645 research outputs found

    Localized Intersections of Non-Extremal p-branes and S-branes

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    A class of solutions to Supergravity in 10 or 11 dimensions is presented which extends the non-standard or semi-local intersections of Dp-branes to the case of non-extremal p-branes. The type of non-extremal solutions involved in the intersection is free and we provide two examples involving black-branes and/or D-\bar{D} systems. After a rotation among the time coordinate and a relatively transverse radial direction the solutions admit the interpretation of an intersection among D-branes and S-branes. We speculate on the relevance of these configurations both to study time dependent phenomena in the AdS/CFT correspondence as well as to construct cosmological brane-world scenarios within String Theory admitting accelerating expansion of the Universe.Comment: 31 pages, latex file; v2: typos corrected and references adde

    Neuronal Function and Dysfunction of Drosophila dTDP

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    Background: TDP-43 is an RNA- and DNA-binding protein well conserved in animals including the mammals, Drosophila, and C. elegans. In mammals, the multi-function TDP-43 encoded by the TARDBP gene is a signature protein of the ubiquitinpositive inclusions (UBIs) in the diseased neuronal/glial cells of a range of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-U). Methodology/Principal Findings: We have studied the function and dysfunction of the Drosophila ortholog of the mammalian TARDBP gene, dTDP, by genetic, behavioral, molecular, and cytological analyses. It was found that depletion of dTDP expression caused locomotion defect accompanied with an increase of the number of boutons at the neuromuscular junctions (NMJ). These phenotypes could be rescued by overexpression of Drosophila dTDP in the motor neurons. In contrast, overexpression of dTDP in the motor neurons also resulted in reduced larval and adult locomotor activities, but this was accompanied by a decrease of the number of boutons and axon branches at NMJ. Significantly, constitutive overexpression of dTDP in the mushroom bodies caused smaller axonal lobes as well as severe learning deficiency. On the other hand, constitutive mushroom body-specific knockdown of dTDP expression did not affect the structure of the mushroom bodies, but it impaired the learning ability of the flies, albeit moderately. Overexpression of dTDP also led to the formation of cytosolic dTDP (+) aggregates

    ISG15 facilitates cellular antiviral response to dengue and west nile virus infection in vitro

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    <p>Abstract</p> <p>Background</p> <p>Dengue virus (DENV) and West Nile virus (WNV), close siblings of the <it>Flaviviridae </it>family, are the causative agents of Dengue hemorraghic shock or West Nile meningoencephalitis respectively. Vaccines against these two flaviviruses are currently unavailable. Interferon- Stimulated Gene 15 (<it>ISG15</it>), encoding an ubiquitin-like protein, is significantly induced by type I interferons or viral infections. Its roles in viral infections, however, vary with viruses, being either anti- or pro-viral. The exact roles of ISG15 in DENV and WNV infections remain unknown. In the current study, we evaluated the relevancies of ISG15 to DENV and WNV infection of a mouse macrophage cell line RAW264.7.</p> <p>Findings</p> <p>Quantitative PCR showed that mouse <it>Isg15 </it>was dramatically induced in DENV or WNV- infected RAW264.7 cells compared with non-infected cells. <it>Isg15 </it>and two other Jak-Stat related genes, <it>Socs1 </it>and <it>Socs3</it>, were silenced using siRNA mediated RNA interference. The intracellular DENV and WNV loads, as determined by quantitative PCR, were significantly higher in <it>Isg15 </it>silenced cells than control cells. The expression levels of interferon beta 1 (<it>Ifnb1</it>) were increased significantly in <it>Isg15</it>, <it>Socs1 </it>or <it>Socs3 </it>siRNA treated cells. Further investigation indicated that protein modification by ISG15, so called ISGylation, was significantly enhanced in DENV-infected cells compared to that in non-infected cells.</p> <p>Conclusions</p> <p>These findings suggest that ISG15 plays an anti-DENV/WNV function via protein ISGylation.</p

    Properties of Graphene: A Theoretical Perspective

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    In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic

    Dimensional analysis of MINMOD leads to definition of the disposition index of glucose regulation and improved simulation algorithm

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    BACKGROUND: Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) together with its mathematical model, the minimal model (MINMOD), have become important clinical tools to evaluate the metabolic control of glucose in humans. Dimensional analysis of the model is up to now not available. METHODS: A formal dimensional analysis of MINMOD was carried out and the degree of freedom of MINMOD was examined. Through re-expressing all state variable and parameters in terms of their reference scales, MINMOD was transformed into a dimensionless format. Previously defined physiological indices including insulin sensitivity, glucose effectiveness, and first and second phase insulin responses were re-examined in this new formulation. Further, the parameter estimation from FSIVGTT was implemented using both the dimensional and the dimensionless formulations of MINMOD, and the performances were compared utilizing Monte Carlo simulation as well as real human FSIVGTT data. RESULTS: The degree of freedom (DOF) of MINMOD was found to be 7. The model was maximally simplified in the dimensionless formulation that normalizes the variation in glucose and insulin during FSIVGTT. In the new formulation, the disposition index (Dl), a composite parameter known to be important in diabetes pathology, was naturally defined as one of the dimensionless parameters in the system. The numerical simulation using the dimensionless formulation led to a 1.5–5 fold gain in speed, and significantly improved accuracy and robustness in parameter estimation compared to the dimensional implementation. CONCLUSION: Dimensional analysis of MINMOD led to simplification of the model, direct identification of the important composite factors in the dynamics of glucose metabolic control, and better simulations algorithms

    Supercritical fluid technology as a tool to prepare gradient multifunctional architectures towards regeneration of osteochondral injuries

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    Platelet lysates (PLs) are a natural source of growth factors (GFs) known for its stimulatory role on stem cells which can be obtained after activation of platelets from blood plasma. The possibility to use PLs as growth factor source for tissue healing and regeneration has been pursued following different strategies. Platelet lysates are an enriched pool of growth factors which can be used as either a GFs source or as a three-dimensional (3D) hydrogel. However, most of current PLs-based hydrogels lack stability, exhibiting significant shrinking behavior. This chapter focuses on the application of supercritical fluid technology to develop three-dimensional architectures of PL constructs, crosslinked with genipin. The proposed technology allows in a single step operation the development of mechanically stable porous structures, through chemical crosslinking of the growth factors present in the PL pool, followed by supercritical drying of the samples. Furthermore gradient structures of PL-based structures with bioactive glass are also presented and are described as an interesting approach to the treatment of osteochondral defects.info:eu-repo/semantics/publishedVersio

    Bananas as an Energy Source during Exercise: A Metabolomics Approach

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    This study compared the acute effect of ingesting bananas (BAN) versus a 6% carbohydrate drink (CHO) on 75-km cycling performance and post-exercise inflammation, oxidative stress, and innate immune function using traditional and metabolomics-based profiling. Trained cyclists (Nβ€Š=β€Š14) completed two 75-km cycling time trials (randomized, crossover) while ingesting BAN or CHO (0.2 g/kg carbohydrate every 15 min). Pre-, post-, and 1-h-post-exercise blood samples were analyzed for glucose, granulocyte (GR) and monocyte (MO) phagocytosis (PHAG) and oxidative burst activity, nine cytokines, F2-isoprostanes, ferric reducing ability of plasma (FRAP), and metabolic profiles using gas chromatography-mass spectrometry. Blood glucose levels and performance did not differ between BAN and CHO (2.41Β±0.22, 2.36Β±0.19 h, Pβ€Š=β€Š0.258). F2-isoprostanes, FRAP, IL-10, IL-2, IL-6, IL-8, TNFΞ±, GR-PHAG, and MO-PHAG increased with exercise, with no trial differences except for higher levels during BAN for IL-10, IL-8, and FRAP (interaction effects, Pβ€Š=β€Š0.003, 0.004, and 0.012). Of 103 metabolites detected, 56 had exercise time effects, and only one (dopamine) had a pattern of change that differed between BAN and CHO. Plots from the PLS-DA model visualized a distinct separation in global metabolic scores between time points [R2Y(cum)β€Š=β€Š0.869, Q2(cum)β€Š=β€Š0.766]. Of the top 15 metabolites, five were related to liver glutathione production, eight to carbohydrate, lipid, and amino acid metabolism, and two were tricarboxylic acid cycle intermediates. BAN and CHO ingestion during 75-km cycling resulted in similar performance, blood glucose, inflammation, oxidative stress, and innate immune levels. Aside from higher dopamine in BAN, shifts in metabolites following BAN and CHO 75-km cycling time trials indicated a similar pattern of heightened production of glutathione and utilization of fuel substrates in several pathways

    Dephosphorylated NSSR1 Is Induced by Androgen in Mouse Epididymis and Phosphorylated NSSR1 Is Increased during Sperm Maturation

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    NSSR1 (Neural salient serine/arginine rich protein 1, alternatively SRp38) is a newly identified RNA splicing factor and predominantly expressed in neural tissues. Here, by Western blot analysis and immunofluorescent staining, we showed that the expression of dephosphorylated NSSR1 increased significantly during development of the caput epididymis. In adult mice, phosphorylated NSSR1 was mainly expressed in the apical side of epithelial cells, and dephosphorylated NSSR1 in caput epididymis was upregulated in a testosterone dependent manner. In addition, subcellular immunoreactive distribution of NSSR1 varied in different regions of the epididymis. With respect to the sperm, phosphorylated NSSR1 was detected in the mid-piece of the tail as well as the acrosome. Furthermore, NSSR1 was released from the sperm head during the capacitation and acrosome reaction. These findings for the first time provide the evidence for the potential roles of NSSR1 in sperm maturation and fertilization

    Activation of Thromboxane A2 Receptor (TP) Increases the Expression of Monocyte Chemoattractant Protein -1 (MCP-1)/Chemokine (C-C motif) Ligand 2 (CCL2) and Recruits Macrophages to Promote Invasion of Lung Cancer Cells

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    Thromboxane synthase (TXAS) and thromboxane A2 receptor (TP), two critical components for thromboxane A2 (TXA2) signaling, have been suggested to be involved in cancer invasion and metastasis. However, the mechanisms by which TXA2 promotes these processes are still unclear. Here we show that TXA2 mimetic, I-BOP, induced monocyte chemoattractant protein -1(MCP-1)/chemokine (C-C motif) ligand 2 (CCL2) expression at both mRNA and protein levels in human lung adenocarcinoma A549 cells stably over-expressing TP receptor Ξ± isoform (A549-TPΞ±). The induction of MCP-1 was also found in other lung cancer cells H157 and H460 that express relatively high levels of endogenous TP. Using specific inhibitors of several signaling molecules and promoter/luciferase assay, we identified that transcription factor SP1 mediates I-BOP-induced MCP-1 expression. Furthermore, supernatants from I-BOP-treated A549-TPΞ± cells enhanced MCP-1-dependent migration of RAW 264.7 macrophages. Moreover, co-culture of A549 cells with RAW 264.7 macrophages induced expression of MMPs, VEGF and MCP-1 genes, and increased the invasive potential in A549 cells. These findings suggest that TXA2 may stimulate invasion of cancer cells through MCP-1-mediated macrophage recruitment
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