiya, Zhang; Bo, Liu; Wei, Wei; Yongmei, Guan

    2009-12-01

    Mutations in the plasminogen activator inhibitor-1 (PAI-1) gene, along with increased PAI-1 levels, have been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). We investigated a possible influence of the promoter polymorphism (-844 A/G and -675 4G/5G) in the PAI-1 gene on plasma PAI-1 levels in 126 PCOS patients and 97 healthy controls. Levels of total testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), fasting plasma glucose (FPG), fasting insulin, and PAI-1 were measured, and body mass index (BMI), waist-to-hip ratio (WHR), LH/FSH ratio, and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. PAI-1 -675 4G/5G and -844 A/G gene polymorphisms were also performed. Total testosterone, fasting insulin, and PAI-1 levels; BMI, LH/FSH, and HOMA-IR were significantly higher in PCOS patients than controls (P < 0.05). The odds ratio of 4G/4G genotype, 4G allele, and the combination genotype of 4G/4G and -844 A/A were 2.49 (95% confidence interval (CI), 1.4-4.44), 2.1 (95% CI, 1.43-3.08), and 2.9 (95% CI, 1.41-5.98), respectively, (P < 0.001). In the PCOS group, the PAI-1 level of the A/A was significantly higher than that of the A/G or G/G genotype, similarly was 4G/4G genotype compared with 4G/5G or 5G/5G genotype. The plasma PAI-1 levels of the combination of the PAI-1 -844 A/A and -675 4G/4G or 4G/5G genotypes, or the coadunation of 4G/4G and -844 non-G/G (A/A + A/G) genotypes were significantly high in PCOS women compared with controls. A trend to a positive interaction between PAI-1 -675 4G/5G and -844 A/G gene polymorphism may elevate plasma PAI-1 levels and hypofibrinolysis, which is probably an important hereditary risk factor in PCOS.

  17. Predictability in cellular automata.

    PubMed

    Agapie, Alexandru; Andreica, Anca; Chira, Camelia; Giuclea, Marius

    2014-01-01

    Modelled as finite homogeneous Markov chains, probabilistic cellular automata with local transition probabilities in (0, 1) always posses a stationary distribution. This result alone is not very helpful when it comes to predicting the final configuration; one needs also a formula connecting the probabilities in the stationary distribution to some intrinsic feature of the lattice configuration. Previous results on the asynchronous cellular automata have showed that such feature really exists. It is the number of zero-one borders within the automaton's binary configuration. An exponential formula in the number of zero-one borders has been proved for the 1-D, 2-D and 3-D asynchronous automata with neighborhood three, five and seven, respectively. We perform computer experiments on a synchronous cellular automaton to check whether the empirical distribution obeys also that theoretical formula. The numerical results indicate a perfect fit for neighbourhood three and five, which opens the way for a rigorous proof of the formula in this new, synchronous case.

  18. 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.

  19. Measurement Techniques for Cellular Biomechanics In Vitro

    PubMed Central

    Addae-Mensah, Kweku A; Wikswo, John P

    2014-01-01

    Living cells and tissues experience mechanical forces in their physiological environments that are known to affect many cellular processes. Also of importance are the mechanical properties of cells, as well as the microforces generated by cellular processes themselves in their microenvironments. The difficulty associated with studying these phenomena in vivo has led to alternatives such as using in vitro models. The need for experimental techniques for investigating cellular biomechanics and mechanobiology in vitro has fueled an evolution in the technology used in these studies. Particularly noteworthy are some of the new biomicroelectromechanical systems (BioMEMs) devices and techniques that have been introduced to the field. We describe some of the cellular micromechanical techniques and methods that have been developed for in vitro studies, and provide summaries of the ranges of measured values of various biomechanical quantities. We also briefly address some of our experiences in using these methods and include modifications we have introduced in order to improve them. PMID:18445766

  20. Evaluation of the Tobacco Heating System 2.2. Part 7: Systems toxicological assessment of a mentholated version revealed reduced cellular and molecular exposure effects compared with mentholated and non-mentholated cigarette smoke.

    PubMed

    Kogel, Ulrike; Titz, Bjoern; Schlage, Walter K; Nury, Catherine; Martin, Florian; Oviedo, Alberto; Lebrun, Stefan; Elamin, Ashraf; Guedj, Emmanuel; Trivedi, Keyur; Ivanov, Nikolai V; Vanscheeuwijck, Patrick; Peitsch, Manuel C; Hoeng, Julia

    2016-11-30

    Modified risk tobacco products (MRTPs) are being developed with the aim of reducing smoking-related health risks. The Tobacco Heating System 2.2 (THS2.2) is a candidate MRTP that uses the heat-not-burn principle. Here, systems toxicology approaches were engaged to assess the respiratory effects of mentholated THS2.2 (THS2.2M) in a 90-day rat inhalation study (OECD test guideline 413). The standard endpoints were complemented by transcriptomics and quantitative proteomics analyses of respiratory nasal epithelium and lung tissue and by lipidomics analysis of lung tissue. The adaptive response of the respiratory nasal epithelium to conventional cigarette smoke (CS) included squamous cell metaplasia and an inflammatory response, with high correspondence between the molecular and histopathological results. In contrast to CS exposure, the adaptive tissue and molecular changes to THS2.2M aerosol exposure were much weaker and were limited mostly to the highest THS2.2M concentration in female rats. In the lung, CS exposure induced an inflammatory response, triggered cellular stress responses, and affected sphingolipid metabolism. These responses were not observed or were much lower after THS2.2M aerosol exposure. Overall, this system toxicology analysis complements and reconfirms the results from classical toxicological endpoints and further suggests potentially reduced health risks of THS2.2M.

  1. Cellular senescence and protein degradation

    PubMed Central

    Deschênes-Simard, Xavier; Lessard, Frédéric; Gaumont-Leclerc, Marie-France; Bardeesy, Nabeel; Ferbeyre, Gerardo

    2014-01-01

    Autophagy and the ubiquitin–proteasome pathway (UPP) are the major protein degradation systems in eukaryotic cells. Whereas the former mediate a bulk nonspecific degradation, the UPP allows a rapid degradation of specific proteins. Both systems have been shown to play a role in tumorigenesis, and the interest in developing therapeutic agents inhibiting protein degradation is steadily growing. However, emerging data point to a critical role for autophagy in cellular senescence, an established tumor suppressor mechanism. Recently, a selective protein degradation process mediated by the UPP was also shown to contribute to the senescence phenotype. This process is tightly regulated by E3 ubiquitin ligases, deubiquitinases, and several post-translational modifications of target proteins. Illustrating the complexity of UPP, more than 600 human genes have been shown to encode E3 ubiquitin ligases, a number which exceeds that of the protein kinases. Nevertheless, our knowledge of proteasome-dependent protein degradation as a regulated process in cellular contexts such as cancer and senescence remains very limited. Here we discuss the implications of protein degradation in senescence and attempt to relate this function to the protein degradation pattern observed in cancer cells. PMID:24866342

  2. The FGFR4-G388R single-nucleotide polymorphism alters pancreatic neuroendocrine tumor progression and response to mTOR inhibition therapy.

    PubMed

    Serra, Stefano; Zheng, Lei; Hassan, Manal; Phan, Alexandria T; Woodhouse, Linda J; Yao, James C; Ezzat, Shereen; Asa, Sylvia L

    2012-11-15

    Pancreatic neuroendocrine tumors (pNET), also known as islet cell tumors, exhibit a wide range of biologic behaviors ranging from long dormancy to rapid progression. Currently, there are few molecular biomarkers that can be used to predict recurrence/metastasis or response to therapy. This study examined the predictive and prognostic value of a single nucleotide polymorphism substituting an arginine (R) for glycine (G) in codon 388 of the FGFR4 transmembrane domain. We established the FGFR4 genotype of 71 patients with pNETs and correlated genotype with biologic behavior. We created an in vivo model of pNET with BON1 cells and transfected them with either FGFR4-G388 or FGFR4-R388 to determine the mechanism of action and to examine response to the mTOR inhibitor everolimus. We then validated the predictive results of experimental studies in a group of patients treated with everolimus. FGFR4-R388 is associated with more aggressive clinical behavior in patients with pNETs with a statistically significant higher risk of advanced tumor stage and liver metastasis. Using an orthotopic mouse xenograft model, we show that FGFR4-R388 promotes tumor progression by increasing intraperitoneal spread and metastatic growth within the liver. Unlike FGFR4-G388, FGFR4-R388 BON1 tumors exhibited diminished responsiveness to everolimus. Concordantly, there was a statistically significant reduction in response to everolimus in patients with FGFR4-R388. Our findings highlight the importance of the FGFR4 allele in pNET progression and identify a predictive marker of potential therapeutic importance in this disease.

  3. The association of ICAM-1 Exon 6 (E469K) but not of ICAM-1 Exon 4 (G241R) and PECAM-1 Exon 3 (L125V) polymorphisms with the development of differentiation syndrome in acute promyelocytic leukemia.

    PubMed

    Dore, Adriana I; Santana-Lemos, Barbara A A; Coser, Virginia M; Santos, Flávia L S; Dalmazzo, Leandro F; Lima, Ana S G; Jacomo, Rafael H; Elias, Jorge; Falcão, Roberto Passetto; Pereira, Waldir V; Rego, Eduardo M

    2007-11-01

    The use of all trans-retinoic acid (ATRA) is the basis of treatment of acute promyelocytic leukemia (APL) and represents the paradigm of differentiation therapy. In general, ATRA is well-tolerated but may be associated with a potentially lethal side-effect, referred to as retinoic acid or differentiation syndrome (DS). The cellular and molecular mechanisms of DS are poorly understood and involve changes in the adhesive qualities and cytokine secretion of leukemic cells during ATRA-induced differentiation. As leukocyte extravasation is a key event in DS pathogenesis, we analyzed the association between the polymorphisms at Exon 4 (G241R) and Exon 6 (E469K) of ICAM-1 and Exon 3 (L125V) of PECAM-1 genes with DS development in APL patients treated with ATRA and anthracyclines. DS was diagnosed in 23/127 (18.1%) APL patients at an average of 11.5 days after the start of ATRA. All patients presented respiratory distress associated with increased ground-glass opacity in chest radiographies. Other accompanying symptoms were: fever not attributable to infection (65.2%), generalized edema (37.5%), weight gain (37.5%), and impairment of renal function (8.6%). We detected an association between development of DS and the AA genotype at Codon 469 of ICAM-1 (odds ratio of 3.5; 95% confidence interval: 1.2-10.2). Conversely, no significant association was detected between G241R or L125V polymorphisms at Exon 4 of ICAM-1 and Exon 3 of PECAM-1, respectively. Our results suggest that susceptibility to DS in APL patients may be influenced by genetic variation in adhesion molecule loci.

  4. 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.

  5. 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

  6. Oral Cellular Neurothekeoma

    PubMed Central

    Emami, Nader; Zawawi, Faisal; Ywakim, Rania; Daniel, Sam J.

    2013-01-01

    Cellular neurothekeoma is known as a cutaneous tumor with uncertain histogenesis. Very little involvement of mucosal membrane has been reported in the literature so far. This is a case report of an intraoral lesion in a 15-years-old girl. Histopathologic evaluation showed a tumor-consists of spindle to epitheloid cells forming micronodules in a concentric whorled shape pattern. Tumor cells were positive for CD63, vimentin, and NKI-C3. Total excision was performed and no recurrence happened after 16-month followup. PMID:23691398

  7. An emerging role for voltage-gated Na+ channels in cellular migration: regulation of central nervous system development and potentiation of invasive cancers.

    PubMed

    Brackenbury, William J; Djamgoz, Mustafa B A; Isom, Lori L

    2008-12-01

    Voltage-gated Na(+) channels (VGSCs) exist as macromolecular complexes containing a pore-forming alpha subunit and one or more beta subunits. The VGSC alpha subunit gene family consists of 10 members, which have distinct tissue-specific and developmental expression profiles. So far, four beta subunits (beta1-beta4) and one splice variant of beta1 (beta1A, also called beta1B) have been identified. VGSC beta subunits are multifunctional, serving as modulators of channel activity, regulators of channel cell surface expression, and as members of the immunoglobulin superfamily, cell adhesion molecules (CAMs). beta subunits are substrates of beta-amyloid precursor protein-cleaving enzyme (BACE1) and gamma-secretase, yielding intracellular domains (ICDs) that may further modulate cellular activity via transcription. Recent evidence shows that beta1 regulates migration and pathfinding in the developing postnatal CNS in vivo. The alpha and beta subunits, together with other components of the VGSC signaling complex, may have dynamic interactive roles depending on cell/tissue type, developmental stage, and pathophysiology. In addition to excitable cells like nerve and muscle, VGSC alpha and beta subunits are functionally expressed in cells that are traditionally considered nonexcitable, including glia, vascular endothelial cells, and cancer cells. In particular, the alpha subunits are up-regulated in line with metastatic potential and are proposed to enhance cellular migration and invasion. In contrast to the alpha subunits, beta1 is more highly expressed in weakly metastatic cancer cells, and evidence suggests that its expression enhances cellular adhesion. Thus, novel roles are emerging for VGSC alpha and beta subunits in regulating migration during normal postnatal development of the CNS as well as during cancer metastasis.

  8. 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.

  9. [Changes of focal and brainstem neurologic signs in patients with traumatic brain injury and their dependence on the -675 4G/5G polymorphism in the PAI-1 gene].

    PubMed

    Potapov, O; Kmyta, O

    2014-09-01

    Regressive course of neurological signs and symptoms is an important factor of evaluating the clinical course and treatment efficacy of traumatic brain injury. This article presents changes evaluation of focal and brainstem symptoms in 200 patients with traumatic brain injury, and determines the association between these changes and the -675 4G/5G polymorphism in the PAI-1 gene. We have found a connection between 4G/4G and 4G/5G genotypes for the studied polymorphism and the changes of focal and brainstem symptoms in patients with traumatic brain injury. Thus, we have demonstrated that the clinical course of traumatic brain injury is influenced by the -675 4G/5G polymorphism in the PAI-1 gene.

  10. Revisiting Cardiac Cellular Composition

    PubMed Central

    Pinto, Alexander R.; Ilinykh, Alexei; Ivey, Malina J.; Kuwabara, Jill T.; D'Antoni, Michelle L.; Debuque, Ryan; Chandran, Anjana; Wang, Lina; Arora, Komal; Rosenthal, Nadia; Tallquist, Michelle D.

    2015-01-01

    Rationale Accurate knowledge of the cellular composition of the heart is essential to fully understand the changes that occur during pathogenesis and to devise strategies for tissue engineering and regeneration. Objective To examine the relative frequency of cardiac endothelial cells, hematopoietic-derived cells and fibroblasts in the mouse and human heart. Methods and Results Using a combination of genetic tools and cellular markers, we examined the occurrence of the most prominent cell types in the adult mouse heart. Immunohistochemistry revealed that endothelial cells constitute over 60%, hematopoietic-derived cells 5–10%, and fibroblasts under 20% of the non-myocytes in the heart. A refined cell isolation protocol and an improved flow cytometry approach provided an independent means of determining the relative abundance of non-myocytes. High dimensional analysis and unsupervised clustering of cell populations confirmed that endothelial cells are the most abundant cell population. Interestingly, fibroblast numbers are smaller than previously estimated, and two commonly assigned fibroblast markers, Sca-1 and CD90, underrepresent fibroblast numbers. We also describe an alternative fibroblast surface marker that more accurately identifies the resident cardiac fibroblast population. Conclusions This new perspective on the abundance of different cell types in the heart demonstrates that fibroblasts comprise a relatively minor population. By contrast, endothelial cells constitute the majority of non-cardiomyocytes and are likely to play a greater role in physiologic function and response to injury than previously appreciated. PMID:26635390

  11. Multifunctional periodic cellular metals.

    PubMed

    Wadley, Haydn N G

    2006-01-15

    Periodic cellular metals with honeycomb and corrugated topologies are widely used for the cores of light weight sandwich panel structures. Honeycombs have closed cell pores and are well suited for thermal protection while also providing efficient load support. Corrugated core structures provide less efficient and highly anisotropic load support, but enable cross flow heat exchange opportunities because their pores are continuous in one direction. Recent advances in topology design and fabrication have led to the emergence of lattice truss structures with open cell structures. These three classes of periodic cellular metals can now be fabricated from a wide variety of structural alloys. Many topologies are found to provide adequate stiffness and strength for structural load support when configured as the cores of sandwich panels. Sandwich panels with core relative densities of 2-10% and cell sizes in the millimetre range are being assessed for use as multifunctional structures. The open, three-dimensional interconnected pore networks of lattice truss topologies provide opportunities for simultaneously supporting high stresses while also enabling cross flow heat exchange. These highly compressible structures also provide opportunities for the mitigation of high intensity dynamic loads created by impacts and shock waves in air or water. By filling the voids with polymers and hard ceramics, these structures have also been found to offer significant resistance to penetration by projectiles.

  12. A real-time digital bio-imaging system to quantify cellular cytotoxicity as an alternative to the standard chromium-51 release assay.

    PubMed

    Fassy, Julien; Tsalkitzi, Kyriaki; Salavagione, Emie; Hamouda-Tekaya, Nedra; Braud, Véronique M

    2016-12-22

    Reliable measurement of cellular cytotoxicity is essential for the characterization of immune responses and for the monitoring of antibody treatment efficacy. Until now, the standard (51) Cr-release assay has remained the sole sensitive assay that measures cellular cytotoxicity. Alternative non-radioactive assays have been developed but they do not provide accurate measurement of target cell cytotoxicity. The cost and hazard of handling radioactivity are strong incentives to find alternative solutions to (51) Cr. We took advantage of the recent development of cell-imaging multimode readers to develop a novel non-radioactive and real-time cytotoxic assay that demonstrates good reproducibility and sensitivity. The extent of target-cell cytotoxicity is monitored over time by imaging and quantifying live fluorescent target cells in 96-well plates. We have developed classical natural killer cell assays in the presence or absence of blocking antibodies and antibody-dependent cell-mediated cytotoxicity. We show that in these assays, cell killing occurs within the first 2 hr with half maximum killing reached after 30 min. This technology has numerous applications such as natural killer and T-cell cytotoxicity assays and can be extended to cell survival and apoptosis measurement assays.

  13. Supporting performance and configuration management of GTE cellular networks

    SciTech Connect

    Tan, Ming; Lafond, C.; Jakobson, G.; Young, G.

    1996-12-31

    GTE Laboratories, in cooperation with GTE Mobilnet, has developed and deployed PERFFEX (PERFormance Expert), an intelligent system for performance and configuration management of cellular networks. PERFEX assists cellular network performance and radio engineers in the analysis of large volumes of cellular network performance and configuration data. It helps them locate and determine the probable causes of performance problems, and provides intelligent suggestions about how to correct them. The system combines an expert cellular network performance tuning capability with a map-based graphical user interface, data visualization programs, and a set of special cellular engineering tools. PERFEX is in daily use at more than 25 GTE Mobile Switching Centers. Since the first deployment of the system in late 1993, PERFEX has become a major GTE cellular network performance optimization tool.

  14. 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.

  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. 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

  17. [Senescence and cellular immortality].

    PubMed

    Trentesaux, C; Riou, J-F

    2010-11-01

    Senescence was originally described from the observation of the limited ability of normal cells to grow in culture, and may be generated by telomere erosion, accumulation of DNA damages, oxidative stress and modulation of oncogenes or tumor suppressor genes. Senescence corresponds to a cellular response aiming to control tumor progression by limiting cell proliferation and thus constitutes an anticancer barrier. Senescence is observed in pre-malignant tumor stages and disappears from malignant tumors. Agents used in standard chemotherapy also have the potential to induce senescence, which may partly explain their therapeutic activities. It is possible to restore senescence in tumors using targeted therapies that triggers telomere dysfunction or reactivates suppressor genes functions, which are essential for the onset of senescence.

  18. Cellular ageing mechanisms in osteoarthritis.

    PubMed

    Sacitharan, P K; Vincent, T L

    2016-08-01

    Age is the strongest independent risk factor for the development of osteoarthritis (OA) and for many years this was assumed to be due to repetitive microtrauma of the joint surface over time, the so-called 'wear and tear' arthritis. As our understanding of OA pathogenesis has become more refined, it has changed our appreciation of the role of ageing on disease. Cartilage breakdown in disease is not a passive process but one involving induction and activation of specific matrix-degrading enzymes; chondrocytes are exquisitely sensitive to changes in the mechanical, inflammatory and metabolic environment of the joint; cartilage is continuously adapting to these changes by altering its matrix. Ageing influences all of these processes. In this review, we will discuss how ageing affects tissue structure, joint use and the cellular metabolism. We describe what is known about pathways implicated in ageing in other model systems and discuss the potential value of targeting these pathways in OA.

  19. Cellular immune mechanisms in myocarditis.

    PubMed

    Noutsias, M; Patil, V J; Maisch, B

    2012-12-01

    The introduction of immunohistological techniques enabled a substantially more reliable diagnosis of inflammatory cardiomyopathy (DCMi) in endomyocardial biopsies (EMB) compared to the histological Dallas criteria. Decisive progress has been made in the understanding of cellular immune mechanisms in DCMi using immunohistological techniques, which apart from the field of diagnosis refinement have had prognostic implications and an influence on the selection criteria of DCMi patients who will likely benefit from immunosuppressive treatment. Digital image analysis systems have been employed to standardize quantification of immunohistological EMB stainings. Quantification of T cell-related genes by a methodologically validated preamplified real-time RT-PCR revealed that the T cells are characterized by differential expression of Th1-, Treg-, and CTL-related markers, while no major role could be confirmed for Th17 cells. The reported virus-associated differential T cell receptor Vbeta dominance suggests an antiviral specificity of virus-induced T cell responses in human DCMi.

  20. 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.

  1. Loss of cone cyclic nucleotide-gated channel leads to alterations in light response modulating system and cellular stress response pathways: a gene expression profiling study

    PubMed Central

    Ma, Hongwei; Thapa, Arjun; Morris, Lynsie M.; Michalakis, Stylianos; Biel, Martin; Frank, Mark Barton; Bebak, Melissa; Ding, Xi-Qin

    2013-01-01

    The cone photoreceptor cyclic nucleotide-gated (CNG) channel is essential for central and color vision and visual acuity. Mutations in the channel subunits CNGA3 and CNGB3 are associated with achromatopsia and cone dystrophy. We investigated the gene expression profiles in mouse retina with CNG channel deficiency using whole genome expression microarrays. As cones comprise only 2 to 3% of the total photoreceptor population in the wild-type mouse retina, the mouse lines with CNG channel deficiency on a cone-dominant background, i.e. Cnga3−/−/Nrl−/− and Cngb3−/−/Nrl−/− mice, were used in our study. Comparative data analysis revealed a total of 105 genes altered in Cnga3−/−/Nrl−/− and 92 in Cngb3−/−/Nrl−/− retinas, relative to Nrl−/− retinas, with 27 genes changed in both genotypes. The differentially expressed genes primarily encode proteins associated with cell signaling, cellular function maintenance and gene expression. Ingenuity pathway analysis (IPA) identified 26 and 9 canonical pathways in Cnga3−/−/Nrl−/− and Cngb3−/−/Nrl−/− retinas, respectively, with 6 pathways being shared. The shared pathways include phototransduction, cAMP/PKA-mediated signaling, endothelin signaling, and EIF2/endoplasmic reticulum (ER) stress, whereas the IL-1, CREB, and purine metabolism signaling were found to specifically associate with Cnga3 deficiency. Thus, CNG channel deficiency differentially regulates genes that affect cell processes such as phototransduction, cellular survival and gene expression, and such regulations play a crucial role(s) in the retinal adaptation to impaired cone phototransduction. Though lack of Cnga3 and Cngb3 shares many common pathways, deficiency of Cnga3 causes more significant alterations in gene expression. This work provides insights into how cones respond to impaired phototransduction at the gene expression levels. PMID:23740940

  2. Increased efficacy of VX-809 in different cellular systems results from an early stabilization effect of F508del-CFTR.

    PubMed

    Farinha, Carlos M; Sousa, Marisa; Canato, Sara; Schmidt, André; Uliyakina, Inna; Amaral, Margarida D

    2015-08-01

    Cystic fibrosis (CF), the most common recessive autosomal disease among Caucasians, is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. The most common mutation, F508del, leads to CFTR impaired plasma membrane trafficking. Therapies modulating CFTR basic defect are emerging, such as VX-809, a corrector of F508del-CFTR traffic which just succeeded in a Phase III clinical trial. We recently showed that VX-809 is additive to two other correctors (VRT-325 and compound 4a). Here, we aimed to determine whether the differential rescuing by these compounds results from cell-specific factors or rather from distinct effects at the early biogenesis and/or processing. The rescuing efficiencies of the above three correctors were first compared in different cellular models (primary respiratory cells, cystic fibrosis bronchial epithelial and baby hamster kidney [BHK] cell lines) by functional approaches: micro-Ussing chamber and iodide efflux. Next, biochemical methods (metabolic labeling, pulse-chase and immunoprecipitation) were used to determine their impact on CFTR biogenesis / processing. Functional analyses revealed that VX-809 has the greatest rescuing efficacy and that the relative efficiencies of the three compounds are essentially maintained in all three cellular models tested. Nevertheless, biochemical data show that VX-809 significantly stabilizes F508del-CFTR immature form, an effect that is not observed for C3 nor C4. VX-809 and C3 also significantly increase accumulation of immature CFTR. Our data suggest that VX-809 increases the stability of F508del-CFTR immature form at an early phase of its biogenesis, thus explaining its increased efficacy when inducing its rescue.

  3. 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.

  4. Very high penetrance and occurrence of Leber’s hereditary optic neuropathy in a large Han Chinese pedigree carrying the ND4 G11778A mutation

    PubMed Central

    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

    2010-01-01

    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, twenty-five (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 24 years 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. PMID:20627642

  5. The Spitzer Survey of Stellar Structure in Galaxies (S4G): Stellar Masses, Sizes, and Radial Profiles for 2352 Nearby Galaxies

    NASA Astrophysics Data System (ADS)

    Muñoz-Mateos, Juan Carlos; Sheth, Kartik; Regan, Michael; Kim, Taehyun; Laine, Jarkko; Erroz-Ferrer, Santiago; Gil de Paz, Armando; Comeron, Sebastien; Hinz, Joannah; Laurikainen, Eija; Salo, Heikki; Athanassoula, E.; Bosma, Albert; Bouquin, Alexandre Y. K.; Schinnerer, Eva; Ho, Luis; Zaritsky, Dennis; Gadotti, Dimitri A.; Madore, Barry; Holwerda, Benne; Menéndez-Delmestre, Karín; Knapen, Johan H.; Meidt, Sharon; Querejeta, Miguel; Mizusawa, Trisha; Seibert, Mark; Laine, Seppo; Courtois, Helene

    2015-07-01

    The Spitzer Survey of Stellar Structure in Galaxies is a volume, magnitude, and size-limited survey of 2352 nearby galaxies with deep imaging at 3.6 and 4.5 μm. In this paper, we describe our surface photometry pipeline and showcase the associated data products that we have released to the community. We also identify the physical mechanisms leading to different levels of central stellar mass concentration for galaxies with the same total stellar mass. Finally, we derive the local stellar mass-size relation at 3.6 μm for galaxies of different morphologies. Our radial profiles reach stellar mass surface densities below ˜ 1 {M}⊙ {{pc}}-2. Given the negligible impact of dust and the almost constant mass-to-light ratio at these wavelengths, these profiles constitute an accurate inventory of the radial distribution of stellar mass in nearby galaxies. From these profiles we have also derived global properties such as asymptotic magnitudes (and the corresponding stellar masses), isophotal sizes and shapes, and concentration indices. These and other data products from our various pipelines (science-ready mosaics, object masks, 2D image decompositions, and stellar mass maps) can be publicly accessed at IRSA (http://irsa.ipac.caltech.edu/data/SPITZER/S4G/).

  6. NMR structure refinement and dynamics of the K+-[d(G3T4G3)]2 quadruplex via particle mesh Ewald molecular dynamics simulations.

    PubMed Central

    Strahan, G D; Keniry, M A; Shafer, R H

    1998-01-01

    The solution structure and dynamical properties of the potassium-stabilized, hairpin dimer quadruplex formed by the oligonucleotide d(G3T4G3) have been elucidated by a combination of high-resolution NMR and molecular dynamics simulations. Refinement calculations were carried out both in vacuo, without internally coordinated K+ cations, and in explicit water, with internally coordinated K+ cations. In the latter case, the electrostatic interactions were calculated using the particle mesh Ewald (PME) method. The NMR restraints indicate that the K+ quadruplex has a folding arrangement similar to that formed by the same oligonucleotide in the presence of sodium, but with significant local differences. Unlike the Na+ quadruplex, the thymine loops found in K+ exhibit considerable flexibility, and appear to interconvert between two preferred conformations. Furthermore, the NMR evidence points toward K+-stabilized guanine quartets of slightly larger diameter relative to the Na+-stabilized structure. The characteristics of the quartet stem are greatly affected by the modeling technique employed: caged cations alter the size and symmetry of the quartets, and explicit water molecules form hydration spines within the grooves. These results provide insight into those factors that determine the overall stability of hairpin dimer quadruplexes and the effects of different cations in modulating the relative stability of the dimeric hairpin and linear, four-stranded, quadruplex forms. PMID:9675197

  7. After fertilization of sea urchin eggs, eIF4G is post-translationally modified and associated with the cap-binding protein eIF4E.

    PubMed

    Oulhen, Nathalie; Salaün, Patrick; Cosson, Bertrand; Cormier, Patrick; Morales, Julia

    2007-02-01

    Release of eukaryotic initiation factor 4E (eIF4E) from its translational repressor eIF4E-binding protein (4E-BP) is a crucial event for the first mitotic division following fertilization of sea urchin eggs. Finding partners of eIF4E following fertilization is crucial to understand how eIF4E functions during this physiological process. The isolation and characterization of cDNA encoding Sphaerechinus granularis eIF4G (SgIF4G) are reported. mRNA of SgIF4G is present as a single 8.5-kb transcript in unfertilized eggs, suggesting that only one ortholog exists in echinoderms. The longest open reading frame predicts a sequence of 5235 nucleotides encoding a deduced polypeptide of 1745 amino acids with a predicted molecular mass of 192 kDa. Among highly conserved domains, SgIF4G protein possesses motifs that correspond to the poly(A) binding protein and eIF4E protein-binding sites. A specific polyclonal antibody was produced and used to characterize the SgIF4G protein in unfertilized and fertilized eggs by SDS-PAGE and western blotting. Multiple differentially migrating bands representing isoforms of sea urchin eIF4G are present in unfertilized eggs. Fertilization triggers modifications of the SgIF4G isoforms and rapid formation of the SgIF4G-eIF4E complex. Whereas rapamycin inhibits the formation of the SgIF4G-eIF4E complex, modification of these SgIF4G isoforms occurs independently from the rapamycin-sensitive pathway. Microinjection of a peptide corresponding to the eIF4E-binding site derived from the sequence of SgIF4G into unfertilized eggs affects the first mitotic division of sea urchin embryos. Association of SgIF4G with eIF4E is a crucial event for the onset of the first mitotic division following fertilization, suggesting that cap-dependent translation is highly regulated during this process. This hypothesis is strengthened by the evidence that microinjection of the cap analog m(7)GDP into unfertilized eggs inhibits the first mitotic division.

  8. Cellular Mechanisms of Central Nervous Modulation.

    DTIC Science & Technology

    1983-06-30

    achieve selective disruption of the neuroglia in the central nervous system 4 of our experimental animal, the cockroach (Periplaneta americana). Such...RD-A147 878 CELLULAR MECHANISMIS OF CENTRAL NERVOUS MODULATION(U) i/i I CAMBRIDGE UNIV (ENGLAND) DEPT OF ZOOLOGY J E TRENERNE 30 JUN 83 DHJA37-8i-C...BOOBI UNCLASSFE F/G 6/16 NL bi L& 2. MICROCOPY RESOLUTION TEST CHART NATIONA BUJREAUJ OF STANDOW-S1963-A [.1 PI CELLULAR MECHANISMIS OF CENTRAL NERVOUS

  9. 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.

  10. Cellular Models for the Study of Prions.

    PubMed

    Holmes, Brandon B; Diamond, Marc I

    2017-02-01

    It is now established that numerous amyloid proteins associated with neurodegenerative diseases, including tau and α-synuclein, have essential characteristics of prions, including the ability to create transmissible cellular pathology in vivo. We have developed cellular bioassays that report on the various features of prion activity using genetic engineering and quantitative fluorescence-based detection systems. We have exploited these biosensors to measure the binding and uptake of tau seeds into cells in culture and to quantify seeding activity in brain samples. These cell models have also been used to propagate tau prion strains indefinitely in culture. In this review, we illustrate the utility of cellular biosensors to gain mechanistic insight into prion transmission and to study neurodegenerative diseases in a reductionist fashion.

  11. Cellular immunity to Bacteroides fragilis capsular polysaccharide

    PubMed Central

    1982-01-01

    The polysaccharide capsule of Bacteroides fragilis has been shown to be important in the virulence of the organism. The capsular polysaccharide (CP) of B. fragilis has been extensively purified. Using a murine model of intraabdominal abscess formation, we have been able to demonstrate cellular immunity to the capsular polysaccharide of B. fragilis. Immunization of C57BL/10J mice with the CP over 5 wk prevents abscess formation when the mice are challenged with B. fragilis intraperitoneally. This immunity can be transferred to naive mice with spleen cells from immune animals. The immune cells bear Thy-1.2 and Ly- 2.2 antigens. The immune response has been shown to be antigen specific, but not H-2 restricted. The possibility that these immune cells are suppressor T cells is discussed. The experimental system presented provides a model for the examination of the cellular interactions responsible for abscess formation and the cellular response to bacterial pathogens. PMID:6174672

  12. Magnetic fields, radicals and cellular activity.

    PubMed

    Montoya, Ryan D

    2017-01-01

    Some effects of low-intensity magnetic fields on the concentration of radicals and their influence on cellular functions are reviewed. These fields have been implicated as a potential modulator of radical recombination rates. Experimental evidence has revealed a tight coupling between cellular function and radical pair chemistry from signaling pathways to damaging oxidative processes. The effects of externally applied magnetic fields on biological systems have been extensively studied, and the observed effects lack sufficient mechanistic understanding. Radical pair chemistry offers a reasonable explanation for some of the molecular effects of low-intensity magnetic fields, and changes in radical concentrations have been observed to modulate specific cellular functions. Applied external magnetic fields have been shown to induce observable cellular changes such as both inhibiting and accelerating cell growth. These and other mechanisms, such as cell membrane potential modulation, are of great interest in cancer research due to the variations between healthy and deleterious cells. Radical concentrations demonstrate similar variations and are indicative of a possible causal relationship. Radicals, therefore, present a possible mechanism for the modulation of cellular functions such as growth or regression by means of applied external magnetic fields.

  13. Assessment of Cellular Estrogenic Activity Based on Estrogen Receptor-Mediated Reduction of Soluble-Form Catechol-O-Methyltransferase (COMT) Expression in an ELISA-Based System

    PubMed Central

    Ho, Philip Wing-Lok; Tse, Zero Ho-Man; Liu, Hui-Fang; Lu, Song; Ho, Jessica Wing-Man; Kung, Michelle Hiu-Wai; Ramsden, David Boyer; Ho, Shu-Leong

    2013-01-01

    Xenoestrogens are either natural or synthetic compounds that mimic the effects of endogenous estrogen. These compounds, such as bisphenol-A (BPA), and phthalates, are commonly found in plastic wares. Exposure to these compounds poses major risk to human health because of the potential to cause endocrine disruption. There is huge demand for a wide range of chemicals to be assessed for such potential for the sake of public health. Classical in vivo assays for endocrine disruption are comprehensive but time-consuming and require sacrifice of experimental animals. Simple preliminary in vitro screening assays can reduce the time and expense involved. We previously demonstrated that catechol-O-methyltransferase (COMT) is transcriptionally regulated by estrogen via estrogen receptor (ER). Therefore, detecting corresponding changes of COMT expression in estrogen-responsive cells may be a useful method to estimate estrogenic effects of various compounds. We developed a novel cell-based ELISA to evaluate cellular response to estrogenicity by reduction of soluble-COMT expression in ER-positive MCF-7 cells exposed to estrogenic compounds. In contrast to various existing methods that only detect bioactivity, this method elucidates direct physiological effect in a living cell in response to a compound. We validated our assay using three well-characterized estrogenic plasticizers - BPA, benzyl butyl phthalate (BBP), and di-n-butyl phthalate (DBP). Cells were exposed to either these plasticizers or 17β-estradiol (E2) in estrogen-depleted medium with or without an ER-antagonist, ICI 182,780, and COMT expression assayed. Exposure to each of these plasticizers (10-9-10-7M) dose-dependently reduced COMT expression (p<0.05), which was blocked by ICI 182,780. Reduction of COMT expression was readily detectable in cells exposed to picomolar level of E2, comparable to other in vitro assays of similar sensitivity. To satisfy the demand for in vitro assays targeting different cellular

  14. Assessment of cellular estrogenic activity based on estrogen receptor-mediated reduction of soluble-form catechol-O-methyltransferase (COMT) expression in an ELISA-based system.

    PubMed

    Ho, Philip Wing-Lok; Tse, Zero Ho-Man; Liu, Hui-Fang; Lu, Song; Ho, Jessica Wing-Man; Kung, Michelle Hiu-Wai; Ramsden, David Boyer; Ho, Shu-Leong

    2013-01-01

    Xenoestrogens are either natural or synthetic compounds that mimic the effects of endogenous estrogen. These compounds, such as bisphenol-A (BPA), and phthalates, are commonly found in plastic wares. Exposure to these compounds poses major risk to human health because of the potential to cause endocrine disruption. There is huge demand for a wide range of chemicals to be assessed for such potential for the sake of public health. Classical in vivo assays for endocrine disruption are comprehensive but time-consuming and require sacrifice of experimental animals. Simple preliminary in vitro screening assays can reduce the time and expense involved. We previously demonstrated that catechol-O-methyltransferase (COMT) is transcriptionally regulated by estrogen via estrogen receptor (ER). Therefore, detecting corresponding changes of COMT expression in estrogen-responsive cells may be a useful method to estimate estrogenic effects of various compounds. We developed a novel cell-based ELISA to evaluate cellular response to estrogenicity by reduction of soluble-COMT expression in ER-positive MCF-7 cells exposed to estrogenic compounds. In contrast to various existing methods that only detect bioactivity, this method elucidates direct physiological effect in a living cell in response to a compound. We validated our assay using three well-characterized estrogenic plasticizers - BPA, benzyl butyl phthalate (BBP), and di-n-butyl phthalate (DBP). Cells were exposed to either these plasticizers or 17β-estradiol (E2) in estrogen-depleted medium with or without an ER-antagonist, ICI 182,780, and COMT expression assayed. Exposure to each of these plasticizers (10(-9)-10(-7)M) dose-dependently reduced COMT expression (p<0.05), which was blocked by ICI 182,780. Reduction of COMT expression was readily detectable in cells exposed to picomolar level of E2, comparable to other in vitro assays of similar sensitivity. To satisfy the demand for in vitro assays targeting different cellular

  15. 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.

  16. 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

  17. 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

  18. 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'.

  19. 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.

  20. Cellular localization of lead using an antibody-based detection system and enzyme activity changes in the gills and digestive gland of the blue mussel Mytilus edulis.

    PubMed

    Einsporn, Sonja; Bressling, Jana; Koehler, Angela

    2009-02-01

    Marine organisms are continuously exposed to heavy metals in their environment. Bivalve mollusks such as the blue mussel Mytilus edulis accumulate high levels of heavy metals effecting cellular homeostasis and functions. Lead (Pb) exposure (2.5 mg/L of lead (II) nitrate for 10 d) and depuration (10 d in clean seawater) experiments were conducted to study its intracellular fate in the gills and digestive gland of M. edulis. For this purpose, an antibody-based detection method for ultrastructural localization and a subcellular fractionation approach for chemical analysis of Pb were used. In addition, effects of Pb on enzyme activities involved in oxyradical scavenging, such as the conjugative enzyme glutathione-S-transferase and the antioxidative enzyme catalase, were determined. The ultrastructural studies showed that Pb was mainly detected in lysosomes of gill epithelial cells and digestive cells. Lead was also detected in cell nuclei and granular hemocytes. Higher metal concentrations were measured by chemical analysis in subcellular fractions of the gills compared to those of the digestive gland. Increased activities of glutathione-S-transferase were found in gills after exposure and remained elevated during the depuration period, whereas glutathione-S-transferase activity remained unaffected in the digestive gland. Catalase activities showed no changes after Pb exposure, neither in the gills nor in the digestive gland. We conclude that gill cells are major sites of uptake and accumulation for dissolved Pb and are involved in sequestration and detoxification of this metal in M. edulis.

  1. High-level intra- and extra-cellular production of D-psicose 3-epimerase via a modified xylose-inducible expression system in Bacillus subtilis.

    PubMed

    Chen, Jingqi; Zhu, Yueming; Fu, Gang; Song, Yafeng; Jin, Zhaoxia; Sun, Yuanxia; Zhang, Dawei

    2016-11-01

    D-Psicose 3-epimerase (DPEase) converts D-fructose into D-psicose which exists in nature in limited quantities and has key physiological functions. In this study, RDPE (DPEase from Ruminococcus sp. 5_1_39BFAA) was successfully constitutively expressed in Bacillus subtilis, which is the first report of its kind. Three sugar-inducible promoters were compared, and the xylose-inducible promoter P xylA was proved to be the most efficient for RDPE production. Based on the analysis of the inducer concentration and RDPE expression, we surmised that there was an extremely close correlation between the intracellular RDPE expression and xylose accumulation level. Subsequently, after the metabolic pathway of xylose was blocked by deletion of xylAB, the intra- and extra-cellular RDPE expression was significantly enhanced. Meanwhile, the optimal xylose induction concentration was reduced from 4.0 to 0.5 %. Eventually, the secretion level of RDPE reached 95 U/mL and 2.6 g/L in a 7.5-L fermentor with the fed-batch fermentation, which is the highest production of DPEase by a microbe to date.

  2. Crystal structure of the human eIF4AIII–CWC22 complex shows how a DEAD-box protein is inhibited by a MIF4G domain

    PubMed Central

    Buchwald, Gretel; Schüssler, Steffen; Basquin, Claire; Le Hir, Hervé; Conti, Elena

    2013-01-01

    DEAD-box proteins are involved in all aspects of RNA processing. They bind RNA in an ATP-dependent manner and couple ATP hydrolysis to structural and compositional rearrangements of ribonucleoprotein particles. Conformational control is a major point of regulation for DEAD-box proteins to act on appropriate substrates and in a timely manner in vivo. Binding partners containing a middle domain of translation initiation factor 4G (MIF4G) are emerging as important regulators. Well-known examples are eIF4G and Gle1, which bind and activate the DEAD-box proteins eIF4A and Dbp5. Here, we report the mechanism of an inhibiting MIF4G domain. We determined the 2.0-Å resolution structure of the complex of human eIF4AIII and the MIF4G domain of the splicing factor Complexed With Cef1 (CWC22), an essential prerequisite for exon junction complex assembly by the splicing machinery. The CWC22 MIF4G domain binds both RecA domains of eIF4AIII. The mode of RecA2 recognition is similar to that observed in the activating complexes, yet is specific for eIF4AIII. The way the CWC22 MIF4G domain latches on the eIF4AIII RecA1 domain is markedly different from activating complexes. In the CWC22–eIF4AIII complex, the RNA-binding and ATP-binding motifs of the two RecA domains do not face each other, as would be required in the active state, but are in diametrically opposite positions. The binding mode of CWC22 to eIF4AIII reveals a facet of how MIF4G domains use their versatile structural frameworks to activate or inhibit DEAD-box proteins. PMID:24218557

  3. Gravitational studies in cellular and developmental biology

    NASA Technical Reports Server (NTRS)

    Spooner, B. S.

    1992-01-01

    The paucity of data on the role of gravity in cellular and developmental biology has been examined, and a hypothesis has been generated that unifies potential gravity sensitivity in both plant and animal systems. This hypothesis considers the macromolecular order and functional importance of the extracellular matrix compartment, the intracellular cytoskeleton compartment, and the connecting plasma membrane-signal transduction compartment of plant and animal systems as potentially sensitive to alterations in the unit gravity environment in which they evolved.

  4. 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.

  5. 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.

  6. 5-Methylcytosine DNA glycosylase activity is also present in the human MBD4 (G/T mismatch glycosylase) and in a related avian sequence.

    PubMed

    Zhu, B; Zheng, Y; Angliker, H; Schwarz, S; Thiry, S; Siegmann, M; Jost, J P

    2000-11-01

    A 1468 bp cDNA coding for the chicken homolog of the human MBD4 G/T mismatch DNA glycosylase was isolated and sequenced. The derived amino acid sequence (416 amino acids) shows 46% identity with the human MBD4 and the conserved catalytic region at the C-terminal end (170 amino acids) has 90% identity. The non-conserved region of the avian protein has no consensus sequence for the methylated DNA binding domain. The recombinant proteins from human and chicken have G/T mismatch as well as 5-methylcytosine (5-MeC) DNA glycosylase activities. When tested by gel shift assays, human recombinant protein with or without the methylated DNA binding domain binds equally well to symmetrically, hemimethylated DNA and non-methylated DNA. However, the enzyme has only 5-MeC DNA glycosylase activity with the hemimethylated DNA. Footprinting of human MBD4 and of an N-terminal deletion mutant with partially depurinated and depyrimidinated substrate reveal a selective binding of the proteins to the modified substrate around the CpG. As for 5-MeC DNA glycosylase purified from chicken embryos, MBD4 does not use oligonucleotides containing mCpA, mCpT or mCpC as substrates. An mCpG within an A+T-rich oligonucleotide is a much better substrate than an A+T-poor sequence. The K:(m) of human MBD4 for hemimethylated DNA is approximately 10(-7) M with a V:(max) of approximately 10(-11) mol/h/microgram protein. Deletion mutations show that G/T mismatch and 5-MeC DNA glycosylase are located in the C-terminal conserved region. In sharp contrast to the 5-MeC DNA glycosylase isolated from the chicken embryo DNA demethylation complex, the two enzymatic activities of MBD4 are strongly inhibited by RNA. In situ hybridization with antisense RNA indicate that MBD4 is only located in dividing cells of differentiating embryonic tissues.

  7. Bioimage informatics for understanding spatiotemporal dynamics of cellular processes.

    PubMed

    Yang, Ge

    2013-01-01

    The inner environment of the cell is highly dynamic and heterogeneous yet exquisitely organized. Successful completion of cellular processes within this environment depends on the right molecules or molecular complexes to function at the right place at the right time. Understanding spatiotemporal behaviors of cellular processes is therefore essential to understanding their molecular mechanisms at the systems level. These behaviors are usually visualized and recorded using imaging techniques. However, to infer from them systems-level molecular mechanisms, computational analysis and understanding of recorded image data is crucial, not only for acquiring quantitative behavi