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Sample records for factor induces local

  1. AMPA receptor-induced local brain-derived neurotrophic factor signaling mediates motor recovery after stroke.

    Science.gov (United States)

    Clarkson, Andrew N; Overman, Justine J; Zhong, Sheng; Mueller, Rudolf; Lynch, Gary; Carmichael, S Thomas

    2011-03-09

    Stroke is the leading cause of adult disability. Recovery after stroke shares similar molecular and cellular properties with learning and memory. A main component of learning-induced plasticity involves signaling through AMPA receptors (AMPARs). We systematically tested the role of AMPAR function in motor recovery in a mouse model of focal stroke. AMPAR function controls functional recovery beginning 5 d after the stroke. Positive allosteric modulators of AMPARs enhance recovery of limb control when administered after a delay from the stroke. Conversely, AMPAR antagonists impair motor recovery. The contributions of AMPARs to recovery are mediated by release of brain-derived neurotrophic factor (BDNF) in periinfarct cortex, as blocking local BDNF function in periinfarct cortex blocks AMPAR-mediated recovery and prevents the normal pattern of motor recovery. In contrast to a delayed AMPAR role in motor recovery, early administration of AMPAR agonists after stroke increases stroke damage. These findings indicate that the role of glutamate signaling through the AMPAR changes over time in stroke: early potentiation of AMPAR signaling worsens stroke damage, whereas later potentiation of the same signaling system improves functional recovery.

  2. Outer mitochondrial membrane localization of apoptosis-inducing factor: mechanistic implications for release

    Directory of Open Access Journals (Sweden)

    Seong‑Woon Yu

    2009-11-01

    Full Text Available Poly(ADP-ribose polymerase-1-dependent cell death (known as parthanatos plays a pivotal role in many clinically important events including ischaemia/reperfusion injury and glutamate excitotoxicity. A recent study by us has shown that uncleaved AIF (apoptosis-inducing factor, but not calpain-hydrolysed truncated-AIF, was rapidly released from the mitochondria during parthanatos, implicating a second pool of AIF that might be present in brain mitochondria contributing to the rapid release. In the present study, a novel AIF pool is revealed in brain mitochondria by multiple biochemical analyses. Approx. 30% of AIF loosely associates with the outer mitochondrial membrane on the cytosolic side, in addition to its main localization in the mitochondrial intermembrane space attached to the inner membrane. Immunogold electron microscopic analysis of mouse brain further supports AIF association with the outer, as well as the inner, mitochondrial membrane in vivo. In line with these observations, approx. 20% of uncleaved AIF rapidly translocates to the nucleus and functionally causes neuronal death upon NMDA (N-methyl-d-aspartate treatment. In the present study we show for the first time a second pool of AIF in brain mitochondria and demonstrate that this pool does not require cleavage and that it contributes to the rapid release of AIF. Moreover, these results suggest that this outer mitochondrial pool of AIF is sufficient to cause cell death during parthanatos. Interfering with the release of this outer mitochondrial pool of AIF during cell injury paradigms that use parthanatos hold particular promise for novel therapies to treat neurological disorders.

  3. Outer Mitochondrial Membrane Localization of Apoptosis-Inducing Factor: Mechanistic Implications for Release

    Directory of Open Access Journals (Sweden)

    Seong-Woon Yu

    2009-10-01

    Full Text Available Poly(ADP-ribose polymerase-1-dependent cell death (known as parthanatos plays a pivotal role in many clinically important events including ischaemia/reperfusion injury and glutamate excitotoxicity. A recent study by us has shown that uncleaved AIF (apoptosis-inducing factor, but not calpain-hydrolysed truncated-AIF, was rapidly released from the mitochondria during parthanatos, implicating a second pool of AIF that might be present in brain mitochondria contributing to the rapid release. In the present study, a novel AIF pool is revealed in brain mitochondria by multiple biochemical analyses. Approx. 30% of AIF loosely associates with the outer mitochondrial membrane on the cytosolic side, in addition to its main localization in the mitochondrial intermembrane space attached to the inner membrane. Immunogold electron microscopic analysis of mouse brain further supports AIF association with the outer, as well as the inner, mitochondrial membrane in vivo. In line with these observations, approx. 20% of uncleaved AIF rapidly translocates to the nucleus and functionally causes neuronal death upon NMDA (N-methyl-d-aspartate treatment. In the present study we show for the first time a second pool of AIF in brain mitochondria and demonstrate that this pool does not require cleavage and that it contributes to the rapid release of AIF. Moreover, these results suggest that this outer mitochondrial pool of AIF is sufficient to cause cell death during parthanatos. Interfering with the release of this outer mitochondrial pool of AIF during cell injury paradigms that use parthanatos hold particular promise for novel therapies to treat neurological disorders.

  4. Activation-induced cytidine deaminase (AID) is localized to subnuclear domains enriched in splicing factors

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Yi, E-mail: yihooyi@gmail.com; Ericsson, Ida, E-mail: ida.ericsson@ntnu.no; Doseth, Berit, E-mail: berit.doseth@ntnu.no; Liabakk, Nina B., E-mail: nina.beate.liabakk@ntnu.no; Krokan, Hans E., E-mail: hans.krokan@ntnu.no; Kavli, Bodil, E-mail: bodil.kavli@ntnu.no

    2014-03-10

    Activation-induced cytidine deaminase (AID) is the mutator enzyme in adaptive immunity. AID initiates the antibody diversification processes in activated B cells by deaminating cytosine to uracil in immunoglobulin genes. To some extent other genes are also targeted, which may lead to genome instability and B cell malignancy. Thus, it is crucial to understand its targeting and regulation mechanisms. AID is regulated at several levels including subcellular compartmentalization. However, the complex nuclear distribution and trafficking of AID has not been studied in detail previously. In this work, we examined the subnuclear localization of AID and its interaction partner CTNNBL1 and found that they associate with spliceosome-associated structures including Cajal bodies and nuclear speckles. Moreover, protein kinase A (PKA), which activates AID by phosphorylation at Ser38, is present together with AID in nuclear speckles. Importantly, we demonstrate that AID physically associates with the major spliceosome subunits (small nuclear ribonucleoproteins, snRNPs), as well as other essential splicing components, in addition to the transcription machinery. Based on our findings and the literature, we suggest a transcription-coupled splicing-associated model for AID targeting and activation. - Highlights: • AID and its interaction partner CTNNBL1 localize to Cajal bodies and nuclear speckles. • AID associates with its activating kinase PKA in nuclear speckles. • AID is linked to the splicing machinery in switching B-cells. • Our findings suggest a transcription-coupled splicing associated mechanism for AID targeting and activation.

  5. Analysis of rainfall-induced slope instability using a field of local factor of safety

    Science.gov (United States)

    Lu, Ning; Şener-Kaya, Başak; Wayllace, Alexandra; Godt, Jonathan W.

    2012-01-01

    Slope-stability analyses are mostly conducted by identifying or assuming a potential failure surface and assessing the factor of safety (FS) of that surface. This approach of assigning a single FS to a potentially unstable slope provides little insight on where the failure initiates or the ultimate geometry and location of a landslide rupture surface. We describe a method to quantify a scalar field of FS based on the concept of the Coulomb stress and the shift in the state of stress toward failure that results from rainfall infiltration. The FS at each point within a hillslope is called the local factor of safety (LFS) and is defined as the ratio of the Coulomb stress at the current state of stress to the Coulomb stress of the potential failure state under the Mohr-Coulomb criterion. Comparative assessment with limit-equilibrium and hybrid finite element limit-equilibrium methods show that the proposed LFS is consistent with these approaches and yields additional insight into the geometry and location of the potential failure surface and how instability may initiate and evolve with changes in pore water conditions. Quantitative assessments applying the new LFS field method to slopes under infiltration conditions demonstrate that the LFS has the potential to overcome several major limitations in the classical FS methodologies such as the shape of the failure surface and the inherent underestimation of slope instability. Comparison with infinite-slope methods, including a recent extension to variably saturated conditions, shows further enhancement in assessing shallow landslide occurrence using the LFS methodology. Although we use only a linear elastic solution for the state of stress with no post-failure analysis that require more sophisticated elastoplastic or other theories, the LFS provides a new means to quantify the potential instability zones in hillslopes under variably saturated conditions using stress-field based methods.

  6. AMPA Receptor-Induced Local Brain-Derived Neurotrophic Factor Signaling Mediates Motor Recovery after Stroke

    OpenAIRE

    Clarkson, Andrew N.; Overman, Justine J; Zhong, Sheng; Mueller, Rudolf; Lynch, Gary; Carmichael, S. Thomas

    2011-01-01

    Stroke is the leading cause of adult disability. Recovery after stroke shares similar molecular and cellular properties with learning and memory. A main component of learning-induced plasticity involves signaling through AMPA receptors (AMPARs). We systematically tested the role of AMPAR function in motor recovery in a mouse model of focal stroke. AMPAR function controls functional recovery beginning 5 d after the stroke. Positive allosteric modulators of AMPARs enhance recovery of limb contr...

  7. Local Overexpression of V1a-Vasopressin Receptor Enhances Regeneration in Tumor Necrosis Factor-Induced Muscle Atrophy

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    Alessandra Costa

    2014-01-01

    Full Text Available Skeletal muscle atrophy occurs during disuse and aging, or as a consequence of chronic diseases such as cancer and diabetes. It is characterized by progressive loss of muscle tissue due to hypotrophic changes, degeneration, and an inability of the regeneration machinery to replace damaged myofibers. Tumor necrosis factor (TNF is a proinflammatory cytokine known to mediate muscle atrophy in many chronic diseases and to inhibit skeletal muscle regeneration. In this study, we investigated the role of Arg-vasopressin-(AVP-dependent pathways in muscles in which atrophy was induced by local overexpression of TNF. AVP is a potent myogenesis-promoting factor and is able to enhance skeletal muscle regeneration by stimulating Ca2+/calmodulin-dependent kinase and calcineurin signaling. We performed morphological and molecular analyses and demonstrated that local over-expression of the AVP receptor V1a enhances regeneration of atrophic muscle. By upregulating the regeneration/differentiation markers, modulating the inflammatory response, and attenuating fibrogenesis, the stimulation of AVP-dependent pathways creates a favourable environment for efficient and sustained muscle regeneration and repair even in the presence of elevated levels of TNF. This study highlights a novel in vivo role for AVP-dependent pathways, which may represent an interesting strategy to counteract muscle decline in aging or in muscular pathologies.

  8. Frizzled-Induced Van Gogh Phosphorylation by CK1ε Promotes Asymmetric Localization of Core PCP Factors in Drosophila

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    Lindsay K. Kelly

    2016-07-01

    Full Text Available Epithelial tissues are polarized along two axes. In addition to apical-basal polarity, they are often polarized within the plane of the epithelium, so-called Planar Cell Polarity (PCP. PCP depends upon Wnt/Frizzled (Fz signaling factors, including Fz itself and Van Gogh (Vang/Vangl. We sought to understand how Vang interaction with other core PCP factors affects Vang function. We find that Fz induces Vang phosphorylation in a cell-autonomous manner. Vang phosphorylation occurs on conserved N-terminal serine/threonine residues, is mediated by CK1ε/Dco, and is critical for polarized membrane localization of Vang and other PCP proteins. This regulatory mechanism does not require Fz signaling through Dishevelled and thus represents a cell-autonomous upstream interaction between Fz and Vang. Furthermore, this signaling event appears to be related to Wnt5a-mediated Vangl2 phosphorylation during mouse limb patterning and may thus be a general mechanism underlying Wnt-regulated PCP establishment.

  9. Frizzled-Induced Van Gogh Phosphorylation by CK1ε Promotes Asymmetric Localization of Core PCP Factors in Drosophila.

    Science.gov (United States)

    Kelly, Lindsay K; Wu, Jun; Yanfeng, Wang A; Mlodzik, Marek

    2016-07-12

    Epithelial tissues are polarized along two axes. In addition to apical-basal polarity, they are often polarized within the plane of the epithelium, so-called Planar Cell Polarity (PCP). PCP depends upon Wnt/Frizzled (Fz) signaling factors, including Fz itself and Van Gogh (Vang/Vangl). We sought to understand how Vang interaction with other core PCP factors affects Vang function. We find that Fz induces Vang phosphorylation in a cell-autonomous manner. Vang phosphorylation occurs on conserved N-terminal serine/threonine residues, is mediated by CK1ε/Dco, and is critical for polarized membrane localization of Vang and other PCP proteins. This regulatory mechanism does not require Fz signaling through Dishevelled and thus represents a cell-autonomous upstream interaction between Fz and Vang. Furthermore, this signaling event appears to be related to Wnt5a-mediated Vangl2 phosphorylation during mouse limb patterning and may thus be a general mechanism underlying Wnt-regulated PCP establishment. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Prostaglandin E2 induces hypoxia-inducible factor-1alpha stabilization and nuclear localization in a human prostate cancer cell line.

    Science.gov (United States)

    Liu, Xin Hua; Kirschenbaum, Alexander; Lu, Min; Yao, Shen; Dosoretz, Amy; Holland, James F; Levine, Alice C

    2002-12-20

    Hypoxia-induced up-regulation of vascular endothelial growth factor (VEGF) expression is a critical event leading to tumor neovascularization. Hypoxia stimulates hypoxia-inducible factor-1alpha (HIF-1alpha), a transcriptional activator of VEGF. Cyclooxygenase (COX)-2, an inducible enzyme that catalyzes the formation of prostaglandins (PGs) from arachidonic acid, is also induced by hypoxia. We reported previously that COX-2 inhibition prevents hypoxic up-regulation of VEGF in human prostate cancer cells and that prostaglandin E(2) (PGE(2)) restores hypoxic effects on VEGF. We hypothesized that PGE(2) mediates hypoxic effects on VEGF by modulating HIF-1alpha expression. Addition of PGE(2) to PC-3ML human prostate cancer cells had no effect on HIF-1alpha mRNA levels. However, PGE(2) significantly increased HIF-1alpha protein levels, particularly in the nucleus. This effect of PGE(2) largely results from the promotion of HIF-1alpha translocation from the cytosol to the nucleus. PGE(2) addition to PC-3 ML cells transfected with a GFP-HIF-1alpha vector induced a time-dependent nuclear accumulation of the HIF-1alpha protein. Two selective COX-2 inhibitors, meloxicam and NS398, decreased HIF-1alpha levels and nuclear localization, under both normoxic and hypoxic conditions. Of several prostaglandins tested, only PGE(2) reversed the effects of a COX-2 inhibitor in hypoxic cells. Finally, PGE(2) effects on HIF-1alpha were specifically inhibited by PD98059 (a MAPK inhibitor). These data demonstrate that PGE(2) production via COX-2-catalyzed pathway plays a critical role in HIF-1alpha regulation by hypoxia and imply that COX-2 inhibitors can prevent hypoxic induction of HIF-mediated gene transcription in cancer cells.

  11. Hypoxia-Inducible Factor Pathway Inhibition Resolves Tumor Hypoxia and Improves Local Tumor Control After Single-Dose Irradiation

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    Helbig, Linda [OncoRay–National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Koi, Lydia [OncoRay–National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Deutsches Konsortium für Translationale Krebsforschung, Site Dresden, Dresden (Germany); Brüchner, Kerstin [Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Institute of Radiooncology Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Gurtner, Kristin [Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Hess-Stumpp, Holger; Unterschemmann, Kerstin [Global Drug Discovery, Bayer Pharma, Berlin (Germany); Pruschy, Martin [Radiation Oncology, University of Zurich, Zurich (Switzerland); and others

    2014-01-01

    Purpose: To study the effects of BAY-84-7296, a novel orally bioavailable inhibitor of mitochondrial complex I and hypoxia-inducible factor 1 (HIF-1) activity, on hypoxia, microenvironment, and radiation response of tumors. Methods and Materials: UT-SCC-5 and UT-SCC-14 human squamous cell carcinomas were transplanted subcutaneously in nude mice. When tumors reached 4 mm in diameter BAY-84-7296 (Bayer Pharma AG) or carrier was daily administered to the animals. At 7 mm tumors were either excised for Western blot and immunohistologic investigations or were irradiated with single doses. After irradiation animals were randomized to receive BAY-84-7296 maintenance or carrier. Local tumor control was evaluated 150 days after irradiation, and the dose to control 50% of tumors (TCD{sub 50}) was calculated. Results: BAY-84-7296 decreased nuclear HIF-1α expression. Daily administration of inhibitor for approximately 2 weeks resulted in a marked decrease of pimonidazole hypoxic fraction in UT-SCC-5 (0.5% vs 21%, P<.0001) and in UT-SCC-14 (0.3% vs 19%, P<.0001). This decrease was accompanied by a significant increase in fraction of perfused vessels in UT-SCC-14 but not in UT-SCC-5. Bromodeoxyuridine and Ki67 labeling indices were significantly reduced only in UT-SCC-5. No significant changes were observed in vascular area or necrosis. BAY-84-7296 before single-dose irradiation significantly decreased TCD{sub 50}, with an enhancement ratio of 1.37 (95% confidence interval [CI] 1.13-1.72) in UT-SCC-5 and of 1.55 (95% CI 1.26-1.94) in UT-SCC-14. BAY-84-7296 maintenance after irradiation did not further decrease TCD{sub 50}. Conclusions: BAY-84-7296 resulted in a marked decrease in tumor hypoxia and substantially reduced radioresistance of tumor cells with the capacity to cause a local recurrence after irradiation. The data suggest that reduction of cellular hypoxia tolerance by BAY-84-7296 may represent the primary biological mechanism underlying the observed enhancement of

  12. Increased sister chromatid cohesion and DNA damage response factor localization at an enzyme-induced DNA double-strand break in vertebrate cells.

    LENUS (Irish Health Repository)

    Dodson, Helen

    2009-10-01

    The response to DNA damage in vertebrate cells involves successive recruitment of DNA signalling and repair factors. We used light microscopy to monitor the genetic dependencies of such localization to a single, induced DNA double strand break (DSB) in vertebrate cells. We used an inducible version of the rare-cutting I-SceI endonuclease to cut a chromosomally integrated I-SceI site beside a Tet operator array that was visualized by binding a Tet repressor-GFP fusion. Formation of gamma-H2AX foci at a single DSB was independent of ATM or Ku70. ATM-deficient cells showed normal kinetics of 53Bp1 recruitment to DSBs, but Rad51 localization was retarded. 53Bp1 and Rad51 foci formation at a single DSB was greatly reduced in H2AX-null DT40 cells. We also observed decreased inter-sister chromatid distances after DSB induction, suggesting that cohesin loading at DSBs causes elevated sister chromatid cohesion. Loss of ATM reduced DSB-induced cohesion, consistent with cohesin being an ATM target in the DSB response. These data show that the same genetic pathways control how cells respond to single DSBs and to multiple lesions induced by whole-cell DNA damage.

  13. Endothelial Barrier Protection by Local Anesthetics: Ropivacaine and Lidocaine Block Tumor Necrosis Factor-α–induced Endothelial Cell Src Activation

    Science.gov (United States)

    Piegeler, Tobias; Votta-Velis, E. Gina; Bakhshi, Farnaz R.; Mao, Mao; Carnegie, Graeme; Bonini, Marcelo G.; Schwartz, David E.; Borgeat, Alain; Beck-Schimmer, Beatrice; Minshall, Richard D.

    2014-01-01

    Background Pulmonary endothelial barrier dysfunction mediated in part by Src-kinase activation plays a crucial role in acute inflammatory disease. Proinflammatory cytokines, such as tumor necrosis factor-α (TNFα), activate Src via phosphatidylinositide 3-kinase/Akt-dependent nitric oxide generation, a process initiated by recruitment of phosphatidylinositide 3-kinase regulatory subunit p85 to TNF-receptor-1. Because amide-linked local anesthetics have well-established anti-inflammatory effects, the authors hypothesized that ropivacaine and lidocaine attenuate inflammatory Src signaling by disrupting the phosphatidylinositide 3-kinase–Akt–nitric oxide pathway, thus blocking Src-dependent neutrophil adhesion and endothelial hyperpermeability. Methods Human lung microvascular endothelial cells, incubated with TNFα in the absence or presence of clinically relevant concentrations of ropivacaine and lidocaine, were analyzed by Western blot, probing for phosphorylated/activated Src, endothelial nitric oxide synthase, Akt, intercellular adhesion molecule-1, and caveolin-1. The effect of ropivacaine on TNFα-induced nitric oxide generation, co-immunoprecipitation of TNF-receptor-1 with p85, neutrophil adhesion, and endothelial barrier disruption were assessed. Results Ropivacaine and lidocaine attenuated TNFα-induced Src activation (half-maximal inhibitory concentration [IC50] = 8.611 × 10−10 M for ropivacaine; IC50 = 5.864 × 10−10 M for lidocaine) and endothelial nitric oxide synthase phosphorylation (IC50 = 7.572 × 10−10 M for ropivacaine; IC50 = 6.377 × 10−10 M for lidocaine). Akt activation (n = 7; P = 0.006) and stimulus-dependent binding of TNF-receptor-1 and p85 (n = 6; P = 0.043) were blocked by 1 nM of ropivacaine. TNFα-induced neutrophil adhesion and disruption of endothelial monolayers via Src-dependent intercellular adhesion molecule-1- and caveolin-1-phosphorylation, respectively, were also attenuated. Conclusions Ropivacaine and lidocaine

  14. Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Local Osteoporotic Canine Mandible Model for the Evaluation of Peri-Implant Bone Regeneration.

    Science.gov (United States)

    Chang, Ah Ryum; Cho, Tae Hyung; Hwang, Soon Jung

    2017-08-24

    The canine mandible is useful for studying bone regeneration after dental implant placement. However, it is limited in investigations of peri-implant osteogenesis under osteoporotic conditions due to the insignificant osteoporotic effect of ovariectomy. This study aimed at establishing a local osteoporotic model without ovariectomy by using receptor activator of nuclear factor kappa-B ligand (RANKL) in a canine mandible model. This new model was used to evaluate the effects of injectable β-tricalcium phosphate (TCP) microsphere bone grafts on peri-implant bone regeneration under osteoporotic conditions with combinations of recombinant human bone morphogenetic protein-2 (rhBMP-2). A local osteoporotic canine mandible model was designed by creating a hole in the mandibular alveolar bone, then implanting a collagen sponge soaked with 20, 40, or 60 μg RANKL into the hole, and leaving it for 2 weeks. After the establishment of the dose for maximum osteoporotic bone loss at 40 μg of RANKL, the main surgery was performed. RANKL-soaked collagen sponges were removed, and dental implants were placed with bone grafts in five groups: implant only, TCP, and TCP + rhBMP-2 at 5, 15, and 45 μg. Peri-implant bone generation was determined by radiologic and histologic evaluations at 6 weeks after dental implant placement. On performing micro-computed tomography analysis, the group with TCP + 5 μg rhBMP-2 showed the highest bone volume than the other groups and a 22% increase (p model was useful for peri-implant bone regeneration under osteoporotic conditions such as those found in geriatric patients. The injectable β-TCP bone grafts used in this study were effective in peri-implant bone generation under osteoporotic conditions, and their efficiency was enhanced at 5 μg BMP-2 compared with higher concentrations of BMP-2.

  15. Local CO2-induced swelling of shales

    Science.gov (United States)

    Pluymakers, Anne; Dysthe, Dag Kristian

    2017-04-01

    In heterogeneous shale rocks, CO2 adsorbs more strongly to organic matter than to the other components. CO2-induced swelling of organic matter has been shown in coal, which is pure carbon. The heterogeneity of the shale matrix makes an interesting case study. Can local swelling through adsorption of CO2 to organic matter induce strain in the surrounding shale matrix? Can fractures close due to CO2-induced swelling of clays and organic matter? We have developed a new generation of microfluidic high pressure cells (up to 100 bar), which can be used to study flow and adsorption phenomena at the microscale in natural geo-materials. The devices contain one transparent side and a shale sample on the other side. The shale used is the Pomeranian shale, extracted from 4 km depth in Poland. This formation is a potential target of a combined CO2-storage and gas extraction project. To answer the first question, we place the pressure cell under a Veeco NT1100 Interferometer, operated in Vertical Scanning Interferometry mode and equipped with a Through Transmissive Media objective. This allows for observation of local swelling or organic matter with nanometer vertical resolution and micrometer lateral resolution. We expose the sample to CO2 atmospheres at different pressures. Comparison of the interferometry data and using SEM-EDS maps plus optical microscopy delivers local swelling maps where we can distinguish swelling of different mineralogies. Preliminary results indicate minor local swelling of organic matter, where the total amount is both time- and pressure-dependent.

  16. Acquired Localized Hypertrichosis Induced by Rivastigmine

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    Imbernón-Moya, Adrian; Podlipnik, Sebastian; Burgos, Fernando; Vargas-Laguna, Elena; Aguilar-Martínez, Antonio; Fernández-Cogolludo, Eva; Gallego-Valdes, Miguel Angel

    2016-01-01

    Hypertrichosis is the excessive hair growth in any area of the skin surface. Acquired localized hypertrichosis may be secondary to multiple causes and there is a secondary form due to several drugs, which is usually reversible with discontinuation of the causative agent. Rivastigmine is a reversible and competitive inhibitor of acetylcholinesterase and butyrylcholinesterase used for symptomatic treatment of Alzheimer dementia and Parkinson's disease. It has an adequate safety profile and cutaneous side effects are unusual. Irritant contact dermatitis, allergic dermatitis, baboon syndrome, and cutaneous rash due to rivastigmine have been reported. We report on a Caucasian 80-year-old male with personal history of Alzheimer's disease. The patient started therapy with oral rivastigmine one month prior to clinical presentation of localized hypertrichosis on both forearms. Norgalanthamine has been shown to promote hair growth activity via the proliferation of dermal papilla. Acetylcholinesterase inhibitors can induce hair growth. PMID:27073702

  17. Acquired Localized Hypertrichosis Induced by Rivastigmine

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    Adrian Imbernón-Moya

    2016-01-01

    Full Text Available Hypertrichosis is the excessive hair growth in any area of the skin surface. Acquired localized hypertrichosis may be secondary to multiple causes and there is a secondary form due to several drugs, which is usually reversible with discontinuation of the causative agent. Rivastigmine is a reversible and competitive inhibitor of acetylcholinesterase and butyrylcholinesterase used for symptomatic treatment of Alzheimer dementia and Parkinson’s disease. It has an adequate safety profile and cutaneous side effects are unusual. Irritant contact dermatitis, allergic dermatitis, baboon syndrome, and cutaneous rash due to rivastigmine have been reported. We report on a Caucasian 80-year-old male with personal history of Alzheimer’s disease. The patient started therapy with oral rivastigmine one month prior to clinical presentation of localized hypertrichosis on both forearms. Norgalanthamine has been shown to promote hair growth activity via the proliferation of dermal papilla. Acetylcholinesterase inhibitors can induce hair growth.

  18. Local brain heavy ion irradiation induced Immunosuppression

    Science.gov (United States)

    Lei, Runhong; Deng, Yulin; Huiyang Zhu, Bitlife.; Zhao, Tuo; Wang, Hailong; Yu, Yingqi; Ma, Hong; Wang, Xiao; Zhuang, Fengyuan; Qing, Hong

    Purpose: To investigate the long term effect of acute local brain heavy ion irradiation on the peripheral immune system in rat model. Methodology: Only the brain of adult male Wistar rats were radiated by heavy ions at the dose of 15 Gy. One, two and three months after irradiation, thymus and spleen were analyzed by four ways. Tunel assay was performed to evaluate the percentage of apoptotic cells in thymus and spleen, level of Inflammatory cytokines (IL-2, IL-6, SSAO, and TNF-α) was detected by ELISA assay, the differentiation of thymus T lymphocyte subsets were measured by flow cytometry and the relative expression levels of genes related to thymus immune cell development were measured by using quantitative real-time PCR. Results: Thymus and spleen showed significant atrophy from one month to three months after irradiation. A high level of apoptosis in thymus and spleen were obtained and the latter was more vulnerable, also, high level of inflammatory cytokines were found. Genes (c-kit, Rag1, Rag2 and Sca1) related to thymus lymphocytes’ development were down-regulated. Conclusion: Local area radiation in the rat brain would cause the immunosuppression, especially, the losing of cell-mediated immune functions. In this model, radiation caused inflammation and then induced apoptosis of cells in the immune organs, which contributed to immunosuppression.

  19. Mitochondria localization and dimerization are required for CIDE-B to induce apoptosis.

    Science.gov (United States)

    Chen, Z; Guo, K; Toh, S Y; Zhou, Z; Li, P

    2000-07-28

    Cell death-inducing DFF45-like effector (CIDE)-B is a member of the novel family of apoptosis-inducing factors that share homology with the N-terminal region of DFF, the DNA fragmentation factor. The molecular mechanism of CIDE-B-induced apoptosis is unclear. We have shown here that CIDE-B protein is localized in mitochondria and forms homodimers and heterodimers with other family members. Serial deletion analyses suggest that the mitochondria localization signal and dimerization interface are overlapped and localized to the 30 amino acid residues at the C-terminal region of CIDE-B. Mitochondria localization and dimerization are both required for CIDE-B-induced apoptosis. Our study has thus revealed a mechanism for CIDE-B-induced apoptosis by localization to mitochondria and the formation of a high affinity homo- or heterodimeric complex.

  20. Local communities’ consolidation process: political factors

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    V. V. Fedorenko

    2017-04-01

    It has been underlined that the local communities’ consolidation process in the contemporary world is the problem which has both empirical and theoretical importance. Depending on the size of the local area, local polices are taking different forms. As usual, they provide an agreement and compromise solutions based on issues that are important to the local community. The experience of the developed democracies has shown that local assemblies ensure the establishment of coalitions based on short-termed procedures. The study has tested that an important aspect of the formation of local communities consolidated position is based on development issues and civil participation. It is especially visible in the United States and the EU countries. The municipality level determines the quality of local political bodies, which is formed on party basis. For contemporary Ukraine important tools for provision of political responsibility are forces, which take care about the local communities and determine their development for a long period. Overall, the consolidation of political forces in the local government system is an important task that determines the need for the adoption of regulatory instruments which would ensure the harmonious and constructive political cooperation regardless of their ideological positions.

  1. Unified entropic measures of quantum correlations induced by local measurements

    Science.gov (United States)

    Bosyk, G. M.; Bellomo, G.; Zozor, S.; Portesi, M.; Lamberti, P. W.

    2016-11-01

    We introduce quantum correlation measures based on the minimal change in unified entropies induced by local rank-one projective measurements, divided by a factor that depends on the generalized purity of the system in the case of nonadditive entropies. In this way, we overcome the issue of the artificial increasing of the value of quantum correlation measures based on nonadditive entropies when an uncorrelated ancilla is appended to the system, without changing the computability of our entropic correlation measures with respect to the previous ones. Moreover, we recover as limiting cases the quantum correlation measures based on von Neumann and Rényi entropies (i.e., additive entropies), for which the adjustment factor becomes trivial. In addition, we distinguish between total and semiquantum correlations and obtain some inequalities between them. Finally, we obtain analytical expressions of the entropic correlation measures for typical quantum bipartite systems.

  2. Perceptual factors contribute more than acoustic factors to sound localization abilities with virtual sources

    Directory of Open Access Journals (Sweden)

    Guillaume eAndeol

    2015-01-01

    Full Text Available Human sound localization abilities rely on binaural and spectral cues. Spectral cues arise from interactions between the sound wave and the listener’s body (head related transfer function, HRTF. Large individual differences were reported in localization abilities, even in young normal-hearing adults. Several studies have attempted to determine whether localization abilities depend mostly on acoustic cues or on perceptual processes involved in the analysis of these cues. These studies have yielded inconsistent findings, which could result from methodological issues. Here, we measured sound localization performance with normal and modified acoustic cues (i.e., with individual and non-individual HRTFs, respectively in 20 naïve listeners. Test conditions were chosen to address most methodological issues from past studies. Procedural training was provided prior to sound localization tests. The results showed no direct relationship between behavioral results and an acoustical metric (spectral-shape prominence of individual HRTFs. Despite uncertainties due to technical issues with the normalization of the HRTFs, large acoustic differences between individual and non-individual HRTFs seemed to be needed to produce behavioral effects. A subset of 15 listeners then trained in the sound localization task with individual HRTFs. Training included either visual correct-answer feedback (for the test group or no feedback (for the control group, and was assumed to elicit perceptual learning for the test group only. Few listeners from the control group, but most listeners from the test group, showed significant training-induced learning. For the test group, learning was related to pre-training performance (the poorer the pre-training performance, the greater the learning amount and was retained after one month.The results are interpreted as being in favor of a larger contribution of perceptual factors than of acoustic factors to sound localization abilities

  3. Lake destratification induced by local air injection

    NARCIS (Netherlands)

    Kranenburg, C.

    1979-01-01

    Mathematical and physical modelling makes possible quantitative predictions regarding the destratification process brought about by the local injection of air at the bottom of a thermally stratified lake or reservoir. The mathematical model developed distinguishes between a near field and a far fiel

  4. Local inflammation induces complement crosstalk which amplifies the antimicrobial response.

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    2009-01-01

    Full Text Available By eliciting inflammatory responses, the human immunosurveillance system notably combats invading pathogens, during which acute phase proteins (CRP and cytokines are elevated markedly. However, the Pseudomonas aeruginosa is a persistent opportunistic pathogen prevalent at the site of local inflammation, and its acquisition of multiple antibiotic-resistance factors poses grave challenges to patient healthcare management. Using blood samples from infected patients, we demonstrate that P. aeruginosa is effectively killed in the plasma under defined local infection-inflammation condition, where slight acidosis and reduced calcium levels (pH 6.5, 2 mM calcium typically prevail. We showed that this powerful antimicrobial activity is provoked by crosstalk between two plasma proteins; CRPratioL-ficolin interaction led to communication between the complement classical and lectin pathways from which two amplification events emerged. Assays for C4 deposition, phagocytosis, and protein competition consistently proved the functional significance of the amplification pathways in boosting complement-mediated antimicrobial activity. The infection-inflammation condition induced a 100-fold increase in CRPratioL-ficolin interaction in a pH- and calcium-sensitive manner. We conclude that the infection-induced local inflammatory conditions trigger a strong interaction between CRPratioL-ficolin, eliciting complement-amplification pathways which are autonomous and which co-exist with and reinforce the classical and lectin pathways. Our findings provide new insights into the host immune response to P. aeruginosa infection under pathological conditions and the potential development of new therapeutic strategies against bacterial infection.

  5. QUANTIFYING LOCAL RADIATION-INDUCED LUNG DAMAGE FROM COMPUTED TOMOGRAPHY

    NARCIS (Netherlands)

    Ghobadi, Ghazaleh; Hogeweg, Laurens E.; Faber, Hette; Tukker, Wim G. J.; Schippers, Jacobus M.; Brandenburg, Sytze; Langendijk, Johannes A.; Coppes, Robert P.; van Luijk, Peter

    2010-01-01

    Purpose: Optimal implementation of new radiotherapy techniques requires accurate predictive models for normal tissue complications. Since clinically used dose distributions are nonuniform, local tissue damage needs to be measured and related to local tissue dose. In lung, radiation-induced damage re

  6. Measurement of the profiles of disorder-induced localized resonances by local tuning

    CERN Document Server

    Lian, J; Yüce, E; Combrié, S; De Rossi, A; Mosk, A P; .,

    2016-01-01

    Near the band edge of photonic crystal waveguides, localized modes appear due to disorder. We demonstrate a new method to elucidate spatial profile of the localized modes in such systems using precise local tuning. Using deconvolution with the known thermal profile, the spatial profile of a localized mode with quality factor ($Q$) $>10^5$ is successfully reconstructed with a resolution of $2.5 \\ \\mu $m.

  7. Local Modulation of Double Electromagnetically Induced Transparency Spectrum

    Institute of Scientific and Technical Information of China (English)

    HOU Bang-Pin; WANG Shun-Jin; YU Wan-Lun; SUN Wei-Li

    2007-01-01

    The double electromagnetically induced transparency induced by two coupling fields can be realized in a fourlevel tripod-type atom. Such double transparency spectra can be locally modulated by using the weak coherent fields to perturb the coupling transitions. These investigations within this scheme can be independent of Doppler broadening by properly orienting these fields.

  8. Noise-Induced Subdiffusion in Strongly Localized Quantum Systems

    Science.gov (United States)

    Gopalakrishnan, Sarang; Islam, K. Ranjibul; Knap, Michael

    2017-07-01

    We consider the dynamics of strongly localized systems subject to dephasing noise with arbitrary correlation time. Although noise inevitably induces delocalization, transport in the noise-induced delocalized phase is subdiffusive in a parametrically large intermediate-time window. We argue for this intermediate-time subdiffusive regime both analytically and using numerical simulations on single-particle localized systems. Furthermore, we show that normal diffusion is restored in the long-time limit, through processes analogous to variable-range hopping. With numerical simulations based on Lanczos exact diagonalization, we demonstrate that our qualitative conclusions are also valid for interacting systems in the many-body localized phase.

  9. Field patching, factorization and local-global principles

    CERN Document Server

    Krashen, Daniel

    2009-01-01

    In this paper we first describe the method of field patching, developed by Harbater and Hartmann, paying special attention to the relationship between factorization and local-global principles, and second, we extend the basic factorization result previously known for rational groups to the case of retract rational groups.

  10. Socio-economic, cultural and livelihood factors influencing local ...

    African Journals Online (AJOL)

    Socio-economic, cultural and livelihood factors influencing local people ... The social and economic circumstances prevailing in Tanzania today have made ... sociocultural and livelihood factors that influence community participation in ... Increased capacity for conservation skills was the most important driver of community ...

  11. Complexity of OM factorizations of polynomials over local fields

    CERN Document Server

    Bauch, Jens-Dietrich; Stainsby, Hayden D

    2012-01-01

    Let $k$ be a locally compact complete field with respect to a discrete valuation $v$. Let $\\oo$ be the valuation ring, $\\m$ the maximal ideal and $F(x)\\in\\oo[x]$ a monic separable polynomial of degree $n$. Let $\\delta=v(\\dsc(F))$. The Montes algorithm computes an OM factorization of $F$. The single-factor lifting algorithm derives from this data a factorization of $F \\md{\\m^\

  12. The avian head induces cues for sound localization in elevation.

    Directory of Open Access Journals (Sweden)

    Hans A Schnyder

    Full Text Available Accurate sound source localization in three-dimensional space is essential for an animal's orientation and survival. While the horizontal position can be determined by interaural time and intensity differences, localization in elevation was thought to require external structures that modify sound before it reaches the tympanum. Here we show that in birds even without external structures like pinnae or feather ruffs, the simple shape of their head induces sound modifications that depend on the elevation of the source. Based on a model of localization errors, we show that these cues are sufficient to locate sounds in the vertical plane. These results suggest that the head of all birds induces acoustic cues for sound localization in the vertical plane, even in the absence of external ears.

  13. The avian head induces cues for sound localization in elevation.

    Science.gov (United States)

    Schnyder, Hans A; Vanderelst, Dieter; Bartenstein, Sophia; Firzlaff, Uwe; Luksch, Harald

    2014-01-01

    Accurate sound source localization in three-dimensional space is essential for an animal's orientation and survival. While the horizontal position can be determined by interaural time and intensity differences, localization in elevation was thought to require external structures that modify sound before it reaches the tympanum. Here we show that in birds even without external structures like pinnae or feather ruffs, the simple shape of their head induces sound modifications that depend on the elevation of the source. Based on a model of localization errors, we show that these cues are sufficient to locate sounds in the vertical plane. These results suggest that the head of all birds induces acoustic cues for sound localization in the vertical plane, even in the absence of external ears.

  14. Glutamine synthetase localization in cortisol-induced chick embryo retinas

    OpenAIRE

    1980-01-01

    We report here for the first time, in chick retina, Muller cell localization of glutamine synthetase (GS) activity by an immunohistochemical technique, in agreement with previous reports of glial localization of this enzyme in rat brain and retina. Age- dependent changes in the endogenous enzyme activity as well as cortisol- induced changes in GS activity, both in ovo and in vitro, measured biochemically, reflect the changes observed by staining.

  15. Immunohistochemical localization of epidermal growth factor in rat and man

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1986-01-01

    Epidermal growth factor (EGF) is a peptide which stimulates cell mitotic activity and differentiation, has a cytoprotective effect on the gastroduodenal mucosa, and inhibits gastric acid secretion. The immunohistochemical localization of EGF in the Brunner's glands and the submandibular glands...... is well documented. The localization of EGF in other tissues is still unclarified. In the present study, the immunohistochemical localization of EGF in tissues from rat, man and a 20 week human fetus were investigated. In man and rat, immunoreaction was found in the submandibular glands, the serous glands...

  16. Nonnegative Matrix Factorizations Performing Object Detection and Localization

    Directory of Open Access Journals (Sweden)

    G. Casalino

    2012-01-01

    Full Text Available We study the problem of detecting and localizing objects in still, gray-scale images making use of the part-based representation provided by nonnegative matrix factorizations. Nonnegative matrix factorization represents an emerging example of subspace methods, which is able to extract interpretable parts from a set of template image objects and then to additively use them for describing individual objects. In this paper, we present a prototype system based on some nonnegative factorization algorithms, which differ in the additional properties added to the nonnegative representation of data, in order to investigate if any additional constraint produces better results in general object detection via nonnegative matrix factorizations.

  17. Matrix Factorizations for Local F-Theory Models

    CERN Document Server

    Omer, Harun

    2016-01-01

    I use matrix factorizations to describe branes at simple singularities as they appear in elliptic fibrations of local F-theory models. Each node of the corresponding Dynkin diagrams of the ADE-type singularities is associated with one indecomposable matrix factorization which can be deformed into one or more factorizations of lower rank. Branes with internal fluxes arise naturally as bound states of the indecomposable factorizations. Describing branes in such a way avoids the need to resolve singularities and encodes information which is neglected in conventional F-theory treatments. This paper aims to show how branes arising in local F-theory models around simple singularities can be described in this framework.

  18. Two-dimensional atom localization induced by a squeezed vacuum

    Science.gov (United States)

    Wang, Fei; Xu, Jun

    2016-10-01

    A scheme of two-dimensional (2D) atom localization induced by a squeezed vacuum is proposed, in which the three-level V-type atoms interact with two classical standing-wave fields. It is found that when the environment is changed from an ordinary vacuum to a squeezed vacuum, the 2D atom localization is realized by detecting the position-dependent resonance fluorescence spectrum. For comparison, we demonstrate that the atom localization originating from the quantum interference effect is distinct from that induced by a squeezed vacuum. Furthermore, the combined effects of the squeezed vacuum and quantum interference are also discussed under appropriate conditions. The internal physical mechanism is analyzed in terms of dressed-state representation. Project supported by the National Natural Science Foundation of China (Grant Nos. 11574179 and 11204099) and the Natural Science Foundation of Hubei Province, China (Grant No. 2014CFC1148).

  19. Factores para la sostenibilidad del desarrollo local de Maracaibo

    Directory of Open Access Journals (Sweden)

    Fernando Torres Granadillo

    2012-01-01

    Full Text Available El objetivo central del trabajo es describir los factores para la sostenibilidad del desarrollo local de Maracaibo. El tipo de investigación fue descriptiva, bajo un diseño transeccional y de campo. La población estuvo conformada por 475 empresas, bajo un muestreo no probabilístico de tipo intensional se aplicó un cuestionario estructurado, validado por expertos y la confiabilidad de acuerdo a Alpha de Cronbach a 85 empresas, en 7 sectores economicos prepondantes en la econonía local, a saber: actividades financieras y de seguro, comercio, construcción, industrias manufactureras (elaboración de alimentos, servicios sociales y salud, servicios tecnológicos y transporte, almacenamiento y comunicaciones. Los resultados indicaron que la detección de debilidades en las interconectividades de los factores capital social, innovación y empredimiento genera una endeble sostenibilidad del desarrollo local Marabino.

  20. Evaluating Academic Journals Using Impact Factor and Local Citation Score

    Science.gov (United States)

    Chung, Hye-Kyung

    2007-01-01

    This study presents a method for journal collection evaluation using citation analysis. Cost-per-use (CPU) for each title is used to measure cost-effectiveness with higher CPU scores indicating cost-effective titles. Use data are based on the impact factor and locally collected citation score of each title and is compared to the cost of managing…

  1. FACTORES FINANCIEROS LOCALES INFLUYEN LAS ACTIVIDADES DE LOS BANCOS COOPERATIVOS GRIEGOS / LOCAL FINANCIAL FACTORS INFLUENCING ACTIVITIES OF GREEK COOPERATIVE BANKS

    Directory of Open Access Journals (Sweden)

    GEORGE KONTEOS

    2010-09-01

    Full Text Available Este artículo examina la influencia de las condiciones locales en las actividades bancarias centrandose en el caso de los 14 bancos cooperativos en Grecia durante el período 1999-2007. Estos bancos han sido seleccionados por su carácter local y en consecuencia, están más influenciadas por las condiciones locales, en comparación con los bancos con red nacional e incluso internacional. Las condiciones locales pueden ser endógenas y exógenas al banco. Las endógenas al banco es la red bancaria que se desarrolla a nivel local o regional asi como a los miembros de los bancos que son la parte principal de la clientela de estas. Una macroeconómica y exógena condición del banco es la cantidad de ahorros en la localidad donde opera. Las actividades bancarias que han sido examinadas incluyen los depósitos y los préstamos que constituyen la parte principal de las actividades bancarias de los bancos cooperativos en Grecia. El crecimiento de la red bancaria es el principal factor de aumento de las actividades del banco; el crecimiento de los miembros de las cooperativas y el aumento de las economías locales tienen una influencia positiva, pero menos importante en las actividades de los bancos cooperativos./This paper examines the influence of local conditions on banking activities focusing on the case of 14 cooperative banks in Greece for the period 1999-2007. These banks have been chosen because of their local character and consequently they are more influenced by local conditions in comparison to banks having a national and even international network. Local conditions could be endogenous and exogenous to the bank. The endogenous to the bank are the banking network developed locally or regionally, and the members of the banks who are the main part of the banks’ clientele. A macroeconomic and exogenous to the bank condition is the amount of savings in the prefecture in which the cooperative bank operates. The banking activities which have

  2. Mitochondrial localized STAT3 is involved in NGF induced neurite outgrowth.

    Directory of Open Access Journals (Sweden)

    Lihan Zhou

    Full Text Available BACKGROUND: Signal transducer and activator of transcription 3 (STAT3 plays critical roles in neural development and is increasingly recognized as a major mediator of injury response in the nervous system. Cytokines and growth factors are known to phosphorylate STAT3 at tyrosine(705 with or without the concomitant phosphorylation at serine(727, resulting in the nuclear localization of STAT3 and subsequent transcriptional activation of genes. Recent evidence suggests that STAT3 may control cell function via alternative mechanisms independent of its transcriptional activity. Currently, the involvement of STAT3 mono-phosphorylated at residue serine(727 (P-Ser-STAT3 in neurite outgrowth and the underlying mechanism is largely unknown. PRINCIPAL FINDINGS: In this study, we investigated the role of nerve growth factor (NGF induced P-Ser-STAT3 in mediating neurite outgrowth. NGF induced the phosphorylation of residue serine(727 but not tyrosine(705 of STAT3 in PC12 and primary cortical neuronal cells. In PC12 cells, serine but not tyrosine dominant negative mutant of STAT3 was found to impair NGF induced neurite outgrowth. Unexpectedly, NGF induced P-Ser-STAT3 was localized to the mitochondria but not in the nucleus. Mitochondrial STAT3 was further found to be intimately involved in NGF induced neurite outgrowth and the production of reactive oxygen species (ROS. CONCLUSION: Taken together, the findings herein demonstrated a hitherto unrecognized novel transcription independent mechanism whereby the mitochondria localized P-Ser-STAT3 is involved in NGF induced neurite outgrowth.

  3. Canceling disorder-induced localization in nanophotonic cavity arrays

    CERN Document Server

    Sokolov, Sergei; Yüce, Emre; Combrié, Sylvain; De Rossi, Alfredo; Mosk, Allard P

    2016-01-01

    Optical circuits containing high-Q photonic crystal nanocavities have been proposed for delay lines, optical memory storage, optomechanics and quantum communication. However, unavoidable fabrication disorder in nanophotonic structures causes scattering which leads to frequency detuning, signal attenuation, and eventually localizes optical modes which ruins the transmission properties of the whole system. Even state-of-the-art nanofabrication with random spatial variations of only $\\Delta x=1\\ \\rm{nm}$ can lead to resonance wavelength detunings of more than $\\Delta \\lambda =1\\ \\rm{nm}$. In this work, we present a new method to cancel disorder-induced localization of light in a system of coupled nanocavities. We use holographic laser-induced heating to tune individual cavities, introduce a thermal response matrix approach and as a result we observe fully hybridized resonances of three coupled nanocavities, indicating that the effect of the disorder has been canceled. Our method is scalable to large arrays and e...

  4. Electrical signaling in Aloe vera induced by localized thermal stress.

    Science.gov (United States)

    Volkov, Alexander G; Lang, Ryan D; Volkova-Gugeshashvili, Maia I

    2007-11-01

    Action potentials in higher plants are theorized as the information carriers in intercellular and intracellular communication in the presence of environmental stressors. Among the most common stressors is heat shock. Under stressful conditions, the response reactions of plant tissues and organs can be local or transmitted over long distances. In this article, the speeds of propagation of thermally induced action potentials in green plants are discussed, and their speeds were found to be comparable to those occurring in various mammalian species. These rapid action potentials in green plants were recorded in real time using modern data acquisition techniques. According to our measurements, a single application of localized heat stress induces fast action potentials in Aloe vera (67 m/s). Electrical signals propagated along all leaves of the A. vera plants were studied. Possible pathways for electrical signal propagation in vascular plants are also discussed.

  5. Local and regional factors influencing bacterial community assembly.

    Science.gov (United States)

    Lindström, Eva S; Langenheder, Silke

    2012-02-01

    The classical view states that microbial biogeography is not affected by dispersal barriers or historical events, but only influenced by the local contemporary habitat conditions (species sorting). This has been challenged during recent years by studies suggesting that also regional factors such as mass effect, dispersal limitation and neutral assembly are important for the composition of local bacterial communities. Here we summarize results from biogeography studies in different environments, i.e. in marine, freshwater and soil as well in human hosts. Species sorting appears to be the most important mechanism. However, this result might be biased since this is the mechanism that is easiest to measure, detect and interpret. Hence, the importance of regional factors may have been underestimated. Moreover, our survey indicates that different assembly mechanisms might be important for different parts of the total community, differing, for example, between generalists and specialists, and between taxa of different dispersal ability and motility. We conclude that there is a clear need for experimental studies, first, to clearly separate regional and local factors in order to study their relative importance, and second, to test whether there are differences in assembly mechanisms depending on different taxonomic or functional groups.

  6. Permittivity disorder induced Anderson localization in magnetophotonic crystals

    Energy Technology Data Exchange (ETDEWEB)

    Abdi-Ghaleh, R., E-mail: r.abdi@bonabu.ac.ir [Department of Laser and Optical Engineering, University of Bonab, 5551761167 Bonab (Iran, Islamic Republic of); Namdar, A. [Faculty of Physics, University of Tabriz, 5166614766 Tabriz (Iran, Islamic Republic of)

    2016-11-15

    This theoretical study was carried out to investigate the permittivity disorder induced Anderson localization of light in one-dimensional magnetophotonic crystals. It was shown that the disorder create the resonant transmittance modes associated with enhanced Faraday rotations inside the photonic band gap. The average localization length of the right- and left-handed circular polarizations (RCP and LCP), the total transmittance together with the ensemble average of the RCP and LCP phases, and the Faraday rotation of the structure were also investigated. For this purpose, the off-diagonal elements of the permittivity tensor were varied for various wavelengths of incident light. The obtained results revealed the nonreciprocal property of circular eigen modes. This study can potentially open up a new aspect for utilizing the disorder magnetophotonic structures in nonreciprocal systems such as isolators and circulators. - Highlights: • We theoretically investigated the permittivity disorder induced Anderson localization of light in magnetophotonic crystals. • The disorder considered in the diagonal elements of the permittivity tensor of magneto-optical layers. • The disorder create the resonant transmittance modes associated with enhanced Faraday rotations in the photonic band gap. • The average localization length of the circular polarizations and the ensemble average of their phases were investigated. • The obtained results revealed the nonreciprocal property of circular eigen modes.

  7. PROGNOSTIC FACTORS OF BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY FOR LOCALIZED AND LOCALLY-ADVANCED PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    V. A. Chernyaev

    2014-08-01

    Full Text Available Purpose. To reveal prognostic factors of PSA-failure following radical prostatectomy in patients with localized and locally-advanced prostate cancer.Materials and methods. Medical data of 386 consecutive patients with localized and locally-advanced prostate cancer who underwent radical prostatectomy from 1997 to 2011 were analyzed. Median age was 61.0 years. Median PSA before surgery – 10.3 ng/ml. Plasma levels of VEGF, VEGFR2, VEGFR3, TGF-β1, CD105, IL-6 were measured using Enzyme Linked-Immuno-Sorbent Assay (ELISA before radical prostatectomy in 77 patients. Postoperatively the tumours were categorized as pT2 in 288 (59.1 %, pT3 – in 144 (37.3 %, pT4 – in 14 (3.6; pN+ – in 34 (8.8 % cases. Gleason score < 7 was present in 254 (65.8 %,  7 – in 132 (34.2 % specimens. Perineural invasion was identified in 188 (48.7 %, angiolymphatic invasion – in 126 (32.6 cases.Results. Biochemical recurrence occurred in 64 (16.6 % out of 386 patients at a median follow-up of 30.5 (12−164 months. Independent predictors of biochemical recurrence were PSA (HR 0.161 (95% CI:0.058−0.449; р = 0.001, Gleason sum in surgical specimens (HR 0.496 (95 % CI:0.268−0.917; p = 0.025, pN (HR 0.415 (95 % CI:0.181−0.955; p = 0.039. The patients were divided into 3 prognostic groups: good (0 factor, intermediate (1 factor, poor (2 factors and very poor (3 factors (AUC – 0.720 (95% CI: 0.656−0.784. High preoperative levels VEGF ( 67 pg/ml (р = 0.005, VEGFR2 ( 3149 pg/ml (р = 0.036, VEGFR3 ( 2268 pg/ml (р = 0.001, TGF-β1 ( 14473 pg/ml (р = 0.052 were identified as unfavorable prognostic factors for survival without PSA-failure. Conclusion. Independent prognostic factors of biochemical recurrence after prostatectomy were PSA, Gleason sum and pN. Joint effect of the factors allows to predict PSA-relapse with accuracy 0.720. Preoperative serum levels VEGF, VEGFR2, VEGFR3, TGF-β1 potentially are perspective markers for PSA-failure after

  8. PROGNOSTIC FACTORS OF BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY FOR LOCALIZED AND LOCALLY-ADVANCED PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    V. A. Chernyaev

    2012-01-01

    Full Text Available Purpose. To reveal prognostic factors of PSA-failure following radical prostatectomy in patients with localized and locally-advanced prostate cancer.Materials and methods. Medical data of 386 consecutive patients with localized and locally-advanced prostate cancer who underwent radical prostatectomy from 1997 to 2011 were analyzed. Median age was 61.0 years. Median PSA before surgery – 10.3 ng/ml. Plasma levels of VEGF, VEGFR2, VEGFR3, TGF-β1, CD105, IL-6 were measured using Enzyme Linked-Immuno-Sorbent Assay (ELISA before radical prostatectomy in 77 patients. Postoperatively the tumours were categorized as pT2 in 288 (59.1 %, pT3 – in 144 (37.3 %, pT4 – in 14 (3.6; pN+ – in 34 (8.8 % cases. Gleason score < 7 was present in 254 (65.8 %,  7 – in 132 (34.2 % specimens. Perineural invasion was identified in 188 (48.7 %, angiolymphatic invasion – in 126 (32.6 cases.Results. Biochemical recurrence occurred in 64 (16.6 % out of 386 patients at a median follow-up of 30.5 (12−164 months. Independent predictors of biochemical recurrence were PSA (HR 0.161 (95% CI:0.058−0.449; р = 0.001, Gleason sum in surgical specimens (HR 0.496 (95 % CI:0.268−0.917; p = 0.025, pN (HR 0.415 (95 % CI:0.181−0.955; p = 0.039. The patients were divided into 3 prognostic groups: good (0 factor, intermediate (1 factor, poor (2 factors and very poor (3 factors (AUC – 0.720 (95% CI: 0.656−0.784. High preoperative levels VEGF ( 67 pg/ml (р = 0.005, VEGFR2 ( 3149 pg/ml (р = 0.036, VEGFR3 ( 2268 pg/ml (р = 0.001, TGF-β1 ( 14473 pg/ml (р = 0.052 were identified as unfavorable prognostic factors for survival without PSA-failure. Conclusion. Independent prognostic factors of biochemical recurrence after prostatectomy were PSA, Gleason sum and pN. Joint effect of the factors allows to predict PSA-relapse with accuracy 0.720. Preoperative serum levels VEGF, VEGFR2, VEGFR3, TGF-β1 potentially are perspective markers for PSA-failure after

  9. Nuclear localization of the mitochondrial factor HIGD1A during metabolic stress.

    Directory of Open Access Journals (Sweden)

    Kurosh Ameri

    Full Text Available Cellular stress responses are frequently governed by the subcellular localization of critical effector proteins. Apoptosis-inducing Factor (AIF or Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH, for example, can translocate from mitochondria to the nucleus, where they modulate apoptotic death pathways. Hypoxia-inducible gene domain 1A (HIGD1A is a mitochondrial protein regulated by Hypoxia-inducible Factor-1α (HIF1α. Here we show that while HIGD1A resides in mitochondria during physiological hypoxia, severe metabolic stress, such as glucose starvation coupled with hypoxia, in addition to DNA damage induced by etoposide, triggers its nuclear accumulation. We show that nuclear localization of HIGD1A overlaps with that of AIF, and is dependent on the presence of BAX and BAK. Furthermore, we show that AIF and HIGD1A physically interact. Additionally, we demonstrate that nuclear HIGD1A is a potential marker of metabolic stress in vivo, frequently observed in diverse pathological states such as myocardial infarction, hypoxic-ischemic encephalopathy (HIE, and different types of cancer. In summary, we demonstrate a novel nuclear localization of HIGD1A that is commonly observed in human disease processes in vivo.

  10. Herpes simplex virus induces the marked up-regulation of the zinc finger transcriptional factor INSM1, which modulates the expression and localization of the immediate early protein ICP0

    Directory of Open Access Journals (Sweden)

    Kimura Hiroshi

    2011-05-01

    Full Text Available Abstract Background Herpes simplex viruses (HSVs rapidly shut off macromolecular synthesis in host cells. In contrast, global microarray analyses have shown that HSV infection markedly up-regulates a number of host cell genes that may play important roles in HSV-host cell interactions. To understand the regulatory mechanisms involved, we initiated studies focusing on the zinc finger transcription factor insulinoma-associated 1 (INSM1, a host cell protein markedly up-regulated by HSV infection. Results INSM1 gene expression in HSV-1-infected normal human epidermal keratinocytes increased at least 400-fold 9 h after infection; INSM1 promoter activity was also markedly stimulated. Expression and subcellular localization of the immediate early HSV protein ICP0 was affected by INSM1 expression, and chromatin immunoprecipitation (ChIP assays revealed binding of INSM1 to the ICP0 promoter. Moreover, the role of INSM1 in HSV-1 infection was further clarified by inhibition of HSV-1 replication by INSM1-specific siRNA. Conclusions The results suggest that INSM1 up-regulation plays a positive role in HSV-1 replication, probably by binding to the ICP0 promoter.

  11. Growth factor deprivation induces cytosolic translocation of SIRT1

    Science.gov (United States)

    Meng, Chengbo; Xing, Da; Wu, Shengnan; Huang, Lei

    2010-02-01

    Sirtuin type 1 (SIRT1), a NAD+-dependent histone deacetylases, plays a critical role in cellular senescence, aging and longevity. In general, SIRT1 is localized in nucleus and is believed as a nuclear protein. Though overexpression of SIRT1 delays senescence, SIRT1-protein levels decline naturally in thymus and heart during aging. In the present studies, we investigated the subcellular localization of SIRT1 in response to growth factor deprivation in African green monkey SV40-transformed kidney fibroblast cells (COS-7). Using SIRT1-EGFP fluorescence reporter, we found that SIRT1 localized to nucleus in physiological conditions. We devised a model enabling cell senescence via growth factor deprivation, and we found that SIRT1 partially translocated to cytosol under the treatment, suggesting a reduced level of SIRT1's activity. We found PI3K/Akt pathway was involved in the inhibition of SIRT1's cytosolic translocation, because inhibition of these kinases significantly decreased the amount of SIRT1 maintained in nucleus. Taken together, we demonstrated that growth factor deprivation induces cytosolic translocation of SIRT1, which suggesting a possible connection between cytoplasm-localized SIRT1 and the aging process.

  12. Caspase-6 Induces 7A6 Antigen Localization to Mitochondria During FAS-induced Apoptosis of Jurkat Cells.

    Science.gov (United States)

    Suita, Hiroaki; Shinomiya, Takahisa; Nagahara, Yukitoshi

    2017-04-01

    Mitochondria are central to apoptosis. However, apoptosis progression involving mitochondria is not fully understood. A factor involved in mitochondria-mediated apoptosis is 7A6 antigen. 7A6 localizes to mitochondria from the cytosol during apoptosis, which seems to involve 'effector' caspases. In this study, we investigated the precise role of effector caspases in 7A6 localization to mitochondria during apoptosis. Human T-cell lymphoma Jurkat cells were treated with an antibody against FAS. 7A6 localization was analyzed by confocal laser scanning microscopy and flow cytometry. Caspases activation was determined by western blot analysis. 7A6 localization to mitochondria during anti-FAS-induced apoptosis was significantly reduced by the caspase-6 inhibitor, N-acetyl-Val-Glu-Ile-Asp-aldehyde, but not by the caspase-3 inhibitor, N-acetyl-Asp-Asn-Leu-Asp-aldehyde, nor caspase-7/3 inhibitor, N-acetyl-Asp-Gln-Thr-Asp-aldehyde. Moreover, caspase-6 down-regulation suppressed 7A6 localization to mitochondria. Caspase-6 regulates 7A6 localization to mitochondria during anti-FAS-induced apoptosis of Jurkat cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  13. Influence of selected factors on induced syneresis

    Directory of Open Access Journals (Sweden)

    Jovanović Snežana T.

    2004-01-01

    Full Text Available Syneresis is the process of whey separation induced by gel contraction resulting in rearranging or restructuring of casein matrix formed during enzymatic coagulation. Numerous factors can influence the process of syneresis. The influences of pH, calcium concentration, temperature of coagulation of milk and applied heat treatment on the syneresis induced by different intensity of centrifugal force have been investigated. Coagulated samples were centrifuged at 1000, 2000 and 3000 rpm for 5 min, respectively. Reconstituted skim milk powder (control sample and reconstituted non-fat milk heat treated at 87ºC/10 min (experimental sample are coagulated at temperatures of 30ºC and 35ºC, at pH value of 5.8 and 6.2, and with the addition of 100, 200 and 400 mg/l of CaCl2, respectively. Centrifugation at 1000 rpm of both control and experimental samples didn’t recover any sera, regardless of the applied coagulation conditions. This indicates that the intensity of centrifugal force wasn’t strong enough to disrupt gel structure and cause syneresis. When the intensity of centrifugal force was increased up to 2000 rpm, the syneresis was induced, but the degree of syneresis depended on the applied factors of coagulation, primary on the applied heat treatments and temperature of coagulation. The amount of added CaCl2 didn’t have a significant influence on the induced syneresis at 2000 rpm. The induced syneresis was very significant for both control and experimental samples when the intensity of centrifugal force of 3000 rpm was applied. It was also noted that curd produced from heat treated milk in which milk protein coaggregates were formed, released less sera regardless of the applied coagulation factors.

  14. Socioeconomic Factors Affecting Local Support for Black Bear Recovery Strategies

    Science.gov (United States)

    Morzillo, Anita T.; Mertig, Angela G.; Hollister, Jeffrey W.; Garner, Nathan; Liu, Jianguo

    2010-06-01

    There is global interest in recovering locally extirpated carnivore species. Successful efforts to recover Louisiana black bear in Louisiana have prompted interest in recovery throughout the species’ historical range. We evaluated support for three potential black bear recovery strategies prior to public release of a black bear conservation and management plan for eastern Texas, United States. Data were collected from 1,006 residents living in proximity to potential recovery locations, particularly Big Thicket National Preserve. In addition to traditional logistic regression analysis, we used conditional probability analysis to statistically and visually evaluate probabilities of public support for potential black bear recovery strategies based on socioeconomic characteristics. Allowing black bears to repopulate the region on their own (i.e., without active reintroduction) was the recovery strategy with the greatest probability of acceptance. Recovery strategy acceptance was influenced by many socioeconomic factors. Older and long-time local residents were most likely to want to exclude black bears from the area. Concern about the problems that black bears may cause was the only variable significantly related to support or non-support across all strategies. Lack of personal knowledge about black bears was the most frequent reason for uncertainty about preferred strategy. In order to reduce local uncertainty about possible recovery strategies, we suggest that wildlife managers focus outreach efforts on providing local residents with general information about black bears, as well as information pertinent to minimizing the potential for human-black bear conflict.

  15. Extraordinary Light-Induced Local Angular Momentum near Metallic Nanoparticles.

    Science.gov (United States)

    Alabastri, Alessandro; Yang, Xiao; Manjavacas, Alejandro; Everitt, Henry O; Nordlander, Peter

    2016-04-26

    The intense local field induced near metallic nanostructures provides strong enhancements for surface-enhanced spectroscopies, a major focus of plasmonics research over the past decade. Here we consider that plasmonic nanoparticles can also induce remarkably large electromagnetic field gradients near their surfaces. Sizeable field gradients can excite dipole-forbidden transitions in nearby atoms or molecules and provide unique spectroscopic fingerprinting for chemical and bimolecular sensing. Specifically, we investigate how the local field gradients near metallic nanostructures depend on geometry, polarization, and wavelength. We introduce the concept of the local angular momentum (LAM) vector as a useful figure of merit for the design of nanostructures that provide large field gradients. This quantity, based on integrated fields rather than field gradients, is particularly well-suited for optimization using numerical grid-based full wave electromagnetic simulations. The LAM vector has a more compact structure than the gradient matrix and can be straightforwardly associated with the angular momentum of the electromagnetic field incident on the plasmonic structures.

  16. Physics of defect induced local moments in pnictide superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Grinenko, Vadim; Drechsler, Stefan-Ludwig; Abdel-Hafiez, Mahmoud; Aswartham, Saicharan; Wolter-Giraud, Anja; Hess, Christian; Kumar, Manoj; Wurmehl, Sabine; Fuchs, Guenter; Nenkov, Konstantin; Hammerath, Franziska; Lang, Guillaume; Grafe, Hans-Joachim; Holzapfel, Bernhard; Brink, Jeroen van den; Buechner, Bernd; Schultz, Ludwig [IFW Dresden (Germany); Kikoin, Konstatin [School of Physics and Astronomy, Tel-Aviv University (Israel)

    2012-07-01

    Many unusual physical properties of Fe-pnictide superconductors are related to the presence of local magnetic moments induced by point-defects, e.g. As-vacancies. In the La-1111 system they improve the superconducting properties as compared with As-stoichiometric samples enhancing T{sub c} and the -dH{sub c2}/dT at T{sub c}. But they also enhance strongly the spin susceptibility, which governs the Pauli limiting behavior of the As-deficient La-1111. In heavily hole doped K-122 superconducting single crystals the local moments leads to a complex phase diagram with a Griffith and a spin glass phase. The local moments picture explains also the observed non-Fermi-liquid behavior and the large effective mass enhancement of the quasi-particles in K-122. In Co-doped Ba-122 superconducting single crystals the local moments form also a spin glass state and lead to a strong Pauli limiting behavior.

  17. Localization of Cortical Oscillations Induced by SCS Using Coherence

    Directory of Open Access Journals (Sweden)

    P. Sovka

    2007-12-01

    Full Text Available This paper suggests a method based on coherence analysis and scalp mapping of coherence suitable for more accurate localization of cortical oscillations induced by electric stimulation of the dorsal spinal cord (SCS, which were previously detected using spectral analysis. While power spectral density shows the increase of power during SCS only at small number of electrodes, coherence extends this area and sharpens its boundary simultaneously. Parameters of the method were experimentally optimized to maximize its reliability. SCS is applied to suppress chronic, intractable pain by patients, whom pharmacotherapy does not relieve. In our study, the pain developed in lower back and lower extremity as the result of unsuccessful vertebral discotomy, which is called failed-back surgery syndrome (FBSS. Our method replicated the results of previous analysis using PSD and extended them with more accurate localization of the area influenced by SCS.

  18. Permittivity disorder induced Anderson localization in magnetophotonic crystals

    Science.gov (United States)

    Abdi-Ghaleh, R.; Namdar, A.

    2016-11-01

    This theoretical study was carried out to investigate the permittivity disorder induced Anderson localization of light in one-dimensional magnetophotonic crystals. It was shown that the disorder create the resonant transmittance modes associated with enhanced Faraday rotations inside the photonic band gap. The average localization length of the right- and left-handed circular polarizations (RCP and LCP), the total transmittance together with the ensemble average of the RCP and LCP phases, and the Faraday rotation of the structure were also investigated. For this purpose, the off-diagonal elements of the permittivity tensor were varied for various wavelengths of incident light. The obtained results revealed the nonreciprocal property of circular eigen modes. This study can potentially open up a new aspect for utilizing the disorder magnetophotonic structures in nonreciprocal systems such as isolators and circulators.

  19. A local factorization of the fermion determinant in lattice QCD

    CERN Document Server

    Cè, Marco; Schaefer, Stefan

    2016-01-01

    We introduce a factorization of the fermion determinant in lattice QCD with Wilson-type fermions that leads to a bosonic action local in the block fields. The interaction among gauge fields on distant blocks is mediated by multiboson fields located on the boundaries of the blocks. The resultant multiboson domain-decomposed hybrid Monte Carlo passes extensive numerical tests carried out by measuring standard gluonic observables. The combination of the determinant factorization and of the one of the propagator, that we put forward recently, paves the way for multilevel Monte Carlo integration in presence of fermions. We test this possibility by computing the disconnected correlator of two flavor-diagonal pseudoscalar densities, and we observe a significant increase of the signal-to-noise ratio due to a two-level integration.

  20. A local factorization of the fermion determinant in lattice QCD

    Energy Technology Data Exchange (ETDEWEB)

    Ce, Marco [Scuola Normale Superiore, Pisa (Italy); INFN, Pisa (Italy); Giusti, Leonardo [Milano-Bicocca Univ. (Italy). Dipartimento di Fisica; INFN, Milano-Bicocca (Italy); Schaefer, Stefan [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC

    2016-09-15

    We introduce a factorization of the fermion determinant in lattice QCD with Wilson-type fermions that leads to a bosonic action which is local in the block fields. The interaction among gauge fields on distant blocks is mediated by multiboson fields located on the boundaries of the blocks. The resultant multiboson domain-decomposed hybrid Monte Carlo passes extensive numerical tests carried out by measuring standard gluonic observables. The combination of the determinant factorization and of the one of the propagator, that we put forward recently, paves the way for multilevel Monte Carlo integration in the presence of fermions. We test this possibility by computing the disconnected correlator of two flavor-diagonal pseudoscalar densities, and we observe a significant increase of the signal-to-noise ratio due to a two-level integration.

  1. Training-induced plasticity of auditory localization in adult mammals.

    Directory of Open Access Journals (Sweden)

    Oliver Kacelnik

    2006-04-01

    Full Text Available Accurate auditory localization relies on neural computations based on spatial cues present in the sound waves at each ear. The values of these cues depend on the size, shape, and separation of the two ears and can therefore vary from one individual to another. As with other perceptual skills, the neural circuits involved in spatial hearing are shaped by experience during development and retain some capacity for plasticity in later life. However, the factors that enable and promote plasticity of auditory localization in the adult brain are unknown. Here we show that mature ferrets can rapidly relearn to localize sounds after having their spatial cues altered by reversibly occluding one ear, but only if they are trained to use these cues in a behaviorally relevant task, with greater and more rapid improvement occurring with more frequent training. We also found that auditory adaptation is possible in the absence of vision or error feedback. Finally, we show that this process involves a shift in sensitivity away from the abnormal auditory spatial cues to other cues that are less affected by the earplug. The mature auditory system is therefore capable of adapting to abnormal spatial information by reweighting different localization cues. These results suggest that training should facilitate acclimatization to hearing aids in the hearing impaired.

  2. Risk factors for amiodarone-induced thyroid dysfunction in Japan

    Directory of Open Access Journals (Sweden)

    Sayoko Kinoshita

    2016-12-01

    Conclusion: DCM and cardiac sarcoidosis were identified as risk factors for amiodarone-induced hyperthyroidism. Risk factors for amiodarone-induced hypothyroidism included higher baseline TSH level and lower baseline free T4 level, suggesting that subclinical hypothyroidism may be a potential risk factor for the development of amiodarone-induced hypothyroidism.

  3. Embryogenesis of esophageal atresia: Is localized vascular accident a factor?

    Directory of Open Access Journals (Sweden)

    Dutta Hemonta

    2009-01-01

    Full Text Available Several theories on embryogenesis of esophageal atresia have been proposed, none could explain the whole spectrum of this anomaly. We report a new variant of esophageal atresia in which the two blind pouches were joined by an atretic band. Histology of the atretic part showed groups of striated muscle arranged haphazardly without any lumen. The existing theories on etiology of esophageal atresia cannot explain this variant. However, localized vascular accident during intrauterine life resulting in disturbances in regional microcirculation could be a possible factor as demonstrated by Louw and Barnard in relation to jejunoileal atresia. This is contrary to the current understanding that disproportionate growth of the horizontal esophageal folds results in esophageal atresia.

  4. Measurement-Induced Localization of an Ultracold Lattice Gas

    Science.gov (United States)

    Patil, Y. S.; Chakram, S.; Vengalattore, M.

    2015-10-01

    The process of measurement can modify the state of a quantum system and its subsequent evolution. Here, we demonstrate the control of quantum tunneling in an ultracold lattice gas by the measurement backaction imposed by the act of imaging the atoms, i.e., light scattering. By varying the rate of light scattering from the atomic ensemble, we show the crossover from the weak measurement regime, where position measurements have little influence on tunneling dynamics, to the strong measurement regime, where measurement-induced localization causes a large suppression of tunneling—a manifestation of the quantum Zeno effect. Our study realizes an experimental demonstration of the paradigmatic Heisenberg microscope and sheds light on the implications of measurement on the coherent evolution of a quantum system.

  5. Factor models on locally tree-like graphs

    CERN Document Server

    Dembo, Amir; Sun, Nike

    2011-01-01

    We consider homogeneous factor models on uniformly sparse graph sequences converging locally to a (unimodular) random tree T, and study the existence of the free energy density phi, the limit of the log-partition function divided by the number of vertices n as n tends to infinity. We provide a new interpolation scheme and use it to prove existence of, and to explicitly compute, the quantity phi subject to uniqueness of a relevant Gibbs measure for the factor model on T. By way of example we compute phi for the independent set (or hard-core) model at low fugacity, for the ferromagnetic Ising model at all parameter values, and for the ferromagnetic Potts model with both weak enough and strong enough interactions. Even beyond uniqueness our interpolation provides useful explicit bounds on phi. In the regimes in which we establish existence of the limit, we show that it coincides with the Bethe free energy functional evaluated at a suitable fixed point of the belief propagation recursions on T. In the special cas...

  6. Pressure-Induced Local Structure Distortions in Cu(pyz)F(2)(H(2)O)(2)

    Energy Technology Data Exchange (ETDEWEB)

    J Musfeldt; Z Liu; S Li; J Kang; C Lee; P Jena; J Manson; J Schlueter; G Carr; M Whangbo

    2011-12-31

    We employed infrared spectroscopy along with complementary lattice dynamics and spin density calculations to investigate pressure-driven local structure distortions in the copper coordination polymer Cu(pyz)F{sub 2}(H{sub 2}O){sub 2}. Here, pyz is pyrazine. Our study reveals rich and fully reversible local lattice distortions that buckle the pyrazine ring, disrupt the bc-plane O-H {hor_ellipsis} F hydrogen-bonding network, and reinforce magnetic property switching. The resiliency of the soft organic ring is a major factor in the stability of this material. Interestingly, the collective character of the lattice vibrations masks direct information on the Cu-N and Cu-O linkages through the series of pressure-induced Jahn-Teller axis switching transitions, although Cu-F bond softening is clearly identified above 3 GPa. These findings illustrate the importance of combined bulk and local probe techniques for microscopic structure determination in complex materials.

  7. Pressure Induced Local Structure Distortions in Cu(pyz)F2(H2O)2

    Energy Technology Data Exchange (ETDEWEB)

    Musfeldt, J.L.; Carr, G.; Liu, Z.; Li, S.; Kang, C.L., Jena, P.; Manson, J.L.; Schlueter, J.A. Whangbo, M.H.

    2011-06-06

    We employed infrared spectroscopy along with complementary lattice dynamics and spin density calculations to investigate pressure-driven local structure distortions in the copper coordination polymer Cu(pyz)F{sub 2}(H{sub 2}O){sub 2}. Here, pyz is pyrazine. Our study reveals rich and fully reversible local lattice distortions that buckle the pyrazine ring, disrupt the bc-plane O-H {hor_ellipsis} F hydrogen-bonding network, and reinforce magnetic property switching. The resiliency of the soft organic ring is a major factor in the stability of this material. Interestingly, the collective character of the lattice vibrations masks direct information on the Cu-N and Cu-O linkages through the series of pressure-induced Jahn-Teller axis switching transitions, although Cu-F bond softening is clearly identified above 3 GPa. These findings illustrate the importance of combined bulk and local probe techniques for microscopic structure determination in complex materials.

  8. Localization of 1-deoxysphingolipids to mitochondria induces mitochondrial dysfunction.

    Science.gov (United States)

    Alecu, Irina; Tedeschi, Andrea; Behler, Natascha; Wunderling, Klaus; Lamberz, Christian; Lauterbach, Mario A R; Gaebler, Anne; Ernst, Daniela; Van Veldhoven, Paul P; Al-Amoudi, Ashraf; Latz, Eicke; Othman, Alaa; Kuerschner, Lars; Hornemann, Thorsten; Bradke, Frank; Thiele, Christoph; Penno, Anke

    2017-01-01

    1-Deoxysphingolipids (deoxySLs) are atypical sphingolipids that are elevated in the plasma of patients with type 2 diabetes and hereditary sensory and autonomic neuropathy type 1 (HSAN1). Clinically, diabetic neuropathy and HSAN1 are very similar, suggesting the involvement of deoxySLs in the pathology of both diseases. However, very little is known about the biology of these lipids and the underlying pathomechanism. We synthesized an alkyne analog of 1-deoxysphinganine (doxSA), the metabolic precursor of all deoxySLs, to trace the metabolism and localization of deoxySLs. Our results indicate that the metabolism of these lipids is restricted to only some lipid species and that they are not converted to canonical sphingolipids or fatty acids. Furthermore, exogenously added alkyne-doxSA [(2S,3R)-2-aminooctadec-17-yn-3-ol] localized to mitochondria, causing mitochondrial fragmentation and dysfunction. The induced mitochondrial toxicity was also shown for natural doxSA, but not for sphinganine, and was rescued by inhibition of ceramide synthase activity. Our findings therefore indicate that mitochondrial enrichment of an N-acylated doxSA metabolite may contribute to the neurotoxicity seen in diabetic neuropathy and HSAN1. Hence, we provide a potential explanation for the characteristic vulnerability of peripheral nerves to elevated levels of deoxySLs.

  9. Light-induced electron localization in a quantum Hall system

    Science.gov (United States)

    Arikawa, T.; Hyodo, K.; Kadoya, Y.; Tanaka, K.

    2017-07-01

    An insulating bulk state is a prerequisite for the protection of topological edge states. In quantum Hall systems, the thermal excitation of delocalized electrons is the main route to breaking bulk insulation. In equilibrium, the only way to achieve a clear bulk gap is to use a high-quality crystal under high magnetic field at low temperature. However, bulk conduction could also be suppressed in a system driven out of equilibrium such that localized states in the Landau levels are selectively occupied. Here we report a transient suppression of bulk conduction induced by terahertz wave excitation between the Landau levels in a GaAs quantum Hall system. Strikingly, the Hall resistivity almost reaches the quantized value at a temperature where the exact quantization is normally disrupted by thermal fluctuations. The electron localization is realized by the long-range potential fluctuations, which are a unique and inherent feature of quantum Hall systems. Our results demonstrate a new means of effecting dynamical control of topology by manipulating bulk conduction using light.

  10. Localizing evoked and induced responses to faces using magnetoencephalography.

    Science.gov (United States)

    Perry, Gavin; Singh, Krish D

    2014-05-01

    A rich pattern of responses in frequency, time and space are known to be generated in the visual cortex in response to faces. Recently, a number of studies have used magnetoencephalography (MEG) to try to record these responses non-invasively - in many cases using source analysis techniques based on the beamforming method. Here we sought both to characterize best practice for measuring face-specific responses using MEG beamforming, and to determine whether the results produced by the beamformer match evidence from other modalities. We measured activity to visual presentation of face stimuli and phase-scrambled control stimuli, and performed source analyses of both induced and evoked responses using Synthetic Aperture Magnetometry. We localized the gamma-band response to bilateral lateral occipital cortex, and both the gamma-band response and the M170-evoked response to the right fusiform gyrus. Differences in the gamma-band response between faces and scrambled stimuli were confined to the frequency range 50-90 Hz; gamma-band activity at higher frequencies did not differ between the two stimulus categories. We additionally identified a component of the M220-evoked response - localized to the parieto-occipital sulcus - which was enhanced for scrambled vs. unscrambled faces. These findings help to establish that MEG beamforming can localize face-specific responses in time, frequency and space with good accuracy (when validated against established findings from functional magnetic resonance imaging and intracranial recordings), as well as contributing to the establishment of best methodological practice for the use of the beamformer method to measure face-specific responses.

  11. Measurement of the profiles of disorder-induced localized resonances in photonic crystal waveguides by local tuning

    Science.gov (United States)

    Lian, Jin; Sokolov, Sergei; Yüce, Emre; Combrié, Sylvain; De Rossi, Alfredo; Mosk, Allard P.

    2016-09-01

    Near the band edge of photonic crystal waveguides, localized modes appear due to disorder. We demonstrate a new method to elucidate spatial profile of the localized modes in such systems using precise local tuning. Using deconvolution with the known thermal profile, the spatial profile of a localized mode with quality factor ($Q$) $>10^5$ is successfully reconstructed with a resolution of $2.5 \\ \\mu $m.

  12. The factor of local cultural specificity and process of globalization.

    Science.gov (United States)

    Rudnev, Viacheslav

    2012-12-01

    , especially farming traditions in small-scale, non-industrial societies, has been based not only on the technologies that are "friendly" to Nature, but also (and first of all) on the perception that soil (earth) is the source of all life. This sort of perception was particularly widespread among peoples of pre-industrial societies. The problem of searching for a way to increase long-term productivity in food grain production is complicated. This problem is of global importance for today and the future. The active interest of Modern society in the Folk experiences of using the Nature to achieve sustainable economies is yet to come, but we have much to learn from these small-scale non-industrial societies. Food production needs to be increased. At the same time, the fertility of the soil must be maintained. Achieving a balance between these two necessities is the problem. Changing the present modern human outlook from its egocentric position to one that understands and respects the natural environment, based on ideas of "ecological ethics", looks especially complex, and is directly connected with the problem of forming a new culture. Actually, the global ecological crisis and related ecological problems take priority and the transition to a new model of thinking promises to be accelerated. In this context, making use of Folk heritage, Folk knowledge and experience in observing Nature and using Nature to achieve harmonious interrelations in a "Nature - Society" system, and for the elaboration of a change of attitudes is quite important for modern society on a Global level to achieve ways of Sustainability. Lucius Seneca maintains that subjugation of a Nature is possible only if obeying to Nature. Modern epoch of Globalization in economy and Financial systems creating a potential of high risks for mankind on the Global level. Special attention to local factors (local experience in Nature using, local Folk experience in Life-support activity) in context of globalization problems

  13. The university as a factor of sustainable local development

    Directory of Open Access Journals (Sweden)

    Ariel González Hernández

    2013-01-01

    Full Text Available A domestic reality where we find areas of high deprivation and poverty, we analyze the participation of the university, as manager of the local development, considering that it is generating knowledge, able to process from global to local and from the local to global. To ensure that local development is efficient, it is necessary to propose strategies between development actors and local public and private institutions, including the university human resources management and cognitive development can be local. This work aims to make a conceptual review of the theoretical or the endogenous local development and institutional functionalism, establish a relationship between requirements, development agents and college. In this sense, Boisier, 2001 suggests that endogenous development but an analysis model is an interpretation action-oriented public policy, in which local actors, through their decisions and initiatives mark the path of development. In this framework, the university as a generator and disseminator of knowledge, should define its role as manager of the local development, which would answer the third mission (García, 1999, that contemporary society has assigned.

  14. Critical Factors for Inducing Curved Somatosensory Saccades

    Directory of Open Access Journals (Sweden)

    Tamami Nakano

    2011-10-01

    Full Text Available We are able to make a saccade toward a tactile stimuli to one hand, but trajectories of many saccades curved markedly when the arms were crossed (Groh & Sparks, 2006. However, it remains unknown why some curved and others did not. We therefore examined critical factors for inducing the curved somatosensory saccades. Participants made a saccade as soon as possible from a central fixation point toward a tactile stimulus delivered to one of the two hands, and switched between arms-crossed and arms-uncrossed postures every 6 trials. Trajectories were generally straight when the arms were uncrossed, but all participants made curved saccades when the arms were crossed (12–64%. We found that the probability of curved saccades depended critically on the onset latency: the probability was less than 5% when the latency was larger than 250 ms, but the probability increased up to 70–80% when the onset latency was 160 ms. This relationship was shared across participants. The results suggest that a touch in the arms-crossed posture was always mapped to the wrong hand in the initial phase up to 160 ms, and then remapped to the correct hand during the next 100 ms by some fundamental neural mechanisms shared across participants.

  15. Structural integration in hypoxia-inducible factors

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Dalei; Potluri, Nalini; Lu, Jingping; Kim, Youngchang; Rastinejad, Fraydoon

    2015-08-20

    The hypoxia-inducible factors (HIFs) coordinate cellular adaptations to low oxygen stress by regulating transcriptional programs in erythropoiesis, angiogenesis and metabolism. These programs promote the growth and progression of many tumours, making HIFs attractive anticancer targets. Transcriptionally active HIFs consist of HIF-alpha and ARNT (also called HIF-1 beta) subunits. Here we describe crystal structures for each of mouse HIF-2 alpha-ARNT and HIF-1 alpha-ARNT heterodimers in states that include bound small molecules and their hypoxia response element. A highly integrated quaternary architecture is shared by HIF-2 alpha-ARNT and HIF-1 alpha-ARNT, wherein ARNT spirals around the outside of each HIF-alpha subunit. Five distinct pockets are observed that permit small-molecule binding, including PAS domain encapsulated sites and an interfacial cavity formed through subunit heterodimerization. The DNA-reading head rotates, extends and cooperates with a distal PAS domain to bind hypoxia response elements. HIF-alpha mutations linked to human cancers map to sensitive sites that establish DNA binding and the stability of PAS domains and pockets.

  16. Factors that mitigate war-induced anxiety and mental distress.

    Science.gov (United States)

    Almedom, Astier M

    2004-07-01

    The effects of war-induced anxiety and mental distress on individuals and groups can either be mitigated or exacerbated by 'humanitarian action'. This paper focuses on two key factors that protect the mental well-being of war-affected populations: organized displacement or assisted relocation; and coordinated humanitarian aid operations that are responsive to local needs. Qualitative data from two internally displaced person (IDP) camps in Eritrea are presented. Analysis of these data serves to substantiate and refine a working hypothesis: that social support of the right type, provided at the right time and level, can mitigate the worst effects of war and displacement on victims/survivors. An integrated model of psychosocial transition is suggested. The implications of this approach for humanitarian policy and practice are discussed in the wider context of current debates and lamentations of the 'humanitarian idea'.

  17. Porphyromonas gingivalis-induced production of reactive oxygen species, tumor necrosis factor-α, interleukin-6, CXCL8 and CCL2 by neutrophils from localized aggressive periodontitis and healthy donors

    DEFF Research Database (Denmark)

    Damgaard, C; Kantarci, A; Holmstrup, P

    2017-01-01

    in both groups, but reduced the generation of ROS in the group of healthy controls, and showed a similar tendency in the group of subjects with LAgP. RvE1 had no impact on the production of intracellular ROS, TNF-α, IL-6, CXCL8 and CCL2 by neutrophils from either group, but tended to reduce the generation...... healthy controls release the proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor α (TNF-α), the chemokine (C-X-C motif) ligand 8 (CXCL8; also known as IL-8) and chemokine (C-C motif) ligand 2 (CCL2; also known as monocyte chemotactic protein-1) and intracellular reactive oxygen species...... of neutrophils were investigated. RESULTS: Upon stimulation with P. gingivalis, neutrophils from subjects with LAgP and healthy controls released similar quantities of IL-6, TNF-α, CXCL8, CCL2 and intracellular ROS. The presence of RBCs amplified the release of IL-6, TNF-α and CCL2 statistically significant...

  18. The impact of vascular factors on language localization in the superior temporal sulcus.

    Science.gov (United States)

    Wilson, Stephen M

    2014-08-01

    The left superior temporal sulcus (STS) has been shown in numerous functional imaging studies to be a critical region for language processing, as it is reliably activated when language comprehension is compared with acoustically matched control conditions. Studies in non-human primates have demonstrated several subdivisions in the STS, yet the precise region(s) within the STS that are important for language remain unclear, in large part because the presence of draining veins in the sulcus makes it difficult to determine whether neural activity is localized to the dorsal or ventral bank of the sulcus. We used functional MRI to localize language regions, and then acquired several additional sequences in order to account for the impact of vascular factors. A breath-holding task was used to induce hypercapnia in order to normalize voxel-wise differences in blood oxygen level-dependent (BOLD) responsivity, and veins were identified on susceptibility-weighted and T2*-weighted BOLD images, and masked out. We found that the precise locations of language areas in individual participants were strongly influenced by vascular factors, but that these vascular effects could be ameliorated by hypercapnic normalization and vein masking. After these corrections were applied, the majority of regions activated by language processing were localized to the dorsal bank of the STS.

  19. Pressure ulcer accelerated healing with local injections of granulocyte macrophage-colony stimulating factor.

    Science.gov (United States)

    El Saghir, N S; Bizri, A R; Shabb, N S; Husami, T W; Salem, Z; Shamseddine, A I

    1997-09-01

    This is the first report of granulocyte macrophage-colony stimulating factor (GM-CSF) inducing accelerated healing of a sacral pressure ulcer in a bedridden patient with bilateral hemiplegia. GM-CSF was diluted and injected locally around and into the ulcer bed every 2-3 days for 2 weeks, then weekly for 4 weeks until complete healing occurred. A new firm granulation tissue was noted within a few days. The ulcer showed 85% healing within 2 weeks and 100% by 2 months. Healing started from the periphery and from within the ulcer bed at sites of GM-CSF injections. It was slower at areas where there was complete necrosis and detachment of skin from underlying tissue. The ulcer remained closed until the patient's sudden death 9 months later. A biopsy of granulation tissue showed inflammatory cells and reactive fibroblasts. The potential role of GM-CSF and growth factors in pressure ulcer therapy and wound healing are discussed.

  20. Trait-specific responses of wild bee communities to landscape composition, configuration and local factors.

    Directory of Open Access Journals (Sweden)

    Sebastian Hopfenmüller

    Full Text Available Land-use intensification and loss of semi-natural habitats have induced a severe decline of bee diversity in agricultural landscapes. Semi-natural habitats like calcareous grasslands are among the most important bee habitats in central Europe, but they are threatened by decreasing habitat area and quality, and by homogenization of the surrounding landscape affecting both landscape composition and configuration. In this study we tested the importance of habitat area, quality and connectivity as well as landscape composition and configuration on wild bees in calcareous grasslands. We made detailed trait-specific analyses as bees with different traits might differ in their response to the tested factors. Species richness and abundance of wild bees were surveyed on 23 calcareous grassland patches in Southern Germany with independent gradients in local and landscape factors. Total wild bee richness was positively affected by complex landscape configuration, large habitat area and high habitat quality (i.e. steep slopes. Cuckoo bee richness was positively affected by complex landscape configuration and large habitat area whereas habitat specialists were only affected by the local factors habitat area and habitat quality. Small social generalists were positively influenced by habitat area whereas large social generalists (bumblebees were positively affected by landscape composition (high percentage of semi-natural habitats. Our results emphasize a strong dependence of habitat specialists on local habitat characteristics, whereas cuckoo bees and bumblebees are more likely affected by the surrounding landscape. We conclude that a combination of large high-quality patches and heterogeneous landscapes maintains high bee species richness and communities with diverse trait composition. Such diverse communities might stabilize pollination services provided to crops and wild plants on local and landscape scales.

  1. The hypoxia-inducible factor-1α activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia

    Science.gov (United States)

    Zhang, Qian; Doucet, Michele; Tomlinson, Ryan E; Han, Xiaobin; Quarles, L Darryl; Collins, Michael T; Clemens, Thomas L

    2016-01-01

    Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which ectopic production of fibroblast growth factor 23 (FGF23) by non-malignant mesenchymal tumors causes phosphate wasting and bone fractures. Recent studies have implicated the hypoxia-inducible factor-1α (HIF-1α) in other phosphate wasting disorders caused by elevated FGF23, including X-linked hypophosphatemic rickets and autosomal dominant hypophosphatemia. Here we provide evidence that HIF-1α mediates aberrant FGF23 in TIO by transcriptionally activating its promoter. Immunohistochemical studies in phosphaturic mesenchymal tumors resected from patients with documented TIO showed that HIF-1α and FGF23 were co-localized in spindle-shaped cells adjacent to blood vessels. Cultured tumor tissue produced high levels of intact FGF23 and demonstrated increased expression of HIF-1α protein. Transfection of MC3T3-E1 and Saos-2 cells with a HIF-1α expression construct induced the activity of a FGF23 reporter construct. Prior treatment of tumor organ cultures with HIF-1α inhibitors decreased HIF-1α and FGF23 protein accumulation and inhibited HIF-1α-induced luciferase reporter activity in transfected cells. Chromatin immunoprecipitation assays confirmed binding to a HIF-1α consensus sequence within the proximal FGF23 promoter, which was eliminated by treatment with a HIF-1α inhibitor. These results show for the first time that HIF-1α is a direct transcriptional activator of FGF23 and suggest that upregulation of HIF-1α activity in TIO contributes to the aberrant FGF23 production in these patients. PMID:27468359

  2. A mouse model for pathogen-induced chronic inflammation at local and systemic sites.

    Science.gov (United States)

    Papadopoulos, George; Kramer, Carolyn D; Slocum, Connie S; Weinberg, Ellen O; Hua, Ning; Gudino, Cynthia V; Hamilton, James A; Genco, Caroline A

    2014-08-08

    Chronic inflammation is a major driver of pathological tissue damage and a unifying characteristic of many chronic diseases in humans including neoplastic, autoimmune, and chronic inflammatory diseases. Emerging evidence implicates pathogen-induced chronic inflammation in the development and progression of chronic diseases with a wide variety of clinical manifestations. Due to the complex and multifactorial etiology of chronic disease, designing experiments for proof of causality and the establishment of mechanistic links is nearly impossible in humans. An advantage of using animal models is that both genetic and environmental factors that may influence the course of a particular disease can be controlled. Thus, designing relevant animal models of infection represents a key step in identifying host and pathogen specific mechanisms that contribute to chronic inflammation. Here we describe a mouse model of pathogen-induced chronic inflammation at local and systemic sites following infection with the oral pathogen Porphyromonas gingivalis, a bacterium closely associated with human periodontal disease. Oral infection of specific-pathogen free mice induces a local inflammatory response resulting in destruction of tooth supporting alveolar bone, a hallmark of periodontal disease. In an established mouse model of atherosclerosis, infection with P. gingivalis accelerates inflammatory plaque deposition within the aortic sinus and innominate artery, accompanied by activation of the vascular endothelium, an increased immune cell infiltrate, and elevated expression of inflammatory mediators within lesions. We detail methodologies for the assessment of inflammation at local and systemic sites. The use of transgenic mice and defined bacterial mutants makes this model particularly suitable for identifying both host and microbial factors involved in the initiation, progression, and outcome of disease. Additionally, the model can be used to screen for novel therapeutic strategies

  3. Production of Tuber-Inducing Factor

    Science.gov (United States)

    Stutte, Gary W.; Yorio, Neil C.

    2006-01-01

    A process for making a substance that regulates the growth of potatoes and some other economically important plants has been developed. The process also yields an economically important by-product: potatoes. The particular growth-regulating substance, denoted tuber-inducing factor (TIF), is made naturally by, and acts naturally on, potato plants. The primary effects of TIF on potato plants are reducing the lengths of the main shoots, reducing the numbers of nodes on the main stems, reducing the total biomass, accelerating the initiation of potatoes, and increasing the edible fraction (potatoes) of the overall biomass. To some extent, these effects of TIF can override environmental effects that typically inhibit the formation of tubers. TIF can be used in the potato industry to reduce growth time and increase harvest efficiency. Other plants that have been observed to be affected by TIF include tomatoes, peppers, radishes, eggplants, marigolds, and morning glories. In the present process, potatoes are grown with their roots and stolons immersed in a nutrient solution in a recirculating hydroponic system. From time to time, a nutrient replenishment solution is added to the recirculating nutrient solution to maintain the required nutrient concentration, water is added to replace water lost from the recirculating solution through transpiration, and an acid or base is added, as needed, to maintain the recirculating solution at a desired pH level. The growing potato plants secrete TIF into the recirculating solution. The concentration of TIF in the solution gradually increases to a range in which the TIF regulates the growth of the plants.

  4. Climate vs. soil factors in local adaptation of two common plant species

    NARCIS (Netherlands)

    Macel, M.; Lawson, C.S.; Mortimer, S.R.; Smilauerova, M.; Bischoff, A.; Crémieux, L.; Dolezal, J.; Edwards, A.R.; Lanta, V.; Bezemer, T.M.; Putten, van der W.H.; Igual, J.M.; Rodriguez-Barrueco, C.; Müller-Schärer, H.; Steinger, T.

    2007-01-01

    Evolutionary theory suggests that divergent natural selection in heterogeneous environments can result in locally adapted plant genotypes. To understand local adaptation it is important to study the ecological factors responsible for divergent selection. At a continental scale, variation in climate

  5. A Histologically Distinctive Interstitial Pneumonia Induced by Overexpression of the Interleukin 6, Transforming Growth Factor β1, or Platelet-Derived Growth Factor B Gene

    Science.gov (United States)

    Yoshida, Mitsuhiro; Sakuma, Junko; Hayashi, Seiji; Abe, Kin'ya; Saito, Izumu; Harada, Shizuko; Sakatani, Mitsunoir; Yamamoto, Satoru; Matsumoto, Norinao; Kaneda, Yasufumi; Kishmoto, Tadamitsu

    1995-10-01

    Interstitial pneumonia is characterized by alveolitis with resulting fibrosis of the interstitium. To determine the relevance of humoral factors in the pathogenesis of interstitial pneumonia, we introduced expression vectors into Wistar rats via the trachea to locally overexpress humoral factors in the lungs. Human interleukin (IL) 6 and IL-6 receptor genes induced lymphocytic alveolitis without marked fibroblast proliferation. In contrast, overexpression of human transforming growth factor β1 or human platelet-derived growth factor B gene induced only mild or apparent cellular infiltration in the alveoli, respectively. However, both factors induced significant proliferation of fibroblasts and deposition of collagen fibrils. These histopathologic changes induced by the transforming growth factor β1 and platelet-derived growth factor B gene are partly akin to those changes seen in lung tissues from patients with pulmonary fibrosis and markedly contrast with the changes induced by overexpression of the IL-6 and IL-6 receptor genes that mimics lymphocytic interstitial pneumonia.

  6. Glucocorticoid-induced tumour necrosis factor receptor (GITR) and its ligand (GITRL) in atopic dermatitis

    DEFF Research Database (Denmark)

    Baumgartner-Nielsen, Jane; Vestergaard, Christian; Thestrup-Pedersen, K.

    2006-01-01

    The glucocorticoid-induced tumour necrosis factor receptor-related gene (GITR) is expressed on regulatory T-cells (Treg), which are CD4+CD25+ lymphocytes. Binding of the GITR-ligand (GITRL) leads to downregulation of the regulatory function of Tregs. Patients suffering from a defect in their Treg......-cells are localized in the vicinity of GITRL-expressing cells in atopic dermatitis skin, the GITR/GITRL interaction may serve to perpetuate the inflammation locally....

  7. Purely nonlinear disorder-induced localizations and their parametric amplification

    CERN Document Server

    Folli, Viola; Conti, Claudio

    2013-01-01

    We investigate spatial localization in a quadratic nonlinear medium in the presence of randomness. By means of numerical simulations and theoretical analyses we show that, in the down conversion regime, the transverse random modulation of the nonlinear susceptibility generates localizations of the fundamental wave that grow exponentially in propagation. The localization length is optically controlled by the pump intensity which determines the amplification rate. The results also apply to cubic nonlinearities.

  8. Factors underlying restricted crossover localization in barley meiosis.

    Science.gov (United States)

    Higgins, James D; Osman, Kim; Jones, Gareth H; Franklin, F Chris H

    2014-01-01

    Meiotic recombination results in the formation of cytological structures known as chiasmata at the sites of genetic crossovers (COs). The formation of at least one chiasma/CO between homologous chromosome pairs is essential for accurate chromosome segregation at the first meiotic division as well as for generating genetic variation. Although DNA double-strand breaks, which initiate recombination, are widely distributed along the chromosomes, this is not necessarily reflected in the chiasma distribution. In many species there is a tendency for chiasmata to be distributed in favored regions along the chromosomes, whereas in others, such as barley and some other grasses, chiasma localization is extremely pronounced. Localization of chiasma to the distal regions of barley chromosomes restricts the genetic variation available to breeders. Studies reviewed herein are beginning to provide an explanation for chiasma localization in barley. Moreover, they suggest a potential route to manipulating chiasma distribution that could be of value to plant breeders.

  9. Localized microstructures induced by fluid flow in directional solidification.

    Science.gov (United States)

    Jamgotchian, H; Bergeon, N; Benielli, D; Voge, P; Billia, B; Guérin, R

    2001-10-15

    The dynamical process of microstructure localization by multiscale interaction between instabilities is uncovered in directional solidification of transparent alloy. As predicted by Chen and Davis, morphological instability of the interface is observed at inward flow-stagnation regions of the cellular convective field. Depending on the driving force of fluid flow, focus-type and honeycomb-type localized patterns form in the initial transient of solidification, that then evolves with time. In the case of solute-driven flow, the analysis of the onset of thermosolutal convection in initial transient of solidification enables a complete understanding of the dynamics and of the localization of morphological instability.

  10. Frequency-dependent local field factors in dielectric liquids by a polarizable force field and molecular dynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    Davari, Nazanin; Haghdani, Shokouh; Åstrand, Per-Olof [Department of Chemistry, Norwegian University of Science and Technology (NTNU), Trondheim (Norway)

    2015-12-31

    A force field model for calculating local field factors, i.e. the linear response of the local electric field for example at a nucleus in a molecule with respect to an applied electric field, is discussed. It is based on a combined charge-transfer and point-dipole interaction model for the polarizability, and thereby it includes two physically distinct terms for describing electronic polarization: changes in atomic charges arising from transfer of charge between the atoms and atomic induced dipole moments. A time dependence is included both for the atomic charges and the atomic dipole moments and if they are assumed to oscillate with the same frequency as the applied electric field, a model for frequency-dependent properties are obtained. Furthermore, if a life-time of excited states are included, a model for the complex frequency-dependent polariability is obtained including also information about excited states and the absorption spectrum. We thus present a model for the frequency-dependent local field factors through the first molecular excitation energy. It is combined with molecular dynamics simulations of liquids where a large set of configurations are sampled and for which local field factors are calculated. We are normally not interested in the average of the local field factor but rather in configurations where it is as high as possible. In electrical insulation, we would like to avoid high local field factors to reduce the risk for electrical breakdown, whereas for example in surface-enhanced Raman spectroscopy, high local field factors are desired to give dramatically increased intensities.

  11. Vasoconstriction Potency Induced by Aminoamide Local Anesthetics Correlates with Lipid Solubility

    Directory of Open Access Journals (Sweden)

    Hui-Jin Sung

    2012-01-01

    Full Text Available Aminoamide local anesthetics induce vasoconstriction in vivo and in vitro. The goals of this in vitro study were to investigate the potency of local anesthetic-induced vasoconstriction and to identify the physicochemical property (octanol/buffer partition coefficient, pKa, molecular weight, or potency of local anesthetics that determines their potency in inducing isolated rat aortic ring contraction. Cumulative concentration-response curves to local anesthetics (levobupivacaine, ropivacaine, lidocaine, and mepivacaine were obtained from isolated rat aorta. Regression analyses were performed to determine the relationship between the reported physicochemical properties of local anesthetics and the local anesthetic concentration that produced 50% (ED50 of the local anesthetic-induced maximum vasoconstriction. We determined the order of potency (ED50 of vasoconstriction among local anesthetics to be levobupivacaine > ropivacaine > lidocaine > mepivacaine. The relative importance of the independent variables that affect the vasoconstriction potency is octanol/buffer partition coefficient > potency > pKa > molecular weight. The ED50 in endothelium-denuded aorta negatively correlated with the octanol/buffer partition coefficient of local anesthetics (r2=0.9563; P<0.001. The potency of the vasoconstriction in the endothelium-denuded aorta induced by local anesthetics is determined primarily by lipid solubility and, in part, by other physicochemical properties including potency and pKa.

  12. The Drosophila speciation factor HMR localizes to genomic insulator sites.

    Science.gov (United States)

    Gerland, Thomas Andreas; Sun, Bo; Smialowski, Pawel; Lukacs, Andrea; Thomae, Andreas Walter; Imhof, Axel

    2017-01-01

    Hybrid incompatibility between Drosophila melanogaster and D. simulans is caused by a lethal interaction of the proteins encoded by the Hmr and Lhr genes. In D. melanogaster the loss of HMR results in mitotic defects, an increase in transcription of transposable elements and a deregulation of heterochromatic genes. To better understand the molecular mechanisms that mediate HMR's function, we measured genome-wide localization of HMR in D. melanogaster tissue culture cells by chromatin immunoprecipitation. Interestingly, we find HMR localizing to genomic insulator sites that can be classified into two groups. One group belongs to gypsy insulators and another one borders HP1a bound regions at active genes. The transcription of the latter group genes is strongly affected in larvae and ovaries of Hmr mutant flies. Our data suggest a novel link between HMR and insulator proteins, a finding that implicates a potential role for genome organization in the formation of species.

  13. Analysis of Specific Binding and Subcellular Localization of Wheat ERF Transcription Factor W17

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yun-xiang; LIU Pei; XU Zhao-shi; CHEN Ming; LI Lian-cheng; CHEN Yao-feng; XIONG Xiang-jin; MA You-zhi

    2008-01-01

    The study aims to detect the subcellular localization of ERF (ethylene-responsive element binding factor) transcription factor W17 protein, the interaction between W17 and cis-acting regulatory elements GCC-box and DRE in vitro, the binding and transactivating ability in vivo, and the role of W17 in higher plant stress-signal pathway. Recombinant plasmid W17/163hGFP was introduced into onion epidermal cells by the particle bombardment method with a PDS1000/He. Transformed cells were incubated for 24h at 22℃ in the dark and green fluorescence was monitored under a confocal microscope. The gene W17 was fused N-terminus of GST (glutathione-S-transferase) in prokaryotic expression vector pGEX-4T-1 and then transformed into E. coli strain BL21 (DE3). IPTG (0.5mmol L-1) was added to induce the expression of recombinant GST/W17 for 3h. The fused proteins were purified by GST purification columns, and then subjected to gel retardation assay with a 32P-labeled GCC or DRE sequence. The different reporter and effector plasmids were introduced into tobacco leaves through agroinfiltration, then transformed leaves stained by X-Gluc, faded with 75% alcohol and monitored under a Stereozooming microscope. The GFP fused with W17 protein was localized in the nuclei; SDS-PAGE assay demonstrated that the fused protein GST/W17 could be induced and purified with molecular weight at around 42.2kD under the induction of IPTG. Purified fused protein was able to specifically bind to both the wild-type GCC-box and DRE element, but had no interaction with either the mutant DRE or GCC-box; W17 protein can bind to GCC-box and transactive downstream GUS gene in vivo. W17 can localize into the nuclei, and it may be involved not only in biotic stresses controlled by GCC-box, but also in abiotic stresses (e. g., salt-) induced signaling pathway.

  14. Imperfect traveling chimera states induced by local synaptic gradient coupling

    Science.gov (United States)

    Bera, Bidesh K.; Ghosh, Dibakar; Banerjee, Tanmoy

    2016-07-01

    In this paper, we report the occurrence of chimera patterns in a network of neuronal oscillators, which are coupled through local, synaptic gradient coupling. We discover a new chimera pattern, namely the imperfect traveling chimera state, where the incoherent traveling domain spreads into the coherent domain of the network. Remarkably, we also find that chimera states arise even for one-way local coupling, which is in contrast to the earlier belief that only nonlocal, global, or nearest-neighbor local coupling can give rise to chimera state; this find further relaxes the essential connectivity requirement of getting a chimera state. We choose a network of identical bursting Hindmarsh-Rose neuronal oscillators, and we show that depending upon the relative strength of the synaptic and gradient coupling, several chimera patterns emerge. We map all the spatiotemporal behaviors in parameter space and identify the transitions among several chimera patterns, an in-phase synchronized state, and a global amplitude death state.

  15. Localizing an atom using electromagnetically induced transparency in three dimensions

    Science.gov (United States)

    Chen, Jinyu; Song, Fei; Ma, Yangcheng; Wang, Zhiping; Yu, Benli

    2017-09-01

    A new scheme for three-dimensional (3D) atom localization is proposed, in which the atomic system is driven by three orthogonal standing-wave lasers. Because of the space-dependent atom-field interaction, the position probability distribution of the atom can be directly determined by measuring the probe absorption. It is found that, by properly varying the parameters of the system, the probability of finding the atom in 3D space can be almost 100%. Our scheme opens a promising way to achieve high-precision and high-efficiency 3D atom localization, which provides some potential applications in laser cooling or atom nano-lithography via atom localization.

  16. Trachoma Prevalence and Risk Factors in Eight Local Government ...

    African Journals Online (AJOL)

    2010 and July 2011 using a two-stage sampling with probability proportional to size. ... control were used in planning the survey, while the risk factors assessment was based on ... Chi‑square analysis shows access to latrine, knowledge of trachoma as a disease, and ... design effect of 4; and a nonresponse of 10% to cover.

  17. Monitoring Locally Induced Hyperthermia with Magnetic Resonance Imaging

    NARCIS (Netherlands)

    M.W. Vogel (M.)

    2005-01-01

    markdownabstract__Abstract__ Magnetic resonance thermometry is a relatively new and unique technology for non-invasive monitoring of (local) therapeutic temperature changes that is not yet in common use. Temperature measurements using magnetic resonance heat thermometry can be performed in several

  18. Tissue localization of human trefoil factors 1, 2, and 3

    DEFF Research Database (Denmark)

    Madsen, Jens; Nielsen, Ole; Tornøe, Ida

    2007-01-01

    pattern of the three trefoil factors analyzing mRNA from a panel of 20 human tissues by conventional reverse transcriptase (RT) PCR and, in addition, by real-time PCR. These findings were supported by immunohistochemical analysis of paraffin-embedded human tissues using rabbit polyclonal antibodies raised...... against these factors. TFF1 showed highest expression in the stomach and colon, whereas TFF2 and TFF3 showed highest expression in stomach and colon, respectively. All three TFFs were found in the ducts of pancreas. Whereas TFF2 was found to be restricted to these two tissues, the structurally more...... closely related TFF1 and TFF3 showed a more general tissue distribution and were found to colocalize on an array of mucosal surfaces. This is the first thorough parallel description of the tissue distribution of TFFs in normal tissues, and it provides a baseline for similar analysis in diseased tissues...

  19. Scale Factor Study for 1:30 Local Scour Model

    Science.gov (United States)

    2016-08-01

    Sedimentation engineering : ASCE manuals and reports on engineering practice, No. 54. Reston, VA: American Society of Civil Engineers ...Jeremy A. Sharp, Ronald E. Heath, Howard E. Park, and Tate O. McAlpin PURPOSE: This Coastal and Hydraulics Engineering Technical Note (CHETN... Engineer Research and Development Center, Vicksburg, MS. ERDC/CHL CHETN-VII-15 August 2016 8 For implementation, the scale factor was applied to the

  20. Automatic Blocking Of QR and LU Factorizations for Locality

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Q; Kennedy, K; You, H; Seymour, K; Dongarra, J

    2004-03-26

    QR and LU factorizations for dense matrices are important linear algebra computations that are widely used in scientific applications. To efficiently perform these computations on modern computers, the factorization algorithms need to be blocked when operating on large matrices to effectively exploit the deep cache hierarchy prevalent in today's computer memory systems. Because both QR (based on Householder transformations) and LU factorization algorithms contain complex loop structures, few compilers can fully automate the blocking of these algorithms. Though linear algebra libraries such as LAPACK provides manually blocked implementations of these algorithms, by automatically generating blocked versions of the computations, more benefit can be gained such as automatic adaptation of different blocking strategies. This paper demonstrates how to apply an aggressive loop transformation technique, dependence hoisting, to produce efficient blockings for both QR and LU with partial pivoting. We present different blocking strategies that can be generated by our optimizer and compare the performance of auto-blocked versions with manually tuned versions in LAPACK, both using reference BLAS, ATLAS BLAS and native BLAS specially tuned for the underlying machine architectures.

  1. Control of the renal renin system by local factors

    DEFF Research Database (Denmark)

    Wagner, C; Jensen, B L; Krämer, B K

    1998-01-01

    prostanoid, both stimulate renin secretion and renin gene expression by activating cAMP formation in JG cells. Although the direct effect of NO on JG cells is less clear, its overall effect in vivo seems to be to stimulate the renin system. Evidence is emerging that stimulation by NO is related to the c......AMP pathway, and cGMP-induced inhibition of cAMP-phosphodiesterase III (PDE-III) may mediate this effect. ETs, on the other hand, appear to inhibit the renin system, in particular in those pathways activated by cAMP, acting via Ca2+- and protein kinase C-related mechanisms. There is increasing evidence...... that both NO and PGs could be involved in the physiological regulatory mechanisms by which salt intake affects the renin system....

  2. Local zeta factors and geometries under Spec Z

    Science.gov (United States)

    Manin, Yu I.

    2016-08-01

    The first part of this note shows that the odd-period polynomial of each Hecke cusp eigenform for the full modular group produces via the Rodriguez-Villegas transform ([1]) a polynomial satisfying the functional equation of zeta type and having non-trivial zeros only in the middle line of its critical strip. The second part discusses the Chebyshev lambda-structure of the polynomial ring as Borger's descent data to \\mathbf{F}_1 and suggests its role in a possible relation of the Γ\\mathbf{R}-factor to 'real geometry over \\mathbf{F}_1' (cf. [2]).

  3. Localization Factors and Inward Foreign Direct Investment in Greece

    Directory of Open Access Journals (Sweden)

    Nuno Carlos LEITÃO

    2010-06-01

    Full Text Available This study examines the foreign direct investment (FDI attractiveness for Greece as a host country in the period 1998-2007. The purpose of this paper is to analyze the impact of variables, such as market size, labour costs, trade openness, taxes, inflation and economic stability. The manuscript applies a panel data approach (Fixed Effects estimator and GMM system estimator. In contrast to previous studies, this paper used a dynamic panel data to solve the problems of serial correlation and endogeneity. The empirical results indicate that the market size, trade openness, and labour costs are significant factors to explain inward FDI to Greece. These results indicate that the FDI attracting will be influenced by market size. Our results also show that Greece has some problems of macroeconomic stability, which discourages the investors.

  4. Quasi-steady multiple flux tubes induced by localized current perturbation in toroidal plasma

    Science.gov (United States)

    Yun, Gunsu

    2015-11-01

    Quasi-steady helical modes with dual, triple, or more flux tubes are easily produced by localized current drive in the core of sawtoothing plasma on the KSTAR tokamak. Individual flux tubes have m / n = 1 / 1 helicity, co-rotate around the magnetic axis, and later merge into a single m = 1 mode. The merged mode eventually crashes with rapid collapse of the core pressure and the next cycle repeats the same pattern, exhibiting sawtooth-like oscillations in the core pressure. The generation mechanism of multiple flux tubes (MFTs) has been studied in two different approaches to understand the observed trend that the number of flux tubes increases as the current drive location moves away from the magnetic axis up to about the magnetic surface of the safety factor q = 1 at the mode collapse: (1) nonlinear reduced MHD simulation with a localized current source modeling the time-varying interaction between the current source and flux tubes and (2) linear MHD simulation with a prescribed q profile with a radially localized current blip. Both studies show that MFTs can be produced only in plasmas with nearly flat q profile close to unity, suggesting the collapse of the m = 1 mode (i.e., sawtooth crash) is complete. Recent observation of long-lived MFTs induced by localized current drive in non-sawtoothing plasma suggests that q profile evolution toward lower- m instability is required for the merging and crash of MFTs. Work supported by the National Research Foundation of Korea, US D.O.E., and Japan Society for the Promotion of Science.

  5. Factors affecting survivability of local Rohilkhand goats under organized farm

    Directory of Open Access Journals (Sweden)

    D. Upadhyay

    2015-10-01

    Full Text Available Aim: To study the pattern of mortality as affected by age, season and various diseases in local goats of Rohilkhand region maintained at the Indian Veterinary Research Institute, Bareilly. Materials and Methods: Post-mortem records of 12 years (2000-01 to 2011-12 were used, and total 243 mortality data were collected and analyzed. The causes of mortality were classified into seven major classes viz. digestive disorders, respiratory disorders, cardiovascular disorders, musculoskeletal disorder, parasitic disorders, mixed disorders (combination of digestive, respiratory, parasitic, and cardiovascular disorders and miscellaneous disorders (cold, hypoglycemia, emaciation, endometritis, traumatic injury, etc.. Results: The average mortality was 10.93%. The overall mortality was more during rainy season followed by winter and summer season. The mortality in 4-6 months of age was high (2.52% followed by 0-1 month (2.34% and 2-3 months (1.35%. The average mortality among adult age groups (>12 months was 3.42%. The mortality showed declining trend with the advancement of age up to 3 months and then again increased in 4-6 months age group. The digestive diseases (3.51% followed by respiratory diseases (1.89% and parasitic diseases (1.48% contributed major share to the total mortality occurred and the remaining disorders were of lesser significance in causing death in goats. There is significant (p<0.01; χ2=55.62 association between year with season and age with the season (p<0.05, χ2=16.083 found in the present study. Conclusion: This study confirms that overall mortality rate averaged 10.93% (ranged between 1.10% and 25.56% over 12 years under semi-intensive farm condition. It was generally higher in rainy season. The mortality remains higher in kids particularly under 1 month of age. The digestive diseases contributed major share to overall mortality.

  6. Comparison of sweat rate during graded exercise and the local rate induced by pilocarpine

    Directory of Open Access Journals (Sweden)

    Vimieiro-Gomes A.C.

    2005-01-01

    Full Text Available Centrally stimulated sweat rate produced by graded exercise until exhaustion was compared to the local sweat rate induced by pilocarpine, often used as a sweating index for healthy individuals. Nine young male volunteers (22 ± 4 years were studied in temperate environment in two situations: at rest and during progressive exercise with 25 W increases every 2 min until exhaustion, on a cycle ergometer. In both situations, sweating was induced on the right forearm with 5 ml 0.5% pilocarpine hydrochloride applied by iontophoresis (1.5 mA, 5 min, with left forearm used as control. Local sweat rate was measured for 15 min at rest. During exercise, whole-body sweat rate was calculated from the body weight variation. Local sweat rate was measured from the time when heart rate reached 150 bpm until exhaustion and was collected using absorbent filter paper. Pharmacologically induced local sweat rate at rest (0.4 ± 0.2 mg cm-2 min-1 and mean exercise-induced whole-body sweat rate (0.4 ± 0.1 mg cm-2 min-1 were the same (P > 0.05 but were about five times smaller than local exercise-induced sweat rate (control = 2.1 ± 1.4; pilocarpine = 2.7 ± 1.2 mg cm-2 min-1, indicating different sudorific mechanisms. Both exercise-induced whole-body sweat rate (P < 0.05 and local sweat rate (P < 0.05 on control forearm correlated positively with pilocarpine-induced local sweat rate at rest. Assuming that exercise-induced sweating was a result of integrated physiological mechanisms, we suggest that local and whole-body sweat rate measured during graded exercise could be a better sweating index than pilocarpine.

  7. Myeloid-Derived Vascular Endothelial Growth Factor and Hypoxia-Inducible Factor Are Dispensable for Ocular Neovascularization—Brief Report

    Science.gov (United States)

    Liyanage, Sidath E.; Fantin, Alessandro; Villacampa, Pilar; Lange, Clemens A.; Denti, Laura; Cristante, Enrico; Smith, Alexander J.; Ali, Robin R.; Luhmann, Ulrich F.

    2016-01-01

    Objective— Ocular neovascularization (ONV) is a pathological feature of sight-threatening human diseases, such as diabetic retinopathy and age-related macular degeneration. Macrophage depletion in mouse models of ONV reduces the formation of pathological blood vessels, and myeloid cells are widely considered an important source of the vascular endothelial growth factor A (VEGF). However, the importance of VEGF or its upstream regulators hypoxia-inducible factor-1α (HIF1α) and hypoxia-inducible factor-2α (HIF2α) as myeloid-derived regulators of ONV remains to be determined. Approach and Results— We used 2 mouse models of ONV, choroidal neovascularization and oxygen-induced retinopathy, to show that Vegfa is highly expressed by several cell types, but not myeloid cells during ONV. Moreover, myeloid-specific VEGF ablation did not reduce total ocular VEGF during choroidal neovascularization or oxygen-induced retinopathy. In agreement, the conditional inactivation of Vegfa, Hif1a, or Epas1 in recruited and resident myeloid cells that accumulated at sites of neovascularization did not significantly reduce choroidal neovascularization or oxygen-induced retinopathy. Conclusions— The finding that myeloid cells are not a significant local source of VEGF in these rodent models of ONV suggests that myeloid function in neovascular eye disease differs from skin wound healing and other neovascular pathologies. PMID:26603154

  8. Local strain-induced band gap fluctuations and exciton localization in aged WS2 monolayers

    Science.gov (United States)

    Krustok, J.; Kaupmees, R.; Jaaniso, R.; Kiisk, V.; Sildos, I.; Li, B.; Gong, Y.

    2017-06-01

    Optical properties of aged WS2 monolayers grown by CVD method on Si/SiO2 substrates are studied using temperature dependent photoluminescence and reflectance contrast spectroscopy. Aged WS2 monolayers have a typical surface roughness about 0.5 nm and, in addition, a high density of nanoparticles (nanocaps) with the base diameter about 30 nm and average height of 7 nm. The A-exciton of aged monolayer has a peak position at 1.951 eV while in as-grown monolayer the peak is at about 24 meV higher energy at room temperature. This red-shift is explained using local tensile strain concept, where strain value of 2.1% was calculated for these nanocap regions. Strained nanocaps have lower band gap energy and excitons will funnel into these regions. At T=10K a double exciton and trion peaks were revealed. The separation between double peaks is about 20 meV and the origin of higher energy peaks is related to the optical band gap energy fluctuations caused by random distribution of local tensile strain due to increased surface roughness. In addition, a wide defect related exciton band XD was found at about 1.93 eV in all aged monolayers. It is shown that the theory of localized excitons describes well the temperature dependence of peak position and halfwidth of the A-exciton band. The possible origin of nanocaps is also discussed.

  9. Inducing and Aggravating Factors of Gastroesophageal Reflux Symptoms

    Directory of Open Access Journals (Sweden)

    Radhiyatam Mardhiyah

    2016-12-01

    Full Text Available Gastroesophageal reflux disease (subsequently abbreviated as GERD is a disease commonly found in the community. Several factors have been recognized as inducing and aggravating factors of GERD symptoms such as older age, female gender, obesity, smoking habit, alcohol consumption, certain diet and poor eating habit like eating fatty, spicy, and acid food.

  10. Quantum non-Markovianity induced by Anderson localization

    Science.gov (United States)

    Lorenzo, Salvatore; Lombardo, Federico; Ciccarello, Francesco; Palma, G. Massimo

    2017-02-01

    As discovered by P. W. Anderson, excitations do not propagate freely in a disordered lattice, but, due to destructive interference, they localise. As a consequence, when an atom interacts with a disordered lattice, one indeed observes a non-trivial excitation exchange between atom and lattice. Such non-trivial atomic dynamics will in general be characterised also by a non-trivial quantum information backflow, a clear signature of non-Markovian dynamics. To investigate the above scenario, we consider a quantum emitter, or atom, weakly coupled to a uniform coupled-cavity array (CCA). If initially excited, in the absence of disorder, the emitter undergoes a Markovian spontaneous emission by releasing all its excitation into the CCA (initially in its vacuum state). By introducing static disorder in the CCA the field normal modes become Anderson-localized, giving rise to a non-Markovian atomic dynamics. We show the existence of a functional relationship between a rigorous measure of quantum non-Markovianity and the CCA localization. We furthermore show that the average non-Markovianity of the atomic dynamics is well-described by a phenomenological model in which the atom is coupled, at the same time, to a single mode and to a standard - Markovian - dissipative bath.

  11. Quantum non-Markovianity induced by Anderson localization

    Science.gov (United States)

    Lorenzo, Salvatore; Lombardo, Federico; Ciccarello, Francesco; Palma, G. Massimo

    2017-01-01

    As discovered by P. W. Anderson, excitations do not propagate freely in a disordered lattice, but, due to destructive interference, they localise. As a consequence, when an atom interacts with a disordered lattice, one indeed observes a non-trivial excitation exchange between atom and lattice. Such non-trivial atomic dynamics will in general be characterised also by a non-trivial quantum information backflow, a clear signature of non-Markovian dynamics. To investigate the above scenario, we consider a quantum emitter, or atom, weakly coupled to a uniform coupled-cavity array (CCA). If initially excited, in the absence of disorder, the emitter undergoes a Markovian spontaneous emission by releasing all its excitation into the CCA (initially in its vacuum state). By introducing static disorder in the CCA the field normal modes become Anderson-localized, giving rise to a non-Markovian atomic dynamics. We show the existence of a functional relationship between a rigorous measure of quantum non-Markovianity and the CCA localization. We furthermore show that the average non-Markovianity of the atomic dynamics is well-described by a phenomenological model in which the atom is coupled, at the same time, to a single mode and to a standard - Markovian - dissipative bath. PMID:28205542

  12. Vismodegib induces significant clinical response in locally advanced trichoblastic carcinoma.

    Science.gov (United States)

    Lepesant, P; Crinquette, M; Alkeraye, S; Mirabel, X; Dziwniel, V; Cribier, B; Mortier, L

    2015-10-01

    Patients with advanced basal cell carcinoma due to local extension or metastatic disease were previously at a therapeutic impasse. Targeted inhibition of the sonic hedgehog pathway by vismodegib represents a new therapeutic strategy. Adnexal carcinomas are rare malignant skin tumours derived from epithelial annexes. Conventional treatment of adnexal tumours is based on surgical excision. Although the radiosensitivity of adnexal carcinomas has not been established, radiotherapy could be offered alone or in combination in locally advanced or inoperable disease. Chemotherapy represents a therapeutic option in the treatment of metastatic adnexal tumours. Currently there is no effective treatment for these tumours when they become metastatic or unresectable, and treatment is palliative. Sunitinib represents a new therapeutic strategy, with efficiency described in the literature for a small number of patients. However, its efficacy is partial, and its tolerance is not always good. We report a patient with trichoblastic carcinoma, initially diagnosed as basal cell carcinoma, treated effectively with vismodegib. The remarkable response we have observed in this patient suggests an encouraging therapeutic role of vismodegib in trichoblastic carcinoma that should be evaluated in a carefully designed trial.

  13. [Risk factors and subjective symptoms of drug-induced leucopenia].

    Science.gov (United States)

    Hayashi, Kyoko; Ohtsu, Fumiko; Yano, Reiko; Sakakibara, Jinsaku; Goto, Nobuyuki

    2011-01-01

    The present study investigated risk factors and subjective symptoms associated with drug-induced leucopenia. We selected 248 patients with drug-induced leucopenia from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 47000 case reports of adverse drug reactions and assigned them to a case group. We also randomly selected 743 cases of adverse drug reactions not associated with leucopenia as a control group. A comparison of patient characteristic data between the two groups using logistic-regression analysis revealed that female sex, autoimmune disease and renal damage were background risk factors for drug-induced leucopenia. In addition, thiamazole, ritodrine, propylthiouracil, ticlopidine, allopurinol, minocycline and captopril administration significantly increased the risk of drug-induced leucopenia. A significant association was also found for fever, chills and pharyngeal abnormalities. Based on these findings, we developed two estimated regression equations to help prevent drug-induced leucopenia in the community pharmacy setting.

  14. Chronic gastritis rat model and role of inducing factors

    Institute of Scientific and Technical Information of China (English)

    Zun Xiang; Jian-Min Si; Huai-De Huang

    2004-01-01

    AIM: To establish an experimental animal model of chronic gastritis in a short term and to investigate the effects of several potential inflammation-inducing factors on rat gastric mucosa.METHODS: Twenty-four healthy, male SD rats were treated with intragastric administration of 600 mL/L alcohol, 20mmol/L sodium deoxycholate and 0.5 g/L ammonia (factor A), forage containing low levels of vitamins (factor B), and/or indomethacin (factor C), according to an L8(27)orthogonal design. After 12 wk, gastric antral and body mucosae were pathologically examined.RESULTS: Chronic gastritis model was successfully induced in rats treated with factor A for 12 wk. After the treatment of animals, the gastric mucosal inflammation was significantly different from that in controls, and the number of pyloric glands at antrum and parietal cells at body were obviously reduced (P<0.01). Indomethacin induced gastritis but without atrophy, and short-term vitamin deficiency failed to induce chronic gastritis and gastric atrophy, In addition,indomethacin and vitamin deficiency had no synergistic effect in inducing gastritis with the factor A. No atypical hyperplasia and intestinal metaplasia in the gastric antrum and body were observed in all rats studied.CONCLUSION: Combined intragastric administration of 600 mL/L alcohol, 20 mmol/L sodium deoxycholate and 0.5 g/L ammonia induces chronic gastritis and gastric atrophy in rats. Indomethacin induces chronic gastritis only.The long-term roles of these factors in gastric inflammation and carcinogenesis need to be further elucidated.

  15. Localization of type I interferon receptor limits interferon-induced TLR-3 in epithelial cells

    Science.gov (United States)

    This study aimed to expand on the role of type I IFNs in the influenza-induced upregulation of TLR3 and determine whether and how the localization of the IFN-alpha/beta receptor (IFNAR) in respiratory epithelial cells could modify IFN-induced responses. Using differentiated prima...

  16. Localization of type I interferon receptor limits interferon-induced TLR-3 in epithelial cells

    Science.gov (United States)

    This study aimed to expand on the role of type I IFNs in the influenza-induced upregulation of TLR3 and determine whether and how the localization of the IFN-alpha/beta receptor (IFNAR) in respiratory epithelial cells could modify IFN-induced responses. Using differentiated prima...

  17. Wounding induces local resistance but systemic susceptibility to Botrytis cinerea in pepper plants.

    Science.gov (United States)

    García, Tania; Gutiérrez, Jorge; Veloso, Javier; Gago-Fuentes, Raquel; Díaz, José

    2015-03-15

    Cotyledon wounding in pepper caused the early generation of hydrogen peroxide both locally (cotyledons) and systemically (upper true leaves). However, 72 h later there is a different wound response between local and systemic organs, as shown by resistance to the pathogenic fungus Botrytis cinerea, that increased locally and decreased systemically. Signaling by ethylene and jasmonic acid was assessed by using two inhibitors: 1-methylcyclopropene (MCP, inhibitor of ethylene receptors) and ibuprofen (inhibitor of jasmonate biosynthesis). MCP did not affect the modulation of resistance levels to Botrytis by wounding, ruling out the involvement of ethylene signaling. Ibuprofen did not inhibit wound-induced resistance at the local level, but inhibited wound-induced systemic susceptibility. Moreover, changes of biochemical and structural defenses in response to wounding were studied. Peroxidase activity and the expression of a peroxidase gene (CAPO1) increased locally as a response to wounding, but no changes were observed systemically. Lignin deposition was induced in wounded cotyledons, but was repressed in systemic leaves of wounded plants, whereas soluble phenolics did not change locally and decreased systemically. The expression of two other genes involved in plant defense (CABPR1 and CASC1) was also differentially regulated locally and systemically, pointing to a generalized increase in plant defenses at the local level and a systemic decrease as a response to wounding. Wound-induced defenses at the local level coincided with resistance to the necrotroph fungus B. cinerea, whereas depleted defenses in systemic leaves of wounded plants correlated to induced susceptibility against this pathogen. It may be that the local response acts as a sink of energy resources to mount a defense against pathogens, whereas in systemic organs the resources for defense are lower.

  18. Localized linear IgA dermatosis induced by UV light-treatment for herpes zoster.

    Science.gov (United States)

    He, Chundi; Xu, Honghui; Xiao, Ting; Geng, Long; Chen, Hong-Duo

    2007-05-01

    We report a case of localized linear IgA dermatosis (LID). The patient suffered from herpes zoster on the right waist and received three localized ultraviolet (UV) light treatments. One month later he presented with bullae on the same site. Direct immunofluorescence showed deposition of linear IgA and weak C3 along the basement membrane zone. Indirect immunofluorescence on the salt-split human skin demonstrated that IgA antibodies were bound to the epidermal side. To our knowledge, this is the first case of localized LID induced by UV light treatment for herpes zoster. It is also the third case of LID induced by UV light.

  19. EVALUATION OF THE PREVALENCE OF THE PERIODONTAL DISEASE VERSUS SYSTEMIC AND LOCAL RISK FACTORS

    OpenAIRE

    Silvia MÂRŢU; Sorina SOLOMON; Oana POTÂRNICHIE; Liliana PĂSĂRIN; Alexandra MÂRŢU; O. NICOLAICIUC; Irina URSARESCU

    2013-01-01

    Introduction: The periodontal disease represents a malady characterized by an extremely high incidence. The manifestations and evolution of the periodontal diseases vary for each form in part, being influenced by systemic and local risk factors. Scope of the study: To evaluate the periodontal status on a group of patients, versus the syste‐ mic and local factors. Materials and method: The study was performed on a group of 170 patients, whose odonto‐periodontal status was evaluated by strict c...

  20. Effects of Brain-Derived Neurotrophic Factor on Local Inflammation in Experimental Stroke of Rat

    OpenAIRE

    Yongjun Jiang; Ning Wei; Juehua Zhu; Tingting Lu; Zhaoyao Chen; Gelin Xu; Xinfeng Liu

    2010-01-01

    This study was aimed to investigate whether brain-derived neurotrophic factor (BDNF) can modulate local cerebral inflammation in ischemic stroke. Rats were subjected to ischemia by occluding the right middle cerebral artery (MCAO) for 2 hours. Rats were randomized as control, BDNF, and antibody groups. The local inflammation was evaluated on cellular, cytokine, and transcription factor levels with immunofluorescence, enzyme-linked immunosorbent assay, real-time qPCR, and electrophoretic mobil...

  1. 修正的局部稳定性因子%MODIFIED LOCAL STABILITY FACTOR

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    In the past,stability evaluation of engineering rockmass is often based on the distribution of stress and deformation in engineering rockmass. Some scholars have put forward the concept of local stability factor of rockmass and its calculating method. But its condition is too harsh. The concept of is put forward and its formula is deduced based on the rockmass mechanics principle and strength criteria. The modified local stability factor has been used to evaluate the stability of surrounding rockmass of tunnel.

  2. Local Quark-Hadron Duality and Magnetic Form Factors of Bound Proton

    Institute of Scientific and Technical Information of China (English)

    WANG Hong-Min; ZHANG Ben-Ai

    2005-01-01

    We discuss the consequence of local duality for elastic scattering, and derive a model-independent equation between structure functions at x ~ 1 and elastic electromagnetic form factors. Then the electromagnetic form factors of proton are discussed using the quark-hadron duality theory. We also debate the form factor of proton in a bound state.It may be an effective approach to study the form factor of proton in media.

  3. A Systematic Analysis of Factors Localized to Damaged Chromatin Reveals PARP-Dependent Recruitment of Transcription Factors

    Directory of Open Access Journals (Sweden)

    Lior Izhar

    2015-06-01

    Full Text Available Localization to sites of DNA damage is a hallmark of DNA damage response (DDR proteins. To identify DDR factors, we screened epitope-tagged proteins for localization to sites of chromatin damaged by UV laser microirradiation and found >120 proteins that localize to damaged chromatin. These include the BAF tumor suppressor complex and the amyotrophic lateral sclerosis (ALS candidate protein TAF15. TAF15 contains multiple domains that bind damaged chromatin in a poly-(ADP-ribose polymerase (PARP-dependent manner, suggesting a possible role as glue that tethers multiple PAR chains together. Many positives were transcription factors; > 70% of randomly tested transcription factors localized to sites of DNA damage, and of these, ∼90% were PARP dependent for localization. Mutational analyses showed that localization to damaged chromatin is DNA-binding-domain dependent. By examining Hoechst staining patterns at damage sites, we see evidence of chromatin decompaction that is PARP dependent. We propose that PARP-regulated chromatin remodeling at sites of damage allows transient accessibility of DNA-binding proteins.

  4. An update on risk factors for drug-induced arrhythmias.

    Science.gov (United States)

    Vlachos, Konstantinos; Georgopoulos, Stamatis; Efremidis, Michael; Sideris, Antonios; Letsas, Konstantinos P

    2016-01-01

    A variety of drugs, either anti-arrhythmics or non-antiarrhythmics, have been associated with drug-induced arrhythmias. Drug-induced arrhythmias are usually observed in the presence of long QT interval or Brugada electrocardiographic pattern. Clinical risk factors, such as female gender, structural heart disease, metabolic and electrolyte abnormalities, bradycardia and conduction disease, increased drug bioavailability, and silent channelopathies act as ''effect amplifiers'' which can make an otherwise relatively safe drug dangerous with regard to risk for polymorphic ventricular tachycardia in the setting of QT interval prolongation. A drug-induced type 1 electrocardiographic pattern of Brugada syndrome is considered highly proarrhythmic. Specific electrocardiographic markers including the corrected QT interval, QRS duration, Tpeak-Tend/QT ratio, and others may predict the risk of arrhythmias in both situations. The present review highlights on the current clinical and electrocardiographic risk factors for prediction of drug-induced arrhythmias.

  5. Interferon-gamma-induced local leukocytoclastic vasculitis at the subcutaneous injection site*

    Science.gov (United States)

    Wang, Fang; Liu, Juan-Hua; Zhao, Yu-Kun; Luo, Di-Qing

    2016-01-01

    Cutaneous reactions associated with interferons (IFNs) treatment are either localized or generalized. The most common presentation of localized reactions at IFNs injection site is usually an erythematous patch or plaque. Local leukocytoclastic vasculitis presenting with cutaneous necrosis is extremely rare. We report a 19-year-old man with hepatitis B who had local leukocytoclastic vasculitis induced by interferon-gama injection at the injection site. After changing the injection sites and using the combined treatment of prednisone and colchicine, the previous lesion healed and no other cutaneous lesion occurred. We also made a mini review of such cases.

  6. Hypoxia-Inducible Factor as an Angiogenic Master Switch

    Science.gov (United States)

    Hashimoto, Takuya; Shibasaki, Futoshi

    2015-01-01

    Hypoxia-inducible factors (HIFs) regulate the transcription of genes that mediate the response to hypoxia. HIFs are constantly expressed and degraded under normoxia, but stabilized under hypoxia. HIFs have been widely studied in physiological and pathological conditions and have been shown to contribute to the pathogenesis of various vascular diseases. In clinical settings, the HIF pathway has been studied for its role in inhibiting carcinogenesis. HIFs might also play a protective role in the pathology of ischemic diseases. Clinical trials of therapeutic angiogenesis after the administration of a single growth factor have yielded unsatisfactory or controversial results, possibly because the coordinated activity of different HIF-induced factors is necessary to induce mature vessel formation. Thus, manipulation of HIF activity to simultaneously induce a spectrum of angiogenic factors offers a superior strategy for therapeutic angiogenesis. Because HIF-2α plays an essential role in vascular remodeling, manipulation of HIF-2α is a promising approach to the treatment of ischemic diseases caused by arterial obstruction, where insufficient development of collateral vessels impedes effective therapy. Eukaryotic initiation factor 3 subunit e (eIF3e)/INT6 interacts specifically with HIF-2α and induces the proteasome inhibitor-sensitive degradation of HIF-2α, independent of hypoxia and von Hippel-Lindau protein. Treatment with eIF3e/INT6 siRNA stabilizes HIF-2α activity even under normoxic conditions and induces the expression of several angiogenic factors, at levels sufficient to produce functional arteries and veins in vivo. We have demonstrated that administration of eIF3e/INT6 siRNA to ischemic limbs or cold-injured brains reduces ischemic damage in animal models. This review summarizes the current understanding of the relationship between HIFs and vascular diseases. We also discuss novel oxygen-independent regulatory proteins that bind HIF-α and the implications

  7. Retrospective analysis of prognostic factors for sixty osteosarcoma patients with local recurrence

    Institute of Scientific and Technical Information of China (English)

    Jingjing Sha; Weixiang Qi; Haiyan Hu; Yuanjue Sun; Zan Shen; Yang Yao

    2013-01-01

    Objective: The aim of this study was to identify prognostic factors and imply the appropriate management for lo-cal recurrent osteosarcoma. Methods: The clinical records of 60 patients with local recurrence osteosarcoma were reviewed between January 2002 and December 2010. The mean followed-up time for these patients was 49.1 months (range 13 to 143 months). The factors of age, gender, tumor site, tumor size, surgical procedure, neoadjuvant chemotherapy, frequency of primary postoperative adjuvant chemotherapy, lung metastasis, metastasis of other sites (except for lung) and treatment after local recurrence were selected as the measurements for this analysis. Kaplan-Meier method was used to measure the overall survival and post-recurrence survival. The univariate analysis was used to determine the prognostic factors related with survival by Log-rank test. The COX proportional-hazard regression model was used to analyze the correlation between the prognostic factor and the survival. Results: The median post-recurrence survival and overall survival of 60 patients were 32 months (95% confidence interval: 16.2-47.8) and 55 months (95% confidence interval: 39.3–70.7) respectively. The 2- and 3-year cumulative survival rates were 81.7% and 55.4%, respectively. The Log-rank univariate analysis showed that age, gender, tumor size, metastasis of other sites (except for lung) and treatment after local recurrence were associated with the prognosis of osteosarcoma with local recurrence (P 0.05). Conclusion: The independent prognostic factors for local recurrent osteosarcoma were the metastasis of other site (except for lung) and the treatment after local recurrence. The aggressive surgical treatment for local recurrence and distant metastasis could effectively improve the survival of local recurrent osteosarcoma.

  8. Local expert experiences and perceptions of environmentally induced migration from Bangladesh to India

    NARCIS (Netherlands)

    Stojanov, Robert; Boas, Ingrid; Kelman, Ilan; Duží, Barbora

    2017-01-01

    This study investigates local expert perceptions of the role of environmental factors, especially in terms of contemporary climate change, in population movements from Bangladesh to India. The aim is to delve into locally held understandings of the phenomenon and to gain a better understanding of

  9. Inducible control of subcellular RNA localization using a synthetic protein-RNA aptamer interaction.

    Directory of Open Access Journals (Sweden)

    Brian J Belmont

    Full Text Available Evidence is accumulating in support of the functional importance of subcellular RNA localization in diverse biological contexts. In different cell types, distinct RNA localization patterns are frequently observed, and the available data indicate that this is achieved through a series of highly coordinated events. Classically, cis-elements within the RNA to be localized are recognized by RNA-binding proteins (RBPs, which then direct specific localization of a target RNA. Until now, the precise control of the spatiotemporal parameters inherent to regulating RNA localization has not been experimentally possible. Here, we demonstrate the development and use of a chemically-inducible RNA-protein interaction to regulate subcellular RNA localization. Our system is composed primarily of two parts: (i the Tet Repressor protein (TetR genetically fused to proteins natively involved in localizing endogenous transcripts; and (ii a target transcript containing genetically encoded TetR-binding RNA aptamers. TetR-fusion protein binding to the target RNA and subsequent localization of the latter are directly regulated by doxycycline. Using this platform, we demonstrate that enhanced and controlled subcellular localization of engineered transcripts are achievable. We also analyze rules for forward engineering this RNA localization system in an effort to facilitate its straightforward application to studying RNA localization more generally.

  10. Locally Resonant Gaps of Phononic Beams Induced by Periodic Arrays of Resonant Shunts

    Institute of Scientific and Technical Information of China (English)

    CHEN Sheng-Bing; WEN Ji-Hong; WANG Gang; HAN Xiao-Yun; WEN Xi-Sen

    2011-01-01

    @@ Periodic arrays of shunted piezoelectric patches are employed to control the propagation of elastic waves in phononic beams.Each piezo-patch is connected to a single resistance-inductance-capacitance shunting circuit.Therefore,the resonances of the shunting circuits will produce locally resonant gaps in the phononic beam.However,the existence of locally resonant gaps induced by resonant shunts has not been clearly proved by experiment so far.In this work,the locally resonant gap in a piezo-shunted phononic beam is investigated theoretically and verified by experiment.The results prove that resonances of shunting circuits can produce locally resonant gaps in phononic beams.%Periodic arrays of shunted piezoelectric patches are employed to control the propagation of elastic waves in phononic beams. Each piezo-patch is connected to a single resistance-inductance-capacitance shunting circuit. Therefore, the resonances of the shunting circuits will produce locally resonant gaps in the phononic beam. However, the existence of locally resonant gaps induced by resonant shunts has not been clearly proved by experiment so far. In this work, the locally resonant gap in a piezo-shunted phononic beam is investigated theoretically and verified by experiment. The results prove that resonances of shunting circuits can produce locally resonant gaps in phononic beams.

  11. Improved localization accuracy in stochastic super-resolution fluorescence microscopy by K-factor image deshadowing.

    Science.gov (United States)

    Ilovitsh, Tali; Meiri, Amihai; Ebeling, Carl G; Menon, Rajesh; Gerton, Jordan M; Jorgensen, Erik M; Zalevsky, Zeev

    2013-12-16

    Localization of a single fluorescent particle with sub-diffraction-limit accuracy is a key merit in localization microscopy. Existing methods such as photoactivated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM) achieve localization accuracies of single emitters that can reach an order of magnitude lower than the conventional resolving capabilities of optical microscopy. However, these techniques require a sparse distribution of simultaneously activated fluorophores in the field of view, resulting in larger time needed for the construction of the full image. In this paper we present the use of a nonlinear image decomposition algorithm termed K-factor, which reduces an image into a nonlinear set of contrast-ordered decompositions whose joint product reassembles the original image. The K-factor technique, when implemented on raw data prior to localization, can improve the localization accuracy of standard existing methods, and also enable the localization of overlapping particles, allowing the use of increased fluorophore activation density, and thereby increased data collection speed. Numerical simulations of fluorescence data with random probe positions, and especially at high densities of activated fluorophores, demonstrate an improvement of up to 85% in the localization precision compared to single fitting techniques. Implementing the proposed concept on experimental data of cellular structures yielded a 37% improvement in resolution for the same super-resolution image acquisition time, and a decrease of 42% in the collection time of super-resolution data with the same resolution.

  12. EVALUATION OF THE PREVALENCE OF THE PERIODONTAL DISEASE VERSUS SYSTEMIC AND LOCAL RISK FACTORS

    Directory of Open Access Journals (Sweden)

    Silvia MÂRŢU

    2013-07-01

    Full Text Available Introduction: The periodontal disease represents a malady characterized by an extremely high incidence. The manifestations and evolution of the periodontal diseases vary for each form in part, being influenced by systemic and local risk factors. Scope of the study: To evaluate the periodontal status on a group of patients, versus the syste‐ mic and local factors. Materials and method: The study was performed on a group of 170 patients, whose odonto‐periodontal status was evaluated by strict clinical and paraclinical examinations, on establishing the inflammation indices and the periodontal diagnosis. Results: The main cause of the analysis was gingival ble‐ eding; an increased number of smokers was registered among the patients. Out of the local factors, especially important were edentations and malocclusions. Also, a higher number of aggressive generalized periodontites has been noticed. Discussion: The forms of the periodontal diseases are obviously influenced by the systemic context, while the forms of localized chronic periodontitis associa‐ ted with generalized chronic gingivitis reflect the role pla‐ yed by the local risk factors. Conclusions: Stress and smoking represent significant risk factors in the installation of periodontal pathology, with a really alarming preva‐ lence. The aggressive forms of periodontitis showed a higher frequency than that recorded in literature.

  13. Growth factor involvement in tension-induced skeletal muscle growth

    Science.gov (United States)

    Vandenburgh, Herman H.

    1993-01-01

    Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

  14. Factors Constraining Local Food Crop Production in Indonesia: Experiences from Kulon Progo Regency, Yogyakarta Special Province

    Directory of Open Access Journals (Sweden)

    RADEN RIJANTA

    2013-01-01

    Full Text Available Local food crops are believed to be important alternatives in facing the problems of continuously growing price of food stuff worldwide. There has been a strong bias in national agricultural development policy towards the production of rice as staple food in Indonesia. Local food crops have been neglected in the agricultural development policy in the last 50 years, leading to the dependency on imported commodities and creating a vulnerability in the national food security. This paper aims at assessing the factors constraining local food production in Indonesia based on empirical experiences drawn from a research in Kulon Progo Regency, Yogyakarta Province. The government of Kulon Progo Regency has declared its commitment in the development of local food commodities as a part of its agricultural development policy, as it is mentioned in the long-term and medium-term development planning documents. There is also a head regency decree mandating the use of local food commodities in any official events organized by the government organisations. The research shows that there are at least six policy-related problems and nine technical factors constraining local food crops production in the regency. Some of the policy-related and structural factors hampering the production of local food crops consist of (1 long-term policy biases towards rice, (2 strong biases on rice diet in the community, (3 difficulties in linking policy to practices, (4 lack of information on availability of local food crops across the regency and (5 external threat from the readily available instant food on local market and (6 past contra-productive policy to the production of local food crops. The technical factors constraining local food production comprises (1 inferiority of the food stuff versus the instantly prepared food, (2 difficulty in preparation and risk of contagion of some crops, lack of technology for processing, (3 continuity of supply (some crops are seasonally

  15. IMMUNOELECTRON MICROSCOPIC LOCALIZATION OFGROWTH FACTORS AND OTHER MARKERS IN HUMAN LONG-TERM BONE MARROW CULTURES

    Institute of Scientific and Technical Information of China (English)

    刘杰文; WynterEde; TestaNG; DxterTM; AllenTD

    1996-01-01

    Ultrastructural immunocytochemical characterization of human long-term bone marrow cultures hasshown positive localization for growth factors on cell surface and on extracellular matrix (ECM). In somecases double-labelling indicated co-locallzation of growth factors and specific cell surface labels. Specific markers for endothelial cells and fibroblasts showed that growth factor (GM-CSF, G-CSF and b-FGF) were present at the surface of these cell types. Both scanning and transmision electron micrcscopy indicated intense labelling for growth factors on the extracellular matrix. Double-labelling of heparan sulphate proteoglycans and GM-CSF showed a co-localization of the labelling, which indicated thebinding of growth factor to the extracellular matrix.

  16. Leukemia Inhibitory Factor Induces Neurotransmitter Switching in Transgenic Mice

    Science.gov (United States)

    Bamber, Bruce A.; Masters, Brian A.; Hoyle, Gary W.; Brinster, Ralph L.; Palmiter, Richard D.

    1994-08-01

    Leukemia inhibitory factor (LIF) is a cytokine growth factor that induces rat sympathetic neurons to switch their neurotransmitter phenotype from noradrenergic to cholinergic in vitro. To test whether LIF can influence neuronal differentiation in vivo, we generated transgenic mice that expressed LIF in pancreatic islets under the control of the insulin promoter and evaluated the neurotransmitter phenotype of the pancreatic sympathetic innervation. We also used the insulin promoter to coexpress nerve growth factor in the islets, which greatly increased the density of sympathetic innervation and facilitated analysis of the effects of LIF. Our data demonstrate that tyrosine hydroxylase and catecholamines declined and choline acetyltransferase increased in response to LIF. We conclude that LIF can induce neurotransmitter switching of sympathetic neurons in vivo.

  17. A stated preference experiment to value access to quiet areas and other local environmental factors

    OpenAIRE

    Bristow, Abigail; Wardman, Mark; Shires, Jeremy; Chintakayala, Phani; Nellthorp, John

    2012-01-01

    International audience; The local environment influences people’s perceptions of their quality of life and their overall well-being in many different ways. Whilst there are a wide range of local environmental factors that can impact on individuals’ well-being, there is relatively little empirical evidence on this subject. In particular, there is a dearth of knowledge on their economic valuation, commonly expressed in terms of how much money individuals are prepared to pay for improved conditi...

  18. Local Infection after Placement of Percutaneous Endoscopic Gastrostomy Tubes: A Prospective Study Evaluating Risk Factors

    Directory of Open Access Journals (Sweden)

    Y Zopf

    2008-01-01

    Full Text Available BACKGROUND: Due to its high efficacy and technical simplicity, percutaneous endoscopic gastrostomy (PEG has gained wide-spread use. Local infection, occurring in approximately 2% to 39% of procedures, is the most common complication in the short term. Risk factors for local infection are largely unknown and therefore – apart from calculated antibiotic prophylaxis – preventive strategies have yet to be determined.

  19. Measurement of Microbially Induced Transformation of Magnetic Iron Minerals in Soils Allows Localization of Hydrocarbon Contamination

    Science.gov (United States)

    Kappler, A.; Porsch, K.; Rijal, M.; Appel, E.

    2007-12-01

    Soil contamination by crude oil and other hydrocarbons represents a severe environmental problem, but often the location and extent of contamination is not known. Hydrocarbons, or their degradation products, can stimulate iron-metabolizing microorganisms, leading to the formation or dissolution of (magnetic) iron minerals and an associated change of soil magnetic properties. Therefore, the screening of soil magnetic properties has the potential to serve as an efficient and inexpensive tool to localize such contaminations. In order to identify the influence of different biogeochemical factors on the microbially influenced changes of magnetic iron minerals after hydrocarbon contamination, oil spills were simulated in laboratory batch experiments. The parameters tested in these experiments included soils with different bedrocks, type and amount of added hydrocarbon, and microbiological parameters (sterile and autochthonous microorganisms). In order to follow the changes of the soil magnetic properties, the magnetic susceptibility of the samples was measured weekly. First results show that changes in the magnetic mineralogy are caused by microbial activity, as sterile samples showed no changes. In the microbially active set-ups, the magnetic susceptibility increased or decreased up to 10% in comparison to the initial magnetic susceptibility within a few weeks. In one iron-rich soil even a decrease of the magnetic susceptibility of ~40% was observed. Although the amount and type of hydrocarbons did not effect the changes in magnetic susceptibility, DGGE fingerprints revealed that they influenced microbial communities. These results show that the magnetic susceptibility changes in the presence of hydrocarbons and that this change is microbially induced. This suggests that the screening of soil magnetic properties can be applied to localize and assess hydrocarbon contamination. In order to understand the biogeochemical processes better, the change of the iron mineralogy

  20. Factors that modify risks of radiation-induced cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J.I.

    1988-11-01

    The collective influence of biologic and physical factors that modify risks of radiation-induced cancer introduces uncertainties sufficient to deny precision of estimates of human cancer risk that can be calculated for low-dose radiation in exposed populations. The important biologic characteristics include the tissue sites and cell types, baseline cancer incidence, minimum latent period, time-to-tumor recognition, and the influence of individual host (age and sex) and competing etiologic influences. Physical factors include radiation dose, dose rate, and radiation quality. Statistical factors include time-response projection models, risk coefficients, and dose-response relationships. Other modifying factors include other carcinogens, and other biological sources (hormonal status, immune status, hereditary factors).

  1. Factors that modify risks of radiation-induced cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J.I.

    1988-11-01

    The collective influence of biologic and physical factors that modify risks of radiation-induced cancer introduces uncertainties sufficient to deny precision of estimates of human cancer risk that can be calculated for low-dose radiation in exposed populations. The important biologic characteristics include the tissue sites and cell types, baseline cancer incidence, minimum latent period, time-to-tumor recognition, and the influence of individual host (age and sex) and competing etiologic influences. Physical factors include radiation dose, dose rate, and radiation quality. Statistical factors include time-response projection models, risk coefficients, and dose-response relationships. Other modifying factors include other carcinogens, and other biological sources (hormonal status, immune status, hereditary factors).

  2. [Predictive factors for locally recurrent rectal cancer after primary curative surgery].

    Science.gov (United States)

    Gao, Haoji; Zhang, Tao; Zhao, Ren

    2015-11-01

    Local recurrence is a major clinical challenge after primary rectal cancer surgery. Although there is a possibility that R0 resection can be achieved, the outcome is still not favorable due to the low R0 resection rate and complexity of the surgery. Therefore prevention has a higher priority over treatment afterwards. As TME principle is accepted worldwide, the local recurrence rate has been reduced dramatically. And there are other factors associated with local recurrence including CRM, operation type, staging and PNI. Proper chemoradiotherapy may reduce the risk, however benefit always comes with side effect, therefore risk stratification is important.

  3. Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma

    DEFF Research Database (Denmark)

    Jensen, Hanne Krogh; Donskov, Frede; Marcussen, Niels;

    2009-01-01

    PURPOSE: We have previously demonstrated a significant negative impact of intratumoral neutrophils in metastatic renal cell carcinoma. This study assessed intratumoral neutrophils in localized clear cell renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised 121 consecutive patients...... neutrophils was also an independent prognostic factor for cancer-specific survival (HR, 3.5; 95% CI, 1.9 to 6.4; P .... CONCLUSION: The presence of intratumoral neutrophils is a new, strong, independent prognostic factor for short recurrence-free, cancer-specific, and overall survival in localized clear cell RCC....

  4. local

    Directory of Open Access Journals (Sweden)

    Abílio Amiguinho

    2005-01-01

    Full Text Available The process of socio-educational territorialisation in rural contexts is the topic of this text. The theme corresponds to a challenge to address it having as main axis of discussion either the problem of social exclusion or that of local development. The reasons to locate the discussion in this last field of analysis are discussed in the first part of the text. Theoretical and political reasons are there articulated because the question is about projects whose intentions and practices call for the political both in the theoretical debate and in the choices that anticipate intervention. From research conducted for several years, I use contributions that aim at discuss and enlighten how school can be a potential locus of local development. Its identification and recognition as local institution (either because of those that work and live in it or because of those that act in the surrounding context are crucial steps to progressively constitute school as a partner for development. The promotion of the local values and roots, the reconstruction of socio-personal and local identities, the production of sociabilities and the equation and solution of shared problems were the dimensions of a socio-educative intervention, markedly globalising. This scenario, as it is argued, was also, intentionally, one of transformation and of deliberate change of school and of the administration of the educative territoires.

  5. Leukaemia inhibitory factor--an exercise-induced myokine

    DEFF Research Database (Denmark)

    Broholm, Christa; Pedersen, Bente Klarlund

    2010-01-01

    During and following exercise skeletal muscle synthesises and releases a number of myokines that exert their effects either systemically or locally within the muscle. Several of these myokines influence metabolism, regeneration and/or hypertrophy and are therefore considered to be important...... to oscillations in intracellular Ca2+ concentrations. However, circulating levels of LIF are not increased with exercise suggesting that LIF exerts its effect locally. LIF stimulates muscle satellite cell proliferation and is involved in muscle hypertrophy and regeneration. Thus, LIF may be produced by skeletal...... contributing factors in muscle homeostasis and muscle adaptation to exercise training. Leukaemia inhibitory factor (LIF) is produced and released from muscle cells in vitro and from intact skeletal muscle in vivo. During exercise, skeletal muscle potently up-regulates LIF mRNA expression, likely due...

  6. Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension.

    Science.gov (United States)

    Spradley, Frank T; Tan, Adelene Y; Joo, Woo S; Daniels, Garrett; Kussie, Paul; Karumanchi, S Ananth; Granger, Joey P

    2016-04-01

    Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and vascular endothelial growth factor are both natural ligands for sFlt-1, vascular endothelial growth factor also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to 4 groups: normal pregnant or RUPP±infusion of recombinant human PlGF (180 μg/kg per day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than normal pregnant rats. Infusion of recombinant human PlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that recombinant human PlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia.

  7. Elastase induces lung epithelial cell autophagy through placental growth factor

    Science.gov (United States)

    Hou, Hsin-Han; Cheng, Shih-Lung; Chung, Kuei-Pin; Kuo, Mark Yen-Ping; Yeh, Cheng-Chang; Chang, Bei-En; Lu, Hsuan-Hsuan; Wang, Hao-Chien; Yu, Chong-Jen

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a devastating disease, which is associated with increasing mortality and morbidity. Therefore, there is a need to clearly define the COPD pathogenic mechanism and to explore effective therapies. Previous studies indicated that cigarette smoke (CS) induces autophagy and apoptosis in lung epithelial (LE) cells. Excessive ELANE/HNE (elastase, neutrophil elastase), a factor involved in protease-antiprotease imbalance and the pathogenesis of COPD, causes LE cell apoptosis and upregulates the expression of several stimulus-responsive genes. However, whether or not elastase induces autophagy in LE cell remains unknown. The level of PGF (placental growth factor) is higher in COPD patients than non-COPD controls. We hypothesize that elastase induces PGF expression and causes autophagy in LE cells. In this study, we demonstrated that porcine pancreatic elastase (PPE) induced PGF expression and secretion in LE cells in vitro and in vivo. The activation of MAPK8/JNK1 (mitogen-activated protein kinase 8) and MAPK14/p38alpha MAPK signaling pathways was involved in the PGF mediated regulation of the TSC (tuberous sclerosis complex) pathway and autophagy in LE cells. Notably, PGF-induced MAPK8 and MAPK14 signaling pathways mediated the inactivation of MTOR (mechanistic target of rapamycin), the upregulation of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β) and the increase of autophagosome formation in mice. Furthermore, the PPE-induced autophagy promotes further apoptosis in vitro and in vivo. In summary, elastase-induced autophagy promotes LE cell apoptosis and pulmonary emphysema through the upregulation of PGF. PGF and its downstream MAPK8 and MAPK14 signaling pathways are potential therapeutic targets for the treatment of emphysema and COPD. PMID:24988221

  8. Light-Induced Local Heating for Thermophoretic Manipulation of DNA in Polymer Micro- and Nanochannels

    DEFF Research Database (Denmark)

    Thamdrup, Lasse Højlund; Larsen, Niels Bent; Kristensen, Anders

    2010-01-01

    We present a method for making polymer chips with a narrow-band near-infrared absorber layer that enables light-induced local heating of liquids inside fluidic micro- and nanochannels fabricated by thermal imprint in polymethyl methacrylate. We have characterized the resulting liquid temperature...

  9. On Characterizing the Local Pooling Factor of Greedy Maximal Scheduling in Random Graphs

    OpenAIRE

    Wildman, Jeffrey; Weber, Steven

    2014-01-01

    The study of the optimality of low-complexity greedy scheduling techniques in wireless communications networks is a very complex problem. The Local Pooling (LoP) factor provides a single-parameter means of expressing the achievable capacity region (and optimality) of one such scheme, greedy maximal scheduling (GMS). The exact LoP factor for an arbitrary network graph is generally difficult to obtain, but may be evaluated or bounded based on the network graph's particular structure. In this pa...

  10. Genome Scans for Detecting Footprints of Local Adaptation Using a Bayesian Factor Model

    Science.gov (United States)

    Duforet-Frebourg, Nicolas; Bazin, Eric; Blum, Michael G.B.

    2014-01-01

    There is a considerable impetus in population genomics to pinpoint loci involved in local adaptation. A powerful approach to find genomic regions subject to local adaptation is to genotype numerous molecular markers and look for outlier loci. One of the most common approaches for selection scans is based on statistics that measure population differentiation such as FST. However, there are important caveats with approaches related to FST because they require grouping individuals into populations and they additionally assume a particular model of population structure. Here, we implement a more flexible individual-based approach based on Bayesian factor models. Factor models capture population structure with latent variables called factors, which can describe clustering of individuals into populations or isolation-by-distance patterns. Using hierarchical Bayesian modeling, we both infer population structure and identify outlier loci that are candidates for local adaptation. In order to identify outlier loci, the hierarchical factor model searches for loci that are atypically related to population structure as measured by the latent factors. In a model of population divergence, we show that it can achieve a 2-fold or more reduction of false discovery rate compared with the software BayeScan or with an FST approach. We show that our software can handle large data sets by analyzing the single nucleotide polymorphisms of the Human Genome Diversity Project. The Bayesian factor model is implemented in the open-source PCAdapt software. PMID:24899666

  11. Investigation on a new local control technology with near-infrared spectroscopy for laser induced interstitial thermotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Hua Guoran; Zhang Hua; Qian Aiping; Qian Zhiyu, E-mail: nuaazhh@126.com, E-mail: ntuzhh@ntu.edu.cn [School of Mechanical Engineering, Nantong University, Nantong, Jiangsu 226019 (China)

    2011-02-01

    In order to control the treatment of laser-induced interstitial thermotherapy, a new local control technique is put forward, which use a functional near infrared spectroscopy (fNIRS) system. The temperature of biological tissue is regarded as the most important indicator for treatment of LITT. So, based on the experiments of LITT being performed on a liver cancer, the temperature and reducing scattering coefficient have been obtained in real time, respectively, with probe-type thermometer and fNIRS system. The results of the two factors have the same trend with different power of laser. It is confirmed that the fNIRS can be a useful local control technology for LITT.

  12. Spider diversity in cereal fields: comparing factors at local, landscape and regional scales

    NARCIS (Netherlands)

    Clough, Y.; Kruess, A.; Kleijn, D.; Tscharntke, T.

    2005-01-01

    Aim Factors acting at various scales may affect biodiversity, demanding analyses at multiple spatial scales in order to understand how community richness is determined. Here, we adopted a hierarchical approach to test the contribution of region, landscape heterogeneity, local management (organic vs.

  13. Sequential process in brain-derived neurotrophic factor-induced functional periodontal tissue regeneration.

    Science.gov (United States)

    Konishi, Akihiro; Takeda, Katsuhiro; Fujita, Tsuyoshi; Kajiya, Mikihito; Matsuda, Shinji; Kittaka, Mizuho; Shiba, Hideki; Kurihara, Hidemi

    2016-04-01

    We recently demonstrated that brain-derived neurotrophic factor (BDNF) promotes periodontal tissue regeneration. The purpose of this study was to establish an essential component of a rational approach for the clinical application of BDNF in periodontal regenerative therapy. Here, we assessed the sequence of early events in BDNF-induced periodontal tissue regeneration, especially from the aspect of cementum regeneration. Brain-derived neurotrophic factor was applied into experimental periodontal defects in Beagle dogs. The localization of cells positive for neurotrophic tyrosine kinase, receptor, type 2, proliferating cell nuclear antigen, osteopontin, integrin αVβ3, and integrin α2β1 was evaluated by immunohistochemistry. The effects of BDNF on adhesion of cultured human periodontal ligament cells was examined by an in vitro study. The results suggest that BDNF could induce rapid cementum regeneration by stimulating adhesion, proliferation, and differentiation of periodontal ligament cells in the early regenerative phase, resulting in enhancement of periodontal tissue regeneration.

  14. Evidence for a diffusible factor that induces susceptibility in the Colletotrichum-maize disease interaction.

    Science.gov (United States)

    Torres, Maria F; Cuadros, Diego F; Vaillancourt, Lisa J

    2014-01-01

    Colletotrichum graminicola, the causal agent of maize anthracnose, is a hemibiotrophic fungus that initially infects living host cells via primary hyphae surrounded by a membrane. A nonpathogenic mutant disrupted in a gene encoding a component of the signal peptidase complex, and believed to be deficient in protein processing and secretion, regained pathogenicity when it was inoculated onto maize leaf sheaths close to the wild-type fungus. Evidence is presented suggesting that the wild-type produces a diffusible factor(s) that induces the localized susceptibility of host cells at the borders of expanding colonies, causing them to become receptive to biotrophic invasion. The induced susceptibility effect is limited to a distance of approximately eight cells from the edge of the wild-type colony, is dosage dependent and is specific to C. graminicola. © 2013 BSPP AND JOHN WILEY & SONS LTD.

  15. Engineering Design Handbook: Environmental Series. Part Three. Induced Environmental Factors

    Science.gov (United States)

    1976-01-20

    3-18 3-12. Instruments for Sample Collection 9-19 3-13. Major Deserts of the World 3-20 3-14. Corrosion of Open- hearth Steel...lightning, but otherwise is overshadowed by artificial sources. Each of these induced environmental factors is also influenced greatly by natural...identification: 1. Open- hearth furnaces 2. Incineration 3. Cement plants 4. Fuel oil combustion 5. Coal combustion plus diffraction effects apply

  16. Vectorology and Factor Delivery in Induced Pluripotent Stem Cell Reprogramming

    OpenAIRE

    Hu, Kejin

    2014-01-01

    Induced pluripotent stem cell (iPSC) reprogramming requires sustained expression of multiple reprogramming factors for a limited period of time (10–30 days). Conventional iPSC reprogramming was achieved using lentiviral or simple retroviral vectors. Retroviral reprogramming has flaws of insertional mutagenesis, uncontrolled silencing, residual expression and re-activation of transgenes, and immunogenicity. To overcome these issues, various technologies were explored, including adenoviral vect...

  17. Local recurrence following lung cancer surgery: incidence, risk factors, and outcomes.

    Science.gov (United States)

    Fedor, David; Johnson, W Rainey; Singhal, Sunil

    2013-09-01

    To date, few large-scale original studies have focused specifically on local recurrence following curative lung cancer surgery. This review seeks to consolidate and analyze data from these studies regarding local recurrence incidence, risk factors, salvage treatments, and outcomes to increase awareness in the Oncology community and to spark new research in this area. PubMed literature was searched for large-scale cohort studies involving recurrence following lung cancer surgery. Studies with a primary focus on local recurrence and studies that examined overall recurrence but provided relevant numerical data on local recurrence were included. Each chosen study's methods were critically analyzed to reconcile as best as possible large differences in reported results across the studies. Up to 24% of patients recur locally following lung cancer surgery. Risk of local recurrence increases with the stage of the primary cancer, but even stage I patients experience local recurrence up to 19% of the time. Overall survival time following local recurrence varies widely across studies, from 7 to 26 months, and may be related to frequency of follow-up visits. Salvage therapy appears to increase survival time. However, estimates of this increase vary widely, and measurements of benefits of the various salvage options are confounded by lack of control of subjects' condition at the time of salvage therapy administration. Local recurrence following lung cancer surgery is a significant problem warranting additional research. At present, data on this topic is scarce. We recommend initiation of additional large-scale studies to clearly define the parameters of local recurrence in order to provide useful guidance to clinicians. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Clinical Aspects of Hypoxia-inducible Factors in Colorectal Cancer

    DEFF Research Database (Denmark)

    Havelund, Birgitte Mayland; Spindler, Karen-Lise Garm; Sørensen, Flemming Brandt;

    to a standardized scheme. 2. The prognostic value of HIF-1α is investigated by SNP analysis and HIF-1α expression in tissue from 300 patients operated for colorectal cancer and the results is validated in a prospectively population of 200 patients. 3. The predictive value of HIF-1α will be investigated in patients......Clinical Aspects of Hypoxia-inducible Factors in Colorectal Cancer   Birgitte Mayland Havelund1,4 MD, Karen-Lise Garm Spindler1,4 MD, PhD, Flemming Brandt Sørensen2,4 MD, DMSc, Ivan Brandslund3 MD, DMSc, Anders Jakobsen1,4 MD, DMSc. 1Department of Oncology, 2Pathology and 3Biochemistry, Vejle...... Hospital, Vejle, Denmark 4Institute of Regional Health Services Research, University of Southern Denmark, Odense Denmark Background Prognostic and predictive markers are needed for individualizing the treatment of colorectal cancer. Hypoxia-inducible factor 1α (HIF-1α) is a transcription-inducing factor...

  19. Interaction-Induced Characteristic Length in Strongly Many-Body Localized Systems

    CERN Document Server

    He, Rong-Qiang

    2016-01-01

    We propose a numerical method for explicitly constructing a complete set of local integrals of motion (LIOM) and definitely show the existence of LIOM for strongly many-body localized systems. The method starts with a complete set of maximally localized guessed LIOM, gradually deforms it into a complete set of true LIOM. By using this method we find that for strongly disordered and weakly interacting systems, there are two characteristic lengths in the LIOM. The first one is governed by disorder and is of Anderson-localization nature. The second one is induced by interaction but independent of the strength of interaction, showing a nonperturbative nature. We prove that the entanglement and correlation in any eigenstate extend not longer than twice the second length.

  20. Functional pathway mapping analysis for hypoxia-inducible factors.

    Science.gov (United States)

    Chuang, Chia-Sheng; Pai, Tun-Wen; Hu, Chin-Hua; Tzou, Wen-Shyong; Dah-Tsyr Chang, Margaret; Chang, Hao-Teng; Chen, Chih-Chia

    2011-06-20

    Hypoxia-inducible factors (HIFs) are transcription factors that play a crucial role in response to hypoxic stress in living organisms. The HIF pathway is activated by changes in cellular oxygen levels and has significant impacts on the regulation of gene expression patterns in cancer cells. Identifying functional conservation across species and discovering conserved regulatory motifs can facilitate the selection of reference species for empirical tests. This paper describes a cross-species functional pathway mapping strategy based on evidence of homologous relationships that employs matrix-based searching techniques for identifying transcription factor-binding sites on all retrieved HIF target genes. HIF-related orthologous and paralogous genes were mapped onto the conserved pathways to indicate functional conservation across species. Quantitatively measured HIF pathways are depicted in order to illustrate the extent of functional conservation. The results show that in spite of the evolutionary process of speciation, distantly related species may exhibit functional conservation owing to conservative pathways. The novel terms OrthRate and ParaRate are proposed to quantitatively indicate the flexibility of a homologous pathway and reveal the alternative regulation of functional genes. The developed functional pathway mapping strategy provides a bioinformatics approach for constructing biological pathways by highlighting the homologous relationships between various model species. The mapped HIF pathways were quantitatively illustrated and evaluated by statistically analyzing their conserved transcription factor-binding elements. hypoxia-inducible factor (HIF), hypoxia-response element (HRE), transcription factor (TF), transcription factor binding site (TFBS), KEGG (Kyoto Encyclopedia of Genes and Genomes), cross-species comparison, orthology, paralogy, functional pathway.

  1. How habitat area, local and regional factors shape plant assemblages in isolated closed depressions

    Science.gov (United States)

    Herault, Bruno; Thoen, Daniel

    2009-05-01

    Classifying species by shared life-history traits is important if common ecological response groups are to be identified among different species. We investigated how habitat area, local and regional factors shape plant communities in small isolated closed depressions, and how the species richness is related to the interplay between environmental factors and specific life-history trait combinations. In Central-Western Europe, 169 closed depressions were completely surveyed for plant presence in two highly contrasted landscapes (forested and open landscapes). All species were clustered into 9 Emergent Groups based on 10 life-history traits related to plant dispersal, establishment and persistence. Habitat areas were related to species presence using logistic regressions. Most Emergent Groups were more area-dependent in open than in forested landscapes, owing to heterogeneous light levels in forest weakening the species-area relationship. In open landscapes, Floating Hydrophytes were severely underrepresented in very small depressions, owing to the absence of waterfowl population. Local environmental and regional factors were related to species richness using Generalized Linear Models. In open landscapes, local environmental factors such as water conductivity or soil productivity are respectively the main predictors. In forested landscapes, the abundance of most Emergent Groups was better predicted by regional factors, i.e., habitat connectivity and distance to the forest edge. Forested landscapes strongly impeded the closed depressions' colonization by the less mobile Emergent Groups such as Large-seeded Perennials.

  2. Effects of brain-derived neurotrophic factor on local inflammation in experimental stroke of rat.

    Science.gov (United States)

    Jiang, Yongjun; Wei, Ning; Zhu, Juehua; Lu, Tingting; Chen, Zhaoyao; Xu, Gelin; Liu, Xinfeng

    2010-01-01

    This study was aimed to investigate whether brain-derived neurotrophic factor (BDNF) can modulate local cerebral inflammation in ischemic stroke. Rats were subjected to ischemia by occluding the right middle cerebral artery (MCAO) for 2 hours. Rats were randomized as control, BDNF, and antibody groups. The local inflammation was evaluated on cellular, cytokine, and transcription factor levels with immunofluorescence, enzyme-linked immunosorbent assay, real-time qPCR, and electrophoretic mobility shift assay, respectively. Exogenous BDNF significantly improved motor-sensory, sensorimotor function, and vestibulomotor function, while BDNF did not decrease the infarct volume. Exogenous BDNF increased the number of both activated and phagocytotic microglia in brain. BDNF upregulated interleukin10 and its mRNA expression, while downregulated tumor necrosis factor α and its mRNA expression. BDNF also increased DNA-binding activity of nuclear factor-kappa B. BDNF antibody, which blocked the activity of endogenous BDNF, showed the opposite effect of exogenous BDNF. Our data indicated that BDNF may modulate local inflammation in ischemic brain tissues on the cellular, cytokine, and transcription factor levels.

  3. Effects of Brain-Derived Neurotrophic Factor on Local Inflammation in Experimental Stroke of Rat

    Directory of Open Access Journals (Sweden)

    Yongjun Jiang

    2010-01-01

    Full Text Available This study was aimed to investigate whether brain-derived neurotrophic factor (BDNF can modulate local cerebral inflammation in ischemic stroke. Rats were subjected to ischemia by occluding the right middle cerebral artery (MCAO for 2 hours. Rats were randomized as control, BDNF, and antibody groups. The local inflammation was evaluated on cellular, cytokine, and transcription factor levels with immunofluorescence, enzyme-linked immunosorbent assay, real-time qPCR, and electrophoretic mobility shift assay, respectively. Exogenous BDNF significantly improved motor-sensory, sensorimotor function, and vestibulomotor function, while BDNF did not decrease the infarct volume. Exogenous BDNF increased the number of both activated and phagocytotic microglia in brain. BDNF upregulated interleukin10 and its mRNA expression, while downregulated tumor necrosis factor α and its mRNA expression. BDNF also increased DNA-binding activity of nuclear factor-kappa B. BDNF antibody, which blocked the activity of endogenous BDNF, showed the opposite effect of exogenous BDNF. Our data indicated that BDNF may modulate local inflammation in ischemic brain tissues on the cellular, cytokine, and transcription factor levels.

  4. Interaction between human monocytes and vascular smooth muscle cells induces vascular endothelial growth factor expression.

    Science.gov (United States)

    Hojo, Y; Ikeda, U; Maeda, Y; Takahashi, M; Takizawa, T; Okada, M; Funayama, H; Shimada, K

    2000-05-01

    The objective of this study was to investigate whether synthesis of vascular endothelial growth factor (VEGF), a major mitogen for vascular endothelial cells, was induced by a cell-to-cell interaction between monocytes and vascular smooth muscle cells (VSMCs). Human VSMCs and THP-1 cells (human monocytoid cell) were cocultured. VEGF levels in the coculture medium were determined by enzyme-linked immunosorbent assay. Northern blot analysis of VEGF mRNA was performed using a specific cDNA probe. Immunohistochemistry was performed to determine which types of cell produce VEGF. Adding THP-1 cells to VSMCs for 24 h increased VEGF levels of the culture media, 8- and 10-fold relative to those of THP-1 cells and VSMCs alone, respectively. Northern blot analysis showed that VEGF mRNA expression was induced in the cocultured cells and peaked after 12 h. Immunohistochemistry disclosed that both types of cell in the coculture produced VEGF. Separate coculture experiments revealed that both direct contact and a soluble factor(s) contributed to VEGF production. Neutralizing anti-interleukin (IL)-6 antibody inhibited VEGF production by the coculture of THP-1 cells and VSMCs. A cell-to-cell interaction between monocytes and VSMCs induced VEGF synthesis in both types of cell. An IL-6 mediated mechanism is at least partially involved in VEGF production by the cocultures. Local VEGF production induced by a monocyte-VSMC interaction may play an important role in atherosclerosis and vascular remodeling.

  5. Retinoic acid exerts dual regulatory actions on the expression and nuclear localization of interferon regulatory factor-1.

    Science.gov (United States)

    Luo, Xin M; Ross, A Catharine

    2006-05-01

    Interferon regulatory factor-1 (IRF-1), a transcription factor and tumor suppressor involved in cell growth regulation and immune responses, has been shown to be induced by all-trans retinoic acid (ATRA). However, the factors controlling the cellular location and activity of IRF-1 are not well understood. In this study, we examined the expression of IRF-1 and its nuclear localization, DNA-binding activity, and target gene expression in human mammary epithelial MCF10A cells, a model of breast epithelial cell differentiation and carcinogenesis. Following initial treatment with ATRA, IRF-1 mRNA and protein were induced within 2 hrs, reached a peak (>30-fold induction) at 8 hrs, and declined afterwards. IRF-1 protein was predominantly cytoplasmic during this treatment. Although a second dose of ATRA or Am580 (a related retinoid selective for retinoic acid receptor-alpha [RARalpha]), given 16 hrs after the first dose, restimulated IRF-1 mRNA and protein levels to a similar level to that obtained by the first dose, IRF-1 was predominantly concentrated in the nucleus after restimulation. ATRA and Am580 also increased nuclear RARalpha, whereas retinoid X receptor-alpha (RXRalpha)--a dimerization partner for RARalpha, was localized to the nucleus upon second exposure to ATRA. However, ATRA and Am580 did not regulate the expression or activation of signal transducer and activator of transcription-1 (STAT-1), a transcription factor capable of inducing the expression of IRF-1, indicating an STAT-1-independent mechanism of regulation by ATRA and Am580. The increase in nuclear IRF-1 after retinoid restimulation was accompanied by enhanced binding to an IRF-E DNA response element, and elevated expression of an IRF-1 target gene, 2',5'-oligoadenylate synthetase-2. The dual effect of retinoids in increasing IRF-1 mRNA and protein and in augmenting the nuclear localization of IRF-1 protein may be essential for maximizing the tumor suppressor activity and the immunosurveillance

  6. Differential localization of P-selectin and von Willebrand factor during megakaryocyte maturation

    DEFF Research Database (Denmark)

    Zingariello, M; Fabucci, M E; Bosco, D;

    2010-01-01

    An important step in megakaryocyte maturation is the appropriate assembly of at least two distinct subsets of alpha-granules. The mechanism that sorts the alpha-granule components into distinct structures and mediates their release in response to specific stimuli is now emerging. P-selectin and von...... Willebrand factor are two proteins present in the alpha-granules that recognize P-selectin glycoprotein ligand on neutrophils and collagen in the subendothelial matrix. These proteins may play an important role in determining the differential release of the alpha-granule contents in response to external...... stimuli. If P-selectin and von Willebrand factor are localized in the same or different alpha-granules is not known. To clarify this question, we analyzed by immunoelectron microscopy the localization of von Willebrand factor and P-selectin during the maturation of wild-type and Gata1(low) megakaryocytes...

  7. Factors of Innate and Adaptive Local Immunity in Children with Primary Deficiencies of Antibody Formation

    Directory of Open Access Journals (Sweden)

    L.I. Chernyshova

    2013-11-01

    Full Text Available In 40 children with various types of primary immunodeficiencies (PID of antibody formation we examined factors of local immunity in saliva. It is found that in the saliva of children with PID of antibody formation in comparison with immunocompetent children the concentration of factors of adaptive immunity is significantly reduced. Lack of adaptive immunity in the PID of antibody formation to some extent is compensated by increased concentrations of innate immune factors on the mucous membranes — the free Sc, as well as lactoferrin in selective immunodeficiency of IgA. At PID of antibody formation we observed increased TNF-α level in the saliva, which may indicate the persistence of local inflammation on the membranes of the respiratory tract.

  8. Role of myeloid growth factors in chemotherapy induced neutropenia

    Directory of Open Access Journals (Sweden)

    Ravinutala Srinath Bharadwaj

    2016-10-01

    Full Text Available Neutropenia is a major dose limiting toxicity of many chemo therapeutic regimens. Haemopoietic colony - stimulating factors (CSFs have been shown to reduce the duration and severity of chemotherapy induced neutropenia (CIN and risk of febrile neutropenia. Supportive care with myeloid growth factors improve chemotherapy delivery by minimizing chemotherapy dose reductions or treatment delays by enabling the delivery of full dose chemotherapy (dose dense in short time intervals. The goal of this article is to give comprehensive review of current literature regarding medical practice guidelines and risk assessment models for appropriate use of myeloid growth factors and management of febrile neutropenia. [Int J Basic Clin Pharmacol 2016; 5(5.000: 1715-1721

  9. Aqueous Leaf Extract of Jatropha mollissima (Pohl) Bail Decreases Local Effects Induced by Bothropic Venom

    Science.gov (United States)

    Gomes, Jacyra Antunes dos Santos; Geraldo Amaral, Juliano; Lopes, Norberto Peporine; Tabosa do Egito, Eryvaldo Sócrates; da Silva-Júnior, Arnóbio Antônio; Maria Zucolotto, Silvana

    2016-01-01

    Snakebites are a serious worldwide public health problem. In Brazil, about 90% of accidents are attributed to snakes from the Bothrops genus. The specific treatment consists of antivenom serum therapy, which has some limitations such as inability to neutralize local effects, difficult access in some regions, risk of immunological reactions, and high cost. Thus, the search for alternative therapies to treat snakebites is relevant. Jatropha mollissima (Euphorbiaceae) is a medicinal plant popularly used in folk medicine as an antiophidic remedy. Therefore, this study aims to evaluate the effect of the aqueous leaf extract from J. mollissima on local effects induced by Bothrops venoms. High Performance Liquid Chromatography with Diode Array Detection analysis and Mass Spectrometry analysis of aqueous leaf extract confirmed the presence of the flavonoids isoschaftoside, schaftoside, isoorientin, orientin, vitexin, and isovitexin. This extract, at 50–200 mg/kg doses administered by intraperitoneal route, showed significant inhibitory potential against local effects induced by Bothrops erythromelas and Bothrops jararaca snake venoms. Local skin hemorrhage, local edema, leukocyte migration, and myotoxicity were significantly inhibited by the extract. These results demonstrate that J. mollissima extract possesses inhibitory potential, especially against bothropic venoms, suggesting its potential as an adjuvant in treatment of snakebites. PMID:27847818

  10. Aqueous Leaf Extract of Jatropha mollissima (Pohl Bail Decreases Local Effects Induced by Bothropic Venom

    Directory of Open Access Journals (Sweden)

    Jacyra Antunes dos Santos Gomes

    2016-01-01

    Full Text Available Snakebites are a serious worldwide public health problem. In Brazil, about 90% of accidents are attributed to snakes from the Bothrops genus. The specific treatment consists of antivenom serum therapy, which has some limitations such as inability to neutralize local effects, difficult access in some regions, risk of immunological reactions, and high cost. Thus, the search for alternative therapies to treat snakebites is relevant. Jatropha mollissima (Euphorbiaceae is a medicinal plant popularly used in folk medicine as an antiophidic remedy. Therefore, this study aims to evaluate the effect of the aqueous leaf extract from J. mollissima on local effects induced by Bothrops venoms. High Performance Liquid Chromatography with Diode Array Detection analysis and Mass Spectrometry analysis of aqueous leaf extract confirmed the presence of the flavonoids isoschaftoside, schaftoside, isoorientin, orientin, vitexin, and isovitexin. This extract, at 50–200 mg/kg doses administered by intraperitoneal route, showed significant inhibitory potential against local effects induced by Bothrops erythromelas and Bothrops jararaca snake venoms. Local skin hemorrhage, local edema, leukocyte migration, and myotoxicity were significantly inhibited by the extract. These results demonstrate that J. mollissima extract possesses inhibitory potential, especially against bothropic venoms, suggesting its potential as an adjuvant in treatment of snakebites.

  11. The inhibitory effect of locally injected dexmedetomidine on carrageenan-induced nociception in rats.

    Science.gov (United States)

    Honda, Yuka; Higuchi, Hitoshi; Matsuoka, Yoshikazu; Yabuki-Kawase, Akiko; Ishii-Maruhama, Minako; Tomoyasu, Yumiko; Maeda, Shigeru; Morimatsu, Hiroshi; Miyawaki, Takuya

    2015-10-05

    Recent studies showed that the administration of dexmedetomidine relieved hyperalgesia in the presence of neuropathic pain. These findings have led to the hypothesis that the local administration of dexmedetomidine is useful for relieving acute inflammatory nociception, such as postoperative pain. Thus, we evaluated the inhibitory effect of locally injected dexmedetomidine on acute inflammatory nociception. Acute inflammatory nociception was induced by an intraplantar injection of 1% carrageenan into the hindpaws of rats, and dexmedetomidine was also injected combined with carrageenan. The paw withdrawal threshold based on von Frey filament stimulation was measured until 12 h after injection. We compared the area under the time-curve (AUC) between carrageenan and carrageenan with dexmedetomidine. To clarify that the action of dexmedetomidine was via α2-adrenoceptors, we evaluated the effect of yohimbine, a selective antagonist of α2-adrenoceptors, on the anti-nociception of dexmedetomidine. As the results, the intraplantar injection of carrageenan with over 10 μM dexmedetomidine significantly increased AUC, compared to that with only carrageenan injection. This effect of dexmedetomidine was reversed by the addition of yohimbine to carrageenan and dexmedetomidine. These results demonstrated that the locally injected dexmedetomidine was effective against carrageenan-induced inflammatory nociception via α2-adrenoceptors. The findings suggest that the local injection of dexmedetomidine is useful for relieving local acute inflammatory nociception.

  12. TMS-induced cortical potentiation during wakefulness locally increases slow wave activity during sleep.

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    Reto Huber

    Full Text Available BACKGROUND: Sleep slow wave activity (SWA is thought to reflect sleep need, increasing in proportion to the length of prior wakefulness and decreasing during sleep. However, the process responsible for SWA regulation is not known. We showed recently that SWA increases locally after a learning task involving a circumscribed brain region, suggesting that SWA may reflect plastic changes triggered by learning. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis directly, we used transcranial magnetic stimulation (TMS in conjunction with high-density EEG in humans. We show that 5-Hz TMS applied to motor cortex induces a localized potentiation of TMS-evoked cortical EEG responses. We then show that, in the sleep episode following 5-Hz TMS, SWA increases markedly (+39.1+/-17.4%, p<0.01, n = 10. Electrode coregistration with magnetic resonance images localized the increase in SWA to the same premotor site as the maximum TMS-induced potentiation during wakefulness. Moreover, the magnitude of potentiation during wakefulness predicts the local increase in SWA during sleep. CONCLUSIONS/SIGNIFICANCE: These results provide direct evidence for a link between plastic changes and the local regulation of sleep need.

  13. Movement Induces the Use of External Spatial Coordinates for Tactile Localization in Congenitally Blind Humans.

    Science.gov (United States)

    Heed, Tobias; Möller, Johanna; Röder, Brigitte

    2015-01-01

    To localize touch, the brain integrates spatial information coded in anatomically based and external spatial reference frames. Sighted humans, by default, use both reference frames in tactile localization. In contrast, congenitally blind individuals have been reported to rely exclusively on anatomical coordinates, suggesting a crucial role of the visual system for tactile spatial processing. We tested whether the use of external spatial information in touch can, alternatively, be induced by a movement context. Sighted and congenitally blind humans performed a tactile temporal order judgment task that indexes the use of external coordinates for tactile localization, while they executed bimanual arm movements with uncrossed and crossed start and end postures. In the sighted, start posture and planned end posture of the arm movement modulated tactile localization for stimuli presented before and during movement, indicating automatic, external recoding of touch. Contrary to previous findings, tactile localization of congenitally blind participants, too, was affected by external coordinates, though only for stimuli presented before movement start. Furthermore, only the movement's start posture, but not the planned end posture affected blind individuals' tactile performance. Thus, integration of external coordinates in touch is established without vision, though more selectively than when vision has developed normally, and possibly restricted to movement contexts. The lack of modulation by the planned posture in congenitally blind participants suggests that external coordinates in this group are not mediated by motor efference copy. Instead the task-related frequent posture changes, that is, movement consequences rather than planning, appear to have induced their use of external coordinates.

  14. Tumor producing fibroblast growth factor 23 localized by two-staged venous sampling.

    NARCIS (Netherlands)

    Boekel, G.A.J van; Ruinemans-Koerts, J.; Joosten, F.; Dijkhuizen, P.; Sorge, A van; Boer, H de

    2008-01-01

    BACKGROUND: Tumor-induced osteomalacia is a rare paraneoplastic syndrome characterized by hypophosphatemia, renal phosphate wasting, suppressed 1,25-dihydroxyvitamin D production, and osteomalacia. It is caused by a usually benign mesenchymal tumor producing fibroblast growth factor 23 (FGF-23). Sur

  15. Diabetic Foot Ulcers and Epidermal Growth Factor: Revisiting the Local Delivery Route for a Successful Outcome

    Directory of Open Access Journals (Sweden)

    Jorge Berlanga-Acosta

    2017-01-01

    Full Text Available Soon after epidermal growth factor (EGF discovery, some in vivo models appeared demonstrating its property to enhance cutaneous wound healing. EGF was the first growth factor (GF introduced in the clinical arena as a healing enhancer, exerting its mitogenic effects on epithelial, fibroblastoid, and endothelial cells via a tyrosine kinase membrane receptor. Compelling evidences from the 90s documented that, for EGF, locally prolonged bioavailability and hourly interaction with the receptor were necessary for a successful tissue response. Eventually, the enthusiasm on the clinical use of EGF to steer the healing process was wiped out as the topical route to deliver proteins started to be questioned. The simultaneous in vivo experiments, emphasizing the impact of the parenterally administered EGF on epithelial and nonepithelial organs in terms of mitogenesis and cytoprotection, rendered the theoretical fundamentals for the injectable use of EGF and shaped the hypothesis that locally infiltrating the diabetic ulcers would lead to an effective healing. Although the diabetic chronic wounds microenvironment is hostile for local GFs bioavailability, EGF local infiltration circumvented the limitations of its topical application, thus expanding its therapeutic prospect. Our clinical pharmacovigilance and basic studies attest the significance of the GF local infiltration for chronic wounds healing.

  16. The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; Maldonado, Carola; Adasme, Tatiana; Carrasco, Loreto; Ocaranza, Paula; Bravo, Roberto; Gonzalez, Leticia; Diaz-Araya, Guillermo [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Hidalgo, Cecilia [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Lavandero, Sergio, E-mail: slavander@uchile.cl [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile)

    2009-10-09

    Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal {alpha}-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

  17. Effect of a Local Reinforcement on the Stress Intensity Factor of a Cracked Plate

    Institute of Scientific and Technical Information of China (English)

    JIANGCui-xiang; ZHA0Yao; LIUTu-guang

    2004-01-01

    Stress intensity factors are calculated for a cracked plate reinforced locally subject to mode I loading.The stiffeners are considered to have both longitudinal and transverse stiffness.There is no relative displacement between the plate and the stiffener.It is considered that the shear stresses are lumped at a finite number of locations,the result is obtained by summation.The influence of the stiffener location and the stiffener relative stiffness on cracked plate is included.The stress intensity factor depends on all these factors.Case study shows that the shear stress acting parallel to the stiffener gives more effect on the stress intensity factor than the shear stress acting perpendicular to the stiffener.To increase the relative stiffness of stiffener avails to reduce the stress intensity factor of the cracked plate.

  18. Sub-Half-Wavelength Atom Localization Based on Phase-Dependent Electromagnetically Induced Transparency

    Institute of Scientific and Technical Information of China (English)

    GONG cheng; HU Xiang-Ming; PENG Yan-Dong

    2008-01-01

    We present a realistic and efficient scheme for sub-half-wavelength atom localization.This scheme is based on the phase-dependent elecaromagnetically induced transparency in a four-level system in the double-Λ configuration.We use a strong bichromatic field(one component of which is standing-wave field)as the driving components,and a weak bichromatic field as the probe components.By choosing the collective phase of the four applied components,the atom js localized in either of the two half-wavelength regions with 50% detecting probability when the absorption to the probe fields is detected.

  19. Noscapine induces apoptosis in human glioma cells by an apoptosis-inducing factor-dependent pathway.

    Science.gov (United States)

    Newcomb, Elizabeth W; Lukyanov, Yevgeniy; Smirnova, Iva; Schnee, Tona; Zagzag, David

    2008-07-01

    Previously, we identified noscapine as a small molecule inhibitor of the hypoxia-inducible factor-1 pathway in hypoxic human glioma cells and human umbilical vein endothelial cells. Noscapine is a nontoxic ingredient in cough medicine currently used in clinical trials for patients with non-Hodgkin's lymphoma or chronic lymphocytic leukemia to assess antitumor efficacy. Here, we have evaluated the sensitivity of four human glioma cell lines to noscapine-induced apoptosis. Noscapine was a potent inhibitor of proliferation and inducer of apoptosis. Induction of apoptosis was associated with activation of the c-jun N-terminal kinase signaling pathway concomitant with inactivation of the extracellular signal regulated kinase signaling pathway and phosphorylation of the antiapoptotic protein Bcl-2. Noscapine-induced apoptosis was associated with the release of mitochondrial proteins apoptosis-inducing factor (AIF) and/or cytochrome c. In some glioma cell lines, only AIF release occurred without cytochrome c release or poly (ADP-ribose) polymerase cleavage. Knock-down of AIF decreased noscapine-induced apoptosis. Our results suggest the potential importance of noscapine as a novel agent for use in patients with glioblastoma owing to its low toxicity profile and its potent anticancer activity.

  20. In Vivo Imaging of Local Gene Expression Induced by Magnetic Hyperthermia

    Science.gov (United States)

    Sandre, Olivier; Genevois, Coralie; Garaio, Eneko; Adumeau, Laurent; Mornet, Stéphane; Couillaud, Franck

    2017-01-01

    The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and noninvasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter. Iron oxide nanoparticles dispersions were applied topically on the mouse skin or injected subcutaneously with Matrigel™ to generate so-called pseudotumors. Temperature was monitored continuously with a feedback loop to control the power of the magnetic field generator and to avoid overheating. Thermo-induced luciferase expression was followed by bioluminescence imaging 6 h after heating. We showed that dextran-coated magnetic iron oxide nanoparticle dispersions were able to induce in vivo mild hyperthermia compatible with thermo-induced gene expression in surrounding tissues and without impairing cell viability. These data open new therapeutic perspectives for using mild magnetic hyperthermia as noninvasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release. PMID:28208731

  1. In Vivo Imaging of Local Gene Expression Induced by Magnetic Hyperthermia

    Directory of Open Access Journals (Sweden)

    Olivier Sandre

    2017-02-01

    Full Text Available The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and noninvasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter. Iron oxide nanoparticles dispersions were applied topically on the mouse skin or injected subcutaneously with Matrigel™ to generate so-called pseudotumors. Temperature was monitored continuously with a feedback loop to control the power of the magnetic field generator and to avoid overheating. Thermo-induced luciferase expression was followed by bioluminescence imaging 6 h after heating. We showed that dextran-coated magnetic iron oxide nanoparticle dispersions were able to induce in vivo mild hyperthermia compatible with thermo-induced gene expression in surrounding tissues and without impairing cell viability. These data open new therapeutic perspectives for using mild magnetic hyperthermia as noninvasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release.

  2. Endothelin-1 induces connective tissue growth factor expression in cardiomyocytes.

    Science.gov (United States)

    Recchia, Anna Grazia; Filice, Elisabetta; Pellegrino, Daniela; Dobrina, Aldo; Cerra, Maria Carmela; Maggiolini, Marcello

    2009-03-01

    Endothelin (ET)-1 is a vasoconstrictor involved in cardiovascular diseases. Connective tissue growth factor/CCN2 (CTGF) is a fibrotic mediator overexpressed in human atherosclerotic lesions, myocardial infarction, and hypertension. In different cell types CTGF regulates cell proliferation/apoptosis, migration, and extracellular matrix (ECM) accumulation and plays important roles in angiogenesis, chondrogenesis, osteogenesis, tissue repair, cancer and fibrosis. In the present study, we investigated the ET-1 signaling which triggers CTGF expression in cultured adult mouse atrial-muscle HL-1 cells used as a model system. ET-1 activated the CTGF promoter and induced CTGF expression at both mRNA and protein levels. Real-time PCR analysis revealed CTGF induction also in isolated rat heart preparations perfused with ET-1. Several intracellular signals elicited by ET-1 via ET receptors and even Epidermal Growth Factor Receptor (EGFR) contributed to the up-regulation of CTGF, including ERK activation and induction of the AP-1 components c-fos and c-jun, as also evaluated by ChIP analysis. Moreover, in cells treated with ET-1 the expression of ECM component decorin was abolished by CTGF silencing, indicating that CTGF is involved in ET-1 induced ECM accumulation not only in a direct manner but also through downstream effectors. Collectively, our data indicate that CTGF could be a mediator of the profibrotic effects of ET-1 in cardiomyocytes. CTGF inhibitors should be considered in setting a comprehensive pharmacological approach towards ET-1 induced cardiovascular diseases.

  3. Factors Associated with Incidence of Induced Abortion in Hamedan, Iran.

    Science.gov (United States)

    Hosseini, Hatam; Erfani, Amir; Nojomi, Marzieh

    2017-05-01

    There is limited reliable information on abortion in Iran, where abortion is illegal and many women of reproductive age seek clandestine abortion to end their unintended pregnancy. This study aims to examine the determinants of induced abortion in the city of Hamedan, Iran. The study utilizes recent data from the 2015 Hamedan Survey of Fertility, conducted in a representative sample of 3,000 married women aged 15-49 years in the city of Hamedan, Iran. Binary logistic regression models are used to examine factors associated with the incidence of abortion. Overall, 3.8% of respondents reported having had an induced abortion in their life. Multivariate results showed that the incidence of abortion was strongly associated with women's education, type of contraceptive and family income level, after controlling for confounding factors. Women using long-acting contraceptive methods, those educated under high school diploma or postsecondary education, and those with high level of income were more likely to report having an induced abortion. The high incidence of abortion among less or more educated women and those with high income level signifies unmet family planning needs among these women, which must be addressed by focused reproductive health and family planning programs.

  4. Non-local dynamics governing the self-induced motion of a planar vortex filament

    Science.gov (United States)

    Van Gorder, Robert A.

    2015-06-01

    While the Hasimoto planar vortex filament is one of the few exact solutions to the local induction approximation (LIA) approximating the self-induced motion of a vortex filament, it is natural to wonder whether such a vortex filament solution would exist for the non-local Biot-Savart dynamics exactly governing the filament motion, and if so, whether the non-local effects would drastically modify the solution properties. Both helical vortex filaments and vortex rings are known to exist under both the LIA and non-local Biot-Savart dynamics; however, the planar filament is a bit more complicated. In the present paper, we demonstrate that a planar vortex filament solution does exist for the non-local Biot-Savart formulation, provided that a specific non-linear integral equation (governing the spatial structure of such a filament) has a non-trivial solution. By using the Poincaré-Lindstedt method, we are able to obtain an accurate analytical approximation to the solution of this integral equation under physically reasonable assumptions. To obtain these solutions, we approximate local effects near the singularity of the integral equation using the LIA and non-local effects using the Biot-Savart formulation. Mathematically, the results constitute an analytical solution to an interesting nonlinear singular integro-differential equation in space and time variables. Physically, these results show that planar vortex filaments exist and maintain their forms under the non-local Biot-Savart formulation, as one would hope. Due to the regularization approach utilized, we are able to compare the structure of the planar filaments obtained under both LIA and Biot-Savart formulations in a rather straightforward manner, in order to determine the role of the non-locality on the structure of the planar filament.

  5. Demarcation of local neighborhoods to study relations between contextual factors and health

    Directory of Open Access Journals (Sweden)

    Chor Dora

    2010-06-01

    Full Text Available Abstract Background Several studies have highlighted the importance of collective social factors for population health. One of the major challenges is an adequate definition of the spatial units of analysis which present properties potentially related to the target outcomes. Political and administrative divisions of urban areas are the most commonly used definition, although they suffer limitations in their ability to fully express the neighborhoods as social and spatial units. Objective This study presents a proposal for defining the boundaries of local neighborhoods in Rio de Janeiro city. Local neighborhoods are constructed by means of aggregation of contiguous census tracts which are homogeneous regarding socioeconomic indicators. Methodology Local neighborhoods were created using the SKATER method (TerraView software. Criteria used for socioeconomic homogeneity were based on four census tract indicators (income, education, persons per household, and percentage of population in the 0-4-year age bracket considering a minimum population of 5,000 people living in each local neighborhood. The process took into account the geographic boundaries between administrative neighborhoods (a political-administrative division larger than a local neighborhood, but smaller than a borough and natural geographic barriers. Results The original 8,145 census tracts were collapsed into 794 local neighborhoods, distributed along 158 administrative neighborhoods. Local neighborhoods contained a mean of 10 census tracts, and there were an average of five local neighborhoods per administrative neighborhood. The local neighborhood units demarcated in this study are less socioeconomically heterogeneous than the administrative neighborhoods and provide a means for decreasing the well-known statistical variability of indicators based on census tracts. The local neighborhoods were able to distinguish between different areas within administrative neighborhoods

  6. BMP2-induced inflammation can be suppressed by the osteoinductive growth factor NELL-1.

    Science.gov (United States)

    Shen, Jia; James, Aaron W; Zara, Janette N; Asatrian, Greg; Khadarian, Kevork; Zhang, James B; Ho, Stephanie; Kim, Hyun Ju; Ting, Kang; Soo, Chia

    2013-11-01

    Bone-morphogenetic protein 2 (BMP2) is currently the only Food and Drug Administration-approved osteoinductive growth factor used in clinical settings for bone regeneration and repair. However, the use of BMP2 is encumbered by numerous clinical complications, including postoperative inflammation and life-threatening cervical swelling. Thus, methods to prevent BMP2-induced inflammation would have far-reaching clinical implications toward improving current BMP2-based methods for bone regeneration. For the first time, we investigate the potential role of the growth factor Nel-like molecule-1 (NELL-1) in inhibiting BMP2-induced inflammation. Adult rats underwent a femoral bone onlay procedure, treated with either BMP2 protein (4 mg/mL), NELL-1 protein (4 mg/mL), or both proteins combined. Animals were evaluated at 3, 7, and 14 days postoperatively by histology, histomorphometry, immunohistochemistry, and real-time PCR for markers of inflammation (TNFα, IL6). The relative levels of TNFα and IL6 in serum were also detected by ELISA. The mechanism for NELL-1's anti-inflammatory effect was further assessed through examining inflammatory markers and generation of reactive oxygen species (ROS) in the mouse embryonic fibroblast NIH3T3 cells. BMP2 significantly induced local inflammation, including an early and pronounced polymorphonuclear cell infiltration accompanied by increased expression of TNFα and IL6. Treatment with NELL-1 alone elicited no significant inflammatory response. However, NELL-1 significantly attenuated BMP2-induced inflammation by all markers and at all timepoints. These local findings were also confirmed using systemic serum inflammatory biomarkers (TNFα, IL6). In each case, NELL-1 fully reversed BMP2-induced systemic inflammation. Lastly, our findings were recapitulated in vitro, where NELL-1 suppressed BMP2 induced expression of inflammatory markers, as well as NF-κB transcriptional activity and generation of ROS. BMP2-induced inflammation is a

  7. Measurement of the profiles of disorder-induced localized resonances in photonic crystal waveguides by local tuning

    NARCIS (Netherlands)

    Lian, J.; Sokolov, S.; Yuce, E.; Combrie, S.; Rossi, de A.; Mosk, A.P.

    2016-01-01

    Near the band edge of photonic crystal waveguides, localized modes appear due to disorder. We demonstrate a new method to elucidate spatial profile of the localized modes in such systems using precise local tuning. Using deconvolution with the known thermal profile, the spatial profile of a localize

  8. Genetic risk factors of cisplatin induced ototoxicity in adult patients.

    Science.gov (United States)

    Talach, T; Rottenberg, J; Gal, B; Kostrica, R; Jurajda, M; Kocak, I; Lakomy, R; Vogazianos, E

    2016-01-01

    Ototoxicity is an important adverse effect of using Cisplatin (cis-diamminedichloroplatinum) (CDDP) as a form of chemotherapy. The clinical picture of CDDP induced ototoxicity includes perceptive hearing impairment (reversible or permanent) and tinnitus. Ototoxicity manifests with considerable variability between patients. The objective of this prospective study was to investigate a possible genetic background to this variability. We assessed ototoxicity induced by therapeutic doses of CDDP in adult patients with germinative testicular tumors, or other tumors treated with an identical CDDP dosage scheme. Audiological examination before, during and after the treatment has shown deterioration in hearing; first in the high-frequencies and with increased CDDP cumulative doses, impairment in other frequencies as well. Occurrence of tinnitus was not dependent on the administered dose of CDDP, or the other risk factors examined in this study. The association of CDDP induced ototoxicity with genetic polymorphisms in candidate genes was examined. Our study has demonstrated an association of early onset of CDDP induced ototoxicity with the presence of two copies of GSTT1 gene (p=0,009) and with T allele of rs9332377 polymorphism in COMT gene (p=0,001).

  9. Large eddies induced by local impulse at wall of boundary layer with pressure gradients

    Institute of Scientific and Technical Information of China (English)

    Changgen Lu; Weidong Cao; Yanmei Zhang; Jintao Peng

    2008-01-01

    Large eddies induced by local impulse at the wall with pressure gradients in the boundary layer was studied by direct numerical sim-ulations. The results show that the amplitude evolution, the high and low speed stripes, the formation of streamwise vortices, the ejection and sweeping, inflexions and distortion at the mean velocity profiles, as well as other characteristics, are consistent with the experimental and other numerical results. It is also found that large eddies are easy to be excited with adverse pressure gradient in the boundary layer,and the growth of amplitudes, formation of streamwise vortices and the influencing area etc., are much larger than those with favorable pressure gradient in the boundary layer. In contrast, large eddies are hardly to be induced through local impulse disturbance at the wall with favorable pressure gradients in the boundary layer.

  10. Lipid Emulsions Enhance the Norepinephrine-Mediated Reversal of Local Anesthetic-Induced Vasodilation at Toxic Doses

    Science.gov (United States)

    Lee, Soo Hee; Sung, Hui-Jin; Ok, Seong-Ho; Yu, Jongsun; Choi, Mun-Jeoung; Lim, Jin Soo

    2013-01-01

    Purpose Intravenous lipid emulsions have been used to treat the systemic toxicity of local anesthetics. The goal of this in vitro study was to examine the effects of lipid emulsions on the norepinephrine-mediated reversal of vasodilation induced by high doses of levobupivacaine, ropivacaine, and mepivacaine in isolated endothelium-denuded rat aorta, and to determine whether such effects are associated with the lipid solubility of local anesthetics. Materials and Methods The effects of lipid emulsions (0.30, 0.49, 1.40, and 2.61%) on norepinephrine concentration-responses in high-dose local anesthetic (6×10-4 M levobupivacaine, 2×10-3 M ropivacaine, and 7×10-3 M mepivacaine)-induced vasodilation of isolated aorta precontracted with 60 mM KCl were assessed. The effects of lipid emulsions on local anesthetic- and diltiazem-induced vasodilation in isolated aorta precontracted with phenylephrine were also assessed. Results Lipid emulsions (0.30%) enhanced norepinephrine-induced contraction in levobupivacaine-induced vasodilation, whereas 1.40 and 2.61% lipid emulsions enhanced norepinephrine-induced contraction in both ropivacaine- and mepivacaine-induced vasodilation, respectively. Lipid emulsions (0.20, 0.49 and 1.40%) inhibited vasodilation induced by levobupivacaine and ropivacaine, whereas 1.40 and 2.61% lipid emulsions slightly attenuated mepivacaine (3×10-3 M)-induced vasodilation. In addition, lipid emulsions attenuated diltiazem-induced vasodilation. Lipid emulsions enhanced norepinephrine-induced contraction in endothelium-denuded aorta without pretreatment with local anesthetics. Conclusion Taken together, these results suggest that lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic anesthetic doses and inhibit local anesthetic-induced vasodilation in a manner correlated with the lipid solubility of a particular local anesthetic. PMID:24142661

  11. Viral Carcinogenesis: Factors Inducing DNA Damage and Virus Integration

    Directory of Open Access Journals (Sweden)

    Yan Chen

    2014-10-01

    Full Text Available Viruses are the causative agents of 10%–15% of human cancers worldwide. The most common outcome for virus-induced reprogramming is genomic instability, including accumulation of mutations, aberrations and DNA damage. Although each virus has its own specific mechanism for promoting carcinogenesis, the majority of DNA oncogenic viruses encode oncogenes that transform infected cells, frequently by targeting p53 and pRB. In addition, integration of viral DNA into the human genome can also play an important role in promoting tumor development for several viruses, including HBV and HPV. Because viral integration requires the breakage of both the viral and the host DNA, the integration rate is believed to be linked to the levels of DNA damage. DNA damage can be caused by both endogenous and exogenous factors, including inflammation induced by either the virus itself or by co-infections with other agents, environmental agents and other factors. Typically, cancer develops years to decades following the initial infection. A better understanding of virus-mediated carcinogenesis, the networking of pathways involved in transformation and the relevant risk factors, particularly in those cases where tumorigenesis proceeds by way of virus integration, will help to suggest prophylactic and therapeutic strategies to reduce the risk of virus-mediated cancer.

  12. A Novel Endometriosis Inducing Factor In Women with Endometriosis

    Directory of Open Access Journals (Sweden)

    Ramzy A,

    2010-01-01

    menstruation may, in certain conditions, overcome local defense mechanisms, implant, and proliferate19. However, the occurrence of endometriosis in sites very remote from pelvic organs directed the research towards other theories such as genetic background20, embryonic rest theory21 and stem cell dysfunction22.Stem cells are primitive cells which are known for their capacity to self renew as well as to differentiate into one or more mature cell types23. A growing body of evidence has implicated stem cells as possible endometrial progenitors. In one study, bone marrow-derived stem cells have been identified in the endometrium of women who were bone marrow transplant recipients; these cells appear histologically indistinguishable from endogenous endometrial cells and express markers of glandular and stromal differentiation24. The examination of a sexually dimorphic organ such as the uterus demonstrates the ability of male bone marrow, which cannot harbor circulating endometrial cells, to generate endometrium de novo and proves their mesenchymal stem cell origin. In addition, finding Y chromosome bearing endometrial cells demonstrates the potential to recapitulate embryonic developmental pathways that were never activated in males22.The aim of this study was to confirm the hypothesis of the presence of a possible endometriosis inducing factor(s (EIF in the blood of women with endometriosis that transforms allogenic stem cells into endometrial like cells.Study Design: This was prospective case control experimental study that acquired the approval of Bioethical Committee of the National Research Center under number 09-079. Setting: The study was carried out in collaboration between the Obstetrics and Gynecology Department, Cairo University; Unit of Biochemistry and Molecular Biology, Medical Biochemistry Department, Cairo University; Reproductive Health Research Department, National Research Centre; and Biomedical Technology Department, National Research Center. Patients and

  13. Delay-induced depinning of localized structures in a spatially inhomogeneous Swift-Hohenberg model

    Science.gov (United States)

    Tabbert, Felix; Schelte, Christian; Tlidi, Mustapha; Gurevich, Svetlana V.

    2017-03-01

    We report on the dynamics of localized structures in an inhomogeneous Swift-Hohenberg model describing pattern formation in the transverse plane of an optical cavity. This real order parameter equation is valid close to the second-order critical point associated with bistability. The optical cavity is illuminated by an inhomogeneous spatial Gaussian pumping beam and subjected to time-delayed feedback. The Gaussian injection beam breaks the translational symmetry of the system by exerting an attracting force on the localized structure. We show that the localized structure can be pinned to the center of the inhomogeneity, suppressing the delay-induced drift bifurcation that has been reported in the particular case where the injection is homogeneous, assuming a continuous wave operation. Under an inhomogeneous spatial pumping beam, we perform the stability analysis of localized solutions to identify different instability regimes induced by time-delayed feedback. In particular, we predict the formation of two-arm spirals, as well as oscillating and depinning dynamics caused by the interplay of an attracting inhomogeneity and destabilizing time-delayed feedback. The transition from oscillating to depinning solutions is investigated by means of numerical continuation techniques. Analytically, we use an order parameter approach to derive a normal form of the delay-induced Hopf bifurcation leading to an oscillating solution. Additionally we model the interplay of an attracting inhomogeneity and destabilizing time delay by describing the localized solution as an overdamped particle in a potential well generated by the inhomogeneity. In this case, the time-delayed feedback acts as a driving force. Comparing results from the later approach with the full Swift-Hohenberg model, we show that the approach not only provides an instructive description of the depinning dynamics, but also is numerically accurate throughout most of the parameter regime.

  14. Analysis of the Determinant Factors Development of Maintenance Culture in Malaysian Local Authorities

    Directory of Open Access Journals (Sweden)

    Sani S.I.A.

    2014-01-01

    Full Text Available Malaysia is a fast growing developing country and its vision is becoming a developed country with a first class infrastructure. Towards this vision, the assets and facilities were developed, owned or leased by public sector especially buildings, constructions and infrastructures to fulfill administrative and social needs as well as economic responsibilities to general public. In Malaysia, public asset and facilities is owned by three major levels of government, which are the federal government, state government and the local government also known as local authority. Between these three forms of government, Local Authorities hold a large number of facilities that place demands on resources. They have a responsibility to use and maintain a wide range of property assets including classified and heritage buildings, single purpose facilities and state of the art multipurpose facilities. Over the years, the local authorities in Malaysia currently have been soundly criticized by public caused poor maintenance culture. The assets especially public buildings and infrastructures are not maintained properly. Thus, developing the maintenance culture is essential to increase the awareness about maintenance activity on public facilities and assets in Malaysian Local Authorities. Regarding this scenario, the purpose of this study is to determine the determinant factors affecting development of maintenance culture identified based on the review of previous research. As a guide to achieve the research objective, a questionnaire survey was conducted to investigate the significance of ten determinant factors identified in the research study and their related affecting to development of maintenance culture in local authority as a respondent in this research. The collected data was then analyzed using quantitative approaches such as mean analysis, relative important index as well as others.

  15. Retention factors of management staff in the maintenance phase of their careers in local government

    Directory of Open Access Journals (Sweden)

    Mervin Munsamy

    2009-04-01

    Full Text Available Organisations require an employer value proposition (EVP to attract and retain people in management. This study was undertaken to understand the key retention factors that influence experienced management employees, in the maintenance phase of their careers, to remain employed at a local government organisation. Retention factors inform the organisation’s EVP. A qualitative, empirical-analytical research paradigm with a modernist approach was adopted. Data were obtained through purposive sampling (n = 10 by way of semi-structured interviews. A theoretical framework was used against which data could be deducted and compared. Sixteen key factors were identified, of which Job Aligned with Personal Meaning or Passion emerged as the strongest retention factor among the study’s participants.

  16. Impact of whey proteins on the systemic and local intestinal level of mice with diet induced obesity.

    Science.gov (United States)

    Swiątecka, D; Złotkowska, D; Markiewicz, L H; Szyc, A M; Wróblewska, B

    2017-04-19

    Obesity is a serious public health problem and being multifactorial is difficult to tackle. Since the intestinal ecosystem's homeostasis is, at least partially, diet-dependent, its modulation may be triggered by food components that are designed to exert a modulatory action leading to a health-promoting effect. Milk whey proteins, are considered as such promising factors since they influence satiation as well as body weight and constitute the source of biologically active peptides which may modulate health status locally and systemically. This way, whey proteins are associated with obesity. Therefore, this paper is aimed at the estimation of the impact of whey proteins using a commercially available whey protein isolate on the physiological response of mice with diet-induced obesity. The physiological response was evaluated on the local-intestinal level, scrutinizing intestinal microbiota as one of the important factors in obesity and on the systemic level, analyzing the response of the organism. Whey proteins brought about the decrease of the fat mass with a simultaneous increase of the lean mass of animals with diet induced obesity, which is a promising, health-promoting effect. Whey proteins also proved to act beneficially helping restore the number of beneficial bifidobacteria in obese animals and decreasing the calorie intake and fat mass as well as the LDL level. Overall, supplementation of the high fat diet with whey proteins acted locally by restoration of the intestinal ecosystem, thus preventing dysbiosis and its effects and also acted systemically by strengthening the organism increasing the lean mass and thus hindering obesity-related detrimental effects.

  17. Association of p75(NTR) with caveolin and localization of neurotrophin-induced sphingomyelin hydrolysis to caveolae.

    Science.gov (United States)

    Bilderback, T R; Grigsby, R J; Dobrowsky, R T

    1997-04-18

    Caveolae are plasma membrane microdomains that are enriched in caveolin, the structural protein of caveolae, sphingomyelin, and other signaling molecules. We previously suggested that neurotrophin-induced p75(NTR)-dependent sphingomyelin hydrolysis may be localized to the plasma membrane. Therefore, we examined if caveolae were a major site of p75(NTR)-dependent sphingomyelin hydrolysis in p75(NTR)-NIH 3T3 fibroblasts. Caveolin-enriched membranes (CEMs) were prepared by either detergent or detergent-free extraction and separated from noncaveolar membranes by centrifugation through sucrose gradients. Immunoblot analysis of the individual gradient fractions indicated that caveolin and p75(NTR) were enriched in CEMs. The localization of p75(NTR) to CEMs was not an artifact of receptor overexpression in the fibroblasts because a similar distribution of p75(NTR) was evident from PC12 cells, which endogenously express p75(NTR). In the p75(NTR) fibroblasts, nerve growth factor induced a time-dependent hydrolysis of sphingomyelin only in CEMs with no hydrolysis detected in noncaveolar membranes. Intriguingly, endogenous p75(NTR) was found to co-immunoprecipitate with caveolin, suggesting that p75(NTR) may associate with caveolin in vivo. This interaction was confirmed in vitro by the co-immunoprecipitation of a glutathione S-transferase fusion protein expressing the cytoplasmic domain of p75(NTR) with caveolin. Collectively, these results demonstrate that neurotrophin-induced p75(NTR)-dependent sphingomyelin hydrolysis localizes to CEMs and suggest that the interaction of p75(NTR) with caveolin may affect signaling through p75(NTR).

  18. Carrier induced local moment magnetization in p-type Sn1-xMnxTe

    Science.gov (United States)

    Behera, Sashi S.; Tripathi, Pratibha; Nayak, Sanjeev K.; Tripathi, Gouri S.

    2017-08-01

    We derive a theory of carrier induced local moment magnetization of p-type Sn1-xMnxTe based on the Hubbard model, k → · π → electronic structure method (k → is the electronic wave vector and π → is the relativistic momentum operator) and the statistical paramagnetic approach for the localized moments. The Hubbard model is used to derive an internal exchange magnetic field. The difference in exchange self-energy is expressed in terms of an internal exchange field that is proportional to the parameter U, the onsite Coulomb repulsion, and the spin-density of carriers. In the present theory, the k → · π → + U model is integrated with the statistical paramagnetic theory for localized spins, which is then solved in a self-consistent manner by adding the exchange field to the applied field. The technique is applied to study the magnetic properties of p-type Sn1-xMnxTe, an important material for spintronics devices. The local moment magnetization calculated using the total magnetic field self-consistently agrees with the experimental observations. Magnetization and the exchange field studied as functions of the applied field, temperature and carrier concentration yield results on expected lines. Ours is a mechanism that is different from the RKKY interaction, normally invoked for carrier induced ferromagnetism and is thus a novelty.

  19. CONTRIBUTING FACTORS OF EMPLOYEE’S PERFORMANCE: A CASE STUDY OF LOCAL NGOs IN PESHAWAR CITY

    Directory of Open Access Journals (Sweden)

    Saqib Shahzad

    2015-06-01

    Full Text Available The research study has been focused to study the contributing factors towards employee’s performance. Performance of employees is one of the most significant factors for the growth and success of every organization. Data was collected through the distribution of questionnaires. 120 questionnaires as the sample size were distributed among the employees of local NGOs. The returned questionnaires were 106 having a response rate of 88.33%. The findings of the study found that job security, relationship with colleagues, relationship with supervisor, working conditions and employee’s empowerment were found to have significant impact on employee’s performance.

  20. Evaluation of natural factors in town planning and strategic programming of development local community

    Directory of Open Access Journals (Sweden)

    Lješević Milutin

    2009-01-01

    Full Text Available The natural components are very important aspect of human life and work. The nature is place is place wherever to happened majority of human activity, working vacation and survival, although are some areas is technicality and desecrating to denaturalization. Because of that, it is necessary to study all valid of natural factors, when to programs new contents which are in function of human living, work or holiday. We can find great differences in exploration of some natural factors depending of level in programming of development (general or detail urban planning and strategic programming or local community or projecting. .

  1. Oral health of patients with HIV-AIDS: influence of local and systemic factors

    OpenAIRE

    Batista, Anne Margareth

    2013-01-01

    ABSTRACT The research entitled "Oral Health of HIV-AIDS patients: influence of local and systemic factors" was held during the year 2012 in Diamantina, Minas Gerais. The aim of this research was to evaluate the oral and systemic conditions of patients with HIV / AIDS attended by Municipal DST-AIDS of Diamantina, from 24 cities of Jequitinhonha Valley. To do this, 118 patients with HIV-AIDS were evaluated. The patients were observed about their conditions of oral and general health, socioecono...

  2. Enfermedad periodontal y factores locales y sistémicos asociados

    Directory of Open Access Journals (Sweden)

    María Elena González Díaz

    2002-12-01

    Full Text Available Se realizó un estudio epidemiológico transversal en 3 áreas de salud del municipio Santa Clara en el período de enero a diciembre de 1999, con el objetivo de determinar la condición periodontal de los encuestados y establecer sus nexos con factores locales y sistémicos existentes. Se determinó la prevalencia y gravedad de la enfermedad periodontal mediante la aplicación del índice de necesidad de tratamiento periodontal en la comunidad, y se relacionaron sus categorizaciones con factores locales y generales explorados durante el estudio. La prevalencia fue alta, vinculada con la edad y con el grado de higiene bucal. El hábito de fumar se asoció con la enfermedad ya establecida, la caries dental con estados incipientes; los casos con maloclusiones eran mayoritariamente enfermos y la patología sistémica más asociada con la enfermedad periodontal fue la diabetes.A cross-sectional epidemiological study was conducted in 3 health areas of the municipality of Santa Clara from January to December, 1999, with the aim of determining the periodontal conditions of the surveyed and to establish its links with the existing local and systemic factors. The prevalence and severity of the periodontal disease was determined by applying the index of need of periodontal treatment in the community and its categorizations were related to local and general factors explored during the study. The prevalence was high related to the age and to the degree of oral hygiene. Smoking was associated with the already established disease, whereas dental caries were associated with incipient states. Most of the cases with malocclusions were sick and diabetes was the systemic pathology most associated with periodontal disease.

  3. Non-local form factors for curved-space antisymmetric fields

    CERN Document Server

    Netto, Tiberio de Paula

    2016-01-01

    In the recent paper Buchbinder, Kirillova and Pletnev presented formal arguments concerning quantum equivalence of free massive antisymmetric tensor fields of second and third rank to the free Proca theory and massive scalar field with minimal coupling to gravity, respectively. We confirm this result using explicit covariant calculations of non-local form factors based on the heart-kernel technique, and discuss the discontinuity of quantum contributions in the massless limit.

  4. Climate drives fire synchrony but local factors control fire regime change in northern Mexico

    Science.gov (United States)

    Larissa L. Yocom Kent; Peter Z. Fulé; Peter M. Brown; Julián Cerano-Paredes; Eladio Cornejo-Oviedo; Citlali Cortés Montaño; Stacy A. Drury; Donald A. Falk; Jed Meunier; Helen M. Poulos; Carl N. Skinner; Scott L. Stephens; José Villanueva-Díaz

    2017-01-01

    The occurrence of wildfire is influenced by a suite of factors ranging from “top-down” influences (e.g., climate) to “bottom-up” localized influences (e.g., ignitions, fuels, and land use). We carried out the first broad-scale assessment of wildland fire patterns in northern Mexico to assess the relative influence of top-down and bottom-up drivers of fire in a...

  5. Nodularin Exposure Induces SOD1 Phosphorylation and Disrupts SOD1 Co-localization with Actin Filaments

    Directory of Open Access Journals (Sweden)

    Kari E. Fladmark

    2012-12-01

    Full Text Available Apoptotic cell death is induced in primary hepatocytes by the Ser/Thr protein phosphatase inhibiting cyanobacterial toxin nodularin after only minutes of exposure. Nodularin-induced apoptosis involves a rapid development of reactive oxygen species (ROS, which can be delayed by the Ca2+/calmodulin protein kinase II inhibitor KN93. This apoptosis model provides us with a unique population of highly synchronized dying cells, making it possible to identify low abundant phosphoproteins participating in apoptosis signaling. Here, we show that nodularin induces phosphorylation and possibly also cysteine oxidation of the antioxidant Cu,Zn superoxide dismutase (SOD1, without altering enzymatic SOD1 activity. The observed post-translational modifications of SOD1 could be regulated by Ca2+/calmodulin protein kinase II. In untreated hepatocytes, a high concentration of SOD1 was found in the sub-membranous area, co-localized with the cortical actin cytoskeleton. In the early phase of nodularin exposure, SOD1 was found in high concentration in evenly distributed apoptotic buds. Nodularin induced a rapid reorganization of the actin cytoskeleton and, at the time of polarized budding, SOD1 and actin filaments no longer co-localized.

  6. Effect of Inducible Cyclooxygenase Expression on Local Microvessel Blood Flow in Acute Interstitial Pancreatitis

    Directory of Open Access Journals (Sweden)

    Zong-Guang Zhou

    2004-04-01

    Conclusions: The correlations between increased COX-2 expression and decreased capillary perfusion and blood flow and increased oedema following AIP may show that COX-2 expression can induce neutrophil sequestration to the pancreas, which may be one of the cascading inflammatory factors in the development of AIP.

  7. Controlling successive ionic layer absorption and reaction cycles to optimize silver nanoparticle-induced localized surface plasmon resonance effects on the paper strip

    Science.gov (United States)

    Lee, Jae-Chul; Kim, Wansun; Park, Hun-Kuk; Choi, Samjin

    2017-03-01

    This study investigates why a silver nanoparticle (SNP)-induced surface-enhanced Raman scattering (SERS) paper chip fabricated at low successive ionic layer absorption and reaction (SILAR) cycles leads to a high SERS enhancement factor (7 × 108) with an inferior nanostructure and without generating a hot spot effect. The multi-layered structure of SNPs on cellulose fibers, verified by magnified scanning electron microscopy (SEM) and analyzed by a computational simulation method, was hypothesized as the reason. The pattern of simulated local electric field distribution with respect to the number of SILAR cycles showed good agreement with the experimental Raman intensity, regardless of the wavelength of the excitation laser sources. The simulated enhancement factor at the 785-nm excitation laser source (2.8 × 109) was 2.5 times greater than the experimental enhancement factor (1.1 × 109). A 532-nm excitation laser source exhibited the highest maximum local electric field intensity (1.9 × 1011), particularly at the interparticle gap called a hot spot. The short wavelength led to a strong electric field intensity caused by strong electromagnetic coupling arising from the SNP-induced local surface plasmon resonance (LSPR) effects through high excitation energy. These findings suggest that our paper-based SILAR-fabricated SNP-induced LSPR model is valid for understanding SNP-induced LSPR effects.

  8. Lipid raft localization of epidermal growth factor receptor alters matrix metalloproteinase-1 expression in SiHa cells via the MAPK/ERK signaling pathway

    Science.gov (United States)

    Zhang, Zongfeng; Wang, Lina; Du, Juan; Li, Yuanbo; Yang, Huilun; Li, Chenxi; Li, Hui; Hu, Haiyang

    2016-01-01

    Matrix metalloproteinase-1 (MMP-1) has been identified as an important participant in tumor invasion, metastasis and angiogenesis. The purpose of the present study was to investigate the effects of epidermal growth factor receptor (EGFR) localization to lipid rafts on signaling pathways involved in the regulation of MMP-1 expression in SiHa cells, a cervical cancer cell line. EGFR activation by EGF specifically induced MMP-1 expression at both the messenger RNA and protein levels. Additionally, it was observed that EGFR localized to lipid rafts, and that the redistribution of EGFR induced by lipid raft disruption strengthened EGF-induced MMP-1 expression. MMP-1 induction was blocked by the mitogen-activated protein kinase (MAPK) kinase inhibitors PD98059 and U0126. Our results suggested that lipid rafts provide a platform to inhibit EGFR regulation of MMP-1 in SiHa cells through the MAPK/extracellular signal-regulated kinase signaling pathway.

  9. Local anaesthetic toxicity in a pregnant patient undergoing lignocaine-induced intravenous regional anaesthesia.

    LENUS (Irish Health Repository)

    Coleman, M

    2012-02-03

    A pregnant patient at 38 weeks\\' gestation developed symptoms of local anaesthetic toxicity following intravenous regional anaesthesia (IVRA) for hand surgery, using a standard dose of lignocaine. Reports suggest that a number of factors, both physiological and pharmacological, combine to increase the likelihood of local anaesthetic (LA) toxicity in pregnancy despite employment of a conventional "safe" IVRA technique. It is suggested that for IVRA, pregnant patients are premedicated with a benzodiazepine, the tourniquet time is increased and the concentration of LA is decreased to reduce the risks of LA toxicity.

  10. Platelet-Released Growth Factors Induce Differentiation of Primary Keratinocytes

    Directory of Open Access Journals (Sweden)

    Andreas Bayer

    2017-01-01

    Full Text Available Autologous thrombocyte concentrate lysates, for example, platelet-released growth factors, (PRGFs or their clinically related formulations (e.g., Vivostat PRF® came recently into the physicians’ focus as they revealed promising effects in regenerative and reparative medicine such as the support of healing of chronic wounds. To elucidate the underlying mechanisms, we analyzed the influence of PRGF and Vivostat PRF on human keratinocyte differentiation in vitro and on epidermal differentiation status of skin wounds in vivo. Therefore, we investigated the expression of early (keratin 1 and keratin 10 and late (transglutaminase-1 and involucrin differentiation markers. PRGF treatment of primary human keratinocytes decreased keratin 1 and keratin 10 gene expression but induced involucrin and transglutaminase-1 gene expression in an epidermal growth factor receptor- (EGFR- dependent manner. In concordance with these results, microscopic analyses revealed that PRGF-treated human keratinocytes displayed morphological features typical of keratinocytes undergoing terminal differentiation. In vivo treatment of artificial human wounds with Vivostat PRF revealed a significant induction of involucrin and transglutaminase-1 gene expression. Together, our results indicate that PRGF and Vivostat PRF induce terminal differentiation of primary human keratinocytes. This potential mechanism may contribute to the observed beneficial effects in the treatment of hard-to-heal wounds with autologous thrombocyte concentrate lysates in vivo.

  11. Placental Induced Growth Factor (PIGf) in Coronary Artery Disease

    Science.gov (United States)

    Sundaresan, Alamelu; Carabello, Blaise; Mehta, Satish; Schlegel, Todd; Pellis, Neal; Ott, Mark; Pierson, Duane

    2010-01-01

    Our previous studies on normal human lymphocytes have shown a five-fold increase (p less than 0.001) in angiogenic inducers such as Placental Induced Growth Factor (PIGf) in physiologically stressful environments such as modeled microgravity, a space analog. This suggests de-regulation of cardiovascular signalling pathways indicated by upregulation of PIGf. In the current study, we measured PIGf in the plasma of 33 patients with and without coronary artery disease (CAD) to investigate whether such disease is associated with increased levels of PIGf. A control consisting of 31 sex matched apparently healthy subjects was also included in the study. We observed that the levels of PIGf in CAD patients were significantly increased compared to those in healthy control subjects (p less than 0.001) and usually increased beyond the clinical threshold level (greater than 27ng/L). The mechanisms leading to up-regulation of angiogenic factors and the adaptation of organisms to stressful environments such as isolation, high altitude, hypoxia, ischemia, microgravity, increased radiation, etc are presently unknown and require further investigation in spaceflight and these other physiologically stressed environments.

  12. Platelet-Activating Factor Induces Th17 Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Anne-Marie Drolet

    2011-01-01

    Full Text Available Th17 cells have been implicated in a number of inflammatory and autoimmune diseases. The phospholipid mediator platelet-activating factor (PAF is found in increased concentrations in inflammatory lesions and has been shown to induce IL-6 production. We investigated whether PAF could affect the development of Th17 cells. Picomolar concentrations of PAF induced IL-23, IL-6, and IL-1β expression in monocyte-derived Langerhans cells (LCs and in keratinocytes. Moreover, when LC were pretreated with PAF and then cocultured with anti-CD3- and anti-CD28-activated T cells, the latter developed a Th17 phenotype, with a significant increase in the expression of the transcriptional regulator RORγt and enhanced expression of IL-17, IL-21, and IL-22. PAF-induced Th17 development was prevented by the PAF receptor antagonist WEB2086 and by neutralizing antibodies to IL-23 and IL-6R. This may constitute a previously unknown stimulus for the development and persistence of inflammatory processes that could be amenable to pharmacologic intervention.

  13. Chromosomal localization of a novel retinoic acid induced gene RA28 and the protein distribution of its encoded protein

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Gene RA28 is a retinoic acid induced novel gene isolated in our laboratory previously. All-trans retinoic acid (ATRA) was used to induce lung adenocarcinoma cell line GLC-82, and RA28 was obtained by subtractive hybridization. Green fluorescent protein (GFP) has emerged as a unique tool for examining introcellular phenomena in living cells. GFP possesses an intrinsic fluorescence at 488 nm that does not require other co-factors. In this report, an eukaryotic expression plasmid pEGFP-C1-RA28 was constructed and transfected with parental cell line GLC-82 to analyze protein expression and its distribution in living cells. Moreover, radiation hybrid (RH) technique was used to localize RA28 to the chromosome. The results show that gene RA28 is mapped to the chromosome 19q13.1 region, its encoded protein is distributed on cell membrane. All the results further demonstrate that GFP and RH techniques are accurate, fast, repetitive, and will be powerful methods for investigating the gene and protein localization.

  14. Comparison and characterization of α-amylase inducers in Aspergillus nidulans based on nuclear localization of AmyR

    OpenAIRE

    Murakoshi, Yuriko; Makita, Tomohiro; Kato, Masashi; Kobayashi, Tetsuo

    2012-01-01

    AmyR, a fungal transcriptional activator responsible for induction of amylolytic genes in Aspergillus nidulans, localizes to the nucleus in response to the physiological inducer isomaltose. Maltose, kojibiose, and d-glucose were also found to trigger the nuclear localization of GFP-AmyR. Isomaltose- and kojibiose-triggered nuclear localization was not inhibited by the glucosidase inhibitor, castanospermine, while maltose-triggered localization was inhibited. Thus, maltose itself does not appe...

  15. The association of osteoarthritis risk factors with localized, regional and diffuse knee pain.

    Science.gov (United States)

    Thompson, L R; Boudreau, R; Newman, A B; Hannon, M J; Chu, C R; Nevitt, M C; Kent Kwoh, C

    2010-10-01

    To identify determinants of different patterns of knee pain with a focus on risk factors for knee osteoarthritis (OA). The Knee Pain Map is an interviewer-administered assessment that asks subjects to characterize their knee pain as localized, regional, or diffuse. A total of 2677 participants from the Osteoarthritis Initiative were studied. We used multinomial logistic regression to examine the relationship between risk factors for OA and knee pain patterns. We examined the bivariate and multivariate relationships of knee pain pattern with age, body mass index (BMI), sex, race, family history of total joint replacement, knee injury, knee surgery, and hand OA. We compared 2462 knees with pain to 1805 knees without pain. In the bivariate analysis, age, sex, BMI, injury, surgery, and hand OA were associated with at least one pain pattern. In the multivariate model, all of these variables remained significantly associated with at least one pattern. When compared to knees without pain, higher BMI, injury, and surgery were associated with all patterns. BMI had its strongest association with diffuse pain. Older age was less likely to be associated with localized pain while female sex was associated with regional pain. We have shown that specific OA risk factors are associated with different knee pain patterns. Better understanding of the relationship between OA risk factors and knee pain patterns may help to characterize the heterogeneous subsets of knee OA. Published by Elsevier Ltd.

  16. Prognostic Factors for Local, Loco-regional and Systemic Recurrence in Early-stage Breast Cancer.

    Science.gov (United States)

    Kümmel, A; Kümmel, S; Barinoff, J; Heitz, F; Holtschmidt, J; Weikel, W; Lorenz-Salehi, F; du Bois, A; Harter, P; Traut, A; Blohmer, J U; Ataseven, B

    2015-07-01

    Aim: The risk of recurrence in breast cancer depends on factors such as treatment but also on the intrinsic subtype. We analyzed the risk factors for local, loco-regional and systemic recurrence, evaluated the differences and analyzed the risk of recurrence for different molecular subtypes. Material and Methods: A total of 3054 breast cancer patients who underwent surgery followed by adjuvant treatment at HSK hospital or Essen Mitte Hospital between 1998 and 2011 were analyzed. Based on immunohistochemical parameters, cancers were divided into the following subgroups: luminal A, luminal B (HER2-), luminal B (HER2+), HER2+ and TNBC (triple negative breast cancer). Results: 67 % of tumors were classified as luminal A, 13 % as luminal B (HER2-), 6 % as luminal B (HER2+), 3 % as HER2+ and 11 % as TNBC. After a median follow-up time of 6.6 years there were 100 local (3.3 %), 32 loco-regional (1 %) and 248 distant recurrences (8 %). Five-year recurrence-free survival for the overall patient collective was 92 %. On multivariate analysis, positive nodal status, TNBC subtype and absence of radiation therapy were found to be independent risk factors for all forms of recurrence. Age loco-regional recurrence was low. In addition to nodal status, subgroup classification was found to be an important factor affecting the risk of recurrence.

  17. Interacting factors and cellular localization of SR protein-specific kinase Dsk1

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Zhaohua, E-mail: ztang@jsd.claremont.edu [W.M. Keck Science Center, The Claremont Colleges, Claremont, CA 91711 (United States); Luca, Maria; Taggart-Murphy, Laura; Portillio, Jessica; Chang, Cathey; Guven, Ayse [W.M. Keck Science Center, The Claremont Colleges, Claremont, CA 91711 (United States); Lin, Ren-Jang [Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010 (United States); Murray, Johanne; Carr, Antony [Genome Damage and Stability Center, University of Sussex, Falmer, BN1 9RQ (United Kingdom)

    2012-10-01

    Schizosaccharomyces pombe Dsk1 is an SR protein-specific kinase (SRPK), whose homologs have been identified in every eukaryotic organism examined. Although discovered as a mitotic regulator with protein kinase activity toward SR splicing factors, it remains largely unknown about what and how Dsk1 contributes to cell cycle and pre-mRNA splicing. In this study, we investigated the Dsk1 function by determining interacting factors and cellular localization of the kinase. Consistent with its reported functions, we found that pre-mRNA processing and cell cycle factors are prominent among the proteins co-purified with Dsk1. The identification of these factors led us to find Rsd1 as a novel Dsk1 substrate, as well as the involvement of Dsk1 in cellular distribution of poly(A){sup +} RNA. In agreement with its role in nuclear events, we also found that Dsk1 is mainly localized in the nucleus during G{sub 2} phase and at mitosis. Furthermore, we revealed the oscillation of Dsk1 protein in a cell cycle-dependent manner. This paper marks the first comprehensive analysis of in vivo Dsk1-associated proteins in fission yeast. Our results reflect the conserved role of SRPK family in eukaryotic organisms, and provide information about how Dsk1 functions in pre-mRNA processing and cell-division cycle.

  18. Local perceptions on factors influencing the introduction of international healthcare accreditation in Pakistan.

    Science.gov (United States)

    Sax, Sylvia; Marx, Michael

    2014-12-01

    One contributor to poor health outcomes in developing countries is weak health systems; key to strengthening them are interventions to improve quality of health services. Though the value of healthcare accreditation is increasingly recognized, there are few case studies exploring its adaptation in developing countries. The aim of our study in Pakistan was to identify perceived factors influencing the adaptation of international healthcare accreditation within a developing country context. We used qualitative methods including semi-structured interviews, a structured group discussion, focus groups and non-participant observation of management meetings. Data analysis used a grounded theory approach and a conceptual framework adapted from implementation science. Using our conceptual framework categories of 'inner' and 'outer' setting, we found six perceived inner health system factors that could influence the introduction of healthcare accreditation and two 'outer' setting factors, perceived as external to the health system but able to influence its introduction. Our research identified that there is no 'one size fits all' approach to introducing healthcare accreditation as a means to improve healthcare quality. Those planning to support healthcare accreditation, such as national and provincial ministries and international development partners, need to understand how the three components of healthcare accreditation fit into the local health system and into the broader political and social environment. In our setting this included moving to supportive and transparent external evaluation mechanisms, with a first step of using locally developed and agreed standards. In addition, sustainable implementation of the three components was seen as a major challenge, especially establishment of a well-managed, transparent accreditation agency able to lead processes such as training and support for peer surveyors. Consideration of local change mechanisms and cultural practices is

  19. Exploring Local Level Factors Shaping the Implementation of a Blended Learning Module for Information and Geospatial Literacy in Ontario

    Science.gov (United States)

    Vine, Michelle M.; Chiappetta-Swanson, Catherine; Maclachlan, John; Brodeur, Jason J.; Bagg, Julianne

    2016-01-01

    The objectives of this research study were to examine local level factors shaping the implementation of a blended pedagogical approach for geospatial- and information-literacy, and to understand implementer satisfaction. As such, we addressed the following research questions: What local-level factors shape the implementation of the blended…

  20. Neutralizing Interleukin-1β (IL-1β) Induces β-Cell Survival by Maintaining PDX1 Protein Nuclear Localization*

    Science.gov (United States)

    Ardestani, Amin; Sauter, Nadine S.; Paroni, Federico; Dharmadhikari, Gitanjali; Cho, Jae-Hyoung; Lupi, Roberto; Marchetti, Piero; Oberholzer, José; Conte, Julie Kerr; Maedler, Kathrin

    2011-01-01

    The transcription factor PDX1 plays a critical role during β-cell development and in glucose-induced insulin gene transcription in adult β-cells. Acute glucose exposure leads to translocalization of PDX1 to the nucleoplasm, whereas under conditions of oxidative stress, PDX1 shuttles from the nucleus to the cytosol. Here we show that cytosolic PDX1 expression correlated with β-cell failure in diabetes. In isolated islets from patients with type 2 diabetes and from diabetic mice, we found opposite regulation of insulin and PDX1 mRNA; insulin was decreased in diabetes, but PDX1 was increased. This suggests that elevated PDX1 mRNA levels may be insufficient to regulate insulin. In diabetic islets, PDX1 protein was localized in the cytosol, whereas in non-diabetic controls, PDX1 was in the nucleus. In contrast, overexpression of either IL-1 receptor antagonist or shuttling-deficient PDX1 restored β-cell survival and function and PDX1 nuclear localization. Our results show that nuclear localization of PDX1 is essential for a functional β-cell and provides a novel mechanism of the protective effect of IL-1 receptor antagonist on β-cell survival and function. PMID:21393239

  1. Cytoplasmic localization of p21 protects trophoblast giant cells from DNA damage induced apoptosis.

    Science.gov (United States)

    de Renty, Christelle; DePamphilis, Melvin L; Ullah, Zakir

    2014-01-01

    Proliferating trophoblast stem cells (TSCs) can differentiate into nonproliferating but viable trophoblast giant cells (TGCs) that are resistant to DNA damage induced apoptosis. Differentiation is associated with selective up-regulation of the Cip/Kip cyclin-dependent kinase inhibitors p57 and p21; expression of p27 remains constant. Previous studies showed that p57 localizes to the nucleus in TGCs where it is essential for endoreplication. Here we show that p27 also remains localized to the nucleus during TSC differentiation where it complements the role of p57. Unexpectedly, p21 localized to the cytoplasm where it was maintained throughout both the G- and S-phases of endocycles, and where it prevented DNA damage induced apoptosis. This unusual status for a Cip/Kip protein was dependent on site-specific phosphorylation of p21 by the Akt1 kinase that is also up-regulated in TGCs. Although cytoplasmic p21 is widespread among cancer cells, among normal cells it has been observed only in monocytes. The fact that it also occurs in TGCs reveals that p57 and p21 serve nonredundant functions, and suggests that the role of p21 in suppressing apoptosis is restricted to terminally differentiated cells.

  2. Cytoplasmic localization of p21 protects trophoblast giant cells from DNA damage induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Christelle de Renty

    Full Text Available Proliferating trophoblast stem cells (TSCs can differentiate into nonproliferating but viable trophoblast giant cells (TGCs that are resistant to DNA damage induced apoptosis. Differentiation is associated with selective up-regulation of the Cip/Kip cyclin-dependent kinase inhibitors p57 and p21; expression of p27 remains constant. Previous studies showed that p57 localizes to the nucleus in TGCs where it is essential for endoreplication. Here we show that p27 also remains localized to the nucleus during TSC differentiation where it complements the role of p57. Unexpectedly, p21 localized to the cytoplasm where it was maintained throughout both the G- and S-phases of endocycles, and where it prevented DNA damage induced apoptosis. This unusual status for a Cip/Kip protein was dependent on site-specific phosphorylation of p21 by the Akt1 kinase that is also up-regulated in TGCs. Although cytoplasmic p21 is widespread among cancer cells, among normal cells it has been observed only in monocytes. The fact that it also occurs in TGCs reveals that p57 and p21 serve nonredundant functions, and suggests that the role of p21 in suppressing apoptosis is restricted to terminally differentiated cells.

  3. Growth Factors and Tension-Induced Skeletal Muscle Growth

    Science.gov (United States)

    Vandenburgh, Herman H.

    1994-01-01

    The project investigated biochemical mechanisms to enhance skeletal muscle growth, and developed a computer based mechanical cell stimulator system. The biochemicals investigated in this study were insulin/(Insulin like Growth Factor) IGF-1 and Steroids. In order to analyze which growth factors are essential for stretch-induced muscle growth in vitro, we developed a defined, serum-free medium in which the differentiated, cultured avian muscle fibers could be maintained for extended periods of time. The defined medium (muscle maintenance medium, MM medium) maintains the nitrogen balance of the myofibers for 3 to 7 days, based on myofiber diameter measurements and myosin heavy chain content. Insulin and IGF-1, but not IGF-2, induced pronounced myofiber hypertrophy when added to this medium. In 5 to 7 days, muscle fiber diameters increase by 71 % to 98% compared to untreated controls. Mechanical stimulation of the avian muscle fibers in MM medium increased the sensitivity of the cells to insulin and IGF-1, based on a leftward shift of the insulin dose/response curve for protein synthesis rates. (54). We developed a ligand binding assay for IGF-1 binding proteins and found that the avian skeletal muscle cultures produced three major species of 31, 36 and 43 kD molecular weight (54) Stretch of the myofibers was found to have no significant effect on the efflux of IGF-1 binding proteins, but addition of exogenous collagen stimulated IGF-1 binding protein production 1.5 to 5 fold. Steroid hormones have a profound effect on muscle protein turnover rates in vivo, with the stress-related glucocorticoids inducing rapid skeletal muscle atrophy while androgenic steroids induce skeletal muscle growth. Exercise in humans and animals reduces the catabolic effects of glucocorticoids and may enhance the anabolic effects of androgenic steroids on skeletal muscle. In our continuing work on the involvement of exogenrus growth factors in stretch-induced avian skeletal muscle growth, we

  4. Exploring Factor Model Parameters across Continuous Variables with Local Structural Equation Models.

    Science.gov (United States)

    Hildebrandt, Andrea; Lüdtke, Oliver; Robitzsch, Alexander; Sommer, Christopher; Wilhelm, Oliver

    2016-01-01

    Using an empirical data set, we investigated variation in factor model parameters across a continuous moderator variable and demonstrated three modeling approaches: multiple-group mean and covariance structure (MGMCS) analyses, local structural equation modeling (LSEM), and moderated factor analysis (MFA). We focused on how to study variation in factor model parameters as a function of continuous variables such as age, socioeconomic status, ability levels, acculturation, and so forth. Specifically, we formalized the LSEM approach in detail as compared with previous work and investigated its statistical properties with an analytical derivation and a simulation study. We also provide code for the easy implementation of LSEM. The illustration of methods was based on cross-sectional cognitive ability data from individuals ranging in age from 4 to 23 years. Variations in factor loadings across age were examined with regard to the age differentiation hypothesis. LSEM and MFA converged with respect to the conclusions. When there was a broad age range within groups and varying relations between the indicator variables and the common factor across age, MGMCS produced distorted parameter estimates. We discuss the pros of LSEM compared with MFA and recommend using the two tools as complementary approaches for investigating moderation in factor model parameters.

  5. The financial impact of hospitals on the local economy--2 new factors.

    Science.gov (United States)

    Rotarius, Timothy; Liberman, Aaron

    2014-01-01

    This research effort presents a descriptive analysis of the financial impact that several hospitals have on their local economy. An earlier study published by the authors included 3 distinct, yet overlapping components of financial impact: (1) the hospital system as a major health care provider, (2) the hospital system as a large employer, and (3) the hospital system as an entity whose employees contribute greatly to their local community. This new study added additional financial impact factors: (4) the hospital system as an organization committed to major construction projects in pursuit of its health services mission, and (5) the hospital system as an entity that pays taxes to government agencies. The inextricable relationship of these 5 categories both increases and enhances the impact of the hospital system on the local region. The results of this updated and expanded analysis suggest strongly that the hospital system represents 1 of the primary contributors to the economy of the region. The hospital system adds $3 billion to the $28 billion local economy, which means that the hospital system and its employees are responsible for 10.7% of the total economic prowess of the region.

  6. Dauricine inhibits insulin-like growth factor-Ⅰ-induced hypoxia inducible factor 1α protein accumulation and vascular endothelial growth factor expression in human breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xu-dong TANG; Xin ZHOU; Ke-yuan ZHOU

    2009-01-01

    Aim: To investigate the effects of dauricine (Dau) on insulin-like growth factor-Ⅰ (IGF-Ⅰ)-induced hypoxia inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression in human breast cancer cells (MCF-7).Methods: Serum-starved MCF-7 cells were pretreated for 1 h with different concentrations of Dau, followed by incubation with IGF-Ⅰ for 6 h. HIF-1α and VEGF protein expression levels were analyzed by Western blotting and ELISA, respectively.HIF-1α and VEGF mRNA levels were determined by real-time PCR. In vitro angiogenesis was observed via the human umbilical vein endothelial cell (HUVEC) tube formation assay. An in vitro invasion assay on HUVECs was performed.Results: Dau significantly inhibited IGF-Ⅰ-induced HIF-1α protein expression but had no effect on HIF-1α mRNA expression. However, Dau remarkably suppressed VEGF expression at both protein and mRNA levels in response to IGF-Ⅰ.Mechanistically, Dau suppressed IGF-Ⅰ-induced HIF-1α and VEGF protein expression mainly by blocking the activation of PI-3K/AKT/mTOR signaling pathway. In addition, Dan reduced IGF-Ⅰ-induced HIF-1α protein accumulation by inhibiting its synthesis as well as by promoting its degradation. Functionally, Dau inhibited angiogenesis in vitro. Moreover, Dau had a direct effect on IGF-Ⅰ-induced invasion of HUVECs.Conclusion: Dau inhibits human breast cancer angiogenesis by suppressing HIF-1α protein accumulation and VEGF expression, which may provide a novel potential mechanism for the anticancer activities of Dau in human breast cancer.

  7. Local social environmental factors are associated with household food insecurity in a longitudinal study of children

    Directory of Open Access Journals (Sweden)

    Carter Megan Ann

    2012-11-01

    Full Text Available Abstract Background Food insecurity is a significant public health problem in North America and elsewhere. The prevalence of food insecurity varies by country of residence; within countries, it is strongly associated with household socioeconomic status, but the local environment may also play an important role. In this study, we analyzed secondary data from a population-based survey conducted in Québec, Canada, to determine if five local environmental factors: material and social deprivation, social cohesion, disorder, and living location were associated with changes in household food insecurity over a period of 6 years, while adjusting for household socioeconomic status (SES and other factors. Methods Data from the Québec Longitudinal Study of Child Development, following same-aged children from 4–10 y of age, were analyzed using generalized estimating equations, to determine the longitudinal association between these environmental factors and food insecurity over a period of 6 years. Results Of the 2120 children originally included in the cohort, 1746 (82% were included in the present analysis. The prevalence of food insecurity was 9.2% when children were 4 y of age (95% CI: 7.8 – 10.6% but no significant changes were observed over time. On average over the 6 year period, three environmental factors were positively related to food insecurity: high social deprivation (OR 1.62, 95%CI: 1.16 – 2.26, low social cohesion (OR 1.45 95%CI: 1.10 – 1.92, and high disorder (OR 1.76, 95%CI: 1.37 – 2.27, while living location and material deprivation were not related to food insecurity. These associations were independent of household SES and other social variables. Conclusion These results highlight the potential role of the local social environment in preventing and ameliorating food insecurity at the household level. Stakeholders providing food security interventions at the community level should consider interactions with local social

  8. Expression and subcellular localization of mechano-growth factor in osteoblasts under mechanical stretch

    Institute of Scientific and Technical Information of China (English)

    ZHANG BingBing; XIAN ChengYu; LUO YanFeng; WANG YuanLiang

    2009-01-01

    Mechano-growth factor (MGF) is a stretch sensitive factor in myocytes, and it might also be produced by other mechanocytes under mechanical stimulation. In this study, both the mRNA and protein expression of MGF were detected in stretched osteoblasts. Quantitative analysis showed that a cyclic stretching stimulation caused a quick and sharp increase of MGF mRNA and protein expression from a low basal level under no stretch; the mRNA and protein levels respectively peaked in 6 and 12 h to 5 and 5.2 fold over the basal level and returned to normal by 24 h. The subcellular distribution of MGF protein was revealed by immunofluorescence analysis to be restricted to the nucleus. We concluded that cyclic stretching stimulation could induce MGF expression in osteoblasts in a pulsing fashion; and the nuclear distribution of MGF suggested that MGF might act in mechanocytes as an autocrine growth factor.

  9. Expression, content, and localization of insulin-like growth factor I in human achilles tendon

    DEFF Research Database (Denmark)

    Olesen, Jens L; Heinemeier, Katja M; Langberg, Henning;

    2006-01-01

    by immunoflourometric assay, real-time PCR, and immunohistochemistry used to localize and determine expression of IGF-I and IGFBP-4 in 6 postmortem human Achilles tendons. Tendon tissue concentrations of IGF-I were found to be 0.53 +/- 0.10 ng/g. Furthermore, we demonstrated that IGF-I and IGFBP-4 are localized around......In animals insulin-like growth factor I (IGF-I) stimulates collagen production by fibroblasts and is expressed in tendons together with its binding protein 4 (IGFBP-4). However, the presence of IGF-I and IGFBP-4 in human tendon tissue is not described. Tissue IGF-I content was examined...... the tendon fibroblasts and that mRNA for IGF-I and IGFBP-4 can be determined in human tendon tissue. The present study adds support for the roles of IGF-I and IGFBP-4 in the regulation of tendon adaptive responses to mechanical loading....

  10. Subcellular localization and mechanism of secretion of vascular endothelial growth factor in human skeletal muscle

    DEFF Research Database (Denmark)

    Høier, Birgitte; Prats Gavalda, Clara; Qvortrup, Klaus

    2013-01-01

    The subcellular distribution and secretion of vascular endothelial growth factor (VEGF) was examined in skeletal muscle of healthy humans. Skeletal muscle biopsies were obtained from m.v. lateralis before and after a 2 h bout of cycling exercise. VEGF localization was conducted on preparations...... of teased muscle fibers by transmission electron microscopy (TEM) and confocal microscopy (CM). Muscle interstitial fluid was sampled from microdialysis probes placed in the thigh muscle. TEM and CM analysis revealed two primary sites of localization of VEGF: in vesicles located in the subsarcolemmal...... regions and between the contractile elements within the muscle fibers; and in pericytes situated on the skeletal muscle capillaries. Quantitation of the subsarcolemmal density of VEGF vesicles, calculated on top of myonuclei, in the muscle fibers revealed a ∼50% increase (P...

  11. Sulindac metabolites induce proteosomal and lysosomal degradation of the epidermal growth factor receptor.

    Science.gov (United States)

    Pangburn, Heather A; Ahnen, Dennis J; Rice, Pamela L

    2010-04-01

    The epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptor tyrosine kinases. In response to ligand, EGFR is internalized and degraded by the ubiquitin-proteasome/lysosome pathway. We previously reported that metabolites of the nonsteroidal anti-inflammatory drug sulindac downregulate the expression of EGFR and inhibit basal and EGF-induced EGFR signaling through extracellular signal-regulated kinase 1/2. We now have evaluated the mechanisms of sulindac metabolite-induced downregulation of EGFR. EGF-induced downregulation of EGFR occurs within 10 minutes and lasts for 24 hours. By contrast, downregulation of EGFR by sulindac sulfide and sulindac sulfone was first evident at 4 and 24 hours, respectively, with maximal downregulation at 72 hours. Pretreatment with either the lysosomal inhibitor chloroquine or the proteosomal inhibitor MG132 blocked sulindac metabolite-induced downregulation of EGFR. Sulindac metabolites also increased the ubiquitination of EGFR. Whereas sulindac metabolites inhibited phosphorylation of EGFR pY1068, they increased phosphorylation of EGFR pY1045, the docking site where c-Cbl binds, thereby enabling receptor ubiquitination and degradation. Immunofluorescence analysis of EGF and EGFR distribution confirmed the biochemical observations that sulindac metabolites alter EGFR localization and EGFR internalization in a manner similar to that seen with EGF treatment. Expression of ErbB family members HER2 and HER3 was also downregulated by sulindac metabolites. We conclude that downregulation of EGFR expression by sulindac metabolites is mediated via lysosomal and proteosomal degradation that may be due to drug-induced phosphorylation at pY1045 with resultant ubiquitination of EGFR. Thus, sulindac metabolite-induced downregulation of EGFR seems to be mediated through mechanism(s) similar, at least in part, to those involved in EGF-induced downregulation of EGFR.

  12. Effects of hypoxia-inducible factor 1 on ischemic cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    Yongjie Luo; Xiaoping Wang; Hongbin Sun

    2008-01-01

    Hypoxia-inducible factor I, a nuclear transcription factor, is induced by hypoxia. Hypoxia-inducible factor I, a heterodimeric DNA-binding protein, is composed of hypoxia-inducible factor 1α and hypoxia-inducible factor 1 β subunits, which are family members of the basic helix-loop-helix-PER, ARNT, SIM (PAS) protein. O2 concentration regulates hypoxia-inducible factor 1 activity via this subunit. Hypoxia-inducible factor 1α plays a major role in response to hypoxia and transcriptional activation, as well as in the target gene specificity of the DNA enhancer. Hypoxia-inducible factor 1β cannot be induced by hypoxia. This effect may be due to hypoxia-inducible factor 1 stability and activated conformation due to dimerization. Previous studies have shown that hypoxia-inducible factor 1 mRNA expression increases in the penumbra following ischemia/hypoxia. Hypoxia-inducible factor 1 plays an important role in brain tissue injury alter ischemia by affecting a series of target genes, elevating tolerance to hypoxia, and ensuring survival of neural cells. This article summarizes the structure, function, expression, regulatory mechanisms, biological effects, and significance of hypoxia-inducible factor 1 in patients with ischemic cerebrovascular disease. As a transcriptional activator, hypoxia- inducible factor 1 plays a key role in hypoxic responses by stabilizing the internal environment. It also has been shown to regulate the expression of several genes. The regulatory effects of hypoxia-inducible factor 1 in patients with ischemic cerebrovascular disease have been described. The present review re-examined the concept of brain protection at the level of gene regulation.

  13. Into the Paradigm of Local Factors as Contributors for Peri-implant Disease: Short Communication.

    Science.gov (United States)

    Monje, Alberto; Galindo-Moreno, Pablo; Tözüm, Tolga Fikret; Suárez-López del Amo, Fernando; Wang, Hom-Lay

    2016-01-01

    Although some systemic conditions have been associated with peri-implant disease, local contributing factors largely remain to be determined. This study aimed at evaluating, based on clinical photographs obtained from peri-implantitis treatment publications, the possible local contributing factors involved in its development based upon a survey obtained from three experienced clinicians (> 20 years of expertise). Cohen's kappa index was used to test the interexaminer reliability. "Too-buccal implant position" was the only parameter to reach almost perfect interexaminer agreement (κ = 0.81). "Thin-tissue biotype" and "minimal presence of keratinized mucosa" demonstrated moderate agreement (κ = 0.43 and κ = 0.58, respectively). The rest of the parameters studied based on clinical photographs were fair or poor. Therefore, based on this clinicians' survey, implants too buccally placed, minimal or a lack of keratinized mucosa, and thin-tissue biotype might contribute to a higher susceptibility of developing peri-implantitis. These factors must be the focus of attention in future cross-sectional studies on the incidence of peri-implant diseases.

  14. Sumoylation delays the ATF7 transcription factor subcellular localization and inhibits its transcriptional activity.

    Science.gov (United States)

    Hamard, Pierre-Jacques; Boyer-Guittaut, Michaël; Camuzeaux, Barbara; Dujardin, Denis; Hauss, Charlotte; Oelgeschläger, Thomas; Vigneron, Marc; Kedinger, Claude; Chatton, Bruno

    2007-01-01

    Over the past few years, small ubiquitin-like modifier (SUMO) modification has emerged as an important regulator of diverse pathways and activities including protein localization and transcriptional regulation. We identified a consensus sumoylation motif (IKEE), located within the N-terminal activation domain of the ATF7 transcription factor and thus investigated the role of this modification. ATF7 is a ubiquitously expressed transcription factor, homologous to ATF2, that binds to CRE elements within specific promoters. This protein is able to heterodimerize with Jun or Fos proteins and its transcriptional activity is mediated by interaction with TAF12, a subunit of the general transcription factor TFIID. In the present article, we demonstrate that ATF7 is sumoylated in vitro (using RanBP2 as a E3-specific ligase) and in vivo. Moreover, we show that ATF7 sumoylation affects its intranuclear localization by delaying its entry into the nucleus. Furthermore, SUMO conjugation inhibits ATF7 transactivation activity by (i) impairing its association with TAF12 and (ii) blocking its binding-to-specific sequences within target promoters.

  15. Impact of skeletal unloading on bone formation: Role of systemic and local factors

    Science.gov (United States)

    Bikle, Daniel D.; Halloran, Bernard P.; Morey-Holton, Emily

    We have developed a model of skeletal unloading using growing rats whose hindlimbs are unweighted by tail suspension. The bones in the hindlimbs undergo a transient cessation of bone growth; when reloaded bone formation is accelerated until bone mass is restored. These changes do not occur in the normally loaded bones of the forelimbs. Associated with the fall in bone formation is a fall in 1,25(OH) 2D 3 production and osteocalcin levels. In contrast, no changes in parathyroid hormone, calcium, or corticosterone levels are seen. To examine the role of locally produced growth factors, we have measured the mRNA and protein levels of insulin like growth factor-1 (IGF-1) in bone during tail suspension. Surprisingly, both the mRNA and protein levels of IGF-1 increase during tail suspension as bone formation is reduced. Furthermore, the bones in the hindlimbs of the suspended animals develop a resistance to the growth promoting effects of both growth hormone and IGF-1 when given parenterally. Thus, the cessation of bone growth with skeletal unloading is apparently associated with a resistance to rather than failure to produce local growth factors. The cause of this resistance remains under active investigation.

  16. Poliovirus infection induces the co-localization of cellular protein SRp20 with TIA-1, a cytoplasmic stress granule protein.

    Science.gov (United States)

    Fitzgerald, Kerry D; Semler, Bert L

    2013-09-01

    Different types of environmental stress cause mammalian cells to form cytoplasmic foci, termed stress granules, which contain mRNPs that are translationally silenced. These foci are transient and dynamic, and contain components of the cellular translation machinery as well as certain mRNAs and RNA binding proteins. Stress granules are known to be induced by conditions such as hypoxia, nutrient deprivation, and oxidative stress, and a number of cellular factors have been identified that are commonly associated with these foci. More recently it was discovered that poliovirus infection also induces the formation of stress granules, although these cytoplasmic foci appear to be somewhat compositionally unique. Work described here examined the punctate pattern of SRp20 (a host cell mRNA splicing protein) localization in the cytoplasm of poliovirus-infected cells, demonstrating the partial co-localization of SRp20 with the stress granule marker protein TIA-1. We determined that SRp20 does not co-localize with TIA-1, however, under conditions of oxidative stress, indicating that the close association of these two proteins during poliovirus infection is not representative of a general response to cellular stress. We confirmed that the expression of a dominant negative version of TIA-1 (TIA-1-PRD) results in the dissociation of stress granules. Finally, we demonstrated that expression of wild type TIA-1 or dominant negative TIA-1-PRD in cells during poliovirus infection does not dramatically affect viral translation. Taken together, these studies provide a new example of the unique cytoplasmic foci that form during poliovirus infection.

  17. Localization of quantum objects in an expanding universe and cosmologically induced classicality

    CERN Document Server

    Herzenberg, C L

    2010-01-01

    Independent studies by different authors have proposed that classicality may be induced in quantum objects by cosmological constraints presented by an expanding universe of finite extent in space-time. Cosmological effects on a quantum system can be explored in one approach by considering an object at rest in space with a universal Hubble expansion taking place away from it, and developing a Schroedinger type governing differential equation incorporating an intrinsic expansion speed. Wave function solutions to this governing equation exhibit pronounced central localization. The extent of concentration of probability depends on mass; objects with small masses tend to behave in a delocalized manner as ordinary quantum objects do in a static space, while quantum objects with large masses are concentrated into much smaller regions. To develop a criterion for classicality, we consider that if the size of the localized region of concentrated probability density is larger than the size of the corresponding extended ...

  18. Laser-Induced Fluorescence Bronchoscopy for Detection and Localization of Early Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    XIE Shusen; LI Buhong; LI Hui; ZHENG Wei; LU Zukang

    2001-01-01

    Experimenatal results on the development of a Laser-Induced Fluorescence Bronchoscopy(LIFB) for the detection and localization of early lung cancer are reported in this paper. The system utilizes fluorescence of photosensitizer drug to provide real time video imaging for the examined lung tissue. Color filters are used to differentiate signal from background and a computer image processing technique is also applied to subtract the background. Moreover, a pseudocolor contrast enhancement method was developed to enhance the fluorescence image displayed on the vidio monitor. Suspicious areas are identified by pseudocolor image to guide biopsy, and several clinical trials show that sensitivity and contrast capability of the system should permit the detection and localization of early lung cancer.

  19. Local Peltier-effect-induced reversible metal-insulator transition in VO2 nanowires

    Science.gov (United States)

    Takami, Hidefumi; Kanki, Teruo; Tanaka, Hidekazu

    2016-06-01

    We report anomalous resistance leaps and drops in VO2 nanowires with operating current density and direction, showing reversible and nonvolatile switching. This event is associated with the metal-insulator phase transition (MIT) of local nanodomains with coexistence states of metallic and insulating phases induced by thermoelectric cooling and heating effects. Because the interface of metal and insulator domains has much different Peltier coefficient, it is possible that a significant Peltier effect would be a source of the local MIT. This operation can be realized by one-dimensional domain configuration in VO2 nanowires because one straight current path through the electronic domain-interface enables theoretical control of thermoelectric effects. This result will open a new method of reversible control of electronic states in correlated electron materials.

  20. Local Peltier-effect-induced reversible metal–insulator transition in VO2 nanowires

    Directory of Open Access Journals (Sweden)

    Hidefumi Takami

    2016-06-01

    Full Text Available We report anomalous resistance leaps and drops in VO2 nanowires with operating current density and direction, showing reversible and nonvolatile switching. This event is associated with the metal–insulator phase transition (MIT of local nanodomains with coexistence states of metallic and insulating phases induced by thermoelectric cooling and heating effects. Because the interface of metal and insulator domains has much different Peltier coefficient, it is possible that a significant Peltier effect would be a source of the local MIT. This operation can be realized by one-dimensional domain configuration in VO2 nanowires because one straight current path through the electronic domain-interface enables theoretical control of thermoelectric effects. This result will open a new method of reversible control of electronic states in correlated electron materials.

  1. Factors related to induced abortion among young women in Edo State, Nigeria.

    Science.gov (United States)

    Murray, Nancy; Winfrey, William; Chatterji, Minki; Moreland, Scott; Dougherty, Leanne; Okonofua, Friday

    2006-12-01

    Sub-Saharan Africa has the highest death rate from induced abortion in the world, and young women in southern Nigeria are particularly likely to terminate their pregnancies. This study assesses the prevalence of and factors associated with induced abortion among 602 young women aged 15-24 who were surveyed in Edo State, Nigeria, in 2002. We find that 41 percent of all pregnancies reported by the young women surveyed were terminated, and we estimate the age-specific abortion rate for 15-19-year-olds in Edo State at 49 abortions per 1,000 women, which is slightly higher than previous local estimates and nearly double the countrywide estimate for women aged 15-49. We construct explanatory multivariate models to predict the likelihood that a young woman has experienced sexual intercourse, has become pregnant, and has undergone an induced abortion, controlling for important demographic and risk-behavior factors. Young women unmarried at the time of the interview are found to be significantly more likely than married women to have had an abortion. Young women who have experienced transactional or forced sex are also significantly more likely to report ever having had an abortion, as are young women who have experienced more than one pregnancy. We conclude with suggestions for modifying the content and target populations of behavioral change messages and programs in the area.

  2. Alliances for local development success factors. Comparative experiences of Spain and Peru

    Directory of Open Access Journals (Sweden)

    Elsa Del Castillo Mory

    2015-09-01

    Full Text Available Alliances are formed to overcome the constraints partners face to achieve certain goals. When the goal is to promote local development, it requires the participation of stakeholders: private sector, local government, civil associations and community groups, among others. This article seeks, through the comparative analysis of three experiences of local development led by the district of Villa El Salvador (Lima - Peru, the mining company Yanacocha (Cajamarca -Peru and the Spanish Agency for Development Iraugi Lantzen (Basque Country - Spain, to identify the success factors of cooperation agreements for local development. We believe that a better understanding of the factors associated with the success of partnerships could help those who seek the challenge of looking for possible partners, as well as those concerned with the effective management of partnerships in place. The case of Villa El Salvador shows how government support was fundamental in the establishment of the district, but the achievements of this group could not be explained without the active participation of the community. On the other hand, the experience of the company Yanacocha reminds the reader that there is still a big gap to fill in Peru in terms of the joint efforts between private enterprises and stakeholders, and that is necessary to learn from the experiences of those who have gone through part of this path. A different case is shown by the experience of the Spanish Agency Iraugi Lantzen, highlighting the challenges and opportunities that arise from a concerted action between municipal entities pursuing local development. Overall, it can be said that although there are context and situational conditions that favor the development of alliances for development, there are other factors that mediate the success of partnerships. The case studies show that the most successful cooperation experiences are those where there are key individuals that are leaders

  3. Caffeic acid phenethyl ester inhibits 3-MC-induced CYP1A1 expression through induction of hypoxia-inducible factor-1α

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyung Gyun [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Han, Eun Hee [Division of Life Science, Korea Basic Science Institute, Daejeon (Korea, Republic of); Im, Ji Hye; Lee, Eun Ji; Jin, Sun Woo [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of)

    2015-09-25

    Caffeic acid phenethyl ester (CAPE), a natural component of propolis, is reported to have anticarcinogenic properties, although its precise chemopreventive mechanism remains unclear. In this study, we examined the effects of CAPE on 3-methylcholanthrene (3-MC)-induced CYP1A1 expression and activities. CAPE reduced the formation of the benzo[a]pyrene-DNA adduct. Moreover, CAPE inhibited 3-MC-induced CYP1A1 activity, mRNA expression, protein level, and promoter activity. CAPE treatment also decreased 3-MC-inducible xenobiotic-response element (XRE)-linked luciferase, aryl hydrocarbons receptor (AhR) transactivation and nuclear localization. CAPE induced hypoxia inducible factor-1α (HIF-1α) protein level and HIF-1α responsible element (HRE) transcriptional activity. CAPE-mediated HIF-1α reduced 3-MC-inducible CYP1A1 protein expression. Taken together, CAPE decreases 3-MC-mediated CYP1A1 expression, and this inhibitory response is associated with inhibition of AhR and HIF-1α induction. - Highlights: • CAPE reduced the formation of the benzo[a]pyrene-DNA adduct. • CAPE inhibited 3-MC-induced CYP1A1 expression. • CAPE induced HIF-1α induction. • CAPE-mediated HIF-1α reduced 3-MC-inducible CYP1A1 expression.

  4. Prolonged local forearm hyperinsulinemia induces sustained enhancement of nitric oxide-dependent vasodilation in healthy subjects

    DEFF Research Database (Denmark)

    Hermann, Thomas S; Ihlemann, Nikolaj; Dominguez, Helena;

    2005-01-01

    -dependent and -independent vasodilation.N(G)-monomethyl-L-arginine (L-NMMA) was coinfused to test the degree of nitric oxide (NO)-mediated vasodilation. Insulin infusion for 60 min enhanced serotonin-induced vasodilation by 37% compared to vehicle, p = .016. This increase was maintained for 4 h and was blocked by L......-NMMA. The SNP response was increased by insulin but the increment was inhibited by L-NMMA. Four hours of local forearm hyperinsulinemia causes a sustained increase in endothelium dependent vasodilation in resistance vessels, which is mediated by NO....

  5. Multipartite non-locality and entanglement signatures of a field-induced quantum phase transition

    Science.gov (United States)

    Batle, Josep; Alkhambashi, Majid; Farouk, Ahmed; Naseri, Mosayeb; Ghoranneviss, Mahmood

    2017-02-01

    Quantum correlation measures are limited in practice to a few number of parties, since no general theory is still capable of reaching the thermodynamic limit. In the present work we study entanglement and non-locality for a cluster of spins belonging to a compound that displays a magnetocaloric effect. A quantum phase transition (QPT) is induced by an external magnetic field B, in such a way that the corresponding quantum fluctuations are reproduced at a much smaller scale than the experimental outcomes, and then described by means of the aforementioned quantum measures.

  6. Impurity-induced localization of Bose-Einstein condensates in one-dimensional optical lattices

    Institute of Scientific and Technical Information of China (English)

    Wang Jian-Jun; Zhang Ai-Xia; Xue Ju-Kui

    2011-01-01

    The impurity-induced localization of two-component Bose-Einstein condensates loaded into deep one-dimensional optical lattices is studied both analytically and numerically.It is shown that,the analytical criteria for self-trapping and moving soliton/breather of the primary-component condensate are modified significantly by an admixture of an impurity component(the second component).The realization of the self-trapped state and the moving soliton/breather states of the primary-component becomes more easy with the minor admixture of the impurity-component,even if the two components are partly overlapped.

  7. Direct laser writing of polymeric nanostructures via optically induced local thermal effect

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Quang Cong [Laboratoire de Photonique Quantique et Moléculaire, UMR 8537, École Normale Supérieure de Cachan, CentraleSupélec, CNRS, Université Paris-Saclay, 61 avenue du Président Wilson, 94235 Cachan (France); Institute of Materials Science, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, 10000 Hanoi (Viet Nam); Nguyen, Dam Thuy Trang; Do, Minh Thanh; Luong, Mai Hoang; Journet, Bernard; Ledoux-Rak, Isabelle; Lai, Ngoc Diep, E-mail: nlai@lpqm.ens-cachan.fr [Laboratoire de Photonique Quantique et Moléculaire, UMR 8537, École Normale Supérieure de Cachan, CentraleSupélec, CNRS, Université Paris-Saclay, 61 avenue du Président Wilson, 94235 Cachan (France)

    2016-05-02

    We demonstrate the fabrication of desired structures with feature size below the diffraction limit by use of a positive photoresist. The direct laser writing technique employing a continuous-wave laser was used to optically induce a local thermal effect in a positive photoresist, which then allowed the formation of solid nanostructures. This technique enabled us to realize multi-dimensional sub-microstructures by use of a positive photoresist, with a feature size down to 57 nm. This mechanism acting on positive photoresists opens a simple and low-cost way for nanofabrication.

  8. Postoperative internal carotid artery restenosis after local anesthesia: presence of risk factors versus intraoperative shunt.

    Science.gov (United States)

    Hudorovic, Narcis; Lovricevic, Ivo; Hajnic, Hrvoje; Ahel, Zaky

    2010-08-01

    Published data suggest that the regional anesthetic technique used for carotid endarterectomy (CEA) increases the systolic arterial blood pressure and heart rate. At the same time local anesthesia reduced the shunt insertion rate. This study aimed to analyze risk factors and ischemic symptomatology in patients with postoperative internal carotid artery restenosis. The current retrospective study was undertaken to assess the results of CEA in 8000 patients who were operated during a five-year period in six regional cardiovascular centers. Carotid color coded flow imaging, medical history, clinical findings and atherosclerotic risk factors were analyzed. Among them, there were 33 patients (0.4%) with postoperative re-occlusion after CEA. The patients with restenosis were re-examined with carotid color coded flow imaging and data were compared with 33 consecutive patients with satisfactory postoperative findings to serve as a control group. In the restenosis group eight risk factors were analyzed (hypertension, smoking, hyperlipidemia, diabetes mellitus, history of stroke, transitory ischemic attack, heart attack and coronary disease), and compared with risk factors in control group. Study results suggested that early postoperative internal carotid artery restenosis was not caused by atherosclerosis risk factors but by intraoperative shunt usage.

  9. Some Non Genetic Factors Effects on Morphostructural Growth of Local Kids in Tunisian Arid Area

    Directory of Open Access Journals (Sweden)

    Ben Ammar Elgaaied Amel

    2008-01-01

    Full Text Available Data corresponding of 276 local kids` periodic control, harvested during 4 years (2001-2005 under pastoral mode in Tunisian arid region, was used to study some factors effects upon body parts evolution after birth. Morphostructural variables were; body length, height-at-withers and heart girth. The linear measurement periodically registered at every control day from birth and till 5 months age. For each kid, performances were standardized at typical ages; birth, 30, 60, 90, 120 and 150 days. Statistical analysis were achieved by GLM procedure and SNK (a = 5% means comparison test to identify factors effects upon studied variables and the homogeneous classes. The kid`s body parts seem affected (p<0.05 by several environmental factors, sex, type of birth and age of dam. The type of birth and the age of dam exerts a high effect (p<0.01 on all characters after the birth. However, the factors statistical effects depend to the kid`s age. The sex acts differently on the morphometric characters before and afterwards of two month age. Thus, phenotypic individual differences can be elapsed by environmental factors of arid harsh conditions. Such conclusion underlines the necessity to study the particularities of the genetic expression of adapted populations towards restrictive resources.

  10. The relationship between transcription initiation RNAs and CCCTC-binding factor (CTCF localization

    Directory of Open Access Journals (Sweden)

    Taft Ryan J

    2011-08-01

    Full Text Available Abstract Background Transcription initiation RNAs (tiRNAs are nuclear localized 18 nucleotide RNAs derived from sequences immediately downstream of RNA polymerase II (RNAPII transcription start sites. Previous reports have shown that tiRNAs are intimately correlated with gene expression, RNA polymerase II binding and behaviors, and epigenetic marks associated with transcription initiation, but not elongation. Results In the present work, we show that tiRNAs are commonly found at genomic CCCTC-binding factor (CTCF binding sites in human and mouse, and that CTCF sites that colocalize with RNAPII are highly enriched for tiRNAs. To directly investigate the relationship between tiRNAs and CTCF we examined tiRNAs originating near the intronic CTCF binding site in the human tumor suppressor gene, p21 (cyclin-dependent kinase inhibitor 1A gene, also known as CDKN1A. Inhibition of CTCF-proximal tiRNAs resulted in increased CTCF localization and increased p21 expression, while overexpression of CTCF-proximal tiRNA mimics decreased CTCF localization and p21 expression. We also found that tiRNA-regulated CTCF binding influences the levels of trimethylated H3K27 at the alternate upstream p21 promoter, and affects the levels of alternate p21 (p21alt transcripts. Extending these studies to another randomly selected locus with conserved CTCF binding we found that depletion of tiRNA alters nucleosome density proximal to sites of tiRNA biogenesis. Conclusions Taken together, these data suggest that tiRNAs modulate local epigenetic structure, which in turn regulates CTCF localization.

  11. Epidermal growth factor signaling induces behavioral quiescence in Caenorhabditis elegans.

    Science.gov (United States)

    Van Buskirk, Cheryl; Sternberg, Paul W

    2007-10-01

    The epidermal growth factor receptor (EGFR)/ErbB receptor tyrosine kinases regulate several aspects of development, including the development of the mammalian nervous system. ErbB signaling also has physiological effects on neuronal function, with influences on synaptic plasticity and daily cycles of activity. However, little is known about the effectors of EGFR activation in neurons. Here we show that EGF signaling has a nondevelopmental effect on behavior in Caenorhabditis elegans. Ectopic expression of the EGF-like ligand LIN-3 at any stage induces a reversible cessation of feeding and locomotion. These effects are mediated by neuronal EGFR (also called LET-23) and phospholipase C-gamma (PLC-gamma), diacylglycerol-binding proteins, and regulators of synaptic vesicle release. Activation of EGFR within a single neuron, ALA, is sufficient to induce a quiescent state. This pathway modulates the cessation of pharyngeal pumping and locomotion that normally occurs during the lethargus period that precedes larval molting. Our results reveal an evolutionarily conserved role for EGF signaling in the regulation of behavioral quiescence.

  12. Factors associated with induced abortion among women in Hohoe, Ghana.

    Science.gov (United States)

    Mote, Charity V; Otupiri, Easmon; Hindin, Michelle J

    2010-12-01

    In Hohoe, Ghana, induced abortion is the second highest cause of hospital admissions. We aimed to describe factors influencing induced abortion among 408 randomly selected women aged 15-49 years. 21% of the women had had an abortion; of those, 36% said they did not want to disrupt their education or employment; 66% of the abortions were performed by doctors. Bivariate logistic regression showed that compared with women with secondary education, women with basic education (OR = 0.31, 95% CI: 0.18-0.54) and uneducated women (OR = 0.24, 95% CI: 0.07-0.70) were significantly less likely to have had an abortion. Women who were married (OR = 1.83, 95% CI: 1.10-3.04), peri-urban residents (OR = 1.88, 95% CI: 0.95-3.94), and women with formal employment (OR = 2.22, 95% CI: 0.86-5.45) were more likely to have had an abortion. Stakeholders should improve access to effective contraception to lower the chance of needing an abortion and target education programmes at those with unmet need for contraception.

  13. Immunohistochemical localization of atrial natriuretic factor (ANF) in the excretory system of the rabbit parotid gland.

    Science.gov (United States)

    Valentino, B; Farina Lipari, E; Carini, F; Valenza, V

    1999-01-01

    The immunohistochemical localization of atrial natriuretic factor (ANF) in the rabbit parotid gland was performed using an antibody against rabbit ANF and avidin-biotin or streptoavidin as detector. Results showed positivity in cuboidal and columnar cells of intralobular ducts and in basal cells of extralobular and main excretory duct. These data support the hypothesis that ANF produced by intralobular ducts could act through a paracrine mechanism; ANF produced by extralobular and main ducts may play a role in the regulation of salivary composition.

  14. Local Franck-Condon factors in suspended carbon nanotube quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Cavaliere, Fabio; Mariani, Eros; Leturcq, Renaud; Stampfer, Christoph; Sassetti, Maura, E-mail: cavalier@fisica.unige.i

    2010-11-01

    We investigate the effects of the coupling between quantized vibrational modes (vibrons) and electronic degrees of freedom in suspended carbon nanotube quantum dots. The elastic deformations couple both to the total dot charge and to its spatial density fluctuations. The latter, neglected in the Anderson-Holstein model, have profound consequences if the size of the vibron and of the dot do not coincide, as is generically the case in experimental devices. When the vibron is smaller than the quantum dot, spatially varying local Franck-Condon factors emerge with striking effects on the transport properties of the system. The theoretical results are supported by our experimental observations.

  15. Role of mucus in gastric mucosal injury induced by local ischemia/reperfusion.

    Science.gov (United States)

    Seno, K; Joh, T; Yokoyama, Y; Itoh, M

    1995-09-01

    The role of gastric mucus was evaluated in a rat model of gastric epithelial damage induced by local ischemia/reperfusion (I/R) stress. In this model, blood-to-lumen chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) clearance served as an index of injury. Tetraprenyl acetone (TPA; 100 mg, 200 mg/kg IP) was used to stimulate mucus production. Administration of TPA increased both the hexosamine content in gastric tissue and the amount of alcian blue-periodic acid Schiff (AB-PAS) stained mucus in the mucosa in a dose-dependent manner. Increases in 51Cr-EDTA clearance induced by I/R were significantly attenuated by TPA in a dose-dependent manner. N-acetyl-L-cysteine (NAC; 0.6%, 0.8%) was perfused into the gastric lumen to assess the effect of reduction in mucus on the injury induced by I/R. Although mean values of hexosamine content were increased by perfusion with NAC, AB-PAS-stained mucus in the mucosa was significantly decreased in a dose-dependent manner. Perfusion of NAC did not change basal 51Cr-EDTA clearance but significantly exacerbated the increase in clearance induced by I/R in a dose-dependent manner. These results indicate that gastric mucus protects the gastric mucosa against I/R stress in vivo.

  16. Factors related to the local treatment failure of γ knife surgery for metastatic brain tumors.

    Science.gov (United States)

    Woo, Hyun Jin; Hwang, Sung Kyoo; Park, Seong Hyun; Hwang, Jeong Hyun; Hamm, In Suk

    2010-11-01

    Radiosurgery (RS) is regarded as a standard therapy for metastatic brain tumors, but local failure requiring repeated therapy for the same lesion remains an unsolved problem. The authors analyzed outcomes of gamma knife surgery (GKS) for metastatic lesions to identify factors of local treatment failure. The hospital records of 103 patients with a metastatic brain tumor and monitored for more than 6 months were analyzed. Lesion response to RS was analyzed in 77 patients with available gamma plan data. Local treatment failure was defined as lesion regrowth or repeat GKS within 6 months. In cases with multiple lesions, largest masses were evaluated. Primary sites, metastatic location, Karnofsky scale, tumor size, number of metastatic lesions, and various radiosurgical prescription parameters, namely, Paddick's conformity index (CI), Radiation Therapy Oncology Group (RTOG)-CI, and gradient index, were analyzed. Of the 103 study subjects, 58 were male and 45 were female. Primary sites were lung (n = 58), breast (n = 12), colon (n = 6), kidney (n = 7), rectum (n = 6), and others (n = 14). Median survival duration from the diagnosis of brain metastasis was 25 months. Local treatment failure occurred in 14 of 77 the patients (77 lesions) with available gamma plan data. A lung cancer primary site was found to have a lower GKS failure rate than a breast or a renal site (p < 0.05). Lesions with a high Paddicks' CI or a low RTOG-CI had a higher rate of treatment failure (p < 0.05). Multivariate analysis revealed that primary tumor site and Paddick's CI were related to treatment failure (p < 0.05). Brain metastases from renal and breast cancers had higher rates of local GKS treatment failure than those from lung cancer. Furthermore, high Paddick's CI revealed higher rate of local recurrence, and was not contributory to prevent local treatment failure. However, the enlargement of the diameter of the tumor after RS in the early follow

  17. Overexpression of Hypoxia-Inducible Factor-1α Exacerbates Endothelial Barrier Dysfunction Induced by Hypoxia

    Directory of Open Access Journals (Sweden)

    Pei Wang

    2013-09-01

    Full Text Available Background/Aims: The mechanisms involved in endothelial barrier dysfunction induced by hypoxia are incompletely understood. There is debate about the role of hypoxia-inducible factor-1α (HIF-1α in endothelial barrier disruption. The aim of this study was to investigate the effect of genetic overexpression of HIF-1α on barrier function and the underlying mechanisms in hypoxic endothelial cells. Methods: The plasmid pcDNA3.1/V5-His-HIF-1α was stably transfected into human endothelial cells. The cells were exposed to normoxia or hypoxia. The mRNA and protein expressions of HIF-1α were detected by RT-PCR and Western blot respectively. The barrier function was assessed by measuring the transendothelial electrical resistance (TER. The Western blot analysis was used to determine the protein expression of glucose transporter-1 (GLUT-1, zonular occludens-1 (ZO-1, occludin, and myosin light chain kinase (MLCK in endothelial cells. The mRNA expression of proinflammatory cytokines was detected by qRT-PCR. Results: Genetic overexpression of HIF-1α significantly increased the mRNA and protein expression of HIF-1α in endothelial cells. The overexpression of HIF-1α enhanced the hypoxia-induced increase of HIF-1α and GLUT-1 protein expression. HIF-1α overexpression not only exacerbated hypoxia-induced endothelial barrier dysfunction but also augmented hypoxia-induced up-regulation of MLCK protein expression. HIF-1α overexpression also enhanced IL-1β, IL-6 and TNF-α mRNA expression. Conclusion: We provide evidence that genetic overexpression of HIF-1α aggravates the hypoxia-induced endothelial barrier dysfunction via enhancing the up-regulation of MLCK protein expression caused by hypoxia, suggesting a potential role for HIF-1α in the pathogenesis of endothelial barrier dysfunction in hypoxia.

  18. Characterization of LPS-induced TNFα factor (LITAF) from orange-spotted grouper, Epinephelus coioides.

    Science.gov (United States)

    Cai, Jia; Huang, Youhua; Wei, Shina; Ouyang, Zhengliang; Huang, Xiaohong; Qin, Qiwei

    2013-12-01

    Lipopolysaccharide-induced TNFα factor (LITAF) is an important transcription factor that mediates cell apoptosis and inflammatory response. In the present study, we cloned and characterized a LITAF gene from orange-spotted grouper (Epinephelus coioides) (Ec-LITAF). Ec-LITAF encoded a predicted 142 amino acid protein which shared 74% identity to sablefish (Anoplopoma fimbria) LITAF homolog. Multiple amino acid alignment showed that Ec-LITAF contained a typical LITAF domain with two CXXC motifs. Phylogenetic analysis indicated that Ec-LITAF was closely related to that of sablefish. Ec-LITAF mRNA was widely expressed in different tissues and its expression level in spleen was up-regulated after Singapore grouper iridovirus (SGIV) infection. Subcellular localization analysis revealed that the distribution of Ec-LITAF showed diffuse and aggregated patterns in cytoplasm. Interestingly, the distribution of Ec-LITAF overlayed with a viral LITAF homolog (vLITAF) encoded by SGIV. Overexpression of Ec-LITAF in vitro up-regulated the expression of tumor necrosis factors (TNF1 and TNF2) and TNF receptors (TNFR1 and TNFR2), and the expression of itself initiated apoptosis in fish cells. In addition, overexpression of Ec-LITAF not only accelerated SGIV infection induced CPE and cell death, but also increased viral gene transcription. Taken together, our data suggested that Ec-LITAF might play crucial roles during SGIV replication.

  19. Investigating the Effective Factors on Entering into International Markets by Presenting the Local Islamic Model

    Directory of Open Access Journals (Sweden)

    Sayyed Mohammad Ali Alamolhodaei

    2015-03-01

    Full Text Available The internationalization of small and medium size businesses is regarded as one of the most leading general policies in many of the world’s countries. The reason is that it is often the small and medium size companies which have a vital role in industrial innovation and gain profit for their societies through economic development. This research has investigated and identified the effective factors (organizational factors and business etiquette in Islam on entering into international markets by presenting local Islamic model in the companies of incubator of Science and Technology Park. The statistical population of the research includes the existing companies of Incubator of Mashhad Science and Technology Park. The statistical sample was investigated through simple random sampling from managers of active companies in export in Science and Technology Park. AMOS and SPSS software were applied for data analysis to identify the effects among variables survey research methodology and questionnaire tools were used.

  20. Hypoxia-inducible factor 3 biology: complexities and emerging themes.

    Science.gov (United States)

    Duan, Cunming

    2016-02-15

    The hypoxia-inducible factor (HIF) family has three distinct members in most vertebrates. All three HIFs consist of a unique and oxygen-labile α-subunit and a common and stable β-subunit. While HIF-1 and HIF-2 function as master regulators of the transcriptional response to hypoxia, much less is known about HIF-3. The HIF-3α gene gives rise to multiple HIF-3α variants due to the utilization of different promoters, different transcription initiation sites, and alternative splicing. These HIF-3α variants are expressed in different tissues, at different developmental stages, and are differentially regulated by hypoxia and other factors. Recent studies suggest that different HIF-3α variants have different and even opposite functions. There is strong evidence that full-length HIF-3α protein functions as an oxygen-regulated transcription activator and that it activates a unique transcriptional program in response to hypoxia. Many HIF-3α target genes have been identified. While some short HIF-3α variants act as dominant-negative regulators of HIF-1/2α actions, other HIF-3α variants can inhibit HIF-1/2α actions by competing for the common HIF-β. There are also a number of HIF-3α variants yet to be explored. Future studies of these naturally occurring HIF-3α variants will provide new and important insights into HIF biology and may lead to the development of new therapeutic strategies.

  1. Epithelial Barrier Regulation by Hypoxia-Inducible Factor.

    Science.gov (United States)

    Glover, Louise E; Colgan, Sean P

    2017-09-01

    Mucosal tissues represent surfaces that are exposed to the outside world and provide a conduit for internal and external communication. Tissues such as the intestine and the lung are lined by layer(s) of epithelial cells that, when organized in three dimensions, provide a critical barrier to the flux of luminal contents. This selective barrier is provided through the regulated expression of junctional proteins and mucins. Tissue oxygen metabolism is central to the maintenance of homeostasis in the mucosa. In some organs (e.g., the colon), low baseline Po2 determines tissue metabolism and results in basal expression of the transcription factor, hypoxia-inducible factor (HIF), which is enhanced after ischemia/inflammation. Recent studies have indicated that HIF contributes fundamentally to the expression of barrier-related genes and in the regulation of barrier-adaptive responses within the mucosa. Here, we briefly review recent literature on the topic of hypoxia and HIF regulation of barrier in mucosal health and during disease.

  2. Musashi mediates translational repression of the Drosophila hypoxia inducible factor

    Science.gov (United States)

    Bertolin, Agustina P.; Katz, Maximiliano J.; Yano, Masato; Pozzi, Berta; Acevedo, Julieta M.; Blanco-Obregón, Dalmiro; Gándara, Lautaro; Sorianello, Eleonora; Kanda, Hiroshi; Okano, Hideyuki; Srebrow, Anabella; Wappner, Pablo

    2016-01-01

    Adaptation to hypoxia depends on a conserved α/β heterodimeric transcription factor called Hypoxia Inducible Factor (HIF), whose α-subunit is regulated by oxygen through different concurrent mechanisms. In this study, we have identified the RNA binding protein dMusashi, as a negative regulator of the fly HIF homologue Sima. Genetic interaction assays suggested that dMusashi participates of the HIF pathway, and molecular studies carried out in Drosophila cell cultures showed that dMusashi recognizes a Musashi Binding Element in the 3′ UTR of the HIFα transcript, thereby mediating its translational repression in normoxia. In hypoxic conditions dMusashi is downregulated, lifting HIFα repression and contributing to trigger HIF-dependent gene expression. Analysis performed in mouse brains revealed that murine Msi1 protein physically interacts with HIF-1α transcript, suggesting that the regulation of HIF by Msi might be conserved in mammalian systems. Thus, Musashi is a novel regulator of HIF that inhibits responses to hypoxia specifically when oxygen is available. PMID:27141964

  3. Thioredoxin interacting protein inhibits hypoxia-inducible factor transcriptional activity

    Science.gov (United States)

    Farrell, Michael R; Rogers, Lynette K; Liu, Yusen; Welty, Stephen E; Tipple, Trent E

    2010-01-01

    Vascular endothelial growth factor (VEGF) is required for proper lung development and is transcriptionally regulated in alveolar epithelial cells by hypoxia inducible factor (HIF). Previous findings in a newborn mouse model of bronchopulmonary dysplasia (BPD) suggest that thioredoxin interacting protein (Txnip) is a novel regulator of VEGF expression. The present studies were designed to test the hypothesis that Txnip negatively regulates VEGF through effects on HIF-mediated gene expression. To test this hypothesis, we first examined the levels of VEGF and Txnip protein in the lungs of 1 day-old newborn and E19 embryos and detected a significant inverse correlation. To elucidate the mechanisms underlying this relationship, we studied the effects of Txnip overexpression on HIF-mediated transcription using murine lung epithelial (MLE-12) cells. Overexpression of Txnip inhibited HIF-mediated reporter activity in both hypoxia and room air. Suppression of HIF activity by Txnip appeared to be independent of the ability of Txnip to bind to thioredoxin. Thus, our studies support a model in which Txnip is a potentially critical regulator of HIF-mediated gene transcription in the murine lung. Alterations in Txnip expression could alter lung VEGF expression in prematurely born human infants and contribute to the development of BPD. PMID:20692333

  4. Bone healing induced by local delivery of an engineered parathyroid hormone prodrug.

    Science.gov (United States)

    Arrighi, Isabelle; Mark, Silke; Alvisi, Monica; von Rechenberg, Brigitte; Hubbell, Jeffrey A; Schense, Jason C

    2009-03-01

    Regenerative medicine requires innovative therapeutic designs to accommodate high morphogen concentrations in local depots, provide their sustained presence, and enhance cellular invasion and directed differentiation. Here we present an example for inducing local bone regeneration with a matrix-bound engineered active fragment of human parathyroid hormone (PTH(1-34)), linked to a transglutaminase substrate for binding to fibrin as a delivery and cell-invasion matrix with an intervening plasmin-sensitive link (TGplPTH(1-34)). The precursor form displays very little activity and signaling to osteoblasts, whereas the plasmin cleavage product, as it would be induced under the enzymatic influence of cells remodeling the matrix, was highly active. In vivo animal bone-defect experiments showed dose-dependent bone formation using the PTH-fibrin matrix, with evidence of both osteoconductive and osteoinductive bone-healing mechanisms. Results showed that this PTH-derivatized matrix may have potential utility in humans as a replacement for bone grafts or to repair bone defects.

  5. Quantitative probing of tip-induced local cooling with a resistive nanoheater/thermometer

    Science.gov (United States)

    Hamian, Sina; Yun, Jeonghoon; Park, Inkyu; Park, Keunhan

    2016-12-01

    This article reports the investigation of tip-induced local cooling when an atomic force microscope (AFM) cantilever tip scans over a joule-heated Pt nanowire. We fabricated four-point-probe Pt resistive nanothermometers having a sensing area of 250 nm × 350 nm by combining electron-beam lithography and photolithography. The electrical resistance of a fabricated nanothermometer is ˜27.8 Ω at room temperature and is linearly proportional to the temperature increase up to 350 K. The equivalent temperature coefficient of resistance is estimated to be (7.0 ±0.1 )×10-4 K-1. We also joule-heated a nanothermometer to increase its sensing area temperature up to 338.5 ± 0.2 K, demonstrating that the same device can be used as a nanoheater. An AFM probe tip scanning over a heated nanoheater/thermometer's sensing area induces local cooling due to heat conduction through solid-solid contact, water meniscus, and surrounding air. The effective contact thermal conductance is 32.5 ± 0.8 nW/K. These results contribute to the better understanding of tip-substrate thermal interactions, which is the fundamental subject in tip-based thermal engineering applications.

  6. Traditional risk factors are predictive on segmental localization of coronary artery disease.

    Science.gov (United States)

    Tacoy, Gulten; Balcioglu, Akif Serhat; Akinci, Sinan; Erdem, Güliz; Kocaman, Sinan Altan; Timurkaynak, Timur; Cengel, Atiye

    2008-01-01

    The aim of this study was to investigate the relationship between established risk factors and segmental localization of coronary artery disease. A total of 2760 patients who underwent coronary angiography were enrolled into the study. Coronary angiographic segmental evaluation was performed according to the scheme of American Heart Association. Patients were classified into 2 groups (group 1: normal coronary artery segments, group 2: coronary artery segments with coronary artery disease). Smoking was highly related with left main coronary artery disease (odds ratio = 7.5; P = .005). Diabetes mellitus and male sex increased the risk of atherosclerosis in all coronary vasculature (odds ratio = 2.7-2.2; P < .001-P < .001). Hypertension was correlated with distal coronary artery (odds ratio = 1.4; P < .001) and family history with distal circumflex lesions (odds ratio = 4.5; P = .005) High triglyceride levels were associated with right coronary artery lesions (odds ratio = 1.00; P =.03). The effect of advanced age was small (odds ratio = 1.08; P < .001). Risk factors may be predictive for segmental localization.

  7. Prevalence and factors influencing depression among elderly living in the urban poor locality of Bengaluru city

    Directory of Open Access Journals (Sweden)

    T V Sanjay

    2014-01-01

    Full Text Available Background: The Indian elderly population is currently the second largest in the world. Mental disorders have got high prevalence and low priority among elderly in most of the countries around the world, of which depression being the most common treatable condition. In India, there is scarcity of research on prevalence and factors influencing depression among elderly from urban poor locality by adopting a geriatric depression scale-15 (GDS-15 scale. Objectives: (1 To find out the prevalence of geriatric depression, (2 to find out the factors associated with depression. Methodology: A cross-sectional study was conducted at urban poor locality of Bengaluru on 100 elderly people by applying GDS-15 Kannada version to assess the prevalence of depression and information regarding the sociodemographic characteristics, financial status, and comorbid conditions were collected. Results: The prevalence of depression assessed by using GDS-15 Kannada version was found to be 36%. Depression was more among 12 (70.6% from medium standard of living index (SLI group compared to 24 (28.9% from high SLI group, which was shown to be statistically significant. Among the elderly with depression, 31 (86.1% had some medical comorbidities when compared with 33 (51.6% elderly without depression, which was found to be statistically significant. Conclusions: The current research has shown prevalence of depression according to GDS-15 (Kannada version as 36% and influenced by SLI, hold on assets, insomnia and comorbidities, which needs to be confirmed by undertaking further studies.

  8. Turnover and vacancy rates for registered nurses: do local labor market factors matter?

    Science.gov (United States)

    Rondeau, Kent V; Williams, Eric S; Wagar, Terry H

    2008-01-01

    Turnover of nursing staff is a significant issue affecting health care cost, quality, and access. In recent years, a worldwide shortage of skilled nurses has resulted in sharply higher vacancy rates for registered nurses in many health care organizations. Much research has focused on the individual, group, and organizational determinants of turnover. Labor market factors have also been suggested as important contributors to turnover and vacancy rates but have received limited attention by scholars. This study proposes and tests a conceptual model showing the relationships of organization-market fit and three local labor market factors with organizational turnover and vacancy rates. The model is tested using ordinary least squares regression with data collected from 713 Canadian hospitals and nursing homes. Results suggest that, although modest in their impact, labor market and the organization-market fit factors do make significant yet differential contributions to turnover and vacancy rates for registered nurses. Knowledge of labor market factors can substantially shape an effective campaign to recruit and retain nurses. This is particularly true for employers who are perceived to be "employers-of-choice."

  9. Hypoxia-inducible factor-1α induces multidrug resistance protein in colon cancer

    Directory of Open Access Journals (Sweden)

    Lv Y

    2015-07-01

    Full Text Available Yingqian Lv, Shan Zhao, Jinzhu Han, Likang Zheng, Zixin Yang, Li Zhao Department of Oncology, The Second Hospital, Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China Abstract: Multidrug resistance is the major cause of chemotherapy failure in many solid tumors, including colon cancer. Hypoxic environment is a feature for all solid tumors and is important for the development of tumor resistance to chemotherapy. Hypoxia-inducible factor (HIF-1α is the key transcription factor that mediates cellular response to hypoxia. HIF-1α has been shown to play an important role in tumor resistance; however, the mechanism is still not fully understood. Here, we found that HIF-1α and the drug resistance-associated gene multidrug resistance associated protein 1 (MRP1 were induced by treatment of colon cancer cells with the hypoxia-mimetic agent cobalt chloride. Inhibition of HIF-1α by RNA interference and dominant-negative protein can significantly reduce the induction of MRP1 by hypoxia. Bioinformatics analysis showed that a hypoxia response element is located at -378 to -373 bp upstream of the transcription start site of MRP1 gene. Luciferase reporter assay combined with mutation analysis confirmed that this element is essential for hypoxia-mediated activation of MRP gene. Furthermore, RNA interference revealed that HIF-1α is necessary for this hypoxia-driven activation of MRP1 promoter. Importantly, chromatin immunoprecipitation analysis demonstrated that HIF-1α could directly bind to this HRE site in vivo. Together, these data suggest that MRP1 is a downstream target gene of HIF-1α, which provides a potential novel mechanism for HIF-1α-mediated drug resistance in colon cancer and maybe other solid tumors as well. Keywords: hypoxia, hypoxia-inducible factor-1α, multidrug resistance associated protein, transcriptional regulation, chemotherapy tolerance

  10. The role of hypoxia inducible factor-1 alpha in bypassing oncogene-induced senescence.

    Directory of Open Access Journals (Sweden)

    Mehtap Kilic Eren

    Full Text Available Oncogene induced senescence (OIS is a sustained anti-proliferative response acutely induced in primary cells via activation of mitogenic oncogenes such as Ras/BRAF. This mechanism acts as an initial barrier preventing normal cells transformation into malignant cell. Besides oncogenic activation and DNA damage response (DDR, senescence is modulated by a plethora of other factors, and one of the most important one is oxygen tension of the tissue. The aim of this study was to determine the impact of hypoxia on RasV12-induced senescence in human diploid fibroblasts (HDFs. We showed here that hypoxia prevents execution of oncogene induced senescence (OIS, through a strong down-regulation of senescence hallmarks, such as SA- β-galactosidase, H3K9me3, HP1γ, p53, p21CIP1 and p16INK4a in association with induction of hypoxia inducible factor-1α (HIF-1α. In addition, hypoxia also decreased marks of H-RasV12-induced DDR in both cell lines through down-regulation of ATM/ATR, Chk1 and Chk2 phosphorylation as well as decreased γ-H2AX positivity. Utilizing shRNA system targeting HIF-1α we show that HIF-1α is directly involved in down regulation of p53 and its target p21CIP1 but not p16INK4a. In line with this finding we found that knock down of HIF-1α leads to a strong induction of apoptotic response, but not restoration of senescence in Ras expressing HDFs in hypoxia. This indicates that HIF-1α is an important player in early steps of tumorigenesis, leading to suppression of senescence through its negative regulation of p53 and p21CIP1. In our work we describe a mechanism through which hypoxia and specifically HIF-1α preclude cells from maintaining senescence-driven anti proliferative response. These findings indicate the possible mechanism through which hypoxic environment helps premalignant cells to evade impingement of cellular failsafe pathways.

  11. Localized states induced by an oxygen vacancy in rutile TiO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chungwei; Shin, Donghan; Demkov, Alexander A., E-mail: demkov@physics.utexas.edu [Department of Physics, University of Texas at Austin, Austin, Texas 78712 (United States)

    2015-06-14

    Using density functional theory and model Hamiltonian analysis, we investigate the localized states induced by an oxygen vacancy in rutile TiO{sub 2}. We identify two classes of localized states—the hybrid and the polaron. The hybrid state is caused by the orbital overlap between three Ti atoms next to a vacancy and is mainly derived from the Ti e{sub g} orbitals. The polaron state is caused by the local lattice distortion and is mainly composed of one particular t{sub 2g} orbital from a single Ti atom. The first principles calculation shows that the polaron state is energetically favored, and the tight-binding analysis reveals the underlying connection between the bulk band structure and the orbital character of the polaron. The magnetic coupling between two nearby polaron states is found to be ferromagnetic. Using this picture, we analyze the results of recent theoretical calculations and experiments and discuss the connection to vacancies in SrTiO{sub 3}.

  12. A new mathematical model to simulate AVA cold-induced vasodilation reaction to local cooling

    Science.gov (United States)

    Rida, Mohamad; Karaki, Wafaa; Ghaddar, Nesreen; Ghali, Kamel; Hoballah, Jamal

    2014-01-01

    The purpose of this work was to integrate a new mathematical model with a bioheat model, based on physiology and first principles, to predict thermoregulatory arterio-venous anastomoses (AVA) and cold-induced vasodilation (CIVD) reaction to local cooling. The transient energy balance equations of body segments constrained by thermoregulatory controls were solved numerically to predict segmental core and skin temperatures, and arterial blood flow for given metabolic rate and environmental conditions. Two similar AVA-CIVD mechanisms were incorporated. The first was activated during drop in local skin temperature (hand immersions in cold fluid. When compared with published data, the model predicted accurately the onset time of CIVD at 25 min and T CIVD,min at 10 °C for hand exposure to still air at 0 °C. Good agreement was also obtained between predicted finger skin temperature and experimentally published values for repeated immersion in cold water at environmental conditions of 30, 25, and 20 °C. The CIVD thermal response was found related to core body temperature, finger skin temperature, and initial finger sensible heat loss rate upon exposure to cold fluid. The model captured central and local stimulations of the CIVD and accommodated observed variability reported in literature of onset time of CIVD reaction and T CIVD,min.

  13. Investigation of the local thermodynamic equilibrium of laser-induced aluminum plasma by Thomson scattering technique

    Energy Technology Data Exchange (ETDEWEB)

    Mendys, A., E-mail: agata.mendys@uj.edu.pl [Instytut Fizyki im. M. Smoluchowskiego, Uniwersytet Jagielloński, ul. Reymonta 4, 30-059 Kraków (Poland); Kański, M. [Instytut Fizyki im. M. Smoluchowskiego, Uniwersytet Jagielloński, ul. Reymonta 4, 30-059 Kraków (Poland); Farah-Sougueh, A. [Instytut Fizyki im. M. Smoluchowskiego, Uniwersytet Jagielloński, ul. Reymonta 4, 30-059 Kraków (Poland); GREMI — site de Bourges, Université d' Orléans, CNRS, rue Gaston Berger BP 4043, 18028 Bourges (France); Pellerin, S. [GREMI — site de Bourges, Université d' Orléans, CNRS, rue Gaston Berger BP 4043, 18028 Bourges (France); Pokrzywka, B. [Obserwatorium Astronomiczne na Suhorze, Uniwersytet Pedagogiczny, ul. Podchorażych 2, 30-084 Kraków (Poland); Dzierżęga, K. [Instytut Fizyki im. M. Smoluchowskiego, Uniwersytet Jagielloński, ul. Reymonta 4, 30-059 Kraków (Poland)

    2014-06-01

    A laser Thomson scattering method was applied to investigate the local Saha–Boltzmann equilibrium in aluminum laser-induced plasma. Plasma was created in ambient air using 4.5 ns pulses from a Nd:YAG laser at 532 nm, focused on an Al target. Spatially resolved measurements, performed for the time interval between 600 ns and 3 μs, show electron density and temperature to decrease from 3.4 × 10{sup 23} m{sup −3} to 0.5 × 10{sup 23} m{sup −3} and from 61,000 K to 13,000 K in the plasma core. The existence of local thermodynamic equilibria in the plasma was verified by comparing the rates of the collisional to radiative processes (the McWhirter criterion), as well as relaxation times and diffusion lengths of different plasma species, with the appropriate rate of electron density evolution and its gradients at given, experimentally determined, electron temperatures. We found these criteria to be much easier to satisfy for metallic plasma species than for nitrogen. The criteria are also easier to satisfy in the plasma core of higher electron density. - Highlights: • Laser Thomson scattering method was applied to investigate aluminum laser-induced plasma. • Spatio-temporal evolution of electron temperature and density was determined. • Three criteria for existence of local thermodynamic equilibrium were verified. • Criteria are much easier to satisfy for metallic plasma species than for nitrogen. • Criteria are easier to satisfy at earlier times and in the plasma core.

  14. Expression of transcription factors Slug in the lens epithelial cells undergoing epithelial-mesenchymal transition induced by connective tissue growth factor

    Directory of Open Access Journals (Sweden)

    Ying-Na Wang

    2015-10-01

    Full Text Available AIM:To investigate the expression of transcription factors Slug in human lens epithelial cells (HLECs undergoing epithelial-mesenchymal transition (EMT induced by connective tissue growth factor (CTGF.METHODS: HLECs were treated with CTGF of different concentrations (20, 50 and 100 ng/mL or without CTGF (control for 24h. The morphological changes of HLECs were analysed by microscopy. The expression and cellular localization of Slug was evaluated by immumo-fluorescence. Expressions of Slug, E-cadherin and alpha smooth muscle actin (α-SMA were further determined by Western blot analysis. RESULTS: HLECs showed spidle fibrolasts-like characteristics and loosely connected each other after CTGF treatment. The immuno-fluorescence staining indicated that Slug was localized in the nuclei and its expression was induced by CTGF. The relative expressions of Slug protein were 1.64±0.11, 1.96 ±0.03, 3.12 ±0.10, and 4.08±0.14, respectively, in response to control group and treatment with CTGF of 20, 50 and 100 ng/mL (F=443.86, PCONCLUSION: Transcription factor Slug may be involved in EMT of HLECs induced by CTGF in vitro.

  15. Detecting and Monitoring for Induced Seismicity without a Local Seismic Network: Application to the Youngstown, Ohio Induced Seismic Sequence

    Science.gov (United States)

    Holtkamp, S. G.; Brudzinski, M. R.; Currie, B. S.

    2013-12-01

    From March to December 2011, the Ohio Department of Natural Resources Ohio Seismic Network (ODNR OSN) recorded 11 earthquakes in Youngstown, OH. Pumping stopped after a local seismic network was installed in December and showed the earthquakes were nucleating near a nearby wastewater injection well. Unfortunately, 11 events identified by ODNR plus the local data represent a limited characterization of the sequence, making it difficult to confirm a causal relationship between injection and the earthquakes. This is a limitation of traditional seismic techniques, which required an earthquake to be M>~2.0 to be identified by ODNR before the local deployment. While local seismic deployments can provide adequate resolution to test triggering hypotheses, they suffer from two disadvantages: (1) these deployments are costly and scientifically focused, and (2) they only monitor seismicity after they are installed, and so are unable to characterize the beginning of the seismic sequence. Since there are over 200,000 wells associated with energy technologies in the US, it is not reasonable to install or expect local seismic observational capabilities with each potential case of induced seismicity. To address this limitation, we have developed a multiple station template matching (waveform cross correlation) algorithm, which is able to detect events ~10x smaller than traditional techniques, utilizing regional broadband seismometers located within 200km of the earthquakes. With this technique, we detect ~280 earthquakes in the Youngstown earthquake sequence, allowing us to test the correlation between seismicity and injection. We find that the earthquakes started two weeks after injection began and ended 2 weeks after injection ended. Our improved catalog shows that the rate of earthquakes closely follows the injection history, with a gradual rate increase at the beginning of the sequence and an abrupt reduction in earthquake rate after injection ceased. A combination of relative

  16. Using local lexicalized rules to identify heart disease risk factors in clinical notes.

    Science.gov (United States)

    Karystianis, George; Dehghan, Azad; Kovacevic, Aleksandar; Keane, John A; Nenadic, Goran

    2015-12-01

    Heart disease is the leading cause of death globally and a significant part of the human population lives with it. A number of risk factors have been recognized as contributing to the disease, including obesity, coronary artery disease (CAD), hypertension, hyperlipidemia, diabetes, smoking, and family history of premature CAD. This paper describes and evaluates a methodology to extract mentions of such risk factors from diabetic clinical notes, which was a task of the i2b2/UTHealth 2014 Challenge in Natural Language Processing for Clinical Data. The methodology is knowledge-driven and the system implements local lexicalized rules (based on syntactical patterns observed in notes) combined with manually constructed dictionaries that characterize the domain. A part of the task was also to detect the time interval in which the risk factors were present in a patient. The system was applied to an evaluation set of 514 unseen notes and achieved a micro-average F-score of 88% (with 86% precision and 90% recall). While the identification of CAD family history, medication and some of the related disease factors (e.g. hypertension, diabetes, hyperlipidemia) showed quite good results, the identification of CAD-specific indicators proved to be more challenging (F-score of 74%). Overall, the results are encouraging and suggested that automated text mining methods can be used to process clinical notes to identify risk factors and monitor progression of heart disease on a large-scale, providing necessary data for clinical and epidemiological studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Water-level changes induced by local and distant earthquakes at Long Valley caldera, California

    Science.gov (United States)

    Roeloffs, E.; Sneed, M.; Galloway, D.L.; Sorey, M.L.; Farrar, C.D.; Howle, J.F.; Hughes, J.

    2003-01-01

    Distant as well as local earthquakes have induced groundwater-level changes persisting for days to weeks at Long Valley caldera, California. Four wells open to formations as deep as 300 m have responded to 16 earthquakes, and responses to two earthquakes in the 3-km-deep Long Valley Exploratory Well (LVEW) show that these changes are not limited to weathered or unconsolidated near-surface rocks. All five wells exhibit water-level variations in response to earth tides, indicating they can be used as low-resolution strainmeters. Earthquakes induce gradual water-level changes that increase in amplitude for as long as 30 days, then return more slowly to pre-earthquake levels. The gradual water-level changes are always drops at wells LKT, LVEW, and CH-10B, and always rises at well CW-3. At a dilatometer just outside the caldera, earthquake-induced strain responses consist of either a step followed by a contractional strain-rate increase, or a transient contractional signal that reaches a maximum in about seven days and then returns toward the pre-earthquake value. The sizes of the gradual water-level changes generally increase with earthquake magnitude and decrease with hypocentral distance. Local earthquakes in Long Valley produce coseismic water-level steps; otherwise the responses to local earthquakes and distant earthquakes are indistinguishable. In particular, water-level and strain changes in Long Valley following the 1992 M7.3 Landers earthquake, 450 km distant, closely resemble those initiated by a M4.9 local earthquake on November 22, 1997, during a seismic swarm with features indicative of fluid involvement. At the LKT well, many of the response time histories are identical for 20 days after each earthquake, and can be matched by a theoretical solution giving the pore pressure as a function of time due to diffusion of a nearby, instantaneous, pressure drop. Such pressure drops could be produced by accelerated inflation of the resurgent dome by amounts too

  18. Acoustic and non-acoustic factors in modeling listener-specific performance of sagittal-plane sound localization

    Directory of Open Access Journals (Sweden)

    Piotr eMajdak

    2014-04-01

    Full Text Available The ability of sound-source localization in sagittal planes (along the top-down and front-back dimension varies considerably across listeners. The directional acoustic spectral features, described by head-related transfer functions (HRTFs, also vary considerably across listeners, a consequence of the listener-specific shape of the ears. It is not clear whether the differences in localization ability result from differences in the encoding of directional information provided by the HRTFs, i.e., acoustic factors, or from differences in auditory processing of those cues (e.g., spectral-shape sensitivity, i.e., non-acoustic factors.We addressed this issue by analyzing the listener-specific localization ability in terms of localization performance. Directional responses to spatially distributed broadband stimuli from 18 listeners were used. A model of sagittal-plane localization was fit individually for each listener by considering the actual localization performance, the listener-specific HRTFs representing the acoustic factor, and an uncertainty parameter representing the non-acoustic factors. The model was configured to simulate the condition of complete calibration of the listener to the tested HRTFs. Listener-specifically calibrated model predictions yielded correlations of, on average, 0.93 with the actual localization performance. Then, the model parameters representing the acoustic and non-acoustic factors were systematically permuted across the listener group.While the permutation of HRTFs affected the localization performance, the permutation of listener-specific uncertainty had a substantially larger impact. Our findings suggest that across-listener variability in sagittal-plane localization ability is only marginally determined by the acoustic factor, i.e., the quality of directional cues found in typical human HRTFs. Rather, the non-acoustic factor, supposed to represent the listeners' efficiency in processing directional cues, appears

  19. Novel Smad proteins localize to IR-induced double-strand breaks: interplay between TGFβ and ATM pathways

    Science.gov (United States)

    Wang, Minli; Saha, Janapriya; Hada, Megumi; Anderson, Jennifer A.; Pluth, Janice M.; O’Neill, Peter; Cucinotta, Francis A.

    2013-01-01

    Cellular damage from ionizing radiation (IR) is in part due to DNA damage and reactive oxygen species, which activate DNA damage response (DDR) and cytokine signaling pathways, including the ataxia telangiectasia mutated (ATM) and transforming growth factor (TGF)β/Smad pathways. Using classic double-strand breaks (DSBs) markers, we studied the roles of Smad proteins in DDR and the crosstalk between TGFβ and ATM pathways. We observed co-localization of phospho-Smad2 (pSmad2) and Smad7 with DSB repair proteins following low and high linear energy transfer (LET) radiation in human fibroblasts and epithelial cells. The decays of both foci were similar to that of γH2AX foci. Irradiation with high LET particles induced pSmad2 and Smad7 foci tracks indicating the particle trajectory through cells. pSmad2 foci were absent in S phase cells, while Smad7 foci were present in all phases of cell cycle. pSmad2 (but not Smad7) foci were completely abolished when ATM was depleted or inactivated. In contrast, a TGFβ receptor 1 (TGFβR1) inhibitor abrogated Smad7, but not pSmad2 foci at DSBs sites. In summary, we suggest that Smad2 and Smad7 contribute to IR-induced DSB signaling in an ATM or TGFβR1-dependent manner, respectively. PMID:23221633

  20. Nerve growth factor partially recovers inflamed skin from stress-induced worsening in allergic inflammation.

    Science.gov (United States)

    Peters, Eva M J; Liezmann, Christiane; Spatz, Katharina; Daniltchenko, Maria; Joachim, Ricarda; Gimenez-Rivera, Andrey; Hendrix, Sven; Botchkarev, Vladimir A; Brandner, Johanna M; Klapp, Burghard F

    2011-03-01

    Neuroimmune dysregulation characterizes atopic disease, but its nature and clinical impact remain ill-defined. Induced by stress, the neurotrophin nerve growth factor (NGF) may worsen cutaneous inflammation. We therefore studied the role of NGF in the cutaneous stress response in a mouse model for atopic dermatitis-like allergic dermatitis (AlD). Combining several methods, we found that stress increased cutaneous but not serum or hypothalamic NGF in telogen mice. Microarray analysis showed increased mRNAs of inflammatory and growth factors associated with NGF in the skin. In stress-worsened AlD, NGF-neutralizing antibodies markedly reduced epidermal thickening together with NGF, neurotrophin receptor (tyrosine kinase A and p75 neurotrophin receptor), and transforming growth factor-β expression by keratinocytes but did not alter transepidermal water loss. Moreover, NGF expression by mast cells was reduced; this corresponded to reduced cutaneous tumor necrosis factor-α (TNF-α) mRNA levels but not to changes in mast cell degranulation or in the T helper type 1 (Th1)/Th2 cytokine balance. Also, eosinophils expressed TNF receptor type 2, and we observed reduced eosinophil infiltration after treatment with NGF-neutralizing antibodies. We thus conclude that NGF acts as a local stress mediator in perceived stress and allergy and that increased NGF message contributes to worsening of cutaneous inflammation mainly by enhancing epidermal hyperplasia, pro-allergic cytokine induction, and allergy-characteristic cellular infiltration.

  1. Determining the torus covering factors for a sample of type 1 AGN in the local Universe

    CERN Document Server

    Ezhikode, Savithri H; Done, Chris; Ward, Martin; Dewangan, Gulab C; Misra, Ranjeev; Philip, Ninan Sajeeth

    2016-01-01

    The unification scheme of active galactic nuclei (AGN) proposes the presence of a dusty torus around the central source, governing the differences between AGN spectral properties. A fraction of the AGN luminosity is absorbed by the dusty torus and is re-radiated in the infrared (IR) band. Thus the fraction of the sky covered by the torus as seen from the central source, known as the covering factor f_c, can be obtained from the ratio of the IR to the bolometric luminosities of the source. However, because of the uncertainty in determining bolometric luminosities, the estimation of covering factors has proven difficult, especially in the local Universe where the peak of the observed spectral energy distributions (SEDs) lie in the ultraviolet. In this work, we determine the covering factors of an X-ray/optically selected sample of 51 type 1 AGN analysed by Jin et al. The bolometric luminosities of these sources can be derived using a self-consistent, energy-conserving model that estimates the contribution in th...

  2. Detection of localized tooth-related factors that predispose to periodontal infections.

    Science.gov (United States)

    Matthews, Debora C; Tabesh, Moe

    2004-01-01

    The primary goal of periodontal therapy is to produce an environment that is conducive to oral health. This is achieved by eliminating the subgingival infection and implementing supragingival plaque control measures designed to prevent the re-colonization of the sulcus. Local etiologic factors, as described above, my prevent the removal of subgingival plaque, and may even contribute to destruction of the periodontal tissues. Thus, it is crucial to be able to recognize and, when possible, eliminate any plaque-retentive factor that could contribute to disease progression. Iatrogenic factors such as subgingival margins, restorative overhangs, overcontoured restorations and unpolished surfaces can be altered. Similarly, cervical enamel projections, enamel pearls and, in certain instances, palatal grooves can be removed or recontoured to enable the patient to access the area for good plaque control. There are some things that we cannot alter. Anatomic anomalies, particularly in posterior teeth, cannot be changed. However, awareness of potential anatomic variations and early detection of them may be able to prevent future attachment loss.

  3. Nasal administration of interleukin-33 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma surrogate.

    Science.gov (United States)

    Shan, Shan; Li, Yan; Wang, Jingjing; Lv, Zhe; Yi, Dawei; Huang, Qiong; Corrigan, Chris J; Wang, Wei; Quangeng, Zhang; Ying, Sun

    2016-05-01

    The T-helper cell type 2-promoting cytokine interleukin-33 (IL-33) has been implicated in asthma pathogenesis. Angiogenesis is a feature of airways remodelling in asthma. We hypothesized that IL-33 induces airways angiogenesis and expression of angiogenic factors in an established murine surrogate of asthma. In the present study, BALB/c mice were subjected to serial intranasal challenge with IL-33 alone for up to 70 days. In parallel, ovalbumin (OVA) -sensitized mice were subjected to serial intranasal challenge with OVA or normal saline to serve as positive and negative controls, respectively. Immunohistochemical analysis of expression of von Willebrand factor and erythroblast transformation-specific-related gene, both blood vessel markers, and angiogenic factors angiogenin, insulin-like growth factor-1, endothelin-1, epidermal growth factor and amphiregulin was performed in lung sections ex vivo. An established in-house assay was used to test whether IL-33 was able to induce microvessel formation by human vascular endothelial cells. Results showed that serial intranasal challenge of mice with IL-33 or OVA resulted in proliferation of peribronchial von Willebrand factor-positive blood vessels to a degree closely related to the total expression of the angiogenic factors amphiregulin, angiogenin, endothelin-1, epidermal growth factor and insulin-like growth factor-1. IL-33 also induced microvessel formation by human endothelial cells in a concentration-dependent fashion in vitro. Our data are consistent with the hypothesis that IL-33 has the capacity to induce angiogenesis at least partly by increasing local expression of multiple angiogenic factors in an allergen-independent murine asthma surrogate, and consequently that IL-33 or its receptor is a potential novel molecular target for asthma therapy.

  4. Copper is required for cobalt-induced transcriptional activity of hypoxia-inducible factor-1.

    Science.gov (United States)

    Qiu, Liying; Ding, Xueqin; Zhang, Zhen; Kang, Y James

    2012-08-01

    Cobalt inhibits prolyl hydroxylases, leading to the accumulation of hypoxia-inducible factor-1α (HIF-1α) and a concomitant increase in the transcriptional activity of HIF-1. Therefore, cobalt has been under development as a drug for activating HIF-1 under some disease conditions. However, it has been shown that ischemic conditions resulted in the loss of copper, and the activation of HIF-1 would not occur unless copper was supplemented. The present study was undertaken to test the hypothesis that copper is also required for the cobalt activation of HIF-1 transcriptional activity. Human umbilical vein endothelial cells subjected to treatment with cobalt chloride (CoCl(2)) at concentrations above 25 μM for 2 h resulted in an accumulation of HIF-1α, which was determined by Western blot analysis, and an increase in the expression of vascular endothelial growth factor (VEGF), which was determined by real-time reverse transcription-polymerase chain reaction analysis for mRNA levels and enzyme-linked immunosorbent assay analysis for protein levels. The copper chelator tetraethylenepentamine at 25 μM did not significantly affect the accumulation of HIF-1α but blocked increases in VEGF mRNA and protein levels, an effect that could be reversed by the addition of 25 μM copper sulfate (CuSO(4)). In addition, gene silencing of the copper chaperone for Cu,Zn-superoxide dismutase blocked VEGF expression with little effect on cobalt-induced HIF-1α accumulation. The present study thus demonstrates that copper was required for cobalt-activated transcriptional activity of HIF-1, although copper did not affect cobalt-induced accumulation of HIF-1α in the cells.

  5. LPS-inducible factor(s) from activated macrophages mediates cytolysis of Naegleria fowleri amoebae

    Energy Technology Data Exchange (ETDEWEB)

    Cleary, S.F.; Marciano-Cabral, F.

    1986-03-01

    Soluble cytolytic factors of macrophage origin have previously been described with respect to their tumoricidal activity. The purpose of this study was to investigate the mechanism and possible factor(s) responsible for cytolysis of the amoeba Naegleria fowleri by activated peritoneal macrophages from B6C3F1 mice. Macrophages or conditioned medium (CM) from macrophage cultures were incubated with /sup 3/H-Uridine labeled amoebae. Percent specific release of label served as an index of cytolysis. Bacille Calmette-Guerin (BCG) and Corynebacterium parvum macrophages demonstrated significant cytolysis of amoebae at 24 h with an effector to target ratio of 10:1. Treatment of macrophages with inhibitors of RNA or protein synthesis blocked amoebicidal activity. Interposition of a 1 ..mu..m pore membrane between macrophages and amoebae inhibited killing. Inhibition in the presence of the membrane was overcome by stimulating the macrophages with LPS. CM from SPS-stimulated, but not unstimulated, cultures of activated macrophages was cytotoxic for amoebae. The activity was heat sensitive and was recovered from ammonium sulfate precipitation of the CM. Results indicate that amoebicidal activity is mediated by a protein(s) of macrophage origin induced by target cell contact or stimulation with LPS.

  6. Hypoxia-inducible factor 1 alpha and vascular endothelial growth factor overexpression in ischemic colitis

    Institute of Scientific and Technical Information of China (English)

    Tomoyuki Okuda; Takeshi Azuma; Masahiro Ohtani; Ryuho Masaki; Yoshiyuki Ito; Yukinao Yamazaki; Shigeji Ito; Masaru Kuriyama

    2005-01-01

    AIM: To examine the etiology and pathophysiology in human ischemic colitis from the viewpoint of ischemic favors such as hypoxia-inducible factor 1 alpha (HIF-1alpha and vascular endothelial growth factor (VEGF).METHODS: Thirteen patients with ischemic colitis and 21 normal controls underwent colonoscopy. The follow-up colonoscopy was performed in 8 patients at 7 to 10 d after theoccurrence of ischemic colitis. Biopsy samples were subjected to real-time RT-PCR and immunohistochemistry to detect the expression of HIF-1 alpha and VEGF.RESULTS: HIF-1 alpha and VEGF expression were found in the normal colon tissues by RT-PCR and immunohistochemistry.HIF-1 alpha and VEGF were overexpressed in the lesions of ischemic colitis. Overexpressed HIF-1 alpha and VEGF RNA quickly decreased to the normal level in the scar regions at 7 to 10 d after the occurrence of ischemic colitis.CONCLUSION: Constant expression of HIF-1 alpha and VEGF in normal human colon tissue suggested that HIF-1alpha and VEGF play an important role in maintaining tissue integrity. We confirmed the ischemic crisis in ischemic colitis at the molecular level, demonstrating overexpression of HIF-1 alpha and VEGF in ischemic lesions. These ischemic factors may play an important role in the pathophysiology of ischemic colitis.

  7. Mechanics of Coriolis stimulus and inducing factors of motion sickness.

    Science.gov (United States)

    Isu, N; Shimizu, T; Sugata, K

    2001-12-01

    To specify inducing factors of motion sickness comprised in Coriolis stimulus, or cross-coupled rotation, the sensation of rotation derived from the semicircular canal system during and after Coriolis stimulus under a variety of stimulus conditions, was estimated by an approach from mechanics with giving minimal hypotheses and simplifications on the semicircular canal system and the sensory nervous system. By solving an equation of motion of the endolymph during Coriolis stimulus, rotating angle of the endolymph was obtained, and the sensation of rotation derived from each semicircular canal was estimated. Then the sensation derived from the whole semicircular canal system was particularly considered in two cases of a single Coriolis stimulus and cyclic Coriolis stimuli. The magnitude and the direction of sensation of rotation were shown to depend on an angular velocity of body rotation and a rotating angle of head movement (amplitude of head oscillation when cyclic Coriolis stimuli) irrespective of initial angle (center angle) of the head relative to the vertical axis. The present mechanical analysis of Coriolis stimulus led a suggestion that the severity of nausea evoked by Coriolis stimulus is proportional to the effective value of the sensation of rotation caused by the Coriolis stimulus.

  8. Drug-induced proarrhythmia: risk factors and electrophysiological mechanisms.

    Science.gov (United States)

    Frommeyer, Gerrit; Eckardt, Lars

    2016-01-01

    Drug-induced ventricular tachyarrhythmias can be caused by cardiovascular drugs, noncardiovascular drugs, and even nonprescription agents. They can result in arrhythmic emergencies and sudden cardiac death. If a new arrhythmia or aggravation of an existing arrhythmia develops during therapy with a drug at a concentration usually considered not to be toxic, the situation can be defined as proarrhythmia. Various cardiovascular and noncardiovascular drugs can increase the occurrence of polymorphic ventricular tachycardia of the 'torsade de pointes' type. Antiarrhythmic drugs, antimicrobial agents, and antipsychotic and antidepressant drugs are the most important groups. Age, female sex, and structural heart disease are important risk factors for the occurrence of torsade de pointes. Genetic predisposition and individual pharmacodynamic and pharmacokinetic sensitivity also have important roles in the generation of arrhythmias. An increase in spatial or temporal dispersion of repolarization and a triangular action-potential configuration have been identified as crucial predictors of proarrhythmia in experimental models. These studies emphasized that sole consideration of the QT interval is not sufficient to assess the proarrhythmic risk. In this Review, we focus on important triggers of proarrhythmia and the underlying electrophysiological mechanisms that can enhance or prevent the development of torsade de pointes.

  9. Acute vascular endothelial growth factor expression during hypertrophy is muscle phenotype specific and localizes as a striated pattern within fibres.

    Science.gov (United States)

    Parvaresh, Kevin C; Huber, Ashley M; Brochin, Robert L; Bacon, Phoebe L; McCall, Gary E; Huey, Kimberly A; Hyatt, Jon-Philippe K

    2010-11-01

    Skeletal muscle hypertrophy requires the co-ordinated expression of locally acting growth factors that promote myofibre growth and concurrent adaptive changes in the microvasculature. These studies tested the hypothesis that vascular endothelial growth factor (VEGF) and heparin-binding epidermal growth factor (HB-EGF) expression are upregulated during the early stages of compensatory muscle growth induced by chronic functional overload (FO). Bilateral FO of the plantaris and soleus muscles was induced for 3 or 7 days in the hindlimbs of adult female Sprague-Dawley rats (n = 5 per group) and compared with control (non-FO) rats. Relative muscle mass (in mg (kg body weight)(-1)) increased by 18 and 24% after 3 days and by 20 and 33% after 7 days in the plantaris and soleus muscles, respectively. No differences in HB-EGF mRNA or protein were observed in either muscle of FO rats relative to control muscles. The VEGF mRNA was similar in the soleus muscles of FO and control rats, whereas a significant elevation occurred at 3 and 7 days of FO in the plantaris muscle. However, VEGF protein expression after 3 days of FO exhibited a differential response; expression in the soleus muscle decreased 1.6-fold, whereas that in the plantaris muscle increased 1.8-fold compared with the control muscle. After 7 days of FO, VEGF protein remained elevated within the plantaris muscle, but returned to basal levels in the soleus. Robust basal HB-EGF and VEGF protein expression was consistently seen in control muscles. In all groups, immunohistochemistry for VEGF protein displayed a distinct striated expression pattern within myofibres, with considerably less labelling in extracellular spaces. Constitutive expression of HB-EGF and VEGF in control myofibres is consistent with housekeeping roles for these growth factors in skeletal muscle tissue. However, the specific patterns of VEGF expression in these muscles during FO may reflect the chronic changes in neural recruitment between muscles

  10. Local dynamics of proteins and DNA evaluated from crystallographic B factors

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Bohdan, E-mail: bohdan.schneider@gmail.com [Institute of Biotechnology AS CR, Videnska 1083, 142 20 Prague (Czech Republic); Gelly, Jean-Christophe; Brevern, Alexandre G. de [INSERM, U1134, DSIMB, 75739 Paris (France); Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1134, 75739 Paris (France); Institut National de la Transfusion Sanguine (INTS), 75739 Paris (France); Laboratoire d’Excellence GR-Ex, 75739 Paris (France); Černý, Jiří [Institute of Biotechnology AS CR, Videnska 1083, 142 20 Prague (Czech Republic)

    2014-09-01

    Distributions of scaled B factors from 704 protein–DNA complexes reflect primarily the neighbourhood of amino-acid and nucleotide residues: their flexibility grows from the protein core to protein–protein and protein–DNA interfaces, to solvent-exposed residues. Some of the findings clearly observed at higher resolution structures can no longer be observed for structures at low resolution indicating problems in refinement protocols. The dynamics of protein and nucleic acid structures is as important as their average static picture. The local molecular dynamics concealed in diffraction images is expressed as so-called B factors. To find out how the crystal-derived B factors represent the dynamic behaviour of atoms and residues of proteins and DNA in their complexes, the distributions of scaled B factors from a carefully curated data set of over 700 protein–DNA crystal structures were analyzed [Schneider et al. (2014 ▶), Nucleic Acids Res.42, 3381–3394]. Amino acids and nucleotides were categorized based on their molecular neighbourhood as solvent-accessible, solvent-inaccessible (i.e. forming the protein core) or lying at protein–protein or protein–DNA interfaces; the backbone and side-chain atoms were analyzed separately. The B factors of two types of crystal-ordered water molecules were also analyzed. The analysis confirmed several expected features of protein and DNA dynamics, but also revealed surprising facts. Solvent-accessible amino acids have B factors that are larger than those of residues at the biomolecular interfaces, and core-forming amino acids are the most restricted in their movement. A unique feature of the latter group is that their side-chain and backbone atoms are restricted in their movement to the same extent; in all other amino-acid groups the side chains are more floppy than the backbone. The low values of the B factors of water molecules bridging proteins with DNA and the very large fluctuations of DNA phosphates are

  11. Built environmental factors and adults' travel behaviors: Role of street layout and local destinations.

    Science.gov (United States)

    Koohsari, Mohammad Javad; Owen, Neville; Cole, Rachel; Mavoa, Suzanne; Oka, Koichiro; Hanibuchi, Tomoya; Sugiyama, Takemi

    2017-03-01

    Street layout is consistently associated with adults' travel behaviors, however factors influencing this association are unclear. We examined associations of street layout with travel behaviors: walking for transport (WT) and car use; and, the extent to which these relationships may be accounted for by availability of local destinations. A 24-h travel diary was completed in 2009 by 16,345 adult participants of the South-East Queensland Household Travel Survey, Australia. Three travel-behavior outcomes were derived: any home-based WT; over 30min of home-based WT; and, over 60min of car use. For street layout, a space syntax measure of street integration was calculated for each Statistical Area 1 (SA1, the smallest geographic unit in Australia). An objective measure of availability of destinations - Walk Score - was also derived for each SA1. Logistic regression examined associations of street layout with travel behaviors. Mediation analyses examined to what extent availability of destinations explained the associations. Street integration was significantly associated with travel behaviors. Each one-decile increment in street integration was associated with an 18% (95%CI: 1.15, 1.21) higher odds of any home-based WT; a 10% (95%CI: 1.06, 1.15) higher odds of over 30min of home-based WT; and a 5% (95%CI: 0.94, 0.96) lower odds of using a car over 60min. Local destinations partially mediated the effects of street layout on travel behaviors. Well-connected street layout contributes to active travel partially through availability of more local destinations. Urban design strategies need to address street layout and destinations to promote active travel among residents.

  12. Local and Landscape Factors Determining Occurrence of Phyllostomid Bats in Tropical Secondary Forests

    Science.gov (United States)

    Avila-Cabadilla, Luis Daniel; Sanchez-Azofeifa, Gerardo Arturo; Stoner, Kathryn Elizabeth; Alvarez-Añorve, Mariana Yolotl; Quesada, Mauricio; Portillo-Quintero, Carlos Alonso

    2012-01-01

    Neotropical forests are being increasingly replaced by a mosaic of patches of different successional stages, agricultural fields and pasture lands. Consequently, the identification of factors shaping the performance of taxa in anthropogenic landscapes is gaining importance, especially for taxa playing critical roles in ecosystem functioning. As phyllostomid bats provide important ecological services through seed dispersal, pollination and control of animal populations, in this study we assessed the relationships between phyllostomid occurrence and the variation in local and landscape level habitat attributes caused by disturbance. We mist-netted phyllostomids in 12 sites representing 4 successional stages of a tropical dry forest (initial, early, intermediate and late). We also quantitatively characterized the habitat attributes at the local (vegetation structure complexity) and the landscape level (forest cover, area and diversity of patches). Two focal scales were considered for landscape characterization: 500 and 1000 m. During 142 sampling nights, we captured 606 individuals representing 15 species and 4 broad guilds. Variation in phyllostomid assemblages, ensembles and populations was associated with variation in local and landscape habitat attributes, and this association was scale-dependent. Specifically, we found a marked guild-specific response, where the abundance of nectarivores tended to be negatively associated with the mean area of dry forest patches, while the abundance of frugivores was positively associated with the percentage of riparian forest. These results are explained by the prevalence of chiropterophilic species in the dry forest and of chiropterochorous species in the riparian forest. Our results indicate that different vegetation classes, as well as a multi-spatial scale approach must be considered for evaluating bat response to variation in landscape attributes. Moreover, for the long-term conservation of phyllostomids in anthropogenic

  13. Dynamic form factor of two-component plasmas beyond the static local field approximation

    CERN Document Server

    Daligault, J

    2003-01-01

    The spectrum of ion density fluctuations in a strongly coupled plasma is described both within the static G(k, 0) and high-frequency G(k, infinity) local field approximation. By a direct comparison with molecular dynamics data, we find that for large coupling, G(k, 0) is inadequate. Based on this result, we employ the Zwanzig-Mori memory function approach to model the Thomson scattering cross section, i.e. the electron dynamic form factor S sub e sub e (k, omega) of a dense two-component plasma. We show the sensitivity of S sub e sub e (k, omega) to three approximations for G(k, omega).

  14. Immunohistochemical localization of epidermal growth factor in the second-trimester human fetus

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Kryger-Baggesen, N; Nexø, Ebba

    1996-01-01

    Epidermal growth factor (EGF) is considered to be important in mammalian neonatal growth and development. In order to clarify its developmental role, we have investigated, by immunohistochemistry, the localization of EGF and the time of its first appearance in various organs from a series of 25...... midtrimester human fetuses with a gestational age ranging from 13 to 22 weeks. The first detectable EGF immunoreactivity occurred in week 15-16 fetuses in the placenta, the skin, the distal tubules of the kidney, the surface epithelium of the stomach, and the tips of the small intestinal villi, as well...... as in a few Paneth cells. Glandular structures, such as the glands of the cardia and the pyloric part of the stomach, Brunner's glands of the duodenum, the pancreas, and the submucous glands of the trachea, showed positive EGF immunoreactivity later (week 17). Thus, apart from the kidney, staining...

  15. AFM characterization of the shape of surface structures with localization factor.

    Science.gov (United States)

    Bonyár, Attila

    2016-08-01

    Although with the use of scanning probe microscopy (SPM) methods the topographical imaging of surfaces is now widely available, the characterization of surface structures, especially their shape, and the processes which change these features is not trivial with the existing surface describing parameters. In this work the application of a parameter called localization factor is demonstrated for the quantitative characterization of surface structures and for processes which alter the shape of these structures. The theory and optimal operation range of this parameter are discussed with three application examples: microstructure characterization of gold thin films, characterization of the changes in the grain structure of these films during thermal annealing, and finally, characterization of the oxidation processes on a polished tin surface.

  16. Spatial and topological organization of DNA chains induced by gene co-localization.

    Directory of Open Access Journals (Sweden)

    Ivan Junier

    2010-02-01

    Full Text Available Transcriptional activity has been shown to relate to the organization of chromosomes in the eukaryotic nucleus and in the bacterial nucleoid. In particular, highly transcribed genes, RNA polymerases and transcription factors gather into discrete spatial foci called transcription factories. However, the mechanisms underlying the formation of these foci and the resulting topological order of the chromosome remain to be elucidated. Here we consider a thermodynamic framework based on a worm-like chain model of chromosomes where sparse designated sites along the DNA are able to interact whenever they are spatially close by. This is motivated by recurrent evidence that there exist physical interactions between genes that operate together. Three important results come out of this simple framework. First, the resulting formation of transcription foci can be viewed as a micro-phase separation of the interacting sites from the rest of the DNA. In this respect, a thermodynamic analysis suggests transcription factors to be appropriate candidates for mediating the physical interactions between genes. Next, numerical simulations of the polymer reveal a rich variety of phases that are associated with different topological orderings, each providing a way to increase the local concentrations of the interacting sites. Finally, the numerical results show that both one-dimensional clustering and periodic location of the binding sites along the DNA, which have been observed in several organisms, make the spatial co-localization of multiple families of genes particularly efficient.

  17. Role of tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) axis in rheumatic diseases

    Institute of Scientific and Technical Information of China (English)

    ZHU Li-xiu; ZHANG Hai-hong; MEI Yi-fang; ZHAO Yan-ping; ZHANG Zhi-yi

    2012-01-01

    Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily of structurally related cytokines and is known to induce proliferation,migration,differentiation,apoptotic cell death,inflammation,and angiogenesis.These physiological processes are induced by the binding of TWEAK to fibroblast growth factor-inducible 14 (Fn14),a highly inducible cell-surface receptor that is linked to several intracellular signaling pathways,including the nuclear factor-κB (NF-κB) pathway.This review discusses the role of the TWEAK-Fn14 axis in several rheumatic diseases and the potential therapeutic benefits of modulation of the TWEAK-Fn14 pathway.

  18. Spatial Outlier Detection of CO2 Monitoring Data Based on Spatial Local Outlier Factor

    Directory of Open Access Journals (Sweden)

    Liu Xin

    2015-12-01

    Full Text Available Spatial local outlier factor (SLOF algorithm was adopted in this study for spatial outlier detection because of the limitations of the traditional static threshold detection. Based on the spatial characteristics of CO2 monitoring data obtained in the carbon capture and storage (CCS project, the K-Nearest Neighbour (KNN graph was constructed using the latitude and longitude information of the monitoring points to identify the spatial neighbourhood of the monitoring points. Then SLOF was adopted to calculate the outlier degrees of the monitoring points and the 3σ rule was employed to identify the spatial outlier. Finally, the selection of K value was analysed and the optimal one was selected. The results show that, compared with the static threshold method, the proposed algorithm has a higher detection precision. It can overcome the shortcomings of the static threshold method and improve the accuracy and diversity of local outlier detection, which provides a reliable reference for the safety assessment and warning of CCS monitoring.

  19. Diffusion in the presence of a local attracting factor: Theory and interdisciplinary applications

    Science.gov (United States)

    Veermäe, Hardi; Patriarca, Marco

    2017-06-01

    In many complex diffusion processes the drift of random walkers is not caused by an external force, as in the case of Brownian motion, but by local variations of fitness perceived by the random walkers. In this paper, a simple but general framework is presented that describes such a type of random motion and may be of relevance in different problems, such as opinion dynamics, cultural spreading, and animal movement. To this aim, we study the problem of a random walker in d dimensions moving in the presence of a local heterogeneous attracting factor expressed in terms of an assigned position-dependent "attractiveness function." At variance with standard Brownian motion, the attractiveness function introduced here regulates both the advection and diffusion of the random walker, thus providing testable predictions for a specific form of fluctuation-relations. We discuss the relation between the drift-diffusion equation based on the attractiveness function and that describing standard Brownian motion, and we provide some explicit examples illustrating its relevance in different fields, such as animal movement, chemotactic diffusion, and social dynamics.

  20. Subcellular localization and mechanism of secretion of vascular endothelial growth factor in human skeletal muscle.

    Science.gov (United States)

    Hoier, Birgitte; Prats, Clara; Qvortrup, Klaus; Pilegaard, Henriette; Bangsbo, Jens; Hellsten, Ylva

    2013-09-01

    The subcellular distribution and secretion of vascular endothelial growth factor (VEGF) was examined in skeletal muscle of healthy humans. Skeletal muscle biopsies were obtained from m.v. lateralis before and after a 2 h bout of cycling exercise. VEGF localization was conducted on preparations of teased muscle fibers by transmission electron microscopy (TEM) and confocal microscopy (CM). Muscle interstitial fluid was sampled from microdialysis probes placed in the thigh muscle. TEM and CM analysis revealed two primary sites of localization of VEGF: in vesicles located in the subsarcolemmal regions and between the contractile elements within the muscle fibers; and in pericytes situated on the skeletal muscle capillaries. Quantitation of the subsarcolemmal density of VEGF vesicles, calculated on top of myonuclei, in the muscle fibers revealed a ∼50% increase (P<0.05) after exercise. The observation of more VEGF vesicles close to sarcolemma after exercise, combined with a 5-fold increase (P<0.05) in VEGF in the interstitial fluid, suggest that VEGF-containing vesicles redistribute to sarcolemma and that VEGF is secreted to the extracellular fluid. This study provides the first evidence in humans for a mechanism by which skeletal muscle fibers can control capillary growth by releasing VEGF from intracellular vesicles during contraction.

  1. Locally applied nerve growth factor enhances bone consolidation in a rabbit model of mandibular distraction osteogenesis.

    Science.gov (United States)

    Wang, Lei; Zhou, Shuxia; Liu, Baolin; Lei, Delin; Zhao, Yinghua; Lu, Chao; Tan, Aixing

    2006-12-01

    Distraction osteogenesis is widely used in treating deformities, defects, and fractures of both long bones and craniofacial bones. Demands for acceleration of bone consolidation are increased in distraction osteogenesis. Nerve growth factor (NGF) can enhance innervation and bone regeneration in a fracture model and stimulate differentiation of osteoblastic cells. In this study, we tested the ability of locally applied NGF to enhance bone regeneration in a rabbit model of mandibular distraction osteogenesis. Twenty rabbits underwent bilateral distraction osteogenesis with a rate of 0.5 mm per 12 h. Two times 0.04 mg human NGFbeta (hNGFbeta) in buffer was injected into the callus after distraction. The contralateral side received placebo injections. Rabbits were euthanized at consolidation times of 14 and 28 days. Specimens were subjected to radiography, callus dimensions measurement, mechanical testing, and bone histological and histomorphometric analysis. The maximum load, bone volume/total volume, mineral apposition rate of the 1st to 11th day, and mineralized bone percentage were significantly higher in the hNGFbeta side at 14 and 28 days (p<0.05). The data indicate that locally applied hNGFbeta can accelerate callus maturation and may be an option to shorten the consolidation period in distraction osteogenesis.

  2. Acceleration of Medpor implant fibrovascularization with local vascular endothelial growth-factor injections: An experimental study

    Directory of Open Access Journals (Sweden)

    Mert Demirel

    2015-12-01

    Full Text Available Objective: Medpor is a biocompatible, high-density porous polyethylene implant that is used for multiple indications in plastic surgery. The most frequent complications associated with the Medpor implant are infection and implant exposure. The primary cause of these complications is poor fibrovascularization of the Medpor implant and poor nourishment of the overlying skin. The present experimental study aimed to determine whether vascular endothelial growth factor (VEGF could accelerate and increase Medpor implant fibrovascularization in vivo, and thereby improve local nourishment and prevent complications. Materials and Methods: The Medpor implant was inserted under the dorsal skin area in 40 Sprague-Dawley rats. 20 rats receiving local VEGF injections comprised the study group. The control group received saline injections. Fibrovascularization of the Medpor implants was compared. Results: In the rats injected with VEGF, the Medpor implant fibrovascularized faster, and there were more newly formed blood vessels, as compared with those in the control group. Conclusion: These findings have led to our use of VEGF-like agents that the accelerate angiogenesis in the Medpor implant as a means to reduce the incidence of such complications as infection and implant exposure. [Arch Clin Exp Surg 2015; 4(4.000: 196-201

  3. El factor inducible por la hipoxia y la actividad física hypoxia-inducible factor and physical activity

    Directory of Open Access Journals (Sweden)

    Juan Camilo Calderón Vélez

    2007-04-01

    Full Text Available Los animales superiores dependen de un adecuado flujo de oxígeno. Los mecanismos involucrados en los procesos de percibir la hipoxia y responder a ella se han ido aclarando, desde hace unos 15 años, con el descubrimiento de las subunidades α y β del factor inducible por la hipoxia (HIF, por su sigla en inglés y de las hidroxilasas involucradas en su regulación. Las especies reactivas de oxígeno (ERO, al parecer, también participan en el proceso de percibir y responder a la hipoxia. Las células musculares podrían ser un modelo útil para estudiar la interrelación hipoxia-ERO-HIF- respuesta celular, con importantes implicaciones básico-clínicas. Sin embargo, apenas comienza el estudio de esta relación en el músculo esquelético. Se revisan en este artículo algunos aspectos interesantes de la investigación en el músculo esquelético y se plantean algunas preguntas e hipótesis que podrían ser evaluadas en este tipo de células. Higher animals depend on an adequate oxygen flux. Mechanisms involved in the process of sensing and responding to hypoxia have become clearer in the last 15 years with the discovery of the y hypoxia-inducible factor (HIF subunits and hydroxylases involved in their regulation. Reactive oxygen species seem to play some role in the process of sensing and responding to hypoxia. Skeletal muscle cells seem to be a suitable model for studying the hypoxia-reactive oxygen species-HIF-cellular response relationship. Its study has important basic and clinic implications. However, the study of this relationship just begins. Some interesting aspects regarding skeletal muscle research are reviewed in this article, and some questions and hypotheses suitable for being evaluated with muscle cells are discussed.

  4. Local Risk Factors in Genital Human Papilloma Virus Infection in Cervical Smears

    Science.gov (United States)

    Ojiyi, EC; Dike, IE; Okeudo, C; Ejikem, C; Nzewuihe, AC; Agbata, A

    2013-01-01

    Background: Infection with human papilloma virus (HPV) is the main cause of cervical cancer, but the local risk factors have not been sufficiently assessed. Aim: The study is aimed at determining the prevalence and to evaluate the local risk factors of HPV infection in cervical smears at the Imo State University Teaching Hospital, Orlu, Nigeria. Subjects and Methods: The participants involved 445 randomly selected sexually active women attending the antenatal, postnatal, gynecology and family planning clinics in the Department of Obstetrics and Gynecology of the university between April 2004 and May 2012. A questionnaire assessing various socio-demographic characteristics of the participants was administered. The pap smears of the participants were examined microscopically for evidence of HPV infection. The SPSS version 17.0 (Chicago, Illinois, USA) was used to compute and analyze the results. The results were presented in tables as simple percentages. Tests of significance using the Chi-square and fisher exact tests were applied where appropriate. Results: The prevalence rate of HPV was 10.3%. The peak age-specific prevalence of 11.7% occurred in the 15-19 years age group. There were significant associations between the occurrence of HPV and multiple sexual partners, coital frequency, multiparity, contraceptive use, marital status, low socio-economic status, abnormal vaginal discharge, irregular menstruation, post-coital and post-menopausal bleeding, (P < 0.05). Conclusion: All sexually active women including teenagers should be screened for cervical HPV infection in an organized systematic program equipped with a good call and recall system. There is, therefore, a need to move emphasis from the current practice of opportunistic screening to a systematic screening of the whole population at risk despite cost implications. PMID:24380003

  5. Tumor Volume Reduction Rate After Preoperative Chemoradiotherapy as a Prognostic Factor in Locally Advanced Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yeo, Seung-Gu [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan (Korea, Republic of); Kim, Dae Yong, E-mail: radiopiakim@hanmail.net [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Park, Ji Won; Oh, Jae Hwan; Kim, Sun Young; Chang, Hee Jin; Kim, Tae Hyun; Kim, Byung Chang; Sohn, Dae Kyung; Kim, Min Ju [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)

    2012-02-01

    Purpose: To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and Materials: In total, 430 primary LARC (cT3-4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume - post-CRT tumor volume) Multiplication-Sign 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27-99 months) for survivors. Endpoints were disease-free survival (DFS) and overall survival (OS). Results: The median TVRR was 70.2% (mean, 64.7% {+-} 22.6%; range, 0-100%). Downstaging (ypT0-2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS. Conclusions: Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.

  6. Electromagnetically induced transparency metamaterial based on spoof localized surface plasmons at terahertz frequencies

    Science.gov (United States)

    Liao, Zhen; Liu, Shuo; Ma, Hui Feng; Li, Chun; Jin, Biaobing; Cui, Tie Jun

    2016-06-01

    We numerically and experimentally demonstrate a plasmonic metamaterial whose unit cell is composed of an ultrathin metallic disk and four ultrathin metallic spiral arms at terahertz frequencies, which supports both spoof electric and magnetic localized surface plasmon (LSP) resonances. We show that the resonant wavelength is much larger than the size of the unit particle, and further find that the resonant wavelength is very sensitive to the particle’s geometrical dimensions and arrangements. It is clearly illustrated that the magnetic LSP resonance exhibits strong dependence to the incidence angle of terahertz wave, which enables the design of metamaterials to achieve an electromagnetically induced transparency effect in the terahertz frequencies. This work opens up the possibility to apply for the surface plasmons in functional devices in the terahertz band.

  7. Local circular polarizations in nanostructures induced by linear polarization via optical near-fields

    CERN Document Server

    Naruse, Makoto; Inoue, Tetsuya; Yasuda, Hideki; Hori, Hirokazu; Naya, Masayuki

    2015-01-01

    We previously reported [Naruse, et al. Sci. Rep. 4, 6077, 2014] that the geometrical randomness of disk-shaped silver nanoparticles, which exhibit high reflection at near-infrared wavelengths, serves as the origin of a particle-dependent localization and hierarchical distribution of optical near-fields in the vicinity of the nanostructure. In this study, we show that the induced polarizations are circular, particularly at resonant wavelengths. We formulate optical near-field processes between nanostructures, accounting for their polarizations and geometries, and attribute circular polarization to the layout-dependent phase difference between the electrical susceptibilities associated with longitudinal and transverse-electric components. This study clarifies the fundamental optical properties of random nanostructured matter and offers generic theoretical concepts for implementing nanoscale polarizations of optical near-fields.

  8. Large positive in-plane magnetoresistance induced by localized states at nanodomain boundaries in graphene

    Science.gov (United States)

    Wu, Han-Chun; Chaika, Alexander N.; Hsu, Ming-Chien; Huang, Tsung-Wei; Abid, Mourad; Abid, Mohamed; Aristov, Victor Yu; Molodtsova, Olga V.; Babenkov, Sergey V.; Niu, Yuran; Murphy, Barry E.; Krasnikov, Sergey A.; Lübben, Olaf; Liu, Huajun; Chun, Byong Sun; Janabi, Yahya T.; Molotkov, Sergei N.; Shvets, Igor V.; Lichtenstein, Alexander I.; Katsnelson, Mikhail I.; Chang, Ching-Ray

    2017-02-01

    Graphene supports long spin lifetimes and long diffusion lengths at room temperature, making it highly promising for spintronics. However, making graphene magnetic remains a principal challenge despite the many proposed solutions. Among these, graphene with zig-zag edges and ripples are the most promising candidates, as zig-zag edges are predicted to host spin-polarized electronic states, and spin-orbit coupling can be induced by ripples. Here we investigate the magnetoresistance of graphene grown on technologically relevant SiC/Si(001) wafers, where inherent nanodomain boundaries sandwich zig-zag structures between adjacent ripples of large curvature. Localized states at the nanodomain boundaries result in an unprecedented positive in-plane magnetoresistance with a strong temperature dependence. Our work may offer a tantalizing way to add the spin degree of freedom to graphene.

  9. Possible enhancement of SASE FEL output field intensity induced by local phase jump

    Science.gov (United States)

    Varfolomeev, A. A.; Yarovoi, T. V.; Bousine, P. V.

    1998-02-01

    A possible influence on the FEL dynamics of a locally induced phase jump between the FEL radiation and electron beam is considered. A numerical study has been made for the SASE mode FEL supposing that the phase jumps are introduced at different depths inside the undulator. The FEL evolution starting from a small input signal was studied in 1D high gain approach. It was shown that the FEL radiation output is sensitive to the phase jump value if it is introduced at the depth where saturation of output power takes places. In the steady state regime, the phase displacement of order ˜π provides enhancement of the peak output power up to 50%. Some kind of optical tapering is also possible giving further FEL efficiency enhancement.

  10. hypoxia-inducible factors activate CD133 promoter through ETS family transcription factors.

    Directory of Open Access Journals (Sweden)

    Shunsuke Ohnishi

    Full Text Available CD133 is a cellular surface protein that has been reported to be a cancer stem cell marker, and thus it is considered to be a potential target for cancer treatment. However, the mechanism regulating CD133 expression is not yet understood. In this study, we analyzed the activity of five putative promoters (P1-P5 of CD133 in human embryonic kidney (HEK 293 cells and colon cancer cell line WiDr, and found that the activity of promoters, particularly of P5, is elevated by overexpression of hypoxia-inducible factors (HIF-1α and HIF-2α. Deletion and mutation analysis identified one of the two E-twenty six (ETS binding sites (EBSs in the P5 region as being essential for its promoter activity induced by HIF-1α and HIF-2α. In addition, a chromatin imunoprecipitation assay demonstrated that HIF-1α and HIF-2α bind to the proximal P5 promoter at the EBSs. The immunoprecipitation assay showed that HIF-1α physically interacts with Elk1; however, HIF-2α did not bind to Elk1 or ETS1. Furthermore, knockdown of both HIF-1α and HIF-2α resulted in a reduction of CD133 expression in WiDr. Taken together, our results revealed that HIF-1α and HIF-2α activate CD133 promoter through ETS proteins.

  11. Pressure-induced local structure distortions in Cu(pyz)F{sub 2}(H{sub 2}O){sub 2}.

    Energy Technology Data Exchange (ETDEWEB)

    Musfeldt, J. L.; Liu, Z.; Li, S.; Kang, J.; Lee, C.; Jena, P.; Manson, J. L.; Schlueter, J. A.; Carr, G. L.; Whangbo, M.-H. (Materials Science Division); (Univ. of Tennessee); (Carnegie Inst. of Washington); (Virginia Commonwealth Univ.); (North Carolina State Univ.); (Eastern Washington Univ.); (BNL)

    2011-06-06

    We employed infrared spectroscopy along with complementary lattice dynamics and spin density calculations to investigate pressure-driven local structure distortions in the copper coordination polymer Cu(pyz)F{sub 2}(H{sub 2}O){sub 2}. Here, pyz is pyrazine. Our study reveals rich and fully reversible local lattice distortions that buckle the pyrazine ring, disrupt the bc-plane O-H {hor_ellipsis} F hydrogen-bonding network, and reinforce magnetic property switching. The resiliency of the soft organic ring is a major factor in the stability of this material. Interestingly, the collective character of the lattice vibrations masks direct information on the Cu-N and Cu-O linkages through the series of pressure-induced Jahn-Teller axis switching transitions, although Cu-F bond softening is clearly identified above 3 GPa. These findings illustrate the importance of combined bulk and local probe techniques for microscopic structure determination in complex materials.

  12. Improvement of traditional local rice varieties through induced mutations using nuclear techniques

    Energy Technology Data Exchange (ETDEWEB)

    Pham Van Ro; Do Huu At [Cuu Long Delta Rice Research Institute (Viet Nam)

    2001-03-01

    'Improvement of local rice varieties for high yield, resistance to disease and insect pests (brown plant hopper and rice blast) and export quality through induced mutations for the Mekong Delta' started in 1993. After six years, it showed effecting on the field in the MD as well as at the south of Vietnam. TNDB-100 manifest very wide adaptation and yield stable variety. THDB is suitable for deepwater rice region, coastal area, where rice cultivation effected by acid sulphate and salinity conditions. Both varieties are good example for the method. Thank to good Co-operation from extension center from provinces, hundred classes of extension were organized to recommend to the farmers. And thank to the strongly supporting from IAEA so that nearly 400,000 ha of TNDB-100 occupied at the south of Vietnam as well as nearly 15,000 ha of THDB grown in the coastal as well as rainfed lowland rice areas at the South of Vietnam. To continue the rice improvement by this technique, seeds of six traditional local varieties were exposed under different dose of gamma rays to create new mutants. At present day hundred improved breeding lines were selected, a dozen of uniform lines were isolated and entranced the yield trail as well as regional testing program. From these improved varieties would be selected to contribute to the rice cultivation at the south of Vietnam in the next years. (author)

  13. Regional estimation of geomagnetically induced currents based on the local magnetic or electric field

    Directory of Open Access Journals (Sweden)

    Viljanen Ari

    2015-01-01

    Full Text Available Previous studies have demonstrated a close relationship between the time derivative of the horizontal geomagnetic field vector (dH/dt and geomagnetically induced currents (GIC at a nearby location in a power grid. Similarly, a high correlation exists between GIC and the local horizontal geoelectric field (E, typically modelled from a measured magnetic field. Considering GIC forecasting, it is not feasible to assume that detailed prediction of time series will be possible. Instead, other measures summarising the activity level over a given period are preferable. In this paper, we consider the 30-min maximum of dH/dt or E as a local activity indicator (|dH/dt|30 or |E|30. Concerning GIC, we use the sum of currents through the neutral leads at substations and apply its 30-min maximum as a regional activity measure (GIC30. We show that |dH/dt|30 at a single point yields a proxy for GIC activity in a larger region. A practical consequence is that if |dH/dt|30 can be predicted at some point then it is also possible to assess the expected GIC level in the surrounding area. As is also demonstrated, |E|30 and GIC30 depend linearly on |dH/dt|30, so there is no saturation with increasing geomagnetic activity contrary to often used activity indices.

  14. Effects of relaxation and stress on the capsaicin-induced local inflammatory response.

    Science.gov (United States)

    Lutgendorf, S; Logan, H; Kirchner, H L; Rothrock, N; Svengalis, S; Iverson, K; Lubaroff, D

    2000-01-01

    Although stress is known to modulate the inflammatory response, there has been little experimental examination of the effects of stress and stress reduction on inflammation in humans. In particular, the effects of stress and relaxation on neurogenic inflammation have been minimally studied. This study examines the effects of three experimental manipulations: mental stress, relaxation, and control on the local inflammatory response evoked by the intradermal injection of capsaicin, the active ingredient in chili peppers. Fifty subjects (28 men and 22 women) were pretrained in relaxation using an imagery-based relaxation tape and then randomized to experimental condition. Subjects participated in an evening reactivity session including 20 minutes of a stress (Stroop test), relaxation (tape), or control (video) manipulation, followed by a capsaicin injection in the forearm. Digitized flare measurements were taken for 1 hour postcapsaicin, and measurements of cardiovascular variables, cortisol, adrenocorticotrophic hormone, and norepinephrine were taken at regular intervals. The size of the maximum capsaicin-induced flare was significantly smaller in the relaxation condition than in the stress or control conditions, which did not differ from each other. Increases in norepinephrine, heart rate, and systolic blood pressure during the experimental task, but not after capsaicin, significantly predicted size of maximum flare and total area under the curve of flare measurements. These findings suggest that stress reduction may affect local inflammatory processes. Results are consistent with sympathetic modulation of the effects of relaxation on the flare response.

  15. Modeling of fuel vapor jet eruption induced by local droplet heating

    KAUST Repository

    Sim, Jaeheon

    2014-01-10

    The evaporation of a droplet by non-uniform heating is numerically investigated in order to understand the mechanism of the fuel-vapor jet eruption observed in the flame spread of a droplet array under microgravity condition. The phenomenon was believed to be mainly responsible for the enhanced flame spread rate through a droplet cloud at microgravity conditions. A modified Eulerian-Lagrangian method with a local phase change model is utilized to describe the interfacial dynamics between liquid droplet and surrounding air. It is found that the localized heating creates a temperature gradient along the droplet surface, induces the corresponding surface tension gradient, and thus develops an inner flow circulation commonly referred to as the Marangoni convection. Furthermore, the effect also produces a strong shear flow around the droplet surface, thereby pushing the fuel vapor toward the wake region of the droplet to form a vapor jet eruption. A parametric study clearly demonstrated that at realistic droplet combustion conditions the Marangoni effect is indeed responsible for the observed phenomena, in contrast to the results based on constant surface tension approximation

  16. Albatross as Sentinels of Heavy Metal Pollution: Local and Global Factors

    Science.gov (United States)

    Sentman, W.; Edwards, S. V.; Vo, A. E.; Bank, M. S.

    2012-12-01

    Heavy metal pollution in the Pacific Ocean has garnered significant attention in recent years, especially with regard to rising mercury emissions from Asia. Uncertainty exists over the extent to which mercury in biota may have resulted from increases in anthropogenic emissions over time. Albatrosses, including those inhabiting the North Pacific, are wide-ranging, long-lived, keystone, avian predators. Consequently, they serve as ideal sentinel species for investigating the effects of historical and contemporary pollution as well as local and global factors related to heavy metal bioaccumulation, exposure, and ecotoxicological risk. To date, high levels of mercury and lead have been documented in albatross species throughout the Pacific. To address biotic exposure to these multiple stressors, here we synthesize and conduct meta-analyses of total mercury, methylmercury, and lead exposure data in Black-footed albatross (Phoebastria nigripes) and Laysan albatross (Phoebastria immutabilis). Our approach uses data from the field and literature and for methyl mercury uses museum feathers spanning the past 130 years for Black-Footed albatross. We discuss the use and application of stable isotopes (δ15N and δ13C) as a way to control for temporal changes in trophic structure and diet and the importance of conducting speciation analyses, for mercury, to account for curator mediated inorganic mercury in older specimens. Our data showed higher levels of inorganic mercury in older specimens of Black-Footed albatross as well as two non-pelagic species (control samples) lacking historical sources of bioavailable mercury exposure, which suggests that studies on bioaccumulation should measure methylmercury rather than total mercury when utilizing museum collections. Additionally, at the local scale, previous research has reported that lead paint exposure from buildings was also an important environmental stressor for Laysan albatross, suggesting that albatross species face heavy

  17. Phase mixing induced by granular fluid pump during mantle strain localization

    Science.gov (United States)

    Précigout, Jacques; Prigent, Cécile; Palasse, Laurie; Pochon, Anthony

    2014-05-01

    Mantle viscous strain localization is often attributed to feedbacks between grain boundary sliding (GBS) and phase mixing, as GBS could promote mixing through grain switching, and phase mixing would enhance grain-size-sensitive granular flow through grain boundary pinning. However, although GBS and phase mixing are intimately related, recent data show that GBS alone cannot end-up with randomly mixed phases. Here we show natural observations of an ultramylonitic shear zone from the Ronda peridotite (Spain) where both GBS and phase mixing occur. Microprobe analyses and coupled EDX/EBSD data first document enrichment in pyroxenes and amphibole concomitant with both phase mixing and complete randomization of the olivine fabric in fine-grained layers (5-20 microns) where strain has been localized. Both the fabric randomization and some microstructural observations indicate that these layers mostly deformed by granular flow, i.e., by GBS. Based on petrological pseudo-sections, we also show that phase enrichment does not result from metamorphic reaction, but instead from dissolution-precipitation phenomena. Finally, we document in adjacent areas a change of olivine fabric geometry that highlights syn-tectonic water draining towards fine-grained layers. While olivine fabric switches from E-type (moderately hydrated fabric) to C-type (highly hydrated fabric) towards fine-grained layers, it changes from E-type to D-type (highly hydrated fabric) in coarse-grained bands between E/C-type layers. Altogether, our findings suggest that water converges as a result of GBS-induced creep cavitation and subsequent granular fluid pump in fine-grained layers. We propose that phase mixing originates here from such a creep cavitation through dissolution-precipitation of secondary phases in newly formed cavities, giving rise to a key process for the relationships between GBS and phase mixing, and hence, for the origin of viscous strain localization in the upper mantle.

  18. Holes localized in nanostructures in an external magnetic field: g-factor and mixing of states

    Energy Technology Data Exchange (ETDEWEB)

    Semina, M. A.; Suris, R. A., E-mail: suris@theory.ioffe.ru [Russian Academy of Sciences, Ioffe Physical-Technical Institute (Russian Federation)

    2015-06-15

    The energy spectrum and wave functions of holes in the valence band in semiconductor nanosystems, including quantum wells, quantum wires, and quantum dots, in an external magnetic field are theoretically investigated. The dependence of Zeeman splitting of the hole ground state upon variation in the size-quantization parameters with regard to the complex structure of the valence band and magnetic field-induced mixing of hole states is traced. Analytical formulas for describing the Zeeman effect in the valence band in the limiting cases of a quantum disk, spherically symmetric quantum dot, and quantum wire are presented. It is demonstrated that the g-factor of a hole is extremely sensitive to the hole-state composition (heavy or light hole) and, consequently, to the geometry of the size-quantization potential.

  19. Interleukin-1beta inhibits paw oedema induced by local administration of latex of Calotropis procera extracts.

    Science.gov (United States)

    Arya, Soneera; Kumar, Vijay L

    2004-01-01

    Interleukin-1beta (IL-1beta), a pro-inflammatory cytokine, has been reported to exhibit anti-inflammatory properties in the carrageenan-induced paw oedema model. In the present study, we have evaluated the anti-inflammatory activity of IL-1beta against inflammation induced by local administration of the methanol extract of dried latex of Calotropis procera (MeDL) and compared it with that against carrageenan. The anti-inflammatory activity of standard anti-inflammatory drugs, phenylbutazone (PBZ) and dexamethasone (DEX), was also evaluated against both inflammagens. Injection of an aqueous solution of dried latex and MeDL into the sub-plantar surface of the rat paw produced intense inflammation with a peak response occurring within 2 h, while the peak inflammatory response with carrageenan was obtained at 3 h. Subcutaneous injection of IL-1beta was found to be more effective against the inflammatory response elicited by carrageenan (70% inhibition) as compared to MeDL (50% inhibition) at 20microg/kg dose. On the other hand, PBZ effectively inhibited the inflammatory response elicited by both MeDL and carrageenan, while DEX was more effective against carrageenan. Thus, our study indicates that the difference in the anti-inflammatory effect of IL-1beta against latex of C. procera extract and carrageenan is due to the release of different mediators released by these inflammagens.

  20. Characterization and localization of metal-responsive-element-binding transcription factors from tilapia

    Energy Technology Data Exchange (ETDEWEB)

    Cheung, Andrew Pok-Lap; Au, Candy Yee-Man; Chan, William Wai-Lun [Department of Biochemistry, Chinese University of Hong Kong, Sha Tin, N.T., Hong Kong (Hong Kong); Chan, King Ming, E-mail: kingchan@cuhk.edu.hk [Department of Biochemistry, Chinese University of Hong Kong, Sha Tin, N.T., Hong Kong (Hong Kong)

    2010-08-01

    Two isoforms of MTF-1, MTF-1L (long form) and MTF-1S (short form), were cloned in tilapia (Ti) and characterized in a tilapia liver cell line, Hepa-T1. The cloned tiMTF-1L has the characteristics of all of the tiMTF-1S identified so far with the zinc finger domain having six fingers, the acidic-rich, proline-rich, and serine/threonine-rich domains; however, the short form encodes for the zinc finger domain with five zinc fingers only and no other domains. The transient transfection of tiMTF-1L into human HepG2 cells showed both constitutive and zinc-induced metal-responsive-element (MRE)-driven reporter gene expression. However, the transfection of tiMTF-1S (which lacks all three transactivation domains) into a human cell line showed reduced transcriptional activities compared with an endogenous control in both basal- and Zn{sup 2+}-induced conditions. The tiMTF-1 isoforms were tagged with GFP and transfected into Hepa-T1 cells (tilapia hepatocytes). The nuclear translocation of tiMTF-1L was observed when the cells were exposed to a sufficient concentration of metals for 6 h. However, tiMTF-1S, was localized in the nucleus with or without metal treatment. Electrophoretic mobility shift assay (EMSA) confirmed that both of the isoforms were able to bind to the MRE specifically in vitro. Tissue distribution studies showed that tiMTF-1L was more abundant than tiMTF-1S in all of the tissues tested.

  1. Analysis of factors affecting local tumor progression of colorectal cancer liver metastasis after radiofrequency ablation

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Seong Hee; Cho, Yun Ku; Choi, Seung A; Kim, Mi Young; Lee, Ho Suk [Veterans Health Service Medical Center, Seoul (Korea, Republic of)

    2017-03-15

    The purpose of this study was to evaluate the independent predictive factors for local tumor progression (LTP) of colorectal liver metastasis (CRLM) after radiofrequency ablation (RFA). Patients with CRLM were included in the analysis if nodules were up to five in number, each nodule was ≤ 5 cm, and RFA was performed in our center from January 2006 to December 2015. Univariate and multivariate analyses to identify the predictors of LTP were performed by using a Cox proportional hazard model. Overall, 58 tumors from 38 patients were included in this study. LTP occurred in 14 tumors from 9 patients. The overall 1- and 3-year LTP rates were 23.5% and 29.4%, respectively. Multivariate analysis showed that tumor size > 2 cm and insufficient ablative margin were two independently significant adverse prognostic factors for LTP (p = 0.045 and 0.022, respectively). The 3-year LTP rates for 33 and 25 tumors with and without sufficient ablative margin were 4.5% and 61.2%, respectively. The difference was statistically significant (p < 0.001). The difference in the 3-year LTP rates according to the tumor size was not statistically significant (p = 0.791). Insufficient ablative margin seems to be the most potent predictor of LTP after RFA of CRLM.

  2. Factors Influencing Local Communities' Satisfaction Levels with Different Forest Management Approaches of Kakamega Forest, Kenya

    Science.gov (United States)

    Guthiga, Paul M.; Mburu, John; Holm-Mueller, Karin

    2008-05-01

    Satisfaction of communities living close to forests with forest management authorities is essential for ensuring continued support for conservation efforts. However, more often than not, community satisfaction is not systematically elicited, analyzed, and incorporated in conservation decisions. This study attempts to elicit levels of community satisfaction with three management approaches of Kakamega forest in Kenya and analyze factors influencing them. Three distinct management approaches are applied by three different authorities: an incentive-based approach of the Forest Department (FD), a protectionist approach of the Kenya Wildlife Service (KWS), and a quasi-private incentive-based approach of Quakers Church Mission (QCM). Data was obtained from a random sample of about 360 households living within a 10-km radius around the forest margin. The protectionist approach was ranked highest overall for its performance in forest management. Results indicate that households are influenced by different factors in their ranking of management approaches. Educated households and those located far from market centers are likely to be dissatisfied with all the three management approaches. The location of the households from the forest margin influences negatively the satisfaction with the protectionist approach, whereas land size, a proxy for durable assets, has a similar effect on the private incentive based approach of the QCM. In conclusion, this article indicates a number of policy implications that can enable the different authorities and their management approaches to gain approval of the local communities.

  3. Local spatial and temporal factors influencing population and societal vulnerability to natural disasters.

    Science.gov (United States)

    Zhou, Yang; Li, Ning; Wu, Wenxiang; Wu, Jidong; Shi, Peijun

    2014-04-01

    The identification of societal vulnerable counties and regions and the factors contributing to social vulnerability are crucial for effective disaster risk management. Significant advances have been made in the study of social vulnerability over the past two decades, but we still know little regarding China's societal vulnerability profiles, especially at the county level. This study investigates the county-level spatial and temporal patterns in social vulnerability in China from 1980 to 2010. Based on China's four most recent population censuses of 2,361 counties and their corresponding socioeconomic data, a social vulnerability index for each county was created using factor analysis. Exploratory spatial data analysis, including global and local autocorrelations, was applied to reveal the spatial patterns of county-level social vulnerability. The results demonstrate that the dynamic characteristics of China's county-level social vulnerability are notably distinct, and the dominant contributors to societal vulnerability for all of the years studied were rural character, development (urbanization), and economic status. The spatial clustering patterns of social vulnerability to natural disasters in China exhibited a gathering-scattering-gathering pattern over time. Further investigations indicate that many counties in the eastern coastal area of China are experiencing a detectable increase in social vulnerability, whereas the societal vulnerability of many counties in the western and northern areas of China has significantly decreased over the past three decades. These findings will provide policymakers with a sound scientific basis for disaster prevention and mitigation decisions.

  4. Hypoxia and hypoxia-inducible factors in leukaemias

    Directory of Open Access Journals (Sweden)

    Margaux eDeynoux

    2016-02-01

    Full Text Available Despite huge improvements in the treatment of leukaemia, the percentage of patients suffering relapse still remains significant. Relapse most often results from a small number of leukaemic stem cells (LSCs within the bone marrow, which are able to self-renew and therefore re-establish the full tumour. The marrow microenvironment contributes considerably in supporting the protection and development of leukaemic cells. LSCs share specific niches with normal haematopoietic stem cells with the niche itself being composed of a variety of cell types including mesenchymal stem/stromal cells, bone cells, immune cells, neuronal cells and vascular cells. A hallmark of the haematopoietic niche is low oxygen partial pressure, indeed this hypoxia is necessary for the long-term maintenance of HSCs. Hypoxia is a strong signal, principally maintained by members of the hypoxia-inducible factor family. In solid tumours, it has been well-established that hypoxia triggers intrinsic metabolic changes and microenvironmental modifications, such as the stimulation of angiogenesis, through activation of HIFs. As leukaemia is not considered a solid tumour, the role of oxygen in the disease was presumed to be inconsequential and remained long overlooked. This view has now been revised since hypoxia has been shown to influence leukaemic cell proliferation, differentiation and resistance to chemotherapy. However, the role of HIF proteins remains controversial with HIFs being considered as either oncogenes or tumour suppressor genes, depending on the study and model. The purpose of this review is to highlight our knowledge of hypoxia and HIFs in leukaemic development and therapeutic resistance, and to discuss the recent hypoxia-based strategies proposed to eradicate leukaemias.

  5. Local recurrence following mastectomy and autologous breast reconstruction: incidence, risk factors, and management

    Directory of Open Access Journals (Sweden)

    Wu S

    2016-11-01

    Full Text Available Siyu Wu,1,2 Miao Mo,3 Yujie Wang,1,2 Na Zhang,1,2 Jianwei Li,1,2 Genhong Di,1,2 Zhimin Shao,1,2 Jiong Wu,1,2 Guangyu Liu1,2 1Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Clinical Statistics Center, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China Background: Breast reconstruction (BR, including autologous breast reconstruction (ABR after mastectomy (MST, has been gaining popularity all around the world, especially in the People’s Republic of China during the past decade. However, there is a small proportion, but a significant number, of patients who develop local recurrence (LR of breast cancer postoperatively. The purpose of this study is to examine the incidence of LR, discuss risk factors associated with LR, and management of LR following MST and ABR. Methods: A total of 397 patients who underwent MST and ABR after diagnosis of breast cancer were included in this retrospective study. Data were analyzed by the Kaplan–Meier method, the log-rank statistical test, and Cox proportional hazards model. Results: From January 1999 to December 2011, 400 ABRs were performed in 397 patients in Fudan University Shanghai Cancer Center. The median follow-up time in the study was 3.6 years. LR occurred in 11 of 397 patients, with a median time to LR of 2.9 years. In univariate and multivariate analyses, tumor stage, hormonal therapy (yes or no, and tumor type (multifocal or nonmultifocal were significantly associated with LR after ABR following MST. Conclusion: ABR is an oncologically safe surgical procedure with an acceptable LR rate of 2.8%. Risk factors associated with high rate of LR were higher tumor stage, absence of hormonal therapy, and multifocal tumor type. Keywords: local recurrence, autologous breast reconstruction, incidence, risk factors, management

  6. Subthalamic and Cortical Local Field Potentials Associated with Pilocarpine-Induced Oral Tremor in the Rat.

    Science.gov (United States)

    Long, Lauren L; Podurgiel, Samantha J; Haque, Aileen F; Errante, Emily L; Chrobak, James J; Salamone, John D

    2016-01-01

    Tremulous jaw movements (TJMs) are rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus. In rodents, TJMs are induced by neurochemical conditions that parallel those seen in human Parkinsonism, including neurotoxic or pharmacological depletion of striatal dopamine (DA), DA antagonism, and cholinomimetic administration. Moreover, TJMs in rodents can be attenuated by antiparkinsonian agents, including levodopa (L-DOPA), DA agonists, muscarinic antagonists, and adenosine A2A antagonists. In human Parkinsonian patients, exaggerated physiological synchrony is seen in the beta frequency band in various parts of the cortical/basal ganglia/thalamic circuitry, and activity in the tremor frequency range (3-7 Hz) also has been recorded. The present studies were undertaken to determine if tremor-related local field potential (LFP) activity could be recorded from motor cortex (M1) or subthalamic nucleus (STN) during the TJMs induced by the muscarinic agonist pilocarpine, which is a well-known tremorogenic agent. Pilocarpine induced a robust TJM response that was marked by rhythmic electromyographic (EMG) activity in the temporalis muscle. Compared to periods with no tremor activity, TJM epochs were characterized by increased LFP activity in the tremor frequency range in both neocortex and STN. Tremor activity was not associated with increased synchrony in the beta frequency band. These studies identified tremor-related LFP activity in parts of the cortical/basal ganglia circuitry that are involved in the pathophysiology of Parkinsonism. This research may ultimately lead to identification of the oscillatory neural mechanisms involved in the generation of tremulous activity, and promote development of novel treatments for tremor disorders.

  7. In-situ strain localization analysis in low density transformation-twinning induced plasticity steel using digital image correlation

    Science.gov (United States)

    Eskandari, M.; Yadegari-Dehnavi, M. R.; Zarei-Hanzaki, A.; Mohtadi-Bonab, M. A.; Basu, R.; Szpunar, J. A.

    2015-04-01

    The effect of deformation temperature on the strain localization has been evaluated by an adapted digital image correlation (DIC) technique during tensile deformation. The progress of strain localization was traced by the corresponding strain maps. The electron backscatter diffraction analysis and tint etching technique were utilized to determine the impact of martensitic transformation and deformation twinning on the strain localization in both elastic and plastic regimes. In elastic regime the narrow strain bands which are aligned perpendicular to the tension direction were observed in temperature range of 25 to 180 °C due to the stress-assisted epsilon martensite. The strain bands were disappeared by increasing the temperature to 300 °C and reappeared at 400 °C due to the stress-assisted deformation twinning. In plastic regime strain localization continued at 25 °C and 180 °C due to the strain-induced alfa-martensite and deformation twinning, respectively. The intensity of plastic strain localization was increased by increasing the strain due to the enhancement of martensite and twin volume fraction. The plastic strain showed more homogeneity at 300 °C due to the lack of both strain-induced martensite and deformation twinning. Effect of deformation mechanism by changing temperature on strain localization is investigated by digital image correlation. EBSD technique is served to validate deformation mechanism as well as microstructural evolution. Strain induced martensite as well as deformation twinning is activated in the present steel affecting strain localization.

  8. Overweight and obesity as poor prognostic factors in locally advanced breast cancer patients.

    Science.gov (United States)

    Arce-Salinas, C; Aguilar-Ponce, J L; Villarreal-Garza, C; Lara-Medina, F U; Olvera-Caraza, D; Alvarado Miranda, A; Flores-Díaz, D; Mohar, A

    2014-07-01

    Obesity and overweight are established risk factors for the development of breast cancer. They are also associated with poor prognosis for higher risk of disease recurrence and lower overall survival (OS). The aim of this study was to evaluate the influence of overweight and obesity in OS in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy. This is a retrospective analysis that included 819 patients diagnosed with LABC between January 2004 and December 2008. The patients were treated with neoadjuvant chemotherapy (NAT) based on anthracyclines, taxanes, or both, followed by surgery. For comparison, patients were divided into the normal weight (NW) group or the overweight/obesity (OW/OB) group. The prevalence of overweight/obesity was 74 %. General characteristics of the patients, including age, tumor size, clinical stage, nuclear grade, hormone receptors, and HER2 expression, were similar between both groups. At a median follow-up of 28 months, we found a statistically significant difference in OS between the two groups, achieving a 91.5 % in NW patients versus 85.9 % in the OW/OB group (P = 0.050). Cox multivariate analysis demonstrated that obesity was an independent factor for poor prognosis, with a hazard ratio of 1.79 (95 % CI (Confidence Interval) 1.09-2.96; P = 0.022). This is the first Mexican study that confirms the role of OW/OB as a risk factor for poor outcome among patients with LABC. Obesity in our country is a public health problem and requires strong preventive intervention strategies for its control, especially among patients diagnosed with breast cancer.

  9. The local structure factor near an interface; beyond extended capillary-wave models

    Science.gov (United States)

    Parry, A. O.; Rascón, C.; Evans, R.

    2016-06-01

    We investigate the local structure factor S (zq) at a free liquid-gas interface in systems with short-ranged intermolecular forces and determine the corrections to the leading-order, capillary-wave-like, Goldstone mode divergence of S (zq) known to occur for parallel (i.e. measured along the interface) wavevectors q\\to 0 . We show from explicit solution of the inhomogeneous Ornstein-Zernike equation that for distances z far from the interface, where the profile decays exponentially, S (zq) splits unambiguously into bulk and interfacial contributions. On each side of the interface, the interfacial contributions can be characterised by distinct liquid and gas wavevector dependent surface tensions, {σ l}(q) and {σg}(q) , which are determined solely by the bulk two-body and three-body direct correlation functions. At high temperatures, the wavevector dependence simplifies and is determined almost entirely by the appropriate bulk structure factor, leading to positive rigidity coefficients. Our predictions are confirmed by explicit calculation of S (zq) within square-gradient theory and the Sullivan model. The results for the latter predict a striking temperature dependence for {σ l}(q) and {σg}(q) , and have implications for fluctuation effects. Our results account quantitatively for the findings of a recent very extensive simulation study by Höfling and Dietrich of the total structure factor in the interfacial region, in a system with a cut-off Lennard-Jones potential, in sharp contrast to extended capillary-wave models which failed completely to describe the simulation results.

  10. Clinical and dosimetric factors of radiation-induced esophageal injury: Radiation-induced esophageal toxicity

    Institute of Scientific and Technical Information of China (English)

    Wen-Bo Qiao; Yan-Hui Zhao; Yan-Bin Zhao; Rui-Zhi Wang

    2005-01-01

    AIM: To analyze the clinical and dosimetric predictive factors for radiation-induced esophageal injury in patients with non-small-cell lung cancer (NSCLC) during threedimensional conformal radiotherapy (3D-CRT). METHODS: We retrospectively analyzed 208 consecutive patients (146 men and 62 women) with NSCLC treated with 3D-CRT. The median age of the patients was 64 years (range 35-87 years). The clinical and treatment parameters including gender, age, performance status, sequential chemotherapy, concurrent chemotherapy, presence of carinal or subcarinal lymph nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy were studied. Clinical and dosimetric factors for radiation-induced acute and late grade 3-5 esophageal injury were analyzed according to Radiation Therapy Oncology Group (RTOG) criteria.RESULTS: Twenty-five (12%) of the two hundred and eight patients developed acute or late grade 3-5 esophageal injury. Among them, nine patients had both acute and late grade 3-5 esophageal injury, two died of late esophageal perforation. Concurrent chemotherapy and maximal point dose to the esophagus ≥60 Gy were significantly associated with the risk of grade 3-5 esophageal injury. Fifty-four (26%) of the two hundred and eight patients received concurrent chemotherapy. Among them, 25 (46%) developed grade 3-5 esophageal injury (P = 0.0001<0.01). However, nograde 3-5 esophageal injury occurred in patients who received a maximal point dose to the esophagus <60 Gy (P= 0.0001<0.01).CONCLUSION: Concurrent chemotherapy and the maximal esophageal point dose ≥60 Gy are significantly associated with the risk of grade 3-5 esophageal injury in patients with NSCLC treated with 3D-CRT.

  11. TCDD induces the hypoxia-inducible factor (HIF)-1α regulatory pathway in human trophoblastic JAR cells.

    Science.gov (United States)

    Liao, Tien-Ling; Chen, Su-Chee; Tzeng, Chii-Reuy; Kao, Shu-Huei

    2014-09-30

    The exposure to dioxin can compromise pregnancy outcomes and increase the risk of preterm births. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been demonstrated to induce placental hypoxia at the end of pregnancy in a rat model, and hypoxia has been suggested to be the cause of abnormal trophoblast differentiation and placental insufficiency syndromes. In this study, we demonstrate that the non-hypoxic stimulation of human trophoblastic cells by TCDD strongly increased hypoxia inducible factor-1 alpha (HIF-1α) stabilization. TCDD exposure induced the generation of reactive oxygen species (ROS) and nitric oxide. TCDD-induced HIF-1α stabilization and Akt phosphorylation was inhibited by pretreatment with wortmannin (a phosphatidylinositol 3-kinase (PI3K) inhibitor) or N-acetylcysteine (a ROS scavenger). The augmented HIF-1α stabilization by TCDD occurred via the ROS-dependent activation of the PI3K/Akt pathway. Additionally, a significant increase in invasion and metallomatrix protease-9 activity was found in TCDD-treated cells. The gene expression of vascular endothelial growth factor and placental growth factor was induced upon TCDD stimulation, whereas the protein levels of peroxisome proliferator-activated receptor γ (PPARγ), PPARγ coactivator-1α, mitochondrial transcription factor, and uncoupling protein 2 were decreased. Our results indicate that an activated HIF-1α pathway, elicited oxidative stress, and induced metabolic stress contribute to TCDD-induced trophoblastic toxicity. These findings may provide molecular insight into the TCDD-induced impairment of trophoblast function and placental development.

  12. Sevoflurane anesthesia induces neither contextual fear memory impairment nor alterations in local population connectivity of medial prefrontal cortex local field potentials networks in aged rats.

    Science.gov (United States)

    Xu, Xinyu; Zhang, Qian; Tian, Xin; Wang, Guolin

    2016-08-01

    Sevoflurane has been found to increase apoptosis and pathologic markers associated with Alzheimer disease, provoking concern over their potential contribution to postoperative cognitive dysfunction. This study aimed to determine the effects of sevoflurane on contextual fear memory of aged rats and to characterize local population connectivity of local field potentials (LFPs) in medial prefrontal cortex (mPFC) of aged rats during contextual fear memory. Eighteen-month-old male SD rats were implanted with one multichannel electrode array in mPFC. The aged rats were divided into control group, sevoflurane group (1 MAC sevoflurane for 2 h) and surgical group with 1.0 MAC sevoflurane for 2 h. We then assessed the effect of the anesthesia on contextual fear memory, and alterations in the local population connectivity of mPFC LFP networks by partial directed coherence (PDC). Surgery impaired contextual fear memory and reduced local population connectivity of mPFC LFP networks in aged rats at day 1 after the surgery and anesthesia. 1 MAC Sevoflurane anesthesia induced neither contextual fear memory impairment nor alterations in local population connectivity of mPFC LFP networks in aged rats when tested 1, 7, 15 and 30 days after exposure (P > 0.05). PDC values of theta band mPFC LFPs became strongly increased during contextual fear memory at 1, 7, 15, and 30 days after anesthesia. Our results suggest that 1 MAC sevoflurane anesthesia does not induce contextual fear memory impairment in aged rats and suggest that the increased local population connectivity in theta bands LFPs of mPFC plays a role in contextual fear memory.

  13. Preliminary Study of Local Immunotherapy with Autologous Cytokine-Induced Killer Cells for Glioma Patients

    Institute of Scientific and Technical Information of China (English)

    Li Lin; Yonggao Mu; Zhongping Chen

    2008-01-01

    OBJECTIVE Cytokine-induced killer (CIK) cells are T-cells that display effective anti-tumor activity. In this study, we investigated the anti-tumor activity of CIK cells in vitro, and conducted a preliminary investigation using autologous CIK cells to treat glioma patients through local administration.METHODS The CIK cells were derived from peripheral blood monocytes (PBMCs) of the glioma patients. The anti-tumor activity of the CIK cells against human T98-G glioma cell was tested In vitro. In addition, the autologous CIK cells were locally administrated into the tumor cavity in the malignant glioma patients through an Ommaya reservoir which was pre-inserted during tumor resection. The 4×108 CIK cells in a 5 ml suspension were injected once a week 2 times per cycle. Five hundreds KU of IL-2 was injected every other day.RESULTS (I) With incubation, the CIK cells showed dual staining of CD3+CD56+ with a positive rate of 3.45% on day 10 and 55.2% on day 30. In vitro anti-tumor activity (againstT98-G cells) of the CIK cells reached the highest level after 18 days of incubation with different effector/target (E:T) ratios. (ii)Six patients received autologous CIK cell treatment (10 cycles).Two patients showed no recurrence and are still alive (24 and 10 months), while 4 cases had a recurrence 3 of which have died. The mean survival time from the first CIK cell treatment to the end of follow-up was 12.5 months. The main side-effects of the local CIK cell treatment was brain edema, which was controlled by mannitol in most of the cases. However for one patient injection of CIK cells and IL-2 had to be discontinued.CONCLUSION In vitro CIK cells are effective anti-glioma T-cells. Local therapy with CIK cells has potential anti-glioma efficacy and tolerable side-effects.

  14. The impact of locally multiply damaged sites (LMDS) induced by ionizing radiation in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Averbeck, D.; Boucher, D. [Institut Curie-Section de Recherche, UMR2027 CNRS, LCR-V28 du CEA, Centre Universitaire, 91405 Orsay Cedex (France)

    2006-07-01

    Monte Carlo calculations have shown that ionising radiations produce a specific type of clustered cell damage called locally multiply damaged sites or LMDS. These lesions consist of closely positioned single-strand breaks, (oxidative) base damage and DNA double-strand breaks (DSB) in between one helical turn of DNA. As specific markers of radiation-induced damage these lesions are likely to condition biological responses and are thus of great interest for radiation protection. Calculations indicate that there should be more LMDS induced by high than by low LET radiation, and they should be absent in un-irradiated cells. Processes like K-shell activation and local Auger electron emission can be expected to add complex DSB or LMDS, producing significant chromosomal damage. In the discussion of the specificity of ionising radiation in comparison to other genotoxic agents, many arguments have been put forward that these lesions should be particularly deleterious for living cells. Complex lesions of that type should represent big obstacles for DNA repair and give rise to high lethality. Moreover, cellular attempts to repair them could accentuate harm, leading to mutations, genetic instability and cancer. In vitro experiments with oligonucleotides containing an artificially introduced set of base damage and SSB in different combinations have shown that depending on the close positioning of the damage on DNA, repair enzymes, and even whole cell extracts, are unable to repair properly and may stimulate mis-repair. Pulsed field gel electrophoresis (PFGE) in conjunction with enzymatic treatments has been used to detect LMDS in mammalian cells after high and low LET radiation. In order to further define the importance of LMDS for radiation induced cellular responses, we studied the induction of LMDS as a function of radiation dose and dose rate in mammalian cells (CHO and MRC5) using {sup 137}Cs gamma-radiation. Using PFGE and specific glycosylases to convert oxidative damage

  15. Role of nuclear factor-kappaB in interleukin-1-induced collagen degradation by corneal fibroblasts.

    Science.gov (United States)

    Lu, Ying; Fukuda, Ken; Li, Qin; Kumagai, Naoki; Nishida, Teruo

    2006-09-01

    The proinflammatory cytokine interleukin (IL)-1 is implicated in corneal ulceration. The role of nuclear factor (NF)-kappaB in the IL-1-induced degradation of collagen by corneal fibroblasts that underlies corneal ulceration was investigated. Rabbit corneal fibroblasts were cultured in three-dimensional gels of type I collagen with or without IL-1 and sulfasalazine, an inhibitor of NF-kappaB activation. Collagen degradation was assessed from the amount of hydroxyproline generated by acid-heat hydrolysis of culture supernatants. The release of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) into culture supernatants was examined by immunoblot analysis and gelatin zymography, and the cellular abundance of MMP and TIMP mRNAs was determined by reverse transcription and real-time polymerase chain reaction analysis. The phosphorylation and degradation of the NF-kappaB-inhibitory protein IkappaB-alpha were examined by immunoblot analysis. The subcellular localization and DNA binding activity of the p65 subunit of NF-kappaB were evaluated by immunofluorescence analysis and with a colorimetric assay, respectively. The transactivation activity of NF-kappaB was assessed with a reporter gene assay. Sulfasalazine inhibited IL-1-induced collagen degradation by corneal fibroblasts in a concentration-dependent manner. It also inhibited the stimulatory effects of IL-1 on the synthesis or activation of various MMPs in a concentration-dependent manner. IL-1 induced the phosphorylation and degradation of IkappaB-alpha, the nuclear translocation and up-regulation of the DNA binding activity of the p65 subunit of NF-kappaB, and the activation of NF-kappaB in a manner sensitive to sulfasalazine. These results suggest that NF-kappaB contributes to the IL-1-induced degradation of collagen by corneal fibroblasts and is therefore a potential therapeutic target for treatment of corneal ulcers.

  16. Non-linear optics and local-field factors in liquid chloroform: A time-dependent density-functional theory study

    Science.gov (United States)

    Strubbe, David A.; Andrade, Xavier; Rubio, Angel; Louie, Steven G.

    2010-03-01

    Chloroform is often used as a solvent when measuring non-linear optical properties of organic molecules. We assess the influence of the solution environment on the molecular properties by calculating directly the non-linear susceptibilities of liquid chloroform at optical frequencies. We use the Sternheimer equation in time-dependent density-functional theory [J. Chem. Phys. 126, 184106 (2007)], on snapshots from ab initio molecular dynamics. We compare the results to those in the gas and solid phases, and to experimental values. We also calculate ab initio local-field factors, used to analyze electric-field-induced second-harmonic generation (EFISH) and hyper-Rayleigh scattering (HRS) experiments.

  17. Hypoxia-inducible factor and vascular endothelial growth factor in the neuroretina and retinal blood vessels after retinal ischemia

    DEFF Research Database (Denmark)

    Håkansson, Gisela; Gesslein, Bodil; Gustafsson, Lotta

    2010-01-01

    Retinal ischemia arises from circulatory failure. As the retinal blood vessels are key organs in circulatory failure, our aim was to study the retinal vasculature separately from the neuroretina to elucidate the role of hypoxia-inducible factor (HIF) 1α and 1β and vascular endothelial growth factor...

  18. Localization and function of a eukaryotic-initiation-factor-2-associated 67-kDa glycoprotein

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To study the localization and function of a eukaryotic initiation factor 2 (eIF2α)-associated 67-kDa glycoprotein (p67).METHODS: Immunofluorescence staining,35S-Met/Cys metabolic labeling,Western blotting analysis,sucrose gradient centrifugation and high speed centrifugation were used to determine the localization of proteins in transiently transfected COS-1 cells.Transient co-transfection followed by co-immunoprecipitation was used to study the interaction between p67 and double-stranded RNA (dsRNA)-dependent protein kinase (PKR).Wheat germ agglutinin agarose beads were used to absorb glycosylated proteins.In vivo 32P-labeling followed by immunoprecipitation and Western blotting were used to measure PKR autophosphorylation,eIF2α phosphorylation,and p67 expression in normal and breast cancer cells.RESULTS: The image from immunofluorescence staining showed that p67 was overexpressed in the cytosol but not in the nucleus.In a sucrose gradient,approxi-mately 30% of the overexpressed p67 was bound with ribosomes.p67 interacted with the kinase domain,butnot the dsRNA-binding domains of PKR.Only the glycosylated p67 was associated with the ribosome,and p67 did not compete with PKR for ribosome binding.In breast cancer cells,there was increased autophosphorylation of PKR but no phosphorylation of eIF2α,compared with normal breast cells.α The ratio of glycosylated/deglycosylated p67 was altered in breast cancer cells.CONCLUSION: Glycosylation of p67 is required for its ribosomal association and can potentially inhibit PKR via interaction with the kinase domain of PKR.

  19. Primary localization and tumor thickness as prognostic factors of survival in patients with mucosal melanoma.

    Directory of Open Access Journals (Sweden)

    Tarun Mehra

    Full Text Available Data on survival with mucosal melanoma and on prognostic factors of are scarce. It is still unclear if the disease course allows for mucosal melanoma to be treated as primary cutaneous melanoma or if differences in overall survival patterns require adapted therapeutic approaches. Furthermore, this investigation is the first to present 10-year survival rates for mucosal melanomas of different anatomical localizations.116 cases from Sep 10 1984 until Feb 15 2011 retrieved from the Comprehensive Cancer Center and of the Central Register of the German Dermatologic Society databases in Tübingen were included in our analysis. We recorded anatomical location and tumor thickness, and estimated overall survival at 2, 5 and 10 years and the mean overall survival time. Survival times were analyzed with the Kaplan-Meier method. The log-rank test was used to compare survival times by localizations and by T-stages.We found a median overall survival time of 80.9 months, with an overall 2-year survival of 71.7%, 5-year survival of 55.8% and 10-year survival of 38.3%. The 10-year survival rates for patients with T1, T2, T3 or T4 stage tumors were 100.0%, 77.9%, 66.3% and 10.6% respectively. 10-year survival of patients with melanomas of the vulva was 64.5% in comparison to 22.3% of patients with non-vulva mucosal melanomas.Survival times differed significantly between patients with melanomas of the vulva compared to the rest (p = 0.0006. It also depends on T-stage at the time of diagnosis (p < 0.0001.

  20. Pressure-induced transition from localized electron toward band antiferromagnetism in LaMnO(3).

    Science.gov (United States)

    Zhou, J-S; Goodenough, J B

    2002-08-19

    The temperature dependence of the ac susceptibility under pressure has been used to track the Néel temperature T(N) of the Mott insulators LaMnO3, CaMnO3, and YCrO3. Bloch's rule relating T(N) to volume V, viz., alpha=dlog(T(N)/dlog(V=-3.3, is obeyed in YCrO3 and CaMnO3; it fails in LaMnO3. This breakdown is interpreted to be due to a sharp increase in the factor [U(-1)+(2Delta)(-1)] entering the superexchange perturbation formula. A first-order change at 7 kbar indicates that the transition from localized-electron to band magnetism is not smooth.

  1. Welding of Semiconductor Nanowires by Coupling Laser-Induced Peening and Localized Heating

    Science.gov (United States)

    Rickey, Kelly M.; Nian, Qiong; Zhang, Genqiang; Chen, Liangliang; Suslov, Sergey; Bhat, S. Venkataprasad; Wu, Yue; Cheng, Gary J.; Ruan, Xiulin

    2015-11-01

    We demonstrate that laser peening coupled with sintering of CdTe nanowire films substantially enhances film quality and charge transfer while largely maintaining basic particle morphology. During the laser peening phase, a shockwave is used to compress the film. Laser sintering comprises the second step, where a nanosecond pulse laser beam welds the nanowires. Microstructure, morphology, material content, and electrical conductivities of the films are characterized before and after treatment. The morphology results show that laser peening can decrease porosity and bring nanowires into contact, and pulsed laser heating fuses those contacts. Multiphysics simulations coupling electromagnetic and heat transfer modules demonstrate that during pulsed laser heating, local EM field enhancement is generated specifically around the contact areas between two semiconductor nanowires, indicating localized heating. The characterization results indicate that solely laser peening or sintering can only moderately improve the thin film quality; however, when coupled together as laser peen sintering (LPS), the electrical conductivity enhancement is dramatic. LPS can decrease resistivity up to a factor of ~10,000, resulting in values on the order of ~105 Ω-cm in some cases, which is comparable to CdTe thin films. Our work demonstrates that LPS is an effective processing method to obtain high-quality semiconductor nanocrystal films.

  2. Welding of Semiconductor Nanowires by Coupling Laser-Induced Peening and Localized Heating

    Science.gov (United States)

    Rickey, Kelly M.; Nian, Qiong; Zhang, Genqiang; Chen, Liangliang; Suslov, Sergey; Bhat, S. Venkataprasad; Wu, Yue; Cheng, Gary J.; Ruan, Xiulin

    2015-01-01

    We demonstrate that laser peening coupled with sintering of CdTe nanowire films substantially enhances film quality and charge transfer while largely maintaining basic particle morphology. During the laser peening phase, a shockwave is used to compress the film. Laser sintering comprises the second step, where a nanosecond pulse laser beam welds the nanowires. Microstructure, morphology, material content, and electrical conductivities of the films are characterized before and after treatment. The morphology results show that laser peening can decrease porosity and bring nanowires into contact, and pulsed laser heating fuses those contacts. Multiphysics simulations coupling electromagnetic and heat transfer modules demonstrate that during pulsed laser heating, local EM field enhancement is generated specifically around the contact areas between two semiconductor nanowires, indicating localized heating. The characterization results indicate that solely laser peening or sintering can only moderately improve the thin film quality; however, when coupled together as laser peen sintering (LPS), the electrical conductivity enhancement is dramatic. LPS can decrease resistivity up to a factor of ~10,000, resulting in values on the order of ~105 Ω-cm in some cases, which is comparable to CdTe thin films. Our work demonstrates that LPS is an effective processing method to obtain high-quality semiconductor nanocrystal films. PMID:26527570

  3. Hypoxia-Inducible Factor-1α in carcinogenesis and progression of breast cancer

    NARCIS (Netherlands)

    Bos, R.

    2004-01-01

    This thesis is primarily focused on the previously hardly explored role of HIF-1 in breast cancer. HIF-1 is a transcription factor induced by hypoxia, but also by some oncogenes, tumor suppressor genes and growth factors. Activated HIF-1 can induce angiogenesis, glycolysis, erythropoiesis, and other

  4. Requirement for Tumor Necrosis Factor Receptor 2 Expression on Vascular Cells To Induce Experimental Cerebral Malaria

    OpenAIRE

    Stoelcker, Benjamin; Hehlgans, Thomas; Weigl, Karin; Bluethmann, Horst; Grau, Georges E.; Männel, Daniela N

    2002-01-01

    Using tumor necrosis factor receptor type 2 (TNFR2)-deficient mice and generating bone marrow chimeras which express TNFR2 on either hematopoietic or nonhematopoietic cells, we demonstrated the requirement for TNFR2 expression on tissue cells to induce lethal cerebral malaria. Thus, TNFR2 on the brain vasculature mediates tumor necrosis factor-induced neurovascular lesions in experimental cerebral malaria.

  5. Lipid emulsion-mediated reversal of toxic-dose aminoamide local anesthetic-induced vasodilation in isolated rat aorta

    OpenAIRE

    Ok, Seong-Ho; Han, Jeong Yeol; Lee, Soo Hee; Shin, Il-Woo; Lee, Heon Keun; Chung, Young-Kyun; Choi, Mun-Jeoung; Sohn, Ju-Tae

    2013-01-01

    Background Intravenous lipid emulsion has been used to treat systemic toxicity of local anesthetics. The goals of this in vitro study were to determine the ability of two lipid emulsions (Intralipid® and Lipofundin® MCT/LCT) to reverse toxic dose local anesthetic-induced vasodilation in isolated rat aortas. Methods Isolated endothelium-denuded aortas were suspended for isometric tension recording. Vasodilation was induced by bupivacaine (3 × 10-4 M), ropivacaine (10-3 M), lidocaine (3 × 10-3 ...

  6. Disruption of oligomerization induces nucleocytoplasmic shuttling of leukemia-associated rho Guanine-nucleotide exchange factor.

    Science.gov (United States)

    Grabocka, Elda; Wedegaertner, Philip B

    2007-10-01

    The rgsRhoGEFs comprise a subfamily of three guanine nucleotide exchange factors, which function in linking heterotrimeric G-proteins to the monomeric RhoGTPase. Here, we reveal the novel finding that oligomerization of leukemia-associated RhoGEF (LARG) functions to prevent nucleocytoplasmic shuttling and to retain LARG in the cytoplasm. We establish that oligomerization is mediated by a predicted coiled-coil sequence (amino acids 1507-1520) in the extreme C terminus of LARG and that substitution of isoleucines 1507/1510 with alanines disrupts homo-oligomerization and leads to nucleocytoplasmic shuttling via the CRM1 nuclear transport pathway. In addition, we demonstrate that induced dimerization of an otherwise nuclear monomeric LARG mutant promotes cytoplasmic localization. Furthermore, we establish that nuclear import of monomeric LARG is mediated by the nuclear localization sequence (29)PTDKKQK(35) in the extreme N terminus. We propose that nucleocytoplasmic shuttling provides a mechanism for spatially regulating the activity of LARG toward its cytoplasmic targets and potentially new nuclear targets.

  7. Evolution of the Therapeutic Effects of Induced Local Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    B. Basiri

    2011-04-01

    Full Text Available Introduction & Objective: Hypoxic-ischemic encephalopathy is one of the most important causes of permanent damage to brain tissue that redound to mortality and/or late sequelae such as cerebral palsy or delayed neural development. 15-20 percent of Hypoxic-ischemic encephalopathy (HIE cases die during neonatal period and 25-30 percent of those who survive suffer from neural development problems such as cerebral palsy and mental retardation. Hypothermia or lowering temperature of brain or total body is a new and promising treatment. The present study was done to assess therapeutic effects of induced local hypothermia in hypoxic-ischemic encephalopathy (HIE among neonates admitted to Fatemieh and Beset hospitals of Hamadan city.Materials & Method: The present study was performed as a randomized clinical trial upon 36 neonates who had inclusion criteria to be imported into the study. In the first 6 hours after birth, the neonates were randomly classified into two 18 person groups. In the control group the neonates were managed with routine treatments consisted of preservative measures and anti-convulsive treatments, if necessary. In the case group the neonates received induced local hypothermia for 6 hours in addition to routine therapeutic managements. The data were analyzed using SPSS Version 13.Results: 72.7% of the neonates of the case and control groups were male. There was no significant difference between the case and control groups in sex, birth weight, gestational age and perinatal obstetric complications. The mean duration of admission was 7.72±4.23 days in the case group and 10.06±5.99 days in the control group with no significant difference between the two groups (P=0.199. The mean time of starting oral feeding was 3.44±3.11 days and 4.53±2.74 days in the control and case groups respectively and this difference was not statistically significant either (P=0.737.The mean time of regaining consciousness was 3.72±3.19 days in the case

  8. Surprisingly low compliance to local guidelines for risk factor based screening for gestational diabetes mellitus - A population-based study

    Directory of Open Access Journals (Sweden)

    Winkvist Anna

    2009-11-01

    Full Text Available Abstract Background Screening for gestational diabetes mellitus (GDM is routine during pregnancy in many countries in the world. The screening programs are either based on general screening offered to all pregnant women or risk factor based screening stipulated in local clinical guidelines. The aims of this study were to investigate: 1 the compliance with local guidelines of screening for GDM and 2 the outcomes of pregnancy and birth in relation to risk factors of GDM and whether or not exposed to oral glucose tolerance test (OGTT. Methods This study design was a population-based retrospective cross-sectional study of 822 women. A combination of questionnaire data and data collected from medical records was applied. Compliance to the local guidelines of risk factor based screening for GDM was examined and a comparison of outcomes of pregnancy and delivery in relation to risk factor groups for GDM was performed. Results Of the 822 participants, 257 (31.3% women fulfilled at least one criterion for being exposed to screening for GDM according to the local clinical guidelines. However, only 79 (30.7% of these women were actually exposed to OGTT and of those correctly exposed for screening, seven women were diagnosed with GDM. Women developing risk factors for GDM during pregnancy had a substantially increased risk of giving birth to an infant with macrosomia. Conclusion Surprisingly low compliance with the local clinical guidelines for screening for GDM during pregnancy was found. Furthermore, the prevalence of the risk factors of GDM in our study was almost doubled compared to previous Swedish studies. Pregnant women developing risk factors of GDM during pregnancy were found to be at substantially increased risk of giving birth to an infant with macrosomia. There is a need of actions improving compliance to the local guidelines.

  9. Differential contribution of Clavibacter michiganensis ssp. michiganensis virulence factors to systemic and local infection in tomato.

    Science.gov (United States)

    Chalupowicz, Laura; Barash, Isaac; Reuven, Michal; Dror, Orit; Sharabani, Galit; Gartemann, Karl-Heinz; Eichenlaub, Rudolf; Sessa, Guido; Manulis-Sasson, Shulamit

    2017-04-01

    Clavibacter michiganensis ssp. michiganensis (Cmm) causes substantial economic losses in tomato production worldwide. The disease symptoms observed in plants infected systemically by Cmm are wilting and canker on the stem, whereas blister-like spots develop in locally infected leaves. A wide repertoire of serine proteases and cell wall-degrading enzymes has been implicated in the development of wilt and canker symptoms. However, virulence factors involved in the formation of blister-like spots, which play an important role in Cmm secondary spread in tomato nurseries, are largely unknown. Here, we demonstrate that Cmm virulence factors play different roles during blister formation relative to wilting. Inoculation with a green fluorescent protein (GFP)-labelled Cmm382 indicates that penetration occurs mainly through trichomes. When spray inoculated on tomato leaves, the wild-type Cmm382 and Cmm100 (lacking plasmids pCM1 and pCM2) strains form blister-like spots on leaves, whereas Cmm27 (lacking the chp/tomA pathogenicity island) is non-pathogenic, indicating that plasmid-borne genes, which have a crucial role in wilting, are not required for blister formation. Conversely, mutations in chromosomal genes encoding serine proteases (chpC and sbtA), cell wall-degrading enzymes (pgaA and endX/Y), a transcriptional regulator (vatr2), a putative perforin (perF) and a putative sortase (srtA) significantly affect disease incidence and the severity of blister formation. The transcript levels of these genes, as measured by quantitative reverse transcription-polymerase chain reaction, showed that, during blister formation, they are expressed early at 8-16 h after inoculation, whereas, during wilting, they are expressed after 24-72 h or expressed at low levels. Plant gene expression studies suggest that chpC is involved in the suppression of host defence. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  10. Prognostic factors and sites of metastasis in unresectable locally advanced pancreatic cancer.

    Science.gov (United States)

    Peixoto, Renata D'Alpino; Speers, Caroline; McGahan, Colleen E; Renouf, Daniel J; Schaeffer, David F; Kennecke, Hagen F

    2015-08-01

    Due to differences in natural history and therapy, clinical trials of patients with advanced pancreatic cancer have recently been subdivided into unresectable locally advanced pancreatic cancer (LAPC) and metastatic disease. We aimed to evaluate prognostic factors in LAPC patients who were treated with first-line chemotherapy and describe patterns of disease progression. Patients with LAPC who initiated first-line palliative chemotherapy, 2001-2011 at the BC Cancer Agency were included. A retrospective chart review was conducted to identify clinicopathologic variables, treatment, and subsequent sites of metastasis. Kaplan-Meier and Cox-regression survival analyses were performed. A total of 244 patients were included in this study. For the majority of patients (94.3%), first-line therapy was single-agent gemcitabine. About 144 (59%) patients developed distant metastatic disease and the most frequent metastatic sites included peritoneum/omentum (42.3%), liver (41%), lungs (13.9%), and distant lymph nodes (9%). Median overall survival (OS) for the entire cohort was 11.7 months (95% CI, 10.6-12.8). Development of distant metastases was associated with significantly inferior survival (HR 3.56, 95% CI 2.57-4.93), as was ECOG 2/3 versus 0/1 (HR 1.69, 95% CI 1.28-2.23), CA 19.9 > 1000 versus ≤ 1000 (HR 1.59, 95% CI 1.19-2.14) and female gender, (HR 1.57, 95% CI 1.19-2.08). In this population-based study, 41% of LAPC patients treated with first-line chemotherapy died without evidence of distant metastases. Prognostic factors for LAPC were baseline performance status, elevated CA 19.9, gender, and development of distant metastasis. Results highlight the heterogeneity of LAPC and the importance of locoregional tumor control.

  11. Anti-nutritional factors in the roots of a local cultivar of Moringa oleifera (Lam).

    Science.gov (United States)

    Igwilo, I O; Ezeonu, F C; Ezekwesili-Ofili, J O; Igwilo, S N; Nsofor, C I; Abdulsalami, M S; Obi, E

    2014-01-01

    The evergreen plant, Moringa oleifera (Lam) has been known to have both medicinal and nutritional properties, thus its wide use in traditional medicine in Africa and Asia. The roots, in particular, have been reported to possess antibiotic, anti-tumour and anti-oxidative activities. This study therefore seeks to determine the levels of the anti-nutritional factors and other proximate analyses in the roots of a local cultivar of Moringa oleifera which might be responsible for such activities. The concentrations of oxalates and phytates in the roots were determined using the methods of Munro and Bassir and Griffith and Thomas, respectively. The methods of Association of Analytical Chemists (AOAC) were used to estimate the amount of tannins, saponins and cyanogenic glycosides while the Technicon sequential Multi-sample amino acid analyzer (TSM) was used determine the amino acid concentration in the roots. Tannins (45 mg 100 g(-1)) and oxalates (17.08 mg 100 g(-1)) were present in the roots at higher levels while saponins (4.20mg 100 g(-1)), cyanogenic glycosides (2.72 mg 100 g(-1)) and phytates (0.07 mg 100 g(-1)) occurred at much lower levels. The roots contained (Mean +/- Standard Error of mean) %crude lipid (6.33 +/- 1.64), %crude proteins (5.02 +/- 1.52), %carbohydrates (76.75), %ash (4.97 +/- 0.53) and %moisture (6.93 +/- 0.58). The roots lacked the water-soluble vitamins pyridoxine, riboflavin and thiamine but contained ascorbic acid (48.13 mg 100 g(-1)) and niacin (5.83 mg 100 g(-1)). This study has shown that Moringa oleifera roots are rich in anti-nutritional factors and that is why they are widely used in traditional medicine in Africa, Asia and Americas for its medicinal importance.

  12. Gastrointestinal microbiota and local inflammation during oxazolone-induced dermatitis in BALB/cA mice

    DEFF Research Database (Denmark)

    Lundberg, Randi; Clausen, Susanne; Pang, Wanyong

    2012-01-01

    At present, laboratory animals are not standardized with regard to the gastrointestinal microbiota (GM), but differences in this feature may alter various parameters in animal models. We hypothesized that variation in the GM correlated with variation in clinical parameters of a murine oxazolone......-induced skin inflammation model of atopic dermatitis. BALB/cA mice were sensitized with oxazolone over a 28-d period and variation in gastrointestinal microbiota in fecal and cecal samples was assessed by PCR-denaturing gradient gel electrophoresis. Clinical parameters included transepidermal water loss, ear...... thickness, inflammatory factors in ear tissue and plasma, and histopathologic evaluation. The fecal microbiota before induction of skin inflammation strongly correlated with the levels of some proinflammatory cytokines (IFNγ, IL1β, IL12, and TNFα), the antiinflammatory cytokines IL4 and IL10...

  13. Sustainability in a global context: How does local factor affect the outcomes of CSR activities in international business units?

    DEFF Research Database (Denmark)

    Thomsen, Christa; Lauring, Jakob

    In recent years CSR has become increasingly important for the activities and branding of MNCs. While some studies have investigated CSR management and branding in domestic situations, fewer studies exist in the case of international business units (subsidiaries, joint ventures, and franchises...... as CSR branding outcomes). Our findings show that local values were positively associated with external CSR engagement and that employee relations were positively related to both internal and external CSR engagement. None of the local factors were significantly associated with CSR branding outcomes......). In this study, we use a sample consisting of 119 Danish business units that are located in China. We set out to investigate the relationship between local factors (the local business unit’s Chinese values and internal employee relations in the unit) and CSR outcomes (internal and external CSR engagement as well...

  14. Methoxychlor induces atresia by altering Bcl2 factors and inducing caspase activity in mouse ovarian antral follicles in vitro.

    Science.gov (United States)

    Basavarajappa, Mallikarjuna S; Karman, Bethany N; Wang, Wei; Gupta, Rupesh K; Flaws, Jodi A

    2012-12-01

    Methoxychlor (MXC) is an organochlorine pesticide widely used in many countries against various species of insects that attack crops and domestic animals. MXC reduces fertility by increasing atresia (death) of antral follicles in vivo. MXC also induces atresia of antral follicles after 96 h in vitro. The current work tested the hypothesis that MXC induces morphological atresia at early time points (24 and 48 h) by altering pro-apoptotic (Bax, Bok, Casp3, and caspase activity) and anti-apoptotic (Bcl2 and Bcl-xL) factors in the follicles. The results indicate that at 24 h, MXC increased Bcl-xL and Bax mRNA levels and increased the ratio of Bax/Bcl2. At 48-96 h, MXC induced morphological atresia. At 24-96 h, MXC increased caspase activities. These data suggest that MXC may induce atresia by altering Bcl2 factors and inducing caspase activities in antral follicles.

  15. Localization of damage in the human leg muscles induced by downhill running.

    Science.gov (United States)

    Maeo, Sumiaki; Ando, Yukino; Kanehisa, Hiroaki; Kawakami, Yasuo

    2017-07-18

    We investigated localization of damage within the knee extensors (KEs) and plantar flexors (PFs) induced by downhill running (DR) by using transverse relaxation time (T2)-weighted magnetic resonance imaging (MRI). Fourteen young adults performed 45-min DR (-15% slope) at their maximal tolerable velocity. At pre- and 24, 48, and 72 h post-exercise, T2-MRI was scanned and T2 values for each muscle composing KEs and PFs at proximal, middle, and distal sites were calculated. Maximal isometric torque and rate of torque development (RTD: 0-30, 0-50, 0-100, 0-200 ms) were also measured. Maximal torque significantly decreased in KEs (14-17%) and PFs (6-8%) at 24-48 h post-exercise, with greater reductions for KEs. RTD in all phases, except for 0-200 ms in PFs, significantly decreased in KEs (11-42%) and PFs (13-23%) at least at one time point post-exercise. T2 significantly increased at several sites (3-5%) in both muscle groups at 24 and/or 48 h post-exercise. Among the T2-increased sites, the peak effect size (Cohen's d) regarding T2 change was pronounced at proximal (1.05) and middle (1.64) vastus intermedius compared to the other sites (0.72-0.77). These results suggest that DR induces damage in both KEs and PFs, and especially affects proximal-middle sites of the vastus intermedius.

  16. Upregulated gene expression of local brain-derived neurotrophic factor and nerve growth factor after intracisternal administration of marrow stromal cells in rats with traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    胡德志; 周良辅; 朱剑虹; 毛颖; 吴雪海

    2005-01-01

    Objective: To examine the effects of rat marrow stromal cells (rMSCs) on gene expression of local brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) after injection of rMSCs into Cistern Magnum of adult rats subjected to traumatic brain injury(TBI).Results: Group cell transplantation had higher BDNF and NGF gene expressions than Group saline control during a period of less than 3 weeks (P<0.05).Conclusions: rMSCs transplantation via Cistern Magnum in rats subjected to traumatic brain injury can enhance expressions of local brain NGF and BDNF to a certain extent.

  17. Local gene regulation details a recognition code within the LacI transcriptional factor family.

    Directory of Open Access Journals (Sweden)

    Francisco M Camas

    Full Text Available The specific binding of regulatory proteins to DNA sequences exhibits no clear patterns of association between amino acids (AAs and nucleotides (NTs. This complexity of protein-DNA interactions raises the question of whether a simple set of wide-coverage recognition rules can ever be identified. Here, we analyzed this issue using the extensive LacI family of transcriptional factors (TFs. We searched for recognition patterns by introducing a new approach to phylogenetic footprinting, based on the pervasive presence of local regulation in prokaryotic transcriptional networks. We identified a set of specificity correlations--determined by two AAs of the TFs and two NTs in the binding sites--that is conserved throughout a dominant subgroup within the family regardless of the evolutionary distance, and that act as a relatively consistent recognition code. The proposed rules are confirmed with data of previous experimental studies and by events of convergent evolution in the phylogenetic tree. The presence of a code emphasizes the stable structural context of the LacI family, while defining a precise blueprint to reprogram TF specificity with many practical applications.

  18. Predicting transcription factor binding sites using local over-representation and comparative genomics

    Directory of Open Access Journals (Sweden)

    Touzet Hélène

    2006-08-01

    Full Text Available Abstract Background Identifying cis-regulatory elements is crucial to understanding gene expression, which highlights the importance of the computational detection of overrepresented transcription factor binding sites (TFBSs in coexpressed or coregulated genes. However, this is a challenging problem, especially when considering higher eukaryotic organisms. Results We have developed a method, named TFM-Explorer, that searches for locally overrepresented TFBSs in a set of coregulated genes, which are modeled by profiles provided by a database of position weight matrices. The novelty of the method is that it takes advantage of spatial conservation in the sequence and supports multiple species. The efficiency of the underlying algorithm and its robustness to noise allow weak regulatory signals to be detected in large heterogeneous data sets. Conclusion TFM-Explorer provides an efficient way to predict TFBS overrepresentation in related sequences. Promising results were obtained in a variety of examples in human, mouse, and rat genomes. The software is publicly available at http://bioinfo.lifl.fr/TFM-Explorer.

  19. Immunoelectron microscopic localization of epidermal growth factor in the eccrine and apocrine sweat glands.

    Science.gov (United States)

    Saga, K; Takahashi, M

    1992-02-01

    We studied the localization of the epidermal growth factor (EGF) in eccrine and apocrine sweat glands with light microscopic and electron microscopic immunohistochemistry. Anti-human EGF (anti-hEGF) polyclonal antiserum and anti-hEGF monoclonal antibody (MAb) were used for the study. Light microscopic immunohistochemistry with monoclonal and polyclonal antibodies showed that hEGF-like immunoreactivity was strongly positive in the myoepithelial cells and weakly positive in the secretory cells of eccrine sweat glands. In apocrine sweat glands, it was strongly positive in the secretory cells as well as in the myoepithelial cells. Immunoelectron microscopy with polyclonal antibody showed that hEGF-like immunoreactivity was present in secretory granules of apocrine secretory cells. These granules had mitochondrion-like internal structure. No reactivity was observed on the eccrine secretory cells by immunoelectron microscopy. Neither dark cell granules nor mitochondria in eccrine secretory cells were labeled with anti-hEGF antibody. In both eccrine and apocrine sweat glands, hEGF-like immunoreactivity was diffusely present in the cytoplasm of myoepithelial cells. However, nuclei and mitochondria of myoepithelial cells were devoid of immunoreactivity for hEGF. Our observations indicate that apocrine sweat glands may secrete more hEGF in the sweat than eccrine sweat glands.

  20. Calibration of Local Area Weather Radar—Identifying significant factors affecting the calibration

    Science.gov (United States)

    Pedersen, Lisbeth; Jensen, Niels Einar; Madsen, Henrik

    2010-07-01

    A Local Area Weather Radar (LAWR) is an X-band weather radar developed to meet the needs of high resolution rainfall data for hydrological applications. The LAWR system and data processing methods are reviewed in the first part of this paper, while the second part of the paper focuses on calibration. The data processing for handling the partial beam filling issue was found to be essential to the calibration. LAWR uses a different calibration process compared to conventional weather radars, which use a power-law relationship between reflectivity and rainfall rate. Instead LAWR uses a linear relationship of reflectivity and rainfall rate as result of the log transformation carried out by the logarithmic receiver as opposed to the linear receiver of conventional weather radars. Based on rain gauge data for a five month period from a dense network of nine gauges within a 500 × 500 m area and data from a nearby LAWR, the existing calibration method was tested and two new methods were developed. The three calibration methods were verified with three external gauges placed in different locations. It can be concluded that the LAWR calibration uncertainties can be reduced by 50% in two out of three cases when the calibration is based on a factorized 3 parameter linear model instead of a single parameter linear model.

  1. Influences of local factors on permafrost occurrence and their implications for Qinghai-Xizang Railway design

    Institute of Scientific and Technical Information of China (English)

    CHENG; Guodong

    2004-01-01

    The construction of the Qinghai-Xizang Railway is facing some challenges posed by the presence of warm and ice-rich permafrost and predicted climate warming. To resolve these issues and ensure the railway a success, adjustments will have to be made in design strategies and principles. This paper presents several examples of permafrost-distribution anomaly caused by site-specific conditions. It analyzes the mechanism through which these local factors influence the occurrence and preservation of permafrost by modifying the heat convection and conduction patterns, and the amount of solar radiation received by the ground surface. A good understanding of these anomalies in permafrost occurrence is significant as it may provide some hints on the techniques and measures we can use to artificially simulate similar effects. A number of measures can be taken to lower ground temperature and to counter the effect of climate warming. These measures include use of proper roadbed material and configuration, in order to adjust solar radiation, heat convection and conduction patterns. It is recommended that a new proactive approach be adopted in the railway design. This approach emphasizes the use of all the above-mentioned measures to cool down the roadbed. This is different from previous methods of preventing permafrost from thawing by utilizing more thermal resistant materials.

  2. Reduced Pulsatility Induces Periarteritis in Kidney: Role of the Local Renin-Angiotensin System

    Science.gov (United States)

    Ootaki, Chiyo; Yamashita, Michifumi; Ootaki, Yoshio; Kamohara, Keiji; Weber, Stephan; Klatte, Ryan S.; Smith, William A.; Massiello, Alex L.; Emancipator, Steven N.; Golding, Leonard A.R.; Fukamachi, Kiyotaka

    2008-01-01

    Background The need for pulsatility in the circulation during long-term mechanical support has been a subject of debate. We compared histological changes in calf renal arteries subjected to various degrees of pulsatile circulation in vivo. We addressed the hypothesis that the local reninangiotensin system (RAS) may be implicated in these histological changes. Methods and Results Sixteen calves were implanted with devices giving differing degrees of pulsatile circulation: six had a continuous flow left ventricular assist device (LVAD); six had a continuous flow right ventricular assist device (RVAD); and four had a pulsatile total artificial heart (TAH). Six other calves were histological and immunohistochemical controls. In the LVAD group, the pulsatility index was significantly lower (0.28 ± 0.07 LVAD vs 0.56 ± 0.08 RVAD, vs 0.53 ± 0.10 TAH; p < 0.01), and we observed severe periarteritis in all cases in the LVAD group. The number of angiotensin II type 1 receptor (AT1R)-positive cells and angiotensin converting enzyme (ACE)-positive cells in periarterial areas was significantly higher in the LVAD group (AT1R: 350 ± 139 LVAD vs 8 ± 6 RVAD, vs 3 ± 2 TAH, vs 3 ± 2 in control; p < 0.001 and ACE: 325 ± 59 LVAD vs 6 ± 4 RVAD, vs 6 ± 5 TAH, vs 3 ± 1 control; p < 0.001). Conclusions The reduced pulsatility produced by a continuous flow LVAD implantation induced severe periarteritis in the kidney. The local RAS was upregulated in the inflammatory cells only in the continuous flow LVAD group. ULTAMINI-ABSTRACT We compared histological changes in calf renal arteries subjected to various degrees of pulsatile circulation; continuous flow left ventricular assist device (LVAD), continuous flow right ventricular assist device, pulsatile total artificial heart and control. We observed severe periarteritis, and upregulation of local renin angiotensin system only in the LVAD group. The necessity of maintaining pulsatility in the systemic circulation during long

  3. Albatross as Sentinels of Heavy Metal Pollution: Local and Global Factors

    Directory of Open Access Journals (Sweden)

    Bank M.S.

    2014-07-01

    Full Text Available Heavy metal pollution in the Pacific Ocean has garnered significant attention in recent years, especially with regard to rising mercury emissions from Asia. Uncertainty exists over the extent to which mercury in biota may have resulted from increases in anthropogenic emissions over time. Albatrosses, including those inhabiting the North Pacific, are wide-ranging, long-lived, keystone, avian predators. Consequently, they serve as ideal sentinel species for investigating the effects of historical and contemporary pollution as well as local and global factors related to heavy metal exposure, bioaccumulation, and ecotoxicological risk. To date, high levels of mercury and lead have been documented in albatross species throughout the Pacific. To address biotic exposure to these multiple stressors, here we synthesize and conduct meta-analyses of total mercury, methylmercury, and lead exposure data in Black-footed albatross (Phoebastria nigripes and Laysan albatross (Phoebastria immutabilis. Our approach includes data from the field and literature, and for total mercury and methyl mercury, we use measurements from museum feathers spanning the past 130 years for Black-Footed albatross. We discuss the use and application of stable isotopes (δ15N and δ13C as a way to control for temporal changes in trophic structure and diet and we demonstrate the importance of conducting speciation analyses for mercury to account for historical, curator-mediated, inorganic mercury contamination of specimens. Our data showed higher levels of inorganic mercury in older specimens of Black-Footed albatross as well as two non-pelagic species (control samples lacking historical sources of bioavailable mercury exposure, which suggests that studies on bioaccumulation should measure methylmercury rather than total mercury when utilizing museum collections. Changes in methylmercury levels in Black-Footed albatross were consistent with historical global and recent regional

  4. Expression and localization of forkhead transcriptional factor 2 (Foxl2 in the gonads of protogynous wrasse, Halichoeres trimaculatus

    Directory of Open Access Journals (Sweden)

    Kobayashi Yasuhisa

    2010-11-01

    Full Text Available Abstract Background Three-spot wrasse, Halichoeres trimaculatus, is a marine protogynous hermaphrodite fish. Individuals mature either as initial phase (IP males or females. Appropriate social cues induce the sex change from IP female to terminal phase (TP male. However, the molecular mechanisms behind such a sex change remain largely unknown. Recently, the forkhead transcription factor 2 (Foxl2 was identified as an essential regulator of vertebrate ovarian development/function/phenotype. Inspired by this information, we characterized the expression patterns of Foxl2 in the protogynous wrasse assuming Foxl2 as the female-specific marker in this species. Methods First, we clonedFoxl2 cDNA from ovary by reverse transcription polymerase chain reaction (RT-PCR followed by rapid amplification of cDNA ends (RACE. Next, we analysed expression pattern of Foxl2 messenger RNA (mRNA and protein in gonads of different sexual phases by real time quantitative PCR assay and flour fluorescence immunohistochemical method, respectively. Additionally, we studied the changes in Foxl2 expression pattern during aromatase inhibitor (AI-induced sex change. Results The amino acid sequence (306 AA of wrasse Foxl2, especially the forkhead domain, shows high identity with that of other reported teleost Foxl2s. Quite unexpectedly, no sexual dimorphism was observable between the testes and ovary in the expression pattern of Foxl2. In female phase fish, signals for Foxl2 protein were detectable in the granulosa cells, but not the theca cells. Transcript levels of Foxl2 in the testes of IP and TP males were identical to that in the ovaries of females and, further, Foxl2 protein was found to be localized in the interstitial cells including tubules and Leydig cells. Treatment with AI induced sex change in male gonads and an up-regulation was seen in the expression of Foxl2 in these gonads. Conclusions Unlike in other vertebrates, including teleosts, Foxl2 may have a different

  5. Adenovirus-mediated hypoxia-inducible factor-1 alpha gene transfer induces angiogenesis and neurogenesis following cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    Wanfu Wu; Xiu Chen; Zhen Yu; Changlin Hu; Wenqin Cai

    2008-01-01

    BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) accumulates under conditions of hypoxia. HIF-1α target genes have pleiotropic effects on neurogenesis, neuroprotection and angiogenesis in the brain.OBJECTIVE: To investigate whether a recombinant adenovirus carrying HIF-1α can increase the expression of HIF-1α in vivo and thus promote angiogenesis and neurogenesis in a rat model of focal cerebral ischemia.DESIGN, TIME AND SETTING: The randomized, controlled experiment was performed at the Department of Neurobiology, Third Military Medical University of Chinese PLA from September 2006 to October 2007.MATERIALS: 68 healthy adult male Sprague-Dawley (SD) rats, weighing 230-250 g, were used. HIF-1α antibody was purchased from Wuhan Boster Company. Vascular endothelial growth factor (VEGF) antibody was purchased from Santa Cruz Biotech Company.METHODS: All 68 rats were induced with a transient middle cerebral artery occlusion (MCAO), according to the method of intra-luminal vascular occlusion. 54 rats, in which MCAO was successfully induced, were randomly divided into adenovirus (Ad) group and recombinant adenovirus with HIF-1αgene (Ad-HIF-1α) group (27 rats for each group). Rats were injected with 10 μL Ad (Ad group) or Ad-HIF-1α (Ad-HIF-1α group) into the lateral ventricle, 1 day after MCAO induction. MAIN OUTCOME MEASURES: Reverse transcription polymerase chain reaction was used to measure the expression of HIF-1α and of VEGF. Immunohistochemistry was used to detect the localization of HIF-1α, VEGF and factor Ⅷ in ischemic penumbra. Rat newborn nerve cells were labeled with 5-bromodeoxyuridine (BrdU) after ischemia. BrdU/neurofilament 200 (NF200) and BrdU/glial fibrillary acidic protein (GFAP) double labeled immunofluorescent histochemistry was used to identify the differentiation of newborn cells. Neurological function was evaluated using the modified neurological severity score (NSS).RESULTS: Compared with Ad, Ad-HIF-1αenhanced the expression of HIF-1

  6. Risk factors related to interfractional variation in whole pelvic irradiation for locally advanced pelvic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, W.S.; Yang, D.S.; Lee, J.A.; Lee, S.; Park, Y.J.; Kim, C.Y. [Korea Univ. Medical Center, Seoul (Korea, Republic of). Dept. of Radiation Oncology

    2012-05-15

    Purpose: The goal of the present study was to demonstrate risk factors affecting the interfractional variation in whole pelvic irradiation. Patients and methods: Daily image acquisitions of 101 patients with locally advanced pelvic malignancy were undertaken using a kilo-voltage orthogonal on-board imager. The baseline deviation (the shift between the initial treatment and each fraction; Value{sub Base}) and day-to-day variation (the shift between the previous treatment and each fraction; Value{sub DD}) were measured. The standard deviations (SD) along the x- (right-left), y- (cranial-caudal), and z- (anterior-posterior) axes (SD[x], SD[y], and SD[z], respectively), the 3D vector of the SD (SD[3D]), and the mean of 3D shift (mean[3D]) were calculated in each patient. Various clinical factors, lumbar pelvic balance and rotation, and the shift of 5 consecutive fractions from the initial treatment (Value{sub 5Fx}) were investigated as risk factors. Results: The prone set-up showed a larger mean{sub Base}[3D] than in the supine position (p =0.063). A body mass index (BMI) {>=} 30 kg/m{sup 2} resulted in the largest mean{sub DD}[3D] (p = 0.078) and SD{sub DD}[3D] (p = 0.058). All the SD{sub 5Fx} along the x-, y-, and z-axes had moderate linear relationships with SD{sub Base} and SD{sub DD} (p < 0.001). The SD{sub 5Fx}[3D] also had a moderate linear relationship with the mean{sub Base}[3D], mean{sub DD}[3D], SD{sub Base}[3D], and SD{sub DD}[3D] (p < 0.001). In multivariate analysis, the SD{sub 5Fx} had the same significant relationship with SD{sub Base} and SD{sub DD} (p < 0.001). A BMI {>=} 30 kg/m{sup 2} was associated with the largest SD{sub DD}[x] (p = 0.003). Conclusion: Close surveillance through high-quality and frequent image guidance is recommended for patients with extensive variations of the initial five consecutive fractions or obesity. (orig.)

  7. Enhanced boundary lubrication properties of engineered menisci by lubricin localization with insulin-like growth factor I treatment.

    Science.gov (United States)

    Bonnevie, Edward D; Puetzer, Jennifer L; Bonassar, Lawrence J

    2014-06-27

    In this study we analyzed the effects of IGF-I on the boundary lubricating ability of engineered meniscal tissue using a high density collagen gel seeded with meniscal fibrochondrocytes. Biochemical, histological, immunohistochemical, and tribological analyses were carried out to determine a construct's ability to functionally localize lubricin. Our study revealed that supplementation with IGF-I enhanced both the proliferation of cells within the construct as well as enhanced the anabolic activity of the seeded cells. Growth factor supplementation also facilitated the localization of ECM constituents (i.e. fibronectin and type II collagen) near the tissue surface that are important for the localization of lubricin, a boundary lubricant. Consequently, we found localized lubricin in the constructs supplemented with IGF-I. Tribologically, we demonstrated that lubricin serves as a boundary lubricant adsorbed to native meniscal surfaces. Lubricin removal from the native meniscus surface increased boundary friction coefficient by 40%. For the engineered constructs, the lubricin localization facilitated by growth factor supplementation also reduced friction coefficient by a similar margin, but similar results were not evident in control constructs. This study demonstrates that the use of growth factors in meniscal tissue engineering can enhance tribological properties by facilitating the localization of boundary lubricants at the surface of engineered tissue.

  8. Epidermal growth factor inhibits cysteamine-induced duodenal ulcers

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1983-01-01

    The effect of the duodenal ulcerogen cysteamine on secretion of epidermal growth factor from Brunner's gland pouches was studied in the rat. Total output of immunoreactive epidermal growth factor was reduced to approximately 55%, compared with controls, 5 h after administration of cysteamine (300...... mg/kg, s.c.). Furthermore, measurements on tissue extracts of the pouches revealed that 5 h after cysteamine treatment, Brunner's glands were depleted of epidermal growth factor. The effect on ulcer development of intraduodenally applied exogenous epidermal growth factor (1 micrograms/kg . h) also...... factor used, when tested on chronic fistula rats, had no effect on acid secretion and did not influence bicarbonate secretion from Brunner's gland pouches. These results demonstrate that epidermal growth factor has a cytoprotective effect on the duodenal mucosa, and it is suggested that inhibition...

  9. Regulatory Role of Gonadotropins and Local Factors Produced by Ovarian Follicles on In Vitro Resistin Expression and Action on Porcine Follicular Steroidogenesis.

    Science.gov (United States)

    Rak, Agnieszka; Drwal, Eliza; Karpeta, Anna; Gregoraszczuk, Ewa Ł

    2015-06-01

    Resistin, a hormone secreted by adipocytes, is thought to be important in reproduction. Our previous study demonstrated resistin expression in porcine ovarian follicles and its direct effect on steroidogenesis. The aim of the current study was to evaluate the effect of gonadotropins and the local ovarian factors, such as insulin-like growth factor type 1 (IGF1) and steroids (progesterone, testosterone, and 17 beta-estradiol), on the expression and secretion of resistin, as well as its steroidogenic action. Porcine ovarian follicles were exposed to follicle-stimulating hormone (FSH) and luteinizing hormone (LH) at 50-150 ng/ml, IGF1 (10-100 ng/ml), and steroids at 10(-8) to 10(-6) M for 24 h. Then, mRNA, protein expression, and medium concentration of resistin were determined using real-time PCR, Western blot analysis, and ELISA, respectively. In the subsequent experiments, ovarian follicles were exposed to resistin and/or FSH, LH, IGF1, and steroids, and ovarian steroidogenesis was analyzed. Additionally, we examined the direct effect of resistin on the protein expression of receptors for gonadotropins and investigated local factors. The results showed that gonadotropins and steroids have stimulatory effects but that IGF1 has an inhibitory effect on resistin expression and secretion. Resistin decreased gonadotropins and local hormone-induced steroid secretion and inhibited 3beta-hydroxysteroid dehydrogenase, 17beta-hydroxysteroid dehydrogenase, and cytochrome P450 aromatase protein expression. Additionally, we demonstrated that resistin increased the expression of receptors for progesterone and testosterone. These findings all show that the expression and function of resistin are regulated by gonadotropins and local factors produced by ovarian follicles.

  10. Intracellular mediators of transforming growth factor β superfamily signaling localize to endosomes in chicken embryo and mouse lenses in vivo

    Directory of Open Access Journals (Sweden)

    Ishii Shunsuke

    2007-06-01

    Full Text Available Abstract Background Endocytosis is a key regulator of growth factor signaling pathways. Recent studies showed that the localization to endosomes of intracellular mediators of growth factor signaling may be required for their function. Although there is substantial evidence linking endocytosis and growth factor signaling in cultured cells, there has been little study of the endosomal localization of signaling components in intact tissues or organs. Results Proteins that are downstream of the transforming growth factor-β superfamily signaling pathway were found on endosomes in chicken embryo and postnatal mouse lenses, which depend on signaling by members of the TGFβ superfamily for their normal development. Phosphorylated Smad1 (pSmad1, pSmad2, Smad4, Smad7, the transcriptional repressors c-Ski and TGIF and the adapter molecules Smad anchor for receptor activation (SARA and C184M, localized to EEA-1- and Rab5-positive vesicles in chicken embryo and/or postnatal mouse lenses. pSmad1 and pSmad2 also localized to Rab7-positive late endosomes. Smad7 was found associated with endosomes, but not caveolae. Bmpr1a conditional knock-out lenses showed decreased nuclear and endosomal localization of pSmad1. Many of the effectors in this pathway were distributed differently in vivo from their reported distribution in cultured cells. Conclusion Based on the findings reported here and data from other signaling systems, we suggest that the localization of activated intracellular mediators of the transforming growth factor-β superfamily to endosomes is important for the regulation of growth factor signaling.

  11. Internet-induced marketing techniques: Critical factors of viral marketing

    OpenAIRE

    Woerndl, M; Papagiannidis, S; Bourlakis, M. A.; Li, F.

    2008-01-01

    The rapid diffusion of the Internet and the emergence of various social constructs facilitated by Internet technologies are changing the drivers that define how marketing techniques are developed and refined. This paper identifies critical factors for viral marketing, an Internet-based ‘word-of-mouth’ marketing technique. Based on existing knowledge, five types of viral marketing factors that may critically influence the success of viral marketing campaigns are identified. These factors are t...

  12. Using Electromyography to Detect the Weightings of the Local Muscle Factors to the Increase of Perceived Exertion During Stepping Exercise

    Directory of Open Access Journals (Sweden)

    Miao-Ju Hsu

    2008-06-01

    Full Text Available Rate of perceived exertion (RPE is a clinically convenient indicator for monitoring exercise intensity in cardiopulmonary rehabilitation. It might not be sensitive enough for clinicians to determine the patients’ physiological status because its association with the cardiovascular system and local muscle factors is unknown. This study used the electromyographic sensor to detect the local muscle fatigue and stabilization of patella, and analyzed the relationship between various local muscle and cardiovascular factors and the increase of RPE during stepping exercise, a common exercise program provided in cardiopulmonary rehabilitation. Ten healthy adults (4 males and 6 females participated in this study. Each subject used their right bare foot to step up onto a 23-cm-high step at a constant speed until the RPE score reached 20. The RPE, heart rate (HR, and surface EMG of the rectus femoris (RF, vastus medialis, and vastus lateralis were recorded at 1-minute intervals during the stepping exercise. The generalized estimating equations (GEE analysis indicated that the increase in RPE significantly correlated with the increase in HR, and decrease in median frequency (MF of the EMG power spectrum of the RF. Experimental results suggest that the increase in RPE during stepping exercise was influenced by the cardiovascular status, localized muscle fatigue in the lower extremities. The weighting of the local muscle factors was more than half of the weighting of the cardiovascular factor.

  13. Dietary inclusion of local salt substitutes induces oxidative stress and renal dysfunction in rats.

    Science.gov (United States)

    Akinyemi, Ayodele J; Oboh, Ganiyu; Ademiluyi, Adedayo O; Araoye, Obafemi O; Oyeleye, Sunday I

    2014-01-01

    Our earlier report has shown that salt substitutes (Obu-Otoyo) contain some toxic heavy metals. This study, therefore, investigated the effect of the dietary inclusion of salt substitutes (Obu-Otoyo), namely, salt "A" and "B", on biomarkers of oxidative stress and renal function in rats. Salt "A", which has a gray color, is the product of a process in which ash is produced by burning palm kernel shaft soaked in water overnight and extracting the residue to produce the salt substitute while Salt "B", which has a white color, is a rock salt mined from a local site at Ilobu town, Osun-State, Nigeria. Salt substitutes were fed to normal rats as dietary inclusion at 0.5% and 1.0% for 21 days. The dietary inclusion of the salt substitutes caused a significant (psalt substitutes caused a significant (psalt substitute Obu-Otoyo. Therefore, this finding indicates that Obu-Otoyo induces nephrotoxicity in rats. The nephrotoxicity of Obu-Otoyo could be attributed to the induction of oxidative stress as a result of the presence of some heavy metals, suggesting possible health hazards in subjects who consume it.

  14. Exogenous cardiolipin localizes to mitochondria and prevents TAZ knockdown-induced apoptosis in myeloid progenitor cells.

    Science.gov (United States)

    Ikon, Nikita; Su, Betty; Hsu, Fong-Fu; Forte, Trudy M; Ryan, Robert O

    2015-08-21

    The concentration and composition of cardiolipin (CL) in mitochondria are altered in age-related heart disease, Barth Syndrome, and other rare genetic disorders, resulting in mitochondrial dysfunction. To explore whether exogenous CL can be delivered to cells, CL was combined with apolipoprotein A-I to generate water-soluble, nanoscale complexes termed nanodisks (ND). Mass spectrometry of HL60 myeloid progenitor cell extracts revealed a 30-fold increase in cellular CL content following incubation with CL-ND. When CL-ND containing a fluorescent CL analogue was employed, confocal microscopy revealed CL localization to mitochondria. The ability of CL-ND to elicit a physiological response was examined in an HL60 cell culture model of Barth Syndrome neutropenia. siRNA knockdown of the phospholipid transacylase, tafazzin (TAZ), induced apoptosis in these cells. When TAZ knockdown cells were incubated with CL-ND, the apoptotic response was attenuated. Thus, CL-ND represent a potential intervention strategy for replenishment of CL in Barth Syndrome, age-related heart disease, and other disorders characterized by depletion of this key mitochondrial phospholipid.

  15. Raman study of localized recrystallization of amorphous silicon induced by laser beam

    KAUST Repository

    Tabet, Nouar A.

    2012-06-01

    The adoption of amorphous silicon based solar cells has been drastically hindered by the low efficiency of these devices, which is mainly due to a low hole mobility. It has been shown that using both crystallized and amorphous silicon layers in solar cells leads to an enhancement of the device performance. In this study the crystallization of a-Si prepared by PECVD under various growth conditions has been investigated. The growth stresses in the films are determined by measuring the curvature change of the silicon substrate before and after film deposition. Localized crystallization is induced by exposing a-Si films to focused 532 nm laser beam of power ranging from 0.08 to 8 mW. The crystallization process is monitored by recording the Raman spectra after various exposures. The results suggest that growth stresses in the films affect the minimum laser power (threshold power). In addition, a detailed analysis of the width and position of the Raman signal indicates that the silicon grains in the crystallized regions are of few nm diameter. © 2012 IEEE.

  16. The Use of Recently Developed Histochemical Markers for Localizing Neurotoxicant Induced Regional Brain Pathologies

    Directory of Open Access Journals (Sweden)

    Sumit Sarkar

    2014-04-01

    Full Text Available Neuronal and vascular brain components are interrelated morphologically, physiologically and developmentally. Due to this close interrelationship, it is often difficult to understand the cause and effect relationship between neuronal vs. vascular dysfunction and pathology. This review will discuss four of the more promising recent developments for detecting vascular pathology, and will compare them with the labeling pattern seen with markers of glial and neuronal pathology; following exposure to well characterized neurotoxicants. To detect the vascular dysfunction in the brain, we recently developed a Fluoro-Turquoise gelatin conjugate (FT-gel, a fluorescent probe that helps to delineate between healthy vs. sclerotic vessels. Similarly, we have investigated the potential for Fluoro-Gold to label in vivo all the endothelial cells in the brain as they co-localize with RECA, an endothelial cell marker. We have also developed Amylo-Glo, a fluorescent tracer that can detect neurotoxic A-beta aggregates in the brain. In this article, we will discuss the potential use of these novel histochemical markers to study the neurotoxicant induced brain. We will also discuss neurovascular strategies that may offer novel therapeutic opportunities for neurodegenerative disorders.

  17. Investigation of gamma radiation induced changes in local structure of borosilicate glass by TDPAC and EXAFS

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Ashwani, E-mail: kashwani@barc.gov.in [Bhabha Atomic Research Centre, Radioanalytical Chemistry Division (India); Nayak, C.; Rajput, P. [Bhabha Atomic Research Centre, Atomic and Molecular Physics Division (India); Mishra, R. K. [Bhabha Atomic Research Centre, Waste Management Division (India); Bhattacharyya, D. [Bhabha Atomic Research Centre, Atomic and Molecular Physics Division (India); Kaushik, C. P. [Bhabha Atomic Research Centre, Waste Management Division (India); Tomar, B. S. [Bhabha Atomic Research Centre, Radioanalytical Chemistry Division (India)

    2016-12-15

    Gamma radiation induced changes in local structure around the probe atom (Hafnium) were investigated in sodium barium borosilicate (NBS) glass, used for immobilization of high level liquid waste generated from the reprocessing plant at Trombay, Mumbai. The (NBS) glass was doped with {sup 181}Hf as a probe for time differential perturbed angular correlation (TDPAC) spectroscopy studies, while for studies using extended X-ray absorption fine structure (EXAFS) spectroscopy, the same was doped with 0.5 and 2 % (mole %) hafnium oxide. The irradiated as well as un-irradiated glass samples were studied by TDPAC and EXAFS techniques to obtain information about the changes (if any) around the probe atom due to gamma irradiation. TDPAC spectra of unirradiated and irradiated glasses were similar and reminescent of amorphous materials, indicating negligible effect of gamma radiation on the microstructure around Hafnium probe atom, though the quaqdrupole interaction frequency (ω{sub Q}) and asymmetry parameter (η) did show a marginal decrease in the irradiated glass compared to that in the unirradiated glass. EXAFS measurements showed a slight decrease in the Hf-O bond distance upon gamma irradiation of Hf doped NBS glass indicating densification of the glass matrix, while the cordination number around hafnium remains unchanged.

  18. A two-photon laser induced fluorescence diagnostic with improved sensitivity, localization, and measurement rate

    Science.gov (United States)

    Elliott, Drew; Scime, Earl; Short, Zachary

    2016-10-01

    A two-photon absorption laser induced fluorescence diagnostic has been developed for measuring neutrals in fusion plasmas. Implementation of this diagnostic on the HIT-SI3 spheromak has demonstrated the sensitivity of the diagnostic and shown that measurements taken over several plasma pulses are possible. These measurements yielded an unexpected loss of signal when complex collection optics were utilized. Simulations show that this loss of signal can be explained by chromatic aberrations caused by the disparate Kr and D emission. This loss of signal has been addressed with the development of a new calibration scheme involving xenon gas. The Xe calibration scheme emission occurs at 656.00 nm while the deuterium emission is 656.09 nm. This nearly identical emission allows for advanced optical techniques such as confocal collection/injection and spatial filtering to be employed without loss of signal. Spatial filtering has been demonstrated to decrease noise while improving measurement localization, while confocal collection/injection allows for probing and measuring to occur through one viewport. The Xe scheme also allows for a Doppler-free hydrogen measurement. Doppler-free measurements eliminate the need to scan the laser spectrally thus greatly increasing the rate of measurement.

  19. Local and global ligand-induced changes in the structure of the GABA(A) receptor.

    Science.gov (United States)

    Muroi, Yukiko; Czajkowski, Cynthia; Jackson, Meyer B

    2006-06-13

    Ligand-gated channels mediate synaptic transmission through conformational transitions triggered by the binding of neurotransmitters. These transitions are well-defined in terms of ion conductance, but their structural basis is poorly understood. To probe these changes in structure, GABA(A) receptors were expressed in Xenopus oocytes and labeled at selected sites with environment-sensitive fluorophores. With labels at two different residues in the alpha1 subunit in loop E of the GABA-binding pocket, GABA elicited fluorescence changes opposite in sign. This pattern of fluorescence changes is consistent with a closure of the GABA-binding cavity at the subunit interface. The competitive antagonist SR-95531 inverted this pattern of fluorescence change, but the noncompetitive antagonist picrotoxin failed to elicit optical signals. In response to GABA (but not SR-95531), labels at the homologous residues in the beta2 subunit showed the same pattern of fluorescence change as the alpha1-subunit labels, indicating a global transition with comparable movements in homologous regions of different subunits. Incorporation of the gamma2 subunit altered the fluorescence changes of alpha1-subunit labels and eliminated them in beta2-subunit labels. Thus, the ligand-induced structural changes in the GABA(A) receptor can extend over considerable distances or remain highly localized, depending upon subunit composition and ligand.

  20. Propagation of the state change induced by external forces in local interactions

    Science.gov (United States)

    Lu, Jianjun; Tokinaga, Shozo

    2016-10-01

    This paper analyses the propagation of the state changes of agents that are induced by external forces applied to a plane. In addition, we propose two models for the behavior of the agents placed on a lattice plane, both of which are affected by local interactions. We first assume that agents are allowed to move to another site to maximise their satisfaction. Second, we utilise a model in which the agents choose activities on each site. The results show that the migration (activity) patterns of agents in both models achieve stability without any external forces. However, when we apply an impulsive external force to the state of the agents, we then observe the propagation of the changes in the agents' states. Using simulation studies, we show the conditions for the propagation of the state changes of the agents. We also show the propagation of the state changes of the agents allocated in scale-free networks and discuss the estimation of the agents' decisions in real state changes. Finally, we discuss the estimation of the agents' decisions in real state temporal changes using economic and social data from Japan and the United States.

  1. Experiments on Linear and Nonlinear Localization of Optical Vortices in Optically Induced Photonic Lattices

    Directory of Open Access Journals (Sweden)

    Daohong Song

    2012-01-01

    Full Text Available We provide a brief overview on our recent experimental work on linear and nonlinear localization of singly charged vortices (SCVs and doubly charged vortices (DCVs in two-dimensional optically induced photonic lattices. In the nonlinear case, vortex propagation at the lattice surface as well as inside the uniform square-shaped photonic lattices is considered. It is shown that, apart from the fundamental (semi-infinite gap discrete vortex solitons demonstrated earlier, the SCVs can self-trap into stable gap vortex solitons under the normal four-site excitation with a self-defocusing nonlinearity, while the DCVs can be stable only under an eight-site excitation inside the photonic lattices. Moreover, the SCVs can also turn into stable surface vortex solitons under the four-site excitation at the surface of a semi-infinite photonics lattice with a self-focusing nonlinearity. In the linear case, bandgap guidance of both SCVs and DCVs in photonic lattices with a tunable negative defect is investigated. It is found that the SCVs can be guided at the negative defect as linear vortex defect modes, while the DCVs tend to turn into quadrupole-like defect modes provided that the defect strength is not too strong.

  2. Mitochondria localization induced self-assembly of peptide amphiphiles for cellular dysfunction.

    Science.gov (United States)

    Jeena, M T; Palanikumar, L; Go, Eun Min; Kim, Inhye; Kang, Myoung Gyun; Lee, Seonik; Park, Sooham; Choi, Huyeon; Kim, Chaekyu; Jin, Seon-Mi; Bae, Sung Chul; Rhee, Hyun Woo; Lee, Eunji; Kwak, Sang Kyu; Ryu, Ja-Hyoung

    2017-06-21

    Achieving spatiotemporal control of molecular self-assembly associated with actuation of biological functions inside living cells remains a challenge owing to the complexity of the cellular environments and the lack of characterization tools. We present, for the first time, the organelle-localized self-assembly of a peptide amphiphile as a powerful strategy for controlling cellular fate. A phenylalanine dipeptide (FF) with a mitochondria-targeting moiety, triphenyl phosphonium (Mito-FF), preferentially accumulates inside mitochondria and reaches the critical aggregation concentration to form a fibrous nanostructure, which is monitored by confocal laser scanning microscopy and transmission electron microscopy. The Mito-FF fibrils induce mitochondrial dysfunction via membrane disruption to cause apoptosis. The organelle-specific supramolecular system provides a new opportunity for therapeutics and in-depth investigations of cellular functions.Spatiotemporal control of intracellular molecular self-assembly holds promise for therapeutic applications. Here the authors develop a peptide consisting of a phenylalanine dipeptide with a mitochondrial targeting moiety to form self-assembling fibrous nanostructures within mitochondria, leading to apoptosis.

  3. Elicitor-induced prolyl hydroxylase from French bean (Phaseolus vulgaris). Localization, purification and properties.

    Science.gov (United States)

    Bolwell, G P; Robbins, M P; Dixon, R A

    1985-08-01

    The enzyme prolyl hydroxylase (proline: 2-oxoglutarate dioxygenase, EC 1.14.11.12), induced in suspension-cultured cells of Phaseolus vulgaris L. (French bean) by treatment with an elicitor preparation from the phytopathogenic fungus Colletotrichum lindemuthianum, has been investigated. The enzyme, which catalyses the hydroxylation of poly-L-proline with the stoichiometric decarboxylation of 2-oxoglutarate, has been shown to be localized mainly in smooth endoplasmic reticulum. After solubilization from microsomal membranes, the hydroxylase was purified by ion-exchange chromatography and affinity chromatography on poly-L-proline-Sepharose 4B. The subunit Mr, as assessed by sodium dodecyl sulphate/poly-acrylamide-gel electrophoresis, was 65 000, the subunit apparently being recovered as a doublet: the subunits associate under non-denaturing conditions to give at least a tetramer. The bean hydroxylase has kinetic properties and cofactor requirements similar to those previously reported for the enzyme from other plants. Elicitor treatment of suspension-cultured bean cells leads to a rapid induction of prolyl hydroxylase activity concomitant with induction of a protein: arabinosyl-transferase and increased levels of an arabinosylated hydroxyproline-rich protein.

  4. IFN-λ: A New Inducer of Local Immunity against Cancer and Infections

    Science.gov (United States)

    Lasfar, Ahmed; Zloza, Andrew; de la Torre, Andrew; Cohen-Solal, Karine A.

    2016-01-01

    IFN-λ is the newly established type III IFN with unique immunomodulatory functions. In contrast to the IFN-α/β family and to some extent IFN-γ, IFN-λ is apparently acting in specific areas of the body to activate resident immune cells and induces a local immunity, instrumental in preventing particular infections and also keeping transformed cells under control. Mucosal areas of lung and gastrointestinal tracts are now under scrutiny to elucidate the immune mechanisms triggered by IFN-λ and leading to viral protection. New evidence also indicates the crucial role of IFN-λ in promoting innate immunity in solid cancer models. Based on its unique biological activities among the IFN system, new immunotherapeutic approaches are now emerging for the treatment of cancer, infection, and autoimmune diseases. In the present review, we highlight the recent advances of IFN-λ immunomodulatory functions. We also discuss the perspectives of IFN-λ as a therapeutic agent. PMID:28018361

  5. Investigation of gamma radiation induced changes in local structure of borosilicate glass by TDPAC and EXAFS

    Science.gov (United States)

    Kumar, Ashwani; Nayak, C.; Rajput, P.; Mishra, R. K.; Bhattacharyya, D.; Kaushik, C. P.; Tomar, B. S.

    2016-12-01

    Gamma radiation induced changes in local structure around the probe atom (Hafnium) were investigated in sodium barium borosilicate (NBS) glass, used for immobilization of high level liquid waste generated from the reprocessing plant at Trombay, Mumbai. The (NBS) glass was doped with 181Hf as a probe for time differential perturbed angular correlation (TDPAC) spectroscopy studies, while for studies using extended X-ray absorption fine structure (EXAFS) spectroscopy, the same was doped with 0.5 and 2 % (mole %) hafnium oxide. The irradiated as well as un-irradiated glass samples were studied by TDPAC and EXAFS techniques to obtain information about the changes (if any) around the probe atom due to gamma irradiation. TDPAC spectra of unirradiated and irradiated glasses were similar and reminescent of amorphous materials, indicating negligible effect of gamma radiation on the microstructure around Hafnium probe atom, though the quaqdrupole interaction frequency ( ω Q) and asymmetry parameter ( η) did show a marginal decrease in the irradiated glass compared to that in the unirradiated glass. EXAFS measurements showed a slight decrease in the Hf-O bond distance upon gamma irradiation of Hf doped NBS glass indicating densification of the glass matrix, while the cordination number around hafnium remains unchanged.

  6. Regulation of Hippo pathway transcription factor TEAD by p38 MAPK-induced cytoplasmic translocation.

    Science.gov (United States)

    Lin, Kimberly C; Moroishi, Toshiro; Meng, Zhipeng; Jeong, Han-Sol; Plouffe, Steven W; Sekido, Yoshitaka; Han, Jiahuai; Park, Hyun Woo; Guan, Kun-Liang

    2017-07-28

    The Hippo pathway controls organ size and tissue homeostasis, with deregulation leading to cancer. The core Hippo components in mammals are composed of the upstream serine/threonine kinases Mst1/2, MAPK4Ks and Lats1/2. Inactivation of these upstream kinases leads to dephosphorylation, stabilization, nuclear translocation and thus activation of the major functional transducers of the Hippo pathway, YAP and its paralogue TAZ. YAP/TAZ are transcription co-activators that regulate gene expression primarily through interaction with the TEA domain DNA-binding family of transcription factors (TEAD). The current paradigm for regulation of this pathway centres on phosphorylation-dependent nucleocytoplasmic shuttling of YAP/TAZ through a complex network of upstream components. However, unlike other transcription factors, such as SMAD, NF-κB, NFAT and STAT, the regulation of TEAD nucleocytoplasmic shuttling has been largely overlooked. In the present study, we show that environmental stress promotes TEAD cytoplasmic translocation via p38 MAPK in a Hippo-independent manner. Importantly, stress-induced TEAD inhibition predominates YAP-activating signals and selectively suppresses YAP-driven cancer cell growth. Our data reveal a mechanism governing TEAD nucleocytoplasmic shuttling and show that TEAD localization is a critical determinant of Hippo signalling output.

  7. Heat shock-induced accumulation of translation elongation and termination factors precedes assembly of stress granules in S. cerevisiae.

    Directory of Open Access Journals (Sweden)

    Tomas Grousl

    Full Text Available In response to severe environmental stresses eukaryotic cells shut down translation and accumulate components of the translational machinery in stress granules (SGs. Since they contain mainly mRNA, translation initiation factors and 40S ribosomal subunits, they have been referred to as dominant accumulations of stalled translation preinitiation complexes. Here we present evidence that the robust heat shock-induced SGs of S. cerevisiae also contain translation elongation factors eEF3 (Yef3p and eEF1Bγ2 (Tef4p as well as translation termination factors eRF1 (Sup45p and eRF3 (Sup35p. Despite the presence of the yeast prion protein Sup35 in heat shock-induced SGs, we found out that its prion-like domain is not involved in the SGs assembly. Factors eEF3, eEF1Bγ2 and eRF1 were accumulated and co-localized with Dcp2 foci even upon a milder heat shock at 42°C independently of P-bodies scaffolding proteins. We also show that eEF3 accumulations at 42°C determine sites of the genuine SGs assembly at 46°C. We suggest that identification of translation elongation and termination factors in SGs might help to understand the mechanism of the eIF2α factor phosphorylation-independent repression of translation and SGs assembly.

  8. Inducing goat pluripotent stem cells with four transcription factor mRNAs that activate endogenous promoters.

    Science.gov (United States)

    Chen, Hao; Zuo, Qisheng; Wang, Yingjie; Song, Jiuzhou; Yang, Huilin; Zhang, Yani; Li, Bichun

    2017-02-13

    Traditional approaches for generating goat pluripotent stem cells (iPSCs) suffer from complexity and low preparation efficiency. Therefore, we tried to derive goat iPSCs with a new method by transfecting exogenous Oct4, Sox2, Klf4 and c-Myc mRNAs into goat embryonic fibroblasts (GEFs), and explore the mechanisms regarding the transcription regulation of the reprogramming factors in goat iPSCs induction. mRNAs of the four reprogramming factors were transfected into GEFs, and were localized in nucleus with approximately 90% transfection efficiency. After five consecutive transfections, GEFs tended to aggregate by day 10. Clones appeared on day 15-18, and typical embryonic stem cell -like clones formed on day 20. One thousand AKP staining positive clones were achieved in 10(4) GEFs, with approximately 1.0% induction efficiency. Immunofluorescence staining and qRT-PCR detection of the ESCs markers confirmed the properties of the goat iPSCs. The achieved goat iPSCs could be cultured to 22nd passage, which showed normal karyotype. The goat iPSCs were able to differentiate into embryoid bodies with three germ layers. qRT-PCR and western blot showed activated endogenous pluripotent factors expression in the later phase of mRNA-induced goat iPSCs induction. Epigenetic analysis of the endogenous pluripotent gene Nanog revealed its demethylation status in derived goat iPSCs. Core promoter regions of the four reprogramming factors were determined. Transcription factor binding sites, including Elf-1, AP-2, SP1, C/EBP and MZF1, were identified to be functional in the core promoter regions of these reprogramming genes. Demethylation and deacetylation of the promoters enhanced their transcription activities. We successfully generated goat iPSCs by transfection of Oct4, Sox2, Klf4 and c-Myc mRNAs into GEFs, which initiated the endogenous reprogramming network and altered the methylation status of pluripotent genes. Core promoter regions and functional transcription binding sites of

  9. On the distance to the North Polar Spur and the local CO-H2 factor

    Science.gov (United States)

    Lallement, R.; Snowden, S.; Kuntz, K. D.; Dame, T. M.; Koutroumpa, D.; Grenier, I.; Casandjian, J. M.

    2016-11-01

    Aims: Most models identify the X-ray bright North Polar Spur (NPS) with a hot interstellar (IS) bubble in the Sco-Cen star-forming region at ≃130 pc. An opposite view considers the NPS as a distant structure associated with Galactic nuclear outflows. Constraints on the NPS distance can be obtained by comparing the foreground IS gas column inferred from X-ray absorption to the distribution of gas and dust along the line of sight. Absorbing columns toward shadowing molecular clouds simultaneously constrain the CO-H2 conversion factor. Methods: We derived the columns of X-ray absorbing matter NHabs from spectral fitting of dedicated XMM-Newton observations toward the NPS southern terminus (lII ≃ 29°, bII ≃ + 5 to + 11°). The distribution of the IS matter was obtained from absorption lines in new stellar spectra, 3D dust maps, and emission data, including high spatial resolution CO measurements recorded for this purpose. Results: NHabs varies from ≃4.3 to ≃1.3 × 1021 cm-2 along the 19 fields. Relationships between X-ray brightness, absorbing column, and hardness ratio demonstrate a brightness increase with latitude that is governed by increasing absorption. The comparison with absorption data and local and large-scale dust maps rules out an NPS source near-side closer than 300 pc. The correlation between NHabs and the reddening increases with the sightline length from 300 pc to 4 kpc and is the tightest with Planck τ353 GHz-based reddening, suggesting a much larger distance. N(H)/E(B-V)τ ≃ 4.1 × 1021 cm-2 mag-1, close to Fermi-Planck determinations. NHabs absolute values are compatible with HI-CO clouds at -5 ≤ VLSR ≤ + 25 to +45 km s-1 and an NPS potentially far beyond the Local Arm. A shadow cast by a b = + 9° molecular cloud constrains XCO in that direction to ≤1.0 × 1020 cm-2 K-1 km-1 s. The average XCO over the fields is ≤0.75 × 1020 cm-2 K-1 km-1 s. Based on observations obtained with XMM-Newton, an ESA science mission with

  10. Physiological and receptor-selective retinoids modulate interferon gamma signaling by increasing the expression, nuclear localization, and functional activity of interferon regulatory factor-1.

    Science.gov (United States)

    Luo, Xin M; Ross, A Catharine

    2005-10-28

    Synergistic actions between all-trans-retinoic acid (atRA) and interferon gamma (IFNgamma) on modulation of cellular functions have been reported both in vitro and in vivo. However, the mechanism of atRA-mediated regulation of IFNgamma signaling is poorly understood. In this study, we have used the human lung epithelial cell line A549 to examine the effect of atRA on IFNgamma-induced expression of IFN regulatory factor-1 (IRF-1), an important transcription factor involved in cell growth and apoptosis, differentiation, and antiviral and antibacterial immune responses. At least 4 h of pretreatment with atRA followed by suboptimal concentrations of IFNgamma induced a faster, higher, and more stable expression of IRF-1 than IFNgamma alone. Actinomycin D completely blocked the induction of IRF-1 by the combination, suggesting regulation at the transcriptional level. Further, we found that activation of signal transducer and activator of transcription-1 was induced more dramatically by atRA and IFNgamma than by IFNgamma alone. Expression of IFNgamma receptor-1 on the cell surface was also increased upon atRA pretreatment. Experiments using receptor-selective retinoids revealed that ligands for retinoic acid receptor-alpha (RARalpha), including atRA, 9-cis-retinoic acid, and Am580, sequentially increased the levels of IFNgamma receptor-1, activated signal transducer and activator of transcription-1, and IRF-1 and that an RARalpha antagonist was able to inhibit the effects of atRA and Am580. In addition, atRA pretreatment affected the transcriptional functions of IFNgamma-induced IRF-1, increasing its nuclear localization and DNA binding activity as well as the transcript levels of IRF-1 target genes. These results suggest that atRA, an RARalpha ligand, regulates IFNgamma-induced IRF-1 by affecting multiple components of the IFNgamma signaling pathway, from the plasma membrane to the nuclear transcription factors.

  11. Detection of local inflammation induced by repeated exposure to contact allergens by use of IVIS SpectrumCT analyses

    DEFF Research Database (Denmark)

    Nielsen, Morten M; Schmidt, Jonas Damgård; Christensen, Jan P

    2017-01-01

    BACKGROUND: Contact allergy is characterized by local skin inflammation that, in some cases, can result in systemic immune activation. OBJECTIVES: To investigate whether IVIS SpectrumCT analyses can be used to detect the immune response induced by contact allergens. METHODS: Mice were repeatedly ...

  12. Pricing of common cosmetic surgery procedures: local economic factors trump supply and demand.

    Science.gov (United States)

    Richardson, Clare; Mattison, Gennaya; Workman, Adrienne; Gupta, Subhas

    2015-02-01

    The pricing of cosmetic surgery procedures has long been thought to coincide with laws of basic economics, including the model of supply and demand. However, the highly variable prices of these procedures indicate that additional economic contributors are probable. The authors sought to reassess the fit of cosmetic surgery costs to the model of supply and demand and to determine the driving forces behind the pricing of cosmetic surgery procedures. Ten plastic surgery practices were randomly selected from each of 15 US cities of various population sizes. Average prices of breast augmentation, mastopexy, abdominoplasty, blepharoplasty, and rhytidectomy in each city were compared with economic and demographic statistics. The average price of cosmetic surgery procedures correlated substantially with population size (r = 0.767), cost-of-living index (r = 0.784), cost to own real estate (r = 0.714), and cost to rent real estate (r = 0.695) across the 15 US cities. Cosmetic surgery pricing also was found to correlate (albeit weakly) with household income (r = 0.436) and per capita income (r = 0.576). Virtually no correlations existed between pricing and the density of plastic surgeons (r = 0.185) or the average age of residents (r = 0.076). Results of this study demonstrate a correlation between costs of cosmetic surgery procedures and local economic factors. Cosmetic surgery pricing cannot be completely explained by the supply-and-demand model because no association was found between procedure cost and the density of plastic surgeons. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  13. Effects of local and landscape factors on population dynamics of a cotton pest.

    Directory of Open Access Journals (Sweden)

    Yves Carrière

    Full Text Available BACKGROUND: Many polyphagous pests sequentially use crops and uncultivated habitats in landscapes dominated by annual crops. As these habitats may contribute in increasing or decreasing pest density in fields of a specific crop, understanding the scale and temporal variability of source and sink effects is critical for managing landscapes to enhance pest control. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated how local and landscape characteristics affect population density of the western tarnished plant bug, Lygus hesperus (Knight, in cotton fields of the San Joaquin Valley in California. During two periods covering the main window of cotton vulnerability to Lygus attack over three years, we examined the associations between abundance of six common Lygus crops, uncultivated habitats and Lygus population density in these cotton fields. We also investigated impacts of insecticide applications in cotton fields and cotton flowering date. Consistent associations observed across periods and years involved abundances of cotton and uncultivated habitats that were negatively associated with Lygus density, and abundance of seed alfalfa and cotton flowering date that were positively associated with Lygus density. Safflower and forage alfalfa had variable effects, possibly reflecting among-year variation in crop management practices, and tomato, sugar beet and insecticide applications were rarely associated with Lygus density. Using data from the first two years, a multiple regression model including the four consistent factors successfully predicted Lygus density across cotton fields in the last year of the study. CONCLUSIONS/SIGNIFICANCE: Our results show that the approach developed here is appropriate to characterize and test the source and sink effects of various habitats on pest dynamics and improve the design of landscape-level pest management strategies.

  14. Some factors affecting the valinomycin-induced leak from liposomes

    NARCIS (Netherlands)

    Blok, M.C.; Gier, J. de; Deenen, L.L.M. van

    1974-01-01

    Experiments dealing with the valinomycin-induced K+ leak from egg lecithin liposomes have demonstrated the importance of the enclosed anion. Except when lipophilic anions are enclosed, the addition of both valinomycin and a uncoupler, e.g. carbonylcyanide p-trifluoromethoxyphenylhydrazone, is necess

  15. Bone mineralization is regulated by signaling cross talk between molecular factors of local and systemic origin: the role of fibroblast growth factor 23.

    Science.gov (United States)

    Sapir-Koren, Rony; Livshits, Gregory

    2014-01-01

    Body phosphate homeostasis is regulated by a hormonal counter-balanced intestine-bone-kidney axis. The major systemic hormones involved in this axis are parathyroid hormone (PTH), 1,25-dihydroxyvitamin-D, and fibroblast growth factor-23 (FGF23). FGF23, produced almost exclusively by the osteocytes, is a phosphaturic hormone that plays a major role in regulation of the bone remodeling process. Remodeling composite components, bone mineralization and resorption cycles create a continuous influx-efflux loop of the inorganic phosphate (Pi) through the skeleton. This "bone Pi loop," which is formed, is controlled by local and systemic factors according to phosphate homeostasis demands. Although FGF23 systemic actions in the kidney, and for the production of PTH and 1,25-dihydroxyvitamin-D are well established, its direct involvement in bone metabolism is currently poorly understood. This review presents the latest available evidence suggesting two aspects of FGF23 bone local activity: (a) Regulation of FGF23 production by both local and systemic factors. The suggested local factors include extracellular levels of Pi and pyrophosphate (PPi), (the Pi/PPi ratio), and another osteocyte-derived protein, sclerostin. In addition, 1,25-dihydroxyvitamin-D, synthesized locally by bone cells, may contribute to regulation of FGF23 production. The systemic control is achieved via PTH and 1,25-dihydroxyvitamin-D endocrine functions. (b) FGF23 acts as a local agent, directly affecting bone mineralization. We support the assumption that under balanced physiological conditions, sclerostin, by para- autocrine signaling, upregulates FGF23 production by the osteocyte. FGF23, in turn, acts as a mineralization inhibitor, by stimulating the generation of the major mineralization antagonist-PPi.

  16. Two-dimensional metal-insulator transition as a strong localization induced crossover phenomenon

    Science.gov (United States)

    Das Sarma, S.; Hwang, E. H.

    2014-06-01

    Low-disorder and high-mobility two-dimensional (2D) electron (or hole) systems confined in semiconductor heterostructures undergo an apparent metal-insulator transition (MIT) at low temperatures as the carrier density (n) is varied. In some situations, the 2D MIT can be caused at a fixed low carrier density by changing an externally applied in-plane magnetic field parallel to the 2D layer. The goal of the current work is to obtain the critical density (nc) for the 2D MIT with the system being an effective metal (Anderson insulator) for density n above (below) nc. We study the 2D MIT phenomenon theoretically as a possible strong localization induced crossover process controlled by the Ioffe-Regel criterion, kFl=1, where kF(n) is the 2D Fermi wave vector and l (n) is the disorder-limited quantum mean free path on the metallic side. Calculating the quantum mean free path in the effective metallic phase from a realistic Boltzmann transport theory including disorder scattering effects, we solve the integral equation (with l depending on n through multidimensional integrals) defined by the Ioffe-Regel criterion to obtain the nonuniversal critical density nc as a function of the applicable physical experimental parameters including disorder strength, in-plane magnetic field, spin and valley degeneracy, background dielectric constant and carrier effective mass, and temperature. The key physics underlying the nonuniversal parameter dependence of the critical density is the density dependence of the screened Coulomb disorder. Our calculated results for the crossover critical density nc appear to be in qualitative and semiquantitative agreement with the available experimental data in different 2D semiconductor systems lending credence to the possibility that the apparent 2D MIT signals the onset of the strong localization crossover in disordered 2D systems. We also compare the calculated critical density obtained from the Ioffe-Regel criterion with that obtained from a

  17. Local administration of platelet-derived growth factor B (PDGFB) improves follicular development and ovarian angiogenesis in a rat model of Polycystic Ovary Syndrome.

    Science.gov (United States)

    Di Pietro, Mariana; Scotti, Leopoldina; Irusta, Griselda; Tesone, Marta; Parborell, Fernanda; Abramovich, Dalhia

    2016-09-15

    Alterations in ovarian angiogenesis are common features in Polycystic Ovary Syndrome (PCOS) patients; the most studied of these alterations is the increase in vascular endothelial growth factor (VEGF) production by ovarian cells. Platelet-derived growth factor B (PDGFB) and D (PDGFD) are decreased in follicular fluid of PCOS patients and in the ovaries of a rat model of PCOS. In the present study, we aimed to analyze the effects of local administration of PDGFB on ovarian angiogenesis, follicular development and ovulation in a DHEA-induced PCOS rat model. Ovarian PDGFB administration to PCOS rats partially restored follicular development, decreased the percentage of cysts, increased the percentage of corpora lutea, and decreased the production of anti-Müllerian hormone. In addition, PDGFB administration improved ovarian angiogenesis by reversing the increase in periendothelial cell area and restoring VEGF levels. Our results shed light into the mechanisms that lead to altered ovarian function in PCOS and provide new data for potential therapeutic strategies.

  18. TCDD Induces the Hypoxia-Inducible Factor (HIF-1α Regulatory Pathway in Human Trophoblastic JAR Cells

    Directory of Open Access Journals (Sweden)

    Tien-Ling Liao

    2014-09-01

    Full Text Available The exposure to dioxin can compromise pregnancy outcomes and increase the risk of preterm births. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD has been demonstrated to induce placental hypoxia at the end of pregnancy in a rat model, and hypoxia has been suggested to be the cause of abnormal trophoblast differentiation and placental insufficiency syndromes. In this study, we demonstrate that the non-hypoxic stimulation of human trophoblastic cells by TCDD strongly increased hypoxia inducible factor-1 alpha (HIF-1α stabilization. TCDD exposure induced the generation of reactive oxygen species (ROS and nitric oxide. TCDD-induced HIF-1α stabilization and Akt phosphorylation was inhibited by pretreatment with wortmannin (a phosphatidylinositol 3-kinase (PI3K inhibitor or N-acetylcysteine (a ROS scavenger. The augmented HIF-1α stabilization by TCDD occurred via the ROS-dependent activation of the PI3K/Akt pathway. Additionally, a significant increase in invasion and metallomatrix protease-9 activity was found in TCDD-treated cells. The gene expression of vascular endothelial growth factor and placental growth factor was induced upon TCDD stimulation, whereas the protein levels of peroxisome proliferator-activated receptor γ (PPARγ, PPARγ coactivator-1α, mitochondrial transcription factor, and uncoupling protein 2 were decreased. Our results indicate that an activated HIF-1α pathway, elicited oxidative stress, and induced metabolic stress contribute to TCDD-induced trophoblastic toxicity. These findings may provide molecular insight into the TCDD-induced impairment of trophoblast function and placental development.

  19. Roscovitine sensitizes leukemia and lymphoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis

    OpenAIRE

    Molinsky, J.; Klánová, M.; Koc, M; Beranová, L. (Lenka); Anděra, L. (Ladislav); Ludvíková, Z.; Bohmova, M.; Gasova, Z.; Strnad, M.; Ivánek, R. (Robert); Trněný, M.; Nečas, E.; Živný, J.; Klener, P.

    2013-01-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand with selective antitumor activity. However, many primary tumors are TRAIL resistant. Previous studies reported that roscovitine, a cyclin-dependent kinase inhibitor, sensitized various solid cancer cells to TRAIL. We show that roscovitine and TRAIL demonstrate synergistic cytotoxicity in hematologic malignant cell lines and primary cells. Pretreatment of TRAIL-resistant leukemia cells with roscovitine induced en...

  20. Regulation of Ras exchange factors and cellular localization of Ras activation by lipid messengers in T cells

    Directory of Open Access Journals (Sweden)

    Jesse E. Jun

    2013-09-01

    Full Text Available The Ras-MAPK signaling pathway is highly conserved throughout evolution and is activated downstream of a wide range of receptor stimuli. Ras guanine nucleotide exchange factors (RasGEFs catalyze GTP loading of Ras and play a pivotal role in regulating receptor-ligand induced Ras activity. In T cells, three families of functionally important RasGEFs are expressed: RasGRF, RasGRP, and SOS-family GEFs.Early on it was recognized that Ras activation is critical for T cell development and that the RasGEFs play an important role herein. More recent work has revealed that nuances in Ras activation appear to significantly impact T cell development and selection. These nuances include distinct biochemical patterns of analog versus digital Ras activation, differences in cellular localization of Ras activation, and intricate interplays between the RasGEFs during distinct T cell developmental stages as revealed by various new mouse models. In many instances, the exact nature of these nuances in Ras activation or how these may result from fine-tuning of the RasGEFs is not understood.One large group of biomolecules critically involved in the control of Ras-GEFs´functions are lipid second messengers. Multiple, yet distinct lipid products are generated following T cell receptor (TCR stimulation and bind to different domains in the RasGRP and SOS RasGEFs to facilitate the activation of the membrane-anchored Ras GTPases. In this review we highlight how different lipid-based elements are generated by various enzymes downstream of the TCR and other receptors and how these dynamic and interrelated lipid products may fine-tune Ras activation by RasGEFs in developing T cells.

  1. Local administration of AAV-BDNF to subventricular zone induces functional recovery in stroke rats.

    Directory of Open Access Journals (Sweden)

    Seong-Jin Yu

    Full Text Available Migration of new neuroprogenitor cells (NPCs from the subventricular zone (SVZ plays an important role in neurorepair after injury. Previous studies have shown that brain derived neurotrophic factor (BDNF enhances the migration of NPCs from SVZ explants in neonatal mice in vitro. The purpose of this study was to identify the role of BDNF in SVZ cells using AAV-BDNF in an animal model of stroke. BDNF protein production after AAV-BDNF infection was verified in primary neuronal culture. AAV-BDNF or AAV-RFP was injected into the left SVZ region of adult rats at 14 days prior to right middle cerebral artery occlusion (MCAo. SVZ tissues were collected from the brain and placed in Metrigel cultures 1 day after MCAo. Treatment with AAV-BDNF significantly increased the migration of SVZ cells in the stroke brain in vitro. In another set of animals, AAV-GFP was co-injected with AAV-BDNF or AAV-RFP to label cells in left SVZ prior to right MCAo. Local administration of AAV-BDNF significantly enhanced recovery of locomotor function and migration of GFP-positive cells from the SVZ toward the lesioned hemisphere in stroke rats. Our data suggest that focal administration of AAV-BDNF to the SVZ increases behavioral recovery post stroke, possibly through the enhancement of migration of cells from SVZ in stroke animals. Regional manipulation of BDNF expression through AAV may be a novel approach for neurorepair in stroke brains.

  2. Local administration of AAV-BDNF to subventricular zone induces functional recovery in stroke rats.

    Science.gov (United States)

    Yu, Seong-Jin; Tseng, Kuan-Yin; Shen, Hui; Harvey, Brandon K; Airavaara, Mikko; Wang, Yun

    2013-01-01

    Migration of new neuroprogenitor cells (NPCs) from the subventricular zone (SVZ) plays an important role in neurorepair after injury. Previous studies have shown that brain derived neurotrophic factor (BDNF) enhances the migration of NPCs from SVZ explants in neonatal mice in vitro. The purpose of this study was to identify the role of BDNF in SVZ cells using AAV-BDNF in an animal model of stroke. BDNF protein production after AAV-BDNF infection was verified in primary neuronal culture. AAV-BDNF or AAV-RFP was injected into the left SVZ region of adult rats at 14 days prior to right middle cerebral artery occlusion (MCAo). SVZ tissues were collected from the brain and placed in Metrigel cultures 1 day after MCAo. Treatment with AAV-BDNF significantly increased the migration of SVZ cells in the stroke brain in vitro. In another set of animals, AAV-GFP was co-injected with AAV-BDNF or AAV-RFP to label cells in left SVZ prior to right MCAo. Local administration of AAV-BDNF significantly enhanced recovery of locomotor function and migration of GFP-positive cells from the SVZ toward the lesioned hemisphere in stroke rats. Our data suggest that focal administration of AAV-BDNF to the SVZ increases behavioral recovery post stroke, possibly through the enhancement of migration of cells from SVZ in stroke animals. Regional manipulation of BDNF expression through AAV may be a novel approach for neurorepair in stroke brains.

  3. Integrating climate change adaptation into Dutch local policies and the role of contextual factors.

    NARCIS (Netherlands)

    Berg, van den M.M.; Coenen, F.H.J.M.

    2012-01-01

    Moving towards a more sustainable adaptation process requires closer integration of policies related to the environment. An important actor in this is the local government. This paper examines to what extend adaptation is currently being integrated into Dutch local policies, and what the role is of

  4. Analysis of the local kinetics and localization of interleukin-1 alpha, tumour necrosis factor-alpha and transforming growth factor-beta, during the course of experimental pulmonary tuberculosis.

    Science.gov (United States)

    Hernandez-Pando, R; Orozco, H; Arriaga, K; Sampieri, A; Larriva-Sahd, J; Madrid-Marina, V

    1997-01-01

    A mouse model of pulmonary tuberculosis induced by the intratracheal instillation of live and virulent mycobacteria strain H37-Rv was used to examine the relationship of the histopathological findings with the local kinetics production and cellular distribution of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and transforming growth factor-beta (TGF-beta). The histopathological and immunological studies showed two phases of the disease: acute or early and chronic or advanced. The acute phase was characterized by inflammatory infiltrate in the alveolar-capillary interstitium, blood vessels and bronchial wall with formation of granulomas. During this acute phase, which lasted from 1 to 28 days, high percentages of TNF-alpha and IL-1 alpha immunostained activated macrophages were observed principally in the interstium-intralveolar inflammatory infiltrate and in granulomas. Electron microscopy studies of these cells, showed extensive rough endoplasmic reticulum, numerous lysosomes and occasional mycobacteria. Double labelling with colloid gold showed that TNF-alpha and IL-1 alpha were present in the same cells, but were confined to separate vacuoles near the Golgi area, and mixed in larger vacuoles near to cell membrane. The concentration of TNF-alpha and IL-1 alpha as well as their respective mRNAs were elevated in the early phase, particularly at day 3 when the bacillary count decreased. A second peak was seen at days 14 and 21-28 when granulomas appeared and evolved to full maturation. In contrast, TGF-beta production and numbers of immunoreactive cells were low in comparison with the advanced phase of the disease. The chronic phase was characterized by histopathological changes indicative of more severity (i.e. pneumonia, focal necrosis and extensive interstitial fibrosis) with a decrease in the TNF-alpha and IL-1 alpha production that coincided with the highest level of TGF-beta. The bacillary counts were highest as the macrophages

  5. Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway.

    Science.gov (United States)

    Zhang, Mingdi; Cai, Shizhong; Zuo, Bin; Gong, Wei; Tang, Zhaohui; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Wang, Shouhua; Liu, Jun; Ma, Fei; Quan, Zhiwei

    2017-05-01

    Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.

  6. A Taiwanese Propolis Derivative Induces Apoptosis through Inducing Endoplasmic Reticular Stress and Activating Transcription Factor-3 in Human Hepatoma Cells

    Directory of Open Access Journals (Sweden)

    Fat-Moon Suk

    2013-01-01

    Full Text Available Activating transcription factor-(ATF- 3, a stress-inducible transcription factor, is rapidly upregulated under various stress conditions and plays an important role in inducing cancer cell apoptosis. NBM-TP-007-GS-002 (GS-002 is a Taiwanese propolin G (PPG derivative. In this study, we examined the antitumor effects of GS-002 in human hepatoma Hep3B and HepG2 cells in vitro. First, we found that GS-002 significantly inhibited cell proliferation and induced cell apoptosis in dose-dependent manners. Several main apoptotic indicators were found in GS-002-treated cells, such as the cleaved forms of caspase-3, caspase-9, and poly(ADP-ribose polymerase (PARP. GS-002 also induced endoplasmic reticular (ER stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78, growth arrest- and DNA damage-inducible gene 153 (GADD153, phosphorylated eukaryotic initiation factor 2α (eIF2α, phosphorylated protein endoplasmic-reticular-resident kinase (PERK, and ATF-3. The induction of ATF-3 expression was mediated by mitogen-activated protein kinase (MAPK signaling pathways in GS-002-treated cells. Furthermore, we found that GS-002 induced more cell apoptosis in ATF-3-overexpressing cells. These results suggest that the induction of apoptosis by the propolis derivative, GS-002, is partially mediated through ER stress and ATF-3-dependent pathways, and GS-002 has the potential for development as an antitumor drug.

  7. Helicobacter pylori induces vascular endothelial growth factor production in gastric epithelial cells through hypoxia-inducible factor-1α-dependent pathway.

    Science.gov (United States)

    Kang, Min-Jung; Song, Eun-Jung; Kim, Bo-Yeon; Kim, Dong-Jae; Park, Jong-Hwan

    2014-12-01

    Although Helicobacter pylori have been known to induce vascular endothelial growth factor (VEGF) production in gastric epithelial cells, the precise mechanism for cellular signaling is incompletely understood. In this study, we investigated the role of bacterial virulence factor and host cellular signaling in VEGF production of H. pylori-infected gastric epithelial cells. We evaluated production of VEGF, activation of nuclear factor nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) and hypoxia-inducible factor-1α (HIF-1α) stabilization in gastric epithelial cells infected with H. pylori WT or isogenic mutants deficient in type IV secretion system (T4SS). H. pylori induced VEGF production in gastric epithelial cells via both T4SS-dependent and T4SS-independent pathways, although T4SS-independent pathway seems to be the dominant signaling. The inhibitor assay implicated that activation of NF-κB and MAPKs is dispensable for H. pylori-induced VEGF production in gastric epithelial cells. H. pylori led to HIF-1α stabilization in gastric epithelial cells independently of T4SS, NF-κB, and MAPKs, which was essential for VEGF production in these cells. N-acetyl-cysteine (NAC), a reactive oxygen species (ROS) inhibitor, treatment impaired H. pylori-induced HIF-1α stabilization and VEGF production in gastric epithelial cells. We defined the important role of ROS-HIF-1α axis in VEGF production of H. pylori-infected gastric epithelial cells, and bacterial T4SS has a minor role in H. pylori-induced VEGF production of gastric epithelial cells. © 2014 John Wiley & Sons Ltd.

  8. Type I Insulin-like Growth Factor Receptor Induces Pulmonary Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Nicolle M. Linnerth

    2009-07-01

    Full Text Available Despite the type I insulin-like growth factor receptor (IGF-IR being highly expressed in more than 80% of human lung tumors, a transgenic model of IGF-IR overexpression in the lung has not been created. We produced two novel transgenic mouse models in which IGF-IR is overexpressed in either lung type II alveolar cells (surfactant protein C [SPC]-IGFIR or Clara cells (CCSP-IGFIR in a doxycycline-inducible manner. Overexpression of IGF-IR in either cell type caused multifocal adenomatous alveolar hyperplasia with papillary and solid adenomas. These tumors expressed thyroid transcription factor 1 and Kruppel-like factor 5 in most tumor cells. Similar to our previous work with lung tumors that developed in the mouse mammary tumor virus-IGF-II transgenic mice, the lung tumors that develop in the SPC-IGFIR and CCSP-IGFIR transgenic mice expressed high levels of the cyclic adenosine monophosphate response element binding protein that was localized primarily to the nucleus. Although elevated IGF-IR expression can initiate lung tumor development, tumors can become independent of IGF-IR signaling as IGF-IR down-regulation in established tumors produced tumor regression in some, but not all, of the tumors. These findings implicate IGF-IR as an important initiator of lung tumorigenesis and suggest that the SPC-IGFIR and CCSP-IGFIR transgenic mice can be used to further our understanding of human lung cancer and the role IGF-IR plays in this disease.

  9. Osteogenic Differentiation of Adipose-Derived Stem Cells Is Hypoxia-Inducible Factor-1 Independent

    Science.gov (United States)

    Sahai, Suchit; Williams, Amanda; Skiles, Matthew L.

    2013-01-01

    Tissue engineering is a promising approach to repair critical-size defects in bone. Damage to vasculature at the defect site can create a lower O2 environment compared with healthy bone. Local O2 levels influence stem cell behavior, as O2 is not only a nutrient, but also a signaling molecule. The hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates a wide range of O2-related genes and its contribution in bone repair/formation is an important area that can be exploited. In this study, we examined the effect of low O2 environments (1% and 2% O2) on the osteogenic differentiation of adipose-derived stem cells in both two-dimensional (2-D) and three-dimensional (3-D) culture systems. To determine the role of HIF-1 in the differentiation process, an inhibitor was used to block the HIF-1 activity. The samples were examined for osteogenesis markers as measured by quantification of the alkaline phosphatase (ALP) activity, mineral deposition, and expression of osteonectin (ON) and osteopontin (OPN). Results show a downregulation of the osteogenic markers (ALP activity, mineralization, ON, OPN) in both 1% and 2% O2 when compared to 20% O2 in both 2-D and 3-D culture. Vascular endothelial growth factor secretion over 28 days was significantly higher in low O2 environments and HIF-1 inhibition reduced this effect. The inhibition of the HIF-1 activity did not have a significant impact on the expression of the osteogenic markers, suggesting HIF-1-independent inhibition of osteogenic differentiation in hypoxic conditions. PMID:23394201

  10. Modeling the influence of local environmental factors on malaria transmission in Benin and its implications for cohort study.

    Science.gov (United States)

    Cottrell, Gilles; Kouwaye, Bienvenue; Pierrat, Charlotte; le Port, Agnès; Bouraïma, Aziz; Fonton, Noël; Hounkonnou, Mahouton Norbert; Massougbodji, Achille; Corbel, Vincent; Garcia, André

    2012-01-01

    Malaria remains endemic in tropical areas, especially in Africa. For the evaluation of new tools and to further our understanding of host-parasite interactions, knowing the environmental risk of transmission--even at a very local scale--is essential. The aim of this study was to assess how malaria transmission is influenced and can be predicted by local climatic and environmental factors.As the entomological part of a cohort study of 650 newborn babies in nine villages in the Tori Bossito district of Southern Benin between June 2007 and February 2010, human landing catches were performed to assess the density of malaria vectors and transmission intensity. Climatic factors as well as household characteristics were recorded throughout the study. Statistical correlations between Anopheles density and environmental and climatic factors were tested using a three-level Poisson mixed regression model. The results showed both temporal variations in vector density (related to season and rainfall), and spatial variations at the level of both village and house. These spatial variations could be largely explained by factors associated with the house's immediate surroundings, namely soil type, vegetation index and the proximity of a watercourse. Based on these results, a predictive regression model was developed using a leave-one-out method, to predict the spatiotemporal variability of malaria transmission in the nine villages.This study points up the importance of local environmental factors in malaria transmission and describes a model to predict the transmission risk of individual children, based on environmental and behavioral characteristics.

  11. Relationship among local and functional factors in the development of denture stomatitis in denture wearers in northern Brazil

    Directory of Open Access Journals (Sweden)

    Lurdete Maria Rocha GAUCH

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the relationship among functional and qualitative factors in the development of denture stomatitis (DS (according to Newton's classification in acrylic-based denture wearers residents from northern Brazil.MATERIAL AND METHOD: A total of 99 patients who wore partial or total acrylic resin-based upper dentures were included in this study. The subjects completed an epidemiological data form that includes the patient's gender, age, local factors (hygiene habits, remove denture to sleep, use of mouthwash, present condition of the denture, age of the denture and functional factors (vertical dimension at rest, vertical dimension of occlusion, occlusion, retention, and static and dynamic stability. To detect yeasts, samples were collected from the inner surface of the dentures and from the palatal mucosa in contact with it. Subsequently, the samples were cultured on Sabouraud dextrose agar, observing macro and microscopic characteristics.RESULT: In the present study, we did not find any significant relationship between the gender and disease onset. Based on the Newton classification, 36.3% of the patients presented with DS and 89.0% were colonized by yeasts; of these subjects, 50% had type I lesions, 33.3% had type II lesions, and 16.6% had type III lesions. All of the qualitative and local factors, except the use of mouthwash, were clinically relevant to the development of disease.CONCLUSION: Denture stomatitis in denture users in northern Brazil was multifactorial, involving local, functional and microbiological factors.

  12. Oximetry: a new non-invasive method to detect metabolic effects induced by a local application of mechanical vibration

    Science.gov (United States)

    Felici, A.; Trombetta, C.; Abundo, P.; Foti, C.; Rosato, N.

    2012-10-01

    Mechanical vibrations application is increasingly common in clinical practice due to the effectiveness induced by these stimuli on the human body. Local vibration (LV) application allows to apply and act only where needed, focusing the treatment on the selected body segment. An experimental device for LV application was used to generate the vibrations. The aim of this study was to detect and analyze the metabolic effects induced by LV on the brachial bicep muscle by means of an oximeter. This device monitors tissue and muscle oxygenation using NIRS (Near Infrared Spectroscopy) and is able to determine the concentration of haemoglobin and oxygen saturation in the tissue. In a preliminary stage we also investigated the effects induced by LV application, by measuring blood pressure, heart rate, oxygen saturation and temperature. These data confirmed that the effects induced by LV application are actually localized. The results of the measurements obtained using the oximeter during the vibration application, have shown a variation of the concentrations. In particular an increase of oxygenate haemoglobin was shown, probably caused by an increased muscle activity and/or a rise in local temperature detected during the application.

  13. Sphingosine kinase 2 is a chikungunya virus host factor co-localized with the viral replication complex.

    Science.gov (United States)

    Reid, St Patrick; Tritsch, Sarah R; Kota, Krishna; Chiang, Chih-Yuan; Dong, Lian; Kenny, Tara; Brueggemann, Ernest E; Ward, Michael D; Cazares, Lisa H; Bavari, Sina

    2015-10-01

    Chikungunya virus (CHIKV) is a re-emerging alphavirus which causes severe and prolonged arthralgic febrile illness. The recent global spread of the virus and lack of approved therapeutic options makes it imperative to gain greater insight into the molecular mechanisms underlying CHIKV pathogenesis, in particular host factors recruited by the virus. In the current study, we identify sphingosine kinase 2 (SK2) as a CHIKV host factor co-localized with the viral replication complex (VRC) during infection. SK2 was demonstrated to co-localize with viral RNA and nonstructural proteins. Targeted impairment of SK2 expression or function significantly inhibited CHIKV infection. Furthermore, affinity purification-mass spectrometry studies revealed that SK2 associates with a number of proteins involved in cellular gene expression specifically during viral infection, suggesting a role in replication. Collectively these results identify SK2 as a novel CHIKV host factor.

  14. Investigations on the local structure and factors for the interstitial Ti3+ in TiO2

    Indian Academy of Sciences (India)

    L H Wei; S Y Wu; Z H Zhang; X F Wang; Y X Hu

    2008-07-01

    The EPR factors ( = , , ) for the interstitial Ti3+ in rutile are theoretically studied from the perturbation formulas of these parameters for a 3d1 ion in rhombically compressed octahedra. The ligand octahedron in the impurity center is found to be less compressed than that on the host interstitial site due to the Jahn–Teller effect. The local compression parameter (≈ 0.026) and the rhombic distortion angle ' (≈ 0.7°) around the impurity Ti3+ are smaller than the host values (≈ 0.091 and 3.5°). The theoretical factors based on the above local structural parameters are in good agreement with the experimental data. In addition, the factors for a tetragonal interstitial Ti3+ center are also reasonably interpreted.

  15. Pion Form Factor in QCD Sum Rules with Nonlocal Condensates and in the Local-Duality Approach

    CERN Document Server

    Bakulev, Alexander P; Stefanis, N G

    2009-01-01

    We discuss the QCD sum-rule approach for the spacelike electromagnetic pion form factor in the $O(\\alpha_s)$ approximation. We show that the nonlocality of the condensates is a key point to include nonperturbative contributions to the pion form factor. We compare our results with the Local-Duality predictions and show that the continuum threshold $s_0(Q^2)$ parameter is highly underestimated in the Local-Duality approach at $Q^2\\gtrsim 2$ GeV$^2$. Using our fit for this parameter, $s_0^\\text{LD}(Q^2)$, and applying the fractional analytic perturbation theory, we estimate with an accuracy of the order of 1% the $O(\\alpha_s^2)$ contribution to the pion's form factor.

  16. Role of hypoxia-inducible factor in diabetic myocardial hypertrophy

    African Journals Online (AJOL)

    under prolonged high glucose, the low expression of HIF-1α led to low expressions of Glut-1, HXK-2 and enolase. ... role in the regulation of physiological and .... significantly altered glucose and lipid metabolism .... growth factor and its receptors in insulin-resistant and ... density, and activation of cell survival signaling. Eur J.

  17. Internet-induced marketing techniques: Critical factors of viral marketing

    Directory of Open Access Journals (Sweden)

    Woerndl, M.

    2008-01-01

    Full Text Available The rapid diffusion of the Internet and the emergence of various social constructs facilitated by Internet technologies are changing the drivers that define how marketing techniques are developed and refined. This paper identifies critical factors for viral marketing, an Internet-based ‘word-of-mouth’ marketing technique. Based on existing knowledge, five types of viral marketing factors that may critically influence the success of viral marketing campaigns are identified. These factors are the overall structure of the campaign, the characteristics of the product or service, the content of the message, the characteristics of the diffusion and, the peer-to-peer information conduit. The paper discusses three examples of viral marketing campaigns and identifies the specific factors in each case that influence its success. The paper concludes with a viral marketing typology differentiating between viral marketing communications, unintended viral marketing and commercial viral marketing. This is still a rapidly evolving area and further research is clearly needed to monitor new developments and make sense of the radical changes these developments bring to the market.

  18. Bovine trophectoderm cell lines induced from bovine fibroblasts with reprogramming factors

    Science.gov (United States)

    Bovine trophectoderm (TE) cells were induced [induced bovine trophectoderm-like (iBT)] from bovine fetal liver-derived fibroblasts, and other bovine fetal fibroblasts, after viral-vector transduction with either four or six reprogramming factors (RF), including POU5F1, KLF4, SOX2, C-MYC, SV40 large ...

  19. Radon induced hyperplasia: effective adaptation reducing the local doses in the bronchial epithelium.

    Science.gov (United States)

    Madas, Balázs G

    2016-09-01

    There is experimental and histological evidence that chronic irritation and cell death may cause hyperplasia in the exposed tissue. As the heterogeneous deposition of inhaled radon progeny results in high local doses at the peak of the bronchial bifurcations, it was proposed earlier that hyperplasia occurs in these deposition hot spots upon chronic radon exposure. The objective of the present study is to quantify how the induction of basal cell hyperplasia modulates the microdosimetric consequences of a given radon exposure. For this purpose, computational epithelium models were constructed with spherical cell nuclei of six different cell types based on histological data. Basal cell hyperplasia was modelled by epithelium models with additional basal cells and increased epithelium thickness. Microdosimetry for alpha-particles was performed by an own-developed Monte-Carlo code. Results show that the average tissue dose, and the average hit number and dose of basal cells decrease by the increase of the measure of hyperplasia. Hit and dose distribution reveal that the induction of hyperplasia may result in a basal cell pool which is shielded from alpha-radiation. It highlights that the exposure history affects the microdosimetric consequences of a present exposure, while the biological and health effects may also depend on previous exposures. The induction of hyperplasia can be considered as a radioadaptive response at the tissue level. Such an adaptation of the tissue challenges the validity of the application of the dose and dose rate effectiveness factor from a mechanistic point of view. As the location of radiosensitive target cells may change due to previous exposures, dosimetry models considering the tissue geometry characteristic of normal conditions may be inappropriate for dose estimation in case of protracted exposures. As internal exposures are frequently chronic, such changes in tissue geometry may be highly relevant for other incorporated radionuclides.

  20. Incidence and risk factors for capecitabine-induced symptomatic cardiotoxicity

    DEFF Research Database (Denmark)

    Polk, Anne; Shahmarvand, Nahid; Vistisen, Kirsten

    2016-01-01

    arrest with lethal outcome. 4 of 6 patients (66%) retreated with capecitabine had recurrent symptoms at retreatment. Cardiac comorbidity (p=0.001), hypercholesterolaemia (p=0.005) and current smoking (p=0.023) were risk factors for cardiotoxicity in univariate analyses and remained significant when...... adjusted for age. Patients with cardiac comorbidity were 5.5 times (95% CI 2.0 to 14.8) more likely to develop cardiotoxicity. In the subgroup of patients with apparently no cardiac comorbidity, the incidence of cardiotoxicity was lower (3.7%) and hypercholesterolaemia (p=0.035) and current smoking (p=0.......020) were risk factors of cardiotoxicity. Conclusions The incidence of cardiotoxicity from capecitabine resembles that of intravenous 5-FU (â ‰5%). Cardiac comorbidity, hypercholesterolaemia and current smoking were associated with development of cardiotoxicity....

  1. Incidence and risk factors for capecitabine-induced symptomatic cardiotoxicity

    DEFF Research Database (Denmark)

    Polk, Anne; Shahmarvand, Nahid; Vistisen, Kirsten

    2016-01-01

    OBJECTIVES: Case reports of capecitabine cardiotoxicity resemble those seen with intravenous 5-fluorouracil (5-FU) with chest pain as the predominant manifestation, but few studies of capecitabine cardiotoxicity are available. We aimed to determine the incidence of symptomatic cardiotoxicity from.......020) were risk factors of cardiotoxicity. CONCLUSIONS: The incidence of cardiotoxicity from capecitabine resembles that of intravenous 5-FU (≈5%). Cardiac comorbidity, hypercholesterolaemia and current smoking were associated with development of cardiotoxicity....

  2. A chloroplast-localized and auxin-induced glutathione S-transferase from phreatophyte Prosopis juliflora confer drought tolerance on tobacco.

    Science.gov (United States)

    George, Suja; Venkataraman, Gayatri; Parida, Ajay

    2010-03-01

    Plant growth and productivity are adversely affected by various abiotic stress factors. In our previous study, we used Prosopis juliflora, a drought-tolerant tree species of Fabaceae, as a model plant system for mining genes functioning in abiotic stress tolerance. Large-scale random EST sequencing from a cDNA library obtained from drought-stressed leaves of 2-month-old P. juliflora plants resulted in identification of three different auxin-inducible glutathione S-transferases. In this paper, we report the cellular localization and the ability to confer drought tolerance in transgenic tobacco of one of these GSTs (PjGSTU1). PjGSTU1 was overexpressed in Escherichia coli and GST and GPX activities in total protein samples were assayed and compared with controls. The results indicated that PjGSTU1 protein forms a functional homo-dimer in recombinant bacteria with glutathione transferase as well as glutathione peroxidase activities. PjGSTU1 transgenic tobacco lines survived better under conditions of 15% PEG stress compared with control un-transformed plants. In vivo localization studies for PjGSTU1 using GFP fusion revealed protein localization in chloroplasts of transgenic plants. The peroxidase activity of PjGSTU1 and its localization in the chloroplast indicates a possible role for PjGSTU1 in ROS removal.

  3. An Expandable, Inducible Hemangioblast State Regulated by Fibroblast Growth Factor

    Directory of Open Access Journals (Sweden)

    David T. Vereide

    2014-12-01

    Full Text Available During development, the hematopoietic and vascular lineages are thought to descend from common mesodermal progenitors called hemangioblasts. Here we identify six transcription factors, Gata2, Lmo2, Mycn, Pitx2, Sox17, and Tal1, that “trap” murine cells in a proliferative state and endow them with a hemangioblast potential. These “expandable” hemangioblasts (eHBs are capable, once released from the control of the ectopic factors, to give rise to functional endothelial cells, multilineage hematopoietic cells, and smooth muscle cells. The eHBs can be derived from embryonic stem cells, from fetal liver cells, or poorly from fibroblasts. The eHBs reveal a central role for fibroblast growth factor, which not only promotes their expansion, but also facilitates their ability to give rise to endothelial cells and leukocytes, but not erythrocytes. This study serves as a demonstration that ephemeral progenitor states can be harnessed in vitro, enabling the creation of tractable progenitor cell lines.

  4. Emission enhancement of laser-induced breakdown spectroscopy by localized surface plasmon resonance for analyzing plant nutrients.

    Science.gov (United States)

    Ohta, Takayuki; Ito, Masafumi; Kotani, Takashi; Hattori, Takeaki

    2009-05-01

    We demonstrate the monitoring of plant nutrients in leaves of Citrus unshiu and Rhododendron obtusum using low-energy (laser-induced breakdown spectroscopy. The raw plant leaf was successfully ablated without desiccation before laser irradiation, by applying metallic colloidal particles to the leaf surface. The emission intensity with the metallic particles was larger than that without the particles. This result indicates an improvement of the sensitivity and the detection limit of laser-induced breakdown spectroscopy. The emission enhancement was caused by localized surface plasmon resonance and was dependent on the size and material of metallic particles.

  5. Heterogeneous nuclear ribonucleoprotein K inhibits heat shock-induced transcriptional activity of heat shock factor 1.

    Science.gov (United States)

    Kim, Hee-Jung; Lee, Jae-Jin; Cho, Jin-Hwan; Jeong, Jaeho; Park, A Young; Kang, Wonmo; Lee, Kong-Joo

    2017-08-04

    When cells are exposed to heat shock and various other stresses, heat shock factor 1 (HSF1) is activated, and the heat shock response (HSR) is elicited. To better understand the molecular regulation of the HSR, we used 2D-PAGE-based proteome analysis to screen for heat shock-induced post-translationally modified cellular proteins. Our analysis revealed that two protein spots typically present on 2D-PAGE gels and containing heterogeneous nuclear ribonucleoprotein K (hnRNP K) with trioxidized Cys(132) disappeared after the heat shock treatment and reappeared during recovery, but the total amount of hnRNP K protein remained unchanged. We next tested whether hnRNP K plays a role in HSR by regulating HSF1 and found that hnRNP K inhibits HSF1 activity, resulting in reduced expression of hsp70 and hsp27 mRNAs. hnRNP K also reduced binding affinity of HSF1 to the heat shock element by directly interacting with HSF1 but did not affect HSF1 phosphorylation-dependent activation or nuclear localization. hnRNP K lost its ability to induce these effects when its Cys(132) was substituted with Ser, Asp, or Glu. These findings suggest that hnRNP K inhibits transcriptional activity of HSF1 by inhibiting its binding to heat shock element and that the oxidation status of Cys(132) in hnRNP K is critical for this inhibition. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Sustainability in a global context: How does local factor affect the outcomes of CSR activities in international business units?

    DEFF Research Database (Denmark)

    Thomsen, Christa; Lauring, Jakob

    In recent years CSR has become increasingly important for the activities and branding of MNCs. While some studies have investigated CSR management and branding in domestic situations, fewer studies exist in the case of international business units (subsidiaries, joint ventures, and franchises...... as CSR branding outcomes). Our findings show that local values were positively associated with external CSR engagement and that employee relations were positively related to both internal and external CSR engagement. None of the local factors were significantly associated with CSR branding outcomes...

  7. Therapeutic angiogenesis induced by human hepatocyte growth factor gene in hindlimb ischemia of dogs

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A preclinical study of treating peripheral artery occlusive disease (PAD) was performed by using a hepatocyte growth factor (HGF) gene-expressing vector, plasmid pUDKH, in a dog model with complete ischemia of one hindlimb. After ligation of femoral artery of one hindlimb, pUDKH was transferred directly into the ischemic limb muscles. The angiogenic activity of the plasmid pUDKH was evaluated. On D 30 after injecting once of pUDKH at different doses into local muscles immediately after operation, the degree of augmentation of collateral vessel formation was significantly greater than that treated by blank vector. In addition, the blood flow rate of femoral artery in dogs treated with pUDKH was recovered on D 90, while the flow rate was only 1/5 to 1/3 in control dogs. The pulse amplitude of pUDKH-treated dogs was recovered on D 90, but it was hardly detectable in most of the control dogs. The side effects of intramuscular transfection of pUDKH were also investigated, and no significant positive change was found. It is suggested that angiogenesis induced by HGF gene has the potential for clinical use in the treatment of peripheral arterial diseases.

  8. Role of apoptosis-inducing factor (AIF in programmed nuclear death during conjugation in Tetrahymena thermophila

    Directory of Open Access Journals (Sweden)

    Endoh Hiroshi

    2010-02-01

    Full Text Available Abstract Background Programmed nuclear death (PND, which is also referred to as nuclear apoptosis, is a remarkable process that occurs in ciliates during sexual reproduction (conjugation. In Tetrahymena thermophila, when the new macronucleus differentiates, the parental macronucleus is selectively eliminated from the cytoplasm of the progeny, concomitant with apoptotic nuclear events. However, the molecular mechanisms underlying these events are not well understood. The parental macronucleus is engulfed by a large autophagosome, which contains numerous mitochondria that have lost their membrane potential. In animals, mitochondrial depolarization precedes apoptotic cell death, which involves DNA fragmentation and subsequent nuclear degradation. Results We focused on the role of mitochondrial apoptosis-inducing factor (AIF during PND in Tetrahymena. The disruption of AIF delays the normal progression of PND, specifically, nuclear condensation and kilobase-size DNA fragmentation. AIF is localized in Tetrahymena mitochondria and is released into the macronucleus prior to nuclear condensation. In addition, AIF associates and co-operates with the mitochondrial DNase to facilitate the degradation of kilobase-size DNA, which is followed by oligonucleosome-size DNA laddering. Conclusions Our results suggest that Tetrahymena AIF plays an important role in the degradation of DNA at an early stage of PND, which supports the notion that the mitochondrion-initiated apoptotic DNA degradation pathway is widely conserved among eukaryotes.

  9. Police-induced confessions, risk factors, and recommendations: looking ahead.

    Science.gov (United States)

    Kassin, Saul M; Drizin, Steven A; Grisso, Thomas; Gudjonsson, Gisli H; Leo, Richard A; Redlich, Allison D

    2010-02-01

    Reviewing the literature on police-induced confessions, we identified suspect characteristics and interrogation tactics that influence confessions and their effects on juries. We concluded with a call for the mandatory electronic recording of interrogations and a consideration of other possible reforms. The preceding commentaries make important substantive points that can lead us forward-on the effects of videotaping of interrogations on case dispositions; on the study of non-custodial methods, such as the controversial Mr. Big technique; and on an analysis of why confessions, once withdrawn, elicit such intractable responses compared to statements given by child and adult victims. Toward these ends, we hope that this issue provides a platform for future research aimed at improving the diagnostic value of confession evidence.

  10. Relative importance of local habitat complexity and regional factors for assemblages of oribatid mites (Acari: Oribatida) in Sphagnum peat bogs.

    Science.gov (United States)

    Minor, M A; Ermilov, S G; Philippov, D A; Prokin, A A

    2016-11-01

    We investigated communities of oribatid mites in five peat bogs in the north-west of the East European plain. We aimed to determine the extent to which geographic factors (latitude, separation distance), local environment (Sphagnum moss species, ground water level, biogeochemistry) and local habitat complexity (diversity of vascular plants and bryophytes in the surrounding plant community) influence diversity and community composition of Oribatida. There was a significant north-to-south increase in Oribatida abundance. In the variance partitioning, spatial factors explained 33.1 % of variability in abundance across samples; none of the environmental factors were significant. Across all bogs, Oribatida species richness and community composition were similar in Sphagnum rubellum and Sphagnum magellanicum, but significantly different and less diverse in Sphagnum cuspidatum. Sphagnum microhabitat explained 52.2 % of variability in Oribatida species richness, whereas spatial variables explained only 8.7 %. There was no distance decay in community similarity between bogs with increased geographical distance. The environmental variables explained 34.9 % of the variance in community structure, with vascular plants diversity, bryophytes diversity, and ground water level all contributing significantly; spatial variables explained 15.1 % of the total variance. Overall, only 50 % of the Oribatida community variance was explained by the spatial structure and environmental variables. We discuss relative importance of spatial and local environmental factors, and make general inferences about the formation of fauna in Sphagnum bogs.

  11. Trajectories of childhood weight gain: the relative importance of local environment versus individual social and early life factors.

    Directory of Open Access Journals (Sweden)

    Megan A Carter

    Full Text Available OBJECTIVE: To determine the association between local environmental factors with child weight status in a longitudinal study, using a semi-parametric, group-based method, while also considering social and early life factors. METHODS: Standardized, directly measured BMI from 4-10 y of age, and group-based trajectory modeling (PROC TRAJ were used to estimate developmental trajectories of weight change in a Québec birth cohort (n = 1,566. Associations between the weight trajectories and living location, social cohesion, disorder, and material and social deprivation were estimated after controlling for social and early life factors. RESULTS: FOUR WEIGHT TRAJECTORY GROUPS WERE ESTIMATED: low-increasing (9.7%; low-medium, accelerating (36.2%; medium-high, increasing (43.0%; and high-stable (11.1%. In the low-increasing and medium-high trajectory groups, living in a semi-urban area was inversely related to weight, while living in a rural area was positively related to weight in the high-stable group. Disorder was inversely related to weight in the low-increasing group only. Other important risk factors for high-stable weight included obesity status of the mother, smoking during pregnancy, and overeating behaviors. CONCLUSIONS: In this study, associations between local environment factors and weight differed by trajectory group. Early life factors appear to play a more consistent role in weight status. Further work is needed to determine the influence of place on child weight.

  12. Effects of exposure to a DNA damaging agent on the hypoxia inducible factors in organogenesis stage mouse limbs.

    Directory of Open Access Journals (Sweden)

    Chunwei Huang

    Full Text Available Hypoxia plays a critical role in coordinating cell survival, differentiation and death in normal embryogenesis; during limb pattern formation, hypoxia affects two key processes, chondrogenesis and cell death. Hypoxia promotes chondrocyte differentiation and cartilage matrix synthesis and suppresses terminal differentiation. Depending on the context, hypoxia may induce cell cycle arrest, pro- or anti-apoptotic genes, or autophagy. The response to hypoxia is controlled by hypoxia inducible transcription factors, specifically Hif1a, Hif2a and Hif3a. Under normoxia, the hypoxia-inducible factors respond to a variety of stimuli that include several well established teratogens, such as retinoic acid, heavy metals and hyperglycemia. We hypothesize that teratogenic exposures disrupt limb development by altering the hypoxia signalling pathway. To test this hypothesis, we assessed the effects of a DNA damaging alkylating agent, 4-hydroperoxycyclophosphamide, on the hypoxia inducible factor (HIF transcription factors and on hypoxia in the murine limb bud culture system. 4-Hydroperoxycyclophosphamide exposure increased HIF1 DNA binding activity and HIF1A and HIF2A, but not HIF3A, protein concentrations. HIF1A and HIF2A immunoreactivities were detected in the apical ectodermal ridge and interdigital regions, where cell death sculpts the limb; 4-hydroperoxycyclophosphamide treatment enhanced their immunoreactivities, specifically in these regions. In contrast, hypoxia was localized to areas of chondrogenesis, the cartilaginous anlagen of the developing long bone and phalanges, and was not enhanced by drug exposure. Thus, the exposure of limb buds in vitro to a DNA damaging teratogen triggered a hypoxia signalling response that was associated with cell death. During limb development the HIFs have oxygen-independent functions.

  13. Local Structural Distortion Induced Uniaxial Negative Thermal Expansion in Nanosized Semimetal Bismuth.

    Science.gov (United States)

    Li, Qiang; Zhu, He; Zheng, Lirong; Fan, Longlong; Ren, Yang; Chen, Jun; Deng, Jinxia; Xing, Xianran

    2016-11-01

    The corrugated layer structure bismuth has been successfully tailored into negative thermal expansion along c axis by size effect. Pair distribution function and extended X-ray absorption fine structure are combined to reveal the local structural distortion for nanosized bismuth. The comprehensive method to identify the local structure of nanomaterials can benefit the regulating and controlling of thermal expansion in nanodivices.

  14. Sea level changes induced by local winds on the west coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Mehra, P.; Tsimplis, M.N.; Desai, R.G.P.; Joseph, A.; Shaw, A.G.P.; Somayajulu, Y.K.; Cipollini, P.

    The contribution of atmospheric pressure and local wind to sea level variability at Goa (West coast of India) for the period 2007–2008 is investigated. Sea level data from a tide gauge are compared with measured local surface meteorological as well...

  15. Ways of making-sense: Local gamma synchronization reveals differences between semantic processing induced by music and language.

    Science.gov (United States)

    Barraza, Paulo; Chavez, Mario; Rodríguez, Eugenio

    2016-01-01

    Similar to linguistic stimuli, music can also prime the meaning of a subsequent word. However, it is so far unknown what is the brain dynamics underlying the semantic priming effect induced by music, and its relation to language. To elucidate these issues, we compare the brain oscillatory response to visual words that have been semantically primed either by a musical excerpt or by an auditory sentence. We found that semantic violation between music-word pairs triggers a classical ERP N400, and induces a sustained increase of long-distance theta phase synchrony, along with a transient increase of local gamma activity. Similar results were observed after linguistic semantic violation except for gamma activity, which increased after semantic congruence between sentence-word pairs. Our findings indicate that local gamma activity is a neural marker that signals different ways of semantic processing between music and language, revealing the dynamic and self-organized nature of the semantic processing.

  16. Evidence for strain-induced local conductance modulations in single-layer graphene on SiO2.

    Science.gov (United States)

    Teague, M L; Lai, A P; Velasco, J; Hughes, C R; Beyer, A D; Bockrath, M W; Lau, C N; Yeh, N-C

    2009-07-01

    Graphene has emerged as an electronic material that is promising for device applications and for studying two-dimensional electron gases with relativistic dispersion near two Dirac points. Nonetheless, deviations from Dirac-like spectroscopy have been widely reported with varying interpretations. Here we show evidence for strain-induced spatial modulations in the local conductance of single-layer graphene on SiO(2) substrates from scanning tunneling microscopic (STM) studies. We find that strained graphene exhibits parabolic, U-shaped conductance vs bias voltage spectra rather than the V-shaped spectra expected for Dirac fermions, whereas V-shaped spectra are recovered in regions of relaxed graphene. Strain maps derived from the STM studies further reveal direct correlation with the local tunneling conductance. These results are attributed to a strain-induced frequency increase in the out-of-plane phonon mode that mediates the low-energy inelastic charge tunneling into graphene.

  17. Local hyperthermia treatment of tumors induces CD8+ T cell-mediated resistance against distal and secondary tumors

    Science.gov (United States)

    Zhang, Peisheng; Chen, Lei; Baird, Jason R.; Demidenko, Eugene; Turk, Mary Jo; Hoopes, P. Jack; Conejo-Garcia, Jose R.; Fiering, Steven

    2014-01-01

    Combinatorial use of iron oxide nanoparticles (IONPs) and an alternating magnetic filed (AMF) can induce local hyperthermia in tumors in a controlled and uniform manner. Heating B16 primary tumors at 43°C for 30 minutes activated dendritic cells (DCs) and subsequently CD8+ T cells in the draining lymph node (dLN) and conferred resistance against rechallenge with B16 (but not unrelated Lewis Lung carcinoma) given 7 days post hyperthermia on both the primary tumor side and the contralateral side in a CD8+ T cell-dependent manner. Mice with heated primary tumors also resisted rechallenge given 30 days post hyperthermia. Mice with larger heated primary tumors had greater resistance to secondary tumors. No rechallenge resistance occurred when tumors were heated at 45°C. Our results demonstrate the promising potential of local hyperthermia treatment applied to identified tumors in inducing anti-tumor immune responses that reduce the risk of recurrence and metastasis. PMID:24566274

  18. A novel Rieske-type protein derived from an apoptosis-inducing factor-like (AIFL) transcript with a retained intron 4 induces change in mitochondrial morphology and growth arrest

    Energy Technology Data Exchange (ETDEWEB)

    Murata, Yasuhiko, E-mail: 97318@ib.k.u-tokyo.ac.jp [Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561 (Japan); Furuyama, Isao; Oda, Shoji [Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561 (Japan); Mitani, Hiroshi, E-mail: mitani@k.u-tokyo.ac.jp [Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561 (Japan)

    2011-04-01

    Highlights: {yields} A novel major transcript, AIFL-I4, is found. {yields} Nuclear localization of AIFL-I4 induces mitochondrial morphology change and suppression of cell proliferation. {yields} AIFL-I4 mutant with a lesion in [2Fe-2S] cluster binding site does not induce these phenotypes. {yields} [2Fe-2S] cluster binding site is essential for these phenotypes. -- Abstract: Apoptosis-inducing factor-like (AIFL) protein contains a Rieske domain and pyridine nucleotide-disulfide oxidoreductase (Pyr{sub r}edox) domain that shows 35% homology to that of apoptosis-inducing factor (AIF) protein. We identified a novel major transcript of the medaka (Oryzias latipes) AIFL gene that retained intron 4 (AIFL-I4) in embryos and tissues from adult fish. The product of this transcript, AIFL-I4 protein, lacked the Pyr{sub r}edox domain because of a nonsense codon in intron 4. Both AIFL-I4 and full-length AIFL (fAIFL) transcripts were highly expressed in the brain and late embryos, and relative fAIFL and AIFL-I4 expression levels differed among tissues. Transient expression of AIFL-I4 and fAIFL tagged with GFP showed that AIFL-I4 localized in the nucleus, while fAIFL localized throughout the cytoplasm. We also found that overexpression of AIFL-I4 induced a change in mitochondrial morphology and suppression of cell proliferation. AIFL-I4 mutant with a lesion in [2Fe-2S] cluster binding site of the Rieske domain did not induce these phenotypes. This report is the first to demonstrate nuclear localization of a Rieske-type protein translated from the AIFL gene. Our data suggested that the [2Fe-2S] cluster binding site was essential for the nuclear localization and involved in mitochondrial morphology and suppression of cell proliferation.

  19. Effect of Local Nasal Immunotherapy on Nasal Blockage in Pollen-Induced Allergic Rhinitis of Guinea Pigs

    OpenAIRE

    Takeshi Nabe; Kayoko Kubota; Nobuaki Mizutani; Masanori Fujii; Tetsuya Terada; Hiroshi Takenaka; Shigekatsu Kohno

    2008-01-01

    Background: As a non-injection route for immunotherapy, local nasal immunotherapy has been examined in allergic rhinitis patients. However, it is unclear how the immunotherapy affects sneezing, biphasic nasal blockage and nasal hyperresponsiveness. Thus, we evaluated the therapeutic effects of nasal immunotherapy on the symptoms of guinea pig allergic rhinitis. Additionally, we also evaluated whether the immunotherapy relieved pollen-induced allergic conjunctivitis. Methods: Sensitized ani...

  20. Local serotonin mediates cyclic strain-induced phenotype transformation, matrix degradation, and glycosaminoglycan synthesis in cultured sheep mitral valves.

    Science.gov (United States)

    Lacerda, Carla M R; Kisiday, John; Johnson, Brennan; Orton, E Christopher

    2012-05-15

    This study addressed the following questions: 1) Does cyclic tensile strain induce protein expression patterns consistent with myxomatous degeneration in mitral valves? 2) Does cyclic strain induce local serotonin synthesis in mitral valves? 3) Are cyclic strain-induced myxomatous protein expression patterns in mitral valves dependent on local serotonin? Cultured sheep mitral valve leaflets were subjected to 0, 10, 20, and 30% cyclic strain for 24 and 72 h. Protein levels of activated myofibroblast phenotype markers, α-smooth muscle actin (α-SMA) and nonmuscle embryonic myosin (SMemb); matrix catabolic enzymes, matrix metalloprotease (MMP) 1 and 13, and cathepsin K; and sulfated glycosaminoglycan (GAG) content in mitral valves increased with increased cyclic strain. Serotonin was present in the serum-free media of cultured mitral valves and concentrations increased with cyclic strain. Expression of the serotonin synthetic enzyme tryptophan hydroxylase 1 (TPH1) increased in strained mitral valves. Pharmacologic inhibition of the serotonin 2B/2C receptor or TPH1 diminished expression of phenotype markers (α-SMA and SMemb) and matrix catabolic enzyme (MMP1, MMP13, and cathepsin K) expression in 10- and 30%-strained mitral valves. These results provide first evidence that mitral valves synthesize serotonin locally. The results further demonstrate that tensile loading modulates local serotonin synthesis, expression of effector proteins associated with mitral valve degeneration, and GAG synthesis. Inhibition of serotonin diminishes strain-mediated protein expression patterns. These findings implicate serotonin and tensile loading in mitral degeneration, functionally link the pathogeneses of serotoninergic (carcinoid, drug-induced) and degenerative mitral valve disease, and have therapeutic implications.

  1. One- and two-photon induced fluorescence spectroscopy enabling the detection of localized aflatoxin contamination in individual maize kernels

    Science.gov (United States)

    Smeesters, L.; Meulebroeck, W.; Raeymaekers, S.; Thienpont, H.

    2016-04-01

    The presence of carcinogenic aflatoxins in food and feed products is a major worldwide problem. To date, the aflatoxin contamination can only be detected by the use of destructive sample-based chemical analyses. Therefore, we developed an optical setup able to detect the localized aflatoxin contamination in individual maize kernels, on the basis of one- and two- photon induced fluorescence spectroscopy. Our developed optical configuration comprises a tunable titanium-sapphire laser (710nm-830nm) in combination with second harmonic wavelength generation (355nm-415nm), enabling the measurement of both one- and two-photon induced fluorescence spectra. Moreover, an accurate scanning of the kernel's surface was induced by the use of automated translation stages, allowing to study the localized maize contamination. First, the operation of the setup is validated by the characterization of pure aflatoxin B1 powder. Second, the fluorescence spectra of healthy (maize kernels (>70ppb aflatoxin B1) were measured, after excitation with 365nm, 730nm, 750nm and 780nm. For both the one- and two- photon induced fluorescence processes, the presence of the aflatoxin inside the contaminated maize kernels influenced the intrinsic fluorescence signals. Based on the fluorescence spectrum between 400nm and 550nm, we defined a detection criterion to identify the contaminated maize kernels. Furthermore, we demonstrate the sensing of the localized contamination level, indicating both contaminated maize kernels with a high contamination level in a limited surface area (as small as 1mm2) as with a lower contamination spread over a large surface area (up to 20mm2). As a result, our developed measurement methodology allows the identification of the localized aflatoxin contamination, paving the way to the non-destructive, real-time and high-sensitive industrial scanning-based detection of aflatoxins in food products.

  2. Tumor necrosis factor-alpha induced enhancement of cryosurgery

    Science.gov (United States)

    Goel, Raghav; Paciotti, Guilio F.; Bischof, John C.

    2008-02-01

    Local recurrence of cancer after cryosurgery is related to the inability to monitor and predict destruction of cancer (temperatures > -40°C) within an iceball. We previously reported that a cytokine adjuvant TNF-α could be used to achieve complete cancer destruction at the periphery of an iceball (0 to -40°C). This study is a further development of that work in which cryosurgery was performed using cryoprobes operating at temperatures > -40°C. LNCaP Pro 5 tumor grown in a dorsal skin fold chamber (DSFC) was frozen at -6°C after TNF-α incubation for 4 or 24 hours. Tumors grown in the hind limb were frozen with a probe tip temperature of -40°C, 4 or 24 hours after systemic injection with TNF-α. Both cryosurgery alone or TNF-α treatment alone caused only a minimal damage to the tumor tissue at the conditions used in the study. The combination of TNF-α and cryosurgery produced a significant damage to the tumor tissue in both the DSFC and the hind limb model system. This augmentation in cryoinjury was found to be time-dependent with 4-hour time period between the two treatments being more effective than 24-hour. These results suggests the possibility of cryotreatment at temperatures > -40°C with the administration of TNF-α.

  3. Crystal structures of bacterial lipoprotein localization factors, LolA and LolB

    OpenAIRE

    Takeda, Kazuki; Miyatake, Hideyuki; Yokota, Naoko; Matsuyama, Shin-ichi; Tokuda, Hajime; Miki, Kunio

    2003-01-01

    Lipoproteins having a lipid-modified cysteine at the N-terminus are localized on either the inner or the outer membrane of Escherichia coli depending on the residue at position 2. Five Lol proteins involved in the sorting and membrane localization of lipoprotein are highly conserved in Gram-negative bacteria. We determined the crystal structures of a periplasmic chaperone, LolA, and an outer membrane lipoprotein receptor, LolB. Despite their dissimilar amino acid sequences, the structures of ...

  4. Minimal change-like glomerular alterations induced by a human plasma factor

    NARCIS (Netherlands)

    Cheung, PK; Klok, PA; Bakker, WW

    1996-01-01

    Circulating factors, including the plasma protease (100KF) described previously, have been suspected to play a role in the pathogenesis of minimal change disease (MCD) for several decades. This factor was able to induce MCD-like alterations in kidney tissue in vitro, i.e. impairment of glomerular po

  5. Effect of montelukast on platelet activating factor- and tachykinin induced mucus secretion in the rat

    Directory of Open Access Journals (Sweden)

    Groneberg David A

    2008-02-01

    Full Text Available Abstract Background Platelet activating factor and tachykinins (substance P, neurokinin A, neurokinin B are important mediators contributing to increased airway secretion in the context of different types of respiratory diseases including acute and chronic asthma. Leukotriene receptor antagonists are recommended as add-on therapy for this disease. The cys-leukotriene-1 receptor antagonist montelukast has been used in clinical asthma therapy during the last years. Besides its inhibitory action on bronchoconstriction, only little is known about its effects on airway secretions. Therefore, the aim of this study was to evaluate the effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity. Methods The effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity in the rat were assessed by quantification of secreted 35SO4 labelled mucus macromolecules using the modified Ussing chamber technique. Results Platelet activating factor potently stimulated airway secretion, which was completely inhibited by the platelet activating factor receptor antagonist WEB 2086 and montelukast. In contrast, montelukast had no effect on tachykinin induced tracheal secretory activity. Conclusion Cys-leukotriene-1 receptor antagonism by montelukast reverses the secretagogue properties of platelet activating factor to the same degree as the specific platelet activating factor antagonist WEB 2086 but has no influence on treacheal secretion elicited by tachykinins. These results suggest a role of montelukast in the signal transduction pathway of platelet activating factor induced secretory activity of the airways and may further explain the beneficial properties of cys-leukotriene-1 receptor antagonists.

  6. Epidermal growth factor receptor signalling contributes to house dust mite-induced epithelial barrier dysfunction

    NARCIS (Netherlands)

    Heijink, I H; van Oosterhout, A; Kapus, A

    2010-01-01

    Impaired airway epithelial barrier function has emerged as a key factor in the pathogenesis of allergic asthma. We aimed to discern the involvement of the epidermal growth factor receptor (EGFR) in allergen-induced epithelial barrier impairment, as we previously observed that house dust mite (HDM) s

  7. A RNA antagonist of hypoxia-inducible factor-1alpha, EZN-2968, inhibits tumor cell growth

    DEFF Research Database (Denmark)

    Greenberger, Lee M; Horak, Ivan D; Filpula, David

    2008-01-01

    Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays a critical role in angiogenesis, survival, metastasis, drug resistance, and glucose metabolism. Elevated expression of the alpha-subunit of HIF-1 (HIF-1alpha), which occurs in response to hypoxia or activation of growth facto...

  8. Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis

    DEFF Research Database (Denmark)

    Villa, Elizabeth; Sengupta, Jayati; Trabuco, Leonard G.

    2009-01-01

    In translation, elongation factor Tu (EF-Tu) molecules deliver aminoacyl-tRNAs to the mRNA-programmed ribosome. The GTPase activity of EF-Tu is triggered by ribosome-induced conformational changes of the factor that play a pivotal role in the selection of the cognate aminoacyl-tRNAs. We present a...

  9. Hinokitiol protects primary neuron cells against prion peptide-induced toxicity via autophagy flux regulated by hypoxia inducing factor-1.

    Science.gov (United States)

    Moon, Ji-Hong; Lee, Ju-Hee; Lee, You-Jin; Park, Sang-Youel

    2016-05-24

    Prion diseases are fatal neurodegenerative disorders that are derived from structural changes of the native PrPc. Recent studies indicated that hinokitiol induced autophagy known to major function that keeps cells alive under stressful conditions. We investigated whether hinokitiol induces autophagy and attenuates PrP (106-126)-induced neurotoxicity. We observed increase of LC3-II protein level, GFP-LC3 puncta by hinokitiol in neuronal cells. Addition to, electron microscopy showed that hinokitiol enhanced autophagic vacuoles in neuronal cells. We demonstrated that hinokitiol protects against PrP (106-126)-induced neurotoxicity via autophagy by using autophagy inhibitor, wortmannin and 3MA, and ATG5 small interfering RNA (siRNA). We checked hinokitiol activated the hypoxia-inducible factor-1α (HIF-1α) and identified that hinokitiol-induced HIF-1α regulated autophagy. Taken together, this study is the first report demonstrating that hinokitiol protected against prion protein-induced neurotoxicity via autophagy regulated by HIF-1α. We suggest that hinokitiol is a possible therapeutic strategy in neuronal disorders including prion disease.

  10. Growth factors have a protective effect on neomycin-induced hair cell loss.

    Science.gov (United States)

    Lou, Xiangxin; Yuan, Huihua; Xie, Jing; Wang, Xianliu; Yang, Liangliang; Zhang, Yanzhong

    2015-01-01

    We have demonstrated that selected growth factors are involved in regulating survival and proliferation of progenitor cells derived from the neonatal rat organ of Corti (OC). The protective and regenerative effects of these defined growth factors on the injured organ of Corti were therefore investigated. The organ of Corti dissected from the Wistar rat pups (P3-P5) was split into apical, middle, and basal parts, explanted and cultured with or without neomycin and growth factors. Insulin-like growth factor-1 (IGF-1), fibroblast growth factor-2 (FGF-2), and epidermal growth factor (EGF) protected the inner hair cells (IHCs) and outer hair cells (OHCs) from neomycin ototoxicity. Using EGF, IGF-1, and FGF-2 alone induced no protective effect on the survival of auditory hair cells. Combining 2 growth factors (EGF + IGF-1, EGF + FGF-2, or IGF-1 + FGF-2) gave statistically protective effects. Similarly, combining all three growth factors effectively protected auditory hair cells from the ototoxic insult. None of the growth factors induced regeneration of hair cells in the explants injured with neomycin. Thus various combinations of the three defined factors (IGF-1, FGF-2, and EGF) can protect the auditory hair cells from the neomycin-induced ototoxic damage, but no regeneration was seen. This offers a possible novel approach to the treatment of hearing loss.

  11. The estrogen receptor alpha nuclear localization sequence is critical for fulvestrant-induced degradation of the receptor.

    Science.gov (United States)

    Casa, Angelo J; Hochbaum, Daniel; Sreekumar, Sreeja; Oesterreich, Steffi; Lee, Adrian V

    2015-11-01

    Fulvestrant, a selective estrogen receptor down-regulator (SERD) is a pure competitive antagonist of estrogen receptor alpha (ERα). Fulvestrant binds ERα and reduces the receptor's half-life by increasing protein turnover, however, its mechanism of action is not fully understood. In this study, we show that removal of the ERα nuclear localization sequence (ERΔNLS) resulted in a predominantly cytoplasmic ERα that was degraded in response to 17-β-estradiol (E2) but was resistant to degradation by fulvestrant. ERΔNLS bound the ligands and exhibited receptor interaction similar to ERα, indicating that the lack of degradation was not due to disruption of these processes. Forcing ERΔNLS into the nucleus with a heterologous SV40-NLS did not restore degradation, suggesting that the NLS domain itself, and not merely receptor localization, is critical for fulvestrant-induced ERα degradation. Indeed, cloning of the endogenous ERα NLS onto the N-terminus of ERΔNLS significantly restored both its nuclear localization and turnover in response to fulvestrant. Moreover, mutation of the sumoylation targets K266 and K268 within the NLS impaired fulvestrant-induced ERα degradation. In conclusion, our study provides evidence for the unique role of the ERα NLS in fulvestrant-induced degradation of the receptor.

  12. Surfactant protein-A modulates LPS-induced TLR4 localization and signaling via β-arrestin 2.

    Directory of Open Access Journals (Sweden)

    Vicky Sender

    Full Text Available The soluble C-type lectin surfactant protein (SP-A mediates lung immune responses partially via its direct effects on alveolar macrophages (AM, the main resident leukocytes exposed to antigens. SP-A modulates the AM threshold of lipopolysaccharide (LPS activity towards an anti-inflammatory phenotype both in vitro and in vivo through various mechanisms. LPS responses are tightly regulated via distinct pathways including subcellular TLR4 localization and thus ligand sensing. The cytosolic scaffold and signaling protein β-arrestin 2 acts as negative regulator of LPS-induced TLR4 activation. Here we show that SP-A neither increases TLR4 abundancy nor co-localizes with TLR4 in primary AM. SP-A significantly reduces the LPS-induced co-localization of TLR4 with the early endosome antigen (EEA 1 by promoting the co-localization of TLR4 with the post-Golgi compartment marker Vti1b in freshly isolated AM from rats and wild-type (WT mice, but not in β-arrestin 2(-/- AM. Compared to WT mice pulmonary LPS-induced TNF-α release in β-arrestin 2(-/- mice is accelerated and enhanced and exogenous SP-A fails to inhibit both lung LPS-induced TNF-α release and TLR4/EEA1 positioning. SP-A, but not LPS, enhances β-arrestin 2 protein expression in a time-dependent manner in primary rat AM. The constitutive expression of β-arrestin 2 in AM from SP-A(-/- mice is significantly reduced compared to SP-A(+/+ mice and is rescued by SP-A. Prolonged endosome retention of LPS-induced TLR4 in AM from SP-A(-/- mice is restored by exogenous SP-A, and is antagonized by β-arrestin 2 blocking peptides. LPS induces β-arrestin 2/TLR4 association in primary AM which is further enhanced by SP-A. The data demonstrate that SP-A modulates LPS-induced TLR4 trafficking and signaling in vitro and in vivo engaging β-arrestin 2.

  13. Local Muscle Metabolic Demand Induced by Neuromuscular Electrical Stimulation and Voluntary Contractions at Different Force Levels: A NIRS Study.

    Science.gov (United States)

    Muthalib, Makii; Kerr, Graham; Nosaka, Kazunori; Perrey, Stephane

    2016-06-13

    Functional Muscle metabolic demand during contractions evoked by neuromuscular electrical stimulation (NMES) has been consistently documented to be greater than voluntary contractions (VOL) at the same force level (10-50% maximal voluntary contraction-MVC). However, we have shown using a near-infrared spectroscopy (NIRS) technique that local muscle metabolic demand is similar between NMES and VOL performed at MVC levels, thus controversy exists. This study therefore compared biceps brachii muscle metabolic demand (tissue oxygenation index-TOI and total hemoglobin volume-tHb) during a 10s isometric contraction of the elbow flexors between NMES (stimulation frequency of 30Hz and current level to evoke 30% MVC) and VOL at 30% MVC (VOL-30%MVC) and MVC (VOL-MVC) level in 8 healthy men (23-33-y). Greater changes in TOI and tHb induced by NMES than VOL-30%MVC confirm previous studies of a greater local metabolic demand for NMES than VOL at the same force level. The same TOI and tHb changes for NMES and VOL-MVC suggest that local muscle metabolic demand and intramuscular pressure were similar between conditions. In conclusion, these findings indicate that NMES induce a similar local muscle metabolic demand as that of maximal VOL.

  14. Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Manuel Modolell

    Full Text Available The balance between T helper (Th 1 and Th2 cell responses is a major determinant of the outcome of experimental leishmaniasis, but polarized Th1 or Th2 responses are not sufficient to account for healing or nonhealing. Here we show that high arginase activity, a hallmark of nonhealing disease, is primarily expressed locally at the site of pathology. The high arginase activity causes local depletion of L-arginine, which impairs the capacity of T cells in the lesion to proliferate and to produce interferon-gamma, while T cells in the local draining lymph nodes respond normally. Healing, induced by chemotherapy, resulted in control of arginase activity and reversal of local immunosuppression. Moreover, competitive inhibition of arginase as well as supplementation with L-arginine restored T cell effector functions and reduced pathology and parasite growth at the site of lesions. These results demonstrate that in nonhealing leishmaniasis, arginase-induced L-arginine depletion results in impaired T cell responses. Our results identify a novel mechanism in leishmaniasis that contributes to the failure to heal persistent lesions and suggest new approaches to therapy.

  15. Snail transcription factor NLS and importin β1 regulate the subcellular localization of Cathepsin L and Cux1.

    Science.gov (United States)

    Burton, Liza J; Henderson, Veronica; Liburd, Latiffa; Odero-Marah, Valerie A

    2017-09-09

    Several recent studies have highlighted an additional unexpected localization and site of action for Cathepsin L (Cat L) protease within the nucleus in breast, colon and prostate cancer, however, its role in the nucleus was unclear. It was proposed to mediate proteolytic processing of the transcription factor CCAAT-displacement protein/cut homeobox transcription factor (Cux1) from the full-length p200 isoform to generate the p110 and p90 isoforms, of which the p110 isoform was shown to act as a cell cycle regulator to accelerate entry into the S phase. The p110 isoform has also been shown to bind to the promoter regions of Snail and E-cadherin to activate Snail and inactivate E-cadherin transcription, thus promoting epithelial mesenchymal transition (EMT). Mechanistic studies on what drives Cat L nuclear localization have not been reported. Our hypothesis is that Snail shuttles into the nucleus with Cat L through binding to importin-β. Snail knockdown with siRNA in MDA-MB-468 breast cancer cells led to nuclear to cytoplasmic shuttling of Cat L and decreased levels of Cux1, while overexpression of Snail in MCF-7 breast cancer cells or HEK-293 human embryonic kidney cells led to increased nuclear expression of both Cat L and Cux1. Additionally, transient transfection of Snail NLS mutants not only abrogated Snail nuclear localization but also nuclear localization of Cat L and Cux1. Interestingly, importin β1 knockdown with siRNA decreased Snail and Cux1 levels, as well as nuclear localization of Cat L. Therefore, we show for the first time that the nuclear localization of Cat L and its substrate Cux1can be positively regulated by Snail NLS and importin β1, suggesting that Snail, Cat L and Cux1 all utilize importin β1 for nuclear import. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Assessing the extent to which temporal changes in waterbird community composition are driven by either local, regional or global factors

    DEFF Research Database (Denmark)

    Tomankova, Irena; Reid, Neil; Boland, Helen

    2013-01-01

    1. Lough Neagh and Lough Beg Special Protection Area (SPA, hereafter Lough Neagh) is an important non-estuarine site in Britain and Ireland for overwintering wildfowl. Multivariate analysis of the winter counts showed a state-shift in the waterbird community following winter 2000/2001, mostly due...... to rapid declines in abundance (46–57% declines in the mean mid-winter January counts between 1993–2000 and 2002–2009) of members of the diving duck guild (pochard Aythya ferina, tufted duck Aythya fuligula and goldeneye Bucephala clangula) and coot (Fulica atra), a submerged macrophyte feeder. 2. Only...... suggest that local factors (such as loss of submerged macrophytes and benthic invertebrates) were involved. An assessment of the food supply, local disturbance and other factors at Lough Neagh is required to find an explanation for the observed adverse trends in wintering numbers of the affected species...

  17. Intracellular Localization and Cellular Factors Interaction of HTLV-1 and HTLV-2 Tax Proteins: Similarities and Functional Differences

    Directory of Open Access Journals (Sweden)

    Maria Grazia Romanelli

    2011-05-01

    Full Text Available Human T-lymphotropic viruses type 1 (HTLV-1 and type 2 (HTLV-2 present very similar genomic structures but HTLV-1 is more pathogenic than HTLV-2. Is this difference due to their transactivating Tax proteins, Tax-1 and Tax-2, which are responsible for viral and cellular gene activation? Do Tax-1 and Tax-2 differ in their cellular localization and in their interaction pattern with cellular factors? In this review, we summarize Tax-1 and Tax-2 structural and phenotypic properties, their interaction with factors involved in signal transduction and their localization-related behavior within the cell. Special attention will be given to the distinctions between Tax-1 and Tax-2 that likely play an important role in their transactivation activity.

  18. Maximum tumor diameter is not an independent prognostic factor in high-risk localized prostate cancer

    NARCIS (Netherlands)

    Oort, van I.M.; Witjes, J.A.; Kok, D.E.G.; Kiemeney, L.A.; Hulsbergen-van de Kaa, C.A.

    2008-01-01

    Previous studies suggest that maximum tumor diameter (MTD) is a predictor of recurrence in prostate cancer (PC). This study investigates the prognostic value of MTD for biochemical recurrence (BCR) in patients with PC, after radical prostatectomy (RP), with emphasis on high-risk localized prostate c

  19. Maximum tumor diameter is not an independent prognostic factor in high-risk localized prostate cancer.

    NARCIS (Netherlands)

    Oort, I.M. van; Witjes, J.A.M.; Kok, D.E.; Kiemeney, L.A.L.M.; Hulsbergen- van de Kaa, C.A.

    2008-01-01

    OBJECTIVES: Previous studies suggest that maximum tumor diameter (MTD) is a predictor of recurrence in prostate cancer (PC). This study investigates the prognostic value of MTD for biochemical recurrence (BCR) in patients with PC, after radical prostatectomy (RP), with emphasis on high-risk localize

  20. Nonlinear Local Bending Response and Bulging Factors for Longitudinal Cracks in Pressurized Cylindrical Shells

    Science.gov (United States)

    Rose, Cheryl A.; Young, Richard D.; Starnes, James H., Jr.

    1999-01-01

    Results of a geometrically nonlinear finite element parametric study to determine curvature correction factors or "bulging factors" that account for increased stresses due to curvature for longitudinal cracks in unstiffened pressurized cylindrical shells are presented. Geometric parameters varied in the study include the shell radius, the shell wall thickness, and the crack length. The major results are presented in graphs of the bulging factor as a function of the applied load and as a function of geometric parameters that include the shell radius, the shell thickness and the crack length. The computed bulging factors are compared with solutions based on linear shallow shell theory, and with semi-empirical solutions that approximately account for the nonlinear deformation in the vicinity of the crack. The effect of biaxial loads on the computed bulging factors is also discussed.

  1. Novel oscillator model with damping factor for plasmon induced transparency in waveguide systems.

    Science.gov (United States)

    Zhao, Mingzhuo; Li, Hongjian; He, Zhihui; Chen, Zhiquan; Xu, Hui; Zheng, Mingfei

    2017-09-06

    We introduce a novel two-oscillator model with damping factor to describe the plasmon induced transparency (PIT) in a bright-dark model plasmonic waveguide system. The damping factor γ in the model can be calculated from metal conductor damping factor γ c and dielectric damping factor γ d . We investigate the influence of geometry parameters and damping factor γ on transmission spectra as well as slow-light effects in the plasmonic waveguide system. We can find an obvious PIT phenomenon and realize a considerable slow-light effect in the double-cavities system. This work may provide guidance for optical switching and plasmon-based information processing.

  2. Modeling Threshold of Stress Intensity Factor in Iodine Induced Stress Corrosion Crack of Zirconium

    Institute of Scientific and Technical Information of China (English)

    SHANG; Xin-yuan; CHEN; Peng

    2013-01-01

    KISCC,which is the threshold of stress intensity factor of iodine induced stress corrosion crack(ISCC)of Zirconium,reflects the susceptibility of ISCC of zirconium.Once the stress intensity factor surpasses the threshold,the cracking propagation modality in material will transform to transgranular from intergranular immediately and the velocity of the cracking will increase rapidly.Four key factors that’s

  3. Long-Term Outcome of Definitive Radiotherapy for Early Glottic Cancer: Prognostic Factors and Patterns of Local Failure

    OpenAIRE

    Lim, Yu Jin; Wu, Hong-Gyun; Kwon, Tack-Kyun; Hah, J. Hun; Sung, Myung-Whun; Kim, Kwang Hyun; Park, Charn Il

    2015-01-01

    Purpose This study evaluates the long-term results of definitive radiotherapy (RT) for early glottic cancer. Clinical and treatment factors related to local control and patterns of failure are analyzed. Materials and Methods We retrospectively reviewed 222 patients with T1-2N0 squamous cell carcinoma of the glottic larynx treated with definitive RT from 1981 to 2010. None of the patients received elective nodal RT or combined chemotherapy. The median total RT dose was 66 Gy. The daily fractio...

  4. Analyzing Factors to Improve Service Quality of Local Specialties Restaurants: A Comparison with Fast Food Restaurants in Southern Vietnam

    OpenAIRE

    Lai Wang Wang; Thanh Tuyen Tran

    2014-01-01

    The top fast food restaurant brands like KFC and MacDonald?s have gone global and demonstrated their successful business strategies through providing quick-service and convenience for customers. Meanwhile, local specialty food has recently emerged as a phenomenon attracting customers? attention on traditional value of ethnic food culture. The purpose of this study is to conduct a regional survey in Vietnamese restaurant companies to identify some key factors that make customers interested in ...

  5. Localized occipital region abnormity of infantile EEG and its influence factors%小儿脑电波局限性异常及其影响因素

    Institute of Scientific and Technical Information of China (English)

    刘娟

    2009-01-01

    Objective To explore pediatric EEG in localized region abnormity and influence factors. Methods 51 children with EEG abnormity were retrospectively analyzed. Results In this group,there are 45 children with EEG abnormity in normal situation,and 6 of 51 childrened appear abnormity in induced tests. All the 51 childrened appeal abnormai brain wave in occipital region in varying degree. Conclusion Pediatric occipital region localization abnormal EEG may be hints related to children paroxysmal disorder, Miscellaneous factors can influence children paroxysmal disorder include all kinds of etiology, pathologic physiology signs and symptoms, age and individual variation ect.%目的 探讨小儿脑电波局限性异常及其影响囚素.方法 回顾性分析51例小儿脑电波枕区局限性异常的检查结果.结果 51例小儿脑电图常规描记异常45例,另6例在诱发试验中出现异常.51例患儿均在枕区出现不同程度的异常脑波.结论 小儿局限性枕区脑电波异常提示可能与发作性疾病有一定关系.

  6. Localization of ionization-induced trapping in a laser wakefield accelerator using a density down-ramp

    CERN Document Server

    Hansson, M.; Ekerfelt, H.; Aurand, B.; Gallardo Ganzalez, I.; Desforges, F. G.; Davoine, X.; Maitrallain, A.; Reymond, S.; Monot, P.; Persson, A.; Dobosz Dufrénoy S.; Wahlström C-G.; Cros, B.; Lundh, O.

    2016-01-01

    We report on a study on controlled trapping of electrons, by field ionization of nitrogen ions, in laser wakefield accelerators in variable length gas cells. In addition to ionization-induced trapping in the density plateau inside the cells, which results in wide, but stable, electron energy spectra, a regime of ionization-induced trapping localized in the density down-ramp at the exit of the gas cells, is found. The resulting electron energy spectra are peaked, with 10% shot-to-shot fluctuations in peak energy. Ionization-induced trapping of electrons in the density down-ramp is a way to trap and accelerate a large number of electrons, thus improving the efficiency of the laser-driven wakefield acceleration.

  7. Hybridization-Induced Carrier Localization at the C60/ZnO Interface

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Leah L.; Racke, David A.; Kim, Hyungchul; Ndione, Paul; Sigdel, Ajaya K.; Berry, Joseph J.; Graham, Samuel; Nordlund, Dennis; Monti, Oliver L. A.

    2016-05-25

    Electronic coupling and ground-state charge transfer at the C60/ZnO hybrid interface is shown to localize carriers in the C60 phase. This effect, revealed by resonant X-ray photoemission, arises from interfacial hybridization between C60 and ZnO. Such localization at carrier-selective electrodes and interlayers may lead to severely reduced carrier harvesting efficiencies and increased recombination rates in organic electronic devices.

  8. Impurity-induced local modes in one-dimensional dusty plasma chains

    Institute of Scientific and Technical Information of China (English)

    Ren Yong-Chao; Wang Xin-Shang; Wang Xiao-Gang

    2012-01-01

    The effects of impurity on eigenmodes in one-dimensional dusty plasma lattices are studied.It is found that local modes can be excited besides lattice waves,due to the existence of an impurity particle.The dispersion relations of the modes are derived accordingly.Properties of the lattice and local modes are also analyzed and discussed,particularly for their symmetric features and conditions of the mode excitation.

  9. Experimental Study of Slabbing and Rockburst Induced by True-Triaxial Unloading and Local Dynamic Disturbance

    Science.gov (United States)

    Du, Kun; Tao, Ming; Li, Xi-bing; Zhou, Jian

    2016-09-01

    Slabbing/spalling and rockburst are unconventional types of failure of hard rocks under conditions of unloading and various dynamic loads in environments with high and complex initial stresses. In this study, the failure behaviors of different rock types (granite, red sandstone, and cement mortar) were investigated using a novel testing system coupled to true-triaxial static loads and local dynamic disturbances. An acoustic emission system and a high-speed camera were used to record the real-time fracturing processes. The true-triaxial unloading test results indicate that slabbing occurred in the granite and sandstone, whereas the cement mortar underwent shear failure. Under local dynamically disturbed loading, none of the specimens displayed obvious fracturing at low-amplitude local dynamic loading; however, the degree of rock failure increased as the local dynamic loading amplitude increased. The cement mortar displayed no failure during testing, showing a considerable load-carrying capacity after testing. The sandstone underwent a relatively stable fracturing process, whereas violent rockbursts occurred in the granite specimen. The fracturing process does not appear to depend on the direction of local dynamic loading, and the acoustic emission count rate during rock fragmentation shows that similar crack evolution occurred under the two test scenarios (true-triaxial unloading and local dynamically disturbed loading).

  10. Polymethylmethacrylate-induced release of bone-resorbing factors

    Energy Technology Data Exchange (ETDEWEB)

    Herman, J.H.; Sowder, W.G.; Anderson, D.; Appel, A.M.; Hopson, C.N. (Univ. of Cincinnati College of Medicine, OH (USA))

    1989-12-01

    A pseudomembranous structure that has the histological characteristics of a foreign-body-like reaction invariably develops at the bone-cement interface in the proximity of resorption of bone around aseptically loosened cemented prostheses. This study was an attempt to implicate polymethylmethacrylate in this resorptive process. Unfractionated peripheral-blood mononuclear cells (consisting of lymphocytes and monocytes) and surface-adherent cells (monocyte-enriched) were prepared from control subjects who did and did not have clinical evidence of osteoarthrosis and from patients who had osteoarthrosis and were having a revision for failure of a cemented hip or knee implant. Cells were cultured for varying periods in the presence and absence of nonpolymerized methacrylate (one to two-micrometer spherules), pulverized polymerized material, or culture chambers that were pre-coated with polymerized cement. Conditioned media that were derived from both methacrylate-stimulated cell populations were shown to contain specific bone-resorbing mediators (interleukin-1, tumor necrosis factor, or prostaglandin E2) and to directly affect bone resorption in 45Ca-labeled murine limb-bone assays.

  11. Identification of a phosphorylation-dependent nuclear localization motif in interferon regulatory factor 2 binding protein 2.

    Directory of Open Access Journals (Sweden)

    Allen C T Teng

    Full Text Available BACKGROUND: Interferon regulatory factor 2 binding protein 2 (IRF2BP2 is a muscle-enriched transcription factor required to activate vascular endothelial growth factor-A (VEGFA expression in muscle. IRF2BP2 is found in the nucleus of cardiac and skeletal muscle cells. During the process of skeletal muscle differentiation, some IRF2BP2 becomes relocated to the cytoplasm, although the functional significance of this relocation and the mechanisms that control nucleocytoplasmic localization of IRF2BP2 are not yet known. METHODOLOGY/PRINCIPAL FINDINGS: Here, by fusing IRF2BP2 to green fluorescent protein and testing a series of deletion and site-directed mutagenesis constructs, we mapped the nuclear localization signal (NLS to an evolutionarily conserved sequence (354ARKRKPSP(361 in IRF2BP2. This sequence corresponds to a classical nuclear localization motif bearing positively charged arginine and lysine residues. Substitution of arginine and lysine with negatively charged aspartic acid residues blocked nuclear localization. However, these residues were not sufficient because nuclear targeting of IRF2BP2 also required phosphorylation of serine 360 (S360. Many large-scale phosphopeptide proteomic studies had reported previously that serine 360 of IRF2BP2 is phosphorylated in numerous human cell types. Alanine substitution at this site abolished IRF2BP2 nuclear localization in C(2C(12 myoblasts and CV1 cells. In contrast, substituting serine 360 with aspartic acid forced nuclear retention and prevented cytoplasmic redistribution in differentiated C(2C(12 muscle cells. As for the effects of these mutations on VEGFA promoter activity, the S360A mutation interfered with VEGFA activation, as expected. Surprisingly, the S360D mutation also interfered with VEGFA activation, suggesting that this mutation, while enforcing nuclear entry, may disrupt an essential activation function of IRF2BP2. CONCLUSIONS/SIGNIFICANCE: Nuclear localization of IRF2BP2 depends on

  12. Local and global synchronization transitions induced by time delays in small-world neuronal networks with chemical synapses.

    Science.gov (United States)

    Yu, Haitao; Wang, Jiang; Du, Jiwei; Deng, Bin; Wei, Xile

    2015-02-01

    Effects of time delay on the local and global synchronization in small-world neuronal networks with chemical synapses are investigated in this paper. Numerical results show that, for both excitatory and inhibitory coupling types, the information transmission delay can always induce synchronization transitions of spiking neurons in small-world networks. In particular, regions of in-phase and out-of-phase synchronization of connected neurons emerge intermittently as the synaptic delay increases. For excitatory coupling, all transitions to spiking synchronization occur approximately at integer multiples of the firing period of individual neurons; while for inhibitory coupling, these transitions appear at the odd multiples of the half of the firing period of neurons. More importantly, the local synchronization transition is more profound than the global synchronization transition, depending on the type of coupling synapse. For excitatory synapses, the local in-phase synchronization observed for some values of the delay also occur at a global scale; while for inhibitory ones, this synchronization, observed at the local scale, disappears at a global scale. Furthermore, the small-world structure can also affect the phase synchronization of neuronal networks. It is demonstrated that increasing the rewiring probability can always improve the global synchronization of neuronal activity, but has little effect on the local synchronization of neighboring neurons.

  13. Tumor volume as a prognostic factor for local control and overall survival in advanced larynx cancer

    NARCIS (Netherlands)

    Timmermans, A.J.; Lange, C.A.H.; de Bois, J.A.; van Werkhoven, E.; Hamming-Vrieze, O.; Hilgers, F.J.M.; van den Brekel, M.W.M.

    2015-01-01

    Keywords: Head and neck cancer; larynx cancer; organ preservation; total laryngectomy; imaging; tumor volume;prognosis; outcome Objectives/Hypothesis Tumor volume has been postulated to be an important prognostic factor for oncological outcome after radiotherapy or chemoradiotherapy. This postulate

  14. Protein kinase A regulates 3-phosphatidylinositide dynamics during platelet-derived growth factor-induced membrane ruffling and chemotaxis.

    Science.gov (United States)

    Deming, Paula B; Campbell, Shirley L; Baldor, Linda C; Howe, Alan K

    2008-12-12

    Spatial regulation of the cAMP-dependent protein kinase (PKA) is required for chemotaxis in fibroblasts; however, the mechanism(s) by which PKA regulates the cell migration machinery remain largely unknown. Here we report that one function of PKA during platelet-derived growth factor (PDGF)-induced chemotaxis was to promote membrane ruffling by regulating phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) dynamics. Inhibition of PKA activity dramatically altered membrane dynamics and attenuated formation of peripheral membrane ruffles in response to PDGF. PKA inhibition also significantly decreased the number and size of PIP(3)-rich membrane ruffles in response to uniform stimulation and to gradients of PDGF. This ruffling defect was quantified using a newly developed method, based on computer vision edge-detection algorithms. PKA inhibition caused a marked attenuation in the bulk accumulation of PIP(3) following PDGF stimulation, without effects on PI3-kinase (PI3K) activity. The deficits in PIP(3) dynamics correlated with a significant inhibition of growth factor-induced membrane recruitment of endogenous Akt and Rac activation in PKA-inhibited cells. Simultaneous inhibition of PKA and Rac had an additive inhibitory effect on growth factor-induced ruffling dynamics. Conversely, the expression of a constitutively active Rac allele was able to rescue the defect in membrane ruffling and restore the localization of a fluorescent PIP(3) marker to membrane ruffles in PKA-inhibited cells, even in the absence of PI3K activity. These data demonstrate that, like Rac, PKA contributes to PIP(3) and membrane dynamics independently of direct regulation of PI3K activity and suggest that modulation of PIP(3)/3-phosphatidylinositol (3-PI) lipids represents a major target for PKA in the regulation of PDGF-induced chemotactic events.

  15. Function of GATA transcription factors in hydroxyurea-induced HEL cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    HEL cells, a human erythroleukemia cell line, mainly express the fetal (γ)globin gene and trace amount of the embryonic (ε)globin gene, but not adult (β) globin gene. Here we show that hydroxyurea (HU) can induce HEL cells to express adult (β) globin gene and lead these cells to terminal differentiation. Results showed in Gel mobility shift assays that GATA factors could specifically bind to the regulatory elements of humanβ- globin gene, including the proximal regulatory element (theβ- promoter) and the distal regulatory elements (the DNase I hypersensitive sites in the LCR, HS2-HS4 core sequences). However, the DNA binding patterns of GATA factors were quite different between HU-induced and uninduced HEL cells. Western-blot analysis of nuclear extracts from both the uninduced and HU- induced HEL cells revealed that the level of GATA-2 transcription factor decreased, whereas the level of GATA-1 transcription factor increased following the time of hydroxyurea induction. Furthermore, using RT-PCR analysis the expression of human β-globin gene in HU-induced HEL cells could be blocked again when HEL cells were incubated in the presence of antisense oligonucleotides for hGATA-1, suggesting that the upregulation of hGATA-1 transcription factor might be critical for the expression of humanβ- globin gene in HU-induced HEL cells.

  16. Hypoxia-induced cell death and changes in hypoxia-inducible factor-1 activity in PC12 cells upon exposure to nerve growth factor.

    Science.gov (United States)

    Charlier, Nico; Leclere, Norbert; Felderhoff, Ursula; Heldt, Julia; Kietzmann, Thomas; Obladen, Michael; Gross, Johann

    2002-07-15

    The transcription factor hypoxia-inducible factor-1 (HIF-1) strongly contributes to the expression of adaptive genes under hypoxic conditions. In addition, HIF-1 has been implicated in the regulation of delayed neuronal cell death. Suspension-grown and adherent PC12 cells treated with NGF were used as an experimental model for studying the relationship between hypoxia-induced cell death and activation of HIF-1. Cell damage was assessed by flow cytometry of double-stained (Annexin V and propidiumiodide) cells, and by analysis of the overall death parameters LDH and mitochondrial dehydrogenase. In parallel, cells were transfected with a control and a three-hypoxia-responsive-elements (HRE)-containing vector and HIF-1-driven luciferase activity was determined. Exposure of NGF-treated PC12 cells to hypoxia resulted in a higher cell death rate when compared to untreated controls. PC12 cells exposed for 2 days to NGF exhibited a decrease of HIF-1 activity up to a factor of ten. This decrease may contribute to the enhanced hypoxia-induced cell death via reduced expression of HIF-1alpha-regulated genes responsible for adaptation to hypoxia, like those for glucose transport proteins and enzymes of the glycolytic chain. The decrease in HIF-1 activity and the increase in hypoxia sensitivity may suggest that NGF act as an hierarchically organized signaling molecule.

  17. [Evaluation of genotoxicity induced by repetitive administration of local anaesthetics: an experimental study in rats].

    Science.gov (United States)

    Nai, Gisele Alborghetti; de Oliveira, Mariliza Casanova; de Oliveira Tavares, Graziela; Pereira, Laís Fabrício Fonseca; Soares, Nádia Derli Salvador Lemes; Silva, Patrícia Gatti

    2015-01-01

    Previous studies regarding the effects of some local anaesthetics have suggested that these agents can cause genetic damage. However, they have not been tested for genotoxicity related to repetitive administration. The aim of this study was to evaluate the genotoxic potential of local anaesthetics upon repetitive administration. 80 male Wistar rats were divided into: group A - 16 rats intraperitoneally injected with lidocaine hydrochloride 2%; group B - 16 rats IP injected with mepivacaine 2%; group C - 16 rats intraperitoneally injected with articaine 4%; group D - 16 rats IP injected with prilocaine 3% (6.0mg/kg); group E - 8 rats subcutaneously injected with a single dose of cyclophosphamide; and group F - 8 rats intraperitoneally injected with saline. Eight rats from groups A to D received a single dose of anaesthetic on Day 1 of the experiment; the remaining rats were dosed once a day for 5 days. The median number of micronuclei in the local anaesthetics groups exposed for 1 or 5 days ranged from 0.00 to 1.00, in the cyclophosphamide-exposed group was 10.00, and the negative control group for 1 and 5 days was 1.00 and 0.00, respectively (plocal anaesthetic groups (p=0.0001), but not between the negative control group and the local anaesthetic groups (p>0.05). No genotoxicity effect was observed upon repetitive exposure to any of the local anaesthetics evaluated. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  18. Expression of DDX3 is directly modulated by hypoxia inducible factor-1 alpha in breast epithelial cells.

    Directory of Open Access Journals (Sweden)

    Mahendran Botlagunta

    Full Text Available DEAD box protein, DDX3, is aberrantly expressed in breast cancer cells ranging from weakly invasive to aggressive phenotypes and functions as an important regulator of cancer cell growth and survival. Here, we demonstrate that hypoxia inducible factor-1α is a transcriptional activator of DDX3 in breast cancer cells. Within the promoter region of the human DDX3 gene, we identified three putative hypoxia inducible factor-1 responsive elements. By luciferase reporter assays in combination with mutated hypoxia inducible factor-1 responsive elements, we determined that the hypoxia inducible factor-1 responsive element at position -153 relative to the translation start site is essential for transcriptional activation of DDX3 under hypoxic conditions. We also demonstrated that hypoxia inducible factor-1 binds to the DDX3 promoter and that the binding is specific, as revealed by siRNA against hypoxia inducible factor-1 and chromatin immunoprecipitation assays. Thus, the activation of DDX3 expression during hypoxia is due to the direct binding of hypoxia inducible factor-1 to hypoxia responsive elements in the DDX3 promoter. In addition, we observed a significant overlap in the protein expression pattern of hypoxia inducible factor-1α and DDX3 in MDA-MB-231 xenograft tumors. Taken together, our results demonstrate, for the first time, the role of DDX3 as a hypoxia-inducible gene that exhibits enhanced expression through the interaction of hypoxia inducible factor-1 with hypoxia inducible factor-1 responsive elements in its promoter region.

  19. Expression of DDX3 is directly modulated by hypoxia inducible factor-1 alpha in breast epithelial cells.

    Science.gov (United States)

    Botlagunta, Mahendran; Krishnamachary, Balaji; Vesuna, Farhad; Winnard, Paul T; Bol, Guus M; Patel, Arvind H; Raman, Venu

    2011-03-23

    DEAD box protein, DDX3, is aberrantly expressed in breast cancer cells ranging from weakly invasive to aggressive phenotypes and functions as an important regulator of cancer cell growth and survival. Here, we demonstrate that hypoxia inducible factor-1α is a transcriptional activator of DDX3 in breast cancer cells. Within the promoter region of the human DDX3 gene, we identified three putative hypoxia inducible factor-1 responsive elements. By luciferase reporter assays in combination with mutated hypoxia inducible factor-1 responsive elements, we determined that the hypoxia inducible factor-1 responsive element at position -153 relative to the translation start site is essential for transcriptional activation of DDX3 under hypoxic conditions. We also demonstrated that hypoxia inducible factor-1 binds to the DDX3 promoter and that the binding is specific, as revealed by siRNA against hypoxia inducible factor-1 and chromatin immunoprecipitation assays. Thus, the activation of DDX3 expression during hypoxia is due to the direct binding of hypoxia inducible factor-1 to hypoxia responsive elements in the DDX3 promoter. In addition, we observed a significant overlap in the protein expression pattern of hypoxia inducible factor-1α and DDX3 in MDA-MB-231 xenograft tumors. Taken together, our results demonstrate, for the first time, the role of DDX3 as a hypoxia-inducible gene that exhibits enhanced expression through the interaction of hypoxia inducible factor-1 with hypoxia inducible factor-1 responsive elements in its promoter region.

  20. Chemotherapy, brachytherapy and surgery of locally evolved uterine cervix carcinomas: prognosis factors of local control and global survival; Chimioradiotherapie, curietherapie et chirurgie des cancers du col uterin localement evolues: facteurs pronostiques de controle local et de survie globale

    Energy Technology Data Exchange (ETDEWEB)

    Laude, C.; Montella, A.; Montbarbon, X.; Malet, C.; Racadot, S.; Pommier, P. [Centre Leon-Berard, 69 - Lyon (France); Mathevet, P. [Hopital Femme-Mere-Enfant, Hospices Civils de Lyon, 69 - Lyon (France); Buenerd, A. [Centre de Pathologie Est, Hospices Civils de Lyon, 69 - Lyon (France)

    2009-10-15

    The protocol used allows an excellent local control of the uterine cervix carcinoma with an acceptable morbidity. To anticipate the presence of a tumor residue can be an evolution in the therapy management after external radiotherapy, particularly in optimized image-guided brachytherapy (MRI and PET)New utero vaginal applicators with parameters implantation allow to realise the dose complement at the distal parameters. These advances make consider an improvement of results in the management of locally evolved uterine cervix carcinomas. (N.C.)

  1. Cross-regional analysis of multiple factors associated with childhood obesity in India: a national or local challenge?

    Science.gov (United States)

    Gregori, Dario; Gulati, Achal; Paramesh, Elizabeth Cherian; Arockiacath, Powlin; Comoretto, Rosanna; Paramesh, Haralappa; Hochdorn, Alexander; Baldi, Ileana

    2014-09-01

    To investigate obesogenic co-causing factors, promoting rise of weight in children, associated to local differences in India. Overall 1,680 children, aged 3-11 and balanced by gender, were recruited in school contexts distributed in seven major Indian cities. All children were weighted and measured in order to calculate their BMI. A validated cultural specific questionnaire was administered to children's parents for assessing socio-demographic data, eating habits, physical activity, etc. Furthermore children's brand awareness scores were computed in order to analyze their affiliation towards food-based advertisement. Descriptive statistics of frequencies, duration and intensity of the various factors were performed. Chi-square tests or Wilcoxon signed rank test were used for evaluating significance of differences in factors distribution across Indian cities. Four factors, promoting rise of children's weight, were individuated as associated to urban differences, namely meal times consumed in the family, parents' BMI, brand awareness and physical activity. These aspects exercised a significant impact on children's body size in Kolkata and Chennai. Hyderabad and Mumbai, instead, were the cities where religion played some role in influencing children's weight gain. Such findings underline the need to frame obesity as a situated phenomenon rather than a national problem. Health policies, implemented in treating and preventing obesity, should be therefore specifically focused on locally situated peculiarities.