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Sample records for ck-b facilitates cell

  1. Local ATP generation by brain-type creatine kinase (CK-B facilitates cell motility.

    Directory of Open Access Journals (Sweden)

    Jan W P Kuiper

    Full Text Available BACKGROUND: Creatine Kinases (CK catalyze the reversible transfer of high-energy phosphate groups between ATP and phosphocreatine, thereby playing a storage and distribution role in cellular energetics. Brain-type CK (CK-B deficiency is coupled to loss of function in neural cell circuits, altered bone-remodeling by osteoclasts and complement-mediated phagocytotic activity of macrophages, processes sharing dependency on actomyosin dynamics. METHODOLOGY/PRINCIPAL FINDINGS: Here, we provide evidence for direct coupling between CK-B and actomyosin activities in cortical microdomains of astrocytes and fibroblasts during spreading and migration. CK-B transiently accumulates in membrane ruffles and ablation of CK-B activity affects spreading and migration performance. Complementation experiments in CK-B-deficient fibroblasts, using new strategies to force protein relocalization from cytosol to cortical sites at membranes, confirmed the contribution of compartmentalized CK-B to cell morphogenetic dynamics. CONCLUSION/SIGNIFICANCE: Our results provide evidence that local cytoskeletal dynamics during cell motility is coupled to on-site availability of ATP generated by CK-B.

  2. Mechanically facilitated cell-cell electrofusion.

    OpenAIRE

    Jaroszeski, M. J.; Gilbert, R.; Fallon, P.G.; Heller, R

    1994-01-01

    Apparatus and methods were developed to enable mechanically facilitated cell-cell electrofusion to be performed. The apparatus and methods mechanically place cells in contact before fusion. The key component of this fusion system was a newly developed fusion chamber. The chamber was composed of two functionally identical electrodes that were housed in a multi-layer structure. The layers functioned as support for the electrodes. They also allowed adjustment of the distance between opposing ele...

  3. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

  4. Branch-specific heterosynaptic facilitation in Aplysia siphon sensory cells

    OpenAIRE

    Clark, Gregory A.; Kandel, Eric R.

    1984-01-01

    Aplysia siphon sensory cells exhibit heterosynaptic facilitation of transmitter release during both sensitization and classical conditioning of the siphon withdrawal response. In the present study, we asked whether facilitation must invariably enhance transmission at all terminals of a neuron or whether facilitation can instead occur at one set of terminals without also occurring at other terminals of the same cell. To examine this question, we compared effects of local application of seroton...

  5. Eccentric exercise facilitates mesenchymal stem cell appearance in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    M Carmen Valero

    Full Text Available Eccentric, or lengthening, contractions result in injury and subsequently stimulate the activation and proliferation of satellite stem cells which are important for skeletal muscle regeneration. The discovery of alternative myogenic progenitors in skeletal muscle raises the question as to whether stem cells other than satellite cells accumulate in muscle in response to exercise and contribute to post-exercise repair and/or growth. In this study, stem cell antigen-1 (Sca-1 positive, non-hematopoetic (CD45⁻ cells were evaluated in wild type (WT and α7 integrin transgenic (α7Tg mouse muscle, which is resistant to injury yet liable to strain, 24 hr following a single bout of eccentric exercise. Sca-1⁺CD45⁻ stem cells were increased 2-fold in WT muscle post-exercise. The α7 integrin regulated the presence of Sca-1⁺ cells, with expansion occurring in α7Tg muscle and minimal cells present in muscle lacking the α7 integrin. Sca-1⁺CD45⁻ cells isolated from α7Tg muscle following exercise were characterized as mesenchymal-like stem cells (mMSCs, predominantly pericytes. In vitro multiaxial strain upregulated mMSC stem cells markers in the presence of laminin, but not gelatin, identifying a potential mechanistic basis for the accumulation of these cells in muscle following exercise. Transplantation of DiI-labeled mMSCs into WT muscle increased Pax7⁺ cells and facilitated formation of eMHC⁺DiI⁻ fibers. This study provides the first demonstration that mMSCs rapidly appear in skeletal muscle in an α7 integrin dependent manner post-exercise, revealing an early event that may be necessary for effective repair and/or growth following exercise. The results from this study also support a role for the α7 integrin and/or mMSCs in molecular- and cellular-based therapeutic strategies that can effectively combat disuse muscle atrophy.

  6. Eccentric exercise facilitates mesenchymal stem cell appearance in skeletal muscle.

    Science.gov (United States)

    Valero, M Carmen; Huntsman, Heather D; Liu, Jianming; Zou, Kai; Boppart, Marni D

    2012-01-01

    Eccentric, or lengthening, contractions result in injury and subsequently stimulate the activation and proliferation of satellite stem cells which are important for skeletal muscle regeneration. The discovery of alternative myogenic progenitors in skeletal muscle raises the question as to whether stem cells other than satellite cells accumulate in muscle in response to exercise and contribute to post-exercise repair and/or growth. In this study, stem cell antigen-1 (Sca-1) positive, non-hematopoetic (CD45⁻) cells were evaluated in wild type (WT) and α7 integrin transgenic (α7Tg) mouse muscle, which is resistant to injury yet liable to strain, 24 hr following a single bout of eccentric exercise. Sca-1⁺CD45⁻ stem cells were increased 2-fold in WT muscle post-exercise. The α7 integrin regulated the presence of Sca-1⁺ cells, with expansion occurring in α7Tg muscle and minimal cells present in muscle lacking the α7 integrin. Sca-1⁺CD45⁻ cells isolated from α7Tg muscle following exercise were characterized as mesenchymal-like stem cells (mMSCs), predominantly pericytes. In vitro multiaxial strain upregulated mMSC stem cells markers in the presence of laminin, but not gelatin, identifying a potential mechanistic basis for the accumulation of these cells in muscle following exercise. Transplantation of DiI-labeled mMSCs into WT muscle increased Pax7⁺ cells and facilitated formation of eMHC⁺DiI⁻ fibers. This study provides the first demonstration that mMSCs rapidly appear in skeletal muscle in an α7 integrin dependent manner post-exercise, revealing an early event that may be necessary for effective repair and/or growth following exercise. The results from this study also support a role for the α7 integrin and/or mMSCs in molecular- and cellular-based therapeutic strategies that can effectively combat disuse muscle atrophy. PMID:22253772

  7. Osteogenic Matrix Cell Sheets Facilitate Osteogenesis in Irradiated Rat Bone

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    Yoshinobu Uchihara

    2015-01-01

    Full Text Available Reconstruction of large bone defects after resection of malignant musculoskeletal tumors is a significant challenge in orthopedic surgery. Extracorporeal autogenous irradiated bone grafting is a treatment option for bone reconstruction. However, nonunion often occurs because the osteogenic capacity is lost by irradiation. In the present study, we established an autogenous irradiated bone graft model in the rat femur to assess whether osteogenic matrix cell sheets improve osteogenesis of the irradiated bone. Osteogenic matrix cell sheets were prepared from bone marrow-derived stromal cells and co-transplanted with irradiated bone. X-ray images at 4 weeks after transplantation showed bridging callus formation around the irradiated bone. Micro-computed tomography images at 12 weeks postoperatively showed abundant callus formation in the whole circumference of the irradiated bone. Histology showed bone union between the irradiated bone and host femur. Mechanical testing showed that the failure force at the irradiated bone site was significantly higher than in the control group. Our study indicates that osteogenic matrix cell sheet transplantation might be a powerful method to facilitate osteogenesis in irradiated bones, which may become a treatment option for reconstruction of bone defects after resection of malignant musculoskeletal tumors.

  8. Carnosine facilitates nitric oxide production in endothelial f-2 cells.

    Science.gov (United States)

    Takahashi, Satoru; Nakashima, Yukiko; Toda, Ken-Ichi

    2009-11-01

    We examined the effect of carnosine (beta-alanyl-histidine) on nitric oxide (NO) production and endothelial NO synthase (eNOS) activation in endothelial F-2 cells. Carnosine enhanced NO production in a dose-dependent manner, and the stimulatory effect of carnosine was observed at concentrations exceeding 5 mM. The carnosine-stimulated NO production was inhibited by N(G)-nitro-L-arginine methyl ester, but not by N(G)-nitro-D-arginine methyl ester. In contrast, beta-alanine, histidine (carnosine components) and anserine (N-methyl carnosine) failed to increase NO production. Carnosine had no effect on NO production for the initial 5 min, but thereafter resulted in a gradual increase in NO production up to 15 min. Carnosine did not induce phosphorylation of eNOS at Ser1177. The carnosine-induced increase in NO production was observed even when extracellular Ca2+ was depleted by ethylene glycol bis(2-aminoethyl ether)-N,N,N'-N'-tetraacetic acid however, the effect was abolished upon depletion of intracellular Ca2+ by BAPTA. After F-2 cells were incubated with carnosine for 4 min, intracellular Ca2+ concentration gradually increased. The carnosine-induced increase in intracellular Ca2+ concentration occurred even in the absence of extracellular Ca2+. These results indicate that carnosine facilitates NO production in endothelial F-2 cells. It is also suggested that eNOS is activated by Ca2+, which might be released from intracellular Ca2+ stores in response to carnosine. PMID:19881293

  9. Cell contractility facilitates alignment of cells and tissues to static uniaxial stretch

    CERN Document Server

    Rens, Elisabeth G

    2016-01-01

    During animal development and homeostasis, the structure of tissues, including muscles, blood vessels and connective tissues adapts to mechanical strains in the extracellular matrix (ECM). These strains originate from the differential growth of tissues or forces due to muscle contraction or gravity. Here we show using a computational model that by amplifying local strain cues, active cell contractility can facilitate and accelerate the reorientation of single cells to static strains. At the collective cell level, the model simulations show that active cell contractility can facilitate the formation of strings along the orientation of stretch. The computational model is based on a hybrid cellular Potts and finite-element simulation framework describing a mechanical cell-substrate feedback, where: 1) cells apply forces on the ECM, such that 2) local strains are generated in the ECM, and 3) cells preferentially extend protrusions along the strain orientation. In accordance with experimental observations, simulat...

  10. Lung Dendritic Cells Facilitate Extrapulmonary Bacterial Dissemination during Pneumococcal Pneumonia

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    Alva eRosendahl

    2013-06-01

    Full Text Available Streptococcus pneumoniae is a leading cause of bacterial pneumonia worldwide. Given the critical role of dendritic cells (DCs in regulating and modulating the immune response to pathogens, we investigated here the role of DCs in S. pneumoniae lung infections. Using a well-established transgenic mouse line which allows the conditional transient depletion of DCs, we showed that ablation of DCs resulted in enhanced resistance to intranasal challenge with S. pneumoniae. DC-depleted mice exhibited delayed bacterial systemic dissemination, significantly reduced bacterial loads in the infected organs and lower levels of serum inflammatory mediators than non-depleted animals. The increased resistance of DC-depleted mice to S. pneumoniae was associated with a better capacity to restrict pneumococci extrapulmonary dissemination. Furthermore, we demonstrated that S. pneumoniae disseminated from the lungs into the regional lymph nodes in a cell-independent manner and that this direct way of dissemination was much more efficient in the presence of DCs. We also provide evidence that S. pneumoniae induces expression and activation of matrix metalloproteinase-9 (MMP-9 in cultured bone marrow-derived DCs. MMP-9 is a protease involved in the breakdown of extracellular matrix proteins and is critical for DC trafficking across extracellular matrix and basement membranes during the migration from the periphery to the lymph nodes. MMP-9 was also significantly up-regulated in the lungs of mice after intranasal infection with S. pneumoniae. Notably, the expression levels of MMP-9 in the infected lungs were significantly decreased after depletion of DCs suggesting the involvement of DCs in MMP-9 production during pneumococcal pneumonia. Thus, we propose that S. pneumoniae can exploit the DC-derived proteolysis to open tissue barriers thereby facilitating its own dissemination from the local site of infection.

  11. Mesenchymal stem cell-derived exosomes facilitate nasopharyngeal carcinoma progression

    OpenAIRE

    Shi, Si; Zhang, Qicheng; Xia, Yunfei; You, Bo; Shan, Ying; Bao, Lili; Li, Li; You, Yiwen; Gu, Zhifeng

    2016-01-01

    Mesenchymal stem cells (MSCs), which are capable of differentiating into multiple cell types, are reported to exert multiple effects on tumor development. However, the relationship between MSCs and nasopharyngeal carcinoma (NPC) cells remains unclear. Exosomes are small membrane vesicles that can be released by several cell types, including MSCs. Exosomes, which can carry membrane and cytoplasmic constituents, have been described as participants in a novel mechanism of cell-to-cell communicat...

  12. Integrin receptors on tumor cells facilitate NK cell-mediated antibody-dependent cytotoxicity.

    Science.gov (United States)

    Anikeeva, Nadia; Steblyanko, Maria; Fayngerts, Svetlana; Kopylova, Natalya; Marshall, Deborah J; Powers, Gordon D; Sato, Takami; Campbell, Kerry S; Sykulev, Yuri

    2014-08-01

    NK cells that mediate ADCC play an important role in tumor-specific immunity. We have examined factors limiting specific lysis of tumor cells by CD16.NK-92 cells induced by CNTO 95LF antibodies recognizing αV integrins that are overexpressed on many tumor cells. Although all tested tumor cells were killed by CD16.NK-92 effectors in the presence of the antibodies, the killing of target cells with a low level of ICAM-1 expression revealed a dramatic decrease in their specific lysis at high antibody concentration, revealing a dose limiting effect. A similar effect was also observed with primary human NK cells. The effect was erased after IFN-γ treatment of tumor cells resulting in upregulation of ICAM-1. Furthermore, killing of the same tumor cells induced by Herceptin antibody was significantly impaired in the presence of CNTO 95Ala-Ala antibody variant that blocks αV integrins but is incapable of binding to CD16. These data suggest that αV integrins on tumor cells could compensate for the loss of ICAM-1 molecules, thereby facilitating ADCC by NK cells. Thus, NK cells could exercise cytolytic activity against ICAM-1 deficient tumor cells in the absence of proinflammatory cytokines, emphasizing the importance of NK cells in tumor-specific immunity at early stages of cancer. PMID:24810893

  13. Eccentric Exercise Facilitates Mesenchymal Stem Cell Appearance in Skeletal Muscle

    OpenAIRE

    M Carmen Valero; Huntsman, Heather D.; Jianming Liu; Kai Zou; Boppart, Marni D.

    2012-01-01

    Eccentric, or lengthening, contractions result in injury and subsequently stimulate the activation and proliferation of satellite stem cells which are important for skeletal muscle regeneration. The discovery of alternative myogenic progenitors in skeletal muscle raises the question as to whether stem cells other than satellite cells accumulate in muscle in response to exercise and contribute to post-exercise repair and/or growth. In this study, stem cell antigen-1 (Sca-1) positive, non-hemat...

  14. Labile complexes facilitate cadmium uptake by Caco-2 cells

    International Nuclear Information System (INIS)

    The Free Ion Activity Model (FIAM) predicts that metal uptake in biota is related to the free ion activity in the external solution and that metal complexes do not contribute. However, studies with plants have shown that labile metal complexes enhance metal bioavailability when the uptake is rate-limited by transport of the free ion in solution to the uptake site. Here, the role of labile complexes of Cd on metal bioavailability was assessed using Caco-2 cells, the cell model for intestinal absorption. At low Cd2+ concentration (1 nM), the CdCln2−n complexes contributed to the uptake almost to the same extent as the free ion. At large Cd2+ concentration (10 μM), the contribution of the complexes was much smaller. At constant Cd2+ concentration, Cd intake in the cells from solutions containing synthetic ligands such as EDTA increased as the dissociation rate of the cadmium complexes increased, and correlated well with the Cd diffusion flux in solution measured with the Diffusive Gradient in Thin Films technique (DGT). The Cd intake fluxes in the cells were well predicted assuming that the specific uptake is limited by diffusion of the free Cd2+ ion to the cell surface. Our results underline that speciation of Cd has a major effect on its uptake by intestinal cells, but the availability is not simply related to the free ion concentration. Labile complexes of Cd enhance metal bioavailability in these cells, likely by alleviating diffusive limitations. - Highlights: ► We examined the role of labile complexes on the uptake of Cd and Zn by Caco-2 cells. ► The availability of Cd and Zn is not simply related to the free ion activity. ► Labile complexes of Cd enhance metal bioavailability in the Caco-2 cells at low free ion activities. ► The active uptake is limited by diffusion of the free Cd2+ ion to the cell surface.

  15. Angiotensin II facilitates breast cancer cell migration and metastasis.

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    Sylvie Rodrigues-Ferreira

    Full Text Available Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pre-treatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors.

  16. Do epidermal lens cells facilitate the absorptance of diffuse light?

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    Brodersen, Craig R; Vogelmann, Thomas C

    2007-07-01

    Many understory plants rely on diffuse light for photosynthesis because direct light is usually scattered by upper canopy layers before it strikes the forest floor. There is a considerable gap in the literature concerning the interaction of direct and diffuse light with leaves. Some understory plants have well-developed lens-shaped epidermal cells, which have long been thought to increase the absorption of diffuse light. To assess the role of epidermal cell shape in capturing direct vs. diffuse light, we measured leaf reflectance and transmittance with an integrating sphere system using leaves with flat (Begonia erythrophylla, Citrus reticulata, and Ficus benjamina) and lens-shaped epidermal cells (B. bowerae, Colocasia esculenta, and Impatiens velvetea). In all species examined, more light was absorbed when leaves were irradiated with direct as opposed to diffuse light. When leaves were irradiated with diffuse light, more light was transmitted and more was reflected in both leaf types, resulting in absorptance values 2-3% lower than in leaves irradiated with direct light. These data suggest that lens-shaped epidermal cells do not aid the capture of diffuse light. Palisade and mesophyll cell anatomy and leaf thickness appear to have more influence in the capture and absorption of light than does epidermal cell shape. PMID:21636475

  17. Conditioning the cochlea to facilitate survival and integration of exogenous cells into the auditory epithelium.

    Science.gov (United States)

    Park, Yong-Ho; Wilson, Kevin F; Ueda, Yoshihisa; Tung Wong, Hiu; Beyer, Lisa A; Swiderski, Donald L; Dolan, David F; Raphael, Yehoash

    2014-04-01

    The mammalian auditory epithelium (AE) cannot replace supporting cells and hair cells once they are lost. Therefore, sensorineural hearing loss associated with missing cells is permanent. This inability to regenerate critical cell types makes the AE a potential target for cell replacement therapies such as stem cell transplantation. Inserting stem cells into the AE of deaf ears is a complicated task due to the hostile, high potassium environment of the scala media in the cochlea, and the robust junctional complexes between cells in the AE that resist stem cell integration. Here, we evaluate whether temporarily reducing potassium levels in the scala media and disrupting the junctions in the AE make the cochlear environment more receptive and facilitate survival and integration of transplanted cells. We used sodium caprate to transiently disrupt the AE junctions, replaced endolymph with perilymph, and blocked stria vascularis pumps with furosemide. We determined that these three steps facilitated survival of HeLa cells in the scala media for at least 7 days and that some of the implanted cells formed a junctional contact with native AE cells. The data suggest that manipulation of the cochlear environment facilitates survival and integration of exogenously transplanted HeLa cells in the scala media. PMID:24394296

  18. Dexamethasone facilitates erythropoiesis in murine embryonic stem cells differentiating into hematopoietic cells in vitro

    International Nuclear Information System (INIS)

    Differentiating embryonic stem (ES) cells are increasingly emerging as an important source of hematopoietic progenitors with a potential to be useful for both basic and clinical research applications. It has been suggested that dexamethasone facilitates differentiation of ES cells towards erythrocytes but the mechanism responsible for sequential expression of genes regulating this process are not well-understood. Therefore, we in vitro induced differentiation of murine ES cells towards erythropoiesis and studied the sequential expression of a set of genes during the process. We hypothesized that dexamethasone-activates its cognate nuclear receptors inducing up-regulation of erythropoietic genes such as GATA-1, Flk-1, Epo-R, and direct ES cells towards erythropoietic differentiation. ES cells were cultured in primary hematopoietic differentiation media containing methyl-cellulose, IMDM, IL-3, IL-6, and SCF to promote embryoid body (EB) formation. Total RNA of day 3, 5, and 9-old EBs was isolated for gene expression studies using RT-PCR. Cells from day 9 EBs were subjected to secondary differentiation using three different cytokines and growth factors combinations: (1) SCF, EPO, dexamethasone, and IGF; (2) SCF, IL-3, IL-6, and TPO; and (3) SCF IL-3, IL-6, TPO, and EPO. Total RNA from day 12 of secondary differentiated ES cells was isolated to study the gene expression pattern during this process. Our results demonstrate an up-regulation of GATA-1, Flk-1, HoxB-4, Epo-R, and globin genes (α-globin, βH-1 globin, β-major globin, ε -globin, and ζ-globin) in the 9-day-old EBs, whereas, RNA from 5-day-old EBs showed expression of HoxB-4, ε-globin, γ-globin, βH1-globin, and Flk-1. Three-day-old EBs showed only HoxB-4 and Flk-1 gene expression and lacked expression of all globin genes. These findings indicate that erythropoiesis-specific genes are activated later in the course of differentiation. Gene expression studies on the ES cells of secondary EB origin cultured

  19. Up-regulation of Kir2.1 by ER stress facilitates cell death of brain capillary endothelial cells

    International Nuclear Information System (INIS)

    Highlights: → We found that application of endoplasmic reticulum (ER) stress with tunicamycin to brain capillary endothelial cells (BCECs) induced cell death. → The ER stress facilitated the expression of inward rectifier K+ channel (Kir2.1) and induced sustained membrane hyperpolarization. → The membrane hyperpolarization induced sustained Ca2+ entry through voltage-independent nonspecific cation channels and consequently facilitated cell death. → The Kir2.1 up-regulation by ER stress is, at least in part, responsible for cell death of BCECs under pathological conditions. -- Abstract: Brain capillary endothelial cells (BCECs) form blood brain barrier (BBB) to maintain brain homeostasis. Cell turnover of BCECs by the balance of cell proliferation and cell death is critical for maintaining the integrity of BBB. Here we found that stimuli with tunicamycin, endoplasmic reticulum (ER) stress inducer, up-regulated inward rectifier K+ channel (Kir2.1) and facilitated cell death in t-BBEC117, a cell line derived from bovine BCECs. The activation of Kir channels contributed to the establishment of deeply negative resting membrane potential in t-BBEC117. The deep resting membrane potential increased the resting intracellular Ca2+ concentration due to Ca2+ influx through non-selective cation channels and thereby partly but significantly regulated cell death in t-BBEC117. The present results suggest that the up-regulation of Kir2.1 is, at least in part, responsible for cell death/cell turnover of BCECs induced by a variety of cellular stresses, particularly ER stress, under pathological conditions.

  20. Characterization of host lymphoid cells in antibody-facilitated bone marrow chimeras

    International Nuclear Information System (INIS)

    The authors have produced stable murine antibody-facilitated (AF) chimeras by the simultaneous injection of P1 bone marrow cells and anti-P2 monoclonal antibody into normal (unirradiated) adult (P1 X P2)F1 recipients. These AF chimeras are healthy, long-lived, and exhibit no overt signs of graft-versus-host disease. They are immunocompetent and tolerant of host, P2-encoded alloantigens. Donor cell engraftment and takeover, monitored by glucosephosphate isomerase isozyme patterns, is usually complete (greater than 95%) in the peripheral blood, bone marrow, and hemopoietic stem cell compartments of long-term (greater than 3 months posttransplantation) AF chimeras. The authors report here, however, that splenic, lymph node, and thymic leukocytes of AF chimeras represent donor/host chimeric populations. Spleen cell populations of AF chimeras exhibit substantial chimera-to-chimera variation in the preponderant residual host cell type(s) present. Interpretations of the implications of these findings are discussed

  1. HMGB1 interacts with XPA to facilitate the processing of DNA interstrand crosslinks in human cells.

    Science.gov (United States)

    Mukherjee, Anirban; Vasquez, Karen M

    2016-02-18

    Many effective agents used in cancer chemotherapy cause DNA interstrand crosslinks (ICLs), which covalently link both strands of the double helix together resulting in cytotoxicity. ICLs are thought to be processed by proteins from a variety of DNA repair pathways; however, a clear understanding of ICL recognition and repair processing in human cells is lacking. Previously, we found that the high mobility group box 1 (HMGB1) protein bound to triplex-directed psoralen ICLs (TFO-ICLs) in vitro, cooperatively with NER damage recognition proteins, promoted removal of UVC-induced lesions and facilitated error-free repair of TFO-ICLs in mouse fibroblasts. Here, we demonstrate that HMGB1 recognizes TFO-ICLs in human cells, and its depletion increases ICL-induced mutagenesis in human cells without altering the mutation spectra. In contrast, HMGB1 depletion in XPA-deficient human cells significantly altered the ICL-induced mutation spectrum from predominantly T→A to T→G transversions. Moreover, the recruitment of XPA and HMGB1 to the ICLs is co-dependent. Finally, we show that HMGB1 specifically introduces negative supercoils in ICL-containing plasmids in HeLa cell extracts. Taken together, our data suggest that in human cells, HMGB1 functions in association with XPA on ICLs and facilitates the formation of a favorable architectural environment for ICL repair processing. PMID:26578599

  2. Myeloid-derived suppressor cells (MDSC) facilitate distant metastasis of malignancies by shielding circulating tumor cells (CTC) from immune surveillance.

    Science.gov (United States)

    Liu, Qiaofei; Liao, Quan; Zhao, Yupei

    2016-02-01

    The mechanisms of distant metastasis of malignancies largely remain unknown. Circulating tumor cells (CTC) derived from the primary cancer initiate distant metastasis by entering and traversing the bloodstream. Current methods to detect CTC are based on the notion that CTC do not express the common leukocyte antigen CD45. However, these methods neglect the fact that CTC can directly adhere to platelets and immune cells and therefore appear to be CD45-positive. The potential effects of interactions between CTC and adhesive immune cells have been largely overlooked, despite the fact that most CTC are killed by immune effector cells and only those that evade immune surveillance result in clonal expansion and metastatic lesions. It is crucial to define the characteristics that allow a select CTC population to escape immune surveillance; particularly, it must be determined whether interactions between CTC and adhesive immune cells provide a protective effect on CTC survival. If interactions between CTC and adhesive immune cells offer a selective advantage to those CTC cells, the next consideration is which characteristics of a CTC-immune cell population allow sufficient protection to facilitate immune evasion. Myeloid-derived suppressor cells (MDSC) are a large heterogeneous population of immature myeloid cells that accumulate during cancer progression to induce extensively systemic and local immunosuppression, a phenomenon that has been demonstrated to facilitate cancer distant metastasis. We hypothesize, therefore, that CTC populations interacting with adhesive immune cells will have different biological behavior than CTC populations alone. Further, we hypothesize that CTC can create a defensive shield consisting of adhesive MDSC, which allows evasion of immune surveillance and therefore facilitates distant metastatic lesions. This possibility highlights the importance of direct interactions between CTC and adhesive immune cells and suggests the potential target that

  3. Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination.

    Science.gov (United States)

    Hu, Hongbo; Wang, Hui; Xiao, Yichuan; Jin, Jin; Chang, Jae-Hoon; Zou, Qiang; Xie, Xiaoping; Cheng, Xuhong; Sun, Shao-Cong

    2016-03-01

    Signal transduction from the T cell receptor (TCR) is crucial for T cell-mediated immune responses and, when deregulated, also contributes to the development of autoimmunity. How TCR signaling is regulated is incompletely understood. In this study, we demonstrate a ubiquitin-dependent mechanism in which the deubiquitinase Otud7b has a crucial role in facilitating TCR signaling. Upon TCR ligation, Otud7b is rapidly recruited to the tyrosine kinase Zap70, a central mediator of TCR-proximal signaling. Otud7b deficiency attenuates the activation of Zap70 and its downstream pathways and impairs T cell activation and differentiation, rendering mice refractory to T cell-mediated autoimmune and inflammatory responses. Otud7b facilitated Zap70 activation by deubiquitinating Zap70, thus preventing the association of Zap70 with the negative-regulatory phosphatases Sts1 and Sts2. These findings establish Otud7b as a positive regulator of TCR-proximal signaling and T cell activation, highlighting the importance of deubiquitination in regulating Zap70 function. PMID:26903241

  4. Facilitating Electron Transportation in Perovskite Solar Cells via Water-Soluble Fullerenol Interlayers.

    Science.gov (United States)

    Cao, Tiantian; Wang, Zhaowei; Xia, Yijun; Song, Bo; Zhou, Yi; Chen, Ning; Li, Yongfang

    2016-07-20

    TiO2 is widely used in perovskite solar cells (Pero-SCs), but its low electrical conductivity remains a drawback for application in electron transport layer (ETL). To overcome this problem, an easily accessible hydroxylated fullerene, fullerenol, was employed herein as ETL modified on ITO in n-i-p type (ITO as cathode) Pero-SCs for the first time. The results showed that the insertion of a single layer of fullerenol between perovskite and TiO2 dramatically facilitates the charge transportation and decreases the interfacial resistance. As a consequence, the device performance was greatly improved, and a higher power conversion efficiency of 14.69% was achieved, which is ∼17.5% enhancement compared with that (12.50%) of the control device without the fullerenol interlayer. This work provides a new candidate of interfacial engineering for facilitating the electron transportation in Pero-SCs. PMID:27311625

  5. Integrin Receptors on Tumor Cells Facilitate NK cell-mediated Antibody-dependent Cytotoxicity

    OpenAIRE

    Anikeeva, Nadia; Steblyanko, Maria; Fayngerts, Svetlana; Kopylova, Natalya; Marshall, Deborah J.; Powers, Gordon D.; Sato, Takami; Campbell, Kerry S.; Sykulev, Yuri

    2014-01-01

    NK cells that mediate ADCC play an important role in tumor-specific immunity. We have examined factors limiting specific lysis of tumor cells by CD16.NK-92 cells induced by CNTO 95LF antibodies recognizing αV integrins that are overexpressed on many tumor cells. Although all tested tumor cells were killed by CD16.NK-92 effectors in the presence of the antibodies, the killing of target cells with a low level of ICAM-1 expression revealed a dramatic decrease in their specific lysis at high anti...

  6. The p75NTR tumor suppressor induces cell cycle arrest facilitating caspase mediated apoptosis in prostate tumor cells

    International Nuclear Information System (INIS)

    The p75 neurotrophin receptor (p75NTR) is a death receptor which belongs to the tumor necrosis factor receptor super-family of membrane proteins. This study shows that p75NTR retarded cell cycle progression by induced accumulation of cells in G0/G1 and a reduction in the S phase of the cell cycle. The rescue of tumor cells from cell cycle progression by a death domain deleted (ΔDD) dominant-negative antagonist of p75NTR showed that the death domain transduced anti-proliferative activity in a ligand-independent manner. Conversely, addition of NGF ligand rescued retardation of cell cycle progression with commensurate changes in components of the cyclin/cdk holoenzyme complex. In the absence of ligand, p75NTR-dependent cell cycle arrest facilitated an increase in apoptotic nuclear fragmentation of the prostate cancer cells. Apoptosis of p75NTR expressing cells occurred via the intrinsic mitochondrial pathway leading to a sequential caspase-9 and -7 cascade. Since the death domain deleted dominant-negative antagonist of p75NTR rescued intrinsic caspase associated apoptosis in PC-3 cells, this shows p75NTR was integral to ligand independent induction of apoptosis. Moreover, the ability of ligand to ameliorate the p75NTR-dependent intrinsic apoptotic cascade indicates that NGF functioned as a survival factor for p75NTR expressing prostate cancer cells

  7. Amiloride enhances antigen specific CTL by faciliting HBV DNA vaccine entry into cells.

    Directory of Open Access Journals (Sweden)

    Shuang Geng

    Full Text Available The induction of relatively weak immunity by DNA vaccines in humans can be largely attributed to the low efficiency of transduction of somatic cells. Although formulation with liposomes has been shown to enhance DNA transduction of cultured cells, little, if any, effect is observed on the transduction of somatic tissues and cells. To improve the rate of transduction, DNA vaccine delivery by gene gun and the recently developed electroporation techniques have been employed. We report here that to circumvent requirement for such equipment, amiloride, a drug that is prescribed for hypertension treatment, can accelerate plasmid entry into antigen presenting cells (APCs both in vitro and in vivo. The combination induced APCs more dramatically in both maturation and cytokine secretion. Amiloride enhanced development of full CD8 cytolytic function including induction of high levels of antigen specific CTL and expression of IFN-γ+perforin+granzymeB+ in CD8+ T cells. Thus, amiloride is a facilitator for DNA transduction into host cells which in turn enhances the efficiency of the immune responses.

  8. Aquatic flower-inspired cell culture platform with simplified medium exchange process for facilitating cell-surface interaction studies.

    Science.gov (United States)

    Hong, Hyeonjun; Park, Sung Jea; Han, Seon Jin; Lim, Jiwon; Kim, Dong Sung

    2016-02-01

    Establishing fundamentals for regulating cell behavior with engineered physical environments, such as topography and stiffness, requires a large number of cell culture experiments. However, cell culture experiments in cell-surface interaction studies are generally labor-intensive and time-consuming due to many experimental tasks, such as multiple fabrication processes in sample preparation and repetitive medium exchange in cell culture. In this work, a novel aquatic flower-inspired cell culture platform (AFIP) is presented. AFIP aims to facilitate the experiments on the cell-surface interaction studies, especially the medium exchange process. AFIP was devised to capture and dispense cell culture medium based on interactions between an elastic polymer substrate and a liquid medium. Thus, the medium exchange can be performed easily and without the need of other instruments, such as a vacuum suction and pipette. An appropriate design window of AFIP, based on scaling analysis, was identified to provide a criterion for achieving stability in medium exchange as well as various surface characteristics of the petal substrates. The developed AFIP, with physically engineered petal substrates, was also verified to exchange medium reliably and repeatedly. A closed structure capturing the medium was sustained stably during cell culture experiments. NIH3T3 proliferation results also demonstrated that AFIP can be applied to the cell-surface interaction studies as an alternative to the conventional method. PMID:26683462

  9. Puerarin Facilitates T-Tubule Development of Murine Embryonic Stem Cell-Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Lu Wang

    2014-07-01

    Full Text Available Aims: The embryonic stem cell-derived cardiomyocytes (ES-CM is one of the promising cell sources for repopulation of damaged myocardium. However, ES-CMs present immature structure, which impairs their integration with host tissue and functional regeneration. This study used murine ES-CMs as an in vitro model of cardiomyogenesis to elucidate the effect of puerarin, the main compound found in the traditional Chinese medicine the herb Radix puerariae, on t-tubule development of murine ES-CMs. Methods: Electron microscope was employed to examine the ultrastructure. The investigation of transverse-tubules (t-tubules was performed by Di-8-ANEPPS staining. Quantitative real-time PCR was utilized to study the transcript level of genes related to t-tubule development. Results: We found that long-term application of puerarin throughout cardiac differentiation improved myofibril array and sarcomeres formation, and significantly facilitated t-tubules development of ES-CMs. The transcript levels of caveolin-3, amphiphysin-2 and junctophinlin-2, which are crucial for the formation and development of t-tubules, were significantly upregulated by puerarin treatment. Furthermore, puerarin repressed the expression of miR-22, which targets to caveolin-3. Conclusion: Our data showed that puerarin facilitates t-tubule development of murine ES-CMs. This might be related to the repression of miR-22 by puerarin and upregulation of Cav3, Bin1 and JP2 transcripts.

  10. Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells

    International Nuclear Information System (INIS)

    Cancer cells exhibit increased glycolysis for ATP production (the Warburg effect) and macromolecular biosynthesis; it is also linked with therapeutic resistance that is generally associated with compromised respiratory metabolism. Molecular mechanisms underlying radio-resistance linked to elevated glycolysis remain incompletely understood. We stimulated glycolysis using mitochondrial respiratory modifiers (MRMs viz. di-nitro phenol, DNP; Photosan-3, PS3; Methylene blue, MB) in established human cell lines (HEK293, BMG-1 and OCT-1). Glucose utilization and lactate production, levels of glucose transporters and glycolytic enzymes were investigated as indices of glycolysis. Clonogenic survival, DNA repair and cytogenetic damage were studied as parameters of radiation response. MRMs induced the glycolysis by enhancing the levels of two important regulators of glucose metabolism GLUT-1 and HK-II and resulted in 2 fold increase in glucose consumption and lactate production. This increase in glycolysis resulted in resistance against radiation-induced cell death (clonogenic survival) in different cell lines at an absorbed dose of 5 Gy. Inhibition of glucose uptake and glycolysis (using fasentin, 2-deoxy-D-glucose and 3-bromopyruvate) in DNP treated cells failed to increase the clonogenic survival of irradiated cells, suggesting that radio-resistance linked to inhibition of mitochondrial respiration is glycolysis dependent. Elevated glycolysis also facilitated rejoining of radiation-induced DNA strand breaks by activating both non-homologous end joining (NHEJ) and homologous recombination (HR) pathways of DNA double strand break repair leading to a reduction in radiation-induced cytogenetic damage (micronuclei formation) in these cells. These findings suggest that enhanced glycolysis generally observed in cancer cells may be responsible for the radio-resistance, partly by enhancing the repair of DNA damage

  11. Mitochondrial respiratory modifiers confer survival advantage by facilitating DNA repair in cancer cells

    International Nuclear Information System (INIS)

    High rate of aerobic glycolysis (Warburg effect), one of the primary hallmarks of cancer cells, acquired during the multistep development of tumors is also responsible for therapeutic resistance. Underlying this hallmark is the compromised respiratory metabolism that contributes to the acquisition of the glycolytic phenotype for sustained ATP production and cell proliferation. Nevertheless, the exact mechanisms underlying the glycolysis-linked radio-resistance in cancer cells remain elusive. In this study, we transiently elevated glycolysis by treating human cell lines (HEK293, BMG-1 and OCT-1) with mitochondrial respiratory modifiers (MRMs) viz. 2,4-dinitrophenol, Photosan-3, and Methylene blue to examine if transient stimulation of glycolysis before irradiation using MRMs is sufficient to confer radioresistance. Treatment with MRMs led to a significant (two-fold) increase in glucose consumption and lactate production together with a robust increase in the protein levels of two key regulators of glucose metabolism, i.e. GLUT-1 and HK-II. MRMs also enhanced the clonogenic survival and facilitated DNA repair by activating both non-homologous end joining (NHEJ) and homologous recombination (HR) pathways of DNA double strand break repair leading to reduction in radiation-induced cytogenetic damage (micronuclei formation) in these cells. Inhibition of glucose uptake by inhibitors like 2-deoxy-D-glucose (2-DG), 3-bromo pyruvate (3-BP) and fasentin under conditions of stimulated glycolysis not only reversed the effect but also sensitized the cells to radiation more profoundly. The inhibition of glycolysis using 2-DG also reduced the levels of Ku 70 (NHEJ) and Rad-51 (HR) proteins. Thus, our results suggest that enhanced glycolysis in cancer cells may confer radio-resistance and offers survival advantage partly by enhancing the repair of DNA damage. (author)

  12. Loss of P53 facilitates invasion and metastasis of prostate cancer cells.

    Science.gov (United States)

    Wang, Yi; Zhang, Y X; Kong, C Z; Zhang, Z; Zhu, Y Y

    2013-12-01

    Prostate cancer is a lethal cancer for the invasion and metastasis in its earlier period. P53 is a tumor suppressor gene which plays a critical role on safeguarding the integrity of genome. However, loss of P53 facilitates or inhibits the invasion and metastasis of tumor is still suspended. In this study, we are going to explain whether loss of P53 affect the invasion and metastasis of prostate cancer cells. To explore whether loss of P53 influences the invasion and metastasis ability of prostate cancer cells, we first compared the invasion ability of si-P53 treated cells and control cells by wound healing, transwell assay, and adhesion assay. We next tested the activity of MMP-2, MMP-9, and MMP-14 by western blot and gelatin zymography. Moreover, we employed WB and IF to identify the EMT containing E-cad, N-cad, vimentin, etc. We also examined the expression of cortactin, cytoskeleton, and paxillin by immunofluorescence, and tested the expression of ERK and JNK by WB. Finally, we applied WB to detect the expression of FAK, Src, and the phosphorylation of them to elucidate the mechanism of si-P53 influencing invasion and metastasis. According to the inhibition rate of si-P53, we choose the optimized volume of si-P53. With the volume, we compare the invasion and metastasis ability of Du145 and si-P53 treated cells. We find si-P53 promotes the invasion and metastasis in prostate cancer cells, increases the expression and activity of MMP-2/9 and MMP-14. Also, si-P53 promotes EMT and cytoskeleton rearrangement. Further analyses explain that this effect is associated with FAK-Src signaling pathway. Loss of P53 promotes the invasion and metastasis ability of prostate cancer cells and the mechanism is correlated with FAK-Src signaling pathway. P53 is involved in the context of invasion and metastasis. PMID:23982184

  13. Proteome-wide analysis of neural stem cell differentiation to facilitate transition to cell replacement therapies

    Czech Academy of Sciences Publication Activity Database

    Žižková, Martina; Suchá, Rita; Tylečková, Jiřina; Jarkovská, Karla; Mairychová, Kateřina; Kotrčová, Eva; Marsala, M.; Gadher, S. J.; Kovářová, Hana

    2015-01-01

    Roč. 12, č. 1 (2015), s. 83-95. ISSN 1478-9450 R&D Projects: GA MŠk ED2.1.00/03.0124; GA TA ČR(CZ) TA01011466 Institutional support: RVO:67985904 Keywords : cell therapy * immunomodulation * neural stem cell differentiation * neural subpopulation * neurodegenerative disease Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.896, year: 2014

  14. Heparanase facilitates cell adhesion and spreading by clustering of cell surface heparan sulfate proteoglycans.

    Directory of Open Access Journals (Sweden)

    Flonia Levy-Adam

    Full Text Available Heparanase is a heparan sulfate (HS degrading endoglycosidase participating in extracellular matrix degradation and remodeling. Apart of its well characterized enzymatic activity, heparanase was noted to exert also enzymatic-independent functions. Non-enzymatic activities of heparanase include enhanced adhesion of tumor-derived cells and primary T-cells. Attempting to identify functional domains of heparanase that would serve as targets for drug development, we have identified heparin binding domains of heparanase. A corresponding peptide (residues Lys(158-Asp(171, termed KKDC was demonstrated to physically associate with heparin and HS, and to inhibit heparanase enzymatic activity. We hypothesized that the pro-adhesive properties of heparanase are mediated by its interaction with cell surface HS proteoglycans, and utilized the KKDC peptide to examine this possibility. We provide evidence that the KKDC peptide interacts with cell membrane HS, resulting in clustering of syndecan-1 and syndecan-4. We applied classical analysis of cell morphology, fluorescent and time-lapse microscopy and demonstrated that the KKDC peptide efficiently stimulates the adhesion and spreading of various cell types, mediated by PKC, Src, and the small GTPase Rac1. These results support, and further substantiate the notion that heparanase function is not limited to its enzymatic activity.

  15. A Cbx8-containing polycomb complex facilitates the transition to gene activation during ES cell differentiation.

    Directory of Open Access Journals (Sweden)

    Catherine Creppe

    2014-12-01

    Full Text Available Polycomb proteins play an essential role in maintaining the repression of developmental genes in self-renewing embryonic stem cells. The exact mechanism allowing the derepression of polycomb target genes during cell differentiation remains unclear. Our project aimed to identify Cbx8 binding sites in differentiating mouse embryonic stem cells. Therefore, we used a genome-wide chromatin immunoprecipitation of endogenous Cbx8 coupled to direct massive parallel sequencing (ChIP-Seq. Our analysis identified 171 high confidence peaks. By crossing our data with previously published microarray analysis, we show that several differentiation genes transiently recruit Cbx8 during their early activation. Depletion of Cbx8 partially impairs the transcriptional activation of these genes. Both interaction analysis, as well as chromatin immunoprecipitation experiments support the idea that activating Cbx8 acts in the context of an intact PRC1 complex. Prolonged gene activation results in eviction of PRC1 despite persisting H3K27me3 and H2A ubiquitination. The composition of PRC1 is highly modular and changes when embryonic stem cells commit to differentiation. We further demonstrate that the exchange of Cbx7 for Cbx8 is required for the effective activation of differentiation genes. Taken together, our results establish a function for a Cbx8-containing complex in facilitating the transition from a Polycomb-repressed chromatin state to an active state. As this affects several key regulatory differentiation genes this mechanism is likely to contribute to the robust execution of differentiation programs.

  16. A device to facilitate preparation of high-density neural cell cultures in MEAs.

    Science.gov (United States)

    Mok, S Y; Lim, Y M; Goh, S Y

    2009-05-15

    A device to facilitate high-density seeding of dissociated neural cells on planar multi-electrode arrays (MEAs) is presented in this paper. The device comprises a metal cover with two concentric cylinders-the outer cylinder fits tightly on to the external diameter of a MEA to hold it in place and an inner cylinder holds a central glass tube for introducing a cell suspension over the electrode area of the MEA. An O-ring is placed at the bottom of the inner cylinder and the glass tube to provide a fluid-tight seal between the glass tube and the MEA electrode surface. The volume of cell suspension in the glass tube is varied according to the desired plating density. After plating, the device can be lifted from the MEA without leaving any residue on the contact surface. The device has enabled us to increase and control the plating density of neural cell suspension with low viability, and to prepare successful primary cultures from cryopreserved neurons and glia. The cultures of cryopreserved dissociated cortical neurons that we have grown in this manner remained spontaneously active over months, exhibited stable development and similar network characteristics as reported by other researchers. PMID:19428539

  17. Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer

    OpenAIRE

    Flores, L M; Kindelberger, D W; Ligon, A H; Capelletti, M.; Fiorentino, M.; Loda, M; Cibas, E S; Jänne, P.A.; Krop, I. E.

    2010-01-01

    Background: Circulating tumour cells (CTCs) offer a non-invasive approach to obtain and characterise metastatic tumour cells, but their usefulness has been limited by low CTC yields from conventional isolation methods. Methods: To improve CTC yields and facilitate their molecular characterisation we compared the Food and Drug Administration-approved CellSearch Epithelial Kit (CEK) to a simplified CTC capture method, CellSearch Profile Kit (CPK), on paired blood samples from patients with meta...

  18. Mononuclear phagocyte intercellular crosstalk facilitates transmission of cell-targeted nanoformulated antiretroviral drugs to human brain endothelial cells

    Directory of Open Access Journals (Sweden)

    Kanmogne GD

    2012-05-01

    Full Text Available Georgette D Kanmogne1, Sangya Singh1, Upal Roy1, Xinming Liu1, JoEllyn McMillan1, Santhi Gorantla1, Shantanu Balkundi1, Nathan Smith1, Yazen Alnouti2, Nagsen Gautam2, You Zhou3, Larisa Poluektova1, Alexander Kabanov2, Tatiana Bronich2, Howard E Gendelman11Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, 2Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE; 3Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, USAAbstract: Despite the successes of antiretroviral therapy (ART, HIV-associated neurocognitive disorders remain prevalent in infected people. This is due, in part, to incomplete ART penetration across the blood–brain barrier (BBB and lymph nodes and to the establishment of viral sanctuaries within the central nervous system. In efforts to improve ART delivery, our laboratories developed a macrophage-carriage system for nanoformulated crystalline ART (nanoART (atazanavir, ritonavir, indinavir, and efavirenz. We demonstrate that nanoART transfer from mononuclear phagocytes (MP to human brain microvascular endothelial cells (HBMEC can be realized through cell-to-cell contacts, which can facilitate drug passage across the BBB. Coculturing of donor MP containing nanoART with recipient HBMEC facilitates intercellular particle transfer. NanoART uptake was observed in up to 52% of HBMEC with limited cytotoxicity. Folate coating of nanoART increased MP to HBMEC particle transfer by up to 77%. To translate the cell assays into relevant animal models of disease, ritonavir and atazanavir nanoformulations were injected into HIV-1-infected NOD/scid-γcnull mice reconstituted with human peripheral blood lymphocytes. Atazanavir and ritonavir levels in brains of mice treated with folate-coated nanoART were three- to four-fold higher than in mice treated with noncoated particles. This was associated with decreased viral load in the spleen and

  19. Polyurethane scaffolds seeded with CD34(+) cells maintain early stem cells whilst also facilitating prolonged egress of haematopoietic progenitors.

    Science.gov (United States)

    Severn, Charlotte E; Macedo, Hugo; Eagle, Mark J; Rooney, Paul; Mantalaris, Athanasios; Toye, Ashley M

    2016-01-01

    We describe a 3D erythroid culture system that utilises a porous polyurethane (PU) scaffold to mimic the compartmentalisation found in the bone marrow. PU scaffolds seeded with peripheral blood CD34(+) cells exhibit a remarkable reproducibility of egress, with an increased output when directly compared to human bone scaffolds over 28 days. Immunofluorescence demonstrated the persistence of CD34(+) cells within the scaffolds for the entirety of the culture. To characterise scaffold outputs, we designed a flow cytometry panel that utilises surface marker expression observed in standard 2D erythroid and megakaryocyte cultures. This showed that the egress population is comprised of haematopoietic progenitor cells (CD36(+)GPA(-/low)). Control cultures conducted in parallel but in the absence of a scaffold were also generally maintained for the longevity of the culture albeit with a higher level of cell death. The harvested scaffold egress can also be expanded and differentiated to the reticulocyte stage. In summary, PU scaffolds can behave as a subtractive compartmentalised culture system retaining and allowing maintenance of the seeded "CD34(+) cell" population despite this population decreasing in amount as the culture progresses, whilst also facilitating egress of increasingly differentiated cells. PMID:27573994

  20. Polyurethane scaffolds seeded with CD34+ cells maintain early stem cells whilst also facilitating prolonged egress of haematopoietic progenitors

    Science.gov (United States)

    Severn, Charlotte E.; Macedo, Hugo; Eagle, Mark J.; Rooney, Paul; Mantalaris, Athanasios; Toye, Ashley M.

    2016-01-01

    We describe a 3D erythroid culture system that utilises a porous polyurethane (PU) scaffold to mimic the compartmentalisation found in the bone marrow. PU scaffolds seeded with peripheral blood CD34+ cells exhibit a remarkable reproducibility of egress, with an increased output when directly compared to human bone scaffolds over 28 days. Immunofluorescence demonstrated the persistence of CD34+ cells within the scaffolds for the entirety of the culture. To characterise scaffold outputs, we designed a flow cytometry panel that utilises surface marker expression observed in standard 2D erythroid and megakaryocyte cultures. This showed that the egress population is comprised of haematopoietic progenitor cells (CD36+GPA−/low). Control cultures conducted in parallel but in the absence of a scaffold were also generally maintained for the longevity of the culture albeit with a higher level of cell death. The harvested scaffold egress can also be expanded and differentiated to the reticulocyte stage. In summary, PU scaffolds can behave as a subtractive compartmentalised culture system retaining and allowing maintenance of the seeded “CD34+ cell” population despite this population decreasing in amount as the culture progresses, whilst also facilitating egress of increasingly differentiated cells. PMID:27573994

  1. Differentiation of porcine mesenchymal stem cells into epithelial cells as a potential therapeutic application to facilitate epithelial regeneration.

    Science.gov (United States)

    Kokubun, Kelsey; Pankajakshan, Divya; Kim, Min-Jung; Agrawal, Devendra K

    2016-02-01

    Epithelial denudation is one of the characteristics of chronic asthma. To restore its functions, the airway epithelium has to rapidly repair the injuries and regenerate its structure and integrity. Mesenchymal stem cells (MSCs) have the ability to differentiate into many cell lineages. However, the differentiation of MSCs into epithelial cells has not been fully studied. Here, we examined the differentiation of MSCs into epithelial cells using three different media compositions with various growth supplementations. The MSCs were isolated from porcine bone marrow by density gradient centrifugation. The isolated MSCs were CD11(-) CD34(-) CD45(-) CD44(+) CD90(+) and CD105(+) by immunostaining and flow cytometry. MSCs were stimulated with EpiGRO (Millipore), BEpiCM (ScienCell) and AECGM (PromoCell) media for 5 and 10 days, and epithelial differentiation was assessed by qPCR (keratin 14, 18 and EpCAM), fluorometry (cytokeratin 7-8, cytokeratin 14-15-16-19 and EpCAM), western blot analysis (pancytokeratin, EpCAM) and flow cytometry (cytokeratin 7-8, cytokeratin 14-15-16-19 and EpCAM). The functional marker MUC1 was also assessed after 10 days of air-liquid interface (ALI) culture in optimized media. Cells cultured in BEpiCM containing fibroblast growth factor and prostaglandin E2 showed the highest expression of the epithelial markers: CK7-8 (85.90%); CK-14-15-16-19 (10.14%); and EpCAM (64.61%). The cells also expressed functional marker MUC1 after ALI culture. The differentiated MSCs when cultured in BEpiCM medium ex vivo in a bioreactor on a decellularized trachea for 10 days retained the epithelial-like phenotype. In conclusion, porcine bone marrow-derived MSCs demonstrate commitment to the epithelial lineage and might be a potential therapy for facilitating the repair of denuded airway epithelium. PMID:23696537

  2. Expression of type 3 complement receptor on activated CD8+ T cells facilitates homing to inflammatory sites

    DEFF Research Database (Denmark)

    Nielsen, H V; Christensen, Jan Pravsgaard; Andersson, E C; Marker, O; Thomsen, Allan Randrup

    1994-01-01

    CD8+ cells, the majority of which are CD11b+. Adoptive transfer experiments involving i.v. transplantation of Ag-primed donor cells revealed that preincubation of the cells with 5C6 delayed the virus-specific delayed-type hypersensitivity reaction under conditions in which the recipient delivered the...... anti-CR3 treatment inhibits extravasation of both the Ag-specific and the nonspecific cellular components of the lymphocytic choriomeningitis virus-induced, CD8+ cell-dependent inflammatory reaction. Thus, expression of CR3 seems to facilitate T cell homing to sites of inflammation....

  3. Chimeric molecules facilitate the degradation of androgen receptors and repress the growth of LNCaP cells

    Institute of Scientific and Technical Information of China (English)

    Yue-Qing Tang; Bang-Min Han; Xin-Quan Yao; Yan Hong; Yan Wang; Fu-Jun Zhao; Sheng-Qiang Yu; Xiao-Wen Sun; Shu-Jie Xia

    2009-01-01

    Post-translational degradation of protein plays an important role in cell life.We employed chimeric molecules (dihydrotestosterone-based proteolysis-targeting chimeric molecule [DHT-PROTAC]) to facilitate androgen receptor (AR) degradation via the ubiquitin-proteasome pathway (UPP) and to investigate the role of AR in cell proliferation and viability in androgen-sensitive prostate cancer cells.Western blot analysis and immunohistochemistry were applied to analyse AR levels in LNCaP cells after DHT-PROTAC treatment.Cell counting and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell viability assay were used to evaluate cell proliferation and viability after AR elimination in both LNCaP and PC-3 cells.AR was tagged for elimination via the UPP by DHT-PROTAC,and this could be blocked by proteasome inhibitors.Degradation of AR depended on DHT-PROTAC concentration,and either DHT or an ALAPYIP-(arg)s peptide could compete with DHT-PROTAC.Inhibition of cell proliferation and decreased viability were observed in LNCaP cells,but not in PC-3 or 786-O cells after DHT-PROTAC treatment.These data indicate that AR elimination is facilitated via the UPP by DHT-PROTAC,and that the growth of LNCaP cells is repressed after AR degradation.

  4. Hypoxic stress up-regulates Kir2.1 expression and facilitates cell proliferation in brain capillary endothelial cells.

    Science.gov (United States)

    Yamamura, Hideto; Suzuki, Yoshiaki; Yamamura, Hisao; Asai, Kiyofumi; Imaizumi, Yuji

    2016-08-01

    The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4-5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba(2+)-sensitive inward rectifier K(+) current in t-BBEC117 cells after hypoxic culture. Western blot and real-time PCR analyses showed that Kir2.1 expression was significantly up-regulated at protein level but not at mRNA level after the hypoxic culture. Ca(2+) imaging study revealed that the hypoxic stress enhanced store-operated Ca(2+) (SOC) entry, which was significantly reduced in the presence of 100 μM Ba(2+). On the other hand, the expression of SOC channels such as Orai1, Orai2, and transient receptor potential channels was not affected by hypoxic stress. MTT assay showed that the hypoxic stress significantly enhanced t-BBEC117 cell proliferation, which was inhibited by approximately 60% in the presence of 100 μM Ba(2+). We first show here that moderate cellular stress by cultivation under hypoxic conditions hyperpolarizes membrane potential via the up-regulation of functional Kir2.1 expression and presumably enhances Ca(2+) entry, resulting in the facilitation of BCEC proliferation. These findings suggest potential roles of Kir2.1 expression in functional changes of BCECs in BBB following ischemia. PMID:27235552

  5. Human Brain Microvascular Endothelial Cells and Umbilical Vein Endothelial Cells Differentially Facilitate Leukocyte Recruitment and Utilize Chemokines for T Cell Migration

    Directory of Open Access Journals (Sweden)

    Shumei Man

    2008-02-01

    Full Text Available Endothelial cells that functionally express blood brain barrier (BBB properties are useful surrogates for studying leukocyte-endothelial cell interactions at the BBB. In this study, we compared two different endothelial cellular models: transfected human brain microvascular endothelial cells (THBMECs and human umbilical vein endothelial cells (HUVECs. With each grow under optimal conditions, confluent THBMEC cultures showed continuous occludin and ZO-1 immunoreactivity, while HUVEC cultures exhibited punctate ZO-1 expression at sites of cell-cell contact only. Confluent THBMEC cultures on 24-well collagen-coated transwell inserts had significantly higher transendothelial electrical resistance (TEER and lower solute permeability than HUVECs. Confluent THBMECs were more restrictive for mononuclear cell migration than HUVECs. Only THBMECs utilized abluminal CCL5 to facilitate T-lymphocyte migration in vitro although both THBMECs and HUVECs employed CCL3 to facilitate T cell migration. These data establish baseline conditions for using THBMECs to develop in vitro BBB models for studying leukocyte-endothelial interactions during neuroinflammation.

  6. Dominant-Negative Rho, Rac, and Cdc42 Facilitate the Invasion Process of Vibrio parahaemolyticus into Caco-2 Cells

    OpenAIRE

    Akeda, Yukihiro; Kodama, Toshio; Kashimoto, Takashige; Cantarelli, Vlademir; Horiguchi, Yasuhiko; Nagayama, Kenichi; Iida, Tetsuya; Honda, Takeshi

    2002-01-01

    To clarify the invasive process of Vibrio parahaemolyticus, an invasion assay was performed using cells expressing dominant negative small GTPases of the Rho family. This assay showed that the dominant negative host phenotype facilitates bacterial invasion, suggesting that the mechanism of V. parahaemolyticus invasion differs from that reported for other invasive bacteria.

  7. From Accumulation to Degradation: Reprogramming Polyamine Metabolism Facilitates Dark-Induced Senescence in Barley Leaf Cells

    Science.gov (United States)

    Sobieszczuk-Nowicka, Ewa; Kubala, Szymon; Zmienko, Agnieszka; Małecka, Arleta; Legocka, Jolanta

    2016-01-01

    The aim of this study was to analyze whether polyamine (PA) metabolism is involved in dark-induced Hordeum vulgare L. ‘Nagrad’ leaf senescence. In the cell, the titer of PAs is relatively constant and is carefully controlled. Senescence-dependent increases in the titer of the free PAs putrescine, spermidine, and spermine occurred when the process was induced, accompanied by the formation of putrescine conjugates. The addition of the anti-senescing agent cytokinin, which delays senescence, to dark-incubated leaves slowed the senescence-dependent PA accumulation. A feature of the senescence process was initial accumulation of PAs at the beginning of the process and their subsequent decrease during the later stages. Indeed, the process was accompanied by both enhanced expression of PA biosynthesis and catabolism genes and an increase in the activity of enzymes involved in the two metabolic pathways. To confirm whether the capacity of the plant to control senescence might be linked to PA, chlorophyll fluorescence parameters, and leaf nitrogen status in senescing barley leaves were measured after PA catabolism inhibition and exogenously applied γ-aminobutyric acid (GABA). The results obtained by blocking putrescine oxidation showed that the senescence process was accelerated. However, when the inhibitor was applied together with GABA, senescence continued without disruption. On the other hand, inhibition of spermidine and spermine oxidation delayed the process. It could be concluded that in dark-induced leaf senescence, the initial accumulation of PAs leads to facilitating their catabolism. Putrescine supports senescence through GABA production and spermidine/spermine supports senescence-dependent degradation processes, is verified by H2O2 generation. PMID:26779231

  8. Cytotoxic factor secreted by Escherichia coli associated with sepsis facilitates transcytosis through human umbilical vein endothelial cell monolayers.

    Science.gov (United States)

    Tibo, Luiz Henrique Soares; Bertol, Jéssica Wildgrube; Bernedo-Navarro, Robert Alvin; Yano, Tomomasa

    2016-01-01

    Culture supernatant of sepsis-associated Escherichia coli (SEPEC) isolated from patients with sepsis caused loss of intercellular junctions and elongation of human umbilical vein endothelial cells (HUVEC). The cytotoxic factor was purified from culture supernatant of SEPEC 15 (serogroup O153) by liquid chromatography process. PAGE (polyacrylamide gel electrophoresis) showed that the purified SEPEC cytotoxic factor had a molecular mass of ∼150kDa and consisted of at least two subunits. At the concentration of 1 CD50 (40μg/mL) did facilitate transcytosis through the HUVEC cells monolayer of SEPEC 15 as much as E. coli K12 within 30min without affecting cell viability. These results suggest that this cytotoxic factor, named as SPF (SEPEC's permeabilizing factor), may be an important SEPEC virulence factor that facilitates bacterial access to the bloodstream. PMID:26963151

  9. HIV-associated disruption of tight and adherens junctions of oral epithelial cells facilitates HSV-1 infection and spread.

    Directory of Open Access Journals (Sweden)

    Irna Sufiawati

    Full Text Available Herpes simplex virus (HSV types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD. Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals.

  10. Conditioning the Cochlea to Facilitate Survival and Integration of Exogenous Cells into the Auditory Epithelium

    OpenAIRE

    Park, Yong-Ho; Wilson, Kevin F.; Ueda, Yoshihisa; Tung Wong, Hiu; Lisa A. Beyer; Donald L. Swiderski; Dolan, David F.; Raphael, Yehoash

    2014-01-01

    The mammalian auditory epithelium (AE) cannot replace supporting cells and hair cells once they are lost. Therefore, sensorineural hearing loss associated with missing cells is permanent. This inability to regenerate critical cell types makes the AE a potential target for cell replacement therapies such as stem cell transplantation. Inserting stem cells into the AE of deaf ears is a complicated task due to the hostile, high potassium environment of the scala media in the cochlea, and the robu...

  11. Structural plasticity in hippocampal cells related to the facilitative effect of intracranial self-stimulation on a spatial memory task.

    Science.gov (United States)

    Chamorro-López, Jacobo; Miguéns, Miguel; Morgado-Bernal, Ignacio; Kastanauskaite, Asta; Selvas, Abraham; Cabané-Cucurella, Alberto; Aldavert-Vera, Laura; DeFelipe, Javier; Segura-Torres, Pilar

    2015-12-01

    Posttraining intracranial self-stimulation (SS) in the lateral hypothalamus facilitates the acquisition and retention of several implicit and explicit memory tasks. Here, intracellular injections of Lucifer yellow were used to assess morphological changes in hippocampal neurons that might be specifically related to the facilitative posttraining SS effect upon the acquisition and retention of a distributed spatial task in the Morris water maze. We examined the structure, size and branching complexity of cornus ammonis 1 (CA1) cells, and the spine density of CA1 pyramidal neurons and granular cells of the dentate gyrus (DG). Animals that received SS after each acquisition session performed faster and better than Sham ones--an improvement that was also evident in a probe trial 3 days after the last training session. The neuromorphological analysis revealed an increment in the size and branching complexity in apical CA1 dendritic arborization in SS-treated subjects as compared with Sham animals. Furthermore, increased spine density was observed in the CA1 field in SS animals, whereas no effects were observed in DG cells. Our results support the hypothesis that the facilitating effect of SS on the acquisition and retention of a spatial memory task could be related to structural plasticity in CA1 hippocampal cells. PMID:26501173

  12. Stomatal Spacing Safeguards Stomatal Dynamics by Facilitating Guard Cell Ion Transport Independent of the Epidermal Solute Reservoir.

    Science.gov (United States)

    Papanatsiou, Maria; Amtmann, Anna; Blatt, Michael R

    2016-09-01

    Stomata enable gaseous exchange between the interior of the leaf and the atmosphere through the stomatal pore. Control of the pore aperture depends on osmotic solute accumulation by, and its loss from the guard cells surrounding the pore. Stomata in most plants are separated by at least one epidermal cell, and this spacing is thought to enhance stomatal function, although there are several genera that exhibit stomata in clusters. We made use of Arabidopsis (Arabidopsis thaliana) stomatal patterning mutants to explore the impact of clustering on guard cell dynamics, gas exchange, and ion transport of guard cells. These studies showed that stomatal clustering in the Arabidopsis too many mouths (tmm1) mutant suppressed stomatal movements and affected CO2 assimilation and transpiration differentially between dark and light conditions and were associated with alterations in K(+) channel gating. These changes were consistent with the impaired dynamics of tmm1 stomata and were accompanied by a reduced accumulation of K(+) ions in the guard cells. Our findings underline the significance of spacing for stomatal dynamics. While stomatal spacing may be important as a reservoir for K(+) and other ions to facilitate stomatal movements, the effects on channel gating, and by inference on K(+) accumulation, cannot be explained on the basis of a reduced number of epidermal cells facilitating ion supply to the guard cells. PMID:27406168

  13. GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

    Energy Technology Data Exchange (ETDEWEB)

    Boku, Shuken, E-mail: shuboku@med.hokudai.ac.jp [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Nakagawa, Shin [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Takamura, Naoki [Pharmaceutical Laboratories, Dainippon Sumitomo Pharma Co. Ltd., Osaka (Japan); Kato, Akiko [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Takebayashi, Minoru [Department of Psychiatry, National Hospital Organization Kure Medical Center, Kure (Japan); Hisaoka-Nakashima, Kazue [Department of Pharmacology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima (Japan); Omiya, Yuki; Inoue, Takeshi; Kusumi, Ichiro [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan)

    2013-05-17

    Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.

  14. GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

    International Nuclear Information System (INIS)

    Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis

  15. OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo.

    Science.gov (United States)

    Chen, Xiaoli; Zhao, Qianhao; Li, Chen; Geng, Yang; Huang, Ke; Zhang, Jian; Wang, Xiaoshan; Yang, Jiaqi; Wang, Tongjie; Xia, Chengxiang; Liu, Xiaofei; Meng, Minghui; Yang, Dan; Zheng, Yi; Du, Juan; Zhang, Xiangzhong; Chen, Jiekai; Pan, Guangjin; Wang, Jinyong

    2015-09-01

    Generating engraftable hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) is an ideal approach for obtaining induced HSCs for cell therapy. However, the path from PSCs to robustly induced HSCs (iHSCs) in vitro remains elusive. We hypothesize that the modification of hematopoietic niche cells by transcription factors facilitates the derivation of induced HSCs from PSCs. The Lhx2 transcription factor is expressed in fetal liver stromal cells but not in fetal blood cells. Knocking out Lhx2 leads to a fetal hematopoietic defect in a cell non-autonomous role. In this study, we demonstrate that the ectopic expression of Lhx2 in OP9 cells (OP9-Lhx2) accelerates the hematopoietic differentiation of PSCs. OP9-Lhx2 significantly increased the yields of hematopoietic progenitor cells via co-culture with PSCs in vitro. Interestingly, the co-injection of OP9-Lhx2 and PSCs into immune deficient mice also increased the proportion of hematopoietic progenitors via the formation of teratomas. The transplantation of phenotypic HSCs from OP9-Lhx2 teratomas but not from the OP9 control supported a transient repopulating capability. The upregulation of Apln gene by Lhx2 is correlated to the hematopoietic commitment property of OP9-Lhx2. Furthermore, the enforced expression of Apln in OP9 cells significantly increased the hematopoietic differentiation of PSCs. These results indicate that OP9-Lhx2 is a good cell line for regeneration of hematopoietic progenitors both in vitro and in vivo. PMID:26339946

  16. OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Xiaoli Chen

    2015-09-01

    Full Text Available Generating engraftable hematopoietic stem cells (HSCs from pluripotent stem cells (PSCs is an ideal approach for obtaining induced HSCs for cell therapy. However, the path from PSCs to robustly induced HSCs (iHSCs in vitro remains elusive. We hypothesize that the modification of hematopoietic niche cells by transcription factors facilitates the derivation of induced HSCs from PSCs. The Lhx2 transcription factor is expressed in fetal liver stromal cells but not in fetal blood cells. Knocking out Lhx2 leads to a fetal hematopoietic defect in a cell non-autonomous role. In this study, we demonstrate that the ectopic expression of Lhx2 in OP9 cells (OP9-Lhx2 accelerates the hematopoietic differentiation of PSCs. OP9-Lhx2 significantly increased the yields of hematopoietic progenitor cells via co-culture with PSCs in vitro. Interestingly, the co-injection of OP9-Lhx2 and PSCs into immune deficient mice also increased the proportion of hematopoietic progenitors via the formation of teratomas. The transplantation of phenotypic HSCs from OP9-Lhx2 teratomas but not from the OP9 control supported a transient repopulating capability. The upregulation of Apln gene by Lhx2 is correlated to the hematopoietic commitment property of OP9-Lhx2. Furthermore, the enforced expression of Apln in OP9 cells significantly increased the hematopoietic differentiation of PSCs. These results indicate that OP9-Lhx2 is a good cell line for regeneration of hematopoietic progenitors both in vitro and in vivo.

  17. PCR amplification of 16S rDNA from lyophilized cell cultures facilitates studies in molecular systematics

    Science.gov (United States)

    Wisotzkey, J. D.; Jurtshuk, P. Jr; Fox, G. E.

    1990-01-01

    The sequence of the major portion of a Bacillus cycloheptanicus strain SCH(T) 16S rRNA gene is reported. This sequence suggests that B. cycloheptanicus is genetically quite distinct from traditional Bacillus strains (e.g., B. subtilis) and may be properly regarded as belonging to a different genus. The sequence was determined from DNA that was produced by direct amplification of ribosomal DNA from a lyophilized cell pellet with straightforward polymerase chain reaction (PCR) procedures. By obviating the need to revive cell cultures from the lyophile pellet, this approach facilitates rapid 16S rDNA sequencing and thereby advances studies in molecular systematics.

  18. Up-regulation of K{sub ir}2.1 by ER stress facilitates cell death of brain capillary endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kito, Hiroaki [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Yamazaki, Daiju [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Department of Biological Chemistry, Kyoto University, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Ohya, Susumu; Yamamura, Hisao [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Asai, Kiyofumi [Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Imaizumi, Yuji, E-mail: yimaizum@phar.nagoya-cu.ac.jp [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan)

    2011-07-29

    Highlights: {yields} We found that application of endoplasmic reticulum (ER) stress with tunicamycin to brain capillary endothelial cells (BCECs) induced cell death. {yields} The ER stress facilitated the expression of inward rectifier K{sup +} channel (K{sub ir}2.1) and induced sustained membrane hyperpolarization. {yields} The membrane hyperpolarization induced sustained Ca{sup 2+} entry through voltage-independent nonspecific cation channels and consequently facilitated cell death. {yields} The K{sub ir}2.1 up-regulation by ER stress is, at least in part, responsible for cell death of BCECs under pathological conditions. -- Abstract: Brain capillary endothelial cells (BCECs) form blood brain barrier (BBB) to maintain brain homeostasis. Cell turnover of BCECs by the balance of cell proliferation and cell death is critical for maintaining the integrity of BBB. Here we found that stimuli with tunicamycin, endoplasmic reticulum (ER) stress inducer, up-regulated inward rectifier K{sup +} channel (K{sub ir}2.1) and facilitated cell death in t-BBEC117, a cell line derived from bovine BCECs. The activation of K{sub ir} channels contributed to the establishment of deeply negative resting membrane potential in t-BBEC117. The deep resting membrane potential increased the resting intracellular Ca{sup 2+} concentration due to Ca{sup 2+} influx through non-selective cation channels and thereby partly but significantly regulated cell death in t-BBEC117. The present results suggest that the up-regulation of K{sub ir}2.1 is, at least in part, responsible for cell death/cell turnover of BCECs induced by a variety of cellular stresses, particularly ER stress, under pathological conditions.

  19. Apoptotic Susceptibility to DNA Damage of Pluripotent Stem Cells Facilitates Pharmacologic Purging of Teratoma Risk

    OpenAIRE

    Smith, Alyson J.; Nelson, Natalie G.; Oommen, Saji; Hartjes, Katherine A.; Folmes, Clifford D.; Terzic, Andre; Nelson, Timothy J.

    2012-01-01

    The pluripotent cell-purging assay validated herein demonstrates that pluripotent cells are selectively hypersensitive to DNA damage-induced apoptosis as a function of the specific apoptotic inducer protein Puma. Risk of dysregulated growth is decreased and the safety profile of transplant-ready, bioengineered progenitor cells is augmented.

  20. Aquaporin 1 Facilitated Hepatocellular Carcinoma SMMC7221 Cell Migration Associated with Water Permeability

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ai-li; LI Jiang; WANG Yan-qing; ZAKNROU Zohra; MA Tong-hui; LI Xiao-meng

    2011-01-01

    The authors investigated the regulation of human aquaporin l(hAQPl) and the involvement of aquaporin l(AQPl) in the migration of human hepatocellular carcinoma SMMC-7221 cells using RNA intereference technology.Firstly, two short hairpin RNA(shRNA) constructs in PBSU6 vector were reconstructed and their knockdown effects were identified in SMMC-7221 cells. Next, the involvement of endogenous hAQPl in regulating the migration of SMMC-7221 cells was investigated via siRNA technology. HAQPl-shRNA can specifically inhibit AQPl dependent osmotic water permeability. Meanwhile the migration of SMMC-7221 cells was inhibited remarkably after silencing AQPl by performing transwell cell migration assay and in vitro wound healing assay. Furthermore, in the presence of an inhibitor HgCl2, the water permeability of the cell membrane was remarkably decreased, the expression of AQPl was upregulated after HgCl2 treatment and the cell movement was decreased at the moment. Increased AQPl cannot attenuate cell migration ability when cell membrane loses its water permeability function. This demonstrates that the cell migration was remarkably related to the transporting water function of cell membrane.

  1. Trade Facilitation

    OpenAIRE

    Ujiie, Teruo

    2006-01-01

    The issue of trade facilitation has been increasingly highlighted among business and trading communities as they would like to reduce the costs of international transactions of goods and services. Trade facilitation is a broad term: there are a number of international agreements relating to trade facilitation, and a number of international organizations involved in this area. Recognizing the importance of trade facilitation and after several years of exploratory work on government trade facil...

  2. Biomimetic coating of apatite/collagen composite on poly L-lactic acid facilitates cell seeding

    OpenAIRE

    Chen, Y; Mak, AFT; Wang, M; Li, J.

    2005-01-01

    Collagen and apatite were co-precipitated as a composite coating on poly L-lactic acid (PLLA) in an accelerated biomimetic process. The coating formed on PLLA films after 24 hours incubation was characterized. Saos-2 osteoblast-like cells were used to evaluate the cell seeding on this biomimetic composite coating. It was shown that cell seeding on PLLA films with the composite coating was greatly improved. PLLA coated with submicron collagen fibrils and submicron apatite paticulates can facil...

  3. STEM CELL-PAVED BIOBRIDGE FACILITATES NEURAL REPAIR IN TRAUMATIC BRAIN INJURY

    Directory of Open Access Journals (Sweden)

    Ernest Yankee

    2014-06-01

    Full Text Available Modified mesenchymal stromal cells (MSCs display a unique mechanism of action during the repair phase of traumatic brain injury by exhibiting the ability to build a biobridge between the neurogenic niche and the site of injury. Immunohistochemistry and laser capture assay have visualized this biobridge in the area between the neurogenic subventricular zone and the injured cortex. This biobridge expresses high levels of extracellular matrixmetalloproteinases (MMPs, which are initially co-localized with a stream of transplanted MSCs, but later this region contains only few to non-detectable grafts and becomes overgrown by newly recruited host cells. We have reported that long-distance migration of host cells from the neurogenic niche to the injured brain site can be attained via these transplanted stem cell-paved biobridges, which serve as a key regenerative process for the initiation of endogenous repair mechanisms. Thus far the two major schools of discipline in stem cell repair mechanisms support the idea of “cell replacement” and the bystander effects of “trophic factor secretion.” Our novel observation of stem cell-paved biobridges as pathways for directed migration of host cells from neurogenic niche towards the injured brain site adds another mode of action underlying stem cell therapy. More in-depth investigations on graft-host interaction will likely aid translational research focused on advancing this stem cell-paved biobridge from its current place, as an equally potent repair mechanism as cell replacement and trophic factor secretion, into a new treatment strategy for traumatic brain injury and other neurological disorders.

  4. Xeroderma Pigmentosum Group A Promotes Autophagy to Facilitate Cisplatin Resistance in Melanoma Cells through the Activation of PARP1.

    Science.gov (United States)

    Ge, Rui; Liu, Lin; Dai, Wei; Zhang, Weigang; Yang, Yuqi; Wang, Huina; Shi, Qiong; Guo, Sen; Yi, Xiuli; Wang, Gang; Gao, Tianwen; Luan, Qi; Li, Chunying

    2016-06-01

    Xeroderma pigmentosum group A (XPA), a key protein in the nucleotide excision repair pathway, has been shown to promote the resistance of tumor cells to chemotherapeutic drugs by facilitating the DNA repair process. However, the role of XPA in the resistance of melanoma to platinum-based drugs like cisplatin is largely unknown. In this study, we initially found that XPA was expressed at higher levels in cisplatin-resistant melanoma cells than in cisplatin-sensitive ones. Furthermore, the knockdown of XPA not only increased cellular apoptosis but also inhibited cisplatin-induced autophagy, which rendered the melanoma cells more sensitive to cisplatin. Moreover, we discovered that the increased XPA in resistant melanoma cells promoted poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) activation and that the inhibition of PARP1 could attenuate the cisplatin-induced autophagy. Finally, we proved that the inhibition of PARP1 and the autophagy process made resistant melanoma cells more susceptible to cisplatin treatment. Our study shows that XPA can promote cell-protective autophagy in a DNA repair-independent manner by enhancing the activation of PARP1 in melanoma cells resistant to cisplatin and that the XPA-PARP1-mediated autophagy process can be targeted to overcome cisplatin resistance in melanoma chemotherapy. PMID:26880244

  5. Freezing-induced uptake of trehalose into mammalian cells facilitates cryopreservation.

    Science.gov (United States)

    Zhang, Miao; Oldenhof, Harriëtte; Sieme, Harald; Wolkers, Willem F

    2016-06-01

    The aim of this study was to investigate if membrane-impermeable molecules are taken up by fibroblasts when exposing the cells to membrane phase transitions and/or freezing-induced osmotic forces. The membrane-impermeable fluorescent dye lucifer yellow (LY) was used to visualize and quantify uptake during endocytosis, and after freezing-thawing. In addition, trehalose uptake after freezing and thawing was studied. Fourier transform infrared spectroscopic studies showed that fibroblasts display a minor non-cooperative phase transition during cooling at suprazero temperatures, whereas cells display strong highly cooperative fluid-to-gel membrane phase transitions during freezing, both in the absence and presence of protectants. Cells do not show uptake of LY upon passing the suprazero membrane phase transition at 30-10°C, whereas after freezing and thawing cells show intracellular LY equally distributed within the cell. Both, LY and trehalose are taken up by fibroblasts after freezing and thawing with loading efficiencies approaching 50%. When using 250 mM extracellular trehalose during cryopreservation, intracellular concentrations greater than 100 mM were determined after thawing. A plot of cryosurvival versus the cooling rate showed a narrow inverted-'U'-shaped curve with an optimal cooling rate of 40°C min(-1). Diluting cells cryopreserved with trehalose in isotonic cell culture medium resulted in a loss of cell viability, which was attributed to intracellular trehalose causing an osmotic imbalance. Taken together, mammalian cells can be loaded with membrane-impermeable compounds, including the protective agent trehalose, by subjecting the cells to freezing-induced osmotic stress. PMID:27003129

  6. Nanoparticle-facilitated autophagy inhibition promotes the efficacy of chemotherapeutics against breast cancer stem cells.

    Science.gov (United States)

    Sun, Rong; Shen, Song; Zhang, Yun-Jiao; Xu, Cong-Fei; Cao, Zhi-Ting; Wen, Long-Ping; Wang, Jun

    2016-10-01

    Cancer stem cells (CSCs) have garnered increasing attention over the past decade, as they are believed to play a crucial role in tumor initiation, progression and metastasis, relapse and drug resistance. Therapeutic strategies which simultaneously exterminate both bulk tumor cells and the rare CSC subpopulation may produce striking response and result in long-term tumor remission. Accumulating evidence provides insight into the function of autophagy in maintenance, plasticity and survival of CSCs. The role of autophagy in the susceptibility of breast CSCs to chemotherapeutics was investigated in the present work, reduced 'stemness' and increased susceptibility to chemotherapy drugs (doxorubicin, DOX and docetaxel, DTXL) were observed after chloroquine (CQ)-mediated autophagy inhibition in sorted ALDH(hi) cells of breast cancer cell line MDA-MB-231. We further proved that nanoparticle-mediated autophagy inhibition promoted the efficacy of chemotherapeutics against ALDH(hi) MDA-MB-231 cells in vitro. Administration of drug delivery systems significantly prolonged the circulation half-life and augmented enrichment of two different drugs in tumor tissues and ALDH(hi) cells. More importantly, compared with single treatment, the combined delivery systems NPCQ/NPDOX and NPCQ/DOX (NPCQ/NPDTXL and NPCQ/DTXL) showed most effective and persistent tumor growth inhibitory effect by eliminating bulk tumor cells as well as CSCs (p breast cancer. PMID:27376558

  7. Diphtheria toxin entry into cells is facilitated by low pH

    OpenAIRE

    1980-01-01

    At neutral pH, NH4Cl and chloroquine protected cells against diphtheria toxin. A brief exposure of the cells to low pH (4.5-5.5) at 37 degrees completely abolished this protection. When, to cells preincubated with diphtheria toxin and NH4Cl, neutralizing amounts of anti-diphtheria toxin were added before the pH was lowered, the toxic effect was considerably reduced, but it was not completely abolished. A much stronger toxic effect was seen when antibodies were added immediately after incubati...

  8. The p53 Protein Does Not Facilitate Adenovirus Type 5 Replication in Normal Human Cells

    OpenAIRE

    Chahal, Jasdave S.; Flint, S J

    2013-01-01

    Although several adenovirus type 5 (Ad5) proteins prevent deleterious consequences of activation of p53, it has been reported that viral replication proceeds more efficiently when human tumor cells produce wild-type compared to mutant p53. We have now exploited RNA interference and lentiviral vectors to achieve essentially complete knockdown of p53 in normal human cells: no effects on the kinetics or efficiency of viral gene expression or production of infectious particles were observed.

  9. Modification of gellan gum with nanocrystalline hydroxyapatite facilitates cell expansion and spontaneous osteogenesis.

    Science.gov (United States)

    Jamshidi, Parastoo; Chouhan, Gurpreet; Williams, Richard L; Cox, Sophie C; Grover, Liam M

    2016-07-01

    Nanocomposites composed of hydrogels and calcium phosphates are of great interest in the development of bone graft replacements since they may have a structural and compositional resemblance to bone. Culture beads formed from such materials could be used in stirred tank culture and thereby enable cell expansion in a sufficiently efficient manner to allow for the generation of enough large number of cells for large-scale bone reconstruction. Although combinations of materials such as alginate, collagens, and various calcium phosphates have been investigated as culture beads, these materials are unsuitable for application since they have been shown to rapidly degrade in physiological conditions and enable relatively little tailoring of mechanical properties. In this study, gellan gum-nano sized hydroxyapatite (nHA) composites, which have been shown to be resistant to degradation and easily modified with respect to modulus, were formulated and characterized as regards their ability to enable cell attachment and proliferation. It was shown that the addition of 5 wt% of nHA to the culture beads enabled cell attachment and that an increase in nHA concentration to up to 25 wt% enhanced the rate of cell proliferation. Most importantly, it was demonstrated that the addition of nHA to the cell culture beads enabled the formation of nodules in culture of MC3T3-E1 cells and strikingly stimulated the osteogenic differentiation of bone marrow stromal cells in the absence of osteogenic media when compared with tissue culture plastic (TCP) with the same condition. Biotechnol. Bioeng. 2016;113: 1568-1576. © 2016 Wiley Periodicals, Inc. PMID:26704737

  10. A TNFR2-Agonist Facilitates High Purity Expansion of Human Low Purity Treg Cells

    OpenAIRE

    Xuehui He; Sija Landman; Stijn C G Bauland; Juliette van den Dolder; Koenen, Hans J.P.M.; Irma Joosten

    2016-01-01

    Regulatory T cells (Treg) are important for immune homeostasis and are considered of great interest for immunotherapy. The paucity of Treg numbers requires the need for ex vivo expansion. Although therapeutic Treg flow-sorting is feasible, most centers aiming at Treg-based therapy focus on magnetic bead isolation of CD4+CD25+ Treg using a good manufacturing practice compliant closed system that achieves lower levels of cell purity. Polyclonal Treg expansion protocols commonly use anti-CD3 plu...

  11. Human breast cancer-derived soluble factors facilitate CCL19-induced chemotaxis of human dendritic cells.

    Science.gov (United States)

    Hwang, Hyundoo; Shin, Changsik; Park, Juhee; Kang, Enoch; Choi, Bongseo; Han, Jae-A; Do, Yoonkyung; Ryu, Seongho; Cho, Yoon-Kyoung

    2016-01-01

    Breast cancer remains as a challenging disease with high mortality in women. Increasing evidence points the importance of understanding a crosstalk between breast cancers and immune cells, but little is known about the effect of breast cancer-derived factors on the migratory properties of dendritic cells (DCs) and their consequent capability in inducing T cell immune responses. Utilizing a unique 3D microfluidic device, we here showed that breast cancers (MCF-7, MDA-MB-231, MDA-MB-436 and SK-BR-3)-derived soluble factors increase the migration of DCs toward CCL19. The enhanced migration of DCs was mainly mediated via the highly activated JNK/c-Jun signaling pathway, increasing their directional persistence, while the velocity of DCs was not influenced, particularly when they were co-cultured with triple negative breast cancer cells (TNBCs or MDA-MB-231 and MDA-MB-436). The DCs up-regulated inflammatory cytokines IL-1β and IL-6 and induced T cells more proliferative and resistant against activation-induced cell death (AICD), which secret high levels of inflammatory cytokines IL-1β, IL-6 and IFN-γ. This study demonstrated new possible evasion strategy of TNBCs utilizing their soluble factors that exploit the directionality of DCs toward chemokine responses, leading to the building of inflammatory milieu which may support their own growth. PMID:27451948

  12. Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice.

    Directory of Open Access Journals (Sweden)

    Karsten Buschard

    Full Text Available BACKGROUND: Ethanol ('alcohol' is a partly hydrophobic detergent that may affect the accessibility of glycolipids thereby influencing immunological effects of these molecules. METHODS: The study included cellular in vitro tests using α-galactosylceramide (αGalCer, and in vivo NOD mice experiments detecting diabetes incidence and performing behavioural and bacterial analyses. RESULTS: Alcohol in concentrations from 0.6% to 2.5% increased IL-2 production from NKT cells stimulated with αGalCer by 60% (p<0.05. CD1d expressed on HeLa cells contained significantly increasing amounts of αGalCer with increasing concentrations of alcohol, suggesting that alcohol facilitated the passive loading of αGalCer to CD1d. NOD mice were found to tolerate 5% ethanol in their drinking water without signs of impairment in liver function. Giving this treatment, the diabetes incidence declined significantly. Higher numbers of CD3+CD49b+ NKT cells were found in spleen and liver of the alcohol treated compared to the control mice (p<0.05, whereas the amount of CD4+Foxp3+ regulator T cells did not differ. Increased concentrations of IFN-γ were detected in 24-hour blood samples of alcohol treated mice. Behavioural studies showed no change in attitude of the ethanol-consuming mice, and bacterial composition of caecum samples was not affected by alcohol, disqualifying these as protective mechanisms. CONCLUSION: Alcohol facilitates the uptake of glycolipids and the stimulation of NKT cells, which are known to counteract Type 1 diabetes development. We propose that this is the acting mechanism by which treatment with alcohol reduces the incidence of diabetes in NOD mice. This is corroborated by epidemiology showing beneficial effect of alcohol to reduce the severity of atherosclerosis and related diseases.

  13. Neuregulin facilitates nerve regeneration by speeding Schwann cell migration via ErbB2/3-dependent FAK pathway.

    Directory of Open Access Journals (Sweden)

    Hung-Ming Chang

    Full Text Available BACKGROUND: Adequate migration of Schwann cells (Sc is crucial for axon-guidance in the regenerative process after peripheral nerve injury (PNI. Considering neuregulin-erbB-FAK signaling is an essential pathway participating in the regulation of Sc migration during development, the present study is aimed to examine whether neuregulin would exert its beneficial effects on adult following PNI and further determine the potential changes of downstream pathway engaged in neuro-regeneration by both in vitro and in vivo approaches. METHODOLOGY AND PRINCIPAL FINDINGS: Cultured RSC96 cells treated with neuregulin were processed for erbB2/3 immunofluorescence and FAK immunoblotings. The potential effects of neuregulin on Sc were assessed by cell adherence, spreading, and migration assays. In order to evaluate the functional significance of neuregulin on neuro-regeneration, the in vivo model of PNI was performed by chronic end-to-side neurorrhaphy (ESN. In vitro studies indicated that after neuregulin incubation, erbB2/3 were not only expressed in cell membranes, but also distributed throughout the cytoplasm and nucleus of RSC96 cells. Activation of erbB2/3 was positively correlated with FAK phosphorylation. Neuregulin also increases Sc adherence, spreading, and migration by 127.2 ± 5.0%, 336.8 ± 3.0%, and 80.0 ± 5.7%, respectively. As for in vivo study, neuregulin significantly accelerates the speed of Sc migration and increases Sc expression in the distal stump of injured nerves. Retrograde labeling and compound muscle action potential recordings (CMAP also showed that neuregulin successfully facilitates nerve regeneration by eliciting noticeably larger CMAP and promoting quick re-innervation of target muscles. CONCLUSIONS: As neuregulin successfully improves axo-glial interaction by speeding Sc migration via the erbB2/3-FAK pathway, therapeutic use of neuregulin may thus serve as a promising strategy to facilitate the progress of nerve regeneration

  14. Interferon-γ facilitates hepatic antiviral T cell retention for the maintenance of liver-induced systemic tolerance.

    Science.gov (United States)

    Zeng, Zhutian; Li, Lu; Chen, Yongyan; Wei, Haiming; Sun, Rui; Tian, Zhigang

    2016-05-30

    Persistent exposure to liver pathogens leads to systemic antigen-specific tolerance, a major cause of chronicity during hepatotropic infection. The mechanism regarding how this systemic tolerance is maintained remains poorly elucidated. In a well established mouse model of hepatitis B virus (HBV) persistence-induced systemic tolerance, we observed that interferon-γ (IFN-γ) deficiency led to complete loss of tolerance, resulting in robust anti-HBV responses upon peripheral vaccination. The recovery of vaccine-induced anti-HBV responses was mainly caused by the retained antigen-specific CD4(+) T cells rather than decreased functional inhibitory cells in the periphery. Mechanistically, HBV persistence induced sustained hepatic CD4(+) T cell-derived IFN-γ production. IFN-γ was found to promote CXCL9 secretion from liver-resident macrophages. This T cell chemokine facilitated the retention of antiviral CD4(+) T cells in the liver in a CXCR3-dependent manner. Hepatic sequestrated antiviral CD4(+) T cells subsequently underwent local apoptotic elimination partially via cytotoxic T lymphocyte-associated protein 4 ligation. These findings reveal an unexpected tolerogenic role for IFN-γ during viral persistence in the liver, providing new mechanistic insights regarding the maintenance of systemic antigen-specific tolerance during HBV persistence. PMID:27139489

  15. Facilitation of allogeneic bone marrow transplantation by a T cell-specific immunotoxin containing daunomycin

    International Nuclear Information System (INIS)

    Daunomycin coupled via an acid-sensitive spacer to monoclonal Thy-1.2-specific antibody was used to purge T lymphocytes from a 1:1 mixture of murine C57BL/6J bone marrow and spleen cells prior to engraftment in fully allogeneic, irradiated BALB/c recipients. Treatment of bone marrow with the immunotoxin at a concentration used for purging had no effect on the viability of committed hematopoietic progenitor or multipotent stem cells. All of the recipients of purged bone marrow were at least 80% chimeric for donor peripheral blood cells and none developed graft-versus-host disease. Out of 50 chimeras, 49 were still alive more than 200 days posttransplantation. The chimeras were shown to be tolerant to donor tissue as tested by mixed lymphocyte reactivity, cell-mediated cytotoxicity, and skin grafting. The same tests revealed full immunocompetence of chimeras to third-party alloantigens. In vivo IgM and IgG antibody responses to sheep red blood cells were similar in magnitude in allogeneically and syngeneically reconstituted mice

  16. Autophagy inhibition facilitates erlotinib cytotoxicity in lung cancer cells through modulation of endoplasmic reticulum stress.

    Science.gov (United States)

    Wang, Zhongliang; Du, Tingting; Dong, Xiaorong; Li, Zhenyu; Wu, Gang; Zhang, Ruiguang

    2016-06-01

    Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized the treatment for non-small cell lung cancer patients, but acquired resistance limit the efficiency of this treatment. As a homeostatic cellular recycling mechanism, autophagy has been proposed to participate in the EGFR-TKI resistance. However, the role of autophagy in lung cancer treatment and the underlying mechanisms have not been clarified. In this study, we found the sensitivity to erlotinib, a well-used EGFR-TKI, was correlated with basal autophagy level. Erlotinib was able to induce autophagy not only in TKI-sensitive, but also TKI-resistant cancer cells. Inhibition of autophagy significantly enhanced cytotoxicity of erlotinib in TKI-resistant cancer cells via modulation of endoplasmic reticulum (ER) stress induced apoptosis. In this process, CCAAT/enhancer binding protein homologous protein (CHOP) acted as an executioner. Downregulation of CHOP with siRNA blocked the autophagy inhibition and erlotinib co-treatment induced apoptosis and prevented cancer cells from this co-treatment-induced cell death. Our findings suggest that autophagy inhibition overcomes erlotinib resistance through modulation of ER stress mediated apoptosis. PMID:27035631

  17. Design of the dye cell of a dye laser to facilitate repetitive operation in the single longitudinal mode

    International Nuclear Information System (INIS)

    A dye cell was designed and fabricated to facilitate high repetition rate single longitudinal mode (SLM) operation with low viscosity solvents such as ethanol. The flow circulation (vortex) in the dye cell was eliminated by reducing the flow cross section from 10 to 5 mm2 with optimized flow entry. The physical dimension of dye cell is very important for short cavity SLM lasers in terms of keeping the cavity length small. Flow visualization of various geometries in the dye cell was carried out using commercial computational fluid dynamics (CFD) software. It was found that the slit as well as tubular entry to the dye cell of cross section 1 × 10 mm2 shows flow circulation (a vortex) near the entry to the dye cell. The SLM was obtained from a 10 mm2 flow cross section dye cell with a high viscosity solvent such as binary solvent (200 cP) or glycerol (1400 cP) with a higher bandwidth. The pulse to pulse fluctuations in the bandwidth and wavelength are generally associated with dye flow instabilities. These flow related instabilities reduced with higher viscosity solvents, which results in an increased bandwidth of the SLM dye laser (by nearly 40%). A specially designed dye cell was fabricated and used for SLM operation at two different pump lasers having different pulse repetition rates ranging from 20 to 6000 Hz. SLM operation was demonstrated for longitudinal pumping of the dye cell with low viscosity solvents. Time averaged SLM line widths of 400 and 175 MHz were obtained with a copper vapor laser (CVL) and Nd:YAG laser, respectively. A single pulse line width of 315 MHz was obtained with a CVL pumped dye laser. (paper)

  18. Cell spreading and viability on zein films may be facilitated by transglutaminase.

    Science.gov (United States)

    Cui, Hemiao; Liu, Gang L; Padua, Graciela W

    2016-09-01

    Zein is a biocompatible corn protein potentially useful in the development of biomaterials. In this study, the deposition of zein on oxygen plasma treated glass cover slips significantly enhanced cell spreading and viability. The mechanism for cellular response to zein coated surfaces was thought to involve the polyglutamine peptides on the zein structure. We hypothesized that zein was a substrate for tissue transglutaminase (tTG), an extracellular enzyme involved in cell-surface interactions. SDS-PAGE results suggested an interaction between zein and tTG, where zein was the glutamine donor. Cross-linking between zein and tTG may be the first step in successful cell adhesion and spreading. PMID:27315332

  19. Transplanted Human Umbilical Cord Mesenchymal Stem Cells Facilitate Lesion Repair in B6.Fas Mice

    Directory of Open Access Journals (Sweden)

    Guang-ping Ruan

    2014-01-01

    Full Text Available Background. Systemic lupus erythematosus (SLE is a multisystem disease that is characterized by the appearance of serum autoantibodies. No effective treatment for SLE currently exists. Methods. We used human umbilical cord mesenchymal stem cell (H-UC-MSC transplantation to treat B6.Fas mice. Results. After four rounds of cell transplantation, we observed a statistically significant decrease in the levels of mouse anti-nuclear, anti-histone, and anti-double-stranded DNA antibodies in transplanted mice compared with controls. The percentage of CD4+CD25+Foxp3+ T cells in mouse peripheral blood significantly increased after H-UC-MSC transplantation. Conclusions. The results showed that H-UC-MSCs could repair lesions in B6.Fas mice such that all of the relevant disease indicators in B6.Fas mice were restored to the levels observed in normal C57BL/6 mice.

  20. Expression of NR2B in cerebellar granule cells specifically facilitates effect of motor training on motor learning.

    Directory of Open Access Journals (Sweden)

    Jianwei Jiao

    Full Text Available It is believed that gene/environment interaction (GEI plays a pivotal role in the development of motor skills, which are acquired via practicing or motor training. However, the underlying molecular/neuronal mechanisms are still unclear. Here, we reported that the expression of NR2B, a subunit of NMDA receptors, in cerebellar granule cells specifically enhanced the effect of voluntary motor training on motor learning in the mouse. Moreover, this effect was characterized as motor learning-specific and developmental stage-dependent, because neither emotional/spatial memory was affected nor was the enhanced motor learning observed when the motor training was conducted starting at the age of 3 months old in these transgenic mice. These results indicate that changes in the expression of gene(s that are involved in regulating synaptic plasticity in cerebellar granule cells may constitute a molecular basis for the cerebellum to be involved in the GEI by facilitating motor skill learning.

  1. Conceptual Change Text: A Supplementary Material To Facilitate Conceptual Change in Electrochemical Cell Concepts.

    Science.gov (United States)

    Yuruk, Nejla; Geban, Omer

    The main purpose of the study was to investigate the effectiveness of conceptual change text (CCT) oriented instruction over traditionally designed instruction on students' understanding of electrochemical (galvanic and electrolytic) cell concepts. The subjects of the study consisted of 64 students from the two classes of a high school in Turkey.…

  2. Controlled Multi-functionalization Facilitates Targeted Delivery of Nanoparticles to Cancer Cells.

    Science.gov (United States)

    Hudlikar, Manish S; Li, Xiuru; Gagarinov, Ivan A; Kolishetti, Nagesh; Wolfert, Margreet A; Boons, Geert-Jan

    2016-01-22

    A major objective of nanomedicine is to combine in a controlled manner multiple functional entities into a single nanoscale device to target particles with great spatial precision, thereby increasing the selectivity and potency of therapeutic drugs. A multifunctional nanoparticle is described for controlled conjugation of a cytotoxic drug, a cancer cell targeting ligand, and an imaging moiety. The approach is based on the chemical synthesis of polyethylene glycol that at one end is modified by a thioctic acid for controlled attachment to a gold core. The other end of the PEG polymers is modified by a hydrazine, amine, or dibenzocyclooctynol moiety for conjugation with functional entities having a ketone, activated ester, or azide moiety, respectively. The conjugation approach allowed the controlled attachment of doxorubicin through an acid-labile hydrazone linkage, an Alexa Fluor dye through an amide bond, and a glycan-based ligand for the cell surface receptor CD22 of B-cells using strain promoted azide-alkyne cycloaddition. The incorporation of the ligand for CD22 led to rapid entry of the nanoparticle by receptor-mediated endocytosis. Covalent attachment of doxorubicin via hydrazone linkage caused pH-responsive intracellular release of doxorubicin and significantly enhanced the cytotoxicity of nanoparticles. A remarkable 60-fold enhancement in cytotoxicity of CD22 (+) lymphoma cells was observed compared to non- targeted nanoparticles. PMID:26683093

  3. A Long Noncoding RNA Perturbs the Circadian Rhythm of Hepatoma Cells to Facilitate Hepatocarcinogenesis

    Directory of Open Access Journals (Sweden)

    Ming Cui

    2015-01-01

    Full Text Available Clock circadian regulator (CLOCK/brain and muscle arnt-like protein-1 (BMAL1 complex governs the regulation of circadian rhythm through triggering periodic alterations of gene expression. However, the underlying mechanism of circadian clock disruption in hepatocellular carcinoma (HCC remains unclear. Here, we report that a long noncoding RNA (lncRNA, highly upregulated in liver cancer (HULC, contributes to the perturbations in circadian rhythm of hepatoma cells. Our observations showed that HULC was able to heighten the expression levels of CLOCK and its downstream circadian oscillators, such as period circadian clock 1 and cryptochrome circadian clock 1, in hepatoma cells. Strikingly, HULC altered the expression pattern and prolonged the periodic expression of CLOCK in hepatoma cells. Mechanistically, the complementary base pairing between HULC and the 5' untranslated region of CLOCK mRNA underlay the HULC-modulated expression of CLOCK, and the mutants in the complementary region failed to achieve the event. Moreover, immunohistochemistry staining and quantitative real-time polymerase chain reaction validated that the levels of CLOCK were elevated in HCC tissues, and the expression levels of HULC were positively associated with those of CLOCK in clinical HCC samples. In functional experiments, our data exhibited that CLOCK was implicated in the HULC-accelerated proliferation of hepatoma cells in vitro and in vivo. Taken together, our data show that an lncRNA, HULC, is responsible for the perturbations in circadian rhythm through upregulating circadian oscillator CLOCK in hepatoma cells, resulting in the promotion of hepatocarcinogenesis. Thus, our finding provides new insights into the mechanism by which lncRNA accelerates hepatocarcinogenesis through disturbing circadian rhythm of HCC.

  4. Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

    International Nuclear Information System (INIS)

    Highlights: • We identified that CHAF1A was up-regulated in colon tumor mucosa in TMA. • The expression pattern of CHAF1A was validated with qPCR and western-blot. • CHAF1A overexpression is an independent indicator for poor colon cancer survival. • CHAF1A facilitates cell proliferation of colon cancer both in vitro and in vivo. - Abstract: Deregulation of chromatin assembly factor 1, p150 subunit A (CHAF1A) has recently been reported to be involved in the development of some cancer types. In this study, we identified that the frequency of positive CHAF1A staining in primary tumor mucosa (45.8%, 93 of 203 samples) was significantly elevated compared to that in paired normal mucosa (18.7%, 38 of 203 samples). The increased expression was strongly associated with cancer stage, tumor invasion, and histological grade. The five-year survival rate of patients with CHAF1A-positive tumors was remarkably lower than that of patients with CHAF1A-negative tumors. Colon cancer cells with CHAF1A knockdown exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate as well as impaired colon tumorigenicity in nude mice. Hence, CHAF1A upregulation functions as a poor prognostic indicator of colon cancer, potentially contributing to its progression by mediating cancer cell proliferation

  5. Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zehua; Cui, Feifei; Yu, Fudong; Peng, Xiao; Jiang, Tao; Chen, Dawei [Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Lu, Su [Department of Pathology, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Tang, Huamei, E-mail: tanghuamei@gmail.com [Department of Pathology, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Peng, Zhihai, E-mail: zhihai.peng@hotmail.com [Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China)

    2014-06-27

    Highlights: • We identified that CHAF1A was up-regulated in colon tumor mucosa in TMA. • The expression pattern of CHAF1A was validated with qPCR and western-blot. • CHAF1A overexpression is an independent indicator for poor colon cancer survival. • CHAF1A facilitates cell proliferation of colon cancer both in vitro and in vivo. - Abstract: Deregulation of chromatin assembly factor 1, p150 subunit A (CHAF1A) has recently been reported to be involved in the development of some cancer types. In this study, we identified that the frequency of positive CHAF1A staining in primary tumor mucosa (45.8%, 93 of 203 samples) was significantly elevated compared to that in paired normal mucosa (18.7%, 38 of 203 samples). The increased expression was strongly associated with cancer stage, tumor invasion, and histological grade. The five-year survival rate of patients with CHAF1A-positive tumors was remarkably lower than that of patients with CHAF1A-negative tumors. Colon cancer cells with CHAF1A knockdown exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate as well as impaired colon tumorigenicity in nude mice. Hence, CHAF1A upregulation functions as a poor prognostic indicator of colon cancer, potentially contributing to its progression by mediating cancer cell proliferation.

  6. The fibrinolytic system facilitates tumor cell migration across the blood-brain barrier in experimental melanoma brain metastasis

    International Nuclear Information System (INIS)

    Patients with metastatic tumors to the brain have a very poor prognosis. Increased metastatic potential has been associated with the fibrinolytic system. We investigated the role of the fibrinolytic enzyme plasmin in tumor cell migration across brain endothelial cells and growth of brain metastases in an experimental metastatic melanoma model. Metastatic tumors to the brain were established by direct injection into the striatum or by intracarotid injection of B16F10 mouse melanoma cells in C57Bl mice. The role of plasminogen in the ability of human melanoma cells to cross a human blood-brain barrier model was studied on a transwell system. Wild type mice treated with the plasmin inhibitor epsilon-aminocaproic acid (EACA) and plg-/- mice developed smaller tumors and survived longer than untreated wild type mice. Tumors metastasized to the brain of wild type mice treated with EACA and plg-/- less efficiently than in untreated wild type mice. No difference was observed in the tumor growth in any of the three groups of mice. Human melanoma cells were able to cross the human blood-brain barrier model in a plasmin dependent manner. Plasmin facilitates the development of tumor metastasis to the brain. Inhibition of the fibrinolytic system could be considered as means to prevent tumor metastasis to the brain

  7. Condensation by DNA looping facilitates transfer of large DNA molecules into mammalian cells

    OpenAIRE

    Montigny, William J.; Houchens, Christopher R.; Illenye, Sharon; Gilbert, Jonathan; Coonrod, Emily; Chang, Young-Chae; Nicholas H. Heintz

    2001-01-01

    Experimental studies of complete mammalian genes and other genetic domains are impeded by the difficulty of introducing large DNA molecules into cells in culture. Previously we have shown that GST–Z2, a protein that contains three zinc fingers and a proline-rich multimerization domain from the polydactyl zinc finger protein RIP60 fused to glutathione S-transferase (GST), mediates DNA binding and looping in vitro. Atomic force microscopy showed that GST–Z2 is able to condense 1...

  8. Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells

    OpenAIRE

    Bhatt, Anant Narayan; Chauhan, Ankit; Khanna, Suchit; Rai, Yogesh; Singh, Saurabh; Soni, Ravi; Kalra, Namita; Bilikere S Dwarakanath

    2015-01-01

    Background Cancer cells exhibit increased glycolysis for ATP production (the Warburg effect) and macromolecular biosynthesis; it is also linked with therapeutic resistance that is generally associated with compromised respiratory metabolism. Molecular mechanisms underlying radio-resistance linked to elevated glycolysis remain incompletely understood. Methods We stimulated glycolysis using mitochondrial respiratory modifiers (MRMs viz. di-nitro phenol, DNP; Photosan-3, PS3; Methylene blue, MB)...

  9. Expression of arf tumor suppressor in spermatogonia facilitates meiotic progression in male germ cells.

    Directory of Open Access Journals (Sweden)

    Michelle L Churchman

    2011-07-01

    Full Text Available The mammalian Cdkn2a (Ink4a-Arf locus encodes two tumor suppressor proteins (p16(Ink4a and p19(Arf that respectively enforce the anti-proliferative functions of the retinoblastoma protein (Rb and the p53 transcription factor in response to oncogenic stress. Although p19(Arf is not normally detected in tissues of young adult mice, a notable exception occurs in the male germ line, where Arf is expressed in spermatogonia, but not in meiotic spermatocytes arising from them. Unlike other contexts in which the induction of Arf potently inhibits cell proliferation, expression of p19(Arf in spermatogonia does not interfere with mitotic cell division. Instead, inactivation of Arf triggers germ cell-autonomous, p53-dependent apoptosis of primary spermatocytes in late meiotic prophase, resulting in reduced sperm production. Arf deficiency also causes premature, elevated, and persistent accumulation of the phosphorylated histone variant H2AX, reduces numbers of chromosome-associated complexes of Rad51 and Dmc1 recombinases during meiotic prophase, and yields incompletely synapsed autosomes during pachynema. Inactivation of Ink4a increases the fraction of spermatogonia in S-phase and restores sperm numbers in Ink4a-Arf doubly deficient mice but does not abrogate γ-H2AX accumulation in spermatocytes or p53-dependent apoptosis resulting from Arf inactivation. Thus, as opposed to its canonical role as a tumor suppressor in inducing p53-dependent senescence or apoptosis, Arf expression in spermatogonia instead initiates a salutary feed-forward program that prevents p53-dependent apoptosis, contributing to the survival of meiotic male germ cells.

  10. HMGB1 interacts with XPA to facilitate the processing of DNA interstrand crosslinks in human cells

    OpenAIRE

    Mukherjee, Anirban; Vasquez, Karen M.

    2015-01-01

    Many effective agents used in cancer chemotherapy cause DNA interstrand crosslinks (ICLs), which covalently link both strands of the double helix together resulting in cytotoxicity. ICLs are thought to be processed by proteins from a variety of DNA repair pathways; however, a clear understanding of ICL recognition and repair processing in human cells is lacking. Previously, we found that the high mobility group box 1 (HMGB1) protein bound to triplex-directed psoralen ICLs (TFO-ICLs) in vitro,...

  11. Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells

    Science.gov (United States)

    Ko, Sung-Kyun; Kim, Sung Kuk; Share, Andrew; Lynch, Vincent M.; Park, Jinhong; Namkung, Wan; van Rossom, Wim; Busschaert, Nathalie; Gale, Philip A.; Sessler, Jonathan L.; Shin, Injae

    2014-10-01

    Anion transporters based on small molecules have received attention as therapeutic agents because of their potential to disrupt cellular ion homeostasis. However, a direct correlation between a change in cellular chloride anion concentration and cytotoxicity has not been established for synthetic ion carriers. Here we show that two pyridine diamide-strapped calix[4]pyrroles induce coupled chloride anion and sodium cation transport in both liposomal models and cells, and promote cell death by increasing intracellular chloride and sodium ion concentrations. Removing either ion from the extracellular media or blocking natural sodium channels with amiloride prevents this effect. Cell experiments show that the ion transporters induce the sodium chloride influx, which leads to an increased concentration of reactive oxygen species, release of cytochrome c from the mitochondria and apoptosis via caspase activation. However, they do not activate the caspase-independent apoptotic pathway associated with the apoptosis-inducing factor. Ion transporters, therefore, represent an attractive approach for regulating cellular processes that are normally controlled tightly by homeostasis.

  12. Neural stem cells secrete factors facilitating brain regeneration upon constitutive Raf-Erk activation.

    Science.gov (United States)

    Rhee, Yong-Hee; Yi, Sang-Hoon; Kim, Joo Yeon; Chang, Mi-Yoon; Jo, A-Young; Kim, Jinyoung; Park, Chang-Hwan; Cho, Je-Yoel; Choi, Young-Jin; Sun, Woong; Lee, Sang-Hun

    2016-01-01

    The intracellular Raf-Erk signaling pathway is activated during neural stem cell (NSC) proliferation, and neuronal and astrocytic differentiation. A key question is how this signal can evoke multiple and even opposing NSC behaviors. We show here, using a constitutively active Raf (ca-Raf), that Raf-Erk activation in NSCs induces neuronal differentiation in a cell-autonomous manner. By contrast, it causes NSC proliferation and the formation of astrocytes in an extrinsic autocrine/paracrine manner. Thus, treatment of NSCs with medium (CM) conditioned in ca-Raf-transduced NSCs (Raf-CM; RCM) became activated to form proliferating astrocytes resembling radial glial cells (RGCs) or adult-type NSCs. Infusion of Raf-CM into injured mouse brains caused expansion of the NSC population in the subventricular zone, followed by the formation of new neurons that migrated to the damaged site. Our study shows an example how molecular mechanisms dissecting NSC behaviors can be utilized to develop regenerative therapies in brain disorders. PMID:27554447

  13. CCL21 Facilitates Chemoresistance and Cancer Stem Cell-Like Properties of Colorectal Cancer Cells through AKT/GSK-3β/Snail Signals

    Directory of Open Access Journals (Sweden)

    Lin-Lin Lu

    2016-01-01

    Full Text Available Some evidence indicated that chemoresistance associates with the acquisition of cancer stem-like properties. Recent studies suggested that chemokines can promote the chemoresistance and stem cell properties in various cancer cells, while the underling mechanism is still not completely illustrated. In our study, we found that CCL21 can upregulate the expression of P-glycoprotein (P-gp and stem cell property markers such as Bmi-1, Nanog, and OCT-4 in colorectal cancer (CRC HCT116 cells and then improve the cell survival rate and mammosphere formation. Our results suggested that Snail was crucial for CCL21-mediated chemoresistance and cancer stem cell property in CRC cells. Further, we observed that CCL21 treatment increased the protein but not mRNA levels of Snail, which suggested that CCL21 upregulates Snail via posttranscriptional ways. The downstream signals AKT/GSK-3β mediated CCL21 induced the upregulation of Snail due to the fact that CCL21 treatment can obviously phosphorylate both AKT and GSK-3β. The inhibitor of PI3K/Akt, LY294002 significantly abolished CCL21 induced chemoresistance and mammosphere formation of HCT116 cells. Collectively, our results in the present study revealed that CCL21 can facilitate chemoresistance and stem cell property of CRC cells via the upregulation of P-gp, Bmi-1, Nanog, and OCT-4 through AKT/GSK-3β/Snail signals, which suggested a potential therapeutic approach to CRC patients.

  14. CCL21 Facilitates Chemoresistance and Cancer Stem Cell-Like Properties of Colorectal Cancer Cells through AKT/GSK-3β/Snail Signals.

    Science.gov (United States)

    Lu, Lin-Lin; Chen, Xiao-Hui; Zhang, Ge; Liu, Zong-Cai; Wu, Nong; Wang, Hao; Qi, Yi-Fei; Wang, Hong-Sheng; Cai, Shao Hui; Du, Jun

    2016-01-01

    Some evidence indicated that chemoresistance associates with the acquisition of cancer stem-like properties. Recent studies suggested that chemokines can promote the chemoresistance and stem cell properties in various cancer cells, while the underling mechanism is still not completely illustrated. In our study, we found that CCL21 can upregulate the expression of P-glycoprotein (P-gp) and stem cell property markers such as Bmi-1, Nanog, and OCT-4 in colorectal cancer (CRC) HCT116 cells and then improve the cell survival rate and mammosphere formation. Our results suggested that Snail was crucial for CCL21-mediated chemoresistance and cancer stem cell property in CRC cells. Further, we observed that CCL21 treatment increased the protein but not mRNA levels of Snail, which suggested that CCL21 upregulates Snail via posttranscriptional ways. The downstream signals AKT/GSK-3β mediated CCL21 induced the upregulation of Snail due to the fact that CCL21 treatment can obviously phosphorylate both AKT and GSK-3β. The inhibitor of PI3K/Akt, LY294002 significantly abolished CCL21 induced chemoresistance and mammosphere formation of HCT116 cells. Collectively, our results in the present study revealed that CCL21 can facilitate chemoresistance and stem cell property of CRC cells via the upregulation of P-gp, Bmi-1, Nanog, and OCT-4 through AKT/GSK-3β/Snail signals, which suggested a potential therapeutic approach to CRC patients. PMID:27057280

  15. Dengue virus infection induces interferon-lambda1 to facilitate cell migration

    Science.gov (United States)

    Hsu, Yu-Lin; Wang, Mei-Yi; Ho, Ling-Jun; Lai, Jenn-Haung

    2016-01-01

    A marked increase in the rate of dengue virus (DENV) infection has resulted in more than 212 deaths in Taiwan since the beginning of 2015, mostly from fatal outcomes such as dengue hemorrhagic fever and dengue shock syndrome. The pathogenic mechanisms of these fatal manifestations are poorly understood. Cytokines induce an overwhelming immune reaction and thus have crucial roles. Interferon-lambda (IFN-λ), a newly identified IFN subtype, has antiviral effects, but its immunologic effects in DENV infection have not been investigated. In the present study, we show that DENV infection preferentially induced production of IFN-λ1 in human dendritic cells (DCs) and human lung epithelial cells. Virus nonstructural 1 (NS1) glycoprotein was responsible for the effect. DENV-induced production of IFN-λ1 was dependent on signaling pathways involving toll-like receptor (TLR)-3, interferon regulation factor (IRF)-3, and nuclear factor-kappaB (NF-κB). Blocking interaction between IFN-λ1 and its receptor IFN-λR1 through siRNA interference reduced DENV-induced DC migration towards the chemoattractants CCL19 and CCL21, by inhibiting CCR7 expression. Furthermore, IFN-λ1 itself induced CCR7 expression and DC migration. Our study presents the first evidence of the mechanisms and effects of IFN-λ1 induction in DENV-infected DCs and highlights the role of this cytokine in the immunopathogenesis of DENV infection. PMID:27456172

  16. Dengue virus infection induces interferon-lambda1 to facilitate cell migration.

    Science.gov (United States)

    Hsu, Yu-Lin; Wang, Mei-Yi; Ho, Ling-Jun; Lai, Jenn-Haung

    2016-01-01

    A marked increase in the rate of dengue virus (DENV) infection has resulted in more than 212 deaths in Taiwan since the beginning of 2015, mostly from fatal outcomes such as dengue hemorrhagic fever and dengue shock syndrome. The pathogenic mechanisms of these fatal manifestations are poorly understood. Cytokines induce an overwhelming immune reaction and thus have crucial roles. Interferon-lambda (IFN-λ), a newly identified IFN subtype, has antiviral effects, but its immunologic effects in DENV infection have not been investigated. In the present study, we show that DENV infection preferentially induced production of IFN-λ1 in human dendritic cells (DCs) and human lung epithelial cells. Virus nonstructural 1 (NS1) glycoprotein was responsible for the effect. DENV-induced production of IFN-λ1 was dependent on signaling pathways involving toll-like receptor (TLR)-3, interferon regulation factor (IRF)-3, and nuclear factor-kappaB (NF-κB). Blocking interaction between IFN-λ1 and its receptor IFN-λR1 through siRNA interference reduced DENV-induced DC migration towards the chemoattractants CCL19 and CCL21, by inhibiting CCR7 expression. Furthermore, IFN-λ1 itself induced CCR7 expression and DC migration. Our study presents the first evidence of the mechanisms and effects of IFN-λ1 induction in DENV-infected DCs and highlights the role of this cytokine in the immunopathogenesis of DENV infection. PMID:27456172

  17. Rapid membrane disruption by a perforin-like protein facilitates parasite exit from host cells.

    Science.gov (United States)

    Kafsack, Björn F C; Pena, Janethe D O; Coppens, Isabelle; Ravindran, Sandeep; Boothroyd, John C; Carruthers, Vern B

    2009-01-23

    Perforin-like proteins are expressed by many bacterial and protozoan pathogens, yet little is known about their function or mode of action. Here, we describe Toxoplasma perforin-like protein 1 (TgPLP1), a secreted perforin-like protein of the intracellular protozoan pathogen Toxoplasma gondii that displays structural features necessary for pore formation. After intracellular growth, TgPLP1-deficient parasites failed to exit normally, resulting in entrapment within host cells. We show that this defect is due to an inability to rapidly permeabilize the parasitophorous vacuole membrane and host plasma membrane during exit. TgPLP1 ablation had little effect on growth in culture but resulted in a reduction greater than five orders of magnitude of acute virulence in mice. Perforin-like proteins from other intracellular pathogens may play a similar role in microbial egress and virulence. PMID:19095897

  18. The PDZ protein TIP-1 facilitates cell migration and pulmonary metastasis of human invasive breast cancer cells in athymic mice

    International Nuclear Information System (INIS)

    Highlights: ► This study has revealed novel oncogenic functions of TIP-1 in human invasive breast cancer. ► Elevated TIP-1 expression levels in human breast cancers correlate to the disease prognosis. ► TIP-1 knockdown suppressed the cell migration and pulmonary metastasis of human breast cancer cells. ► TIP-1 knockdown suppressed the expression and functionality of motility-related genes. -- Abstract: Tax-interacting protein 1 (TIP-1, also known as Tax1bp3) inhibited proliferation of colon cancer cells through antagonizing the transcriptional activity of beta-catenin. However, in this study, elevated TIP-1 expression levels were detected in human invasive breast cancers. Studies with two human invasive breast cancer cell lines indicated that RNAi-mediated TIP-1 knockdown suppressed the cell adhesion, proliferation, migration and invasion in vitro, and inhibited tumor growth in mammary fat pads and pulmonary metastasis in athymic mice. Biochemical studies showed that TIP-1 knockdown had moderate and differential effects on the beta-catenin-regulated gene expression, but remarkably down regulated the genes for cell adhesion and motility in breast cancer cells. The decreased expression of integrins and paxillin was accompanied with reduced cell adhesion and focal adhesion formation on fibronectin-coated surface. In conclusion, this study revealed a novel oncogenic function of TIP-1 suggesting that TIP-1 holds potential as a prognostic biomarker and a therapeutic target in the treatment of human invasive breast cancers.

  19. A computer-assisted 3D model for analyzing the aggregation of tumorigenic cells reveals specialized behaviors and unique cell types that facilitate aggregate coalescence.

    Directory of Open Access Journals (Sweden)

    Amanda Scherer

    Full Text Available We have developed a 4D computer-assisted reconstruction and motion analysis system, J3D-DIAS 4.1, and applied it to the reconstruction and motion analysis of tumorigenic cells in a 3D matrix. The system is unique in that it is fast, high-resolution, acquires optical sections using DIC microscopy (hence there is no associated photoxicity, and is capable of long-term 4D reconstruction. Specifically, a z-series at 5 μm increments can be acquired in less than a minute on tissue samples embedded in a 1.5 mm thick 3D Matrigel matrix. Reconstruction can be repeated at intervals as short as every minute and continued for 30 days or longer. Images are converted to mathematical representations from which quantitative parameters can be derived. Application of this system to cancer cells from established lines and fresh tumor tissue has revealed unique behaviors and cell types not present in non-tumorigenic lines. We report here that cells from tumorigenic lines and tumors undergo rapid coalescence in 3D, mediated by specific cell types that we have named "facilitators" and "probes." A third cell type, the "dervish", is capable of rapid movement through the gel and does not adhere to it. These cell types have never before been described. Our data suggest that tumorigenesis in vitro is a developmental process involving coalescence facilitated by specialized cells that culminates in large hollow spheres with complex architecture. The unique effects of select monoclonal antibodies on these processes demonstrate the usefulness of the model for analyzing the mechanisms of anti-cancer drugs.

  20. Demonstration of the dorsal pancreatic artery by CTA to facilitate superselective arterial infusion of stem cells into the pancreas

    International Nuclear Information System (INIS)

    Purpose: To investigate the diagnostic performance of 64-section CTA in the detection of dorsal pancreatic artery before interventional therapy for patients with diabetes. Materials and methods: The study was approved by the institutional ethics committee; written informed consent was obtained. Forty-two consecutive patients with diabetes received an experimental treatment of autologous bone marrow-derived stem cell transplantation by means of infusion into the dorsal pancreatic artery. All cases underwent abdominal CTA before angiography of pancreatic arteries in order to locate the origin and course of dorsal pancreatic artery. Angiography of coeliac artery, splenic artery, common hepatic artery and superior mesenteric artery were performed both in CTA and DSA. Superselective catheterization of dorsal pancreatic artery was carried out for the infusion of stem cell. Sensitivity, specificity and accuracy for the detection of dorsal pancreatic artery with CTA were calculated using DSA images as the reference standard. Results: Thirty-five and thirty-six dorsal pancreatic arteries were detected by CTA and DSA respectively. Dorsal pancreatic artery was not visualized in either CTA or DSA in 5 patients. The sensitivity, specificity and accuracy for CTA were 94.4%, 83.3% and 92.9%. Conclusion: 64-section CTA is accurate for the detection of dorsal pancreatic artery. It may be useful for the facilitation of superselective arterial infusion of stem cells to pancreas.

  1. Mast cells facilitate local VEGF release as an early event in the pathogenesis of postoperative peritoneal adhesions.

    LENUS (Irish Health Repository)

    Cahill, Ronan A

    2012-02-03

    BACKGROUND: Peritoneal injury sustained at laparotomy may evoke local inflammatory responses that result in adhesion formation. Peritoneal mast cells are likely to initiate this process, whereas vascular permeability\\/endothelial growth factor (VEGF) may facilitate the degree to which subsequent adhesion formation occurs. METHODS: Mast cell deficient mice (WBB6F1-\\/-), along with their mast cell sufficient counterparts (WBB6F1+\\/+), underwent a standardized adhesion-inducing operation (AIS) with subsequent sacrifice and adhesion assessment 14 days later in a blinded fashion. Additional CD-1 and WBB6F1+\\/+, and WBB6F1-\\/- mice were killed 2, 6, 12, and 24 hours after operation for measurement of VEGF by ELISA in systemic serum and peritoneal lavage fluid. Two further groups of CD-1 mice underwent AIS and received either a single perioperative dose of anti-VEGF monoclonal antibody (10 mug\\/mouse) or a similar volume of IgG isotypic antibody and adhesion formation 2 weeks later was evaluated. RESULTS: WBB6F1-\\/- mice had less adhesions then did their WBB6F1+\\/+ counterparts (median [interquartile range] adhesion score 3[3-3] vs 1.5[1-2] respectively; P < .003). Local VEGF release peaked 6 hours after AIS in both WBB6F1+\\/+ and CD-1 mice whereas levels remained at baseline in WBB6F1-\\/- mice. CD-1 mice treated with a single dose of anti-VEGF therapy during operation had less adhesions than controls (2[1.25-2] vs 3[2.25-3], P = .0002). CONCLUSIONS: Mast cells and VEGF are central to the formation of postoperative intra-abdominal adhesions with mast cells being responsible, either directly or indirectly, for VEGF release into the peritoneal cavity after operation. In tandem with the recent clinical success of anti-VEGF monoclonal antibodies in oncologic practice, our observations suggest an intriguing avenue for research and development of anti-adhesion strategy.

  2. Monocarboxylate transporter 4 facilitates cell proliferation and migration and is associated with poor prognosis in oral squamous cell carcinoma patients.

    Directory of Open Access Journals (Sweden)

    Jiang Zhu

    Full Text Available Monocarboxylate transporter 4 (MCT4 is a cell membrane transporter of lactate. Recent studies have shown that MCT4 is over-expressed in various cancers; however, its role in cancer maintenance and aggressiveness has not been fully demonstrated. This study investigated the role of MCT4 in oral squamous cell carcinoma (OSCC, and found that it is highly expressed in OSCC patients by using immunohistochemistry. Moreover, this over-expression of MCT4 was closely associated with tumor size, TNM classification, lymphatic metastasis, distant metastasis and tumor recurrence, and also poor prognosis. To further study mechanisms of MCT4 in vitro, we used small-interfering RNA to silence its expression in OSCC cell lines. The results showed that knock-down of MCT4 decreased cell proliferation, migration, and invasion. The inhibition of proliferation was associated with down-regulation of p-AKT and p-ERK1/2, while decreased cell migration and invasion may be caused by down-regulation of integrin β4-SRC-FAK and MEK-ERK signaling. Together, these findings provide new insight into the critical role of MCT4 in cell proliferation and metastasis in OSCC.

  3. Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination

    Directory of Open Access Journals (Sweden)

    Watanabe Takafumi

    2012-02-01

    Full Text Available Abstract Background A crucial step in the metastatic spread of ovarian cancer (OC is the adhesion and implantation of tumor cells to the peritoneal mesothelium. In order to study this step in the cascade, we derived a pro-metastatic human ovarian carcinoma cell line (MFOC3 from the non-metastatic FOC3 line. Methods Molecular profiling of the isogeneic lines identified differentially expressed genes, and investigation for a role in dissemination for specific factors was achieved by development of a co-culture adhesion assay utilizing monolayers of human mesothelial cells. Results After murine intraperitoneal inoculation, the FOC3 cell line formed no metastases, but the MFOC3 subline formed metastases in > 80% of SCID mice. MFOC3 cells also adhered 2-3 times more avidly to mesothelial monolayers. This adhesion was inhibited by neutralizing antibodies to IL-1β and enhanced by recombinant IL-1β (p in vitro and significantly reduced metastases in vivo. Immunohistochemical analysis of a cohort of 96 ovarian cancer cases showed that negative IL-1β expression was significantly associated with an improved overall survival rate. Conclusions These results suggest that a IL-1β/β1-integrin axis plays a role in ovarian tumor cell adhesion to mesothelia, a crucial step in ovarian cancer dissemination.

  4. Oxidative Stress Facilitates IFN-γ-Induced Mimic Extracellular Trap Cell Death in A549 Lung Epithelial Cancer Cells.

    Science.gov (United States)

    Lin, Chiou-Feng; Chen, Chia-Ling; Chien, Shun-Yi; Tseng, Po-Chun; Wang, Yu-Chih; Tsai, Tsung-Ting

    2016-01-01

    We previously demonstrated that IFN-γ induces an autophagy-regulated mimic extracellular trap cell death (ETosis) in A549 human lung cancer cells. Regarding reactive oxygen species (ROS) are involved in ETosis, this study investigated the role of oxidative stress. After IFN-γ stimulation, a necrosis-like cell death mimic ETosis occurred accompanied by the inhibition of cell growth, aberrant nuclear staining, and nucleosome release. ROS were generated in a time-dependent manner with an increase in NADPH oxidase component protein expression. STAT1-mediated IFN regulatory factor-1 activation was essential for upregulating ROS production. By genetically silencing p47phox, IFN-γ-induced ROS and mimic ETosis were significantly attenuated. This mechanistic study indicated that ROS may mediate DNA damage followed by histone H3 citrullination. Furthermore, ROS promoted IFN-γ-induced mimic ETosis in cooperation with autophagy. These findings further demonstrate that ROS regulates IFN-γ-induced mimic ETosis in lung epithelial malignancy. PMID:27575372

  5. Flightless I (Drosophila) homolog facilitates chromatin accessibility of the estrogen receptor α target genes in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Kwang Won, E-mail: kwjeong@gachon.ac.kr

    2014-04-04

    Highlights: • H3K4me3 and Pol II binding at TFF1 promoter were reduced in FLII-depleted MCF-7 cells. • FLII is required for chromatin accessibility of the enhancer of ERalpha target genes. • Depletion of FLII causes inhibition of proliferation of MCF-7 cells. - Abstract: The coordinated activities of multiple protein complexes are essential to the remodeling of chromatin structure and for the recruitment of RNA polymerase II (Pol II) to the promoter in order to facilitate the initiation of transcription in nuclear receptor-mediated gene expression. Flightless I (Drosophila) homolog (FLII), a nuclear receptor coactivator, is associated with the SWI/SNF-chromatin remodeling complex during estrogen receptor (ER)α-mediated transcription. However, the function of FLII in estrogen-induced chromatin opening has not been fully explored. Here, we show that FLII plays a critical role in establishing active histone modification marks and generating the open chromatin structure of ERα target genes. We observed that the enhancer regions of ERα target genes are heavily occupied by FLII, and histone H3K4me3 and Pol II binding induced by estrogen are decreased in FLII-depleted MCF-7 cells. Furthermore, formaldehyde-assisted isolation of regulatory elements (FAIRE)-quantitative polymerase chain reaction (qPCR) experiments showed that depletion of FLII resulted in reduced chromatin accessibility of multiple ERα target genes. These data suggest FLII as a key regulator of ERα-mediated transcription through its role in regulating chromatin accessibility for the binding of RNA Polymerase II and possibly other transcriptional coactivators.

  6. Melatonin facilitates adipose-derived mesenchymal stem cells to repair the murine infarcted heart via the SIRT1 signaling pathway.

    Science.gov (United States)

    Han, Dong; Huang, Wei; Li, Xiang; Gao, Lei; Su, Tao; Li, Xiujuan; Ma, Sai; Liu, Tong; Li, Congye; Chen, Jiangwei; Gao, Erhe; Cao, Feng

    2016-03-01

    Mesenchymal stem cells (MSCs)-based therapy provides a promising therapy for the ischemic heart disease (IHD). However, engrafted MSCs are subjected to acute cell death in the ischemic microenvironment, characterized by excessive inflammation and oxidative stress in the host's infarcted myocardium. Melatonin, an indole, which is produced by many organs including pineal gland, has been shown to protect bone marrow MSCs against apoptosis although the mechanism of action remains elusive. Using a murine model of myocardial infarction (MI), this study was designed to evaluate the impact of melatonin on adipose-derived mesenchymal stem cells (AD-MSCs)-based therapy for MI and the underlying mechanism involved with a focus on silent information regulator 1(SIRT1) signaling. Our results demonstrated that melatonin promoted functional survival of AD-MSCs in infarcted heart and provoked a synergetic effect with AD-MSCs to restore heart function. This in vivo effect of melatonin was associated with alleviated inflammation, apoptosis, and oxidative stress in infarcted heart. In vitro studies revealed that melatonin exert cytoprotective effects on AD-MSCs against hypoxia/serum deprivation (H/SD) injury via attenuating inflammation, apoptosis, and oxidative stress. Mechanistically, melatonin enhanced SIRT1 signaling, which was accompanied with the increased expression of anti-apoptotic protein Bcl2, and decreased the expression of Ac-FoxO1, Ac-p53, Ac-NF-ΚB, and Bax. Taken together, our findings indicated that melatonin facilitated AD-MSCs-based therapy in MI, possibly through promoting survival of AD-MSCs via SIRT1 signaling. Our data support the promise of melatonin as a novel strategy to improve MSC-based therapy for IHD, possibly through SIRT1 signaling evocation. PMID:26607398

  7. Flightless I (Drosophila) homolog facilitates chromatin accessibility of the estrogen receptor α target genes in MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Highlights: • H3K4me3 and Pol II binding at TFF1 promoter were reduced in FLII-depleted MCF-7 cells. • FLII is required for chromatin accessibility of the enhancer of ERalpha target genes. • Depletion of FLII causes inhibition of proliferation of MCF-7 cells. - Abstract: The coordinated activities of multiple protein complexes are essential to the remodeling of chromatin structure and for the recruitment of RNA polymerase II (Pol II) to the promoter in order to facilitate the initiation of transcription in nuclear receptor-mediated gene expression. Flightless I (Drosophila) homolog (FLII), a nuclear receptor coactivator, is associated with the SWI/SNF-chromatin remodeling complex during estrogen receptor (ER)α-mediated transcription. However, the function of FLII in estrogen-induced chromatin opening has not been fully explored. Here, we show that FLII plays a critical role in establishing active histone modification marks and generating the open chromatin structure of ERα target genes. We observed that the enhancer regions of ERα target genes are heavily occupied by FLII, and histone H3K4me3 and Pol II binding induced by estrogen are decreased in FLII-depleted MCF-7 cells. Furthermore, formaldehyde-assisted isolation of regulatory elements (FAIRE)-quantitative polymerase chain reaction (qPCR) experiments showed that depletion of FLII resulted in reduced chromatin accessibility of multiple ERα target genes. These data suggest FLII as a key regulator of ERα-mediated transcription through its role in regulating chromatin accessibility for the binding of RNA Polymerase II and possibly other transcriptional coactivators

  8. Praziquantel facilitates IFN-γ-producing CD8+ T cells (Tc1 and IL-17-producing CD8+ T cells (Tc17 responses to DNA vaccination in mice.

    Directory of Open Access Journals (Sweden)

    Qiang Zou

    Full Text Available BACKGROUND: CD8(+ cytotoxic T lymphocytes (CTLs are crucial for eliminating hepatitis B virus (HBV infected cells. DNA vaccination, a novel therapeutic strategy for chronic virus infection, has been shown to induce CTL responses. However, accumulated data have shown that CTLs could not be effectively induced by HBV DNA vaccination. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that praziquantel (PZQ, an anti-schistoma drug, could act as an adjuvant to overcome the lack of potent CTL responses by HBV DNA vaccination in mice. PZQ in combination with HBV DNA vaccination augmented the induction of CD8(+ T cell-dependent and HBV-specific delayed hypersensitivity responses (DTH in C57BL/6 mice. Furthermore, the induced CD8(+ T cells consisted of both Tc1 and Tc17 subtypes. By using IFN-γ knockout (KO mice and IL-17 KO mice, both cytokines were found to be involved in the DTH. The relevance of these findings to HBV immunization was established in HBsAg transgenic mice, in which PZQ also augmented the induction of HBV-specific Tc1 and Tc17 cells and resulted in reduction of HBsAg positive hepatocytes. Adoptive transfer experiments further showed that PZQ-primed CD8(+ T cells from wild type mice, but not the counterpart from IFN-γ KO or IL-17 KO mice, resulted in elimination of HBsAg positive hepatocytes. CONCLUSIONS/SIGNIFICANCE: Our results suggest that PZQ is an effective adjuvant to facilitate Tc1 and Tc17 responses to HBV DNA vaccination, inducing broad CD8(+ T cell-based immunotherapy that breaks tolerance to HBsAg.

  9. Accurate Dna Assembly And Direct Genome Integration With Optimized Uracil Excision Cloning To Facilitate Engineering Of Escherichia Coli As A Cell Factory

    DEFF Research Database (Denmark)

    Cavaleiro, Mafalda; Kim, Se Hyeuk; Nørholm, Morten

    2015-01-01

    Plants produce a vast diversity of valuable compounds with medical properties, but these are often difficult to purify from the natural source or produce by organic synthesis. An alternative is to transfer the biosynthetic pathways to an efficient production host like the bacterium Escherichia co......-excision-based cloning and combining it with a genome-engineering approach to allow direct integration of whole metabolic pathways into the genome of E. coli, to facilitate the advanced engineering of cell factories....

  10. TALENs Facilitate Single-step Seamless SDF Correction of F508del CFTR in Airway Epithelial Submucosal Gland Cell-derived CF-iPSCs.

    Science.gov (United States)

    Suzuki, Shingo; Sargent, R Geoffrey; Illek, Beate; Fischer, Horst; Esmaeili-Shandiz, Alaleh; Yezzi, Michael J; Lee, Albert; Yang, Yanu; Kim, Soya; Renz, Peter; Qi, Zhongxia; Yu, Jingwei; Muench, Marcus O; Beyer, Ashley I; Guimarães, Alessander O; Ye, Lin; Chang, Judy; Fine, Eli J; Cradick, Thomas J; Bao, Gang; Rahdar, Meghdad; Porteus, Matthew H; Shuto, Tsuyoshi; Kai, Hirofumi; Kan, Yuet W; Gruenert, Dieter C

    2016-01-01

    Cystic fibrosis (CF) is a recessive inherited disease associated with multiorgan damage that compromises epithelial and inflammatory cell function. Induced pluripotent stem cells (iPSCs) have significantly advanced the potential of developing a personalized cell-based therapy for diseases like CF by generating patient-specific stem cells that can be differentiated into cells that repair tissues damaged by disease pathology. The F508del mutation in airway epithelial cell-derived CF-iPSCs was corrected with small/short DNA fragments (SDFs) and sequence-specific TALENs. An allele-specific PCR, cyclic enrichment strategy gave ~100-fold enrichment of the corrected CF-iPSCs after six enrichment cycles that facilitated isolation of corrected clones. The seamless SDF-based gene modification strategy used to correct the CF-iPSCs resulted in pluripotent cells that, when differentiated into endoderm/airway-like epithelial cells showed wild-type (wt) airway epithelial cell cAMP-dependent Cl ion transport or showed the appropriate cell-type characteristics when differentiated along mesoderm/hematopoietic inflammatory cell lineage pathways. PMID:26730810

  11. Mouse Pancreas Tissue Slice Culture Facilitates Long-Term Studies of Exocrine and Endocrine Cell Physiology in situ

    OpenAIRE

    Speier, Stephan; Marciniak, Anja; Selck, Claudia; Friedrich, Betty

    2013-01-01

    Studies on pancreatic cell physiology rely on the investigation of exocrine and endocrine cells in vitro. Particularly, in the case of the exocrine tissue these studies have suffered from a reduced functional viability of acinar cells in culture. As a result not only investigations on dispersed acinar cells and isolated acini were limited in their potential, but also prolonged studies on pancreatic exocrine and endocrine cells in an intact pancreatic tissue environment were unfeasible. To ove...

  12. A Burkholderia pseudomallei type III secreted protein, BopE, facilitates bacterial invasion of epithelial cells and exhibits guanine nucleotide exchange factor activity

    OpenAIRE

    M.P. Stevens; Friebel, A; Taylor, L A; Wood, M W; Brown, P. J.; Hardt, W D; Galyov, E E

    2003-01-01

    We report the characterization of BopE, a type III secreted protein that is encoded adjacent to the Burkholderia pseudomallei bsa locus and is homologous to Salmonella enterica SopE/SopE2. Inactivation of bopE impaired bacterial entry into HeLa cells, indicating that BopE facilitates invasion. Consistent with this notion, BopE expressed in eukaryotic cells induced rearrangements in the subcortical actin cytoskeleton, and purified BopE exhibited guanine nucleotide exchange factor activity for ...

  13. The neural cell adhesion molecule-derived peptide FGL facilitates long-term plasticity in the dentate gyrus in vivo

    DEFF Research Database (Denmark)

    Dallérac, Glenn; Zerwas, Meike; Novikova, Tatiana;

    2011-01-01

    beneficial impact on normal memory functioning, as well as to rescue some pathological cognitive impairments. Whether its facilitating impact may be mediated through promoting neuronal plasticity is not known. The present study was therefore designed to test whether FGL modulates the induction and...... maintenance of synaptic plasticity in the dentate gyrus (DG) in vivo. For this, we first assessed the effect of the FGL peptide on synaptic functions at perforant path-dentate gyrus synapses in the anesthetized rat. FGL, or its control inactive peptide, was injected locally 60 min before applying high......-frequency stimulation (HFS) to the medial perforant path. The results suggest that although FGL did not alter basal synaptic transmission, it facilitated both the induction and maintenance of LTP. Interestingly, FGL also modified the heterosynaptic plasticity observed at the neighboring lateral perforant path synapses...

  14. Recombinant adeno-associated viruses (rAAV2) facilitate the intraperitoneal gene delivery to cancer cells

    OpenAIRE

    Malecki, Maciej; PROCZKA, ROBERT; Chorostowska-Wynimko, Joanna; Swoboda, Paweł; DELBANI, ANNA; Pachecka, Jan

    2010-01-01

    Peritoneal dissemination of cancer cells is characteristic of advanced stages of ovarian, breast and lung cancers, and is associated with poor patient survival. The presence of cancer cells in effusions complicates treatment protocols, while cell eradication is seriously limited. One of the novel options available is cancer gene therapy with recombinant adeno-associated viruses. This combination represents the most promising gene delivery vehicles to neoplasmatic cells within serosal cavities...

  15. Specially modified stromal and immune microenvironment in injected bone marrow following intrabone transplantation facilitates allogeneic hematopoietic stem cell engraftment.

    Science.gov (United States)

    Chen, Chen; Su, Yingjun; Chen, Jianwu; Song, Yajuan; Zhuang, Ran; Xiao, Bo; Guo, Shuzhong

    2016-07-01

    For allogeneic hematopoietic stem cell transplantation (HSCT), the first key step is the engraftment of hematopoietic stem cells (HSCs) across the major histocompatibility complex (MHC) barrier. Intrabone bone marrow transplantation (IBBMT) could replace more recipient stromal cells with donor cells and facilitate allogeneic organ transplantation compared with the conventional intravenous approach. However, it remains unknown whether and how IBBMT reconstructs the immune microenvironment for allogeneic HSCs. We explored where the BM microenvironment changes by determining BM stromal cell chimerism and measuring the change in CXCL-12 expression and regulatory T cells in recipient BM. We found that most stromal cells were replaced by allogeneic cells in the injected BM, with higher expression of immune regulatory cytokines (interleukin-10) compared with the contralateral BM and the intravenous group BM. This difference was independent of injury caused by intrabone injection. Consistent with the microenvironment modification, the allogeneic the engraftment rate and reconstitution capacity of HSCs were enhanced in the injected BM compared with the contralateral BM and intravenous group BM. Surgical removal of the injected bone at 7 days rather than 21 days reduced the levels of allogeneic granulocytes and HSCs in the peripheral blood. In conclusion, IBBMT specially modifies stromal cells in the injected BM which provide immune protective cues that improve the engraftment of allogeneic HSCs in an early period. PMID:27090963

  16. Asymmetric Wnt Pathway Signaling Facilitates Stem Cell-Like Divisions via the Nonreceptor Tyrosine Kinase FRK-1 in Caenorhabditis elegans.

    Science.gov (United States)

    Mila, Danielle; Calderon, Adriana; Baldwin, Austin T; Moore, Kelsey M; Watson, McLane; Phillips, Bryan T; Putzke, Aaron P

    2015-11-01

    Asymmetric cell division is critical during development, as it influences processes such as cell fate specification and cell migration. We have characterized FRK-1, a homolog of the mammalian Fer nonreceptor tyrosine kinase, and found it to be required for differentiation and maintenance of epithelial cell types, including the stem cell-like seam cells of the hypodermis. A genomic knockout of frk-1, allele ok760, results in severely uncoordinated larvae that arrest at the L1 stage and have an excess number of lateral hypodermal cells that appear to have lost asymmetry in the stem cell-like divisions of the seam cell lineage. frk-1(ok760) mutants show that there are excess lateral hypodermal cells that are abnormally shaped and smaller in size compared to wild type, a defect that could be rescued only in a manner dependent on the kinase activity of FRK-1. Additionally, we observed a significant change in the expression of heterochronic regulators in frk-1(ok760) mutants. However, frk-1(ok760) mutants do not express late, nonseam hypodermal GFP markers, suggesting the seam cells do not precociously differentiate as adult-hyp7 cells. Finally, our data also demonstrate a clear role for FRK-1 in seam cell proliferation, as eliminating FRK-1 during the L3-L4 transition results in supernumerary seam cell nuclei that are dependent on asymmetric Wnt signaling. Specifically, we observe aberrant POP-1 and WRM-1 localization that is dependent on the presence of FRK-1 and APR-1. Overall, our data suggest a requirement for FRK-1 in maintaining the identity and proliferation of seam cells primarily through an interaction with the asymmetric Wnt pathway. PMID:26358719

  17. A triad of lys12, lys41, arg78 spatial domain, a novel identified heparin binding site on tat protein, facilitates tat-driven cell adhesion.

    Directory of Open Access Journals (Sweden)

    Jing Ai

    Full Text Available Tat protein, released by HIV-infected cells, has a battery of important biological effects leading to distinct AIDS-associated pathologies. Cell surface heparan sulfate protoglycans (HSPGs have been accepted as endogenous Tat receptors, and the Tat basic domain has been identified as the heparin binding site. However, findings that deletion or substitution of the basic domain inhibits but does not completely eliminate Tat-heparin interactions suggest that the basic domain is not the sole Tat heparin binding site. In the current study, an approach integrating computational modeling, mutagenesis, biophysical and cell-based assays was used to elucidate a novel, high affinity heparin-binding site: a Lys12, Lys41, Arg78 (KKR spatial domain. This domain was also found to facilitate Tat-driven β1 integrin activation, producing subsequent SLK cell adhesion in an HSPG-dependent manner, but was not involved in Tat internalization. The identification of this new heparin binding site may foster further insight into the nature of Tat-heparin interactions and subsequent biological functions, facilitating the rational design of new therapeutics against Tat-mediated pathological events.

  18. Polystyrene nanoparticles facilitate the internalization of impermeable biomolecules in non-tumour and tumour cells from colon epithelium

    International Nuclear Information System (INIS)

    Advanced colon cancer has a poor prognosis due to the limited effectiveness of current chemotherapies. Treatment failures may be avoided by the utilization of nanoparticles, which can enhance the effects of antitumor drugs, reduce their side effects and increase their directionality. Polystyrene nanoparticles have shown high biocompatibility and appropriate physicochemical properties and may represent a novel and more effective approach against colon cancer. In the present study, polystyrene nanoparticles were synthesized and fluorescently labelled, analyzing their cell internalization, intracellular localization and capacity to release transported molecules in tumour and non-tumour human colon cell lines (T84 and CCD-18). Flow cytometry and fluorescence microscopy studies demonstrated that polystyrene nanoparticles are an effective vehicle for the intracellular delivery of small molecules into colon epithelium cells. The percentage cell uptake was around 100 % in both T84 and CCD-18 cell lines after only 24 h of exposure and was cell confluence-independent. The polystyrene nanoparticles showed no cytotoxicity in either colon cell line. It was found that small molecules can be efficiently delivered into colon cells by using a disulphide bridge as release strategy. Analysis of the influence of the functionalization of the polystyrene nanoparticles surface on the internalization efficiency revealed some morphological changes in these cells. These results demonstrate that polystyrene nanoparticles may improve the transport of biomolecules into colon cells which could have a potential application in chemotherapeutic treatment against colon cancer

  19. Polystyrene nanoparticles facilitate the internalization of impermeable biomolecules in non-tumour and tumour cells from colon epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Cabeza, Laura [University of Granada, Department of Human Anatomy and Embryology, Institute of Biopathology and Regenerative Medicine (IBIMER) (Spain); Cano-Cortés, Victoria; Rodríguez, María J. [University of Granada, Department of Pharmaceutical and Organic Chemistry (Spain); Vélez, Celia; Melguizo, Consolación, E-mail: melguizo@ugr.es [University of Granada, Department of Human Anatomy and Embryology, Institute of Biopathology and Regenerative Medicine (IBIMER) (Spain); Sánchez-Martín, Rosario M., E-mail: rmsanchez@ugr.es [University of Granada, Department of Pharmaceutical and Organic Chemistry (Spain); Prados, Jose [University of Granada, Department of Human Anatomy and Embryology, Institute of Biopathology and Regenerative Medicine (IBIMER) (Spain)

    2015-01-15

    Advanced colon cancer has a poor prognosis due to the limited effectiveness of current chemotherapies. Treatment failures may be avoided by the utilization of nanoparticles, which can enhance the effects of antitumor drugs, reduce their side effects and increase their directionality. Polystyrene nanoparticles have shown high biocompatibility and appropriate physicochemical properties and may represent a novel and more effective approach against colon cancer. In the present study, polystyrene nanoparticles were synthesized and fluorescently labelled, analyzing their cell internalization, intracellular localization and capacity to release transported molecules in tumour and non-tumour human colon cell lines (T84 and CCD-18). Flow cytometry and fluorescence microscopy studies demonstrated that polystyrene nanoparticles are an effective vehicle for the intracellular delivery of small molecules into colon epithelium cells. The percentage cell uptake was around 100 % in both T84 and CCD-18 cell lines after only 24 h of exposure and was cell confluence-independent. The polystyrene nanoparticles showed no cytotoxicity in either colon cell line. It was found that small molecules can be efficiently delivered into colon cells by using a disulphide bridge as release strategy. Analysis of the influence of the functionalization of the polystyrene nanoparticles surface on the internalization efficiency revealed some morphological changes in these cells. These results demonstrate that polystyrene nanoparticles may improve the transport of biomolecules into colon cells which could have a potential application in chemotherapeutic treatment against colon cancer.

  20. Mouse pancreas tissue slice culture facilitates long-term studies of exocrine and endocrine cell physiology in situ.

    Directory of Open Access Journals (Sweden)

    Anja Marciniak

    Full Text Available Studies on pancreatic cell physiology rely on the investigation of exocrine and endocrine cells in vitro. Particularly, in the case of the exocrine tissue these studies have suffered from a reduced functional viability of acinar cells in culture. As a result not only investigations on dispersed acinar cells and isolated acini were limited in their potential, but also prolonged studies on pancreatic exocrine and endocrine cells in an intact pancreatic tissue environment were unfeasible. To overcome these limitations, we aimed to establish a pancreas tissue slice culture platform to allow long-term studies on exocrine and endocrine cells in the intact pancreatic environment. Mouse pancreas tissue slice morphology was assessed to determine optimal long-term culture settings for intact pancreatic tissue. Utilizing optimized culture conditions, cell specificity and function of exocrine acinar cells and endocrine beta cells were characterized over a culture period of 7 days. We found pancreas tissue slices cultured under optimized conditions to have intact tissue specific morphology for the entire culture period. Amylase positive intact acini were present at all time points of culture and acinar cells displayed a typical strong cell polarity. Amylase release from pancreas tissue slices decreased during culture, but maintained the characteristic bell-shaped dose-response curve to increasing caerulein concentrations and a ca. 4-fold maximal over basal release. Additionally, endocrine beta cell viability and function was well preserved until the end of the observation period. Our results show that the tissue slice culture platform provides unprecedented maintenance of pancreatic tissue specific morphology and function over a culture period for at least 4 days and in part even up to 1 week. This analytical advancement now allows mid -to long-term studies on the cell biology of pancreatic disorder pathogenesis and therapy in an intact surrounding in situ.

  1. Autophagy induction by Bcr-Abl-expressing cells facilitates their recovery from a targeted or nontargeted treatment.

    LENUS (Irish Health Repository)

    Crowley, Lisa C

    2012-01-31

    Although Imatinib has transformed the treatment of chronic myeloid leukemia (CML), it is not curative due to the persistence of resistant cells that can regenerate the disease. We have examined how Bcr-Abl-expressing cells respond to two mechanistically different therapeutic agents, etoposide and Imatinib. We also examined Bcr-Abl expression at low and high levels as elevated expression has been associated with treatment failure. Cells expressing low levels of Bcr-Abl undergo apoptosis in response to the DNA-targeting agent (etoposide), whereas high-Bcr-Abl-expressing cells primarily induce autophagy. Autophagic populations engage a delayed nonapoptotic death; however, sufficient cells evade this and repopulate following the withdrawal of the drug. Non-Bcr-Abl-expressing 32D or Ba\\/F3 cells induce both apoptosis and autophagy in response to etoposide and can recover. Imatinib treatment induces both apoptosis and autophagy in all Bcr-Abl-expressing cells and populations rapidly recover. Inhibition of autophagy with ATG7 and Beclin1 siRNA significantly reduced the recovery of Imatinib-treated K562 cells, indicating the importance of autophagy for the recovery of treated cells. Combination regimes incorporating agents that disrupt Imatinib-induced autophagy would remain primarily targeted and may improve response to the treatment in CML.

  2. A novel Cre recombinase reporter mouse strain facilitates selective and efficient infection of primary immune cells with adenoviral vectors.

    Science.gov (United States)

    Heger, Klaus; Kober, Maike; Rieß, David; Drees, Christoph; de Vries, Ingrid; Bertossi, Arianna; Roers, Axel; Sixt, Michael; Schmidt-Supprian, Marc

    2015-06-01

    Replication-deficient recombinant adenoviruses are potent vectors for the efficient transient expression of exogenous genes in resting immune cells. However, most leukocytes are refractory to efficient adenoviral transduction as they lack expression of the coxsackie/adenovirus receptor (CAR). To circumvent this obstacle, we generated the R26/CAG-CARΔ1(StopF) (where R26 is ROSA26 and CAG is CMV early enhancer/chicken β actin promoter) knock-in mouse line. This strain allows monitoring of in situ Cre recombinase activity through expression of CARΔ1. Simultaneously, CARΔ1 expression permits selective and highly efficient adenoviral transduction of immune cell populations, such as mast cells or T cells, directly ex vivo in bulk cultures without prior cell purification or activation. Furthermore, we show that CARΔ1 expression dramatically improves adenoviral infection of in vitro differentiated conventional and plasmacytoid dendritic cells (DCs), basophils, mast cells, as well as Hoxb8-immortalized hematopoietic progenitor cells. This novel dual function mouse strain will hence be a valuable tool to rapidly dissect the function of specific genes in leukocyte physiology. PMID:25787118

  3. Exploring the Use of MXit: A Cell-Phone Social Network to Facilitate Learning in Distance Education

    Science.gov (United States)

    Makoe, Mpine

    2010-01-01

    The aim of this paper is to investigate the pedagogical suitability of using cell phones to enhance learning through social interaction in distance education. Social interaction was used as a conceptual framework to explore the potential for using "MXit"--a cell-phone instant messaging system--to support and enhance learning for distance education…

  4. Multi-cellular rosettes in the mouse visceral endoderm facilitate the ordered migration of anterior visceral endoderm cells.

    Directory of Open Access Journals (Sweden)

    Georgios Trichas

    2012-02-01

    Full Text Available The visceral endoderm (VE is a simple epithelium that forms the outer layer of the egg-cylinder stage mouse embryo. The anterior visceral endoderm (AVE, a specialised subset of VE cells, is responsible for specifying anterior pattern. AVE cells show a stereotypic migratory behaviour within the VE, which is responsible for correctly orientating the anterior-posterior axis. The epithelial integrity of the VE is maintained during the course of AVE migration, which takes place by intercalation of AVE and other VE cells. Though a continuous epithelial sheet, the VE is characterised by two regions of dramatically different behaviour, one showing robust cell movement and intercalation (in which the AVE migrates and one that is static, with relatively little cell movement and mixing. Little is known about the cellular rearrangements that accommodate and influence the sustained directional movement of subsets of cells (such as the AVE within epithelia like the VE. This study uses an interdisciplinary approach to further our understanding of cell movement in epithelia. Using both wild-type embryos as well as mutants in which AVE migration is abnormal or arrested, we show that AVE migration is specifically linked to changes in cell packing in the VE and an increase in multi-cellular rosette arrangements (five or more cells meeting at a point. To probe the role of rosettes during AVE migration, we develop a mathematical model of cell movement in the VE. To do this, we use a vertex-based model, implemented on an ellipsoidal surface to represent a realistic geometry for the mouse egg-cylinder. The potential for rosette formation is included, along with various junctional rearrangements. Simulations suggest that while rosettes are not essential for AVE migration, they are crucial for the orderliness of this migration observed in embryos. Our simulations are similar to results from transgenic embryos in which Planar Cell Polarity (PCP signalling is disrupted

  5. Oct2 and Obf1 as facilitators of B:T cell collaboration during a humoral immune response

    Directory of Open Access Journals (Sweden)

    Lynn M Corcoran

    2014-03-01

    Full Text Available The Oct2 protein, encoded by the Pou2f2 gene, was originally predicted to act as a DNA binding transcriptional activator of immunoglobulin (Ig in B lineage cells. This prediction flowed from the earlier observation that an 8 bp sequence, the octamer motif, was a highly conserved component of most Ig gene promoters and enhancers, and evidence from over-expression and reporter assays confirmed Oct2-mediated, octamer-dependent gene expression. Complexity was added to the story when Oct1, an independently encoded protein, ubiquitously expressed from the Pou2f 1 gene, was characterised and found to bind to the octamer motif with almost identical specificity, and later, when the co-activator Obf1 (OCA-B, Bob.1, encoded by the Pou2af1 gene, was cloned. Obf1 joins Oct2 (and Oct1 on the DNA of a subset of octamer motifs to enhance their transactivation strength. While these proteins variously carried the mantle of determinants of Ig gene expression in B cells for many years, such a role has not been borne out for them by characterisation of mice lacking functional copies of the genes, either as single or as compound mutants. Instead, we and others have shown that Oct2 and Obf1 are required for B cells to mature fully in vivo, for B cells to respond to the T cell cytokines IL5 and IL4, and for B cells to produce IL6 normally during a T cell dependent immune response. We show here that Oct2 affects Syk gene expression, thus influencing B cell receptor signalling, and that Oct2 loss blocks Slamf1 expression in vivo as a result of incomplete B cell maturation. Upon IL4 signalling, Stat6 up-regulates Obf1, indirectly via Xbp1, to enable plasma cell differentiation. Thus, Oct2 and Obf1 enable B cells to respond normally to antigen receptor signals, to express surface receptors that mediate physical interaction with T cells, or to produce and respond to cytokines that are critical drivers of B cell and T cell differentiation during a humoral immune response.

  6. Increased expression of mitochondrial benzodiazepine receptors following low-level light treatment facilitates enhanced protoporphyrin IX production in glioma-derived cells in vitro

    Science.gov (United States)

    Bisland, S. K.; Hassanali, N. S.; Johnson, C.; Wilson, B. C.

    2007-02-01

    This study investigates whether low level light treatment (LLLT) can enhance the expression of Peripheral-type mitochondrial benzodiazepine receptors (PBRs) on the glioma-derived tumour cell line, CNS-1, and by doing so promote the synthesis of protoporphyrin IX (PpIX) and increase the photodynamic therapy (PDT)-induced cell kill using 5-aminolevulinic acid (ALA). The endogenous photosensitizer, (PpIX) and related metabolites including coproporphyrin III are known to traffic via the PBRs on the outer mitochondrial membrane on their passage into or out of the mitochondria. Astrocyte-derived cells within the brain express PBRs, while neurons express the central-type of benzodiazepine receptor. CNS-1 cells were exposed to a range of differing low-level light protocols immediately prior to PDT. LLLT involved using broad-spectrum light or monochromatic laser light specific to 635 or 905 nm wavelength. Cells (5μ10 5) were exposed to a range of LLLT doses (0, 1 or 5 J/cm2) using a fixed intensity of 10 mW/cm2 and subsequently harvested for cell viability, immunofluorescence or western blot analysis of PBR expression. The amount of PpIX within the cells was determined using chemical extraction techniques. Results confirm the induction of PBR following LLLT is dependent on the dose and wavelength of light used. Broadspectrum light provided the greatest cell kill following PDT, although LLLT with 635 nm or 905 nm also increased cell kill as compared to PDT alone. All LLLT regimens increased PBR expression compared to controls with corresponding increases in PpIX production. These data suggest that by selectively increasing PBR expression in tumour cells, LLLT may facilitate enhanced cell kill using ALA-PDT without damaging surrounding normal brain.

  7. Thioredoxin-like protein 2b facilitates colon cancer cell proliferation and inhibits apoptosis via NF-κB pathway.

    Science.gov (United States)

    Lu, Yuanyuan; Zhao, Xiaodi; Luo, Guanhong; Shen, Gaofei; Li, Kai; Ren, Gui; Pan, Yan; Wang, Xin; Fan, Daiming

    2015-07-28

    Our previous work identified thioredoxin-like protein 2 (Txl-2), a novel thioredoxin family member, as the target of the monoclonal antibody MC3 which can detect colon cancer with high sensitivity and specificity. In the present study, the function of the most abundant isoform Txl-2b in cell proliferation and apoptosis was investigated. Txl-2 overexpression correlated with increased clinical stages. Inhibition of Txl-2b suppressed cell proliferation, induced cell cycle arrest at the G1/S phase, and led to responsiveness to the vincristine-induced apoptosis in SW620 cells. Txl-2b overexpression in LoVo cells had the opposite effect, which was dependent on Trx domain function. In vivo studies validated that Txl-2b expression promoted colon cancer tumorigenesis in nude mice. Further studies revealed that nuclear factor-κB (NF-κB) signaling was activated by Txl-2b. Inhibition of NF-κB activation partly abrogated the pro-proliferation and anti-apoptotic phenotypes mediated by Txl-2b via reduced Cyclin D1, Bcl-2, Bcl-xL and Survivin expression and increased Caspase-3 activation. Overall, our results indicate that Txl-2b expression stimulates cancer cell proliferation, accelerates the cell cycle and contributes to apoptosis resistance in colon cancer and provides a potential therapeutic target for colon cancer treatment. PMID:25555669

  8. Macrophages facilitate coal tar pitch extract-induced tumorigenic transformation of human bronchial epithelial cells mediated by NF-κB.

    Directory of Open Access Journals (Sweden)

    Feifei Feng

    facilitated CTPE-induced tumorigenic transformation of BEAS-2B cells, which may be mediated by NF-κB.

  9. p53 facilitates pRb cleavage in IL-3-deprived cells: novel pro-apoptotic activity of p53.

    OpenAIRE

    Gottlieb, E; Oren, M.

    1998-01-01

    In the interleukin-3 (IL-3)-dependent lymphoid cell line DA-1, functional p53 is required for efficient apoptosis in response to IL-3 withdrawal. Activation of p53 in these cells, by either DNA damage or p53 overexpression, results in a vital growth arrest in the presence of IL-3 and in accelerated apoptosis in its absence. Thus, IL-3 can control the choice between p53-dependent cell-cycle arrest and apoptosis. Here we report that the cross-talk between p53 and IL-3 involves joint control of ...

  10. Communication between corneal epithelial cells and trigeminal neurons is facilitated by purinergic (P2 and glutamatergic receptors.

    Directory of Open Access Journals (Sweden)

    Duane J Oswald

    Full Text Available Previously, we demonstrated that nucleotides released upon mechanical injury to corneal epithelium activate purinergic (P2 receptors resulting in mobilization of a Ca(2+ wave. However, the tissue is extensively innervated and communication between epithelium and neurons is critical and not well understood. Therefore, we developed a co-culture of primary trigeminal neurons and human corneal limbal epithelial cells. We demonstrated that trigeminal neurons expressed a repertoire of P2Yand P2X receptor transcripts and responded to P2 agonists in a concentration-dependent manner. Mechanical injuries to epithelia in the co-cultures elicited a Ca(2+ wave that mobilized to neurons and was attenuated by Apyrase, an ectonucleotidase. To elucidate the role of factors released from each cell type, epithelial and neuronal cells were cultured, injured, and the wound media from one cell type was collected and added to the other cell type. Epithelial wound media generated a rapid Ca(2+ mobilization in neuronal cells that was abrogated in the presence of Apyrase, while neuronal wound media elicited a complex response in epithelial cells. The rapid Ca(2+ mobilization was detected, which was abrogated with Apyrase, but it was followed by Ca(2+ waves that occurred in cell clusters. When neuronal wound media was preincubated with a cocktail of N-methyl-D-aspartate (NMDA receptor inhibitors, the secondary response in epithelia was diminished. Glutamate was detected in the neuronal wound media and epithelial expression of NMDA receptor subunit transcripts was demonstrated. Our results indicate that corneal epithelia and neurons communicate via purinergic and NMDA receptors that mediate the wound response in a highly orchestrated manner.

  11. Tumor-Derived G-CSF Facilitates Neoplastic Growth through a Granulocytic Myeloid-Derived Suppressor Cell-Dependent Mechanism

    OpenAIRE

    Waight, Jeremy D.; Hu, Qiang; Miller, Austin; Liu, Song; Abrams, Scott I.

    2011-01-01

    Myeloid-derived suppressor cells (MDSC) are induced under diverse pathologic conditions, including neoplasia, and suppress innate and adaptive immunity. While the mechanisms by which MDSC mediate immunosuppression are well-characterized, details on how they develop remain less understood. This is complicated further by the fact that MDSC comprise multiple myeloid cell types, namely monocytes and granulocytes, reflecting diverse stages of differentiation and the proportion of these subpopulati...

  12. Hsc70 facilitates TGF-β-induced activation of Smad2/3 in fibroblastic NRK-49F cells.

    Science.gov (United States)

    Ikezaki, Midori; Higashimoto, Natsuki; Matsumura, Ko; Ihara, Yoshito

    2016-08-26

    Heat-shock cognate protein 70 (Hsc70), a molecular chaperone constitutively expressed in the cell, is involved in the regulation of several cellular signaling pathways. In this study, we found that TGF-β-induced phosphorylation and nuclear translocation of Smad2/3 were suppressed in fibroblastic NRK-49F cells treated with small interfering RNA (siRNA) for Hsc70. In the cells underexpressing Hsc70, transcriptional induction of connective tissue growth factor (CTGF), a target gene of the TGF-β signaling, was also suppressed in the early phase of TGF-β stimulation. Upon stimulation with TGF-β, Hsc70 interacted with Smad2/3, suggesting functional interactions of Hsc70 and Smad2/3 for the activation of TGF-β-induced Smad signaling. Although the expression of heat-shock protein 70 (Hsp70) was upregulated in the cells treated with Hsc70 siRNA, TGF-β-induced Smad activation was not affected in the cells overexpressing Hsp70. Collectively, these results indicate that Hsc70, but not Hsp70, supportively regulates TGF-β-induced Smad signaling in NRK-49F cells. PMID:27320859

  13. DSG3 facilitates cancer cell growth and invasion through the DSG3-plakoglobin-TCF/LEF-Myc/cyclin D1/MMP signaling pathway.

    Directory of Open Access Journals (Sweden)

    Yin-Ju Chen

    Full Text Available Desmoglein 3 (DSG3 is a component of the desmosome, which confers strong cell-cell adhesion. Previously, an oncogenic function of DSG3 has been found in head neck cancer (HNC. Here, we investigated how this molecule contributes to the malignant phenotype. Because DSG3 is associated with plakoglobin, we examined whether these phenotypic alterations were mediated through the plakoglobin molecule. Immunoprecipitation and immunofluorescence staining revealed that DSG3 silencing disrupted its interaction with plakoglobin and induced plakoglobin translocation from the cytoplasm to the nucleus. Knockdown of DSG3 significantly increased the interaction of plakoglobin with the transcriptional factor TCF and suppressed the TCF/LEF transcriptional activity. These effects further conferred to reduced expression of the TCF/LEF downstream target genes, including c-myc, cyclin D1, and MMP-7. Functional analyses showed that DSG3 silencing reduced cell growth and arrested cells at G0/G1 phase. Besides, cell migration and invasion abilities were also decreased. These cellular results were confirmed using tumor xenografts in mice, as DSG3 silencing led to the suppressed tumor growth, plakoglobin translocation and reduced expression of TCF/LEF target genes in tumors. Therefore, our study shows that the desmosomal protein DSG3 additionally functions to regulate malignant phenotypes via nuclear signaling. In conclusion, we found that DSG3 functions as an oncogene and facilitates cancer growth and invasion in HNC cells through the DSG3-plakoglobin-TCF/LEF pathway.

  14. Mesenchymal stromal cells: a novel and effective strategy for facilitating engraftment and accelerating hematopoietic recovery after transplantation?

    Science.gov (United States)

    Bernardo, M E; Cometa, A M; Locatelli, F

    2012-03-01

    MSCs are multipotent cells that can be isolated from several human tissues and expanded ex vivo for clinical use. They comprise a heterogeneous population of cells, which, through production of growth factors, cell-to-cell interactions and secretion of matrix proteins, has a role in the regulation of hematopoiesis. In recent years, several experimental studies have shown that MSCs are endowed with immunomodulatory properties and with the capacity to promote graft survival in animal models. In view of these properties, MSCs have been tested in pilot studies aimed at preventing/treating graft rejection and at accelerating recovery after hematopoietic cell transplantation (HCT). The available clinical evidence deriving from these studies indicates that MSC infusion is safe and promising in terms of capacity of preventing graft failure. More debated is the effect of MSCs for what concerns their capacity of accelerating hematopoietic reconstitution after HCT. Whether the favorable effect of MSCs largely depends on the type of transplantation remains also a field of future investigation. Moreover, future researches should be oriented to gain more insights on MSC biological and functional mechanisms relevant for exploiting their use in the modulation of alloreactivity and in the promotion of hematopoietic reconstitution. PMID:21552300

  15. Inducible viral inoculation system with cultured plant cells facilitates a biochemical approach for virus-induced RNA silencing.

    Science.gov (United States)

    Tamai, Atsushi; Dohi, Koji; Mori, Masasi; Meshi, Tetsuo; Ishikawa, Masayuki

    2010-03-01

    An inducible virus infection system was demonstrated to be an efficient protein expression system for inducing synchronous virus vector multiplication in suspension-cultured plant cells. A GFP-tagged tomato mosaic virus (ToMV-GFP) derivative that has a defect in its 130 K protein, a silencing suppressor of ToMV, was synchronously infected to tobacco BY2 cultured cells using this system. In the infection-induced cells, viral RNA was degraded rapidly, and a cytosol extract prepared from the infected cells showed RNA degradation activity specific for ToMV- or GFP-related sequences. In lysate prepared from cells infected by ToMV-GFP carrying the wild-type 130 K protein, sequence-specific RNA degradation activity was suppressed, although siRNA derived from the virus was generated. Furthermore, the 130 K protein interfered with 3'-end methylation of siRNA. The inducible virus infection system may provide a method for biochemical analysis of antiviral RNA silencing and silencing suppression by ToMV. PMID:20035436

  16. Application of Antrodia camphorata Promotes Rat’s Wound Healing In Vivo and Facilitates Fibroblast Cell Proliferation In Vitro

    Directory of Open Access Journals (Sweden)

    Zahra A. Amin

    2015-01-01

    Full Text Available Antrodia camphorata is a parasitic fungus from Taiwan, it has been documented to possess a variety of pharmacological and biological activities. The present study was undertaken to evaluate the potential of Antrodia camphorata ethanol extract to accelerate the rate of wound healing closure and histology of wound area in experimental rats. The safety of Antrodia camphorata was determined in vivo by the acute toxicity test and in vitro by fibroblast cell proliferation assay. The scratch assay was used to evaluate the in vitro wound healing in fibroblast cells and the excision model of wound healing was tested in vivo using four groups of adult Sprague Dawley rats. Our results showed that wound treated with Antrodia camphorata extract and intrasite gel significantly accelerates the rate of wound healing closure than those treated with the vehicle. Wounds dressed with Antrodia camphorata extract showed remarkably less scar width at wound closure and granulation tissue contained less inflammatory cell and more fibroblast compared to wounds treated with the vehicle. Masson’s trichrom stain showed granulation tissue containing more collagen and less inflammatory cell in Antrodia camphorata treated wounds. In conclusion, Antrodia camphorata extract significantly enhanced the rate of the wound enclosure in rats and promotes the in vitro healing through fibroblast cell proliferation.

  17. Rhinovirus 3C protease facilitates specific nucleoporin cleavage and mislocalisation of nuclear proteins in infected host cells.

    Directory of Open Access Journals (Sweden)

    Erin J Walker

    Full Text Available Human Rhinovirus (HRV infection results in shut down of essential cellular processes, in part through disruption of nucleocytoplasmic transport by cleavage of the nucleoporin proteins (Nups that make up the host cell nuclear pore. Although the HRV genome encodes two proteases (2A and 3C able to cleave host proteins such as Nup62, little is known regarding the specific contribution of each. Here we use transfected as well as HRV-infected cells to establish for the first time that 3C protease is most likely the mediator of cleavage of Nup153 during HRV infection, while Nup62 and Nup98 are likely to be targets of HRV2A protease. HRV16 3C protease was also able to elicit changes in the appearance and distribution of the nuclear speckle protein SC35 in transfected cells, implicating it as a key mediator of the mislocalisation of SC35 in HRV16-infected cells. In addition, 3C protease activity led to the redistribution of the nucleolin protein out of the nucleolus, but did not affect nuclear localisation of hnRNP proteins, implying that complete disruption of nucleocytoplasmic transport leading to relocalisation of hnRNP proteins from the nucleus to the cytoplasm in HRV-infected cells almost certainly requires 2A in addition to 3C protease. Thus, a specific role for HRV 3C protease in cleavage and mislocalisation of host cell nuclear proteins, in concert with 2A, is implicated for the first time in HRV pathogenesis.

  18. Contrasuppression in autoimmunity. Abnormal contrasuppression facilitates expression of nephritogenic effector T cells and interstitial nephritis in kdkd mice

    OpenAIRE

    1987-01-01

    We have used the murine model of spontaneous autoimmune interstitial nephritis in kdkd mice to examine the importance of abnormal immunoregulation in the expression of disease. T cells from naive congenic CBA/Ca mice suppress both histologic renal injury in the kdkd strain as well as the DTH reactivity to CBA/Ca renal tubular antigens mediated by lymphocytes from nephritic kdkd mice. These antigen- specific suppressor T cells are Lyt-2+, L3T4+, I-Jk+, genetically dominant and I-Jk restricted....

  19. Kruppel-like factor KLF4 facilitates cutaneous wound healing by promoting fibrocyte generation from myeloid-derived suppressor cells.

    Science.gov (United States)

    Ou, Lingling; Shi, Ying; Dong, Wenqi; Liu, Chunming; Schmidt, Thomas J; Nagarkatti, Prakash; Nagarkatti, Mitzi; Fan, Daping; Ai, Walden

    2015-05-01

    Pressure ulcers (PUs) are serious skin injuries whereby the wound healing process is frequently stalled in the inflammatory phase. Myeloid-derived suppressor cells (MDSCs) accumulate as a result of inflammation and promote cutaneous wound healing by mechanisms that are not fully understood. Recently, MDSCs have been shown to differentiate into fibrocytes, which serve as emerging effector cells that enhance cell proliferation in wound healing. We postulate that in wound healing MDSCs not only execute their immunosuppressive function to regulate inflammation but also stimulate cell proliferation once they differentiate into fibrocytes. In the current study, by using full-thickness and PU mouse models, we found that Kruppel-like factor 4 (KLF4) deficiency resulted in decreased accumulation of MDSCs and fibrocytes, and wound healing was significantly delayed. Conversely, KLF4 activation by the plant-derived product Mexicanin I increased the number of MDSCs and fibrocytes and accelerated the wound healing. Collectively, our study revealed a previously unreported function of MDSCs in cutaneous wound healing and identified Mexicanin I as a potential agent to accelerate PU wound healing. PMID:25581502

  20. Long non-coding RNA FEZF1-AS1 facilitates cell proliferation and migration in colorectal carcinoma

    Science.gov (United States)

    Xu, Qiong; Yang, Minhui; Wang, Dan; Peng, Man; Ding, Yanqing; Wang, Shuang; Zhou, Jun

    2016-01-01

    Long non-coding RNAs (lncRNA) have been shown to play important roles in the development and progression of cancer. Here, we discovered a novel long noncoding RNA (lncRNA) FEZF1 antisense RNA1 (FEZF1-AS1) is markedly upregulated in human primary colorectal carcinoma (CRC) and associated with CRC metastasis and poor prognosis. Moreover, the downregulation of FEZF1-AS1 expression significantly inhibited the CRC cells proliferation, migration and invasiveness, suppressed S-phase entry in vitro, and repressed tumor growth and metastasis in vivo. In contrast, overexpression of FEZF1-AS1 could promote the aggressive behaviors of CRC cells. We further discovered that the downregulation of FEZF1-AS1 reduced its sense-cognate gene FEZF1 mRNA and protein expression in CRC cells. There was a positive correlation between FEZF1-AS1 and FEZF1 expression in CRC. Moreover, FEZF1 knockdown also significantly suppressed CRC cell proliferation, migration, and invasion. Our findings indicate that the dysregulation of FEZF1-AS1 participates in colorectal tumorigenesis and progression, which might be achieved, at least in part, through FEZF1 induction. PMID:26848625

  1. Cyclodextrin-facilitated bioconversion of 17 beta-estradiol by a phenoloxidase from Mucuna pruriens cell cultures

    NARCIS (Netherlands)

    Woerdenbag, H.J.; Pras, N.; Frijlink, H.W.; Lerk, C.F.; Malingré, T.M.

    1990-01-01

    After complexation with beta-cyclodextrin, the phenolic steroid 17 beta-estradiol could be ortho-hydroxylated into a catechol, mainly 4-hydroxyestradiol, by a phenoloxidase from in vitro grown cells of Mucuna pruriens. By complexation with beta-cyclodextrin the solubility of the steroid increased fr

  2. An Efficient Solution-Processed Intermediate Layer for Facilitating Fabrication of Organic Multi-Junction Solar Cells

    DEFF Research Database (Denmark)

    Ning Li; Baran, Derya; Forberich, Karen;

    2013-01-01

    ):poly(styrenesulfonate) (PEDOT:PSS) is demonstrated for series-connected multi-junction organic solar cells (OSCs). Drying at 80 °C in air is sufficient for this solution-processed IML to obtain excellent functionality and reliability, which allow the use of most of high performance donor materials in the tandem structure. An...

  3. Stress-induced filament fragmentation of Calothrix elenkiniiI (Cyanobacteria) is facilitated by death of high-fluorescence cells

    Czech Academy of Sciences Publication Activity Database

    Adamec, František; Kaftan, David; Nedbal, Ladislav

    2005-01-01

    Roč. 41, - (2005), s. 835-839. ISSN 0022-3646 Institutional research plan: CEZ:AV0Z50510513; CEZ:AV0Z6087904 Keywords : cyanobacteria * high-fluorescence cells Subject RIV: EE - Microbiology, Virology Impact factor: 2.502, year: 2005

  4. Tet2 facilitates the derepression of myeloid target genes during CEBPα-induced transdifferentiation of pre-B cells

    DEFF Research Database (Denmark)

    Kallin, Eric M; Rodríguez-Ubreva, Javier; Christensen, Jesper Aagaard;

    2012-01-01

    The methylcytosine hydroxylase Tet2 has been implicated in hematopoietic differentiation and the formation of myeloid malignancies when mutated. An ideal system to study the role of Tet2 in myelopoeisis is CEBPα-induced transdifferentiation of pre-B cells into macrophages. Here we found that CEBP...

  5. The perfect host: a mouse host embryo facilitating more efficient germ line transmission of genetically modified embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Robert A Taft

    Full Text Available There is a continual need to improve efficiency in creating precise genetic modifications in mice using embryonic stem cells (ESCs. We describe a novel approach resulting in 100% germline transmission from competent injected ESCs. We developed an F1 mouse host embryo (Perfect Host, PH that selectively ablates its own germ cells via tissue-specific induction of diphtheria toxin. This approach allows competent microinjected ESCs to fully dominate the germline, eliminating competition for this critical niche in the developing and adult animal. This is in contrast to conventional methods, where competition from host germ cells results in offspring derived from host cells and ESCs, necessitating extensive breeding of chimeras and genotyping to identify germline. The germline transmission process is also complicated by variability in the actual number of ESCs that colonize the germline niche and the proportion that are germline competent. To validate the PH approach we used ESC lines derived from 129 F1, BALB/cByJ, and BTBR backgrounds as well as an iPS line. Resulting chimeric males produced 194 offspring, all paternally derived from the introduced stem cells, with no offspring being derived from the host genome. We further tested this approach using eleven genetically modified C57BL/6N ESC lines (International Knockout Mouse Consortium. ESC germline transmission was observed in 9/11 (82% lines using PH blastocysts, compared to 6/11 (55% when conventional host blastocysts were used. Furthermore, less than 35% (83/240 of mice born in the first litters from conventional chimeras were confirmed to be of ESC-origin. By comparison, 100% (137/137 of the first litter offspring of PH chimeras were confirmed as ESC-derived. Together, these data demonstrate that the PH approach increases the probability of germline transmission and speeds the generation of ESC derived animals from chimeras. Collectively, this approach reduces the time and costs inherent in the

  6. Effect of monosaccharide sugars on LH-induced differentiation and sugar transport facilitator (SLC2A) expression in sheep theca cells in vitro.

    Science.gov (United States)

    Campbell, B K; Kendall, N R; Onions, V; Guo, L; Scaramuzzi, R J

    2014-03-01

    The aim of the present study was to investigate the effects of glucose, galactose and fructose on the LH-induced differentiation and mRNA expression of sugar transport facilitators (SLC2A) by sheep thecal cells derived from small antral follicles cultured under serum-free conditions for 6 days. The dose and type of monosaccharide had a significant effect on LH-induced androstenedione production by theca cells and there was a significant interaction (Pculture were comparable. Pharmacological doses of glucose (16.7 mM) inhibited steroidogenesis (Pcultured with fructose were lower than for cells cultured with either glucose or galactose (Pcultured theca cells. Large doses (16.7 mM) of glucose and fructose, but not galactose, suppressed (P<0.05) SLC2A expression. The results show that glucose and galactose, but not fructose, are readily metabolised via oxidative pathways to support LH-induced differentiation of sheep theca cells. Further work is required to determine the mechanisms resulting in these differences in relation to the established effects of nutrition on reproductive function. PMID:23711112

  7. Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation.

    Science.gov (United States)

    Li, Jasmine; Hardy, Kristine; Phetsouphanh, Chan; Tu, Wen Juan; Sutcliffe, Elissa L; McCuaig, Robert; Sutton, Christopher R; Zafar, Anjum; Munier, C Mee Ling; Zaunders, John J; Xu, Yin; Theodoratos, Angelo; Tan, Abel; Lim, Pek Siew; Knaute, Tobias; Masch, Antonia; Zerweck, Johannes; Brezar, Vedran; Milburn, Peter J; Dunn, Jenny; Casarotto, Marco G; Turner, Stephen J; Seddiki, Nabila; Kelleher, Anthony D; Rao, Sudha

    2016-06-15

    Memory T cells are characterized by their rapid transcriptional programs upon re-stimulation. This transcriptional memory response is facilitated by permissive chromatin, but exactly how the permissive epigenetic landscape in memory T cells integrates incoming stimulatory signals remains poorly understood. By genome-wide ChIP-sequencing ex vivo human CD4(+) T cells, here, we show that the signaling enzyme, protein kinase C theta (PKC-θ) directly relays stimulatory signals to chromatin by binding to transcriptional-memory-responsive genes to induce transcriptional activation. Flanked by permissive histone modifications, these PKC-enriched regions are significantly enriched with NF-κB motifs in ex vivo bulk and vaccinia-responsive human memory CD4(+) T cells. Within the nucleus, PKC-θ catalytic activity maintains the Ser536 phosphorylation on the p65 subunit of NF-κB (also known as RelA) and can directly influence chromatin accessibility at transcriptional memory genes by regulating H2B deposition through Ser32 phosphorylation. Furthermore, using a cytoplasm-restricted PKC-θ mutant, we highlight that chromatin-anchored PKC-θ integrates activating signals at the chromatin template to elicit transcriptional memory responses in human memory T cells. PMID:27149922

  8. Disruptive cell cycle regulation involving epigenetic downregulation of Cdkn2a (p16Ink4a) in early-stage liver tumor-promotion facilitating liver cell regeneration in rats

    International Nuclear Information System (INIS)

    Cell cycle aberration was immunohistochemically examined in relation to preneoplastic liver cell foci expressing glutathione S-transferase placental form (GST-P) at early stages of tumor-promotion in rats with thioacetamide (TAA), a hepatocarcinogen facilitating liver cell regeneration. Immunoexpression of p16Ink4a following exposure to other hepatocarcinogens/promoters and its DNA methylation status were also analyzed during early and late tumor-promotion stages. GST-P+ liver cell foci increased cell proliferation and decreased apoptosis when compared with surrounding liver cells. In concordance with GST-P+ foci, checkpoint proteins at G1/S (p21Cip1, p27Kip1 and p16Ink4a) and G2/M (phospho-checkpoint kinase 1, Cdc25c and phospho-Wee1) were either up- or downregulated. Cellular distribution within GST-P+ foci was either increased or decreased with proteins related to G2-M phase or DNA damage (topoisomerase IIα, phospho-histone H2AX, phospho-histone H3 and Cdc2). In particular, p16Ink4a typically downregulated in GST-P+ foci and regenerative nodules at early tumor-promotion stage with hepatocarcinogens facilitating liver cell regeneration and in neoplastic lesions at late tumor-promotion stage with hepatocarcinogens/promoters irrespective of regenerating potential. Hypermethylation at exon 2 of Cdkn2a was detected at both early- and late-stages. Thus, diverse disruptive expression of G1/S and G2/M proteins, which allows for clonal selection of GST-P+ foci, results in the acquisition of multiple aberrant phenotypes to disrupt checkpoint function. Moreover, increased DNA-damage responses within GST-P+ foci may be the signature of genetic alterations. Intraexonic hypermethylation may be responsible for p16Ink4a-downregulation, which facilitates cell cycle progression in early preneoplastic lesions produced by repeated cell regeneration and late-stage neoplastic lesions irrespective of the carcinogenic mechanism.

  9. The Zen of Facilitation.

    Science.gov (United States)

    Killion, Joellen P.; Simmons, Lynn A.

    1992-01-01

    Distinguishes between training and facilitation, examines the belief system of a facilitator, and shares a process for moving from the familiar mind-set of the trainer to the zen (the practice of seeking the truth) of facilitation. (GLR)

  10. Retinoic acid facilitates inactivated transmissible gastroenteritis virus induction of CD8+ T-cell migration to the porcine gut

    OpenAIRE

    Xiaojuan Chen; Chongzhi Tu; Tao Qin; Liqi Zhu; Yinyan Yin; Qian Yang

    2016-01-01

    The digestive tract is the entry site for transmissible gastroenteritis virus (TGEV). TGEV transmission can be prevented if local immunity is established with increased lymphocytes. The current parenteral mode of vaccination stimulates systemic immunity well, but it does not induce sufficient mucosal immunity. Retinoic acid (RA) plays an important role in the induction of cells that imprint gut-homing molecules. We examined whether RA assist parenteral vaccination of pigs could improve mucosa...

  11. Targeting translesion synthesis to facilitate the eradication of ovarian cancer stem cells by platinum-based therapy

    OpenAIRE

    Srivastava, Amit Kumar; Wang, Qi-En

    2015-01-01

    Understanding the mechanisms by which cancer stem cells (CSCs) survive chemotherapy is essential for the development of new therapies. Recently, we demonstrated that ovarian CSCs survive cisplatin treatment through enhanced expression of DNA polymerase η (Pol η). Identification of micro RNA-93 (miR-93) as the regulator of Pol η provides a novel target to improve the outcome of platinum-based therapy.

  12. Targeting translesion synthesis to facilitate the eradication of ovarian cancer stem cells by platinum-based therapy.

    Science.gov (United States)

    Srivastava, Amit Kumar; Wang, Qi-En

    2016-01-01

    Understanding the mechanisms by which cancer stem cells (CSCs) survive chemotherapy is essential for the development of new therapies. Recently, we demonstrated that ovarian CSCs survive cisplatin treatment through enhanced expression of DNA polymerase η (Pol η). Identification of micro RNA-93 (miR-93) as the regulator of Pol η provides a novel target to improve the outcome of platinum-based therapy. PMID:27308560

  13. Complete Sperm Suppression in Rats With Dienogest Plus Testosterone Undecanoate Is Facilitated Through Apoptosis in Testicular Cells

    OpenAIRE

    Meena, Rekha; Misro, Man Mohan; Ghosh, Debidas

    2013-01-01

    Complete suppression of the production of sperm in rats with dienogest (DNG, 40 mg/kg body weight [bw]) plus testosterone undecanoate (TU, 25 mg/kg bw), every 45 days, was found to be associated with a significant increase in germ cell apoptosis. Caspase 3 activity and expression in testis were simultaneously upregulated. Rise in the activities of caspase 8 and 9 was associated with overexpression of upstream marker proteins from extrinsic (Fas [Fatty acid synthase], FasL [Fatty acid synthase...

  14. HMGB1 enhances immune suppression by facilitating the differentiation and suppressive activity of myeloid-derived suppressor cells

    OpenAIRE

    Parker, Katherine; Sinha, Pratima; Horn, Lucas A.; Clements, Virginia K.; Yang, Huan; Li, Jianhua; Tracey, Kevin J.; Ostrand-Rosenberg, Suzanne

    2014-01-01

    Chronic inflammation often precedes malignant transformation and later drives tumor progression. Likewise, subversion of the immune system plays a role in tumor progression, with tumoral immune escape now well recognized as a crucial hallmark of cancer. Myeloid-derived suppressor cells (MDSC) are elevated in most individuals with cancer, where their accumulation and suppressive activity are driven by inflammation. Thus, MDSC may define an element of the pathogenic inflammatory processes that ...

  15. Path to facilitate the prediction of functional amino acid substitutions in red blood cell disorders--a computational approach.

    Directory of Open Access Journals (Sweden)

    Rajith B

    Full Text Available BACKGROUND: A major area of effort in current genomics is to distinguish mutations that are functionally neutral from those that contribute to disease. Single Nucleotide Polymorphisms (SNPs are amino acid substitutions that currently account for approximately half of the known gene lesions responsible for human inherited diseases. As a result, the prediction of non-synonymous SNPs (nsSNPs that affect protein functions and relate to disease is an important task. PRINCIPAL FINDINGS: In this study, we performed a comprehensive analysis of deleterious SNPs at both functional and structural level in the respective genes associated with red blood cell metabolism disorders using bioinformatics tools. We analyzed the variants in Glucose-6-phosphate dehydrogenase (G6PD and isoforms of Pyruvate Kinase (PKLR & PKM2 genes responsible for major red blood cell disorders. Deleterious nsSNPs were categorized based on empirical rule and support vector machine based methods to predict the impact on protein functions. Furthermore, we modeled mutant proteins and compared them with the native protein for evaluation of protein structure stability. SIGNIFICANCE: We argue here that bioinformatics tools can play an important role in addressing the complexity of the underlying genetic basis of Red Blood Cell disorders. Based on our investigation, we report here the potential candidate SNPs, for future studies in human Red Blood Cell disorders. Current study also demonstrates the presence of other deleterious mutations and also endorses with in vivo experimental studies. Our approach will present the application of computational tools in understanding functional variation from the perspective of structure, expression, evolution and phenotype.

  16. Cdh11 acts as a tumor suppressor in a murine retinoblastoma model by facilitating tumor cell death.

    Directory of Open Access Journals (Sweden)

    Mellone N Marchong

    2010-04-01

    Full Text Available CDH11 gene copy number and expression are frequently lost in human retinoblastomas and in retinoblastomas arising in TAg-RB mice. To determine the effect of Cdh11 loss in tumorigenesis, we crossed Cdh11 null mice with TAg-RB mice. Loss of Cdh11 had no gross morphological effect on the developing retina of Cdh11 knockout mice, but led to larger retinal volumes in mice crossed with TAg-RB mice (p = 0.01. Mice null for Cdh11 presented with fewer TAg-positive cells at postnatal day 8 (PND8 (p = 0.01 and had fewer multifocal tumors at PND28 (p = 0.016, compared to mice with normal Cdh11 alleles. However, tumor growth was faster in Cdh11-null mice between PND8 and PND84 (p = 0.003. In tumors of Cdh11-null mice, cell death was decreased 5- to 10-fold (p<0.03 for all markers, while proliferation in vivo remained unaffected (p = 0.121. Activated caspase-3 was significantly decreased and beta-catenin expression increased in Cdh11 knockdown experiments in vitro. These data suggest that Cdh11 displays tumor suppressor properties in vivo and in vitro in murine retinoblastoma through promotion of cell death.

  17. Retinoic acid facilitates inactivated transmissible gastroenteritis virus induction of CD8(+) T-cell migration to the porcine gut.

    Science.gov (United States)

    Chen, Xiaojuan; Tu, Chongzhi; Qin, Tao; Zhu, Liqi; Yin, Yinyan; Yang, Qian

    2016-01-01

    The digestive tract is the entry site for transmissible gastroenteritis virus (TGEV). TGEV transmission can be prevented if local immunity is established with increased lymphocytes. The current parenteral mode of vaccination stimulates systemic immunity well, but it does not induce sufficient mucosal immunity. Retinoic acid (RA) plays an important role in the induction of cells that imprint gut-homing molecules. We examined whether RA assist parenteral vaccination of pigs could improve mucosal immunity. We demonstrated that elevated numbers of gut-homing CD8(+) T cells (which express α4β7 and CCR9 molecules) were presented in porcine inguinal lymph nodes and were recruited to the small intestine by RA. Intestinal mucosal immunity (IgA titre) and systemic immunity (serum IgG titre) were enhanced by RA. Therefore, we hypothesized that RA could induce DCs to form an immature mucosal phenotype and could recruit them to the small intestinal submucosa. Porcine T-cells expressed β7 integrin and CCR9 receptors and migrated to CCL25 by a mechanism that was dependent of activation by RA-pretreated DCs, rather than direct activation by RA. Together, our results provide powerful evidence that RA can assist whole inactivated TGEV (WI-TGEV) via subcutaneous (s.c.) immunization to generate intestinal immunity, and offer new vaccination strategies against TGEV. PMID:27080036

  18. Leptin facilitates proliferation of hepatic stellate cells through up-regulation of platelet-derived growth factor receptor

    International Nuclear Information System (INIS)

    In the present study, we investigated the effect of leptin on proliferation of hepatic stellate cells (HSCs) in vitro. Proliferation of 3-day cultured rat HSCs was assessed by incorporation of 5-bromo-2'-deoxyuridine (BrdU) into the nuclei. The percentages of BrdU-positive cells were increased in the presence of PDGF-BB (5 ng/ml) for 8 h as expected. Co-incubation with leptin (10-100 nM) potentiates this PDGF-dependent increase in BrdU positive cells in a dose-dependent manner. Messenger RNA for PDGF receptor α and β subunits was increased almost 2- to 3-fold by incubation with leptin for 6 h. Further, pre-incubation with leptin for 6 h enhanced PDGF-induced increases in phospho-p44/42 MAP kinase and phospho-Akt levels in a dose-dependent manner. In the same condition, however, leptin per se did not increase phospho-STAT 3 and phospho-p44/42 MAP kinase levels. Instead, leptin increased phospho-Akt levels in HSCs within 30 min, suggesting that the phosphatidylinositol 3 kinase (PI3K)/Akt pathway is involved in the mechanism by which leptin accelerates the proliferation of HSCs. In conclusion, the present study clearly indicated that leptin potentiates PDGF-dependent proliferative responses of HSCs in vitro

  19. Up-regulation of Hsp27 by ERα/Sp1 facilitates proliferation and confers resistance to apoptosis in human papillary thyroid cancer cells.

    Science.gov (United States)

    Mo, Xiao-Mei; Li, Li; Zhu, Ping; Dai, Yu-Jie; Zhao, Ting-Ting; Liao, Ling-Yao; Chen, George G; Liu, Zhi-Min

    2016-08-15

    17β-estradiol (E2) has been suggested to play a role in the development and progression of papillary thyroid cancer. Heat shock protein 27 (Hsp27) is a member of the Hsp family that is responsible for cell survival under stressful conditions. Previous studies have shown that the 5'-promoter region of Hsp27 gene contains a specificity protein-1 (Spl) and estrogen response element half-site (ERE-half), which contributes to Hsp27 induction by E2 in breast cancer cells. However, it is unclear whether Hsp27 can be up-regulated by E2 and which estrogen receptor (ER) isoform and tethered transcription factor are involved in this regulation in papillary thyroid cancer cells. In the present study, we demonstrated that Hsp27 can be effectively up-regulated by E2 at mRNA and protein levels in human K1 and BCPAP papillary thyroid cancer cells which have more than two times higher level of ERα than that of ERβ. The up-regulation of Hsp27 by E2 is mediated by ERα/Sp1 and ERβ has repressive effect on this ERα/Sp1-mediated up-regulation of Hsp27. Moreover, we showed that the up-regulation of Hsp27 by ERα/Sp1 facilitates proliferation and confers resistance to apoptosis through interaction with procaspase-3. Targeting this pathway may be a potential strategy for therapy of papillary thyroid cancer. PMID:27179757

  20. Culture of low density E. coli cells in alginate-chitosan microcapsules facilitates stress resistance by up-regulating luxS/AI-2 system.

    Science.gov (United States)

    Gao, Meng; Song, Huiyi; Zheng, Huizhen; Ren, Ying; Li, Shen; Liu, Xiudong; Yu, Weiting; Ma, Xiaojun

    2016-05-01

    Entrapped low density cells with culture (ELDCwc) have been proved as a more effective way than direct entrapped high density cells (dEHDC) and free cells to protect probiotics from harsh environment, that is, to improve their stress resistance. The aim of this study was to investigate whether bacterial quorum sensing (QS) facilitated the stress resistance of Escherichia coli in microcapsules by detecting the expression of luxS/AI-2 system. As a result, both the expression of luxS gene and the concentration of autoinducer-2 (AI-2, QS signal molecule) have been discovered higher in ELDCwc than in dEHDC and free cells. Besides that, the luxS mutant E. coli strain was used as a negative control of QS to verify the influence of QS on bacterial stress resistance in microcapsules. The significantly decreased viability of luxS mutant strain in simulated gastric fluid also indicated that the QS played a critical role in protecting microorganisms from severe environment. PMID:26877008

  1. Rapid oriented fibril formation of fish scale collagen facilitates early osteoblastic differentiation of human mesenchymal stem cells.

    Science.gov (United States)

    Matsumoto, Rena; Uemura, Toshimasa; Xu, Zhefeng; Yamaguchi, Isamu; Ikoma, Toshiyuki; Tanaka, Junzo

    2015-08-01

    We studied the effect of fibril formation of fish scale collagen on the osteoblastic differentiation of human mesenchymal stem cells (hMSCs). We found that hMSCs adhered easily to tilapia scale collagen, which remarkably accelerated the early stage of osteoblastic differentiation in hMSCs during in vitro cell culture. Osteoblastic markers such as ALP activity, osteopontin, and bone morphogenetic protein 2 were markedly upregulated when the hMSCs were cultured on a tilapia collagen surface, especially in the early osteoblastic differentiation stage. We hypothesized that this phenomenon occurs due to specific fibril formation of tilapia collagen. Thus, we examined the time course of collagen fibril formation using high-speed atomic force microscopy. Moreover, to elucidate the effect of the orientation of fibril formation on the differentiation of hMSCs, we measured ALP activity of hMSCs cultured on two types of tilapia scale collagen membranes with different degrees of fibril formation. The ALP activity in hMSCs cultured on a fibrous collagen membrane was significantly higher than on a non-fibrous collagen membrane even before adding osteoblastic differentiation medium. These results showed that the degree of the fibril formation of tilapia collagen was essential for the osteoblastic differentiation of hMSCs. PMID:25546439

  2. The ex vivo Microenviroments in MLTC of Poorly Immunogenic Tumor Cells Facilitate Polarization of CD4+CD25+ Regulatory T Cells

    Institute of Scientific and Technical Information of China (English)

    Le Zhou; Hongyan Wang; Juxiang Xiao; Lusheng Si; Yili Wang

    2006-01-01

    CD4+CD25+ regulatory T (TR) cells play an important role in maintaining a balanced peripheral immune system.Recent studies have shown that TR cells may also play a key role in suppressing anti-tumor immune response. In order to investigate the tumor immune microenvironment and its influence on TR polarization, poorly immunogenic tumor cell line D5 (C57BL/6, H-2b), immunogenic tumor cell lines FBL3 (C57BL/6, H-2b) and H22 BALB/c, H-2d) were used to establish the syngeneic/allogeneic, poorly immunogenic/immunogenic mixed lymphocytes-tumor cell culture (MLTC). Our results revealed that the proportion of CD4+CD25+ T cells in MLTC of syngeneic primed splenocytes stimulated with D5 tumor cells was higher than that with H22 cells (0.43% vs 0.044%, and the similar results appeared in allogeneic splenocytes stimulated with D5 tumor cells (0.39% vs 0.04%).The splenocytes stimulated with supernatant from syngeneic MLTC of D5 tumor cells demonstrated higher proportion of CD4+CD25+ cells than that from allogeneic MLTC of D5 tumor cells, and the splenocytes stimulated with supernatant from syngeneic or allogeneic MLTC of H22 tumor cells generated lower proportion of CD4+CD25+ T cells than that of D5 tumor cells. The TGF-β1 and Th2-oriented cytokines (IL-4 and IL-10) were dominated in supernatants of syngeneic MLTC of poorly immunogenic tumor cells. Our results provided useful information for studying the mechanisms underlying tumor immune surveillance as well as for the tumor immunotherapy.

  3. Single-Cell-Genomics-Facilitated Read Binning of Candidate Phylum EM19 Genomes from Geothermal Spring Metagenomes.

    Science.gov (United States)

    Becraft, Eric D; Dodsworth, Jeremy A; Murugapiran, Senthil K; Ohlsson, J Ingemar; Briggs, Brandon R; Kanbar, Jad; De Vlaminck, Iwijn; Quake, Stephen R; Dong, Hailiang; Hedlund, Brian P; Swingley, Wesley D

    2016-02-01

    The vast majority of microbial life remains uncatalogued due to the inability to cultivate these organisms in the laboratory. This "microbial dark matter" represents a substantial portion of the tree of life and of the populations that contribute to chemical cycling in many ecosystems. In this work, we leveraged an existing single-cell genomic data set representing the candidate bacterial phylum "Calescamantes" (EM19) to calibrate machine learning algorithms and define metagenomic bins directly from pyrosequencing reads derived from Great Boiling Spring in the U.S. Great Basin. Compared to other assembly-based methods, taxonomic binning with a read-based machine learning approach yielded final assemblies with the highest predicted genome completeness of any method tested. Read-first binning subsequently was used to extract Calescamantes bins from all metagenomes with abundant Calescamantes populations, including metagenomes from Octopus Spring and Bison Pool in Yellowstone National Park and Gongxiaoshe Spring in Yunnan Province, China. Metabolic reconstruction suggests that Calescamantes are heterotrophic, facultative anaerobes, which can utilize oxidized nitrogen sources as terminal electron acceptors for respiration in the absence of oxygen and use proteins as their primary carbon source. Despite their phylogenetic divergence, the geographically separate Calescamantes populations were highly similar in their predicted metabolic capabilities and core gene content, respiring O2, or oxidized nitrogen species for energy conservation in distant but chemically similar hot springs. PMID:26637598

  4. Fluorescent reporter signals, EGFP and DsRed, encoded in HIV-1 facilitate the detection of productively infected cells and cell-associated viral replication levels

    Directory of Open Access Journals (Sweden)

    Kazutaka eTerahara

    2012-01-01

    Full Text Available Flow cytometric analysis is a reliable and convenient method for investigating molecules at the single cell level. Previously, recombinant human immunodeficiency virus type 1 (HIV-1 strains were constructed that express a fluorescent reporter, either enhanced green fluorescent protein or DsRed, which allow the monitoring of HIV-1-infected cells by flow cytometry. The present study further investigated the potential of these recombinant viruses in terms of whether the HIV-1 fluorescent reporters would be helpful in evaluating viral replication based on fluorescence intensity. When primary CD4+ T cells were infected with recombinant viruses, the fluorescent reporter intensity measured by flow cytometry was associated with the level of CD4 downmodulation and Gag p24 expression in infected cells. Interestingly, some HIV-1-infected cells, in which CD4 was only moderately downmodulated, were reporter-positive but Gag p24-negative. Furthermore, when the activation status of primary CD4+ T cells was modulated by T cell receptor-mediated stimulation, we confirmed the preferential viral production upon strong stimulation and showed that the intensity of the fluorescent reporter within a proportion of HIV-1-infected cells was correlated with the viral replication level. These findings indicate that a fluorescent reporter encoded within HIV-1 is useful for the sensitive detection of productively-infected cells at different stages of infection and for evaluating cell-associated viral replication at the single cell level.

  5. An apoA-I mimetic peptide facilitates off-loading cholesterol from HDL to liver cells through scavenger receptor BI

    Directory of Open Access Journals (Sweden)

    Xuelei Song, Paul Fischer, Xun Chen, Charlotte Burton, Jun Wang

    2009-01-01

    Full Text Available Apolipoprotein A-I (apoA-I mimetic peptides have been pursued as new therapeutic agents for the treatment of atherosclerosis, yet their precise mechanism responsible for atheroprotection remains unclear. Like apoA-I itself, most of these peptides are capable of stimulating cholesterol efflux from macrophages or foam cells, and some of them stimulate lecithin cholesterol acyltransferase (LCAT activity in the reverse cholesterol transport (RCT pathway. However, the ability of mimetic peptides to deliver cholesterol into hepatocytes (off-loading, the last step of the RCT pathway, has not been demonstrated. In this study, we compared a mimetic peptide D-4F to purified apoA-I, to address the role that mimetics play during the off-loading process. Both D-4F and apoA-I formed spherical nano-particles when reconstituted with cholesteryl ester and phospholipids. Compared to apoA-I, D-4F particles were 20 times more efficient in off-loading cholesterol to HepG2 hepatocytes with an apparent Kt (transport of 0.74 μg/mL. Furthermore, D-4F also facilitated cholesteryl ester offloading from HDL particles into HepG2 cells when it was pre-incubated with these HDL particles. Using an inducible HEK293 cell line, we demonstrated that these nano-particles were able to be taken up through SR-BI, a HDL selective receptor. Cholesterol uptake by HepG2 cells was completely blocked by a neutralizing monoclonal antibody against SR-BI, demonstrating that D-4F particles, similar to HDL, specifically off-loaded cholesterol through SR-BI. Overall our data provides evidence that D-4F is capable of mimicking apoA-I to form HDL-like particles, and off-loads cholesterol for catabolism and excretion, thus completing RCT.

  6. IGF-1/IGFBP-1 increases blastocyst formation and total blastocyst cell number in mouse embryo culture and facilitates the establishment of a stem-cell line

    Directory of Open Access Journals (Sweden)

    Hsu Teng-Tsao

    2003-09-01

    Full Text Available Abstract Background Apoptosis occurs frequently for blastocysts cultured in vitro, where conditions are suboptimal to those found in the natural environment. Insulin-like growth factor-1 (IGF-1 plays an important role in preventing apoptosis in the early development of the embryo, as well as in the progressive regulation of organ development. We hypothesize that IGF-1 and its dephosphorylated binding protein (IGFBP-1 may be able to improve embryo culture with an associated reduced cell death, and that the resultant increase in the total cell number of the embryo could increase the chances of establishing an embryonic stem-cell line. Results In vivo fertilized zygotes were cultured in medium containing supplementary IGF-1, or IGFBP-1/IGF-1. The stages of the resultant embryos were evaluated at noon on day five post-hCG injection. The extent of apoptosis and necrosis was evaluated using Annexin V and propidium iodine staining under fluorescent microscopy. The establishment of embryonic stem-cell lines was performed using the hatching blastocysts that were cultured in the presence of IGF-1 or IGFBP-1/IGF-1. The results show that the rate of blastocyst formation in a tissue-culture system in the presence of IGF-1 was 88.7% and IGFBP-1/IGF-1 it was 94.6%, respectively, and that it was significantly greater than the figure for the control group (81.9%. IGFBP-1/IGF-1 also resulted in a higher hatching rate than was the case for the control group (68.8% vs. 48.6% respectively. IGF-1 also increased the number of Annexin V-free and propidium iodine-free blastocysts in culture (86.8% vs. 75.9% respectively. Total cell number of blastocyst in culture was increased by 18.9% for those examples cultured with dephosphorylated IGFBP-1/IGF-1. For subsequent stem-cell culture, the chances of the successful establishment of a stem-cell line was increased for the IGF-1 and IGFBP-1/IGF-1 groups (IGF-1 vs. IGFBP-1/IGF-1 vs. control: 45.8% vs. 59.6% vs. 27

  7. Candida soluble cell wall β-glucan facilitates ovalbumin-induced allergic airway inflammation in mice: Possible role of antigen-presenting cells

    Directory of Open Access Journals (Sweden)

    Tamura Hiroshi

    2009-07-01

    Full Text Available Abstract Background Although fungi have been implicated as initiating/deteriorating factors for allergic asthma, their contributing components have not been fully elucidated. We previously isolated soluble β-glucan from Candida albicans (CSBG (Ohno et al., 2007. In the present study, the effects of CSBG exposure on airway immunopathology in the presence or absence of other immunogenic allergen was investigated in vivo, and their cellular mechanisms were analyzed both in vivo and in vitro. Methods In vivo, ICR mice were divided into 4 experimental groups: vehicle, CSBG (25 μg/animal, ovalbumin (OVA: 2 μg/animal, and CSBG + OVA were repeatedly administered intratracheally. The bronchoalveolar lavage cellular profile, lung histology, levels of cytokines and chemokines in the lung homogenates, the expression pattern of antigen-presenting cell (APC-related molecules in the lung digests, and serum immunoglobulin values were studied. In vitro, the impacts of CSBG (0–12.5 μg/ml on the phenotype and function of immune cells such as splenocytes and bone marrow-derived dendritic cells (BMDCs were evaluated in terms of cell proliferation, the surface expression of APC-related molecules, and OVA-mediated T-cell proliferating activity. Results In vivo, repeated pulmonary exposure to CSBG induced neutrophilic airway inflammation in the absence of OVA, and markedly exacerbated OVA-related eosinophilic airway inflammation with mucus metaplasia in mice, which was concomitant with the amplified lung expression of Th2 cytokines and IL-17A and chemokines related to allergic response. Exposure to CSBG plus OVA increased the number of cells bearing MHC class II with or without CD80 in the lung compared to that of others. In vitro, CSBG significantly augmented splenocyte proliferation in the presence or absence of OVA. Further, CSBG increased the expression of APC-related molecules such as CD80, CD86, and DEC205 on BMDCs and amplified OVA-mediated T-cell

  8. Praziquantel Facilitates IFN-γ-Producing CD8+ T Cells (Tc1) and IL-17-Producing CD8+ T Cells (Tc17) Responses to DNA Vaccination in Mice

    OpenAIRE

    Qiang Zou; Xin Yao; Jin Feng; Zhinan Yin; Richard Flavell; Yanxin Hu; Guoxing Zheng; Jin Jin; Youmin Kang; Bing Wu; Xiaoxuan Liang; Congcong Feng; Hu Liu; Weiyi Li; Xianzheng Wang

    2011-01-01

    BACKGROUND: CD8(+) cytotoxic T lymphocytes (CTLs) are crucial for eliminating hepatitis B virus (HBV) infected cells. DNA vaccination, a novel therapeutic strategy for chronic virus infection, has been shown to induce CTL responses. However, accumulated data have shown that CTLs could not be effectively induced by HBV DNA vaccination. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that praziquantel (PZQ), an anti-schistoma drug, could act as an adjuvant to overcome the lack of potent CTL res...

  9. Visual explorer facilitator's guide

    CERN Document Server

    Palus, Charles J

    2010-01-01

    Grounded in research and practice, the Visual Explorer™ Facilitator's Guide provides a method for supporting collaborative, creative conversations about complex issues through the power of images. The guide is available as a component in the Visual Explorer Facilitator's Letter-sized Set, Visual Explorer Facilitator's Post card-sized Set, Visual Explorer Playing Card-sized Set, and is also available as a stand-alone title for purchase to assist multiple tool users in an organization.

  10. Training facilitators and supervisors

    DEFF Research Database (Denmark)

    Kjær, Louise Binow; O Connor, Maja; Krogh, Kristian;

    At the Master’s program in Medicine at Aarhus University, Denmark, we have developed a faculty development program for facilitators and supervisors in 4 progressing student modules in communication, cooperation, and leadership. 1) A course for module 1 and 3 facilitators inspired by the apprentic...

  11. Vascular endothelial cells facilitated HCC invasion and metastasis through the Akt and NF-κB pathways induced by paracrine cytokines

    OpenAIRE

    Wang, Yao-Hui; Dong, Yin-Ying; Wang, Wei-Min; Xie, Xiao-Ying; Wang, Zhi-Ming; Chen, Rong-xin; Chen, Jie; Gao, Dong-Mei; Cui, Jie-Feng; Ren, Zheng-Gang

    2013-01-01

    Background It is well documented that cancer cells secrete angiogenic factors to recruit and sustain tumor vascular networks. However, little is known about the effects of endothelial cells on the behavior of tumor cells. The study here was to determine the roles of endothelial cells in HCC cell growth, migration and invasion. Methods A mixture of highly metastatic MHCC97H cells and HUVEC cells, as well as MHCC97H cells alone were subcutaneously injected into nude mice to observe the effects ...

  12. Facilitation of CRISPR adaptation

    OpenAIRE

    Abedon, Stephen T.

    2011-01-01

    CRISPR systems, as bacterial defenses against phages, logically must display in their functioning a sequence of at least three major steps. These, in order of occurrence, are “facilitation,” adaptation and interference, where the facilitation step is the main issue considered in this commentary. Interference is the blocking of phage infections as mediated in part by CRISPR spacer sequences. Adaptation, at least as narrowly defined, is the acquisition of these spacer sequences by CRISPR loci. ...

  13. Facilitating Knowledge Sharing

    DEFF Research Database (Denmark)

    Holdt Christensen, Peter

    Abstract This paper argues that knowledge sharing can be conceptualized as different situations of exchange in which individuals relate to each other in different ways, involving different rules, norms and traditions of reciprocity regulating the exchange. The main challenge for facilitating...... and the intermediaries regulating the exchange, and facilitating knowledge sharing should therefore be viewed as a continuum of practices under the influence of opportunistic behaviour, obedience or organizational citizenship behaviour. Keywords: Knowledge sharing, motivation, organizational settings, situations...

  14. Coal export facilitation

    International Nuclear Information System (INIS)

    There is a wide range of trade barriers, particularly tariffs, in current and potential coal market. Commonwealth departments in Australia play a crucial role in supporting government industry policies. This article summarises some of more recent activities of the Department of Primary Industries and Energy (DPIE) in facilitating the export of Australian Coals. Coal export facilitation activities are designed to assist the Australian coal industry by directing Commonwealth Government resources towards issues which would be inappropriate or difficult for the industry to address itself

  15. Facilitating leadership team communication

    OpenAIRE

    Hedman, Eerika

    2015-01-01

    The purpose of this study is to understand and describe how to facilitate competent communication in leadership teamwork. Grounded in the premises of social constructionism and informed by such theoretical frameworks as coordinated management of meaning theory (CMM), dialogic organization development (OD), systemic-constructionist leadership, communication competence, and reflexivity, this study seeks to produce further insights into understanding leadership team communicati...

  16. From Teaching to Facilitation

    DEFF Research Database (Denmark)

    de Graaff, Erik

    2013-01-01

    A shift from teaching to learning is characteristic of the introduction of Problem Based Learning (PBL) in an existing school. As a consequence the teaching staff has to be trained in skills like facilitating group work and writing cases. Most importantly a change in thinking about teaching and...

  17. STAT6 Transcription Factor Is a Facilitator of the Nuclear Receptor PPARγ-Regulated Gene Expression in Macrophages and Dendritic Cells

    OpenAIRE

    Szanto, Attila; Balint, Balint L.; Nagy, Zsuzsanna S.; Barta, Endre; Dezso, Balazs; Pap, Attila; Szeles, Lajos; Poliska, Szilard; Oros, Melinda; Ronald M. Evans; Barak, Yaacov; Schwabe, John; Nagy, Laszlo

    2010-01-01

    Summary Peroxisome proliferator-activated receptor γ (PPARγ) is a lipid-activated transcription factor regulating lipid metabolism and inflammatory response in macrophages and dendritic cells (DCs). These immune cells exposed to distinct inflammatory milieu show cell type specification as a result of altered gene expression. We demonstrate here a mechanism how inflammatory molecules modulate PPARγ signaling in distinct subsets of cells. Proinflammatory molecules inhibited whereas interleukin-...

  18. Disruption of TGF-β signaling prevents the generation of tumor-sensitized T-reg cells and facilitates therapeutic antitumor immunity

    OpenAIRE

    Petrausch, Ulf; Jensen, Shawn; Twitty, Christopher; Poehlein, Christian; Haley, Daniel; Walker, Edwin; Fox, Bernard

    2009-01-01

    Regulatory T cells (T-reg) represent a major roadblock to the induction of anti-tumor immunity through vaccine approaches. TGF-β is a cytokine implicated in the generation and maintenance of T-reg cells, as well as their suppressive function. These experiments examined whether the generation of tumor-sensitized T-reg cells was TGF-β dependent and evaluated whether TGF-β produced by T-reg cells blocked the priming of tumor-specific T cells in vaccinated reconstituted-lymphopenic mice (RLM). We...

  19. Wisp2/CCN5 up-regulated in the central nervous system of GM3-only mice facilitates neurite formation in Neuro2a cells via integrin-Akt signaling

    Energy Technology Data Exchange (ETDEWEB)

    Ohkawa, Yuki, E-mail: tomilbio@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Ohmi, Yuhsuke, E-mail: ooumi82@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Tajima, Orie, E-mail: oriet@isc.chubu.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto-cho, Kasugai 487-8501 (Japan); Yamauchi, Yoshio, E-mail: yyoshio@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Furukawa, Keiko, E-mail: keikofu@isc.chubu.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto-cho, Kasugai 487-8501 (Japan); Furukawa, Koichi, E-mail: koichi@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan)

    2011-08-05

    Highlights: {yields} Wisp2/CCN5 was up-regulated in nervous tissues of GM3-only mutant mice. {yields} Wisp2/CCN5 was found in neurons more strongly in the mutant mice. {yields} Wisp2/CCN5 induces Akt phosphorylation via integrins and facilitates neurite formation. {yields} Wisp2/CCN5 conferred resistance to H{sub 2}O{sub 2}-induced apoptosis. {yields} Up-regulation of Wisp2/CCN5 in GM3-only mice seemed for protection of brains from neurodegeneration. -- Abstract: Wisp2/CCN5 belongs to CCN family proteins which are involved in cell proliferation, angiogenesis, tumorigenesis and wound healing. Although a number of studies on the roles of Wisp2/CCN5 in cancers have been reported, no study on the expression and function of Wisp2/CCN5 in the central nervous system has been reported. In this study, we focused on Wisp2/CCN5 that was up-regulated in nervous tissues in GM3-only mice. Over-expression of Wisp2/CCN5 enhanced neurite outgrowth potently after serum withdrawal with increased phosphorylation levels of Akt and ERKs. When cells were cultured with recombinant Wisp2/CCN5 proteins, more and longer neurites were formed than in the controls. Thus, we demonstrated for the first time that Wisp2/CCN5 facilitates neurite formation in a mouse neuroblastoma cell line, Neuro2a. Akt phosphorylation induced by recombinant Wisp2/CCN5 was suppressed after knockdown of integrin {beta}1. Moreover, Wisp2/CCN5-over-expressing cells were resistant to apoptosis induced by H{sub 2}O{sub 2}. These results suggested that secreted Wisp2/CCN5 induces Akt and ERK phosphorylation via integrins, and consequently facilitates neurite formation and conferred resistance to apoptosis. Up-regulation of Wisp2/CCN5 in GM3-only mice should be, therefore, a reaction to protect nervous tissues from neurodegeneration caused by ganglioside deficiency.

  20. Mindfulness for group facilitation

    DEFF Research Database (Denmark)

    Adriansen, Hanne Kirstine; Krohn, Simon

    2014-01-01

    In this paper, we argue that mindfulness techniques can be used for enhancing the outcome of group performance. The word mindfulness has different connotations in the academic literature. Broadly speaking there is ‘mindfulness without meditation’ or ‘Western’ mindfulness which involves active...... thinking and ‘Eastern’ mindfulness which refers to an open, accepting state of mind, as intended with Buddhist-inspired techniques such as meditation. In this paper, we are interested in the latter type of mindfulness and demonstrate how Eastern mindfulness techniques can be used as a tool for facilitation....... A brief introduction to the physiology and philosophy of Eastern mindfulness constitutes the basis for the arguments of the effect of mindfulness techniques. The use of mindfulness techniques for group facilitation is novel as it changes the focus from individuals’ mindfulness practice to that of...

  1. Facilitating Knowledge Sharing

    OpenAIRE

    Holdt Christensen, Peter

    2005-01-01

    Abstract This paper argues that knowledge sharing can be conceptualized as different situations of exchange in which individuals relate to each other in different ways, involving different rules, norms and traditions of reciprocity regulating the exchange. The main challenge for facilitating knowledge sharing is to ensure that the exchange is seen as equitable for the parties involved, and by viewing the problems of knowledge sharing as motivational problems situated in different organization...

  2. Single-epitope DNA vaccination prevents exhaustion and facilitates a broad antiviral CD8+ T cell response during chronic viral infection

    DEFF Research Database (Denmark)

    Bartholdy, Christina; Stryhn, Anette; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2004-01-01

    Induction of a monospecific antiviral CD8+ T cell response may pose a risk to the host due to the narrow T cell response induced. At the individual level, this may result in selection of CD8+ T cell escape variants, particularly during chronic viral infection. Second, prior immunization toward a...... single dominant epitope may suppress the response to other viral epitopes, and this may lead to increased susceptibility to reinfection with escape variants circulating in the host population. To address these issues, we induced a memory response consisting solely of monospecific, CD8+ T cells by use of...... DNA vaccines encoding immunodominant epitopes of lymphocytic choriomeningitis virus (LCMV). We analyzed the spectrum of the CD8+ T cell response and the susceptibility to infection in H-2(b) and H-2(d) mice. Priming for a monospecific, CD8+ T cell response did not render mice susceptible to viral...

  3. Mycobacterium avium subsp. paratuberculosis Fibronectin Attachment Protein Facilitates M-Cell Targeting and Invasion through a Fibronectin Bridge with Host Integrins

    OpenAIRE

    Secott, T. E.; Lin, T. L.; Wu, C. C.

    2004-01-01

    Efficient attachment and ingestion of Mycobacterium avium subsp. paratuberculosis by cultured epithelial cells requires the expression of a fibronectin (FN) attachment protein homologue (FAP-P) which mediates FN binding by M. avium subsp. paratuberculosis. Invasion of Peyer's patches by M. avium subsp. paratuberculosis occurs through M cells, which, unlike other intestinal epithelial cells, express integrins on their luminal faces. We sought to determine if the interaction between FAP-P of M....

  4. Turnover of Ia-peptide complexes is facilitated in viable antigen-presenting cells: biosynthetic turnover of Ia vs. peptide exchange.

    OpenAIRE

    Harding, C V; Roof, R W; Unanue, E R

    1989-01-01

    Macrophages and B cells process antigens to produce antigenic peptides that associate with class II major histocompatibility complex molecules (e.g., Ia molecules); these Ia-peptide complexes are recognized by CD4+ T lymphocytes. Processing of the antigen hen egg white lysozyme was inhibited by cycloheximide in peritoneal exudate cells (PECs, largely macrophages), but not in TA3 B-lymphoma cells. The uptake and metabolism of hen egg white lysozyme was largely intact in cycloheximide-treated P...

  5. Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients.

    Science.gov (United States)

    Knights, Ashley J; Nuber, Natko; Thomson, Christopher W; de la Rosa, Olga; Jäger, Elke; Tiercy, Jean-Marie; van den Broek, Maries; Pascolo, Steve; Knuth, Alexander; Zippelius, Alfred

    2009-03-01

    The development of effective anti-cancer vaccines requires precise assessment of vaccine-induced immunity. This is often hampered by low ex vivo frequencies of antigen-specific T cells and limited defined epitopes. This study investigates the applicability of modified, in vitro-transcribed mRNA encoding a therapeutically relevant tumour antigen to analyse T cell responses in cancer patients. In this study transfection of antigen presenting cells, by mRNA encoding the tumour antigen NY-ESO-1, was optimised and applied to address spontaneous and vaccine-induced T cell responses in cancer patients. Memory CD8+ T cells from lung cancer patients having detectable humoral immune responses directed towards NY-ESO-1 could be efficiently detected in peripheral blood. Specific T cells utilised a range of different T cell receptors, indicating a polyclonal response. Specific killing of a panel of NY-ESO-1 expressing tumour cell lines indicates recognition restricted to several HLA allelic variants, including a novel HLA-B49 epitope. Using a modified mRNA construct targeting the translated antigen to the secretory pathway, detection of NY-ESO-1-specific CD4+ T cells in patients could be enhanced, which allowed the in-depth characterisation of established T cell clones. Moreover, broad CD8+ and CD4+ T cell responses covering multiple epitopes were detected following mRNA stimulation of patients treated with a recombinant vaccinia/fowlpox NY-ESO-1 vaccine. This approach allows for a precise monitoring of responses to tumour antigens in a setting that addresses the breadth and magnitude of antigen-specific T cell responses, and that is not limited to a particular combination of known epitopes and HLA-restrictions. PMID:18663444

  6. The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8+ T Cells, Facilitating Protection from Local Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Jenny Tosca Thom

    2015-11-01

    Full Text Available Tissue-resident memory T cells (TRM reside in barrier tissues and provide local immediate protective immunity. Here, we show that the salivary gland (SG most-effectively induces CD8+ and CD4+ TRM cells against murine cytomegalovirus (MCMV, which persists in and spreads from this organ. TRM generation depended on local antigen for CD4+, but not CD8+, TRM cells, highlighting major differences in T cell subset-specific demands for TRM development. CMV-specific CD8+ T cells fail to control virus replication upon primary infection in the SG due to CMV-induced MHC I downregulation in glandular epithelial cells. Using intraglandular infection, we challenge this notion and demonstrate that memory CD8+ T cells confer immediate protection against locally introduced MCMV despite active viral immune evasion, owing to early viral tropism to cells that largely withstand MHC I downregulation. Thus, we unravel a yet-unappreciated role for memory CD8+ T cells in protecting mucosal tissues against CMV infection.

  7. Treatment with 5-Aza-2'-Deoxycytidine Induces Expression of NY-ESO-1 and Facilitates Cytotoxic T Lymphocyte-Mediated Tumor Cell Killing

    Science.gov (United States)

    Klar, Agnes S.; Gopinadh, Jakka; Kleber, Sascha; Wadle, Andreas; Renner, Christoph

    2015-01-01

    Background NY-ESO-1 belongs to the cancer/testis antigen (CTA) family and represents an attractive target for cancer immunotherapy. Its expression is induced in a variety of solid tumors via DNA demethylation of the promoter of CpG islands. However, NY-ESO-1 expression is usually very low or absent in some tumors such as breast cancer or multiple myeloma. Therefore, we established an optimized in vitro treatment protocol for up-regulation of NY-ESO-1 expression by tumor cells using the hypomethylating agent 5-aza-2'-deoxycytidine (DAC). Methodology/Principal Findings We demonstrated de novo induction of NY-ESO-1 in MCF7 breast cancer cells and significantly increased expression in U266 multiple myeloma cells. This effect was time- and dose-dependent with the highest expression of NY-ESO-1 mRNA achieved by the incubation of 10 μM DAC for 72 hours. NY-ESO-1 activation was also confirmed at the protein level as shown by Western blot, flow cytometry, and immunofluorescence staining. The detection and quantification of single NY-ESO-1 peptides presented at the tumor cell surface in the context of HLA-A*0201 molecules revealed an increase of 100% and 50% for MCF7 and U266 cells, respectively. Moreover, the enhanced expression of NY-ESO-1 derived peptides at the cell surface was accompanied by an increased specific lysis of MCF7 and U266 cells by HLA-A*0201/NY-ESO-1(157–165) peptide specific chimeric antigen receptor (CAR) CD8+ T cells. In addition, the killing activity of CAR T cells correlated with the secretion of higher IFN-gamma levels. Conclusions/Significance These results indicate that NY-ESO-1 directed immunotherapy with specific CAR T cells might benefit from concomitant DAC treatment. PMID:26447882

  8. Expert and novice facilitated modelling

    DEFF Research Database (Denmark)

    Tavella, Elena; Papadopoulos, Thanos

    2015-01-01

    This paper provides an empirical study based on action research in which expert and novice facilitators in facilitated modelling workshops are compared. There is limited empirical research analysing the differences between expert and novice facilitators. Aiming to address this gap we study the...... behaviour of one expert and two novice facilitators during a Viable System Model workshop. The findings suggest common facilitation patterns in the behaviour of experts and novices. This contrasts literature claiming that experts and novices behave and use their available knowledge differently, and...... facilitation strategies in contexts in which external, expert facilitation is not always possible are also discussed, and limitations of this study are provided....

  9. Facilitation as a teaching strategy : experiences of facilitators

    Directory of Open Access Journals (Sweden)

    E Lekalakala-Mokgele

    2006-09-01

    Full Text Available Changes in nursing education involve the move from traditional teaching approaches that are teacher-centred to facilitation, a student centred approach. The studentcentred approach is based on a philosophy of teaching and learning that puts the learner on centre-stage. The aim of this study was to identify the challenges of facilitators of learning using facilitation as a teaching method and recommend strategies for their (facilitators development and support. A qualitative, explorative and contextual design was used. Four (4 universities in South Africa which utilize facilitation as a teaching/ learning process were identified and the facilitators were selected to be the sample of the study. The main question posed during in-depth group interviews was: How do you experience facilitation as a teaching/learning method?. Facilitators indicated different experiences and emotions when they first had to facilitate learning. All of them indicated that it was difficult to facilitate at the beginning as they were trained to lecture and that no format for facilitation was available. They experienced frustrations and anxieties as a result. The lack of knowledge of facilitation instilled fear in them. However they indicated that facilitation had many benefits for them and for the students. Amongst the ones mentioned were personal and professional growth. Challenges mentioned were the fear that they waste time and that they do not cover the content. It is therefore important that facilitation be included in the training of nurse educators.

  10. Increased expression of long noncoding RNAs LOC100652951 and LOC100506036 in T cells from patients with rheumatoid arthritis facilitates the inflammatory responses.

    Science.gov (United States)

    Lu, Ming-Chi; Yu, Hui-Chun; Yu, Chia-Li; Huang, Hsien-Bin; Koo, Malcolm; Tung, Chien-Hsueh; Lai, Ning-Sheng

    2016-04-01

    The aim of this study was to evaluate whether the presence of aberrantly expressed lncRNAs could promote T cell inflammatory responses in patients with RA. The expression levels of 10 potential aberrantly expressed lncRNAs were evaluated in T cells from 39 patients with RA and 17 controls using real-time reverse transcription polymerase chain reaction. The aberrantly expressed lncRNAs were measured in Jurkat cells co-cultured with or without ionomycin and phorbol 12-myristate 13-acetate. Transfection studies using small interfering RNA (siRNA) were conducted for biological functions, and microarray analysis was performed to search for target genes of specific lncRNAs. We confirmed that the expression levels of LOC100652951 and LOC100506036 were higher in RA T cells compared with controls. RA patients treated with biologic agents had lower expression levels of LOC100652951, and female RA patients had lower LOC100506036 expression levels after multivariate analysis. After activation, the expression levels of LOC100506036, but not LOC100652951, increased in Jurkat cells. Transfection of siRNA targeting LOC100506036 inhibited interferon gamma production and the expression of nuclear factor of activated T cells in activated Jurkat cells. After the microarray analysis with validation, inhibition of LOC100506036 expression by siRNA leaded to the decreased expression of sphingomyelin phosphodiesterase 1 (SMPD1). In conclusion, the expression levels of LOC100652951 and LOC100506036 were increased in RA T cells. Treatment with biologic agents could lower the expression of LOC100652951 in RA T cells. LOC100506036 could regulate the expression of SMPD1 and NFAT1 and could contribute to the inflammatory responses in RA. PMID:26616293

  11. Interleukin-22 as a molecular adjuvant facilitates IL-17-producing CD8+ T cell responses against a HBV DNA vaccine in mice

    OpenAIRE

    Wu, Bing; Zou, Qiang; Hu, Yanxin; Wang, Bin

    2013-01-01

    Interleukin-22 (IL-22) is mainly produced by activated Th1 cells, Th17 cells and NK cells and promotes anti-microbial defense, pro-inflammatory and tissue remodeling responses. However, its potential use as a vaccine adjuvant has not been tested. In this study, we tested if a DNA construct expressing IL-22 (pVAX-IL-22) could be used as a molecular adjuvant to enhance host immune responses induced by HBV DNA vaccination (pcD-S2). After immunizing mice with pcD-S2 combined with pVAX-IL-22, we d...

  12. Facilitated Asymmetric Exclusion

    OpenAIRE

    Gabel, Alan; Krapivsky, P. L.; Redner, S.

    2010-01-01

    We introduce a class of facilitated asymmetric exclusion processes in which particles are pushed by neighbors from behind. For the simplest version in which a particle can hop to its vacant right neighbor only if its left neighbor is occupied, we determine the steady state current and the distribution of cluster sizes on a ring. We show that an initial density downstep develops into a rarefaction wave that can have a jump discontinuity at the leading edge, while an upstep results in a shock w...

  13. Essence: Facilitating Software Innovation

    DEFF Research Database (Denmark)

    Aaen, Ivan

    2008-01-01

      This paper suggests ways to facilitate creativity and innovation in software development. The paper applies four perspectives – Product, Project, Process, and People –to identify an outlook for software innovation. The paper then describes a new facility–Software Innovation Research Lab (SIRL......) – and a new method concept for software innovation – Essence – based on views, modes, and team roles. Finally, the paper reports from an early experiment using SIRL and Essence and identifies further research....

  14. Bumetanide hyperpolarizes Madin-Darby canine kidney cells and enhances cellular gentamicin uptake via elevating cytosolic Ca2+ thus facilitating intermediate conductance Ca2+-activated potassium channels

    OpenAIRE

    Wang, Tian; Yang, Yu-Qin; Karasawa, Takatoshi; Wang, Qi; Phillips, Amanda; Guan, Bing-Cai; Ma, Ke-Tao; Jiang, Meiyan; Xie, Ding-Hua; Peter S. Steyger; Jiang, Zhi-Gen

    2013-01-01

    Loop diuretics such as bumetanide and furosemide enhance aminoglycoside ototoxicity when co-administered to patients and animal models. The underlying mechanism(s) is poorly understood. We investigated the effect of these diuretics on cellular uptake of aminoglycosides, using Texas Red-tagged gentamicin (GTTR), and intracellular/whole-cell recordings of Madin-Darby Canine kidney (MDCK) cells. We found that bumetanide and furosemide concentration-dependently enhanced cytoplasmic GTTR fluoresce...

  15. An automated approach to improve efficacy in detecting residual malignant cancer cell for facilitating prognostic assessment of leukemia: an initial study

    Science.gov (United States)

    Qiu, Yuchen; Lu, Xianglan; Tan, Maxine; Li, Shibo; Liu, Hong; Zheng, Bin

    2015-03-01

    The purpose of this study is to investigate the feasibility of applying automatic interphase FISH cells analysis method for detecting the residual malignancy of post chemotherapy leukemia patients. In the experiment, two clinical specimens with translocation between chromosome No. 9 and 22 or No. 11 and 14 were selected from the patients underwent leukemia diagnosis and treatment. The entire slide of each specimen was first digitalized by a commercial fluorescent microscope using a 40× objective lens. Then, the scanned images were processed by a computer-aided detecting (CAD) scheme to identify the analyzable FISH cells, which is accomplished by applying a series of features including the region size, Brenner gradient and maximum intensity. For each identified cell, the scheme detected and counted the number of the FISH signal dots inside the nucleus, using the adaptive threshold of the region size and distance of the labeled FISH dots. The results showed that the new CAD scheme detected 8093 and 6675 suspicious regions of interest (ROI) in two specimens, among which 4546 and 3807 ROI contain analyzable interphase FISH cell. In these analyzable ROIs, CAD selected 334 and 405 residual malignant cancer cells, which is substantially more than those visually detected in a cytogenetic laboratory of our medical center (334 vs. 122, 405 vs. 160). This investigation indicates that an automatic interphase FISH cell scanning and CAD method has the potential to improve the accuracy and efficiency of the prognostic assessment for leukemia and other genetic related cancer patients in the future.

  16. Interleukin-22 as a molecular adjuvant facilitates IL-17-producing CD8+ T cell responses against a HBV DNA vaccine in mice.

    Science.gov (United States)

    Wu, Bing; Zou, Qiang; Hu, Yanxin; Wang, Bin

    2013-10-01

    Interleukin-22 (IL-22) is mainly produced by activated Th1 cells, Th17 cells and NK cells and promotes anti-microbial defense, pro-inflammatory and tissue remodeling responses. However, its potential use as a vaccine adjuvant has not been tested. In this study, we tested if a DNA construct expressing IL-22 (pVAX-IL-22) could be used as a molecular adjuvant to enhance host immune responses induced by HBV DNA vaccination (pcD-S2). After immunizing mice with pcD-S2 combined with pVAX-IL-22, we didn't find enhancement of HBsAg-specific antibody responses in comparison to mice immunized with pcD-S2 alone. However, there was an enhancement of the level of IL-17 expression in antigen specific CD8(+) cytotoxic T lymphocytes (Tc17). By using CD8 T-cell knockout (KO) and IL-17 KO mice, Tc17 cells were found to be a dominant population driving cytotoxicity. Importantly, there was a correlation between pVAX-IL-22 enhancement of T lymphocytes and a reduction of HBsAg-positive hepatocytes in HBsAg transgenic mice. These results demonstrate that IL-22 might be used as an effective adjuvant to enhance cellular immune responses during HBsAg DNA vaccination since it can induce Tc17 cells to break tolerance in HBsAg transgenic mice. PMID:23941891

  17. Neutrophil-induced transmigration of tumour cells treated with tumour-conditioned medium is facilitated by granulocyte-macrophage colony-stimulating factor.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    OBJECTIVE: To investigate the effect of different cytokines that are present in tumour-conditioned medium on human neutrophil (PMN)-induced tumour cell transmigration. DESIGN: Laboratory study. SETTING: University hospital, Ireland. MATERIAL: Isolated human PMN and cultured human breast tumour cell line, MDA-MB-231. Interventions: Human PMN treated with either tumour-conditioned medium or different media neutralised with monoclonal antibodies (MoAb), and MDA-MB-231 cells were plated on macrovascular and microvascular endothelial monolayers in collagen-coated transwells to assess migration of tumour cells. MAIN OUTCOME MEASURES: Cytokines present in tumour-conditioned medium, PMN cytocidal function and receptor expression, and tumour cell transmigration. RESULTS: tumour-conditioned medium contained high concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8), but not granulocyte colony-stimulating factor (G-CSF) and interleukin 3 (IL-3). Anti-GM-CSF MoAb significantly reduced PMN-induced transmigration of tumour cells treated with tumour-conditioned medium (p < 0.05), whereas anti-VEGF and anti-IL-8 MoAbs did not affect their migration. In addition, anti-GM-CSF MoAb, but not anti-VEGF or anti-IL-8 MoAb, reduced PMN CD11b and CD18 overexpression induced by tumour-conditioned medium (p < 0.05). CONCLUSION: These results indicate that the GM-CSF that is present in tumour-conditioned medium may be involved, at least in part, in alterations in PMN function mediated by the medium and subsequently PMN-induced transmigration of tumour cells.

  18. Functionalization of polycaprolactone scaffolds with hyaluronic acid and β-TCP facilitates migration and osteogenic differentiation of human dental pulp stem cells in vitro.

    Science.gov (United States)

    Jensen, Jonas; Kraft, David Christian Evar; Lysdahl, Helle; Foldager, Casper Bindzus; Chen, Muwan; Kristiansen, Asger Albæk; Rölfing, Jan Hendrik Duedal; Bünger, Cody Eric

    2015-02-01

    In this study, we sought to assess the osteogenic potential of human dental pulp stem cells (DPSCs) on three different polycaprolactone (PCL) scaffolds. The backbone structure of the scaffolds was manufactured by fused deposition modeling (PCL scaffold). The composition and morphology was functionalized in two of the scaffolds. The first underwent thermal induced phase separation of PCL infused into the pores of the PCL scaffold. This procedure resulted in a highly variable micro- and nanostructured porous (NSP), interconnected, and isotropic tubular morphology (NSP-PCL scaffold). The second scaffold type was functionalized by dip-coating the PCL scaffold with a mixture of hyaluronic acid and β-TCP (HT-PCL scaffold). The scaffolds were cylindrical and measured 5 mm in height and 10 mm in diameter. They were seeded with 1×10(6) human DPSCs, a cell type known to express bone-related markers, differentiate into osteoblasts-like cells, and to produce a mineralized bone-like extracellular matrix. DPSCs were phenotypically characterized by flow cytometry for CD90(+), CD73(+), CD105(+), and CD14(-). DNA, ALP, and Ca(2+) assays and real-time quantitative polymerase chain reaction for genes involved in osteogenic differentiation were analyzed on day 1, 7, 14, and 21. Cell viability and distribution were assessed on day 1, 7, 14, and 21 by fluorescent-, scanning electron-, and confocal microscopy. The results revealed that the DPSCs expressed relevant gene expression consistent with osteogenic differentiation. The NSP-PCL and HT-PCL scaffolds promoted osteogenic differentiation and Ca(2+) deposition after 21 days of cultivation. Different gene expressions associated with mature osteoblasts were upregulated in these two scaffold types, suggesting that the methods in which the scaffolds promote osteogenic differentiation, depends on functionalization approaches. However, only the HT-PCL scaffold was also able to support cell proliferation and cell migration resulting in

  19. PaKRP, a cyclin-dependent kinase inhibitor from avocado, may facilitate exit from the cell cycle during fruit growth.

    Science.gov (United States)

    Sabag, Michal; Ben Ari, Giora; Zviran, Tali; Biton, Iris; Goren, Moshe; Dahan, Yardena; Sadka, Avi; Irihimovitch, Vered

    2013-12-01

    Previous studies using 'Hass' avocado cultivar showed that its small-fruit (SF) phenotype is limited by cell number. To explore the molecular components affecting avocado cell production, we isolated four cDNAs encoding: an ICK/KRP protein, known to play cell cycle-regulating roles through modulation of CDK function; two CDK proteins and a D-type cyclin, and monitored their expression patterns, comparing NF (normal fruit) versus SF profiles. The accumulation of PaKRP gradually deceased during growth in both fruit populations. Despite these similarities, SF exhibited higher levels of PaKRP accumulation at early stages of growth. Moreover, in NF, augmented PaKRP expression coincided with a decrease in CDK and PaCYCD1 levels, whereas in SF, enhanced PaKPR expression was coupled with an earlier decline of CDK and PaCYCD1 levels. For both NF and SF, enhanced mesocarp PaKRP transcript accumulation, was associated with elevated abscisic acid (ABA) and ABA catabolites content. Nevertheless, the collective ABA levels, including catabolites, were substantially higher in SF tissues, as compared with NF tissues. Finally, additional expression analysis revealed that in cultured cells, PaKRP could be induced by ABA. Together, our data links PaKRP with exit from the fruit cell cycle and suggest a role for ABA in controlling its expression. PMID:24157204

  20. Inhibition of Connexin 26/43 and Extracellular-Regulated Kinase Protein Plays a Critical Role in Melatonin Facilitated Gap Junctional Intercellular Communication in Hydrogen Peroxide-Treated HaCaT Keratinocyte Cells

    Directory of Open Access Journals (Sweden)

    Hyo-Jung Lee

    2012-01-01

    Full Text Available Though melatonin was known to regulate gap junctional intercellular communication (GJIC in chick astrocytes and mouse hepatocytes, the underlying mechanism by melatonin was not elucidated in hydrogen peroxide- (H2O2- treated HaCaT keratinocyte cells until now. In the current study, though melatonin at 2 mM and hydrogen peroxide (H2O2 at 300 μM showed weak cytotoxicity in HaCaT keratinocyte cells, melatonin significantly suppressed the formation of reactive oxygen species (ROS in H2O2-treated HaCaT cells compared to untreated controls. Also, the scrape-loading dye-transfer assay revealed that melatonin enhances the intercellular communication by introducing Lucifer Yellow into H2O2-treated cells. Furthermore, melatonin significantly enhanced the expression of connexin 26 (Cx26 and connexin 43 (Cx43 at mRNA and protein levels, but not that of connexin 30 (Cx30 in H2O2-treated HaCaT cells. Of note, melatonin attenuated the phosphorylation of extracellular signal-regulated protein kinases (ERKs more than p38 MAPK or JNK in H2O2-treated HaCaT cells. Conversely, ERK inhibitor PD98059 promoted the intercellular communication in H2O2-treated HaCaT cells. Furthermore, combined treatment of melatonin (200 μM and vitamin C (10 μg/mL significantly reduced ROS production in H2O2-treated HaCaT cells. Overall, these findings support the scientific evidences that melatonin facilitates gap junctional intercellular communication in H2O2-treated HaCaT keratinocyte cells via inhibition of connexin 26/43 and ERK as a potent chemopreventive agent.

  1. The passage of cells can improve the detection rate of avian leukosis virus to facilitate the elimination of avian leukosis in chickens

    OpenAIRE

    Wang, Xiuzhen; Wang, Bo; Zhang, Peipei; Cheng, Hegang; Sun, Shuhong

    2013-01-01

    Avian leukosis (AL) is one of the most harmful diseases to the poultry industry in China. The detection of the avian leukosis virus (ALV) p27 antigen plays a decisive role in the elimination of avian leukosis. To explore the influence of passaging cells on the detection rate of the ALV p27 antigen, 21 aseptic anticoagulated blood samples were collected from 21 chickens for which the cloacal swabs were positive for the p27 antigen to inoculate two sets of cell culture plates containing DF1 cel...

  2. Conditional ligands for Asian HLA variants facilitate the definition of CD8+ T-cell responses in acute and chronic viral diseases

    DEFF Research Database (Denmark)

    Chang, Cynthia X L; Tan, Anthony T; Or, Ming Yan;

    2013-01-01

    exchange was accomplished for all variants as demonstrated by an ELISA-based MHC stability assay. HLA tetramers with redirected specificity could detect antigen-specific CD8(+) T-cell responses against human cytomegalovirus, hepatitis B (HBV), dengue virus (DENV), and Epstein-Barr virus (EBV) infections...

  3. Spinal cord hemisection facilitates aromatic L-amino acid decarboxylase cells to produce serotonin in the subchronic but not the chronic phase

    DEFF Research Database (Denmark)

    Azam, Bushra; Wienecke, Jacob; Jensen, Dennis Bo;

    2015-01-01

    Neuromodulators, such as serotonin (5-hydroxytryptamine, 5-HT) and noradrenalin, play an essential role in regulating the motor and sensory functions in the spinal cord. We have previously shown that in the rat spinal cord the activity of aromatic L-amino acid decarboxylase (AADC) cells to produce...

  4. Lipid raft facilitated ligation of K-α1-tubulin by specific antibodies on epithelial cells: Role in pathogenesis of chronic rejection following human lung transplantation

    International Nuclear Information System (INIS)

    Research highlights: → Addition of KAT Abs (+) sera to NHBE culture causes upregulation of growth factors. → Cholesterol depletion causes down regulation of growth factor expression. → Cholesterol depletion is accompanied by loss of membrane bound caveolin. → Thus, we demonstrate lipid raft are critical for efficient ligation of the KAT Abs. -- Abstract: Long term function of human lung allografts is hindered by development of chronic rejection manifested as Bronchiolitis Obliterans Syndrome (BOS). We have previously identified the development of antibodies (Abs) following lung transplantation to K-α1-tubulin (KAT), an epithelial surface gap junction cytoskeletal protein, in patients who develop BOS. However, the biochemical and molecular basis of the interactions and signaling cascades mediated by KAT Abs are yet to be defined. In this report, we investigated the biophysical basis of the epithelial cell membrane surface interaction between KAT and its specific Abs. Towards this, we analyzed the role of the lipid raft-domains in the membrane interactions which lead to cell signaling and ultimately increased growth factor expression. Normal human bronchial epithelial (NHBE) cells, upon specific ligation with Abs to KAT obtained either from the serum of BOS(+) patients or monoclonal KAT Abs, resulted in upregulation of growth factors VEGF, PDGF, and bFGF (6.4 ± 1.1-, 3.2 ± 0.9-, and 3.4 ± 1.1-fold increase, respectively) all of which are important in the pathogenesis of BOS. To define the role for lipid raft in augmenting surface interactions, we analyzed the changes in the growth factor expression pattern upon depletion and enrichment with lipid raft following the ligation of the epithelial cell membranes with Abs specific for KAT. NHBE cells cultured in the presence of β-methyl cyclodextran (βMCD) had significantly reduced growth factor expression (1.3 ± 0.3, vs βMCD untreated being 6.4 ± 1.1-fold increase) upon stimulation with KAT Abs. Depletion

  5. Facilitative root interactions in intercrops

    DEFF Research Database (Denmark)

    Hauggaard-Nielsen, H.; Jensen, E.S.

    2005-01-01

    Facilitation takes place when plants ameliorate the environment of their neighbours, and increase their growth and survival. Facilitation occurs in natural ecosystems as well as in agroecosystems. We discuss examples of facilitative root interactions in intercropped agroecosystems; including...... root architecture, exudation of growth stimulating substances, and biofumigation. Facilitative root interactions are most likely to be of importance in nutrient poor soils and in low-input agroecosystems due to critical interspecific competition for plant growth factors. However, studies from more...

  6. Pyrolysed 3D-Carbon Scaffolds Induce Spontaneous Differentiation of Human Neural Stem Cells and Facilitate Real-Time Dopamine Detection

    DEFF Research Database (Denmark)

    Amato, Letizia; Heiskanen, Arto; Caviglia, Claudia;

    2014-01-01

    carbon material induces spontaneous hNSC differentiation into mature dopamine-producing neurons and the 3D-topography promotes neurite elongation. In the presence and absence of DF, ≈73–82% of the hNSCs obtain dopaminergic properties on pyrolysed carbon, a to-date unseen efficiency in both two......Structurally patterned pyrolysed three-dimensional carbon scaffolds (p3Dcarbon) are fabricated and applied for differentiation of human neural stem cells (hNSCs) developed for cell replacement therapy and sensing of released dopamine. In the absence of differentiation factors (DF) the pyrolysed......-dimensional (2D) and 3D environment. Due to conductive properties and 3D environment, the p3D-carbon serves as a neurotransmitter trap, enabling electrochemical detection of a signifi cantly larger dopamine fraction released by the hNSC derived neurons than on conventional 2D electrodes. This is the first study...

  7. Functionalization of Polycaprolactone Scaffolds with Hyaluronic Acid and β-TCP Facilitates Migration and Osteogenic Differentiation of Human Dental Pulp Stem Cells In Vitro

    OpenAIRE

    Jensen, Jonas; Kraft, David Christian Evar; Lysdahl, Helle; Foldager, Casper Bindzus; Chen, Muwan; Kristiansen, Asger Albæk; Rölfing, Jan Hendrik Duedal; Bünger, Cody Eric

    2014-01-01

    In this study, we sought to assess the osteogenic potential of human dental pulp stem cells (DPSCs) on three different polycaprolactone (PCL) scaffolds. The backbone structure of the scaffolds was manufactured by fused deposition modeling (PCL scaffold). The composition and morphology was functionalized in two of the scaffolds. The first underwent thermal induced phase separation of PCL infused into the pores of the PCL scaffold. This procedure resulted in a highly variable micro- and nanostr...

  8. Calpain-1 Regulation of Matrix Metalloprotease 2 Activity in Vascular Smooth Muscle Cells Facilitates age-associated aortic wall Calcification and Fibrosis

    OpenAIRE

    Jiang, Liqun; Zhang, Jing; Monticone, Robert E.; Telljohann, Richard; Wu, James; Wang, Mingyi; Lakatta, Edward G.

    2012-01-01

    Age-associated central arterial wall stiffness is linked to extracellular matrix (ECM) remodeling, including fibrosis and vascular calcification. Angiotensin II induces both matrix metalloproteinase type 2 (MMP2) and calpain-1 expression and activity in the arterial wall. But the role of calpain-1 in MMP2 activation and ECM remodeling remains unknown. Dual histo-immunolabeling demonstrates co-localization of calpain-1 and MMP2 within old rat vascular smooth muscle cells. Over-expression of ca...

  9. Tet2 facilitates the de-repression of myeloid target genes during C/EBPa induced transdifferentiation of pre-B cells

    OpenAIRE

    Kallin, Eric M.; Rodríguez-Ubreva, Javier; Christensen, J esper; Cimmino, Luisa; Aifantis, Iannis; Helin, Kristian; Ballestar, Esteban; Graf, Thomas

    2012-01-01

    The methylcytosine hydroxylase Tet2 has been implicated in hematopoietic differentiation and the formation of myeloid malignancies when mutated. An ideal system to study the role of Tet2 in myelopoeisis is C/EBPa induced transdifferentiation of pre-B cells into macrophages. Here we found that C/EBPa binds to upstream regions of Tet2 and that the gene becomes activated. Tet2 knockdowns impaired the upregulation of macrophage markers as well as phagocytic capacity, suggesting that the enzyme is...

  10. Recursion-based depletion of human immunodeficiency virus-specific naive CD4(+) T cells may facilitate persistent viral replication and chronic viraemia leading to acquired immunodeficiency syndrome.

    Science.gov (United States)

    Tsukamoto, Tetsuo; Yamamoto, Hiroyuki; Okada, Seiji; Matano, Tetsuro

    2016-09-01

    Although antiretroviral therapy has made human immunodeficiency virus (HIV) infection a controllable disease, it is still unclear how viral replication persists in untreated patients and causes CD4(+) T-cell depletion leading to acquired immunodeficiency syndrome (AIDS) in several years. Theorists tried to explain it with the diversity threshold theory in which accumulated mutations in the HIV genome make the virus so diverse that the immune system will no longer be able to recognize all the variants and fail to control the viraemia. Although the theory could apply to a number of cases, macaque AIDS models using simian immunodeficiency virus (SIV) have shown that failed viral control at the set point is not always associated with T-cell escape mutations. Moreover, even monkeys without a protective major histocompatibility complex (MHC) allele can contain replication of a super infected SIV following immunization with a live-attenuated SIV vaccine, while those animals are not capable of fighting primary SIV infection. Here we propose a recursion-based virus-specific naive CD4(+) T-cell depletion hypothesis through thinking on what may happen in individuals experiencing primary immunodeficiency virus infection. This could explain the mechanism for impairment of virus-specific immune response in the course of HIV infection. PMID:27515208

  11. Reversing multidrug resistance in breast cancer cells by silencing ABC transporter genes with nanoparticle-facilitated delivery of target siRNAs

    Directory of Open Access Journals (Sweden)

    Li YT

    2012-06-01

    Full Text Available Yong Tsuey Li,1 Ming Jang Chua,1 Anil Philip Kunnath,1 Ezharul Hoque Chowdhury,1,21Faculty of Medicine and Health Science, International Medical University (IMU, No 126, Jalan 19/155B, Bukit Jalil, 57000 Kuala Lumpur, Malaysia; 2Jeffrey Cheah School of Medicine and Health Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University Kuala Lumpur, MalaysiaBackground: Multidrug resistance, a major impediment to successful cancer chemotherapy, is the result of overexpression of ATP-binding cassette (ABC transporters extruding internalized drugs. Silencing of ABC transporter gene expression with small interfering RNA (siRNA could be an attractive approach to overcome multidrug resistance of cancer, although delivery of siRNA remains a major hurdle to fully exploit the potential of siRNA-based therapeutics. Recently, we have developed pH-sensitive carbonate apatite nanoparticles to efficiently carry and transport siRNA across the cell membrane, enabling knockdown of the cyclin B1 gene and consequential induction of apoptosis in synergy with anti-cancer drugs.Methods and results: We report that carbonate apatite-mediated delivery of the siRNAs targeting ABCG2 and ABCB1 gene transcripts in human breast cancer cells which constitutively express both of the transporter genes dose-dependently enhanced chemosensitivity to doxorubicin, paclitaxel and cisplatin, the traditionally used chemotherapeutic agents. Moreover, codelivery of two specific siRNAs targeting ABCB1 and ABCG2 transcripts resulted in a more robust increase of chemosensitivity in the cancer cells, indicating the reversal of ABC transporter-mediated multidrug resistance.Conclusion: The delivery concept of multiple siRNAs against ABC transporter genes is highly promising for preclinical and clinical investigation in reversing the multidrug resistance phenotype of breast cancer.Keywords: carbonate apatite, siRNA, gene expression, transfection, breast cancer, ABC transporter

  12. Particulate Matter Facilitates C6 Glioma Cells Activation and the Release of Inflammatory Factors Through MAPK and JAK2/STAT3 Pathways.

    Science.gov (United States)

    Li, Ting; Zhao, Jianya; Ge, Jianbin; Yang, Jianbin; Song, Xinjian; Wang, Cheng; Mao, Jiamin; Zhang, Yan; Zou, Ye; Liu, Yanmei; Chen, Gang

    2016-08-01

    It has been widely accepted that astrocytes, play a role in regulating almost every physiological system. In the present study, we investigated the role of particulate matter (PM) in regulating activation of astrocytes. The glial cell strain C6 was cloned from a rat glioma which was induced by N-nitrosomethylurea. The C6 cells were plated at a density of 5 × 10(6) cells/10 cm diameter dish and incubated with different concentrations (0, 12, 25, 50, 100, 200, and 400 μg/mL) of PM for 24 h and different time (0, 1, 3, 6, 8,12, and 24 h) with 100 μg/mL at 37 °C. The study revealed that PM stimulated the expression of inducible nitric oxide synthase (iNOS) as well as the production of IL-1β in a dose- and time-dependent manner. Furthermore, activation of JAK2/STAT3 and p38/JNK/ERK MAPKs was found in astrocytes following PM treatment. Blockage of JAK and p38/JNK/ERK MAPKs with their specific inhibitors, AG490, SB202190, SP600125 and U0126 significantly reduced PM-induced iNOS expression and IL-1β production. In addition, it was demonstrated that inhibition of p38, JNK and JAK prevented STAT3 tyrosine phosphorylation induced by PM, while blocking ERK did not. MAPKs (p38 and JNK) could regulate tyrosine STAT3 phosphorylation, which suggested that the JAK2/STAT3 pathway might be the downstream of p38/JNK MAPK pathways. PMID:27068033

  13. Nrf2 facilitates repair of radiation induced DNA damage through homologous recombination repair pathway in a ROS independent manner in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jayakumar, Sundarraj; Pal, Debojyoti; Sandur, Santosh K., E-mail: sskumar@barc.gov.in

    2015-09-15

    Highlights: • Nrf2 inhibition in A549 cells led to attenuated DNA repair and radiosensitization. • Influence of Nrf2 on DNA repair is not linked to its antioxidant function. • Nrf2 influences DNA repair through homologous recombination (HR) repair pathway. • Many genes involved in HR pathway show ARE sequences in their upstream region. - Abstract: Nrf2 is a redox sensitive transcription factor that is involved in the co-ordinated transcription of genes involved in redox homeostasis. But the role of Nrf2 in DNA repair is not investigated in detail. We have employed A549 and MCF7 cells to study the role of Nrf2 on DNA repair by inhibiting Nrf2 using all-trans retinoic acid (ATRA) or by knock down approach prior to radiation exposure (4 Gy). DNA damage and repair analysis was studied by γH2AX foci formation and comet assay. Results suggested that the inhibition of Nrf2 in A549 or MCF7 cells led to significant slowdown in DNA repair as compared to respective radiation controls. The persistence of residual DNA damage even in the presence of free radical scavenger N-acetyl cysteine, suggested that the influence of Nrf2 on DNA repair was not linked to its antioxidant functions. Further, its influence on non-homologous end joining repair pathway was studied by inhibiting both Nrf2 and DNA-PK together. This led to synergistic reduction of survival fraction, indicating that Nrf2 may not be influencing the NHEJ pathway. To investigate the role of homologous recombination repair (HR) pathway, RAD51 foci formation was monitored. There was a significant reduction in the foci formation in cells treated with ATRA or shRNA against Nrf2 as compared to their respective radiation controls. Further, Nrf2 inhibition led to significant reduction in mRNA levels of RAD51. BLAST analysis was also performed on upstream regions of DNA repair genes to identify antioxidant response element and found that many repair genes that are involved in HR pathway may be regulated by Nrf2

  14. An Alternative Method to Facilitate cDNA Cloning for Expression Studies in Mammalian Cells by Introducing Positive Blue White Selection in Vaccinia Topoisomerase I-Mediated Recombination

    OpenAIRE

    Udo, Hiroshi

    2015-01-01

    One of the most basic techniques in biomedical research is cDNA cloning for expression studies in mammalian cells. Vaccinia topoisomerase I-mediated cloning (TOPO cloning by Invitrogen) allows fast and efficient recombination of PCR-amplified DNAs. Among TOPO vectors, a pcDNA3.1 directional cloning vector is particularly convenient, since it can be used for expression analysis immediately after cloning. However, I found that the cloning efficiency was reduced when RT-PCR products were used as...

  15. Nrf2 facilitates repair of radiation induced DNA damage through homologous recombination repair pathway in a ROS independent manner in cancer cells

    International Nuclear Information System (INIS)

    Highlights: • Nrf2 inhibition in A549 cells led to attenuated DNA repair and radiosensitization. • Influence of Nrf2 on DNA repair is not linked to its antioxidant function. • Nrf2 influences DNA repair through homologous recombination (HR) repair pathway. • Many genes involved in HR pathway show ARE sequences in their upstream region. - Abstract: Nrf2 is a redox sensitive transcription factor that is involved in the co-ordinated transcription of genes involved in redox homeostasis. But the role of Nrf2 in DNA repair is not investigated in detail. We have employed A549 and MCF7 cells to study the role of Nrf2 on DNA repair by inhibiting Nrf2 using all-trans retinoic acid (ATRA) or by knock down approach prior to radiation exposure (4 Gy). DNA damage and repair analysis was studied by γH2AX foci formation and comet assay. Results suggested that the inhibition of Nrf2 in A549 or MCF7 cells led to significant slowdown in DNA repair as compared to respective radiation controls. The persistence of residual DNA damage even in the presence of free radical scavenger N-acetyl cysteine, suggested that the influence of Nrf2 on DNA repair was not linked to its antioxidant functions. Further, its influence on non-homologous end joining repair pathway was studied by inhibiting both Nrf2 and DNA-PK together. This led to synergistic reduction of survival fraction, indicating that Nrf2 may not be influencing the NHEJ pathway. To investigate the role of homologous recombination repair (HR) pathway, RAD51 foci formation was monitored. There was a significant reduction in the foci formation in cells treated with ATRA or shRNA against Nrf2 as compared to their respective radiation controls. Further, Nrf2 inhibition led to significant reduction in mRNA levels of RAD51. BLAST analysis was also performed on upstream regions of DNA repair genes to identify antioxidant response element and found that many repair genes that are involved in HR pathway may be regulated by Nrf2

  16. Facilitating post traumatic growth

    Directory of Open Access Journals (Sweden)

    Cox Helen

    2004-07-01

    Full Text Available Abstract Background Whilst negative responses to traumatic injury have been well documented in the literature, there is a small but growing body of work that identifies posttraumatic growth as a salient feature of this experience. We contribute to this discourse by reporting on the experiences of 13 individuals who were traumatically injured, had undergone extensive rehabilitation and were discharged from formal care. All participants were injured through involvement in a motor vehicle accident, with the exception of one, who was injured through falling off the roof of a house. Methods In this qualitative study, we used an audio-taped in-depth interview with each participant as the means of data collection. Interviews were transcribed verbatim and analysed thematically to determine the participants' unique perspectives on the experience of recovery from traumatic injury. In reporting the findings, all participants' were given a pseudonym to assure their anonymity. Results Most participants indicated that their involvement in a traumatic occurrence was a springboard for growth that enabled them to develop new perspectives on life and living. Conclusion There are a number of contributions that health providers may make to the recovery of individuals who have been traumatically injured to assist them to develop new views of vulnerability and strength, make changes in relationships, and facilitate philosophical, physical and spiritual growth.

  17. Return of the glucoreceptor: Glucose activates the glucose-sensing receptor T1R3 and facilitates metabolism in pancreatic β-cells.

    Science.gov (United States)

    Kojima, Itaru; Nakagawa, Yuko; Ohtsu, Yoshiaki; Hamano, Kunihisa; Medina, Johan; Nagasawa, Masahiro

    2015-05-01

    Subunits of the sweet taste receptor, namely T1R2 and T1R3, are expressed in mouse pancreatic islets. Quantitatively, the expression of messenger ribonucleic acid for T1R2 is much lower than that of T1R3, and immunoreactive T1R2 is in fact undetectable. Presumably, a homodimer of T1R3 could function as a signaling receptor. Activation of this receptor by adding an artificial sweetener, sucralose, leads to an increase in intracellular adenosine triphosphate ([ATP]c). This increase in [ATP]c is observed in the absence of ambient glucose. Sucralose also augments elevation of [ATP]c induced by methylsuccinate, a substrate for mitochondria. Consequently, activation of T1R3 promotes metabolism in mitochondria and increases [ATP]c. 3-O-Methylglucose, a non-metabolizable analog of glucose, also increases [ATP]c. Conversely, knockdown of T1R3 attenuates elevation of [ATP]c induced by glucose. Hence, glucose promotes its own metabolism by activating T1R3 and augmenting ATP production. Collectively, a homodimer of T1R3 functions as a cell surface glucose-sensing receptor and participates in the action of glucose on insulin secretion. The glucose-sensing receptor T1R3 might be the putative glucoreceptor proposed decades ago by Niki et al. The glucose-sensing receptor is involved in the action of glucose and modulates glucose metabolism in pancreatic β-cells. PMID:25969708

  18. Phospholipase Cϵ Activates Nuclear Factor-κB Signaling by Causing Cytoplasmic Localization of Ribosomal S6 Kinase and Facilitating Its Phosphorylation of Inhibitor κB in Colon Epithelial Cells.

    Science.gov (United States)

    Wakita, Masahiro; Edamatsu, Hironori; Li, Mingzhen; Emi, Aki; Kitazawa, Sohei; Kataoka, Tohru

    2016-06-10

    Phospholipase Cϵ (PLCϵ), an effector of Ras and Rap small GTPases, plays a crucial role in inflammation by augmenting proinflammatory cytokine expression. This proinflammatory function of PLCϵ is implicated in its facilitative role in tumor promotion and progression during skin and colorectal carcinogenesis, although their direct link remains to be established. Moreover, the molecular mechanism underlying these functions of PLCϵ remains unknown except that PKD works downstream of PLCϵ. Here we show by employing the colitis-induced colorectal carcinogenesis model, where Apc(Min) (/+) mice are administered with dextran sulfate sodium, that PLCϵ knock-out alleviates the colitis and suppresses the following tumorigenesis concomitant with marked attenuation of proinflammatory cytokine expression. In human colon epithelial Caco2 cells, TNF-α induces sustained expression of proinflammatory molecules and sustained activation of nuclear factor-κB (NF-κB) and PKD, the late phases of which are suppressed by not only siRNA-mediated PLCϵ knockdown but also treatment with a lysophosphatidic acid (LPA) receptor antagonist. Also, LPA stimulation induces these events in an early time course, suggesting that LPA mediates TNF-α signaling in an autocrine manner. Moreover, PLCϵ knockdown results in inhibition of phosphorylation of IκB by ribosomal S6 kinase (RSK) but not by IκB kinases. Subcellular fractionation suggests that enhanced phosphorylation of a scaffolding protein, PEA15 (phosphoprotein enriched in astrocytes 15), downstream of the PLCϵ-PKD axis causes sustained cytoplasmic localization of phosphorylated RSK, thereby facilitating IκB phosphorylation in the cytoplasm. These results suggest the crucial role of the TNF-α-LPA-LPA receptor-PLCϵ-PKD-PEA15-RSK-IκB-NF-κB pathway in facilitating inflammation and inflammation-associated carcinogenesis in the colon. PMID:27053111

  19. Expression of IL-1Rrp2 by human myelomonocytic cells is unique to DCs and facilitates DC maturation by IL-1F8 and IL-1F9.

    Science.gov (United States)

    Mutamba, Shilla; Allison, Asher; Mahida, Yashwant; Barrow, Paul; Foster, Neil

    2012-03-01

    We report for the first time that expression of the novel IL-1 cytokine receptor IL-1Rrp2 (IL-1R6) is unique to DCs within the human myelomonocytic lineage. IL-1Rrp2 was expressed by monocyte-derived dendritic cells (MDDCs) which was dose-dependently increased by IL-4 and correlated with increased numbers of differentiated MDDCs. Human plasmacytoid DCs also express IL-1Rrp2 but the receptor is not expressed by either myeloid DC type 1 (mDC1) or mDC2 cells. We also show that IL-1F8 or IL-1F9 cytokines, which signal through IL-1Rrp2, induce maturation of MDDCs, as measured by increased expression of HLA-DR and CD83 and decreased expression of CD1a. Furthermore, IL-1F8 stimulated increased CD40 and CD80 expression and IL-18 and IL-12 p70 production by MDDCs, which induced proliferation of IFN-γ-producing CD3(+) lymphocytes (indicative of inflammatory Th1 subsets). IL-1F8 and IL-1F2 were equipotent in their ability to stimulate IL-18 secretion from MDDCs but IL-1F8 was not as potent as IL-1F2 in stimulating secretion of IL-12p70 from MDDCs or inducing lymphocyte proliferation Therefore, IL-1Rrp2 expression by some DC subsets may have an important function in the human immune response in vivo via its role in differentiation of inflammatory Th1 lymphocytes. PMID:22144259

  20. An Alternative Method to Facilitate cDNA Cloning for Expression Studies in Mammalian Cells by Introducing Positive Blue White Selection in Vaccinia Topoisomerase I-Mediated Recombination.

    Directory of Open Access Journals (Sweden)

    Hiroshi Udo

    Full Text Available One of the most basic techniques in biomedical research is cDNA cloning for expression studies in mammalian cells. Vaccinia topoisomerase I-mediated cloning (TOPO cloning by Invitrogen allows fast and efficient recombination of PCR-amplified DNAs. Among TOPO vectors, a pcDNA3.1 directional cloning vector is particularly convenient, since it can be used for expression analysis immediately after cloning. However, I found that the cloning efficiency was reduced when RT-PCR products were used as inserts (about one-quarter. Since TOPO vectors accept any PCR products, contaminating fragments in the insert DNA create negative clones. Therefore, I designed a new mammalian expression vector enabling positive blue white selection in Vaccinia topoisomerase I-mediated cloning. The method utilized a short nontoxic LacZα peptide as a linker for GFP fusion. When cDNAs were properly inserted into the vector, minimal expression of the fusion proteins in E. coli (harboring lacZΔM15 resulted in formation of blue colonies on X-gal plates. This method improved both cloning efficiency (75% and directional cloning (99% by distinguishing some of the negative clones having non-cording sequences, since these inserts often disturbed translation of lacZα. Recombinant plasmids were directly applied to expression studies using GFP as a reporter. Utilization of the P2A peptide allowed for separate expression of GFP. In addition, the preparation of Vaccinia topoisomerase I-linked vectors was streamlined, which consisted of successive enzymatic reactions with a single precipitation step, completing in 3 hr. The arrangement of unique restriction sites enabled further modification of vector components for specific applications. This system provides an alternative method for cDNA cloning and expression in mammalian cells.

  1. Topogenesis and cell surface trafficking of GPR34 are facilitated by positive-inside rule that effects through a tri-basic motif in the first intracellular loop.

    Science.gov (United States)

    Hasegawa, Haruki; Patel, Neha; Ettehadieh, Elham; Li, Peng; Lim, Ai Ching

    2016-07-01

    Protein folding, topogenesis and intracellular targeting of G protein-coupled receptors (GPCRs) must be precisely coordinated to ensure correct receptor localization. To elucidate how different steps of GPCR biosynthesis work together, we investigated the process of membrane topology determination and how it relates to the acquisition of cell surface trafficking competence in human GPR34. By monitoring a fused FLAG-tag and a conformation-sensitive native epitope during the expression of GPR34 mutant panel, a tri-basic motif in the first intracellular loop was identified as the key topogenic signal that dictates the orientation of transmembrane domain-1 (TM1). Charge disruption of the motif perturbed topogenic processes and resulted in the conformational epitope loss, post-translational processing alteration, and trafficking arrest in the Golgi. The placement of a cleavable N-terminal signal sequence as a surrogate topogenic determinant overcame the effects of tri-basic motif mutations and rectified the TM1 orientation; thereby restored the conformational epitope, post-translational modifications, and cell surface trafficking altogether. Progressive N-tail truncation and site-directed mutagenesis revealed that a proline-rich segment of the N-tail and all four cysteines individually located in the four separate extracellular regions must simultaneously reside in the ER lumen to muster the conformational epitope. Oxidation of all four cysteines was necessary for the epitope formation, but the cysteine residues themselves were not required for the trafficking event. The underlying biochemical properties of the conformational epitope was therefore the key to understand mechanistic processes propelled by positive-inside rule that simultaneously regulate the topogenesis and intracellular trafficking of GPR34. PMID:27086875

  2. The Long Non-coding RNA HIF1A-AS2 Facilitates the Maintenance of Mesenchymal Glioblastoma Stem-like Cells in Hypoxic Niches

    Directory of Open Access Journals (Sweden)

    Marco Mineo

    2016-06-01

    Full Text Available Long non-coding RNAs (lncRNAs have an undefined role in the pathobiology of glioblastoma multiforme (GBM. These tumors are genetically and phenotypically heterogeneous with transcriptome subtype-specific GBM stem-like cells (GSCs that adapt to the brain tumor microenvironment, including hypoxic niches. We identified hypoxia-inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2 as a subtype-specific hypoxia-inducible lncRNA, upregulated in mesenchymal GSCs. Its deregulation affects GSC growth, self-renewal, and hypoxia-dependent molecular reprogramming. Among the HIF1A-AS2 interactome, IGF2BP2 and DHX9 were identified as direct partners. This association was needed for maintenance of expression of their target gene, HMGA1. Downregulation of HIF1A-AS2 led to delayed growth of mesenchymal GSC tumors, survival benefits, and impaired expression of HMGA1 in vivo. Our data demonstrate that HIF1A-AS2 contributes to GSCs’ speciation and adaptation to hypoxia within the tumor microenvironment, acting directly through its interactome and targets and indirectly by modulating responses to hypoxic stress depending on the subtype-specific genetic context.

  3. Ins(1,4,5)P3 facilitates ATP accumulation via phosphocreatine/creatine kinase in the endoplasmic reticulum extracted from MDCK cells

    International Nuclear Information System (INIS)

    So far, the content and accumulation of ATP in isolated endoplasmic reticulum (ER) are little understood. First, we confirmed using electron microscopic and Western blotting techniques that the samples extracted from MDCK cells are endoplasmic reticulum (ER). The amounts of ATP in the extracted ER were measured from the filtrate after a spinning down of ultrafiltration spin column packed with ER. When the ER sample (5 μg) after 3 days freezing was suspended in intracellular medium (ICM), 0.1% Triton X and ultrapure water (UPW), ATP amounts from the ER with UPW were the highest and over 10 times compared with that from the control with ICM, indicating that UPW is the most effective tool in destroying the ER membrane. After a 10-min-incubation with ICM containing phosphocreatine (PCr)/creatine kinase (CK) of the fresh ER. ATP amounts in the filtrate obtained by spinning down were not changed from that in the control (no PCr/CK). However, ATP amounts in the filtrate from the second spinning down of the ER (treated with PCr/CK) suspended in UPW became over 10-fold compared with the control. When 1 μM inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) was added in the incubation medium (ICM with PCr/CK), ATP amounts from the filtrate after the second spinning down were further enhanced around three times. This enhancement was almost canceled by Ca2+-removal from ICM and by adding thapsigargin, a Ca2+-ATPase inhibitor, but not by 2-APB and heparin, Ins(1,4,5)P3 receptor antagonists. Administration of 500 μM adenosine to the incubation medium (with PCr/CK) failed to enhance the accumulation of ATP in the ER. These findings suggest that the ER originally contains ATP and ATP accumulation in the ER is promoted by PCr/CK and Ins(1,4,5)P3.

  4. Propofol facilitates excitatory inputs of cerebellar Purkinje cells by depressing molecular layer interneuron activity during sensory information processing in vivo in mice.

    Science.gov (United States)

    He, Yuan-Yuan; Jin, Ri; Jin, Wen-Zhe; Liu, Heng; Chu, Chun-Ping; Qiu, De-Lai

    2015-10-21

    Propofol is a rapid-acting sedative-hypnotic medication that has been widely used for the induction and maintenance of anesthesia; it has specific actions on different areas of the brain, such as sensory information transmission in the somatosensory cortex. However, the effects of propofol on the properties of sensory stimulation-evoked responses in cerebellar Purkinje cells (PCs) are currently unclear. In the present study, we studied the effects of propofol on facial stimulation-evoked responses in cerebellar PCs and molecular level interneurons (MLIs) in urethane-anesthetized mice using electrophysiological and pharmacological methods. Our results showed that cerebellar surface perfusion with propofol induced a decrease in the amplitude of the gamma-aminobutyric acid (GABA)-ergic component (P1) in a dose-dependent manner, but induced a significant increase in the amplitude of the excitatory response (N1). The IC50 of propofol-induced inhibition of P1 was 217.3 μM. In contrast, propofol (100 μM) depressed the spontaneous activity and tactile-evoked responses in MLIs. In addition, blocking GABA(A) receptor activity abolished the propofol (300 μM)-induced inhibition of the tactile-evoked inhibitory response and the increase in the sensory stimulation-evoked spike firing rate of PCs. These results indicated that propofol depressed the tactile stimulation-evoked spike firing of MLIs, resulting in a decrease in the amplitude of the tactile-evoked inhibitory response and an increase in the amplitude of the excitatory response in the cerebellar PCs of mice. Our results suggest that propofol modulates sensory information processing in cerebellar cortical PCs and MLIs through the activation of GABA(A) receptors. PMID:26317477

  5. Ins(1,4,5)P{sub 3} facilitates ATP accumulation via phosphocreatine/creatine kinase in the endoplasmic reticulum extracted from MDCK cells

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jing [Medical Research Center, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Department of Dental Implantology, School of Stomatology, Tongji University, Shanghai 200072 (China); Ogata, Shigenori [Joint Laboratory for Frontier Medical Science, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Segawa, Masaru [Central Laboratory for Pathology and Morphology, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Usune, Sadaharu [Research Laboratory of Biodynamics, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Zhao, Yumei [Department of Pediatric Dentistry, School of Dentistry of Shanghai Tongji University, Shanghai 200072 (China); Katsuragi, Takeshi, E-mail: katsurag@fukuoka-u.ac.jp [Medical Research Center, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan)

    2010-07-02

    So far, the content and accumulation of ATP in isolated endoplasmic reticulum (ER) are little understood. First, we confirmed using electron microscopic and Western blotting techniques that the samples extracted from MDCK cells are endoplasmic reticulum (ER). The amounts of ATP in the extracted ER were measured from the filtrate after a spinning down of ultrafiltration spin column packed with ER. When the ER sample (5 {mu}g) after 3 days freezing was suspended in intracellular medium (ICM), 0.1% Triton X and ultrapure water (UPW), ATP amounts from the ER with UPW were the highest and over 10 times compared with that from the control with ICM, indicating that UPW is the most effective tool in destroying the ER membrane. After a 10-min-incubation with ICM containing phosphocreatine (PCr)/creatine kinase (CK) of the fresh ER. ATP amounts in the filtrate obtained by spinning down were not changed from that in the control (no PCr/CK). However, ATP amounts in the filtrate from the second spinning down of the ER (treated with PCr/CK) suspended in UPW became over 10-fold compared with the control. When 1 {mu}M inositol(1,4,5)trisphosphate (Ins(1,4,5)P{sub 3}) was added in the incubation medium (ICM with PCr/CK), ATP amounts from the filtrate after the second spinning down were further enhanced around three times. This enhancement was almost canceled by Ca{sup 2+}-removal from ICM and by adding thapsigargin, a Ca{sup 2+}-ATPase inhibitor, but not by 2-APB and heparin, Ins(1,4,5)P{sub 3} receptor antagonists. Administration of 500 {mu}M adenosine to the incubation medium (with PCr/CK) failed to enhance the accumulation of ATP in the ER. These findings suggest that the ER originally contains ATP and ATP accumulation in the ER is promoted by PCr/CK and Ins(1,4,5)P{sub 3}.

  6. Facilitating Dialogues about Racial Realities

    Science.gov (United States)

    Quaye, Stephen John

    2014-01-01

    Background/Context: Facilitating dialogues about racial issues in higher education classroom settings continues to be a vexing problem facing postsecondary educators. In order for students to discuss race with their peers, they need skilled facilitators who are knowledgeable about racial issues and able to support students in these difficult…

  7. Learning to Facilitate (Online) Meetings

    DEFF Research Database (Denmark)

    Reimann, Peter; Bull, Susan; Vatrapu, Ravi

    2013-01-01

    We describe an approach to teaching collaboration skills directly by building on competences for meeting facilitation. (Online) meetings provide a rich arena to practice collaboration since they can serve multiple purposes: learning, problem solving, decision making, idea generation and advancement...

  8. Facilitation Skills for Library Professionals

    OpenAIRE

    O'Shea, Anne; Matheson, Laura

    2010-01-01

    Session summary: Brainstorming, problem-solving, team-building and group communication – all of these things can be made easier through facilitation! Come to this fun, interactive workshop to learn techniques and exercises to boost your group meetings. Taught by two information professionals with formal facilitation training and experience, this workshop will give you theory, hands-on practice time and feedback. What participants will learn: Participants will learn techniques to he...

  9. Specific Armadillo Repeat Sequences Facilitate β-Catenin Nuclear Transport in Live Cells via Direct Binding to Nucleoporins Nup62, Nup153, and RanBP2/Nup358*

    Science.gov (United States)

    Sharma, Manisha; Jamieson, Cara; Johnson, Michael; Molloy, Mark P.; Henderson, Beric R.

    2012-01-01

    β-Catenin transduces the Wnt signal from the membrane to nucleus, and certain gene mutations trigger its nuclear accumulation leading to cell transformation and cancer. β-Catenin shuttles between the nucleus and cytoplasm independent of classical Ran/transport receptor pathways, and this movement was previously hypothesized to involve the central Armadillo (Arm) domain. Fluorescence recovery after photobleaching (FRAP) assays were used to delineate functional transport regions of the Arm domain in living cells. The strongest nuclear import/export activity was mapped to Arm repeats R10–12 using both in vivo FRAP and in vitro export assays. By comparison, Arm repeats R3–8 of β-catenin were highly active for nuclear import but displayed a comparatively weak export activity. We show for the first time using purified components that specific Arm sequences of β-catenin interact directly in vitro with the FG repeats of the nuclear pore complex (NPC) components Nup62, Nup98, and Nup153, indicating an independent ability of β-catenin to traverse the NPC. Moreover, a proteomics screen identified RanBP2/Nup358 as a binding partner of Arm R10–12, and β-catenin was confirmed to interact with endogenous and ectopic forms of Nup358. We further demonstrate that knock-down of endogenous Nup358 and Nup62 impeded the rate of nuclear import/export of β-catenin to a greater extent than that of importin-β. The Arm R10–12 sequence facilitated transport even when β-catenin was bound to the Arm-binding partner LEF-1, and its activity was stimulated by phosphorylation at Tyr-654. These findings provide functional evidence that the Arm domain contributes to regulated β-catenin transport through direct interaction with the NPC. PMID:22110128

  10. Memory facilitation educed by food intake.

    Science.gov (United States)

    Oomura, Y; Sasaki, K; Li, A J

    1993-09-01

    Acidic fibroblast growth factor (aFGF) in rat CSF increased 1000 times in the 2-h period after food intake, or IP, or ICV glucose infusion. The ICV application of aFGF dose dependently depresses and anti-aFGF antibody facilitates food intake. aFGF is produced in the ependymal cells and released into the CSF in response to increased glucose in the CSF caused by food intake. Released aFGF diffused into the brain parenchyma and was taken up into neurons in the hypothalamus, hippocampus, amygdala, etc. IP injection of glucose 2 h before a task that combined acquisition with passive avoidance significantly increased retention of avoidance by mice tested 24 h later. In a Morris water maze task, IP glucose injection 2 h before a first trial block reduced time to find and climb onto a platform hidden just below the water surface. The glucose facilitation of these affective and spatial memory were abolished by pretreatment with anti-aFGF antibody applied ICV. Continuous ICV infusion of aFGF into rats also significantly increased the reliability of passive avoidance for several days. After food intake, centrally released aFGF reaches the hippocampus and facilitates memory; peripherally released cholecystokinin reaches the endings of the afferent vagal nerves in the portal vein and changes their activity, which modulates hippocampal activity, to lead to memory facilitation. This, however, is blocked by vagotomy below the diaphragm. The results indicate the importance of food intake, not only to maintain homeostasis, but also to prepare a readiness state for memory facilitation. PMID:7692459

  11. Gli1-Mediated Regulation of Sox2 Facilitates Self-Renewal of Stem-Like Cells and Confers Resistance to EGFR Inhibitors in Non–Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Namrata Bora-Singhal

    2015-07-01

    Full Text Available Non–small cell lung cancer (NSCLC patients have very low survival rates because the current therapeutic strategies are not fully effective. Although EGFR tyrosine kinase inhibitors are effective for NSCLC patients harboring EGFR mutations, patients invariably develop resistance to these agents. Alterations in multiple signaling cascades have been associated with the development of resistance to EGFR inhibitors. Sonic Hedgehog and associated Gli transcription factors play a major role in embryonic development and have recently been found to be reactivated in NSCLC, and elevated Gli1 levels correlate with poor prognosis. The Hedgehog pathway has been implicated in the functions of cancer stem cells, although the underlying molecular mechanisms are not clear. In this context, we demonstrate that Gli1 is a strong regulator of embryonic stem cell transcription factor Sox2. Depletion of Gli1 or inhibition of the Hedgehog signaling significantly abrogated the self-renewal of stem-like side-population cells from NSCLCs as well as vascular mimicry of such cells. Gli1 was found to transcriptionally regulate Sox2 through its promoter region, and Gli1 could be detected on the Sox2 promoter. Inhibition of Hedgehog signaling appeared to work cooperatively with EGFR inhibitors in markedly reducing the viability of NSCLC cells as well as the self-renewal of stem-like cells. Thus, our study demonstrates a cooperative functioning of the EGFR signaling and Hedgehog pathways in governing the stem-like functions of NSCLC cancer stem cells and presents a novel therapeutic strategy to combat NSCLC harboring EGFR mutations.

  12. Facilitation of learning: part 1.

    Science.gov (United States)

    Warburton, Tyler; Trish, Houghton; Barry, Debbie

    2016-04-01

    This article, the fourth in a series of 11, discusses the context for the facilitation of learning. It outlines the main principles and theories for understanding the process of learning, including examples which link these concepts to practice. The practical aspects of using these theories in a practice setting will be discussed in the fifth article of this series. Together, these two articles will provide mentors and practice teachers with knowledge of the learning process, which will enable them to meet the second domain of the Nursing and Midwifery Council's Standards to Support Learning and Assessment in Practice on facilitation of learning. PMID:27050014

  13. Gli1-Mediated Regulation of Sox2 Facilitates Self-Renewal of Stem-Like Cells and Confers Resistance to EGFR Inhibitors in Non–Small Cell Lung Cancer 1

    OpenAIRE

    Namrata Bora-Singhal; Deepak Perumal; Jonathan Nguyen; Srikumar Chellappan

    2015-01-01

    Non–small cell lung cancer (NSCLC) patients have very low survival rates because the current therapeutic strategies are not fully effective. Although EGFR tyrosine kinase inhibitors are effective for NSCLC patients harboring EGFR mutations, patients invariably develop resistance to these agents. Alterations in multiple signaling cascades have been associated with the development of resistance to EGFR inhibitors. Sonic Hedgehog and associated Gli transcription factors play a major role in embr...

  14. Producing gestures facilitates route learning.

    Directory of Open Access Journals (Sweden)

    Wing Chee So

    Full Text Available The present study investigates whether producing gestures would facilitate route learning in a navigation task and whether its facilitation effect is comparable to that of hand movements that leave physical visible traces. In two experiments, we focused on gestures produced without accompanying speech, i.e., co-thought gestures (e.g., an index finger traces the spatial sequence of a route in the air. Adult participants were asked to study routes shown in four diagrams, one at a time. Participants reproduced the routes (verbally in Experiment 1 and non-verbally in Experiment 2 without rehearsal or after rehearsal by mentally simulating the route, by drawing it, or by gesturing (either in the air or on paper. Participants who moved their hands (either in the form of gestures or drawing recalled better than those who mentally simulated the routes and those who did not rehearse, suggesting that hand movements produced during rehearsal facilitate route learning. Interestingly, participants who gestured the routes in the air or on paper recalled better than those who drew them on paper in both experiments, suggesting that the facilitation effect of co-thought gesture holds for both verbal and nonverbal recall modalities. It is possibly because, co-thought gesture, as a kind of representational action, consolidates spatial sequence better than drawing and thus exerting more powerful influence on spatial representation.

  15. Producing gestures facilitates route learning.

    Science.gov (United States)

    So, Wing Chee; Ching, Terence Han-Wei; Lim, Phoebe Elizabeth; Cheng, Xiaoqin; Ip, Kit Yee

    2014-01-01

    The present study investigates whether producing gestures would facilitate route learning in a navigation task and whether its facilitation effect is comparable to that of hand movements that leave physical visible traces. In two experiments, we focused on gestures produced without accompanying speech, i.e., co-thought gestures (e.g., an index finger traces the spatial sequence of a route in the air). Adult participants were asked to study routes shown in four diagrams, one at a time. Participants reproduced the routes (verbally in Experiment 1 and non-verbally in Experiment 2) without rehearsal or after rehearsal by mentally simulating the route, by drawing it, or by gesturing (either in the air or on paper). Participants who moved their hands (either in the form of gestures or drawing) recalled better than those who mentally simulated the routes and those who did not rehearse, suggesting that hand movements produced during rehearsal facilitate route learning. Interestingly, participants who gestured the routes in the air or on paper recalled better than those who drew them on paper in both experiments, suggesting that the facilitation effect of co-thought gesture holds for both verbal and nonverbal recall modalities. It is possibly because, co-thought gesture, as a kind of representational action, consolidates spatial sequence better than drawing and thus exerting more powerful influence on spatial representation. PMID:25426624

  16. Corpus Linguistics Facilitates English Teaching

    Institute of Scientific and Technical Information of China (English)

    朱思亲

    2014-01-01

    Corpus linguistics has been widely applied in English teaching. Corpus linguistics has changed the way to teach English. The essay discusses two approaches in English teaching based on corpus, corpus-driven approach and corpus-based approach. It finds out that both corpus-driven approach and corpus-based approach facilitate English teaching in their own ways.

  17. A novel function for serotonin-mediated short-term facilitation in Aplysia: Conversion of a transient, cell-wide homosynaptic Hebbian plasticity into a persistent, protein synthesis-independent synapse-specific enhancement

    OpenAIRE

    Bailey, Craig H.; Giustetto, Maurizio; Zhu, Hiuxiang; Chen, Mary; Kandel, Eric R.

    2000-01-01

    Studies of sensitization and classical conditioning of the gill-withdrawal reflex in Aplysia have shown that the synaptic connections between identified glutamatergic sensory neurons and motor neurons can be enhanced in one of two ways: by a heterosynaptic (modulatory input-dependent) mechanism that gives rise with repetition to long-term facilitation and by a homosynaptic (activity-dependent) mechanism that gives rise with repetition to a facilitation that is part...

  18. Positive Emotion Facilitates Audiovisual Binding

    OpenAIRE

    Kitamura, Miho S.; Watanabe, Katsumi; Kitagawa, Norimichi

    2016-01-01

    It has been shown that positive emotions can facilitate integrative and associative information processing in cognitive functions. The present study examined whether emotions in observers can also enhance perceptual integrative processes. We tested 125 participants in total for revealing the effects of emotional states and traits in observers on the multisensory binding between auditory and visual signals. Participants in Experiment 1 observed two identical visual disks moving toward each oth...

  19. How We Think and Talk about Facilitation

    Science.gov (United States)

    Kato, Fumitoshi

    2010-01-01

    Over the past few years, the notion of "facilitation" has been increasingly gaining attention and acceptance in Japan, especially in the context of education and training. Today, Japanese educators think and talk about facilitation, even if it is not yet clear what facilitation is. Interestingly enough, the term "facilitation" does not exist in…

  20. Stochastic facilitation in the brain?

    Science.gov (United States)

    Ward, Lawrence M.; Greenwood, Priscilla E.

    2016-05-01

    We describe the context for three unsolved problems of noise in the brain as well as provide some new results relevant to one of them. The problems are: are neural oscillations better described as noisy limit cycles or as noise-driven quasicycles, does noise facilitate synchronization and information transmission in the brain, and do noise-driven spatial patterns (quasipatterns) coexist with noise-driven quasicycles in the brain? We provide a few new results indicating that, in models at least, spatial quasipatterns of quasicycles can occur, and resemble patterns observed in other areas, such as predator-prey systems and chemical reactions.

  1. GIS-facilitated spatial narratives

    DEFF Research Database (Denmark)

    Møller-Jensen, Lasse; Jeppesen, Henrik; Kofie, Richard Y.

    2008-01-01

    thematically and narrative linking of a set of locations within an area. A spatial narrative that describes the - largely unsuccessful - history of Danish plantations on the Gold Coast (1788-1850) is implemented through the Google Earth client. This client is seen both as a type of media in itself for ‘home......-based' exploration of sites related to the narrative and as a tool that facilitates the design of spatial narratives before implementation within portable GIS devices. The Google Earth-based visualization of the spatial narrative is created by a Python script that outputs a web-accessible KML format file. The KML...

  2. Facilitating Collaboration through Design Games

    DEFF Research Database (Denmark)

    Brandt, Eva; Messeter, Jørn

    2004-01-01

    In recent years both companies and research communities call for collaborative work practices and user-centered approaches in various design fields. There are several challenges and issues to take into consideration. For instance there is a need to find ways of collaborating across various...... in collaboration with industrial partners and potential users, and use of the games in three educational settings.The overall aim of the design games is to help facilitate a user-centered design process for cross-disciplinary design groups early in the design process. Framing collaborative design...

  3. External facilitators and interprofessional facilitation teams: a qualitative study of their roles in supporting practice change

    OpenAIRE

    Lessard, Sylvie; Bareil, Céline; Lalonde, Lyne; Duhamel, Fabie; Hudon, Eveline; Goudreau, Johanne; Lévesque, Lise

    2016-01-01

    Background Facilitation is a powerful approach to support practice change. The purpose of this study is to better understand the facilitation roles exercised by both external facilitators and interprofessional facilitation teams to foster the implementation of change. Building on Dogherty et al.’s taxonomy of facilitation activities, this study uses an organizational development lens to identify and analyze facilitation roles. It includes a concise definition of what interprofessional facilit...

  4. Voice congruency facilitates word recognition.

    Directory of Open Access Journals (Sweden)

    Sandra Campeanu

    Full Text Available Behavioral studies of spoken word memory have shown that context congruency facilitates both word and source recognition, though the level at which context exerts its influence remains equivocal. We measured event-related potentials (ERPs while participants performed both types of recognition task with words spoken in four voices. Two voice parameters (i.e., gender and accent varied between speakers, with the possibility that none, one or two of these parameters was congruent between study and test. Results indicated that reinstating the study voice at test facilitated both word and source recognition, compared to similar or no context congruency at test. Behavioral effects were paralleled by two ERP modulations. First, in the word recognition test, the left parietal old/new effect showed a positive deflection reflective of context congruency between study and test words. Namely, the same speaker condition provided the most positive deflection of all correctly identified old words. In the source recognition test, a right frontal positivity was found for the same speaker condition compared to the different speaker conditions, regardless of response success. Taken together, the results of this study suggest that the benefit of context congruency is reflected behaviorally and in ERP modulations traditionally associated with recognition memory.

  5. Facilitation of learning: part 2.

    Science.gov (United States)

    Warburton, Tyler; Houghton, Trish; Barry, Debbie

    2016-04-27

    The previous article in this series of 11, Facilitation of learning: part 1, reviewed learning theories and how they relate to clinical practice. Developing an understanding of these theories is essential for mentors and practice teachers to enable them to deliver evidence-based learning support. This is important given that effective learning support is dependent on an educator who possesses knowledge of their specialist area as well as the relevent tools and methods to support learning. The second domain of the Nursing and Midwifery Council's Standards to Support Learning and Assessment in Practice relates to the facilitation of learning. To fulfil this domain, mentors and practice teachers are required to demonstrate their ability to recognise the needs of learners and provide appropriate support to meet those needs. This article expands on some of the discussions from part 1 of this article and considers these from a practical perspective, in addition to introducing some of the tools that can be used to support learning. PMID:27191319

  6. Positive Emotion Facilitates Audiovisual Binding.

    Science.gov (United States)

    Kitamura, Miho S; Watanabe, Katsumi; Kitagawa, Norimichi

    2015-01-01

    It has been shown that positive emotions can facilitate integrative and associative information processing in cognitive functions. The present study examined whether emotions in observers can also enhance perceptual integrative processes. We tested 125 participants in total for revealing the effects of emotional states and traits in observers on the multisensory binding between auditory and visual signals. Participants in Experiment 1 observed two identical visual disks moving toward each other, coinciding, and moving away, presented with a brief sound. We found that for participants with lower depressive tendency, induced happy moods increased the width of the temporal binding window of the sound-induced bounce percept in the stream/bounce display, while no effect was found for the participants with higher depressive tendency. In contrast, no effect of mood was observed for a simple audiovisual simultaneity discrimination task in Experiment 2. These results provide the first empirical evidence of a dependency of multisensory binding upon emotional states and traits, revealing that positive emotions can facilitate the multisensory binding processes at a perceptual level. PMID:26834585

  7. Facilitating Value Co-Creation

    DEFF Research Database (Denmark)

    Veith, Anne; Assaf, Albert; Josiassen, Alexander

    2013-01-01

    ) introduced a new dominant logic in the marketing literature, the Service-Dominant Logic (S-D Logic), in which service, interactions, and enhanced experiences help create value, and this potential for value is what attracts consumers. Therefore organizations must be customer-centric in order to facilitate...... unique, positive experiences. As the name indicates, both organizations and consumers (should) obtain value when co-creating, which is why both parties are willing to increase their degree of involvement, e.g. spending more resources, sharing tacit knowledge, etc., because a high degree of involvement......). Therefore, for instance, being part of the process is a key incentive for consumers. Postmodern consumers' search for unique experiences calls for individualization, personalization, etc. Although Prahalad & Ramaswamy (2004), Karpen et al. (2008), and Karpen et al. (2011) have presented S-D Logic...

  8. Tonoplast Aquaporins Facilitate Lateral Root Emergence.

    Science.gov (United States)

    Reinhardt, Hagen; Hachez, Charles; Bienert, Manuela Désirée; Beebo, Azeez; Swarup, Kamal; Voß, Ute; Bouhidel, Karim; Frigerio, Lorenzo; Schjoerring, Jan K; Bennett, Malcolm J; Chaumont, Francois

    2016-03-01

    Aquaporins (AQPs) are water channels allowing fast and passive diffusion of water across cell membranes. It was hypothesized that AQPs contribute to cell elongation processes by allowing water influx across the plasma membrane and the tonoplast to maintain adequate turgor pressure. Here, we report that, in Arabidopsis (Arabidopsis thaliana), the highly abundant tonoplast AQP isoforms AtTIP1;1, AtTIP1;2, and AtTIP2;1 facilitate the emergence of new lateral root primordia (LRPs). The number of lateral roots was strongly reduced in the triple tip mutant, whereas the single, double, and triple tip mutants showed no or minor reduction in growth of the main root. This phenotype was due to the retardation of LRP emergence. Live cell imaging revealed that tight spatiotemporal control of TIP abundance in the tonoplast of the different LRP cells is pivotal to mediating this developmental process. While lateral root emergence is correlated to a reduction of AtTIP1;1 and AtTIP1;2 protein levels in LRPs, expression of AtTIP2;1 is specifically needed in a restricted cell population at the base, then later at the flanks, of developing LRPs. Interestingly, the LRP emergence phenotype of the triple tip mutants could be fully rescued by expressing AtTIP2;1 under its native promoter. We conclude that TIP isoforms allow the spatial and temporal fine-tuning of cellular water transport, which is critically required during the highly regulated process of LRP morphogenesis and emergence. PMID:26802038

  9. Facilitating submetering implementation. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Bowers, M.A.

    1996-05-01

    Residential submetering is the measurement and billing of electric use in individual apartments in master-metered buildings. In master-metered building situations, residents do not bear electricity costs in proportion to consumption levels. As a result, studies have confirmed that residents in master-metered buildings tend to consume more electricity than residents with individual apartment metering, and have established electrical submetering as an effective energy conservation measure. The New York State Energy Research & Development Authority (NYSERDA) has commissioned a project called Facilitating Submetering Implementation to identify and analyze barriers to the implementation of residential electrical submetering in New York and to formulate recommendations that would facilitate the removal of these barriers, streamlining the process. Experienced professionals in the technical, legal, regulatory, analytical, financial, and other aspects of submetering were retained to interview key interested parties and conduct public forums. This and other data were then analyzed to ascertain the barriers to submetering and develop recommendations designed to reduce or eliminate these barriers. The key barriers to submetering implementation were found to be the Public Service Commission (PSC) requirement for a vote of a majority of shareholders (for coops and condos) and the high initial cost that cannot easily be recouped by owners of both rental and shareholder-owned buildings. The key recommendations are to repeal the voting requirement, maintain the utility incentives, adopt a uniform dispute resolution mechanism, and increase awareness through an Ad-hoc Submetering Committee and supporting educational materials. Other funding sources not fully available can also be made available with regulatory agency support.

  10. Microbial metabolite butyrate facilitates M2 macrophage polarization and function

    OpenAIRE

    Jian Ji; Dingming Shu; Mingzhu Zheng; Jie Wang; Chenglong Luo; Yan Wang; Fuyou Guo; Xian Zou; Xiaohui Lv; Ying Li; Tianfei Liu; Hao Qu

    2016-01-01

    Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells. Whether the microbial metabolites influence macrophage polarization, however, is poorly understood. Here, we show that the large bowel microbial fermentation product, butyrate, facilitates M2 macrophage polarization, in vitro and in vivo. The supernatant from butyrate-treated M2 macrophage increased the migration and enhanced the wound closure rate of MLE-12 cells. ...

  11. Evaluation of the Facilitated Communication Pilot

    Science.gov (United States)

    Cooper-Martin, Elizabeth

    2014-01-01

    The Office of Special Education and Student Services asked the Office of Shared Accountability to evaluate the "Facilitated Communication Pilot." In facilitated communication (FC), people with communication impairments express themselves by typing with the aid of a communication partner, called a facilitator, who provides physical (and…

  12. Facilitation of decommissioning light water reactors

    International Nuclear Information System (INIS)

    Information on design features, special equipment, and construction methods useful in the facilitation of decommissioning light water reactors is presented. A wide range of facilitation methods - from improved documentation to special decommissioning tools and techniques - is discussed. In addition, estimates of capital costs, cost savings, and radiation dose reduction associated with these facilitation methods are given

  13. Arousal facilitates involuntary eye movements.

    Science.gov (United States)

    DiGirolamo, Gregory J; Patel, Neha; Blaukopf, Clare L

    2016-07-01

    Attention plays a critical role in action selection. However, the role of attention in eye movements is complicated as these movements can be either voluntary or involuntary, with, in some circumstances (antisaccades), these two actions competing with each other for execution. But attending to the location of an impending eye movement is only one facet of attention that may play a role in eye movement selection. In two experiments, we investigated the effect of arousal on voluntary eye movements (antisaccades) and involuntary eye movements (prosaccadic errors) in an antisaccade task. Arousal, as caused by brief loud sounds and indexed by changes in pupil diameter, had a facilitation effect on involuntary eye movements. Involuntary eye movements were both significantly more likely to be executed and significantly faster under arousal conditions (Experiments 1 and 2), and the influence of arousal had a specific time course (Experiment 2). Arousal, one form of attention, can produce significant costs for human movement selection as potent but unplanned actions are benefited more than planned ones. PMID:26928432

  14. Open rhinoplasty concepts in facilitating tip reconstruction.

    Science.gov (United States)

    Carminati, Marcello; Robotti, Enrico

    2014-06-01

    The nose is a frequent site for skin cancer, accounting for approximately 26% of basal cell carcinomas and approximately 13% of spinal cell carcinomas of the facial district. Also melanomas, mostly as lentigo maligna melanomas, are frequently located at the nasal pyramid. Although defects can be of varying size and depth, some even involving the whole trilaminar structure of the nose, most remain superficial and seldom reach and infiltrate the underlying framework. In contrast, they can be wide, thus requesting large flaps to resurface the defect. Although a technically well-planned and well-performed surgery can lead to excellent aesthetic results, scars from both donor and recipient sites can be noticeable. Since skin cancers generally affect older people, we often deal with aged noses. Such noses typically present some common features such as plunging tip, increased length, and a prominent hump due to several reasons, already well described in the literature. In this scenario, by reducing and addressing the framework, we can obtain a variable quota of downsizing of the original defect, thus requiring less skin for coverage, and thus reducing the size of needed flaps and consequent scars. This is greatly facilitated by the open rhinoplasty approach. Most of the maneuvers aimed at reducing the framework are indeed the same. PMID:24918706

  15. Using facilitative skills in project management

    DEFF Research Database (Denmark)

    Rasmussen, Lauge Baungaard; Hansen, Mette Sanne; Jacobsen, Peter

    2013-01-01

    facilitating workshops for company managers, public administrators, NGO’s and university professors / students around the world. In addition, this paper is based on the author’s many years of experience in supervising engineering students from for instance China, South Korea, Canada, US, Ghana and various...... European countries who have come to learn and practise facilitating skills as international students at Technical University of Denmark. The paper identifies facilitation skills at three different levels: the intellectual, emotional and synergistic level. An analysis is conducted based on a practical...... ways of knowing in a facilitation course for university students and future project managers....

  16. Ghana - Land Tenure Facilitation Impact Evaluation

    Data.gov (United States)

    Millenium Challenge Corporation — The MCC-supported Land Title Facilitation Activity (LTF) in Ghana was designed to increase investment and productivity by strengthening property rights. In Ghana,...

  17. Oxytocin: the Great Facilitator of Life

    Science.gov (United States)

    Lee, Heon-Jin; Macbeth, Abbe H.; Pagani, Jerome; Young, W. Scott

    2009-01-01

    Oxytocin (Oxt) is a nonapeptide hormone best known for its role in lactation and parturition. Since 1906 when its uterine-contracting properties were described until 50 years later when its sequence was elucidated, research focused on its peripheral roles in reproduction. Only over the past several decades have researchers focused on what functions Oxt might have in the brain, the subject of this review. Immunohistochemical studies revealed that magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei are the neurons of origin for the Oxt released from the posterior pituitary. Smaller cells in various parts of the brain, as well as release from magnocellular dendrites, provide the Oxt responsible for modulating various behaviors at its only identified receptor. Although Oxt is implicated in a variety of “non-social” behaviors, such as learning, anxiety, feeding and pain perception, it is Oxt’s roles in various social behaviors that have come to the fore recently. Oxt is important for social memory and attachment, sexual and maternal behavior, and aggression. Recent work implicates Oxt in human bonding and trust as well. Human disorders characterized by aberrant social interactions, such as autism and schizophrenia, may also involve Oxt expression. Many, if not most, of Oxt’s functions, from social interactions (affiliation, aggression) and sexual behavior to eventual parturition, lactation and maternal behavior, may be viewed as specifically facilitating PMID:19482229

  18. Anthocyanins facilitate tungsten accumulation in Brassica

    Energy Technology Data Exchange (ETDEWEB)

    Hale, K.L.

    2002-11-01

    Accumulation of molybdenum in Brassica was recently found to be correlated with anthocyanin content, involving the formation of a blue complex. Here the role of anthocyanins in tungsten sequestration was investigated using three species of Brassica: B. rapa (cv. Fast plants), B. juncea (Indian mustard) and B. oleracea (red cabbage). Seedlings of B. rapa and B. juncea turned blue when supplied with colourless tungstate. The blue compound co-localized with anthocyanins in the peripheral cell layers, and the degree of blueness was correlated with anthocyanin content. The direct involvement of anthocyanins in the blue coloration was evident when purified anthocyanins showed a colour change from pink to blue in vitro upon addition of tungstate, over a wide pH range. Anthocyanin production was upregulated 3-fold by W in B. juncea, possibly reflecting a function for anthocyanins in W tolerance or sequestration. The presence of anthocyanins facilitated W accumulation in B. rapa: anthocyanin-containing seedlings accumulated 3-fold more W than an anthocyaninless mutant. There was no correlation between anthocyanin content and W tolerance under these conditions. The nature of the interaction between anthocyanins and tungstate was investigated. X-ray absorption spectroscopy showed no change in the local chemical environment of Wupon uptake of tungstate by the plant; HPLC analysis of purified anthocyanin with or without tungstate showed no peak shift after metal treatment.

  19. Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

    International Nuclear Information System (INIS)

    Previously, we reported that CARM1 undergoes ubiquitination-dependent degradation in renal podocytes. It was also reported that CARM1 is necessary for fasting-induced hepatic gluconeogenesis. Based on these reports, we hypothesized that treatment with insulin, a hormone typically present under the ‘fed’ condition, would inhibit gluconeogenesis via CARM1 degradation. HepG2 cells, AML-12 cells, and rat primary hepatocytes were treated with insulin to confirm CARM1 downregulation. Surprisingly, insulin treatment increased CARM1 expression in all cell types examined. Furthermore, treatment with insulin increased histone 3 methylation at arginine 17 and 26 in HepG2 cells. To elucidate the role of insulin-induced CARM1 upregulation, the HA-CARM1 plasmid was transfected into HepG2 cells. CARM1 overexpression did not increase the expression of lipogenic proteins generally increased by insulin signaling. Moreover, CARM1 knockdown did not influence insulin sensitivity. Insulin is known to facilitate hepatic proliferation. Like insulin, CARM1 overexpression increased CDK2 and CDK4 expression. In addition, CARM1 knockdown reduced the number of insulin-induced G2/M phase cells. Moreover, GFP-CARM1 overexpression increased the number of G2/M phase cells. Based on these results, we concluded that insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. These observations indicate that CARM1 plays an important role in liver pathophysiology. - Highlights: • Insulin treatment increases CARM1 expression in hepatocytes. • CARM1 overexpression does not increase the expression of lipogenic proteins. • CARM1 knockdown does not influence insulin sensitivity. • Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

  20. Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Yeom, Chul-gon; Kim, Dong-il; Park, Min-jung; Choi, Joo-hee [College of Veterinary Medicine, Chonnam National University, Gwangju 500-757 (Korea, Republic of); Jeong, Jieun; Wi, Anjin; Park, Whoashig [Jeollanamdo Forest Resources Research Institute, Naju 520-833 (Korea, Republic of); Han, Ho-jae [College of Veterinary Medicine, Seoul National University, Seoul 151-741 (Korea, Republic of); Park, Soo-hyun, E-mail: parksh@chonnam.ac.kr [College of Veterinary Medicine, Chonnam National University, Gwangju 500-757 (Korea, Republic of)

    2015-06-05

    Previously, we reported that CARM1 undergoes ubiquitination-dependent degradation in renal podocytes. It was also reported that CARM1 is necessary for fasting-induced hepatic gluconeogenesis. Based on these reports, we hypothesized that treatment with insulin, a hormone typically present under the ‘fed’ condition, would inhibit gluconeogenesis via CARM1 degradation. HepG2 cells, AML-12 cells, and rat primary hepatocytes were treated with insulin to confirm CARM1 downregulation. Surprisingly, insulin treatment increased CARM1 expression in all cell types examined. Furthermore, treatment with insulin increased histone 3 methylation at arginine 17 and 26 in HepG2 cells. To elucidate the role of insulin-induced CARM1 upregulation, the HA-CARM1 plasmid was transfected into HepG2 cells. CARM1 overexpression did not increase the expression of lipogenic proteins generally increased by insulin signaling. Moreover, CARM1 knockdown did not influence insulin sensitivity. Insulin is known to facilitate hepatic proliferation. Like insulin, CARM1 overexpression increased CDK2 and CDK4 expression. In addition, CARM1 knockdown reduced the number of insulin-induced G2/M phase cells. Moreover, GFP-CARM1 overexpression increased the number of G2/M phase cells. Based on these results, we concluded that insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. These observations indicate that CARM1 plays an important role in liver pathophysiology. - Highlights: • Insulin treatment increases CARM1 expression in hepatocytes. • CARM1 overexpression does not increase the expression of lipogenic proteins. • CARM1 knockdown does not influence insulin sensitivity. • Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation.

  1. Escaping Homelessness: Anticipated and Perceived Facilitators

    Science.gov (United States)

    Patterson, Allisha; Tweed, Roger

    2009-01-01

    One study with two distinct sections was conducted to identify factors facilitating escape from homelessness. In Section 1, 58 homeless individuals rated possible facilitators of escape (factors they believed would help them become more independent and self-sufficient). In Section 2, 80 participants who had already exited homelessness rated the…

  2. Toward Facilitative Mentoring and Catalytic Interventions

    Science.gov (United States)

    Smith, Melissa K.; Lewis, Marilyn

    2015-01-01

    In TESOL teacher mentoring, giving advice can be conceptualized as a continuum, ranging from directive to facilitative feedback. The goal, over time, is to lead toward the facilitative end of the continuum and specifically to catalytic interventions that encourage self-reflection and autonomous learning. This study begins by examining research on…

  3. 50 CFR 17.107 - Facilitating enforcement.

    Science.gov (United States)

    2010-10-01

    ... Protection Areas § 17.107 Facilitating enforcement. Water vehicles operating in manatee sanctuary or refuge... 50 Wildlife and Fisheries 5 2010-10-01 2010-10-01 true Facilitating enforcement. 17.107 Section 17.107 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE...

  4. Reconceptualizing the Pedagogical Value of Student Facilitation

    Science.gov (United States)

    Oztok, Murat

    2016-01-01

    Sustained discourse is critical to the learning potential of online courses. And, while research has surfaced many factors that mediate interaction, it further suggests that sustained interaction remains elusive. In this paper, I propose that student facilitation may have an impact on the quality of facilitators' interactions following a week of…

  5. Facilitating Reflective Thought in Novice Teachers.

    Science.gov (United States)

    Pultorak, Edward G.

    1993-01-01

    This study examined the facilitation of reflection among novice teachers using three types of journal writing and reflective interviews to encourage novice teachers to reflect upon their teaching. The procedures solicited different types of reflection in the student teachers, suggesting that facilitation of teacher reflectivity is vital in teacher…

  6. White Educators Facilitating Discussions about Racial Realities

    Science.gov (United States)

    Quaye, Stephen John

    2012-01-01

    Facilitating democratic discussions about race among students in classroom environments continues to be a problem facing educators. When these discussions occur, they are facilitated mostly by faculty of color. However, given the underrepresentation of faculty of color within higher education institutions and that white students respond…

  7. No facilitator required for membrane transport of hydrogen sulfide

    OpenAIRE

    Mathai, John C.; Missner, Andreas; Kügler, Philipp; Saparov, Sapar M.; Zeidel, Mark L.; Lee, John K.; Pohl, Peter

    2009-01-01

    Hydrogen sulfide (H2S) has emerged as a new and important member in the group of gaseous signaling molecules. However, the molecular transport mechanism has not yet been identified. Because of structural similarities with H2O, it was hypothesized that aquaporins may facilitate H2S transport across cell membranes. We tested this hypothesis by reconstituting the archeal aquaporin AfAQP from sulfide reducing bacteria Archaeoglobus fulgidus into planar membranes and by monitoring the resulting fa...

  8. Practical-theological facilitation as skilled helping

    Directory of Open Access Journals (Sweden)

    Elmo Pienaar

    2013-11-01

    Full Text Available The article discussed the idea of skilled helping in relation to what has been put forward as practical theological facilitation. It has been argued that various helping relationships, amongst which the author refers to coaching, facilitation, and therapy has more in common than what differentiates them if epistemology is viewed as a unifying concept. As such the scope of practical theology in terms of the contexts and themes in which it might be involved is said to widen. The public dimension of the organisational context, more so than the congregational context, has been put forward as an important habitus of practical-theological facilitation. The organisational involvement of the practical-theological facilitator in terms of professional-vocational skilled helping takes on an actual role through facilitation and other helping modalities.

  9. Facilitating the discharge of patients with dementia.

    Science.gov (United States)

    2016-09-01

    Significant numbers of older people with dementia use general hospital services, and facilitating the safe discharge of patients with poor cognition, impaired judgement, misperception or reduced risk awareness is challenging for many healthcare professionals. PMID:27581918

  10. Facilitating lifelong learning with OpenU

    OpenAIRE

    Rubens, Wilfred; Counotte, Anda

    2012-01-01

    Rubens, W., & Counotte, A. (2012). Facilitating lifelong learning with OpenU. In R. Jacobi, & N. van der Woert (Eds.), Trendreport Open Educational Resources 2012 (pp. 22-26). Utrecht: SURF Foundation - Special Interest Group Open Educational Resources SURF.

  11. Do general chemistry textbooks facilitate conceptual understanding?

    OpenAIRE

    Mansoor Niaz

    2005-01-01

    Research in chemistry education has recognized the need for facilitating students' understanding of different concepts. In contrast, most general chemistry curricula and textbooks not only ignore the context in which science progresses but also emphasize rote learning and algorithmic strategies. A historical reconstruction of scientific progress shows that it inevitably leads to controversy and debate, which can arouse students' interest and thus facilitate understanding. The objective of thi...

  12. Facilitated inter-firm collaboration in Ghana

    DEFF Research Database (Denmark)

    Kuada, John Ernest; Sørensen, Olav Jull

    2005-01-01

    Since the mid-1980s, aid agencies have endorsed the need to support private enterprise development in developing countries as an instrument for overall economic development and poverty reduction. Facilitation of collaboration between developed and developing country firms has become one of the most...... mechanisms of third-party inter-firm facilitation and assesses how effective the catalyst institutions are in nurturing collaborations between companies in developed and developing countries. The discussions are illustrated with case examples drawn from Ghana....

  13. Facilitated diffusion buffers noise in gene expression

    OpenAIRE

    Schoech, Armin; Zabet, Nicolae Radu

    2014-01-01

    Transcription factors perform facilitated diffusion (3D diffusion in the cytosol and 1D diffusion on the DNA) when binding to their target sites to regulate gene expression. Here, we investigated the influence of this binding mechanism on the noise in gene expression. Our results showed that, for biologically relevant parameters, the binding process can be represented by a two-state Markov model and that the accelerated target finding due to facilitated diffusion leads to a reduction in both ...

  14. How Facilitation May Interfere with Ecological Speciation

    Directory of Open Access Journals (Sweden)

    P. Liancourt

    2012-01-01

    Full Text Available Compared to the vast literature linking competitive interactions and speciation, attempts to understand the role of facilitation for evolutionary diversification remain scarce. Yet, community ecologists now recognize the importance of positive interactions within plant communities. Here, we examine how facilitation may interfere with the mechanisms of ecological speciation. We argue that facilitation is likely to (1 maintain gene flow among incipient species by enabling cooccurrence of adapted and maladapted forms in marginal habitats and (2 increase fitness of introgressed forms and limit reinforcement in secondary contact zones. Alternatively, we present how facilitation may favour colonization of marginal habitats and thus enhance local adaptation and ecological speciation. Therefore, facilitation may impede or pave the way for ecological speciation. Using a simple spatially and genetically explicit modelling framework, we illustrate and propose some first testable ideas about how, when, and where facilitation may act as a cohesive force for ecological speciation. These hypotheses and the modelling framework proposed should stimulate further empirical and theoretical research examining the role of both competitive and positive interactions in the formation of incipient species.

  15. Singing can facilitate foreign language learning.

    Science.gov (United States)

    Ludke, Karen M; Ferreira, Fernanda; Overy, Katie

    2014-01-01

    This study presents the first experimental evidence that singing can facilitate short-term paired-associate phrase learning in an unfamiliar language (Hungarian). Sixty adult participants were randomly assigned to one of three "listen-and-repeat" learning conditions: speaking, rhythmic speaking, or singing. Participants in the singing condition showed superior overall performance on a collection of Hungarian language tests after a 15-min learning period, as compared with participants in the speaking and rhythmic speaking conditions. This superior performance was statistically significant (p musical ability and training. These results suggest that a "listen-and-sing" learning method can facilitate verbatim memory for spoken foreign language phrases. PMID:23860945

  16. Yeast Fps1 glycerol facilitator functions as a homotetramer.

    Science.gov (United States)

    Beese-Sims, Sara E; Lee, Jongmin; Levin, David E

    2011-12-01

    The Saccharomyces cerevisiae Fps1 glycerol channel is a member of the major intrinsic protein (MIP) family of plasma membrane channel proteins that functions in osmoregulatory pathways to transport glycerol passively out of the cell. The MIP family is subdivided into members that are selectively permeable to water (aquaporins) and those permeated by glycerol (aquaglyceroporins or glycerol facilitators). Although aquaporins function as homo-tetramers with each monomer possessing its own channel, previous studies have suggested that aquaglyceroporins may function as monomers. Here we provide both genetic and biochemical evidence that Fps1 functions as a homotetramer to regulate glycerol transport in yeast. PMID:22030956

  17. The Resourceful Facilitator: Teacher Leaders Constructing Identities as Facilitators of Teacher Peer Groups

    Science.gov (United States)

    Allen, David

    2016-01-01

    The use of teacher peer groups is a prevalent strategy for school-based professional development and instructional improvement. Facilitation of such groups is an increasingly vital dimension of teacher leadership as a component of school improvement efforts. Drawing on a qualitative study of facilitation of teacher peer groups, the article…

  18. Drug facilitated sexual assault with lethal outcome

    DEFF Research Database (Denmark)

    Mehling, Lena-Maria; Johansen, Sys Stybe; Wang, Xin;

    2016-01-01

    A very serious case of DFSA (drug facilitated sexual assault) is presented, in which a six-year-old girl died following sedation with γ-hydroxybutyric acid (GHB). She had been sexually abused by a relative. Samples of cardiac blood, bile, vitreous humour, liver, kidney, brain tissues and hair were...

  19. Mild Traumatic Brain Injury: Facilitating School Success.

    Science.gov (United States)

    Hux, Karen; Hacksley, Carolyn

    1996-01-01

    A case study is used to demonstrate the effects of mild traumatic brain injury on educational efforts. Discussion covers factors complicating school reintegration, ways to facilitate school reintegration, identification of cognitive and behavioral consequences, minimization of educators' discomfort, reintegration program design, and family…

  20. Facilitating Team Learning through Transformational Leadership

    Science.gov (United States)

    Raes, Elisabeth; Decuyper, Stefan; Lismont, Bart; Van den Bossche, Piet; Kyndt, Eva; Demeyere, Sybille; Dochy, Filip

    2013-01-01

    This article investigates when and how teams engage in team learning behaviours (TLB). More specifically, it looks into how different leadership styles facilitate TLB by influencing the social conditions that proceed them. 498 healthcare workers from 28 nursery teams filled out a questionnaire measuring the concepts leadership style, TLB, social…

  1. Facilitating Second Language Learning with Music

    Science.gov (United States)

    Bae, Su-Young

    2006-01-01

    The use of music in facilitating second language (as well as first language) learning is supported by evidence that points to the musical nature of even preverbal infants. Music and language have been found to develop similarly, and researchers have noted advantages to using song in learning. The author observed her Korean 21-month-old for …

  2. Facilitating peer learning in study groups

    DEFF Research Database (Denmark)

    Adriansen, Hanne Kirstine; Madsen, Lene Møller

    2009-01-01

    In 2008 University of Aarhus, Denmark, issued a report concerning student experience with the study environment. Among the university's eight faculties, the Danish School of Education (DPU) held the sad record of having the lowest student well-being. This led to an action research project 'Facili...... done by relying on the students' own resources, using peer-learning and facilitating these activities....

  3. Facilitated subcutaneous immunoglobulin administration (fSCIg)

    DEFF Research Database (Denmark)

    Blau, Igor-Wolfgang; Conlon, Niall; Petermann, Robert;

    2016-01-01

    and diverse medical needs that treatments for SID management should strive to meet. In this special report, we study the opportunities provided by facilitated subcutaneous immunoglobulin administration (fSCIg) to treat patients for whom the conventional routes (intravenous and subcutaneous) are sub...

  4. Facilitation of Retention by White Noise

    Science.gov (United States)

    Baumeister, Alfred A.; Kistler, Doris

    1975-01-01

    This study attempted to determine if white noise (an arousing stimulus), when presented at the time of recall, facilitates performance of second and fifth grade students, and if this effect generalizes across different kinds of learning tasks. Findings indicate that white noise produces improvements in performance in both age groups. (GO)

  5. Embeddedness as a facilitator of sustainable entrepreneurship

    OpenAIRE

    Dufays, Frédéric

    2015-01-01

    This conceptual paper builds on stakeholder theory and the embeddedness argument to shift from the "what" to the "how" question on sustainable entrepreneurship. It shows that sustainable entrepreneurship is a highly embedded process and that this high embeddedness facilitates the sustainability character of entrepreneurship. Peer reviewed

  6. How academic teachers perceive and facilitate creativity

    DEFF Research Database (Denmark)

    Bjørner, Thomas; Kofoed, Lise B.

    2013-01-01

    We will present a case study result from a cross-disciplinary education called Medialogy, which is taught in the Technical and Science Faculty at Aalborg University. The aim of Medialogy is to facilitate creativity within technical solutions. The intention of this paper is to answer the following...

  7. Facilitating Learning Spaces in Forum Theatre

    Science.gov (United States)

    Rae, Jan

    2013-01-01

    Purpose: The purpose of this paper is to evaluate the extent to which forum theatre interventions can support non-hierarchical approaches to learning, development and change management initiatives in organisations. Design/methodology/approach: Semi-structured interviews were carried out with theatre consultancies, actors/facilitators,…

  8. Facilitating Critical Thinking in Clinical Practice.

    Science.gov (United States)

    Persaud, Deanna; And Others

    Activities to promote the transfer of theoretical knowledge into clinical practice have been developed to facilitate learning by individuals with various learning styles, reduce student stress, and improve teaching methods in a baccalaureate nursing program at the California State University, Chico. Specific activities included innovative…

  9. Facilitated IEP Meetings. PHP-c90

    Science.gov (United States)

    PACER Center, 2004

    2004-01-01

    To help special education planning teams reach agreements, the Minnesota Department of Education and the Minnesota Special Education Mediation Service (MNSEMS) provide the option of facilitated IEP meetings. This option is available for IEP (Individualized Education Program), IIIP (Individual Interagency Intervention Plan), and IFSP (Individual…

  10. The Creative Music Workshop: Event, Facilitation, Gift

    Science.gov (United States)

    Higgins, Lee

    2008-01-01

    The purpose of this article is to explore the desires and tensions inherent within the act of facilitating creative music-making workshops. Following the introduction, the article is divided into three sections: (1) a discussion of the workshop event as a contingent structure through which creative music-making may take place; (2) an exploration…

  11. Facilitating Engagement by Differentiating Independent Reading

    Science.gov (United States)

    Kelley, Michelle J.; Clausen-Grace, Nicki

    2009-01-01

    The authors provide teachers with a rationale for engaging students in independent reading using a differentiated approach. By profiling types of readers, sharing observational tools, and offering teaching suggestions for each type of reader the authors give practical suggestions to facilitate reading engagement and make independent reading more…

  12. Body Posture Facilitates Retrieval of Autobiographical Memories

    Science.gov (United States)

    Dijkstra, Katinka; Kaschak, Michael P.; Zwaan, Rolf A.

    2007-01-01

    We assessed potential facilitation of congruent body posture on access to and retention of autobiographical memories in younger and older adults. Response times were shorter when body positions during prompted retrieval of autobiographical events were similar to the body positions in the original events than when body position was incongruent.…

  13. Social Facilitation of Laughter in Children

    Science.gov (United States)

    Chapman, Antony J.

    1973-01-01

    The present study is concerned primarily with demonstrating that laughter can be socially facilitated. It showed that children, presented aurally with laughter-provoking material, laugh more in the presence of a companion, whether or not the companion can hear the material. (Author/RK)

  14. Unique structural features facilitate lizard tail autotomy

    DEFF Research Database (Denmark)

    Sanggaard, Kristian W; Danielsen, Carl Chr; Wogensen, Lise;

    2012-01-01

    that tail shedding by the Tokay gecko (Gekko gecko) and the associated extracellular matrix (ECM) rupture were independent of proteolysis. Instead, lizard caudal autotomy relied on biological adhesion facilitated by surface microstructures. Results based on bio-imaging techniques demonstrated that the tail...

  15. Corticosterone facilitates fluoxetine-induced neuronal plasticity in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Katsunori Kobayashi

    Full Text Available The hippocampal dentate gyrus has been implicated in a neuronal basis of antidepressant action. We have recently shown a distinct form of neuronal plasticity induced by the serotonergic antidepressant fluoxetine, that is, a reversal of maturation of the dentate granule cells in adult mice. This "dematuration" is induced in a large population of dentate neurons and maintained for at least one month after withdrawal of fluoxetine, suggesting long-lasting strong influence of dematuration on brain functioning. However, reliable induction of dematuration required doses of fluoxetine higher than suggested optimal doses for mice (10 to 18 mg/kg/day, which casts doubt on the clinical relevance of this effect. Since our previous studies were performed in naive mice, in the present study, we reexamined effects of fluoxetine using mice treated with chronic corticosterone that model neuroendocrine pathophysiology associated with depression. In corticosterone-treated mice, fluoxetine at 10 mg/kg/day downregulated expression of mature granule cell markers and attenuated strong frequency facilitation at the synapse formed by the granule cell axon mossy fiber, suggesting the induction of granule cell dematuration. In addition, fluoxetine caused marked enhancement of dopaminergic modulation at the mossy fiber synapse. In vehicle-treated mice, however, fluoxetine at this dose had no significant effects. The plasma level of fluoxetine was comparable to that in patients taking chronic fluoxetine, and corticosterone did not affect it. These results indicate that corticosterone facilitates fluoxetine-induced plastic changes in the dentate granule cells. Our finding may provide insight into neuronal mechanisms underlying enhanced responsiveness to antidepressant medication in certain pathological conditions.

  16. A secretory pathway-localized cation diffusion facilitator confers plant manganese tolerance

    OpenAIRE

    Peiter, Edgar; Montanini, Barbara; Gobert, Anthony; Pedas, Pai; Husted, Søren; Maathuis, Frans J. M.; Blaudez, Damien; Chalot, Michel; Sanders, Dale

    2007-01-01

    Manganese toxicity is a major problem for plant growth in acidic soils, but cellular mechanisms that facilitate growth in such conditions have not been clearly delineated. Established mechanisms that counter metal toxicity in plants involve chelation and cytoplasmic export of the metal across the plasma or vacuolar membranes out of the cell or sequestered into a large organelle, respectively. We report here that expression of the Arabidopsis and poplar MTP11 cation diffusion facilitators in a...

  17. Impact of Pharmacist Facilitated Discharge Medication Reconciliation

    Directory of Open Access Journals (Sweden)

    Todd M. Super

    2014-07-01

    Full Text Available Preventable adverse drug events occur frequently at transitions in care and are a problem for many patients following hospital discharge. Many of these problems can be attributed to poor medication reconciliation. The purpose of this study was to assess the impact that direct pharmacist involvement in the discharge medication reconciliation process had on medication discrepancies, patient outcomes, and satisfaction. A cohort study of 70 patients was designed to assess the impact of pharmacist facilitated discharge medication reconciliation at a 204-bed community hospital in Battle Creek, Michigan, USA. Discharge summaries were analyzed to compare patients who received standard discharge without pharmacist involvement to those having pharmacist involvement. The total number of discrepancies in the group without pharmacist involvement was significantly higher than that of the pharmacist facilitated group.

  18. Facilitative glucose transporters in livestock species

    OpenAIRE

    Hocquette, Jean-François; Abe, Hiroyuki

    2000-01-01

    Les transporteurs du glucose à diffusion facilitée chez les animaux de ferme. L'étude des transporteurs du glucose à diffusion facilitée (GLUT) nécessite des techniques en immunologie ou en biologie moléculaire précises et sensibles pour étudier la régulation de leur expression au niveau ARNm ou protéique. Le clonage d'ADNc des différents GLUT a montré que GLUT4 et GLUT1 divergent moins entre espèces que les autres isoformes de GLUT. Le rôle important des GLUT dans le contrôle de l'homéostasi...

  19. Facilitating value co-creation in networks

    DEFF Research Database (Denmark)

    Rasmussen, Mette Apollo

    2016-01-01

    symbolic interactionism in the study. Two in-depth ethnographic case studies provide the empirical basis for the dissertation. The dissertation has constructed ethnographic narratives of the following two networks in Ringsted Municipality: •Network 1: CSR network •Network 2: Network for managing directors...... networks led participants to create imaginative values, but that the network participants also continuously struggled to escape the impression of imaginative value through reflexive strategies. Further, it is discussed how boundary objects and trust are phenomena with importance for processes of value co...... “socializing” facilitator, who interacts with participants in a network over time and comes to know them well. The facilitator’s role is extended with processes of Managing networks during timeout, highlighting how and when a socializing facilitator has an important role to play in networks....

  20. Facilitating value co-creation in networks

    DEFF Research Database (Denmark)

    Rasmussen, Mette Apollo

    The dissertation investigates through two ethnographic case studies how value co-creation takes place in inter-organizational networks that have been facilitated by a municipality. The contribution of the study to business network research is the emphasis on development phases of networks...... by a municipality and how participants in such networks come to experience the value of networking over time. The overall research question is: How do processes of network facilitation support value co-creation in local business networks? The dissertation is positioned within the field of inter......-organizational network studies. Based on Newell, it is argued that two major streams of literature about networking can be identified: 1) Network as channels and 2) Network as communities (Newell et al., 2009). Yet, these say little about how business networks may be dynamically created within a local context and how...

  1. Facilitating phenomenological interviewing by means of reflexology

    Directory of Open Access Journals (Sweden)

    E Ross

    2005-09-01

    Full Text Available The aim of this article is to show how reflexology could facilitate phenomenological interviewing by probing the lifeworld of individual participants. It presents a hybrid study of phenomenological interviewing and reflexology as a holistic method of health care. In this sense, it is an interparadigmatic study, since it rests on the interface of Western and Oriental thought. This article reports on seven cases which were included in the qualitative, empirical investigation. During the sessions, reflexological readings served as impetus for inquiry into the experiences of the participants, as congestions on reflex points and along meridians were interpreted in terms of physical organs and functions. These readings were related to corresponding emotions as accepted within the reflexology paradigm. It was, however, up to the participants to inform the researcher of events and/or circumstances that caused the emotions. Thus, nonverbal data communicated information that facilitated verbal exchange concerning the life-world of each individual participant.

  2. 3D printing facilitated scaffold-free tissue unit fabrication.

    Science.gov (United States)

    Tan, Yu; Richards, Dylan J; Trusk, Thomas C; Visconti, Richard P; Yost, Michael J; Kindy, Mark S; Drake, Christopher J; Argraves, William Scott; Markwald, Roger R; Mei, Ying

    2014-06-01

    Tissue spheroids hold great potential in tissue engineering as building blocks to assemble into functional tissues. To date, agarose molds have been extensively used to facilitate fusion process of tissue spheroids. As a molding material, agarose typically requires low temperature plates for gelation and/or heated dispenser units. Here, we proposed and developed an alginate-based, direct 3D mold-printing technology: 3D printing microdroplets of alginate solution into biocompatible, bio-inert alginate hydrogel molds for the fabrication of scaffold-free tissue engineering constructs. Specifically, we developed a 3D printing technology to deposit microdroplets of alginate solution on calcium containing substrates in a layer-by-layer fashion to prepare ring-shaped 3D hydrogel molds. Tissue spheroids composed of 50% endothelial cells and 50% smooth muscle cells were robotically placed into the 3D printed alginate molds using a 3D printer, and were found to rapidly fuse into toroid-shaped tissue units. Histological and immunofluorescence analysis indicated that the cells secreted collagen type I playing a critical role in promoting cell-cell adhesion, tissue formation and maturation. PMID:24717646

  3. A facilitated mentoring process for engineers

    Energy Technology Data Exchange (ETDEWEB)

    Donald, L.; Clark, M.

    1993-11-01

    Mentoring has been occurring in organizations for many, many years through a natural pairing process of people wanting to help one another. The numerous benefits of mentoring to both the protege and the mentor are widely known. In this paper we describe a Facilitated Mentoring Pilot Program for engineers, successfully completed in June, 1993. This career development tool can help make ``Every Engineer a Leader.``

  4. Sleep facilitates long-term face adaptation

    OpenAIRE

    Ditye, T.; A.H Javadi; Carbon, C.C.; Walsh, V

    2013-01-01

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted imag...

  5. Methylphenidate facilitates learning-induced amygdala plasticity

    OpenAIRE

    Tye, Kay M.; Tye, Lynne D.; Cone, Jackson J.; Hekkelman, Evelien F; Janak, Patricia H.; Bonci, Antonello

    2010-01-01

    Although methylphenidate (Ritalin) has been used therapeutically for nearly 60 years, the mechanisms by which it acutely modifies behavioral performance are poorly understood. Here we combined intra–lateral amygdala in vivo pharmacology and ex vivo electrophysiology to show that acute administration of methylphenidate, as well as a selective dopamine transporter inhibitor, facilitated learning-induced strengthening of cortico-amygdala synapses through a postsynaptic increase in AMPA receptor–...

  6. Writing reports to facilitate patent applications.

    Energy Technology Data Exchange (ETDEWEB)

    Libman, George H.; Doerry, Armin Walter

    2004-06-01

    Brief disclosures may often be sufficient for the filing of a Technical Advance with Sandia's Intellectual Property Center, but still be inadequate to facilitate an optimum patent application where more detail and explanation are required. Consequently, the crafting of a patent application may require considerably more additional interaction between the application preparer and the inventors. This inefficiency can be considerably mitigated if the inventors address some critical aspects of a patent application when they write a technical report.

  7. Music training facilitates lexical stress processing

    OpenAIRE

    Kolinsky, Régine; Cuvelier, René; Goetry, Vincent; Peretz, Isabelle; Morais, Jose

    2009-01-01

    We investigated whether music training facilitates the processing of lexical stress in natives of a language that does not use lexical stress contrasts. Musically trained (musicians) or untrained (nonmusicians) French natives were presented with two tasks: speeded classification that required them to focus on a segmental contrast and ignore irrelevant stress variations, and sequence repetition involving either segmental or stress contrasts. In the latter situation, French natives are usually ...

  8. Contracts as a Facilitator of Resource Evolution

    OpenAIRE

    Mouzas, Stefanos; Ford, David

    2012-01-01

    The formality of contracts is not external to the substance of business interactions, but a way of articulating, facilitating and simplifying the complexity of business interactions. An umbrella contract, in particular, is an abstraction of possibility and a refined version of the substance of business interaction in which resource leveraging may or may not occur. Umbrella contracts circumscribe an in-built platform or ‘architecture’ that enables regular and repeated knowledge-intensive inter...

  9. Spatial part-set cuing facilitation.

    Science.gov (United States)

    Kelley, Matthew R; Parasiuk, Yuri; Salgado-Benz, Jennifer; Crocco, Megan

    2016-07-01

    Cole, Reysen, and Kelley [2013. Part-set cuing facilitation for spatial information. Journal of Experimental Psychology: Learning, Memory, & Cognition, 39, 1615-1620] reported robust part-set cuing facilitation for spatial information using snap circuits (a colour-coded electronics kit designed for children to create rudimentary circuit boards). In contrast, Drinkwater, Dagnall, and Parker [2006. Effects of part-set cuing on experienced and novice chess players' reconstruction of a typical chess midgame position. Perceptual and Motor Skills, 102(3), 645-653] and Watkins, Schwartz, and Lane [1984. Does part-set cuing test for memory organization? Evidence from reconstructions of chess positions. Canadian Journal of Psychology/Revue Canadienne de Psychologie, 38(3), 498-503] showed no influence of part-set cuing for spatial information when using chess boards. One key difference between the two procedures was that the snap circuit stimuli were explicitly connected to one another, whereas chess pieces were not. Two experiments examined the effects of connection type (connected vs. unconnected) and cue type (cued vs. uncued) on memory for spatial information. Using chess boards (Experiment 1) and snap circuits (Experiment 2), part-set cuing facilitation only occurred when the stimuli were explicitly connected; there was no influence of cuing with unconnected stimuli. These results are potentially consistent with the retrieval strategy disruption hypothesis, as well as the two- and three-mechanism accounts of part-set cuing. PMID:26252760

  10. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids.

    Science.gov (United States)

    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-05-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders. PMID:26514583

  11. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids

    Science.gov (United States)

    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-01-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders. PMID:26514583

  12. COGNITIVE FATIGUE FACILITATES PROCEDURAL SEQUENCE LEARNING

    Directory of Open Access Journals (Sweden)

    Guillermo eBorragán

    2016-03-01

    Full Text Available Enhanced procedural learning has been evidenced in conditions where cognitive control is diminished, including hypnosis, disruption of prefrontal activity and non-optimal time of the day. Another condition depleting the availability of controlled resources is cognitive fatigue. We tested the hypothesis that cognitive fatigue, eventually leading to diminished cognitive control, facilitates procedural sequence learning. In a two-day experiment, twenty-three young healthy adults were administered a serial reaction time task (SRTT following the induction of high or low levels of cognitive fatigue, in a counterbalanced order. Cognitive fatigue was induced using the Time load Dual-back (TloadDback paradigm, a dual working memory task that allows tailoring cognitive load levels to the individual's optimal performance capacity. In line with our hypothesis, reaction times in the SRTT were faster in the high- than in the low-level fatigue condition, and performance improvement showed more of a benefit from the sequential components than from motor. Altogether, our results suggest a paradoxical, facilitating impact of cognitive fatigue on procedural motor sequence learning. We propose that facilitated learning in the high-level fatigue condition stems from a reduction in the cognitive resources devoted to cognitive control processes that normally oppose automatic procedural acquisition mechanisms.

  13. Facilitating electron transfer in bioelectrocatalytic systems

    OpenAIRE

    Sekretaryova, Alina

    2016-01-01

    Bioelectrocatalytic systems are based on biological entities, such as enzymes, whole cells, parts of cells or tissues, which catalyse electrochemical processes that involve the interaction between chemical change and electrical energy. In all cases, biocatalysis is implemented by enzymes, isolated or residing inside cells or part of cells. Electron transfer (ET) phenomena, within the protein molecules and between biological redox systems and electronics, enable the development of various bioe...

  14. The Effects of Facilitation on Cognitive Restructuring in Online Discussion

    Science.gov (United States)

    Chang, Shujen L.

    2005-01-01

    This study compared the effects of system-initiated (low-level) facilitation with that of facilitator-initiated plus system-initiated (high-level) facilitation on cognitive restructuring and learning achievement. Graduate students participated in facilitated online discussion within a web course for one semester. This study found no significant…

  15. 3D printing facilitated scaffold-free tissue unit fabrication

    International Nuclear Information System (INIS)

    Tissue spheroids hold great potential in tissue engineering as building blocks to assemble into functional tissues. To date, agarose molds have been extensively used to facilitate fusion process of tissue spheroids. As a molding material, agarose typically requires low temperature plates for gelation and/or heated dispenser units. Here, we proposed and developed an alginate-based, direct 3D mold-printing technology: 3D printing microdroplets of alginate solution into biocompatible, bio-inert alginate hydrogel molds for the fabrication of scaffold-free tissue engineering constructs. Specifically, we developed a 3D printing technology to deposit microdroplets of alginate solution on calcium containing substrates in a layer-by-layer fashion to prepare ring-shaped 3D hydrogel molds. Tissue spheroids composed of 50% endothelial cells and 50% smooth muscle cells were robotically placed into the 3D printed alginate molds using a 3D printer, and were found to rapidly fuse into toroid-shaped tissue units. Histological and immunofluorescence analysis indicated that the cells secreted collagen type I playing a critical role in promoting cell–cell adhesion, tissue formation and maturation. (paper)

  16. Facilitating functional annotation of chicken microarray data

    Directory of Open Access Journals (Sweden)

    Gresham Cathy R

    2009-10-01

    Full Text Available Abstract Background Modeling results from chicken microarray studies is challenging for researchers due to little functional annotation associated with these arrays. The Affymetrix GenChip chicken genome array, one of the biggest arrays that serve as a key research tool for the study of chicken functional genomics, is among the few arrays that link gene products to Gene Ontology (GO. However the GO annotation data presented by Affymetrix is incomplete, for example, they do not show references linked to manually annotated functions. In addition, there is no tool that facilitates microarray researchers to directly retrieve functional annotations for their datasets from the annotated arrays. This costs researchers amount of time in searching multiple GO databases for functional information. Results We have improved the breadth of functional annotations of the gene products associated with probesets on the Affymetrix chicken genome array by 45% and the quality of annotation by 14%. We have also identified the most significant diseases and disorders, different types of genes, and known drug targets represented on Affymetrix chicken genome array. To facilitate functional annotation of other arrays and microarray experimental datasets we developed an Array GO Mapper (AGOM tool to help researchers to quickly retrieve corresponding functional information for their dataset. Conclusion Results from this study will directly facilitate annotation of other chicken arrays and microarray experimental datasets. Researchers will be able to quickly model their microarray dataset into more reliable biological functional information by using AGOM tool. The disease, disorders, gene types and drug targets revealed in the study will allow researchers to learn more about how genes function in complex biological systems and may lead to new drug discovery and development of therapies. The GO annotation data generated will be available for public use via AgBase website and

  17. Facilitated exclusion process and Pfaffian Schur processes

    OpenAIRE

    Baik, Jinho; Barraquand, Guillaume; Corwin, Ivan; Suidan, Toufic

    2016-01-01

    We study the Facilitated TASEP, an interacting particle system on the one dimensional integer lattice. We prove that starting from step initial condition, the position of the rightmost particle has Tracy Widom GSE statistics on a cube root time scale, while the statistics in the bulk of the rarefaction fan are GUE. This uses a mapping with last-passage percolation in a half-quadrant, which we study using the formalism of Pfaffian Schur processes. For the model with exponential weights, we pro...

  18. Intracellular facilitated diffusion: searchers, crowders and blockers

    CERN Document Server

    Brackley, C A; Marenduzzo, D

    2013-01-01

    In bacteria, regulatory proteins search for a specific DNA binding target via "facilitated diffusion": a series of rounds of 3D diffusion in the cytoplasm, and 1D linear diffusion along the DNA contour. Using large scale Brownian dynamics simulations we find that each of these steps is affected differently by crowding proteins, which can either be bound to the DNA acting as a road block to the 1D diffusion, or freely diffusing in the cytoplasm. Macromolecular crowding can strongly affect mechanistic features such as the balance between 3D and 1D diffusion, but leads to surprising robustness of the total search time.

  19. Correlation length facilitates Voigt wave propagation

    CERN Document Server

    Mackay, Tom G

    2004-01-01

    Under certain circumstances, Voigt waves can propagate in a biaxial composite medium even though the component material phases individually do not support Voigt wave propagation. This phenomenon is considered within the context of the strong--permittivity--fluctuation theory. A generalized implementation of the theory is developed in order to explore the propagation of Voigt waves in any direction. It is shown that the correlation length--a parameter characterizing the distributional statistics of the component material phases--plays a crucial role in facilitating the propagation of Voigt waves in the homogenized composite medium.

  20. Golgi localized barley MTP8 proteins facilitate Mn transport

    DEFF Research Database (Denmark)

    Pedas, Pai Rosager; Schiller, Michaela; Hegelund, Josefine Nymark;

    2014-01-01

    Many metabolic processes in plants are regulated by manganese (Mn) but limited information is available on the molecular mechanisms controlling cellular Mn homeostasis. In this study, a yeast assay was used to isolate and characterize two genes, MTP8.1 and MTP8.2 , which encode membrane-bound pro......Many metabolic processes in plants are regulated by manganese (Mn) but limited information is available on the molecular mechanisms controlling cellular Mn homeostasis. In this study, a yeast assay was used to isolate and characterize two genes, MTP8.1 and MTP8.2 , which encode membrane......-bound proteins belonging to the cation diffusion facilitator (CDF) family in the cereal species barley (Hordeum vulgare). Transient expression in onion epidermal cells showed that MTP8.1 and MTP8.2 proteins fused to the green fluorescent protein (GFP) are localized to Golgi. When heterologously expressed......8 proteins are involved in Mn loading to the Golgi apparatus and play a role in Mn homeostasis by delivering Mn to Mn-dependent enzymes and/or by facilitating Mn efflux via secretory vesicles. This study highlights the importance of MTP transporters in Mn homeostasis and is the first report of Golgi...

  1. Corticotomy facilitated orthodontics: Review of a technique.

    Science.gov (United States)

    Alghamdi, Ali Saad Thafeed

    2010-01-01

    Corticotomy found to be effective in accelerating orthodontic treatment. The most important factors in the success of this technique is proper case selection and careful surgical and orthodontic treatment. Corticotomy facilitated orthodontics advocated for comprehensive fixed orthodontic appliances in conjunction with full thickness flaps and labial and lingual corticotomies around teeth to be moved. Bone graft should be applied directly over the bone cuts and the flap sutured in place. Tooth movement should be initiated two weeks after the surgery, and every two weeks thereafter by activation of the orthodontic appliance. Orthodontic treatment time with this technique will be reduced to one-third the time of conventional orthodontics. Alveolar augmentation of labial and lingual cortical plates were used in an effort to enhance and strengthen the periodontium, reasoning that the addition of bone to alveolar housing of the teeth, using modern bone grafting techniques, ensures root coverage as the dental arch expanded. Corticotomy facilitated orthodontics is promising procedure but only few cases were reported in the literature. Controlled clinical and histological studies are needed to understand the biology of tooth movement with this procedure, the effect on teeth and bone, post-retention stability, measuring the volume of mature bone formation, and determining the status of the periodontium and roots after treatment. PMID:23960473

  2. Transposable elements: powerful facilitators of evolution.

    Science.gov (United States)

    Oliver, Keith R; Greene, Wayne K

    2009-07-01

    Transposable elements (TEs) are powerful facilitators of genome evolution, and hence of phenotypic diversity as they can cause genetic changes of great magnitude and variety. TEs are ubiquitous and extremely ancient, and although harmful to some individuals, they can be very beneficial to lineages. TEs can build, sculpt, and reformat genomes by both active and passive means. Lineages with active TEs or with abundant homogeneous inactive populations of TEs that can act passively by causing ectopic recombination are potentially fecund, adaptable, and taxonate readily. Conversely, taxa deficient in TEs or possessing heterogeneous populations of inactive TEs may be well adapted in their niche, but tend to prolonged stasis and may risk extinction by lacking the capacity to adapt to change, or diversify. Because of recurring intermittent waves of TE infestation, available data indicate a compatibility with punctuated equilibrium, in keeping with widely accepted interpretations of evidence from the fossil record. We propose a general and holistic synthesis on how the presence of TEs within genomes makes them flexible and dynamic, so that genomes themselves are powerful facilitators of their own evolution. PMID:19415638

  3. Dynamic characteristics of multisensory facilitation and inhibition.

    Science.gov (United States)

    Wang, W Y; Hu, L; Valentini, E; Xie, X B; Cui, H Y; Hu, Y

    2012-10-01

    Multimodal integration, which mainly refers to multisensory facilitation and multisensory inhibition, is the process of merging multisensory information in the human brain. However, the neural mechanisms underlying the dynamic characteristics of multimodal integration are not fully understood. The objective of this study is to investigate the basic mechanisms of multimodal integration by assessing the intermodal influences of vision, audition, and somatosensory sensations (the influence of multisensory background events to the target event). We used a timed target detection task, and measured both behavioral and electroencephalographic responses to visual target events (green solid circle), auditory target events (2 kHz pure tone) and somatosensory target events (1.5 ± 0.1 mA square wave pulse) from 20 normal participants. There were significant differences in both behavior performance and ERP components when comparing the unimodal target stimuli with multimodal (bimodal and trimodal) target stimuli for all target groups. Significant correlation among reaction time and P3 latency was observed across all target conditions. The perceptual processing of auditory target events (A) was inhibited by the background events, while the perceptual processing of somatosensory target events (S) was facilitated by the background events. In contrast, the perceptual processing of visual target events (V) remained impervious to multisensory background events. PMID:24082962

  4. Angiopoietin-1 facilitates recovery of hematopoiesis in radiated mice.

    Science.gov (United States)

    Sun, Lan; Zhang, Huaibao; Bi, Laixi; Shi, Yi-Fen; Xing, Chongyun; Tang, Liyuan; Jiang, Songfu; Yu, Kang

    2016-01-01

    Angiopoietin-1 (Ang-1) plays a critical role in the regulation of endothelial cell survival and vascular maturation and stability. However, its role in hematopoiesis is not clear. Here, we determined effect of Ang-1 on the recovery of hematopoiesis in radiated mice. By injecting an Ang-1 plasmid, we found that Ang-1 was preferentially expressed in bone marrow (BM) of femur from radiated mice. This injection resulted in elevated blood counts and serum VEGF level. The blockade in S phase of cell cycle in mouse BM stromal cells following radiation was attenuated by injection of Ang-1 plasmid. In addition, injection of Ang-1 plasmid attenuated the radiation-mediated inhibition of Tie2 expression. Furthermore, through analyzing Notch1 expression, we found that injection of Ang-1 plasmid increased Notch mRNA expression in radiated mice. In conclusion, these findings suggest that Ang-1 facilitates the recovery of hematopoiesis in radiated mice with the involvement of Notch signaling pathway. PMID:27347310

  5. Mutual inactivation of Notch receptors and ligands facilitates developmental patterning.

    Directory of Open Access Journals (Sweden)

    David Sprinzak

    2011-06-01

    Full Text Available Developmental patterning requires juxtacrine signaling in order to tightly coordinate the fates of neighboring cells. Recent work has shown that Notch and Delta, the canonical metazoan juxtacrine signaling receptor and ligand, mutually inactivate each other in the same cell. This cis-interaction generates mutually exclusive sending and receiving states in individual cells. It generally remains unclear, however, how this mutual inactivation and the resulting switching behavior can impact developmental patterning circuits. Here we address this question using mathematical modeling in the context of two canonical pattern formation processes: boundary formation and lateral inhibition. For boundary formation, in a model motivated by Drosophila wing vein patterning, we find that mutual inactivation allows sharp boundary formation across a broader range of parameters than models lacking mutual inactivation. This model with mutual inactivation also exhibits robustness to correlated gene expression perturbations. For lateral inhibition, we find that mutual inactivation speeds up patterning dynamics, relieves the need for cooperative regulatory interactions, and expands the range of parameter values that permit pattern formation, compared to canonical models. Furthermore, mutual inactivation enables a simple lateral inhibition circuit architecture which requires only a single downstream regulatory step. Both model systems show how mutual inactivation can facilitate robust fine-grained patterning processes that would be difficult to implement without it, by encoding a difference-promoting feedback within the signaling system itself. Together, these results provide a framework for analysis of more complex Notch-dependent developmental systems.

  6. Balancing Design Project Supervision and Learning Facilitation

    DEFF Research Database (Denmark)

    Nielsen, Louise Møller

    2012-01-01

    In design there is a long tradition for apprenticeship, as well as tradition for learning through design projects. Today many design educations are positioned within the University context, and have to be aligned with the learning culture and structure, which they represent. This raises a specific...... set of demands to the design lecturer. On one hand she is the facilitator of the learning process, where the students are in charge of their own projects, and where learning happens through the students’ own experiences, successes and mistakes and on the other hand she is a supervisor, who uses her...... experiences and expertise to guide the students’ decisions in relation to the design project. This paper focuses on project supervision in the context of design education – and more specifically on how this supervision is unfolded in a Problem Based Learning culture. The paper explores the supervisor...

  7. Facilitating critical discourse through "meaningful disagreement" online.

    Science.gov (United States)

    Dalley-Hewer, Jayne; Clouder, Deanne Lynn; Jackson, Ann; Goodman, Simon; Bluteau, Patricia; Davies, Bernadette

    2012-11-01

    This paper is concerned with identifying ways of facilitating "meaningful disagreement" amongst students in interprofessional online discussion forums. It builds on previous research that identified a trend toward polite agreement and only limited evidence of disagreement in this setting. Given the suggestion that disagreement indicates a deeper level of engagement in group discussion and therefore leads to deeper learning, our aim was to critique the pedagogical approach adopted by analyzing whether we were promoting a particular interprofessional discourse amongst students that favored agreement and therefore limited potential learning. Agreement in this context has been conceptualized as a form of online interprofessional "netiquette" existing amongst participants. Findings suggest that creating an online context for critical discourse is challenging; however, the careful construction of learning outcomes, trigger material/resources and learning activities, as well as attention to students' stage of study and life experience, can provoke the desired effects. PMID:22897367

  8. Facilitating effects of exercise on information processing.

    Science.gov (United States)

    Davranche, Karen; Audiffren, Michel

    2004-05-01

    The aim of this study was to examine the facilitating effects of moderate physical exercise on the reaction process to gain a better understanding of the interaction between physiological and cognitive processes. Sixteen participants with specific expertise in decision-making sports performed a double task consisting of choice reaction time while cycling. Signal quality, stimulus-response compatibility and time uncertainty were manipulated. Participants were tested at rest and while cycling at 20% and at 50% of their maximal aerobic power. A mood assessment questionnaire and a critical flicker fusion test were administered before and after the choice reaction time task. The results showed that moderate-intensity exercise (50% maximal aerobic power) improves cognitive performance and that low-intensity exercise (20% maximal aerobic power) enables participants to compensate the negative dual-task effect. PMID:15160595

  9. BTFS: The Border Trade Facilitation System

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, L.R.

    1999-03-18

    The author demonstrates the Border Trade Facilitation System (BTFS), an agent-based bilingual e-commerce system built to expedite the regulation, control, and execution of commercial trans-border shipments during the delivery phase. The system was built to serve maquila industries at the US/Mexican border. The BTFS uses foundation technology developed here at Sandia Laboratories' Advanced Information Systems Lab (AISL), including a distributed object substrate, a general-purpose agent development framework, dynamically generated agent-human interaction via the World-Wide Web, and a collaborative agent architecture. This technology is also the substrate for the Multi-Agent Simulation Management System (MASMAS) proposed for demonstration at this conference. The BTFS executes authenticated transactions among agents performing open trading over the Internet. With the BTFS in place, one could conduct secure international transactions from any site with an Internet connection and a web browser. The BTFS is currently being evaluated for commercialization.

  10. Semantic facilitation in bilingual first language acquisition.

    Science.gov (United States)

    Bilson, Samuel; Yoshida, Hanako; Tran, Crystal D; Woods, Elizabeth A; Hills, Thomas T

    2015-07-01

    Bilingual first language learners face unique challenges that may influence the rate and order of early word learning relative to monolinguals. A comparison of the productive vocabularies of 435 children between the ages of 6 months and 7 years-181 of which were bilingual English learners-found that monolinguals learned both English words and all-language concepts faster than bilinguals. However, bilinguals showed an enhancement of an effect previously found in monolinguals-the preference for learning words with more associative cues. Though both monolinguals and bilinguals were best fit by a similar model of word learning, semantic network structure and growth indicated that the two groups were learning English words in a different order. Further, in comparison with a model of two-monolinguals-in-one-mind, bilinguals overproduced translational equivalents. Our results support an emergent account of bilingual first language acquisition, where learning a word in one language facilitates its acquisition in a second language. PMID:25909582

  11. The effect of Dimethyl sulfoxide on facilitating the absorption of hepatitis B virus in HepG 2 cells%二甲基亚砜促进乙型肝炎病毒对 HepG2细胞的吸附作用

    Institute of Scientific and Technical Information of China (English)

    任玲龙; 郭永建; 罗玉兰

    2015-01-01

    Ag on HepG2 cells were detected by using indirect immunofluorescence .Results HepG2 cell volume in the DMSO inducing group was obviously in‐creased .HBV DNA was found in HepG2 cells both in DMSO inducing group and control group ,and DMSO inducing group ex‐pressed much stronger .The results of IIF shown that green fluorescent signals of cell membrane and cytoplasm of HepG 2 cells in the DMSO inducing group were increased obviously ,while the results of HBV DNA and IIF both were negative in the negative con‐trol group .Conclusion DMSO could facilitate adsorption of HBsAg in some extent ,which are benefit for completing the process of early infection .

  12. Facilitator control as automatic behavior: A verbal behavior analysis

    OpenAIRE

    Hall, Genae A.

    1993-01-01

    Several studies of facilitated communication have demonstrated that the facilitators were controlling and directing the typing, although they appeared to be unaware of doing so. Such results shift the focus of analysis to the facilitator's behavior and raise questions regarding the controlling variables for that behavior. This paper analyzes facilitator behavior as an instance of automatic verbal behavior, from the perspective of Skinner's (1957) book Verbal Behavior. Verbal behavior is autom...

  13. Trade Facilitation beyond the Doha Round of Negotiations

    OpenAIRE

    Yann Duval

    2007-01-01

    this paper succinctly explores three emerging (in the case of customs valuation, re-emerging) issues, drawing from recent ARTNeT working papers as well as other relevant literature: (a) trade facilitation and regional trade agreements and initiatives; (b) trade facilitation and customs valuation; and (c) trade facilitation and services.

  14. Positive experiences with a specialist as facilitator in general practice

    DEFF Research Database (Denmark)

    Kousgaard, Marius Brostrøm; Thorsen, Thorkil

    2012-01-01

    The use of facilitators for quality improvement in general practice has accelerated during the past decade. As general practitioners (GPs) or pharmacists have typically been used as facilitators, there is a lack of knowledge of how other professionals function as facilitators. This article explores...

  15. The Dynamics of Syntax Acquisition: Facilitation between Syntactic Structures

    Science.gov (United States)

    Keren-Portnoy, Tamar; Keren, Michael

    2011-01-01

    This paper sets out to show how facilitation between different clause structures operates over time in syntax acquisition. The phenomenon of facilitation within given structures has been widely documented, yet inter-structure facilitation has rarely been reported so far. Our findings are based on the naturalistic production corpora of six toddlers…

  16. Role of customs in security and facilitation

    International Nuclear Information System (INIS)

    The World Customs Organization (WCO) is an intergovernmental organization representing 161 customs administrations worldwide. In June 2002 the membership of the WCO passed the Resolution on Security and Facilitation of the International Trade Supply Chain. This Resolution represents a new dimension for governments and their customs administrations. Every country is now faced with the challenge of protecting its national territory from acts of terrorism and organized crime while making every effort to facilitate legitimate trade. This initiative, which is supported by the G8 countries, the International Maritime Organization, the IAEA, the International Chamber of Commerce, the International Criminal Police Organization, the World Shipping Council, the International Chamber of Shipping and many other international bodies, is helping to safeguard national territories and create a new international framework for safe and secure international trade. As part of this process, customs administrations must be recognized as being one of the key agencies, since their special competence at the frontier is needed in managing the risks relating to passengers and freight moving internationally. Existing procedures developed by the WCO that are being adapted to take into account anti terrorism requirements include: Revised WCO Kyoto Convention; Provides an international standard and framework for customs procedures applying risk management; WCO Customs Data Model and Unique Consignment Reference; Provides a world standard for transmitting, tracking and tracing consignments; WCO Guidelines for Advance Passenger Information; Assists in the management of risks associated with the movement of air passengers; A modern multilateral instrument on mutual administrative assistance; Provides the legal basis for administrative assistance between customs administrations and the sharing of information for security screening. There has been a close cooperation between the WCO and the IAEA

  17. Facilitating facial retinization through barrier improvement.

    Science.gov (United States)

    Draelos, Zoe Diana; Ertel, Keith D; Berge, Cynthia A

    2006-10-01

    The utility of topical tretinoin as a treatment for improving the appearance of photodamaged skin is limited by irritation that occurs during the early phases of facial retinization. The observed side effects are consistent with stratum corneum barrier compromise. This paired double-blinded study was conducted to determine if preconditioning the skin with a barrier-enhancing cosmetic facial moisturizer before beginning tretinoin therapy and continuing moisturizer application during therapy would mitigate these side effects. Women with facial photodamage were recruited and randomly assigned to apply one cosmetic moisturizer to one side of the face and the other cosmetic moisturizer to the other side of the face twice daily for 10 weeks. One moisturizer contained a mixture of vitamins (niacinamide, panthenol, and tocopheryl acetate) to enhance stratum corneum barrier function, and the other moisturizer contained similar moisturizing ingredients but no vitamins. Daily full-face treatment with tretinoin cream 0.025% commenced 2 weeks into the study. Subjects' facial skin condition was monitored via investigator assessments, instrumental measurements, and subject self-assessments. The results show that improving stratum corneum barrier function before beginning topical tretinoin therapy and continuing use of a barrier-enhancing cosmetic moisturizer during therapy facilitates the early phase of facial retinization and augments the treatment response. PMID:17121065

  18. Teacher as Learning Facilitator in ELT

    Directory of Open Access Journals (Sweden)

    Badea Elena Codruta

    2012-05-01

    Full Text Available The classroom is the magic active scenery where many educational things take place simultaneously.Intellectual, emotional, socio-cultural, motivational and curricular factors corroborate their influence onclassroom environments, whether we deal with traditional models of teaching or with the constructivistapproaches. The growing demand for language teachers, English in particular, has determined a new vision oflanguage teaching strategies. The cutting-edge technology has created a fertile ground which successfullyfosters the teacher –student communication, emphasizing the teacher’s role to guide students and to generate achange in their learning approach and in eliciting useable knowledge. This way, the teacher has a larger abilityto convert knowledge into practical information that is of real help and value to students. Students are involvedin a continuous educational scheme and are tested on what they have learned. This ensures they can alwaysenjoy the benefits of active learning from expert teachers. The present paper deals with a brief analysis of therole of teacher as learning facilitator and its importance for student acquisition process, eliciting some strategiesin support of collaborative and student-centered learning.

  19. Sleep facilitates long-term face adaptation.

    Science.gov (United States)

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-10-22

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as 'storage'. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation--which are usually not considered to play a relevant role in mnemonic processes--with learning and memory, and at the same time reveal a new function of sleep in cognition. PMID:23986109

  20. Free radical facilitated damage of ungual keratin.

    Science.gov (United States)

    Khengar, Rajeshree H; Brown, Marc B; Turner, Rob B; Traynor, Matthew J; Holt, Katherine B; Jones, Stuart A

    2010-09-01

    Thioglycolic acid (TA) and urea hydrogen peroxide (urea H(2)O(2)) are thought to disrupt alpha-keratin disulfide links in the nail. However, optimal clinical use of these agents to improve the treatment of nail disorders is currently hindered by a lack of fundamental data to support their mechanism of action. The aim of this study was to investigate how the redox environment of ungual keratin, when manipulated by TA and urea H(2)O(2), influenced the properties of the nail barrier. Potentiometric and voltammetric measurements demonstrated that urea H(2)O(2) obeyed the Nernst equation for a proton coupled one-electron transfer redox process while TA underwent a series of redox reactions that was complicated by electrode adsorption and dimer formation. The functional studies demonstrated that nail permeability, measured through TBF penetration (38.51+/-10.94 microg/cm(2)/h) and nail swelling (244.10+/-14.99% weight increase), was greatest when relatively low concentrations of the thiolate ion were present in the applied solution. Limiting the thiolate ion to low levels in the solution retards thiolate dimerisation and generates thiyl free radicals. It appeared that this free radical generation was fundamental in facilitating the redox-mediated keratin disruption of the ungual membrane. PMID:20550963

  1. Facilitating Service Discovery with Semantic Overlay

    Institute of Scientific and Technical Information of China (English)

    Hai Jin; Hao Wu; Xiao-Min Ning

    2006-01-01

    Service Oriented Architecture (SOA) and Peer-to-Peer (P2P) computing share many common characteristics.It is believed that the combination of the two emerging techniques is a very promising method in promoting the web services (WS). Because the service discovery plays a key role in the integration, here a P2P-based framework to manage the knowledge of service and locating services is proposed. In this paper, the details of the principle, constructing and maintaining of service semantic overlay architecture have been described, and the way how the semantic overlay facilitates discovery of service resources is illustrated. To enable the semantic web service superiority, Service Ontology, which is considered as the service semantic model, is employed to depict service. The service discovery includes two phases: searching on the service semantic overlay; and local discovery in peer's service repository. Various solutions have been proposed to realize those two phases.Furthermore, tests are carried out to evaluate service discovery on the architecture.

  2. Training facilitates object recognition in cubist paintings

    Directory of Open Access Journals (Sweden)

    Martin Wiesmann

    2010-03-01

    Full Text Available To the naïve observer, cubist paintings contain geometrical forms in which familiar objects are hardly recognizable, even in the presence of a meaningful title. We used fMRI to test whether a short training session about Cubism would facilitate object recognition in paintings by Picasso, Braque and Gris. Subjects, who had no formal art education, were presented with titled or untitled cubist paintings and scrambled images, and performed object recognition tasks. Relative to the control group, trained subjects recognized more objects in the paintings, their response latencies were significantly shorter, and they showed enhanced activation in the parahippocampal cortex, with a parametric increase in the amplitude of the fMRI signal as a function of the number of recognized objects. Moreover, trained subjects were slower to report not recognizing any familiar objects in the paintings and these longer response latencies were correlated with activation in a fronto-parietal network. These findings suggest that trained subjects adopted a visual search strategy and used contextual associations to perform the tasks. Our study supports the proactive brain framework, according to which the brain uses associations to generate predictions.

  3. Small Molecules Facilitate Single Factor-Mediated Hepatic Reprogramming

    Directory of Open Access Journals (Sweden)

    Kyung Tae Lim

    2016-04-01

    Full Text Available Recent studies have shown that defined factors could lead to the direct conversion of fibroblasts into induced hepatocyte-like cells (iHeps. However, reported conversion efficiencies are very low, and the underlying mechanism of the direct hepatic reprogramming is largely unknown. Here, we report that direct conversion into iHeps is a stepwise transition involving the erasure of somatic memory, mesenchymal-to-epithelial transition, and induction of hepatic cell fate in a sequential manner. Through screening for additional factors that could potentially enhance the conversion kinetics, we have found that c-Myc and Klf4 (CK dramatically accelerate conversion kinetics, resulting in remarkably improved iHep generation. Furthermore, we identified small molecules that could lead to the robust generation of iHeps without CK. Finally, we show that Hnf1α supported by small molecules is sufficient to efficiently induce direct hepatic reprogramming. This approach might help to fully elucidate the direct conversion process and also facilitate the translation of iHep into the clinic.

  4. Novice facilitators and the use of scripts for managing facilitated modelling workshops

    DEFF Research Database (Denmark)

    Tavella, Elena; Papadopoulos, Thanos

    2015-01-01

    and achieve outcomes. This illustration is based on a micro-level analysis of a transcript from a Viable System Model workshop held in a food cooperative in Copenhagen, Denmark. Through our findings we identify two distinct script-supported FM behaviours and related script-supported facilitation...... practices to different workshop outcomes, thereby extending script-supported FM theory. Best practice guidelines for the development and use of scripts by novices are also provided....

  5. NIA Aging Cell Repository

    Data.gov (United States)

    Federal Laboratory Consortium — To facilitate aging research on cells in culture, the NIA provides support for the NIA Aging Cell Repository, located at the Coriell Institute for Medical Research...

  6. Urine alkalization facilitates uric acid excretion

    Directory of Open Access Journals (Sweden)

    Seyama Issei

    2010-10-01

    Full Text Available Abstract Background Increase in the incidence of hyperuricemia associated with gout as well as hypertension, renal diseases and cardiovascular diseases has been a public health concern. We examined the possibility of facilitated excretion of uric acid by change in urine pH by managing food materials. Methods Within the framework of the Japanese government's health promotion program, we made recipes which consist of protein-rich and less vegetable-fruit food materials for H+-load (acid diet and others composed of less protein but vegetable-fruit rich food materials (alkali diet. Healthy female students were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+ and anions (Cl-,SO42-,PO4- necessary for the estimation of acid-base balance were measured. Results Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42-] +organic acid-gut alkai were linearly related with those of the excretion of acid (titratable acidity+ [NH4+] - [HCO3-], indicating that H+ in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, where uric acid excretion increased from 302 mg/day at pH 5.9 to 413 mg/day at pH 6.5, despite the fact that the alkali diet contained a smaller purine load than the acid diet. Conclusion We conclude that alkalization of urine by eating nutritionally well-designed food is effective for removing uric acid from the body.

  7. Extracellular Matrix Molecules Facilitating Vascular Biointegration

    Directory of Open Access Journals (Sweden)

    Martin K.C. Ng

    2012-08-01

    Full Text Available All vascular implants, including stents, heart valves and graft materials exhibit suboptimal biocompatibility that significantly reduces their clinical efficacy. A range of biomolecules in the subendothelial space have been shown to play critical roles in local regulation of thrombosis, endothelial growth and smooth muscle cell proliferation, making these attractive candidates for modulation of vascular device biointegration. However, classically used biomaterial coatings, such as fibronectin and laminin, modulate only one of these components; enhancing endothelial cell attachment, but also activating platelets and triggering thrombosis. This review examines a subset of extracellular matrix molecules that have demonstrated multi-faceted vascular compatibility and accordingly are promising candidates to improve the biointegration of vascular biomaterials.

  8. Uptake of palmitate by hepatocyte suspensions: facilitation by albumin?

    Science.gov (United States)

    Pond, S M; Davis, C K; Bogoyevitch, M A; Gordon, R A; Weisiger, R A; Bass, L

    1992-05-01

    Albumin-dependent uptake of unbound [3H]palmitic acid by hepatocytes isolated from female rat livers was studied and the experimental results compared with the predictions of a noncompartmental diffusion-reaction theory for the cellular uptake of protein-bound ligands. The outright theoretical predictions involve values for the parameters of the system, some newly measured (hepatocyte radii and the rate constant for the dissociation of palmitate-albumin complex) and some taken from the literature (diffusion coefficients and the equilibrium association constant for the palmitate-albumin complex). The measured unbound clearance of [3H]palmitic acid, defined as the initial uptake velocity divided by the unbound [3H]palmitic acid concentration in the medium, was enhanced 6.6-fold as the concentration of human serum albumin was increased from approximately 5 to 480 microM. This enhancement factor was predicted by the theory, according to which the enhancement reflects codiffusion of bound ligand across the unstirred layer adjacent to the cell membrane and, therefore, an increased delivery of unbound ligand to the cell surface. In contrast, the absolute magnitude of the unbound clearance was consistent with the theory only for the lowest published value for the equilibrium association constant, 15 microM-1. For higher published values (62 and 94 microM-1), the magnitude of the unbound clearance observed experimentally was severalfold higher than that predicted by the theory. If in fact the association constant exceeds 30 microM-1, the data would imply that an albumin-dependent facilitation mechanism exists which enhances the availability of palmitate to the cell over and above the enhancement predicted by the diffusion-reaction theory. PMID:1590397

  9. Facilitation of acetylcholine signaling by the dithiocarbamate fungicide propineb.

    Science.gov (United States)

    Marinovich, Marina; Viviani, Barbara; Capra, Valerie; Corsini, Emanuela; Anselmi, Laura; D'Agostino, Gianluigi; Di Nucci, Amalia; Binaglia, Marco; Tonini, Marcello; Galli, Corrado L

    2002-01-01

    Dithiocarbamates (DTCs) are used mainly in agriculture as pesticides and as alcohol deterrent drugs. Neurological complications as well as movement disorders characterized by plastic rigidity, muscle twitch and paralysis are the prevailing symptoms in chronically exposed animals and humans. We investigated whether propineb interfered with peripheral cholinergic transmission in various isolated model systems. In electrically stimulated longitudinal muscle-myenteric plexus preparations (LMMPs), propineb (0.01-1000 nM) concentration-dependently enhanced the amplitude of both neurogenic twitch contractions and tritiated acetylcholine ([3H]ACh) release. The maximum percent increase was achieved by 10 nM propineb and was 19% and 14%, respectively. The effect on twitch contractions was partially antagonized by hexamethonium, a ganglionic nicotinic receptor blocker. In unstimulated LMMPs, propineb (10 pM, 10 nM, 10 microM) did not affect contractions to applied acetylcholine (ACh; 1 nM-10 microM), a finding indicating that propineb has no anticholinesterase activity. In human neuroblastoma cells (SH-SY5Y), propineb facilitated ACh release evoked by KCl depolarization. The increase in ACh release was not associated with detectable alterations of intracellular Ca2+([Ca2+]i) homeostasis. Binding studies carried out with alpha-bungarotoxin in striated muscle cells (L6) failed to demonstrate any influence of propineb on both affinity and capacity of skeletal muscle nicotinic receptors. In conclusion, propineb was found to interfere with cholinergic transmission in LMMPs and SH-SY5Y cells. In LMMPs, the potentiation of cholinergic transmission is partly dependent on the activation of ganglionic nicotinic receptors. Other targets relevant to cholinergic transmission seem not to be affected by propineb. PMID:11800594

  10. UHRF1 is a genome caretaker that facilitates the DNA damage response to γ-irradiation

    Directory of Open Access Journals (Sweden)

    Mistry Helena

    2010-06-01

    Full Text Available Abstract Background DNA double-strand breaks (DSBs caused by ionizing radiation or by the stalling of DNA replication forks are among the most deleterious forms of DNA damage. The ability of cells to recognize and repair DSBs requires post-translational modifications to histones and other proteins that facilitate access to lesions in compacted chromatin, however our understanding of these processes remains incomplete. UHRF1 is an E3 ubiquitin ligase that has previously been linked to events that regulate chromatin remodeling and epigenetic maintenance. Previous studies have demonstrated that loss of UHRF1 increases the sensitivity of cells to DNA damage however the role of UHRF1 in this response is unclear. Results We demonstrate that UHRF1 plays a critical role for facilitating the response to DSB damage caused by γ-irradiation. UHRF1-depleted cells exhibit increased sensitivity to γ-irradiation, suggesting a compromised cellular response to DSBs. UHRF1-depleted cells show impaired cell cycle arrest and an impaired accumulation of histone H2AX phosphorylation (γH2AX in response to γ-irradiation compared to control cells. We also demonstrate that UHRF1 is required for genome integrity, in that UHRF1-depleted cells displayed an increased frequency of chromosomal aberrations compared to control cells. Conclusions Our findings indicate a critical role for UHRF1 in maintenance of chromosome integrity and an optimal response to DSB damage.

  11. Saturated Zone Colloid-Facilitated Transport

    Energy Technology Data Exchange (ETDEWEB)

    A. Wolfsberg; P. Reimus

    2001-12-18

    The purpose of the Saturated Zone Colloid-Facilitated Transport Analysis and Modeling Report (AMR), as outlined in its Work Direction and Planning Document (CRWMS M&O 1999a), is to provide retardation factors for colloids with irreversibly-attached radionuclides, such as plutonium, in the saturated zone (SZ) between their point of entrance from the unsaturated zone (UZ) and downgradient compliance points. Although it is not exclusive to any particular radionuclide release scenario, this AMR especially addresses those scenarios pertaining to evidence from waste degradation experiments, which indicate that plutonium and perhaps other radionuclides may be irreversibly attached to colloids. This report establishes the requirements and elements of the design of a methodology for calculating colloid transport in the saturated zone at Yucca Mountain. In previous Total Systems Performance Assessment (TSPA) analyses, radionuclide-bearing colloids were assumed to be unretarded in their migration. Field experiments in fractured tuff at Yucca Mountain and in porous media at other sites indicate that colloids may, in fact, experience retardation relative to the mean pore-water velocity, suggesting that contaminants associated with colloids should also experience some retardation. Therefore, this analysis incorporates field data where available and a theoretical framework when site-specific data are not available for estimating plausible ranges of retardation factors in both saturated fractured tuff and saturated alluvium. The distribution of retardation factors for tuff and alluvium are developed in a form consistent with the Performance Assessment (PA) analysis framework for simulating radionuclide transport in the saturated zone. To improve on the work performed so far for the saturated-zone flow and transport modeling, concerted effort has been made in quantifying colloid retardation factors in both fractured tuff and alluvium. The fractured tuff analysis used recent data

  12. Genome-Facilitated Analyses of Geomicrobial Processes

    Energy Technology Data Exchange (ETDEWEB)

    Kenneth H. Nealson

    2012-05-02

    This project had the goal(s) of understanding the mechanism(s) of extracellular electron transport (EET) in the microbe Shewanella oneidensis MR-1, and a number of other strains and species in the genus Shewanella. The major accomplishments included sequencing, annotation, and analysis of more than 20 Shewanella genomes. The comparative genomics enabled the beginning of a systems biology approach to this genus. Another major contribution involved the study of gene regulation, primarily in the model organism, MR-1. As part of this work, we took advantage of special facilities at the DOE: e.g., the synchrotron radiation facility at ANL, where we successfully used this system for elemental characterization of single cells in different metabolic states (1). We began work with purified enzymes, and identification of partially purified enzymes, leading to initial characterization of several of the 42 c-type cytochromes from MR-1 (2). As the genome became annotated, we began experiments on transcriptome analysis under different conditions of growth, the first step towards systems biology (3,4). Conductive appendages of Shewanella, called bacterial nanowires were identified and characterized during this work (5, 11, 20,21). For the first time, it was possible to measure the electron transfer rate between single cells and a solid substrate (20), a rate that has been confirmed by several other laboratories. We also showed that MR-1 cells preferentially attach to cells at a given charge, and are not attracted, or even repelled by other charges. The interaction with the charged surfaces begins with a stimulation of motility (called electrokinesis), and eventually leads to attachment and growth. One of the things that genomics allows is the comparative analysis of the various Shewanella strains, which led to several important insights. First, while the genomes predicted that none of the strains looked like they should be able to degrade N-acetyl glucosamine (NAG), the monomer

  13. Using creative writing to explore facilitation skills in practice

    OpenAIRE

    Ann Price; Kathrin Hirter; Clare Lippiatt; Kerry O’Neill

    2016-01-01

    Background: Facilitation skills are key to the effective use of practice development strategies. Students on a masters degree in practice development and innovation undertake a module on facilitation skills that incorporates the use of a creative writing piece to explore facilitation. The aim of this article is to critically reflect on the use of creative writing within an assignment from the lecturer’s perspective. Critical reflection: The Rolfe et al. (2001) model of reflection will be ...

  14. Facilitating peer learning in study groups: student experiences

    OpenAIRE

    Adriansen, Hanne Kirstine; Madsen, Lene Møller

    2009-01-01

    In 2008 University of Aarhus, Denmark, issued a report concerning student experience with the study environment. Among the university's eight faculties, the Danish School of Education (DPU) held the sad record of having the lowest student well-being. This led to an action research project 'Facilitating study environment' at one of DPU's educations in spring 2009. The pilot project consisted of three elements: Facilitated study groups, a student bar with facilitated activities, and academic id...

  15. Porins facilitate nitric oxide-mediated killing of mycobacteria.

    Science.gov (United States)

    Fabrino, Daniela Leite; Bleck, Christopher K E; Anes, Elsa; Hasilik, Andrej; Melo, Rossana C N; Niederweis, Michael; Griffiths, Gareth; Gutierrez, Maximiliano Gabriel

    2009-09-01

    Non-pathogenic mycobacteria such us Mycobacterium smegmatis reside in macrophages within phagosomes that fuse with late endocytic/lysosomal compartments. This sequential fusion process is required for the killing of non-pathogenic mycobacteria by macrophages. Porins are proteins that allow the influx of hydrophilic molecules across the mycobacterial outer membrane. Deletion of the porins MspA, MspC and MspD significantly increased survival of M. smegmatis in J774 macrophages. However, the mechanism underlying this observation is unknown. Internalization of wild-type M. smegmatis (SMR5) and the porin triple mutant (ML16) by macrophages was identical indicating that the viability of the porin mutant in vivo was enhanced. This was not due to effects on phagosome trafficking since fusion of phagosomes containing the mutant with late endocytic compartments was unaffected. Moreover, in ML16-infected macrophages, the generation of nitric oxide (NO) was similar to the wild type-infected cells. However, ML16 was significantly more resistant to the effects of NO in vitro compared to SMR5. Our data provide evidence that porins render mycobacteria vulnerable to killing by reactive nitrogen intermediates within phagosomes probably by facilitating uptake of NO across the mycobacterial outer membrane. PMID:19460455

  16. Ammonia excretion in mytilid mussels is facilitated by ciliary beating.

    Science.gov (United States)

    Thomsen, J; Himmerkus, N; Holland, N; Sartoris, F J; Bleich, M; Tresguerres, M

    2016-08-01

    The excretion of nitrogenous waste products in the form of ammonia (NH3) and ammonium (NH4 (+)) is a fundamental process in aquatic organisms. For mytilid bivalves, little is known about the mechanisms and sites of excretion. This study investigated the localization and the mechanisms of ammonia excretion in mytilid mussels. An Rh protein was found to be abundantly expressed in the apical cell membrane of the plicate organ, which was previously described as a solely respiratory organ. The Rh protein was also expressed in the gill, although at significantly lower concentrations, but was not detectable in mussel kidney. Furthermore, NH3/NH4 (+) was not enriched in the urine, suggesting that kidneys are not involved in active NH3/NH4 (+) excretion. Exposure to elevated seawater pH of 8.5 transiently reduced NH3/NH4 (+) excretion rates, but they returned to control values following 24 h acclimation. These mussels had increased abundance of V-type H(+)-ATPase in the apical membranes of plicate organ cells; however, NH3/NH4 (+) excretion rates were not affected by the V-type H(+)-ATPase specific inhibitor concanamycin A (100 nmol l(-1)). In contrast, inhibition of ciliary beating with dopamine and increased seawater viscosity significantly reduced NH3 excretion rates under control pH (8.0). These results suggest that NH3/NH4 (+) excretion in mytilid mussels takes place by passive NH3 diffusion across respiratory epithelia via the Rh protein, facilitated by the water current produced for filter feeding, which prevents accumulation of NH3 in the boundary layer. This mechanism would be energy efficient for sessile organisms, as they already generate water currents for filter feeding. PMID:27489216

  17. Inherent phenotypic plasticity facilitates progression of head and neck cancer: Endotheliod characteristics enable angiogenesis and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Meng, E-mail: tong.59@osu.edu [Division of Oral Pathology and Radiology, The Ohio State University College of Dentistry, Columbus, OH 43210 (United States); Han, Byungdo B.; Holpuch, Andrew S.; Pei, Ping; He, Lingli; Mallery, Susan R. [Division of Oral Pathology and Radiology, The Ohio State University College of Dentistry, Columbus, OH 43210 (United States)

    2013-04-15

    The presence of the EMT (epithelial-mesenchymal transition), EndMT (endothelial-mesenchymal transition) and VM (vasculogenic mimicry) demonstrates the multidirectional extent of phenotypic plasticity in cancers. Previous findings demonstrating the crosstalk between head and neck squamous cell carcinoma (HNSCC) and vascular endothelial growth factor (VEGF) imply that HNSCC cells share some functional commonalities with endothelial cells. Our current results reveal that cultured HNSCC cells not only possess endothelial-specific markers, but also display endotheliod functional features including low density lipoprotein uptake, formation of tube-like structures on Matrigel and growth state responsiveness to VEGF and endostatin. HNSCC cell subpopulations are also highly responsive to transforming growth factor-β1 and express its auxiliary receptor, endoglin. Furthermore, the endotheliod characteristics observed in vitro recapitulate phenotypic features observed in human HNSCC tumors. Conversely, cultured normal human oral keratinocytes and intact or ulcerated human oral epithelia do not express comparable endotheliod characteristics, which imply that assumption of endotheliod features is restricted to transformed keratinocytes. In addition, this phenotypic state reciprocity facilitates HNSCC progression by increasing production of factors that are concurrently pro-proliferative and pro-angiogenic, conserving cell energy stores by LDL internalization and enhancing cell mobility. Finally, recognition of this endotheliod phenotypic transition provides a solid rationale to evaluate the antitumorigenic potential of therapeutic agents formerly regarded as exclusively angiostatic in scope. - Highlights: ► HNSCC tumor cells express endothelial specific markers VE-cadherin, CD31 and vimentin. ► Similarly, cultured HNSCC cells retain expression of these markers. ► HNSCC cells demonstrate functional endotheliod characteristics i.e. AcLDL uptake. ► HNSCC cell

  18. Inherent phenotypic plasticity facilitates progression of head and neck cancer: Endotheliod characteristics enable angiogenesis and invasion

    International Nuclear Information System (INIS)

    The presence of the EMT (epithelial-mesenchymal transition), EndMT (endothelial-mesenchymal transition) and VM (vasculogenic mimicry) demonstrates the multidirectional extent of phenotypic plasticity in cancers. Previous findings demonstrating the crosstalk between head and neck squamous cell carcinoma (HNSCC) and vascular endothelial growth factor (VEGF) imply that HNSCC cells share some functional commonalities with endothelial cells. Our current results reveal that cultured HNSCC cells not only possess endothelial-specific markers, but also display endotheliod functional features including low density lipoprotein uptake, formation of tube-like structures on Matrigel and growth state responsiveness to VEGF and endostatin. HNSCC cell subpopulations are also highly responsive to transforming growth factor-β1 and express its auxiliary receptor, endoglin. Furthermore, the endotheliod characteristics observed in vitro recapitulate phenotypic features observed in human HNSCC tumors. Conversely, cultured normal human oral keratinocytes and intact or ulcerated human oral epithelia do not express comparable endotheliod characteristics, which imply that assumption of endotheliod features is restricted to transformed keratinocytes. In addition, this phenotypic state reciprocity facilitates HNSCC progression by increasing production of factors that are concurrently pro-proliferative and pro-angiogenic, conserving cell energy stores by LDL internalization and enhancing cell mobility. Finally, recognition of this endotheliod phenotypic transition provides a solid rationale to evaluate the antitumorigenic potential of therapeutic agents formerly regarded as exclusively angiostatic in scope. - Highlights: ► HNSCC tumor cells express endothelial specific markers VE-cadherin, CD31 and vimentin. ► Similarly, cultured HNSCC cells retain expression of these markers. ► HNSCC cells demonstrate functional endotheliod characteristics i.e. AcLDL uptake. ► HNSCC cell

  19. Using Text Mining to Characterize Online Discussion Facilitation

    Science.gov (United States)

    Ming, Norma; Baumer, Eric

    2011-01-01

    Facilitating class discussions effectively is a critical yet challenging component of instruction, particularly in online environments where student and faculty interaction is limited. Our goals in this research were to identify facilitation strategies that encourage productive discussion, and to explore text mining techniques that can help…

  20. Trade Facilitation and Economic Development : Measuring the Impact

    OpenAIRE

    Wilson, John S.; Catherine L. Mann; Otsuki, Tsunehiro

    2003-01-01

    The authors analyze the relationship between trade facilitation, trade flows, and GDP per capita in the Asia-Pacific region for the goods sector. They define and measure trade facilitation using four broad indicators. These are constructed using country-specific data for port efficiency, customs environment, regulatory environment, and electronic-business usage. They estimate the relationship ...

  1. Demystifying Facilitation of Multi-Actor Learning Processes

    NARCIS (Netherlands)

    Groot, A.E.

    2002-01-01

     This thesis aims to demystify the facilitation of participatory processes in order to improve the performance of the facilitation professional. As our society is increasingly recognised as pluralistic, characterised by multiple actors with different interests, values and perception

  2. Facilitating Cross-Cultural Online Discussion Groups: Implications for Practice.

    Science.gov (United States)

    Williams, Saundra Wall; Watkins, Karen; Daley, Barbara; Courtenay, Bradley; Davis, Mike; Dymock, Darryl

    2001-01-01

    Discusses research that examined the issues and challenges experienced by facilitators in cross-cultural group discussions in a Web conferencing program, using action research methods of data collection and analysis. Considers questioning, participation, interpersonal and group dynamics, facilitator expectations, and student expectations.…

  3. Fine Points of Facilitation: It's Exhilarating, Challenging, Fulfilling

    Science.gov (United States)

    Jobst, Lou

    2004-01-01

    This firsthand account through the eyes of a facilitator describes meaningful moments of someone learning the job. Working primarily with new teachers in a large high school, this facilitator experienced the challenges and the fulfillment in helping colleagues, and discovered that the benefit of helping others grow may be one's own growth.

  4. Goals and Strategies of a Problem-Based Learning Facilitator

    Science.gov (United States)

    Hmelo-Silver, Cindy E.; Barrows, Howard S.

    2006-01-01

    This paper describes an analysis of facilitation of a student-centered problem-based learning group. The focus of this analysis was to understand the goals and strategies of an expert facilitator in support of collaborative learning. This was accomplished through interaction analysis using video data and stimulated recall to examine two PBL group…

  5. What Facilitates the Use of Telehealth Applications Among Nurses?

    Science.gov (United States)

    Koivunen, Marita; Saranto, Kaija

    2016-01-01

    This presentation describes the preliminary results of the facilitators of the use of telehealth applications from nurses' point of view based on a qualitative systematic literature review synthetizing 25 previously published papers. The study brought out two main categories that facilitate the use of telehealth among nurses: 1) Nurses' skills and attitudes, and 3) Changes in nurses' work and operations. PMID:27332423

  6. Facilitated transport of copper with hydroxyapatite nanoparticles in saturated sand

    Science.gov (United States)

    Saturated packed column experiments were conducted to investigate the facilitated transport of Cu with hydroxyapatite nanoparticles (nHAP) at different pore water velocities (0.22-2.2 cm min–1), solution pH (6.2-9.0), and fraction of Fe oxide coating on grain surfaces (', 0-0.36). The facilitated tr...

  7. Substrate specificity and transport properties of the glycerol facilitator of Escherichia coli.

    OpenAIRE

    Heller, K B; Lin, E C; Wilson, T H

    1980-01-01

    The specificity of the glycerol facilitator (glpF) of Escherichia coli was studied with an osmotic method. This transport system allowed the entry of polyols (glycerol and erythritol), pentitols, and hexitols. The analogous sugars were not transported. However, urea, glycine, and DL-glyceraldehyde could use this pathway to enter the cell. The glpF protein allowed the rapid efflux of preequilibrated xylitol. Glycerol surprisingly did not inhibit the uptake of xylitol, and xylitol only slightly...

  8. Twelve tips for facilitating team-based learning

    Science.gov (United States)

    Gullo, Charles; Ha, Tam Cam; Cook, Sandy

    2015-01-01

    Abstract Background: Team-based learning (TBL) has become a more commonly recognized and implemented pedagogical approach in curricula of numerous disciplines. The desire to place more autonomy on the student and spend less in-class time delivering content has resulted in complete or partial adoption of this style of learning in many educational settings. Aim: Provide faculty with tools that foster a well facilitated and interactive TBL learning environment. Methods: We examined the published literature in the area of facilitation – specifically in TBL environments, and explored learning theories associated with team learning and our own experiences to create these facilitation tips. Results: We created 12 tips for TBL facilitation designed to assist faculty to achieve an effective and engaging TBL learning environment. Conclusions: Applying these twelve tips while facilitating a TBL classroom session will help to ensure maximal participation and optimal learning in a safe yet stimulating environment. PMID:25665624

  9. Endogenous protein kinase C facilitation of transmitter release differs from phorbol ester facilitation

    International Nuclear Information System (INIS)

    Full text: Protein kinase C (PKC) is a family of enzymes that are implicated in the modulation of neurotransmitter release in a variety of neurones (Majewski and lannazzo, 1998). Phorbol esters, being potent activators of both the conventional and novel isoforms of this enzyme, have been used repeatedly to study the functions of protein kinase C. However, they may not be specifically targeted to individual isoforms of PKC, hence in this study we use isoform selective inhibitors of PKC to investigate its role on transmitter release. Outbred Sprague-Dawley rats were decapitated and rat cortical slices prepared and incubated with [3H]-noradrenaline which was used as an index of stimulation-induced (S-I) noradrenaline release. We incubated the cortical slices with isoform selective inhibitors either on their own or in the presence of phorbol esters to determine which isoforms of this enzyme may be involved in S-I transmitter release. The inhibitors used were polymyxin B (PXB), a non-selective PKC inhibitor, the myristoylated PKC inhibitor peptide (selective for PKC α and β), bisindolylmaleimide I (selective for PKC α, β, γ and δ) and GO6976 (selective for PKC α, β and γ). The phorbol ester, phorbol dibutyrate (1 μM), markedly facilitated S-I noradrenaline release (172.86 ± 16.73 %, n=12, P33P]-orthophosphoric acid, whereby the basal phosphorylation of B-50 was lowered by the inhibitors, with only PXB attenuating phorbol-ester facilitation of B-50 phosphorylation. This suggests that the PKC isoforms involved in the endogenous modulation of transmitter release are different to those involved in phorbol ester enhancement of noradrenaline release. Copyright (2001) Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists

  10. Group I metabotropic glutamate receptors reduce excitotoxic injury and may facilitate neurogenesis

    DEFF Research Database (Denmark)

    Baskys, Andrius; Bayazitov, Ildar; Fang, Liwei;

    2005-01-01

    Group I metabotropic glutamate receptor (mGluR) agonist DHPG reduced nerve cell death caused by their exposure to NMDA ("neuroprotective effect") and attenuated NMDA receptor-mediated currents [Blaabjerg, M., Baskys, A., Zimmer, J., Vawter, M. P., 2003b. Changes in hippocampal gene expression aft......GluRs reduces nerve cell susceptibility to excitotoxic injury in a PLC-dependent manner; (2) this reduction is associated with a PLC-dependent depression of excitatory synaptic transmission; and (3) mGluR1 activation may facilitate neurogenesis....

  11. CD248 facilitates tumor growth via its cytoplasmic domain

    International Nuclear Information System (INIS)

    Stromal fibroblasts participate in the development of a permissive environment for tumor growth, yet molecular pathways to therapeutically target fibroblasts are poorly defined. CD248, also known as endosialin or tumor endothelial marker 1 (TEM1), is a transmembrane glycoprotein expressed on activated fibroblasts. We recently showed that the cytoplasmic domain of CD248 is important in facilitating an inflammatory response in a mouse model of arthritis. Others have reported that CD248 gene inactivation in mice results in dampened tumor growth. We hypothesized that the conserved cytoplasmic domain of CD248 is important in regulating tumor growth. Mice lacking the cytoplasmic domain of CD248 (CD248CyD/CyD) were generated and evaluated in tumor models, comparing the findings with wild-type mice (CD248WT/WT). As compared to the response in CD248WT/WT mice, growth of T241 fibrosarcomas and Lewis lung carcinomas was significantly reduced in CD248CyD/CyD mice. Tumor size was similar to that seen with CD248-deficient mice. Conditioned media from CD248CyD/CyD fibroblasts were less effective at supporting T241 fibrosarcoma cell survival. In addition to our previous observation of reduced release of activated matrix metalloproteinase (MMP)-9, CD248CyD/CyD fibroblasts also had impaired PDGF-BB-induced migration and expressed higher transcripts of tumor suppressor factors, transgelin (SM22α), Hes and Hey1. The multiple pathways regulated by the cytoplasmic domain of CD248 highlight its potential as a therapeutic target to treat cancer

  12. CD248 facilitates tumor growth via its cytoplasmic domain

    Directory of Open Access Journals (Sweden)

    Janssens Tom

    2011-05-01

    Full Text Available Abstract Background Stromal fibroblasts participate in the development of a permissive environment for tumor growth, yet molecular pathways to therapeutically target fibroblasts are poorly defined. CD248, also known as endosialin or tumor endothelial marker 1 (TEM1, is a transmembrane glycoprotein expressed on activated fibroblasts. We recently showed that the cytoplasmic domain of CD248 is important in facilitating an inflammatory response in a mouse model of arthritis. Others have reported that CD248 gene inactivation in mice results in dampened tumor growth. We hypothesized that the conserved cytoplasmic domain of CD248 is important in regulating tumor growth. Methods Mice lacking the cytoplasmic domain of CD248 (CD248CyD/CyD were generated and evaluated in tumor models, comparing the findings with wild-type mice (CD248WT/WT. Results As compared to the response in CD248WT/WT mice, growth of T241 fibrosarcomas and Lewis lung carcinomas was significantly reduced in CD248CyD/CyD mice. Tumor size was similar to that seen with CD248-deficient mice. Conditioned media from CD248CyD/CyD fibroblasts were less effective at supporting T241 fibrosarcoma cell survival. In addition to our previous observation of reduced release of activated matrix metalloproteinase (MMP-9, CD248CyD/CyD fibroblasts also had impaired PDGF-BB-induced migration and expressed higher transcripts of tumor suppressor factors, transgelin (SM22α, Hes and Hey1. Conclusions The multiple pathways regulated by the cytoplasmic domain of CD248 highlight its potential as a therapeutic target to treat cancer.

  13. TbRGG2 facilitates kinetoplastid RNA editing initiation and progression past intrinsic pause sites.

    Science.gov (United States)

    Ammerman, Michelle L; Presnyak, Vladimir; Fisk, John C; Foda, Bardees M; Read, Laurie K

    2010-11-01

    TbRGG2 is an essential kinetoplastid RNA editing accessory factor that acts specifically on pan-edited RNAs. To understand the mechanism of TbRGG2 action, we undertook an in-depth analysis of edited RNA populations in TbRGG2 knockdown cells and an in vitro examination of the biochemical activities of the protein. We demonstrate that TbRGG2 down-regulation more severely impacts editing at the 5' ends of pan-edited RNAs than at their 3' ends. The initiation of editing is reduced to some extent in TbRGG2 knockdown cells. In addition, TbRGG2 plays a post-initiation role as editing becomes stalled in TbRGG2-depleted cells, resulting in an overall decrease in the 3' to 5' progression of editing. Detailed analyses of edited RNAs from wild-type and TbRGG2-depleted cells reveal that TbRGG2 facilitates progression of editing past intrinsic pause sites that often correspond to the 3' ends of cognate guide RNAs (gRNAs). In addition, noncanonically edited junction regions are either absent or significantly shortened in TbRGG2-depleted cells, consistent with impaired gRNA transitions. Sequence analysis further suggests that TbRGG2 facilitates complete utilization of certain gRNAs. In vitro RNA annealing and in vivo RNA unwinding assays demonstrate that TbRGG2 can modulate RNA-RNA interactions. Collectively, these data are consistent with a model in which TbRGG2 facilitates initiation and 3' to 5' progression of editing through its ability to affect gRNA utilization, both during the transition between specific gRNAs and during usage of certain gRNAs. PMID:20855539

  14. Colloid-Facilitated Transport of Radionuclides Through The Vadose Zone

    International Nuclear Information System (INIS)

    The main purpose of this project was to advance the basic scientific understanding of colloid and colloid-facilitated Cs transport of radionuclides in the vadose zone. We focused our research on the hydrological and geochemical conditions beneath the leaking waste tanks at the USDOE Hanford reservation. Specific objectives were (1) to determine the lability and thermodynamic stability of colloidal materials, which form after reacting Hanford sediments with simulated Hanford Tank Waste, (2) to characterize the interactions between colloidal particles and contaminants, i.e., Cs and Eu, (3) to determine the potential of Hanford sediments for in situ mobilization of colloids, (4) to evaluate colloid-facilitated radionuclide transport through sediments under unsaturated flow, (5) to implement colloid-facilitated contaminant transport mechanisms into a transport model, and (6) to improve conceptual characterization of colloid-contaminant-soil interactions and colloid-facilitated transport for clean-up procedures and long-term risk assessment

  15. Evidence for social facilitation of preening in the common tern.

    Science.gov (United States)

    Palestis; Burger

    1998-11-01

    Social facilitation of reproductive behaviour has been studied extensively in gulls and terns, but social facilitation of preening has been reported only anecdotally, and has not been previously quantified. We studied a common tern, Sterna hirundo, colony during the summers of 1996 and 1997 to test for socially facilitated preening. Scan sampling provided evidence of spatial and temporal synchrony of preening behaviour. Preening occurred more often than expected in groups of three or more neighbours. Breeding pairs also preened simultaneously more often than expected. In loafing (resting) areas, the proportion of preeners present increased with tern density. Behavioural observations suggest that preening spread from neighbour to neighbour. The observed clumping in preening behaviour could not be explained by differences in date, time of day or weather. Social facilitation of preening and other maintenance behaviour may be an important aspect of group living that is often overlooked. Copyright 1998 The Association for the Study of Animal Behaviour. PMID:9819325

  16. Facilitation: a novel way to improve students' well-being

    DEFF Research Database (Denmark)

    Adriansen, Hanne Kirstine; Madsen, Lene Møller

    2013-01-01

    In this article we analyze a project that used facilitation techniques, which are known from training in industry, to improve the study environment at a public research university in Denmark. In 2009, the project was initiated in one graduate program; and it has subsequently been modified and ins...... facilitation makes study groups more inclusive, and they provide the potential for deep learning by structuring the learning situation....... institutionalized. The project did not change the teaching format, but introduced facilitated study-groups using peer learning. It was successful in increasing students’ well-being. While peer learning and study groups are well-known in higher education, facilitation is a different and novel tool. We argue that...

  17. Evaluation of Eight Case Studies of Facilitated Communication.

    Science.gov (United States)

    Moore, Susan; And Others

    1993-01-01

    The ability of eight adults with mental retardation (and in some cases cerebral palsy) to communicate using facilitated communication was assessed by a multidisciplinary team. Not one of the subjects demonstrated an ability to communicate using the technique. (JDD)

  18. Facilitating Online Learning Conversations : Exploring tool affordances in higher education

    NARCIS (Netherlands)

    Pol, J. van der

    2007-01-01

    This dissertation aims to facilitate students’ online learning conversations in higher education, using asynchronous online forum discussion. Despite offering a great learning potential, online discussions also present several obstacles for conducting effective learning conversations. Therefore, thi

  19. Distraction As A Source Of Drive In Social Facilitation Research

    Science.gov (United States)

    Baron, Robert Steven; And Others

    1978-01-01

    Demonstrates that in a replication of a well known social facilitation study, subjects show indications across several measures of being more distracted in audience conditions than when they are alone. Subjects were 55 college students. (MP)

  20. Psychoanalysis and Education for the Facilitation of Positive Human Qualities

    Science.gov (United States)

    Ekstein, Rudolph

    1972-01-01

    This paper discusses psychoanalytic contributions concerning both the development and the facilitation of qualities such as empathy, love for neighbor social-mindedness, identification, sympathy, and altruism; and neurotic manifestations of altruism and of other positive qualities. (Author/JM)

  1. Dynamics of group knowledge production in facilitated modelling workshops

    DEFF Research Database (Denmark)

    Tavella, Elena; Franco, L. Alberto

    2015-01-01

    , the workshop. Drawing on the knowledge-perspective of group communication, we conducted a micro-level analysis of a transcript of a facilitated modelling workshop held with the management team of an Alternative Food Network in the UK. Our analysis suggests that facilitated modelling interactions can take...... the form of three distinct group knowledge production patterns: generative, collaborative and assertive. Further, each pattern is characterised by a particular mix of communicative behaviours and model-supported interactions that has implications for the creation of new knowledge within the workshop. Our......The term ‘facilitated modelling’ is used in the literature to characterise an approach to structuring problems, developing options and evaluating decisions by groups working in a model-supported workshop environment, and assisted by a facilitator. The approach involves an interactive process...

  2. Social Media to Facilitate Public Participation in IA

    NARCIS (Netherlands)

    Naber, A.C.; Enserink, B.

    2012-01-01

    Social media are web-based and mobile technologies that facilitate interaction between organizations, communities and individuals. Important characteristics are that the technologies are ubiquitous, communication instantaneous and that they enable the creation and exchange of user-generated content.

  3. Role of "external facilitation" in implementation of research findings: a qualitative evaluation of facilitation experiences in the Veterans Health Administration

    Directory of Open Access Journals (Sweden)

    Hagedorn Hildi

    2006-10-01

    Full Text Available Abstract Background Facilitation has been identified in the literature as a potentially key component of successful implementation. It has not, however, either been well-defined or well-studied. Significant questions remain about the operational definition of facilitation and about the relationship of facilitation to other interventions, especially to other change agent roles when used in multi-faceted implementation projects. Researchers who are part of the Quality Enhancement Research Initiative (QUERI are actively exploring various approaches and processes, including facilitation, to enable implementation of best practices in the Veterans Health Administration health care system – the largest integrated healthcare system in the United States. This paper describes a systematic, retrospective evaluation of implementation-related facilitation experiences within QUERI, a quality improvement program developed by the US Department of Veterans Affairs. Methods A post-hoc evaluation was conducted through a series of semi-structured interviews to examine the concept of facilitation across several multi-site QUERI implementation studies. The interview process is based on a technique developed in the field of education, which systematically enhances learning through experience by stimulating recall and reflection regarding past complex activities. An iterative content analysis approach relative to a set of conceptually-based interview questions was used for data analysis. Findings Findings suggest that facilitation, within an implementation study initiated by a central change agency, is a deliberate and valued process of interactive problem solving and support that occurs in the context of a recognized need for improvement and a supportive interpersonal relationship. Facilitation was described primarily as a distinct role with a number of potentially crucial behaviors and activities. Data further suggest that external facilitators were likely to use

  4. Object-based attentional facilitation and inhibition are neuropsychologically dissociated.

    OpenAIRE

    Smith, D T; Ball, K.; Swalwell, R.; Schenk, T.

    2016-01-01

    Salient peripheral cues produce a transient shift of attention which is superseded by a sustained inhibitory effect. Cueing part of an object produces an inhibitory cueing effect (ICE) that spreads throughout the object. In dynamic scenes the ICE stays with objects as they move. We examined object-centred attentional facilitation and inhibition in a patient with visual form agnosia. There was no evidence of object-centred attentional facilitation. In contrast, object-centred ICE was observed ...

  5. KCTCCA, a peptide-based facilitator for bioelectrochemistry

    Indian Academy of Sciences (India)

    R Mukhopadhyay

    2004-06-01

    Electrochemical and scanning tunnelling microscopy (STM) studies have been carried out to investigate the suitability of the hexapeptide KCTCCA as a facilitator for bioelectrochemistry. The stable, quasi-reversible electrochemical response of cytochrome 562 on a KCTCCA modified gold electrode and the high degree of surface coverage of KCTCCA on gold (111), as observed by STM, indicate applicability of the molecule as an electrochemical facilitator.

  6. From Facilitated to Independent Tourism Learning Networks Connecting the Dots

    OpenAIRE

    Kelliher , Felicity; Reinl, Leana

    2010-01-01

    Facilitated networks are regularly cited in tourism literature as a means to promote sustainable competitive advantage in small tourism firms. These networks function for a variety of reasons including marketing, innovation and research and development; however learning networks specifically seek to encourage learning among tourism entrepreneurs. Once established, the question remains whether such networks can transition from facilitated cooperative learning strategies to become independent l...

  7. Facilitation of Students’ Creativity in the Studies of Visual Arts

    OpenAIRE

    Kalēja-Gasparoviča, Daiga

    2013-01-01

    Annotation The dissertation of Daiga Kalēja-Gasparoviča, ,,Facilitation of Students’ Creativity in the Studies of Visual Arts”, researching students’ creativity and its facilitation in the studies of visual arts, and discovering the personal activity approach studying visual arts as an opportunity which is significant for students on a personal level – in the development of creativity, develops a theoretically augmented model of obtaining visual arts and carries out empirical tests of its ...

  8. Demystifying Facilitation of Multi-Actor Learning Processes

    OpenAIRE

    Groot, A.E.

    2002-01-01

     This thesis aims to demystify the facilitation of participatory processes in order to improve the performance of the facilitation professional. As our society is increasingly recognised as pluralistic, characterised by multiple actors with different interests, values and perceptions, participation has become a popular means of bringing about social and technical change. Across the globe, whether in agricultural development, poverty alleviation, natural resource management, health promotion o...

  9. Facilitators for Empowering Women in Breastfeeding: a Qualitative Study

    OpenAIRE

    Shahnaz Kohan; Zeinab Heidari; Mahrokh Keshvari

    2016-01-01

    Background  Exclusive breastfeeding for the first six months and continued breastfeeding up to 2 years or more is a desirable approach for infant’s nutrition. A mother's breastfeeding empowerment is considered an important factor in promoting breastfeeding and identifying its facilitating factors can contribute to the development of effective policies and intervention. This study with a qualitative approach carried out aiming to exploring the facilitators for women’s empowerment in breastfeed...

  10. Facilitating complex shape drawing in Williams syndrome and typical development

    OpenAIRE

    Hudson, K. D.; Farran, E.K.

    2013-01-01

    Individuals with Williams syndrome (WS) produce drawings that are disorganised, likely due to an inability to replicate numerous spatial relations between parts. This study attempted to circumvent these drawing deficits in WS when copying complex combinations of one, two and three shapes. Drawing decisions were reduced by introducing a number of facilitators, for example, by using distinct colours and including facilitatory cues on the response sheet. Overall, facilitation improved drawing in...

  11. Proprioceptive neuromuscular facilitation in HTLV-I-associated myelopathy/tropical spastic paraparesis

    Directory of Open Access Journals (Sweden)

    Vera Lúcia Santos de Britto

    2014-01-01

    Full Text Available Introduction: Human T cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP can impact the independence and motricity of patients. The aims of this study were to estimate the effects of physiotherapy on the functionality of patients with HAM/TSP during the stable phase of the disease using proprioceptive neuromuscular facilitation (PNF and to compare two methods of treatment delivery. Methods: Fourteen patients with human T cell lymphotropic virus type I (HTLV-I were randomly allocated into two groups. In group I (seven patients, PNF was applied by the therapist, facilitating the functional activities of rolling, sitting and standing, walking and climbing and descending stairs. In group II (seven patients, PNF was self-administered using an elastic tube, and the same activities were facilitated. Experiments were conducted for 1h twice per week for 12 weeks. Low-back pain, a modified Ashworth scale, the functional independence measure (FIM and the timed up and go test (TUG were assessed before and after the interventions. Results: In the within-group evaluation, low-back pain was significantly reduced in both groups, the FIM improved in group II, and the results of the TUG improved in group I. In the inter-group analysis, only the tone was lower in group II than in group I. Conclusions: Both PNF protocols were effective in treating patients with HAM/TSP.

  12. Crystallization and preliminary X-ray diffraction analysis of the cytosolic domain of a cation diffusion facilitator family protein

    OpenAIRE

    Hattori, Motoyuki; Tanaka, Yoshiki; Ishitani, Ryuichiro; Nureki, Osamu

    2007-01-01

    Selenomethionine-substituted crystals of the cytosolic domain of the cation diffusion facilitator family protein from T. maritima diffracted X-rays to 2.5 Å and belonged to space group R32, with unit-cell parameters a = b = 97.7, c = 83.4 Å.

  13. Self-organization of bacterial biofilms is facilitated by extracellular DNA.

    Science.gov (United States)

    Gloag, Erin S; Turnbull, Lynne; Huang, Alan; Vallotton, Pascal; Wang, Huabin; Nolan, Laura M; Mililli, Lisa; Hunt, Cameron; Lu, Jing; Osvath, Sarah R; Monahan, Leigh G; Cavaliere, Rosalia; Charles, Ian G; Wand, Matt P; Gee, Michelle L; Prabhakar, Ranganathan; Whitchurch, Cynthia B

    2013-07-01

    Twitching motility-mediated biofilm expansion is a complex, multicellular behavior that enables the active colonization of surfaces by many species of bacteria. In this study we have explored the emergence of intricate network patterns of interconnected trails that form in actively expanding biofilms of Pseudomonas aeruginosa. We have used high-resolution, phase-contrast time-lapse microscopy and developed sophisticated computer vision algorithms to track and analyze individual cell movements during expansion of P. aeruginosa biofilms. We have also used atomic force microscopy to examine the topography of the substrate underneath the expanding biofilm. Our analyses reveal that at the leading edge of the biofilm, highly coherent groups of bacteria migrate across the surface of the semisolid media and in doing so create furrows along which following cells preferentially migrate. This leads to the emergence of a network of trails that guide mass transit toward the leading edges of the biofilm. We have also determined that extracellular DNA (eDNA) facilitates efficient traffic flow throughout the furrow network by maintaining coherent cell alignments, thereby avoiding traffic jams and ensuring an efficient supply of cells to the migrating front. Our analyses reveal that eDNA also coordinates the movements of cells in the leading edge vanguard rafts and is required for the assembly of cells into the "bulldozer" aggregates that forge the interconnecting furrows. Our observations have revealed that large-scale self-organization of cells in actively expanding biofilms of P. aeruginosa occurs through construction of an intricate network of furrows that is facilitated by eDNA. PMID:23798445

  14. Handwriting generates variable visual output to facilitate symbol learning.

    Science.gov (United States)

    Li, Julia X; James, Karin H

    2016-03-01

    Recent research has demonstrated that handwriting practice facilitates letter categorization in young children. The present experiments investigated why handwriting practice facilitates visual categorization by comparing 2 hypotheses: that handwriting exerts its facilitative effect because of the visual-motor production of forms, resulting in a direct link between motor and perceptual systems, or because handwriting produces variable visual instances of a named category in the environment that then changes neural systems. We addressed these issues by measuring performance of 5-year-old children on a categorization task involving novel, Greek symbols across 6 different types of learning conditions: 3 involving visual-motor practice (copying typed symbols independently, tracing typed symbols, tracing handwritten symbols) and 3 involving visual-auditory practice (seeing and saying typed symbols of a single typed font, of variable typed fonts, and of handwritten examples). We could therefore compare visual-motor production with visual perception both of variable and similar forms. Comparisons across the 6 conditions (N = 72) demonstrated that all conditions that involved studying highly variable instances of a symbol facilitated symbol categorization relative to conditions where similar instances of a symbol were learned, regardless of visual-motor production. Therefore, learning perceptually variable instances of a category enhanced performance, suggesting that handwriting facilitates symbol understanding by virtue of its environmental output: supporting the notion of developmental change though brain-body-environment interactions. (PsycINFO Database Record PMID:26726913

  15. Object-based attentional facilitation and inhibition are neuropsychologically dissociated.

    Science.gov (United States)

    Smith, Daniel T; Ball, Keira; Swalwell, Robert; Schenk, Thomas

    2016-01-01

    Salient peripheral cues produce a transient shift of attention which is superseded by a sustained inhibitory effect. Cueing part of an object produces an inhibitory cueing effect (ICE) that spreads throughout the object. In dynamic scenes the ICE stays with objects as they move. We examined object-centred attentional facilitation and inhibition in a patient with visual form agnosia. There was no evidence of object-centred attentional facilitation. In contrast, object-centred ICE was observed in 3 out of 4 tasks. These inhibitory effects were strongest where cues to objecthood were highly salient. These data are evidence of a neuropsychological dissociation between the facilitatory and inhibitory effects of attentional cueing. From a theoretical perspective the findings suggest that 'grouped arrays' are sufficient for object-based inhibition, but insufficient to generate object-centred attentional facilitation. PMID:26551577

  16. Facilitating an accelerated experience-based co-design project.

    Science.gov (United States)

    Tollyfield, Ruth

    This article describes an accelerated experience-based co-design (AEBCD) quality improvement project that was undertaken in an adult critical care setting and the facilitation of that process. In doing so the aim is to encourage other clinical settings to engage with their patients, carers and staff alike and undertake their own quality improvement project. Patient, carer and staff experience and its place in the quality sphere is outlined and the importance of capturing patient, carer and staff feedback established. Experience-based co-design (EBCD) is described along with the recently tested accelerated version of the process. An overview of the project and outline of the organisational tasks and activities undertaken by the facilitator are given. The facilitation of the process and key outcomes are discussed and reflected on. Recommendations for future undertakings of the accelerated process are given and conclusions drawn. PMID:24526020

  17. Facilitated Articulation of Implicit Knowledge in Textile Design

    DEFF Research Database (Denmark)

    Bang, Anne Louise

    2009-01-01

    (experiential, implicit and tacit) textile design knowledge should facilitate the articulation process. The paper specifically draws on a series of workshops conducted within the collaborating company inviting all employees to participate. The series of workshops were based on a game-like setting and introduced...... an emergent framework for accessing implicit knowledge in textile design. The framework is based on the distance to the fabric. Present at each workshop were materials, chairs and images as initiators for articulation. In each workshop rules for playing and gaming materials were introduced by the...... author - being a textile designer herself, who functioned as the facilitator. This paper uses two examples from the series of workshops to exemplify a facilitated articulation of implicit knowledge in textile design. From the examples the following themes are synthesised as being important for...

  18. If a Student Takes Control: Facilitator's Tasks and Responsibilities

    Science.gov (United States)

    Väljataga, Terje

    This paper presents initial research results of an intervention into higher educational teaching and studying practices from facilitators‘ point of view. The intervention was implemented into an international Master’s level online course mediated by landscapes of social media tools and services. In this course more emphasis was put on a shift of control from a facilitator to a student or a group of students in the following aspects: setting up one’s study goals, choosing activities, selecting appropriate resources, including technology and defining one’s evaluation criteria. The initial analysis showed that the facilitators gained a lot in terms of understanding the benefits of exploiting social media tools and services for their teaching practices, perceiving a need of having a different role as well as the shortages and problems while being a facilitator in such a course.

  19. Partner Facilitation and Partner Interference in Individuals' Weight Loss Goals.

    Science.gov (United States)

    Theiss, Jennifer A; Carpenter, Amanda M; Leustek, John

    2016-08-01

    Drawing on the logic of the relational turbulence model, this study examined the ways in which romantic partners facilitate and interfere with individuals' weight loss goals. Participants (N = 122) described the ways in which their romantic partner had recently helped or hindered their weight loss at four times over the course of 2 months. We conducted a content analysis of responses to identify themes of partner facilitation (Research Question 1 [RQ1]) and partner interference (RQ2) in individuals' weight loss goals. Results revealed seven themes of partner facilitation: (a) partner enabling diet, (b) motivation and encouragement, (c) emotional support and positive reinforcement, (d) exercising together, (e) partner enabling exercise, (f) dieting together, and (g) relationship influence and priorities. Four themes of partner interference emerged in the data: (a) inability to plan for healthy meals, (b) inability to control the food environment, (c) preventing or discouraging exercise, and (d) emotional or relational discouragement. PMID:25904678

  20. Short-term facilitation may stabilize parametric working memory trace

    Directory of Open Access Journals (Sweden)

    Vladimir Itskov

    2011-10-01

    Full Text Available Networks with continuous set of attractors are considered to be a paradigmatic model for parametric working memory, but require fine-tuning of connections and are thus structurally unstable. Here we analyzed the network with ring attractor, where connections are not perfectly tuned and the activity state therefore drifts in the absence of the stabilizing stimulus. We derive an analytical expression for the drift dynamics and conclude that the network cannot function as working memory for a period of several seconds, a typical delay time in monkey memory experiments. We propose that short-term synaptic facilitation in recurrent connections significantly improves the robustness of the model by slowing down the drift of activity bump. Extending the calculation of the drift velocity to network with synaptic facilitation, we conclude that facilitation can slow down the drift by a large factor, rendering the network suitable as a model of working memory.

  1. 中枢神经系统药物促进干细胞定向分化为神经元的研究进展%Research progress of central nervous system drugs on facilitating directional differentiation of stem cells into neurons

    Institute of Scientific and Technical Information of China (English)

    杜云霞; 王晓虹; 王苏平

    2014-01-01

    干细胞是一类具有自我更新和分化潜能的细胞。目前,通过干细胞移植并使其在体内定向分化为神经元来治疗中枢神经系统疾病已经受到广泛关注。干细胞分化机制和促进干细胞定向分化药物的研究成为干细胞移植研究的热点,国内外有关这方面的研究及药物研发已经取得了重大进展。本文将对干细胞的来源、分类及生物学特性作出总结,并概述干细胞定向分化为神经元的诱导方法及中枢神经系统药物对其定向分化的促进作用。%Stem cells are a kind of cells which have the potential of self -renewal and differen-tiation.At present,it has received extensive attention that through stem cell transplantation and ma -king it directionally differentiated into neurons to offer therapy for central nervous system disease . The research on the differentiation mechanism and the drugs promoting stem cell directional differen -tiation has become a hot topic of stem cells transplantation research ,the research and development of this has received significant progress at home and abroad .The present paper concluded the source , classification and biological characteristics of stem cells ,and summarized the approach to inducing directional differentiation of stem cells and the effect of central nervous system drugs on the direc -tional differentiation of stem cells into neurons .

  2. Live to cheat another day: bacterial dormancy facilitates the social exploitation of β-lactamases.

    Science.gov (United States)

    Medaney, Frances; Dimitriu, Tatiana; Ellis, Richard J; Raymond, Ben

    2016-03-01

    The breakdown of antibiotics by β-lactamases may be cooperative, since resistant cells can detoxify their environment and facilitate the growth of susceptible neighbours. However, previous studies of this phenomenon have used artificial bacterial vectors or engineered bacteria to increase the secretion of β-lactamases from cells. Here, we investigated whether a broad-spectrum β-lactamase gene carried by a naturally occurring plasmid (pCT) is cooperative under a range of conditions. In ordinary batch culture on solid media, there was little or no evidence that resistant bacteria could protect susceptible cells from ampicillin, although resistant colonies could locally detoxify this growth medium. However, when susceptible cells were inoculated at high densities, late-appearing phenotypically susceptible bacteria grew in the vicinity of resistant colonies. We infer that persisters, cells that have survived antibiotics by undergoing a period of dormancy, founded these satellite colonies. The number of persister colonies was positively correlated with the density of resistant colonies and increased as antibiotic concentrations decreased. We argue that detoxification can be cooperative under a limited range of conditions: if the toxins are bacteriostatic rather than bacteridical; or if susceptible cells invade communities after resistant bacteria; or if dormancy allows susceptible cells to avoid bactericides. Resistance and tolerance were previously thought to be independent solutions for surviving antibiotics. Here, we show that these are interacting strategies: the presence of bacteria adopting one solution can have substantial effects on the fitness of their neighbours. PMID:26505830

  3. Novel temperature-responsive polymer brushes with carbohydrate residues facilitate selective adhesion and collection of hepatocytes

    Directory of Open Access Journals (Sweden)

    Naokazu Idota, Mitsuhiro Ebara, Yohei Kotsuchibashi, Ravin Narain and Takao Aoyagi

    2012-01-01

    Full Text Available Temperature-responsive glycopolymer brushes were designed to investigate the effects of grafting architectures of the copolymers on the selective adhesion and collection of hypatocytes. Homo, random and block sequences of N-isopropylacrylamide and 2-lactobionamidoethyl methacrylate were grafted on glass substrates via surface-initiated atom transfer radical polymerization. The galactose/lactose-specific lectin RCA120 and HepG2 cells were used to test for specific recognition of the polymer brushes containing galactose residues over the lower critical solution temperatures (LCSTs. RCA120 showed a specific binding to the brush surfaces at 37 °C. These brush surfaces also facilitated the adhesion of HepG2 cells at 37 °C under nonserum conditions, whereas no adhesion was observed for NIH-3T3 fibroblasts. When the temperature was decreased to 25 °C, almost all the HepG2 cells detached from the block copolymer brush, whereas the random copolymer brush did not release the cells. The difference in releasing kinetics of cells from the surfaces with different grafting architectures can be explained by the correlated effects of significant changes in LCST, mobility, hydrophilicity and mechanical properties of the grafted polymer chains. These findings are important for designing 'on–off' cell capture/release substrates for various biomedical applications such as selective cell separation.

  4. Establishing a course in how to facilitate journal clubs

    DEFF Research Database (Denmark)

    Faebo Larsen, Rikke; Ravnholt, Mette Moesgård; Hølge-Hazelton, Bibi

    2015-01-01

    Aim: To discuss the potentials and barriers of establishing a course in facilitating journal clubs among non-medical health professionals (NMHP). Background: NMHPs and managers had a wish to offer journal clubs. To accomplish this, there was a need of enhancingcompetences among NMHPs with...... and managers mentioned barriers such astime, resources and interest from colleagues. Participants also disputed the management approval. Among the three establishedjournal clubs, the participants stated good management approval, but also a challenge in establishing, preparing and conductingjournal...... clubs. Conclusion: Facilitation journal club courses have the potential to increase knowledge and skills. To secure implementation,further transfer strategies need to be considered as part of the course....

  5. Contextual repetition facilitates word learning via fast mapping.

    Science.gov (United States)

    Axelsson, Emma L; Horst, Jessica S

    2014-10-01

    The current study explores whether contextual repetition during fast mapping facilitates word learning. Three-year-old children completed fast mapping and test trials using a touchscreen computer. For half of the children, the non-targets (competitors) repeated across learning trials and for other children there was no repetition. All children received the same test trials. Children who experienced contextual repetition, that is, children for whom the competitors repeated during the initial fast mapping task, demonstrated word learning. These data demonstrate that children's word learning is facilitated by the presence of extraneous yet predictable information in the initial fast mapping task. PMID:25195163

  6. A theoretical and practical critique of Social Facilitation Theory

    Directory of Open Access Journals (Sweden)

    Loriente Zamora, Cristóbal

    2007-11-01

    Full Text Available Social facilitation theory is one of the most paradigmatic examples of social psychology, understood as an experimental science. However, in this paper we intend to demonstrate that the research that allegedly supports it suffers from a number of defects. It uses biased population samples, and the tasks it sets its experimental subjects are limited to the practical or productive, ignoring the broader range of everyday activities such as conversing or, indeed, urinating. Social facilitation theory, far from being objective, is a microcosm of American social psychology ideology insofar as it ignores basic human functions, and fails to include stigmatized communities such as stutterers and people with bladder problems.

  7. An epistemology of facilitation: A Julian M�ller story

    Directory of Open Access Journals (Sweden)

    H. Elmo Pienaar

    2014-08-01

    Full Text Available The article furthered an epistemology of facilitation. It was created through bringing into focus broad movements in Julian M�ller�s theoretical academic development. Rather than explaining at length the epistemological concepts characterising M�ller�s theoretical development � rightly because of the importance of narrative in Julian M�ller�s work � the article sought to link a social psychological dimension of both M�ller and the author to these concepts. Resulting from M�ller�s work, the author regarded a narrative approach, social constructionism and postfoundationalism as important epistemological conversational partners in practical theological facilitation.

  8. The ING1b tumor suppressor facilitates nucleotide excision repair by promoting chromatin accessibility to XPA

    International Nuclear Information System (INIS)

    ING1b is the most studied ING family protein and perhaps the most ubiquitously and abundantly expressed. This protein is involved in the regulation of various biological functions ranging from senescence, cell cycle arrest, apoptosis, to DNA repair. ING1b is upregulated by UV irradiation and enhances the removal of bulky nucleic acid photoproducts. In this study, we provide evidence that ING1b mediates nucleotide excision repair by facilitating the access to damaged nucleosomal DNA. We demonstrate that ING1b is not recruited to UV-induced DNA lesions but enhances nucleotide excision repair only in XPC-proficient cells, implying an essential role in early steps of the 'access, repair, restore' model. We also find that ING1b alters histone acetylation dynamics upon exposure to UV radiation and induces chromatin relaxation in microccocal nuclease digestion assay, revealing that ING1b may allow better access to nucleotide excision repair machinery. More importantly, ING1b associates with chromatin in a UV-inducible manner and facilitates DNA access to nucleotide excision repair factor XPA. Furthermore, depletion of the endogenous ING1b results to the sensitization of cells at S-phase to UV irradiation. Taken together, these observations establish a role of ING1b acting as a chromatin accessibility factor for DNA damage recognition proteins upon genotoxic injury

  9. Neogenin Facilitates the Induction of Hepcidin Expression by Hemojuvelin in the Liver.

    Science.gov (United States)

    Zhao, Ningning; Maxson, Julia E; Zhang, Richard H; Wahedi, Mastura; Enns, Caroline A; Zhang, An-Sheng

    2016-06-01

    Hemojuvelin (HJV) regulates iron homeostasis by direct interaction with bone morphogenetic protein (BMP) ligands to induce hepcidin expression through the BMP signaling pathway in the liver. Crystallography studies indicate that HJV can simultaneously bind to both BMP2 and the ubiquitously expressed cell surface receptor neogenin. However, the role of the neogenin-HJV interaction in the function of HJV is unknown. Here we identify a mutation in HJV that specifically lowers its interaction with neogenin. Expression of this mutant Hjv in the liver of Hjv(-/-) mice dramatically attenuated its induction of BMP signaling and hepcidin mRNA, suggesting that interaction with neogenin is critical for the iron regulatory function of HJV. Further studies revealed that neogenin co-immunoprecipitated with ALK3, an essential type-I BMP receptor for hepatic hepcidin expression. Neogenin has also been shown to facilitate the cleavage of HJV by furin in transfected cells. Surprisingly, although cleavage of HJV by furin has been implicated in the regulation of HJV function in cell culture models and furin-cleaved soluble Hjv is detectable in the serum of mice, mutating the furin cleavage site did not alter the stimulation of hepcidin expression by Hjv in mice. In vivo studies validated the important role of HJV-BMP interaction for Hjv stimulation of BMP signaling and hepcidin expression. Together these data support a model in which neogenin acts as a scaffold to facilitate assembly of the HJV·BMP·BMP receptor complex to induce hepcidin expression. PMID:27072365

  10. The lncRNA DEANR1 Facilitates Human Endoderm Differentiation by Activating FOXA2 Expression

    Directory of Open Access Journals (Sweden)

    Wei Jiang

    2015-04-01

    Full Text Available Long non-coding RNAs (lncRNAs regulate diverse biological processes, including cell lineage specification. Here, we report transcriptome profiling of human endoderm and pancreatic cell lineages using purified cell populations. Analysis of the data sets allows us to identify hundreds of lncRNAs that exhibit differentiation-stage-specific expression patterns. As a first step in characterizing these lncRNAs, we focus on an endoderm-specific lncRNA, definitive endoderm-associated lncRNA1 (DEANR1, and demonstrate that it plays an important role in human endoderm differentiation. DEANR1 contributes to endoderm differentiation by positively regulating expression of the endoderm factor FOXA2. Importantly, overexpression of FOXA2 is able to rescue endoderm differentiation defects caused by DEANR1 depletion. Mechanistically, DEANR1 facilitates FOXA2 activation by facilitating SMAD2/3 recruitment to the FOXA2 promoter. Thus, our study not only reveals a large set of differentiation-stage-specific lncRNAs but also characterizes a functional lncRNA that is important for endoderm differentiation.

  11. Golgi localized barley MTP8 proteins facilitate Mn transport

    OpenAIRE

    Pedas, Pai Rosager; Schiller, Michaela; Hegelund, Josefine Nymark; Ladegaard, Anne Hald; Schjørring, Jan Kofod; Husted, Søren

    2014-01-01

    Many metabolic processes in plants are regulated by manganese (Mn) but limited information is available on the molecular mechanisms controlling cellular Mn homeostasis. In this study, a yeast assay was used to isolate and characterize two genes, MTP8.1 and MTP8.2 , which encode membrane-bound proteins belonging to the cation diffusion facilitator (CDF) family in the cereal species barley (Hordeum vulgare). Transient expression in onion epidermal cells showed that MTP8.1 and MTP8.2 proteins fu...

  12. Purinergic facilitation of ATP-sensitive potassium current in rat ventricular myocytes

    OpenAIRE

    Babenko, Andrey P.; Vassort, Guy

    1997-01-01

    The effects of different purinergic agonists on the cardiac adenosine 5′-triphosphate (ATP)-sensitive potassium current (IK(ATP)), appearing during dialysis of rat isolated ventricular myocytes with a low-ATP (100 μM) internal solution under whole-cell patch-clamp conditions, were examined in the presence of a P1 purinoceptor antagonist.The extracellular application of ATP in the micromolar range induced, besides known inward currents through cationic and chloride channels, the facilitation o...

  13. Enhancement of electroporation facilitated immunogene therapy via T-reg depletion

    OpenAIRE

    Forde, Patrick F; Sadadcharam, Mira; Hall, Lindsay J.; O'Donovan, T R; de Kruijf, Marcel; Byrne, William L; O'Sullivan, Gerald C.; Soden, Declan M

    2014-01-01

    Regulatory T cells (T-regs) can negatively impact tumor antigen-specific immune responses after infiltration into tumor tissue. However, depletion of T-regs can facilitate enhanced anti-tumor responses, thus augmenting the potential for immunotherapies. Here we focus on treating a highly aggressive form of cancer using a murine melanoma model with a poor prognosis. We utilize a combination of T-reg depletion and immunotherapy plasmid DNA delivered into the B16F10 melanoma tumor model via elec...

  14. Facilitation of the main generator source of earthworm muscle contraction by a peripheral neuron

    Directory of Open Access Journals (Sweden)

    Y.C. Chang

    1998-10-01

    Full Text Available A constant facilitation of responses evoked in the earthworm muscle contraction generator neurons by responses evoked in the neurons of its peripheral nervous system was demonstrated. It is based on the proposal that these two responses are bifurcations of an afferent response evoked by the same peripheral mechanical stimulus but converging again on this central neuron. A single-peaked generator response without facilitation was demonstrated by sectioning the afferent route of the peripheral facilitatory modulatory response, or conditioning response (CR. The multipeaked response could be restored by restimulating the sectioned modulatory neuron with an intracellular substitutive conditioning stimulus (SCS. These multi-peaked responses were proposed to be the result of reverberating the original single peaked unconditioned response (UR through a parallel (P neuronal circuit which receives the facilitation of the peripheral modulatory neuron. This peripheral modulatory neuron was named "Peri-Kästchen" (PK neuron because it has about 20 peripheral processes distributed on the surface of a Kästchen of longitudinal muscle cells on the body wall of this preparation as revealed by the Lucifer Yellow-CH-filling method.

  15. The educator as facilitator: a new kind of leadership.

    Science.gov (United States)

    Musinski, B

    1999-01-01

    As leaders, nurse educators must be aware of each learner's maturity level and learning style. This paper discusses the dependent, independent, and interdependent learner and offers strategies to make the transition from functioning as the teacher to functioning as the facilitator of the learning process. PMID:10426113

  16. Facilitating Conceptual Change in Students' Understanding of Electrochemistry.

    Science.gov (United States)

    Niaz, Mansoor

    2002-01-01

    Constructs a teaching strategy to facilitate conceptual change in freshman students' understanding of electrochemistry. Provides students with the correct response along with alternative responses (teaching experiments), producing a conflicting situation that is conducive to an equilibration of their cognitive structures. Concludes that the…

  17. Teacher’s action zone in facilitating group dynamics

    Directory of Open Access Journals (Sweden)

    Dagmara Gałajda

    2012-01-01

    Full Text Available As believed by many researchers (Dörnyei & Murphey 2003, Hadfield 1992, classroom climate is strongly determined by the dynamics of the learning group and its development over time. For this reason, the role of the teacher in facilitating group processes seems to be of primary importance since it is the teacher who has long been regarded as the group leader in both teacher-centred and learner-centred classrooms.The presentation focuses not only on positive but also on negative forms of classroom dynamics together with management techniques for dealing with conflicts, educational alienation and psychological defensiveness. This, in turn, leads to the concept of facilitator style based on Heron’s (2006 model of facilitation, which consists of six dimensions and three modes. In the paper particular emphasis is placed on the presentation and comparison of various theories of leadership, namely Heron’s system of facilitation, Hersey and Blanchard’s situational-leadership theory (1982 and Bass and Avolio’s transactional versus transformational leadership theory (1984.

  18. Mind Maps as Facilitative Tools in Science Education

    Science.gov (United States)

    Safar, Ammar H.; Jafer,Yaqoub J.; Alqadiri, Mohammad A.

    2014-01-01

    This study explored the perceptions, attitudes, and willingness of pre-service science teachers in the College of Education at Kuwait University about using concept/mind maps and its related application software as facilitative tools, for teaching and learning, in science education. The first level (i.e., reaction) of Kirkpatrick's/Phillips'…

  19. One-to-One Encounters: Facilitators, Participants, and Friendship

    Science.gov (United States)

    Higgins, Lee

    2012-01-01

    In this article, I explore the claim that one-to-one encounters between community music facilitators and music participants can be described as friendships. By exploring the relational structure through the call and the welcome, I make some general comments on friendship before finally tackling the question lying at the heart of this article: How…

  20. Facilitating Chemistry Teachers to Implement Inquiry-Based Laboratory Work

    Science.gov (United States)

    Cheung, Derek

    2008-01-01

    Science teachers generally find inquiry-based laboratory work very difficult to manage. This research project aimed at facilitating chemistry teachers to implement inquiry-based laboratory work in Hong Kong secondary schools. The major concerns of seven chemistry teachers were identified. They were most concerned about the lack of class time,…

  1. Collaboration around Facilitating Emergent Literacy: Role of Occupational Therapy

    Science.gov (United States)

    Asher, Asha; Nichols, Joy D.

    2016-01-01

    The article uses a case study to illustrate transdisciplinary perspectives on facilitating emergent literacy skills of Elsa, a primary grade student with autism. The study demonstrates how a professional learning community implemented motor, sensory, and speech/language components to generate a classroom model supporting emergent literacy skills.…

  2. Do Facilitated Online Dual Credit Classes Result in Deep Learning?

    Science.gov (United States)

    Stark Education Partnership, 2015

    2015-01-01

    This study, with funding from the Jennings Foundation, sought to answer the following broad research question: Do facilitated online dual credit courses result in deep learning? The answer to this question is key to addressing barriers many students face in bridging from high school to college. This report includes a descriptive case study that…

  3. Microfinance as a method of facilitating research in emergency medicine

    DEFF Research Database (Denmark)

    Hallas, Peter; Brabrand, Mikkel; Folkestad, Lars

    2010-01-01

    Microgrants are a novel concept where small grants are used to facilitate research. The concept might have a place in developing emergency medicine research, especially in countries where emergency medicine is not established or in new areas of research. Two examples of the beneficial effects of ...

  4. Using Signs to Facilitate Vocabulary in Children with Language Delays

    Science.gov (United States)

    Lederer, Susan Hendler; Battaglia, Dana

    2015-01-01

    The purpose of this article is to explore recommended practices in choosing and using key word signs (i.e., simple single-word gestures for communication) to facilitate first spoken words in hearing children with language delays. Developmental, theoretical, and empirical supports for this practice are discussed. Practical recommendations for…

  5. A Facilitation of Dyslexia through a Remediation of Shakespeare's Text

    Science.gov (United States)

    Whitfield, Petronilla

    2016-01-01

    This article shares the author's research focusing on the facilitation of acting students with dyslexia in actor-training. For some individuals with dyslexia the translation of the written text into image-based symbols using technological modalities can play a crucial role to access and make concrete the meaning of the words; in this case…

  6. Eating and Emotions in Obese Toddlers: Facilitating Self-Regulation

    Science.gov (United States)

    Chatoor, Irene

    2007-01-01

    Infants and young children have the ability to regulate their food intake according to their energy needs, and parents play an important role in facilitating their children's self-regulation. When overweight children learn to eat in accordance with feelings of hunger and fullness and learn to soothe themselves without eating, they will reduce…

  7. Using a Hybrid Approach to Facilitate Learning Introductory Programming

    Science.gov (United States)

    Cakiroglu, Unal

    2013-01-01

    In order to facilitate students' understanding in introductory programming courses, different types of teaching approaches were conducted. In this study, a hybrid approach including comment first coding (CFC), analogy and template approaches were used. The goal was to investigate the effect of such a hybrid approach on students' understanding in…

  8. Facilitating Navigation in Quality Manuals by Providing Bookmarks or Similar

    International Nuclear Information System (INIS)

    Nuclear Malaysia level quality manuals need to be shared with all divisions. A manual is usually distributed in the form of an electronic document that contains all procedures. Navigation from one heading or procedure to another should be facilitated by providing bookmarks or similar. This paper shows how to do it for Microsoft Word and PDF documents. (author)

  9. Determining the Impact of Online Practicum Facilitation for Inservice Teachers

    Science.gov (United States)

    Frey, Timothy

    2008-01-01

    This study investigated the impact of a project-based graduate practicum experience that was facilitated online. The study investigated the effects of the online practicum experience by: (a) using quantitative data to assess the learning and professional growth of the practicum participants in comparison to a group of teachers that did not…

  10. Facilitating low-carbon investments: Lessons from natural gas

    OpenAIRE

    Neumann, Anne; Neuhoff, Karsten

    2011-01-01

    Decarbonisation of energy and transport infrastructure requires significant private sector investments. The natural gas industry has demonstrated such large scale private sector infrastructure investment over the last decades, typically using long-term contractual arrangements. Are therefore institutional frameworks necessary that facilitate long-term contracting or provide regulation reassuring about future resource streams associated with low-carbon infrastructure - or do factors idiosyncra...

  11. Reviewing a Reading Program: Professional Development Module. Facilitator's Guide

    Science.gov (United States)

    Kosanovich, Marcia; Jordan, Georgia; Arndt, Elissa; VanSciver, Mary; Wahl, Michelle; Rissman, Lila

    2008-01-01

    This "Facilitator's Guide" has been prepared for presenters of the Reviewing a Reading Program professional development training. It is one of three pieces comprising a suite of materials on reviewing reading programs: this "Guide", the "Reviewing a Reading Program Participant's Guide" and the "Reviewing a Reading Program" Professional Development…

  12. Facilitating organisational change in an organic dairy corporation in Denmark

    DEFF Research Database (Denmark)

    Christensen, Dorthe; Sriskandarajah, Nadarajah

    2005-01-01

    The paper sets focus on the notion of sustainable development as the challenge of creating self-referential systems that are continually learning how to persist in a complex and ever-changing environment. For this learning to be accomplished, facilitating it with a systemic perspective may...

  13. Institutional Facilitation in Sustained Volunteering among Older Adult Volunteers

    Science.gov (United States)

    Tang, Fengyan; Morrow-Howell, Nancy; Hong, Songiee

    2009-01-01

    As more nonprofit organizations rely on older adult volunteers to provide services, it is important to retain volunteers for an extended period of time to ensure service quality and the beneficial outcomes of volunteering. Nonprofit organizations are positioned to facilitate older adult volunteers' role performance. Based on an institutional…

  14. Developing a Single Window to Facilitate Trade in Senegal

    OpenAIRE

    Diagne, Ibrahima

    2010-01-01

    In 1995 a reform group headed by Senegal's Ministry of trade introduced a single window system for electronic trade facilitation as part of a reform agenda to improve the country's business environment. Launched in 2004, the system transformed customs clearance, streamlining the process through transparent, electronic transactions initiated by a single request from the importer or exporter...

  15. Systems design and engineering : facilitating multidisciplinary development projects

    NARCIS (Netherlands)

    Bonnema, G. Maarten; Veenvliet, Karel Th.; Broenink, Jan F.

    2016-01-01

    As its name implies, the aim of Systems Design and Engineering: Facilitating Multidisciplinary Development Projects is to help systems engineers develop the skills and thought processes needed to successfully develop and implement engineered systems. Such expertise typically does not come through st

  16. Intellectual property liability of consumers, facilitators, and intermediaries

    NARCIS (Netherlands)

    Heath, C.; Kamperman Sanders, A.W.J.

    2012-01-01

    With reports from all major jurisdictions where the responsibility of facilitators and intermediaries for copyright and trade mark infringement have been litigated, this very useful book is the first comprehensive global survey of the liability regime that intermediaries may face when assisting othe

  17. Facilitating Employees' and Students' Process towards Nascent Entrepreneurship

    Science.gov (United States)

    Hietanen, Lenita

    2015-01-01

    Purpose: The purpose of this paper is to investigate a model for facilitating employees' and full-time, non-business students' entrepreneurial capabilities during their optional entrepreneurship studies at one Finnish Open University. Design/methodology/approach: The case study investigates the course in which transitions from employees or…

  18. Facilitating Transdisciplinary Sustainable Development Research Teams through Online Collaboration

    Science.gov (United States)

    Dale, Ann; Newman, Lenore; Ling, Chris

    2010-01-01

    Purpose: The purpose of this paper is to discuss the potential of online communication technologies to facilitate university-led transdisciplinary sustainable development research and lower the ecological footprints of such research projects. A series of case studies is to be explored. Design/methodology/approach: A one year project is conducted…

  19. Transpersonal Psychology: Facilitating Transformation in Outdoor Experiential Education.

    Science.gov (United States)

    Brown, Michael H.

    1989-01-01

    Explores how outdoor experiential education can facilitate personal growth and transformation by balancing adventure-based activities with inner-directed processes. Discusses transpersonal psychology and research on consciousness and brain functions relevant to the process of transformation. Describes a specific technique to access deeper levels…

  20. A six question screen to facilitate primary cardiovascular disease prevention

    NARCIS (Netherlands)

    N.V. van der Hoeven (Niels V.); M.A.J. Niessen (Maurice); E.S.G. Stroes (Erik S.G.); A. Burdorf (Alex); R.A. Kraaijenhagen (Roderik); B.-J.H. Born (Bert-Jan H.)

    2015-01-01

    textabstractBackground: European guidelines on primary prevention of cardiovascular disease (CVD) recommend the SCORE risk charts for determining CVD risk, which include blood pressure and serum cholesterol as risk parameters. To facilitate cost-effective large-scale screening, we aimed to construct

  1. Facilitation of Play Behavior from Associative to Cooperative Play Stages.

    Science.gov (United States)

    Lounsbury, Karen Rasmussen; Bell, Corinne Reed

    An experimental investigation of the transition from associative play to cooperative play was conducted to determine if cooperative play in young children could be facilitated by (1) presenting a toy that required cooperative responses to make it operate, and (2) instructing the children in the use of the toy prior to having them play with it. A…

  2. Facilitating new ways of learning in Dutch higher education

    NARCIS (Netherlands)

    Beckers, R.; Van der Voordt, D.J.M.

    2013-01-01

    Literature shows that ‘new ways of learning’ cause a shift in learning settings with a growing attention to facilitating autonomy, interaction and knowledge exploration anytime, anywhere. These trends show evident similarities with developments in office environments known for as ‘new ways of workin

  3. Facilitating normative judgments of conditional probability: frequency or nested sets?

    Science.gov (United States)

    Yamagishi, Kimihiko

    2003-01-01

    Recent probability judgment research contrasts two opposing views. Some theorists have emphasized the role of frequency representations in facilitating probabilistic correctness; opponents have noted that visualizing the probabilistic structure of the task sufficiently facilitates normative reasoning. In the current experiment, the following conditional probability task, an isomorph of the "Problem of Three Prisoners" was tested. "A factory manufactures artificial gemstones. Each gemstone has a 1/3 chance of being blurred, a 1/3 chance of being cracked, and a 1/3 chance of being clear. An inspection machine removes all cracked gemstones, and retains all clear gemstones. However, the machine removes 1/2 of the blurred gemstones. What is the chance that a gemstone is blurred after the inspection?" A 2 x 2 design was administered. The first variable was the use of frequency instruction. The second manipulation was the use of a roulette-wheel diagram that illustrated a "nested-sets" relationship between the prior and the posterior probabilities. Results from two experiments showed that frequency alone had modest effects, while the nested-sets instruction achieved a superior facilitation of normative reasoning. The third experiment compared the roulette-wheel diagram to tree diagrams that also showed the nested-sets relationship. The roulette-wheel diagram outperformed the tree diagrams in facilitation of probabilistic reasoning. Implications for understanding the nature of intuitive probability judgments are discussed. PMID:12693194

  4. Part-Set Cuing Facilitation for Spatial Information

    Science.gov (United States)

    Cole, Sydni M.; Reysen, Matthew B.; Kelley, Matthew R.

    2013-01-01

    Part-set cuing "inhibition" refers to the counterintuitive finding that hints--specifically, part of the set of to-be-remembered information--often impair memory performance in free recall tasks. Although inhibition is the most commonly reported result, part-set cuing "facilitation" has been shown with serial order tasks. The…

  5. Facilitating Digital Video Production in the Language Arts Curriculum

    Science.gov (United States)

    McKenney, Susan; Voogt, Joke

    2011-01-01

    Two studies were conducted to facilitate the development of feasible support for the process of integrating digital video making activities in the primary school language arts curriculum. The first study explored which teaching supports would be necessary to enable primary school children to create digital video as a means of fostering…

  6. Facilitating Professional Development for Teachers of English Language Learners

    Science.gov (United States)

    Molle, Daniella

    2013-01-01

    The study explores the process of facilitation in professional development for educators. The study relies on discourse analysis of interaction among K-12 teachers and administrators in a Midwestern U.S. state during a semester-long professional development program especially designed for educators working with English language learners (ELLs).…

  7. Designing an Electronic Educational Game to Facilitate Immersion and Flow

    Science.gov (United States)

    Ma, Yuxin; Williams, Doug; Prejean, Louise

    2014-01-01

    Advocates of electronic educational games often cite the work on motivation to support the use of games in education. However, motivation alone is inadequate to facilitate learning. Many of the educational games that focused their game design solely on the motivational effect failed to be either educational or entertaining. Theory and research is…

  8. Concept of Learning Organization: Facilitators and Flow of Learning

    Directory of Open Access Journals (Sweden)

    Shruti Sachan

    2016-02-01

    Full Text Available Purpose – The purpose of this study is to ascertain that various facilitators of learning such as learning culture, climate, semantic web technology, information communication technology and knowledge management hold importance to facilitate the flow of learning, which begins at individual-group-and ultimately at organizational level in an organization. Design/methodology/approach – This review paper is based on the research papers written by other authors, who have studied the concept of learning organization, importance of conducive learning culture and climate, impact of facilitators on the flow of learning in an enterprise. A model is developed to illustrate the impact of the facilitators of learning on the flow of learning in an organization. Findings – The study expresses that a conducive and harmonious learning culture and climate, web technology, knowledge management leads to smooth flow of learning at individual-group- and organizational level. Such a culture and climate contributes to an ethical organization, has a direct relationship with the performance of an enterprise, learning capability and competitive advantage. Limitations –This study is based on secondary research which has been published by reputed authors in this field. Acronyms – LO (Learning Organization, OL (Organization Learning, KM (Knowledge Management, SWT (Semantic Web Technology, ICT (Information and Communication technology.

  9. Using creative writing to explore facilitation skills in practice

    Directory of Open Access Journals (Sweden)

    Ann Price

    2016-05-01

    Full Text Available Background: Facilitation skills are key to the effective use of practice development strategies. Students on a masters degree in practice development and innovation undertake a module on facilitation skills that incorporates the use of a creative writing piece to explore facilitation. The aim of this article is to critically reflect on the use of creative writing within an assignment from the lecturer’s perspective. Critical reflection: The Rolfe et al. (2001 model of reflection will be used to structure the reflections, considering the questions ‘What?’, ‘So what?’ and ‘Now what?’. This will form the basis of a discussion of concerns about the assessment method, students’ thoughts, relationship to practice development and evidence of effectiveness of the strategy. Examples of creative writing from the students will be used to demonstrate the diversity of the approach. Ethics: All students have given permission for their work to be included. Discussion: Using creative writing can be freeing for students as they can use their voice to explore a topic. For the lecturer, courage is needed to facilitate this expression but it is rewarding as it links to the principles of practice development to embed new ways of working. Important within the process is the need to give students ‘permission’ to use a non-traditional style of writing; lecturers may benefit from practising the technique themselves to feel comfortable with the creative writing strategy. Conclusion: Creative writing offered an opportunity to explore facilitation in different ways and relate it to different aspects of real and imagined life. This paper shows that creative writing can be used successfully by students to engage in novel ways of thinking. However, future actions identify the importance of guidance regarding relevance to academia and ensuring the lecturer is familiar with the aim and techniques of the process when using it for masters-level assessment

  10. Local Controlled Release of Polyphenol Conjugated with Gelatin Facilitates Bone Formation

    Directory of Open Access Journals (Sweden)

    Yoshitomo Honda

    2015-06-01

    Full Text Available Catechins are extensively used in health care treatments. Nevertheless, there is scarce information about the feasibility of local administration with polyphenols for bone regeneration therapy, possibly due to lack of effective delivery systems. Here we demonstrated that the epigallocatechin-3-gallate-conjugated gelatin (EGCG/Gel prepared by an aqueous chemical synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl-4-morpholinium chloride (DMT-MM gradually disintegrated with time and facilitated bone formation in a critical size defect of a mouse calvaria. Conjugation of EGCG with the Gel generated cross-linking between the two molecules, thereby leading to a retardation of the degradation of the EGCG/Gel and to a delayed release of EGCG. The prepared EGCG/Gels represented significant osteogenic capability compared with that of the uncross-linked Gel and the cross-linked Gel with uncombined-EGCG. In vitro experiments disclosed that the EGCG/Gel induced osteoblastogenesis of a mouse mesenchymal stem cell line (D1 cells within 14 days. Using fluorescently-labeled EGCG/Gel, we found that the fraction of EGCG/Gel adsorbed onto the cell membrane of the D1 cells possibly via a Gel-cell interaction. The interaction might confer the long-term effects of EGCG on the cells, resulting in a potent osteogenic capability of the EGCG/Gel in vivo. These results should provide insight into local controlled release of polyphenols for bone therapy.

  11. What can we learn from facilitator and student perceptions of facilitation skills and roles in the first year of a problem-based learning curriculum?

    Directory of Open Access Journals (Sweden)

    McLean Michelle

    2003-10-01

    Full Text Available Abstract Background The small group tutorial is a cornerstone of problem-based learning. By implication, the role of the facilitator is of pivotal importance. The present investigation canvassed perceptions of facilitators with differing levels of experience regarding their roles and duties in the tutorial. Methods In January 2002, one year after problem-based learning implementation at the Nelson R. Mandela School of Medicine, facilitators with the following experience were canvassed: trained and about to facilitate, facilitated once only and facilitated more than one six-week theme. Student comments regarding facilitator skills were obtained from a 2001 course survey. Results While facilitators generally agreed that the three-day training workshop provided sufficient insight into the facilitation process, they become more comfortable with increasing experience. Many facilitators experienced difficulty not providing content expertise. Again, this improved with increasing experience. Most facilitators saw students as colleagues. They agreed that they should be role models, but were less enthusiastic about being mentors. Students were critical of facilitators who were not up to date with curriculum implementation or who appeared disinterested. While facilitator responses suggest that there was considerable intrinsic motivation, this might in fact not be the case. Conclusions Even if they had facilitated on all six themes, facilitators could still be considered as novices. Faculty support is therefore critical for the first few years of problem-based learning, particularly for those who had facilitated once only. Since student and facilitator expectations in the small group tutorial may differ, roles and duties of facilitators must be explicit for both parties from the outset.

  12. FIRE (facilitating implementation of research evidence: a study protocol

    Directory of Open Access Journals (Sweden)

    Seers Kate

    2012-03-01

    Full Text Available Abstract Background Research evidence underpins best practice, but is not always used in healthcare. The Promoting Action on Research Implementation in Health Services (PARIHS framework suggests that the nature of evidence, the context in which it is used, and whether those trying to use evidence are helped (or facilitated affect the use of evidence. Urinary incontinence has a major effect on quality of life of older people, has a high prevalence, and is a key priority within European health and social care policy. Improving continence care has the potential to improve the quality of life for older people and reduce the costs associated with providing incontinence aids. Objectives This study aims to advance understanding about the contribution facilitation can make to implementing research findings into practice via: extending current knowledge of facilitation as a process for translating research evidence into practice; evaluating the feasibility, effectiveness, and cost-effectiveness of two different models of facilitation in promoting the uptake of research evidence on continence management; assessing the impact of contextual factors on the processes and outcomes of implementation; and implementing a pro-active knowledge transfer and dissemination strategy to diffuse study findings to a wide policy and practice community. Setting and sample Four European countries, each with six long-term nursing care sites (total 24 sites for people aged 60 years and over with documented urinary incontinence Methods and design Pragmatic randomised controlled trial with three arms (standard dissemination and two different programmes of facilitation, with embedded process and economic evaluation. The primary outcome is compliance with the continence recommendations. Secondary outcomes include proportion of residents with incontinence, incidence of incontinence-related dermatitis, urinary tract infections, and quality of life. Outcomes are assessed at baseline

  13. The PDZ-domain protein Whirlin facilitates mechanosensory signaling in mammalian proprioceptors.

    Science.gov (United States)

    de Nooij, Joriene C; Simon, Christian M; Simon, Anna; Doobar, Staceyann; Steel, Karen P; Banks, Robert W; Mentis, George Z; Bewick, Guy S; Jessell, Thomas M

    2015-02-18

    Mechanoreception is an essential feature of many sensory modalities. Nevertheless, the mechanisms that govern the conversion of a mechanical force to distinct patterns of action potentials remain poorly understood. Proprioceptive mechanoreceptors reside in skeletal muscle and inform the nervous system of the position of body and limbs in space. We show here that Whirlin/Deafness autosomal recessive 31 (DFNB31), a PDZ-scaffold protein involved in vestibular and auditory hair cell transduction, is also expressed by proprioceptive sensory neurons (pSNs) in dorsal root ganglia in mice. Whirlin localizes to the peripheral sensory endings of pSNs and facilitates pSN afferent firing in response to muscle stretch. The requirement of Whirlin in both proprioceptors and hair cells suggests that accessory mechanosensory signaling molecules define common features of mechanoreceptive processing across sensory systems. PMID:25698744

  14. Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement.

    Directory of Open Access Journals (Sweden)

    Shira Knafo

    2012-02-01

    Full Text Available Cell adhesion molecules and downstream growth factor-dependent signaling are critical for brain development and synaptic plasticity, and they have been linked to cognitive function in adult animals. We have previously developed a mimetic peptide (FGL from the neural cell adhesion molecule (NCAM that enhances spatial learning and memory in rats. We have now investigated the cellular and molecular basis of this cognitive enhancement, using biochemical, morphological, electrophysiological, and behavioral analyses. We have found that FGL triggers a long-lasting enhancement of synaptic transmission in hippocampal CA1 neurons. This effect is mediated by a facilitated synaptic delivery of AMPA receptors, which is accompanied by enhanced NMDA receptor-dependent long-term potentiation (LTP. Both LTP and cognitive enhancement are mediated by an initial PKC activation, which is followed by persistent CaMKII activation. These results provide a mechanistic link between facilitation of AMPA receptor synaptic delivery and improved hippocampal-dependent learning, induced by a pharmacological cognitive enhancer.

  15. DHX36 enhances RIG-I signaling by facilitating PKR-mediated antiviral stress granule formation.

    Directory of Open Access Journals (Sweden)

    Ji-Seung Yoo

    2014-03-01

    Full Text Available RIG-I is a DExD/H-box RNA helicase and functions as a critical cytoplasmic sensor for RNA viruses to initiate antiviral interferon (IFN responses. Here we demonstrate that another DExD/H-box RNA helicase DHX36 is a key molecule for RIG-I signaling by regulating double-stranded RNA (dsRNA-dependent protein kinase (PKR activation, which has been shown to be essential for the formation of antiviral stress granule (avSG. We found that DHX36 and PKR form a complex in a dsRNA-dependent manner. By forming this complex, DHX36 facilitates dsRNA binding and phosphorylation of PKR through its ATPase/helicase activity. Using DHX36 KO-inducible MEF cells, we demonstrated that DHX36 deficient cells showed defect in IFN production and higher susceptibility in RNA virus infection, indicating the physiological importance of this complex in host defense. In summary, we identify a novel function of DHX36 as a critical regulator of PKR-dependent avSG to facilitate viral RNA recognition by RIG-I-like receptor (RLR.

  16. Phytohormone pathways as targets of pathogens to facilitate infection.

    Science.gov (United States)

    Ma, Ka-Wai; Ma, Wenbo

    2016-08-01

    Plants are constantly threatened by potential pathogens. In order to optimize the output of defense against pathogens with distinct lifestyles, plants depend on hormonal networks to fine-tune specific responses and regulate growth-defense tradeoffs. To counteract, pathogens have evolved various strategies to disturb hormonal homeostasis and facilitate infection. Many pathogens synthesize plant hormones; more importantly, toxins and effectors are produced to manipulate hormonal crosstalk. Accumulating evidence has shown that pathogens exert extensive effects on plant hormone pathways not only to defeat immunity, but also modify habitat structure, optimize nutrient acquisition, and facilitate pathogen dissemination. In this review, we summarize mechanisms by which a wide array of pathogens gain benefits from manipulating plant hormone pathways. PMID:26879412

  17. The practical theologian as decentred but influential facilitator

    Directory of Open Access Journals (Sweden)

    H. Elmo Pienaar

    2012-12-01

    Full Text Available Since the 1970s along with the resurgence in practical philosophy new possibilities opened up in our understanding of the place for and purpose of practical theology. The repositioning of practical theology as a fully worthy discipline was important to find its voice amongst theological peer disciplines. Against this background, it was argued that the full measure of what the discipline can contribute, especially outside of the ministry context, has not yet been fully developed or practiced. Towards this end the presentation’s main contention was put forward, in that it is vital for the practical theologian to take up a role of an inscribed facilitator. It signifies a shift from practical theology to practical theologian and is exemplified by the practice of a facilitative approach in, and to practical theology.

  18. Relational Language Facilitates the Development of Cognitive Flexibility

    Directory of Open Access Journals (Sweden)

    Gomila, Antoni

    2013-04-01

    Full Text Available In several papers, Gentner has shown that relational language facilitates spatial analogical reasoning tasks. In this work we set this question in the context of the development of cognitive flexibility, understood not just as at the representation level, but also at the executive one. To this extent, we modify the design by Ratterman & Gentner (1988 by including order of presentation of the elements as a variable, to increase the executive demands of the task so that the elements to be mentally ordered, which also allows to exclude that the successful answer is based on perceptual appearance. Our results confirm the facilitatory effect of relational language on the development of cognitive flexibility. They also point that a disordered presentation also facilitates correct responses.

  19. Online Chemistry Modules: Interaction and Effective Faculty Facilitation

    Science.gov (United States)

    Slocum, Laura E.; Hamby Towns, Marcy; Zielinski, Theresa Julia

    2004-07-01

    Recommendations for online facilitation presented here are based upon an on-going study of Physical Chemistry OnLine Modules. This particular piece of research focused on discussion board interactions and effective faculty facilitation—two implementation issues that emerged as the project progressed. The discussion board archives from the "How Hot Is That Flame?" module run during the fall semester of 2000 were analyzed by message type. The discussion boards were then diagramed by message type, and follow-up messages were connected so that threads could be easily distinguished. Each discussion board was also analyzed using a coding scheme derived from the cooperative learning literature to identify collaborative behaviors. Combining the longest thread in a discussion board with the collaborative coding scheme allowed researchers to craft recommendations for effective online facilitation. The data analysis methods contained in the article present new ways for chemical educators to examine electronic interactions.

  20. Bispectral index monitoring to facilitate early extubation following cardiovascular surgery.

    Science.gov (United States)

    Anderson, Jennifer; Henry, Linda; Hunt, Sharon; Ad, Niv

    2010-01-01

    Frequently, intensive care nurses assume responsibility for extubating patients after undergoing cardiac surgery. Bispectral index (BIS) monitoring assesses level of mental arousal and awareness when sedated. This study was to determine if the BIS might facilitate earlier extubation of patients following cardiac surgery. A study was conducted comparing 25 stable patients returning to the intensive care unit with a BIS with 25 patients managed without the BIS (N = 50). Data collected included age, sex, surgery, pH, CO2, and temperature on arrival/extubation, total intravenous propofol and pain medication, and BIS scores. Student t tests determined that there were no differences between groups for age, amount of propofol and pain medication received, or time to extubation (P > .05). Regression analysis determined that total propofol, total hydromorphone, and age were significant predictors of time to extubation. In this study, the BIS monitor did not facilitate earlier extubation in the stable patient after cardiac surgery. PMID:20404622

  1. Facilitated diffusion on mobile DNA: configurational traps and sequence heterogeneity

    CERN Document Server

    Brackley, C A; Marenduzzo, D; 10.1103/PhysRevLett.109.168103

    2012-01-01

    We present Brownian dynamics simulations of the facilitated diffusion of a protein, modelled as a sphere with a binding site on its surface, along DNA, modelled as a semi-flexible polymer. We consider both the effect of DNA organisation in 3D, and of sequence heterogeneity. We find that in a network of DNA loops, as are thought to be present in bacterial DNA, the search process is very sensitive to the spatial location of the target within such loops. Therefore, specific genes might be repressed or promoted by changing the local topology of the genome. On the other hand, sequence heterogeneity creates traps which normally slow down facilitated diffusion. When suitably positioned, though, these traps can, surprisingly, render the search process much more efficient.

  2. FACILITATING RADICAL FRONT-END INNOVATION THROUGH TARGETED HR PRACTICES

    DEFF Research Database (Denmark)

    Aagaard, Annabeth

    2016-01-01

    This study examines how radical front end innovation can be actively facilitated through selected and targeted HR practices and bundles of HR practices. The empirical field is an explorative case study of front end innovation and HR practices in the pharmaceutical industry, with an in-depth case...... study of the Danish pharmaceutical company, H. Lundbeck A/S, and explorative studies of seven European and American pharmaceutical and biotech companies. The study aims to show how companies can apply HR practices in ways that actively supports the development of radical front end innovation. The value...... added and the contribution of this article to the existing FEI and HR literature therefore lies in the exploration and mapping of how radical front end innovation is and can be facilitated through targeted HR practices; and in identifying the unique opportunities and challenges of innovation...

  3. Facilitators of HIV Medical Care Engagement Among Former Prisoners.

    Science.gov (United States)

    Bracken, Natalie; Hilliard, Charles; McCuller, William J; Harawa, Nina T

    2015-12-01

    Linkage to and retention in medical care is a concern for HIV-positive individuals leaving custody settings in the United States. The minimal existing research points to low rates of entry into care in the months following release and lapsed viral control among releasees who are subsequently reincarcerated. We conducted seven small focus group discussions with 27 HIVpositive individuals who were recently incarcerated in a California State prison to understand those factors that facilitated linkage to and retention in HIV care following their release. We used a consensual approach to code and analyze the focus group transcripts. Four main themes emerged from the analysis: (1) interpersonal relationships, (2) professional relationships, (3) coping strategies and resources, and (4) individual attitudes. Improving HIV-related outcomes among individuals after their release from prison requires strengthening supportive relationships, fostering the appropriate attitudes and skills, and ensuring access to resources that stabilize daily living and facilitate the process of accessing care. PMID:26595268

  4. Designing museum exhibits that facilitate visitor reflection and discussion

    DEFF Research Database (Denmark)

    Skydsgaard, Morten Arnika; Andersen, Hanne Møller; King, Heather

    2016-01-01

    This paper explores how four design principles (curiosity, challenge, narratives and participation) facilitate reflection and discussion among young visitors in the issues-based exhibition Dear, Difficult Body. The investigation is based on a mixed-method approach combining questionnaire and...... interview data. The implementation of design principles resulted in a variety of exhibits which variously prompted reflection and discussion on the part of visitors. Exhibits with narratives, for example, here defined as both personal and expert narratives, were found to be effective in facilitating...... pupils’ attention but also worked well with other design principles to engage the pupils in sustained reflection and discussion. While other contextual factors remain significant in determining visitor responses, this paper argues that the use of design principles can help create visitor experiences that...

  5. Facilitative governance: transforming global health through complexity theory.

    Science.gov (United States)

    Haffeld, Just

    2012-01-01

    Any initiative to coordinate actions, plans, or initiatives to improve the interaction between global health stakeholders finds itself feeding into a vastly complex global system. By utilising complexity theory as part of a new scientific paradigm, complex adaptive behaviour can emerge to create coherence. A suggested global health convention facilitating incremental regime development could be a way to create good governance processes. Minimum specifications could provide wide space for innovation and encourage shared action. Such specifications would be both a product of, and a facilitator for, future generative relationships. The potential empowerment of individuals as a result of this has the potential to transform global health by creating an arena for continual cooperation, interaction and mutual dependence among global stakeholders. PMID:22248181

  6. Microgrants - a method of facilitating research in emergency medicine

    DEFF Research Database (Denmark)

    Hallas, Peter; Brabrand, Mikkel; Folkestad, Lars

    2010-01-01

    ABSTRACT: Microgrants is a novel concept where small grants are used to facilitate research. The concept might have a place in developing emergency medicine research, especially in countries where emergency medicine in not established or in new areas of research. Two examples of the beneficial...... effects of microgrants in emergency medicine research are described. Emergency medicine interest groups and foundations should consider setting up microgrant schemes....

  7. Memory Facilitation effect in Interaction between Video Clips and Music

    OpenAIRE

    Yoshioka, Kenji; Iwanaga, Makoto

    2007-01-01

    Previous studies examined memories of video clips under the condition of affects combination of pictures and music. Video clips, which were combined with music in same impressions, were easy to remember their contents. The present study aimed to examine the memory facilitation about pictures in two perspectives, the strength of affects and the distribution of the processing recourses. Participants were 39 undergraduate volunteers, who were divided into three experimental conditions randomly. ...

  8. Facilitating Access to Emotions: Neural Signature of EMDR Stimulation

    OpenAIRE

    Deborah Herkt; Visal Tumani; Georg Grön; Thomas Kammer; Arne Hofmann; Birgit Abler

    2014-01-01

    Background Eye Movement Desensitisation and Reprocessing (EMDR) is a method in psychotherapy effective in treating symptoms of posttraumatic stress disorder. The client attends to alternating bilateral visual, auditory or sensory stimulation while confronted with emotionally disturbing material. It is thought that the bilateral stimulation as a specific element of EMDR facilitates accessing and processing of negative material while presumably creating new associative links. We hypothesized th...

  9. Social software: facilitating information-, identity- and relationship-management

    OpenAIRE

    Schmidt, Jan

    2006-01-01

    During the last years, a growing number of online-based applications has been developed that facilitate the creation, articulation and maintenance of social networks. They are often referred to as "social software", but up to now there is neither an accepted definition of this rather vague term, nor is there a comprehensive analytical framework to describe and explain the social dynamics that come with the institutionalization of these tools. This paper starts with a proposal for a definition...

  10. The Facilitating Role of L1 in ESL Classes

    OpenAIRE

    Çağrı Tuğrul Mart

    2013-01-01

    It has been widely advocated that insistence on English-only policy and the complete prohibition of L1 would maximize the effect of learning L2 but recent studies demonstrate that the appropriate use of L1 has a facilitating role in L2 classroom. This study attempts to demonstrate that the use of L1 in ESL classes does not hinder foreign language learning.

  11. The Facilitating Role of L1 in ESL Classes

    Directory of Open Access Journals (Sweden)

    Çağrı Tuğrul Mart

    2013-01-01

    Full Text Available It has been widely advocated that insistence on English-only policy and the complete prohibition of L1 would maximize the effect of learning L2 but recent studies demonstrate that the appropriate use of L1 has a facilitating role in L2 classroom. This study attempts to demonstrate that the use of L1 in ESL classes does not hinder foreign language learning.

  12. Facilitating new ways of learning in Dutch higher education

    OpenAIRE

    Beckers, R.; Van der Voordt, D.J.M.

    2013-01-01

    Literature shows that ‘new ways of learning’ cause a shift in learning settings with a growing attention to facilitating autonomy, interaction and knowledge exploration anytime, anywhere. These trends show evident similarities with developments in office environments known for as ‘new ways of working’. The purpose of this paper is to explore how facility managers in Dutch higher education perceive developments in learning and teaching in order to keep the learning facilities aligned to the ch...

  13. Facilitating investment in affordable housing: towards an Australian model. Draft

    OpenAIRE

    Lawson, J. M.; Berry, M; Milligan, V.; Yates, J

    2009-01-01

    This paper argues that sustainable and affordable finance provides a crucial pillar to support the provision of affordable housing in the long term. This finance can take on a variety of forms, comprising grants, public loans, commercial loans as well as shareholder equity. It can be facilitated by various forms of collateral, government guarantees, mortgage insurance and tax privileges, often involving a specialist financial intermediary. Importantly, how this pillar is constructed influence...

  14. How a Practice Facilitator Can Support Your Practice

    OpenAIRE

    Kristin Geonnotti; Erin Fries Taylor; Deborah Peikes; Lisa Schottenfeld; Hannah Burak; Robert McNellis; Janice Genevro

    2015-01-01

    Primary care can be considered the cornerstone of effective and efficient health care that meets the needs of patients, families, and communities. New resources authored by Mathematica’s health experts offer strategies to help build and sustain practices’ ability to continuously and effectively engage in quality improvement activities. This tip sheet describes approaches practice facilitators (also known as coaches) can take to encourage primary care practices to undertake quality improve...

  15. Microfinance as a method of facilitating research in emergency medicine

    Directory of Open Access Journals (Sweden)

    Folkestad Lars

    2010-04-01

    Full Text Available Abstract Microgrants are a novel concept where small grants are used to facilitate research. The concept might have a place in developing emergency medicine research, especially in countries where emergency medicine is not established or in new areas of research. Two examples of the beneficial effects of microgrants in emergency medicine research are described. Emergency medicine interest groups and foundations should consider setting up microgrant schemes.

  16. Microfinance as a method of facilitating research in emergency medicine.

    Science.gov (United States)

    Hallas, Peter; Brabrand, Mikkel; Folkestad, Lars

    2010-01-01

    Microgrants are a novel concept where small grants are used to facilitate research. The concept might have a place in developing emergency medicine research, especially in countries where emergency medicine is not established or in new areas of research. Two examples of the beneficial effects of microgrants in emergency medicine research are described. Emergency medicine interest groups and foundations should consider setting up microgrant schemes. PMID:20412571

  17. Introducing facilitated communication training: an action research project

    OpenAIRE

    Dearden, Jackie

    2005-01-01

    Background: Facilitated Communication Training (FCT) is a controversial approach to supporting people with severe communication difficulties. It is one method of supporting Alternative and Augmentative Communication (AAC). It has the potential for enabling people with severe language impairments to access communication aids. The local education authority had experience of enabling a non-verbal young person with cerebral palsy who uses FCT to access mainstream education and were open to explor...

  18. Innovation Adoption as Facilitated by a Change-Oriented Workplace

    OpenAIRE

    Becan, Jennifer Edwards; Knight, Danica K.; Flynn, Patrick M.

    2011-01-01

    One of the unique contributions of the current study is a glimpse into the process by which counselors decide to try new innovations in their clinical work. Data were collected from 421 counseling staff from 71 outpatient treatment programs in 4 US regions. Using hierarchical linear modeling, results reveal that the propensity to adopt workshop-based interventions is facilitated by two important mechanisms (1) an innovative organization with creative leadership and (2) change-oriented staff a...

  19. From Pauses to Clauses: Prosody Facilitates Learning of Syntactic Constituency

    OpenAIRE

    Hawthorne, Kara; Gerken, LouAnn

    2014-01-01

    Learning to parse the speech stream into syntactic constituents is a crucial prerequisite to adult-like sentence comprehension, and prosody is one source of information that could be used for this task. To test the role of prosody in facilitating constituent learning, 19-month-olds were familiarized with non-word sentences with 1-clause (ABCDEF) or 2-clause (ABC, DEF) prosody and were then tested on sentences that represent a grammatical (DEF, ABC) or ungrammatical (EFA, BCD) 'movement' of th...

  20. Building a Knowledge Experience Base for Facilitating Innovation

    OpenAIRE

    Pasquale Ardimento; Vito Nicola Convertini; Giuseppe Visaggio

    2013-01-01

    This paper presents a framework aimed at supporting knowledge transferring inside and outside an organization for innovation purposes. For this goal, the authors propose a Knowledge Experience Base (KEB), which collects Knowledge Experience Packages (KEP), to support the formalization and packaging of knowledge and experience of innovation stakeholders, encouraging gradual explanation of tacit information of bearers of knowledge to facilitate the transfer, minimizing costs and risks.

  1. Key operations performance factors on trade and transport facilitation

    OpenAIRE

    Batista, Luciano

    2009-01-01

    Purpose: Greater participation in international trade is an essential element of economic growth. Trade and transport facilitation (TTF) measures and instruments are seen as important initiatives to smooth the progress of trade volumes. The measurement of TTF performance provides the basis for the development of initiatives aimed at accelerating the flow of goods across borders as well as optimising customs processes. A key problem is that there is neither uniformity nor standard frameworks o...

  2. Facilitators, barriers, benefits and limitations of a nurse mentoring relationship

    OpenAIRE

    Johnson, Hattie L.

    1993-01-01

    This qualitative study explores the facilitators, barriers, benefits, and limitations of the mentoring relationship between recently graduated nurse mentees and their mentors. These nurses participated in a seven-week New Nurse Internship Mentoring Program in an urban hospital. The study sample consisted of twenty inexperienced and nineteen experienced registered nurses who represented diverse racial, cultural, and clinical nursing specialties. Focus group and open-end...

  3. Exploring the Use of Technology to Facilitate the Writing Process

    OpenAIRE

    Annette Kratcoski; Selena Cottrell; Erin Killeen; Alissa Kruse; Debra Miller

    2007-01-01

    Revising and editing are essential skills to the writing process. Peer editing is an effective way to help students improve their writing, and introducing students early on to the process of peer editing can be very beneficial to building strong writers. This vignette highlights a project at Fishcreek Elementary (Stow-Munroe Falls City Schools) where teacher Debra Miller mentored a team of first grade teachers in using a document camera to facilitate peer editing.

  4. Implementation Intentions Facilitate Response Inhibition in Children with ADHD

    OpenAIRE

    Gawrilow, Caterina; Gollwitzer, Peter M.

    2008-01-01

    Attention Deficit/Hyperactivity Disorder (ADHD) is associated with action control problems such as failure to inhibit inappropriate responses. Two studies investigated whether self-regulation by implementation intentions (if-then plans; Gollwitzer, P. M. (1999). Implementation intentions: Strong effects of simple plans. American Psychologist, 54, 493 503) facilitates response inhibition in children with ADHD. In Study 1, children with ADHD who furnished a suppression goal with implementation ...

  5. Facilitating management learning: Developing critical reflection through reflective tools

    OpenAIRE

    Gray, David E

    2007-01-01

    The aim of this article is to explore how the practice of critical reflection within a management learning process can be facilitated through the application of reflective processes and tools. A distinction is drawn between reflection as a form of individual development (of, say, the reflective practitioner), and critical reflection as a route to collective action and a component of organizational learning and change. Critical reflection, however, is not a process that comes naturally to many...

  6. Facilitated Articulation of Implicit Knowledge in Textile Design

    OpenAIRE

    Bang, Anne Louise

    2009-01-01

    This is a report from an ongoing research project and as such it is work in progress. The paper proposes an exploratory approach in order to enable end-users to contribute with their experiences of emotional values of fabrics in use. It is suggested that the textile designer with her repertoire of (experiential, implicit and tacit) textile design knowledge should facilitate the articulation process. The paper specifically draws on a series of workshops conducted within the collaborating compa...

  7. Towards a theoretically based Group Facilitation Technique for Project Teams

    OpenAIRE

    Witte, E.H.; Engelhardt, Gabriele

    2004-01-01

    A theoretical framework for developing the group facilitation technique PROMOD is presented here. The efficiency of this technique in improving group decision quality is supported by the results of three experimental studies involving different kinds of problem solving tasks. The author points towards the importance of integrating theoretical assumptions, theory testing and basic research with empirical application. Such a compelling strategy can lead to new insights in group performance dyna...

  8. Toward a Group Facilitation Technique for Project Teams

    OpenAIRE

    Witte, Erich H.

    2007-01-01

    Abstract This article presents the development of a group facilitation technique (PROMOD ? Procedural Moderation). The author points toward the importance of integrating theoretical assumptions, theory testing and basic empirical research with practical application. The results are based on the observation of various three-member task groups faced with a complex non-heureka problem. These comprise naturally interacting groups, simple arithmetic assembled groups of individuals witho...

  9. Physical activity barriers and facilitators among working mothers and fathers

    OpenAIRE

    Mailey, Emily L.; Huberty, Jennifer; Dinkel, Danae; McAuley, Edward

    2014-01-01

    Background The transition to parenthood is consistently associated with declines in physical activity. In particular, working parents are at risk for inactivity, but research exploring physical activity barriers and facilitators in this population has been scarce. The purpose of this study was to qualitatively examine perceptions of physical activity among working parents. Methods Working mothers (n = 13) and fathers (n = 12) were recruited to participate in one of four focus group sessions a...

  10. Nurse as a Facilitator to Professional Communication: A Qualitative Study

    OpenAIRE

    Ghiyasvandian, Shahrzad; Zakerimoghadam, Masoumeh; Peyravi, Hamid

    2014-01-01

    Nurses need to establish communication with other healthcare professionals to facilitate the process of care. Healthcare professionals have complementary roles in providing care to patients. As the key members of the healthcare team, nurses also have an important role in establishing communication among other healthcare professionals. The final outcome of professional communication is effective care and improved patient outcomes. The aim of this study was to explore nurses’ role in establishi...

  11. EFFECTS OF SEGMENTATION OF INSTRUCTIONAL ANIMATION IN FACILITATING LEARNING

    OpenAIRE

    Ahmad Zamzuri Mohamad Ali; Ahmad Rizal Madar

    2010-01-01

    The aim of this study was to investigate the effects of segmented-animation, playpause- animation and continuous-animation in facilitating learning of low prior knowledge learners. A courseware prototype entitled Transmission Media was developed for the research purpose. The courseware contains nine animations on various topics in Transmission Media. Pre-test and post-test experimental design was employed on three different groups respectively. The data collected were analyzed statistically b...

  12. The Mindful Coach Seven Roles for Facilitating Leader Development

    CERN Document Server

    Silsbee, Doug

    2010-01-01

    Written for executive coaches, teachers, and other development professionals, the book explores the  seven roles or "Voices" that coaches assume while working with a client. The "Voices" are: Master, Partner, Investigator, Reflector, Teacher, Guide and Contractor. Silsbee illuminates the dynamic relationship between these roles, and integrates them in an intelligent roadmap for any coaching conversation. This book offers a helpful resource for internal and external executive coaches as well as leader coaches, consultants, trainers, teachers, and facilitators.

  13. Twelve tips for facilitating team-based learning

    OpenAIRE

    Gullo, Charles; Ha, Tam Cam; Cook, Sandy

    2015-01-01

    Abstract Background: Team-based learning (TBL) has become a more commonly recognized and implemented pedagogical approach in curricula of numerous disciplines. The desire to place more autonomy on the student and spend less in-class time delivering content has resulted in complete or partial adoption of this style of learning in many educational settings. Aim: Provide faculty with tools that foster a well facilitated and interactive TBL learning environment. Methods: We examined the published...

  14. Facilitation versus inhibition in non-spatial attribute discrimination tasks

    OpenAIRE

    Hu, Frank K.; Samuel, Arthur G.

    2011-01-01

    Inhibition of Return is a delay in initiating attentional shifts to previously inspected locations. It has been explained as a mechanism to facilitate visual search of a scene by inhibiting the allocation of attention to locations that have already been examined. We (Hu, Samuel, & Chan, Journal of Experimental Psychology: General, 2010) recently demonstrated that similar processing costs can appear when a non-spatial attribute (color or shape) repeats—detection of a target stimulus was slower...

  15. Influencing and facilitating conditions for developing reflective assessment practice

    OpenAIRE

    Rønsen, Anne Kristin

    2013-01-01

    By following a professional development project focusing on enhancing assessment competence amongst teachers, the current study examines how teachers use reflective writing and systematic discussions as tools for developing competence in assessment. More specifically, the article aims at identifying conditions that influence and facilitate reflection over time. The study is a small-scale qualitative study from a Norwegian context, and the analysis draws on nine teachers’ written and oral refl...

  16. Open Source Software: How Can Design Metrics Facilitate Architecture Recovery?

    OpenAIRE

    Constantinou, Eleni; Kakarontzas, George; Stamelos, Ioannis

    2011-01-01

    Modern software development methodologies include reuse of open source code. Reuse can be facilitated by architectural knowledge of the software, not necessarily provided in the documentation of open source software. The effort required to comprehend the system's source code and discover its architecture can be considered a major drawback in reuse. In a recent study we examined the correlations between design metrics and classes' architecture layer. In this paper, we apply our methodology in ...

  17. Facilitation as Attenuating of Environmental Stress among Structured Microbial Populations

    OpenAIRE

    Suzana Cláudia Silveira Martins; Sandra Tédde Santaella; Claudia Miranda Martins; Rogério Parentoni Martins

    2016-01-01

    There is currently an intense debate in microbial societies on whether evolution in complex communities is driven by competition or cooperation. Since Darwin, competition for scarce food resources has been considered the main ecological interaction shaping population dynamics and community structure both in vivo and in vitro. However, facilitation may be widespread across several animal and plant species. This could also be true in microbial strains growing under environmental stress. Pure an...

  18. Facilitators for Empowering Women in Breastfeeding: a Qualitative Study

    Directory of Open Access Journals (Sweden)

    Shahnaz Kohan

    2016-01-01

    Full Text Available Background  Exclusive breastfeeding for the first six months and continued breastfeeding up to 2 years or more is a desirable approach for infant’s nutrition. A mother's breastfeeding empowerment is considered an important factor in promoting breastfeeding and identifying its facilitating factors can contribute to the development of effective policies and intervention. This study with a qualitative approach carried out aiming to exploring the facilitators for women’s empowerment in breastfeeding. Material and Methods This study conducted by content analysis method. Thirty-four semi-structured individual interviews with 20 mothers having breastfeeding experience, 4 key family members, and 10 personnel involved in breastfeeding services were carried out. Data analysis was simultaneously performed with data collection. Results Three main categories of "Health system factors", "Family and personal factors" and "Social and cultural factors" were extracted from the participants' explanations, indicating the dimensions of facilitators for empowering women in breastfeeding. Conclusion Participants regarded the acquisition of breastfeeding skills in hospitals and breastfeeding counseling in health centers as important factors in facilitating their empowerment to early initiation of breastfeeding and its continuity. Further analysis showed "a mother's decision to breastfeed" along with her understanding of "positive attitude and her husband and family's participation in breastfeeding" boosts the breastfeeding ability and the support of the community through "positive cultural belief in breastfeeding" and" public education and information" provides an appropriate ground for the continuity of breastfeeding. In order to improve breastfeeding, a comprehensive planning with regard to women's empowerment in breastfeeding should be considered.

  19. Which factors facilitate the management of external knowledge?

    OpenAIRE

    Osmonalieva, Zarina; Rao, Laxmi

    2008-01-01

    Date: 2008-06-04 Course: EIK 034 Masters Thesis Authors: Laxmi Rao & Zarina Osmonalieva Tutor: Ole Liljefors Title: Which factors facilitate the management of external knowledge? Introduction: Today more and more organisations are realising that handling internal and external knowledge is a key issue for successful performance. Different theories describe the importance of this topic, for instance, Porter’s Five Forces model and Hedman & Kalling’s General Business Model demonstrate ho...

  20. Using Hypertext to Facilitate Information Sharing in Biomedical Research Groups

    OpenAIRE

    Chaney, R. Jesse; Shipman, Frank M.; Gorry, G. Anthony

    1989-01-01

    As part of our effort to create an Integrated Academic Information Management System at Baylor College of Medicine, we are developing information technology to support the efforts of scientific work groups. Many of our ideas in this regard are embodied in a system called the Virtual Notebook which is intended to facilitate information sharing and management in such groups. Here we discuss the foundations of that system - a hypertext system that we have developed using a relational data base a...