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Sample records for cell-to-cell interaction progress

  1. Physiopathology of blood platelets: a model system for studies of cell-to-cell interaction. Progress report, November 1, 1979-October 31, 1980

    SciTech Connect

    1980-01-01

    This report covers the studies on basic mechanisms of cellular interactions, utilizing platelets as a model system and, when possible, concentrating on the influence that environmental factors (nutritional, metabolic, cellular, immunologic and others) have on them. The four major sections include: platelet interaction with tumor cells; a model for the study of cell-to-cell interaction; interaction of platelets with vessel walls; and platelet interactions with immune proteins.

  2. Enhancement of Chemotactic Cell Aggregation by Haptotactic Cell-To-Cell Interaction

    PubMed Central

    Kwon, Tae-goo; Yang, Taeseok Daniel; Lee, Kyoung J.

    2016-01-01

    The crawling of biological cell is a complex phenomenon involving various biochemical and mechanical processes. Some of these processes are intrinsic to individual cells, while others pertain to cell-to-cell interactions and to their responses to extrinsically imposed cues. Here, we report an interesting aggregation dynamics of mathematical model cells, when they perform chemotaxis in response to an externally imposed global chemical gradient while they influence each other through a haptotaxis-mediated social interaction, which confers intriguing trail patterns. In the absence of the cell-to-cell interaction, the equilibrium population density profile fits well to that of a simple Keller-Segal population dynamic model, in which a chemotactic current density J→chemo∼∇p competes with a normal diffusive current density J→diff∼∇ρ, where p and ρ refer to the concentration of chemoattractant and population density, respectively. We find that the cell-to-cell interaction confers a far more compact aggregation resulting in a much higher peak equilibrium cell density. The mathematical model system is applicable to many biological systems such as swarming microglia and neutrophils or accumulating ants towards a localized food source. PMID:27128310

  3. Recent progress in research on cell-to-cell movement of rice viruses

    PubMed Central

    Hiraguri, Akihiro; Netsu, Osamu; Sasaki, Nobumitsu; Nyunoya, Hiroshi; Sasaya, Takahide

    2014-01-01

    To adapt to plants as hosts, plant viruses have evolutionally needed the capacity to modify the host plasmodesmata (PD) that connect adjacent cells. Plant viruses have acquired one or more genes that encode movement proteins (MPs), which facilitate the cell-to-cell movement of infectious virus entities through PD to adjacent cells. Because of the diversity in their genome organization and in their coding sequences, rice viruses may each have a distinct cell-to-cell movement strategy. The complexity of their unusual genome organizations and replication strategies has so far hampered reverse genetic research on their genome in efforts to investigate virally encoded proteins that are involved in viral movement. However, the MP of a particular virus can complement defects in cell-to-cell movement of other distantly related or even unrelated viruses. Trans-complementation experiments using a combination of a movement-defective virus and viral proteins of interest to identify MPs of several rice viruses have recently been successful. In this article, we reviewed recent research that has advanced our understanding of cell-to-cell movement of rice viruses. PMID:24904532

  4. Cell-to-cell interactions in changed gravity: ground-based and flight experiments.

    PubMed

    Buravkova, L; Romanov, Yu; Rykova, M; Grigorieva, O; Merzlikina, N

    2005-01-01

    Cell-to-cell interactions play an important role in all physiological processes and are mediated by humoral and mechanical factors. Mechanosensitive cells (e.g., osteocytes, chondrocytes, and fibroblasts) can be studied ex vivo to understand the effects of an altered gravity environment. In particular, cultured endothelial cells (EC) are very sensitive to a broad spectrum of mechanical and biochemical stimuli. Earlier, we demonstrated that clinorotation leads to cytoskeletal remodeling in cultured ECs. Long-term gravity vector changes also modulate the expression of surface adhesion molecules (ICAM-1, E-selectin, VCAM-1) on cultured ECs. To study the interactions of geterological cells, we cocultured endothelial monolayers and human lymphocytes, immune cells and myeloleucemic (K-560) cells. It was found that, although clinorotation did not alter the basal adhesion level of non-activated immune cells on endothelial monolayers, the adhesion of PMA-activated lymphocytes was increased. During flight experiments onboard the Russian segment of the International Space Station, we measured the cytotoxic activity of natural killer (NK) cells incubated with labeled target cells. It was found that immune cells in microgravity retained their ability to contact, recognize, and destroy oncogenic cells in vitro. Together, our data concerning the effects of simulated and real microgravity suggest that, despite changes in the cytoskeleton, cell motility, and expression of adhesion molecules, cell-cell interactions are not compromised, thus preserving the critical physiological functions of immune and endothelial cells.

  5. Effect of Interaction between Chromatin Loops on Cell-to-Cell Variability in Gene Expression

    PubMed Central

    Zhou, Tianshou

    2016-01-01

    According to recent experimental evidence, the interaction between chromatin loops, which can be characterized by three factors—connection pattern, distance between regulatory elements, and communication form, play an important role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effect that addresses the question of how changes in these factors affect variability at the expression level in a systematic rather than case-by-case fashion. Here we make such an effort, based on a mechanic model that maps three fundamental patterns for two interacting DNA loops into a 4–state model of stochastic transcription. We first show that in contrast to side-by-side loops, nested loops enhance mRNA expression and reduce expression noise whereas alternating loops have just opposite effects. Then, we compare effects of facilitated tracking and direct looping on gene expression. We find that the former performs better than the latter in controlling mean expression and in tuning expression noise, but this control or tuning is distance–dependent, remarkable for moderate loop lengths, and there is a limit loop length such that the difference in effect between two communication forms almost disappears. Our analysis and results justify the facilitated chromatin–looping hypothesis. PMID:27153118

  6. The control of neural cell-to-cell interactions through non-contact electrical field stimulation using graphene electrodes.

    PubMed

    Heo, Chaejeong; Yoo, Jeongwan; Lee, Siyoung; Jo, Areum; Jung, Susie; Yoo, Hyosun; Lee, Young Hee; Suh, Minah

    2011-01-01

    Electric field stimulation has become one of the most promising therapies for a variety of neurological diseases. However, the safety and effectiveness of the stimulator are critical in determining the outcome. Because there are few safe and effective in vivo and/or in vitro stimulator devices, we demonstrate a method that allows for non-contact electric field stimulation with a specific strength that is able to control cell-to-cell interaction in vitro. Graphene, a form of graphite, and polyethylene terephthalate (PET) was used to create a non-cytotoxic in vitro graphene/PET film stimulator. A transient non-contact electric field was produced by charge-balanced biphasic stimuli through the graphene/PET film electrodes and applied to cultured neural cells. We found that weak electric field stimulation (pulse duration of 10 s) as low as 4.5 mV/mm for 32 min was particularly effective in shaping cell-to-cell interaction. Under weak electric field stimulation, we observed a significant increase in the number of cells forming new cell-to-cell couplings and in the number of cells strengthening existing cell-to-cell couplings. The underlying mechanism of the altered cellular interactions may be related to an altered regulation of the endogenous cytoskeletal proteins fibronectin, actin, and vinculin. In conclusion, this technique may open a new therapeutic approach for augmenting cell-to-cell coupling in cell transplantation therapy in the central nervous system.

  7. A coiled-coil interaction mediates cauliflower mosaic virus cell-to-cell movement

    NASA Astrophysics Data System (ADS)

    Stavolone, Livia; Villani, Maria Elena; Leclerc, Denis; Hohn, Thomas

    2005-04-01

    The function of the virion-associated protein (VAP) of cauliflower mosaic virus (CaMV) has long been only poorly understood. VAP is associated with the virion but is dispensable for virus morphogenesis and replication. It mediates virus transmission by aphids through simultaneous interaction with both the aphid transmission factor and the virion. However, although insect transmission is not fundamental to CaMV survival, VAP is indispensable for spreading the virus infection within the host plant. We used a GST pull-down technique to demonstrate that VAP interacts with the viral movement protein through coiled-coil domains and surface plasmon resonance to measure the interaction kinetics. We mapped the movement protein coiled-coil to the C terminus of the protein and proved that it self-assembles as a trimer. Immunogold labeling/electron microscopy revealed that the VAP and viral movement protein colocalize on CaMV particles within plasmodesmata. These results highlight the multifunctional potential of the VAP protein conferred by its efficient coiled-coil interaction system and show a plant virus possessing a surface-exposed protein (VAP) mediating viral entry into host cells. movement protein | virion-associated protein | Biacore

  8. Eph/ephrin-B-mediated cell-to-cell interactions govern MTS20(+) thymic epithelial cell development.

    PubMed

    Montero-Herradón, Sara; García-Ceca, Javier; Sánchez Del Collado, Beatriz; Alfaro, David; Zapata, Agustín G

    2016-08-01

    Thymus development is a complex process in which cell-to-cell interactions between thymocytes and thymic epithelial cells (TECs) are essential to allow a proper maturation of both thymic cell components. Although signals that control thymocyte development are well known, mechanisms governing TEC maturation are poorly understood, especially those that regulate the maturation of immature TEC populations during early fetal thymus development. In this study, we show that EphB2-deficient, EphB2LacZ and EphB3-deficient fetal thymuses present a lower number of cells and delayed maturation of DN cell subsets compared to WT values. Moreover, deficits in the production of chemokines, known to be involved in the lymphoid seeding into the thymus, contribute in decreased proportions of intrathymic T cell progenitors (PIRA/B(+)) in the mutant thymuses from early stages of development. These features correlate with increased proportions of MTS20(+) cells but fewer MTS20(-) cells from E13.5 onward in the deficient thymuses, suggesting a delayed development of the first epithelial cells. In addition, in vitro the lack of thymocytes or the blockade of Eph/ephrin-B-mediated cell-to-cell interactions between either thymocytes-TECs or TECs-TECs in E13.5 fetal thymic lobes coursed with increased proportions of MTS20(+) TECs. This confirms, for the first time, that the presence of CD45(+) cells, corresponding at these stages to DN1 and DN2 cells, and Eph/ephrin-B-mediated heterotypic or homotypic cell interactions between thymocytes and TECs, or between TECs and themselves, contribute to the early maturation of MTS20(+) TECs.

  9. Extracellular Membrane Vesicles as Vehicles for Brain Cell-to-Cell Interactions in Physiological as well as Pathological Conditions

    PubMed Central

    Schiera, Gabriella; Di Liegro, Carlo Maria; Di Liegro, Italia

    2015-01-01

    Extracellular vesicles are involved in a great variety of physiological events occurring in the nervous system, such as cross talk among neurons and glial cells in synapse development and function, integrated neuronal plasticity, neuronal-glial metabolic exchanges, and synthesis and dynamic renewal of myelin. Many of these EV-mediated processes depend on the exchange of proteins, mRNAs, and noncoding RNAs, including miRNAs, which occurs among glial and neuronal cells. In addition, production and exchange of EVs can be modified under pathological conditions, such as brain cancer and neurodegeneration. Like other cancer cells, brain tumours can use EVs to secrete factors, which allow escaping from immune surveillance, and to transfer molecules into the surrounding cells, thus transforming their phenotype. Moreover, EVs can function as a way to discard material dangerous to cancer cells, such as differentiation-inducing proteins, and even drugs. Intriguingly, EVs seem to be also involved in spreading through the brain of aggregated proteins, such as prions and aggregated tau protein. Finally, EVs can carry useful biomarkers for the early diagnosis of diseases. Herein we summarize possible roles of EVs in brain physiological functions and discuss their involvement in the horizontal spreading, from cell to cell, of both cancer and neurodegenerative pathologies. PMID:26583089

  10. A host-factor interaction and localization map for a plant-adapted rhabdovirus implicates cytoplasm-tethered transcription activators in cell-to-cell movement.

    PubMed

    Min, Byoung-Eun; Martin, Kathleen; Wang, Renyuan; Tafelmeyer, Petra; Bridges, Max; Goodin, Michael

    2010-11-01

    To identify host factors that play critical roles in processes, including cell-to-cell movement of plant-adapted rhabdoviruses, we constructed and validated a high-resolution Nicotiana benthamiana yeast two-hybrid library. The library was screened with the putative movement protein (sc4), nucleocapsid (N), and matrix (M) proteins of Sonchus yellow net virus (SYNV). This resulted in identification of 31 potential host factors. Steady-state localization studies using autofluorescent protein fusions to full-length clones of interactors were conducted in transgenic N. benthamiana marker lines. Bimolecular fluorescence complementation assays were used to validate two-hybrid interactions. The sc4 interactor, sc4i21, localized to microtubules. The N interactor, Ni67, localized to punctuate loci on the endoplasmic reticulum. These two proteins are 84% identical homologues of the Arabidopsis phloem-associated transcription activator AtVOZ1, and contain functional nuclear localization signals. Sc4i17 is a microtubule-associated motor protein. The M interactor, Mi7, is a nuclear-localized transcription factor. Combined with a binary interaction map for SYNV proteins, our data support a model in which the SYNV nucleocapsids are exported from the nucleus and moved cell-to-cell by transcription activators tethered in the cytoplasm.

  11. Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma

    SciTech Connect

    Fuchigami, Takao; Kibe, Toshiro; Koyama, Hirofumi; Kishida, Shosei; Iijima, Mikio; Nishizawa, Yoshiaki; Hijioka, Hiroshi; Fujii, Tomomi; Ueda, Masahiro; Nakamura, Norifumi; Kiyono, Tohru; Kishida, Michiko

    2014-09-05

    Highlights: • We studied the interaction between tumor cells and fibroblasts in ameloblastoma. • AM-3 ameloblastoma cells secreted significantly high IL-1α levels. • IL-1α derived from AM-3 cells promoted IL-6 and IL-8 secretion of fibroblasts. • IL-6 and IL-8 activated the cellular motility and proliferation of AM-3 cells. - Abstract: Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave

  12. Downregulation of the NbNACa1 gene encoding a movement-protein-interacting protein reduces cell-to-cell movement of Brome mosaic virus in Nicotiana benthamiana.

    PubMed

    Kaido, Masanori; Inoue, Yosuke; Takeda, Yoshika; Sugiyama, Kazuhiko; Takeda, Atsushi; Mori, Masashi; Tamai, Atsushi; Meshi, Tetsuo; Okuno, Tetsuro; Mise, Kazuyuki

    2007-06-01

    The 3a movement protein (MP) plays a central role in the movement of the RNA plant virus, Brome mosaic virus (BMV). To identify host factor genes involved in viral movement, a cDNA library of Nicotiana benthamiana, a systemic host for BMV, was screened with far-Western blotting using a recombinant BMV MP as probe. One positive clone encoded a protein with sequence similarity to the alpha chain of nascent-polypeptide-associated complex from various organisms, which is proposed to contribute to the fidelity of translocation of newly synthesized proteins. The orthologous gene from N. benthamiana was designated NbNACa1. The binding of NbNACa1 to BMV MP was confirmed in vivo with an agroinfiltration-immunoprecipitation assay. To investigate the involvement of NbNACa1 in BMV multiplication, NbNACa1-silenced (GSNAC) transgenic N. benthamiana plants were produced. Downregulation of NbNACa1 expression reduced virus accumulation in inoculated leaves but not in protoplasts. A microprojectile bombardment assay to monitor BMV-MP-assisted viral movement demonstrated reduced virus spread in GSNAC plants. The localization to the cell wall of BMV MP fused to green fluorescent protein was delayed in GSNAC plants. From these results, we propose that NbNACa1 is involved in BMV cell-to-cell movement through the regulation of BMV MP localization to the plasmodesmata.

  13. Interactions between Eph kinases and ephrins provide a mechanism to support platelet aggregation once cell-to-cell contact has occurred

    PubMed Central

    Prevost, Nicolas; Woulfe, Donna; Tanaka, Takako; Brass, Lawrence F.

    2002-01-01

    Eph kinases are receptor tyrosine kinases whose ligands, the ephrins, are also expressed on the surface of cells. Interactions between Eph kinases and ephrins on adjacent cells play a central role in neuronal patterning and vasculogenesis. Here we examine the expression of ephrins and Eph kinases on human blood platelets and explore their role in the formation of the hemostatic plug. The results show that human platelets express EphA4 and EphB1, and the ligand, ephrinB1. Forced clustering of EphA4 or ephrinB1 led to cytoskeletal reorganization, adhesion to fibrinogen, and α-granule secretion. Clustering of ephrinB1 also caused activation of the Ras family member, Rap1B. In platelets that had been activated by ADP and allowed to aggregate, EphA4 formed complexes with two tyrosine kinases, Fyn and Lyn, and the cell adhesion molecule, L1. Blockade of Eph/ephrin interactions prevented the formation of these complexes and caused platelet aggregation at low ADP concentrations to become more readily reversible. We propose that when sustained contacts between platelets have occurred in response to agonists such as collagen, ADP, and thrombin, the binding of ephrins to Eph kinases on adjacent platelets provides a mechanism to perpetuate signaling and promote stable platelet aggregation. PMID:12084815

  14. Proinflammatory interleukins' production by adipose tissue-derived mesenchymal stromal cells: the impact of cell culture conditions and cell-to-cell interaction.

    PubMed

    Andreeva, Elena; Andrianova, Irina; Rylova, Julia; Gornostaeva, Aleksandra; Bobyleva, Polina; Buravkova, Ludmila

    2015-08-01

    The impact of culture conditions and interaction with activated peripheral blood mononuclear cells on the interleukin (IL) gene expression profile and proinflammatory IL-6 and IL-8 production by adipose-derived stromal cells (ASCs) was investigated. A microarray analysis revealed a wide range of IL genes either under standard (20%) or hypoxic (5%) O2 concentrations, some highly up-regulated at hypoxia. IL-6 and IL-8 production was inversely dependent on cell culture density. In early (first-third) passages, IL-6 and IL-8 concentration was higher at 20% O2 and in late (8th-12th) passages under 5% O2. Interaction between ASCs and mononuclear cells in indirect setting was accompanied with a significant decrease of IL-6 and did not result in the elevation of IL-8 concentration. Thereby, the production of proinflammatory interleukins (IL-6 and IL-8) may be affected by the ASC intrinsic features (density in culture, and duration of expansion), as well as by microenvironmental factors, such as hypoxia and the presence of blood-borne cells. These data are important for elucidating ASC paracrine activity regulation in vitro. They would also be on demand for optimisation of the cell therapy protocols, based on the application of ASC biologically active substances. SIGNIFICANCE PARAGRAPH: Ex vivo expansion is widely used for increasing the number of adipose-derived stromal cells (ASCs) and improving of their quality. The present study was designed to elucidate the particular factors influencing the interleukin production in ASCs. The presented data specified the parameters (i.e. cell density, duration of cultivation, hypoxia, etc.) that should be taken in mind when ASCs are intended to be used in protocols implying their paracrine activity. These data would be of considerable interest for researchers and clinicians working in the biomedical science.

  15. Metabolic adaptations of Azospirillum brasilense to oxygen stress by cell-to-cell clumping and flocculation.

    PubMed

    Bible, Amber N; Khalsa-Moyers, Gurusahai K; Mukherjee, Tanmoy; Green, Calvin S; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B; Alexandre, Gladys

    2015-12-01

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacterium Azospirillum brasilense navigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motile A. brasilense cells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Cell-to-cell clumping may thus license diazotrophy to microaerophilic A. brasilense cells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists. PMID:26407887

  16. Metabolic adaptations of Azospirillum brasilense to oxygen stress by cell-to-cell clumping and flocculation.

    PubMed

    Bible, Amber N; Khalsa-Moyers, Gurusahai K; Mukherjee, Tanmoy; Green, Calvin S; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B; Alexandre, Gladys

    2015-12-01

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacterium Azospirillum brasilense navigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motile A. brasilense cells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Cell-to-cell clumping may thus license diazotrophy to microaerophilic A. brasilense cells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists.

  17. Metabolic Adaptations of Azospirillum brasilense to Oxygen Stress by Cell-to-Cell Clumping and Flocculation

    PubMed Central

    Bible, Amber N.; Khalsa-Moyers, Gurusahai K.; Mukherjee, Tanmoy; Green, Calvin S.; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B.

    2015-01-01

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacterium Azospirillum brasilense navigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motile A. brasilense cells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Cell-to-cell clumping may thus license diazotrophy to microaerophilic A. brasilense cells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists. PMID:26407887

  18. Virus Cell-to-Cell Transmission▿

    PubMed Central

    Mothes, Walther; Sherer, Nathan M.; Jin, Jing; Zhong, Peng

    2010-01-01

    Viral infections spread based on the ability of viruses to overcome multiple barriers and move from cell to cell, tissue to tissue, and person to person and even across species. While there are fundamental differences between these types of transmissions, it has emerged that the ability of viruses to utilize and manipulate cell-cell contact contributes to the success of viral infections. Central to the excitement in the field of virus cell-to-cell transmission is the idea that cell-to-cell spread is more than the sum of the processes of virus release and entry. This implies that virus release and entry are efficiently coordinated to sites of cell-cell contact, resulting in a process that is distinct from its individual components. In this review, we will present support for this model, illustrate the ability of viruses to utilize and manipulate cell adhesion molecules, and discuss the mechanism and driving forces of directional spreading. An understanding of viral cell-to-cell spreading will enhance our ability to intervene in the efficient spreading of viral infections. PMID:20375157

  19. Metabolic Adaptations of Azospirillum brasilense to Oxygen Stress by Cell-to-Cell Clumping and Flocculation

    SciTech Connect

    Bible, Amber N.; Khalsa-Moyers, Gurusahai K.; Mukherjee, Tanmoy; Green, Calvin S.; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B.; Alexandre, Gladys

    2015-09-25

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacteriumAzospirillum brasilensenavigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motileA. brasilensecells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Finally, cell-to-cell clumping may thus license diazotrophy to microaerophilicA. brasilensecells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists.

  20. Metabolic Adaptations of Azospirillum brasilense to Oxygen Stress by Cell-to-Cell Clumping and Flocculation

    DOE PAGES

    Bible, Amber N.; Khalsa-Moyers, Gurusahai K.; Mukherjee, Tanmoy; Green, Calvin S.; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B.; Alexandre, Gladys

    2015-09-25

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacteriumAzospirillum brasilensenavigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motileA. brasilensecells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities,more » we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Finally, cell-to-cell clumping may thus license diazotrophy to microaerophilicA. brasilensecells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists.« less

  1. Molecular Mechanisms of HTLV-1 Cell-to-Cell Transmission

    PubMed Central

    Gross, Christine; Thoma-Kress, Andrea K.

    2016-01-01

    The tumorvirus human T-cell lymphotropic virus type 1 (HTLV-1), a member of the delta-retrovirus family, is transmitted via cell-containing body fluids such as blood products, semen, and breast milk. In vivo, HTLV-1 preferentially infects CD4+ T-cells, and to a lesser extent, CD8+ T-cells, dendritic cells, and monocytes. Efficient infection of CD4+ T-cells requires cell-cell contacts while cell-free virus transmission is inefficient. Two types of cell-cell contacts have been described to be critical for HTLV-1 transmission, tight junctions and cellular conduits. Further, two non-exclusive mechanisms of virus transmission at cell-cell contacts have been proposed: (1) polarized budding of HTLV-1 into synaptic clefts; and (2) cell surface transfer of viral biofilms at virological synapses. In contrast to CD4+ T-cells, dendritic cells can be infected cell-free and, to a greater extent, via viral biofilms in vitro. Cell-to-cell transmission of HTLV-1 requires a coordinated action of steps in the virus infectious cycle with events in the cell-cell adhesion process; therefore, virus propagation from cell-to-cell depends on specific interactions between cellular and viral proteins. Here, we review the molecular mechanisms of HTLV-1 transmission with a focus on the HTLV-1-encoded proteins Tax and p8, their impact on host cell factors mediating cell-cell contacts, cytoskeletal remodeling, and thus, virus propagation. PMID:27005656

  2. CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells.

    PubMed

    Witteveldt, Jeroen; Evans, Matthew J; Bitzegeio, Julia; Koutsoudakis, George; Owsianka, Ania M; Angus, Allan G N; Keck, Zhen-Yong; Foung, Steven K H; Pietschmann, Thomas; Rice, Charles M; Patel, Arvind H

    2009-01-01

    Hepatitis C virus (HCV) infects cells by the direct uptake of cell-free virus following virus engagement with specific cell receptors such as CD81. Recent data have shown that HCV is also capable of direct cell-to-cell transmission, although the role of CD81 in this process is disputed. Here, we generated cell culture infectious strain JFH1 HCV (HCVcc) genomes carrying an alanine substitution of E2 residues W529 or D535 that are critical for binding to CD81 and infectivity. Co-cultivation of these cells with naïve cells expressing enhanced green fluorescent protein (EGFP) resulted in a small number of cells co-expressing both EGFP and HCV NS5A, showing that the HCVcc mutants are capable of cell-to-cell spread. In contrast, no cell-to-cell transmission from JFH1(DeltaE1E2)-transfected cells occurred, indicating that the HCV glycoproteins are essential for this process. The frequency of cell-to-cell transmission of JFH1(W529A) was unaffected by the presence of neutralizing antibodies that inhibit E2-CD81 interactions. By using cell lines that expressed little or no CD81 and that were refractive to infection with cell-free virus, we showed that the occurrence of viral cell-to-cell transmission is not influenced by the levels of CD81 on either donor or recipient cells. Thus, our results show that CD81 plays no role in the cell-to-cell spread of HCVcc and that this mode of transmission is shielded from neutralizing antibodies. These data suggest that therapeutic interventions targeting the entry of cell-free HCV may not be sufficient in controlling an ongoing chronic infection, but need to be complemented by additional strategies aimed at disrupting direct cell-to-cell viral transmission. PMID:19088272

  3. Diagram of Cell to Cell Communication

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Diagram depicts the importance of cell-cell communication as central to the understanding of cancer growth and progression, the focus of the NASA bioreactor demonstration system (BDS-05) investigation. Microgravity studies will allow us to unravel the signaling and communication between these cells with the host and potential development of therapies for the treatment of cancer metastasis. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Credit: Emory University.

  4. Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein.

    PubMed

    Bae, Eun-Jin; Yang, Na-Young; Song, Miyoung; Lee, Cheol Soon; Lee, Jun Sung; Jung, Byung Chul; Lee, He-Jin; Kim, Seokjoong; Masliah, Eliezer; Sardi, Sergio Pablo; Lee, Seung-Jae

    2014-01-01

    Deposition of α-synuclein aggregates occurs widely in the central and peripheral nervous systems in Parkinson's disease (PD). Although recent evidence has suggested that cell-to-cell transmission of α-synuclein aggregates is associated with the progression of PD, the mechanism by which α-synuclein aggregates spread remains undefined. Here, we show that α-synuclein aggregates are transmitted from cell to cell through a cycle involving uptake of external aggregates, co-aggregation with endogenous α-synuclein and exocytosis of the co-aggregates. Moreover, we find that glucocerebrosidase depletion, which has previously been strongly associated with PD and increased cognitive impairment, promotes propagation of α-synuclein aggregates. These studies define how α-synuclein aggregates spread among neuronal cells and may provide an explanation for how glucocerebrosidase mutations increase the risk of developing PD and other synucleinopathies. PMID:25156829

  5. Cell-to-cell movement of mitochondria in plants.

    PubMed

    Gurdon, Csanad; Svab, Zora; Feng, Yaping; Kumar, Dibyendu; Maliga, Pal

    2016-03-22

    We report cell-to-cell movement of mitochondria through a graft junction. Mitochondrial movement was discovered in an experiment designed to select for chloroplast transfer from Nicotiana sylvestris into Nicotiana tabacum cells. The alloplasmic N. tabacum line we used carries Nicotiana undulata cytoplasmic genomes, and its flowers are male sterile due to the foreign mitochondrial genome. Thus, rare mitochondrial DNA transfer from N. sylvestris to N. tabacum could be recognized by restoration of fertile flower anatomy. Analyses of the mitochondrial genomes revealed extensive recombination, tentatively linking male sterility to orf293, a mitochondrial gene causing homeotic conversion of anthers into petals. Demonstrating cell-to-cell movement of mitochondria reconstructs the evolutionary process of horizontal mitochondrial DNA transfer and enables modification of the mitochondrial genome by DNA transmitted from a sexually incompatible species. Conversion of anthers into petals is a visual marker that can be useful for mitochondrial transformation. PMID:26951647

  6. Cell-to-cell movement of mitochondria in plants

    PubMed Central

    Gurdon, Csanad; Svab, Zora; Feng, Yaping; Kumar, Dibyendu; Maliga, Pal

    2016-01-01

    We report cell-to-cell movement of mitochondria through a graft junction. Mitochondrial movement was discovered in an experiment designed to select for chloroplast transfer from Nicotiana sylvestris into Nicotiana tabacum cells. The alloplasmic N. tabacum line we used carries Nicotiana undulata cytoplasmic genomes, and its flowers are male sterile due to the foreign mitochondrial genome. Thus, rare mitochondrial DNA transfer from N. sylvestris to N. tabacum could be recognized by restoration of fertile flower anatomy. Analyses of the mitochondrial genomes revealed extensive recombination, tentatively linking male sterility to orf293, a mitochondrial gene causing homeotic conversion of anthers into petals. Demonstrating cell-to-cell movement of mitochondria reconstructs the evolutionary process of horizontal mitochondrial DNA transfer and enables modification of the mitochondrial genome by DNA transmitted from a sexually incompatible species. Conversion of anthers into petals is a visual marker that can be useful for mitochondrial transformation. PMID:26951647

  7. Confirming Impurity Effect in Silver-Point Realization from Cell-to-Cell Comparisons

    NASA Astrophysics Data System (ADS)

    Widiatmo, J. V.; Harada, K.; Yamazawa, K.; Tamba, J.; Arai, M.

    2011-12-01

    As a continuation to earlier work on the silver-point realization, already reported at TEMPMEKO 2007, a new silver-point cell has been fabricated using 6N-nominal grade material that was analyzed by means of glow discharge mass spectrometry (GDMS) by the manufacturer. This new cell is evaluated by a direct cell comparison with one of the existing cells, which was also already reported at TEMPMEKO 2007. One of those existing cells was drawn out from its crucible, and its ingot was analyzed by GDMS at four positions, namely, at around the center of the top, of the middle, of the bottom, and around the outer part of middle areas for the purpose of confirming whether or not there has been differences in the content of impurities before and after the cell fabrication, as well as differences in impurity homogeneity within the ingot. As results of the aforementioned measurements, it was found that the homogeneity of impurities in the silver ingot was on average within 50 %. It was also found that cell-to-cell temperature differences change along with the progressing solidification process. As a consequence, it was concluded that, for an accurate cell-to-cell comparison, the location in the freezing plateau, where the comparison is done, should be determined. Also obtained here is that the slope analysis was consistent with both the cell-to-cell comparison and the impurity analysis.

  8. Cell-to-cell movement of plastids in plants

    PubMed Central

    Thyssen, Gregory; Svab, Zora; Maliga, Pal

    2012-01-01

    Our objective was to test whether or not plastids and mitochondria, the two DNA-containing organelles, move between cells in plants. As our experimental approach, we grafted two different species of tobacco, Nicotiana tabacum and Nicotiana sylvestris. Grafting triggers formation of new cell-to-cell contacts, creating an opportunity to detect cell-to-cell organelle movement between the genetically distinct plants. We initiated tissue culture from sliced graft junctions and selected for clonal lines in which gentamycin resistance encoded in the N. tabacum nucleus was combined with spectinomycin resistance encoded in N. sylvestris plastids. Here, we present evidence for cell-to-cell movement of the entire 161-kb plastid genome in these plants, most likely in intact plastids. We also found that the related mitochondria were absent, suggesting independent movement of the two DNA-containing organelles. Acquisition of plastids from neighboring cells provides a mechanism by which cells may be repopulated with functioning organelles. Our finding supports the universality of intercellular organelle trafficking and may enable development of future biotechnological applications. PMID:22308369

  9. Electron Donor Acceptor Interactions. Final Progress Report

    SciTech Connect

    2002-08-16

    The Gordon Research Conference (GRC) on Electron Donor Acceptor Interactions was held at Salve Regina University, Newport, Rhode Island, 8/11-16/02. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  10. Retrotransposition and Cell-to-Cell Transfer of Foamy Viruses

    PubMed Central

    Heinkelein, Martin; Rammling, Matthias; Juretzek, Thomas; Lindemann, Dirk; Rethwilm, Axel

    2003-01-01

    A remarkable feature of the prototype foamy virus (PFV) replication pathway has been reported to consist of the ability to retrotranspose intracellularly with high efficiency (M. Heinkelein, T. Pietschmann, G. Jármy, M. Dressler, H. Imrich, J. Thurow, D. Lindemann, M. Bock, A. Moebes, J. Roy, O. Herchenröder, and A. Rethwilm, EMBO J. 19:3436-3345, 2000). PFV intracellular retrotransposition (IRT) was reported to be enhanced by coexpression of fusion-defective envelope protein. To investigate the possibility of cell-to-cell transfer of PFV genomes, which could mimic IRT, we performed cocultivation experiments with cells transfected with an IRT-competent and marker gene-expressing PFV vector together with cells expressing a different marker and measured cells positive for both markers. The findings corroborated the initial report on IRT of Env-deficient PFV. Furthermore, they indicated that viral cores that have incorporated fusion-deficient Env can be transferred from cell to cell in a cell type-specific manor. One possible explanation consists of a minor alternative cleavage site in Env that can be used to expose the fusion peptide of the Env transmembrane protein, which appears to be required for virus uptake. PMID:14557671

  11. From single-cell to cell-pool transcriptomes: stochasticity in gene expression and RNA splicing.

    PubMed

    Marinov, Georgi K; Williams, Brian A; McCue, Ken; Schroth, Gary P; Gertz, Jason; Myers, Richard M; Wold, Barbara J

    2014-03-01

    Single-cell RNA-seq mammalian transcriptome studies are at an early stage in uncovering cell-to-cell variation in gene expression, transcript processing and editing, and regulatory module activity. Despite great progress recently, substantial challenges remain, including discriminating biological variation from technical noise. Here we apply the SMART-seq single-cell RNA-seq protocol to study the reference lymphoblastoid cell line GM12878. By using spike-in quantification standards, we estimate the absolute number of RNA molecules per cell for each gene and find significant variation in total mRNA content: between 50,000 and 300,000 transcripts per cell. We directly measure technical stochasticity by a pool/split design and find that there are significant differences in expression between individual cells, over and above technical variation. Specific gene coexpression modules were preferentially expressed in subsets of individual cells, including one enriched for mRNA processing and splicing factors. We assess cell-to-cell variation in alternative splicing and allelic bias and report evidence of significant differences in splice site usage that exceed splice variation in the pool/split comparison. Finally, we show that transcriptomes from small pools of 30-100 cells approach the information content and reproducibility of contemporary RNA-seq from large amounts of input material. Together, our results define an experimental and computational path forward for analyzing gene expression in rare cell types and cell states.

  12. From single-cell to cell-pool transcriptomes: stochasticity in gene expression and RNA splicing.

    PubMed

    Marinov, Georgi K; Williams, Brian A; McCue, Ken; Schroth, Gary P; Gertz, Jason; Myers, Richard M; Wold, Barbara J

    2014-03-01

    Single-cell RNA-seq mammalian transcriptome studies are at an early stage in uncovering cell-to-cell variation in gene expression, transcript processing and editing, and regulatory module activity. Despite great progress recently, substantial challenges remain, including discriminating biological variation from technical noise. Here we apply the SMART-seq single-cell RNA-seq protocol to study the reference lymphoblastoid cell line GM12878. By using spike-in quantification standards, we estimate the absolute number of RNA molecules per cell for each gene and find significant variation in total mRNA content: between 50,000 and 300,000 transcripts per cell. We directly measure technical stochasticity by a pool/split design and find that there are significant differences in expression between individual cells, over and above technical variation. Specific gene coexpression modules were preferentially expressed in subsets of individual cells, including one enriched for mRNA processing and splicing factors. We assess cell-to-cell variation in alternative splicing and allelic bias and report evidence of significant differences in splice site usage that exceed splice variation in the pool/split comparison. Finally, we show that transcriptomes from small pools of 30-100 cells approach the information content and reproducibility of contemporary RNA-seq from large amounts of input material. Together, our results define an experimental and computational path forward for analyzing gene expression in rare cell types and cell states. PMID:24299736

  13. Exploiting nongenetic cell-to-cell variation for enhanced biosynthesis.

    PubMed

    Xiao, Yi; Bowen, Christopher H; Liu, Di; Zhang, Fuzhong

    2016-05-01

    Biosynthesis enables renewable production of manifold compounds, yet often biosynthetic performance must be improved for it to be economically feasible. Nongenetic, cell-to-cell variations in protein and metabolite concentrations are naturally inherent, suggesting the existence of both high- and low-performance variants in all cultures. Although having an intrinsic source of low performers might cause suboptimal ensemble biosynthesis, the existence of high performers suggests an avenue for performance enhancement. Here we develop in vivo population quality control (PopQC) to continuously select for high-performing, nongenetic variants. We apply PopQC to two biosynthetic pathways using two alternative design principles and demonstrate threefold enhanced production of both free fatty acid (FFA) and tyrosine. We confirm that PopQC improves ensemble biosynthesis by selecting for nongenetic high performers. Additionally, we use PopQC in fed-batch FFA production and achieve 21.5 g l(-1) titer and 0.5 g l(-1) h(-1) productivity. Given the ubiquity of nongenetic variation, PopQC should be applicable to a variety of metabolic pathways for enhanced biosynthesis. PMID:26999780

  14. Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases

    PubMed Central

    Guo, Jing L; Lee, Virginia M Y

    2014-01-01

    A common feature of many neurodegenerative diseases is the deposition of β-sheet-rich amyloid aggregates formed by proteins specific to these diseases. These protein aggregates are thought to cause neuronal dysfunction, directly or indirectly. Recent studies have strongly implicated cell-to-cell transmission of misfolded proteins as a common mechanism for the onset and progression of various neurodegenerative disorders. Emerging evidence also suggests the presence of conformationally diverse ‘strains’ of each type of disease protein, which may be another shared feature of amyloid aggregates, accounting for the tremendous heterogeneity within each type of neurodegenerative disease. Although there are many more questions to be answered, these studies have opened up new avenues for therapeutic interventions in neurodegenerative disorders. PMID:24504409

  15. Cell-to-cell communication and cellular environment alter the somatostatin status of delta cells

    SciTech Connect

    Kelly, Catriona; Flatt, Peter R.; McClenaghan, Neville H.

    2010-08-20

    Research highlights: {yields} TGP52 cells display enhanced functionality in pseudoislet form. {yields} Somatostatin content was reduced, but secretion increased in high glucose conditions. {yields} Cellular interactions and environment alter the somatostatin status of TGP52 cells. -- Abstract: Introduction: Somatostatin, released from pancreatic delta cells, is a potent paracrine inhibitor of insulin and glucagon secretion. Islet cellular interactions and glucose homeostasis are essential to maintain normal patterns of insulin secretion. However, the importance of cell-to-cell communication and cellular environment in the regulation of somatostatin release remains unclear. Methods: This study employed the somatostatin-secreting TGP52 cell line maintained in DMEM:F12 (17.5 mM glucose) or DMEM (25 mM glucose) culture media. The effect of pseudoislet formation and culture medium on somatostatin content and release in response to a variety of stimuli was measured by somatostatin EIA. In addition, the effect of pseudoislet formation on cellular viability (MTT and LDH assays) and proliferation (BrdU ELISA) was determined. Results: TGP52 cells readily formed pseudoislets and showed enhanced functionality in three-dimensional form with increased E-cadherin expression irrespective of the culture environment used. However, culture in DMEM decreased cellular somatostatin content (P < 0.01) and increased somatostatin secretion in response to a variety of stimuli including arginine, calcium and PMA (P < 0.001) when compared with cells grown in DMEM:F12. Configuration of TGP52 cells as pseudoislets reduced the proliferative rate and increased cellular cytotoxicity irrespective of culture medium used. Conclusions: Somatostatin secretion is greatly facilitated by cell-to-cell interactions and E-cadherin expression. Cellular environment and extracellular glucose also significantly influence the function of delta cells.

  16. An unusual dependence of human herpesvirus-8 glycoproteins-induced cell-to-cell fusion on heparan sulfate

    SciTech Connect

    Tiwari, Vaibhav; Darmani, Nissar A.; Thrush, Gerald R.; Shukla, Deepak

    2009-12-18

    Human herpesvirus-8 (HHV-8) is known to interact with cell surface heparan sulfate (HS) for entry into a target cell. Here we investigated the role of HS during HHV-8 glycoproteins-induced cell fusion. Interestingly, the observed fusion demonstrated an unusual dependence on HS as evident from following lines of evidence: (1) a significant reduction in cell-to-cell fusion occurred when target cells were treated with heparinase; (2) in a competition assay, when the effector cells expressing HHV-8 glycoproteins were challenged with soluble HS, cell-to-cell fusion was reduced; and, (3) co-expression of HHV-8 glycoproteins gH-gL on target cells resulted in inhibition of cell surface HS expression. Taken together, our results indicate that cell surface HS can play an additional role during HHV-8 pathogenesis.

  17. Sheep stromal-epithelial cell interactions and ovarian tumor progression.

    PubMed

    Wang-Johanning, Feng; Huang, Miao; Liu, Jinsong; Rycaj, Kiera; Plummer, Joshua B; Barnhart, Kirstin F; Satterfield, William C; Johanning, Gary L

    2007-11-15

    Previous studies suggest that underlying ovarian stromal cues may regulate the ovarian surface epithelium. However, little is known about the interaction between ovarian stromal cells (OSC) and ovarian surface epithelial cells (OSE) under normal physiologic and pathologic conditions, largely because of the lack of a suitable model. In the current study, the OSC obtained from a sheep were immortalized with SV-40 T/t antigen (designated IOSC) and telomerase reverse transcriptase (designated IOSCH), followed by transfection with the oncogenic allele of the human H-Ras oncogene (designated IOSChR). IOSC cells transfected with H-Ras before immortalization with telomerase were designated IOSCRH. These sheep OSCs were used in both in vitro and in vivo model systems to evaluate mechanisms by which OSCs influence ovarian tumor progression. Normal sheep OSCs were found to inhibit the growth of SKOV3 and OVCAR3 human ovarian cancer cells, but not normal sheep OSE and human OSE cells (hOSE137 cells). In contrast, IOSChR and IOSCRH cells stimulated the growth of normal sheep and human OSE cells, as well as cancer cells. These findings were confirmed by in vivo studies. Our data provide compelling support for the importance of stromal-epithelial cell interactions during tumor progression, and show for the first time that immortalized and transformed OSCs promote growth of ovarian epithelial tumors.

  18. Identification of a Functional Plasmodesmal Localization Signal in a Plant Viral Cell-To-Cell-Movement Protein

    PubMed Central

    Yuan, Cheng; Lazarowitz, Sondra G.

    2016-01-01

    ABSTRACT Our fundamental knowledge of the protein-sorting pathways required for plant cell-to-cell trafficking and communication via the intercellular connections termed plasmodesmata has been severely limited by the paucity of plasmodesmal targeting sequences that have been identified to date. To address this limitation, we have identified the plasmodesmal localization signal (PLS) in the Tobacco mosaic virus (TMV) cell-to-cell-movement protein (MP), which has emerged as the paradigm for dissecting the molecular details of cell-to-cell transport through plasmodesmata. We report here the identification of a bona fide functional TMV MP PLS, which encompasses amino acid residues between positions 1 and 50, with residues Val-4 and Phe-14 potentially representing critical sites for PLS function that most likely affect protein conformation or protein interactions. We then demonstrated that this PLS is both necessary and sufficient for protein targeting to plasmodesmata. Importantly, as TMV MP traffics to plasmodesmata by a mechanism that is distinct from those of the three plant cell proteins in which PLSs have been reported, our findings provide important new insights to expand our understanding of protein-sorting pathways to plasmodesmata. PMID:26787834

  19. Over-expression of putative transcriptional coactivator KELP interferes with Tomato mosaic virus cell-to-cell movement.

    PubMed

    Sasaki, Nobumitsu; Ogata, Takuya; Deguchi, Masakazu; Nagai, Shoko; Tamai, Atsushi; Meshi, Tetsuo; Kawakami, Shigeki; Watanabe, Yuichiro; Matsushita, Yasuhiko; Nyunoya, Hiroshi

    2009-03-01

    Tomato mosaic virus (ToMV) encodes a movement protein (MP) that is necessary for virus cell-to-cell movement. We have demonstrated previously that KELP, a putative transcriptional coactivator of Arabidopsis thaliana, and its orthologue from Brassica campestris can bind to ToMV MP in vitro. In this study, we examined the effects of the transient over-expression of KELP on ToMV infection and the intracellular localization of MP in Nicotiana benthamiana, an experimental host of the virus. In co-bombardment experiments, the over-expression of KELP inhibited virus cell-to-cell movement. The N-terminal half of KELP (KELPdC), which had been shown to bind to MP, was sufficient for inhibition. Furthermore, the over-expression of KELP and KELPdC, both of which were co-localized with ToMV MP, led to a reduction in the plasmodesmal association of MP. In the absence of MP expression, KELP was localized in the nucleus and the cytoplasm by the localization signal in its N-terminal half. It was also shown that ToMV amplified normally in protoplasts prepared from leaf tissue that expressed KELP transiently. These results indicate that over-expressed KELP interacts with MP in vivo and exerts an inhibitory effect on MP function for virus cell-to-cell movement, but not on virus amplification in individual cells.

  20. The UL49 gene product of BoHV-1: a major factor in efficient cell-to-cell spread.

    PubMed

    Kalthoff, Donata; Granzow, Harald; Trapp, Sascha; Beer, Martin

    2008-09-01

    The role of the UL49 gene product, VP22, of bovine herpesvirus type 1 (BoHV-1) in virus replication was characterized with respect to a putative functional interaction of VP22 with the viral glycoprotein E (gE) during BoHV-1 cell-to-cell spread. Deletion of the open reading frames of UL49 and/or gE from an infectious BoHV-1 bacterial artificial chromosome clone did not severely impair the production of viral progeny in single-step growth experiments. However, plaque sizes induced by a VP22-negative BoHV-1 were reduced by 52%, whilst for the gE/VP22-negative double-deletion mutant a reduction of 83% could be observed in comparison with parental and revertant viruses, which was consistent with a marked reduction in multi-step growth experiments at early time points. These results suggest that gE and VP22 are important for BoHV-1 cell-to-cell spread, and that both are likely to act independently of each other in a critical pathway for virus cell-to-cell spread. PMID:18753236

  1. Myosin-X facilitates Shigella-induced membrane protrusions and cell-to-cell spread

    PubMed Central

    Li, Wei; Dhillon, Jess; Bohil, Aparna B.; Cheney, Richard E.; Hartwig, John H.; Southwick, Frederick S.

    2014-01-01

    Summary The intracellular pathogen Shigella flexneri forms membrane protrusions to spread from cell to cell. As protrusions form, myosin-X (Myo10) localizes to Shigella. Electron micrographs of immunogold-labelled Shigella-infected HeLa cells reveal that Myo10 concentrates at the bases and along the sides of bacteria within membrane protrusions. Time-lapse video microscopy shows that a full-length Myo10 GFP-construct cycles along the sides of Shigella within the membrane protrusions as these structures progressively lengthen. RNAi knock-down of Myo10 is associated with shorter protrusions with thicker stalks, and causes a >80% decrease in confluent cell plaque formation. Myo10 also concentrates in membrane protrusions formed by another intracellular bacteria, Listeria, and knock-down of Myo10 also impairs Listeria plaque formation. In Cos7 cells (contain low concentrations of Myo10), the expression of full-length Myo10 nearly doubles Shigella-induced protrusion length, and lengthening requires the head domain, as well as the tail-PH domain, but not the FERM domain. The GFP-Myo10-HMM domain localizes to the sides of Shigella within membrane protrusions and the GFP-Myo10-PH domain localizes to host cell membranes. We conclude that Myo10 generates the force to enhance bacterial-induced protrusions by binding its head region to actin filaments and its PH tail domain to the peripheral membrane. PMID:23083060

  2. Interactions between biomaterials and the sclera: Implications on myopia progression

    NASA Astrophysics Data System (ADS)

    Su, James

    Myopia prevalence has steadily climbed worldwide in recent decades with the most dramatic impact in East Asian countries. Treatments such as eyeglasses, contact lenses, and laser surgery for the refractive error are widely available, but none cures the underlying cause. In progressive high myopia, invasive surgical procedures using a scleral buckle for mechanical support are performed since the patient is at risk of becoming blind. The treatment outcome is highly dependent on the surgeon's skills and the patient's myopia progression rate, with limited choices in buckling materials. This dissertation, in four main studies, represents efforts made to control high myopia progression through the exploration and development of biomaterials that influence scleral growth. First, mRNA expression levels of the chick scleral matrix metalloproteinases, tissue-inhibitor of matrix metalloproteinases, and transforming growth factor-beta 2 were assessed for temporal and defocus power effects. The first study elucidated the roles that these factors play in scleral growth regulation and suggested potential motifs that can be incorporated in future biomaterials design. Second, poly(vinyl-pyrrolidone) as injectable gels and poly(2-hydroxyethyl methacrylate) as solid strips were implanted in chicks to demonstrate the concept of posterior pole scleral reinforcements. This second study found that placing appropriate biomaterials at the posterior pole of the eye could directly influence scleral remodeling by interacting with the host cells. Both studies advanced the idea that scleral tissue remodeling could be potentially controlled by well-designed biomaterials. These findings led to the exploration of biomimetic hydrogels comprising enzymatically-degradable semi-interpenetrating polymer networks (edsIPNs) to determine their biocompatibility and effects on the chick posterior eye wall. This third study demonstrated the feasibility of stimulating scleral growth by applying biomimetic

  3. Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition.

    PubMed

    Gruel, Gaëtan; Villagrasa, Carmen; Voisin, Pascale; Clairand, Isabelle; Benderitter, Marc; Bottollier-Depois, Jean-François; Barquinero, Joan Francesc

    2016-01-01

    Most studies that aim to understand the interactions between different types of photon radiation and cellular DNA assume homogeneous cell irradiation, with all cells receiving the same amount of energy. The level of DNA damage is therefore generally determined by averaging it over the entire population of exposed cells. However, evaluating the molecular consequences of a stochastic phenomenon such as energy deposition of ionizing radiation by measuring only an average effect may not be sufficient for understanding some aspects of the cellular response to this radiation. The variance among the cells associated with this average effect may also be important for the behaviour of irradiated tissue. In this study, we accurately estimated the distribution of the number of radiation-induced γH2AX foci (RIF) per cell nucleus in a large population of endothelial cells exposed to 3 macroscopic doses of gamma rays from 60Co. The number of RIF varied significantly and reproducibly from cell to cell, with its relative standard deviation ranging from 36% to 18% depending on the macroscopic dose delivered. Interestingly, this relative cell-to-cell variability increased as the dose decreased, contrary to the mean RIF count per cell. This result shows that the dose effect, in terms of the number of DNA lesions indicated by RIF is not as simple as a purely proportional relation in which relative SD is constant with dose. To analyse the origins of this observed variability, we calculated the spread of the specific energy distribution for the different target volumes and subvolumes in which RIF can be generated. Variances, standard deviations and relative standard deviations all changed similarly from dose to dose for biological and calculated microdosimetric values. This similarity is an important argument that supports the hypothesis of the conservation of the association between the number of RIF per nucleus and the specific energy per DNA molecule. This comparison allowed us to

  4. Homotypic NK cell-to-cell communication controls cytokine responsiveness of innate immune NK cells

    PubMed Central

    Kim, Tae-Jin; Kim, Miju; Kim, Hye Mi; Lim, Seon Ah; Kim, Eun-Ok; Kim, Kwanghee; Song, Kwang Hoon; Kim, Jiyoung; Kumar, Vinay; Yee, Cassian; Doh, Junsang; Lee, Kyung-Mi

    2014-01-01

    While stationary organ cells are in continuous contact with neighboring cells, immune cells circulate throughout the body without an apparent requirement for cell-cell contact to persist in vivo. This study challenges current convention by demonstrating, both in vitro and in vivo, that innate immune NK cells can engage in homotypic NK-to-NK cell interactions for optimal survival, activation, and proliferation. Using a specialized cell-laden microwell approach, we discover that NK cells experiencing constant NK-to-NK contact exhibit a synergistic increase in activation status, cell proliferation, and anti-tumor function in response to IL-2 or IL-15. This effect is dependent on 2B4/CD48 ligation and an active cytoskeleton, resulting in amplification of IL-2 receptor signaling, enhanced CD122/CD132 colocalization, CD25 upregulation, and Stat3 activation. Conversely, ‘orphan' NK cells demonstrate no such synergy and fail to persist. Therefore, our data uncover the existence of homotypic cell-to-cell communication among mobile innate lymphocytes, which promotes functional synergy within the cytokine-rich microenvironment. PMID:25475707

  5. Cell-to-cell heterogeneity emerges as consequence of metabolic cooperation in a synthetic yeast community.

    PubMed

    Campbell, Kate; Vowinckel, Jakob; Ralser, Markus

    2016-09-01

    Cells that grow together respond heterogeneously to stress even when they are genetically similar. Metabolism, a key determinant of cellular stress tolerance, may be one source of this phenotypic heterogeneity, however, this relationship is largely unclear. We used self-establishing metabolically cooperating (SeMeCo) yeast communities, in which metabolic cooperation can be followed on the basis of genotype, as a model to dissect the role of metabolic cooperation in single-cell heterogeneity. Cells within SeMeCo communities showed to be highly heterogeneous in their stress tolerance, while the survival of each cell under heat or oxidative stress, was strongly determined by its metabolic specialization. This heterogeneity emerged for all metabolite exchange interactions studied (histidine, leucine, uracil, and methionine) as well as oxidant (H2 O2 , diamide) and heat stress treatments. In contrast, the SeMeCo community collectively showed to be similarly tolerant to stress as wild-type populations. Moreover, stress heterogeneity did not establish as sole consequence of metabolic genotype (auxotrophic background) of the single cell, but was observed only for cells that cooperated according to their metabolic capacity. We therefore conclude that phenotypic heterogeneity and cell to cell differences in stress tolerance are emergent properties when cells cooperate in metabolism.

  6. Microbial linguistics: perspectives and applications of microbial cell-to-cell communication.

    PubMed

    Mitchell, Robert J; Lee, Sung Kuk; Kim, Taesung; Ghim, Cheol-Min

    2011-01-01

    Inter-cellular communication via diffusible small molecules is a defining character not only of multicellular forms of life but also of single-celled organisms. A large number of bacterial genes are regulated by the change of chemical milieu mediated by the local population density of its own species or others. The cell density-dependent "autoinducer" molecules regulate the expression of those genes involved in genetic competence, biofilm formation and persistence, virulence, sporulation, bioluminescence, antibiotic production, and many others. Recent innovations in recombinant DNA technology and micro-/nano-fluidics systems render the genetic circuitry responsible for cell-to-cell communication feasible to and malleable via synthetic biological approaches. Here we review the current understanding of the molecular biology of bacterial intercellular communication and the novel experimental protocols and platforms used to investigate this phenomenon. A particular emphasis is given to the genetic regulatory circuits that provide the standard building blocks which constitute the syntax of the biochemical communication network. Thus, this review gives focus to the engineering principles necessary for rewiring bacterial chemo-communication for various applications, ranging from population-level gene expression control to the study of host-pathogen interactions.

  7. Malaria parasites form filamentous cell-to-cell connections during reproduction in the mosquito midgut.

    PubMed

    Rupp, Ingrid; Sologub, Ludmilla; Williamson, Kim C; Scheuermayer, Matthias; Reininger, Luc; Doerig, Christian; Eksi, Saliha; Kombila, Davy U; Frank, Matthias; Pradel, Gabriele

    2011-04-01

    Physical contact is important for the interaction between animal cells, but it can represent a major challenge for protists like malaria parasites. Recently, novel filamentous cell-cell contacts have been identified in different types of eukaryotic cells and termed nanotubes due to their morphological appearance. Nanotubes represent small dynamic membranous extensions that consist of F-actin and are considered an ancient feature evolved by eukaryotic cells to establish contact for communication. We here describe similar tubular structures in the malaria pathogen Plasmodium falciparum, which emerge from the surfaces of the forming gametes upon gametocyte activation in the mosquito midgut. The filaments can exhibit a length of > 100 μm and contain the F-actin isoform actin 2. They actively form within a few minutes after gametocyte activation and persist until the zygote transforms into the ookinete. The filaments originate from the parasite plasma membrane, are close ended and express adhesion proteins on their surfaces that are typically found in gametes, like Pfs230, Pfs48/45 or Pfs25, but not the zygote surface protein Pfs28. We show that these tubular structures represent long-distance cell-to-cell connections between sexual stage parasites and demonstrate that they meet the characteristics of nanotubes. We propose that malaria parasites utilize these adhesive "nanotubes" in order to facilitate intercellular contact between gametes during reproduction in the mosquito midgut.

  8. Cell-to-cell heterogeneity emerges as consequence of metabolic cooperation in a synthetic yeast community.

    PubMed

    Campbell, Kate; Vowinckel, Jakob; Ralser, Markus

    2016-09-01

    Cells that grow together respond heterogeneously to stress even when they are genetically similar. Metabolism, a key determinant of cellular stress tolerance, may be one source of this phenotypic heterogeneity, however, this relationship is largely unclear. We used self-establishing metabolically cooperating (SeMeCo) yeast communities, in which metabolic cooperation can be followed on the basis of genotype, as a model to dissect the role of metabolic cooperation in single-cell heterogeneity. Cells within SeMeCo communities showed to be highly heterogeneous in their stress tolerance, while the survival of each cell under heat or oxidative stress, was strongly determined by its metabolic specialization. This heterogeneity emerged for all metabolite exchange interactions studied (histidine, leucine, uracil, and methionine) as well as oxidant (H2 O2 , diamide) and heat stress treatments. In contrast, the SeMeCo community collectively showed to be similarly tolerant to stress as wild-type populations. Moreover, stress heterogeneity did not establish as sole consequence of metabolic genotype (auxotrophic background) of the single cell, but was observed only for cells that cooperated according to their metabolic capacity. We therefore conclude that phenotypic heterogeneity and cell to cell differences in stress tolerance are emergent properties when cells cooperate in metabolism. PMID:27312776

  9. Protease inhibitors effectively block cell-to-cell spread of HIV-1 between T cells

    PubMed Central

    2013-01-01

    Background The Human Immunodeficiency Virus type-1 (HIV-1) spreads by cell-free diffusion and by direct cell-to-cell transfer, the latter being a significantly more efficient mode of transmission. Recently it has been suggested that cell-to-cell spread may permit ongoing virus replication in the presence of antiretroviral therapy (ART) based on studies performed using Reverse Transcriptase Inhibitors (RTIs). Protease Inhibitors (PIs) constitute an important component of ART; however whether this class of inhibitors can suppress cell-to-cell transfer of HIV-1 is unexplored. Here we have evaluated the inhibitory effect of PIs during cell-to-cell spread of HIV-1 between T lymphocytes. Results Using quantitative assays in cell line and primary cell systems that directly measure the early steps of HIV-1 infection we find that the PIs Lopinavir and Darunavir are equally potent against both cell-free and cell-to-cell spread of HIV-1. We further show that a protease resistant mutant maintains its resistant phenotype during cell-to-cell spread and is transmitted more efficiently than wild-type virus in the presence of drug. By contrast we find that T cell-T cell spread of HIV-1 is 4–20 fold more resistant to inhibition by the RTIs Nevirapine, Zidovudine and Tenofovir. Notably, varying the ratio of infected and uninfected cells in co-culture impacted on the degree of inhibition, indicating that the relative efficacy of ART is dependent on the multiplicity of infection. Conclusions We conclude that if the variable effects of antiviral drugs on cell-to-cell virus dissemination of HIV-1 do indeed impact on viral replication and maintenance of viral reservoirs this is likely to be influenced by the antiviral drug class, since PIs appear particularly effective against both modes of HIV-1 spread. PMID:24364896

  10. AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells

    PubMed Central

    Saia, Marco; Termanini, Alberto; Rizzi, Nicoletta; Mazza, Massimiliano; Barbieri, Elisa; Valli, Debora; Ciana, Paolo; Gruszka, Alicja M.; Alcalay, Myriam

    2016-01-01

    The AML1/ETO fusion protein found in acute myeloid leukemias functions as a transcriptional regulator by recruiting co-repressor complexes to its DNA binding site. In order to extend the understanding of its role in preleukemia, we expressed AML1/ETO in a murine immortalized pluripotent hematopoietic stem/progenitor cell line, EML C1, and found that genes involved in functions such as cell-to-cell adhesion and cell motility were among the most significantly regulated as determined by RNA sequencing. In functional assays, AML1/ETO-expressing cells showed a decrease in adhesion to stromal cells, an increase of cell migration rate in vitro, and displayed an impairment in homing and engraftment in vivo upon transplantation into recipient mice. Our results suggest that AML1/ETO expression determines a more mobile and less adherent phenotype in preleukemic cells, therefore altering the interaction with the hematopoietic niche, potentially leading to the migration across the bone marrow barrier and to disease progression. PMID:27713544

  11. Differential effect of p7 inhibitors on hepatitis C virus cell-to-cell transmission☆

    PubMed Central

    Meredith, L.W.; Zitzmann, N.; McKeating, J.A.

    2013-01-01

    Inhibitors targeting the hepatitis C virus (HCV) encoded viroporin, p7 prevent virus release in vitro. HCV can transmit by cell-free particle infection of new target cells and via cell-to-cell dependent contact with limited exposure to the extracellular environment. The role of assembly inhibitors in preventing HCV transmission via these pathways has not been studied. We compared the efficacy of three published p7 inhibitors to inhibit cell-free and cell-to-cell transmission of two chimeric HCV strains encoding genotype 2 (GT2) or 5 (GT5) p7 using a recently developed single cycle co-culture assay. The inhibitors reduced the infectivity of extracellular GT2 and GT5 virus by 80–90% and GT2 virus cell-to-cell transmission by 50%. However, all of the p7 inhibitors had minimal effect on GT5 cell contact dependent transmission. Screening a wider panel of diverse viral genotypes demonstrated that p7 viroporin inhibitors were significantly more effective at blocking cell-free virus than cell-to-cell transmission. These results suggest an altered assembly or trafficking of cell-to-cell transmitted compared to secreted virus. These observations have important implications for the validation, therapeutic design and testing of HCV assembly inhibitors. PMID:24157306

  12. Role of Exosome Shuttle RNA in Cell-to-Cell Communication.

    PubMed

    Zhang, Wei; Peng, Peng; Shen, Keng

    2016-08-01

    There are several ways that transpire in cell-to-cell communication,with or without cell contact. Exosomes play an important role in cell-to-cell communication,which do not need cell contact,as that can result in a relatively long-distance influence. Exosome contains RNA components including mRNA and micro-RNA,which are protected by exosomes rigid membranes. This allows those components be passed long distance through the circulatory system. The mRNA components are far different from their donor cells,and the micro-RNA components may reflect the cell they originated. In this article we review the role of exosomes in cell-to-cell communication,with particular focus on their potentials in both diagnostic and therapeutic applications. PMID:27594165

  13. Broadly neutralizing antibodies that inhibit HIV-1 cell to cell transmission

    PubMed Central

    Malbec, Marine; Porrot, Françoise; Rua, Rejane; Horwitz, Joshua; Klein, Florian; Halper-Stromberg, Ari; Scheid, Johannes F.; Eden, Caroline; Mouquet, Hugo; Nussenzweig, Michel C.

    2013-01-01

    The neutralizing activity of anti–HIV-1 antibodies is typically measured in assays where cell-free virions enter reporter cell lines. However, HIV-1 cell to cell transmission is a major mechanism of viral spread, and the effect of the recently described broadly neutralizing antibodies (bNAbs) on this mode of transmission remains unknown. Here we identify a subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes. These antibodies target either the CD4-binding site (NIH45-46 and 3BNC60) or the glycan/V3 loop (10-1074 and PGT121) on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. These antibodies accumulate at virological synapses and impair the clustering and fusion of infected and target cells and the transfer of viral material to uninfected T cells. In addition, they block viral cell to cell transmission to plasmacytoid DCs and thereby interfere with type-I IFN production. Thus, only a subset of bNAbs can efficiently prevent HIV-1 cell to cell transmission, and this property should be considered an important characteristic defining antibody potency for therapeutic or prophylactic antiviral strategies. PMID:24277152

  14. The Arabidopsis synaptotagmin SYTA regulates the cell-to-cell movement of diverse plant viruses

    PubMed Central

    Uchiyama, Asako; Shimada-Beltran, Harumi; Levy, Amit; Zheng, Judy Y.; Javia, Parth A.; Lazarowitz, Sondra G.

    2014-01-01

    Synaptotagmins are a large gene family in animals that have been extensively characterized due to their role as calcium sensors to regulate synaptic vesicle exocytosis and endocytosis in neurons, and dense core vesicle exocytosis for hormone secretion from neuroendocrine cells. Thought to be exclusive to animals, synaptotagmins have recently been characterized in Arabidopsis thaliana, in which they comprise a five gene family. Using infectivity and leaf-based functional assays, we have shown that Arabidopsis SYTA regulates endocytosis and marks an endosomal vesicle recycling pathway to regulate movement protein-mediated trafficking of the Begomovirus Cabbage leaf curl virus (CaLCuV) and the Tobamovirus Tobacco mosaic virus (TMV) through plasmodesmata (Lewis and Lazarowitz, 2010). To determine whether SYTA has a central role in regulating the cell-to-cell trafficking of a wider range of diverse plant viruses, we extended our studies here to examine the role of SYTA in the cell-to-cell movement of additional plant viruses that employ different modes of movement, namely the Potyvirus Turnip mosaic virus (TuMV), the Caulimovirus Cauliflower mosaic virus (CaMV) and the Tobamovirus Turnip vein clearing virus (TVCV), which in contrast to TMV does efficiently infect Arabidopsis. We found that both TuMV and TVCV systemic infection, and the cell-to-cell trafficking of the their movement proteins, were delayed in the Arabidopsis Col-0 syta-1 knockdown mutant. In contrast, CaMV systemic infection was not inhibited in syta-1. Our studies show that SYTA is a key regulator of plant virus intercellular movement, being necessary for the ability of diverse cell-to-cell movement proteins encoded by Begomoviruses (CaLCuV MP), Tobamoviruses (TVCV and TMV 30K protein) and Potyviruses (TuMV P3N-PIPO) to alter PD and thereby mediate virus cell-to-cell spread. PMID:25414709

  15. The Arabidopsis synaptotagmin SYTA regulates the cell-to-cell movement of diverse plant viruses.

    PubMed

    Uchiyama, Asako; Shimada-Beltran, Harumi; Levy, Amit; Zheng, Judy Y; Javia, Parth A; Lazarowitz, Sondra G

    2014-01-01

    Synaptotagmins are a large gene family in animals that have been extensively characterized due to their role as calcium sensors to regulate synaptic vesicle exocytosis and endocytosis in neurons, and dense core vesicle exocytosis for hormone secretion from neuroendocrine cells. Thought to be exclusive to animals, synaptotagmins have recently been characterized in Arabidopsis thaliana, in which they comprise a five gene family. Using infectivity and leaf-based functional assays, we have shown that Arabidopsis SYTA regulates endocytosis and marks an endosomal vesicle recycling pathway to regulate movement protein-mediated trafficking of the Begomovirus Cabbage leaf curl virus (CaLCuV) and the Tobamovirus Tobacco mosaic virus (TMV) through plasmodesmata (Lewis and Lazarowitz, 2010). To determine whether SYTA has a central role in regulating the cell-to-cell trafficking of a wider range of diverse plant viruses, we extended our studies here to examine the role of SYTA in the cell-to-cell movement of additional plant viruses that employ different modes of movement, namely the Potyvirus Turnip mosaic virus (TuMV), the Caulimovirus Cauliflower mosaic virus (CaMV) and the Tobamovirus Turnip vein clearing virus (TVCV), which in contrast to TMV does efficiently infect Arabidopsis. We found that both TuMV and TVCV systemic infection, and the cell-to-cell trafficking of the their movement proteins, were delayed in the Arabidopsis Col-0 syta-1 knockdown mutant. In contrast, CaMV systemic infection was not inhibited in syta-1. Our studies show that SYTA is a key regulator of plant virus intercellular movement, being necessary for the ability of diverse cell-to-cell movement proteins encoded by Begomoviruses (CaLCuV MP), Tobamoviruses (TVCV and TMV 30K protein) and Potyviruses (TuMV P3N-PIPO) to alter PD and thereby mediate virus cell-to-cell spread. PMID:25414709

  16. Collective dynamics of genetic oscillators with cell-to-cell communication: a study case of signal integration

    NASA Astrophysics Data System (ADS)

    Yi, Q. Z.; Zhang, J. J.; Yuan, Z. J.; Zhou, T. S.

    2010-06-01

    This paper investigates the effect of integration of intracellular and extracellular signals on collective dynamics based on a multicellular system with cell-to-cell communication. Using a mathematical model of genetic repressilators coupled to quorum sensing, we show that the changes in parameters of a certain kind of cis-regulatory input function that quantifies the signal integration can lead to the change of coupling type from phase-attractive to phase-repulsive coupling or vice versa. Consequently, the multicellular system can exhibit, in both coupling cases, different collective behaviors in terms of synchronization and clustering. We give a general method of determining coupling type, elucidate the mechanism of generating these phenomena and present a criterion for stability of cluster states, mainly by analyzing phase interaction functions.

  17. Interference of bacterial cell-to-cell communication: a new concept of antimicrobial chemotherapy breaks antibiotic resistance

    PubMed Central

    Hirakawa, Hidetada; Tomita, Haruyoshi

    2013-01-01

    Bacteria use a cell-to-cell communication activity termed “quorum sensing” to coordinate group behaviors in a cell density dependent manner. Quorum sensing influences the expression profile of diverse genes, including antibiotic tolerance and virulence determinants, via specific chemical compounds called “autoinducers”. During quorum sensing, Gram-negative bacteria typically use an acylated homoserine lactone (AHL) called autoinducer 1. Since the first discovery of quorum sensing in a marine bacterium, it has been recognized that more than 100 species possess this mechanism of cell-to-cell communication. In addition to being of interest from a biological standpoint, quorum sensing is a potential target for antimicrobial chemotherapy. This unique concept of antimicrobial control relies on reducing the burden of virulence rather than killing the bacteria. It is believed that this approach will not only suppress the development of antibiotic resistance, but will also improve the treatment of refractory infections triggered by multi-drug resistant pathogens. In this paper, we review and track recent progress in studies on AHL inhibitors/modulators from a biological standpoint. It has been discovered that both natural and synthetic compounds can disrupt quorum sensing by a variety of means, such as jamming signal transduction, inhibition of signal production and break-down and trapping of signal compounds. We also focus on the regulatory elements that attenuate quorum sensing activities and discuss their unique properties. Understanding the biological roles of regulatory elements might be useful in developing inhibitor applications and understanding how quorum sensing is controlled. PMID:23720655

  18. Myosin-Va-dependent cell-to-cell transfer of RNA from Schwann cells to axons.

    PubMed

    Sotelo, José R; Canclini, Lucía; Kun, Alejandra; Sotelo-Silveira, José R; Xu, Lei; Wallrabe, Horst; Calliari, Aldo; Rosso, Gonzalo; Cal, Karina; Mercer, John A

    2013-01-01

    To better understand the role of protein synthesis in axons, we have identified the source of a portion of axonal RNA. We show that proximal segments of transected sciatic nerves accumulate newly-synthesized RNA in axons. This RNA is synthesized in Schwann cells because the RNA was labeled in the complete absence of neuronal cell bodies both in vitro and in vivo. We also demonstrate that the transfer is prevented by disruption of actin and that it fails to occur in the absence of myosin-Va. Our results demonstrate cell-to-cell transfer of RNA and identify part of the mechanism required for transfer. The induction of cell-to-cell RNA transfer by injury suggests that interventions following injury or degeneration, particularly gene therapy, may be accomplished by applying them to nearby glial cells (or implanted stem cells) at the site of injury to promote regeneration.

  19. Multiploid inheritance of HIV-1 during cell-to-cell infection.

    PubMed

    Del Portillo, Armando; Tripodi, Joseph; Najfeld, Vesna; Wodarz, Dominik; Levy, David N; Chen, Benjamin K

    2011-07-01

    During cell-to-cell transmission of human immunodeficiency virus type 1 (HIV-1), many viral particles can be simultaneously transferred from infected to uninfected CD4 T cells through structures called virological synapses (VS). Here we directly examine how cell-free and cell-to-cell infections differ from infections initiated with cell-free virus in the number of genetic copies that are transmitted from one generation to the next, i.e., the genetic inheritance. Following exposure to HIV-1-expressing cells, we show that target cells with high viral uptake are much more likely to become infected. Using T cells that coexpress distinct fluorescent HIV-1 variants, we show that multiple copies of HIV-1 can be cotransmitted across a single VS. In contrast to cell-free HIV-1 infection, which titrates with Poisson statistics, the titration of cell-associated HIV-1 to low rates of overall infection generates a constant fraction of the newly infected cells that are cofluorescent. Triple infection was also readily detected when cells expressing three fluorescent viruses were used as donor cells. A computational model and a statistical model are presented to estimate the degree to which cofluorescence underestimates coinfection frequency. Lastly, direct detection of HIV-1 proviruses using fluorescence in situ hybridization confirmed that significantly more HIV-1 DNA copies are found in primary T cells infected with cell-associated virus than in those infected with cell-free virus. Together, the data suggest that multiploid inheritance is common during cell-to-cell HIV-1 infection. From this study, we suggest that cell-to-cell infection may explain the high copy numbers of proviruses found in infected cells in vivo and may provide a mechanism through which HIV preserves sequence heterogeneity in viral quasispecies through genetic complementation.

  20. Inward rectifying potassium channels facilitate cell-to-cell communication in hamster retractor muscle feed arteries.

    PubMed

    Jantzi, Micaela C; Brett, Suzanne E; Jackson, William F; Corteling, Randolph; Vigmond, Edward J; Welsh, Donald G

    2006-09-01

    This study examined whether inward rectifying K+ (KIR) channels facilitate cell-to-cell communication along skeletal muscle resistance arteries. With the use of feed arteries from the hamster retractor muscle, experiments examined whether KIR channels were functionally expressed and whether channel blockade attenuated the conduction of acetylcholine-induced vasodilation, an index of cell-to-cell communication. Consistent with KIR channel expression, this study observed the following: 1) a sustained Ba2+-sensitive, K+-induced dilation in preconstricted arteries; 2) a Ba2+-sensitive inwardly rectifying K+ current in arterial smooth muscle cells; and 3) KIR2.1 and KIR2.2 expression in the smooth muscle layer of these arteries. It was subsequently shown that the discrete application of acetylcholine elicits a vasodilation that conducts with limited decay along the feed artery wall. In the presence of 100 microM Ba2+, the local and conducted response to acetylcholine was attenuated, a finding consistent with a role for KIR in facilitating cell-to-cell communication. A computational model of vascular communication accurately predicted these observations. Control experiments revealed that in contrast to Ba2+, ATP-sensitive- and large-conductance Ca2+ activated-K+ channel inhibitors had no effect on the local or conducted vasodilatory response to acetylcholine. We conclude that smooth muscle KIR channels play a key role in facilitating cell-to-cell communication along skeletal muscle resistance arteries. We attribute this facilitation to the intrinsic property of negative slope conductance, a biophysical feature common to KIR2.1- and 2.2-containing channels, which enables them to increase their activity as a cell hyperpolarizes. PMID:16617135

  1. Antiretroviral Agents Effectively Block HIV Replication after Cell-to-Cell Transfer

    PubMed Central

    Permanyer, Marc; Ballana, Ester; Ruiz, Alba; Badia, Roger; Riveira-Munoz, Eva; Gonzalo, Encarna; Clotet, Bonaventura

    2012-01-01

    Cell-to-cell transmission of HIV has been proposed as a mechanism contributing to virus escape to the action of antiretrovirals and a mode of HIV persistence during antiretroviral therapy. Here, cocultures of infected HIV-1 cells with primary CD4+ T cells or lymphoid cells were used to evaluate virus transmission and the effect of known antiretrovirals. Transfer of HIV antigen from infected to uninfected cells was resistant to the reverse transcriptase inhibitors (RTIs) zidovudine (AZT) and tenofovir, but was blocked by the attachment inhibitor IgGb12. However, quantitative measurement of viral DNA production demonstrated that all anti-HIV agents blocked virus replication with similar potency to cell-free virus infections. Cell-free and cell-associated infections were equally sensitive to inhibition of viral replication when HIV-1 long terminal repeat (LTR)-driven green fluorescent protein (GFP) expression in target cells was measured. However, detection of GFP by flow cytometry may incorrectly estimate the efficacy of antiretrovirals in cell-associated virus transmission, due to replication-independent Tat-mediated LTR transactivation as a consequence of cell-to-cell events that did not occur in short-term (48-h) cell-free virus infections. In conclusion, common markers of virus replication may not accurately correlate and measure infectivity or drug efficacy in cell-to-cell virus transmission. When accurately quantified, active drugs blocked proviral DNA and virus replication in cell-to-cell transmission, recapitulating the efficacy of antiretrovirals in cell-free virus infections and in vivo. PMID:22696642

  2. To bet or not to bet: deciphering cell to cell variation in protozoan infections.

    PubMed

    Seco-Hidalgo, Víctor; Osuna, Antonio; Pablos, Luis Miguel De

    2015-08-01

    Some of the most crucial phenotypic aspects of parasites, such as an antigen-coated surface, parasite sexual differentiation, virulence, and drug resistance, rely on adaptive plasticity and/or stochastic events. At a population level, cell to cell variability represents an avenue for rapid response to drastic changes in the environment. Single cell approaches can be used to unravel the different strategies used by parasites to survive in the context of regulated transcriptional control (apicomplexa) or in its absence (kinetoplastids).

  3. Regulated cell-to-cell variation in a cell-fate decision system.

    PubMed

    Colman-Lerner, Alejandro; Gordon, Andrew; Serra, Eduard; Chin, Tina; Resnekov, Orna; Endy, Drew; Pesce, C Gustavo; Brent, Roger

    2005-09-29

    Here we studied the quantitative behaviour and cell-to-cell variability of a prototypical eukaryotic cell-fate decision system, the mating pheromone response pathway in yeast. We dissected and measured sources of variation in system output, analysing thousands of individual, genetically identical cells. Only a small proportion of total cell-to-cell variation is caused by random fluctuations in gene transcription and translation during the response ('expression noise'). Instead, variation is dominated by differences in the capacity of individual cells to transmit signals through the pathway ('pathway capacity') and to express proteins from genes ('expression capacity'). Cells with high expression capacity express proteins at a higher rate and increase in volume more rapidly. Our results identify two mechanisms that regulate cell-to-cell variation in pathway capacity. First, the MAP kinase Fus3 suppresses variation at high pheromone levels, while the MAP kinase Kss1 enhances variation at low pheromone levels. Second, pathway capacity and expression capacity are negatively correlated, suggesting a compensatory mechanism that allows cells to respond more precisely to pheromone in the presence of a large variation in expression capacity. PMID:16170311

  4. Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa.

    PubMed

    Pesci, E C; Milbank, J B; Pearson, J P; McKnight, S; Kende, A S; Greenberg, E P; Iglewski, B H

    1999-09-28

    Numerous species of bacteria use an elegant regulatory mechanism known as quorum sensing to control the expression of specific genes in a cell-density dependent manner. In Gram-negative bacteria, quorum sensing systems function through a cell-to-cell signal molecule (autoinducer) that consists of a homoserine lactone with a fatty acid side chain. Such is the case in the opportunistic human pathogen Pseudomonas aeruginosa, which contains two quorum sensing systems (las and rhl) that operate via the autoinducers, N-(3-oxododecanoyl)-L-homoserine lactone and N-butyryl-L-homoserine lactone. The study of these signal molecules has shown that they bind to and activate transcriptional activator proteins that specifically induce numerous P. aeruginosa virulence genes. We report here that P. aeruginosa produces another signal molecule, 2-heptyl-3-hydroxy-4-quinolone, which has been designated as the Pseudomonas quinolone signal. It was found that this unique cell-to-cell signal controlled the expression of lasB, which encodes for the major virulence factor, LasB elastase. We also show that the synthesis and bioactivity of Pseudomonas quinolone signal were mediated by the P. aeruginosa las and rhl quorum sensing systems, respectively. The demonstration that 2-heptyl-3-hydroxy-4-quinolone can function as an intercellular signal sheds light on the role of secondary metabolites and shows that P. aeruginosa cell-to-cell signaling is not restricted to acyl-homoserine lactones.

  5. [Research in elementary particles and interactions]. Technical progress report

    SciTech Connect

    Adair, R.; Sandweiss, J.; Schmidt, M.

    1992-05-01

    Research of the Yale University groups in the areas of elementary particles and their interactions are outlined. Work on the following topics is reported: development of CDF trigger system; SSC detector development; study of heavy flavors at TPL; search for composite objects produced in relativistic heavy-ion collisions; high-energy polarized lepton-nucleon scattering; rare K{sup +} decays; unpolarized high-energy muon scattering; muon anomalous magnetic moment; theoretical high-energy physics including gauge theories, symmetry breaking, string theory, and gravitation theory; study of e{sup +}e{sup {minus}} interactions with the SLD detector at SLAC; and the production and decay of particles containing charm and beauty quarks.

  6. Progress in Long Scale Length Laser-Plasma Interactions

    SciTech Connect

    Glenzer, S H; Arnold, P; Bardsley, G; Berger, R L; Bonanno, G; Borger, T; Bower, D E; Bowers, M; Bryant, R; Buckman, S; Burkhart, S C; Campbell, K; Chrisp, M P; Cohen, B I; Constantin, G; Cooper, F; Cox, J; Dewald, E; Divol, L; Dixit, S; Duncan, J; Eder, D; Edwards, J; Erbert, G; Felker, B; Fornes, J; Frieders, G; Froula, D H; Gardner, S D; Gates, C; Gonzalez, M; Grace, S; Gregori, G; Greenwood, A; Griffith, R; Hall, T; Hammel, B A; Haynam, C; Heestand, G; Henesian, M; Hermes, G; Hinkel, D; Holder, J; Holdner, F; Holtmeier, G; Hsing, W; Huber, S; James, T; Johnson, S; Jones, O S; Kalantar, D; Kamperschroer, J H; Kauffman, R; Kelleher, T; Knight, J; Kirkwood, R K; Kruer, W L; Labiak, W; Landen, O L; Langdon, A B; Langer, S; Latray, D; Lee, A; Lee, F D; Lund, D; MacGowan, B; Marshall, S; McBride, J; McCarville, T; McGrew, L; Mackinnon, A J; Mahavandi, S; Manes, K; Marshall, C; Mertens, E; Meezan, N; Miller, G; Montelongo, S; Moody, J D; Moses, E; Munro, D; Murray, J; Neumann, J; Newton, M; Ng, E; Niemann, C; Nikitin, A; Opsahl, P; Padilla, E; Parham, T; Parrish, G; Petty, C; Polk, M; Powell, C; Reinbachs, I; Rekow, V; Rinnert, R; Riordan, B; Rhodes, M

    2003-11-11

    The first experiments on the National Ignition Facility (NIF) have employed the first four beams to measure propagation and laser backscattering losses in large ignition-size plasmas. Gas-filled targets between 2 mm and 7 mm length have been heated from one side by overlapping the focal spots of the four beams from one quad operated at 351 nm (3{omega}) with a total intensity of 2 x 10{sup 15} W cm{sup -2}. The targets were filled with 1 atm of CO{sub 2} producing of up to 7 mm long homogeneously heated plasmas with densities of n{sub e} = 6 x 10{sup 20} cm{sup -3} and temperatures of T{sub e} = 2 keV. The high energy in a NIF quad of beams of 16kJ, illuminating the target from one direction, creates unique conditions for the study of laser plasma interactions at scale lengths not previously accessible. The propagation through the large-scale plasma was measured with a gated x-ray imager that was filtered for 3.5 keV x rays. These data indicate that the beams interact with the full length of this ignition-scale plasma during the last {approx}1 ns of the experiment. During that time, the full aperture measurements of the stimulated Brillouin scattering and stimulated Raman scattering show scattering into the four focusing lenses of 6% for the smallest length ({approx}2 mm). increasing to 12% for {approx}7 mm. These results demonstrate the NIF experimental capabilities and further provide a benchmark for three-dimensional modeling of the laser-plasma interactions at ignition-size scale lengths.

  7. Interaction of tumor cells and lymphatic vessels in cancer progression.

    PubMed

    Alitalo, A; Detmar, M

    2012-10-18

    Metastatic spread of cancer through the lymphatic system affects hundreds of thousands of patients yearly. Growth of new lymphatic vessels, lymphangiogenesis, is activated in cancer and inflammation, but is largely inactive in normal physiology, and therefore offers therapeutic potential. Key mediators of lymphangiogenesis have been identified in developmental studies. During embryonic development, lymphatic endothelial cells derive from the blood vascular endothelium and differentiate under the guidance of lymphatic-specific regulators, such as the prospero homeobox 1 transcription factor. Vascular endothelial growth factor-C (VEGF-C) and VEGF receptor 3 signaling are essential for the further development of lymphatic vessels and therefore they provide a promising target for inhibition of tumor lymphangiogenesis. Lymphangiogenesis is important for the progression of solid tumors as shown for melanoma and breast cancer. Tumor cells may use chemokine gradients as guidance cues and enter lymphatic vessels through intercellular openings between endothelial cell junctions or, possibly, by inducing larger discontinuities in the endothelial cell layer. Tumor-draining sentinel lymph nodes show enhanced lymphangiogenesis even before cancer metastasis and they may function as a permissive 'lymphovascular niche' for the survival of metastatic cells. Although our current knowledge indicates that the development of anti-lymphangiogenic therapies may be beneficial for the treatment of cancer patients, several open questions remain with regard to the frequency, mechanisms and biological importance of lymphatic metastases.

  8. Cell-to-cell distances between tumor-infiltrating inflammatory cells have the potential to distinguish functionally active from suppressed inflammatory cells.

    PubMed

    Nagl, S; Haas, M; Lahmer, G; Büttner-Herold, M; Grabenbauer, G G; Fietkau, R; Distel, L V

    2016-05-01

    Beyond their mere presence, the distribution pattern of inflammatory cells is of special interest. Our hypothesis was that random distribution may be a clear indicator of being non-functional as a consequence of lack of interaction. Here, we have assessed the implication of cell-to-cell distances among inflammatory cells in anal squamous cell carcinoma and a possible association with survival data. Thirty-eight patients suffering from anal carcinoma were studied using tissue microarrays, double staining immunohistochemistry, whole slide scanning and image analysis software. Therapy consisted of concurrent radiochemotherapy. Numbers of stromal and intraepithelial tumor-infiltrating inflammatory cells (TIC) and the distances between cells were quantified. Double-staining of FoxP3(+) cells with either CD8(+), CD1a(+) or CD20(+) cells was performed. Measured cell-to-cell distances were compared to computer simulated cell-to-cell distances leading to the assumption of non-randomly distributed and therefore functional immune cells. Intraepithelial CD1a(+) and CD20(+) cells were randomly distributed and therefore regarded as non-functional. In contrary, stromal CD20(+) cells had a non-random distribution pattern. A non-random distance between CD20(+) and FoxP3(+) cells was associated with a clearly unfavorable outcome. Measured distances between FoxP3(+) cells were distinctly shorter than expected and indicate a functional active state of the regulatory T cells (Treg). Analysis of cell-to-cell distances between TIC has the potential to distinguish between suppressed non-functional and functionally active inflammatory cells. We conclude that in this tumor model most of the CD1a(+) cells are non-functional as are the intraepithelial CD20(+) cells, while stromal CD20(+) cells and FoxP3(+) cells are functional cells. PMID:27467940

  9. Cell-to-Cell Transmission of HIV-1 Is Required to Trigger Pyroptotic Death of Lymphoid-Tissue-Derived CD4 T Cells.

    PubMed

    Galloway, Nicole L K; Doitsh, Gilad; Monroe, Kathryn M; Yang, Zhiyuan; Muñoz-Arias, Isa; Levy, David N; Greene, Warner C

    2015-09-01

    The progressive depletion of CD4 T cells underlies clinical progression to AIDS in untreated HIV-infected subjects. Most dying CD4 T cells correspond to resting nonpermissive cells residing in lymphoid tissues. Death is due to an innate immune response against the incomplete cytosolic viral DNA intermediates accumulating in these cells. The viral DNA is detected by the IFI16 sensor, leading to inflammasome assembly, caspase-1 activation, and the induction of pyroptosis, a highly inflammatory form of programmed cell death. We now show that cell-to-cell transmission of HIV is obligatorily required for activation of this death pathway. Cell-free HIV-1 virions, even when added in large quantities, fail to activate pyroptosis. These findings underscore the infected CD4 T cells as the major killing units promoting progression to AIDS and highlight a previously unappreciated role for the virological synapse in HIV pathogenesis.

  10. Computing the threshold of the influence of intercellular nanotubes on cell-to-cell communication integrity

    NASA Astrophysics Data System (ADS)

    Mihailović, Dragutin T.; Kostić, Vladimir R.; Balaž, Igor; Kapor, Darko

    2016-10-01

    We examine the threshold of the influence of the tunneling nanotubes (TNTs) on the cell-to-cell communication integrity. A deterministic model is introduced with the Michaelis-Menten dynamics and the intercellular exchange of substance. The influence of TNTs are considered as a functional perturbation of the main communication and treated as the matrix nearness problems. We analyze communication integrity in terms of the \\emph{pseudospectra} of the exchange, to find the \\emph{distance to instability}. The threshold of TNTs influence is computed for Newman-Gastner and Erd\\H{o}s-R\\'enyi gap junction (GJ) networks.

  11. Global Dynamics of a Virus Dynamical Model with Cell-to-Cell Transmission and Cure Rate

    PubMed Central

    Zhang, Tongqian; Meng, Xinzhu; Zhang, Tonghua

    2015-01-01

    The cure effect of a virus model with both cell-to-cell transmission and cell-to-virus transmission is studied. By the method of next generation matrix, the basic reproduction number is obtained. The locally asymptotic stability of the virus-free equilibrium and the endemic equilibrium is considered by investigating the characteristic equation of the model. The globally asymptotic stability of the virus-free equilibrium is proved by constructing suitable Lyapunov function, and the sufficient condition for the globally asymptotic stability of the endemic equilibrium is obtained by constructing suitable Lyapunov function and using LaSalle invariance principal. PMID:26504489

  12. Random Walk Model for Cell-To-Cell Misalignments in Accelerator Structures

    SciTech Connect

    Stupakov, Gennady

    2000-09-08

    Due to manufacturing and construction errors, cells in accelerator structures can be misaligned relative to each other. As a consequence, the beam generates a transverse wakefield even when it passes through the structure on axis. The most important effect is the long-range transverse wakefield that deflects the bunches and causes growth of the bunch train projected emittance. In this paper, the effect of the cell-to-cell misalignments is evaluated using a random walk model that assumes that each cell is shifted by a random step relative to the previous one. The model is compared with measurements of a few accelerator structures.

  13. Host endoplasmic reticulum COPII proteins control cell-to-cell spread of the bacterial pathogen Listeria monocytogenes

    PubMed Central

    Gianfelice, Antonella; Le, Phuong H.B.; Rigano, Luciano A.; Saila, Susan; Dowd, Georgina C.; McDivitt, Tina; Bhattacharya, Nilakshee; Hong, Wanjin; Stagg, Scott M.; Ireton, Keith

    2015-01-01

    SUMMARY Listeria monocytogenes is a food-borne pathogen that uses actin–dependent motility to spread between human cells. Cell-to-cell spread involves the formation by motile bacteria of plasma membrane-derived structures termed ‘protrusions’. In cultured enterocytes, the secreted Listeria protein InlC promotes protrusion formation by binding and inhibiting the human scaffolding protein Tuba. Here we demonstrate that protrusions are controlled by human COPII components that direct trafficking from the endoplasmic reticulum. Co-precipitation experiments indicated that the COPII proteins Sec31A and Sec13 interact directly with a Src Homology 3 domain in Tuba. This interaction was antagonized by InlC. Depletion of Sec31A or Sec13 restored normal protrusion formation to a Listeria mutant lacking inlC, without affecting spread of wild-type bacteria. Genetic impairment of the COPII component Sar1 or treatment of cells with brefeldin A affected protrusions similarly to Sec31A or Sec13 depletion. These findings indicated that InlC relieves a host-mediated restriction of Listeria spread otherwise imposed by COPII. Inhibition of Sec31A, Sec13, or Sar1 or brefeldin A treatment also perturbed the structure of cell-cell junctions. Collectively, these findings demonstrate an important role for COPII in controlling Listeria spread. We propose that COPII may act by delivering host proteins that generate tension at cell junctions. PMID:25529574

  14. Human metapneumovirus Induces Reorganization of the Actin Cytoskeleton for Direct Cell-to-Cell Spread

    PubMed Central

    El Najjar, Farah; Cifuentes-Muñoz, Nicolás; Zhu, Haining; Buchholz, Ursula J.; Moncman, Carole L.; Dutch, Rebecca Ellis

    2016-01-01

    Paramyxovirus spread generally involves assembly of individual viral particles which then infect target cells. We show that infection of human bronchial airway cells with human metapneumovirus (HMPV), a recently identified paramyxovirus which causes significant respiratory disease, results in formation of intercellular extensions and extensive networks of branched cell-associated filaments. Formation of these structures is dependent on actin, but not microtubule, polymerization. Interestingly, using a co-culture assay we show that conditions which block regular infection by HMPV particles, including addition of neutralizing antibodies or removal of cell surface heparan sulfate, did not prevent viral spread from infected to new target cells. In contrast, inhibition of actin polymerization or alterations to Rho GTPase signaling pathways significantly decreased cell-to-cell spread. Furthermore, viral proteins and viral RNA were detected in intercellular extensions, suggesting direct transfer of viral genetic material to new target cells. While roles for paramyxovirus matrix and fusion proteins in membrane deformation have been previously demonstrated, we show that the HMPV phosphoprotein extensively co-localized with actin and induced formation of cellular extensions when transiently expressed, supporting a new model in which a paramyxovirus phosphoprotein is a key player in assembly and spread. Our results reveal a novel mechanism for HMPV direct cell-to-cell spread and provide insights into dissemination of respiratory viruses. PMID:27683250

  15. Apolipoprotein E, but Not Apolipoprotein B, Is Essential for Efficient Cell-to-Cell Transmission of Hepatitis C Virus

    PubMed Central

    Gondar, Virgínia; Molina-Jiménez, Francisca; Hishiki, Takayuki; García-Buey, Luisa; Koutsoudakis, George; Shimotohno, Kunitada

    2015-01-01

    ABSTRACT Hepatitis C virus (HCV) infects hepatocytes through two different routes: (i) cell-free particle diffusion followed by engagement with specific cellular receptors and (ii) cell-to-cell direct transmission mediated by mechanisms not well defined yet. HCV exits host cells in association with very-low-density lipoprotein (VLDL) components. VLDL particles contain apolipoproteins B (ApoB) and E (ApoE), which are required for viral assembly and/or infectivity. Based on these precedents, we decided to study whether these VLDL components participate in HCV cell-to-cell transmission in vitro. We observed that cell-to-cell viral spread was compromised after ApoE interference in donor but not in acceptor cells. In contrast, ApoB knockdown in either donor or acceptor cells did not impair cell-to-cell viral transmission. Interestingly, ApoB participated in the assembly of cell-free infective virions, suggesting a differential regulation of cell-to-cell and cell-free HCV infection. This study identifies host-specific factors involved in these distinct routes of infection that may unveil new therapeutic targets and advance our understanding of HCV pathogenesis. IMPORTANCE This work demonstrates that cell-to-cell transmission of HCV depends on ApoE but not ApoB. The data also indicate that ApoB is required for the assembly of cell-free infective particles, strongly suggesting the existence of mechanisms involving VLDL components that differentially regulate cell-free and cell-to-cell HCV transmission. These data clarify some of the questions regarding the role of VLDL in HCV pathogenesis and the transmission of the virus cell to cell as a possible mechanism of immune evasion and open the door to therapeutic intervention. PMID:26202245

  16. Maternal environment interacts with modifier genes to influence progression of nephrotic syndrome.

    PubMed

    Ratelade, Julien; Lavin, Tiphaine Aguirre; Muda, Andrea Onetti; Morisset, Ludivine; Mollet, Géraldine; Boyer, Olivia; Chen, Deborah S; Henger, Anna; Kretzler, Matthias; Hubner, Norbert; Théry, Clotilde; Gubler, Marie-Claire; Montagutelli, Xavier; Antignac, Corinne; Esquivel, Ernie L

    2008-08-01

    Mutations in the NPHS2 gene, which encodes podocin, are responsible for some cases of sporadic and familial autosomal recessive steroid-resistant nephrotic syndrome. Inter- and intrafamilial variability in the progression of renal disease among patients bearing NPHS2 mutations suggests a potential role for modifier genes. Using a mouse model in which the podocin gene is constitutively inactivated, we sought to identify genetic determinants of the development and progression of renal disease as a result of the nephrotic syndrome. We report that the evolution of renal disease as a result of nephrotic syndrome in Nphs2-null mice depends on genetic background. Furthermore, the maternal environment significantly interacts with genetic determinants to modify survival and progression of renal disease. Quantitative trait locus mapping suggested that these genetic determinants may be encoded for by genes on the distal end of chromosome 3, which are linked to proteinuria, and on the distal end of chromosome 7, which are linked to a composite trait of urea, creatinine, and potassium. These loci demonstrate epistatic interactions with other chromosomal regions, highlighting the complex genetics of renal disease progression. In summary, constitutive inactivation of podocin models the complex interactions between maternal and genetically determined factors on the progression of renal disease as a result of nephrotic syndrome in mice.

  17. Inferring alterations in cell-to-cell communication in HER2+ breast cancer using secretome profiling of three cell models

    PubMed Central

    Klinke, David J.; Kulkarni, Yogesh M.; Wu, Yueting; Byrne-Hoffman, Christina

    2015-01-01

    Challenges in demonstrating durable clinical responses to molecular-targeted therapies has sparked a re-emergence in viewing cancer as an evolutionary process. In somatic evolution, cellular variants are introduced through a random process of somatic mutation and are selected for improved fitness through a competition for survival. In contrast to Darwinian evolution, cellular variants that are retained may directly alter the fitness competition. If cell-to-cell communication is important for selection, the biochemical cues secreted by malignant cells that emerge should be altered to bias this fitness competition. To test this hypothesis, we compared the proteins secreted in vitro by two human HER2+ breast cancer cell lines (BT474 and SKBR3) relative to a normal human mammary epithelial cell line (184A1) using a proteomics workflow that leveraged two-dimensional gel electrophoresis (2DE) and MALDI-TOF mass spectrometry. Supported by the 2DE secretome maps and identified proteins, the two breast cancer cell lines exhibited secretome profiles that were similar to each other and, yet, were distinct from the 184A1 secretome. Using protein-protein interaction and pathway inference tools for functional annotation, the results suggest that all three cell lines secrete exosomes, as confirmed by scanning electron microscopy. Interestingly, the HER2+ breast cancer cell line exosomes are enriched in proteins involved in antigen processing and presentation and glycolytic metabolism. These pathways are associated with two of the emerging hallmarks of cancer: evasion of tumor immunosurveillance and deregulating cellular energetics. PMID:24752654

  18. ENVIRONMENTAL EFFECTS OF OZONE DEPLETION AND ITS INTERACTIONS WITH CLIMATE CHANGE: PROGRESS REPORT 2003

    EPA Science Inventory

    The measures needed for the protection of the Earth's ozone layer are decided regularly by the Parties to the Montreal Protocol. A section of this progress report focuses on the interactive effects of climate change and ozone depletion on biogeochemical cycles.

  19. Cell-to-cell communication in plants, animals, and fungi: a comparative review

    NASA Astrophysics Data System (ADS)

    Bloemendal, Sandra; Kück, Ulrich

    2013-01-01

    Cell-to-cell communication is a prerequisite for differentiation and development in multicellular organisms. This communication has to be tightly regulated to ensure that cellular components such as organelles, macromolecules, hormones, or viruses leave the cell in a precisely organized way. During evolution, plants, animals, and fungi have developed similar ways of responding to this biological challenge. For example, in higher plants, plasmodesmata connect adjacent cells and allow communication to regulate differentiation and development. In animals, two main general structures that enable short- and long-range intercellular communication are known, namely gap junctions and tunneling nanotubes, respectively. Finally, filamentous fungi have also developed specialized structures called septal pores that allow intercellular communication via cytoplasmic flow. This review summarizes the underlying mechanisms for intercellular communication in these three eukaryotic groups and discusses its consequences for the regulation of differentiation and developmental processes.

  20. Small RNA Control of Cell-to-Cell Communication in Vibrio Harveyi and Vibrio Cholerae

    NASA Astrophysics Data System (ADS)

    Svenningsen, Sine Lo

    Quorum sensing is a process of cell-to-cell communication, by which bacteria coordinate gene expression and behavior on a population-wide scale. Quorum sensing is accomplished through production, secretion, and subsequent detection of chemical signaling molecules termed autoinducers. The human pathogen Vibrio cholerae and the marine bioluminescent bacterium Vibrio harveyi incorporate information from multiple autoinducers, and also environmental signals and metabolic cues into their quorum-sensing pathways. At the core of these pathways lie several homologous small regulatory RNA molecules, the Quorum Regulatory RNAs. Small noncoding RNAs have emerged throughout the bacterial and eukaryotic kingdoms as key regulators of behavioral and developmental processes. Here, I review our present understanding of the role of the Qrr small RNAs in integrating quorum-sensing signals and in regulating the individual cells response to this information.

  1. HIV cell-to-cell transmission: effects on pathogenesis and antiretroviral therapy

    PubMed Central

    Agosto, Luis M.; Uchil, Pradeep D.; Mothes, Walther

    2015-01-01

    The human immunodeficiency virus (HIV) spreads more efficiently in vitro when infected cells directly contact uninfected cells to form virological synapses. A hallmark of virological synapses is that viruses can be transmitted at a higher multiplicity of infection (MOI) that, in vitro, results in a higher number of proviruses. Whether HIV also spreads by cell-cell contact in vivo is a matter of debate. Here we discuss recent data that suggest that contact-mediated transmission largely manifests itself in vivo as CD4+ T cell depletion. The assault of a cell by a large number of incoming particles is likely efficiently sensed by the innate cellular surveillance to trigger cell death. The large number of particles transferred across virological synapses has also been implicated in reduced efficacy of antiretroviral therapies. Thus, antiretroviral therapies must remain effective against the high MOI observed during cell-to-cell transmission to inhibit both viral replication and the pathogenesis associated with HIV infection. PMID:25766144

  2. Intrinsically disordered proteins aggregate at fungal cell-to-cell channels and regulate intercellular connectivity

    PubMed Central

    Lai, Julian; Koh, Chuan Hock; Tjota, Monika; Pieuchot, Laurent; Raman, Vignesh; Chandrababu, Karthik Balakrishna; Yang, Daiwen; Wong, Limsoon; Jedd, Gregory

    2012-01-01

    Like animals and plants, multicellular fungi possess cell-to-cell channels (septal pores) that allow intercellular communication and transport. Here, using a combination of MS of Woronin body-associated proteins and a bioinformatics approach that identifies related proteins based on composition and character, we identify 17 septal pore-associated (SPA) proteins that localize to the septal pore in rings and pore-centered foci. SPA proteins are not homologous at the primary sequence level but share overall physical properties with intrinsically disordered proteins. Some SPA proteins form aggregates at the septal pore, and in vitro assembly assays suggest aggregation through a nonamyloidal mechanism involving mainly α-helical and disordered structures. SPA loss-of-function phenotypes include excessive septation, septal pore degeneration, and uncontrolled Woronin body activation. Together, our data identify the septal pore as a complex subcellular compartment and focal point for the assembly of unstructured proteins controlling diverse aspects of intercellular connectivity. PMID:22955885

  3. Tin Oxide Nanowires Suppress Herpes Simplex Virus-1 Entry and Cell-to-Cell Membrane Fusion

    PubMed Central

    Paulowicz, Ingo; Mishra, Yogendra K.; Adelung, Rainer; Shukla, Deepak

    2012-01-01

    The advent of nanotechnology has ushered in the use of modified nanoparticles as potential antiviral agents against diseases such as herpes simplex virus 1 and 2 (HSV-1) (HSV-2), human immunodeficiency virus (HIV), monkeypox virus, and hepatitis B virus. Here we describe the application of tin oxide (SnO2) nanowires as an effective treatment against HSV-1 infection. SnO2 nanowires work as a carrier of negatively charged structures that compete with HSV-1 attachment to cell bound heparan sulfate (HS), therefore inhibiting entry and subsequent cell-to-cell spread. This promising new approach can be developed into a novel form of broad-spectrum antiviral therapy especially since HS has been shown to serve as a cellular co-receptor for a number of other viruses as well, including the respiratory syncytial virus, adeno-associated virus type 2, and human papilloma virus. PMID:23110193

  4. Cell-to-cell communication in plants, animals, and fungi: a comparative review.

    PubMed

    Bloemendal, Sandra; Kück, Ulrich

    2013-01-01

    Cell-to-cell communication is a prerequisite for differentiation and development in multicellular organisms. This communication has to be tightly regulated to ensure that cellular components such as organelles, macromolecules, hormones, or viruses leave the cell in a precisely organized way. During evolution, plants, animals, and fungi have developed similar ways of responding to this biological challenge. For example, in higher plants, plasmodesmata connect adjacent cells and allow communication to regulate differentiation and development. In animals, two main general structures that enable short- and long-range intercellular communication are known, namely gap junctions and tunneling nanotubes, respectively. Finally, filamentous fungi have also developed specialized structures called septal pores that allow intercellular communication via cytoplasmic flow. This review summarizes the underlying mechanisms for intercellular communication in these three eukaryotic groups and discusses its consequences for the regulation of differentiation and developmental processes.

  5. Cell to cell communication and pH in the frog lens.

    PubMed

    Mathias, R T; Riquelme, G; Rae, J L

    1991-12-01

    Fiber cells of the lens are electrically and diffusionally interconnected through extensive gap junctions. These junctions allow fluxes of small solutes to move between inner cells and peripheral cells, where the majority of transmembrane transport takes place. We describe here a method utilizing two intracellular microelectrodes to measure the cell to cell resistance between fiber cells at any given distance into the intact lens. We also use ion-sensitive microelectrodes to record intracellular pH at various depths in the intact lens. We find that gap junctions connecting inner fiber cells differ in pH sensitivity as well as normal coupling resistance from those connecting peripheral cells. The transition occurs in a zone between 500 and 650 microns into the lens. Fiber cells peripheral to this zone have a specific coupling resistance of 1.1 omega cm2, whereas those inside have a specific coupling resistance of 2.7 omega cm2. However, when the cytoplasm of fiber cells is acidified by bubbling with CO2, peripheral cells uncouple and the cell to cell resistance goes up more than 40-fold, whereas junctions inside this zone are essentially unaffected by changes in intracellular pH. In a normal frog lens, the intracellular pH in fiber cells near the lens surface is 7.02, a value significantly alkaline to electrochemical equilibrium. Our data suggest that Na/H exchange and perhaps other Na gradient-dependent mechanisms in the peripheral cells maintain this transmembrane gradient. Deep in the lens, the fiber cell cytoplasm is significantly more acidic (pHi 6.81) due to influx of hydrogen across the inner fiber cell membranes and production of H+ by the inner fiber cells. Because of the normally acid cytoplasm of interior fiber cells, their loss of gap junctional sensitivity to pH may be essential to lens survival.

  6. Mechanical and cell-to-cell adhesive properties of aggregated Methanosarcina.

    PubMed

    Milkevych, V; Donose, B C; Juste-Poinapen, N; Batstone, D J

    2015-02-01

    The mechanical and adhesive properties as well as the turgor pressure of microbes play an important role in cell growth and aggregation. By applying AFM together with finite element modelling, one can determine the cell wall structural homogeneity, mechanical and cell-to-cell adhesive properties for aggregated Methanosarcina barkeri cells. This also allows a novel approach to determine in-aggregate turgor pressure determination. Analyzing the AFM force-indentation response of the aggregates under loads less than 10 nN, our study reveals structural inhomogeneity of the polymeric part of the cell wall material and suggests that the cell wall consists of two layers of methanochondroitin (external: with a thickness of 3 ± 1 nm and internal: with a thickness of 169 ± 30 nm). On average, the hyperelastic finite element model showed that the internal layer is more rigid (μ = 14 ± 4 MPa) than the external layer (μ = 2.8 ± 0.9 MPa). To determine the turgor pressure and adhesiveness of the cells, a specific mode of indentation (under a load of 45 nN), aimed towards the centre of the individual aggregate, was performed. By modelling the AFM induced decohesion of the aggregate, the turgor pressure and the cell-to-cell adhesive interface properties could be determined. On average, the turgor pressure is estimated to be 59 ± 22 kPa, the interface strength is 78 ± 12 kPa and the polymer network extensibility is 2.8 ± 0.9 nm. We predict that internal cell wall comprised highly compressed methanochondroitin chains and we are able to identify a conceptual model for stress dependent inner cell wall growth.

  7. Progress on interacting boundary-layer computations at high Reynolds number

    NASA Technical Reports Server (NTRS)

    Davis, R. T.; Werle, M. J.

    1981-01-01

    The purpose of this paper is to review progress made in the solution of the interacting boundary-layer equations for subsonic flow. The interrelationship of triple deck theory and the interacting boundary-layer approach is discussed with emphasis placed on the development of efficient and reliable algorithms for the solution of the interacting boundary-layer equations. Example studies are presented for laminar and turbulent finite flat plate flow, laminar flow past a flat plate with a separation causing depression, and laminar and turbulent flow past a blunt based trailing edge.

  8. Single-cell genome-wide studies give new insight into nongenetic cell-to-cell variability in animals.

    PubMed

    Golov, Arkadiy K; Razin, Sergey V; Gavrilov, Alexey A

    2016-09-01

    Huge numbers of cells form an adult animal body, ranging from several thousands in Placozoa and small nematodes to many billions in mammals. Cells are classified into separate groups known as cell types by their morphological and biochemical features. Six to several hundreds of spatially ordered cell types are recognized in different animals. This complex organization develops from one cell, a zygote, during ontogeny, and its dynamic equilibrium is often maintained in the adult body. One of the key challenges in biology is to understand the mechanisms that sustain the reproducible development of a complex ordered cell ensemble such as the animal body from a single cell. How cells with identical genomes stably maintain one of the numerous possible phenotypes? How the cell differentiation lineage is selected during development? What genes play a key role in maintaining cell identity, and how do they determine expression of other genes characteristic of the relevant cell type? How does the basically stochastic nature of transcription in an isolated cell affect the stability of cell identity, the selection of a cell lineage, and the variability of cell responses to external stimuli? Better-grounded answers to these questions have become possible with recent progress in single-cell genome-wide analysis techniques, which combine the high throughput of biochemical methods and the differential nature of microscopy. The techniques are still in their infancy, and their further development will certainly revolutionize many fields of life sciences and, in particular, developmental biology. Here, we summarize the main results that have been obtained in single-cell genome-wide analyses and describe the nongenetic cell-to-cell variability in animals. PMID:27412014

  9. The N-terminal region of the Plantago asiatica mosaic virus coat protein is required for cell-to-cell movement but is dispensable for virion assembly.

    PubMed

    Ozeki, Johji; Hashimoto, Masayoshi; Komatsu, Ken; Maejima, Kensaku; Himeno, Misako; Senshu, Hiroko; Kawanishi, Takeshi; Kagiwada, Satoshi; Yamaji, Yasuyuki; Namba, Shigetou

    2009-06-01

    Potexvirus cell-to-cell movement requires coat protein (CP) and movement proteins. In this study, mutations in two conserved in-frame AUG codons in the 5' region of the CP open reading frame of Plantago asiatica mosaic virus (PlAMV) were introduced, and virus accumulation of these mutants was analyzed in inoculated and upper noninoculated leaves. When CP was translated only from the second AUG codon, virus accumulation in inoculated leaves was lower than that of wild-type PlAMV, and the viral spread was impaired. Trans-complementation analysis showed that the leucine residue at the third position (Leu-3) of CP is important for cell-to-cell movement of PlAMV. The 14-amino-acid N-terminal region of CP was dispensable for virion formation. Immunoprecipitation assays conducted with an anti-TGBp1 antibody indicated that PlAMV CP interacts with TGBp1 in vivo and that this interaction is not affected by alanine substitution at Leu-3. These results support the concept that the N-terminal region of potexvirus CP can be separated into two distinct functional domains.

  10. Onset of virus systemic infection in plants is determined by speed of cell-to-cell movement and number of primary infection foci.

    PubMed

    Rodrigo, Guillermo; Zwart, Mark P; Elena, Santiago F

    2014-09-01

    The cornerstone of today's plant virology consists of deciphering the molecular and mechanistic basis of host-pathogen interactions. Among these interactions, the onset of systemic infection is a fundamental variable in studying both within- and between-host infection dynamics, with implications in epidemiology. Here, we developed a mechanistic model using probabilistic and spatio-temporal concepts to explain dynamic signatures of virus systemic infection. The model dealt with the inherent characteristic of plant viruses to use two different and sequential stages for their within-host propagation: cell-to-cell movement from the initial infected cell and systemic spread by reaching the vascular system. We identified the speed of cell-to-cell movement and the number of primary infection foci in the inoculated leaf as the key factors governing this dynamic process. Our results allowed us to quantitatively understand the timing of the onset of systemic infection, describing this global process as a consequence of local spread of viral populations. Finally, we considered the significance of our predictions for the evolution of plant RNA viruses.

  11. Simulated microgravity allows to demonstrate cell-to-cell communication in bacteria

    NASA Astrophysics Data System (ADS)

    Mastroleo, Felice; van Houdt, Rob; Mergeay, Max; Hendrickx, Larissa; Wattiez, Ruddy; Leys, Natalie

    Through the MELiSSA project, the European Space Agency aims to develop a closed life support system for oxygen, water and food production to support human life in space in forth-coming long term space exploration missions. This production is based on the recycling of the missions organic waste, including CO2 and minerals. The photosynthetic bacterium Rhodospir-illum rubrum S1H is used in MELiSSA to degrade organics with light energy and is the first MELiSSA organism that has been studied in space related environmental conditions (Mastroleo et al., 2009). It was tested in actual space flight to the International Space Station (ISS) as well as in ground simulations of ISS-like ionizing radiation and microgravity. In the present study, R. rubrum S1H was cultured in liquid medium in 2 devices simulating microgravity conditions, i.e. the Rotating Wall Vessel (RWV) and the Random Positioning Machine (RPM). The re-sponse of the bacterium was evaluated at both the transcriptomic and proteomic levels using respectively a dedicated whole-genome microarray and high-throughput gel-free quantitative proteomics. Both at transcriptomic and proteomic level, the bacterium showed a significant response to cultivation in simulated microgravity. The response to low fluid shear modeled microgravity in RWV was different than to randomized microgravity in RPM. Nevertheless, both tests pointed out a change in and a likely interrelation between cell-to-cell communica-tion (i.e. quorum sensing) and cell pigmentation (i.e. photosynthesis) for R. rubrum S1H in microgravity conditions. A new type of cell-to-cell communication molecule in R. rubrum S1H was discovered and characterized. It is hypothised that the lack of convection currents and the fluid quiescence in (simulated) microgravity limits communications molecules to be spread throughout the medium. Cultivation in this new artificial environment of simulated micro-gravity has showed new properties of this well know bacterium

  12. The Potato virus X TGBp3 protein associates with the ER network for virus cell-to-cell movement

    NASA Technical Reports Server (NTRS)

    Krishnamurthy, Konduru; Heppler, Marty; Mitra, Ruchira; Blancaflor, Elison; Payton, Mark; Nelson, Richard S.; Verchot-Lubicz, Jeanmarie

    2003-01-01

    Potato virus X (PVX) TGBp3 is required for virus cell-to-cell movement. Cell-to-cell movement of TGBp3 was studied using biolistic bombardment of plasmids expressing GFP:TGBp3. TGBp3 moves between cells in Nicotiana benthamiana, but requires TGBp1 to move in N. tabacum leaves. In tobacco leaves GFP:TGBp3 accumulated in a pattern resembling the endoplasmic reticulum (ER). To determine if the ER network is important for GFP:TGBp3 and for PVX cell-to-cell movement, a single mutation inhibiting membrane binding of TGBp3 was introduced into GFP:TGBp3 and into PVX. This mutation disrupted movement of GFP:TGBp3 and PVX. Brefeldin A, which disrupts the ER network, also inhibited GFP:TGBp3 movement in both Nicotiana species. Two deletion mutations, that do not affect membrane binding, hindered GFP:TGBp3 and PVX cell-to-cell movement. Plasmids expressing GFP:TGBp2 and GFP:TGBp3 were bombarded to several other PVX hosts and neither protein moved between adjacent cells. In most hosts, TGBp2 or TGBp3 cannot move cell-to-cell.

  13. Can Cell to Cell Thermal Runaway Propagation be Prevented in a Li-ion Battery Module?

    NASA Technical Reports Server (NTRS)

    Jeevarajan, Judith; Lopez, Carlos; Orieukwu, Josephat

    2014-01-01

    Increasing cell spacing decreased adjacent cell damage center dotElectrically connected adjacent cells drained more than physically adjacent cells center dotRadiant barrier prevents propagation when fully installed between BP cells center dotBP cells vent rapidly and expel contents at 100% SOC -Slower vent with flame/smoke at 50% -Thermal runaway event typically occurs at 160 degC center dotLG cells vent but do not expel contents -Thermal runaway event typically occurs at 200 degC center dotSKC LFP modules did not propagate; fuses on negative terminal of cell may provide a benefit in reducing cell to cell damage propagation. New requirement in NASA-Battery Safety Requirements document: JSC 20793 Rev C 5.1.5.1 Requirements - Thermal Runaway Propagation a. For battery designs greater than a 80-Wh energy employing high specific energy cells (greater than 80 watt-hours/kg, for example, lithium-ion chemistries) with catastrophic failure modes, the battery shall be evaluated to ascertain the severity of a worst-case single-cell thermal runaway event and the propensity of the design to demonstrate cell-to-cell propagation in the intended application and environment. NASA has traditionally addressed the threat of thermal runaway incidents in its battery deployments through comprehensive prevention protocols. This prevention-centered approach has included extensive screening for manufacturing defects, as well as robust battery management controls that prevent abuse-induced runaway even in the face of multiple system failures. This focused strategy has made the likelihood of occurrence of such an event highly improbable. b. The evaluation shall include all necessary analysis and test to quantify the severity (consequence) of the event in the intended application and environment as well as to identify design modifications to the battery or the system that could appreciably reduce that severity. In addition to prevention protocols, programs developing battery designs with

  14. Polymorphonuclear leukocyte adhesion triggers the disorganization of endothelial cell-to-cell adherens junctions

    PubMed Central

    1996-01-01

    Polymorphonuclear leukocytes (PMN) infiltration into tissues is frequently accompanied by increase in vascular permeability. This suggests that PMN adhesion and transmigration could trigger modifications in the architecture of endothelial cell-to-cell junctions. In the present paper, using indirect immunofluorescence, we found that PMN adhesion to tumor necrosis factor-activated endothelial cells (EC) induced the disappearance from endothelial cell-to-cell contacts of adherens junction (AJ) components: vascular endothelial (VE)-cadherin, alpha-catenin, beta-catenin, and plakoglobin. Immunoprecipitation and Western blot analysis of the VE- cadherin/catenin complex showed that the amount of beta-catenin and plakoglobin was markedly reduced from the complex and from total cell extracts. In contrast, VE-cadherin and alpha-catenin were only partially affected. Disorganization of endothelial AJ by PMN was not accompanied by EC retraction or injury and was specific for VE- cadherin/catenin complex, since platelet/endothelial cell adhesion molecule 1 (PECAM-1) distribution at cellular contacts was unchanged. PMN adhesion to EC seems to be a prerequisite for VE-cadherin/catenin complex disorganization. This phenomenon could be fully inhibited by blocking PMN adhesion with an anti-integrin beta 2 mAb, while it could be reproduced by any condition that induced increase of PMN adhesion, such as addition of PMA or an anti-beta 2-activating mAb. The effect on endothelial AJ was specific for PMN since adherent activated lymphocytes did not induce similar changes. High concentrations of protease inhibitors and oxygen metabolite scavengers were unable to prevent AJ disorganization mediated by PMN. PMN adhesion to EC was accompanied by increase in EC permeability in vitro. This effect was dependent on PMN adhesion, was not mediated by proteases and oxygen- reactive metabolites, and could be reproduced by EC treatment with EGTA. Finally, immunohistochemical analysis showed that VE

  15. BRCA1 interaction of centrosomal protein Nlp is required for successful mitotic progression.

    PubMed

    Jin, Shunqian; Gao, Hua; Mazzacurati, Lucia; Wang, Yang; Fan, Wenhong; Chen, Qiang; Yu, Wei; Wang, Mingrong; Zhu, Xueliang; Zhang, Chuanmao; Zhan, Qimin

    2009-08-21

    Breast cancer susceptibility gene BRCA1 is implicated in the control of mitotic progression, although the underlying mechanism(s) remains to be further defined. Deficiency of BRCA1 function leads to disrupted mitotic machinery and genomic instability. Here, we show that BRCA1 physically interacts and colocalizes with Nlp, an important molecule involved in centrosome maturation and spindle formation. Interestingly, Nlp centrosomal localization and its protein stability are regulated by normal cellular BRCA1 function because cells containing BRCA1 mutations or silenced for endogenous BRCA1 exhibit disrupted Nlp colocalization to centrosomes and enhanced Nlp degradation. Its is likely that the BRCA1 regulation of Nlp stability involves Plk1 suppression. Inhibition of endogenous Nlp via the small interfering RNA approach results in aberrant spindle formation, aborted chromosomal segregation, and aneuploidy, which mimic the phenotypes of disrupted BRCA1. Thus, BRCA1 interaction of Nlp might be required for the successful mitotic progression, and abnormalities of Nlp lead to genomic instability.

  16. Environmental effects of ozone depletion and its interactions with climate change: progress report, 2015.

    PubMed

    2016-02-01

    The Environmental Effects Assessment Panel (EEAP) is one of three Panels that regularly informs the Parties (countries) to the Montreal Protocol on the effects of ozone depletion and the consequences of climate change interactions with respect to human health, animals, plants, biogeochemistry, air quality, and materials. The Panels provide a detailed assessment report every four years. The most recent 2014 Quadrennial Assessment by the EEAP was published as a special issue of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). The next Quadrennial Assessment will be published in 2018/2019. In the interim, the EEAP generally produces an annual update or progress report of the relevant scientific findings. The present progress report for 2015 assesses some of the highlights and new insights with regard to the interactive nature of the effects of UV radiation, atmospheric processes, and climate change.

  17. Environmental effects of ozone depletion and its interactions with climate change: progress report, 2015.

    PubMed

    2016-02-01

    The Environmental Effects Assessment Panel (EEAP) is one of three Panels that regularly informs the Parties (countries) to the Montreal Protocol on the effects of ozone depletion and the consequences of climate change interactions with respect to human health, animals, plants, biogeochemistry, air quality, and materials. The Panels provide a detailed assessment report every four years. The most recent 2014 Quadrennial Assessment by the EEAP was published as a special issue of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). The next Quadrennial Assessment will be published in 2018/2019. In the interim, the EEAP generally produces an annual update or progress report of the relevant scientific findings. The present progress report for 2015 assesses some of the highlights and new insights with regard to the interactive nature of the effects of UV radiation, atmospheric processes, and climate change. PMID:26822392

  18. Quantum computing with atomic qubits and Rydberg interactions: progress and challenges

    NASA Astrophysics Data System (ADS)

    Saffman, M.

    2016-10-01

    We present a review of quantum computation with neutral atom qubits. After an overview of architectural options and approaches to preparing large qubit arrays we examine Rydberg mediated gate protocols and fidelity for two- and multi-qubit interactions. Quantum simulation and Rydberg dressing are alternatives to circuit based quantum computing for exploring many body quantum dynamics. We review the properties of the dressing interaction and provide a quantitative figure of merit for the complexity of the coherent dynamics that can be accessed with dressing. We conclude with a summary of the current status and an outlook for future progress.

  19. Regulation of cell-to-cell variability in divergent gene expression

    PubMed Central

    Yan, Chao; Wu, Shuyang; Pocetti, Christopher; Bai, Lu

    2016-01-01

    Cell-to-cell variability (noise) is an important feature of gene expression that impacts cell fitness and development. The regulatory mechanism of this variability is not fully understood. Here we investigate the effect on gene expression noise in divergent gene pairs (DGPs). We generated reporters driven by divergent promoters, rearranged their gene order, and probed their expressions using time-lapse fluorescence microscopy and single-molecule fluorescence in situ hybridization (smFISH). We show that two genes in a co-regulated DGP have higher expression covariance compared with the separate, tandem and convergent configurations, and this higher covariance is caused by more synchronized firing of the divergent transcriptions. For differentially regulated DGPs, the regulatory signal of one gene can stochastically ‘leak' to the other, causing increased gene expression noise. We propose that the DGPs' function in limiting or promoting gene expression noise may enhance or compromise cell fitness, providing an explanation for the conservation pattern of DGPs. PMID:27010670

  20. Transcription factor-mediated cell-to-cell signalling in plants.

    PubMed

    Han, Xiao; Kumar, Dhinesh; Chen, Huan; Wu, Shuwei; Kim, Jae-Yean

    2014-04-01

    Plant cells utilize mobile transcription factors to transmit intercellular signals when they perceive environmental stimuli or initiate developmental programmes. Studies on these novel cell-to-cell signals have accumulated multiple pieces of evidence showing that non-cell-autonomous transcription factors play pivotal roles in most processes related to the formation and development of plant organs. Recent studies have explored the evolution of mobile transcription factors and proposed mechanisms for their trafficking through plasmodesmata, where a selective system exists to facilitate this process. Mobile transcription factors contribute to the diversity of the intercellular signalling network, which is also established by peptides, hormones, and RNAs. Crosstalk between mobile transcription factors and other intercellular molecules leads to the development of complex biological signalling networks in plants. The regulation of plasmodesmata appears to have been another major step in controlling the intercellular trafficking of transcription factors based on studies of many plasmodesmal components. Furthermore, diverse omics approaches are being successfully applied to explore a large number of candidate transcription factors as mobile signals in plants. Here, we review these fascinating discoveries to integrate current knowledge of non-cell-autonomous transcription factors.

  1. Listeria monocytogenes wall teichoic acid decoration in virulence and cell-to-cell spread.

    PubMed

    Spears, Patricia A; Havell, Edward A; Hamrick, Terri S; Goforth, John B; Levine, Alexandra L; Abraham, S Thomas; Heiss, Christian; Azadi, Parastoo; Orndorff, Paul E

    2016-09-01

    Wall teichoic acid (WTA) comprises a class of glycopolymers covalently attached to the peptidoglycan of gram positive bacteria. In Listeria monocytogenes, mutations that prevent addition of certain WTA decorating sugars are attenuating. However, the steps required for decoration and the pathogenic process interrupted are not well described. We systematically examined the requirement for WTA galactosylation in a mouse oral-virulent strain by first creating mutations in four genes whose products conferred resistance to a WTA-binding bacteriophage. WTA biochemical and structural studies indicated that galactosylated WTA was directly required for bacteriophage adsorption and that mutant WTA lacked appreciable galactose in all except one mutant - which retained a level ca. 7% of the parent. All mutants were profoundly attenuated in orally infected mice and were impaired in cell-to-cell spread in vitro. Confocal microscopy of cytosolic mutants revealed that all expressed ActA on their cell surface and formed actin tails with a frequency similar to the parent. However, the mutant tails were significantly shorter - suggesting a defect in actin based motility. Roles for the gene products in WTA galactosylation are proposed. Identification and interruption of WTA decoration pathways may provide a general strategy to discover non-antibiotic therapeutics for gram positive infections. © 2016 John Wiley & Sons Ltd. PMID:26871418

  2. Rate dependence of cell-to-cell variations of lithium-ion cells

    NASA Astrophysics Data System (ADS)

    An, Fuqiang; Chen, Lufan; Huang, Jun; Zhang, Jianbo; Li, Ping

    2016-10-01

    Lithium-ion cells are commonly used in a multicell configuration in power devices and electric vehicles, making the cell-to-cell variation (CtCV) a key factor to consider in system design and management. Previous studies on CtCV have two major limitations: the number of cells is usually less than one hundred, and the cells are usually commercial cells already subjected to cell-screenings. In this article, we first make a statistical analysis on the CtCV of 5473 fresh cells from an automotive battery manufacturer before the cell-screening process. Secondly, 198 cells are randomly selected from these 5473 cells and the rate dependence of the CtCV is examined, focusing on the correlations of capacity versus weight and capacity versus resistance, corresponding to thermodynamic and kinetic factors, respectively. The rate dependence of these two correlations is explained from a phenomenological model. Finally, eight cells from the 198 cells are further characterized with electrochemical impedance spectroscopy method to elucidate the kinetic origins of the CtCV.

  3. Modeling PSA Problems - II: A Cell-to-Cell Transport Theory Approach

    SciTech Connect

    Labeau, P.E.; Izquierdo, J.M.

    2005-06-15

    In the first paper of this series, we presented an extension of the classical theory of dynamic reliability in which the actual occurrence of an event causing a change in the system dynamics is possibly delayed. The concept of stimulus activation, which triggers the realization of an event after a distributed time delay, was introduced. This gives a new understanding of competing events in the sequence delineation process.In the context of the level-2 probabilistic safety analysis (PSA), the information on stimulus activation mainly consists of regions of the process variables space where the activation can occur with a given probability. The evolution equations of the extended theory of probabilistic dynamics are therefore particularized to a transport process between discrete cells defined in phase-space on this basis. Doing so, an integrated and coherent approach to level-2 PSA problems is propounded. This amounts to including the stimulus concept and the associated stochastic delays discussed in the first paper in the frame of a cell-to-cell transport process.In addition, this discrete model provides a theoretical basis for the definition of appropriate numerical schemes for integrated level-2 PSA applications.

  4. Plasmodesmal-mediated cell-to-cell transport in wheat roots is modulated by anaerobic stress

    NASA Technical Reports Server (NTRS)

    Cleland, R. E.; Fujiwara, T.; Lucas, W. J.

    1994-01-01

    Cell-to-cell transport of small molecules and ions occurs in plants through plasmodesmata. Plant roots are frequently subjected to localized anaerobic stress, with a resultant decrease in ATP. In order to determine the effect of this stress on plasmodesmal transport, fluorescent dyes of increasing molecular weight (0.46 to 1OkDa) were injected into epidermal and cortical cells of 3-day-old wheat roots, and their movement into neighboring cells was determined by fluorescence microscopy. Anaerobiosis was generated by N2 gas or simulated by the presence of sodium azide, both of which reduced the ATP levels in the tissue by over 80%. In the absence of such stress, the upper limit for movement, or size exclusion limit (SEL), of cortical plasmodesmata was <1 kDa. The ATP analogue TNP-ADP (mw 681) moved across the plasmodesmata of unstressed roots, indicating that plasmodesmata may be conduits for nucleotide (ATP and ADP) exchange between cells. Upon imposition of stress, the SEL rose to between 5 and 10 kDa. This response of plasmodesmata to a decrease in the level of ATP suggests that they are constricted by an ATP-dependent process so as to maintain a restricted SEL. When roots are subjected to anaerobic stress, an increase in SEL may permit enhanced delivery of sugars to the affected cells of the root where anaerobic respiration could regenerate the needed ATP.

  5. Rate dependence of cell-to-cell variations of lithium-ion cells

    PubMed Central

    An, Fuqiang; Chen, Lufan; Huang, Jun; Zhang, Jianbo; Li, Ping

    2016-01-01

    Lithium-ion cells are commonly used in a multicell configuration in power devices and electric vehicles, making the cell-to-cell variation (CtCV) a key factor to consider in system design and management. Previous studies on CtCV have two major limitations: the number of cells is usually less than one hundred, and the cells are usually commercial cells already subjected to cell-screenings. In this article, we first make a statistical analysis on the CtCV of 5473 fresh cells from an automotive battery manufacturer before the cell-screening process. Secondly, 198 cells are randomly selected from these 5473 cells and the rate dependence of the CtCV is examined, focusing on the correlations of capacity versus weight and capacity versus resistance, corresponding to thermodynamic and kinetic factors, respectively. The rate dependence of these two correlations is explained from a phenomenological model. Finally, eight cells from the 198 cells are further characterized with electrochemical impedance spectroscopy method to elucidate the kinetic origins of the CtCV. PMID:27725767

  6. 6K2-induced vesicles can move cell to cell during turnip mosaic virus infection.

    PubMed

    Grangeon, Romain; Jiang, Jun; Wan, Juan; Agbeci, Maxime; Zheng, Huanquan; Laliberté, Jean-François

    2013-01-01

    To successfully infect plants, viruses replicate in an initially infected cell and then move to neighboring cells through plasmodesmata (PDs). However, the nature of the viral entity that crosses over the cell barrier into non-infected ones is not clear. The membrane-associated 6K2 protein of turnip mosaic virus (TuMV) induces the formation of vesicles involved in the replication and intracellular movement of viral RNA. This study shows that 6K2-induced vesicles trafficked toward the plasma membrane and were associated with plasmodesmata (PD). We demonstrated also that 6K2 moved cell-to-cell into adjoining cells when plants were infected with TuMV. 6K2 was then fused to photo-activable GFP (6K2:PAGFP) to visualize how 6K2 moved intercellularly during TuMV infection. After activation, 6K2:PAGFP-tagged vesicles moved to the cell periphery and across the cell wall into adjacent cells. These vesicles were shown to contain the viral RNA-dependent RNA polymerase and viral RNA. Symplasmic movement of TuMV may thus be achieved in the form of a membrane-associated viral RNA complex induced by 6K2. PMID:24409170

  7. Rice dwarf phytoreovirus segment S6-encoded nonstructural protein has a cell-to-cell movement function.

    PubMed

    Li, Yi; Bao, Yi M; Wei, Chun H; Kang, Zhen S; Zhong, Yong W; Mao, Peng; Wu, Gang; Chen, Zhang L; Schiemann, Joachim; Nelson, Richard S

    2004-05-01

    Rice dwarf virus (RDV) is a member of the genus Phytoreovirus, which is composed of viruses with segmented double-stranded RNA genomes. Proteins that support the intercellular movement of these viruses in the host have not been identified. Microprojectile bombardment was used to determine which open reading frames (ORFs) support intercellular movement of a heterologous virus. A plasmid containing an infectious clone of Potato virus X (PVX) defective in cell-to-cell movement and expressing either beta-glucuronidase or green fluorescent protein (GFP) was used for cobombardment with plasmids containing ORFs from RDV gene segments S1 through S12 onto leaves of Nicotiana benthamiana. Cell-to-cell movement of the movement-defective PVX was restored by cobombardment with a plasmid containing S6. In the absence of S6, no other gene segment supported movement. Identical results were obtained with Nicotiana tabacum, a host that allows fewer viruses to infect and spread within its tissue. S6 supported the cell-to-cell movement of the movement-defective PVX in sink and source leaves of N. benthamiana. A mutant S6 lacking the translation start codon did not complement the cell-to-cell movement of the movement-defective PVX. An S6 protein product (Pns6)-enhanced GFP fusion was observed near or within cell walls of epidermal cells from N. tabacum. By immunocytochemistry, unfused Pns6 was localized to plasmodesmata in rice leaves infected with RDV. S6 thus encodes a protein with characteristics identical to those of other viral proteins required for the cell-to-cell movement of their genome and therefore is likely required for the cell-to-cell movement of RDV.

  8. The Azospirillum brasilense Che1 chemotaxis pathway controls swimming velocity, which affects transient cell-to-cell clumping.

    PubMed

    Bible, Amber; Russell, Matthew H; Alexandre, Gladys

    2012-07-01

    The Che1 chemotaxis-like pathway of Azospirillum brasilense contributes to chemotaxis and aerotaxis, and it has also been found to contribute to regulating changes in cell surface adhesive properties that affect the propensity of cells to clump and to flocculate. The exact contribution of Che1 to the control of chemotaxis and flocculation in A. brasilense remains poorly understood. Here, we show that Che1 affects reversible cell-to-cell clumping, a cellular behavior in which motile cells transiently interact by adhering to one another at their nonflagellated poles before swimming apart. Clumping precedes and is required for flocculation, and both processes appear to be independently regulated. The phenotypes of a ΔaerC receptor mutant and of mutant strains lacking cheA1, cheY1, cheB1, or cheR1 (alone or in combination) or with che1 deleted show that Che1 directly mediates changes in the flagellar swimming velocity and that this behavior directly modulates the transient nature of clumping. Our results also suggest that an additional receptor(s) and signaling pathway(s) are implicated in mediating other Che1-independent changes in clumping identified in the present study. Transient clumping precedes the transition to stable clump formation, which involves the production of specific extracellular polysaccharides (EPS); however, production of these clumping-specific EPS is not directly controlled by Che1 activity. Che1-dependent clumping may antagonize motility and prevent chemotaxis, thereby maintaining cells in a metabolically favorable niche.

  9. The V domain of dog PVRL4 (nectin-4) mediates canine distemper virus entry and virus cell-to-cell spread

    SciTech Connect

    Delpeut, Sebastien; Noyce, Ryan S.; Richardson, Christopher D.

    2014-04-15

    The entry of canine distemper virus (CDV) is a multistep process that involves the attachment of CDV hemagglutinin (H) to its cellular receptor, followed by fusion between virus and cell membranes. Our laboratory recently identified PVRL4 (nectin-4) to be the epithelial receptor for measles and canine distemper viruses. In this study, we demonstrate that the V domain of PVRL4 is critical for CDV entry and virus cell-to-cell spread. Furthermore, four key amino acid residues within the V domain of dog PVRL4 and two within the CDV hemagglutinin were shown to be essential for receptor-mediated virus entry. - Highlights: • PVRL4 (nectin-4) is the epithelial cell receptor for measles and canine distemper viruses. • V domain of PVRL4 is critical for CDV entry, cell-to-cell spread, and syncytia formation. • Chimeric PVRL1 backbone substituted with the V domain of PVRL4 can function as a receptor. • Amino acids (F132/P133/A134/G135) within the V domain are essential for PVRL4 receptor activity. • Amino acids (P493/Y539) within CDV H protein are essential for PVRL4 receptor interaction.

  10. Cellular Interrogation: Exploiting Cell-to-Cell Variability to Discriminate Regulatory Mechanisms in Oscillatory Signalling.

    PubMed

    Estrada, Javier; Andrew, Natalie; Gibson, Daniel; Chang, Frederick; Gnad, Florian; Gunawardena, Jeremy

    2016-07-01

    The molecular complexity within a cell may be seen as an evolutionary response to the external complexity of the cell's environment. This suggests that the external environment may be harnessed to interrogate the cell's internal molecular architecture. Cells, however, are not only nonlinear and non-stationary, but also exhibit heterogeneous responses within a clonal, isogenic population. In effect, each cell undertakes its own experiment. Here, we develop a method of cellular interrogation using programmable microfluidic devices which exploits the additional information present in cell-to-cell variation, without requiring model parameters to be fitted to data. We focussed on Ca2+ signalling in response to hormone stimulation, which exhibits oscillatory spiking in many cell types and chose eight models of Ca2+ signalling networks which exhibit similar behaviour in simulation. We developed a nonlinear frequency analysis for non-stationary responses, which could classify models into groups under parameter variation, but found that this question alone was unable to distinguish critical feedback loops. We further developed a nonlinear amplitude analysis and found that the combination of both questions ruled out six of the models as inconsistent with the experimentally-observed dynamics and heterogeneity. The two models that survived the double interrogation were mathematically different but schematically identical and yielded the same unexpected predictions that we confirmed experimentally. Further analysis showed that subtle mathematical details can markedly influence non-stationary responses under parameter variation, emphasising the difficulty of finding a "correct" model. By developing questions for the pathway being studied, and designing more versatile microfluidics, cellular interrogation holds promise as a systematic strategy that can complement direct intervention by genetics or pharmacology.

  11. Cellular Interrogation: Exploiting Cell-to-Cell Variability to Discriminate Regulatory Mechanisms in Oscillatory Signalling

    PubMed Central

    Gibson, Daniel; Chang, Frederick; Gnad, Florian; Gunawardena, Jeremy

    2016-01-01

    The molecular complexity within a cell may be seen as an evolutionary response to the external complexity of the cell’s environment. This suggests that the external environment may be harnessed to interrogate the cell’s internal molecular architecture. Cells, however, are not only nonlinear and non-stationary, but also exhibit heterogeneous responses within a clonal, isogenic population. In effect, each cell undertakes its own experiment. Here, we develop a method of cellular interrogation using programmable microfluidic devices which exploits the additional information present in cell-to-cell variation, without requiring model parameters to be fitted to data. We focussed on Ca2+ signalling in response to hormone stimulation, which exhibits oscillatory spiking in many cell types and chose eight models of Ca2+ signalling networks which exhibit similar behaviour in simulation. We developed a nonlinear frequency analysis for non-stationary responses, which could classify models into groups under parameter variation, but found that this question alone was unable to distinguish critical feedback loops. We further developed a nonlinear amplitude analysis and found that the combination of both questions ruled out six of the models as inconsistent with the experimentally-observed dynamics and heterogeneity. The two models that survived the double interrogation were mathematically different but schematically identical and yielded the same unexpected predictions that we confirmed experimentally. Further analysis showed that subtle mathematical details can markedly influence non-stationary responses under parameter variation, emphasising the difficulty of finding a “correct” model. By developing questions for the pathway being studied, and designing more versatile microfluidics, cellular interrogation holds promise as a systematic strategy that can complement direct intervention by genetics or pharmacology. PMID:27367445

  12. Modelling the Impact of Cell-To-Cell Transmission in Hepatitis B Virus

    PubMed Central

    2016-01-01

    Cell-free virus is a well-recognized and efficient mechanism for the spread of hepatitis B virus (HBV) infection in the liver. Cell-to-cell transmission (CCT) can be a more efficient means of virus propagation. Despite experimental evidence implying CCT occurs in HBV, its relative impact is uncertain. We develop a 3-D agent-based model where each hepatocyte changes its viral state according to a dynamical process driven by cell-free virus infection, CCT and intracellular replication. We determine the relative importance of CCT in the development and resolution of acute HBV infection in the presence of cytolytic (CTL) and non-CTL mechanisms. T cell clearance number is defined as the minimum number of infected cells needed to be killed by each T cell at peak infection that results in infection clearance within 12 weeks with hepatocyte turnover (HT, number of equivalent livers) ≤3. We find that CCT has very little impact on the establishment of infection as the mean cccDNA copies/cell remains between 15 to 20 at the peak of the infection regardless of CCT strength. In contrast, CCT inhibit immune-mediated clearance of acute HBV infection as higher CCT strength requires higher T cell clearance number and increases the probability of T cell exhaustion. An effective non-CTL inhibition can counter these negative effects of higher strengths of CCT by supporting rapid, efficient viral clearance and with little liver destruction. This is evident as the T cell clearance number drops by approximately 50% when non-CTL inhibition is increased from 10% to 80%. Higher CCT strength also increases the probability of the incidence of fulminant hepatitis with this phenomenon being unlikely to arise for no CCT. In conclusion, we report the possibility of CCT impacting HBV clearance and its contribution to fulminant hepatitis. PMID:27560827

  13. Cell-to-cell transport through plasmodesmata in tree callus cultures.

    PubMed

    Pina, Ana; Errea, Pilar; Schulz, Alexander; Martens, Helle J

    2009-06-01

    One factor that contributes to a successful fruit tree grafting is the establishment of symplasmic contacts in the graft interface to facilitate the transfer of compounds between scion and stock. Using novel experimental and theoretical approaches we investigated whether the localized incompatibility, experienced in some Prunus grafts, could be related to insufficient plasmodesmal coupling at an early stage of development within one of the partners. Dye-coupling analysis using fluorescent tracers combined with confocal laser scanning microscopy were performed in cultured callus from either the plum rootstock (Prunus cerasifera Ehrh. x Prunus munsoniana W. Wight et Hedr.) cv. 'Marianna 2624' or from the apricot (Prunus armeniaca L.) cv. 'Moniqui' growing in vitro. Fluorescein was loaded into callus cells in a caged form. Following photoactivation of fluorescence within single cells, the uncaged fluorescein could be traced as it was spreading cell-to-cell revealing the existence of functional plasmodesmata. This set of experiments was performed within the 'stock' partner in callus fusions ('callus grafts') as well as in ungrafted callus. The results indicated species-related as well as developmental-related differences in plasmodesmal conductivity. The results further pointed to a novel control factor of connectivity that reaches the graft partner and changes its innate rate of communication: when combining the poorly transporting apricot cultivar with the well-transporting plum cultivar, communication between plum callus cells was much reduced, compared to that in plum homografts. For further support of the hypothesis, we carried out a quantitative analysis in which fluorescein was esterloaded into the callus. Fluorescence redistribution after photobleaching of fluorescein in individual cells gave a measure for the plasmodesmal contact between the cells. We found significant differences between the species with regard to mobile fraction and halftime of

  14. Modelling the Impact of Cell-To-Cell Transmission in Hepatitis B Virus.

    PubMed

    Goyal, Ashish; Murray, John M

    2016-01-01

    Cell-free virus is a well-recognized and efficient mechanism for the spread of hepatitis B virus (HBV) infection in the liver. Cell-to-cell transmission (CCT) can be a more efficient means of virus propagation. Despite experimental evidence implying CCT occurs in HBV, its relative impact is uncertain. We develop a 3-D agent-based model where each hepatocyte changes its viral state according to a dynamical process driven by cell-free virus infection, CCT and intracellular replication. We determine the relative importance of CCT in the development and resolution of acute HBV infection in the presence of cytolytic (CTL) and non-CTL mechanisms. T cell clearance number is defined as the minimum number of infected cells needed to be killed by each T cell at peak infection that results in infection clearance within 12 weeks with hepatocyte turnover (HT, number of equivalent livers) ≤3. We find that CCT has very little impact on the establishment of infection as the mean cccDNA copies/cell remains between 15 to 20 at the peak of the infection regardless of CCT strength. In contrast, CCT inhibit immune-mediated clearance of acute HBV infection as higher CCT strength requires higher T cell clearance number and increases the probability of T cell exhaustion. An effective non-CTL inhibition can counter these negative effects of higher strengths of CCT by supporting rapid, efficient viral clearance and with little liver destruction. This is evident as the T cell clearance number drops by approximately 50% when non-CTL inhibition is increased from 10% to 80%. Higher CCT strength also increases the probability of the incidence of fulminant hepatitis with this phenomenon being unlikely to arise for no CCT. In conclusion, we report the possibility of CCT impacting HBV clearance and its contribution to fulminant hepatitis. PMID:27560827

  15. Roles of cell signaling pathways in cell-to-cell contact-mediated Epstein-Barr virus transmission.

    PubMed

    Nanbo, Asuka; Terada, Haruna; Kachi, Kunihiro; Takada, Kenzo; Matsuda, Tadashi

    2012-09-01

    Epstein-Barr virus (EBV), a human gamma herpesvirus, establishes a life-long latent infection in B lymphocytes and epithelial cells following primary infection. Several lines of evidence indicate that the efficiency of EBV infection in epithelial cells is accelerated up to 10(4)-fold by coculturing with EBV-infected Burkitt's lymphoma (BL) cells compared to infection with cell-free virions, indicating that EBV infection into epithelial cells is mainly mediated via cell-to-cell contact. However, the molecular mechanisms involved in this pathway are poorly understood. Here, we establish a novel assay to assess cell-to-cell contact-mediated EBV transmission by coculturing an EBV-infected BL cell line with an EBV-negative epithelial cell line under stimulation for lytic cycle induction. By using this assay, we confirmed that EBV was transmitted from BL cells to epithelial cells via cell-to-cell contact but not via cell-to-cell fusion. The inhibitor treatments of extracellular signal-regulated kinase (ERK) and nuclear factor (NF)-κB pathways blocked EBV transmission in addition to lytic induction. The blockage of the phosphoinositide 3-kinase (PI3K) pathway impaired EBV transmission coupled with the inhibition of lytic induction. Knockdown of the RelA/p65 subunit of NF-κB reduced viral transmission. Moreover, these signaling pathways were activated in cocultured BL cells and in epithelial cells. Finally, we observed that viral replication was induced in cocultured BL cells. Taken together, our data suggest that cell-to-cell contact induces multiple cell signaling pathways in BL cells and epithelial cells, contributing to the induction of the viral lytic cycle in BL cells and the enhancement of viral transmission to epithelial cells. PMID:22718812

  16. Active efflux and diffusion are involved in transport of Pseudomonas aeruginosa cell-to-cell signals.

    PubMed

    Pearson, J P; Van Delden, C; Iglewski, B H

    1999-02-01

    Many gram-negative bacteria communicate by N-acyl homoserine lactone signals called autoinducers (AIs). In Pseudomonas aeruginosa, cell-to-cell signaling controls expression of extracellular virulence factors, the type II secretion apparatus, a stationary-phase sigma factor (sigmas), and biofilm differentiation. The fact that a similar signal, N-(3-oxohexanoyl) homoserine lactone, freely diffuses through Vibrio fischeri and Escherichia coli cells has led to the assumption that all AIs are freely diffusible. In this work, transport of the two P. aeruginosa AIs, N-(3-oxododecanoyl) homoserine lactone (3OC12-HSL) (formerly called PAI-1) and N-butyryl homoserine lactone (C4-HSL) (formerly called PAI-2), was studied by using tritium-labeled signals. When [3H]C4-HSL was added to cell suspensions of P. aeruginosa, the cellular concentration reached a steady state in less than 30 s and was nearly equal to the external concentration, as expected for a freely diffusible compound. In contrast, [3H]3OC12-HSL required about 5 min to reach a steady state, and the cellular concentration was 3 times higher than the external level. Addition of inhibitors of the cytoplasmic membrane proton gradient, such as azide, led to a strong increase in cellular accumulation of [3H]3OC12-HSL, suggesting the involvement of active efflux. A defined mutant lacking the mexA-mexB-oprM-encoded active-efflux pump accumulated [3H]3OC12-HSL to levels similar to those in the azide-treated wild-type cells. Efflux experiments confirmed these observations. Our results show that in contrast to the case for C4-HSL, P. aeruginosa cells are not freely permeable to 3OC12-HSL. Instead, the mexA-mexB-oprM-encoded efflux pump is involved in active efflux of 3OC12-HSL. Apparently the length and/or degree of substitution of the N-acyl side chain determines whether an AI is freely diffusible or is subject to active efflux by P. aeruginosa.

  17. Mechanisms of interaction of radiation with matter. Progress report, July 1, 1991--August 31, 1992

    SciTech Connect

    Geacintov, N.E.; Pope, M.

    1992-08-31

    This project is concerned with studies of biological activity-structure relationships in which the mechanisms of interaction of ionizing radiation and benzopyrene (PB) compounds with DNA are being investigated and compared. Emphasis is focused on effects of DNA conformation on its mechanisms of interaction with ionizing radiation, on the influence of structure and stereochemistry of BP metabolites on mechanisms of DNA damage, and on influence of DNA conformation on interactions between BP metabolites and DNA molecules, and the structures of the complexes and adducts which are formed. One basic theme of this project is the use of photoexcited states of BP and nucleic acids as probes of these interactions. In part I of this report, recent progress on elucidating the structures of selected BP-oligonucleotide model adducts by high resolution NMR and gel electrophoresis techniques is summarized. It is shown that the stereochemical properties of benzo[a]pyrene diol epoxide-DNA adducts play a crucial role in determining their interactions with certain exonucleases. These results provide useful models for deriving a better understanding of differences biological activities of BP compounds and the relationships between mutagenicities and the structure properties of BP-DNA adducts. In Part II of this report, a new time-resolved method based on picosecond laser pulse techniques for elucidating the electronic levels involved in electron photoemission and electron transfer in BP and nucleic acid solids is described.

  18. Progress towards understanding heterotypic interactions in multi-culture models of breast cancer.

    PubMed

    Regier, Mary C; Alarid, Elaine T; Beebe, David J

    2016-06-13

    Microenvironments in primary tumors and metastases include multiple cell types whose dynamic and reciprocal interactions are central to progression of the disease. However, the literature involving breast cancer studied in vitro is dominated by cancer cells in mono-culture or co-cultured with one other cell type. For in vitro studies of breast cancer the inclusion of multiple cell types has led to models that are more representative of in vivo behaviors and functions as compared to more traditional monoculture. Here, we review foundational co-culture techniques and their adaptation to multi-culture (including three or more cell types). Additionally, while macroscale methods involving conditioned media, direct contact, and indirect interactions have been informative, we examined many advances that have been made more recently using microscale systems with increased control over cellular and structural complexity. Throughout this discussion we consider the benefits and limitations of current multi-culture methods and the significant results they have produced.

  19. X-ray emission from interacting wind massive binaries: A review of 15 years of progress

    NASA Astrophysics Data System (ADS)

    Rauw, Gregor; Nazé, Yaël

    2016-09-01

    Previous generations of X-ray observatories revealed a group of massive binaries that were relatively bright X-ray emitters. This was attributed to emission of shock-heated plasma in the wind-wind interaction zone located between the stars. With the advent of the current generation of X-ray observatories, the phenomenon could be studied in much more detail. In this review, we highlight the progress that has been achieved in our understanding of the phenomenon over the last 15 years, both on theoretical and observational grounds. All these studies have paved the way for future investigations using the next generation of X-ray satellites that will provide crucial information on the X-ray emission formed in the innermost part of the wind-wind interaction.

  20. Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein.

    PubMed

    Wyss-Fluehmann, Gaby; Zurbriggen, Andreas; Vandevelde, Marc; Plattet, Philippe

    2010-05-01

    The mechanism of viral persistence, the driving force behind the chronic progression of inflammatory demyelination in canine distemper virus (CDV) infection, is associated with non-cytolytic viral cell-to-cell spread. Here, we studied the molecular mechanisms of viral spread of a recombinant fluorescent protein-expressing virulent CDV in primary canine astrocyte cultures. Time-lapse video microscopy documented that CDV spread was very efficient using cell processes contacting remote target cells. Strikingly, CDV transmission to remote cells could occur in less than 6 h, suggesting that a complete viral cycle with production of extracellular free particles was not essential in enabling CDV to spread in glial cells. Titration experiments and electron microscopy confirmed a very low CDV particle production despite higher titers of membrane-associated viruses. Interestingly, confocal laser microscopy and lentivirus transduction indicated expression and functionality of the viral fusion machinery, consisting of the viral fusion (F) and attachment (H) glycoproteins, at the cell surface. Importantly, using a single-cycle infectious recombinant H-knockout, H-complemented virus, we demonstrated that H, and thus potentially the viral fusion complex, was necessary to enable CDV spread. Furthermore, since we could not detect CD150/SLAM expression in brain cells, the presence of a yet non-identified glial receptor for CDV was suggested. Altogether, our findings indicate that persistence in CDV infection results from intracellular cell-to-cell transmission requiring the CDV-H protein. Viral transfer, happening selectively at the tip of astrocytic processes, may help the virus to cover long distances in the astroglial network, "outrunning" the host's immune response in demyelinating plaques, thus continuously eliciting new lesions.

  1. HSPB7 interacts with dimerized FLNC and its absence results in progressive myopathy in skeletal muscles

    PubMed Central

    Juo, Liang-Yi; Liao, Wern-Chir; Shih, Yen-Ling; Yang, Bih-Ying; Liu, An-Bang

    2016-01-01

    ABSTRACT HSPB7 belongs to the small heat-shock protein (sHSP) family, and its expression is restricted to cardiac and skeletal muscles from embryonic stages to adulthood. Here, we found that skeletal-muscle-specific ablation of the HspB7 does not affect myogenesis during embryonic stages to postnatal day 1 (P1), but causes subsequent postnatal death owing to a respiration defect, with progressive myopathy phenotypes in the diaphragm. Deficiency of HSPB7 in the diaphragm muscle resulted in muscle fibrosis, sarcomere disarray and sarcolemma integrity loss. We identified dimerized filamin C (FLNC) as an interacting partner of HSPB7. Immunofluorescence studies demonstrated that the aggregation and mislocalization of FLNC occurred in the muscle of HspB7 mutant adult mice. Furthermore, the components of dystrophin glycoprotein complex, γ- and δ-sarcoglycan, but not dystrophin, were abnormally upregulated and mislocalized in HSPB7 mutant muscle. Collectively, our findings suggest that HSPB7 is essential for maintaining muscle integrity, which is achieved through its interaction with FLNC, in order to prevent the occurrence and progression of myopathy. PMID:26929074

  2. Relative Roles of Gap Junction Channels and Cytoplasm in Cell-to-Cell Diffusion of Fluorescent Tracers

    NASA Astrophysics Data System (ADS)

    Safranyos, Richard G. A.; Caveney, Stanley; Miller, James G.; Petersen, Nils O.

    1987-04-01

    Intercellular (tissue) diffusion of molecules requires cytoplasmic diffusion and diffusion through gap junctional (or cell-to-cell) channels. The rates of tissue and cytoplasmic diffusion of fluorescent tracers, expressed as an effective diffusion coefficient, De, and a cytoplasmic diffusion coefficient, Dcyt, have been measured among the developing epidermal cells of a larval beetle, Tenebrio molitor L., to determine the contribution of the junctional channels to intercellular diffusion. Tracer diffusion was measured by injecting fluorescent tracers into cells and quantitating the rate of subsequent spread into adjacent cells. Cytoplasmic diffusion was determined by fluorescence photobleaching. These experiments show that gap junctional channels constitute approximately 70-80% of the total cell-to-cell resistance to the diffusion of organic tracers at high concentrations in this tissue. At low concentrations, however, the binding of tracer to cytoplasm slows down the cytoplasmic diffusion, which may limit intercellular diffusion.

  3. Gene I, a potential cell-to-cell movement locus of cauliflower mosaic virus, encodes an RNA-binding protein.

    PubMed Central

    Citovsky, V; Knorr, D; Zambryski, P

    1991-01-01

    Cauliflower mosaic virus (CaMV) is a double-stranded DNA (dsDNA) pararetrovirus capable of cell-to-cell movement presumably through intercellular connections, the plasmodesmata, of the infected plant. This movement is likely mediated by a specific viral protein encoded by the gene I locus. Here we report that the purified gene I protein binds RNA and single-stranded DNA (ssDNA) but not dsDNA regardless of nucleotide sequence specificity. The binding is highly cooperative, and the affinity of the gene I protein for RNA is 10-fold higher than for ssDNA. CaMV replicates by reverse transcription of a 358 RNA that is homologous to the entire genome. We propose that the 35S RNA may be involved in cell-to-cell movement of CaMV as an intermediate that is transported through plasmodesmata as an RNA-gene I protein complex. Images PMID:11607169

  4. Gene I, a potential cell-to-cell movement locus of cauliflower mosaic virus, encodes an RNA-binding protein

    SciTech Connect

    Citovsky, V.; Knorr, D.; Zambryski, P. )

    1991-03-15

    Cauliflower mosaic virus (CaMV) is a double-stranded DNA (dsDNA) pararetrovirus capable of cell-to-cell movement presumably through intercellular connections, the plasmodesmata, of the infected plant. This movement is likely mediated by a specific viral protein encoded by the gene I locus. Here we report that the purified gene I protein binds RNA and single-stranded DNA (ssDNA) but not dsDNA regardless of nucleotide sequence specificity. The binding is highly cooperative, and the affinity of the gene I protein for RNA is 10-fold higher than for ssDNA. CaMV replicates by reverse transcription of a 35S RNA that is homologous to the entire genome. The authors propose that the 35S RNA may be involved in cell-to-cell movement of CaMV as an intermediate that is transported through plasmodesmata as an RNA-gene I protein complex.

  5. Bifurcation analysis of HIV-1 infection model with cell-to-cell transmission and immune response delay.

    PubMed

    Xu, Jinhu; Zhou, Yicang

    2016-04-01

    A within-host viral infection model with both virus-to-cell and cell-to-cell transmissions and time delay in immune response is investigated. Mathematical analysis shows that delay may destabilize the infected steady state and lead to Hopf bifurcation. Moreover, the direction of the Hopf bifurcation and the stability of the periodic solutions are investigated by normal form and center manifold theory. Numerical simulations are done to explore the rich dynamics, including stability switches, Hopf bifurcations, and chaotic oscillations.

  6. HIV-1 Nef promotes the localization of Gag to the cell membrane and facilitates viral cell-to-cell transfer

    PubMed Central

    2013-01-01

    Background Newly synthesized HIV-1 particles assemble at the plasma membrane of infected cells, before being released as free virions or being transferred through direct cell-to-cell contacts to neighboring cells. Localization of HIV-1 Gag precursor at the cell membrane is necessary and sufficient to trigger viral assembly, whereas the GagPol precursor is additionally required to generate a fully matured virion. HIV-1 Nef is an accessory protein that optimizes viral replication through partly defined mechanisms. Whether Nef modulates Gag and/or GagPol localization and assembly at the membrane and facilitates viral cell-to-cell transfer has not been extensively characterized so far. Results We report that Nef increases the total amount of Gag proteins present in infected cells, and promotes Gag localization at the cell membrane. Moreover, the processing of p55 into p24 is improved in the presence of Nef. We also examined the effect of Nef during HIV-1 cell-to-cell transfer. We show that without Nef, viral transfer through direct contacts between infected cells and target cells is impaired. With a nef-deleted virus, the number of HIV-1 positive target cells after a short 2h co-culture is reduced, and viral material transferred to uninfected cells is less matured. At later time points, this defect is associated with a reduction in the productive infection of new target cells. Conclusions Our results highlight a previously unappreciated role of Nef during the viral replication cycle. Nef promotes HIV-1 Gag membrane localization and processing, and facilitates viral cell-to-cell transfer. PMID:23899341

  7. A Functional Assay to Assess Connexin 43-Mediated Cell-to-Cell Communication of Second Messengers in Cultured Bone Cells.

    PubMed

    Stains, Joseph P; Civitelli, Roberto

    2016-01-01

    Cell-to-cell transfer of small molecules is a fundamental way by which multicellular organisms coordinate function. Recent work has highlighted the complexity of biologic responses downstream of gap junctions. As the connexin-regulated effectors are coming into focus, there is a need to develop functional assays that allow specific testing of biologically relevant second messengers. Here, we describe a modification of the classic gap junction parachute assay to assess biologically relevant molecules passed through gap junctions. PMID:27207296

  8. Focus on Extracellular Vesicles: New Frontiers of Cell-to-Cell Communication in Cancer

    PubMed Central

    Ciardiello, Chiara; Cavallini, Lorenzo; Spinelli, Cristiana; Yang, Julie; Reis-Sobreiro, Mariana; de Candia, Paola; Minciacchi, Valentina Renè; Di Vizio, Dolores

    2016-01-01

    Extracellular Vesicles (EVs) have received considerable attention in recent years, both as mediators of intercellular communication pathways that lead to tumor progression, and as potential sources for discovery of novel cancer biomarkers. For many years, research on EVs has mainly investigated either the mechanism of biogenesis and cargo selection and incorporation, or the methods of EV isolation from available body fluids for biomarker discovery. Recent studies have highlighted the existence of different populations of cancer-derived EVs, with distinct molecular cargo, thus pointing to the possibility that the various EV populations might play diverse roles in cancer and that this does not happen randomly. However, data attributing cancer specific intercellular functions to given populations of EVs are still limited. A deeper functional, biochemical and molecular characterization of the various EV classes might identify more selective clinical markers, and significantly advance our knowledge of the pathogenesis and disease progression of many cancer types. PMID:26861306

  9. Progress in sub-grid scale modeling of shock-turbulence interaction

    SciTech Connect

    Buckingham, A.C.; Grun, J.

    1994-12-01

    The authors report on progress in the development of sub grid scale (SGS) closure relationships for the unresolved motion scales in compressible large eddy simulations (LES). At present they are refining the SGS model and overall LES procedure to include: a linearized viscoelastic model for finite thickness shock distortions and shocked turbulence field response; multiple scale asymptotic considerations to improve predictions of average near-wall surface behavior; and a spectral statistical model simulating the effects of high wave number stochastic feed-back from the unresolved SGS nonlinear motion influences on the explicitly resolved grid scale motions. Predicted amplification levels, modal energy partition, shock translational to turbulence kinetic energy transfer, and viscoelastic spatio-temporal response of turbulence to shock interaction are examined in comparison with available experimental evidence. Supplemental hypersonic compressible turbulence experimental information is developed from sub nanosecond interval pulsed shadowgraph evidence of laser impulse generated hypervelocity shocks interacting with intense, previously developed and carefully characterized initial turbulence. Accurate description of the influence of shock-turbulence interactions is vital for predicting their influence on: Supersonic/hypersonic flow field analysis, aerodynamic design, and aerostructural materials selection. Practical applications also include interior supersonic combustion analysis and combustion chamber design. It is also the essential foundation for accurately predicting the development and evolution of flow-field generated thermal and electromagnetic radiation important to hypersonic flight vehicle survivability, detection and communication.

  10. Suppression of local RNA silencing is not sufficient to promote cell-to-cell movement of Turnip crinkle virus in Nicotiana benthamiana

    PubMed Central

    Shi, Yan; Ryabov, Eugene V; van Wezel, Rene; Li, Chunyang; Jin, Mingfei; Wang, Wenjing; Fan, Zaifeng

    2009-01-01

    The biological relationship between suppression of RNA silencing and virus movement poses an intriguing question in virus-plant interactions. Here, we have used a local RNA silencing assay, based on a movement-deficient Turnip crinkle virus TCV/GFPΔCP, to investigate the influence of silencing suppression by three different viral suppressors: the TCV 38K coat protein (CP), the 126K protein of Tobacco mosaic virus (TMV), and P19 of Tomato bushy stunt virus (TBSV) on cell-to-cell movement and long-distance spread of TCV/GFPΔCP. First, we found that TCV CP blocked the induction of local RNA silencing, but failed to support virus trafficking in silencing-suppressed transgenic plants, although it acted as a functional movement protein in non-transformed plants. Second, we demonstrated that the TMV 126K suppressor inhibited TCV/GFPΔCP-mediated RNA silencing, but did not facilitate intercellular spread of the chimaeric carmovirus. However, TMV and TMVΔCP prevented the initiation of RNA silencing by TCV/GFPΔCP and caused TCV/GFPΔCP to move between cells, although only TMV supported its long-distance spread. Third, TBSV P19 functioned as a movement protein for TCV/GFPΔCP and as a silencing suppressor in non-transformed and silencing-suppressed transgenic plants. We further identified three types of mutant P19 proteins that possessed no or varied functionality in silencing suppression and in the facilitation of carmovirus movement. These results suggest that, although suppression of local RNA silencing is essential for the maintenance of viral RNA, recovery of cell-to-cell movement and long-distance spread of movement-deficient carmoviruses is not a direct consequence of such silencing suppression. PMID:19568335

  11. Analyzing Systolic-Diastolic Interval Interaction Characteristics in Diabetic Cardiac Autonomic Neuropathy Progression

    PubMed Central

    Imam, Mohammad Hasan; Jelinek, Herbert F.; Palaniswami, Marimuthu; Khandoker, Ahsan H.

    2015-01-01

    Cardiac autonomic neuropathy (CAN), one of the major complications in diabetes, if detected at the subclinical stage allows for effective treatment and avoiding further complication including cardiovascular pathology. Surface ECG (Electrocardiogram)-based diagnosis of CAN is useful to overcome the limitation of existing cardiovascular autonomic reflex tests traditionally used for CAN identification in clinical settings. The aim of this paper is to analyze the changes in the mechanical function of the ventricles in terms of systolic-diastolic interval interaction (SDI) from a surface ECG to assess the severity of CAN progression [no CAN, early CAN (ECAN) or subclinical CAN, and definite CAN (DCAN) or clinical CAN]. ECG signals recorded in supine resting condition from 72 diabetic subjects without CAN (CAN-) and 70 diabetic subjects with CAN were analyzed in this paper. The severity of CAN was determined by Ewing’s Cardiovascular autonomic reflex tests. Fifty-five subjects of the CAN group had ECAN and 15 subjects had DCAN. In this paper, we propose an improved version of the SDI parameter (i.e., TQ/RR interval ratio) measured from the electrical diastolic interval (i.e., TQ interval) and the heart rate interval (i.e., RR interval). The performance of the proposed SDI measure was compared with the performance of the existing SDI measure (i.e., QT/TQ interval ratio). The proposed SDI parameter showed significant differences among three groups (no CAN, ECAN, and DCAN). In addition, the proposed SDI parameter was found to be more sensitive in detecting CAN progression than other ECG interval-based features traditionally used for CAN diagnosis. The modified SDI parameter might be used as an alternative measure for the Ewing autonomic reflex tests to identify CAN progression for those subjects who are unable to perform the traditional tests. These findings could also complement the echocardiographic findings of the left ventricular diastolic dysfunction by providing

  12. A Study of Cell-to-Cell Interactions and Degradation in Parallel Strings: Implications for the Battery Management System

    NASA Astrophysics Data System (ADS)

    Pastor-Fernández, C.; Bruen, T.; Widanage, W. D.; Gama-Valdez, M. A.; Marco, J.

    2016-10-01

    Vehicle battery systems are usually designed with a high number of cells connected in parallel to meet the stringent requirements of power and energy. The self-balancing characteristic of parallel cells allows a battery management system (BMS) to approximate the cells as one equivalent cell with a single state of health (SoH) value, estimated either as capacity fade (SoHE) or resistance increase (SoHP). A single SoH value is however not applicable if the initial SoH of each cell is different, which can occur when cell properties change due to inconsistent manufacturing processes or in-homogeneous operating environments. As such this work quantifies the convergence of SoHE and SoHP due to initial differences in cell SoH and examines the convergence factors. Four 3 Ah 18650 cells connected in parallel at 25 °C are aged by charging and discharging for 500 cycles. For an initial SoHE difference of 40% and SoHP difference of 45%, SoHE converge to 10% and SoHP to 30% by the end of the experiment. From this, a strong linear correlation between ΔSoHE and ΔSoHP is also observed. The results therefore imply that a BMS should consider a calibration strategy to accurately estimate the SoH of parallel cells until convergence is reached.

  13. Environmental effects of ozone depletion and its interactions with climate change: progress report, 2008.

    PubMed

    Andrady, Anthony; Aucamp, Pieter J; Bais, Alkiviadis; Ballaré, Carlos L; Björn, Lars Olof; Bornman, Janet F; Caldwell, Martyn; Cullen, Anthony P; Erickson, David J; de Gruijl, Frank R; Häder, Donat-P; Ilyas, Mohammad; Kulandaivelu, G; Kumar, H D; Longstreth, Janice; McKenzie, Richard L; Norval, Mary; Paul, Nigel; Redhwi, Halim Hamid; Smith, Raymond C; Solomon, Keith R; Sulzberger, Barbara; Takizawa, Yukio; Tang, Xiaoyan; Teramura, Alan H; Torikai, Ayako; van der Leun, Jan C; Wilson, Stephen R; Worrest, Robert C; Zepp, Richard G

    2009-01-01

    After the enthusiastic celebration of the 20th Anniversary of the Montreal Protocol on Substances that Deplete the Ozone Layer in 2007, the work for the protection of the ozone layer continues. The Environmental Effects Assessment Panel is one of the three expert panels within the Montreal Protocol. This EEAP deals with the increase of the UV irradiance on the Earth's surface and its effects on human health, animals, plants, biogeochemistry, air quality and materials. For the past few years, interactions of ozone depletion with climate change have also been considered. It has become clear that the environmental problems will be long-lasting. In spite of the fact that the worldwide production of ozone depleting chemicals has already been reduced by 95%, the environmental disturbances are expected to persist for about the next half a century, even if the protective work is actively continued, and completed. The latest full report was published in Photochem. Photobiol. Sci., 2007, 6, 201-332, and the last progress report in Photochem. Photobiol. Sci., 2008, 7, 15-27. The next full report on environmental effects is scheduled for the year 2010. The present progress report 2008 is one of the short interim reports, appearing annually.

  14. Small-molecule inhibitors of protein-protein interactions: progressing towards the reality

    PubMed Central

    Arkin, Michelle R.; Tang, Yinyan; Wells, James A.

    2014-01-01

    Summary The past twenty years have seen many advances in our understanding of protein-protein interactions (PPI) and how to target them with small-molecule therapeutics. In 2004, we reviewed some early successes; since then, potent inhibitors have been developed for diverse protein complexes, and compounds are now in clinical trials for six targets. Surprisingly, many of these PPI clinical candidates have efficiency metrics typical of ‘lead-like’ or ‘drug-like’ molecules and are orally available. Successful discovery efforts have integrated multiple disciplines and make use of all the modern tools of target-based discovery - structure, computation, screening, and biomarkers. PPI become progressively more challenging as the interfaces become more complex, i.e., as binding epitopes are displayed on primary, secondary, or tertiary structures. Here, we review the last ten years of progress, focusing on the properties of PPI inhibitors that have advanced to clinical trials and prospects for the future of PPI drug discovery. PMID:25237857

  15. Interaction of a plane progressive sound wave with a functionally graded spherical shell.

    PubMed

    Hasheminejad, Seyyed M; Maleki, M

    2006-12-01

    An exact analysis is carried out to study interaction of a time-harmonic plane progressive sound field with a radially inhomogeneous thick-walled elastic isotropic spherical shell suspended in and filled with compressible ideal fluid mediums. Using the laminated approximation method, a modal state equation with variable coefficients is set up in terms of appropriate displacement and stress functions and their spherical harmonics. Taylor's expansion theorem is then employed to obtain the solution to the modal state equation ultimately leading to calculation of a global transfer matrix. Numerical example is given for a water-submerged/air-filled Aluminum/Zirconia elastic spherical sandwich shell containing a functionally graded interlayer and subjected to an incident progressive plane sound wave. The mechanical properties of the interlayer are assumed to vary smoothly and continuously across the thickness with the change of volume concentration of its constituents. The effect of incident wave frequency, thickness and compositional gradient of the interlayer on the form function amplitude and the average radiation force acting on the composite shell are examined. Limiting cases are considered and fair agreements with well-known solutions are established.

  16. Lithium-ion cell-to-cell variation during battery electric vehicle operation

    NASA Astrophysics Data System (ADS)

    Schuster, Simon F.; Brand, Martin J.; Berg, Philipp; Gleissenberger, Markus; Jossen, Andreas

    2015-11-01

    484 new and 1908 aged lithium-ion cells out of two identical battery electric vehicles (i.e. 954 cells each) were characterized by capacity and impedance measurements to yield a broad set of data for distribution fit analysis. Results prove alteration from normal to Weibull distribution for the parameters of lithium-ion cells with the progress of aging. Cells with abnormal characteristics in the aged state mostly exhibit lower capacities as compared to the distribution mode which is typical for the left-skewed Weibull shape. In addition, the strength of variation and the amount of outliers both are generally increased with the aging progress. Obtained results are compared to vehicles' operational data to provide recommendations with the aim to minimize the increasing parameter spread. However, neither temperature gradients in the battery pack nor an insufficient balancing procedure were determined. As the appearance of cells with suspicious parameters could not be assigned to local weak spots of the battery pack, a random and inevitable type of origin is assumed. Hence, the battery management system must ensure to detect outliers in a reliable manner and to balance resulting drifts of cells' states of charge to guarantee a safe battery storage operation.

  17. Modeling fluid-rock interaction at Yucca Mountain, Nevada; A progress report, April 15, 1992

    SciTech Connect

    Viani, B.E.; Bruton, C.J.

    1992-08-01

    Volcanic rocks at Yucca Mountain, Nevada aie being assessed for their suitability as a potential repository for high-level nuclear waste. Recent progress in modeling fluid-rock interactions, in particular the mineralogical and chemical changes that may accompany waste disposal at Yucca Mountain, will be reviewed in this publication. In Part 1 of this publication, ``Geochemical Modeling of Clinoptilolite-Water Interactions,`` solid-solution and cation-exchange models for the zeolite clinoptilolite are developed and compared to experimental and field observations. At Yucca Mountain, clinoptilolite which is found lining fractures and as a major component of zeolitized tuffs, is expected to play an important role in sequestering radionuclides that may escape from a potential nuclear waste repository. The solid-solution and ion-exchange models were evaluated by comparing predicted stabilities and exchangeable cation distributions of clinoptilolites with: (1) published binary exchange data; (2) compositions of coexisting clinoptilolites and formation waters at Yucca Mountain; (3) experimental sorption isotherms of Cs and Sr on zeolitized tuff, and (4) high temperature experimental data. Good agreement was found between predictions and expertmental data, especially for binary exchange and Cs and Sr sorption on clinoptilolite. Part 2 of this publication, ``Geochemical Simulation of Fluid-Rock Interactions at Yucca Mountain,`` describes preliminary numerical simulations of fluid-rock interactions at Yucca Mountain. The solid-solution model developed in the first part of the paper is used to evaluate the stability and composition of clinciptilolite and other minerals in the host rock under ambient conditions and after waste emplacement.

  18. [Research Progress on the Interaction Effects and Its Neural Mechanisms between Physical Fatigue and Mental Fatigue].

    PubMed

    Zhang, Lixin; Zhang, Chuncui; He, Feng; Zhao, Xin; Qi, Hongzhi; Wan, Baikun; Ming, Dong

    2015-10-01

    Fatigue is an exhaustion state caused by prolonged physical work and mental work, which can reduce working efficiency and even cause industrial accidents. Fatigue is a complex concept involving both physiological and psychological factors. Fatigue can cause a decline of concentration and work performance and induce chronic diseases. Prolonged fatigue may endanger life safety. In most of the scenarios, physical and mental workloads co-lead operator into fatigue state. Thus, it is very important to study the interaction influence and its neural mechanisms between physical and mental fatigues. This paper introduces recent progresses on the interaction effects and discusses some research challenges and future development directions. It is believed that mutual influence between physical fatigue and mental fatigue may occur in the central nervous system. Revealing the basal ganglia function and dopamine release may be important to explore the neural mechanisms between physical fatigue and mental fatigue. Future effort is to optimize fatigue models, to evaluate parameters and to explore the neural mechanisms so as to provide scientific basis and theoretical guidance for complex task designs and fatigue monitoring.

  19. Calcium regulates the cell-to-cell water flow pathway in maize roots during variable water conditions.

    PubMed

    Wu, Yan; Liu, Xiaofang; Wang, Weifeng; Zhang, Suiqi; Xu, Bingcheng

    2012-09-01

    Soil water shortages can decrease root hydraulic conductivity and affect Ca uptake and movement through the plant. In this study, the effects of extra Ca(2+) applied in nutrient solution on the hydraulic properties of the whole roots (Lp(r)) and cortical cells (Lp(cell)) of maize (Zea mays L.) subjected to variable water conditions were investigated. Under well-watered conditions, extra Ca(2+) significantly increased the root Ca content, total root length, and lateral root number; however, it reduced the root cortical cell volume, Lp(r), and Lp(cell). Hg(2+) inhibition experiments suggested that extra Ca(2+) could reduce the contribution of the cell-to-cell water flow pathway. Osmotic stress (10% PEG6000) significantly decreased the cortical cell volume, Lp(r), and Lp(cell) in the control plants, but smaller decreases were observed in the extra Ca(2+) plants. The Hg(2+) treatment reduced the Lp(r) larger in the extra Ca(2+) plants (74.6%) than in the control plants (53.2%), suggesting a higher contribution of the cell-to-cell pathway. The larger Hg(2+) inhibition of the Lp(cell) in the extra Ca(2+) roots (67.2%) when compared to the controls (56.4%) indicated that extra Ca(2+) can mitigate the inhibition of aquaporin expression and/or activity levels via osmotic stress. After 2 d of rehydration, the extra Ca(2+) helped the Lp(r) and Lp(cell) to recover almost completely, but these properties only partially recovered in the control plants. In conclusion, extra Ca(2+) may adjust the contribution of cell-to-cell pathway by regulating the expression and/or activity levels of AQPs according to water availability; this regulation may weaken negative effects and optimize water use. PMID:22841977

  20. Bifurcation analysis of HIV-1 infection model with cell-to-cell transmission and immune response delay.

    PubMed

    Xu, Jinhu; Zhou, Yicang

    2016-04-01

    A within-host viral infection model with both virus-to-cell and cell-to-cell transmissions and time delay in immune response is investigated. Mathematical analysis shows that delay may destabilize the infected steady state and lead to Hopf bifurcation. Moreover, the direction of the Hopf bifurcation and the stability of the periodic solutions are investigated by normal form and center manifold theory. Numerical simulations are done to explore the rich dynamics, including stability switches, Hopf bifurcations, and chaotic oscillations. PMID:27105992

  1. The cognate coat protein is required for cell-to-cell movement of a chimeric brome mosaic virus mediated by the cucumber mosaic virus movement protein.

    PubMed

    Nagano, H; Mise, K; Okuno, T; Furusawa, I

    1999-12-20

    Cucumber mosaic cucumovirus (CMV) and brome mosaic bromovirus (BMV) have many similarities, including the three-dimensional structure of virions, genome organizations, and requirement of the coat protein (CP) for cell-to-cell movement. We have shown that a chimeric BMV with the CMV 3a movement protein (MP) gene instead of its own cannot move from cell to cell in Chenopodium quinoa, a common permissive host for both BMV and CMV. Another chimeric BMV was constructed by replacing both MP and CP genes of BMV with those of CMV (MP/CP-chimera) and tested for its infectivity in C. quinoa, to determine whether the CMV CP has some functions required for the CMV MP-mediated cell-to-cell movement and to exhibit functional difference between CPs of BMV and CMV. Cell-to-cell movement of the MP/CP-chimera occurred, and small local lesions were induced on the inoculated leaves. A frameshift mutation introduced in the CMV CP gene of the MP/CP-chimera resulted in a lack of cell-to-cell movement of the chimeric virus. These results indicate that the viral movement mediated by the CMV MP requires its cognate CP. Deletion of the amino-terminal region in CMV CP, which is not obligatory for CMV movement, also abolished cell-to-cell movement of the MP/CP-chimera. This may suggest some differences in cell-to-cell movement of the MP/CP-chimera and CMV. On the other hand, the sole replacement of BMV CP gene with that of CMV abolished viral cell-to-cell movement, suggesting a possibility that the viral movement mediated by the BMV MP may also require its cognate CP. Functional compatibility between MP and CP in viral cell-to-cell movement is discussed.

  2. Cell-to-cell communication in intact taste buds through ATP signalling from pannexin 1 gap junction hemichannels.

    PubMed

    Dando, Robin; Roper, Stephen D

    2009-12-15

    Isolated taste cells, taste buds and strips of lingual tissue from taste papillae secrete ATP upon taste stimulation. Taste bud receptor (Type II) cells have been identified as the source of ATP secretion. Based on studies on isolated taste buds and single taste cells, we have postulated that ATP secreted from receptor cells via pannexin 1 hemichannels acts within the taste bud to excite neighbouring presynaptic (Type III) cells. This hypothesis, however, remains to be tested in intact tissues. In this report we used confocal Ca(2+) imaging and lingual slices containing intact taste buds to test the hypothesis of purinergic signalling between taste cells in a more integral preparation. Incubating lingual slices with apyrase reversibly blocked cell-to-cell communication between receptor cells and presynaptic cells, consistent with ATP being the transmitter. Inhibiting pannexin 1 gap junction hemichannels with CO(2)-saturated buffer or probenecid significantly reduced cell-cell signalling between receptor cells and presynaptic cells. In contrast, anandamide, a blocker of connexin gap junction channels, had no effect of cell-to-cell communication in taste buds. These findings are consistent with the model for peripheral signal processing via ATP and pannexin 1 hemichannels in mammalian taste buds.

  3. Cell-to-cell communication in intact taste buds through ATP signalling from pannexin 1 gap junction hemichannels

    PubMed Central

    Dando, Robin; Roper, Stephen D

    2009-01-01

    Isolated taste cells, taste buds and strips of lingual tissue from taste papillae secrete ATP upon taste stimulation. Taste bud receptor (Type II) cells have been identified as the source of ATP secretion. Based on studies on isolated taste buds and single taste cells, we have postulated that ATP secreted from receptor cells via pannexin 1 hemichannels acts within the taste bud to excite neighbouring presynaptic (Type III) cells. This hypothesis, however, remains to be tested in intact tissues. In this report we used confocal Ca2+ imaging and lingual slices containing intact taste buds to test the hypothesis of purinergic signalling between taste cells in a more integral preparation. Incubating lingual slices with apyrase reversibly blocked cell-to-cell communication between receptor cells and presynaptic cells, consistent with ATP being the transmitter. Inhibiting pannexin 1 gap junction hemichannels with CO2-saturated buffer or probenecid significantly reduced cell–cell signalling between receptor cells and presynaptic cells. In contrast, anandamide, a blocker of connexin gap junction channels, had no effect of cell-to-cell communication in taste buds. These findings are consistent with the model for peripheral signal processing via ATP and pannexin 1 hemichannels in mammalian taste buds. PMID:19884319

  4. Histochemical approaches to assess cell-to-cell transmission of misfolded proteins in neurodegenerative diseases

    PubMed Central

    Natale, G.; Pompili, E.; Biagioni, F.; Paparelli, S.; Lenzi, P.; Fornai, F.

    2013-01-01

    Formation, aggregation and transmission of abnormal proteins are common features in neurodegenerative disorders including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and Huntington's disease. The mechanisms underlying protein alterations in neurodegenerative diseases remain controversial. Novel findings highlighted altered protein clearing systems as common biochemical pathways which generate protein misfolding, which in turn causes protein aggregation and protein spreading. In fact, proteinaceous aggregates are prone to cell-tocell propagation. This is reminiscent of what happens in prion disorders, where the prion protein misfolds thus forming aggregates which spread to neighbouring cells. For this reason, the term prionoids is currently used to emphasize how several misfolded proteins are transmitted in neurodegenerative diseases following this prion-like pattern. Histochemical techniques including the use of specific antibodies covering both light and electron microscopy offer a powerful tool to describe these phenomena and investigate specific molecular steps. These include: prion like protein alterations; glycation of prion-like altered proteins to form advanced glycation end-products (AGEs); mechanisms of extracellular secretion; interaction of AGEs with specific receptors placed on neighbouring cells (RAGEs). The present manuscript comments on these phenomena aimed to provide a consistent scenario of the available histochemical approaches to dissect each specific step. PMID:23549464

  5. Eavesdropping on altered cell-to-cell signaling in cancer by secretome profiling

    PubMed Central

    Klinke, David J

    2016-01-01

    In the past decade, cumulative clinical experiences with molecular targeted therapies and immunotherapies for cancer have promoted a shift in our conceptual understanding of cancer. This view shifted from viewing solid tumors as a homogeneous mass of malignant cells to viewing tumors as heterogeneous structures that are dynamically shaped by intercellular interactions among the variety of stromal, immune, and malignant cells present within the tumor microenvironment. As in any dynamic system, identifying how cells communicate to maintain homeostasis and how this communication is altered during oncogenesis are key hurdles for developing therapies to restore normal tissue homeostasis. Here, I discuss tissues as dynamic systems, using the mammary gland as an example, and the evolutionary concepts applied to oncogenesis. Drawing from these concepts, I present 2 competing hypotheses for how intercellular communication might be altered during oncogenesis. As an initial test of these competing hypotheses, a recent secretome comparison between normal human mammary and HER2+ breast cancer cell lines suggested that the particular proteins secreted by the malignant cells reflect a convergent evolutionary path associated with oncogenesis in a specific anatomical niche, despite arising in different individuals. Overall, this study illustrates the emerging power of secretome proteomics to probe, in an unbiased way, how intercellular communication changes during oncogenesis. PMID:27308541

  6. Progressive and Regressive Developmental Changes in Neural Substrates for Face Processing: Testing Specific Predictions of the Interactive Specialization Account

    ERIC Educational Resources Information Center

    Joseph, Jane E.; Gathers, Ann D.; Bhatt, Ramesh S.

    2011-01-01

    Face processing undergoes a fairly protracted developmental time course but the neural underpinnings are not well understood. Prior fMRI studies have only examined progressive changes (i.e. increases in specialization in certain regions with age), which would be predicted by both the Interactive Specialization (IS) and maturational theories of…

  7. Revisiting a Progressive Pedagogy. The Developmental-Interaction Approach. SUNY Series, Early Childhood Education: Inquiries and Insights.

    ERIC Educational Resources Information Center

    Nager, Nancy, Ed.; Shapiro, Edna K., Ed.

    This book reviews the history of the developmental-interactive approach, a formulation rooted in developmental psychology and educational practice, progressively informing educational thinking since the early 20th century. The book describes and analyzes key assumptions and assesses the compatibility of new theoretical approaches, focuses on…

  8. PAMP-DAMPs interactions mediates development and progression of multiple sclerosis.

    PubMed

    Hernández-Pedro, Norma; Magana-Maldonado, Roxana; Ramiro, Aleli Salazar; Pérez-De la Cruz, Verónica; Rangel-López, Edgar; Sotelo, Julio; Pineda, Benjamin

    2016-01-01

    Multiple sclerosis (MS) is a disease presumably associated with chronic immune stimulation promoted by either pathogens or autoimmune processes. It has been hypothesized that MS could be the result of previous viral infections rendering a permanent immune stimulation that could be triggered by molecular similarities, or by modulating the antigens expression of major histocompatibility complex (MHC) on target cells, which in turn act as super antigens. During immune stimulation occurs the recruitment of immunological cells, resulting in local tissue damage and leading to the release of damage- associated molecular patterns (DAMPs), which also act as inflammation inducers. Recently, it has been proposed that the association between pathogen-associated molecular patterns (PAMPs) with DAMPs constitutes an additional level of immune regulation. The properties of DAMPs to act as carriers of PAMPs and their role as enhancers or inhibitors of PAMPs could play a role during inflammatory responses triggered by infections. Here, we focused this review in outcomes which support the hypothesis that particular PAMP-DAMPs interactions could regulated the relapse and progressive disability observed in multiple sclerosis.

  9. Accelerating progress in Artificial General Intelligence: Choosing a benchmark for natural world interaction

    NASA Astrophysics Data System (ADS)

    Rohrer, Brandon

    2010-12-01

    Measuring progress in the field of Artificial General Intelligence (AGI) can be difficult without commonly accepted methods of evaluation. An AGI benchmark would allow evaluation and comparison of the many computational intelligence algorithms that have been developed. In this paper I propose that a benchmark for natural world interaction would possess seven key characteristics: fitness, breadth, specificity, low cost, simplicity, range, and task focus. I also outline two benchmark examples that meet most of these criteria. In the first, the direction task, a human coach directs a machine to perform a novel task in an unfamiliar environment. The direction task is extremely broad, but may be idealistic. In the second, the AGI battery, AGI candidates are evaluated based on their performance on a collection of more specific tasks. The AGI battery is designed to be appropriate to the capabilities of currently existing systems. Both the direction task and the AGI battery would require further definition before implementing. The paper concludes with a description of a task that might be included in the AGI battery: the search and retrieve task.

  10. Defect Generation and Propagation in MC-Si Ingots: Influence on Cell-to-Cell Performance Variation

    SciTech Connect

    Sopori, B.; Rupnowski, P.; Shet, S.; Mehta, V.; Seacrist, M.; Shi, G.; Chen, J.; Deshpande, A.

    2011-01-01

    This paper describes results of our study aimed at understanding mechanism(s) of dislocation generation and propagation in multicrystalline silicon (mc-Si) ingots, and evaluating their influence on the solar cell performance. This work was done in two parts: (i) Measurement of dislocation distributions along various bricks, selected from strategic locations within several ingots; and (ii) Theoretical modeling of the cell performance corresponding to the measured dislocation distributions. Solar cells were fabricated on wafers of known dislocation distribution, and the results were compared with the theory. These results show that cell performance can be accurately predicted from the dislocation distribution, and the changes in the dislocation distribution are the primary cause for variations in the cell-to-cell performance. The dislocation generation and propagation mechanisms, suggested by our results, are described in this paper.

  11. Natural isolates of Brome mosaic virus with the ability to move from cell to cell independently of coat protein.

    PubMed

    Takeda, Atsushi; Nakamura, Wakako; Sasaki, Nobumitsu; Goto, Kaku; Kaido, Masanori; Okuno, Tetsuro; Mise, Kazuyuki

    2005-04-01

    Brome mosaic virus (BMV) requires encapsidation-competent coat protein (CP) for cell-to-cell movement and the 3a movement protein (MP) is involved in determining the CP requirement for BMV movement. However, these conclusions have been drawn by using BMV strain M1 (BMV-M1) and a related strain. Here, the ability of the MPs of five other natural BMV strains to mediate the movement of BMV-M1 in the absence of CP was tested. The MP of BMV M2 strain (BMV-M2) efficiently mediated the movement of CP-deficient BMV-M1 and the MPs of two other strains functioned similarly to some extent. Furthermore, BMV-M2 itself moved between cells independently of CP, demonstrating that BMV-M1 and -M2 use different movement modes. Reassortment between CP-deficient BMV-M1 and -M2 showed the involvement of RNA3 in determining the CP requirement for cell-to-cell movement and the involvement of RNAs 1 and 2 in movement efficiency and symptom induction in the absence of CP. Spontaneous BMV MP mutants generated in planta that exhibited CP-independent movement were also isolated and analysed. Comparison of the nucleotide differences of the MP genes of BMV-M1, the natural strains and mutants capable of CP-independent movement, together with further mutational analysis of BMV-M1 MP, revealed that single amino acid differences at the C terminus of MP are sufficient to alter the requirement for CP in the movement of BMV-M1. Based on these findings, a possible virus strategy in which a movement mode is selected in plant viruses to optimize viral infectivity in plants is discussed.

  12. Deciphering Cell-to-Cell Communication in Acquisition of Cancer Traits: Extracellular Membrane Vesicles Are Regulators of Tissue Biomechanics.

    PubMed

    Pokharel, Deep; Wijesinghe, Philip; Oenarto, Vici; Lu, Jamie F; Sampson, David D; Kennedy, Brendan F; Wallace, Vincent P; Bebawy, Mary

    2016-08-01

    Deciphering the role of cell-to-cell communication in acquisition of cancer traits such as metastasis is one of the key challenges of integrative biology and clinical oncology. In this context, extracellular vesicles (EVs) are important vectors in cell-to-cell communication and serve as conduits in the transfer of cellular constituents required for cell function and for the establishment of cellular phenotypes. In the case of malignancy, they have been shown to support the acquisition of common traits defined as constituting the hallmarks of cancer. Cellular biophysics has contributed to our understanding of some of these central traits with changes in tissue biomechanics reflective of cell state. Indeed, much is known about stiffness of the tissue scaffold in the context of cell invasion and migration. This article advances this knowledge frontier by showing for the first time that EVs are mediators of tissue biomechanical properties and, importantly, demonstrates a link between the acquisition of cancer multidrug resistance and increased tissue stiffness of the malignant mass. The methodology used in the study employed optical coherence elastography and atomic force microscopy on breast cancer cell monolayers and tumor spheroids. Specifically, we show here that the acquired changes in tissue stiffness can be attributed to the intracellular transfer of a protein complex comprising ezrin, radixin, moesin, CD44, and P-glycoprotein. This has important implications in facilitating mechano-transduced signaling cascades that regulate the acquisition of cancer traits, such as invasion and metastasis. Finally, this study also introduces novel targets and strategies for diagnostic and therapeutic innovation in oncology, with a view to prevention of metastatic spread and personalized medicine in cancer treatment. PMID:27501296

  13. [Biology of cancer cell-stroma interaction in carcinogenesis and cancer progression].

    PubMed

    Fujita, S; Sugihara, H; Ito, R; Tsuchihashi, Y

    1984-03-01

    Cancer cells are dependent on physical and chemical supports of stroma no less than non-cancerous cells and tissues are. The role of stroma should, therefore, be important in genesis and progression of cancers growing in vivo. But this aspect underlying carcinogenesis and manifestation of human cancers has long been neglected or attracted less attention in the investigations of oncology. Focusing particular attention on parenchyma-stromal interaction in gastrointestinal mucosa, the authors have found that, quite unexpectedly, in normal gastric as well as intestinal mucosa of all the animal species so for studied, vascularity is always poorly developed in the generative cell zones. Cross-sectional area of vascular bed is markedly reduced in this zone. Application of Hagen-Poiseulle law revealed that the reduced total cross-sectional area, resulting in a rapid drop in hydrostatic pressure, creates here a situation particularly favorable for proliferating cell population. Since the transport of water soluble material together with tissue fluid through the capillary wall is driven by the hydrostatic pressure, the generative cell zones are found to be present at the site where the turnover of the material is the most active. Before the zone of the rapid pressure drop, there appears zone of relatively high intravascular hydrostatic pressure, where secretory function seems to be facilitated. This zone, as is well known, corresponds to glandular portion of the mucosa. After the zone of the rapid pressure drop (in surface of the mucosa), zone of a low intravascular hydrostatic pressure appears, where absorptive function is to be facilitated. Within such zones, in gastric mucosa surface epithelium and in intestinal mucosa absorptive villi cells are located. It is likely that architecture of gastrointestinal epithelium and vascular pattern in the stroma is closely correlated and that the former is determined, at least partly, by the latter. When human gastric mucosa shows

  14. ENVIRONMENTAL EFFECTS OF OZONE DEPLETION AND ITS INTERACTIONS WITH CLIMATE CHANGE: PROGRESS REPORT 2004

    EPA Science Inventory

    The measures needed for the protection of the Earth's ozone layer are decided regularly by the Parties to the Montreal Protocol. This progress report is the 2004 update by the Environmental Effects Assessment Panel.

  15. Modelling the effects of cell-to-cell variability on the output of interconnected gene networks in bacterial populations

    PubMed Central

    2015-01-01

    Background The interconnection of quantitatively characterized biological devices may lead to composite systems with apparently unpredictable behaviour. Context-dependent variability of biological parts has been investigated in several studies, measuring its entity and identifying the factors contributing to variability. Such studies rely on the experimental analysis of model systems, by quantifying reporter genes via population or single-cell approaches. However, cell-to-cell variability is not commonly included in predictability analyses, thus relying on predictive models trained and tested on central tendency values. This work aims to study in silico the effects of cell-to-cell variability on the population-averaged output of interconnected biological circuits. Methods The steady-state deterministic transfer function of individual devices was described by Hill equations and lognormal synthetic noise was applied to their output. Two- and three-module networks were studied, where individual devices implemented inducible/repressible functions. The single-cell output of such networks was simulated as a function of noise entity; their population-averaged output was computed and used to investigate the expected variability in transfer function identification. The study was extended by testing different noise models, module logic, intrinsic/extrinsic noise proportions and network configurations. Results First, the transfer function of an individual module was identified from simulated data of a two-module network. The estimated parameter variability among different noise entities was limited (14%), while a larger difference was observed (up to 62%) when estimated and true parameters were compared. Thus, low-variability parameter estimates can be obtained for different noise entities, although deviating from the true parameters, whose measurement requires noise knowledge. Second, the black-box input-output function of a two/three-module network was predicted from the

  16. Dynamic changes in protein interaction between AKAP95 and Cx43 during cell cycle progression of A549 cells

    PubMed Central

    Chen, Xiaoxuan; Kong, Xiangyu; Zhuang, Wenxin; Teng, Bogang; Yu, Xiuyi; Hua, Suhang; Wang, Su; Liang, Fengchao; Ma, Dan; Zhang, Suhui; Zou, Xuan; Dai, Yue; Yang, Wei; Zhang, Yongxing

    2016-01-01

    Here we show that A-kinase anchoring protein 95 (AKAP95) and connexin 43 (Cx43) dynamically interact during cell cycle progression of lung cancer A549 cells. Interaction between AKAP95 and Cx43 at different cell cycle phases was examined by tandem mass spectrometry(MS/MS), confocal immunofluorescence microscopy, Western blot, and co-immunoprecipitation(Co-IP). Over the course of a complete cell cycle, interaction between AKAP95 and Cx43 occurred in two stages: binding stage from late G1 to metaphase, and separating stage from anaphase to late G1. The binding stage was further subdivided into complex binding to DNA in interphase and complex separating from DNA in metaphase. In late G1, Cx43 translocated to the nucleus via AKAP95; in anaphase, Cx43 separated from AKAP95 and aggregated between two daughter nuclei. In telophase, Cx43 aggregated at the membrane of the cleavage furrow. After mitosis, Cx43 was absent from the furrow membrane and was located in the cytoplasm. Binding between AKAP95 and Cx43 was reduced by N-(2-[P-Bromocinnamylamino]-ethyl)-5-isoquinolinesulfonmide (H89) treatment and enhanced by Forskolin. dynamic interaction between AKAP95 and Cx43 varies with cell cycle progression to regulate multiple biological processes. PMID:26880274

  17. Role of Rice Stripe Virus NSvc4 in Cell-to-Cell Movement and Symptom Development in Nicotiana benthamiana.

    PubMed

    Xu, Yi; Zhou, Xueping

    2012-01-01

    Our previous work has demonstrated that the NSvc4 protein of Rice stripe virus (RSV) functions as a cell-to-cell movement protein. However, the mechanisms whereby RSV traffics through plasmodesmata (PD) are unknown. Here we provide evidence that the NSvc4 moves on the actin filament and endoplasmic reticulum network, but not microtubules, to reach cell wall PD. Disruption of cytoskeleton using different inhibitors altered NSvc4 localization to PD, thus impeding RSV infection of Nicotiana benthamiana. Sequence analyses and deletion mutagenesis experiment revealed that the N-terminal 125 amino acids (AAs) of the NSvc4 determine PD targeting and that a transmembrane domain spanning AAs 106-125 is critical for PD localization. We also found that the NSvc4 protein can localize to chloroplasts in infected cells. Analyses using deletion mutants revealed that the N-terminal 73 AAs are essential for chloroplast localization. Furthermore, expression of NSvc4 from a Potato virus X (PVX) vector resulted in more severe disease symptoms than PVX alone in systemically infected N. benthamiana leaves. Expression of NSvc4 in Spodoptera frugiperda 9 cells did not elicit tubule formation, but instead resulted in punctate foci at the plasma membrane. These findings shed new light on our understanding of the movement mechanisms whereby RSV infects host plants. PMID:23233857

  18. Pattern formation in discrete cell tissues under long range filopodia-based direct cell to cell contact.

    PubMed

    Vasilopoulos, Georgios; Painter, Kevin J

    2016-03-01

    Pattern formation via direct cell to cell contact has received considerable attention over the years. In particular the lateral-inhibition mechanism observed in the Notch signalling pathway can generate a regular periodic pattern of differential cell activity, and has been proposed to explain the emergence of patterns in various tissues and organs. The majority of models of this system have focussed on short-range contacts: a cell signals only to its nearest neighbours and the resulting patterns tend to be of fine-scale "salt and pepper" nature. The capacity of certain cells to extend signalling filopodia (cytonemes) over multiple cell lengths, however, inserts a long-range or non-local component into this process. Here we explore how long range signalling can impact on pattern formation. Specifically, we extend a standard model for Notch-like lateral inhibition to include cytoneme-mediated signalling, and investigate how pattern formation depends on the spatial distribution of signal from the signalling cell. We show that a variety of patterns can be obtained, ranging from a sparse pattern of single isolated cells to larger clusters or stripes.

  19. Candidate topical microbicides bind herpes simplex virus glycoprotein B and prevent viral entry and cell-to-cell spread.

    PubMed

    Cheshenko, Natalia; Keller, Marla J; MasCasullo, Veronica; Jarvis, Gary A; Cheng, Hui; John, Minnie; Li, Jin-Hua; Hogarty, Kathleen; Anderson, Robert A; Waller, Donald P; Zaneveld, Lourens J D; Profy, Albert T; Klotman, Mary E; Herold, Betsy C

    2004-06-01

    Topical microbicides designed to prevent acquisition of sexually transmitted infections are urgently needed. Nonoxynol-9, the only commercially available spermicide, damages epithelium and may enhance human immunodeficiency virus transmission. The observation that herpes simplex virus (HSV) and human immunodeficiency virus bind heparan sulfate provided the rationale for the development of sulfated or sulfonated polymers as topical agents. Although several of the polymers have advanced to clinical trials, the spectrum and mechanism of anti-HSV activity and the effects on soluble mediators of inflammation have not been evaluated. The present studies address these gaps. The results indicate that PRO 2000, polystyrene sulfonate, cellulose sulfate, and polymethylenehydroquinone sulfonate inhibit HSV infection 10,000-fold and are active against clinical isolates, including an acyclovir-resistant variant. The compounds formed stable complexes with glycoprotein B and inhibit viral binding, entry, and cell-to-cell spread. The effects may be long lasting due to the high affinity and stability of the sulfated compound-virus complex, as evidenced by surface plasmon resonance studies. The candidate microbicides retained their antiviral activities in the presence of cervical secretions and over a broad pH range. There was little reduction in cell viability following repeated exposure of human endocervical cells to these compounds, although a reduction in secretory leukocyte protease inhibitor levels was observed. These studies support further development and rigorous evaluation of these candidate microbicides. PMID:15155195

  20. Cell-to-cell heterogeneity in cortical tension specifies curvature of contact surfaces in Caenorhabditis elegans embryos.

    PubMed

    Fujita, Masashi; Onami, Shuichi

    2012-01-01

    In the two-cell stage embryos of Caenorhabditis elegans, the contact surface of the two blastomeres forms a curve that bulges from the AB blastomere to the P₁ blastomere. This curve is a consequence of the high intracellular hydrostatic pressure of AB compared with that of P₁. However, the higher pressure in AB is intriguing because AB has a larger volume than P₁. In soap bubbles, which are a widely used model of cell shape, a larger bubble has lower pressure than a smaller bubble. Here, we reveal that the higher pressure in AB is mediated by its higher cortical tension. The cell fusion experiments confirmed that the curvature of the contact surface is related to the pressure difference between the cells. Chemical and genetic interferences showed that the pressure difference is mediated by actomyosin. Fluorescence imaging indicated that non-muscle myosin is enriched in the AB cortex. The cell killing experiments provided evidence that AB but not P₁ is responsible for the pressure difference. Computer simulation clarified that the cell-to-cell heterogeneity of cortical tensions is indispensable for explaining the pressure difference. This study demonstrates that heterogeneity in surface tension results in significant deviations of cell behavior compared to simple soap bubble models, and thus must be taken into consideration in understanding cell shape within embryos. PMID:22253922

  1. Cell-to-Cell Heterogeneity in Cortical Tension Specifies Curvature of Contact Surfaces in Caenorhabditis elegans Embryos

    PubMed Central

    Fujita, Masashi; Onami, Shuichi

    2012-01-01

    In the two-cell stage embryos of Caenorhabditis elegans, the contact surface of the two blastomeres forms a curve that bulges from the AB blastomere to the P1 blastomere. This curve is a consequence of the high intracellular hydrostatic pressure of AB compared with that of P1. However, the higher pressure in AB is intriguing because AB has a larger volume than P1. In soap bubbles, which are a widely used model of cell shape, a larger bubble has lower pressure than a smaller bubble. Here, we reveal that the higher pressure in AB is mediated by its higher cortical tension. The cell fusion experiments confirmed that the curvature of the contact surface is related to the pressure difference between the cells. Chemical and genetic interferences showed that the pressure difference is mediated by actomyosin. Fluorescence imaging indicated that non-muscle myosin is enriched in the AB cortex. The cell killing experiments provided evidence that AB but not P1 is responsible for the pressure difference. Computer simulation clarified that the cell-to-cell heterogeneity of cortical tensions is indispensable for explaining the pressure difference. This study demonstrates that heterogeneity in surface tension results in significant deviations of cell behavior compared to simple soap bubble models, and thus must be taken into consideration in understanding cell shape within embryos. PMID:22253922

  2. Physical and chemical analysis of lithium-ion battery cell-to-cell failure events inside custom fire chamber

    NASA Astrophysics Data System (ADS)

    Spinner, Neil S.; Field, Christopher R.; Hammond, Mark H.; Williams, Bradley A.; Myers, Kristina M.; Lubrano, Adam L.; Rose-Pehrsson, Susan L.; Tuttle, Steven G.

    2015-04-01

    A 5-cubic meter decompression chamber was re-purposed as a fire test chamber to conduct failure and abuse experiments on lithium-ion batteries. Various modifications were performed to enable remote control and monitoring of chamber functions, along with collection of data from instrumentation during tests including high speed and infrared cameras, a Fourier transform infrared spectrometer, real-time gas analyzers, and compact reconfigurable input and output devices. Single- and multi-cell packages of LiCoO2 chemistry 18650 lithium-ion batteries were constructed and data was obtained and analyzed for abuse and failure tests. Surrogate 18650 cells were designed and fabricated for multi-cell packages that mimicked the thermal behavior of real cells without using any active components, enabling internal temperature monitoring of cells adjacent to the active cell undergoing failure. Heat propagation and video recordings before, during, and after energetic failure events revealed a high degree of heterogeneity; some batteries exhibited short burst of sparks while others experienced a longer, sustained flame during failure. Carbon monoxide, carbon dioxide, methane, dimethyl carbonate, and ethylene carbonate were detected via gas analysis, and the presence of these species was consistent throughout all failure events. These results highlight the inherent danger in large format lithium-ion battery packs with regards to cell-to-cell failure, and illustrate the need for effective safety features.

  3. Cell-to-Cell Diversity in a Synchronized Chlamydomonas Culture As Revealed by Single-Cell Analyses

    PubMed Central

    Garz, Andreas; Sandmann, Michael; Rading, Michael; Ramm, Sascha; Menzel, Ralf; Steup, Martin

    2012-01-01

    In a synchronized photoautotrophic culture of Chlamydomonas reinhardtii, cell size, cell number, and the averaged starch content were determined throughout the light-dark cycle. For single-cell analyses, the relative cellular starch was quantified by measuring the second harmonic generation (SHG). In destained cells, amylopectin essentially represents the only biophotonic structure. As revealed by various validation procedures, SHG signal intensities are a reliable relative measure of the cellular starch content. During photosynthesis-driven starch biosynthesis, synchronized Chlamydomonas cells possess an unexpected cell-to-cell diversity both in size and starch content, but the starch-related heterogeneity largely exceeds that of size. The cellular volume, starch content, and amount of starch/cell volume obey lognormal distributions. Starch degradation was initiated by inhibiting the photosynthetic electron transport in illuminated cells or by darkening. Under both conditions, the averaged rate of starch degradation is almost constant, but it is higher in illuminated than in darkened cells. At the single-cell level, rates of starch degradation largely differ but are unrelated to the initial cellular starch content. A rate equation describing the cellular starch degradation is presented. SHG-based three-dimensional reconstructions of Chlamydomonas cells containing starch granules are shown. PMID:23009858

  4. SAMHD1 Restricts HIV-1 Cell-to-Cell Transmission and Limits Immune Detection in Monocyte-Derived Dendritic Cells

    PubMed Central

    Puigdomènech, Isabel; Casartelli, Nicoletta; Porrot, Françoise

    2013-01-01

    SAMHD1 is a viral restriction factor expressed in dendritic cells and other cells, inhibiting infection by cell-free human immunodeficiency virus type 1 (HIV-1) particles. SAMHD1 depletes the intracellular pool of deoxynucleoside triphosphates, thus impairing HIV-1 reverse transcription and productive infection in noncycling cells. The Vpx protein from HIV-2 or simian immunodeficiency virus (SIVsm/SIVmac) antagonizes the effect of SAMHD1 by triggering its degradation. A large part of HIV-1 spread occurs through direct contacts between infected cells and bystander target cells. Here, we asked whether SAMHD1 impairs direct HIV-1 transmission from infected T lymphocytes to monocyte-derived dendritic cells (MDDCs). HIV-1-infected lymphocytes were cocultivated with MDDCs that have been pretreated or not with Vpx or with small interfering RNA against SAMHD1. We show that in the cocultures, SAMHD1 significantly inhibits productive cell-to-cell transmission to target MDDCs and prevents the type I interferon response and expression of the interferon-stimulated gene MxA. Therefore, SAMHD1, by controlling the sensitivity of MDDCs to HIV-1 infection during intercellular contacts, impacts their ability to sense the virus and to trigger an innate immune response. PMID:23269793

  5. Development towards cell-to-cell monolithic integration of a thin-film solar cell and lithium-ion accumulator

    NASA Astrophysics Data System (ADS)

    Agbo, Solomon N.; Merdzhanova, Tsvetelina; Yu, Shicheng; Tempel, Hermann; Kungl, Hans; Eichel, Rüdiger-A.; Rau, Uwe; Astakhov, Oleksandr

    2016-09-01

    This work focuses on the potentials of monolithic integrated thin-film silicon solar cell and lithium ion cell in a simple cell-to-cell integration without any control electronics as a compact power solution for portable electronic devices. To demonstrate this we used triple-junction thin-film silicon solar cell connected directly to a lithium ion battery cell to charge the battery and in turn discharge the battery through the solar cell. Our results show that with appropriate voltage matching the solar cell provides efficient charging for lab-scale lithium ion storage cell. Despite the absence of any control electronics the discharge rate of the Li-ion cell through the non-illuminated solar cell can be much lower than the charging rate when the current voltage (IV) characteristics of the solar cell is matched properly to the charge-discharge characteristics of the battery. This indicates good sustainability of the ultimately simple integrated device. At the maximum power point, solar energy-to-battery charging efficiency of 8.5% which is nearly the conversion efficiency of the solar cell was obtained indicating potential for loss-free operation of the photovoltaic (PV)-battery integration. For the rest of the charging points, an average of 8.0% charging efficiency was obtained.

  6. Origins of stochastic intracellular processes and consequences for cell-to-cell variability and cellular survival strategies.

    PubMed

    Schwabe, A; Dobrzyński, M; Rybakova, K; Verschure, P; Bruggeman, F J

    2011-01-01

    Quantitative analyses of the dynamics of single cells have become a powerful approach in current cell biology. They give us an unprecedented opportunity to study dynamics of molecular networks at a high level of accuracy in living single cells. Genetically identical cells, growing in the same environment and sharing the same growth history, can differ remarkably in their molecular makeup and physiological behaviors. The origins of this cell-to-cell variability have in many cases been traced to the inevitable stochasticity of molecular reactions. Those mechanisms can cause isogenic cells to have qualitatively different life histories. Many studies indicate that molecular noise can be exploited by cell populations to enhance survival prospects in uncertain environments. On the other hand, cells have evolved noise-suppression mechanisms to cope with the inevitable noise in their functioning so as to reduce the hazardous effects of noise. In this chapter, we discuss key experiments, theoretical results, and physiological consequences of molecular stochasticity to introduce this exciting field to a broader community of (systems) biologists. PMID:21943916

  7. Functional characterization of an AQP0 missense mutation, R33C, that causes dominant congenital lens cataract, reveals impaired cell-to-cell adhesion

    PubMed Central

    Kumari, Sindhu S.; Gandhi, Jason; Mustehsan, Mohammed H.; Eren, Semih; Varadaraj, Kulandaiappan

    2013-01-01

    Aquaporin 0 (AQP0) performs dual functions in the lens fiber cells, as a water pore and as a cell-to-cell adhesion molecule. Mutations in AQP0 cause severe lens cataract in both humans and mice. An arginine to cysteine missense mutation at amino acid 33 (R33C) produced congenital autosomal dominant cataract in a Chinese family for five generations. We re-created this mutation in wild type (WT-AQP0) human AQP0 cDNA by site-directed mutagenesis, and cloned and expressed the mutant AQP0 (AQP0-R33C) in heterologous expression systems. Mutant AQP0-R33C showed proper trafficking and membrane localization like WT-AQP0. Functional studies conducted in Xenopus oocytes showed no significant difference (P>0.05) in water permeability between AQP0-R33C and WT-AQP0. However, the cell-to-cell adhesion property of AQP0-R33C was significantly reduced (P< 0.001) compared to that of WT-AQP0, indicated by cell aggregation and cell-to-cell adhesion assays. Scrape-loading assay using Lucifer Yellow dye showed reduction in cell-to-cell adhesion affecting gap junction coupling (P< 0.001). The data provided suggest that this mutation might not have caused significant alterations in protein folding since there was no obstruction in protein trafficking or water permeation. Reduction in cell-to-cell adhesion and development of cataract suggest that the conserved positive charge of Extracellular Loop A may play an important role in bringing fiber cells closer. The proposed schematic models illustrate that cell-to-cell adhesion elicited by AQP0 is vital for lens transparency and homeostasis. PMID:24120416

  8. Reinforcing Efficacy of Interactions with Preferred and Nonpreferred Staff under Progressive-Ratio Schedules

    ERIC Educational Resources Information Center

    Jerome, Jared; Sturmey, Peter

    2008-01-01

    Research has not systematically assessed and validated preferences for staff in adults with developmental disabilities. Three adults with developmental disabilities (aged 32 to 43 years) identified preferred and nonpreferred staff using verbal and pictorial preference assessments. During break-point analyses with progressive-ratio schedules, all 3…

  9. Heparan Sulfate Proteoglycans May Promote or Inhibit Cancer Progression by Interacting with Integrins and Affecting Cell Migration

    PubMed Central

    Soares, Mariana A.; Teixeira, Felipe C. O. B.; Fontes, Miguel; Arêas, Ana Lúcia; Leal, Marcelo G.; Pavão, Mauro S. G.; Stelling, Mariana P.

    2015-01-01

    The metastatic disease is one of the main consequences of tumor progression, being responsible for most cancer-related deaths worldwide. This review intends to present and discuss data on the relationship between integrins and heparan sulfate proteoglycans in health and cancer progression. Integrins are a family of cell surface transmembrane receptors, responsible for cell-matrix and cell-cell adhesion. Integrins' main functions include cell adhesion, migration, and survival. Heparan sulfate proteoglycans (HSPGs) are cell surface molecules that play important roles as cell receptors, cofactors, and overall direct or indirect contributors to cell organization. Both molecules can act in conjunction to modulate cell behavior and affect malignancy. In this review, we will discuss the different contexts in which various integrins, such as α5, αV, β1, and β3, interact with HSPGs species, such as syndecans and perlecans, affecting tissue homeostasis. PMID:26558271

  10. Identification of a Novel Drug Lead That Inhibits HCV Infection and Cell-to-Cell Transmission by Targeting the HCV E2 Glycoprotein

    SciTech Connect

    Al Olaby, Reem R.; Cocquerel, Laurence; Zemla, Adam; Saas, Laure; Dubuisson, Jean; Vielmetter, Jost; Marcotrigiano, Joseph; Khan, Abdul Ghafoor; Catalan, Felipe Vences; Perryman, Alexander L.; Freundlich, Joel S.; Forli, Stefano; Levy, Shoshana; Balhorn, Rod; Azzazy, Hassan M.

    2014-10-30

    We report that Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, two crystal structures of the core of the HCV E2 protein (E2c) have been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2’s interaction with different host factors. Using the E2c structure as a template, we have created a structural model of the E2 protein core (residues 421–645) that contains the three amino acid segments that are not present in either structure. Computational docking of a diverse library of 1,715 small molecules to this model led to the identification of a set of 34 ligands predicted to bind near conserved amino acid residues involved in the HCV E2: CD81 interaction. We used surface plasmon resonance detection to screen the ligand set for binding to recombinant E2 protein, and the best binders were subsequently tested to identify compounds that inhibit the infection of Huh-7 cells by HCV. One compound, 281816, blocked E2 binding to CD81 and inhibited HCV infection in a genotype-independent manner with IC50’s ranging from 2.2 µM to 4.6 µM. 281816 blocked the early and late steps of cell-free HCV entry and also abrogated the cell-to-cell transmission of HCV. Collectively the results obtained with this new structural model of E2c suggest the development of small molecule inhibitors such as 281816 that target E2 and disrupt its interaction with CD81 may provide a new paradigm for HCV treatment.

  11. Identification of a Novel Drug Lead That Inhibits HCV Infection and Cell-to-Cell Transmission by Targeting the HCV E2 Glycoprotein

    DOE PAGES

    Al Olaby, Reem R.; Cocquerel, Laurence; Zemla, Adam; Saas, Laure; Dubuisson, Jean; Vielmetter, Jost; Marcotrigiano, Joseph; Khan, Abdul Ghafoor; Catalan, Felipe Vences; Perryman, Alexander L.; et al

    2014-10-30

    We report that Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, two crystal structures of the core of the HCV E2 protein (E2c) have been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2’smore » interaction with different host factors. Using the E2c structure as a template, we have created a structural model of the E2 protein core (residues 421–645) that contains the three amino acid segments that are not present in either structure. Computational docking of a diverse library of 1,715 small molecules to this model led to the identification of a set of 34 ligands predicted to bind near conserved amino acid residues involved in the HCV E2: CD81 interaction. We used surface plasmon resonance detection to screen the ligand set for binding to recombinant E2 protein, and the best binders were subsequently tested to identify compounds that inhibit the infection of Huh-7 cells by HCV. One compound, 281816, blocked E2 binding to CD81 and inhibited HCV infection in a genotype-independent manner with IC50’s ranging from 2.2 µM to 4.6 µM. 281816 blocked the early and late steps of cell-free HCV entry and also abrogated the cell-to-cell transmission of HCV. Collectively the results obtained with this new structural model of E2c suggest the development of small molecule inhibitors such as 281816 that target E2 and disrupt its interaction with CD81 may provide a new paradigm for HCV treatment.« less

  12. Xanthomonas campestris overcomes Arabidopsis stomatal innate immunity through a DSF cell-to-cell signal-regulated virulence factor.

    PubMed

    Gudesblat, Gustavo E; Torres, Pablo S; Vojnov, Adrián A

    2009-02-01

    Pathogen-induced stomatal closure is part of the plant innate immune response. Phytopathogens using stomata as a way of entry into the leaf must avoid the stomatal response of the host. In this article, we describe a factor secreted by the bacterial phytopathogen Xanthomonas campestris pv campestris (Xcc) capable of interfering with stomatal closure induced by bacteria or abscisic acid (ABA). We found that living Xcc, as well as ethyl acetate extracts from Xcc culture supernatants, are capable of reverting stomatal closure induced by bacteria, lipopolysaccharide, or ABA. Xcc ethyl acetate extracts also complemented the infectivity of Pseudomonas syringae pv tomato (Pst) mutants deficient in the production of the coronatine toxin, which is required to overcome stomatal defense. By contrast, the rpfF and rpfC mutant strains of Xcc, which are unable to respectively synthesize or perceive a diffusible molecule involved in bacterial cell-to-cell signaling, were incapable of reverting stomatal closure, indicating that suppression of stomatal response by Xcc requires an intact rpf/diffusible signal factor system. In addition, we found that guard cell-specific Arabidopsis (Arabidopsis thaliana) Mitogen-Activated Protein Kinase3 (MPK3) antisense mutants were unresponsive to bacteria or lipopolysaccharide in promotion of stomatal closure, and also more sensitive to Pst coronatine-deficient mutants, showing that MPK3 is required for stomatal immune response. Additionally, we found that, unlike in wild-type Arabidopsis, ABA-induced stomatal closure in MPK3 antisense mutants is not affected by Xcc or by extracts from Xcc culture supernatants, suggesting that the Xcc factor might target some signaling component in the same pathway as MPK3. PMID:19091877

  13. Vasodilator-stimulated phosphoprotein restricts cell-to-cell spread of Shigella flexneri at the cell periphery.

    PubMed

    Lee, Soo Young; Gertler, Frank B; Goldberg, Marcia B

    2015-11-01

    Shigella spp. are intracellular bacterial pathogens that cause diarrhoeal disease in humans. Shigella utilize the host actin cytoskeleton to enter cells, move through the cytoplasm of cells and pass into adjacent cells. Ena/VASP family proteins are highly conserved proteins that participate in actin-dependent dynamic cellular processes. We tested whether Ena/VASP family members VASP (vasodilator-stimulated phosphoprotein), Mena (mammalian-enabled) or EVL (Ena-VASP-like) contribute to Shigella flexneri spread through cell monolayers. VASP and EVL restricted cell-to-cell spread without significantly altering actin-based motility, whereas Mena had no effect on these processes. Phosphorylation of VASP on Ser153, Ser235 and Thr274 regulated its subcellular distribution and function. VASP derivatives that lack the Ena/VASP homology 1 (EVH1) domain or contain a phosphoablative mutation of Ser153 were defective in restricting S. flexneri spread, indicating that the EVH1 domain and phosphorylation on Ser153 are required for this process. The EVH1 domain and Ser153 of VASP were required for VASP localization to focal adhesions, and localization of VASP to focal adhesions and/or the leading edge was required for restriction of spread. The contribution of the EVH1 domain was from both the donor and the recipient cell, whereas the contribution of Ser153 phosphorylation was only from the donor cell. Thus, unlike host proteins characterized in Shigella pathogenesis that promote bacterial spread, VASP and EVL function to limit it. The ability of VASP and EVL to limit spread highlights the critical role of focal adhesion complexes and/or the leading edge in bacterial passage between cells.

  14. Myotube formation is affected by adipogenic lineage cells in a cell-to-cell contact-independent manner

    SciTech Connect

    Takegahara, Yuki; Yamanouchi, Keitaro Nakamura, Katsuyuki; Nakano, Shin-ichi; Nishihara, Masugi

    2014-05-15

    Intramuscular adipose tissue (IMAT) formation is observed in some pathological conditions such as Duchenne muscular dystrophy (DMD) and sarcopenia. Several studies have suggested that IMAT formation is not only negatively correlated with skeletal muscle mass but also causes decreased muscle contraction in sarcopenia. In the present study, we examined w hether adipocytes affect myogenesis. For this purpose, skeletal muscle progenitor cells were transfected with siRNA of PPARγ (siPPARγ) in an attempt to inhibit adipogenesis. Myosin heavy chain (MHC)-positive myotube formation was promoted in cells transfected with siPPARγ compared to that of cells transfected with control siRNA. To determine whether direct cell-to-cell contact between adipocytes and myoblasts is a prerequisite for adipocytes to affect myogenesis, skeletal muscle progenitor cells were cocultured with pre- or mature adipocytes in a Transwell coculture system. MHC-positive myotube formation was inhibited when skeletal muscle progenitor cells were cocultured with mature adipocytes, but was promoted when they were cocultured with preadipocytes. Similar effects were observed when pre- or mature adipocyte-conditioned medium was used. These results indicate that preadipocytes play an important role in maintaining skeletal muscle mass by promoting myogenesis; once differentiated, the resulting mature adipocytes negatively affect myogenesis, leading to the muscle deterioration observed in skeletal muscle pathologies. - Highlights: • We examined the effects of pre- and mature adipocytes on myogenesis in vitro. • Preadipocytes and mature adipocytes affect myoblast fusion. • Preadipocytes play an important role in maintaining skeletal muscle mass. • Mature adipocytes lead to muscle deterioration observed in skeletal muscle pathologies.

  15. Vasodilator-stimulated phosphoprotein restricts cell-to-cell spread of Shigella flexneri at the cell periphery.

    PubMed

    Lee, Soo Young; Gertler, Frank B; Goldberg, Marcia B

    2015-11-01

    Shigella spp. are intracellular bacterial pathogens that cause diarrhoeal disease in humans. Shigella utilize the host actin cytoskeleton to enter cells, move through the cytoplasm of cells and pass into adjacent cells. Ena/VASP family proteins are highly conserved proteins that participate in actin-dependent dynamic cellular processes. We tested whether Ena/VASP family members VASP (vasodilator-stimulated phosphoprotein), Mena (mammalian-enabled) or EVL (Ena-VASP-like) contribute to Shigella flexneri spread through cell monolayers. VASP and EVL restricted cell-to-cell spread without significantly altering actin-based motility, whereas Mena had no effect on these processes. Phosphorylation of VASP on Ser153, Ser235 and Thr274 regulated its subcellular distribution and function. VASP derivatives that lack the Ena/VASP homology 1 (EVH1) domain or contain a phosphoablative mutation of Ser153 were defective in restricting S. flexneri spread, indicating that the EVH1 domain and phosphorylation on Ser153 are required for this process. The EVH1 domain and Ser153 of VASP were required for VASP localization to focal adhesions, and localization of VASP to focal adhesions and/or the leading edge was required for restriction of spread. The contribution of the EVH1 domain was from both the donor and the recipient cell, whereas the contribution of Ser153 phosphorylation was only from the donor cell. Thus, unlike host proteins characterized in Shigella pathogenesis that promote bacterial spread, VASP and EVL function to limit it. The ability of VASP and EVL to limit spread highlights the critical role of focal adhesion complexes and/or the leading edge in bacterial passage between cells. PMID:26358985

  16. Role of HGF in epithelial–stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ

    PubMed Central

    2013-01-01

    Introduction Basal-like and luminal breast cancers have distinct stromal–epithelial interactions, which play a role in progression to invasive cancer. However, little is known about how stromal–epithelial interactions evolve in benign and pre-invasive lesions. Methods To study epithelial–stromal interactions in basal-like breast cancer progression, we cocultured reduction mammoplasty fibroblasts with the isogenic MCF10 series of cell lines (representing benign/normal, atypical hyperplasia, and ductal carcinoma in situ). We used gene expression microarrays to identify pathways induced by coculture in premalignant cells (MCF10DCIS) compared with normal and benign cells (MCF10A and MCF10AT1). Relevant pathways were then evaluated in vivo for associations with basal-like subtype and were targeted in vitro to evaluate effects on morphogenesis. Results Our results show that premalignant MCF10DCIS cells express characteristic gene expression patterns of invasive basal-like microenvironments. Furthermore, while hepatocyte growth factor (HGF) secretion is upregulated (relative to normal, MCF10A levels) when fibroblasts are cocultured with either atypical (MCF10AT1) or premalignant (MCF10DCIS) cells, only MCF10DCIS cells upregulated the HGF receptor MET. In three-dimensional cultures, upregulation of HGF/MET in MCF10DCIS cells induced morphological changes suggestive of invasive potential, and these changes were reversed by antibody-based blocking of HGF signaling. These results are relevant to in vivo progression because high expression of a novel MCF10DCIS-derived HGF signature was correlated with the basal-like subtype, with approximately 86% of basal-like cancers highly expressing the HGF signature, and because high expression of HGF signature was associated with poor survival. Conclusions Coordinated and complementary changes in HGF/MET expression occur in epithelium and stroma during progression of pre-invasive basal-like lesions. These results suggest that

  17. MAME Models for 4D Live-cell Imaging of Tumor: Microenvironment Interactions that Impact Malignant Progression

    PubMed Central

    Sameni, Mansoureh; Anbalagan, Arulselvi; Olive, Mary B.; Moin, Kamiar; Mattingly, Raymond R.; Sloane, Bonnie F.

    2012-01-01

    We have developed 3D coculture models, which we term MAME (mammary architecture and microenvironment engineering), and used them for live-cell imaging in real-time of cell:cell interactions. Our overall goal was to develop models that recapitulate the architecture of preinvasive breast lesions to study their progression to an invasive phenotype. Specifically, we developed models to analyze interactions among pre-malignant breast epithelial cell variants and other cell types of the tumor microenvironment that have been implicated in enhancing or reducing the progression of preinvasive breast epithelial cells to invasive ductal carcinomas. Other cell types studied to date are myoepithelial cells, fibroblasts, macrophages and blood and lymphatic microvascular endothelial cells. In addition to the MAME models, which are designed to recapitulate the cellular interactions within the breast during cancer progression, we have developed comparable models for the progression of prostate cancers. Here we illustrate the procedures for establishing the 3D cocultures along with the use of live-cell imaging and a functional proteolysis assay to follow the transition of cocultures of breast ductal carcinoma in situ (DCIS) cells and fibroblasts to an invasive phenotype over time, in this case over twenty-three days in culture. The MAME cocultures consist of multiple layers. Fibroblasts are embedded in the bottom layer of type I collagen. On that is placed a layer of reconstituted basement membrane (rBM) on which DCIS cells are seeded. A final top layer of 2% rBM is included and replenished with every change of media. To image proteolysis associated with the progression to an invasive phenotype, we use dye-quenched (DQ) fluorescent matrix proteins (DQ-collagen I mixed with the layer of collagen I and DQ-collagen IV mixed with the middle layer of rBM) and observe live cultures using confocal microscopy. Optical sections are captured, processed and reconstructed in 3D with Volocity

  18. An Observational Study of Interaction and Progress for the Immigrant in School

    ERIC Educational Resources Information Center

    Ward, J.

    1978-01-01

    Examines factors influencing social interaction and academic performance of immigrant children in British urban elementary schools. Methods are suggested for helping immigrant children adapt to British culture and improve academic performance. (Author/DB)

  19. Elementary particle interactions. Progress report, October 1, 1991--September 30, 1992

    SciTech Connect

    Bugg, W.M.; Condo, G.T.; Handler, T.; Hart, E.L.; Read, K.; Ward, B.F.L.

    1992-10-01

    Work continues on strange particle production in weak interactions using data from a high-energy neutrino exposure in a freon bubble chamber. Meson photoproduction has also consumed considerable effort. Detector research and development activities have been carried out.

  20. Experimental studies of pion-nucleus interactions at intermediate energies. Annual progress report

    SciTech Connect

    Not Available

    1991-12-31

    This report summarizes the work on experimental research in intermediate energy nuclear physics carried out at New Mexico State University in 1991 under a great from the US Department of Energy. Most of these studies have involved investigations of various pion-nucleus interactions. The work has been carried out both with the LAMPF accelerator at the Los Alamos National Laboratory and with the cyclotron at the Paul Scherrer Institute (PSI) near Zurich, Switzerland. Part of the experimental work involves measurements of new data on double-charge-exchange scattering, using facilities at LAMPF which we helped modify, and on pion absorption, using a new detector system at PSI that covers nearly the full solid-angle region which we helped construct. Other work involved preparation for future experiments using polarized nuclear targets and a new high-resolution spectrometer system for detecting {pi}{sup 0} mesons. We also presented several proposals for works to be done in future years, involving studies related to pi-mesonic atoms, fundamental pion-nucleon interactions, studies of the difference between charged and neutral pion interactions with the nucleon, studies of the isospin structure of pion-nucleus interactions, and pion scattering from polarized {sup 3}He targets. This work is aimed at improving our understanding of the pion-nucleon interaction, of the pion-nucleus interaction mechanism, and of nuclear structure.

  1. Mutational analysis of the RNA-binding domain of the Prunus necrotic ringspot virus (PNRSV) movement protein reveals its requirement for cell-to-cell movement

    SciTech Connect

    Carmen Herranz, Ma; Mingarro, Ismael; Pallas, Vicente . E-mail: vpallas@ibmcp.upv.es

    2005-08-15

    The movement protein (MP) of Prunus necrotic ringspot virus (PNRSV) is required for cell-to-cell movement. MP subcellular localization studies using a GFP fusion protein revealed highly punctate structures between neighboring cells, believed to represent plasmodesmata. Deletion of the RNA-binding domain (RBD) of PNRSV MP abolishes the cell-to-cell movement. A mutational analysis on this RBD was performed in order to identify in vivo the features that govern viral transport. Loss of positive charges prevented the cell-to-cell movement even though all mutants showed a similar accumulation level in protoplasts to those observed with the wild-type (wt) MP. Synthetic peptides representing the mutants and wild-type RBDs were used to study RNA-binding affinities by EMSA assays being approximately 20-fold lower in the mutants. Circular dichroism analyses revealed that the secondary structure of the peptides was not significantly affected by mutations. The involvement of the affinity changes between the viral RNA and the MP in the viral cell-to-cell movement is discussed.

  2. Inhibition of cell-to-cell transmission of human T-cell lymphotropic virus type 1 in vitro by carbohydrate-binding agents.

    PubMed

    Balestrieri, Emanuela; Ascolani, Arianna; Igarashi, Yasuhiro; Oki, Toshikazu; Mastino, Antonio; Balzarini, Jan; Macchi, Beatrice

    2008-08-01

    Peripheral blood mononuclear cells (PBMCs) from healthy individuals can be infected by human T-lymphotropic virus type 1 (HTLV-1) upon cocultivation of the PBMCs with irradiated HTLV-1-transformed human MT-2 cells. This model system closely mimics HTLV-1 transmission through cell-to-cell contact. Carbohydrate-binding agents (CBAs) such as the alpha(1,3)/alpha(1,6)mannose-specific Hippeastrum hybrid agglutinin and the GlcNAc-specific Urtica dioica agglutinin, and also the small, nonpeptidic alpha(1,2)-mannose-specific antibiotic pradimicin A, were able to efficiently prevent cell-to-cell HTLV-1 transmission at nontoxic concentrations, as evidenced by the lack of appearance of virus-specific mRNA and of the viral protein Tax in the acceptor cells. Consistently, antivirally active doses of CBAs fully prevented HTLV-1-induced stimulation of PBMC growth. The inhibitory effects of CBAs on HTLV-1 transmission were also evident when HTLV-1-infected C5MJ cells were used in place of MT-2 cells as a virus donor cell line. The anti-HTLV-1 properties of the CBAs highlight the importance of the envelope glycans in events underlying HTLV-1 passage from cell to cell and indicate that CBAs should be further investigated for their potential to prevent HTLV-1 infection, including mother-to-child virus transmission by cell-to-cell contact through breast milk feeding. PMID:18505856

  3. The Roles of Hyaluronan/RHAMM/CD44 and Their Respective Interactions along the Insidious Pathways of Fibrosarcoma Progression

    PubMed Central

    Nikitovic, Dragana; Kouvidi, Katerina; Karamanos, Nikos K.; Tzanakakis, George N.

    2013-01-01

    Fibrosarcomas are rare malignant mesenchymal tumors originating from fibroblasts. Importantly, fibrosarcoma cells were shown to have a high content and turnover of extracellular matrix (ECM) components including hyaluronan (HA), proteoglycans, collagens, fibronectin, and laminin. ECMs are complicated structures that surround and support cells within tissues. During cancer progression, significant changes can be observed in the structural and mechanical properties of the ECM components. Importantly, hyaluronan deposition is usually higher in malignant tumors as compared to benign tissues, predicting tumor progression in some tumor types. Furthermore, activated stromal cells are able to produce tissue structure rich in hyaluronan in order to promote tumor growth. Key biological roles of HA result from its interactions with its specific CD44 and RHAMM (receptor for HA-mediated motility) cell-surface receptors. HA-receptor downstream signaling pathways regulate in turn cellular processes implicated in tumorigenesis. Growth factors, including PDGF-BB, TGFβ2, and FGF-2, enhanced hyaluronan deposition to ECM and modulated HA-receptor expression in fibrosarcoma cells. Indeed, FGF-2 through upregulation of specific HAS isoforms and hyaluronan synthesis regulated secretion and net hyaluronan deposition to the fibrosarcoma pericellular matrix modulating these cells' migration capability. In this paper we discuss the involvement of hyaluronan/RHAMM/CD44 mediated signaling in the insidious pathways of fibrosarcoma progression. PMID:24083250

  4. Cell-to-Cell Contact as an Efficient Mode of Epstein-Barr Virus Infection of Diverse Human Epithelial Cells

    PubMed Central

    Imai, Shosuke; Nishikawa, Jun; Takada, Kenzo

    1998-01-01

    We show clear evidence for direct infection of various human epithelial cells by Epstein-Barr virus (EBV) in vitro. The successful infection was achieved by using recombinant EBV (Akata strain) carrying a selective marker gene but without any other artificial operations, such as introduction of the known EBV receptor (CD21) gene or addition of polymeric immunoglobulin A against viral gp350 in culture. Of 21 human epithelial cell lines examined, 18 became infected by EBV, as ascertained by the detection of EBV-determined nuclear antigen (EBNA) 1 expression in the early period after virus exposure, and the following selection culture easily yielded a number of EBV-infected clones from 15 cell lines. None of the human fibroblasts and five nonhuman-derived cell lines examined was susceptible to the infection. By comparison, cocultivation with virus producers showed ≈800-fold-higher efficiency of infection than cell-free infection did, suggesting the significance of direct cell-to-cell contact as a mode of virus spread in vivo. Most of the epithelial cell lines infectable with EBV were negative for CD21 expression at the protein and mRNA levels. The majority of EBV-infected clones established from each cell line invariably expressed EBNA1, EBV-encoded small RNAs, rightward transcripts from the BamHI-A region of the virus genome, and latent membrane protein (LMP) 2A, but not the other EBNAs or LMP1. This restricted form of latent viral gene expression, which is a central issue for understanding epithelial oncogenesis by EBV, resembled that seen in EBV-associated gastric carcinoma and LMP1-negative nasopharyngeal carcinoma. The results indicate that direct infection of epithelial cells by EBV may occur naturally in vivo, and this could be mediated by an unidentified, epithelium-specific binding receptor for EBV. The EBV convertants are viewed, at least in terms of viral gene expression, as in vitro analogs of EBV-associated epithelial tumor cells, thus facilitating

  5. Ska3 Ensures Timely Mitotic Progression by Interacting Directly With Microtubules and Ska1 Microtubule Binding Domain

    PubMed Central

    Abad, Maria Alba; Zou, Juan; Medina-Pritchard, Bethan; Nigg, Erich A.; Rappsilber, Juri; Santamaria, Anna; Jeyaprakash, A. Arockia

    2016-01-01

    The establishment of physical attachment between the kinetochore and dynamic spindle microtubules, which undergo cycles of polymerization and depolymerization generating straight and curved microtubule structures, is essential for accurate chromosome segregation. The Ndc80 and Ska complexes are the major microtubule-binding factors of the kinetochore responsible for maintaining chromosome-microtubule coupling during chromosome segregation. We previously showed that the Ska1 subunit of the Ska complex binds dynamic microtubules using multiple contact sites in a mode that allows conformation-independent binding. Here, we show that the Ska3 subunit is required to modulate the microtubule binding capability of the Ska complex (i) by directly interacting with tubulin monomers and (ii) indirectly by interacting with tubulin contacting regions of Ska1 suggesting an allosteric regulation. Perturbing either the Ska3-microtubule interaction or the Ska3-Ska1 interactions negatively influences microtubule binding by the Ska complex in vitro and affects the timely onset of anaphase in cells. Thus, Ska3 employs additional modulatory elements within the Ska complex to ensure robust kinetochore-microtubule attachments and timely progression of mitosis. PMID:27667719

  6. Environmental effects of ozone depletion and its interactions with climate change: progress report, 2015

    EPA Science Inventory

    The Environmental Effects Assessment Panel (EEAP) is one of three Panels that regularly informs the Parties (countries) to the Montreal Protocol on the effects of ozone depletion and the consequences of climate change interactions with respect to human health, animals, plants, bi...

  7. Further Progress on a Design for a Super-B Interaction Region

    SciTech Connect

    Sullivan, M; Bertsche, K.; Seeman, J.; Wienands, U.; Biagini, M.E.; Raimondi, P.; Paoloni, E.; Bettoni, S.; /CERN

    2009-05-20

    We present an improved design for a SuperB interaction region. The new design minimizes local bending of the two colliding beams by separating all beam magnetic elements near the Interaction Point (IP). The total crossing angle at the IP is increased from 48 mrad to 60 mrad. The first magnetic element is a six slice Permanent Magnet (PM) quadrupole with an elliptical aperture allowing us to increase the vertical space for the beam. This magnet starts 36 cm from the Interaction Point (IP). This magnet is only seen by the Low-Energy Beam (LEB), the High-Energy Beam (HEB) has a drift space at this location. This allows the preliminary focusing of the LEB which has a smaller beta y* at the IP than the HEB. The rest of the final focusing for both beams is achieved by two super-conducting side-by-side quadrupoles (QD0 and QF1). These sets of magnets are enclosed in a warm bore cryostat located behind the PM quadrupole for the LEB. We describe this design for the interaction region.

  8. Electric Cell-Substrate Impedance Sensing (ECIS) with Microelectrode Arrays for Investigation of Cancer Cell-Fibroblasts Interaction.

    PubMed

    Tran, Trong Binh; Baek, Changyoon; Min, Junhong

    2016-01-01

    The tumor microenvironment, including stromal cells, surrounding blood vessels and extracellular matrix components, has been defined as a crucial factor that influences the proliferation, drug-resistance, invasion and metastasis of malignant epithelial cells. Among other factors, the communications and interaction between cancer cells and stromal cells have been reported to play pivotal roles in cancer promotion and progression. To investigate these relationships, an on-chip co-culture model was developed to study the cellular interaction between A549-human lung carcinoma cells and MRC-5-human lung epithelial cells in both normal proliferation and treatment conditions. In brief, a co-culture device consisting of 2 individual fluidic chambers in parallel, which were separated by a 100 μm fence was utilized for cell patterning. Microelectrodes arrays were installed within each chamber including electrodes at various distances away from the confrontation line for the electrochemical impedimetric sensing assessment of cell-to-cell influence. After the fence was removed and cell-to-cell contact occurred, by evaluating the impedance signal responses representing cell condition and behavior, both direct and indirect cell-to-cell interactions through conditioned media were investigated. The impact of specific distances that lead to different influences of fibroblast cells on cancer cells in the co-culture environment was also defined. PMID:27088611

  9. Electric Cell-Substrate Impedance Sensing (ECIS) with Microelectrode Arrays for Investigation of Cancer Cell – Fibroblasts Interaction

    PubMed Central

    Tran, Trong Binh; Baek, Changyoon; Min, Junhong

    2016-01-01

    The tumor microenvironment, including stromal cells, surrounding blood vessels and extracellular matrix components, has been defined as a crucial factor that influences the proliferation, drug-resistance, invasion and metastasis of malignant epithelial cells. Among other factors, the communications and interaction between cancer cells and stromal cells have been reported to play pivotal roles in cancer promotion and progression. To investigate these relationships, an on-chip co-culture model was developed to study the cellular interaction between A549—human lung carcinoma cells and MRC-5—human lung epithelial cells in both normal proliferation and treatment conditions. In brief, a co-culture device consisting of 2 individual fluidic chambers in parallel, which were separated by a 100 μm fence was utilized for cell patterning. Microelectrodes arrays were installed within each chamber including electrodes at various distances away from the confrontation line for the electrochemical impedimetric sensing assessment of cell-to-cell influence. After the fence was removed and cell-to-cell contact occurred, by evaluating the impedance signal responses representing cell condition and behavior, both direct and indirect cell-to-cell interactions through conditioned media were investigated. The impact of specific distances that lead to different influences of fibroblast cells on cancer cells in the co-culture environment was also defined. PMID:27088611

  10. Experiments on continuum electron capture in atomic hydrogen and collisional interaction of trapped ions. Progress report

    SciTech Connect

    Sellin, I.A.; Elston, S.B.

    1981-01-01

    This section describes the background and scope of as well as progress made on experiments designed to test the present theory of charge exchange to continuum for the case of bare nuclei on atomic hydrogen. The charge transfer process is well known to be an essential ingredient of any attempt to understand the ionization of gaseous media traversed by highly-charged energetic ions. Surprisingly, a sometimes dominant contribution to such ionization remained undiscovered until the past decade. This process, known as charge transfer to the continuum, involves the ionization of electrons from the target species into unbound states closely matched in exit direction and speed to the charged particles which generate them. Subsequent measurements of the resultant forward electron production, performed by University of Tennessee searchers at Oak Ridge and Brookhaven National Laboratories, were unique in employing more highly charged projectiles than previously.

  11. The role of the cell–cell interactions in cancer progression

    PubMed Central

    Kamińska, Katarzyna; Szczylik, Cezary; Bielecka, Zofia F; Bartnik, Ewa; Porta, Camillo; Lian, Fei; Czarnecka, Anna M

    2015-01-01

    In the field of cancer research, scientific investigations are based on analysing differences in the secretome, the proteome, the transcriptome, the expression of cell surface molecules, and the deregulation of signal transduction pathways between neoplastic and normal cells. Accumulating evidence indicates a crucial role in carcinogenesis concerning not only stromal cells but also normal cells from target organs and tissue where tumours emerge. The tumour microenvironment (TME) definitively plays an important role in regulating neighbouring cell behaviour. To date, limited attention has been focused upon interactions between cancer cells and normal cells. This review concentrates on the interactions between stromal and healthy cells from the TME in cancer development. In the article, the authors also describe mutations, genes and proteins expression pattern that are involved in tumour development in target organ. PMID:25598217

  12. PROGRESS ON THE INTERACTION REGION DESIGN AND DETECTOR INTEGRATION AT JLAB'S MEIC

    SciTech Connect

    Morozov, Vasiliy; Brindza, Paul; Camsonne, Alexandre; Derbenev, Yaroslav; Ent, Rolf; Gaskell, David; Lin, Fanglei; Nadel-Turonski, Pawel; Ungaro, Maurizio; Zhang, Yuhong; Hyde, Charles; Park, Kijun; Sullivan, Michael; Zhao, Zhiwen

    2014-07-01

    One of the unique features of JLab's Medium-energy Electron-Ion Collider (MEIC) is a full-acceptance detector with a dedicated, small-angle, high-resolution detection system, capable of covering a wide range of momenta (and charge-to-mass ratios) with respect to the original ion beam to enable access to new physics. We present an interaction region design developed with close integration of the detection and beam dynamical aspects. The dynamical aspect of the design rests on a symmetry-based concept for compensation of non-linear effects. The optics and geometry have been optimized to accommodate the detection requirements and to ensure the interaction region's modularity for ease of integration into the collider ring lattices. As a result, the design offers an excellent detector performance combined with the necessary provisions for non-linear dynamical optimization.

  13. [The interaction of ferredoxin:NADP{sup +} oxidoreductase and ferredoxin:thioredoxin reductase with substrates]. Progress report

    SciTech Connect

    Not Available

    1992-09-01

    We seek to map the ferredoxin-binding sites on three soluble enzymes located in spinach chloroplasts which utilize ferredoxin as an electron donor:Ferredoxin:NADP{sup +}oxidoreductase (FNR); ferredoxin:thioredoxin reductase (FTR) and glutamate synthase. As the availability of amino acid sequences for the enzymes are important in such studies, that the amino acid sequence of glutamate synthase needs be determined, the amino acid sequences of FNR, FTR and ferredoxin are already known. Related to an aim elucidate the binding sites for ferredoxin to determine whether there is a common binding site on all of these ferredoxin-dependent chloroplast enzymes and, if so, to map it. Additionally thioredoxin binding by FTR needs be determine to resolve whether the same site on FTR is involved in binding both ferredoxin and thioredoxin. Considerable progress is reported on the prosthetic groups of glutamate synthase, in establishing the role of arginine and lysine residues in ferredoxin binding by, ferredoxin:nitrite oxidoreductase nitrite reductase, labelling carboxyl groups on ferredoxin with taurine and labelling lysine residues biotinylation, and low potential heme proteins have been isolated and characterized from a non-photosynthetic plant tissue. Although the monoclonal antibodies raised against FNR turned out not to be useful for mapping the FNR/ferredoxin or FNR/NADPinteraction domains, good progress has been made on mapping the FNR/ferredoxin interaction domains by an alternative technique. The techniques developed for differential chemical modification of these two proteins - taurine modification of aspartate and glutamate residues and biotin modification of lysine residues - should be useful for mapping the interaction domains of many proteins that associate through electrostatic interactions.

  14. Progressive acclimation alters interaction between salinity and temperature in experimental Daphnia populations.

    PubMed

    Loureiro, Cláudia; Cuco, Ana P; Claro, Maria Teresa; Santos, Joana I; Pedrosa, M Arminda; Gonçalves, Fernando; Castro, Bruno B

    2015-11-01

    Environmental stressors rarely act in isolation, giving rise to interacting environmental change scenarios. However, the impacts of such interactions on natural populations must consider the ability of organisms to adapt to environmental changes. The phenotypic adaptability of a Daphnia galeata clone to temperature rise and salinisation was investigated in this study, by evaluating its halotolerance at two different temperatures, along a short multigenerational acclimation scenario. Daphniids were acclimated to different temperatures (20°C and 25°C) and salinities (0gL(-1) and 1gL(-1), using NaCl as a proxy) in a fully crossed design. The objective was to understand whether acclimation to environmental stress (combinations of temperature and salinity) influenced the response to the latter exposure to these stressors. We hypothesize that acclimation to different temperature×salinity regimes should elicit an acclimation response of daphniids to saline stress or its interaction with temperature. Acute (survival time) and chronic (juvenile growth) halotolerance measures were obtained at discrete timings along the acclimation period (generations F1, F3 and F9). Overall, exposure temperature was the main determinant of the acute and chronic toxicity of NaCl: daphniid sensitivity (measured as the decrease of survival time or juvenile growth) was consistently higher at the highest temperature, irrespective of background conditions. However, this temperature-dependent effect was nullified after nine generations, but only when animals had been acclimated to both stressors (high salinity and high temperature). Such complex interaction scenarios should be taken in consideration in risk assessment practices.

  15. Interaction of radiation with matter. Research progress report, November 1, 1979-October 31, 1980

    SciTech Connect

    1980-09-01

    The mechanisms of dissipation of energy in organic and inorganic materials, and the application of the technique developed to a study of selected problems of environmental concern in the production of energy from fossil fuels were studied. In the Inorganic Phase of the work the research involves (1) measurements of cross-sections for K and L-shell ionization processes for heavy projectiles in the low velocity region, (2) experimental tests of target dependence of the effective-charge theory for light projectiles, (3) theoretical studies on the energy loss of swift particles in plasmas over a broad density and temperature range. The organic phase of the work falls into a series of closely related areas, all derived from a study of the interaction of radiation with matter. (1) New techniques for the study of small particulates (approx. 1..mu..); composition, mass (to +-1 pg) and charge (+-1 electron) can be determined. (2) External photoelectric effects as a tool in arriving at the electronic structure of organic crystals. (3) The interaction of water with charge carriers in organic crystals, producing reactive chemical species, such as Oh and HSO/sub 3/ radicals. (4) Mechanisms of interaction of air-pollutant polycyclic aromatic carcinogens with DNA and the study of the conformation of the adducts.

  16. Numerical and laboratory experiments on the dynamics of plume-ridge interaction. Progress report

    SciTech Connect

    Kincaid, C.; Gable, C.W.

    1995-09-01

    Mantle plumes and passive upwelling beneath ridges are the two dominant modes of mantle transport and thermal/chemical fluxing between the Earth`s deep interior and surface. While plumes and ridges independently contribute to crustal accretion, they also interact and the dispersion of plumes within the upper mantle is strongly modulated by mid-ocean ridges. The simplest mode of interaction, with the plume centered on the ridge, has been well documented and modeled. The remaining question is how plumes and ridges interact when the plume is located off-axis; it has been suggested that a pipeline-like flow from the off-axis plume to the ridge axis at the base of the rigid lithosphere may develop. Mid-ocean ridges migrating away from hot mantle plumes can be affected by plume discharges over long times and ridge migration distances. Salient feature of this model is that off-axis plumes communicate with the ridge through a channel resulting from the refraction and dispersion of an axi-symmetric plume conduit along the base of the sloping lithosphere. To test the dynamics of this model, a series of numerical and laboratory dynamic experiments on the problem of a fixed ridge and an off-axis buoyant upwelling were conducted. Results are discussed.

  17. Cell-to-cell diffusion of glucose in the mammalian heart is disrupted by high glucose. Implications for the diabetic heart.

    PubMed

    De Mello, Walmor C

    2015-06-10

    The cell-to-cell diffusion of glucose in heart cell pairs isolated from the left ventricle of adult Wistar Kyoto rats was investigated. For this, fluorescent glucose was dialyzed into one cell of the pair using the whole cell clamp technique, and its diffusion from cell-to-cell was investigated by measuring the fluorescence in the dialyzed as well as in non-dialyzed cell as a function of time. The results indicated that: 1) glucose flows easily from cell-to-cell through gap junctions; 2) high glucose solution (25 mM) disrupted chemical communication between cardiac cells and abolished the intercellular diffusion of glucose; 3) the effect of high glucose solution on the cell-to-cell diffusion of glucose was drastically reduced by Bis-1 (10(-9)M) which is a PKC inhibitor; 4) intracellular dialysis of Ang II (100 nM) or increment of intracellular calcium concentration (10(-8)M) also inhibited the intercellular diffusion of glucose; 5) high glucose enhances oxidative stress in heart cells; 6) calculation of gap junction permeability (Pj) (cm/s) indicated a value of 0.74±0.08×10(-4) cm/s (5 animals) for the controls and 0.4±0.001×10(-5) cm/s; n=35 (5 animals) (P<0.05) for cells incubated with high glucose solution for 24h; 7) measurements of Pj for cell pairs treated with high glucose plus Bis-1 (10(-9)M) revealed no significant change of Pj (P>0.05); 8) increase of intracellular Ca(2+) concentration (10(-8)M) drastically decreased Pj (Pj=0.3±0.003×10(-5) cm/s). Conclusions indicate that: 1) glucose flows from cell-to-cell in the heart through gap junctions; 2) high glucose (25 mM) inhibited the intercellular diffusion of glucose-an effect significantly reduced by PKC inhibition; 3) high intracellular Ca(2+) concentration abolished the cell-to-cell diffusion of glucose; 4) intracellular Ang II (100 nM) inhibited the intercellular diffusion of glucose indicating that intracrine Ang II, in part activated by high glucose, severely impairs the exchange of glucose

  18. Pharmacokinetic herb-drug interactions with traditional Chinese medicine: progress, causes of conflicting results and suggestions for future research.

    PubMed

    Ma, Bing-Liang; Ma, Yue-Ming

    2016-01-01

    Traditional Chinese medicine (TCM) has a long history of medical use in China and is still used worldwide. Unexpected herb-drug interactions (HDIs) may lead to adverse drug reactions or loss of therapeutic efficacy of the victim drug. Here, based on searches of Medline, EBSCO, Science Direct and Web of Science using various keywords, we summarize the TCM-derived pharmacokinetic HDIs that were reported from 1990 to 2015 and discuss the underlying mechanisms. In general, many pre-clinical and clinical pharmacokinetic HDIs have been reported. Our searches show that TCMs cause pharmacokinetic interactions with therapeutic drugs mainly by inhibiting or inducing drug-metabolizing enzymes and transporters. However, most of the interactions result from a small number of prescription medications and the actual potential for harm is low. Moreover, such HDIs can be avoided by discontinuing the TCMs. Despite the extensive number of reports on TCM-derived HDIs, the findings are frequently conflicting and can be confusing. The causes of the conflicts vary, but we classified them into three basic categories as follows: (1) complicated nature and poor quality control of TCMs, (2) different responses of various test systems to TCM exposure and (3) diverse study designs. Accordingly, we propose rational study designs for future HDI research. We also propose that a specific authoritative guide be established that provides recommendations for HDI studies. This review provides insights into the progress and challenges in TCM-derived pharmacokinetic HDI research.

  19. In Vivo Analysis of Protein–Protein Interactions with Bioluminescence Resonance Energy Transfer (BRET): Progress and Prospects

    PubMed Central

    Sun, Sihuai; Yang, Xiaobing; Wang, Yao; Shen, Xihui

    2016-01-01

    Proteins are the elementary machinery of life, and their functions are carried out mostly by molecular interactions. Among those interactions, protein–protein interactions (PPIs) are the most important as they participate in or mediate all essential biological processes. However, many common methods for PPI investigations are slightly unreliable and suffer from various limitations, especially in the studies of dynamic PPIs. To solve this problem, a method called Bioluminescence Resonance Energy Transfer (BRET) was developed about seventeen years ago. Since then, BRET has evolved into a whole class of methods that can be used to survey virtually any kinds of PPIs. Compared to many traditional methods, BRET is highly sensitive, reliable, easy to perform, and relatively inexpensive. However, most importantly, it can be done in vivo and allows the real-time monitoring of dynamic PPIs with the easily detectable light signal, which is extremely valuable for the PPI functional research. This review will take a comprehensive look at this powerful technique, including its principles, comparisons with other methods, experimental approaches, classifications, applications, early developments, recent progress, and prospects. PMID:27727181

  20. Interaction between PNPLA3 I148M Variant and Age at Infection in Determining Fibrosis Progression in Chronic Hepatitis C

    PubMed Central

    Aghemo, Alessio; Cheroni, Cristina; D'Ambrosio, Roberta; Pedrazzini, Michele; Marabita, Francesco; Donnici, Lorena; Maggioni, Marco; Fargion, Silvia; Colombo, Massimo; De Francesco, Raffaele; Valenti, Luca

    2014-01-01

    Background and Aims The PNPLA3 I148M sequence variant favors hepatic lipid accumulation and confers susceptibility to hepatic fibrosis and hepatocellular carcinoma. The aim of this study was to estimate the effect size of homozygosity for the PNPLA3 I148M variant (148M/M) on the fibrosis progression rate (FPR) and the interaction with age at infection in chronic hepatitis C (CHC). Methods FPR was estimated in a prospective cohort of 247 CHC patients without alcohol intake and diabetes, with careful estimation of age at infection and determination of fibrosis stage by Ishak score. Results Older age at infection was the strongest determinant of FPR (p<0.0001). PNPLA3 148M/M was associated with faster FPR in individuals infected at older age (above the median, 21 years; −0.64±0.2, n = 8 vs. −0.95±0.3, n = 166 log10 FPR respectively; p = 0.001; confirmed for lower age thresholds, p<0.05), but not in those infected at younger age (p = ns). The negative impact of PNPLA3 148M/M on fibrosis progression was more marked in subjects at risk of altered hepatic lipid metabolism (those with grade 2–3 steatosis, genotype 3, and overweight; p<0.05). At multivariate analysis, PNPLA3 148M/M was associated with FPR (incremental effect 0.08±0.03 log10 fibrosis unit per year; p = 0.022), independently of several confounders, and there was a significant interaction between 148M/M and older age at infection (p = 0.025). The association between 148M/M and FPR remained significant even after adjustment for steatosis severity (p = 0.032). Conclusions We observed an interaction between homozygosity for the PNPLA3 I148M variant and age at infection in determining fibrosis progression in CHC patients. PMID:25171251

  1. Recent Progress on Nonlinear Schrödinger Systems with Quadratic Interactions

    PubMed Central

    Li, Chunhua; Hayashi, Nakao

    2014-01-01

    The study of nonlinear Schrödinger systems with quadratic interactions has attracted much attention in the recent years. In this paper, we summarize time decay estimates of small solutions to the systems under the mass resonance condition in 2-dimensional space. We show the existence of wave operators and modified wave operators of the systems under some mass conditions in n-dimensional space, where n ≥ 2. The existence of scattering operators and finite time blow-up of the solutions for the systems in higher space dimensions is also shown. PMID:25143965

  2. Strong interactions studies with medium energy probes. Progress report, 1993--1994

    SciTech Connect

    Seth, K.K.

    1994-09-01

    This progress report refers to the period August 1993 to September 1994, which includes the second year of the three year period December 1, 1992--November 30, 1995 of our existing research contract. The budget proposal for the third year, December 1, 1994 to November 30, 1995 as originally approved, is also presented. As anticipated in our 1992--1995 proposal, Fermilab E760/E835 on high precision charmonium spectroscopy has remained a major part of our preoccupation and commitment during the last year, and it will remain so in the forthcoming year. In early 1994 we joined the collaboration of the Brookhaven experiment E852 on the spectroscopy of states with exotic quantum numbers. The first successful three month run of E852 was completed on July 31 and preliminary data analysis has been started. Some new commitments have resulted from this collaboration and a separate proposal for supplemental financial support is being prepared for them. At Los Alamos our experiment {number_sign}1274 on search of extremely neutron rich exotic nuclei by pion absorption began making initial measurements a month ago and is expected to take data during the period October 15--November 30, 1994. In addition to the above on-going programs, our Bates proposal (94-01) for a definitive measurement of the quenching of the longitudinal response in quasi-free scattering of electrons from nuclei has been approved with high priority for 600 hours of beam time, and we expect to start the experiment in late 1995.

  3. Quarterly Technical Progress Report - Investigation of Syngas Interaction in Alcohol Synthesis Catalysts

    SciTech Connect

    Murty A. Akundi

    1998-11-10

    This report presents the work done on " Investigation of Syngas Interaction in Alcohol Synthesis Catalysts" during the last quarter. The major activity during this period is on FTIR absorption studies of Co/Cr catalysts using CO as a probe molecule. Transition metals cobalt and copper play significant roles in the conversion of syngas (CO + H2 ) to liquid fuels. With a view to examine the nature of interaction between CO and metal, the FTIR spectra of CO adsorbed on Co-Cr2 O3 composites were investigated. The results indicate that as cobalt loading increases, the intensity of the CO adsorption bands increase and several vibrational modes seem to be promoted. Heat treatment of the sample revealed two distinct processes of adsorption. Bands due to physisorption disappeared while bands due to chemisorption not only increased in intensity but persisted even after desorption. It seems that the physisorption process is more active when the catalyst is fresh and is hindered when carbidic/carbonyl formations occur on the metal surfaces.

  4. Polycyclic aromatic hydrocarbon: protein interactions. Progress report, March 1, 1980-February 28, 1981

    SciTech Connect

    Fujimori, E.

    1980-11-01

    Interacting with bovine serum albumin (BSA), both the very weak carcinogenic hydrocarbon benzo(e)pyrene (Bep) and the powerful carcinogen benzo(a)pyrene (BaP) form pyrene-type compounds, indicating chemical modification at the bay region of the molecules. In constrast to the BaP-BSA reaction apparently similar to the metabolic activation to the bay region oxidation product, the BeP-BSA reaction differs from the known metabolic change of BeP which occurs at the K-region. While the BaP-BSA reaction also produces a BaP radical as well as other uv-fluorescent species, no BeP radical is formed in interaction with BSA and two sharp uv fluorescences at about 330 and 350 nm probably come from the higher excited states of BeP. Furthermore, from fluorescence and excitation spectral studies particularly at low temperature, it is suggested that the uv fluorescences at 320 to 380 nm of the BaP-BSA complex originate from a few distinct species. A new uv fluorescence at 330 nm (preferentially excited at 295 nm), as well as a new excitation peak at 325 nm for the longer wavelength uv fluorescences at 357 and 378 nm, has been found. The extract from the aqueous BaP-BSA solution also emits phosphorescence at 400-440 nm (excited at 310 nm) in EPA solution.

  5. Progress in Spacecraft Environment Interactions: International Space Station (ISS) Development and Operations

    NASA Technical Reports Server (NTRS)

    Koontz, Steve; Suggs, Robb; Schneider, Todd; Minow, Joe; Alred, John; Cooke, Bill; Mikatarian, Ron; Kramer, Leonard; Boeder, paul; Soares, Carlos

    2007-01-01

    The set of spacecraft interactions with the space flight environment that have produced the largest impacts on the design, verification, and operation of the International Space Station (ISS) Program during the May 2000 to May 2007 time frame are the focus of this paper. In-flight data, flight crew observations, and the results of ground-based test and analysis directly supporting programmatic and operational decision-making are reported as are the analysis and simulation efforts that have led to new knowledge and capabilities supporting current and future space explorations programs. The specific spacecraft-environment interactions that have had the greatest impact on ISS Program activities during the first several years of flight are: 1) spacecraft charging, 2) micrometeoroids and orbital debris effects, 3) ionizing radiation (both total dose to materials and single event effects [SEE] on avionics), 4) hypergolic rocket engine plume impingement effects, 5) venting/dumping of liquids, 6) spacecraft contamination effects, 7) neutral atmosphere and atomic oxygen effects, 8) satellite drag effects, and 9) solar ultraviolet effects. Orbital inclination (51.6deg) and altitude (nominally between 350 km and 460 km) determine the set of natural environment factors affecting the performance and reliability of materials and systems on ISS. ISS operates in the F2 region of Earth s ionosphere in well-defined fluxes of atomic oxygen, other ionospheric plasma species, solar UV, VUV, and x-ray radiation as well as galactic cosmic rays, trapped radiation, and solar cosmic rays. The micrometeoroid and orbital debris environment is an important determinant of spacecraft design and operations in any orbital inclination. The induced environment results from ISS interactions with the natural environment as well as environmental factors produced by ISS itself and visiting vehicles. Examples include ram-wake effects, hypergolic thruster plume impingement, materials out-gassing, venting

  6. A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression

    PubMed Central

    Mir, Riyaz A.; Bele, Aditya; Mirza, Sameer; Srivastava, Shashank; Olou, Appolinaire A.; Ammons, Shalis A.; Kim, Jun Hyun; Gurumurthy, Channabasavaiah B.; Qiu, Fang; Band, Hamid

    2015-01-01

    Ecdysoneless (ECD) is an evolutionarily conserved protein whose germ line deletion is embryonic lethal. Deletion of Ecd in cells causes cell cycle arrest, which is rescued by exogenous ECD, demonstrating a requirement of ECD for normal mammalian cell cycle progression. However, the exact mechanism by which ECD regulates cell cycle is unknown. Here, we demonstrate that ECD protein levels and subcellular localization are invariant during cell cycle progression, suggesting a potential role of posttranslational modifications or protein-protein interactions. Since phosphorylated ECD was recently shown to interact with the PIH1D1 adaptor component of the R2TP cochaperone complex, we examined the requirement of ECD phosphorylation in cell cycle progression. Notably, phosphorylation-deficient ECD mutants that failed to bind to PIH1D1 in vitro fully retained the ability to interact with the R2TP complex and yet exhibited a reduced ability to rescue Ecd-deficient cells from cell cycle arrest. Biochemical analyses demonstrated an additional phosphorylation-independent interaction of ECD with the RUVBL1 component of the R2TP complex, and this interaction is essential for ECD's cell cycle progression function. These studies demonstrate that interaction of ECD with RUVBL1, and its CK2-mediated phosphorylation, independent of its interaction with PIH1D1, are important for its cell cycle regulatory function. PMID:26711270

  7. Origins of Cell-to-Cell Bioprocessing Diversity and Implications of the Extracellular Environment Revealed at the Single-Cell Level

    PubMed Central

    Vasdekis, A. E.; Silverman, A. M.; Stephanopoulos, G.

    2015-01-01

    Bioprocess limitations imposed by microbial cell-to-cell phenotypic diversity remain poorly understood. To address this, we investigated the origins of such culture diversity during lipid production and assessed the impact of the fermentation microenvironment. We measured the single-cell lipid production dynamics in a time-invariant microfluidic environment and discovered that production is not monotonic, but rather sporadic with time. To characterize this, we introduce bioprocessing noise and identify its epigenetic origins. We linked such intracellular production fluctuations with cell-to-cell productivity diversity in culture. This unmasked the phenotypic diversity amplification by the culture microenvironment, a critical parameter in strain engineering as well as metabolic disease treatment. PMID:26657999

  8. BCL-2 and mutant NRAS interact physically and functionally in a mouse model of progressive myelodysplasia.

    PubMed

    Omidvar, Nader; Kogan, Scott; Beurlet, Stephanie; le Pogam, Carole; Janin, Anne; West, Robert; Noguera, Maria-Elena; Reboul, Murielle; Soulie, Annie; Leboeuf, Christophe; Setterblad, Niclas; Felsher, Dean; Lagasse, Eric; Mohamedali, Azim; Thomas, N Shaun B; Fenaux, Pierre; Fontenay, Michaela; Pla, Marika; Mufti, Ghulam J; Weissman, Irving; Chomienne, Christine; Padua, Rose Ann

    2007-12-15

    Myelodysplastic syndromes (MDS) are clonal stem cell hematologic disorders that evolve to acute myeloid leukemia (AML) and thus model multistep leukemogenesis. Activating RAS mutations and overexpression of BCL-2 are prognostic features of MDS/AML transformation. Using NRASD12 and BCL-2, we created two distinct models of MDS and AML, where human (h)BCL-2 is conditionally or constitutively expressed. Our novel transplantable in vivo models show that expression of hBCL-2 in a primitive compartment by mouse mammary tumor virus-long terminal repeat results in a disease resembling human MDS, whereas the myeloid MRP8 promoter induces a disease with characteristics of human AML. Expanded leukemic stem cell (Lin(-)/Sca-1(+)/c-Kit(+)) populations and hBCL-2 in the increased RAS-GTP complex within the expanded Sca-1(+) compartment are described in both MDS/AML-like diseases. Furthermore, the oncogenic compartmentalizations provide the proapoptotic versus antiapoptotic mechanisms, by activating extracellular signal-regulated kinase and AKT signaling, in determination of the neoplastic phenotype. When hBCL-2 is switched off with doxycycline in the MDS mice, partial reversal of the phenotype was observed with persistence of bone marrow blasts and tissue infiltration as RAS recruits endogenous mouse (m)BCL-2 to remain active, thus demonstrating the role of the complex in the disease. This represents the first in vivo progression model of MDS/AML dependent on the formation of a BCL-2:RAS-GTP complex. The colocalization of BCL-2 and RAS in the bone marrow of MDS/AML patients offers targeting either oncogene as a therapeutic strategy.

  9. Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection

    PubMed Central

    Lum, Krystal K; Cristea, Ileana M

    2016-01-01

    The integration of proteomic methods to virology has facilitated a significant breadth of biological insight into mechanisms of virus replication, antiviral host responses and viral subversion of host defenses. Throughout the course of infection, these cellular mechanisms rely heavily on the formation of temporally and spatially regulated virus–host protein–protein interactions. Reviewed here are proteomic-based approaches that have been used to characterize this dynamic virus–host interplay. Specifically discussed are the contribution of integrative mass spectrometry, antibody-based affinity purification of protein complexes, cross-linking and protein array techniques for elucidating complex networks of virus–host protein associations during infection with a diverse range of RNA and DNA viruses. The benefits and limitations of applying proteomic methods to virology are explored, and the contribution of these approaches to important biological discoveries and to inspiring new tractable avenues for the design of antiviral therapeutics is highlighted. PMID:26817613

  10. Experimental studies of pion-nucleus interactions at intermediate energies. Annual progress report

    SciTech Connect

    Not Available

    1992-12-31

    This report summarizes investigations of various pion-nucleus interactions and nucleon-nucleus charge-exchange reactions. The work was carried out with the LAMPF accelerator at the Los Alamos National Laboratory and the cyclotrons at the Paul Scherrer Institute (PSI) near Zurich, Switzerland, and at Indiana University (IUCF), as a collaborative effort among several laboratories and universities. The experimental activity at LAMPF involved measurements of new data on pion double-charge-exchange scattering, some initial work on a new Neutral Meson Spectrometer system, a search for deeply-bound pionic atoms, measurements of elastic scattering, and studies of the (n,p) reaction on various nuclei. At PSI measurements of pion quasielastic scattering were carried out, with detection of the recoil proton. Work on the analysis of data from a previous experiment at PSI on pion absorption in nuclei was continued. This experiment involved using a detector system that covered nearly the full solid angle.

  11. Progress in the epidemiological understanding of gene-environment interactions in major diseases: cancer

    PubMed Central

    Clavel, Jacqueline

    2007-01-01

    Cancer epidemiology has undergone marked development since the nineteen-fifties. One of the most spectacular and specific contributions was the demonstration of the massive effect of smoking on the occurrence of lung, larynx and bladder cancer. Major chemical, physical and biological carcinogenic agents have been identified in the working environment and in the overall environment. The chain of events from environmental exposures to cancer requires hundreds of polymorphic genes coding for proteins involved in the transport and metabolism of xenobiotics, or in repair, or in an immune or inflammatory response. The multifactorial and multistage characteristics of cancer create the theoretical conditions for statistical interactions which have been exceptionnally detected. Over the last two decades, a considerable mass of data has been generated, mostly addressing the interactions between smoking and xenobiotic-metabolizing enzymes in smoking-related cancers. They are sometimes considered disappointing but they actually brought a lot of information and raised many methodological issues. In parallel, the number of polymorphisms which can be considered candidate per function increased so much that multiple testing has become a major issue, and genome wide screening approaches have more and more gained in interest. Facing the resulting complexity, some instruments are being set up: our studies are now equipped with carefully sampled biological collections, high-throughput genotyping systems are becoming available, work on statistical methodologies is ongoing, bioinformatics databases are growing larger and access to them is becoming simpler; international consortiums are being organized. The roles of environmental and genetic factors are being jointly elucidated. The basic rules of epidemiology, which are demanding with respect to sampling, with respect to the histological and molecular criteria for cancer classification, with respect to the evaluation of environmental

  12. Two basic (hydrophilic) regions in the movement protein of Parietaria mottle virus have RNA binding activity and are required for cell-to-cell transport.

    PubMed

    Martínez, Carolina; Coll-Bonfill, Nuria; Aramburu, Jose; Pallás, Vicente; Aparicio, Frederic; Galipienso, Luis

    2014-05-12

    The movement protein (MP) of parietaria mottle virus (PMoV) is required for virus cell-to-cell movement. Bioinformatics analysis identified two hydrophilic non-contiguous regions (R1 and R2) rich in the basic amino acids lysine and arginine and with the predicted secondary structure of an α-helix. Different approaches were used to determine the implication of the R1 and R2 regions in RNA binding, plasmodesmata (PD) targeting and cell-to-cell movement. EMSA (Electrophoretic Mobility Shift Assay) showed that both regions have RNA-binding activity whereas that mutational analysis reported that either deletion of any of these regions, or loss of the basic amino acids, interfered with the viral intercellular movement. Subcellular localization studies showed that PMoV MP locates at PD. Mutants designed to impeded cell-to-cell movement failed to accumulate at PD indicating that basic residues in both R1 and R2 are critical for binding the MP at PD.

  13. Cell-to-Cell Propagation of the Bacterial Toxin CNF1 via Extracellular Vesicles: Potential Impact on the Therapeutic Use of the Toxin

    PubMed Central

    Fabbri, Alessia; Cori, Sara; Zanetti, Cristiana; Guidotti, Marco; Sargiacomo, Massimo; Loizzo, Stefano; Fiorentini, Carla

    2015-01-01

    Eukaryotic cells secrete extracellular vesicles (EVs), either constitutively or in a regulated manner, which represent an important mode of intercellular communication. EVs serve as vehicles for transfer between cells of membrane and cytosolic proteins, lipids and RNA. Furthermore, certain bacterial protein toxins, or possibly their derived messages, can be transferred cell to cell via EVs. We have herein demonstrated that eukaryotic EVs represent an additional route of cell-to-cell propagation for the Escherichia coli protein toxin cytotoxic necrotizing factor 1 (CNF1). Our results prove that EVs from CNF1 pre-infected epithelial cells can induce cytoskeleton changes, Rac1 and NF-κB activation comparable to that triggered by CNF1. The observation that the toxin is detectable inside EVs derived from CNF1-intoxicated cells strongly supports the hypothesis that extracellular vesicles can offer to the toxin a novel route to travel from cell to cell. Since anthrax and tetanus toxins have also been reported to engage in the same process, we can hypothesize that EVs represent a common mechanism exploited by bacterial toxins to enhance their pathogenicity. PMID:26556375

  14. Natural gas storage and end user interaction: A progress report, September 30, 1994--March 31, 1995

    SciTech Connect

    Crook, L.R. Jr.; Reich, S.; Godec, M.L.

    1995-07-01

    In late 1994, ICF Resources began a contract with the Morgantown Energy Technology Center (METC) to conduct a study of natural gas storage and end user interaction. This study is being conducted in three phases: the first phase is an assessment of the market requirements for natural gas storage and in particular to identify those end user requirements for storage that could benefit from METC-sponsored research and development (R&D) in storage technology; the second phase will address the particular technical and economic feasibility for expanding conventional storage; and the third phase will address alternative, unconventional technologies. ICF is approaching the conclusion of the first phase of the study and the second phase has begun. This paper summarizes the scope of the study and reports some of the preliminary findings of the first phase. We begin by providing an overview of the goals of the effort and of natural gas storage. We will address the evolving market requirements for storage and the regulatory and institutional changes that are having a major impact on the use of natural gas storage. We address the demand for storage and the alternatives for meeting this demand, with specific reference to regional and end use issues.

  15. Environmental effects of ozone depletion and its interactions with climate change: progress report, 2007.

    PubMed

    2008-01-01

    This year the Montreal Protocol celebrates its 20th Anniversary. In September 1987, 24 countries signed the Montreal Protocol on Substances that Deplete the Ozone Layer. Today 191 countries have signed and have met strict commitments on phasing out of ozone depleting substances with the result that a 95% reduction of these substances has been achieved. The Montreal Protocol has also contributed to slowing the rate of global climate change, since most of the ozone depleting substances are also effective greenhouse gases. Even though much has been achieved, the future of the stratospheric ozone layer relies on full compliance of the Montreal Protocol by all countries for the remaining substances, including methyl bromide, as well as strict monitoring of potential risks from the production of substitute chemicals. Also the ozone depleting substances existing in banks and equipment need special attention to prevent their release to the stratosphere. Since many of the ozone depleting substances already in the atmosphere are long-lived, recovery cannot be immediate and present projections estimate a return to pre-1980 levels by 2050 to 2075. It has also been predicted that the interactions of the effects of the ozone layer and that of other climate change factors will become increasingly important.

  16. Nuclear structure studies via neutron interactions. Progress report, 1 July 1994--30 June 1995

    SciTech Connect

    Carlton, R.F.

    1995-01-01

    Neutron total cross section measurements of {sup 122}Sn has been analyzed over the energy range 0.013 to 0.310 MeV. The R - matrix analysis has resulted in resonance and average parameters which provide for a complete representation of the neutron entrance the s{sub 1/2}, p{sub 1/2}, and p{sub 3/2} contributions. The s - and p - neutron strength functions have been determined to be 0.123 {plus_minus} 0.023 and 2.0 {plus_minus} 0.200, respectively (in units of 10{sup {minus}4}). Limits are placed on level spacings and strength functions for the individual partial wave components. The s - wave potential scattering radius has been determined to be 6.3 {plus_minus} 0.1 fm. Average scattering functions, deduced from the average parameters, have been used to determine the real well depth of an optical model potential which reproduces these functions. We find, as have others, that the real well depth is parity dependent. Two computer codes were developed: (1) a minimization program for finding parameters of a dispersive optical model which reproduce the high resolution data of the ORELA facility, and (2) an X-windows graphical user interface has been developed to permit interactive resonance analysis of the neutron total cross section data using analysis-and-minimization codes developed previously. These will contribute to the more routine analysis of ORELA data.

  17. Heterofunctionality interaction with donor solvent coal liquefaction. Final progress report, August 1982-April 1984

    SciTech Connect

    Cronauer, D.C.

    1984-05-01

    This project was undertaken to understand the role of the coal liquefaction solvent through a study of the interaction between the hydrogen donor solvent characteristics and the heterofunctionality of the solvent. Specifically, hydroxyl- and nitrogen-containing solvents were studied and characterized. A series of coal liquefaction experiments were carried out at 450/sup 0/C in a continuous feed stirred-tank reactor (CSTR) to observe the effect of adding phenolics to anthracene oil (AO) and SRC-II recycle solvents. The addition of phenol to AO at a ratio of 5/65 resulted in a nominal increase in coal conversion to THF solubles, but the amount of asphaltenes more than doubled resulting in a sizable net loss of solvent. The addition of m-cresol to both AO and SRC-II solvents had a positive effect on coal conversion to both THF and pentane solubles (oils). The partial removal of an OH-concentrate from SRC-II solvent was carried out using Amberlyst IRA-904 ion exchange resin. The resin-treated oil was only marginally better than raw SRC-II recycle solvent for coal liquefaction. Hydroaromatics having nitrogen functionality should be good solvents for coal liquefaction considering their effective solvent power, ability to penetrate and swell coal, and their ability to readily transfer hydrogen, particularly in the presence of oxygen functionality. However, these benefits are overshadowed by the strong tendency of the nitrogen-containing species to adduct with themselves and coal-derived materials.

  18. Recent Progress in Treating Protein–Ligand Interactions with Quantum-Mechanical Methods

    PubMed Central

    Yilmazer, Nusret Duygu; Korth, Martin

    2016-01-01

    We review the first successes and failures of a “new wave” of quantum chemistry-based approaches to the treatment of protein/ligand interactions. These approaches share the use of “enhanced”, dispersion (D), and/or hydrogen-bond (H) corrected density functional theory (DFT) or semi-empirical quantum mechanical (SQM) methods, in combination with ensemble weighting techniques of some form to capture entropic effects. Benchmark and model system calculations in comparison to high-level theoretical as well as experimental references have shown that both DFT-D (dispersion-corrected density functional theory) and SQM-DH (dispersion and hydrogen bond-corrected semi-empirical quantum mechanical) perform much more accurately than older DFT and SQM approaches and also standard docking methods. In addition, DFT-D might soon become and SQM-DH already is fast enough to compute a large number of binding modes of comparably large protein/ligand complexes, thus allowing for a more accurate assessment of entropic effects. PMID:27196893

  19. Recent Progress in Treating Protein-Ligand Interactions with Quantum-Mechanical Methods.

    PubMed

    Yilmazer, Nusret Duygu; Korth, Martin

    2016-01-01

    We review the first successes and failures of a "new wave" of quantum chemistry-based approaches to the treatment of protein/ligand interactions. These approaches share the use of "enhanced", dispersion (D), and/or hydrogen-bond (H) corrected density functional theory (DFT) or semi-empirical quantum mechanical (SQM) methods, in combination with ensemble weighting techniques of some form to capture entropic effects. Benchmark and model system calculations in comparison to high-level theoretical as well as experimental references have shown that both DFT-D (dispersion-corrected density functional theory) and SQM-DH (dispersion and hydrogen bond-corrected semi-empirical quantum mechanical) perform much more accurately than older DFT and SQM approaches and also standard docking methods. In addition, DFT-D might soon become and SQM-DH already is fast enough to compute a large number of binding modes of comparably large protein/ligand complexes, thus allowing for a more accurate assessment of entropic effects. PMID:27196893

  20. Interaction of carbon and sulfur on metal catalysts: Technical progress report

    SciTech Connect

    McCarty, J.G.; Vajo, J.

    1989-02-17

    At high coverage, sulfur generally deactivates metal catalysts, but at low coverage, chemisorbed sulfur can have a more subtle effect on catalyst activity and selectivity. The general goal of the current project is to examine fundamental aspects of selective poisoning by fractional monolayers of chemisorbed sulfur on a variety of metal catalysts used for commercially important reactions such as hydrocarbon re-forming, light alkane steam re-forming, and hydrocarbon synthesis. Specific objectives of the research program are to experimentally measure as a function of coverage the influence of chemisorbed sulfur on the thermodynamics, reactivity, and structure of surface and bulk carbon occupying both dispersed and well-characterized metal catalyst surfaces. Special methods, such as reversible sulfur chemisorption on supported metals and temperature-programmed reaction (TPR) characterization of catalyst carbon, have been developed that are well suited to examining the interaction of sulfur and carbon on metal surfaces. New analytical instruments with greatly improved sensitivity have been recently developed and applied: a helium discharge ionization detector (DID) is being used with a gas recirculation thermodynamic system, and the surface analysis by laser ionization (SALI) technique is used with surface carbon segregation systems.

  1. Studies of particle interactions in bubble chamber, spark chambers and counter experiments. Annual progress report

    SciTech Connect

    Holloway, L.E.; O'Halloran, T.A. Jr.; Simmons, R.O.

    1983-07-01

    During the past six years we have carried out and planned experiments which predominantly studied the production and decay of particles containing charmed quarks. A series of photoproduction and neutron production experiments started with the very early observation of the production of J/psi by neutrons and by photons at Fermilab. From subsequent experiments using these neutral beams and the basic detecting system, we have reported results on the photoproduction of the ..lambda../sub c/ charmed baryon and the D and D* charmed mesons. More recent runs are studying the high energy photoproduction of vector mesons including the psi'. The present experiment in this sequence is using neutrons to produce a large number of D mesons. Another series of experiments at Fermilab set out to study the hadronic production of charmed mesons. The Chicago Cyclotron facility was modified with a detector sensitive to various possible production mechanisms. The experiments were a success; clean signals of D mesons were observed to be produced by pions, and also the production of chi/sub c/ with the subsequent decay via a ..gamma..-ray to psi was observed. The charmonium experiments run this year have better photon resolution for measuring the decays of chi/sub c/ to psi. We are part of a collaboration which is working on the Collider Detector Facility for Fermilab. The CDF at Fermilab is a possible source of (weak) intermediate vector bosons from the collisions of protons and anti-protons. Our responsibilities in the CDF include both the construction of the muon detector and the designing, planning, and testing of the FASTBUS electronics. The second part of our weak interaction program is the Neutrino Oscillation experiment which is now under construction at Brookhaven.

  2. Experiments on the nuclear interactions of pions and electrons. Progress report

    SciTech Connect

    Minehart, R.C.; Ziock, K.O.H.

    1992-08-01

    The analysis of the deuterium content in the CD target used in an experiment to study the {pi} + d {yields} 2p reaction at incident pion energies from 4 to 20 MeV was completed. The final paper describing this experiment will be submitted for publication this summer. Analysis of LAMPF Exp. on pion absorption in {sup 4}He is continuing. In 1991, we collaborated with D. Pocanic from the Univ. of Virginia on a measurement at LAMPF of the {pi}{sup 0} production in {pi} + p interactions. This run proved the validity of the method and additional data were obtained in a second run during the summer of 1992, using a new target. Current collaborations at LAMPF include the search for the decay {mu}{sup +} {yields} e{sup +} + {gamma}(MEGA) and a measurement of the Michel {rho} parameter in the decay {mu} {yields} e + v + v. A U.Va.--PSI collaboration is measuring pion beta decay to an accuracy of less than 1%, using a large acceptance CsI detector to measure the {pi}{sup 0} following decay of stopped {pi}{sup +} mesons. Most of the U.Va. effort is devoted to the CEBAF Large Acceptance Spectrometer (CLAS) program to the construction of the CLAS forward calorimeter. An apparatus to measure the properties of the scintillators with light from a N{sub 2} laser was built in the spring of 1992. The electronic circuitry for the energy signal from the EGN detector and the circuitry needed to route the signals from the all the photomultipliers to the TDC and ADC circuits are being developed. Experimental proposals for the study of electroproduction of nucleon resonances at CEBAF, including measurements with polarized beam and targets, are being developed.

  3. Progress in the Development of Techniques for Detection of Chemical Interactions Between the Core and Mantle

    NASA Astrophysics Data System (ADS)

    Walker, R. J.

    2003-12-01

    If some plumes arise from the core-mantle boundary and there is limited chemical interaction between the core and mantle within D", it is possible that these plumes could contain a unique chemical or iso-topic fingerprint that is characteristic of the core. Unequivocal identification of a core component in a plume could potentially settle a major question in geodynamics. The ideal tracers of a core component in a plume are elements that occur in very high abundance in the core relative to the mantle and crust. The most sensitive suite of elements for identifying possible core contributions to plumes that may arise from the core-mantle interface are the highly siderophile elements (HSE = Pt, Re, Os, Ir, Pd, Ru, Rh, Au ), and certain moderately siderophile elements such as Ag, W and Mo. Because of the extreme preference of the HSE for metal relative to sili-cates, the formation of the core nearly quantitatively sequestered the Earth's HSE, and also likely dominates the budget of moderately siderophile elements. Mass balance is potentially optimal for detection of core additions to the mantle. Isotopic systems are of greatest interest in prosecuting this task because characteristic isotopic signals may be immune to subsequent processing in the mantle or crust. Pros and cons in applications, and an overview of existing data will be presented, primarily focusing on the Pt-Re-Os coupled system and the short-lived 182Hf -182W system. Although resolution of isotopic differences may currently be insufficient, W isotopes provide the best complement to Os isotopes in the search for a core component.

  4. Inhibiting DX2-p14/ARF Interaction Exerts Antitumor Effects in Lung Cancer and Delays Tumor Progression.

    PubMed

    Oh, Ah-Young; Jung, Youn Sang; Kim, Jiseon; Lee, Jee-Hyun; Cho, Jung-Hyun; Chun, Ho-Young; Park, Soyoung; Park, Hyunchul; Lim, Sikeun; Ha, Nam-Chul; Park, Jong Sook; Park, Choon-Sik; Song, Gyu-Yong; Park, Bum-Joon

    2016-08-15

    The aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) splice variant designated DX2 is induced by cigarette smoke carcinogens and is often detected in human lung cancer specimens. However, the function of DX2 in lung carcinogenesis is obscure. In this study, we found that DX2 expression was induced by oncogenes in human lung cancer tissues and cells. DX2 prevented oncogene-induced apoptosis and senescence and promoted drug resistance by directly binding to and inhibiting p14/ARF. Through chemical screening, we identified SLCB050, a novel compound that blocks the interaction between DX2 and p14/ARF in vitro and in vivo SLCB050 reduced the viability of human lung cancer cells, especially small cell lung cancer cells, in a p14/ARF-dependent manner. Moreover, in a mouse model of K-Ras-driven lung tumorigenesis, ectopic expression of DX2 induced small cell and non-small cell lung cancers, both of which could be suppressed by SLCB050 treatment. Taken together, our findings show how DX2 promotes lung cancer progression and how its activity may be thwarted as a strategy to treat patients with lung cancers exhibiting elevated DX2 levels. Cancer Res; 76(16); 4791-804. ©2016 AACR. PMID:27302160

  5. Pathological Propagation through Cell-to-Cell Transmission of Non-Prion Protein Aggregates in Neurodegenerative Disorders

    PubMed Central

    Lee, Seung-Jae; Desplats, Paula; Sigurdson, Christina; Tsigelny, Igor; Masliah, Eliezer

    2016-01-01

    Neurodegenerative disorders such as Alzheimer's Disease, Parkinson's Disease, fronto-temporal dementia, Huntington's Disease and Creutzfeldt-Jakob Disease (CJD) are characterized by progressive accumulation of protein aggregates in selected brain regions. Protein misfolding and templated assembly into aggregates might result from an imbalance between protein synthesis, aggregation and clearance. While protein misfolding and aggregation occur in most neurodegenerative disorders, the concept of spreading and infectivity of aggregates in the CNS has been reserved to prion diseases such as CJD and bovine spongiform encephalopathy. Emerging evidence suggests that prion-like spreading may occur in other neurodegenerative disorders, taking place with secreted proteins, such as amyloid-β,) and cytosolic proteins, such as tau, huntingtin and α-synuclein. Underlying molecular mechanisms and therapeutic implications are discussed. PMID:21045796

  6. AKAP95 promotes cell cycle progression via interactions with cyclin E and low molecular weight cyclin E

    PubMed Central

    Kong, Xiang-Yu; Zhang, Deng-Cheng; Zhuang, Wen-Xin; Hua, Su-Hang; Dai, Yue; Yuan, Yang-Yang; Feng, Li-Li; Huang, Qian; Teng, Bo-Gang; Yu, Xiu-Yi; Liu, Wen-Zhi; Zhang, Yong-Xing

    2016-01-01

    AKAP95 in lung cancer tissues showed higher expression than in paracancerous tissues. AKAP95 can bind with cyclin D and cyclin E during G1/S cell cycle transition, but its molecular mechanisms remain unclear. To identify the mechanism of AKAP95 in cell cycle progression, we performed AKAP95 transfection and silencing in A549 cells, examined AKAP95, cyclin E1 and cyclin E2 expression, and the interactions of AKAP95 with cyclins E1 and E2. Results showed that over-expression of AKAP95 promoted cell growth and AKAP95 bound cyclin E1 and E2, low molecular weight cyclin E1 (LWM-E1) and LWM-E2. Additionally AKAP95 bound cyclin E1 and LMW-E2 in the nucleus during G1/S transition, bound LMW-E1 during G1, S and G2/M, and bound cyclin E2 mainly on the nuclear membrane during interphase. Cyclin E2 and LMW-E2 were also detected. AKAP95 over-expression increased cyclin E1 and LMW-E2 expression but decreased cyclin E2 levels. Unlike cyclin E1 and LMW-E2 that were nuclear located during the G1, S and G1/S phases, cyclin E2 and LMW-E1 were expressed in all cell cycle phases, with cyclin E2 present in the cytoplasm and nuclear membrane, with traces in the nucleus. LMW-E1 was present in both the cytoplasm and nucleus. The 20 kDa form of LMW-E1 showed only cytoplasmic expression, while the 40 kDa form was nuclear expressed. The expression of AKAP95, cyclin E1, LMW-E1 and -E2, might be regulated by cAMP. We conclude that AKAP95 might promote cell cycle progression by interacting with cyclin E1 and LMW-E2. LMW-E2, but not cyclin E2, might be involved in G1/S transition. The binding of AKAP95 and LMW-E1 was found throughout cell cycle. PMID:27158371

  7. Remote Sensing of Aerosols from Satellites: Why Has It Been Do Difficult to Quantify Aerosol-Cloud Interactions for Climate Assessment, and How Can We Make Progress?

    NASA Technical Reports Server (NTRS)

    Kahn, Ralph A.

    2015-01-01

    The organizers of the National Academy of Sciences Arthur M. Sackler Colloquia Series on Improving Our Fundamental Understanding of the Role of Aerosol-Cloud Interactions in the Climate System would like to post Ralph Kahn's presentation entitled Remote Sensing of Aerosols from Satellites: Why has it been so difficult to quantify aerosol-cloud interactions for climate assessment, and how can we make progress? to their public website.

  8. Contribution of topology determinants of a viral movement protein to its membrane association, intracellular traffic, and viral cell-to-cell movement.

    PubMed

    Genovés, A; Pallás, V; Navarro, J A

    2011-08-01

    The p7B movement protein (MP) of Melon necrotic spot virus (MNSV) is a single-pass membrane protein associated with the endoplasmic reticulum (ER), the Golgi apparatus (GA), and plasmodesmata (Pd). Experimental data presented here revealed that the p7B transmembrane domain (TMD) was sufficient to target the green fluorescent protein (GFP) to ER membranes. In addition, the short extramembrane regions of p7B were essential for subsequent ER export and transport to the GA and Pd. Microsomal partitioning and bimolecular fluorescence assays supported a type II topology of p7B in planta. Mutations affecting conventional determinants of p7B membrane topology, such as the TMD secondary structure, the overall hydrophobicity profile, the so-called "aromatic belt," and the net charge distribution on either side of the TMD, were engineered into infectious RNAs to investigate the relationship between the MP structure and MNSV cell-to-cell movement. The results revealed that (i) the overall hydrophobic profile and the α-helix integrity of the TMD were relevant for virus movement, (ii) modification of the net charge balance of the regions flanking both TMD sides drastically reduced cell-to-cell movement, (iii) localization of p7B to the GA was necessary but not sufficient for virus movement, and (iv) membrane insertion was essential for p7B function in virus movement. Our results therefore indicate that MNSV cell-to-cell movement requires sequential transport of p7B from the ER via the GA to Pd, which is modulated by a combination of several signals with different strengths in the extramembrane regions and TMD of the MP.

  9. Cell-to-cell movement of green fluorescent protein reveals post-phloem transport in the outer integument and identifies symplastic domains in Arabidopsis seeds and embryos.

    PubMed

    Stadler, Ruth; Lauterbach, Christian; Sauer, Norbert

    2005-10-01

    Developing Arabidopsis (Arabidopsis thaliana) seeds and embryos represent a complex set of cell layers and tissues that mediate the transport and partitioning of carbohydrates, amino acids, hormones, and signaling molecules from the terminal end of the funicular phloem to and between these seed tissues and eventually to the growing embryo. This article provides a detailed analysis of the symplastic domains and the cell-to-cell connectivity from the end of the funiculus to the embryo, and within the embryo during its maturation. The cell-to-cell movement of the green fluorescent protein or of mobile and nonmobile green fluorescent protein fusions was monitored in seeds and embryos of plants expressing the corresponding cDNAs under the control of various promoters (SUC2, SUC3, TT12, and GL2) shown to be active in defined seed or embryo cell layers (SUC3, TT12, and GL2) or only outside the developing Arabidopsis seed (AtSUC2). Cell-to-cell movement was also analyzed with the low-molecular-weight fluorescent dye 8-hydroxypyrene-1,3,6-trisulfonate. The analyses presented identify a phloem-unloading domain at the end of the funicular phloem, characterize the entire outer integument as a symplastic extension of the phloem, and describe the inner integument and the globular stage embryo plus the suspensor as symplastic domains. The results also show that, at the time of hypophysis specification, the symplastic connectivity between suspensor and embryo is reduced or interrupted and that the embryo develops from a single symplast (globular and heart stage) to a mature embryo with new symplastic domains.

  10. Hibiscus Chlorotic Ringspot Virus Coat Protein Is Essential for Cell-to-Cell and Long-Distance Movement but Not for Viral RNA Replication

    PubMed Central

    Niu, Shengniao; Gil-Salas, Francisco M.; Tewary, Sunil Kumar; Samales, Ashwin Kuppusamy; Johnson, John; Swaminathan, Kunchithapadam; Wong, Sek-Man

    2014-01-01

    Hibiscus chlorotic ringspot virus (HCRSV) is a member of the genus Carmovirus in the family Tombusviridae. In order to study its coat protein (CP) functions on virus replication and movement in kenaf (Hibiscus cannabinus L.), two HCRSV mutants, designated as p2590 (A to G) in which the first start codon ATG was replaced with GTG and p2776 (C to G) in which proline 63 was replaced with alanine, were constructed. In vitro transcripts of p2590 (A to G) were able to replicate to a similar level as wild type without CP expression in kenaf protoplasts. However, its cell-to-cell movement was not detected in the inoculated kenaf cotyledons. Structurally the proline 63 in subunit C acts as a kink for β-annulus formation during virion assembly. Progeny of transcripts derived from p2776 (C to G) was able to move from cell-to-cell in inoculated cotyledons but its long-distance movement was not detected. Virions were not observed in partially purified mutant virus samples isolated from 2776 (C to G) inoculated cotyledons. Removal of the N-terminal 77 amino acids of HCRSV CP by trypsin digestion of purified wild type HCRSV virions resulted in only T = 1 empty virus-like particles. Taken together, HCRSV CP is dispensable for viral RNA replication but essential for cell-to-cell movement, and virion is required for the virus systemic movement. The proline 63 is crucial for HCRSV virion assembly in kenaf plants and the N-terminal 77 amino acids including the β-annulus domain is required in T = 3 assembly in vitro. PMID:25402344

  11. Hibiscus chlorotic ringspot virus coat protein is essential for cell-to-cell and long-distance movement but not for viral RNA replication.

    PubMed

    Niu, Shengniao; Gil-Salas, Francisco M; Tewary, Sunil Kumar; Samales, Ashwin Kuppusamy; Johnson, John; Swaminathan, Kunchithapadam; Wong, Sek-Man

    2014-01-01

    Hibiscus chlorotic ringspot virus (HCRSV) is a member of the genus Carmovirus in the family Tombusviridae. In order to study its coat protein (CP) functions on virus replication and movement in kenaf (Hibiscus cannabinus L.), two HCRSV mutants, designated as p2590 (A to G) in which the first start codon ATG was replaced with GTG and p2776 (C to G) in which proline 63 was replaced with alanine, were constructed. In vitro transcripts of p2590 (A to G) were able to replicate to a similar level as wild type without CP expression in kenaf protoplasts. However, its cell-to-cell movement was not detected in the inoculated kenaf cotyledons. Structurally the proline 63 in subunit C acts as a kink for β-annulus formation during virion assembly. Progeny of transcripts derived from p2776 (C to G) was able to move from cell-to-cell in inoculated cotyledons but its long-distance movement was not detected. Virions were not observed in partially purified mutant virus samples isolated from 2776 (C to G) inoculated cotyledons. Removal of the N-terminal 77 amino acids of HCRSV CP by trypsin digestion of purified wild type HCRSV virions resulted in only T = 1 empty virus-like particles. Taken together, HCRSV CP is dispensable for viral RNA replication but essential for cell-to-cell movement, and virion is required for the virus systemic movement. The proline 63 is crucial for HCRSV virion assembly in kenaf plants and the N-terminal 77 amino acids including the β-annulus domain is required in T = 3 assembly in vitro. PMID:25402344

  12. Low-density subculture: a technical note on the importance of avoiding cell-to-cell contact during mesenchymal stromal cell expansion.

    PubMed

    Balint, Richard; Richardson, Stephen M; Cartmell, Sarah H

    2015-10-01

    Numerous scientific studies and clinical trials are carried out each year exploring the use of mesenchymal stromal cells in regenerative medicine and tissue engineering. However, the effective and reliable expansion of this very important cell type remains a challenge. In this study the importance of cell-to-cell contact during expansion has been explored on the proliferation and differentiation potential of the produced cells. Cells were cultured up to passage 5 under conditions where cell-to-cell contact was either probable (40-70% confluence; see supporting information, Protocol A) or where it was unlikely (10-50% confluence; see supporting information, Protocol B). The effect of the two different conditions on expansion efficiency; proliferation rate and tri-lineage differentiation potential was assessed. Differences in immunophenotype, cell size and senescence were also investigated. Protocol B cultures expanded twice as fast as those cultured with Protocol A. In passage 5 experiments low confluence expanded cells displayed a 10% higher overall proliferation rate, and produced 23% more cells in growth, 12% more in osteogenic, 77% more in adipogenic, but 27% less in chondrogenic medium. Differentiation potential wasn't decisively affected at the mRNA level. However, Protocol B favoured bone and cartilage differentiation at the secretional level. Protocol A populations showed reduced purity, expressing CD105 in only 76% compared to the 96.7% in Protocol B cultures. Protocol A populations also contained significantly more (+4.2%) senescent cells, however, no difference was found in cell size between the two protocols. The findings of this study suggest that cell-to-cell contact, and therefore high confluence levels, is detrimental to MSC quality.

  13. PGE2 maintains self-renewal of human adult stem cells via EP2-mediated autocrine signaling and its production is regulated by cell-to-cell contact

    PubMed Central

    Lee, Byung-Chul; Kim, Hyung-Sik; Shin, Tae-Hoon; Kang, Insung; Lee, Jin Young; Kim, Jae-Jun; Kang, Hyun Kyoung; Seo, Yoojin; Lee, Seunghee; Yu, Kyung-Rok; Choi, Soon Won; Kang, Kyung-Sun

    2016-01-01

    Mesenchymal stem cells (MSCs) possess unique immunomodulatory abilities. Many studies have elucidated the clinical efficacy and underlying mechanisms of MSCs in immune disorders. Although immunoregulatory factors, such as Prostaglandin E2 (PGE2), and their mechanisms of action on immune cells have been revealed, their effects on MSCs and regulation of their production by the culture environment are less clear. Therefore, we investigated the autocrine effect of PGE2 on human adult stem cells from cord blood or adipose tissue, and the regulation of its production by cell-to-cell contact, followed by the determination of its immunomodulatory properties. MSCs were treated with specific inhibitors to suppress PGE2 secretion, and proliferation was assessed. PGE2 exerted an autocrine regulatory function in MSCs by triggering E-Prostanoid (EP) 2 receptor. Inhibiting PGE2 production led to growth arrest, whereas addition of MSC-derived PGE2 restored proliferation. The level of PGE2 production from an equivalent number of MSCs was down-regulated via gap junctional intercellular communication. This cell contact-mediated decrease in PGE2 secretion down-regulated the suppressive effect of MSCs on immune cells. In conclusion, PGE2 produced by MSCs contributes to maintenance of self-renewal capacity through EP2 in an autocrine manner, and PGE2 secretion is down-regulated by cell-to-cell contact, attenuating its immunomodulatory potency. PMID:27230257

  14. A Plasmodesmata-Localized Protein Mediates Crosstalk between Cell-to-Cell Communication and Innate Immunity in Arabidopsis[C][W][OA

    PubMed Central

    Lee, Jung-Youn; Wang, Xu; Cui, Weier; Sager, Ross; Modla, Shannon; Czymmek, Kirk; Zybaliov, Boris; van Wijk, Klaas; Zhang, Chong; Lu, Hua; Lakshmanan, Venkatachalam

    2011-01-01

    Plasmodesmata (PD) are thought to play a fundamental role in almost every aspect of plant life, including normal growth, physiology, and developmental responses. However, how specific signaling pathways integrate PD-mediated cell-to-cell communication is not well understood. Here, we present experimental evidence showing that the Arabidopsis thaliana plasmodesmata-located protein 5 (PDLP5; also known as HOPW1-1-INDUCED GENE1) mediates crosstalk between PD regulation and salicylic acid–dependent defense responses. PDLP5 was found to localize at the central region of PD channels and associate with PD pit fields, acting as an inhibitor to PD trafficking, potentially through its capacity to modulate PD callose deposition. As a regulator of PD, PDLP5 was also essential for conferring enhanced innate immunity against bacterial pathogens in a salicylic acid–dependent manner. Based on these findings, a model is proposed illustrating that the regulation of PD closure mediated by PDLP5 constitutes a crucial part of coordinated control of cell-to-cell communication and defense signaling. PMID:21934146

  15. Mutations in the capsid protein of Brome mosaic virus affecting encapsidation eliminate vesicle induction in planta: implications for virus cell-to-cell spread.

    PubMed

    Bamunusinghe, Devinka; Chaturvedi, Sonali; Seo, Jang-Kyun; Rao, A L N

    2013-08-01

    Positive-strand RNA viruses are known to rearrange the endomembrane network to make it more conducive for replication, maturation, or egress. Our previous transmission electron microscopic (TEM) analysis showed that ectopic expression of wild-type (wt) capsid protein (CP) of Brome mosaic virus (BMV) has an intrinsic property of modifying the endoplasmic reticulum (ER) to induce vesicles similar to those present in wt BMV infection. In this study, we evaluated the functional significance of CP-mediated vesicle induction to the BMV infection cycle in planta. Consequently, the cytopathologic changes induced by wt CP or its mutants defective in virion assembly due to mutations engineered in either N- or C-proximal domains were comparatively analyzed by TEM in two susceptible (Nicotiana benthamiana and Chenopodium quinoa) and one nonhost (N. clevelandii) plant species. The results showed that in susceptible hosts, CP-mediated ER-derived vesicle induction is contingent on the expression of encapsidation-competent CP. In contrast, unlike in N. benthamiana and C. quinoa, transient expression of wt CP in nonhost N. clevelandii plants eliminated vesicle induction. Additionally, comparative source-to-sink analysis of virus spread in leaves of N. benthamiana and N. clevelandii coexpressing wt BMV and Cucumber mosaic virus (CMV) showed that despite trans-encapsidation, CMV failed to complement the defective cell-to-cell movement of BMV. The significance and relation of CP-mediated vesicle induction to virus cell-to-cell movement are discussed.

  16. The potato virus X TGBp2 protein association with the endoplasmic reticulum plays a role in but is not sufficient for viral cell-to-cell movement

    NASA Technical Reports Server (NTRS)

    Mitra, Ruchira; Krishnamurthy, Konduru; Blancaflor, Elison; Payton, Mark; Nelson, Richard S.; Verchot-Lubicz, Jeanmarie

    2003-01-01

    Potato virus X (PVX) TGBp1, TGBp2, TGBp3, and coat protein are required for virus cell-to-cell movement. Plasmids expressing GFP fused to TGBp2 were bombarded to leaf epidermal cells and GFP:TGBp2 moved cell to cell in Nicotiana benthamiana leaves but not in Nicotiana tabacum leaves. GFP:TGBp2 movement was observed in TGBp1-transgenic N. tabacum, indicating that TGBp2 requires TGBp1 to promote its movement in N. tabacum. In this study, GFP:TGBp2 was detected in a polygonal pattern that resembles the endoplasmic reticulum (ER) network. Amino acid sequence analysis revealed TGBp2 has two putative transmembrane domains. Two mutations separately introduced into the coding sequences encompassing the putative transmembrane domains within the GFP:TGBp2 plasmids and PVX genome, disrupted membrane binding of GFP:TGBp2, inhibited GFP:TGBp2 movement in N. benthamiana and TGBp1-expressing N. tabacum, and inhibited PVX movement. A third mutation, lying outside the transmembrane domains, had no effect on GFP:TGBp2 ER association or movement in N. benthamiana but inhibited GFP:TGBp2 movement in TGBp1-expressing N. tabacum and PVX movement in either Nicotiana species. Thus, ER association of TGBp2 may be required but not be sufficient for virus movement. TGBp2 likely provides an activity for PVX movement beyond ER association.

  17. Cell-to-cell contact and antimicrobial peptides play a combined role in the death of Lachanchea thermotolerans during mixed-culture alcoholic fermentation with Saccharomyces cerevisiae.

    PubMed

    Kemsawasd, Varongsiri; Branco, Patrícia; Almeida, Maria Gabriela; Caldeira, Jorge; Albergaria, Helena; Arneborg, Nils

    2015-07-01

    The roles of cell-to-cell contact and antimicrobial peptides in the early death of Lachanchea thermotolerans CBS2803 during anaerobic, mixed-culture fermentations with Saccharomyces cerevisiae S101 were investigated using a commercially available, double-compartment fermentation system separated by cellulose membranes with different pore sizes, i.e. 1000 kDa for mixed- and single-culture fermentations, and 1000 and 3.5-5 kDa for compartmentalized-culture fermentations. SDS-PAGE and gel filtration chromatography were used to determine an antimicrobial peptidic fraction in the fermentations. Our results showed comparable amounts of the antimicrobial peptidic fraction in the inner compartments of the mixed-culture and 1000 kDa compartmentalized-culture fermentations containing L. thermotolerans after 4 days of fermentation, but a lower death rate of L. thermotolerans in the 1000 kDa compartmentalized-culture fermentation than in the mixed-culture fermentation. Furthermore, L. thermotolerans died off even more slowly in the 3.5-5 kDa than in the 1000 kDa compartmentalized-culture fermentation, which coincided with the presence of less of the antimicrobial peptidic fraction in the inner compartment of that fermentation than of the 1000 kDa compartmentalized-culture fermentation. Taken together, these results indicate that the death of L. thermotolerans in mixed cultures with S. cerevisiae is caused by a combination of cell-to-cell contact and antimicrobial peptides.

  18. In vitro T-cell activation of monocyte-derived macrophages by soluble messengers or cell-to-cell contact in bovine tuberculosis

    PubMed Central

    Liébana, E; Aranaz, A; Welsh, M; Neill, S D; Pollock, J M

    2000-01-01

    The macrophage plays a dual role in tuberculosis, promoting not only protection against mycobacteria, but also survival of the pathogen. Macrophages inhibit multiplication of mycobacteria but also act in concert with lymphocytes through presentation of antigens to T cells. Studies in animal and human infections have suggested a correlation of in vitro growth rates of mycobacteria with in vivo virulence, using uracil uptake to assess mycobacterial metabolism. This study found that blood-derived, non-activated bovine macrophages were capable of controlling Mycobacterium bovis bacillus Calmette–Guérin growth for up to 96 hr, but were permissive to intracellular growth of virulent M. bovis. The present investigation compared the in vitro modulation of these macrophage activities by cytokine-rich T-cell supernatants or cell-to-cell contact. On the one hand, treatment of cultured monocytes with mitogen-produced T-cell supernatants promoted morphological changes suggestive of an activation status, enhanced the antigen presentation capabilities of monocytes and up-regulated major histocompatibility complex class II expression. However, this activation was not associated with enhanced anti-M. bovis activity. On the other hand, incubation of infected monocytes with T-cell populations resulted in proportionally increased inhibition of M. bovis uracil uptake. This inhibition was also seen using cells from uninfected animals and indicated the necessity for cell-to-cell contact to promote antimycobacterial capability. PMID:10886395

  19. Evolution of stalk/spore ratio in a social amoeba: cell-to-cell interaction via a signaling chemical shaped by cheating risk.

    PubMed

    Uchinomiya, Kouki; Iwasa, Yoh

    2013-11-01

    The social amoeba (or cellular slime mold) is a model system for cell cooperation. When food is depleted in the environment, cells aggregate together. Some of these cells become stalks, raising spores to aid in their dispersal. Differentiation-inducing factor-1 (DIF-1) is a signaling chemical produced by prespore cells and decomposed by prestalk cells. It affects the rate of switching between prestalk and prespore cells, thereby achieving a stable stalk/spore ratio. In this study we analyzed the evolution of the stalk/spore ratio. Strains may differ in the production and decomposition rates of the signaling chemical, and in the sensitivity of cells to switch in response to the signaling chemical exposure. When two strains with the same stalk/spore ratio within their own fruiting body are combined into a single fruiting body, one strain may develop into prespores to a greater degree than the other. Direct evolutionary simulations and quantitative genetic dynamics demonstrate that if a fruiting body is always formed by a single strain, the cells evolve to produce less signaling chemical and become more sensitive to the signaling chemical due to the cost of producing the chemical. In contrast, if a fruiting body is formed by multiple strains, the cells evolve to become less sensitive to the signaling chemical and produce more signaling chemical in order to reduce the risk of being exploited. In contrast, the stalk-spore ratio is less likely to be affected by small cheating risk. PMID:23911583

  20. Evolution of stalk/spore ratio in a social amoeba: cell-to-cell interaction via a signaling chemical shaped by cheating risk.

    PubMed

    Uchinomiya, Kouki; Iwasa, Yoh

    2013-11-01

    The social amoeba (or cellular slime mold) is a model system for cell cooperation. When food is depleted in the environment, cells aggregate together. Some of these cells become stalks, raising spores to aid in their dispersal. Differentiation-inducing factor-1 (DIF-1) is a signaling chemical produced by prespore cells and decomposed by prestalk cells. It affects the rate of switching between prestalk and prespore cells, thereby achieving a stable stalk/spore ratio. In this study we analyzed the evolution of the stalk/spore ratio. Strains may differ in the production and decomposition rates of the signaling chemical, and in the sensitivity of cells to switch in response to the signaling chemical exposure. When two strains with the same stalk/spore ratio within their own fruiting body are combined into a single fruiting body, one strain may develop into prespores to a greater degree than the other. Direct evolutionary simulations and quantitative genetic dynamics demonstrate that if a fruiting body is always formed by a single strain, the cells evolve to produce less signaling chemical and become more sensitive to the signaling chemical due to the cost of producing the chemical. In contrast, if a fruiting body is formed by multiple strains, the cells evolve to become less sensitive to the signaling chemical and produce more signaling chemical in order to reduce the risk of being exploited. In contrast, the stalk-spore ratio is less likely to be affected by small cheating risk.

  1. Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity

    PubMed Central

    McDonald, Karin R.; Pourbozorgi-Langroudi, Parham; Cristea, Ileana M.; Zakian, Virginia A.; Capra, John A.; Sabouri, Nasim

    2016-01-01

    Replicative DNA helicases expose the two strands of the double helix to the replication apparatus, but accessory helicases are often needed to help forks move past naturally occurring hard-to-replicate sites, such as tightly bound proteins, RNA/DNA hybrids, and DNA secondary structures. Although the Schizosaccharomyces pombe 5’-to-3’ DNA helicase Pfh1 is known to promote fork progression, its genomic targets, dynamics, and mechanisms of action are largely unknown. Here we address these questions by integrating genome-wide identification of Pfh1 binding sites, comprehensive analysis of the effects of Pfh1 depletion on replication and DNA damage, and proteomic analysis of Pfh1 interaction partners by immunoaffinity purification mass spectrometry. Of the 621 high confidence Pfh1-binding sites in wild type cells, about 40% were sites of fork slowing (as marked by high DNA polymerase occupancy) and/or DNA damage (as marked by high levels of phosphorylated H2A). The replication and integrity of tRNA and 5S rRNA genes, highly transcribed RNA polymerase II genes, and nucleosome depleted regions were particularly Pfh1-dependent. The association of Pfh1 with genomic integrity at highly transcribed genes was S phase dependent, and thus unlikely to be an artifact of high transcription rates. Although Pfh1 affected replication and suppressed DNA damage at discrete sites throughout the genome, Pfh1 and the replicative DNA polymerase bound to similar extents to both Pfh1-dependent and independent sites, suggesting that Pfh1 is proximal to the replication machinery during S phase. Consistent with this interpretation, Pfh1 co-purified with many key replisome components, including the hexameric MCM helicase, replicative DNA polymerases, RPA, and the processivity clamp PCNA in an S phase dependent manner. Thus, we conclude that Pfh1 is an accessory DNA helicase that interacts with the replisome and promotes replication and suppresses DNA damage at hard-to-replicate sites. These

  2. Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity.

    PubMed

    McDonald, Karin R; Guise, Amanda J; Pourbozorgi-Langroudi, Parham; Cristea, Ileana M; Zakian, Virginia A; Capra, John A; Sabouri, Nasim

    2016-09-01

    Replicative DNA helicases expose the two strands of the double helix to the replication apparatus, but accessory helicases are often needed to help forks move past naturally occurring hard-to-replicate sites, such as tightly bound proteins, RNA/DNA hybrids, and DNA secondary structures. Although the Schizosaccharomyces pombe 5'-to-3' DNA helicase Pfh1 is known to promote fork progression, its genomic targets, dynamics, and mechanisms of action are largely unknown. Here we address these questions by integrating genome-wide identification of Pfh1 binding sites, comprehensive analysis of the effects of Pfh1 depletion on replication and DNA damage, and proteomic analysis of Pfh1 interaction partners by immunoaffinity purification mass spectrometry. Of the 621 high confidence Pfh1-binding sites in wild type cells, about 40% were sites of fork slowing (as marked by high DNA polymerase occupancy) and/or DNA damage (as marked by high levels of phosphorylated H2A). The replication and integrity of tRNA and 5S rRNA genes, highly transcribed RNA polymerase II genes, and nucleosome depleted regions were particularly Pfh1-dependent. The association of Pfh1 with genomic integrity at highly transcribed genes was S phase dependent, and thus unlikely to be an artifact of high transcription rates. Although Pfh1 affected replication and suppressed DNA damage at discrete sites throughout the genome, Pfh1 and the replicative DNA polymerase bound to similar extents to both Pfh1-dependent and independent sites, suggesting that Pfh1 is proximal to the replication machinery during S phase. Consistent with this interpretation, Pfh1 co-purified with many key replisome components, including the hexameric MCM helicase, replicative DNA polymerases, RPA, and the processivity clamp PCNA in an S phase dependent manner. Thus, we conclude that Pfh1 is an accessory DNA helicase that interacts with the replisome and promotes replication and suppresses DNA damage at hard-to-replicate sites. These data

  3. Overexpression of optineurin E50K disrupts Rab8 interaction and leads to a progressive retinal degeneration in mice

    PubMed Central

    Chi, Zai-Long; Akahori, Masakazu; Obazawa, Minoru; Minami, Masayoshi; Noda, Toru; Nakaya, Naoki; Tomarev, Stanislav; Kawase, Kazuhide; Yamamoto, Tetsuya; Noda, Setsuko; Sasaoka, Masaki; Shimazaki, Atsushi; Takada, Yuichiro; Iwata, Takeshi

    2010-01-01

    Glaucoma is one of the leading causes of bilateral blindness affecting nearly 8 million people worldwide. Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs) and is often associated with elevated intraocular pressure (IOP). However, patients with normal tension glaucoma (NTG), a subtype of primary open-angle glaucoma (POAG), develop the disease without IOP elevation. The molecular pathways leading to the pathology of NTG and POAG are still unclear. Here, we describe the phenotypic characteristics of transgenic mice overexpressing wild-type (Wt) or mutated optineurin (Optn). Mutations E50K, H486R and Optn with a deletion of the first (amino acids 153–174) or second (amino acids 426–461) leucine zipper were used for overexpression. After 16 months, histological abnormalities were exclusively observed in the retina of E50K mutant mice with loss of RGCs and connecting synapses in the peripheral retina leading to a thinning of the nerve fiber layer at the optic nerve head at normal IOP. E50K mice also showed massive apoptosis and degeneration of entire retina, leading to approximately a 28% reduction of the retina thickness. At the molecular level, introduction of the E50K mutation disrupts the interaction between Optn and Rab8 GTPase, a protein involved in the regulation of vesicle transport from Golgi to plasma membrane. Wt Optn and an active GTP-bound form of Rab8 complex were localized at the Golgi complex. These data suggest that alternation of the Optn sequence can initiate significant retinal degeneration in mice. PMID:20388642

  4. Liquid Lithium Divertor and Scrape-Off-Layer Interactions on the National Spherical Torus Experiment: 2010 ? 2013 Progress Report

    SciTech Connect

    2013-08-27

    The implementation of the liquid Lithium Divertor (LLD) in NSTX presented a unique opportunity in plasma-material interactions studies. A high density Langmuir Probe (HDLP) array utilizing a dense pack of triple Langmuir probes was built at PPPL and the electronics designed and built by UIUC. It was shown that the HDLP array could be used to characterize the modification of the EEDF during lithium experiments on NSTX as well as characterize the transient particle loads during lithium experiments as a means to study ELMs. With NSTX being upgraded and a new divertor being installed, the HDLP array will not be used in NSTX-U. However UIUC is currently helping to develop two new systems for depositing lithium into NSTX-U, a Liquid Lithium Pellet Dripper (LLPD) for use with the granular injector for ELM mitigation and control studies as well as an Upward-Facing Lithium Evaporator (U-LITER) based on a flash evaporation system using an electron beam. Currently UIUC has Daniel Andruczyk Stationed at PPPL and is developing these systems as well as being involved in preparing the Materials Analysis Particle Probe (MAPP) for use in LTX and NSTX-U. To date the MAPP preparations have been completed. New sample holders were designed by UIUC?s Research Engineer at PPPL and manufactured at PPPL and installed. MAPP is currently being used on LTX to do calibration and initial studies. The LLPD has demonstrated that it can produce pellets. There is still some adjustments needed to control the frequency and particle size. Equipment for the U-LITER has arrived and initial test are being made of the electron beam and design of the U-LITER in progress. It is expected to have these ready for the first run campaign of NSTX-U.

  5. Advanced Ring-Shaped Microelectrode Assay Combined with Small Rectangular Electrode for Quasi-In vivo Measurement of Cell-to-Cell Conductance in Cardiomyocyte Network

    NASA Astrophysics Data System (ADS)

    Nomura, Fumimasa; Kaneko, Tomoyuki; Hamada, Tomoyo; Hattori, Akihiro; Yasuda, Kenji

    2013-06-01

    To predict the risk of fatal arrhythmia induced by cardiotoxicity in the highly complex human heart system, we have developed a novel quasi-in vivo electrophysiological measurement assay, which combines a ring-shaped human cardiomyocyte network and a set of two electrodes that form a large single ring-shaped electrode for the direct measurement of irregular cell-to-cell conductance occurrence in a cardiomyocyte network, and a small rectangular microelectrode for forced pacing of cardiomyocyte beating and for acquiring the field potential waveforms of cardiomyocytes. The advantages of this assay are as follows. The electrophysiological signals of cardiomyocytes in the ring-shaped network are superimposed directly on a single loop-shaped electrode, in which the information of asynchronous behavior of cell-to-cell conductance are included, without requiring a set of huge numbers of microelectrode arrays, a set of fast data conversion circuits, or a complex analysis in a computer. Another advantage is that the small rectangular electrode can control the position and timing of forced beating in a ring-shaped human induced pluripotent stem cell (hiPS)-derived cardiomyocyte network and can also acquire the field potentials of cardiomyocytes. First, we constructed the human iPS-derived cardiomyocyte ring-shaped network on the set of two electrodes, and acquired the field potential signals of particular cardiomyocytes in the ring-shaped cardiomyocyte network during simultaneous acquisition of the superimposed signals of whole-cardiomyocyte networks representing cell-to-cell conduction. Using the small rectangular electrode, we have also evaluated the response of the cell network to electrical stimulation. The mean and SD of the minimum stimulation voltage required for pacing (VMin) at the small rectangular electrode was 166+/-74 mV, which is the same as the magnitude of amplitude for the pacing using the ring-shaped electrode (179+/-33 mV). The results showed that the

  6. Cellular uptake and cell-to-cell transfer of polyelectrolyte microcapsules within a triple co-culture system representing parts of the respiratory tract

    NASA Astrophysics Data System (ADS)

    Kuhn, Dagmar A.; Hartmann, Raimo; Fytianos, Kleanthis; Petri-Fink, Alke; Rothen-Rutishauser, Barbara; Parak, Wolfgang J.

    2015-06-01

    Polyelectrolyte multilayer microcapsules around 3.4 micrometers in diameter were added to epithelial cells, monocyte-derived macrophages, and dendritic cells in vitro and their uptake kinetics were quantified. All three cell types were combined in a triple co-culture model, mimicking the human epithelial alveolar barrier. Hereby, macrophages were separated in a three-dimensional model from dendritic cells by a monolayer of epithelial cells. While passing of small nanoparticles has been demonstrated from macrophages to dendritic cells across the epithelial barrier in previous studies, for the micrometer-sized capsules, this process could not be observed in a significant amount. Thus, this barrier is a limiting factor for cell-to-cell transfer of micrometer-sized particles.

  7. The Envelope Cytoplasmic Tail of HIV-1 Subtype C Contributes to Poor Replication Capacity through Low Viral Infectivity and Cell-to-Cell Transmission

    PubMed Central

    Lemaire, Morgane; Masquelier, Cécile; Beraud, Cyprien; Rybicki, Arkadiusz; Servais, Jean-Yves; Iserentant, Gilles; Schmit, Jean-Claude; Seguin-Devaux, Carole; Perez Bercoff, Danielle

    2016-01-01

    The cytoplasmic tail (gp41CT) of the HIV-1 envelope (Env) mediates Env incorporation into virions and regulates Env intracellular trafficking. Little is known about the functional impact of variability in this domain. To address this issue, we compared the replication of recombinant virus pairs carrying the full Env (Env viruses) or the Env ectodomain fused to the gp41CT of NL4.3 (EnvEC viruses) (12 subtype C and 10 subtype B pairs) in primary CD4+ T-cells and monocyte-derived-macrophages (MDMs). In CD4+ T-cells, replication was as follows: B-EnvEC = B-Env>C-EnvEC>C-Env, indicating that the gp41CT of subtype C contributes to the low replicative capacity of this subtype. In MDMs, in contrast, replication capacity was comparable for all viruses regardless of subtype and of gp41CT. In CD4+ T-cells, viral entry, viral release and viral gene expression were similar. However, infectivity of free virions and cell-to-cell transmission of C-Env viruses released by CD4+ T-cells was lower, suggestive of lower Env incorporation into virions. Subtype C matrix only minimally rescued viral replication and failed to restore infectivity of free viruses and cell-to-cell transmission. Taken together, these results show that polymorphisms in the gp41CT contribute to viral replication capacity and suggest that the number of Env spikes per virion may vary across subtypes. These findings should be taken into consideration in the design of vaccines. PMID:27598717

  8. Role of the C-terminal domain of the HIV-1 glycoprotein in cell-to-cell viral transmission between T lymphocytes

    PubMed Central

    2010-01-01

    Background Mutant HIV (HIV-Env-Tr712) lacking the cytoplasmic tail of the viral glycoprotein (Env-CT) exhibits a cell-type specific replication phenotype such that replicative spread occurs in some T-cell lines (referred to as permissive cells) but fails to do so in most T-cell lines or in PBMCs (referred to as non-permissive cells). We aim to gain insight on the underlying requirement for the Env-CT for viral spread in non-permissive cells. Results We established that in comparison to HIV-Wt, both cell-free and cell-to-cell transmission of mutant HIV-Env-Tr712 from non-permissive cells were severely impaired under naturally low infection conditions. This requirement for Env-CT could be largely overcome by using saturating amounts of virus for infection. We further observed that in permissive cells, which supported both routes of mutant virus transmission, viral gene expression levels, Gag processing and particle release were inherently higher than in non-permissive cells, a factor which may be significantly contributing to their permissivity phenotype. Additionally, and correlating with viral transfer efficiencies in these cell types, HIV-Gag accumulation at the virological synapse (VS) was reduced to background levels in the absence of the Env-CT in conjugates of non-permissive cells but not in permissive cells. Conclusions During natural infection conditions, the HIV-Env-CT is critically required for viral transmission in cultures of non-permissive cells by both cell-free and cell-to-cell routes and is instrumental for Gag accumulation to the VS. The requirement of the Env-CT for these related processes is abrogated in permissive cells, which exhibit higher HIV gene expression levels. PMID:20459872

  9. The Envelope Cytoplasmic Tail of HIV-1 Subtype C Contributes to Poor Replication Capacity through Low Viral Infectivity and Cell-to-Cell Transmission.

    PubMed

    Santos da Silva, Eveline; Mulinge, Martin; Lemaire, Morgane; Masquelier, Cécile; Beraud, Cyprien; Rybicki, Arkadiusz; Servais, Jean-Yves; Iserentant, Gilles; Schmit, Jean-Claude; Seguin-Devaux, Carole; Perez Bercoff, Danielle

    2016-01-01

    The cytoplasmic tail (gp41CT) of the HIV-1 envelope (Env) mediates Env incorporation into virions and regulates Env intracellular trafficking. Little is known about the functional impact of variability in this domain. To address this issue, we compared the replication of recombinant virus pairs carrying the full Env (Env viruses) or the Env ectodomain fused to the gp41CT of NL4.3 (EnvEC viruses) (12 subtype C and 10 subtype B pairs) in primary CD4+ T-cells and monocyte-derived-macrophages (MDMs). In CD4+ T-cells, replication was as follows: B-EnvEC = B-Env>C-EnvEC>C-Env, indicating that the gp41CT of subtype C contributes to the low replicative capacity of this subtype. In MDMs, in contrast, replication capacity was comparable for all viruses regardless of subtype and of gp41CT. In CD4+ T-cells, viral entry, viral release and viral gene expression were similar. However, infectivity of free virions and cell-to-cell transmission of C-Env viruses released by CD4+ T-cells was lower, suggestive of lower Env incorporation into virions. Subtype C matrix only minimally rescued viral replication and failed to restore infectivity of free viruses and cell-to-cell transmission. Taken together, these results show that polymorphisms in the gp41CT contribute to viral replication capacity and suggest that the number of Env spikes per virion may vary across subtypes. These findings should be taken into consideration in the design of vaccines. PMID:27598717

  10. A Millifluidic Study of Cell-to-Cell Heterogeneity in Growth-Rate and Cell-Division Capability in Populations of Isogenic Cells of Chlamydomonas reinhardtii

    PubMed Central

    Damodaran, Shima P.; Eberhard, Stephan; Boitard, Laurent; Rodriguez, Jairo Garnica; Wang, Yuxing; Bremond, Nicolas; Baudry, Jean; Bibette, Jérôme; Wollman, Francis-André

    2015-01-01

    To address possible cell-to-cell heterogeneity in growth dynamics of isogenic cell populations of Chlamydomonas reinhardtii, we developed a millifluidic drop-based device that not only allows the analysis of populations grown from single cells over periods of a week, but is also able to sort and collect drops of interest, containing viable and healthy cells, which can be used for further experimentation. In this study, we used isogenic algal cells that were first synchronized in mixotrophic growth conditions. We show that these synchronized cells, when placed in droplets and kept in mixotrophic growth conditions, exhibit mostly homogeneous growth statistics, but with two distinct subpopulations: a major population with a short doubling-time (fast-growers) and a significant subpopulation of slowly dividing cells (slow-growers). These observations suggest that algal cells from an isogenic population may be present in either of two states, a state of restricted division and a state of active division. When isogenic cells were allowed to propagate for about 1000 generations on solid agar plates, they displayed an increased heterogeneity in their growth dynamics. Although we could still identify the original populations of slow- and fast-growers, drops inoculated with a single progenitor cell now displayed a wider diversity of doubling-times. Moreover, populations dividing with the same growth-rate often reached different cell numbers in stationary phase, suggesting that the progenitor cells differed in the number of cell divisions they could undertake. We discuss possible explanations for these cell-to-cell heterogeneities in growth dynamics, such as mutations, differential aging or stochastic variations in metabolites and macromolecules yielding molecular switches, in the light of single-cell heterogeneities that have been reported among isogenic populations of other eu- and prokaryotes. PMID:25760649

  11. Multi-Scale Characean Experimental System: From Electrophysiology of Membrane Transporters to Cell-to-Cell Connectivity, Cytoplasmic Streaming and Auxin Metabolism.

    PubMed

    Beilby, Mary J

    2016-01-01

    The morphology of characean algae could be mistaken for a higher plant: stem-like axes with leaf-like branchlets anchored in the soil by root-like rhizoids. However, all of these structures are made up of giant multinucleate cells separated by multicellular nodal complexes. The excised internodal cells survive long enough for the nodes to give rise to new thallus. The size of the internodes and their thick cytoplasmic layer minimize impalement injury and allow specific micro-electrode placement. The cell structure can be manipulated by centrifugation, perfusion of cell contents or creation of cytoplasmic droplets, allowing access to both vacuolar and cytoplasmic compartments and both sides of the cell membranes. Thousands of electrical measurements on intact or altered cells and cytoplasmic droplets laid down basis to modern plant electrophysiology. Furthermore, the giant internodal cells and whole thalli facilitate research into many other plant properties. As nutrients have to be transported from rhizoids to growing parts of the thallus and hormonal signals need to pass from cell to cell, Characeae possess very fast cytoplasmic streaming. The mechanism was resolved in the characean model. Plasmodesmata between the internodal cells and nodal complexes facilitate transport of ions, nutrients and photosynthates across the nodes. The internal structure was found to be similar to those of higher plants. Recent experiments suggest a strong circadian influence on metabolic pathways producing indole-3-acetic acid (IAA) and serotonin/melatonin. The review will discuss the impact of the characean models arising from fragments of cells, single cells, cell-to-cell transport or whole thalli on understanding of plant evolution and physiology. PMID:27504112

  12. Multi-Scale Characean Experimental System: From Electrophysiology of Membrane Transporters to Cell-to-Cell Connectivity, Cytoplasmic Streaming and Auxin Metabolism

    PubMed Central

    Beilby, Mary J.

    2016-01-01

    The morphology of characean algae could be mistaken for a higher plant: stem-like axes with leaf-like branchlets anchored in the soil by root-like rhizoids. However, all of these structures are made up of giant multinucleate cells separated by multicellular nodal complexes. The excised internodal cells survive long enough for the nodes to give rise to new thallus. The size of the internodes and their thick cytoplasmic layer minimize impalement injury and allow specific micro-electrode placement. The cell structure can be manipulated by centrifugation, perfusion of cell contents or creation of cytoplasmic droplets, allowing access to both vacuolar and cytoplasmic compartments and both sides of the cell membranes. Thousands of electrical measurements on intact or altered cells and cytoplasmic droplets laid down basis to modern plant electrophysiology. Furthermore, the giant internodal cells and whole thalli facilitate research into many other plant properties. As nutrients have to be transported from rhizoids to growing parts of the thallus and hormonal signals need to pass from cell to cell, Characeae possess very fast cytoplasmic streaming. The mechanism was resolved in the characean model. Plasmodesmata between the internodal cells and nodal complexes facilitate transport of ions, nutrients and photosynthates across the nodes. The internal structure was found to be similar to those of higher plants. Recent experiments suggest a strong circadian influence on metabolic pathways producing indole-3-acetic acid (IAA) and serotonin/melatonin. The review will discuss the impact of the characean models arising from fragments of cells, single cells, cell-to-cell transport or whole thalli on understanding of plant evolution and physiology. PMID:27504112

  13. Multi-Scale Characean Experimental System: From Electrophysiology of Membrane Transporters to Cell-to-Cell Connectivity, Cytoplasmic Streaming and Auxin Metabolism.

    PubMed

    Beilby, Mary J

    2016-01-01

    The morphology of characean algae could be mistaken for a higher plant: stem-like axes with leaf-like branchlets anchored in the soil by root-like rhizoids. However, all of these structures are made up of giant multinucleate cells separated by multicellular nodal complexes. The excised internodal cells survive long enough for the nodes to give rise to new thallus. The size of the internodes and their thick cytoplasmic layer minimize impalement injury and allow specific micro-electrode placement. The cell structure can be manipulated by centrifugation, perfusion of cell contents or creation of cytoplasmic droplets, allowing access to both vacuolar and cytoplasmic compartments and both sides of the cell membranes. Thousands of electrical measurements on intact or altered cells and cytoplasmic droplets laid down basis to modern plant electrophysiology. Furthermore, the giant internodal cells and whole thalli facilitate research into many other plant properties. As nutrients have to be transported from rhizoids to growing parts of the thallus and hormonal signals need to pass from cell to cell, Characeae possess very fast cytoplasmic streaming. The mechanism was resolved in the characean model. Plasmodesmata between the internodal cells and nodal complexes facilitate transport of ions, nutrients and photosynthates across the nodes. The internal structure was found to be similar to those of higher plants. Recent experiments suggest a strong circadian influence on metabolic pathways producing indole-3-acetic acid (IAA) and serotonin/melatonin. The review will discuss the impact of the characean models arising from fragments of cells, single cells, cell-to-cell transport or whole thalli on understanding of plant evolution and physiology.

  14. Prostaglandin E2 Reduces the Release and Infectivity of New Cell-Free Virions and Cell-To-Cell HIV-1 Transfer

    PubMed Central

    Serramía, María Jesús; Martínez-Bonet, Marta; Muñoz-Fernández, María Ángeles

    2014-01-01

    Background The course of human immunodeficiency virus type-1 (HIV-1) infection is influenced by a complex interplay between viral and host factors. HIV infection stimulates several proinflammatory genes, such as cyclooxigense-2 (COX-2), which leads to an increase in prostaglandin (PG) levels in the plasma of HIV-1-infected patients. These genes play an indeterminate role in HIV replication and pathogenesis. The effect of prostaglandin E2 (PGE2) on HIV infection is quite controversial and even contradictory, so we sought to determine the role of PGE2 and the signal transduction pathways involved in HIV infection to elucidate possible new targets for antiretrovirals. Results Our results suggest that PGE2 post-infection treatment acts in the late stages of the viral cycle to reduce HIV replication. Interestingly, viral protein synthesis was not affected, but a loss of progeny virus production was observed. No modulation of CD4 CXCR4 and CCR5 receptor expression, cell proliferation, or activation after PGE2 treatment was detected. Moreover, PGE2 induced an increase in intracellular cAMP (cyclic AMP) levels through the EP2/EP4 receptors. PGE2 effects were mimicked by dbcAMP and by a specific Epac (exchange protein directly activated by cyclic AMP) agonist, 8-Cpt-cAMP. Treatment with PGE2 increased Rap1 activity, decreased RhoA activity and subsequently reduced the polymerization of actin by approximately 30% compared with untreated cells. In connection with this finding, polarized viral assembly platforms enriched in Gag were disrupted, altering HIV cell-to-cell transfer and the infectivity of new virions. Conclusions Our results demonstrate that PGE2, through Epac and Rap activation, alters the transport of newly synthesized HIV-1 components to the assembly site, reducing the release and infectivity of new cell-free virions and cell-to-cell HIV-1 transfer. PMID:24586238

  15. A Scoping Analysis Of The Impact Of SiC Cladding On Late-Phase Accident Progression Involving Core–Concrete Interaction

    SciTech Connect

    Farmer, M. T.

    2015-11-01

    The overall objective of the current work is to carry out a scoping analysis to determine the impact of ATF on late phase accident progression; in particular, the molten core-concrete interaction portion of the sequence that occurs after the core debris fails the reactor vessel and relocates into containment. This additional study augments previous work by including kinetic effects that govern chemical reaction rates during core-concrete interaction. The specific ATF considered as part of this study is SiC-clad UO2.

  16. On the central role of brain connectivity in neurodegenerative disease progression

    PubMed Central

    Iturria-Medina, Yasser; Evans, Alan C.

    2015-01-01

    Increased brain connectivity, in all its variants, is often considered an evolutionary advantage by mediating complex sensorimotor function and higher cognitive faculties. Interaction among components at all spatial scales, including genes, proteins, neurons, local neuronal circuits and macroscopic brain regions, are indispensable for such vital functions. However, a growing body of evidence suggests that, from the microscopic to the macroscopic levels, such connections might also be a conduit for in intra-brain disease spreading. For instance, cell-to-cell misfolded proteins (MP) transmission and neuronal toxicity are prominent connectivity-mediated factors in aging and neurodegeneration. This article offers an overview of connectivity dysfunctions associated with neurodegeneration, with a specific focus on how these may be central to both normal aging and the neuropathologic degenerative progression. PMID:26052284

  17. Investigations of the dynamics and electromagnetic interactions of few-body systems. Progress report, June 30, 1994--September 30, 1995

    SciTech Connect

    Lehman, D.R.

    1995-10-01

    This progress report summarizes the work of The George Washington University (GW) nuclear theory group during the period 1 July 1994 - 30 September 1995 under DOE Grant No. DE-FG02-95-ER40907 mainly dealing with photonuclear reactions and few-body problems of nuclei. This report contains: papers published or in press, submitted for publication, and in preparation; invited talks at conferences and meetings; invited talks at universities and laboratories; contributed papers or abstracts at conferences; visitors to the group; and research progress by topic.

  18. Investigations of the structure and electromagnetic interactions of few-body systems. Progress report, 1 January 1980-1 October 1980

    SciTech Connect

    Harper, E P; Lehman, D R; Prats, F

    1980-11-07

    Considerable progress has been made on the long-range problems described in the original proposal document (1 February 1979 to 31 January 1980) and on the shorter-range problems described in the last renewal proposal (1 February 1980 to 31 January 1981). This progress concerns few-body structure problems (e.g., the existence of isobar components in /sup 3/H, predictions of few-body-hypernuclei properties as a test of hyperon-nucleon interactions, investigation of the A = 6 ground states with exact three-body calculations, and the relation of triton D-state properties to the deuteron's D-state percentage) and electromagnetic properties and interactions of few-body nuclei (e.g., Coulomb effects in calculating and measuring asymptotic normalization constants, and ..gamma.. + /sup 3/He breakup reaction mechanisms at intermediate energies). Descriptions of the progress made indicate where each subject stands at present, and emphasize the significant results obtained. A publication list is attached.

  19. Theory and phenomenology of strong and weak interaction high energy physics. Technical progress report, May 1, 1985-April 30, 1986

    SciTech Connect

    Thews, R.L.; Scadron, M.D.; Patrascioiu, A.; Sucipto, E.

    1986-01-01

    Progress is reported in these areas: dynamical quark mass in QCD; quark s-d self energy in QFD; theory of nonleptonic weak decays; decays of heavy-quark mesons; quarks in nuclei; nonperturbative effects in non-abelian quantum field theory; whether perturbation theory is the asymptotic expansion in lattice gauge theories; and expanding in the gradient at weak coupling. 16 refs. (LEW)

  20. A new cell line for high throughput HIV-specific antibody-dependent cellular cytotoxicity (ADCC) and cell-to-cell virus transmission studies

    PubMed Central

    Orlandi, Chiara; Flinko, Robin; Lewis, George K.

    2016-01-01

    Several lines of evidence indicate that antibody-dependent cellular cytotoxicity (Wren et al., 2013) is important in the pathogenesis of HIV-1 infection. Namely, ADCC is induced during natural HIV-1 infection or in HIV-1 vaccine studies, the latter demonstrated by the RV144 vaccine trial. To expedite the assessment of ADCC in studies of HIV, we have developed a high throughput assay. We have optimized the rapid fluorometric antibody-mediated cytotoxicity assay (RFADCC) by transfecting the EGFP-CEM-NKr cell line to constitutively express SNAP-tagged CCR5. This cell line can then serve as a source of HIV-specific targets when coated with monomeric gp120, spinoculated with inactivated intact virions, infected by cell-free viral diffusion or infected by cell-to-cell transmission of virus. The optimized strategy has two significant advantages over the original RFADCC method: First, the preparation of detectable target cells is less labor intensive and faster as it does not rely on multiple staining and washing steps for target cells. Second, because the target cell markers GFP and SNAP are constitutively expressed, the assay provides highly reproducible data. These strengths make the optimized RFADCC assay suitable not only for studies of HIV-1 specific cytotoxicity but also for studies of cell–cell transmission of virus. In conclusion, this assay provides a new generation T cell line that can expedite large clinical studies as well as research studies in humans or non-human primates. PMID:26969387

  1. The Glycine-Alanine Dipeptide Repeat from C9orf72 Hexanucleotide Expansions Forms Toxic Amyloids Possessing Cell-to-Cell Transmission Properties.

    PubMed

    Chang, Yu-Jen; Jeng, U-Ser; Chiang, Ya-Ling; Hwang, Ing-Shouh; Chen, Yun-Ru

    2016-03-01

    Hexanucleotide expansions, GGGGCC, in the non-coding regions of the C9orf72 gene were found in major frontotemporal lobar dementia and amyotrophic lateral sclerosis patients (C9FTD/ALS). In addition to possible RNA toxicity, several dipeptide repeats (DPRs) are translated through repeat-associated non-ATG-initiated translation. The DPRs, including poly(GA), poly(GR), poly(GP), poly(PR), and poly(PA), were found in the brains and spinal cords of C9FTD/ALS patients. Among the DPRs, poly(GA) is highly susceptible to form cytoplasmic inclusions, which is a characteristic of C9FTD/ALS. To elucidate DPR aggregation, we used synthetic (GA)15 DPR as a model system to examine the aggregation and structural properties in vitro. We found that (GA)15 with 15 repeats fibrillates rapidly and ultimately forms flat, ribbon-type fibrils evidenced by transmission electron microscopy and atomic force microscopy. The fibrils are capable of amyloid dye binding and contain a characteristic cross-β sheet structure, as revealed by x-ray scattering. Furthermore, using neuroblastoma cells, we demonstrated the neurotoxicity and cell-to-cell transmission property of (GA)15 DPR. Overall, our results show the structural and toxicity properties of GA DPR to facilitate future DPR-related therapeutic development. PMID:26769963

  2. Effects of cell-to-cell fuel mal-distribution on fuel cell performance and a means to reduce mal-distribution using MEMS micro-valves

    SciTech Connect

    Hensel, J.P.; Gemmen, R.S.; Thornton, J.D.; Vipperman, J.S.; Clark, W.W.; Bucci, B.A.

    2007-01-10

    Achieving uniform flow among the cells of a fuel cell stack plays a significant role in being able to operate at maximum capability and efficiency. This paper presents experimental data showing the importance of cell-to-cell fuel flow balancing on fuel cell performance, and a fuel cell energy management (FCEM) technique that has demonstrated the ability to improve stack performance. In a specially instrumented four-cell polymer electrolyte fuel cell that allows external control of the air, fuel, and water-cooling flows to each cell, fuel to a single cell was reduced. V–I curves collected under these unbalanced conditions are compared to curves collected when the fuel flow to each cell was balanced. Reducing the fuel flow to a single cell by 11% decreased the V–I curve cutoff load by 10%—demonstrating the degree of negative effect that unbalanced fuel flows can have on stack performance. Typical fuel cell stacks have no dynamic means to keep flows in the stack balanced between the cells, but through the use of custom-built, piezoelectric micro-valves, a simple flow control strategy, and this custom four-cell laboratory stack, the positive effects of FCEM flow balancing at three different fuel flow rates was demonstrated.

  3. Single-cell 5hmC sequencing reveals chromosome-wide cell-to-cell variability and enables lineage reconstruction.

    PubMed

    Mooijman, Dylan; Dey, Siddharth S; Boisset, Jean-Charles; Crosetto, Nicola; van Oudenaarden, Alexander

    2016-08-01

    The epigenetic DNA modification 5-hydroxymethylcytosine (5hmC) has crucial roles in development and gene regulation. Quantifying the abundance of this epigenetic mark at the single-cell level could enable us to understand its roles. We present a single-cell, genome-wide and strand-specific 5hmC sequencing technology, based on 5hmC glucosylation and glucosylation-dependent digestion of DNA, that reveals pronounced cell-to-cell variability in the abundance of 5hmC on the two DNA strands of a given chromosome. We develop a mathematical model that reproduces the strand bias and use this model to make two predictions. First, the variation in strand bias should decrease when 5hmC turnover increases. Second, the strand bias of two sister cells should be strongly anti-correlated. We validate these predictions experimentally, and use our model to reconstruct lineages of two- and four-cell mouse embryos, showing that single-cell 5hmC sequencing can be used as a lineage reconstruction tool.

  4. Cell-Free versus Cell-to-Cell Infection by Human Immunodeficiency Virus Type 1 and Human T-Lymphotropic Virus Type 1: Exploring the Link among Viral Source, Viral Trafficking, and Viral Replication.

    PubMed

    Dutartre, Hélène; Clavière, Mathieu; Journo, Chloé; Mahieux, Renaud

    2016-09-01

    Human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type 1 (HTLV-1) are complex retroviruses mainly infecting CD4(+) T lymphocytes. In addition, antigen-presenting cells such as dendritic cells (DCs) are targeted in vivo by both viruses, although to a lesser extent. Interaction of HIV-1 with DCs plays a key role in viral dissemination from the mucosa to CD4(+) T lymphocytes present in lymphoid organs. While similar mechanisms may occur for HTLV-1 as well, most HTLV-1 data were obtained from T-cell studies, and little is known regarding the trafficking of this virus in DCs. We first compared the efficiency of cell-free versus cell-associated viral sources of both retroviruses at infecting DCs. We showed that both HIV-1 and HTLV-1 cell-free particles are poorly efficient at productively infecting DCs, except when DC-SIGN has been engaged. Furthermore, while SAMHD-1 accounts for restriction of cell-free HIV-1 infection, it is not involved in HTLV-1 restriction. In addition, cell-free viruses lead mainly to a nonproductive DC infection, leading to trans-infection of T-cells, a process important for HIV-1 spread but not for that of HTLV-1. Finally, we show that T-DC cell-to-cell transfer implies viral trafficking in vesicles that may both increase productive infection of DCs ("cis-infection") and allow viral escape from immune surveillance. Altogether, these observations allowed us to draw a model of HTLV-1 and HIV-1 trafficking in DCs.

  5. Interactive radiopharmaceutical facility between Yale Medical Center and Brookhaven National Laboratory. Progress report, June 1981-July 1982

    SciTech Connect

    Gottschalk, A

    1982-01-01

    Progress is reported in the following research areas: (1) evaluation of /sup 14/C-labelled carboxyethyl ester 2-cardoxy methyl ester of arachidonic acid; (2) the effects of drug intervention on cardiac inflammatory response following experimental myocardial infarction using indium-111 labeled autologous leukoyctes; (3) the evaluation of /sup 97/Ru-oxine to label human platelets in autologous plasma; and (4) the specific in vitro radiolabeling of human neutrophils. (ACR)

  6. Vibrational spectroscopic studies of surface chemical interactions in chemisorption and catalysis. Progress status report, 1990--1991

    SciTech Connect

    Yates, J.T. Jr.

    1991-12-31

    Various methods of vibrational spectroscopy are being employed to study the interaction and behavior of catalytically important species on both single crystal and high area catalytic surfaces. A number of interrelated themes are being investigated as shown below.

  7. Radiation/turbulence interactions in pulverized-coal flames. Second year technical progress report, September 30, 1994--September 30, 1995

    SciTech Connect

    Menguec, M.P.; McDonough, J.M.; Manickavsagam, S.; Mukerji, S.; Wang, D.; Ghosal, S.; Swabb, S.

    1995-12-31

    Our goal in this project is to investigate the interaction of radiation and turbulence in coalfired laboratory scale flames and attempt to determine the boundaries of the ``uncertainty domain`` in Figure 3 more rigorously. We have three distinct objectives: (1) To determine from experiments the effect of turbulent fluctuations on the devolatilization/pyrolysis of coal particles and soot yield, and to measure the change in the ``effective`` radiative properties of particulates due to turbulence interactions; (2) To perform local small-scale simulations to investigate the radiation-turbulence interactions in coal-fired flames starting from first principles; and (3) To develop a thorough and rigorous, but computationally practical, turbulence model for coal flames, starting from the experimental observations and small scale simulations.

  8. Natural ageing in the rat liver correlates with progressive stabilisation of DNA-nuclear matrix interactions and withdrawal of genes from the nuclear substructure.

    PubMed

    Maya-Mendoza, Apolinar; Hernández-Muñoz, Rolando; Gariglio, Patricio; Aranda-Anzaldo, Armando

    2005-01-01

    In the interphase nucleus, the DNA of higher eukaryotes is organised in supercoiled loops anchored to a nuclear matrix (NM). Replication, transcription and splicing seem to occur at macromolecular complexes organised upon the NM. Thus, the topological relationship between genes located in the loops and the NM appears to be very important for nuclear physiology. Here, we report that natural ageing in the rat liver correlates with a progressive strengthening of the NM framework and the stabilisation of the DNA loop-NM interactions, as well as with a progressive increase in the relative distance of genes to the NM. Both phenomena correlate with the gradual loss of proliferating potential and progression towards terminal differentiation in the hepatocytes, suggesting that wholesale modifications in the topological relationships within the cell nucleus are markers of tissue ageing and senescence, at least in the mammalian liver. We discuss the possible functional implications of such structural modifications that may underlie both terminal hepatocyte differentiation and their eventual replicative senescence. PMID:15888332

  9. Neurospora crassa Female Development Requires the PACC and Other Signal Transduction Pathways, Transcription Factors, Chromatin Remodeling, Cell-To-Cell Fusion, and Autophagy

    PubMed Central

    Chinnici, Jennifer L.; Fu, Ci; Caccamise, Lauren M.; Arnold, Jason W.; Free, Stephen J.

    2014-01-01

    Using a screening protocol we have identified 68 genes that are required for female development in the filamentous fungus Neurospora crassa. We find that we can divide these genes into five general groups: 1) Genes encoding components of the PACC signal transduction pathway, 2) Other signal transduction pathway genes, including genes from the three N. crassa MAP kinase pathways, 3) Transcriptional factor genes, 4) Autophagy genes, and 5) Other miscellaneous genes. Complementation and RIP studies verified that these genes are needed for the formation of the female mating structure, the protoperithecium, and for the maturation of a fertilized protoperithecium into a perithecium. Perithecia grafting experiments demonstrate that the autophagy genes and the cell-to-cell fusion genes (the MAK-1 and MAK-2 pathway genes) are needed for the mobilization and movement of nutrients from an established vegetative hyphal network into the developing protoperithecium. Deletion mutants for the PACC pathway genes palA, palB, palC, palF, palH, and pacC were found to be defective in two aspects of female development. First, they were unable to initiate female development on synthetic crossing medium. However, they could form protoperithecia when grown on cellophane, on corn meal agar, or in response to the presence of nearby perithecia. Second, fertilized perithecia from PACC pathway mutants were unable to produce asci and complete female development. Protein localization experiments with a GFP-tagged PALA construct showed that PALA was localized in a peripheral punctate pattern, consistent with a signaling center associated with the ESCRT complex. The N. crassa PACC signal transduction pathway appears to be similar to the PacC/Rim101 pathway previously characterized in Aspergillus nidulans and Saccharomyces cerevisiae. In N. crassa the pathway plays a key role in regulating female development. PMID:25333968

  10. Xanthomonas campestris Overcomes Arabidopsis Stomatal Innate Immunity through a DSF Cell-to-Cell Signal-Regulated Virulence Factor1[OA

    PubMed Central

    Gudesblat, Gustavo E.; Torres, Pablo S.; Vojnov, Adrián A.

    2009-01-01

    Pathogen-induced stomatal closure is part of the plant innate immune response. Phytopathogens using stomata as a way of entry into the leaf must avoid the stomatal response of the host. In this article, we describe a factor secreted by the bacterial phytopathogen Xanthomonas campestris pv campestris (Xcc) capable of interfering with stomatal closure induced by bacteria or abscisic acid (ABA). We found that living Xcc, as well as ethyl acetate extracts from Xcc culture supernatants, are capable of reverting stomatal closure induced by bacteria, lipopolysaccharide, or ABA. Xcc ethyl acetate extracts also complemented the infectivity of Pseudomonas syringae pv tomato (Pst) mutants deficient in the production of the coronatine toxin, which is required to overcome stomatal defense. By contrast, the rpfF and rpfC mutant strains of Xcc, which are unable to respectively synthesize or perceive a diffusible molecule involved in bacterial cell-to-cell signaling, were incapable of reverting stomatal closure, indicating that suppression of stomatal response by Xcc requires an intact rpf/diffusible signal factor system. In addition, we found that guard cell-specific Arabidopsis (Arabidopsis thaliana) Mitogen-Activated Protein Kinase3 (MPK3) antisense mutants were unresponsive to bacteria or lipopolysaccharide in promotion of stomatal closure, and also more sensitive to Pst coronatine-deficient mutants, showing that MPK3 is required for stomatal immune response. Additionally, we found that, unlike in wild-type Arabidopsis, ABA-induced stomatal closure in MPK3 antisense mutants is not affected by Xcc or by extracts from Xcc culture supernatants, suggesting that the Xcc factor might target some signaling component in the same pathway as MPK3. PMID:19091877

  11. Dissecting genealogy and cell cycle as sources of cell-to-cell variability in MAPK signaling using high-throughput lineage tracking

    PubMed Central

    Ricicova, Marketa; Hamidi, Mani; Quiring, Adam; Niemistö, Antti; Emberly, Eldon; Hansen, Carl L.

    2013-01-01

    Cells, even those having identical genotype, exhibit variability in their response to external stimuli. This variability arises from differences in the abundance, localization, and state of cellular components. Such nongenetic differences are likely heritable between successive generations and can also be influenced by processes such as cell cycle, age, or interplay between different pathways. To address the contribution of nongenetic heritability and cell cycle in cell-to-cell variability we developed a high-throughput and fully automated microfluidic platform that allows for concurrent measurement of gene expression, cell-cycle periods, age, and lineage information under a large number of temporally changing medium conditions and using multiple strains. We apply this technology to examine the role of nongenetic inheritance in cell heterogeneity of yeast pheromone signaling. Our data demonstrate that the capacity to respond to pheromone is passed across generations and that the strength of the response correlations between related cells is affected by perturbations in the signaling pathway. We observe that a ste50Δ mutant strain exhibits highly heterogeneous response to pheromone originating from a unique asymmetry between mother and daughter response. On the other hand, fus3Δ cells were found to exhibit an unusually high correlation between mother and daughter cells that arose from a combination of extended cell-cycle periods of fus3Δ mothers, and decreased cell-cycle modulation of the pheromone pathway. Our results contribute to the understanding of the origins of cell heterogeneity and demonstrate the importance of automated platforms that generate single-cell data on several parameters. PMID:23803859

  12. An interactive, multitask computer system for heavy-ion physics research with the spin spectrometer: (Progress report, 1982)

    SciTech Connect

    Sarantites, D.G.

    1982-01-01

    The scope of this proposal is to assemble an interactive off-line data analysis system based on a DEC VAX 11/780 computer interfaced with an array processor, which is capable of meeting the needs of modern heavy-ion physics experiments involving data of large dimensionality as created in the Spin Spectrometer at the Holifield Heavy-ion Research Facility, to adapt the existing PDP 11 software for the Spin Spectrometer for this computer system in a form completely compatible with other laboratories with VAX 11 computers, and to develop new general and efficient software for automatic but fully interactive data analysis making use of an attach array processor.

  13. Investigations of the structure and electromagnetic interactions of few-body systems. Progress report, 1 July 1991--30 June 1994

    SciTech Connect

    Lehman, D.R.; Haberzettl, H.; Maximon, L.C.; Parke, W.C.; Bennhold, C.; Ito, Hiroshi; Pratt, R.K.; Najmeddine, M.; Rakei, A.

    1994-07-01

    In order to make it easy for the reader to see the specific research carried out and the progress made, the following report of progress is done by topic. Each item has a format layout of Topic, Investigators, Objective, Significance, and Description of Progress, followed at the end by the relevant references. As is clear from the topics listed, the emphasis of the GW nuclear theory group has been on the structure and electromagnetic interactions of few-body nuclei. Both low- and intermediate-energy electromagnetic disintegration of these nuclei is considered, including coherent photoproduction of {pi} mesons. When the excitation energy of the target nucleus is low, the aim has been to handle the continuum part of the theoretical work numerically with no approximations, that is, by means of full three- or four-body dynamics. When structure questions are the issue, numerically accurate calculations are always carried through, limited only by the underlying two-body or three-body interactions used as input. Implicit in our work is the question of how far one can go within the traditional nuclear physics framework i.e., nucleons and mesons in a nonrelativistic setting. Our central goal is to carry through state-of-the-art few-body calculations that will serve as a means of determining at what point standard nuclear physics requires introduction of relativity and/or quark degrees of freedom in order to understand the phenomena in question. So far, the problems considered were mostly concerned with low- to medium-energy regimes where little evidence was found that requires going beyond the traditional approach.

  14. Investigations of the structure and electromagnetic interactions of few-body systems. Progress report, 1 August 1991--31 July 1992

    SciTech Connect

    Lehman, D.R.; Haberzettl, H.; Maximon, L.C.; Parke, W.C.

    1992-07-01

    In order to make it easy for the reader to see the specific research carried out and the progress made, the following report of progress is done by topic. Each item has a format layout of Topic, Investigators, Objective, Significance, and Description of Progress, followed at the end by the relevant references. As is clear from the topics listed, the emphasis of the George Washington University (GWU) theory group has been on the structure and electromagnetic interactions of few-body nuclei. Both low- and intermediate-energy electromagnetic disintegration of these nuclei is considered. When the excitation energy of the target nucleus is low, the aim has been to handle the continuum part of the theoretical work numerically with no approximations, that is, by means of full three- or four-body dynamics. When structure questions axe the issue, numerically accurate calculations axe always carried through, limited only by the underlying two-body or three-body interactions used as input. Implicit in our work is the question of how far one can go within the traditional nuclear physics framework, i.e., nucleons and mesons in a nonrelativistic setting. Our central goal is to carry through state-of-the-art fewbody calculations that wig serve as a means of determining at what point standard nuclear physics requires quark degrees of freedom in order to understand the phenomena in question. So far, in the problems considered, there has been no evidence of the necessity to go beyond the traditional approach, though we always keep in mind that possibility. As our work is involved with questions in the intermediate-energy realm, moving from a nonrelativistic framework to a relativistic one is always a consideration. Currently, for the problems that have been pursued in this domain of energy, the issues concern far more the mechanisms of the reactions and structural questions than the need to move to relativistic dynamics.

  15. Investigation of syngas interaction in alcohol synthesis catalysts. Quartery technical progress report, July 1, 1995--September 31, 1995

    SciTech Connect

    Akundi, M.A.

    1996-02-01

    This report presents the work done on {open_quotes}Investigation of Syngas Interaction in Alcohol Synthesis Catalysts{close_quotes} during the last three months. In this report the results of the work done on the effect of CO adsorption on the magnetic character of cobalt in the Cu/Co/Cr catalysts is discussed.

  16. Chemical interactions between protein molecules and polymer membrane materials. Annual progress report, August 1, 1992--July 30, 1993

    SciTech Connect

    Belfort, G.; Koehler, J.; Wood, J.

    1993-07-15

    The Surface Force Apparatus is now operable; data collection is automatic. Hen egg lysozyme was chosen as model protein. Protein-protein, protein-mica, protein-polymer, and protein-surfactant interactions were studied. Circular dichroism was used to study changes in protein structure during adsorption.

  17. Social Interaction Analysis of an Elementary School Student and a Videodisc System in an Educational Environment: A Progress Report.

    ERIC Educational Resources Information Center

    Silverstein, Mark A.

    This investigation of the relationship between elementary school students and a videodisc system in an educational environment used a social interaction analysis paradigm to identify meaningful patterns of social behavior and to examine whether: (1) such patterns indicate acceptance of or resistance to the technology; (2) students exhibit more…

  18. Investigation of syngas interaction in alcohol synthesis catalysts. Quarterly technical progress report, April 1, 1996--June 30, 1996

    SciTech Connect

    Akundi, M.A.

    1997-12-31

    This report presents the work done on {open_quotes}Investigation of Syngas Interaction in Alcohol Synthesis Catalysts{close_quotes} during the last three months. In this report the results of the work on the metal precursors of copper, cobalt and chromium using Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) are presented.

  19. Patient-Specific Carotid Plaque Progression Simulation Using 3D Meshless Generalized Finite Difference Models with Fluid-Structure Interactions Based on Serial In Vivo MRI Data.

    PubMed

    Yang, Chun; Tang, Dalin; Atluri, Satya

    2011-01-01

    Previously, we introduced a computational procedure based on three-dimensional meshless generalized finite difference (MGFD) method and serial magnetic resonance imaging (MRI) data to quantify patient-specific carotid atherosclerotic plaque growth functions and simulate plaque progression. Structure-only models were used in our previous report. In this paper, fluid-stricture interaction (FSI) was added to improve on prediction accuracy. One participating patient was scanned three times (T1, T2, and T3, at intervals of about 18 months) to obtain plaque progression data. Blood flow was assumed to laminar, Newtonian, viscous and incompressible. The Navier-Stokes equations with arbitrary Lagrangian-Eulerian (ALE) formulation were used as the governing equations. Plaque material was assumed to be uniform, homogeneous, isotropic, linear, and nearly incompressible. The linear elastic model was used. The 3D FSI plaque model was discretized and solved using a meshless generalized finite difference (GFD) method. Growth functions with a) morphology alone; b) morphology and plaque wall stress (PWS); morphology and flow shear stress (FSS), and d) morphology, PWS and FSS were introduced to predict future plaque growth based on previous time point data. Starting from the T2 plaque geometry, plaque progression was simulated by solving the FSI model and adjusting plaque geometry using plaque growth functions iteratively until T3 is reached. Numerically simulated plaque progression agreed very well with the target T3 plaque geometry with errors ranging from 8.62%, 7.22%, 5.77% and 4.39%, with the growth function including morphology, plaque wall stress and flow shear stress terms giving the best predictions. Adding flow shear stress term to the growth function improved the prediction error from 7.22% to 4.39%, a 40% improvement. We believe this is the first time 3D plaque progression FSI simulation based on multi-year patient-tracking data was reported. Serial MRI-based progression

  20. Base sequence effects on interactions of aromatic mutagens with DNA: Progress report for period March 1, 1988--November 30, 1988

    SciTech Connect

    Geacintov, N.E.

    1988-12-01

    The influence of base sequence on the structure of DNA, and the relationships between these effects and gene expression and regulation, are currently receiving wide attention. This project is focused on the effects of base composition and sequence, as well as on the thermodynamics of the interactions and binding of polynuclear aromatic hydrocarbon (PAH) mutagens with DNA. Such interactions between PHA molecules and cellular DNA are believed to be of critical importance in the expression of the mutagenic and tumorigenic potentials of these compounds. We have studied the interactions, especially noncovalent complex formation between the tetraols derived by the hydrolysis of the bay region diol epoxides of benzo(a)pyrene (BP), benz(a)anthracene (BA), 7,12-dimethylbenz(a)anthracene (DMBA), and 3-methylcholanthrene (3-MC) with single nucleotides, dinucleotides, oligonucleotides, synthetic polynucleotides, and native DNA. The formation of physical complexes depends on the base composition and the base sequence. The differences in the physical binding of these three different tetraol derivatives to native DNA are due to entropic rather than to enthalpic effects. In contrast to the BP and BA tetraols, the 3-MC tetraols do not form intercalation complexes with DNA; this effect is attributed to the steric bulk of the methyl and methylene bridge group which prevents the sandwiching of the 3-MC tetraol between the DNA base pairs. 6 refs., 3 figs., 2 tabs.

  1. Scoping assessments of ATF impact on late-stage accident progression including molten core-concrete interaction

    NASA Astrophysics Data System (ADS)

    Farmer, M. T.; Leibowitz, L.; Terrani, K. A.; Robb, K. R.

    2014-05-01

    Simple scoping models that can be used to evaluate ATF performance under severe accident conditions have been developed. The methodology provides a fundamental technical basis (a.k.a. metric) based on the thermodynamic boundary for evaluating performance relative to that of traditional Zr-based claddings. The initial focus in this study was on UO2 fuel with the advanced claddings 310 SS, D9, FeCrAl, and SiC. The evaluation considered only energy release with concurrent combustible gas production from fuel-cladding-coolant interactions and, separately, molten core-concrete interactions at high temperatures. Other important phenomenological effects that can influence the rate and extent of cladding decomposition (e.g., eutectic interactions, degradation of other core constituents) were not addressed. For the cladding types addressed, potential combustible gas production under both in-vessel and ex-vessel conditions was similar to that for Zr. However, exothermic energy release from cladding oxidation was substantially less for iron-based alloys (by at least a factor of 4), and modestly less (by ∼20%) for SiC. Data on SiC-clad UO2 fuel performance under severe accident conditions are sparse in the literature; thus, assumptions on the nature of the cladding decomposition process were made in order to perform this initial screening evaluation. Experimental data for this system under severe accident conditions is needed for a proper evaluation and comparison to iron-based claddings.

  2. Are the SSB-Interacting Proteins RecO, RecG, PriA and the DnaB-Interacting Protein Rep Bound to Progressing Replication Forks in Escherichia coli?

    PubMed

    Bentchikou, Esma; Chagneau, Carine; Long, Emilie; Matelot, Mélody; Allemand, Jean-François; Michel, Bénédicte

    2015-01-01

    In all organisms several enzymes that are needed upon replication impediment are targeted to replication forks by interaction with a replication protein. In most cases these proteins interact with the polymerase clamp or with single-stranded DNA binding proteins (SSB). In Escherichia coli an accessory replicative helicase was also shown to interact with the DnaB replicative helicase. Here we have used cytological observation of Venus fluorescent fusion proteins expressed from their endogenous loci in live E. coli cells to determine whether DNA repair and replication restart proteins that interact with a replication protein travel with replication forks. A custom-made microscope that detects active replisome molecules provided that they are present in at least three copies was used. Neither the recombination proteins RecO and RecG, nor the replication accessory helicase Rep are detected specifically in replicating cells in our assay, indicating that either they are not present at progressing replication forks or they are present in less than three copies. The Venus-PriA fusion protein formed foci even in the absence of replication forks, which prevented us from reaching a conclusion.

  3. Are the SSB-Interacting Proteins RecO, RecG, PriA and the DnaB-Interacting Protein Rep Bound to Progressing Replication Forks in Escherichia coli?

    PubMed Central

    Matelot, Mélody; Allemand, Jean-François; Michel, Bénédicte

    2015-01-01

    In all organisms several enzymes that are needed upon replication impediment are targeted to replication forks by interaction with a replication protein. In most cases these proteins interact with the polymerase clamp or with single-stranded DNA binding proteins (SSB). In Escherichia coli an accessory replicative helicase was also shown to interact with the DnaB replicative helicase. Here we have used cytological observation of Venus fluorescent fusion proteins expressed from their endogenous loci in live E. coli cells to determine whether DNA repair and replication restart proteins that interact with a replication protein travel with replication forks. A custom-made microscope that detects active replisome molecules provided that they are present in at least three copies was used. Neither the recombination proteins RecO and RecG, nor the replication accessory helicase Rep are detected specifically in replicating cells in our assay, indicating that either they are not present at progressing replication forks or they are present in less than three copies. The Venus-PriA fusion protein formed foci even in the absence of replication forks, which prevented us from reaching a conclusion. PMID:26244508

  4. Investigations of the structure and electromagnetic interactions of few-body systems. Progress report, September 1, 1983-August 31, 1984

    SciTech Connect

    Harper, E.P.; Lehman, D.R.; Prats, F.

    1984-09-26

    The George Washington University nuclear theory group proposes to conduct investigations of the structure and electromagnetic interactions of few-body systems. The structural properties of the very light nuclei are examined by developing theoretical models that begin from the basic interactions between the constituents and that are solved exactly (numerically), i.e., full three or four-body dynamics. Such models are then used in an attempt to understand the details of the strong and electromagnetic interactions of the few-nucleon nuclei after the basic underlying reaction mechanisms are understood with simpler models. Examples of specific work proposed are the following: (1) From exact four-body dynamics, derive the equations that will permit calculation of the /sup 4/He..-->../sup 3/He+n and /sup 4/He..-->..d+d asymptotic normalization constants; (2) Develop a unified picture of the p + d ..-->.. /sup 3/He = ..gamma.., p + d ..-->.. /sup 3/He = ..pi../sup 0/ , p + d ..-->.. /sup 3/H + ..pi../sup +/ reactions at intermediate energies; (3) Calculate the elastic and inelastic (1/sup +/..-->..0/sup +/) form factors for /sup 6/Li with three-body (..cap alpha..NN) wave functions; (4) Calculate static properties (RMS radius, magnetic moment, and quadrupole moment) of /sup 6/Li with three-body wave functions; and (5) Develop the theory for the coincidence reactions /sup 6/Li(p,2p)n..cap alpha.., /sup 6/Li(e,e'p)n..cap alpha.., and /sup 6/Li(e,e'd)..cap alpha... It is anticipated that these efforts will expand the frontiers of our knowledge about few-body nuclei.

  5. [Experiment studies of electron-positron interactions at the Stanford Linear Accelerator Center]. Progress report, calendar year 1993

    SciTech Connect

    Hertzbach, S.S.; Kofler, R.R.

    1993-12-31

    The High Energy Physics group at the University of Massachusetts has continued its` program of experimental studies of electron-positron interactions at the Stanford Linear Accelerator Center (SLAC). The group activities have included: analysis of data taken between 1982 and 1990 with the TPC detector at the PEP facility, continuing data collection and data analysis using the SLC/SLD facility, planning for the newly approved B-factory at SLAC, and participation in design studies for future high energy linear colliders. This report will briefly summarize these activities.

  6. Selectivity, activity, and metal-support interactions of Rh bimetallic catalysts. Progress report, 15 November 1981-15 August 1982

    SciTech Connect

    Haller, G L

    1982-08-01

    We report on a detailed investigation of the effect of TiO/sub 2/ support on Rh-Ag interaction as exhibited in catalytic activity. The temporal evolution of activity over Rh-Ag/TiO/sub 2/ for ethane hydrogenolysis and hydrogen chemisorption as a function of temperature, Ag to Rh ratio, the Rh particle size, Rh loading, and ambient gas were studied. Preliminary extended x-ray absorption fine structure (EXAFS) analysis of Rh/TiO/sub 2/ catalysts indicate that 100% exposed (dispersed) catalyst prepared by ion exchange may be atomically dispersed after low temperature reduction. 7 figures, 1 table.

  7. EGFRvIII/integrin β3 interaction in hypoxic and vitronectinenriching microenvironment promote GBM progression and metastasis

    PubMed Central

    Li, Yongsheng; Zhao, Manli; Xie, Hui; Ju, Huanyu; Wang, He; Zhao, Yu; Zheng, Qifan; Wang, Qixue; Su, Jun; Fang, Chuan; Fu, Songbin; Jiang, Tao; Liu, Jiaren; Li, Xia; Kang, Chunsheng; Ren, Huan

    2016-01-01

    Glioblastoma (GBM) is one of the most lethal brain tumors with a short survival time. EGFR amplification and mutation is the most significant genetic signature in GBM. About half of the GBMs with EGFR amplification express a constitutively autophosphorylated variant of EGFR, known as EGFRvIII. Our in vitro data demonstrated further enhanced EGFRvIII activity and tumor cell invasion in the tumor microenvironment of hypoxia plus extracellular matrix (ECM) vitronectin, in which EGFRvIII and integrin β3 tended to form complexes. The treatment with ITGB3 siRNA or the integrin antagonist cilengetide preferentially interrupted the EGFRvIII/integrin β3 complex, effectively reduced tumor cell invasion and activation of downstream signaling effectors. Cilengitide is recently failed in Phase III CENTRIC trial in unselected patients with GBM. However, we found that cilengitide demonstrated efficacious tumor regression via inhibition of tumor growth and angiogenesis in EGFRvIII orthotopic xenografts. Bioinformatics analysis emphasized key roles of integrin β3, hypoxia and vitronectin and their strong correlations with EGFRvIII expression in malignant glioma patient samples in vivo. In conclusion, we demonstrate that EGFRvIII/integrin β3 complexes promote GBM progression and metastasis in the environment of hypoxia and vitronectin-enrichment, and cilengitide may serve as a promising therapeutics for EGFRvIII-positive GBMs. PMID:26717039

  8. The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression

    PubMed Central

    He, Chunbo; Mao, Dagan; Hua, Guohua; Lv, Xiangmin; Chen, Xingcheng; Angeletti, Peter C; Dong, Jixin; Remmenga, Steven W; Rodabaugh, Kerry J; Zhou, Jin; Lambert, Paul F; Yang, Peixin; Davis, John S; Wang, Cheng

    2015-01-01

    The Hippo signaling pathway controls organ size and tumorigenesis through a kinase cascade that inactivates Yes-associated protein (YAP). Here, we show that YAP plays a central role in controlling the progression of cervical cancer. Our results suggest that YAP expression is associated with a poor prognosis for cervical cancer. TGF-α and amphiregulin (AREG), via EGFR, inhibit the Hippo signaling pathway and activate YAP to induce cervical cancer cell proliferation and migration. Activated YAP allows for up-regulation of TGF-α, AREG, and EGFR, forming a positive signaling loop to drive cervical cancer cell proliferation. HPV E6 protein, a major etiological molecule of cervical cancer, maintains high YAP protein levels in cervical cancer cells by preventing proteasome-dependent YAP degradation to drive cervical cancer cell proliferation. Results from human cervical cancer genomic databases and an accepted transgenic mouse model strongly support the clinical relevance of the discovered feed-forward signaling loop. Our study indicates that combined targeting of the Hippo and the ERBB signaling pathways represents a novel therapeutic strategy for prevention and treatment of cervical cancer. PMID:26417066

  9. Study of the interactions between friction, wear and system rigidity. Progress report, July 1, 1979-June 30, 1980

    SciTech Connect

    Aronov, V.; D'Souza, A.F.; Kalpakjian, S.; Shareef, I.

    1980-03-01

    Progress in friction and wear studies is reported. After an extensive study of various possible systems for friction, wear and vibration measurements, a pin and disk sliding system has been designed to be used on a rigid lathe bed. This versatile design has the capability of controlling the applied load, rigidity and damping of the total frictional system. The design and construction of the pin holding assembly has been completed with certain features to render it suitable for acquisition of appropriate data such as forces and displacements. Special instrumentation has been obtained the major components of which are a tri-axial quartz piezoelectric force transducer, a tri-axial ceramic piezoelectric accelerometer for measurements of vibrations of the slider, charge preamplifiers with dc power supply, and monitoring equipment such as a spectral analyzer and an oscillograph. Preliminary experiments indicate that the system, as designed and constructed, is appropriate for the type of study undertaken in this project. Some preliminary experimental results are included here. The method of describing functions and harmonic balance is being employed for the study of friction induced self-excited vibrations. Some new developments of this method have been obtained to take into account the coupling between the degrees of freedom in the normal and frictional directions.

  10. Glial-neuronal interactions in Alzheimer's disease: the potential role of a 'cytokine cycle' in disease progression.

    PubMed

    Griffin, W S; Sheng, J G; Royston, M C; Gentleman, S M; McKenzie, J E; Graham, D I; Roberts, G W; Mrak, R E

    1998-01-01

    The role of glial inflammatory processes in Alzheimer's disease has been highlighted by recent epidemiological work establishing head trauma as an important risk factor, and the use of anti-inflammatory agents as an important ameliorating factor, in this disease. This review advances the hypothesis that chronic activation of glial inflammatory processes, arising from genetic or environmental insults to neurons and accompanied by chronic elaboration of neuroactive glia-derived cytokines and other proteins, sets in motion a cytokine cycle of cellular and molecular events with neurodegenerative consequences. In this cycle, interleukin-1 is a key initiating and coordinating agent. Interleukin-1 promotes neuronal synthesis and processing of the beta-amyloid precursor protein, thus favoring continuing deposition of beta-amyloid, and activates astrocytes and promotes astrocytic synthesis and release of a number of inflammatory and neuroactive molecules. One of these, S100beta, is a neurite growth-promoting cytokine that stresses neurons through its trophic actions and fosters neuronal cell dysfunction and death by raising intraneuronal free calcium concentrations. Neuronal injury arising from these cytokine-induced neuronal insults can activate microglia with further overexpression of interleukin-1, thus producing feedback amplification and self-propagation of this cytokine cycle. Additional feedback amplification is provided through other elements of the cycle. Chronic propagation of this cytokine cycle represents a possible mechanism for progression of neurodegenerative changes culminating in Alzheimer's disease.

  11. Membrane-membrane interactions in a lipid-containing bacteriophage system. Progress report, October 1, 1980-September 30, 1981

    SciTech Connect

    Snipes, W

    1981-05-01

    Virus-cell interactions and the mechanism of viral entry have been the major focal points of this research. A method of analysis was perfected to investigate the entry process for herpes simplex virus. This technique makes use of a photosensitizing dye, FITC, that covalently binds to viral envelope proteins. Treated virions remain photosensitive until the envelope is shed during the process of infection. Our data strongly support an entry mechanism in which the viral envelope fuses with the cell plasma membrane. Other related projects have involved studies of the virucidal properties of retinoids, plaque development characteristics for viruses surviving treatment with membrane perturbers, and a large plaque effect that occurs when virus are plated on cells pretreated with uv light. In addition, we have characterized a new bacteriophage, investigated the interactions of divalent cations and proteins with phospholipid vesicles, extended our studies of the effects of hydrophobic photosensitizers on cell membranes, and used the spin-trapping technique to elucidate the reaction mechanism for an enzyme-like activity in soil extracts.

  12. Proteometabolomic Study of Compatible Interaction in Tomato Fruit Challenged with Sclerotinia rolfsii Illustrates Novel Protein Network during Disease Progression.

    PubMed

    Ghosh, Sudip; Narula, Kanika; Sinha, Arunima; Ghosh, Rajgourab; Jawa, Priyanka; Chakraborty, Niranjan; Chakraborty, Subhra

    2016-01-01

    Fruit is an assimilator of metabolites, nutrients, and signaling molecules, thus considered as potential target for pathogen attack. In response to patho-stress, such as fungal invasion, plants reorganize their proteome, and reconfigure their physiology in the infected organ. This remodeling is coordinated by a poorly understood signal transduction network, hormonal cascades, and metabolite reallocation. The aim of the study was to explore organ-based proteomic alterations in the susceptibility of heterotrophic fruit to necrotrophic fungal attack. We conducted time-series protein profiling of Sclerotinia rolfsii invaded tomato (Solanum lycopersicum) fruit. The differential display of proteome revealed 216 patho-stress responsive proteins (PSRPs) that change their abundance by more than 2.5-fold. Mass spectrometric analyses led to the identification of 56 PSRPs presumably involved in disease progression; regulating diverse functions viz. metabolism, signaling, redox homeostasis, transport, stress-response, protein folding, modification and degradation, development. Metabolome study indicated differential regulation of organic acid, amino acids, and carbohydrates paralleling with the proteomics analysis. Further, we interrogated the proteome data using network analysis that identified two significant functional protein hubs centered around malate dehydrogenase, T-complex protein 1 subunit gamma, and ATP synthase beta. This study reports, for the first-time, kinetically controlled patho-stress responsive protein network during post-harvest storage in a sink tissue, particularly fruit and constitute the basis toward understanding the onset and context of disease signaling and metabolic pathway alterations. The network representation may facilitate the prioritization of candidate proteins for quality improvement in storage organ. PMID:27507973

  13. Proteometabolomic Study of Compatible Interaction in Tomato Fruit Challenged with Sclerotinia rolfsii Illustrates Novel Protein Network during Disease Progression

    PubMed Central

    Ghosh, Sudip; Narula, Kanika; Sinha, Arunima; Ghosh, Rajgourab; Jawa, Priyanka; Chakraborty, Niranjan; Chakraborty, Subhra

    2016-01-01

    Fruit is an assimilator of metabolites, nutrients, and signaling molecules, thus considered as potential target for pathogen attack. In response to patho-stress, such as fungal invasion, plants reorganize their proteome, and reconfigure their physiology in the infected organ. This remodeling is coordinated by a poorly understood signal transduction network, hormonal cascades, and metabolite reallocation. The aim of the study was to explore organ-based proteomic alterations in the susceptibility of heterotrophic fruit to necrotrophic fungal attack. We conducted time-series protein profiling of Sclerotinia rolfsii invaded tomato (Solanum lycopersicum) fruit. The differential display of proteome revealed 216 patho-stress responsive proteins (PSRPs) that change their abundance by more than 2.5-fold. Mass spectrometric analyses led to the identification of 56 PSRPs presumably involved in disease progression; regulating diverse functions viz. metabolism, signaling, redox homeostasis, transport, stress-response, protein folding, modification and degradation, development. Metabolome study indicated differential regulation of organic acid, amino acids, and carbohydrates paralleling with the proteomics analysis. Further, we interrogated the proteome data using network analysis that identified two significant functional protein hubs centered around malate dehydrogenase, T-complex protein 1 subunit gamma, and ATP synthase beta. This study reports, for the first-time, kinetically controlled patho-stress responsive protein network during post-harvest storage in a sink tissue, particularly fruit and constitute the basis toward understanding the onset and context of disease signaling and metabolic pathway alterations. The network representation may facilitate the prioritization of candidate proteins for quality improvement in storage organ. PMID:27507973

  14. Interaction between EphrinB1 and CNK1 Found to Play Role in Tumor Progression | Poster

    Cancer.gov

    By Nancy Parrish, Staff Writer The family of proteins known as ephrins plays a critical role in a variety of biological processes. In a recent article in the Journal of Biological Chemistry, Hee Jun Cho, Ph.D., and colleagues report on the interaction between proteins CNK1 and ephrinB1 that promotes cell movement. Their findings may have an important implication in developing new therapeutics for reducing metastases in certain cancers. “Eph and ephrin signaling has become an area of intense interest due to the influence these molecules exert on the control of cell adhesion and cell movement,” Cho said. “This signaling affects the formation of tissues during development and has been shown to play an instructive role in angiogenesis, as well as tumor cell invasion.”

  15. High sensitivity tests of the standard model for electroweak interactions. Scientific Progress report, 16 January 1992--15 January 1993

    SciTech Connect

    Koetke, D.D.; Manweiler, R.W.; Shirvel Stanislaus, T.D.

    1993-01-01

    The work done on this project was focused on two LAMPF experiments. The MEGA experiment, a high-sensitivity search for the lepton-family-number-violating decay {mu} {yields} e {gamma} to a sensitivity which, measured in terms of the branching ratio, BR = [{mu} {yields} e {gamma}]/[{mu} {yields} ev{sub {mu}} v{sub e}] {approximately} 10{sup {minus}13}, is over two orders of magnitude better than previously reported values. The second is a precision measurement of the Michel {rho} parameter from the positron energy spectrum of {mu} {yields} ev{sub {mu}} v{sub e} to test the V-A theory of weak interactions. The uncertainty in the measurement of the Michel {rho} parameter is expected to be a factor of three lower than the present reported value.

  16. Trace elements status in diabetes mellitus type 2: possible role of the interaction between molybdenum and copper in the progress of typical complications.

    PubMed

    Flores, Crescencio Rodríguez; Puga, Mónica Preciado; Wrobel, Katarzyna; Garay Sevilla, Ma Eugenia; Wrobel, Kazimierz

    2011-03-01

    It is well established that both, the deficiency and possible overload of mineral micronutrients have adverse health effects. It is also generally accepted that non-essential xenobiotics contribute to oxidative damage, which is considered one of the principal factors in diabetes and its complications. The purpose of this work was to gain an insight on the global role of metal/metalloids in the progress of diabetes mellitus type 2. In such approach, aluminum, vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, selenium, molybdenum, mercury, cadmium and lead were determined by inductively coupled plasma-mass spectrometry (ICP-MS) in serum and urine of 76 diabetic patients (age 52 ± 8 years, 5-16 years of DM2, 52 subjects with slight-to-moderate complications and 24 with severe complications). A series of anthropometric and clinical parameters usually evaluated in the follow-up of patients were assessed by standard methods. Statistical analysis (unpaired t-test, analysis of correlation and principal component analysis) was then carried out in search of possible relationships existing among metals/metalloids and these parameters. The results obtained suggest that antagonistic interaction between molybdenum and copper might be involved in the progress of diabetes complications.

  17. Pegmatite/wallrock interactions, Black Hills, South Dakota: Progressive boron metasomatism adjacent to the Tip Top pegmatite

    USGS Publications Warehouse

    Shearer, C.K.; Papike, J.J.; Simon, S.B.; Laul, J.C.; Christian, R.P.

    1984-01-01

    Interaction between country rock and fluids derived from the Tip Top pegmatite has resulted in a series of boron enriched assemblages. Between unaltered quartz-mica schist to the pegmatite contact is a succession of four mineral assemblages: 1. (1) Quartz-Biotite-Potassium Feldspar assemblage (Q-B-K), which consists essentially of the original metamorphic silicate assemblage plus anomalously high amounts of modal tourmaline 2. (2) Quartz-Biotite-Tourmaline assemblage (Q-B-T) 3. (3) Tourmaline-Quartz-Muscovite assemblage (T-Q-M) 4. (4) Tourmaline-Quartz assemblage (T-Q). Alkali elements (Cs, Rb, K, Li), SiO2, and Ba show a decrease from the Q-B-K assemblage to the T-Q assemblage. A12O3, Ga, B, total Fe and Zn increase moderately from the Q-B-K assemblage to the T-Q assemblage. The mineral chemistries also change considerably. The Mg/(Mg + Fe2+) ratios in biotites range from 0.54 to 0.50 in samples from the Q-B-K assemblage to 0.39 in the (Q-B-T) assemblage. The range in tourmaline end-member components from the Q-B-K assemblage to the T-Q assemblage is as follows: Q-B-K: Dravite.63 Schorl.23 Elbaite.05 Buergerite.09 T-Q: Dravite.23 Schorl.37 Elbaite.17 Buergerite.23. Observed variations in mineral assemblage and whole rock chemistry within the alteration zone appear to a first approximation to be a function of ??B2O3 (boron metasomatism) and ??K2O (alkali leaching). The breakdown of feldspar and biotite may be approximated by reactions: 2HCl + 2(K, Na)AlSi3O8 /ai 2(K, Na)Cl + Al2SiO5 + 5SiO2 + H2O and 2 Annite + SiO2 + 5Al2SiO5 + 2NaCl + 6H3BO3 /ai 2 Tourmaline + 2KCl + 7H2O. The alteration zone may represent either a single episode (B-, Cs-, Li-, Rb-enriched fluid) or multiple episodes (B, Zn, Mn fluid and Cs, Li, Rb fluid) of pegmatite fluid-schist interactions. In both situations, B in the aqueous fluid from the pegmatite reacts with the schist breaking down sheet silicate "traps" for Cs, Rb, Li, and K and forming tourmaline-rich assemblages. ?? 1984.

  18. Selective Hyaluronan-CD44 Signaling Promotes miRNA-21 Expression and Interacts with Vitamin D Function during Cutaneous Squamous Cell Carcinomas Progression Following UV Irradiation.

    PubMed

    Bourguignon, Lilly Y W; Bikle, Daniel

    2015-01-01

    Hyaluronan (HA), the major extracellular matrix component, is often anchored to CD44, a family of structurally/functionally important cell surface receptors. Recent results indicate that UV irradiation (UVR)-induced cutaneous squamous cell carcinomas (SCC) overexpress a variety of CD44 variant isoforms (CD44v), with different CD44v isoforms appear to confer malignant SCC properties. UVR also stimulates HA degradation in epidermal keratinocytes. Both large HA polymers and their UVR-induced catabolic products (small HA) selectively activate CD44-mediated cellular signaling in normal keratinocytes and SCC cells, with all of the downstream processes being mediated by RhoGTPases (e.g., Rac1 and Rho). Importantly, we found that the hormonally active form of vitamin D 1,25(OH)2D3 not only prevents the UVR-induced small HA activation of abnormal keratinocyte behavior and SCC progression, but also enhances large HA stimulation of normal keratinocyte activities and epidermal function(s). The aim of this hypothesis and theory article is to question whether matrix HA and its UVR-induced catabolic products (e.g., large and small HA) can selectively activate CD44-mediated cellular signaling such as GTPase (Rac and RhA) activation. We suggested that large HA-CD44 interaction promotes Rac-signaling and normal keratinocyte differentiation (lipid synthesis), DNA repair, and keratinocyte survival function. Conversely, small HA-CD44 interaction stimulates RhoA activation, NFκB/Stat-3 signaling, and miR-21 production, resulting in inflammation and proliferation as well as SCC progression. We also question whether vitamin D treatment displays any effect on small HA-CD44v-mediated RhoA signaling, inflammation, and SCC progression, as well as large HA-CD44-mediated differentiation, DNA repair, keratinocyte survival, and normal keratinocyte function. In addition, we discussed that the topical application of signaling perturbation agents (e.g., Y27623, a ROK inhibitor) may be used to treat

  19. Interaction between V-ATPase B2 and (Pro) renin Receptors in Promoting the progression of Renal Tubulointerstitial Fibrosis.

    PubMed

    Liu, Yun; Zuo, Sujun; Li, Xiaoyan; Fan, Jinjin; Cao, Xueqin; Yu, Xueqing; Yang, Qiongqiong

    2016-04-28

    To investigate the levels of (Pro) renin receptor [(P) RR], α-smooth muscle actin (α-SMA), fibronectin (FN), and vacuolar H(+)-ATPase (V-ATPase) subunits (B2, E, and c) in rat unilateral ureteral obstruction (UUO) models and rat proximal tubular epithelial cells (NRK-52E) treated with prorenin to elucidate the role of V-ATPase in these processes by activating the (P) RR. UUO significantly upregulated (P) RR, V-ATPase subunits, α-SMA and FN expression in tubulointerstitium or tubular epithelial cells. A marked colocalization of (P) RR and the B2 subunit was also observed. Prorenin treatment upregulated α-SMA, FN, (P) RR, and V-ATPase subunits and activity in NRK52E cell in a dose- and time-dependent manner. The V-ATPase inhibitor bafilomycin A1 partially blocked prorenin-induced (P) RR, FN, and α-SMA expression. Co-immunoprecipitate and immunofluorescence results demonstrated that the V-ATPase B2 subunit bound to the (P) RR, which was upregulated after prorenin stimulation. Either siRNA-mediated (P) RR or B2 subunit knockdown partially reduced V-ATPase activity and attenuated prorenin-induced FN and α-SMA expression. From the data we can assume that activation of (P) RR and V-ATPase may play an important role in tubulointerstitial fibrosis with possible involvement of interaction of V-ATPase B2 subunit and (P)RR.

  20. Chemical interactions between protein molecules and polymer membrane materials. Annual progress report, February 1, 1994--October 31, 1994

    SciTech Connect

    Koehler, J.A.; Belfort, G.

    1994-08-25

    During the past year, the authors have used the Surface Forces Apparatus (SFA) to measure the intermolecular forces between a model protein (hen egg-white lysozyme) and a model hydrophilic surface (mica), between lysozyme and itself and between lysozyme and a model hydrophobic surface composed of a crosslinked alkoxysilane surfactant (hexadecyltriethoxysilane, HTE). As expected, repulsive forces are dominant between the hydrophilic surfaces with the same charge (lysozyme-lysozyme) while attractive forces are dominant between oppositely charged surfaces (lysozyme-mica) and between the lysozyme and the hydrophobic surface. The DLVO theory for charged surfaces was found to agree with the results of the lysozyme-lysozyme interaction. Efforts also have been focused on trying to create a well-formed, defect-free monolayer of the HTE on the surface of the mica using a Langmuir-Blodgett (LB) apparatus. A smooth, defect-free surface is desired for the intermolecular force studies. Atomic force microscopy has been used to determine the topography of the HTE films.

  1. Cytokine and chemokine profiles in multiple myeloma; significance of stromal interaction and correlation of IL-8 production with disease progression.

    PubMed

    Kline, Michael; Donovan, Kathleen; Wellik, Linda; Lust, Christopher; Jin, Wendy; Moon-Tasson, Laurie; Xiong, Yuning; Witzig, Thomas E; Kumar, Shaji; Rajkumar, S Vincent; Lust, John A

    2007-05-01

    Multiple myeloma (MM) is a product of interactions between tumor plasma cells and multiple cell types native to the bone marrow (BM). We have used antibody array technology to examine the proteins produced by BM stromal cells in response to stimulation by BM taken from patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and MM. We observed increased production of the chemokine IL-8 by stromal cells co-cultured with supernatants from bone marrow cells of patients with active myeloma. IL-8 production is correlated with active disease and is dependent upon IL-1beta and NF-kappaB signaling. Consistent with the pro-angiogenic activity of IL-8, increased BM microvessel density (MVD) correlated with stimulation of stromal cell IL-8 production. In addition, the majority of MM cell lines and MM patient plasma cells were found to express IL-8 receptors CXCR1 and CXCR2. We conclude that stromal cell IL-8 production parallels MM disease activity, is IL-1beta induced, and correlates with bone marrow angiogenesis. PMID:16879867

  2. Molecular-level processes governing the interaction of contaminants with iron and manganese oxides. 1997 annual progress report

    SciTech Connect

    Chambers, S.A.; Brown, G.

    1997-06-01

    'The central tenet of this proposal is that a fundamental understanding of specific mineral surface-site reactivities will substantially improve reactive transport models of contaminants in geologic systems, and will allow more effective remediation schemes to be devised. Most large-scale, macroscopic models employ global chemical reaction kinetics and thermochemistry. However, such models do not incorporate molecular-level input critical to the detailed prediction of how contaminants interact with minerals in the subsurface. A first step leading to the incorporation of molecular-level processes in large-scale macroscopic models is the ability to understand which molecular-level processes will dominate the chemistry at the microscopic grain level of minerals. To this end, the research focuses on the fundamental mechanisms of redox chemistry at mineral surfaces. As much of this chemistry in sediments involves the Fe(III)/Fe(II) and Mn(IV)/Mn(II) couples, the authors focus on mineral phases containing these species. Of particular interest is the effect of the local coordination environment of Fe and Mn atoms on their reactivity toward contaminant species. Studies of the impact of local atomic structure on reactivity in combination with knowledge about the types and amounts of various surfaces on natural grain- size minerals provide the data for statistical models. These models in turn form the basis of the larger-scale macroscopic descriptions of reactivity that are needed for reactive transport models. A molecular-level understanding of these mechanisms will enhance the ability to design much greater performance efficiency, cost effectiveness, and remediation strategies that have minimal negative impact on the local environment. For instance, a comprehensive understanding of how minerals that contain Fe(II) reduce oxyanions and chlorinated organics should enable the design of other Fe(II)-containing remediation materials in a way that is synergistic with existing

  3. Jumonji AT-rich interactive domain 1B overexpression is associated with the development and progression of glioma

    PubMed Central

    FANG, LIPING; ZHAO, JIUHAN; WANG, DAN; ZHU, LIYU; WANG, JIAN; JIANG, KUI

    2016-01-01

    Previous studies have suggested that jumonji AT-rich interactive domain 1B (JARID1B) plays an important role in the genesis of some types of cancer, and it is therefore considered to be an important drug target protein. Although the expression of JARID1B has been researched in some types of cancer, little is known about JARID1B expression in glioma and its function in the tumorigenesis of gliomas. In the present study, we examined the expression of JARID1B in glioma. In addition, RT-PCR, western blot analysis and immunohistochemical analysis were performed using glioma tissue samples and the results revealed that JARID1B expression increased according to the histological grade of glioma. However, in the normal brain tissue samples JARID1B expression was barely detected. Kaplan-Meier analysis revealed that higher JARID1B expression in patients with glioma was associated with a poorer prognosis. The overexpression of JARID1B stimulated the proliferation and migration of glioma cells as well as sphere formation, whereas suppressing the expression of JARID1B produced opposite effects. The overexpression of JARID1B increased the tumorigenicity of glioma cells in vivo in a nude mouse xenograft model of glioma. Moreover, the activation of phosphorylated (p-)Smad2 contributes to JARID1B-induced oncogenic activities. These findings suggest that JARID1B is involved in the pathogenesis of glioma, and that the downregulation of JARID1B in glioma cells may be a therapeutic target for the treatment of patients with glioma. PMID:27246838

  4. Adjusting to progress: interactions between the National Library of Medicine and health sciences librarians, 1961–2001*

    PubMed Central

    Humphreys, Betsy L.

    2002-01-01

    Most health sciences librarians would agree that the National Library of Medicine's (NLM's) leadership and its services have been highly beneficial to the field, but this does not prevent specific NLM actions—or lack of action—from being perceived as annoying or infuriating. Over the past forty years, NLM's interactions with health sciences librarians have been affected by significant additions to NLM's mission and services, the expansion of NLM's direct user groups, and the growing range of possible relationships between health sciences librarians and NLM. The greatest friction between NLM and health services librarians occurs when there is a fundamental change in the way NLM carries out its mission—a change that adds to the web of relationships that link librarians and NLM and prompts corresponding changes in the way other libraries do business. Between 1961 and 2001, there were two such fundamental changes: the implementation of the National Network of Libraries of Medicine and the development and promotion of services targeted toward individual health professionals. On a lesser scale, each new service that connects NLM and health sciences librarians is another potential source of irritation, ready to flare up when the service is interrupted, changed, or eliminated. Other factors—including strong personalities, mistakes, and poor communication—add to, but do not cause, the intermittent problems between NLM and its most longstanding and engaged user group. These problems are in essence the price we pay for the leadership and vision of NLM's directors and for NLM's success in developing excellent services and in enhancing them based on advice from librarians and other users. PMID:11838459

  5. The C terminus of the movement protein of Brome mosaic virus controls the requirement for coat protein in cell-to-cell movement and plays a role in long-distance movement.

    PubMed

    Takeda, Atsushi; Kaido, Masanori; Okuno, Tetsuro; Mise, Kazuyuki

    2004-06-01

    The 3a movement protein (MP) plays a central role in the movement of Brome mosaic virus (BMV). To identify the functional regions in BMV MP, 24 alanine-scanning (AS) MP mutants of BMV were constructed. Infectivity of the AS mutants in the host plant Chenopodium quinoa showed that the central region of BMV MP is important for viral movement and both termini of BMV MP have effects on the development of systemic symptoms. A green-fluorescent-protein-expressing RNA3-based BMV vector containing a 2A sequence from Foot-and-mouth disease virus was also constructed. Using this vector, two AS mutants that showed more efficient cell-to-cell movement than wild-type BMV were identified. The MPs of these two AS mutants, which have mutations at their C termini, mediated cell-to-cell movement independently of coat protein (CP), unlike wild-type BMV MP. Furthermore, a BMV mutant with a truncation in the C-terminal 42 amino acids of MP was also able to move from cell to cell without CP, but did not move systemically, even in the presence of CP. These results and an encapsidation analysis suggest that the C terminus of BMV MP is involved in the requirement for CP in cell-to-cell movement and plays a role in long-distance movement. Furthermore, the ability to spread locally and form virions is not sufficient for the long-distance movement of BMV. The roles of MP and CP in BMV movement are discussed.

  6. The Tax-Inducible Actin-Bundling Protein Fascin Is Crucial for Release and Cell-to-Cell Transmission of Human T-Cell Leukemia Virus Type 1 (HTLV-1)

    PubMed Central

    Wiesmann, Veit; Millen, Sebastian; Wittenberg, Thomas; Gettemans, Jan; Thoma-Kress, Andrea K.

    2016-01-01

    The delta-retrovirus Human T-cell leukemia virus type 1 (HTLV-1) preferentially infects CD4+ T-cells via cell-to-cell transmission. Viruses are transmitted by polarized budding and by transfer of viral biofilms at the virological synapse (VS). Formation of the VS requires the viral Tax protein and polarization of the host cytoskeleton, however, molecular mechanisms of HTLV-1 cell-to-cell transmission remain incompletely understood. Recently, we could show Tax-dependent upregulation of the actin-bundling protein Fascin (FSCN-1) in HTLV-1-infected T-cells. Here, we report that Fascin contributes to HTLV-1 transmission. Using single-cycle replication-dependent HTLV-1 reporter vectors, we found that repression of endogenous Fascin by short hairpin RNAs and by Fascin-specific nanobodies impaired gag p19 release and cell-to-cell transmission in 293T cells. In Jurkat T-cells, Tax-induced Fascin expression enhanced virus release and Fascin-dependently augmented cell-to-cell transmission to Raji/CD4+ B-cells. Repression of Fascin in HTLV-1-infected T-cells diminished virus release and gag p19 transfer to co-cultured T-cells. Spotting the mechanism, flow cytometry and automatic image analysis showed that Tax-induced T-cell conjugate formation occurred Fascin-independently. However, adhesion of HTLV-1-infected MT-2 cells in co-culture with Jurkat T-cells was reduced upon knockdown of Fascin, suggesting that Fascin contributes to dissemination of infected T-cells. Imaging of chronically infected MS-9 T-cells in co-culture with Jurkat T-cells revealed that Fascin’s localization at tight cell-cell contacts is accompanied by gag polarization suggesting that Fascin directly affects the distribution of gag to budding sites, and therefore, indirectly viral transmission. In detail, we found gag clusters that are interspersed with Fascin clusters, suggesting that Fascin makes room for gag in viral biofilms. Moreover, we observed short, Fascin-containing membrane extensions

  7. Development of small-bore, high-current-density railgun as testbed for study of plasma-materials interaction. Progress report for October 16,2000 - May 13, 2003

    SciTech Connect

    Kim, Kyekyoon

    2003-05-14

    The present document is a final technical report summarizing the progress made during 10/16/2000 - 05/13/2003 toward the development of a small-bore railgun with transaugmentation as a testbed for investigating plasma-materials interaction.

  8. Interactions between Adipocytes and Breast Cancer Cells Stimulate Cytokine Production and Drive Src/Sox2/miR-302b-Mediated Malignant Progression.

    PubMed

    Picon-Ruiz, Manuel; Pan, Chendong; Drews-Elger, Katherine; Jang, Kibeom; Besser, Alexandra H; Zhao, Dekuang; Morata-Tarifa, Cynthia; Kim, Minsoon; Ince, Tan A; Azzam, Diana J; Wander, Seth A; Wang, Bin; Ergonul, Burcu; Datar, Ram H; Cote, Richard J; Howard, Guy A; El-Ashry, Dorraya; Torné-Poyatos, Pablo; Marchal, Juan A; Slingerland, Joyce M

    2016-01-15

    Consequences of the obesity epidemic on cancer morbidity and mortality are not fully appreciated. Obesity is a risk factor for many cancers, but the mechanisms by which it contributes to cancer development and patient outcome have yet to be fully elucidated. Here, we examined the effects of coculturing human-derived adipocytes with established and primary breast cancer cells on tumorigenic potential. We found that the interaction between adipocytes and cancer cells increased the secretion of proinflammatory cytokines. Prolonged culture of cancer cells with adipocytes or cytokines increased the proportion of mammosphere-forming cells and of cells expressing stem-like markers in vitro. Furthermore, contact with immature adipocytes increased the abundance of cancer cells with tumor-forming and metastatic potential in vivo. Mechanistic investigations demonstrated that cancer cells cultured with immature adipocytes or cytokines activated Src, thus promoting Sox2, c-Myc, and Nanog upregulation. Moreover, Sox2-dependent induction of miR-302b further stimulated cMYC and SOX2 expression and potentiated the cytokine-induced cancer stem cell-like properties. Finally, we found that Src inhibitors decreased cytokine production after coculture, indicating that Src is not only activated by adipocyte or cytokine exposures, but is also required to sustain cytokine induction. These data support a model in which cancer cell invasion into local fat would establish feed-forward loops to activate Src, maintain proinflammatory cytokine production, and increase tumor-initiating cell abundance and metastatic progression. Collectively, our findings reveal new insights underlying increased breast cancer mortality in obese individuals and provide a novel preclinical rationale to test the efficacy of Src inhibitors for breast cancer treatment.

  9. A bioinformatics approach reveals novel interactions of the OVOL transcription factors in the regulation of epithelial – mesenchymal cell reprogramming and cancer progression

    PubMed Central

    2014-01-01

    Background Mesenchymal to Epithelial Transition (MET) plasticity is critical to cancer progression, and we recently showed that the OVOL transcription factors (TFs) are critical regulators of MET. Results of that work also posed the hypothesis that the OVOLs impact MET in a range of cancers. We now test this hypothesis by developing a model, OVOL Induced MET (OI-MET), and sub-model (OI-MET-TF), to characterize differential gene expression in MET common to prostate cancer (PC) and breast cancer (BC). Results In the OI-MET model, we identified 739 genes differentially expressed in both the PC and BC models. For this gene set, we found significant enrichment of annotation for BC, PC, cancer, and MET, as well as regulation of gene expression by AP1, STAT1, STAT3, and NFKB1. Focusing on the target genes for these four TFs plus the OVOLs, we produced the OI-MET-TF sub-model, which shows even greater enrichment for these annotations, plus significant evidence of cooperation among these five TFs. Based on known gene/drug interactions, we prioritized targets in the OI-MET-TF network for follow-on analysis, emphasizing the clinical relevance of this work. Reflecting these results back to the OI-MET model, we found that binding motifs for the TF pair AP1/MYC are more frequent than expected and that the AP1/MYC pair is significantly enriched in binding in cancer models, relative to non-cancer models, in these promoters. This effect is seen in both MET models (solid tumors) and in non-MET models (leukemia). These results are consistent with our hypothesis that the OVOLs impact cancer susceptibility by regulating MET, and extend the hypothesis to include mechanisms not specific to MET. Conclusions We find significant evidence of the OVOL, AP1, STAT1, STAT3, and NFKB1 TFs having important roles in MET, and more broadly in cancer. We prioritize known gene/drug targets for follow-up in the clinic, and we show that the AP1/MYC TF pair is a strong candidate for intervention. PMID

  10. Fluid-rock interaction during progressive migration of carbonatitic fluids, derived from small-scale trace element and Sr, Pb isotope distribution in hydrothermal fluorite

    NASA Astrophysics Data System (ADS)

    Bühn, B.; Schneider, J.; Dulski, P.; Rankin, A. H.

    2003-12-01

    Associated with the Cretaceous Okorusu carbonatite complex (Namibia) is a hydrothermal fluorite mineralization hosted in Pan-African country rock marbles, which resulted from fluid-rock reaction between the marbles and orthomagmatic, carbonatitic fluids expelled from the carbonatite. Yellow fluorite I was deposited in veins up to 5 cm away from the wallrock contact, followed by purple and colorless fluorite II, smoky quartz and barite, a Mn-rich crust on early calcite, and pure calcite. This clear-cut sequence of mineral growth allows an investigation into fluid-rock interaction processes between the marble and the migrating carbonatitic fluid, and element fractionation patterns between the fluid and subsequent hydrothermal precipitates. Fluorite I shows a progressive change in color from dark yellow to colorless with purple laminations over time of deposition. Subsequent fluorite I precipitates show an increase in Ca, and a continuous decrease in F, Sr, REE, Y, Th, U and Pb contents. The ratios (Eu/Eu*) cn, Th/Pb and U/Pb increase whereas Y/Ho, Th/U and (La/Yb) cn decrease. The Sr-isotopic composition remains constant at 87Sr/ 86Sr = 0.70456-0.70459, but with varying, highly radiogenic Pb ( 206Pb/ 204Pb = 32-190, 238U/ 204Pb = 7-63). Fluorite II has 87Sr/ 86Sr = 0.70454-0.70459, 206Pb/ 204Pb = 18.349, and 207Pb/ 204Pb = 15.600, and a chemical composition similar to youngest fluorite I. The Mn-rich crust on early calcite accumulated REE, Ba, Pb, Zr, Cs, Th and U, developing into pure calcite with a prominent negative Ce anomaly and successively more radiogenic Sr. The calculated degrees of fluid-rock interaction, f = weight fraction of fluid/(fluid + marble), decrease from fluorite I and most fluorite II (f = 0.5) to calcite (f = 0.2-0.3) and hydrothermal quartz (f ≪ 0.1). A crush-leach experiment for fluid inclusions in the hydrothermal quartz yielded a Rb-Sr isochron age of 103 ± 12 Ma. Crush-leach analysis for the carbonatitic fluid trapped in the wallrock

  11. Evaluation of possible interaction among drugs contemplated for use during manned space flights. Part 1: Summary from progress report dated 31 October 1973. Part 2: Progress report for the period November 1973 to June 1974

    NASA Technical Reports Server (NTRS)

    1974-01-01

    Possible interactions among drugs contemplated for use during manned spaceflights have been studied in several animal species. The following seven drugs were investigated: nitrofurantoin, chloral hydrate, hexobarbital, phenobarbital, flurazepam, diphenoxylate, and phenazopyridine. Particular combinations included: chloral hydrate, hexobarbital or flurazepam with nitrofurantoin; phenobarbital or flurazepam with phenazopyridine; and diphenoxylate with two dose formulations of nitrofurantoin. The mechanism of action and an explanation of the interaction between diphenoxylate and nitrofurantoin still remains unclear. In man, the interaction does not appear to be significant, affecting only two subjects out of six and with only one dose formulation (Furadantin).

  12. RB-resistant Abl kinase induces delayed cell cycle progression and increases susceptibility to apoptosis upon cellular stresses through interaction with p53.

    PubMed

    Cho, Jae-We; Chung, Junah; Baek, Won-Ki; Suh, Seong-Il; Kwon, Taeg Kyu; Park, Jong-Wook; Suh, Min-Ho

    2003-06-01

    c-Abl, a non-receptor tyrosine kinase, is found in both nucleus and cytoplasm of proliferating fibroblasts. RB negatively regulates the kinase activity of c-Abl. Overexpression of kinase active c-Abl can overcome RB-induced growth arrest in Saos-2 cells. However, we previously reported that disruption of the RB matchmaker function leads to delayed cell cycle progression in the presence of p53. In this study, we investigated whether overexpression of mutant c-Abl (AS2, RB-resistant Abl kinase) not only lead to delayed cell cycle progression but also make cells susceptible to apoptosis under coexpression with a fragment of RB C pocket in human skin fibroblast. AS2 expressing cells showed delayed cell growth rate in normal growth condition. After genotoxic stress such as etoposide treatment, AS2 expressing cells readily progressed into apoptosis through p53 and caspase-3 activations. Our results suggest that expression of AS2 not only induces delayed cell cycle progression but also results in increased sensitivity to apoptosis in the presence of p53. PMID:12738983

  13. Environmental and radiological safety studies: Interaction of /sup 238/PuO/sub 2/ heat sources with terrestrial and aquatic environments. Progress report, September 26-December 25, 1981

    SciTech Connect

    Matlack, G.M.; Patterson, J.H.

    1982-02-01

    Although existing radioisotope thermoelectric generator designs have proved more than adequately safe, more information is continually sought about the heat sources to improve their safety. The work here includes studies of the effects on the heat sources of terrestrial and aquatic environments and also of the effect of the heat sources on various simulated environments. This progress report presents recent data from environmental chamber and aquatic experiments and gives the present status of the experiments.

  14. Environmental and radiological safety studies. Interaction of /sup 238/PuO/sub 2/ heat sources with terrestrial and aquatic environments. Progress report, July 1-September 25, 1981

    SciTech Connect

    Matlack, G.M.; Patterson, J.H.

    1981-11-01

    Although existing radioisotope thermoelectric generator designs have proved more than adequately safe, more information is continually sought about the heat sources to improve their safety. The work here includes studies of the effects on the heat sources of terrestrial and aquatic environments and also of the effects of the heat sources on various simulated environments. This progress report presents recent data from environmental chamber and aquatic experiments and gives the present status of the experiments.

  15. Environmental and radiological safety studies: interaction of /sup 238/PuO/sub 2/ heat sources with terrestrial and aquatic environments. Progress report, April 1- June 30, 1982

    SciTech Connect

    Matlack, G.M.; Patterson, J.H.; Stalnaker, N.D.

    1982-09-01

    Although existing radioisotope thermoelectric generator designs have proved more than adequately safe, more information is continually sought about the heat sources to improve their safety. The work here includes studies of the effects on the heat sources on terrestrial and aquatic environments and also of the effects of the heat sources on various simulated environments. This progress report presents recent data from environmental chamber and aquatic experiments and gives the present status of the experiments.

  16. Environmental and radiological safety studies: interaction of /sup 238/PuO/sub 2/ heat sources with terrestrial and aquatic environments. Progress report, July 1-September 30, 1982

    SciTech Connect

    Matlack, G.M.; Patterson, J.H.; Stalnaker, N.D.

    1982-12-01

    Although existing radioisotope thermoelectric generator designs have proved more than adequately safe, more information is continually sought about the heat sources to improve their safety. The work here includes studies of the effects on the heat sources of terrestrial and aquatic environments and also of the effects of the heat sources on various simulated environments. This progress report presents recent data from environmental chamber and aquatic experiments and gives the present status of the experiments.

  17. Repression of Tropolone Production and Induction of a Burkholderia plantarii Pseudo-Biofilm by Carot-4-en-9,10-diol, a Cell-to-Cell Signaling Disrupter Produced by Trichoderma virens

    PubMed Central

    Wang, Mengcen; Hashimoto, Makoto; Hashidoko, Yasuyuki

    2013-01-01

    Background The tropolone-tolerant Trichoderma virens PS1-7 is a biocontrol agent against Burkholderia plantarii, causative of rice seedling blight. When exposed to catechol, this fungus dose-dependently produced carot-4-en-9,10-diol, a sesquiterpene-type autoregulatory signal molecule that promotes self-conidiation of T. virens PS1-7 mycelia. It was, however, uncertain why T. virens PS1-7 attenuates the symptom development of the rice seedlings infested with B. plantarii. Methodology/Principal Findings To reveal the antagonism by T. virens PS1-7 against B. plantarii leading to repression of tropolone production in a coculture system, bioassay-guided screening for active compounds from a 3-d culture of T. virens PS1-7 was conducted. As a result, carot-4-en-9,10-diol was identified and found to repress tropolone production of B. plantarii from 10 to 200 µM in a dose-dependent manner as well as attenuate virulence of B. plantarii on rice seedlings. Quantitative RT-PCR analysis revealed that transcriptional suppression of N-acyl-L-homoserine lactone synthase plaI in B. plantarii was the main mode of action by which carot-4-en-9,10-diol mediated the quorum quenching responsible for repression of tropolone production. In addition, the unique response of B. plantarii to carot-4-en-9,10-diol in the biofilm formed in the static culture system was also found. Although the initial stage of B. plantarii biofilm formation was induced by both tropolone and carot-4-en-9,10-diol, it was induced in different states. Moreover, the B. plantarii biofilm that was induced by carot-4-en-9,10-diol at the late stage showed defects not only in matrix structure but also cell viability. Conclusions/Significance Our findings demonstrate that carot-4-en-9,10-diol released by T. virens PS1-7 acts as an interkingdom cell-to-cell signaling molecule against B. plantarii to repress tropolone production and induces pseudo-biofilm to the cells. This observation also led to another discovery that

  18. Modeling Interactions Between Leukemia-Specific Chromosomal Changes, Somatic Mutations, and Gene Expression Patterns During Progression of Core-Binding Factor Leukemias

    PubMed Central

    Jones, Dan; Yao, Hui; Romans, Angela; Dando, Caroline; Pierce, Sherry; Borthakur, Gautam; Hamilton, Amy; Bueso-Ramos, Carlos; Ravandi, Farhad; Garcia-Manero, Guillermo; Kantarjian, Hagop

    2014-01-01

    In cancer genomes, changes observed during tumor progression can be difficult to separate from non-specific accumulation of cytogenetic changes due to cancer-associated genetic instability. We studied genetic changes occurring over time in cancers presenting with a relatively simple karyotype, namely two related core-binding factor (CBF) acute myeloid leukemias (AMLs), to assess how specific chromosomal changes are selected based on tumor subtype and acquired somatic mutations. Expression profiles for DNA replication/repair genes and the mutation status of KRAS, NRAS, FLT3, and KIT were compared with the karyotypic changes at diagnosis and relapse(s) in 94 cases of inv(16)(p13.1q22)-AML and 82 cases of t(8;21)(q22;q22)-AML. The majority of both AML types demonstrated a simple aneuploid pattern of cytogenetic progression, with highly distinctive patterns of chromosome copy number changes, such as +22 and +13 exclusively in inv(16)-AML and –Y and –X in t(8;21)-AML. Selection of certain cytogenetic changes correlated with particular somatic mutations, such as +8 with RAS mutation, and absence of kinase pathway mutations in t(8;21)-AML with localized deletions at chromosome band 9q22. Alterations in transcript levels of mitotic spindle kinases such as CHEK1, AURKA, and AURKB were associated with the aneuploid progression pattern, particularly in t(8;21) cases. Despite the similarity in the initiating genetics of the two CBF AML types, highly tumor-specific patterns of limited aneuploidy are noted that persist and continue to accumulate at relapse. Thus, activation of genetic instability, possibly through mitotic spindle dysregulation, leads rapidly to selection of advantageous single chromosome aneuploidy. PMID:19908318

  19. Modeling interactions between leukemia-specific chromosomal changes, somatic mutations, and gene expression patterns during progression of core-binding factor leukemias.

    PubMed

    Jones, Dan; Yao, Hui; Romans, Angela; Dando, Caroline; Pierce, Sherry; Borthakur, Gautam; Hamilton, Amy; Bueso-Ramos, Carlos; Ravandi, Farhad; Garcia-Manero, Guillermo; Kantarjian, Hagop

    2010-02-01

    In cancer genomes, changes observed during tumor progression can be difficult to separate from nonspecific accumulation of cytogenetic changes due to cancer-associated genetic instability. We studied genetic changes occurring over time in cancers presenting with a relatively simple karyotype, namely two related core-binding factor (CBF) acute myeloid leukemias (AMLs), to assess how specific chromosomal changes are selected based on tumor subtype and acquired somatic mutations. Expression profiles for DNA replication/repair genes and the mutation status of KRAS, NRAS, FLT3, and KIT were compared with the karyotypic changes at diagnosis and relapse(s) in 94 cases of inv(16)(p13.1q22)-AML and 82 cases of t(8;21)(q22;q22)-AML. The majority of both AML types demonstrated a simple aneuploid pattern of cytogenetic progression, with highly distinctive patterns of chromosome copy number changes, such as +22 and +13 exclusively in inv(16)-AML and -Y and -X in t(8;21)-AML. Selection of certain cytogenetic changes correlated with particular somatic mutations, such as +8 with RAS mutation, and absence of kinase pathway mutations in t(8;21)-AML with localized deletions at chromosome band 9q22. Alterations in transcript levels of mitotic spindle kinases such as CHEK1, AURKA, and AURKB were associated with the aneuploid progression pattern, particularly in t(8;21) cases. Despite the similarity in the initiating genetics of the two CBF AML types, highly tumor-specific patterns of limited aneuploidy are noted that persist and continue to accumulate at relapse. Thus, activation of genetic instability, possibly through mitotic spindle dysregulation, leads rapidly to the selection of advantageous single chromosome aneuploidy.

  20. Investigations of the structure and electromagnetic interactions of few body systems. Annual progress report, 1 September 1982-31 August 1983

    SciTech Connect

    Harper, E.P.; Lehman, D.R.; Prats, F.

    1983-01-01

    The George Washington University nuclear theory group proposes to conduct investigations of the structure and electromagnetic interactions of few-body systems. The structural properties of the very light nuclei are examined by developing theoretical models that begin from the basic interactions between the constituents and that are solved exactly (numerically), i.e., full three- or four-body dynamics. Such models are then used in an attempt to understand the details of the strong and electromagnetic interactions of the few-nucleon nuclei after the basic underlying reaction mechanisms are understood with simpler models. These efforts are becoming increasingly important with the advent of high duty cycle, high current electron accelerators from which valuable data will be forthcoming that should permit unraveling the structure and interactions of the very-light nuclei. Examples of specific work proposed are the following: 1) Set up the equations for the low-energy photodisintegration of /sup 3/He and /sup 3/H including final-state interactions and the E1 plus E2 operators; 2) Develop a unified picture of the p + d ..-->.. /sup 3/He + ..gamma.., p + d ..-->.. /sup 3/He + ..pi../sup 0/, p + d ..-->.. /sup 3/H + ..pi../sup +/ reactions at intermediate energies; 3) Calculate the elastic and inelastic (1/sup +/..-->..0/sup +/) form factors for /sup 6/Li with three-body (..cap alpha..NN) wave functions; 4) Calculate static properties (RMS radius, magnetic moment, and quadrupole moment) of /sup 6/Li with three-body wave functions; and 5) Develop the theory for the coincidence reactions /sup 6/Li(p,2p)n..cap alpha.., /sup 6/Li(e,e'p)n..cap alpha.., and /sup 6/Li(e,e'd)..cap alpha... It is anticipated that these efforts will expand the frontiers of our knowledge about few-body nuclei.

  1. Mycobacterium tuberculosis modulates the gene interactions to activate the HIV replication and faster disease progression in a co-infected host.

    PubMed

    Toor, Jaideep S; Singh, Sukhvinder; Sharma, Aman; Arora, Sunil K

    2014-01-01

    Understanding of the chronic immune activation, breakdown of immune defense and synergistic effect between HIV and Mycobacterium tuberculosis (Mtb) may provide essential information regarding key factors involved in the pathogenesis of HIV disease. In this study, we aimed to highlight a few of the immunological events that may influence and accelerate the progression of HIV disease in the presence of co-infecting Mtb. A cross-sectional study was performed on cohorts, including anti-tubercular therapy (ATT) naïve active pulmonary tuberculosis (PTB) patients, antiretroviral therapy (ART) naïve HIV-1 infected individuals at different stages of disease, ATT and ART naïve HIV-PTB co-infected individuals and healthy controls. A significantly higher T-regulatory cell (Treg) frequency coupled with the high FoxP3 expression in the CD4 T-cells indicated an immunosuppressive environment in the advance stage of HIV-1 infection. This is further substantiated by high HO-1 expression favoring TB co-infection. Functionally, this change in Treg frequency in HIV-1 infected individuals correlated well with suppression of T-cell proliferation. Mtb infection seems to facilitate the expansion of the Treg pool along with increased expression of FoxP3, specifically the variant-1, as evident from the data in HIV-1 co-infected as well as in patients with only PTB. A significantly lower expression of HO-1 in co-infected individuals compared to patients with only HIV-infection having comparable CD4 count correlated well with increased expression of CCR5 and CxCR4 as well as NF-κB and inflammatory cytokines IL-6 and TNF-α, which collectively may contribute to enhanced viral replication and increased cell death, hence faster disease progression in co-infected individuals.

  2. Investigations of the structure and electromagnetic interactions of few-body systems. Progress report, 1 July 1992--30 June 1993

    SciTech Connect

    Lehman, D.R.; Haberzettl, H.; Maximon, L.C.; Parke, W.C.; Bennhold, C.; Ito, Hiroshi; Pratt, R.K.; Najmeddine, M.; Rakei, A.

    1993-07-01

    The emphasis of the nuclear theory group has been on the structure and electromagnetic interactions of few-body nuclei. Both low- and intermediate-energy electromagnetic disintegration of these nuclei is considered, including coherent photoproduction of {pi} mesons. When the excitation energy of the target nucleus is low, the aim is to handle the continuum part of the theoretical work numerically with no approximations, that is, by means of full three- or four-body dynamics. When structure questions are the issue, numerically accurate calculations are always carried through, limited only by the underlying two-body or three-body interactions used as input. A central goal is to carry through state-of-the-art few-body calculations that will serve as a means of determining at what point standard nuclear physics requires introduction of relativity and/or quark degrees of freedom in order to understand the phenomena in question.

  3. SET Careers Program: An interactive science, engineering, and technology career education exhibit. Annual progress report, September 1, 1992--October 31, 1993

    SciTech Connect

    Cole, P.R.

    1993-03-31

    The New York Hall of Science, in response to the national crisis in education and employment in science and engineering, is developing and pilot testing a unique, interactive, video-based, hypermedia series on energy-related and other science and engineering careers for middle and junior high school students. Working in collaboration with the Consortium for Mathematics and its Applications (COMAP) and the Educational Film Center (EFC), this pilot-demonstration phase will last 14 months, during which time the basic design, production, and testing of eight science and engineering career modules (video and software) will be completed and installed as an interactive educational exhibit at the New York Hall of Science. This career education package will then be distributed to other science technology centers nationwide.

  4. An interactive physics-based unmanned ground vehicle simulator leveraging open source gaming technology: progress in the development and application of the virtual autonomous navigation environment (VANE) desktop

    NASA Astrophysics Data System (ADS)

    Rohde, Mitchell M.; Crawford, Justin; Toschlog, Matthew; Iagnemma, Karl D.; Kewlani, Guarav; Cummins, Christopher L.; Jones, Randolph A.; Horner, David A.

    2009-05-01

    It is widely recognized that simulation is pivotal to vehicle development, whether manned or unmanned. There are few dedicated choices, however, for those wishing to perform realistic, end-to-end simulations of unmanned ground vehicles (UGVs). The Virtual Autonomous Navigation Environment (VANE), under development by US Army Engineer Research and Development Center (ERDC), provides such capabilities but utilizes a High Performance Computing (HPC) Computational Testbed (CTB) and is not intended for on-line, real-time performance. A product of the VANE HPC research is a real-time desktop simulation application under development by the authors that provides a portal into the HPC environment as well as interaction with wider-scope semi-automated force simulations (e.g. OneSAF). This VANE desktop application, dubbed the Autonomous Navigation Virtual Environment Laboratory (ANVEL), enables analysis and testing of autonomous vehicle dynamics and terrain/obstacle interaction in real-time with the capability to interact within the HPC constructive geo-environmental CTB for high fidelity sensor evaluations. ANVEL leverages rigorous physics-based vehicle and vehicle-terrain interaction models in conjunction with high-quality, multimedia visualization techniques to form an intuitive, accurate engineering tool. The system provides an adaptable and customizable simulation platform that allows developers a controlled, repeatable testbed for advanced simulations. ANVEL leverages several key technologies not common to traditional engineering simulators, including techniques from the commercial video-game industry. These enable ANVEL to run on inexpensive commercial, off-the-shelf (COTS) hardware. In this paper, the authors describe key aspects of ANVEL and its development, as well as several initial applications of the system.

  5. Proteomic analysis of FUS interacting proteins provides insights into FUS function and its role in ALS.

    PubMed

    Kamelgarn, Marisa; Chen, Jing; Kuang, Lisha; Arenas, Alexandra; Zhai, Jianjun; Zhu, Haining; Gal, Jozsef

    2016-10-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Mutations in the Fused in Sarcoma/Translocated in Liposarcoma (FUS/TLS) gene cause a subset of familial ALS cases and are also implicated in sporadic ALS. FUS is typically localized to the nucleus. The ALS-related FUS mutations cause cytoplasmic mis-localization and the formation of stress granule-like structures. Abnormal cytoplasmic FUS localization was also found in a subset of frontotemporal dementia (FTLD) cases without FUS mutations. To better understand the function of FUS, we performed wild-type and mutant FUS pull-downs followed by proteomic identification of the interacting proteins. The FUS interacting partners we identified are involved in multiple pathways, including chromosomal organization, transcription, RNA splicing, RNA transport, localized translation, and stress response. FUS interacted with hnRNPA1 and Matrin-3, RNA binding proteins whose mutations were also reported to cause familial ALS, suggesting that hnRNPA1 and Matrin-3 may play common pathogenic roles with FUS. The FUS interactions displayed varied RNA dependence. Numerous FUS interacting partners that we identified are components of exosomes. We found that FUS itself was present in exosomes, suggesting that the secretion of FUS might contribute to the cell-to-cell spreading of FUS pathology. FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. Our results provide insights into the physiological functions of FUS as well as important pathways where mutant FUS can interfere with cellular processes and potentially contribute to the pathogenesis of ALS. PMID:27460707

  6. An investigation of catalytic active phase-support interactions by IR, NMR and x-ray absorption spectroscopies. Progress report, January 15, 1991--July 31, 1993

    SciTech Connect

    Haller, G.L.

    1993-07-01

    Active catalytic phases (metal, mixed metals, oxide or mixed oxides) interacting with oxide support can affect percentage exposed, the morphology of supported particles, the degree of reducibility of cations, etc., in a variety of ways. Solid state {sup 29}Si NMR was used to obtain a new correlation between partial charge on the Si which comprises a part of the SiOHAl Br{o}nsted acid structure in amorphous silica-aluminas. We also describe two potential improvements in solid state NMR applied to catalysts and catalysts supports. One is experimental, dynamic angle spinning NMR, a new technique for obtaining high resolution spectra of quadrupolar nuclei, e.g., {sup 27}Al. The second approach is an alternative to the standard fast Fourier transform of the free induction decay to convert from the time to spectral domain, the maximum entropy method. Effect of different methods of preparation of Pd/L-zeolites is described. By comparison to analogous Pt systems, it is the inherent chemistry of the L-zeolite which results in better dispersion when impregnation preparation is used relative to ion exchange preparation. X-ray absorption spectroscopy is used to compare the effect of support (SiO{sub 2} and L-zeolite) on the degree and kind of Pt-Ni interaction. When supported in L-zeolite and promoted with Ni, Pt has improved stability both with regard to self-poisoning and sulfur catalyzed agglomeration.

  7. Nuclear interactions of high energy heavy ions and applications in astrophysics. Technical progress report, 1 April 1991--31 March 1992

    SciTech Connect

    Wefel, J.P.

    1992-01-23

    This program was established for the purpose of studying projectile fragmentation; (1) as a function of energy, focusing first on the intermediate energy region, < 1 GeV/nucleon, where there have been few previous measurements and no systematic studies, and (2) as a function of projectile mass, starting with light beams and proceeding to species as heavy as nickel (and possibly beyond). The intermediate energy region is important as the transition between the lower energy data, where the interaction appears to be dominated by collective effects and the decay of excited nuclei, and the highest energy results, where nucleon-nucleon interactions are fundamental, ``limiting fragmentation`` applies, and the nucleus may well break-up before any de-excitation. The mass dependence of projectile fragmentation is largely unknown since most detailed work has involved light ion beams. Nuclear structure effects, for example, may well be quite prominent for heavier beams. Furthermore, the nuclear excitation functions for the production of different fragment isotopes have immediate application to the astrophysical interpretation of existing isotopic datasets obtained from balloon and satellite measurements of galactic cosmic rays.

  8. Experimental studies of the quark-gluon structure of nucleons and nuclei and of pion- and proton-nucleus interactions. Progress report, April 1, 1994--March 31, 1997

    SciTech Connect

    1996-10-01

    This report summarizes the work on experimental research in intermediate energy nuclear physics carried out by New Mexico State University from April 1, 1994, through March 31, 1996 under a grant from the US Department of Energy. During this period we began phasing out our programs of study of pion-nucleus and pion-nucleon interaction and of nucleon-nucleus charge-exchange reactions, which have been our major focus of the past two or three years. At the same time we continued moving in a new direction of research on studies of the internal structure of nucleons and nuclei in terms of quarks and gluons. The pion and nucleon work has been aimed at improving our understanding of the nature of pion and proton interactions in the nuclear medium and of various aspects of nuclear structure. The studies of the quark-gluon structure of nucleons are aimed at clarifying such problems as the nature of the quark sea and the relation of the nucleon spin to the spins of the quarks within the nucleon, questions which are of a very fundamental nature.

  9. The Gcn2 Regulator Yih1 Interacts with the Cyclin Dependent Kinase Cdc28 and Promotes Cell Cycle Progression through G2/M in Budding Yeast

    PubMed Central

    Silva, Richard C.; Dautel, Martina; Di Genova, Bruno M.; Amberg, David C.; Castilho, Beatriz A.; Sattlegger, Evelyn

    2015-01-01

    The Saccharomyces cerevisiae protein Yih1, when overexpressed, inhibits the eIF2 alpha kinase Gcn2 by competing for Gcn1 binding. However, deletion of YIH1 has no detectable effect on Gcn2 activity, suggesting that Yih1 is not a general inhibitor of Gcn2, and has no phenotypic defect identified so far. Thus, its physiological role is largely unknown. Here, we show that Yih1 is involved in the cell cycle. Yeast lacking Yih1 displays morphological patterns and DNA content indicative of a delay in the G2/M phases of the cell cycle, and this phenotype is independent of Gcn1 and Gcn2. Accordingly, the levels of phosphorylated eIF2α, which show a cell cycle-dependent fluctuation, are not altered in cells devoid of Yih1. We present several lines of evidence indicating that Yih1 is in a complex with Cdc28. Yih1 pulls down endogenous Cdc28 in vivo and this interaction is enhanced when Cdc28 is active, suggesting that Yih1 modulates the function of Cdc28 in specific stages of the cell cycle. We also demonstrate, by Bimolecular Fluorescence Complementation, that endogenous Yih1 and Cdc28 interact with each other, confirming Yih1 as a bona fide Cdc28 binding partner. Amino acid substitutions within helix H2 of the RWD domain of Yih1 enhance Yih1-Cdc28 association. Overexpression of this mutant, but not of wild type Yih1, leads to a phenotype similar to that of YIH1 deletion, supporting the view that Yih1 is involved through Cdc28 in the regulation of the cell cycle. We further show that IMPACT, the mammalian homologue of Yih1, interacts with CDK1, the mammalian counterpart of Cdc28, indicating that the involvement with the cell cycle is conserved. Together, these data provide insights into the cellular function of Yih1/IMPACT, and provide the basis for future studies on the role of this protein in the cell cycle. PMID:26176233

  10. EDITORIAL: Catalysing progress Catalysing progress

    NASA Astrophysics Data System (ADS)

    Demming, Anna

    2010-01-01

    Examples of the merits of blue-sky research in the history of science are legion. The invention of the laser, celebrating its 50th anniversary this year, is an excellent example. When it was invented it was considered to be 'a solution waiting for a problem', and yet the level to which it has now infiltrated our day-to-day technological landscape speaks volumes. At the same time it is also true to say that the direction of research is also at times rightly influenced by the needs and concerns of the general public. Over recent years, growing concerns about the environment have had a noticeable effect on research in nanotechnology, motivating work on a range of topics from green nanomaterial synthesis [1] to high-efficiency solar cells [2] and hydrogen storage [3]. The impact of the world's energy consumption on the welfare of the planet is now an enduring and well founded concern. In the face of an instinctive reluctance to curtail habits of comfort and convenience and the appendages of culture and consumerism, research into renewable and more efficient energy sources seem an encouraging approach to alleviating an impending energy crisis. Fuel cells present one alternative to traditional combustion cells that have huge benefits in terms of the efficiency of energy conversion and the limited harmful emissions. In last week's issue of Nanotechnology, Chuan-Jian Zhong and colleagues at the State University of New York at Binghamton in the USA presented an overview of research on nanostructured catalysts in fuel cells [4]. The topical review includes insights into the interactions between nanoparticles and between nanoparticles and their substrate as well as control over the composition and nanostructure of catalysts. The review also serves to highlight how the flourishing of nanotechnology research has heralded great progress in the exploitation of catalysts with nanostructures ingeniously controlled to maximize surface area and optimize energetics for synthesis

  11. EDITORIAL: Catalysing progress Catalysing progress

    NASA Astrophysics Data System (ADS)

    Demming, Anna

    2010-01-01

    Examples of the merits of blue-sky research in the history of science are legion. The invention of the laser, celebrating its 50th anniversary this year, is an excellent example. When it was invented it was considered to be 'a solution waiting for a problem', and yet the level to which it has now infiltrated our day-to-day technological landscape speaks volumes. At the same time it is also true to say that the direction of research is also at times rightly influenced by the needs and concerns of the general public. Over recent years, growing concerns about the environment have had a noticeable effect on research in nanotechnology, motivating work on a range of topics from green nanomaterial synthesis [1] to high-efficiency solar cells [2] and hydrogen storage [3]. The impact of the world's energy consumption on the welfare of the planet is now an enduring and well founded concern. In the face of an instinctive reluctance to curtail habits of comfort and convenience and the appendages of culture and consumerism, research into renewable and more efficient energy sources seem an encouraging approach to alleviating an impending energy crisis. Fuel cells present one alternative to traditional combustion cells that have huge benefits in terms of the efficiency of energy conversion and the limited harmful emissions. In last week's issue of Nanotechnology, Chuan-Jian Zhong and colleagues at the State University of New York at Binghamton in the USA presented an overview of research on nanostructured catalysts in fuel cells [4]. The topical review includes insights into the interactions between nanoparticles and between nanoparticles and their substrate as well as control over the composition and nanostructure of catalysts. The review also serves to highlight how the flourishing of nanotechnology research has heralded great progress in the exploitation of catalysts with nanostructures ingeniously controlled to maximize surface area and optimize energetics for synthesis

  12. Experimental study of interactions of highly charged ions with atoms at keV energies. Progress report, August 15, 1990--February 15, 1993

    SciTech Connect

    Kostroun, V.O.

    1993-01-29

    This final progress report summarizes the work carried out during the 29 month period from August 15, 1990 to February 15, 1993 under grant DE-FG02-86ER13519. The following experiments were done. We measured the absolute total and one- and two- electron transfer cross sections for Ar{sup q+} (8{le} q {le} 16) on He and H{sub 2} at 2.3 qkeV, the angular distributions of the scattered projectiles in Ar{sup 8+,9+} collisions, with Ar and Kr at 2.3 qkeV, the electron emissions in low energy Ar{sup q+} on Ar collisions, the recoil ion charge state distributions in low energy Ar{sup q+} -Ar collisions, the absolute total and one-and two-electron transfer cross sections for Ar{sup 8+} on Ar at 2.3 qkeV, and the absolute total and one- and two-electron transfer cross sections for Ar{sup 8+} on Ar as a function of energy. We also used energy gain spectroscopy to study Ar{sup q+} on Ar collisions at 40 and 30 qeV, and time of flight spectroscopy to investigate ionization and dissociation of CO and N{sub 2} in collisions with low energy, highly charged argon ions. In addition, we applied the Goldberger and Watson transition theory to derive transition rates and cross sections for atomic radiative and/or non radiative processes, wrote a computer code TRANSIT which can calculate energies, wave functions and radiative and non radiative rates for atoms and ions. The code is highly modular and can easily be modified to calculate higher order processes. Finally, we have done an Ab-Initio molecular orbital electronic energy level calculation for the (ArAr){sup 8+} system as a function internuclear separation.

  13. Experimental studies of pion-nucleus and nucleon-nucleus interactions at intermediate energies. Progress report, April 1, 1991--March 31, 1994

    SciTech Connect

    1993-09-30

    This report summarizes the work on experimental research in intermediate energy nuclear physics carried out at New Mexico State University in 1991-94 under a grant from the U.S. Department of Energy. Most of these studies involved investigations of various pion-nucleus interactions and nucleon-nucleus charge-exchange reactions. The work was carried out with the LAMPF accelerator at the Los Alamos National Laboratory and the cyclotrons at the Paul Scherrer Institute (PSI) near Zurich, Switzerland, at Indiana University (IUCF), and at TRIUMF in Vancouver, Canada, as collaborative efforts among several laboratories and universities. We have also worked on plans and preparations for new experiments involving studies of the quark structure of nucleons and nuclei, which would be carried out at Fermilab (FNAL), near Chicago, and at the HERA facility at the DESY laboratory in Hamburg, Germany. The NMSU personnel included two faculty members, five postdoctoral research associates, nine graduate students, and one undergraduate student.

  14. gamma-Linolenic acid blocks cell cycle progression by regulating phosphorylation of p27kip1 and p57kip2 and their interactions with other cycle regulators in cancer cells.

    PubMed

    Jiang, W G; Bryce, R P; Horrobin, D F; Mansel, R E

    1998-09-01

    gamma-Linolenic acid (gamma-LA), a n-6 essential fatty acid, has been previously shown to affect cell cycle and growth of cancer cells. This study examined the effects of gamma-LA on the cell cycle and cycle regulators in human colon cancer HT115 and breast cancer MCF7 cells. Brief treatment of cancer cells (<2 h) with gamma-LA resulted in a decrease in the phosphorylation of both cell cycle inhibitors, p27kip1 and p57kip2 as shown by immunoprecipitation and Western blotting. Protein levels of both inhibitors were increased following a prolonged culture of cells with the fatty acid. A co-precipitation study showed that in cells treated with gamma-LA there was an increase in the binding of these inhibitors with CDK4, CDC2, and cyclin E. Flow cytometry study indicated an inhibition of cell cycle progression by gamma-LA (G0/G1 -45.4%, S - 34.6%, G2+M - 20.0% in control, and 70.5%, 21.0%, and 8.5%, respectively, in gamma-LA treated cells). It is concluded that gamma-linolenic acid inhibits cell cycle progression in the cancer cell lines investigated, via its regulation of the phosphorylation and subsequent degradation of p27kip1 and p57kip2 and their interactions with other cycle regulators. PMID:9683802

  15. Epidemiology and interactions of Human Immunodeficiency Virus – 1 and Schistosoma mansoni in sub-Saharan Africa

    PubMed Central

    2013-01-01

    Human Immunodeficiency Virus-1/AIDS and Schistosoma mansoni are widespread in sub-Saharan Africa and co-infection occurs commonly. Since the early 1990s, it has been suggested that the two infections may interact and potentiate the effects of each other within co-infected human hosts. Indeed, S. mansoni infection has been suggested to be a risk factor for HIV transmission and progression in Africa. If so, it would follow that mass deworming could have beneficial effects on HIV-1 transmission dynamics. The epidemiology of HIV in African countries is changing, shifting from urban to rural areas where the prevalence of Schistosoma mansoni is high and public health services are deficient. On the other side, the consequent pathogenesis of HIV-1/S. mansoni co-infection remains unknown. Here we give an account of the epidemiology of HIV-1 and S. mansoni, discuss co-infection and possible biological causal relationships between the two infections, and the potential impact of praziquantel treatment on HIV-1 viral loads, CD4+ counts and CD4+/CD8+ ratio. Our review of the available literature indicates that there is evidence to support the hypothesis that S. mansoni infections can influence the replication of the HIV-1, cell-to-cell transmission, as well as increase HIV progression as measured by reduced CD4+ T lymphocytes counts. If so, then deworming of HIV positive individuals living in endemic areas may impact on HIV-1 viral loads and CD4+ T lymphocyte counts. PMID:23849678

  16. Progress in Development of C60 Nanoparticle Plasma Jet for Diagnostic of Runaway Electron Beam-Plasma Interaction and Disruption Mitigation Study for ITER

    NASA Astrophysics Data System (ADS)

    Bogatu, I. N.; Thompson, J. R.; Galkin, S. A.; Kim, J. S.

    2013-10-01

    We produced a C60 nanoparticle plasma jet (NPPJ) with uniquely fast response-to-delivery time (~ 1 - 2 ms) and unprecedentedly high momentum (~ 0 . 6 g .km/s). The C60 NPPJ was obtained by using a solid state TiH2/C60 pulsed power cartridge producing ~180 mg of C60 molecular gas by sublimation and by electromagnetic acceleration of the C60 plasma in a coaxial gun (~35 cm length, 96 kJ energy) with the output of a high-density (>1023 m-3) hyper-velocity (>4 km/s) plasma jet. The ~ 75 mg C60/C plasma jet has the potential to rapidly and deeply deliver enough mass to significantly increase electron density (to ne ~ 2 . 4 ×1021 m-3, i.e. ~ 60 times larger than typical DIII-D pre-disruption value, ne 0 ~ 4 ×1019 m-3), and to modify the 'critical electric field' and the runaway electrons (REs) collisional drag during different phases of REs dynamics. The C60 NPPJ, as a novel injection technique, allows RE beam-plasma interaction diagnostic by quantitative spectroscopy of C ions visible/UV line intensity. The system is scalable to ~ 1 - 2 g C60/C plasma jet output and technology is adaptable to ITER acceptable materials (BN and Be) for disruption mitigation. Work supported by US DOE DE-FG02-08ER85196 grant.

  17. HCV core/gC1qR interaction arrests T cell cycle progression through stabilization of the cell cycle inhibitor p27Kip1.

    PubMed

    Yao, Zhi Qiang; Eisen-Vandervelde, Audrey; Ray, Suma; Hahn, Young S

    2003-09-15

    Hepatitis C virus (HCV) is efficient in the establishment of persistent infection. We have previously shown that HCV core protein inhibits T cell proliferation through its interaction with the complement receptor, gC1qR. Here we show that HCV core-induced inhibition of T cell proliferation involves a G(0)/G(1) cell cycle arrest, which is reversible upon addition of anti-gC1qR antibody. Correspondingly, the expression of cyclin-dependent kinases (Cdk) 2/4 and cyclin E/D, as well as subsequent phosphorylation of retinoblastoma (pRb), is reduced in core-treated T cells in response to mitogenic stimulation. Remarkably, degradation of p27(Kip1), a negative regulator of both Cdk4/cyclin D and Cdk2/cyclin E complexes, is significantly diminished in T cells treated with HCV core upon mitogenic stimulation. These data indicate that the stability of p27(Kip1) by HCV core is associated with blocking activated T cells for the G(1) to S phase transition and inhibiting T cell proliferation.

  18. Tousled-like kinase in a microbial eukaryote regulates spindle assembly and S-phase progression by interacting with Aurora kinase and chromatin assembly factors.

    PubMed

    Li, Ziyin; Gourguechon, Stéphane; Wang, Ching C

    2007-11-01

    The Tousled-like kinases are an evolutionarily conserved family of proteins implicated in DNA repair, DNA replication and mitosis in metazoans and plants. Their absence from the yeasts and other eukaryotic 'microbes' suggests a specific role for them in the development of multicellular organisms. In this study, two closely related Tousled-like kinase homologs, TLK1 and TLK2, were identified in Trypanosoma brucei, a unicellular protozoan parasite. Only TLK1 plays an essential role in cell growth, and a deficiency in TLK1 led to an enrichment of S-phase cells, defective spindle formation and aberrant chromosome segregation. Although both TLK proteins localize to the nucleus, only TLK1 also concentrates in the spindle poles during mitosis. Both TLK proteins are phosphorylated by the Aurora kinase (AUK1), and both can autophosphorylate and phosphorylate histone H3 and the chromatin assembly factors Asf1A and Asf1B in vitro, but only TLK1 is autophosphorylated and capable of oligomerizing and interacting with AUK1, Asf1A and Asf1B in vivo. These discrepancies between the two TLK proteins can be attributed to minor differences between their N- and C-terminal sequences. In summary, TLK1 cooperates with Aurora kinase to regulate spindle assembly and chromosome segregation, and it performs a role in DNA replication probably by regulating histone modification in trypanosomes. PMID:17940067

  19. Interactive chemistry of coal-petroleum processing: Quarterly progress report for March 15, 1987-June 15, 1987. [Effect of coal or resid on reaction

    SciTech Connect

    Curtis, C.W.; Guin, J.A.; Tarrer, A.R.

    1987-01-01

    The thermal reactions of model compounds NAPH, DMC, PN, BZT, and QN with Maya TLR (topped long resid) showed no reactions. The presence of Maya TLR blocked the intermediate hydrogenation pathway from QN to THQ compared to the reaction without Maya TLR where 13% THQ was formed. Maya TLR served as a strong inhibitor in the catalytic hydrogenations of model compounds, being more detrimental to the hydrogenation and heteroatom removal reactions than coal. The severe inhibition of Maya TLR is caused by the chemical composition of the resid. The resid contains large refractory hydrocarbon species and substantial amounts of metals. Maya TLR was most likely deactivating the NiMo/Al/sub 2/O/sub 3/ catalyst as well as possibly interacting with model species present. Catalyst deactivation due to pore-plugging by petroleum crude and residua reaction products from hydrotreating, i.e., metal sulfides and coke has been studied by Newson. In crude oils and residua, vanadium and nickel compounds are the most abundant organometallic constituents and cause major problems in hydrotreating of residuum oils. At hydroprocessing conditions, these metal compounds deposit on and deactivate the catalyst. Pore mouth plugging in the catalyst by the metal deposit has been known as the major cause in the catalyst deactivation. Tamm and co-workers studied two mechanisms of catalyst deactivation by petroleum feed metals: (1) poisoning of the active surface and (2) physical obstruction of the pore structure. Thus, two possible reasons for the severe deactivation observed in the Maya TLR are metal deposition and carbon laydown on the catalyst surface. Another reason why the Maya TLR had a stronger inhibiting effect than coal is that these reactions are at 350/sup 0/C, where the coal was only partially dissolved; therefore, all the bad actors from coal were not available in the system, while those from the resid were. 3 refs., 4 figs., 36 tabs.

  20. Progression of cervical intraepithelial neoplasia to cervical cancer: interactions of cytochrome P450 CYP2D6 EM and glutathione s-transferase GSTM1 null genotypes and cigarette smoking.

    PubMed Central

    Warwick, A. P.; Redman, C. W.; Jones, P. W.; Fryer, A. A.; Gilford, J.; Alldersea, J.; Strange, R. C.

    1994-01-01

    The factors that determine progression of cervical intraepithelial neoplasia (CIN) to squamous cell carcinoma (SCC) are unknown. Cigarette smoking is an independent risk factor for cervical neoplasia, suggesting that polymorphism at detoxicating enzyme loci such as cytochrome P450 CYP2D6 and glutathione S-transferase GSTM1 may determine susceptibility to these cancers. We have studied the frequencies of genotypes at these loci in women suffering low-grade CIN, high-grade CIN and SCC. A non-cancer control group was provided by women with normal cervical histology suffering menorrhagia. Comparison of the frequency distributions of the CYP2D6 PM, HET and EM genotypes (G-->A transition at intron 3/exon 4 and base pair deletion in exon 5) revealed no significant differences between the menorrhagia and SCC groups. Frequency distributions in the menorrhagia group, however, were significantly different (P < 0.04) from those in the low- and high-grade CIN groups. Thus, the proportion of EM was significantly larger (P < 0.03) and of HET generally lower. We found that the frequency of GSTM1 null in the menorrhagia and case groups was not significantly different. Interactive effects of enzyme genotypes with cigarette smoking were studied by comparing the multinomial frequency distributions of CYP2D6 EM/GSTM1 null/smoking over mutually exclusive categories. These showed no significant differences between the menorrhagia group and SCC or low-grade CIN groups. The frequency distribution in high-grade CIN, however, was significantly different to that in the menorrhagia group and in both SCC and low-grade CIN groups. This study was identified, for the first time, an inherited characteristic in women with high-grade CIN who appear to be at reduced risk of SCC. Thus, women with CYP2D6 EM who smoke have increased susceptibility to high-grade CIN but are less likely to progress to SCC, possibly because they effectively detoxify an unidentified chemical involved in mediating disease

  1. Study of heavy flavored particles. Progress report

    SciTech Connect

    Not Available

    1991-12-31

    This report discusses progress on the following topics: time-of- flight system; charmed baryon production and decays; D decays to baryons; measurement of sigma plus particles magnetic moments; and strong interaction coupling. (LSP)

  2. Method for physiologic phenotype characterization at the single-cell level in non-interacting and interacting cells

    PubMed Central

    Ashili, Shashanka P.; Houkal, Jeff; Smith, Dean; Mohammadreza, Aida; Lee, Kristen B.; Forrester, Jessica; Kumar, Ashok; Anis, Yasser H.; Paulson, Thomas G.; Youngbull, Cody A.; Tian, Yanqing; Holl, Mark R.; Johnson, Roger H.; Meldrum, Deirdre R.

    2012-01-01

    Abstract. Intercellular heterogeneity is a key factor in a variety of core cellular processes including proliferation, stimulus response, carcinogenesis, and drug resistance. However, cell-to-cell variability studies at the single-cell level have been hampered by the lack of enabling experimental techniques. We present a measurement platform that features the capability to quantify oxygen consumption rates of individual, non-interacting and interacting cells under normoxic and hypoxic conditions. It is based on real-time concentration measurements of metabolites of interest by means of extracellular optical sensors in cell-isolating microwells of subnanoliter volume. We present the results of a series of measurements of oxygen consumption rates (OCRs) of individual non-interacting and interacting human epithelial cells. We measured the effects of cell-to-cell interactions by using the system’s capability to isolate two and three cells in a single well. The major advantages of the approach are: 1. ratiometric, intensity-based characterization of the metabolic phenotype at the single-cell level, 2. minimal invasiveness due to the distant positioning of sensors, and 3. ability to study the effects of cell-cell interactions on cellular respiration rates. PMID:22502580

  3. Method for physiologic phenotype characterization at the single-cell level in non-interacting and interacting cells

    NASA Astrophysics Data System (ADS)

    Kelbauskas, Laimonas; Ashili, Shashanka P.; Houkal, Jeff; Smith, Dean; Mohammadreza, Aida; Lee, Kristen B.; Forrester, Jessica; Kumar, Ashok; Anis, Yasser H.; Paulson, Thomas G.; Youngbull, Cody A.; Tian, Yanqing; Holl, Mark R.; Johnson, Roger H.; Meldrum, Deirdre R.

    2012-03-01

    Intercellular heterogeneity is a key factor in a variety of core cellular processes including proliferation, stimulus response, carcinogenesis, and drug resistance. However, cell-to-cell variability studies at the single-cell level have been hampered by the lack of enabling experimental techniques. We present a measurement platform that features the capability to quantify oxygen consumption rates of individual, non-interacting and interacting cells under normoxic and hypoxic conditions. It is based on real-time concentration measurements of metabolites of interest by means of extracellular optical sensors in cell-isolating microwells of subnanoliter volume. We present the results of a series of measurements of oxygen consumption rates (OCRs) of individual non-interacting and interacting human epithelial cells. We measured the effects of cell-to-cell interactions by using the system's capability to isolate two and three cells in a single well. The major advantages of the approach are: 1. ratiometric, intensity-based characterization of the metabolic phenotype at the single-cell level, 2. minimal invasiveness due to the distant positioning of sensors, and 3. ability to study the effects of cell-cell interactions on cellular respiration rates.

  4. Identifying predictive factors in melanoma progression.

    PubMed

    Dabrowska, D M; Elashoff, R M; Ho, W; Morton, D L

    1998-01-01

    Identification of risk factors is a fundamental goal of melanoma studies. The current understanding of melanoma progression is based primarily on two-stage modeling. A multistate Markov chain process combined with Cox proportional hazard regression is used to model the melanoma progression. The model is applied to 3,434 patients initially diagnosed as AJCC stage I or stage II. Parameter estimates are obtained using Cox regression and supplemented by plots of survival probabilities. Age is associated with increased risk of progression from stage I, II to stage III and from stage III to stage IV. Males experienced an increased risk of stage I, II to stage III progression. Primary tumor located on extremities decreased the risk of all transitions. Clark's level of invasion >III and Breslow's depth >1 mm increased the risk of progression from stage I, II to stage III and stage IV. The following interactions among the prognostic factors were identified for the first time in this research: interaction of age and gender in progression from stage I, II to stage III; interactions of level and depth and site by gender were found in the progression from stage I, II to stage III; interaction of site and gender in progression from stage III to stage IV and stage IV to death. Also we identified primary site as a new prognostic factor for the progression from stage IV to death. The study employed a multistate model in order to identify prognostic factors relevant for disease progression. The unique feature is the modeling of interactions among the prognostic factors and their identification. PMID:9538154

  5. Progress report

    NASA Technical Reports Server (NTRS)

    Abhiraman, A.; Collard, D.; Cardelino, B.; Bhatia, S.; Desai, P.; Harruna, I.; Khan, I.; Mariam, Y.; Mensah, T.; Mitchell, M.

    1992-01-01

    The NASA funding allowed Clark Atlanta University (CAU) to establish a High Performance Polymers And Ceramics (HiPPAC) Research Center. The HiPPAC Center is consolidating and expanding the existing polymer and ceramic research capabilities at CAU through the development of interdepartmental and interinstitutional research in: (1) polymer synthesis; (2) polymer characterization and properties; (3) polymer processing; (4) polymer-based ceramic synthesis; and (5) ceramic characterization and properties. This Center has developed strong interactions between scientists and materials scientists of CAU and their counterparts from sister institutions in the Atlanta University Center (AUC) and the Georgia Institute of Technology. As a component of the center, we have started to develop strong collaborations with scientists from other universities and the HBCU's, national and federal agency laboratories, and the private sector during this first year. During this first year we have refined the focus of the research in the HiPPAC Center to three areas with seven working groups that will start programmatic activities on January 1, 1993, as follows: (1) nonlinear optical properties of chitosan derivatives; (2) polymeric electronic materials; (3) nondestructive characterization and prediction of polyimide performance; (4) solution processing of high-performance materials; (5) processable polyimides for composite applications; (6) sol-gel based ceramic materials processing; and (7) synthetic based processing of pre-ceramic polymers.

  6. Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression

    PubMed Central

    Gao, Hui-Ming; Hong, Jau-Shyong

    2016-01-01

    Neurodegenerative diseases are a group of chronic, progressive disorders characterized by the gradual loss of neurons in discrete areas of the central nervous system (CNS). The mechanism(s) underlying their progressive nature remains unknown but a timely and well-controlled inflammatory reaction is essential for the integrity and proper function of the CNS. Substantial evidence has documented a common inflammatory mechanism in various neurodegenerative diseases. We hypothesize that in the diseased CNS, interactions between damaged neurons and dysregulated, overactivated microglia create a vicious self-propagating cycle causing uncontrolled, prolonged inflammation that drives the chronic progression of neurodegenerative diseases. We further propose that dynamic modulation of this inflammatory reaction by interrupting the vicious cycle might become a disease-modifying therapeutic strategy for neurodegenerative diseases. PMID:18599350

  7. Learning numerical progressions.

    PubMed

    Vitz, P C; Hazan, D N

    1974-01-01

    Learning of simple numerical progressions and compound progressions formed by combining two or three simple progressions is investigated. In two experiments, time to solution was greater for compound vs simple progressions; greater the higher the progression's solution level; and greater if the progression consisted of large vs small numbers. A set of strategies is proposed to account for progression learning based on the assumption S computes differences between integers, differences between differences, etc., in a hierarchical fashion. Two measures of progression difficulty, each a summary of the strategies, are proposed; C1 is a count of the number of differences needed to solve a progression; C2 is the same count with higher level differences given more weight. The measures accurately predict in both experiments the mean time to solve 16 different progressions with C2 being somewhat superior. The measures also predict the learning difficulty of 10 other progressions reported by Bjork (1968).

  8. Microorganisms meet solid minerals: interactions and biotechnological applications.

    PubMed

    Ng, Daphne H P; Kumar, Amit; Cao, Bin

    2016-08-01

    In natural and engineered environments, microorganisms often co-exist and interact with various minerals or mineral-containing solids. Microorganism-mineral interactions contribute significantly to environmental processes, including biogeochemical cycles in natural ecosystems and biodeterioration of materials in engineered environments. In this mini-review, we provide a summary of several key mechanisms involved in microorganism-mineral interactions, including the following: (i) solid minerals serve as substrata for biofilm development; (ii) solid minerals serve as an electron source or sink for microbial respiration; (iii) solid minerals provide microorganisms with macro or micronutrients for cell growth; and (iv) (semi)conductive solid minerals serve as extracellular electron conduits facilitating cell-to-cell interactions. We also highlight recent developments in harnessing microbe-mineral interactions for biotechnological applications. PMID:27338573

  9. Microorganisms meet solid minerals: interactions and biotechnological applications.

    PubMed

    Ng, Daphne H P; Kumar, Amit; Cao, Bin

    2016-08-01

    In natural and engineered environments, microorganisms often co-exist and interact with various minerals or mineral-containing solids. Microorganism-mineral interactions contribute significantly to environmental processes, including biogeochemical cycles in natural ecosystems and biodeterioration of materials in engineered environments. In this mini-review, we provide a summary of several key mechanisms involved in microorganism-mineral interactions, including the following: (i) solid minerals serve as substrata for biofilm development; (ii) solid minerals serve as an electron source or sink for microbial respiration; (iii) solid minerals provide microorganisms with macro or micronutrients for cell growth; and (iv) (semi)conductive solid minerals serve as extracellular electron conduits facilitating cell-to-cell interactions. We also highlight recent developments in harnessing microbe-mineral interactions for biotechnological applications.

  10. Progressive Pigmentary Purpura

    MedlinePlus

    ... Category: Share: Yes No, Keep Private Progressive Pigmentary Purpura Share | Progressive pigmentary purpura (we will call it PPP) is a group ... conditions ( Schamberg's disease , Lichenoid dermatitis of Gourgerot-Blum, purpura annularis telangiectodes of Majocchi and Lichen aureus). Schamberg's ...

  11. Cancer progression modeling using static sample data.

    PubMed

    Sun, Yijun; Yao, Jin; Nowak, Norma J; Goodison, Steve

    2014-01-01

    As molecular profiling data continues to accumulate, the design of integrative computational analyses that can provide insights into the dynamic aspects of cancer progression becomes feasible. Here, we present a novel computational method for the construction of cancer progression models based on the analysis of static tumor samples. We demonstrate the reliability of the method with simulated data, and describe the application to breast cancer data. Our findings support a linear, branching model for breast cancer progression. An interactive model facilitates the identification of key molecular events in the advance of disease to malignancy.

  12. Environmental and radiological-safety studies: interaction of /sup 238/PuO/sub 2/ heat sources with terrestrial and aquatic environments. Progress report, January 1-March 31, 1982

    SciTech Connect

    Matlack, G.M.; Patterson, J.H.

    1982-06-01

    Although existing radioisotope thermoelectric generator designs have proved more than adequately safe, more information is continually sought about the heat sources to improve their safety. The work here includes studies of the effects on the heat sources of terrestrial and aquatic environments and also of the effects of the heat sources on various simulated environments. This progress report presents recent data from environmental chamber and aquatic experiments and gives the present status of the experiments.

  13. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation.

    PubMed

    Calafate, Sara; Buist, Arjan; Miskiewicz, Katarzyna; Vijayan, Vinoy; Daneels, Guy; de Strooper, Bart; de Wit, Joris; Verstreken, Patrik; Moechars, Diederik

    2015-05-26

    Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer's disease (AD). Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.

  14. Small Talk: Cell-to-Cell Communication in Bacteria

    ScienceCinema

    Bassler, Bonnie [Princeton University, Princeton, New Jersey, United States

    2016-07-12

    Cell-cell communication in bacteria involves the production, release, and subsequent detection of chemical signaling molecules called autoinducers. This process, called quorum sensing, allows bacteria to regulate gene expression on a population-wide scale. Processes controlled by quorum sensing are usually ones that are unproductive when undertaken by an individual bacterium but become effective when undertaken by the group. For example, quorum sensing controls bioluminescence, secretion of virulence factors, biofilm formation, sporulation, and the exchange of DNA. Thus, quorum sensing is a mechanism that allows bacteria to function as multi-cellular organisms. Bacteria make, detect, and integrate information from multiple autoinducers, some of which are used exclusively for intra-species communication while others enable communication between species. Research is now focused on the development of therapies that interfere with quorum sensing to control bacterial virulence.

  15. Small Talk: Cell-to-Cell Communication in Bacteria

    SciTech Connect

    Bassler, Bonnie

    2008-05-14

    Cell-cell communication in bacteria involves the production, release, and subsequent detection of chemical signaling molecules called autoinducers. This process, called quorum sensing, allows bacteria to regulate gene expression on a population-wide scale. Processes controlled by quorum sensing are usually ones that are unproductive when undertaken by an individual bacterium but become effective when undertaken by the group. For example, quorum sensing controls bioluminescence, secretion of virulence factors, biofilm formation, sporulation, and the exchange of DNA. Thus, quorum sensing is a mechanism that allows bacteria to function as multi-cellular organisms. Bacteria make, detect, and integrate information from multiple autoinducers, some of which are used exclusively for intra-species communication while others enable communication between species. Research is now focused on the development of therapies that interfere with quorum sensing to control bacterial virulence.

  16. Small Talk: Cell-to-Cell Communication in Bacteria

    SciTech Connect

    Bassler, Bonnie

    2008-12-03

    Cell-cell communication in bacteria involves the production, release, and subsequent detection of chemical signaling molecules called autoinducers. This process, called quorum sensing, allows bacteria to regulate gene expression on a population-wide scale. Processes controlled by quorum sensing are usually ones that are unproductive when undertaken by an individual bacterium but become effective when undertaken by the group. For example, quorum sensing controls bioluminescence, secretion of virulence factors, biofilm formation, sporulation, and the exchange of DNA. Thus, quorum sensing is a mechanism that allows bacteria to function as multi-cellular organisms. Bacteria make, detect, and integrate information from multiple autoinducers, some of which are used exclusively for intra-species communication while others enable communication between species. Research is now focused on the development of therapies that interfere with quorum sensing to control bacterial virulence.

  17. Cell-to-cell propagation of infectious cytosolic protein aggregates

    PubMed Central

    Hofmann, Julia P.; Denner, Philip; Nussbaum-Krammer, Carmen; Kuhn, Peer-Hendrik; Suhre, Michael H.; Scheibel, Thomas; Lichtenthaler, Stefan F.; Schätzl, Hermann M.; Bano, Daniele; Vorberg, Ina M.

    2013-01-01

    Prions are self-templating protein conformers that replicate by recruitment and conversion of homotypic proteins into growing protein aggregates. Originally identified as causative agents of transmissible spongiform encephalopathies, increasing evidence now suggests that prion-like phenomena are more common in nature than previously anticipated. In contrast to fungal prions that replicate in the cytoplasm, propagation of mammalian prions derived from the precursor protein PrP is confined to the cell membrane or endocytic vesicles. Here we demonstrate that cytosolic protein aggregates can also behave as infectious entities in mammalian cells. When expressed in the mammalian cytosol, protein aggregates derived from the prion domain NM of yeast translation termination factor Sup35 persistently propagate and invade neighboring cells, thereby inducing a self-perpetuating aggregation state of NM. Cell contact is required for efficient infection. Aggregates can also be induced in primary astrocytes, neurons, and organotypic cultures, demonstrating that this phenomenon is not specific to immortalized cells. Our data have important implications for understanding prion-like phenomena of protein aggregates associated with human diseases and for the growing number of amyloidogenic proteins discovered in mammals. PMID:23509289

  18. A new X-ray-transparent flow-through reaction cell for a μ-CT-based concomitant surveillance of the reaction progress of hydrothermal mineral-fluid interactions

    NASA Astrophysics Data System (ADS)

    Kahl, Wolf-Achim; Hansen, Christian; Bach, Wolfgang

    2016-04-01

    A new flow-through reaction cell consisting of an X-ray-transparent semicrystalline thermoplastic has been developed for percolation experiments. Core holder, tubing and all confining parts are constructed using PEEK (polyetheretherketone) to allow concomitant surveillance of the reaction progress by X-ray microtomography (μ-CT). With this cell setup, corrosive or oversaturated fluids can be forced through rock cores (up to ∅ 19 mm) or powders at pressures up to 100 bar and temperatures up to 200 °C. The reaction progress of the experiment can be monitored without dismantling the sample from the core holder. The combination of this flow-through reaction cell setup with a laboratory X-ray μ-CT system facilitates on-demand monitoring of the reaction progress of (long-term) hydrothermal experiments in the own laboratory, keeping interruption times as short as possible. To demonstrate both the suitability of the cell construction material for X-ray imaging purposes and the experimental performance of the flow-through system, we report the virtually non-existent bias of the PEEK cell setup with distinctive X-ray observations (e.g., differing states of pore fillings: air vs. fluid; detection of delicate fabric elements: filigree zeolite crystals overgrowing weathered muscovite), and the monitoring of the gypsum/anhydrite transition as a case study of a 4-D fabric evolution.

  19. Progress in front propagation research

    NASA Astrophysics Data System (ADS)

    Fort, Joaquim; Pujol, Toni

    2008-08-01

    We review the progress in the field of front propagation in recent years. We survey many physical, biophysical and cross-disciplinary applications, including reduced-variable models of combustion flames, Reid's paradox of rapid forest range expansions, the European colonization of North America during the 19th century, the Neolithic transition in Europe from 13 000 to 5000 years ago, the description of subsistence boundaries, the formation of cultural boundaries, the spread of genetic mutations, theory and experiments on virus infections, models of cancer tumors, etc. Recent theoretical advances are unified in a single framework, encompassing very diverse systems such as those with biased random walks, distributed delays, sequential reaction and dispersion, cohabitation models, age structure and systems with several interacting species. Directions for future progress are outlined.

  20. Cultural Neuroscience: Progress and Promise

    PubMed Central

    Chiao, Joan Y.; Cheon, Bobby K.; Pornpattanangkul, Narun; Mrazek, Alissa J.; Blizinsky, Katherine D.

    2013-01-01

    The nature and origin of human diversity has been a source of intellectual curiosity since the beginning of human history. Contemporary advances in cultural and biological sciences provide unique opportunities for the emerging field of cultural neuroscience. Research in cultural neuroscience examines how cultural and genetic diversity shape the human mind, brain and behavior across multiple time scales: situation, ontogeny and phylogeny. Recent progress in cultural neuroscience provides novel theoretical frameworks for understanding the complex interaction of environmental, cultural and genetic factors in the production of adaptive human behavior. Here, we provide a brief history of cultural neuroscience, theoretical and methodological advances, as well as empirical evidence of the promise of and progress in the field. Implications of this research for population health disparities and public policy are discussed. PMID:23914126

  1. Evolutionary Game Theory Analysis of Tumor Progression

    NASA Astrophysics Data System (ADS)

    Wu, Amy; Liao, David; Sturm, James; Austin, Robert

    2014-03-01

    Evolutionary game theory applied to two interacting cell populations can yield quantitative prediction of the future densities of the two cell populations based on the initial interaction terms. We will discuss how in a complex ecology that evolutionary game theory successfully predicts the future densities of strains of stromal and cancer cells (multiple myeloma), and discuss the possible clinical use of such analysis for predicting cancer progression. Supported by the National Science Foundation and the National Cancer Institute.

  2. Progress in MELCOR development and assessment

    SciTech Connect

    Summers, R.M.; Kmetyk, L.N.; Cole, R.K. Jr.; Smith, R.C.; Elsbernd, A.E.; Stuart, D.S.; Thompson, S.L.

    1995-04-01

    MELCOR models the progression of severe accidents in light water reactor nuclear power plants. Recent efforts in MELCOR development to incorporate CORCON-Mod3 models for core-concrete interactions, new models for advanced reactors, and improvements to several other existing models have resulted in release of MELCOR 1.8.3. In addition, continuing efforts to expand the code assessment database have filled in many of the gaps in phenomenological coverage. Efforts are now under way to develop models for chemical interactions of fission products with structural surfaces and for reactions of iodine in the presence of water, and work is also in progress to improve models for the scrubbing of fission products by water pools, the chemical reactions of boron carbide with steam, and the coupling of flow blockages with the hydrodynamics. Several code assessment analyses are in progress, and more are planned.

  3. Information Loss from Technological Progress

    NASA Astrophysics Data System (ADS)

    Townsend, P. D.

    2014-12-01

    Progress in electronics and optics offers faster computers, and rapid communication via the internet that is matched by ever larger and evolving storage systems. Instinctively one assumes that this must be totally beneficial. However advances in software and storage media are progressing in ways which are frequently incompatible with earlier systems and the economics and commercial pressures rarely guarantee total compatibility with earlier systems. Instead, the industries actively choose to force the users to purchase new systems and software. Thus we are moving forward with new technological variants that may have access to only the most recent systems and we will have lost earlier alternatives. The reality is that increased processing speed and storage capacity are matched by an equally rapid decline in the access and survival lifetime of older information. This pattern is not limited to modern electronic systems but is evident throughout history from writing on stone and clay tablets to papyrus and paper. It is equally evident in image systems from painting, through film, to magnetic tapes and digital cameras. In sound recording we have variously progressed from wax discs to vinyl, magnetic tape and CD formats. In each case the need for better definition and greater capacity has forced the earlier systems into oblivion. Indeed proposed interactive music systems could similarly relegate music CDs to specialist collections. The article will track some of the examples and discuss the consequences as well as noting that this information loss is further compounded by developments in language and changes in cultural views of different societies.

  4. The Science of Interaction

    SciTech Connect

    Pike, William A.; Stasko, John T.; Chang, Remco; O'Connell, Theresa

    2009-09-23

    There is a growing recognition with the visual analytics community that interaction and inquiry are inextricable. It is through the interactive manipulation of a visual interface – the analytic discourse – that knowledge is constructed, tested, refined, and shared. This paper reflects on the interaction challenges raised in the original visual analytics research and development agenda and further explores the relationship between interaction and cognition. It identifies recent exemplars of visual analytics research that have made substantive progress toward the goals of a true science of interaction, which must include theories and testable premises about the most appropriate mechanisms for human-information interaction. Six areas for further work are highlighted as those among the highest priorities for the next five years of visual analytics research: ubiquitous, embodied interaction; capturing user intentionality; knowledge-based interfaces; principles of design and perception; collaboration; and interoperability. Ultimately, the goal of a science of interaction is to support the visual analytics community through the recognition and implementation of best practices in the representation of and interaction with visual displays.

  5. On disciplinary fragmentation and scientific progress.

    PubMed

    Balietti, Stefano; Mäs, Michael; Helbing, Dirk

    2015-01-01

    Why are some scientific disciplines, such as sociology and psychology, more fragmented into conflicting schools of thought than other fields, such as physics and biology? Furthermore, why does high fragmentation tend to coincide with limited scientific progress? We analyzed a formal model where scientists seek to identify the correct answer to a research question. Each scientist is influenced by three forces: (i) signals received from the correct answer to the question; (ii) peer influence; and (iii) noise. We observed the emergence of different macroscopic patterns of collective exploration, and studied how the three forces affect the degree to which disciplines fall apart into divergent fragments, or so-called "schools of thought". We conducted two simulation experiments where we tested (A) whether the three forces foster or hamper progress, and (B) whether disciplinary fragmentation causally affects scientific progress and vice versa. We found that fragmentation critically limits scientific progress. Strikingly, there is no effect in the opposite causal direction. What is more, our results shows that at the heart of the mechanisms driving scientific progress we find (i) social interactions, and (ii) peer disagreement. In fact, fragmentation is increased and progress limited if the simulated scientists are open to influence only by peers with very similar views, or when within-school diversity is lost. Finally, disciplines where the scientists received strong signals from the correct answer were less fragmented and experienced faster progress. We discuss model's implications for the design of social institutions fostering interdisciplinarity and participation in science.

  6. On Disciplinary Fragmentation and Scientific Progress

    PubMed Central

    Balietti, Stefano; Mäs, Michael; Helbing, Dirk

    2015-01-01

    Why are some scientific disciplines, such as sociology and psychology, more fragmented into conflicting schools of thought than other fields, such as physics and biology? Furthermore, why does high fragmentation tend to coincide with limited scientific progress? We analyzed a formal model where scientists seek to identify the correct answer to a research question. Each scientist is influenced by three forces: (i) signals received from the correct answer to the question; (ii) peer influence; and (iii) noise. We observed the emergence of different macroscopic patterns of collective exploration, and studied how the three forces affect the degree to which disciplines fall apart into divergent fragments, or so-called “schools of thought”. We conducted two simulation experiments where we tested (A) whether the three forces foster or hamper progress, and (B) whether disciplinary fragmentation causally affects scientific progress and vice versa. We found that fragmentation critically limits scientific progress. Strikingly, there is no effect in the opposite causal direction. What is more, our results shows that at the heart of the mechanisms driving scientific progress we find (i) social interactions, and (ii) peer disagreement. In fact, fragmentation is increased and progress limited if the simulated scientists are open to influence only by peers with very similar views, or when within-school diversity is lost. Finally, disciplines where the scientists received strong signals from the correct answer were less fragmented and experienced faster progress. We discuss model’s implications for the design of social institutions fostering interdisciplinarity and participation in science. PMID:25790025

  7. Intra-Testicular Signals Regulate Germ Cell Progression and Production of Qualitatively Mature Spermatozoa in Vertebrates

    PubMed Central

    Meccariello, Rosaria; Chianese, Rosanna; Chioccarelli, Teresa; Ciaramella, Vincenza; Fasano, Silvia; Pierantoni, Riccardo; Cobellis, Gilda

    2014-01-01

    Spermatogenesis, a highly conserved process in vertebrates, is mainly under the hypothalamic–pituitary control, being regulated by the secretion of pituitary gonadotropins, follicle stimulating hormone, and luteinizing hormone, in response to stimulation exerted by gonadotropin releasing hormone from hypothalamic neurons. At testicular level, gonadotropins bind specific receptors located on the somatic cells regulating the production of steroids and factors necessary to ensure a correct spermatogenesis. Indeed, besides the endocrine route, a complex network of cell-to-cell communications regulates germ cell progression, and a combination of endocrine and intra-gonadal signals sustains the production of high quality mature spermatozoa. In this review, we focus on the recent advances in the area of the intra-gonadal signals supporting sperm development. PMID:24847312

  8. Recent Progress in Isospin Physics with Heavy-Ion Reactions

    SciTech Connect

    Chen Liewen; Ko, Che Ming; Li Baoan

    2008-11-11

    We review recent progress in the determination of the subsaturation density behavior of the nuclear symmetry energy from heavy-ion collisions as well as the theoretical progress in probing the high density behavior of the symmetry energy in heavy-ion reactions induced by future high energy radioactive beams. Implications of these results for the nuclear effective interactions are also discussed.

  9. Glycan:glycan interactions: High affinity biomolecular interactions that can mediate binding of pathogenic bacteria to host cells

    PubMed Central

    Day, Christopher J.; Tran, Elizabeth N.; Semchenko, Evgeny A.; Tram, Greg; Hartley-Tassell, Lauren E.; Ng, Preston S. K.; King, Rebecca M.; Ulanovsky, Rachel; McAtamney, Sarah; Apicella, Michael A.; Tiralongo, Joe; Morona, Renato; Korolik, Victoria; Jennings, Michael P.

    2015-01-01

    Cells from all domains of life express glycan structures attached to lipids and proteins on their surface, called glycoconjugates. Cell-to-cell contact mediated by glycan:glycan interactions have been considered to be low-affinity interactions that precede high-affinity protein–glycan or protein–protein interactions. In several pathogenic bacteria, truncation of surface glycans, lipooligosaccharide (LOS), or lipopolysaccharide (LPS) have been reported to significantly reduce bacterial adherence to host cells. Here, we show that the saccharide component of LOS/LPS have direct, high-affinity interactions with host glycans. Glycan microarrays reveal that LOS/LPS of four distinct bacterial pathogens bind to numerous host glycan structures. Surface plasmon resonance was used to determine the affinity of these interactions and revealed 66 high-affinity host–glycan:bacterial–glycan pairs with equilibrium dissociation constants (KD) ranging between 100 nM and 50 µM. These glycan:glycan affinity values are similar to those reported for lectins or antibodies with glycans. Cell assays demonstrated that glycan:glycan interaction-mediated bacterial adherence could be competitively inhibited by either host cell or bacterial glycans. This is the first report to our knowledge of high affinity glycan:glycan interactions between bacterial pathogens and the host. The discovery of large numbers of glycan:glycan interactions between a diverse range of structures suggests that these interactions may be important in all biological systems. PMID:26676578

  10. Glycan:glycan interactions: High affinity biomolecular interactions that can mediate binding of pathogenic bacteria to host cells.

    PubMed

    Day, Christopher J; Tran, Elizabeth N; Semchenko, Evgeny A; Tram, Greg; Hartley-Tassell, Lauren E; Ng, Preston S K; King, Rebecca M; Ulanovsky, Rachel; McAtamney, Sarah; Apicella, Michael A; Tiralongo, Joe; Morona, Renato; Korolik, Victoria; Jennings, Michael P

    2015-12-29

    Cells from all domains of life express glycan structures attached to lipids and proteins on their surface, called glycoconjugates. Cell-to-cell contact mediated by glycan:glycan interactions have been considered to be low-affinity interactions that precede high-affinity protein-glycan or protein-protein interactions. In several pathogenic bacteria, truncation of surface glycans, lipooligosaccharide (LOS), or lipopolysaccharide (LPS) have been reported to significantly reduce bacterial adherence to host cells. Here, we show that the saccharide component of LOS/LPS have direct, high-affinity interactions with host glycans. Glycan microarrays reveal that LOS/LPS of four distinct bacterial pathogens bind to numerous host glycan structures. Surface plasmon resonance was used to determine the affinity of these interactions and revealed 66 high-affinity host-glycan:bacterial-glycan pairs with equilibrium dissociation constants (K(D)) ranging between 100 nM and 50 µM. These glycan:glycan affinity values are similar to those reported for lectins or antibodies with glycans. Cell assays demonstrated that glycan:glycan interaction-mediated bacterial adherence could be competitively inhibited by either host cell or bacterial glycans. This is the first report to our knowledge of high affinity glycan:glycan interactions between bacterial pathogens and the host. The discovery of large numbers of glycan:glycan interactions between a diverse range of structures suggests that these interactions may be important in all biological systems. PMID:26676578

  11. RLKs orchestrate the signaling in plant male-female interaction.

    PubMed

    Li, Hongju; Yang, Wei-Cai

    2016-09-01

    Different from animals, sessile plants are equipped with a large receptor-like kinase (RLK) superfamily. RLKs are a family of single trans-membrane proteins with divergent N-terminal extracellular domains capped by a signal peptide and C-terminal intracellular kinase. Researches in the last two decades have uncovered an increasing number of RLKs that regulate plant development, stress response and sexual reproduction, highlighting a dominant role of RLK signaling in cell-to-cell communications. Sexual reproduction in flowering plants is featured by interactions between the male gametophyte and the female tissues to facilitate sperm delivery and fertilization. Emerging evidences suggest that RLKs regulate almost every aspect of plant reproductive process, especially during pollination. Therefore, in this review we will focus mainly on the function and signaling of RLKs in plant male-female interaction and discuss the future prospects on these topics. PMID:27525988

  12. Connexin's Connection in Breast Cancer Growth and Progression

    PubMed Central

    2016-01-01

    Gap junctions are cell-to-cell junctions that are located in the basolateral surface of two adjoining cells. A gap junction channel is composed of a family of proteins called connexins. Gap junction channels maintain intercellular communication between two cells through the exchange of ions, small metabolites, and electrical signals. Gap junction channels or connexins are widespread in terms of their expression and function in maintaining the development, differentiation, and homeostasis of vertebrate tissues. Gap junction connexins play a major role in maintaining intercellular communication among different cell types of normal mammary gland for proper development and homeostasis. Connexins have also been implicated in the pathogenesis of breast cancer. Differential expression pattern of connexins and their gap junction dependent or independent functions provide pivotal cross talk of breast tumor cells with the surrounding stromal cell in the microenvironment. Substantial research from the last 20 years has accumulated ample evidences that allow us a better understanding of the roles that connexins play in the tumorigenesis of primary breast tumor and its metastatic progression. This review will summarize the knowledge about the connexins and gap junction activities in breast cancer highlighting the differential expression and functional dynamics of connexins in the pathogenesis of the disease. PMID:27642298

  13. Connexin's Connection in Breast Cancer Growth and Progression

    PubMed Central

    2016-01-01

    Gap junctions are cell-to-cell junctions that are located in the basolateral surface of two adjoining cells. A gap junction channel is composed of a family of proteins called connexins. Gap junction channels maintain intercellular communication between two cells through the exchange of ions, small metabolites, and electrical signals. Gap junction channels or connexins are widespread in terms of their expression and function in maintaining the development, differentiation, and homeostasis of vertebrate tissues. Gap junction connexins play a major role in maintaining intercellular communication among different cell types of normal mammary gland for proper development and homeostasis. Connexins have also been implicated in the pathogenesis of breast cancer. Differential expression pattern of connexins and their gap junction dependent or independent functions provide pivotal cross talk of breast tumor cells with the surrounding stromal cell in the microenvironment. Substantial research from the last 20 years has accumulated ample evidences that allow us a better understanding of the roles that connexins play in the tumorigenesis of primary breast tumor and its metastatic progression. This review will summarize the knowledge about the connexins and gap junction activities in breast cancer highlighting the differential expression and functional dynamics of connexins in the pathogenesis of the disease.

  14. Connexin's Connection in Breast Cancer Growth and Progression.

    PubMed

    Banerjee, Debarshi

    2016-01-01

    Gap junctions are cell-to-cell junctions that are located in the basolateral surface of two adjoining cells. A gap junction channel is composed of a family of proteins called connexins. Gap junction channels maintain intercellular communication between two cells through the exchange of ions, small metabolites, and electrical signals. Gap junction channels or connexins are widespread in terms of their expression and function in maintaining the development, differentiation, and homeostasis of vertebrate tissues. Gap junction connexins play a major role in maintaining intercellular communication among different cell types of normal mammary gland for proper development and homeostasis. Connexins have also been implicated in the pathogenesis of breast cancer. Differential expression pattern of connexins and their gap junction dependent or independent functions provide pivotal cross talk of breast tumor cells with the surrounding stromal cell in the microenvironment. Substantial research from the last 20 years has accumulated ample evidences that allow us a better understanding of the roles that connexins play in the tumorigenesis of primary breast tumor and its metastatic progression. This review will summarize the knowledge about the connexins and gap junction activities in breast cancer highlighting the differential expression and functional dynamics of connexins in the pathogenesis of the disease. PMID:27642298

  15. Characterization of calculation of in-situ retardation factors of contaminant transport using naturally-radionuclides and rock/water interaction occurring U-Series disequilibria timescales. 1997 annual progress report

    SciTech Connect

    Roback, R.; Murrel, M.; Goldstein, S.; Ku, T.L.; Luo, S.

    1997-01-01

    'The research is directed toward a quantitative assessment of contaminant transport rates in fracture-rock systems using uranium-series radionuclides. Naturally occurring uranium-and thorium-series radioactive disequilibria will provide information on the rates of adsorption-desorption and transport of radioactive contaminants as well as on fluid transport and rock dissolution in a natural setting. This study will also provide an improved characterization of preferential flow and contaminant transport at the Idaho Environmental and Engineering Lab. (INEEL) site. To a lesser extent, the study will include rocks in the unsaturated zone. The authors will produce a realistic model of radionuclide migration under unsaturated and saturated field conditions at the INEEL site, taking into account the retardation processes involved in the rock/water interaction. The major tasks are to (1) determine the natural distribution of U, Th, Pa and Ra isotopes in rock minerals. sorbed phases on the rocks, and in fluids from both saturated and unsaturated zones at the site, and (2) study rock/water interaction processes using U/Th series disequilibrium and a statistical analysis-based model for the Geologic heterogeneity plays an important role in transporting contaminants in fractured rocks. Preferential flow paths in the fractured rocks act as a major pathway for transport of radioactive contaminants in groundwaters. The weathering/dissolution of rock by groundwater also influences contaminant mobility. Thus, it is important to understand the hydrogeologic features of the site and their impact on the migration of radioactive contaminants. In this regard, quantification of the rock weathering/dissolution rate and fluid residence time from the observed decay-series disequilibria will be valuable. By mapping the spatial distribution of the residence time of groundwater in fractured rocks, the subsurface preferential flow paths (with high rock permeability and short fluid residence

  16. Artemisinin blocks prostate cancer growth and cell cycle progression by disrupting Sp1 interactions with the cyclin-dependent kinase-4 (CDK4) promoter and inhibiting CDK4 gene expression.

    PubMed

    Willoughby, Jamin A; Sundar, Shyam N; Cheung, Mark; Tin, Antony S; Modiano, Jaime; Firestone, Gary L

    2009-01-23

    Artemisinin, a naturally occurring component of Artemisia annua, or sweet wormwood, is a potent anti-malaria compound that has recently been shown to have anti-proliferative effects on a number of human cancer cell types, although little is know about the molecular mechanisms of this response. We have observed that artemisinin treatment triggers a stringent G1 cell cycle arrest of LNCaP (lymph node carcinoma of the prostate) human prostate cancer cells that is accompanied by a rapid down-regulation of CDK2 and CDK4 protein and transcript levels. Transient transfection with promoter-linked luciferase reporter plasmids revealed that artemisinin strongly inhibits CDK2 and CDK4 promoter activity. Deletion analysis of the CDK4 promoter revealed a 231-bp artemisinin-responsive region between -1737 and -1506. Site-specific mutations revealed that the Sp1 site at -1531 was necessary for artemisinin responsiveness in the context of the CDK4 promoter. DNA binding assays as well as chromatin immunoprecipitation assays demonstrated that this Sp1-binding site in the CDK4 promoter forms a specific artemisinin-responsive DNA-protein complex that contains the Sp1 transcription factor. Artemisinin reduced phosphorylation of Sp1, and when dephosphorylation of Sp1 was inhibited by treatment of cells with the phosphatase inhibitor okadaic acid, the ability of artemisinin to down-regulate Sp1 interactions with the CDK4 promoter was ablated, rendering the CDK4 promoter unresponsive to artemisinin. Finally, overexpression of Sp1 mostly reversed the artemisinin down-regulation of CDK4 promoter activity and partially reversed the cell cycle arrest. Taken together, our results demonstrate that a key event in the artemisinin anti-proliferative effects in prostate cancer cells is the transcriptional down-regulation of CDK4 expression by disruption of Sp1 interactions with the CDK4 promoter. PMID:19017637

  17. Artemisinin Blocks Prostate Cancer Growth and Cell Cycle Progression by Disrupting Sp1 Interactions with the Cyclin-dependent Kinase-4 (CDK4) Promoter and Inhibiting CDK4 Gene Expression*

    PubMed Central

    Willoughby, Jamin A.; Sundar, Shyam N.; Cheung, Mark; Tin, Antony S.; Modiano, Jaime; Firestone, Gary L.

    2009-01-01

    Artemisinin, a naturally occurring component of Artemisia annua, or sweet wormwood, is a potent anti-malaria compound that has recently been shown to have anti-proliferative effects on a number of human cancer cell types, although little is know about the molecular mechanisms of this response. We have observed that artemisinin treatment triggers a stringent G1 cell cycle arrest of LNCaP (lymph node carcinoma of the prostate) human prostate cancer cells that is accompanied by a rapid down-regulation of CDK2 and CDK4 protein and transcript levels. Transient transfection with promoter-linked luciferase reporter plasmids revealed that artemisinin strongly inhibits CDK2 and CDK4 promoter activity. Deletion analysis of the CDK4 promoter revealed a 231-bp artemisinin-responsive region between -1737 and -1506. Site-specific mutations revealed that the Sp1 site at -1531 was necessary for artemisinin responsiveness in the context of the CDK4 promoter. DNA binding assays as well as chromatin immunoprecipitation assays demonstrated that this Sp1-binding site in the CDK4 promoter forms a specific artemisinin-responsive DNA-protein complex that contains the Sp1 transcription factor. Artemisinin reduced phosphorylation of Sp1, and when dephosphorylation of Sp1 was inhibited by treatment of cells with the phosphatase inhibitor okadaic acid, the ability of artemisinin to down-regulate Sp1 interactions with the CDK4 promoter was ablated, rendering the CDK4 promoter unresponsive to artemisinin. Finally, overexpression of Sp1 mostly reversed the artemisinin down-regulation of CDK4 promoter activity and partially reversed the cell cycle arrest. Taken together, our results demonstrate that a key event in the artemisinin anti-proliferative effects in prostate cancer cells is the transcriptional down-regulation of CDK4 expression by disruption of Sp1 interactions with the CDK4 promoter. PMID:19017637

  18. Progress in renewables

    NASA Astrophysics Data System (ADS)

    San Martin, R. L.

    This is a status report on progress made in the conduct of eleven Federally-supported renewable energy programs. Considerable progress has been made in the establishment and development of an infrastructure to support sustained growth. Unique technical problems led to the research and development of materials and designs which have achieved energy conversion efficiencies of up to 25% for electricity and 92% for heat in solar thermal systems. Overall, enough real progress has been made to provide a sound technology base upon which renewable energy systems industries can reasonably continue development.

  19. Rapidly Progressive Dementia

    PubMed Central

    Geschwind, Michael D.; Shu, Huidy; Haman, Aissa; Sejvar, James J.; Miller, Bruce L.

    2009-01-01

    In contrast with more common dementing conditions that typically develop over years, rapidly progressive dementias can develop subacutely over months, weeks, or even days and be quickly fatal. Because many rapidly progressive dementias are treatable, it is paramount to evaluate and diagnose these patients quickly. This review summarizes recent advances in the understanding of the major categories of RPD and outlines efficient approaches to the diagnosis of the various neurodegenerative, toxic-metabolic, infectious, autoimmune, neoplastic, and other conditions that may progress rapidly. PMID:18668637

  20. Progress and promise.

    PubMed

    Kamphaus, Randy W

    2012-12-01

    This editorial introduces the current issue of the journal School Psychology Quarterly (SPQ).There has been an impressive and promising progress of school psychology science has been reflected in every issue of SPQ, including the current one.

  1. Progressive hemifacial atrophy

    PubMed Central

    Sande, Abhijeet; Risbud, Mukund; Kshar, Avinash; Paranjpe, Arati Oka

    2013-01-01

    Progressive hemifacial atrophy, also known as Parry-Romberg Syndrome, is an uncommon degenerative and poorly understood condition. It is characterized by a slow and progressive but self-limited atrophy affecting one side of the face. The incidence and the cause of this alteration are unknown. A cerebral disturbance of fat metabolism has been proposed as a primary cause. Possible factors that are involved in the pathogenesis include trauma, viral infections, heredity, endocrine disturbances and auto-immunity. The most common complications that appear in association to this disorder are: trigeminal neuralgia, facial paresthesia, severe headache and epilepsy. Characteristically, the atrophy progresses slowly for several years and, it becomes stable. The objective of this work is, through the presentation of a clinical case, to accomplish a literature review concerning general characteristics, etiology, physiopathology and treatment of progressive hemifacial atrophy. PMID:23878573

  2. Orion Progress - Spring 2010

    NASA Video Gallery

    NASA and contractor teams are designing, building and testing the next generation human spacecraft Orion. Progress on Orion is highlighted by employees working on the project, along with video of t...

  3. Comparison of spectacle classical progressive and office progressive lenses.

    PubMed

    Kozlík, Marek; Knollová, Libuse Nováková

    2013-04-01

    This paper elaborates on analysis of progressive spectacle lenses, to correct presbyopia, which are nowadays offered at the market. The paper describes different types of progressive lenses, their parameters, length and width of their progressive segments. It also describes degressive spectacles lenses--progressive lenses on middle and near distance. The main part of the paper is a comparison of functional differences among different types of progressive spectacles lenses. The paper also addresses correctness of choice of progressive lenses for different works and professions. Lastly, it elaborates on differences of centration of different types of progressive lenses and parameters for correct choice of glasses frame for progressive spectacles lenses. PMID:23837232

  4. [Progressive visual agnosia].

    PubMed

    Sugimoto, Azusa; Futamura, Akinori; Kawamura, Mitsuru

    2011-10-01

    Progressive visual agnosia was discovered in the 20th century following the discovery of classical non-progressive visual agnosia. In contrast to the classical type, which is caused by cerebral vascular disease or traumatic injury, progressive visual agnosia is a symptom of neurological degeneration. The condition of progressive visual loss, including visual agnosia, and posterior cerebral atrophy was named posterior cortical atrophy (PCA) by Benson et al. (1988). Progressive visual agnosia is also observed in semantic dementia (SD) and other degenerative diseases, but there is a difference in the subtype of visual agnosia associated with these diseases. Lissauer (1890) classified visual agnosia into apperceptive and associative types, and it in most cases, PCA is associated with the apperceptive type. However, SD patients exhibit symptoms of associative visual agnosia before changing to those of semantic memory disorder. Insights into progressive visual agnosia have helped us understand the visual system and discover how we "perceive" the outer world neuronally, with regard to consciousness. Although PCA is a type of atypical dementia, its diagnosis is important to enable patients to live better lives with appropriate functional support.

  5. Development of a chemical kinetic measurement apparatus and the determination of the reaction rate constants for lithium-lead/water interaction. Technical status progress report, October 1, 1991--March 15, 1993

    SciTech Connect

    Biney, P.O.

    1993-04-01

    An experimental set-up for accurate measurement of hydrogen generation rate in Lithium-Lead (Li{sub 17}Pb{sub 83}) Steam or water interactions has been designed. The most important features of the design include a pneumatic actuated quick opening and closing high temperature all stainless steel valve used to control the reaction time and the placement of most measuring devices below a water line to minimize leakage of the hydrogen collected. A PC based data acquisition and control system provides remote process sequencing, acquisition and control of all major components of the set-up. Initial tests indicate that the first design objective of maintaining leakproof gas collection chamber has been achieved. Initial pressure tests indicated that the pressure drop over a time span of 30 minutes was within the tolerance of the pressure transducer used to measure the pressure (within 0.690 kPa) at a nominal system pressure of 685 kPa. The experimental system hardware, data acquisition and control programs and data analysis program have been completed, tested and are currently functional.

  6. International Study Group Progress Report

    SciTech Connect

    Raubenheimer, Tor O

    2000-07-18

    The focus of the ISG work was on advancing the accelerator design and supporting technologies. This is a complex process which involves a close interaction between theoretical analysis of the collider design and R and D progress on hardware components. The sequence of efforts took place roughly in the following order: (1) Optimization of the collider parameters and definition of system and subsystem requirements, (2) Identification of design strategies and options, and (3) Development of specific technologies to achieve these requirements. Development and testing of the required components, and R and D on manufacturing techniques have been important activities of the ISG. Experiments at the major test facilities such as the ATF at KEK and ASSET at SLAC have also played a significant role in the ISG studies.

  7. Progress towards a dengue vaccine.

    PubMed

    Webster, Daniel P; Farrar, Jeremy; Rowland-Jones, Sarah

    2009-11-01

    The spread of dengue virus throughout the tropics represents a major, rapidly growing public health problem with an estimated 2.5 billion people at risk of dengue fever and the life-threatening disease, severe dengue. A safe and effective vaccine for dengue is urgently needed. The pathogenesis of severe dengue results from a complex interaction between the virus, the host, and, at least in part, immune-mediated mechanisms. Vaccine development has been slowed by fears that immunisation might predispose individuals to the severe form of dengue infection. A pipeline of candidate vaccines now exists, including live attenuated, inactivated, chimeric, DNA, and viral-vector vaccines, some of which are at the stage of clinical testing. In this Review, we present what is understood about dengue pathogenesis and its implications for vaccine design, the progress that is being made in the development of a vaccine, and the future challenges.

  8. LIFE: Recent Developments and Progress

    SciTech Connect

    Anklam, T M

    2011-04-08

    Test results from the NIF show excellent progress toward achieving ignition. Experiments designed to verify coupling of the laser energy to the fusion target have shown that the efficiency meets that needed for ignition. Several tests with the cryogenic targets needed for ignition have been performed, and world-record neutron output produced. The National Ignition Campaign is on schedule to meet its 2012 ignition milestone, with the next phase in the campaign due to start later this month. It has been a busy and very productive year. The NIF is in full 24/7 operations and has progressed markedly in the path toward ignition. The long-standing goal of the National Ignition Campaign to demonstrate ignition by the end of FY 2012 is on track. The LIFE plant design has matured considerably, and a delivery plan established based on close interactions with vendors. National-level reviews of fusion are underway, and are due to present initial findings later this year. A value proposition has been drafted for review. The LIFE project is ready to move into the delivery phase.

  9. The Drosophila selectin furrowed mediates intercellular planar cell polarity interactions via frizzled stabilization.

    PubMed

    Chin, Mei-Ling; Mlodzik, Marek

    2013-09-16

    Establishment of planar cell polarity (PCP) in a tissue requires coordination of directional signals from cell to cell. It is thought that this is mediated by the core PCP factors, which include cell-adhesion molecules. Here, we demonstrate that furrowed, the Drosophila selectin, is required for PCP generation. Disruption of PCP in furrowed-deficient flies results from a primary defect in Fz levels and cell adhesion. Furrowed localizes at or near apical junctions, largely colocalizing with Frizzled and Flamingo (Fmi). It physically interacts with and stabilizes Frizzled, and it mediates intercellular Frizzled-Van Gogh (Vang)/Strabismus interactions, similarly to Fmi. Furrowed does so through a homophilic cell-adhesion role that is distinct from its known carbohydrate-binding function described during vertebrate blood-cell/endothelial cell interactions. Importantly, the carbohydrate function is dispensable for PCP establishment. In vivo studies suggest that Furrowed functions partially redundantly with Fmi, mediating intercellular Frizzled-Vang interactions between neighboring cells.

  10. Progressive multiple sclerosis

    PubMed Central

    Ontaneda, Daniel; Fox, Robert J.

    2015-01-01

    Purpose to Review To highlight the pathological features and clinical aspects of progressive multiple sclerosis (PMS). To highlight results of clinical trial experience to date and review ongoing clinical trials and perspective new treatment options. Explain the challenges of clinical trial design in PMS. Recent Findings MS has been identified as a chronic immune mediated disease, and the progressive phase of the disease appears to have significant neurodegenerative mechanisms. The classification of the course of PMS has been re-organized into categories of active vs. inactive inflammatory disease and the presence vs. absence of gradual disease progression. This differentiation allows clearer conceptualization of PMS and possibly even more efficient recruitment of PMS subjects into clinical trials. Clinical trial experience to date in PMS has been negative with anti-inflammatory medications used in relapsing MS. Simvastatin was recently tested in a phase II trial and showed a 43% reduction on annualized atrophy progression in secondary progressive MS. Ongoing PMS trials are currently being conducted with the phosphodiesterase inhibitor ibudilast, S1P modulator siponimod, and anti-B-cell therapy ocrelizumab. Several efforts for development of outcome measures in PMS are ongoing. Summary PMS represents a significant challenge, as the pathogenesis of the disease is not well understood, no validated outcome metrics have been established, and clinical trial experience to date has been disappointing. Advances in the understanding of the disease and lessons learned in previous clinical trials are paving the way for successful development of disease modifying agents for this disease. PMID:25887766

  11. Interaction of Sesbania Mosaic Virus Movement Protein with VPg and P10: Implication to Specificity of Genome Recognition

    PubMed Central

    Roy Chowdhury, Soumya; Savithri, Handanahal S.

    2011-01-01

    Sesbania mosaic virus (SeMV) is a single strand positive-sense RNA plant virus that belongs to the genus Sobemovirus. The mechanism of cell-to-cell movement in sobemoviruses has not been well studied. With a view to identify the viral encoded ancillary proteins of SeMV that may assist in cell-to-cell movement of the virus, all the proteins encoded by SeMV genome were cloned into yeast Matchmaker system 3 and interaction studies were performed. Two proteins namely, viral protein genome linked (VPg) and a 10-kDa protein (P10) c v gft encoded by OFR 2a, were identified as possible interacting partners in addition to the viral coat protein (CP). Further characterization of these interactions revealed that the movement protein (MP) recognizes cognate RNA through interaction with VPg, which is covalently linked to the 5′ end of the RNA. Analysis of the deletion mutants delineated the domains of MP involved in the interaction with VPg and P10. This study implicates for the first time that VPg might play an important role in specific recognition of viral genome by MP in SeMV and shed light on the possible role of P10 in the viral movement. PMID:21246040

  12. Pesticide reregistration progress report

    SciTech Connect

    Not Available

    1993-01-01

    The report is produced by the Special Review and Reregistration Division (SRRD), Office of Pesticide Programs, U.S. Environmental Protection Agency (EPA), on progress towards pesticide reregistration as mandated under 1988 amendments to the Federal Insecticide, Fungicide, and Rodenticide Act. The report shows the status of reregistration through the first quarter of the 1993 fiscal year. SRRD is in the process of re-evaluating the format and information in the Progress Report, as a result of the October 1992 Customer Survey sent to the recipients of the report. Results of the survey will be incorporated in the April 1993 issue of the report.

  13. Strongly interacting ultracold polar molecules

    NASA Astrophysics Data System (ADS)

    Gadway, Bryce; Yan, Bo

    2016-08-01

    This paper reviews recent advances in the study of strongly interacting systems of dipolar molecules. Heteronuclear molecules feature large and tunable electric dipole moments, which give rise to long-range and anisotropic dipole-dipole interactions. Ultracold samples of dipolar molecules with long-range interactions offer a unique platform for quantum simulations and the study of correlated many-body physics. We provide an introduction to the physics of dipolar quantum gases, both electric and magnetic, and summarize the multipronged efforts to bring dipolar molecules into the quantum regime. We discuss in detail the recent experimental progress in realizing and studying strongly interacting systems of polar molecules trapped in optical lattices, with particular emphasis on the study of interacting spin systems and non-equilibrium quantum magnetism. Finally, we conclude with a brief discussion of the future prospects for studies of strongly interacting dipolar molecules.

  14. Strongly interacting ultracold polar molecules

    NASA Astrophysics Data System (ADS)

    Gadway, Bryce; Yan, Bo

    2016-08-01

    This paper reviews recent advances in the study of strongly interacting systems of dipolar molecules. Heteronuclear molecules feature large and tunable electric dipole moments, which give rise to long-range and anisotropic dipole–dipole interactions. Ultracold samples of dipolar molecules with long-range interactions offer a unique platform for quantum simulations and the study of correlated many-body physics. We provide an introduction to the physics of dipolar quantum gases, both electric and magnetic, and summarize the multipronged efforts to bring dipolar molecules into the quantum regime. We discuss in detail the recent experimental progress in realizing and studying strongly interacting systems of polar molecules trapped in optical lattices, with particular emphasis on the study of interacting spin systems and non-equilibrium quantum magnetism. Finally, we conclude with a brief discussion of the future prospects for studies of strongly interacting dipolar molecules.

  15. 1992 PVUSA progress report

    SciTech Connect

    Ellyn, W.

    1992-12-31

    Photovoltaics for Utility Scale Applications (PVUSA) is a national public-private partnership that is assessing and demonstrating the viability of utility-scale photovoltaic (PV) electric generating systems. This report updates the progress of the PVUSA project, reviews the status and performance of the various PV installations during 1992, and summarizes key accomplishments and conclusions from work to date.

  16. Opportunities and progress.

    PubMed

    Litchfield, John H

    2014-01-01

    In this review, I cover my professional experiences in food science and technology and related areas of applied and industrial microbiology over the span of my career. It emphasizes opportunities and technological problems that I encountered together with my progress in follow-up development of products and processes. PMID:24580071

  17. Basic Measures of Progress.

    ERIC Educational Resources Information Center

    Calkins, Julia; Ling, Thomson; Moore, Eric; Halle, Tamara; Hair, Beth; Moore, Kris; Zaslow, Marty

    This document provides a compilation of measures of progress toward school readiness and three contributing conditions as used in several local, state, and national surveys. The report begins with a legend listing the surveys examined, their acronyms, and contact information. The remainder of the report, in tabular format, lists measures of…

  18. Mystery in Progress.

    ERIC Educational Resources Information Center

    Hall, Kristen

    1989-01-01

    Describes "Mystery in Progress," a traveling exhibit which traces the development of Predynastic Egypt. The exhibit provides a time line for Predynastic Egypt, depicts the history of the Hierakonpolis expedition, documents the formation of Egypt's first centralized nation state, and summarizes the emergence of a unified Egypt. (LS)

  19. Learning Progressions & Climate Change

    ERIC Educational Resources Information Center

    Parker, Joyce M.; de los Santos, Elizabeth X.; Anderson, Charles W.

    2015-01-01

    Our society is currently having serious debates about sources of energy and global climate change. But do students (and the public) have the requisite knowledge to engage these issues as informed citizenry? The learning-progression research summarized here indicates that only 10% of high school students typically have a level of understanding…

  20. MCNP Progress & Performance Improvements

    SciTech Connect

    Brown, Forrest B.; Bull, Jeffrey S.; Rising, Michael Evan

    2015-04-14

    Twenty-eight slides give information about the work of the US DOE/NNSA Nuclear Criticality Safety Program on MCNP6 under the following headings: MCNP6.1.1 Release, with ENDF/B-VII.1; Verification/Validation; User Support & Training; Performance Improvements; and Work in Progress. Whisper methodology will be incorporated into the code, and run speed should be increased.

  1. Progressive Response Surfaces

    NASA Technical Reports Server (NTRS)

    Romero, V. J.; Swiler, L. P.

    2004-01-01

    Response surface functions are often used as simple and inexpensive replacements for computationally expensive computer models that simulate the behavior of a complex system over some parameter space. Progressive response surfaces are ones that are built up progressively as global information is added from new sample points in the parameter space. As the response surfaces are globally upgraded based on new information, heuristic indications of the convergence of the response surface approximation to the exact (fitted) function can be inferred. Sampling points can be incrementally added in a structured fashion, or in an unstructured fashion. Whatever the approach, at least in early stages of sampling it is usually desirable to sample the entire parameter space uniformly. At later stages of sampling, depending on the nature of the quantity being resolved, it may be desirable to continue sampling uniformly over the entire parameter space (Progressive response surfaces), or to switch to a focusing/economizing strategy of preferentially sampling certain regions of the parameter space based on information gained in early stages of sampling (Adaptive response surfaces). Here we consider Progressive response surfaces where a balanced indication of global response over the parameter space is desired.We use a variant of Moving Least Squares to fit and interpolate structured and unstructured point sets over the parameter space. On a 2-D test problem we compare response surface accuracy for three incremental sampling methods: Progressive Lattice Sampling; Simple-Random Monte Carlo; and Halton Quasi-Monte-Carlo sequences. We are ultimately after a system for constructing efficiently upgradable response surface approximations with reliable error estimates.

  2. Drug Interactions

    PubMed Central

    Tong Logan, Angela; Silverman, Andrew

    2012-01-01

    One of the most clinically significant complications related to the use of pharmacotherapy is the potential for drug-drug or drug-disease interactions. The gastrointestinal system plays a large role in the pharmacokinetic profile of most medications, and many medications utilized in gastroenterology have clinically significant drug interactions. This review will discuss the impact of alterations of intestinal pH, interactions mediated by phase I hepatic metabolism enzymes and P-glycoprotein, the impact of liver disease on drug metabolism, and interactions seen with commonly utilized gastrointestinal medications. PMID:22933873

  3. Eph/Ephrins-Mediated Thymocyte–Thymic Epithelial Cell Interactions Control Numerous Processes of Thymus Biology

    PubMed Central

    García-Ceca, Javier; Alfaro, David; Montero-Herradón, Sara; Tobajas, Esther; Muñoz, Juan José; Zapata, Agustín G.

    2015-01-01

    Numerous studies emphasize the relevance of thymocyte–thymic epithelial cell (TECs) interactions for the functional maturation of intrathymic T lymphocytes. The tyrosine kinase receptors, Ephs (erythropoietin-producing hepatocyte kinases) and their ligands, ephrins (Eph receptor interaction proteins), are molecules known to be involved in the regulation of numerous biological systems in which cell-to-cell interactions are particularly relevant. In the last years, we and other authors have demonstrated the importance of these molecules in the thymic functions and the T-cell development. In the present report, we review data on the effects of Ephs and ephrins in the functional maturation of both thymic epithelial microenvironment and thymocyte maturation as well as on their role in the lymphoid progenitor recruitment into the thymus. PMID:26167166

  4. Reciprocal interactions between endothelial cells and macrophages in angiogenic vascular niches

    SciTech Connect

    Baer, Caroline; Squadrito, Mario Leonardo; Iruela-Arispe, M. Luisa; De Palma, Michele

    2013-07-01

    The ability of macrophages to promote vascular growth has been associated with the secretion and local delivery of classic proangiogenic factors (e.g., VEGF-A and proteases). More recently, a series of studies have also revealed that physical contact of macrophages with growing blood vessels coordinates vascular fusion of emerging sprouts. Interestingly, the interactions between macrophages and vascular endothelial cells (ECs) appear to be bidirectional, such that activated ECs also support the expansion and differentiation of proangiogenic macrophages from myeloid progenitors. Here, we discuss recent findings suggesting that dynamic angiogenic vascular niches might also exist in vivo, e.g. in tumors, where sprouting blood vessels and immature myeloid cells like monocytes engage in heterotypic interactions that are required for angiogenesis. Finally, we provide an account of emerging mechanisms of cell-to-cell communication that rely on secreted microvesicles, such as exosomes, which can offer a vehicle for the rapid exchange of molecules and genetic information between macrophages and ECs engaged in angiogenesis. -- Highlights: • Macrophages promote angiogenesis by secreting proangiogenic factors. • Macrophages modulate angiogenesis via cell-to-cell contacts with endothelial cells. • Endothelial cells promote the differentiation of proangiogenic macrophages. • Macrophages and endothelial cells may cooperate to form angiogenic vascular niches.

  5. Progressive cone dystrophy.

    PubMed Central

    Ripps, H; Noble, K G; Greenstein, V C; Siegel, I M; Carr, R E

    1987-01-01

    Psychophysical, reflectometric, and electrophysiological studies were performed on four members of a dominant pedigree with progressive cone dystrophy. The two youngest individuals were asymptomatic at the initial examination, and none of the subjects complained of problems associated with night vision. Absent or grossly reduced cone-mediated ERG responses revealed the widespread loss of cone function. Moderate elevations (1 log unit) in absolute threshold together with reductions in rhodopsin levels in the midperipheral retina provided evidence of a mild impairment of the rod system also, although not to the degree seen in a cone-rod dystrophy. The progressive nature of the disease was apparent from the case histories and the changes in visual performance that occurred on re-test after a 5-year interval. Likewise, the results of incremental threshold measurements at several retinal loci suggested that peripheral cones may be affected earlier and more severely than those in the central retina. PMID:3502298

  6. Progressive compressive imager

    NASA Astrophysics Data System (ADS)

    Evladov, Sergei; Levi, Ofer; Stern, Adrian

    2012-06-01

    We have designed and built a working automatic progressive sampling imaging system based on the vector sensor concept, which utilizes a unique sampling scheme of Radon projections. This sampling scheme makes it possible to progressively add information resulting in tradeoff between compression and the quality of reconstruction. The uniqueness of our sampling is that in any moment of the acquisition process the reconstruction can produce a reasonable version of the image. The advantage of the gradual addition of the samples is seen when the sparsity rate of the object is unknown, and thus the number of needed measurements. We have developed the iterative algorithm OSO (Ordered Sets Optimization) which employs our sampling scheme for creation of nearly uniform distributed sets of samples, which allows the reconstruction of Mega-Pixel images. We present the good quality reconstruction from compressed data ratios of 1:20.

  7. Progress in controlling ICRF-edge interactions in ASDEX upgrade

    SciTech Connect

    Bobkov, Vl. Ochoukov, R.; Bilato, R.; Braun, F.; Carralero, D.; Dux, R.; Faugel, H.; Fünfgelder, H.; Jacquot, J.; Lunt, T.; Potzel, S.; Pütterich, Th.; Jacquet, Ph.; Monakhov, I.; Zhang, W.; Noterdaeme, J.-M.; Stepanov, I.; Colas, L.; Meyer, O.; Czarnecka, A.; and others

    2015-12-10

    RF measurements during variation of the strap voltage balance of the original 2-strap ICRF antenna in ASDEX Upgrade at constant power are consistent with electromagnetic calculations by HFSS and TOPICA, more so for the latter. RF image current compensation is observed at the antenna limiters in the experiment at a local strap voltage of about half of the value of the remote strap, albeit with a non-negligible uncertainty in phasing. The RF-specific tungsten (W) source at the broad-limiter 2-strap antenna correlates strongly with the RF voltage at the local strap at the locations not connected to opposite side of the antenna along magnetic field lines. The trends of the observed increase of the RF loading with injection of local gas are well described by a combined EMC3-Eirene – FELICE calculations, with the most efficient improvement confirmed for the outer-midplane valves, but underestimated by about 1/3. The corresponding deuterium density tailoring is also likely responsible for the decrease of local W sources observed in the experiment.

  8. Interaction of carbon and sulfur on metal catalysts. Progress report

    SciTech Connect

    McCarty, J.G.

    1988-01-21

    Goal is to study selective poisoning by fractional monolayers of chemisorbed sulfur on metal catalysts. A Pt catalyst on alumina support has been synthesized. Stabilized Fe catalysts without and with half monolayers of chemicsorbed S have been prepared. These catalysts, along with a Ni-alumina reference catalyst, will be used in experimental studies. 2 figs.

  9. Progress in Scientific Visualization

    SciTech Connect

    Max, N

    2004-11-15

    Visualization of observed data or simulation output is important to science and engineering. I have been particularly interested in visualizing 3-D structures, and report here my personal impressions on progress in the last 20 years in visualizing molecules, scalar fields, and vector fields and their associated flows. I have tried to keep the survey and list of references manageable, so apologize to those authors whose techniques I have not mentioned, or have described without a reference citation.

  10. COSMIC monthly progress report

    NASA Technical Reports Server (NTRS)

    1994-01-01

    Activities of the Computer Software Management and Information Center (COSMIC) are summarized for the month of January 1994. Tables showing the current inventory of programs available from COSMIC are presented and program processing and evaluation activities are discussed. Marketing and customer service activities in this period are presented as is the progress report of NASTRAN maintenance and support. Tables of disseminations and budget summary conclude the report.

  11. ISABELLE: a progress report

    SciTech Connect

    Hahn, H

    1980-01-01

    This paper discusses the ISABELLE project, which has the objective of constructing a high-energy proton colliding beam facility at Brookhaven National Laboratory. The major technical features of the intersecting storage accelerators with their projected performance are described. Application of over 1000 superconducting magnets in the two rings represents the salient characteristic of the machine. The status of the entire project, the technical progress made so far, and difficulties encountered are reviewed.

  12. Progression of myopia.

    PubMed Central

    Kennedy, R H

    1995-01-01

    BACKGROUND: Myopia is an important public health problem because it is common and is associated with increased risk for chorioretinal degeneration, retinal detachment, and other vision-threatening abnormalities. In animals, ocular elongation and myopia progression can be lessened with atropine treatment. This study provides information about progression of myopia and atropine therapy for myopia in humans. METHODS: A total of 214 residents of Olmsted County, Minnesota (118 girls and 96 boys; median age, 11 years; range, 6 to 15 years) received atropine for myopia from 1967 through 1974. Control subjects were matched by age, sex, refractive error, and date of baseline examination to 194 of those receiving atropine. Duration of treatment with atropine ranged from 18 weeks to 11.5 years (median 3.5 years). RESULTS: Median follow-up from initial to last refraction in the atropine group (11.7 years) was similar to that in the control group (12.4 years). Photophobia and blurred vision were frequently reported, but no serious adverse effects were associated with atropine therapy. Mean myopia progression during atropine treatment adjusted for age and refractive error (0.05 diopters per year) was significantly less than that among control subjects (0.36 diopters per year) (P < .001). Final refractions standardized to the age of 20 years showed a greater mean level of myopia in the control group (3.78 diopters) than in the atropine group (2.79 diopters) (P < .001). CONCLUSIONS: The data support the view that atropine therapy is associated with decreased progression of myopia and that beneficial effects remain after treatment has been discontinued. PMID:8719698

  13. Combustor diffuser interaction program

    NASA Technical Reports Server (NTRS)

    Srinivasan, Ram; Thorp, Daniel

    1986-01-01

    Advances in gas turbine engine performance are achieved by using compressor systems with high stage loading and low part count, which result in high exit Mach numbers. The diffuser and combustor systems in such engines should be optimized to reduce system pressure loss and to maximize the engine thrust-to-weight ratio and minimize length. The state-of-the-art combustor-diffuser systems do not meet these requirements. Detailed understanding of the combustor-diffuser flow field interaction is required for designing advanced gas turbine engines. An experimental study of the combustor-diffuser interaction (CDI) is being conducted to obtain data for the evaluation and improvement of analytical models applicable to a wide variety of diffuser designs. The CDI program consists of four technical phases: Literature Search; Baseline Configuration; Parametric Configurations; and Performance Configurations. Phase 2 of the program is in progress.

  14. Juvenile myopia progression, risk factors and interventions

    PubMed Central

    Myrowitz, Elliott H.

    2011-01-01

    The development and progression of early onset myopia is actively being investigated. While myopia is often considered a benign condition it should be considered a public health problem for its visual, quality of life, and economic consequences. Nearly half of the visually impaired population in the world has uncorrected refractive errors, with myopia a high percent of that group. Uncorrected visual acuity should be screened for and treated in order to improve academic performance, career opportunities and socio-economic status. Genetic and environmental factors contribute to the onset and progression of myopia. Twin studies have supported genetic factors and research continues to identify myopia genetic loci. While multiple myopia genetic loci have been identified establishing myopia as a common complex disorder, there is not yet a genetic model explaining myopia progression in populations. Environmental factors include near work, education levels, urban compared to rural location, and time spent outdoors. In this field of study where there continues to be etiology controversies, there is recent agreement that children who spend more time outdoors are less likely to become myopic. Worldwide population studies, some completed and some in progress, with a common protocol are gathering both genetic and environmental cohort data of great value. There have been rapid population changes in prevalence rates supporting an environmental influence. Interventions to prevent juvenile myopia progression include pharmacologic agents, glasses and contact lenses. Pharmacological interventions over 1–2 year trials have shown benefits. Peripheral vision defocus has been found to affect the emmetropization process and may be affected by wearing glasses or contacts. Accommodation accuracy also has been implicated in myopia progression. Further research will aim to assess both the role and interaction of environmental influences and genetic factors. PMID:23961008

  15. Imagined Interactions

    ERIC Educational Resources Information Center

    Honeycutt, James M.

    2010-01-01

    Social scientists have been studying imagined interactions since the mid-1980s and have measured numerous physiological correlates (Honeycutt, 2010). In this commentary I assess the research reported in Crisp and Turner (May-June 2009) and highlight the underlying mechanisms of imagined interactions that have empirically been laid out across…

  16. Primary-Progressive MS (PPMS)

    MedlinePlus

    ... MS? Types of MS Primary progressive MS (PPMS) Primary progressive MS (PPMS) Share Smaller Text Larger Text Print In this article Overview PPMS is characterized by worsening neurologic function ( ...

  17. Interacting parasites

    USGS Publications Warehouse

    Lafferty, Kevin D.

    2010-01-01

    Parasitism is the most popular life-style on Earth, and many vertebrates host more than one kind of parasite at a time. A common assumption is that parasite species rarely interact, because they often exploit different tissues in a host, and this use of discrete resources limits competition (1). On page 243 of this issue, however, Telfer et al. (2) provide a convincing case of a highly interactive parasite community in voles, and show how infection with one parasite can affect susceptibility to others. If some human parasites are equally interactive, our current, disease-by-disease approach to modeling and treating infectious diseases is inadequate (3).

  18. Technological Progress on Multi-Beam Klystrons

    NASA Astrophysics Data System (ADS)

    Ding, Yaogen

    2006-01-01

    The technological progress on Multi-Beam Klystrons (MBKs) at the Institute of Electronics, Chinese Academy of Sciences (IECAS) is presented in this paper. Topics to be discussed include the development of cathodes with high current densities and low evaporation rates; multi-beam electron guns with reduced chances for breakdown; multi-beam electron optics systems with high beam transmission; RF systems with wide bandwidth and high efficiency; the oscillation and broad spectrum noise caused by non-operational modes and reflecting electrons; and computer simulations of the multi-beam electron optics system and beam-wave interaction. In addition, the research progress of several types of MBKs developed in IECAS is reported. These MBKs range in frequency from L- to X-band with corresponding peak powers ranging from several tens to several hundreds of kilowatts, average powers from several kilowatts to tens of kilowatts, and bandwidths from 3% to 12%.

  19. Progress on the DPASS project

    NASA Astrophysics Data System (ADS)

    Galkin, Sergei A.; Bogatu, I. N.; Svidzinski, V. A.

    2015-11-01

    A novel project to develop Disruption Prediction And Simulation Suite (DPASS) of comprehensive computational tools to predict, model, and analyze disruption events in tokamaks has been recently started at FAR-TECH Inc. DPASS will eventually address the following aspects of the disruption problem: MHD, plasma edge dynamics, plasma-wall interaction, generation and losses of runaway electrons. DPASS uses the 3-D Disruption Simulation Code (DSC-3D) as a core tool and will have a modular structure. DSC is a one fluid non-linear, time-dependent 3D MHD code to simulate dynamics of tokamak plasma surrounded by pure vacuum B-field in the real geometry of a conducting tokamak vessel. DSC utilizes the adaptive meshless technique with adaptation to the moving plasma boundary, with accurate magnetic flux conservation and resolution of the plasma surface current. DSC has also an option to neglect the plasma inertia to eliminate fast magnetosonic scale. This option can be turned on/off as needed. During Phase I of the project, two modules will be developed: the computational module for modeling the massive gas injection and main plasma respond; and the module for nanoparticle plasma jet injection as an innovative disruption mitigation scheme. We will report on this development progress. Work is supported by the US DOE SBIR grant # DE-SC0013727.

  20. Progressive failure of structures

    NASA Technical Reports Server (NTRS)

    Khozeimeh, K.; Toridis, G. T. G.; Zanganeh, S. E.

    1978-01-01

    A procedure is presented for determining the nonlinear behavior of structures subjected to extreme loading and the possibility of development of potential for progressive failure. The methodology takes into account the effect of both material and geometric nonlinearities. At a given stage of analysis, the individual components of the structure are checked against predetermined failure criteria. Subsequently, the failing components are removed and the modified structure is analyzed for overall failure. Examples, obtained from a computer program based on the proposed procedure, showing the applicability of the method are presented.

  1. Progress in Alzheimer's disease.

    PubMed

    Galimberti, Daniela; Scarpini, Elio

    2012-02-01

    After more than one century from Alois Alzheimer and Gaetano Perusini's first report, progress has been made in understanding the pathogenic steps of Alzheimer's disease (AD), as well as in its early diagnosis. This review discusses recent findings leading to the formulation of novel criteria for diagnosis of the disease even in a preclinical phase, by using biological markers. In addition, treatment options will be discussed, with emphasis on new disease-modifying compounds and future trial design suitable to test these drugs in an early phase of the disease.

  2. MEIC Design Progress

    SciTech Connect

    Zhang, Y; Douglas, D; Hutton, A; Krafft, G A; Li, R; Lin, F; Morozov, V S; Nissen, E W; Pilat, F C; Satogata, T; Tennant, C; Terzic, B; Yunn, C; Barber, D P; Filatov, Y; Hyde, C; Kondratenko, A M; Manikonda, S L; Ostroumov, P N; Sullivan, M K

    2012-07-01

    This paper will report the recent progress in the conceptual design of MEIC, a high luminosity medium energy polarized ring-ring electron-ion collider at Jefferson lab. The topics and achievements that will be covered are design of the ion large booster and the ERL-circulator-ring-based electron cooling facility, optimization of chromatic corrections and dynamic aperture studies, schemes and tracking simulations of lepton and ion polarization in the figure-8 collider ring, and the beam-beam and electron cooling simulations. A proposal of a test facility for the MEIC electron cooler will also be discussed.

  3. Drug Interactions

    MedlinePlus

    ... not be taken at the same time as antacids. WHAT CAUSES THE MOST INTERACTIONS WITH HIV MEDICATIONS? ... azole” Some antibiotics (names end in “mycin”) The antacid cimetidine (Tagamet) Some drugs that prevent convulsions, including ...

  4. Conceptions of Progress: How Is Progress Perceived? Mainstream versus Alternative Conceptions of Progress

    ERIC Educational Resources Information Center

    Itay, Anat

    2009-01-01

    Progress is a powerful political concept, encompassing different and sometimes contradictory conceptions. This paper examines the results of a survey on progress conducted at the OECD World Forum entitled "Measuring and Fostering the Progress of Societies" held in Istanbul in June 2007. First, a distinction is drawn between the two approaches to…

  5. Tumour progression and metastasis

    PubMed Central

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour’s survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible. PMID:26913068

  6. Tumour progression and metastasis.

    PubMed

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour's survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible.

  7. Rapidly Progressive Dementia

    PubMed Central

    Geschwind, Michael D.

    2016-01-01

    Purpose of Review This article presents a practical and informative approach to the evaluation of a patient with a rapidly progressive dementia (RPD). Recent Findings Prion diseases are the prototypical causes of RPD, but reversible causes of RPD might mimic prion disease and should always be considered in a differential diagnosis. Aside from prion diseases, the most common causes of RPD are atypical presentations of other neurodegenerative disorders, curable disorders including autoimmune encephalopathies, as well as some infections, and neoplasms. Numerous recent case reports suggest dural arterial venous fistulas sometimes cause RPDs. Summary RPDs, in which patients typically develop dementia over weeks to months, require an alternative differential than the slowly progressive dementias that occur over a few years. Because of their rapid decline, patients with RPDs necessitate urgent evaluation and often require an extensive workup, typically with multiple tests being sent or performed concurrently. Jakob-Creutzfeldt disease, perhaps the prototypical RPD, is often the first diagnosis many neurologists consider when treating a patient with rapid cognitive decline. Many conditions other than prion disease, however, including numerous reversible or curable conditions, can present as an RPD. This chapter discusses some of the major etiologies for RPDs and offers an algorithm for diagnosis. PMID:27042906

  8. Progressive myoclonus epilepsy.

    PubMed

    Girard, Jean-Marie; Turnbull, Julie; Ramachandran, Nivetha; Minassian, Berge A

    2013-01-01

    The progressive myoclonus epilepsies (PMEs) consist of a group of diseases with myoclonic seizures and progressive neurodegeneration, with onset in childhood and/or adolescence. Lafora disease is a neuronal glycogenosis in which normal glycogen is transformed into starch-like polyglucosans that accumulate in the neuronal somatodendritic compartment. It is caused by defects of two genes of yet unknown function, one encoding a glycogen phosphatase (laforin) and the other an ubiquitin E3 ligase (malin). Early cognitive deterioration, visual seizures affecting over half, and slowing down of EEG basic activity are three major diagnostic clues. Unverricht-Lundborg disease is presently thought to be due to damage to neurons by lysosomal cathepsins and reactive oxygen species due to absence of cystatin B, a small protein that inactivates cathepsins and, by ways yet unknown, quenches damaging redox compounds. Preserved cognition and background EEG activity, action myoclonus early morning and vertex spikes in REM sleep are the diagnostic clues. Sialidosis, with cherry-red spot, neuronopathic Gaucher disease, with paralysis of verticality, and ataxia-PME, with ataxia at onset in the middle of the first decade, are also lysosomal diseases. How the lysosomal defect culminates in myoclonus and epilepsy in these conditions remains unknown. PMID:23622396

  9. The Progressive Era.

    PubMed

    Chambers, David W

    2005-01-01

    The American College of Dentists was founded in 1920 for the purpose of encouraging young dentists to continue study and to apply science to their practices. This ideal emerged in the Progressive Era, which lasted roughly from 1895 to 1920. The animating spirit of this period was that the human condition could be improved and that the way to achieve this was through science and the use of experts working together. The Progressive Era saw inventions, such as automobiles and airplanes, telephone and radio, that required mass production and brought people together. It also spawned many political and legislative innovations that we now take for granted. Among these are the Food and Drug Administration, the Department of Commerce, and the Federal Trade Commission. Workers' compensation and other social protections were introduced, as were city commissions; the income tax; women's suffrage; and initiative, referendum, and recall. Medicine, for the first time, became an effective way to treat disease as it developed a scientific foundation. PMID:16350929

  10. Construction progress of the RHIC electron lenses

    SciTech Connect

    Fischer W.; Altinbas, Z.; Anerella, M.; Beebe, E.; et al

    2012-05-20

    In polarized proton operation the RHIC performance is limited by the head-on beam-beam effect. To overcome this limitation two electron lenses are under construction. We give an overview of the construction progress. Guns, collectors and the warm electron beam transport solenoids with their power supplies have been constructed. The superconducting solenoids that guide the electron beam during the interaction with the proton beam are near completion. A test stand has been set up to verify the performance of the gun, collector and some of the instrumentation. The infrastructure is being prepared for installation, and simulations continue to optimize the performance.

  11. Capturing and Analyzing Verbal and Physical Collaborative Learning Interactions at an Enriched Interactive Tabletop

    ERIC Educational Resources Information Center

    Martinez-Maldonado, Roberto; Dimitriadis, Yannis; Martinez-Monés, Alejandra; Kay, Judy; Yacef, Kalina

    2013-01-01

    Interactive tabletops can be used to provide new ways to support face-to-face collaborative learning. A little explored and somewhat hidden potential of these devices is that they can be used to enhance teachers' awareness of students' progress by exploiting captured traces of interaction. These data can make key aspects of collaboration…

  12. Strong Interaction

    SciTech Connect

    Karsch, F.; Vogelsang, V.

    2009-09-29

    We will give here an overview of our theory of the strong interactions, Quantum Chromo Dynamics (QCD) and its properties. We will also briefly review the history of the study of the strong interactions, and the discoveries that ultimately led to the formulation of QCD. The strong force is one of the four known fundamental forces in nature, the others being the electromagnetic, the weak and the gravitational force. The strong force, usually referred to by scientists as the 'strong interaction', is relevant at the subatomic level, where it is responsible for the binding of protons and neutrons to atomic nuclei. To do this, it must overcome the electric repulsion between the protons in an atomic nucleus and be the most powerful force over distances of a few fm (1fm=1 femtometer=1 fermi=10{sup -15}m), the typical size of a nucleus. This property gave the strong force its name.

  13. Progressive Multifocal Leukoencephalopathy

    PubMed Central

    Adang, Laura; Berger, Joseph

    2015-01-01

    Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease with significant morbidity and mortality and no effective, targeted therapies. It is most often observed in association with abnormalities of cell-mediated immunity, in particular human immunodeficiency virus (HIV) infection, but also occurs in association with lymphoproliferative diseases, certain immunosuppressive and immunomodulatory regimens, and other conditions. The etiologic agent of PML is a small, ubiquitous polyomavirus, the JC virus (JCV, also known as JCPyV), for which at least 50% of the adult general population is seropositive. PML results when JCV replicates within cerebral oligodendrocytes and astrocytes, leading to oligodendrocyte death and demyelination. Unfortunately, no treatments have been convincingly demonstrated to be effective, though some have been employed in desperation; treatment otherwise includes attempts to restore any immune system defect, such as the withdrawal of the causative agent if possible, and general supportive care. PMID:26918152

  14. Progressing batch hydrolysis process

    DOEpatents

    Wright, J.D.

    1985-01-10

    A progressive batch hydrolysis process is disclosed for producing sugar from a lignocellulosic feedstock. It comprises passing a stream of dilute acid serially through a plurality of percolation hydrolysis reactors charged with feed stock, at a flow rate, temperature and pressure sufficient to substantially convert all the cellulose component of the feed stock to glucose. The cooled dilute acid stream containing glucose, after exiting the last percolation hydrolysis reactor, serially fed through a plurality of pre-hydrolysis percolation reactors, charged with said feedstock, at a flow rate, temperature and pressure sufficient to substantially convert all the hemicellulose component of said feedstock to glucose. The dilute acid stream containing glucose is cooled after it exits the last prehydrolysis reactor.

  15. Progressing batch hydrolysis process

    DOEpatents

    Wright, John D.

    1986-01-01

    A progressive batch hydrolysis process for producing sugar from a lignocellulosic feedstock, comprising passing a stream of dilute acid serially through a plurality of percolation hydrolysis reactors charged with said feedstock, at a flow rate, temperature and pressure sufficient to substantially convert all the cellulose component of the feedstock to glucose; cooling said dilute acid stream containing glucose, after exiting the last percolation hydrolysis reactor, then feeding said dilute acid stream serially through a plurality of prehydrolysis percolation reactors, charged with said feedstock, at a flow rate, temperature and pressure sufficient to substantially convert all the hemicellulose component of said feedstock to glucose; and cooling the dilute acid stream containing glucose after it exits the last prehydrolysis reactor.

  16. Progress in Stockholm talks

    SciTech Connect

    Borawski, J.

    1986-02-01

    Public interest focuses on whether the superpowers will eventually agree to reduce their strategic nuclear arsenals by 50% or better, and on whether Star Wars should be bargained away or preserved at all costs. Yet progress in arms control quietly proceeded in Stockholm at the multilateral Conference on Confidence- and Security-Building Measures and Disarmament in Europe (CDE), convened on January 17, 1984. The Conference examined ways to reduce the risks of war, but not arbitrarily lowering weapons levels or restricting the deployment of certain systems. Rather, the goal is to lower these risks by clarifying politico-military intentions and regulating the uses of military activities by means of confidence- and security-building measures. Through information exchange, observation, and inspection, along with operational restraints on military activities, these measure seek to diminish the opportunities for wars to start by surprise attack, miscalculation, or accident, and to inhibit the threat or indirect use of force for political intimidation. 2 references.

  17. Progress toward synthetic cells.

    PubMed

    Blain, J Craig; Szostak, Jack W

    2014-01-01

    The complexity of even the simplest known life forms makes efforts to synthesize living cells from inanimate components seem like a daunting task. However, recent progress toward the creation of synthetic cells, ranging from simple protocells to artificial cells approaching the complexity of bacteria, suggests that the synthesis of life is now a realistic goal. Protocell research, fueled by advances in the biophysics of primitive membranes and the chemistry of nucleic acid replication, is providing new insights into the origin of cellular life. Parallel efforts to construct more complex artificial cells, incorporating translational machinery and protein enzymes, are providing information about the requirements for protein-based life. We discuss recent advances and remaining challenges in the synthesis of artificial cells, the possibility of creating new forms of life distinct from existing biology, and the promise of this research for gaining a deeper understanding of the nature of living systems. PMID:24606140

  18. 1992 PVUSA progress report

    SciTech Connect

    1992-12-31

    Photovoltaics for Utility Scale Applications (PVUSA) is a national public-private partnership that is assessing and demonstrating the viability of utility-scale photovoltaic (PV) electric generating systems. This report updates the progress of the PVUSA project, reviews the status and performance of the various PV installations during 1992, and summarizes key accomplishments and conclusions from work to date. Fall PV module costs and rising environmental pressures could make PV a significant source of large-scale power within the next decade. However, utility acceptance of this technology requires knowledge of PV operational characteristics in a utility system and confidence in predicting PV performance, reliability, and economics. PVUSA consists of two types of demonstrations: Emerging Module Technologies (EMTs), which are unproven but promising state-of-the-art PV technologies in 20-kW (nominal) arrays; and Utility Scale (US) systems, which represent more mature PV technologies in 200- to 500-kW (nominal) turnkey systems.

  19. Indochinese power progress

    SciTech Connect

    Hennagir, T.

    1995-07-01

    Fifty years ago, U.S. engineers, fresh with the new-found success of building North America`s landmark dam projects, first considered building a series of multipurpose hydro-electric dams along the ancient Southeast Asian Mekong River descending from Tibet`s snowy plateau to the warm waters of the South China Sea. Recent transmission interconnection agreements such as those between Laos and Thailand and the incorporation of international partnering agreements for power project development are helping to reshape electric industry relationships throughout the region of the Mekong. Former economic pragmatism is being rapidly replaced by a general movement toward positive market forces. Progress continues as international players bring a varied assortment of financial packages and models to the project development table.

  20. Progress in palaeotsunami research

    NASA Astrophysics Data System (ADS)

    Goff, James; Chagué-Goff, Catherine; Nichol, Scott; Jaffe, Bruce; Dominey-Howes, Dale

    2012-01-01

    The study of palaeotsunamis preserved in the sedimentary record has developed over the past three decades to a point where the criteria used to identify these events range from well-tested and accepted to new methods yet to receive wide application. In this paper we review progress with the development of these criteria and identify opportunities for refinements and for extending their application to new settings. The emphasis here is on promoting the use of multiple proxies, selected to best match the context of the site or region of interest. Ultimately, this requires that palaeotsunami research must be a multidisciplinary endeavour and indeed, extend beyond the geological sciences of sedimentology and stratigraphy and, to include knowledge and approaches from field such as archaeology, anthropology and sociology. We also argue that in some instances, despite the use of multiple proxies, the evidence for tsunami inundation of a coast simply may not be preserved.

  1. Progress and Potential

    PubMed Central

    Haspel, Richard L.; Olsen, Randall J.; Berry, Anna; Hill, Charles E.; Pfeifer, John D.; Schrijver, Iris; Kaul, Karen L.

    2014-01-01

    Context Genomic medicine is revolutionizing patient care. Physicians in areas as diverse as oncology, obstetrics, and infectious disease have begun using next-generation sequencing assays as standard diagnostic tools. Objective To review the role of pathologists in genomic testing as well as current educational programs and future training needs in genomic pathology. Data Sources Published literature as well as personal experience based on committee membership and genomic pathology curricular design. Conclusion Pathologists, as the directors of the clinical laboratories, must be prepared to integrate genomic testing into their practice. The pathology community has made significant progress in genomics-related education. A continued coordinated and proactive effort will ensure a future vital role for pathologists in the evolving health care system and also the best possible patient care. PMID:24678680

  2. Rapidly progressive silicon nephropathy.

    PubMed

    Bolton, W K; Suratt, P M; Strugill, B C

    1981-11-01

    Rapidly progressive renal failure developed in four patients with silica exposure. Three presented with manifestations of a connective tissue disorders. All had abnormal proteinuria, hypoalbuminemia and active urinary sediments. Histologically, a distinct constellation of findings was present, consisting of glomerular hypercellularity and sclerosis, crescents, interstitial cellular infiltrates and tubular necrosis with red cell casts as seen on light microscopy. On electron microscopy there was foot process obliteration, characteristic cytoplasmic dense lysosomes, microtubules and dense deposits. Despite vigorous treatment, two patients died of the systemic illness and one is on hemodialysis. The fourth is improved after pulse methylprednisolone therapy. We propose that silica induced this multisystem disease through activation of the immune system and a direct tissue toxic effect.

  3. Progressive Band Selection

    NASA Technical Reports Server (NTRS)

    Fisher, Kevin; Chang, Chein-I

    2009-01-01

    Progressive band selection (PBS) reduces spectral redundancy without significant loss of information, thereby reducing hyperspectral image data volume and processing time. Used onboard a spacecraft, it can also reduce image downlink time. PBS prioritizes an image's spectral bands according to priority scores that measure their significance to a specific application. Then it uses one of three methods to select an appropriate number of the most useful bands. Key challenges for PBS include selecting an appropriate criterion to generate band priority scores, and determining how many bands should be retained in the reduced image. The image's Virtual Dimensionality (VD), once computed, is a reasonable estimate of the latter. We describe the major design details of PBS and test PBS in a land classification experiment.

  4. Sphingosylphosphorylcholine in cancer progress

    PubMed Central

    Yue, Hong-Wei; Jing, Qing-Chuan; Liu, Ping-Ping; Liu, Jing; Li, Wen-Jing; Zhao, Jing

    2015-01-01

    Sphingosylphosphorylcholine (SPC) is a naturally occurring bioactive sphingolipid in blood plasma, metabolizing from the hydrolysis of the membrane sphingolipid. It has been shown to exert multifunctional role in cell physiological regulation either as an intracellular second messenger or as an extracellular agent through G protein coupled receptors (GPCRs). Because of elevated levels of SPC in malicious ascites of patients with cancer, the role of SPC in tumor progression has prompted wide interest. The factor was reported to affect the proliferation and/or migration of many cancer cells, including pancreatic cancer cells, epithelial ovarian carcinoma cells, rat C6 glioma cells, neuroblastoma cells, melanoma cells, and human leukemia cells. This review covers current knowledge of the role of SPC in tumor. PMID:26550104

  5. Progress Towards International Repositories

    SciTech Connect

    McCombie, C.; Chapman, N.

    2002-02-27

    The nuclear fuel cycle is designed to be very international, with some specialist activities (e.g. fuel fabrication, reprocessing, etc.) being confined to a few countries. Nevertheless, political and public opposition has in the past been faced by proposals to internationalise the back-end of the cycle, in particular waste disposal. Attitudes, however, have been changing recently and there is now more acceptance of the general concept of shared repositories and of specific proposals such as that of Pangea. However, as for national facilities, progress towards implementation of shared repositories will be gradual. Moreover, the best vehicle for promoting the concept may not be a commercial type of organization. Consequently the Pangea project team are currently establishing a widely based Association for this purpose.

  6. Weak Interactions

    DOE R&D Accomplishments Database

    Lee, T. D.

    1957-06-01

    Experimental results on the non-conservation of parity and charge conservation in weak interactions are reviewed. The two-component theory of the neutrino is discussed. Lepton reactions are examined under the assumption of the law of conservation of leptons and that the neutrino is described by a two- component theory. From the results of this examination, the universal Fermi interactions are analyzed. Although reactions involving the neutrino can be described, the same is not true of reactions which do not involve the lepton, as the discussion of the decay of K mesons and hyperons shows. The question of the invariance of time reversal is next examined. (J.S.R.)

  7. Interactive Astronomy.

    ERIC Educational Resources Information Center

    Martin, Jean K.

    1997-01-01

    Presents guiding principles for developing interactive lessons for the World Wide Web. Describes "Amazing Space: Education Online from the Hubble Space Telescope", a program where students study spectacular Hubble Space Telescope images of stars and star-forming regions to learn about the life cycle of stars and the creation of atoms. (JRH)

  8. Interacting Compasses

    ERIC Educational Resources Information Center

    Riveros, Hector G.; Betancourt, Julian

    2009-01-01

    The use of multiple compasses to map and visualize magnetic fields is well-known. The magnetic field exerts a torque on the compasses aligning them along the lines of force. Some science museums show the field of a magnet using a table with many compasses in a closely packed arrangement. However, the very interesting interactions that occur…

  9. Interactive Video.

    ERIC Educational Resources Information Center

    Boyce, Carol

    1992-01-01

    A workshop on interactive video was designed for fourth and fifth grade students, with the goals of familiarizing students with laser disc technology, developing a cadre of trained students to train other students and staff, and challenging able learners to utilize higher level thinking skills while conducting a research project. (JDD)

  10. Interactive Television.

    ERIC Educational Resources Information Center

    Bisesi, Michael; Felder, B. Dell

    1986-01-01

    Universities can offer opportunities for workers in high-technology fields to gain state-of-the-art information and skills without traveling to campus, through interactive television training. Careful organization and planning of such programs, including selection of effective faculty and remote site personnel, are essential to their success. (MSE)

  11. Progressive gauge U(1) family symmetry for quarks and leptons

    NASA Astrophysics Data System (ADS)

    Ma, Ernest

    2016-08-01

    The pattern of quark and lepton mass matrices is unexplained in the standard model of particle interactions. I propose the novel idea of a progressive gauge U (1 ) symmetry where it is a reflection of the regressive electroweak symmetry breaking pattern, caused by an extended Higgs scalar sector. Phenomenological implications of this new hypothesis are discussed.

  12. Advising and Progress in the Community College STEM Transfer Pathway

    ERIC Educational Resources Information Center

    Packard, Becky Wai-Ling; Jeffers, Kimberly C.

    2013-01-01

    Community college students enrolled in science and technology fields face many challenges as they pursue transfer pathways to earn a 4-year degree. Despite clear links to student persistence, advising interactions that facilitate or inhibit transfer progress are not clearly understood. In this study, 82 community college students pursuing science…

  13. Using Learning Progressions to Monitor Progress across Grades

    ERIC Educational Resources Information Center

    Hess, Karin K.

    2010-01-01

    Learning progressions (LPs)--descriptive continuums of how students develop and demonstrate more sophisticated understanding over time--have become an increasingly important tool in today's science classrooms. Here the author discusses some of the research behind learning progressions and presents The Science Inquiry Profile for PreK-4. This is a…

  14. Dynamically prioritized progressive transmission

    NASA Astrophysics Data System (ADS)

    Blanford, Ronald

    1992-04-01

    Retrieval of image data from a centralized database may be subject to bandwidth limitations, whether due to a low-bandwidth communications link or to contention from simultaneous accesses over a high-bandwidth link. Progressive transmission can alleviate this problem by encoding image data so that any prefix of the data stream approximates the complete image at a coarse level of resolution. The longer the prefix, the finer the resolution. In many cases, as little at 1 percent of the image data may be sufficient to decide whether to discard the image, to permit the retrieval to continue, or to restrict retrieval to a subsection of the image. Our approach treats resolution not as a fixed attribute of the image, but rather as a resource which may be allocated to portions of the image at the direction of a user-specified priority function. The default priority function minimizes error by allocating more resolution to regions of high variance. The user may also point to regions of interest requesting priority transmission. More advanced target recognition strategies may be incorporated at the user's discretion. Multispectral imagery is supported. The user engineering implications are profounded. There is immediate response to a query that might otherwise take minutes to complete. The data is transmitted in small increments so that no single user dominates the communications bandwidth. The user-directed improvement means that bandwidth is focused on interesting information. The user may continue working with the first coarse approximations while further image data is still arriving. The algorithm has been implemented in C on Sun, Silicon Graphics, and NeXT workstations, and in Lisp on a Symbolics. Transmission speeds reach as high as 60,000 baud using a Sparc or 68040 processor when storing data to memory; somewhat less if also updating a graphical display. The memory requirements are roughly five bytes per image pixel. Both computational and memory costs may be reduced

  15. Nuclear chemistry progress report

    SciTech Connect

    Viola, V.E.; Kwiatkowski, K.

    1993-08-01

    This is the annual progress report for the Indiana University nuclear chemistry program for the 1992/1993 year. Accomplishments include the construction, testing, and initial experimental runs of the Indiana Silicon Sphere (ISiS) 4{pi} charged particle detector. ISiS is designed to study energy dissipation and multifragmentation phenomena in light-ion-induced nuclear reactions at medium-to-high energies. Its second test run was to examine 3.6 GeV {sup 3}He beam reactions at Laboratoire National Saturne (LNS) in Saclay. The development and deployment of this system has occupied a great deal of the groups effort this reporting period. Additional work includes: calculations of isotopic IMF yields in the {sup 4}He + {sup 116,124}Sn reaction; cross sections for A = 6 - 30 fragments from the {sup 4}He + {sup 28}Si reaction at 117 and 198 MeV; charging effects of passivated silicon detectors; neck emission of intermediate-mass fragments in the fission of hot heavy nuclei.

  16. Technical progress report

    SciTech Connect

    1996-10-01

    This report summarizes experimental and theoretical work in basic nuclear physics carried out between October 1, 1995, the closing of our last Progress Report, and September 30, 1996 at the Nuclear Physics Laboratory of the University of Colorado, Boulder, under contracts DE-FG03-93ER-40774 and DE-FG03-95ER-40913 with the United States Department of Energy. The experimental contract supports broadly-based experimental research in intermediate energy nuclear physics. This report includes results from studies of Elementary Systems involving the study of the structure of the nucleon via polarized high-energy positron scattering (the HERMES experiment) and lower energy pion scattering from both polarized and unpolarized nucleon targets. Results from pion- and kaon-induced reactions in a variety of nuclear systems are reported under the section heading Meson Reactions; the impact of these and other results on understanding the nucleus is presented in the Nuclear Structure section. In addition, new results from scattering of high-energy electrons (from CEBAF/TJNAF) and pions (from KEK) from a broad range of nuclei are reported in the section on Incoherent Reactions. Finally, the development and performance of detectors produced by the laboratory are described in the section titled Instrumentation.

  17. PVUSA progress report, 1991

    SciTech Connect

    Ellyn, W.; Jennings, C.

    1991-12-31

    Photovoltaics for Utility Scale Applications (PVUSA) is a national public-private partnership that is assessing and demonstrating the viability of utility-scale photovoltaic (PV) electric generating systems. PVUSA participants include Pacific Gas & Electric (PG&E), the US Department of Energy (DOE), the Electric Power Research Institute (EPRI), the California Energy Commission (CEC), and eight utilities and other agencies. This report updates the progress of the PVUSA project, reviews the status and performance of the various PV installations during 1991, and summarizes key findings and conclusions from work to date. PVUSA offers utilities hands-on experience needed to evaluate and utilize maturing PV technology. The project also provides manufacturers a test bed for their products, encourages technology improvement and cost reductions in PV modules and other system components, and establishes communication channels between utilities and the PV industry. The project consists of two types of demonstrations: Emerging Module Technology (EMT) arrays, which are unproven but promising state-of-the-art PV technologies in 20-kW (nominal) arrays; and Utility Scale (US) systems, which represent more mature PV technologies in 200- to 500-kW turnkey systems.

  18. 1993 PVUSA progress report

    SciTech Connect

    1993-12-31

    Photovoltaics for Utility Scale Applications (PVUSA) is a national public-private partnership that is assessing and demonstrating the viability of utility-scale photovoltaic (PV) electric generation systems and recent developments in module technology. This report updates the progress of the PVUSA project, review the status and performance of all PV installations during 1993, and summarizes key accomplishments and conclusions for the year. The PVUSA project has five objectives designed to narrow the gap between a large utility industry that is unfamiliar with PV, and a small PV industry that is aware of a potentially large utility market but unfamiliar with how to meet its requirements. The objectives are: to evaluate the performance, reliability, and cost of promising PV modules and balance-of-system (BOS) components side-by-side at a single location; to assess PV system operation and maintenance (O and M) in a utility setting; to compare PV technologies in diverse geographic areas; to provide US utilities with hands-on experience in designing, procuring, and operating PV systems; and to document and disseminate knowledge gained from the project.

  19. Progressive cavity pump

    SciTech Connect

    Mueller, J.W.

    1989-04-04

    A progressive cavity pump is described, comprising: a first housing portion defining an inlet; a second housing portion attachable to the first housing portion and defining an outlet; a substantially elastomeric stator comprising an outer portion removably attached to the first and second housing portions, having a first end and a second end spaced from the first end, an inner portion defining a pumping chamber and spaced an annular end portion interconnecting the first ends of the outer and inner portions; a rotor disposed in the inner portion of the stator and extending through the pumping chamber for pumping fluid from the inlet to the outlet in response to rotation of the rotor; and an elongated member disposed in the housing portions and generally annularly between the inner and outer portions of the stator and longitudinally between the annular end portion of the stator and a portion of the second housing portion, the member being removable from the housing portions and separable from the stator.

  20. Annual Technical Progress Report

    SciTech Connect

    Ayman I. Hawari

    2002-10-02

    This report describes the results generated during phase 1 of this project. During this phase, the main tools that are used to compute the thermal neutron scattering kernels for graphite, beryllium, beryllium oxide, zirconium hydride, light water, polyethylene were implemented and tested. This includes a modified NJOY/LEAPR code system, the GASKET code, and the ab initio condensed matter codes VASP and PHONON. Thermal neutron scattering kernels were generated for graphite, beryllium, beryllium oxide. In the case of graphite, new phonon spectra were examined. The first is a spectrum based on experiments performed at Oak Ridge National Laboratory in the early seventies, and the second is generated using the ab initio methods. In the case of beryllium, and beryllium oxide, a synthetic approach for generating the phonon spectra was implemented. In addition, significant progress was made on an experiment to benchmark the graphite scattering kernels was made. The simulations of this experiment show that differences on the order of a few percent, in Pu-239 detector responses, can be expected due to the use of different scattering kernels. (B204) NOT A FINAL REPORT

  1. Progress of AMOLED technology

    NASA Astrophysics Data System (ADS)

    Park, Joon Young

    2005-01-01

    We report the technical progress of AMOLED at Samsung SDI, comparing with other technologies. We introduce the voltage-compensational TFT circuit structure to improve the brightness uniformity of AMOLED, which is based on the low temperature poly-silicon. We have developed not only small molecule emitters (phosphorescence and fluorescence) but also polymeric emitters. From red and green phosphors, we achieved longer lifetime and higher efficiency than fluorophors. With the shadow mask patterning and the bottom-emission structure, 20,000-hour lifetime of QCIF device and the power consumption less than 150 mW at 100 cd/m2 (30% on condition) were obtained. In the case of the top-emission structure, we could get high efficiency also by maximizing the light out-coupling efficiency and enhance the color purity to the level of the NTSC. We have developed another patterning technology, "LITI: Laser Induced Thermal Imaging" and fabricated 17-inch full color AMOLED, which is the largest AMOLED based on the low temperature poly-Silicon.

  2. Quarterly Progress Report

    SciTech Connect

    David Gray; Glen Tomlinson

    1998-11-12

    The Federal Energy Technology Center (FETC) at Pittsburgh contracted with the MJTRE Corporation to perform Research Guidance Studies that will assist the Center and other relevant offices in the Department of Energy in evaluating and prioritizing research in the areas of coal and natural gas conversion. MITRE was reorganized in December 1995, which resulted in the formation of Mitretek Systems Inc. Mitretek has been performing this work on MITRE's behalf awaiting completion of contract novation to Mitretek. The contract was novated in February 1998 to Mitretek Systems. The overall objectives of this contract are to provide support to DOE in the following areas: (1) technical and economic analyses of current and future coal-based energy conversion technologies and other similar emerging technologies such as coal-waste coprocessing, natural gas conversion, and biomass conversion technologies for the production of fuels, chemicals and electric power,(2) monitor progress in these technologies with respect to technical, economic, and environmental impact (including climate change), (3) conduct specific and generic project economic and technical feasibility studies based on these technologies, (4) identify long-range R&D areas that have the greatest potential for process improvements, and (5) investigate optimum configurations and associated costs for production of high quality energy products via refining and their performance in end-use applications.

  3. Microparticles in tumor progression.

    PubMed

    Falanga, Anna; Tartari, Carmen Julia; Marchetti, Marina

    2012-04-01

    Microparticles (MP) are shed from the surface of activated or apoptotic blood cells and their levels in plasma reflect a balance between cell stimulation, proliferation, and death. MP production occurs through vesiculation of cell membranes, and involves cytoskeletal changes and a shift in the normal phospholipid asymmetry. The expression on the majority of MP of the anionic phosphatidylserine (PS) is responsible for the capacity of MP to support blood coagulation activation. In some cases, PS expression is also associated, in the same MP, with the presence of active Tissue Factor, the main activator of blood coagulation. Elevation in plasma levels of MP have been described in numerous clinical conditions, most of which also associated with an increased thrombotic risk. Particularly, MP have been found to be increased in both solid and hematological malignancies, including myeloproliferative neoplasms. A role of MP in tumor progression has been suggested by both in vitro and in vivo studies. Evidence exists that MP of platelet origin are the main players in this process, being rich in pro-angiogenic factors. The utility of measuring MP as a diagnostic and prognostic marker is currently a subject of intense investigation. The possibility to inhibit MP production by pharmacological interventions represents a future challenge. PMID:22682124

  4. Electroweak interactions

    SciTech Connect

    Renton, P.

    1990-01-01

    The central part of the book consists of a comprehensive discussion of many scattering and decay processes involving electromagnetic, weak and strong interactions. A list of topics includes electron-proton scattering, Compton scattering, muon decay, electron-positron annihilation, photon and hadron structure functions, neutrino-nucleus scattering, Cabibbo theory, tau-lepton decays, W and Z boson decays, mixing phenomena and many others. For most processes, the author presents the appropriate Feynman diagrams, first-order matrix elements and the resulting cross sections or decay rates. The last section of Electroweak Interactions discusses some of the open or unanswered questions in the standard model, including the undiscovered top quark, the Higgs mechanism of electroweak symmetry breaking and detailed tests involving radiative effects. The book concludes with a brief account of ideas that extend beyond the standard model, such as left-right symmetric models, grand unified theories, compositeness, supersymmetry and string theory.

  5. [Epithelial-mesenchymal transition in cancer progression].

    PubMed

    Gos, Monika; Miłoszewska, Joanna; Przybyszewska, Małgorzata

    2009-01-01

    According to recently published data, the epithelial-mesenchymal transition--a process important for embryonic development, may be involved in many pathological processes such as wound healing, tissue fibrosis or cancer progression. The EMT process in cell is driven by growth factors (EGF, PDGF, HGF) or other signaling proteins such as TGF-beta, sonic hedgehog (Shh), Wnt/beta-catenin and extracellular matrix (ECM) components that may stimulate cellular growth and migration. During cancer progression, the EMT process is necessary to the conversion of benign tumor to aggressive and highly invasive cancer. This is due to complex changes in cancer cells and their microenvironment that lead to dissolution of intracellular junctions and their detachment from basolateral membrane, and changes in the interactions between cancer cells and ECM. The loss of adhesion is accompanied by molecular and morphologic changes in cancer cells that are essential for the phenotypic change from epithelial to mesenchymal one, and the acquirement of higher migration and invasion potential. During the colonization of distant sites, a reverse process mesenchymal-epithelial transition (MET) takes place and metastatic cancer cells again acquire the epithelial phenotype. The EMT in cancer progression is not only specific for cancer cells. It has been suggested that also cells within tumor microenvironment e.g. cancer associated fibroblasts (CAF) are generated in part from normal epithelial cells in EMT process. The understanding of the role of EMT and MET processes in cancer progression and their relationship with cancer stem cells, cancer associated fibroblasts and other stroma cells might lead to the discovery of new, targeted cancer therapies.

  6. The Progress of Nations, 1999.

    ERIC Educational Resources Information Center

    United Nations Children's Fund, New York, NY.

    This report summarizes the latest available statistics on international progress on children's well-being. Each of the report's sections contains a commentary, related statistics, and a discussion on progress and disparity in the section's particular area. Following a foreword by United Nations Secretary-General Kofi A. Annan, the sections of the…

  7. Progress in NASA Rotorcraft Propulsion

    NASA Technical Reports Server (NTRS)

    DellaCorte, Christopher; Johnson, Susan M.

    2008-01-01

    This presentation reviews recent progress made under NASA s Subsonic Rotary Wing (SRW) propulsion research activities. Advances in engines, drive systems and optimized propulsion systems are discussed. Progress in wide operability compressors, modeling of variable geometry turbine performance, foil gas bearings and multi-speed transmissions are presented.

  8. Road Maps for Learning: A Guide to the Navigation of Learning Progressions

    ERIC Educational Resources Information Center

    Black, Paul; Wilson, Mark; Yao, Shih-Ying

    2011-01-01

    The overall aim of this article is to analyze the relationships between the roles of assessment in pedagogy, the interactions between curriculum assessment and pedagogy, and the study of pupils' progression in learning. It is argued that well-grounded evidence of pupils' progressions in learning is crucial to the work of teachers, so that a method…

  9. Interactive Television: How Interactive is It?

    ERIC Educational Resources Information Center

    Barty, Karin

    1998-01-01

    Discusses how interaction occurs with interactive television in the classroom, examining the introduction of interactive television into Victoria, Australia's schools and investigating two types of interaction (overt and covert) between students and teachers. Notes that the types of interaction that occur with interactive television relate to the…

  10. The Thermochronologist's Progress

    NASA Astrophysics Data System (ADS)

    Zeitler, P. K.

    2011-12-01

    We owe our current understanding of thermochronology less to a series of revolutionary insights than to a somewhat uneven intellectual pilgrimage that over fifty years has progressed in fits and starts. Though hampered at times by overenthusiasm, oversimplification, and misunderstandings, on balance the field advanced thanks to a blend of curiosity-driven research, tool-building motivated by new ideas about Earth science, and improvements in technology. But now that we've exploited most radiogenic systems and the major minerals that host them, and now that our models can devour CPU time along with the best of them, are we done? Have we reached peak thermochron? The answer of course is no, and papers in this session will demonstrate what new technologies and techniques might have to offer in the coming years. However, I will argue that the discipline as a whole has matured to a point where if thermochronology is to remain a mainstream tool as opposed to a weekend sport, we need to get serious about several challenges. The most fundamental challenge is that current geodynamic models (and even more complex models we can envision coding) have outpaced our meagre stockpile of kinetic calibrations, our understanding of detailed isotope systematics, and our ability to generate data with sufficient throughput. These issues will not be addressed adequately through the business-as-usual approach that brought us to our current knowledge, and some community effort will probably be needed to coordinate the hard work that will be required. But any serious attempt to answer important questions with accurate thermal histories that have low and well-defined uncertainties will require that we actually know the kinetics for the specific samples we are analyzing, that we fully understand scatter in the data, that we work with the large sample numbers that are required for some problems like landscape evolution, and that inversion tools fully explore the important aspects of both the

  11. Progress with parasite plastids.

    PubMed

    Wilson, R J M Iain

    2002-05-31

    This review offers a snapshot of our current understanding of the origin, biology, and metabolic significance of the non-photosynthetic plastid organelle found in apicomplexan parasites. These protists are of considerable medical and veterinary importance world-wide, Plasmodium spp., the causative agent of malaria being foremost in terms of human disease. It has been estimated that approximately 8% of the genes currently recognized by the malarial genome sequencing project (now nearing completion) are of bacterial/plastid origin. The bipartite presequences directing the products of these genes back to the plastid have provided fresh evidence that secondary endosymbiosis accounts for this organelle's presence in these parasites. Mounting phylogenetic evidence has strengthened the likelihood that the plastid originated from a red algal cell. Most importantly, we now have a broad understanding of several bacterial metabolic systems confined within the boundaries of the parasite plastid. The primary ones are type II fatty acid biosynthesis and isoprenoid biosynthesis. Some aspects of heme biosynthesis also might take place there. Retention of the plastid's relict genome and its still ill-defined capacity to participate in protein synthesis might be linked to an important house-keeping process, i.e. guarding the type II fatty acid biosynthetic pathway from oxidative damage. Fascinating observations have shown the parasite plastid does not divide by constriction as in typical plants, and that plastid-less parasites fail to thrive after invading a new cell. The modes of plastid DNA replication within the phylum also have provided surprises. Besides indicating the potential of the parasite plastid for therapeutic intervention, this review exposes many gaps remaining in our knowledge of this intriguing organelle. The rapid progress being made shows no sign of slackening.

  12. Benchtop energetics progress

    NASA Astrophysics Data System (ADS)

    Fajardo, Mario; Fossum, Emily C.; Molek, Christopher D.; Lewis, William K.

    2012-03-01

    We have constructed an apparatus for investigating the reactive chemical dynamics of mgscale energetic materials samples. We seek to advance the understanding of the reaction kinetics of energetic materials, and of the chemical influences on energetic materials sensitivity. We employ direct laser irradiation, and indirect laser-driven shock, techniques to initiate thin-film explosive samples contained in a high-vacuum chamber. Expansion of the reacting flow into vacuum quenches the chemistry and preserves reaction intermediates for interrogation via time-of-flight mass spectrometry (TOFMS). By rastering the sample coupon through the fixed laser beam focus, we generate hundreds of repetitive energetic events in a few minutes. A detonation wave passing through an organic explosive, such as pentaerythritol tetranitrate (PETN, C5H8N4O12), is remarkably efficient in converting the solid explosive into final thermodynamically-stable gaseous products (e.g. N2, CO, CO2, H2O…). Termination of a detonation at an explosive-to-vacuum interface produces an expanding pulse of hyperthermal molecular species, with leading-edge velocities ~ 10 km/s. In contrast, deflagration (subsonic combustion) of PETN in vacuum produces mostly reaction intermediates, such as NO and NO2, with much slower molecular velocities; consistent with expansion-quenched thermal decomposition of PETN. We propose to exploit these differences in product chemical identities and molecular species velocities to provide a chemically-based diagnostic for distinguishing between "detonation-like" and deflagration events. We report recent progress towards the quantitative detection of hyperthermal neutral species produced by direct laser ablation of aluminum metal and of organic energetic materials, as a step towards demonstrating the ability to discriminate slow reaction intermediates from fast thermodynamically-stable final products.

  13. Benchtop Energetics Progress

    NASA Astrophysics Data System (ADS)

    Fajardo, Mario

    2011-06-01

    We have constructed an apparatus for investigating the reactive chemical dynamics of mg-scale energetic materials samples. We seek to advance the understanding of the reaction kinetics of energetic materials, and of the chemical influences on energetic materials sensitivity. We employ direct laser irradiation, and indirect laser-driven shock, techniques to initiate thin-film explosive samples contained in a high-vacuum chamber. Expansion of the reacting flow into vacuum quenches the chemistry and preserves reaction intermediates for interrogation via time-of-flight mass spectrometry (TOFMS). By rastering the sample coupon through the fixed laser beam focus, we generate hundreds of repetitive energetic events in a few minutes. A detonation wave passing through an organic explosive, such as pentaerythritol tetranitrate (PETN, C5H4N4O12) , is remarkably efficient in converting the solid explosive into final thermodynamically-stable gaseous products (e . g . N2, CO2, H2O...). Termination of a detonation at an explosive-to-vacuum interface produces an expanding pulse of hyperthermal molecular species, with leading-edge velocities ~10 km/s. In contrast, deflagration (subsonic combustion) of PETN in vacuum produces mostly reaction intermediates, such as NO and NO2, with much slower molecular velocities; consistent with expansion-quenched thermal decomposition of PETN. We propose to exploit these differences in product chemical identities and molecular species velocities to provide a chemically-based diagnostic for distinguishing between detonation and deflagration events. In this talk we also report recent progress towards the quantitative detection of hyperthermal neutral species produced by direct laser ablation of aluminum metal and of organic energetic materials, as a step towards demonstrating the ability to discriminate slow reaction intermediates from fast thermodynamically-stable final products. Work done in collaboration with Emily Fossum, Christopher Molek, and

  14. Quantum simulation with interacting photons

    NASA Astrophysics Data System (ADS)

    Hartmann, Michael J.

    2016-10-01

    Enhancing optical nonlinearities so that they become appreciable on the single photon level and lead to nonclassical light fields has been a central objective in quantum optics for many years. After this has been achieved in individual micro-cavities representing an effectively zero-dimensional volume, this line of research has shifted its focus towards engineering devices where such strong optical nonlinearities simultaneously occur in extended volumes of multiple nodes of a network. Recent technological progress in several experimental platforms now opens the possibility to employ the systems of strongly interacting photons, these give rise to as quantum simulators. Here we review the recent development and current status of this research direction for theory and experiment. Addressing both, optical photons interacting with atoms and microwave photons in networks of superconducting circuits, we focus on analogue quantum simulations in scenarios where effective photon-photon interactions exceed dissipative processes in the considered platforms.

  15. Interaction between Macrophages and Fibroblasts during Wound Healing of Burn Injuries in Rats.

    PubMed

    Oka, Takeshi; Ohta, Keisuke; Kanazawa, Tomonoshin; Nakamura, Kei-Ichiro

    2016-01-01

    Analysis of the structural changes and cell-to-cell interactions occurring during wound healing of burn injuries is essential to elucidate the morphological characteristics of the reconstitution of tissue architecture. However, conventional approaches do not provide sufficient information with respect to cell-to-cell interactions during wound healing. The aim of this study was to evaluate the interaction between bone marrow-derived cells and resident stromal cells throughout the wound healing of burn injuries, using immunohistochemistry and focused ion beam/scanning electron microscope tomography. We induced third-degree burn injuries on the backs of Wistar rats with a heated cylindrical aluminum block (2.0 cm in diameter). At 7 and 14 days after the burn injuries, the burned skin was immunostained with anti-Iba1 and anti-HSP47 antibodies for visualization of bone marrow-derived cells/macrophages and resident stromal cells/fibroblasts, respectively. Normal skin tissue was used as a control. Double-staining immunohistochemistry revealed frequent contacts between macrophages and fibroblasts and a higher contact ratio in the 3 normal skin compared with burned skin, particularly in the areas of granuloma. Three-dimensional ultrastructural analysis with focused ion beam/scanning electron microscope tomography revealed that macrophages and fibroblasts were located closer together in the normal skin than in the burned skin, confirming the analysis by light microscopic observations and ultrastructural analysis from single sections. These results highlight the importance of contact between macrophages and fibroblasts in the maintenance of skin tissue structure and during wound healing. PMID:27237937

  16. The Effects of Interactive Images on Language Acquisition for Adults.

    ERIC Educational Resources Information Center

    Abed, Farough

    1996-01-01

    Progression is an interactive mnemonic strategy using a series of five panels: the first displaying a stimulus item, the last, a response item, and the intermediate panels showing a metamorphosis from the first to the last. Adults viewing progressive displays of foreign words had significantly greater recall of meaning than those viewing…

  17. Targeting ECM Disrupts Cancer Progression

    PubMed Central

    Venning, Freja A.; Wullkopf, Lena; Erler, Janine T.

    2015-01-01

    Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings, the extracellular matrix (ECM). Many ECM proteins are significantly deregulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression. PMID:26539408

  18. Federal Facility Agreement progress report

    SciTech Connect

    Not Available

    1993-10-01

    The (SRS) Federal Facility Agreement (FFA) was made effective by the US. Environmental Protection Agency Region IV (EPA) on August 16, 1993. To meet the reporting requirements in Section XXV of the Agreement, the FFA Progress Report was developed. The FFA Progress Report is the first of a series of quarterly progress reports to be prepared by the SRS. As such this report describes the information and action taken to September 30, 1993 on the SRS units identified for investigation and remediation in the Agreement. This includes; rubble pits, runoff basins, retention basin, seepage basin, burning pits, H-Area Tank 16, and spill areas.

  19. PREFACE: Physics approaches to protein interactions and gene regulation Physics approaches to protein interactions and gene regulation

    NASA Astrophysics Data System (ADS)

    Nussinov, Ruth; Panchenko, Anna R.; Przytycka, Teresa

    2011-06-01

    nor sufficient for transcription factor activity. Transcription regulation is a complex and still not fully understood process involving, in addition to protein-DNA binding, other factors such as epigenetic modifications and three-dimensional DNA organization. In this issue, Levens and Benham discuss another important mechanism which is likely to contribute to overall gene regulation—changes of DNA secondary structure in response to supercoiling-induced stress. Pointing out that DNA is "more than a cipher", they argue that the DNA structural transitions driven by negative supercoiling may have profound consequences for the cell and have to be accounted for in detailed models. There is considerable progress in physical modeling of DNA dynamics in response to stress. Such efforts, supported by experimental data, will bring us closer to an understanding of the role of supercoiling in gene regulation. Large-scale biomolecular interaction networks not only provide a system-level view of cellular processes, but are also increasingly used to model communications between molecules. The lack of sufficient biochemical data and the gigantic scale of the network prevented detailed modeling of network dynamics and have stimulated the development of simplified models such as the information flow approach described by Kim et al in this issue. Importantly, despite their simplicity, such models proved to be extremely useful for identifying network modules, essential nodes, and molecular pathways which are dysregulated in complex diseases such as cancer. Finally, moving from studies of single cells towards populations, one has to recognize the heterogeneity present within a population of cells. In the context of protein abundance, such cell-to-cell variation within clonal populations of cells, referred to as expression noise, has recently become a focus of intense cross-disciplinary research. Concerted efforts of experimentalists, physicists and mathematicians have brought us closer

  20. COSMIC monthly progress report

    NASA Technical Reports Server (NTRS)

    1994-01-01

    Activities of the Computer Software Management and Information Center (COSMIC) are summarized for the month of May 1994. Tables showing the current inventory of programs available from COSMIC are presented and program processing and evaluation activities are summarized. Nine articles were prepared for publication in the NASA Tech Brief Journal. These articles (included in this report) describe the following software items: (1) WFI - Windowing System for Test and Simulation; (2) HZETRN - A Free Space Radiation Transport and Shielding Program; (3) COMGEN-BEM - Composite Model Generation-Boundary Element Method; (4) IDDS - Interactive Data Display System; (5) CET93/PC - Chemical Equilibrium with Transport Properties, 1993; (6) SDVIC - Sub-pixel Digital Video Image Correlation; (7) TRASYS - Thermal Radiation Analyzer System (HP9000 Series 700/800 Version without NASADIG); (8) NASADIG - NASA Device Independent Graphics Library, Version 6.0 (VAX VMS Version); and (9) NASADIG - NASA Device Independent Graphics Library, Version 6.0 (UNIX Version). Activities in the areas of marketing, customer service, benefits identification, maintenance and support, and dissemination are also described along with a budget summary.

  1. Activated Ras Signals Developmental Progression of Recombinase-activating Gene (RAG)-deficient Pro-B Lymphocytes

    PubMed Central

    Shaw, Albert C.; Swat, Wojciech; Ferrini, Roger; Davidson, Laurie; Alt, Frederick W.

    1999-01-01

    To elucidate the intracellular pathways that mediate early B cell development, we directed expression of activated Ras to the B cell lineage in the context of the recombination-activating gene 1 (RAG1)-deficient background (referred to as Ras–RAG). Similar to the effects of an immunoglobulin (Ig) μ heavy chain (HC) transgene, activated Ras caused progression of RAG1–deficient progenitor (pro)-B cells to cells that shared many characteristics with precursor (pre)-B cells, including downregulation of surface CD43 expression plus expression of λ5, RAG2, and germline κ locus transcripts. However, these Ras–RAG pre-B cells also upregulated surface markers characteristic of more mature B cell stages and populated peripheral lymphoid tissues, with an overall phenotype reminiscent of B lineage cells generated in a RAG- deficient background as a result of expression of an Ig μ HC together with a Bcl-2 transgene. Taken together, these findings suggest that activated Ras signaling in pro-B cells induces developmental progression by activating both differentiation and survival signals. PMID:9874569

  2. View-dependent progressive mesh coding for graphic streaming

    NASA Astrophysics Data System (ADS)

    Yang, Sheng; Kim, Chang-Su; Kuo, C.-C. Jay

    2001-11-01

    A view-dependent progressive mesh (VDPM) coding algorithm is proposed in this research to facilitate interactive 3D graphics streaming and browsing. The proposed algorithm splits a 3D graphics model into several partitions, progressively compresses each partition, and reorganizes topological and geometrical data to enable the transmission of visible parts with a higher priority. With the real-time streaming protocol (RTSP), the server is informed of the viewing parameters before transmission. Then, the server can adaptively transmit visible parts in detail, while cutting off invisible parts. Experimental results demonstrate that the proposed algorithm reduces the required transmission bandwidth, and exhibits acceptable visual quality even at low bit rates.

  3. Targeting clotting proteins in cancer therapy - progress and challenges.

    PubMed

    Ruf, Wolfram; Rothmeier, Andrea S; Graf, Claudine

    2016-04-01

    Cancer-associated thrombosis remains a significant complication in the clinical management of cancer and interactions of the hemostatic system with cancer biology continue to be elucidated. Here, we review recent progress in our understanding of tissue factor (TF) regulation and procoagulant activation, TF signaling in cancer and immune cells, and the expanding roles of the coagulation system in stem cell niches and the tumor microenvironment. The extravascular functions of coagulant and anti-coagulant pathways have significant implications not only for tumor progression, but also for the selection of appropriate target specific anticoagulants in the therapy of cancer patients. PMID:27067961

  4. Cosmic Interactions

    NASA Astrophysics Data System (ADS)

    2008-01-01

    An image based on data taken with ESO's Very Large Telescope reveals a triplet of galaxies intertwined in a cosmic dance. ESO PR Photo 02/08 ESO PR Photo 02/08 NGC 7173, 7174, and 7176 The three galaxies, catalogued as NGC 7173 (top), 7174 (bottom right) and 7176 (bottom left), are located 106 million light-years away towards the constellation of Piscis Austrinus (the 'Southern Fish'). NGC 7173 and 7176 are elliptical galaxies, while NGC 7174 is a spiral galaxy with quite disturbed dust lanes and a long, twisted tail. This seems to indicate that the two bottom galaxies - whose combined shape bears some resemblance to that of a sleeping baby - are currently interacting, with NGC 7176 providing fresh material to NGC 7174. Matter present in great quantity around the triplet's members also points to the fact that NGC 7176 and NGC 7173 have interacted in the past. Astronomers have suggested that the three galaxies will finally merge into a giant 'island universe', tens to hundreds of times as massive as our own Milky Way. ESO PR Photo 02/08 ESO PR Photo 02b/08 NGC 7173, 7174, and 7176 The triplet is part of a so-called 'Compact Group', as compiled by Canadian astronomer Paul Hickson in the early 1980s. The group, which is the 90th entry in the catalogue and is therefore known as HCG 90, actually contains four major members. One of them - NGC 7192 - lies above the trio, outside of this image, and is another peculiar spiral galaxy. Compact groups are small, relatively isolated, systems of typically four to ten galaxies in close proximity to one another. Another striking example is Robert's Quartet. Compact groups are excellent laboratories for the study of galaxy interactions and their effects, in particular the formation of stars. As the striking image reveals, there are many other galaxies in the field. Some are distant ones, while others seem to be part of the family. Studies made with other telescopes have indeed revealed that the HCG 90 group contains 16 members

  5. [Domestic violence: any progress?].

    PubMed

    Henrion, Roger

    2014-01-01

    Since the publication of the French national survey of violence against women in 2000, the fight against domestic violence has made steady progress. Knowledge of the phenomenon has significantly improved. A nationwide study of murders and manslaughters perpetrated by one partner of a couple against the other has been published annually since 2006. In 2012, domestic violence resulted in the deaths of 314 persons: 166 women, 31 men, 25 children, 9 collateral victims, 14 rivals, and two former spouses killed by their ex-fathers in law. In addition, 67 perpetrators committed suicide (51 men and3 women). The number of victims fluctuates from year to year but has remained fairly stable since 2006 (n=168). Legislation has improved significantly: eight new laws have been passed since 2004, all designed to protect women and to ensure that violent men are restrained and treated. New measures to inform and protect women have been implemented and others have been improved, such as the anonymous helpline (phone no 3919, "domestic violence information"). An inter-ministerial committee on the protection of women from violence and the prevention of human trafficking (MIPROF) was created on 3 January 2013. A website entitled "Stop violence against women " (Stop violences faites aux femmes) is now available. The "Imminent Danger" mobile phone system, designed to alert police if a suspected or known perpetrator breaches restraint conditions, will be extended to the entire country from January 2014. Referees charged with coordinating comprehensive long-tern care of women victims have been deployed at the county level. Information centers on the rights of women and families (CIDFF) now form a local nationwide network. Routine interviews with a midwife during the fourth month of pregnancy, focusing on the woman's emotional, economic and social conditions, have been implemented in 21 % of maternity units and should gradually be generalized. The authorities who have enforced the law have

  6. [Domestic violence: any progress?].

    PubMed

    Henrion, Roger

    2014-01-01

    Since the publication of the French national survey of violence against women in 2000, the fight against domestic violence has made steady progress. Knowledge of the phenomenon has significantly improved. A nationwide study of murders and manslaughters perpetrated by one partner of a couple against the other has been published annually since 2006. In 2012, domestic violence resulted in the deaths of 314 persons: 166 women, 31 men, 25 children, 9 collateral victims, 14 rivals, and two former spouses killed by their ex-fathers in law. In addition, 67 perpetrators committed suicide (51 men and3 women). The number of victims fluctuates from year to year but has remained fairly stable since 2006 (n=168). Legislation has improved significantly: eight new laws have been passed since 2004, all designed to protect women and to ensure that violent men are restrained and treated. New measures to inform and protect women have been implemented and others have been improved, such as the anonymous helpline (phone no 3919, "domestic violence information"). An inter-ministerial committee on the protection of women from violence and the prevention of human trafficking (MIPROF) was created on 3 January 2013. A website entitled "Stop violence against women " (Stop violences faites aux femmes) is now available. The "Imminent Danger" mobile phone system, designed to alert police if a suspected or known perpetrator breaches restraint conditions, will be extended to the entire country from January 2014. Referees charged with coordinating comprehensive long-tern care of women victims have been deployed at the county level. Information centers on the rights of women and families (CIDFF) now form a local nationwide network. Routine interviews with a midwife during the fourth month of pregnancy, focusing on the woman's emotional, economic and social conditions, have been implemented in 21 % of maternity units and should gradually be generalized. The authorities who have enforced the law have

  7. Progressive-Relapsing MS (PRMS)

    MedlinePlus

    ... the disease process in MS and in MRI technology. Individuals who were previously diagnosed with progressive-relapsing MS would now be ... The National MS Society is Here to Help Need More Information? We ...

  8. Public Attitudes to Technological Progress.

    ERIC Educational Resources Information Center

    Marshall, Eliot

    1979-01-01

    Discusses the probable changes in public attitudes toward science and technology as a result of the engineering accidents of 1979. Results of national polls conducted to identify public confidence in technological progress are included. (HM)

  9. Preventing Breast Cancer: Making Progress

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues Preventing Breast Cancer: Making Progress Past Issues / Fall 2006 Table of ... 000 women will have been diagnosed with invasive breast cancer, and nearly 41,000 women will die from ...

  10. Electroweak interactions

    SciTech Connect

    Haidt, D.; Pietschmann, H

    1988-01-01

    This volume aims at a consistent presentation of the relevant experimental data in the theoretical context of Quantum Flavor Dynamics (QFD). QFD stems from research in the last 15 years and describes successfully all phenomena of so-called electroweak interactions. This allows for a natural and efficient ordering of the vast body of data resulting from many different types of experiments. After an outline of the theoretical foundations, several chapters deal with the three sectors of QFD, i.e. fermions, gauge bosons and Higgs bosons as far as their properties (quantum numbers, lifetime etc.) are concerned. The largest chapter examines the structure of the electromagnetic, the weak neutral and the weak charged currents. Best values for the basic parameters of QFD are suggested, and open questions and new directions are discussed.

  11. Progress in hydrogeochemistry

    SciTech Connect

    Matthess G.

    1992-01-01

    The book contains fifty-seven research papers representing the results of a six-year program, Hydrogeochemical Processes in the Hydrologic Cycle Within the Unsaturated and Saturated Zones, supported by the DFG (the German equivalent of NSF), plus introductory sections and a final chapter by the editors. The work was conducted at fourteen field sites around Germany plus one, a gypsum karst, in Tunisia, and one in Turkey. The papers cover a wide range of topics, as summarized by the subtitle, Organics-Carbonate Systems-Silicate Systems-Microbiology-Models. The Organics Section focuses on isolation and characterization of humic substances and on the interaction of inorganics with humic substances. It is mostly methodology, notably the use of pyrolysis-mass spectrometry, with one paper on field results at the end. The section on Carbonate Systems includes a review of carbonate dissolution kinetics, a review of methodologies for sampling soil solutions, a set of field studies that integrate very well dissolution kinetics and stable-isotope mass balance arguments, and finally three papers on gypsum karst, dedolomitization, and paleokarst sediments in semi-arid regions. Silicate Systems includes several excellent papers on the redox reactions in soils and groundwater, using isotopes of nitrogen and sulfur to constrain the reactions. There are also papers on aluminum speciation and silicate dissolution kinetics. The Microbiology section includes valuable overviews of groundwater microbiology and sampling methods, together with four field studies at different sites. The Modeling section at the end is concerned primarily with chemical and mass balance modeling. The overall focus of the book is on the functioning of the natural system; there is not much mention of anthropogenic pollutants other than acid deposition and fertilizers.

  12. Annual Progress report - General Task

    SciTech Connect

    Wesnousky, S.G.

    1993-09-30

    This report provides a summary of progress for the project {open_quotes}Evaluation of the Geologic Relations and Seismotectonic Stability of the Yucca Mountain Area, Nevada Nuclear Waste Site Investigation (NNWSI).{close_quotes} A similar report was previously provided for the period of 1 October 1991 to 30 September 1992. The report initially covers the activities of the General Task and is followed by sections that describe the progress of the other ongoing tasks.

  13. Helicopter tail rotor orthogonal blade vortex interaction

    NASA Astrophysics Data System (ADS)

    Coton, F. N.; Marshall, J. S.; Galbraith, R. A. McD.; Green, R. B.

    2004-10-01

    The aerodynamic operating environment of the helicopter is particularly complex and, to some extent, dominated by the vortices trailed from the main and tail rotors. These vortices not only determine the form of the induced flow field but also interact with each other and with elements of the physical structure of the flight vehicle. Such interactions can have implications in terms of structural vibration, noise generation and flight performance. In this paper, the interaction of main rotor vortices with the helicopter tail rotor is considered and, in particular, the limiting case of the orthogonal interaction. The significance of the topic is introduced by highlighting the operational issues for helicopters arising from tail rotor interactions. The basic phenomenon is then described before experimental studies of the interaction are presented. Progress in numerical modelling is then considered and, finally, the prospects for future research in the area are discussed.

  14. Genetics Home Reference: Lafora progressive myoclonus epilepsy

    MedlinePlus

    ... Conditions Lafora progressive myoclonus epilepsy Lafora progressive myoclonus epilepsy Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Lafora progressive myoclonus epilepsy is a brain disorder characterized by recurrent seizures ( ...

  15. Designing "Interaction": How Do Interaction Design Students Address Interaction?

    ERIC Educational Resources Information Center

    Karlgren, Klas; Ramberg, Robert; Artman, Henrik

    2016-01-01

    Interaction design is usually described as being concerned with interactions with and through artifacts but independent of a specific implementation. Design work has been characterized as a conversation between the designer and the situation and this conversation poses a particular challenge for interaction design as interactions can be elusive…

  16. Defining secondary progressive multiple sclerosis.

    PubMed

    Lorscheider, Johannes; Buzzard, Katherine; Jokubaitis, Vilija; Spelman, Tim; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, François; Grammond, Pierre; Hupperts, Raymond; Alroughani, Raed; Sola, Patrizia; Boz, Cavit; Pucci, Eugenio; Lechner-Scott, Jeanette; Bergamaschi, Roberto; Oreja-Guevara, Celia; Iuliano, Gerardo; Van Pesch, Vincent; Granella, Franco; Ramo-Tello, Cristina; Spitaleri, Daniele; Petersen, Thor; Slee, Mark; Verheul, Freek; Ampapa, Radek; Amato, Maria Pia; McCombe, Pamela; Vucic, Steve; Sánchez Menoyo, José Luis; Cristiano, Edgardo; Barnett, Michael H; Hodgkinson, Suzanne; Olascoaga, Javier; Saladino, Maria Laura; Gray, Orla; Shaw, Cameron; Moore, Fraser; Butzkueven, Helmut; Kalincik, Tomas

    2016-09-01

    A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple

  17. Defining secondary progressive multiple sclerosis.

    PubMed

    Lorscheider, Johannes; Buzzard, Katherine; Jokubaitis, Vilija; Spelman, Tim; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, François; Grammond, Pierre; Hupperts, Raymond; Alroughani, Raed; Sola, Patrizia; Boz, Cavit; Pucci, Eugenio; Lechner-Scott, Jeanette; Bergamaschi, Roberto; Oreja-Guevara, Celia; Iuliano, Gerardo; Van Pesch, Vincent; Granella, Franco; Ramo-Tello, Cristina; Spitaleri, Daniele; Petersen, Thor; Slee, Mark; Verheul, Freek; Ampapa, Radek; Amato, Maria Pia; McCombe, Pamela; Vucic, Steve; Sánchez Menoyo, José Luis; Cristiano, Edgardo; Barnett, Michael H; Hodgkinson, Suzanne; Olascoaga, Javier; Saladino, Maria Laura; Gray, Orla; Shaw, Cameron; Moore, Fraser; Butzkueven, Helmut; Kalincik, Tomas

    2016-09-01

    A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple

  18. Agnosia for accents in primary progressive aphasia.

    PubMed

    Fletcher, Phillip D; Downey, Laura E; Agustus, Jennifer L; Hailstone, Julia C; Tyndall, Marina H; Cifelli, Alberto; Schott, Jonathan M; Warrington, Elizabeth K; Warren, Jason D

    2013-08-01

    As an example of complex auditory signal processing, the analysis of accented speech is potentially vulnerable in the progressive aphasias. However, the brain basis of accent processing and the effects of neurodegenerative disease on this processing are not well understood. Here we undertook a detailed neuropsychological study of a patient, AA with progressive nonfluent aphasia, in whom agnosia for accents was a prominent clinical feature. We designed a battery to assess AA's ability to process accents in relation to other complex auditory signals. AA's performance was compared with a cohort of 12 healthy age and gender matched control participants and with a second patient, PA, who had semantic dementia with phonagnosia and prosopagnosia but no reported difficulties with accent processing. Relative to healthy controls, the patients showed distinct profiles of accent agnosia. AA showed markedly impaired ability to distinguish change in an individual's accent despite being able to discriminate phonemes and voices (apperceptive accent agnosia); and in addition, a severe deficit of accent identification. In contrast, PA was able to perceive changes in accents, phonemes and voices normally, but showed a relatively mild deficit of accent identification (associative accent agnosia). Both patients showed deficits of voice and environmental sound identification, however PA showed an additional deficit of face identification whereas AA was able to identify (though not name) faces normally. These profiles suggest that AA has conjoint (or interacting) deficits involving both apperceptive and semantic processing of accents, while PA has a primary semantic (associative) deficit affecting accents along with other kinds of auditory objects and extending beyond the auditory modality. Brain MRI revealed left peri-Sylvian atrophy in case AA and relatively focal asymmetric (predominantly right sided) temporal lobe atrophy in case PA. These cases provide further evidence for the

  19. Matrix metalloproteinase-10 promotes tumor progression through regulation of angiogenic and apoptotic pathways in cervical tumors

    PubMed Central

    2014-01-01

    Background Cancer invasion and metastasis develops through a series of steps that involve the loss of cell to cell and cell to matrix adhesion, degradation of extracellular matrix and induction of angiogenesis. Different protease systems (e.g., matrix metalloproteinases, MMPs) are involved in these steps. MMP-10, one of the lesser studied MMPs, is limited to epithelial cells and can facilitate tumor cell invasion by targeting collagen, elastin and laminin. Enhanced MMP-10 expression has been linked to poor clinical prognosis in some cancers, however, mechanisms underlying a role for MMP-10 in tumorigenesis and progression remain largely unknown. Here, we report that MMP-10 expression is positively correlated with the invasiveness of human cervical and bladder cancers. Methods Using commercial tissue microarray (TMA) of cervical and bladder tissues, MMP-10 immunohistochemical staining was performed. Furthermore using a panel of human cells (HeLa and UROtsa), in vitro and in vivo experiments were performed in which MMP-10 was overexpressed or silenced and we noted phenotypic and genotypic changes. Results Experimentally, we showed that MMP-10 can regulate tumor cell migration and invasion, and endothelial cell tube formation, and that MMP-10 effects are associated with a resistance to apoptosis. Further investigation revealed that increasing MMP-10 expression stimulates the expression of HIF-1α and MMP-2 (pro-angiogenic factors) and PAI-1 and CXCR2 (pro-metastatic factors), and accordingly, targeting MMP-10 with siRNA in vivo resulted in diminution of xenograft tumor growth with a concomitant reduction of angiogenesis and a stimulation of apoptosis. Conclusion Taken together, our findings show that MMP-10 can play a significant role in tumor growth and progression, and that MMP-10 perturbation may represent a rational strategy for cancer treatment. PMID:24885595

  20. Interleukin-8 in breast cancer progression.

    PubMed

    Todorović-Raković, Nataša; Milovanović, Jelena

    2013-10-01

    Interleukin-8 (IL-8) is a chemokine that has an autocrine and/or paracrine tumor-promoting role and significant potential as a prognostic and/or predictive cancer biomarker. In breast cancer, which is mostly determined by expression of estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2), IL-8 could play a specific role. IL-8 is highly expressed in ER- breast cancers, but it increases invasiveness and metastatic potential of both ER- and ER+ breast cancer cells. It is also highly expressed in HER2+ breast cancers. Because of the complex crosstalk between these receptors and IL-8, its role is mainly determined by delicate balance in their signaling pathways. Therefore, the main point of this review was to analyze the possible influence of IL-8 in breast cancer progression related to its interaction with ER and HER2 and the consequent therapeutic implications of these relations.