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Sample records for cells mobilize myeloid-derived

  1. High-mobility group box protein 1 promotes the survival of myeloid-derived suppressor cells by inducing autophagy.

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    Parker, Katherine H; Horn, Lucas A; Ostrand-Rosenberg, Suzanne

    2016-09-01

    Myeloid-derived suppressor cells are immune-suppressive cells that are elevated in most individuals with cancer, where their accumulation and suppressive activity are driven by inflammation. As myeloid-derived suppressor cells inhibit anti-tumor immunity and promote tumor progression, we are determining how their viability is regulated. Previous studies have established that the damage-associated molecular pattern molecule high-mobility group box protein 1 drives myeloid-derived suppressor cell accumulation and suppressive potency and is ubiquitously present in the tumor microenvironment. As high-mobility group box protein 1 also facilitates tumor cell survival by inducing autophagy, we sought to determine if high-mobility group box protein 1 regulates myeloid-derived suppressor cell survival through induction of autophagy. Inhibition of autophagy increased the quantity of apoptotic myeloid-derived suppressor cells, demonstrating that autophagy extends the survival and increases the viability of myeloid-derived suppressor cells. Inhibition of high-mobility group box protein 1 similarly increased the level of apoptotic myeloid-derived suppressor cells and reduced myeloid-derived suppressor cell autophagy, demonstrating that in addition to inducing the accumulation of myeloid-derived suppressor cells, high-mobility group box protein 1 sustains myeloid-derived suppressor cell viability. Circulating myeloid-derived suppressor cells have a default autophagic phenotype, and tumor-infiltrating myeloid-derived suppressor cells are more autophagic, consistent with the concept that inflammatory and hypoxic conditions within the microenvironment of solid tumors contribute to tumor progression by enhancing immune-suppressive myeloid-derived suppressor cells. Overall, these results demonstrate that in addition to previously recognized protumor effects, high-mobility group box protein 1 contributes to tumor progression by increasing myeloid-derived suppressor cell viability by

  2. Mast cells mobilize myeloid-derived suppressor cells and Treg cells in tumor microenvironment via IL-17 pathway in murine hepatocarcinoma model.

    Directory of Open Access Journals (Sweden)

    Zhuoshun Yang

    Full Text Available Tumor immunosuppression is commonly braided with chronic inflammation during tumor development. However, the relationship between immunosuppression and inflammation in tumor microenvironment is still unclear. We have demonstrated that mast cells are accumulated and exacerbate the inflammation and immunosuppression in tumor microenvironment via SCF/c-kit signaling pathway. Here, we further elucidate the underlying mechanism, which involves both myeloid-derived suppressor cells (MDSCs and regulatory T (Treg cells. Our data showed that mast cells mobilized the infiltration of MDSCs to tumor and induced the production of IL-17 by MDSCs; MDSCs-derived IL-17 indirectly attracted Treg cells, enhanced their suppressor function, and induced the IL-9 production by Treg cells; in turn, IL-9 strengthened the survival and protumor effect of mast cells in tumor microenvironment. Our findings disclose a closed loop among mast cells, MDSCs and Treg cells in tumor microenvironment, which provides a new insight into the paralleled developments of inflammation and immunosuppression in tumor microenvironment. Based on these findings, we propose that targeting tumor inflammation might be a potential strategy to reverse the immunosuppression of tumor microenvironment, thus facilitating cancer immunotherapy.

  3. Mast cells mobilize myeloid-derived suppressor cells and Treg cells in tumor microenvironment via IL-17 pathway in murine hepatocarcinoma model.

    Science.gov (United States)

    Yang, Zhuoshun; Zhang, Biao; Li, Dapeng; Lv, Meng; Huang, Chunmei; Shen, Guan-Xin; Huang, Bo

    2010-01-01

    Tumor immunosuppression is commonly braided with chronic inflammation during tumor development. However, the relationship between immunosuppression and inflammation in tumor microenvironment is still unclear. We have demonstrated that mast cells are accumulated and exacerbate the inflammation and immunosuppression in tumor microenvironment via SCF/c-kit signaling pathway. Here, we further elucidate the underlying mechanism, which involves both myeloid-derived suppressor cells (MDSCs) and regulatory T (Treg) cells. Our data showed that mast cells mobilized the infiltration of MDSCs to tumor and induced the production of IL-17 by MDSCs; MDSCs-derived IL-17 indirectly attracted Treg cells, enhanced their suppressor function, and induced the IL-9 production by Treg cells; in turn, IL-9 strengthened the survival and protumor effect of mast cells in tumor microenvironment. Our findings disclose a closed loop among mast cells, MDSCs and Treg cells in tumor microenvironment, which provides a new insight into the paralleled developments of inflammation and immunosuppression in tumor microenvironment. Based on these findings, we propose that targeting tumor inflammation might be a potential strategy to reverse the immunosuppression of tumor microenvironment, thus facilitating cancer immunotherapy. PMID:20111717

  4. Mast Cells Mobilize Myeloid-Derived Suppressor Cells and Treg Cells in Tumor Microenvironment via IL-17 Pathway in Murine Hepatocarcinoma Model

    OpenAIRE

    Zhuoshun Yang; Biao Zhang; Dapeng Li; Meng Lv; Chunmei Huang; Guan-Xin Shen; Bo Huang

    2010-01-01

    Tumor immunosuppression is commonly braided with chronic inflammation during tumor development. However, the relationship between immunosuppression and inflammation in tumor microenvironment is still unclear. We have demonstrated that mast cells are accumulated and exacerbate the inflammation and immunosuppression in tumor microenvironment via SCF/c-kit signaling pathway. Here, we further elucidate the underlying mechanism, which involves both myeloid-derived suppressor cells (MDSCs) and regu...

  5. Induction of myeloid-derived suppressor cells by tumor exosomes

    OpenAIRE

    Xiang, Xiaoyu; Poliakov, Anton; Liu, Cunren; Liu, Yuelong; Deng, Zhong-Bin; wang, Jianhua; Cheng, Ziqiang; Shah, Spandan V.; Wang, Gui-Jun; Zhang, Liming; Grizzle, William E.; Mobley, Jim; Zhang, Huang-Ge

    2009-01-01

    Myeloid-derived suppressor cells (MDSCs) promote tumor progression. The mechanisms of MDSC development during tumor growth remain unknown. Tumor exosomes (T-exosomes) have been implicated to play a role in immune regulation, however the role of exosomes in the induction of MDSCs is unclear. Our previous work demonstrated that exosomes isolated from tumor cells are taken up by bone marrow myeloid cells. Here, we extend those findings showing that exosomes isolated from T-exosomes switch the di...

  6. Myeloid-derived suppressor cells as a Trojan horse

    OpenAIRE

    Pan, Ping-Ying; Chen, Hui-Ming; Chen, Shu-Hsia

    2013-01-01

    We have recently demonstrated that oncolytic vesicular stomatitis viruses can be efficiently and selectively delivered to neoplastic lesions by myeloid-derived suppressor cells (MDSCs). Importantly, the loading of viruses onto MDSCs inhibited their immunosuppressive properties and endowed them with immunostimulatory and tumoricidal functions. Our study demonstrates the potential use of MDSCs as a Trojan horse for the tumor-targeted delivery of various anticancer therapeutics.

  7. Tumor-Induced Myeloid-Derived Suppressor Cells.

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    De Sanctis, Francesco; Bronte, Vincenzo; Ugel, Stefano

    2016-06-01

    Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous, immune-suppressive leukocyte population that develops systemically and infiltrates tumors. MDSCs can restrain the immune response through different mechanisms including essential metabolite consumption, reactive oxygen and nitrogen species production, as well as display of inhibitory surface molecules that alter T-cell trafficking and viability. Moreover, MDSCs play a role in tumor progression, acting directly on tumor cells and promoting cancer stemness, angiogenesis, stroma deposition, epithelial-to-mesenchymal transition, and metastasis formation. Many biological and pharmaceutical drugs affect MDSC expansion and functions in preclinical tumor models and patients, often reversing host immune dysfunctions and allowing a more effective tumor immunotherapy.

  8. Myeloid-derived suppressor cell heterogeneity in human cancers.

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    Solito, Samantha; Marigo, Ilaria; Pinton, Laura; Damuzzo, Vera; Mandruzzato, Susanna; Bronte, Vincenzo

    2014-06-01

    The dynamic interplay between cancer and host immune system often affects the process of myelopoiesis. As a consequence, tumor-derived factors sustain the accumulation and functional differentiation of myeloid cells, including myeloid-derived suppressor cells (MDSCs), which can interfere with T cell-mediated responses. Since both the phenotype and mechanisms of action of MDSCs appear to be tumor-dependent, it is important not only to determine the presence of all MDSC subsets in each cancer patient, but also which MDSC subsets have clinical relevance in each tumor environment. In this review, we describe the differences between MDSC populations expanded within different tumor contexts and evaluate the prognostic significance of MDSC expansion in peripheral blood and within tumor masses of neoplastic patients.

  9. Myeloid-derived suppressor cells in Chronic myeloid leukemia

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    Cesarina eGiallongo

    2015-05-01

    Full Text Available The suppression of the immune system create a permissive environment for development and progression of cancer. One population of immunosuppressive cells that have become the focus of intense study is myeloid derived suppressor cells (MDSCs, immature myeloid cells able to induce immune-escape, angiogenesis and tumor progression. Two different subpopulations have been identified and studied: granulocytic and monocytic MDSCs, with a different immunophenotype and immunosuppressive properties. Recently, an accumulation of both Gr-MDSCs and Mo-MDSCs cells has been found in the peripheral blood of chronic myeloid leukemia (CML patients. They are part of the tumor clone showing BCR/ABL expression. Imatinib therapy decreases both MDSCs and arginase 1 levels to normal ones. This review will focus on actual knowledge for human MDSCs and their immunosuppressive activity in CML patients with a critical attention to comparison of Gr-MDSCs and polymorphonuclear cells (PMNs. We will then suggest the monitoring of MDSCs in patients who have discontinued tyrosine kinase inhibitors (TKIs therapy to evaluate if their increase could correlate with disease relapse.

  10. Graft monocytic myeloid-derived suppressor cell content predicts the risk of acute graft-versus-host disease after allogeneic transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood stem cells.

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    Vendramin, Antonio; Gimondi, Silvia; Bermema, Anisa; Longoni, Paolo; Rizzitano, Sara; Corradini, Paolo; Carniti, Cristiana

    2014-12-01

    Myeloid-derived suppressor cells (MDSCs) are powerful immunomodulatory cells that in mice play a role in infectious and inflammatory disorders, including acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. Their relevance in clinical acute GVHD is poorly known. We analyzed whether granulocyte colony-stimulating factor (G-CSF) administration, used to mobilize hematopoietic stem cells, affected the frequency of MDSCs in the peripheral blood stem cell grafts of 60 unrelated donors. In addition, we evaluated whether the MDSC content in the peripheral blood stem cell grafts affected the occurrence of acute GVHD in patients undergoing unrelated donor allogeneic stem cell transplantation. Systemic treatment with G-CSF induces an expansion of myeloid cells displaying the phenotype of monocytic MDSCs (Lin(low/neg)HLA-DR(-)CD11b(+)CD33(+)CD14(+)) with the ability to suppress alloreactive T cells in vitro, therefore meeting the definition of MDSCs. Monocytic MDSC dose was the only graft parameter to predict acute GVHD. The cumulative incidence of acute GVHD at 180 days after transplantation for recipients receiving monocytic MDSC doses below and above the median was 63% and 22%, respectively (P = .02). The number of monocytic MDSCs infused did not impact the relapse rate or the transplant-related mortality rate (P > .05). Although further prospective studies involving larger sample size are needed to validate the exact monocytic MDSC graft dose that protects from acute GVHD, our results strongly suggest the modulation of G-CSF might be used to affect monocytic MDSCs graft cell doses for prevention of acute GVHD.

  11. Drafting the proteome landscape of myeloid-derived suppressor cells.

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    Gato, María; Blanco-Luquin, Idoia; Zudaire, Maribel; de Morentin, Xabier Martínez; Perez-Valderrama, Estela; Zabaleta, Aintzane; Kochan, Grazyna; Escors, David; Fernandez-Irigoyen, Joaquín; Santamaría, Enrique

    2016-01-01

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that are defined by their myeloid origin, immature state, and ability to potently suppress T-cell responses. They regulate immune responses and the population significantly increases in the tumor microenvironment of patients with glioma and other malignant tumors. For their study, MDSCs are usually isolated from the spleen or directly of tumors from a large number of tumor-bearing mice although promising ex vivo differentiated MDSC production systems have been recently developed. During the last years, proteomics has emerged as a powerful approach to analyze MDSCs proteomes using shotgun-based mass spectrometry (MS), providing functional information about cellular homeostasis and metabolic state at a global level. Here, we will revise recent proteome profiling studies performed in MDSCs from different origins. Moreover, we will perform an integrative functional analysis of the protein compilation derived from these large-scale proteomic studies in order to obtain a comprehensive view of MDSCs biology. Finally, we will also discuss the potential application of high-throughput proteomic approaches to study global proteome dynamics and post-translational modifications (PTMs) during the differentiation process of MDSCs that will greatly boost the identification of novel MDSC-specific therapeutic targets to apply in cancer immunotherapy. PMID:26403437

  12. Myeloid-derived suppressor cells in patients with myeloproliferative neoplasm.

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    Wang, Jen Chin; Kundra, Ajay; Andrei, Mirela; Baptiste, Stacey; Chen, Chi; Wong, Ching; Sindhu, Hemant

    2016-04-01

    Although BCR-ABL negative myeloproliferative neoplasms (MPN)--and especially myelofibrosis (MF)--are recognized to be associated with autoimmune phenomena, immune derangements in MPN have been much less studied. Myeloid-derived suppressor cells (MDSC) are one type of important immune modulator cell. Therefore, we studied MDSCs in MPN disease. MDSCs were studied in two cohorts: the first cohort was 55 patients including 16 primary myelofibrosis (PMF), 7 post-polycythemia vera (PV)-MF, 2 post-essential thrombocythemia (ET)-MF, 11 ET, 17 PV, 2 undefined MPN disorder, and 23 normal controls; the second cohort included 38 patients: 17 ET, 7 PMF, 3 ET-MF, 2 PV-MF, 9 PV patients, and 20 normal volunteers. The second cohort was studied using freshly collected specimens and a comparable age group as controls. CD11b(+), CD14(-), and CD33(+) cells were defined as MDSCs in both cohorts by flow cytometry. Since there are no differences in MDSC levels among different MPN categories, they were grouped as MPNs. The results showed that MDSCs were significantly elevated in MPNs compared with controls in both cohorts. We also performed RT-PCR and found that MPN patients have significantly elevated arginase-1 mRNA compared with controls, and sorted MDSCs were found to have suppressor T cell activity in MPNs, substantiating the hypothesis that levels of MDSCs are, in fact, deranged in MPNs. MDSC levels were not correlated with JAK2 status, white blood cells, Hb levels, platelet counts, splenomegaly, or the degree of bone marrow fibrosis (in MF). Further studies in immune therapy involving MDSC inhibitors or differentiation may be developed to treat MPN disease. PMID:26943702

  13. Correlation between myeloid-derived suppressor cells and gastric cancer begin with chronic gastritis

    Institute of Scientific and Technical Information of China (English)

    朱立宁

    2012-01-01

    Objective To investigate the correlation between the ratio change of circulating myeloid-derived suppressor cells(MDSCs) and cellular immune function in healthy volunteers,chronic gastritis patients,gastric intraepithelial neoplasia patients and gastric cancer patients

  14. Myeloid-derived Suppressor Cells Inhibit T Cell Activation by Depleting Cystine and Cysteine

    OpenAIRE

    Minu K Srivastava; Sinha, Pratima; Clements, Virginia K.; Rodriguez, Paulo; Ostrand-Rosenberg, Suzanne

    2009-01-01

    Myeloid-derived suppressor cells (MDSC) are present in most cancer patients and are potent inhibitors of T-cell-mediated anti-tumor immunity. Their inhibitory activity is attributed to production of arginase, reactive oxygen species, inducible nitric oxide synthase, and IL-10. We now report that MDSC also block T cell activation by sequestering cystine and limiting the availability of cysteine. Cysteine is an essential amino acid for T cell activation because T cells lack cystathionase, which...

  15. Myeloid derived suppressor cells-An overview of combat strategies to increase immunotherapy efficacy

    NARCIS (Netherlands)

    Draghiciu, Oana; Lubbers, Joyce; Nijman, Hans W.; Daemen, Toos

    2015-01-01

    Myeloid-derived suppressor cells (MDSCs) contribute to tumor-mediated immune escape and negatively correlate with overall survival of cancer patients. Nowadays, a variety of methods to target MDSCs are being investigated. Based on the intervention stage of MDSCs, namely development, expansion and ac

  16. Histone deacetylase 11: A novel epigenetic regulator of myeloid derived suppressor cell expansion and function

    OpenAIRE

    Sahakian, Eva; Powers, John J.; Chen, Jie; Deng, Susan L.; Cheng, Fengdong; Distler, Allison; Woods, David M.; Rock-Klotz, Jennifer; Laino, Andressa Sodre'; Youn, Je-In; Woan, Karrune V.; Villagra, Alejandro; Gabrilovich, Dmitry,; Sotomayor, Eduardo M.; Pinilla-Ibarz, Javier

    2014-01-01

    Myeloid-derived suppressor cells (MDSC's), a heterogeneous population of cells capable of suppressing anti-tumor T cell function in the tumor microenvironment, represent an imposing obstacle in the development of cancer immunotherapeutics. Thus, identifying elements essential to the development and perpetuation of these cells will undoubtedly improve our ability to circumvent their suppressive impact. HDAC11 has emerged as a key regulator of IL-10 gene expression in myeloid cells, suggesting ...

  17. Pathogenic Fungi Regulate Immunity by Inducing Neutrophilic Myeloid-Derived Suppressor Cells

    OpenAIRE

    Rieber, Nikolaus; Singh, Anurag; ÖZ, Hasan; Carevic, Melanie; Bouzani, Maria; Amich, Jorge; Ost, Michael; Ye, Zhiyong; Ballbach, Marlene; Schäfer, Iris; Mezger, Markus; Klimosch, Sascha N.; Weber, Alexander N.R.; Handgretinger, Rupert; Krappmann, Sven

    2015-01-01

    Summary Despite continuous contact with fungi, immunocompetent individuals rarely develop pro-inflammatory antifungal immune responses. The underlying tolerogenic mechanisms are incompletely understood. Using both mouse models and human patients, we show that infection with the human pathogenic fungi Aspergillus fumigatus and Candida albicans induces a distinct subset of neutrophilic myeloid-derived suppressor cells (MDSCs), which functionally suppress T and NK cell responses. Mechanistically...

  18. Expansion and functions of myeloid-derived suppressor cells in the tumor microenvironment.

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    Qu, Peng; Wang, Li-Zhen; Lin, P Charles

    2016-09-28

    Myeloid derived suppressor cells (MDSCs) are a group of immature myeloid cells accumulated in most cancer patients and mouse tumor models. MDSCs suppress host immune response and concurrently promote tumor angiogenesis, thereby promote tumor growth and progression. In this review, we discuss recent progresses in expansion and activity of tumor MDSCs, and describe new findings about immunosuppressive function of different subtypes of MDSCs in cancer. We also discussed tumor angiogenic activities and pro-tumor invasion/metastatic roles of MDSCs in tumor progression. PMID:26519756

  19. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards.

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    Bronte, Vincenzo; Brandau, Sven; Chen, Shu-Hsia; Colombo, Mario P; Frey, Alan B; Greten, Tim F; Mandruzzato, Susanna; Murray, Peter J; Ochoa, Augusto; Ostrand-Rosenberg, Suzanne; Rodriguez, Paulo C; Sica, Antonio; Umansky, Viktor; Vonderheide, Robert H; Gabrilovich, Dmitry I

    2016-07-06

    Myeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. In recent years, ample evidence supports key contributions of MDSC to tumour progression through both immune-mediated mechanisms and those not directly associated with immune suppression. MDSC are the subject of intensive research with >500 papers published in 2015 alone. However, the phenotypic, morphological and functional heterogeneity of these cells generates confusion in investigation and analysis of their roles in inflammatory responses. The purpose of this communication is to suggest characterization standards in the burgeoning field of MDSC research.

  20. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards

    Science.gov (United States)

    Bronte, Vincenzo; Brandau, Sven; Chen, Shu-Hsia; Colombo, Mario P.; Frey, Alan B.; Greten, Tim F.; Mandruzzato, Susanna; Murray, Peter J.; Ochoa, Augusto; Ostrand-Rosenberg, Suzanne; Rodriguez, Paulo C.; Sica, Antonio; Umansky, Viktor; Vonderheide, Robert H.; Gabrilovich, Dmitry I.

    2016-01-01

    Myeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. In recent years, ample evidence supports key contributions of MDSC to tumour progression through both immune-mediated mechanisms and those not directly associated with immune suppression. MDSC are the subject of intensive research with >500 papers published in 2015 alone. However, the phenotypic, morphological and functional heterogeneity of these cells generates confusion in investigation and analysis of their roles in inflammatory responses. The purpose of this communication is to suggest characterization standards in the burgeoning field of MDSC research. PMID:27381735

  1. Emerging roles of myeloid derived suppressor cells in hepatic inflammation and fibrosis

    OpenAIRE

    Hammerich, Linda; Tacke, Frank

    2015-01-01

    Myeloid derived suppressor cells (MDSC) are a heterogeneous population of immune cells that are potent suppressors of immune responses. MDSC emerge in various compartments in the body, such as blood, bone marrow or spleen, especially in conditions of cancer, infections or inflammation. MDSC usually express CD11b, CD33, and low levels of human leukocyte antigen-DR in humans or CD11b and Gr1 (Ly6C/G) in mice, and they can be further divided into granulocytic or monocytic MDSC. The liver is an i...

  2. Gr1(intCD11b+ myeloid-derived suppressor cells in Mycobacterium tuberculosis infection.

    Directory of Open Access Journals (Sweden)

    Andrés Obregón-Henao

    Full Text Available BACKGROUND: Tuberculosis is one of the world's leading killers, stealing 1.4 million lives and causing 8.7 million new and relapsed infections in 2011. The only vaccine against tuberculosis is BCG which demonstrates variable efficacy in adults worldwide. Human infection with Mycobacterium tuberculosis results in the influx of inflammatory cells to the lung in an attempt to wall off bacilli by forming a granuloma. Gr1(intCD11b(+ cells are called myeloid-derived suppressor cells (MDSC and play a major role in regulation of inflammation in many pathological conditions. Although MDSC have been described primarily in cancer their function in tuberculosis remains unknown. During M. tuberculosis infection it is crucial to understand the function of cells involved in the regulation of inflammation during granuloma formation. Understanding their relative impact on the bacilli and other cellular phenotypes is necessary for future vaccine and drug design. METHODOLOGY/PRINCIPAL FINDINGS: We compared the bacterial burden, lung pathology and Gr1(intCD11b(+ myeloid-derived suppressor cell immune responses in M. tuberculosis infected NOS2-/-, RAG-/-, C3HeB/FeJ and C57/BL6 mice. Gr-1(+ cells could be found on the edges of necrotic lung lesions in NOS2-/-, RAG-/-, and C3HeB/FeJ, but were absent in wild-type mice. Both populations of Gr1(+CD11b(+ cells expressed high levels of arginase-1, and IL-17, additional markers of myeloid derived suppressor cells. We then sorted the Gr1(hi and Gr1(int populations from M. tuberculosis infected NOS-/- mice and placed the sorted both Gr1(int populations at different ratios with naïve or M. tuberculosis infected splenocytes and evaluated their ability to induce activation and proliferation of CD4+T cells. Our results showed that both Gr1(hi and Gr1(int cells were able to induce activation and proliferation of CD4+ T cells. However this response was reduced as the ratio of CD4(+ T to Gr1(+ cells increased. Our results

  3. Gr1intCD11b+ Myeloid-Derived Suppressor Cells in Mycobacterium tuberculosis Infection

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    Obregón-Henao, Andrés; Henao-Tamayo, Marcela; Orme, Ian M.; Ordway, Diane J.

    2013-01-01

    Background Tuberculosis is one of the world’s leading killers, stealing 1.4 million lives and causing 8.7 million new and relapsed infections in 2011. The only vaccine against tuberculosis is BCG which demonstrates variable efficacy in adults worldwide. Human infection with Mycobacterium tuberculosis results in the influx of inflammatory cells to the lung in an attempt to wall off bacilli by forming a granuloma. Gr1intCD11b+ cells are called myeloid-derived suppressor cells (MDSC) and play a major role in regulation of inflammation in many pathological conditions. Although MDSC have been described primarily in cancer their function in tuberculosis remains unknown. During M. tuberculosis infection it is crucial to understand the function of cells involved in the regulation of inflammation during granuloma formation. Understanding their relative impact on the bacilli and other cellular phenotypes is necessary for future vaccine and drug design. Methodology/Principal Findings We compared the bacterial burden, lung pathology and Gr1intCD11b+ myeloid-derived suppressor cell immune responses in M. tuberculosis infected NOS2-/-, RAG-/-, C3HeB/FeJ and C57/BL6 mice. Gr-1+ cells could be found on the edges of necrotic lung lesions in NOS2-/-, RAG-/-, and C3HeB/FeJ, but were absent in wild-type mice. Both populations of Gr1+CD11b+ cells expressed high levels of arginase-1, and IL-17, additional markers of myeloid derived suppressor cells. We then sorted the Gr1hi and Gr1int populations from M. tuberculosis infected NOS-/- mice and placed the sorted both Gr1int populations at different ratios with naïve or M. tuberculosis infected splenocytes and evaluated their ability to induce activation and proliferation of CD4+T cells. Our results showed that both Gr1hi and Gr1int cells were able to induce activation and proliferation of CD4+ T cells. However this response was reduced as the ratio of CD4+ T to Gr1+ cells increased. Our results illustrate a yet unrecognized interplay

  4. The Role and Potential Therapeutic Application of Myeloid-Derived Suppressor Cells in Allo- and Autoimmunity

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    Qi Zhang

    2015-01-01

    Full Text Available Myeloid-derived suppressor cells (MDSCs are a heterogeneous population of cells that consists of myeloid progenitor cells and immature myeloid cells. They have been identified as a cell population that may affect the activation of CD4+ and CD8+ T-cells to regulate the immune response negatively, which makes them attractive targets for the treatment of transplantation and autoimmune diseases. Several studies have suggested the potential suppressive effect of MDSCs on allo- and autoimmune responses. Conversely, MDSCs have also been found at various stages of differentiation, accumulating during pathological situations, not only during tumor development but also in a variety of inflammatory immune responses, bone marrow transplantation, and some autoimmune diseases. These findings appear to be contradictory. In this review, we summarize the roles of MDSCs in different transplantation and autoimmune diseases models as well as the potential to target these cells for therapeutic benefit.

  5. IL-12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors

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    Kerkar, Sid P.; Goldszmid, Romina S.; Muranski, Pawel; Chinnasamy, Dhanalakshmi; Yu, Zhiya; Reger, Robert N.; Leonardi, Anthony J.; Morgan, Richard A.; Wang, Ena; Marincola, Francesco M.; Trinchieri, Giorgio; Rosenberg, Steven A.; Restifo, Nicholas P.

    2011-01-01

    Solid tumors are complex masses with a local microenvironment, or stroma, that supports tumor growth and progression. Among the diverse tumor-supporting stromal cells is a heterogeneous population of myeloid-derived cells. These cells are alternatively activated and contribute to the immunosuppressive environment of the tumor; overcoming their immunosuppressive effects may improve the efficacy of cancer immunotherapies. We recently found that engineering tumor-specific CD8+ T cells to secrete the inflammatory cytokine IL-12 improved their therapeutic efficacy in the B16 mouse model of established melanoma. Here, we report the mechanism underlying this finding. Surprisingly, direct binding of IL-12 to receptors on lymphocytes or NK cells was not required. Instead, IL-12 sensitized bone marrow–derived tumor stromal cells, including CD11b+F4/80hi macrophages, CD11b+MHCIIhiCD11chi dendritic cells, and CD11b+Gr-1hi myeloid–derived suppressor cells, causing them to enhance the effects of adoptively transferred CD8+ T cells. This reprogramming of myeloid-derived cells occurred partly through IFN-γ. Surprisingly, direct presentation of antigen to the transferred CD8+ T cells by tumor was not necessary; however, MHCI expression on host cells was essential for IL-12–mediated antitumor enhancements. These results are consistent with a model in which IL-12 enhances the ability of CD8+ T cells to collapse large vascularized tumors by triggering programmatic changes in otherwise suppressive antigen-presenting cells within tumors and support the use of IL-12 as part of immunotherapy for the treatment of solid tumors. PMID:22056381

  6. Activated T cells sustain myeloid-derived suppressor cell-mediated immune suppression.

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    Pinton, Laura; Solito, Samantha; Damuzzo, Vera; Francescato, Samuela; Pozzuoli, Assunta; Berizzi, Antonio; Mocellin, Simone; Rossi, Carlo Riccardo; Bronte, Vincenzo; Mandruzzato, Susanna

    2016-01-12

    The expansion of myeloid derived suppressor cells (MDSCs), a suppressive population able to hamper the immune response against cancer, correlates with tumor progression and overall survival in several cancer types. We have previously shown that MDSCs can be induced in vitro from precursors present in the bone marrow and observed that these cells are able to actively proliferate in the presence of activated T cells, whose activation level is critical to drive the suppressive activity of MDSCs. Here we investigated at molecular level the mechanisms involved in the interplay between MDSCs and activated T cells. We found that activated T cells secrete IL-10 following interaction with MDSCs which, in turn, activates STAT3 phosphorylation on MDSCs then leading to B7-H1 expression. We also demonstrated that B7-H1+ MDSCs are responsible for immune suppression through a mechanism involving ARG-1 and IDO expression. Finally, we show that the expression of ligands B7-H1 and MHC class II both on in vitro-induced MDSCs and on MDSCs in the tumor microenvironment of cancer patients is paralleled by an increased expression of their respective receptors PD-1 and LAG-3 on T cells, two inhibitory molecules associated with T cell dysfunction. These findings highlight key molecules and interactions responsible for the extensive cross-talk between MDSCs and activated T cells that are at the basis of immune suppression.

  7. Differential Regulation of Myeloid-Derived Suppressor Cells by Candida Species

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    Singh, Anurag; Lelis, Felipe; Braig, Stefanie; Schäfer, Iris; Hartl, Dominik; Rieber, Nikolaus

    2016-01-01

    Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterized by their ability to suppress T-cell responses. Recently, we demonstrated that the human-pathogenic fungi Candida albicans and Aspergillus fumigatus induced a distinct subset of neutrophilic MDSCs. To dissect Candida-mediated MDSC induction in more depth, we studied the relative efficacy of different pathogenic non-albicans Candida species to induce and functionally modulate neutrophilic MDSCs, including C. glabrata, C. parapsilosis, C. dubliniensis, and C. krusei. Our data demonstrate that the extent of MDSC generation is largely dependent on the Candida species with MDSCs induced by C. krusei and C. glabrata showing a higher suppressive activity compared to MDSCs induced by C. albicans. In summary, these studies show that fungal MDSC induction is differentially regulated at the species level and differentially affects effector T-cell responses.

  8. Myeloid-derived suppressor cells impair the quality of dendritic cell vaccines.

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    Poschke, I; Mao, Y; Adamson, L; Salazar-Onfray, F; Masucci, G; Kiessling, R

    2012-06-01

    Myeloid-derived suppressor cells (MDSC) are important regulators of the immune system and key players in tumor-induced suppression of T-cell responses. CD14+HLA-DR-/low MDSC have been detected in a great number of malignancies, including melanoma. MDSC are known to be impaired in their ability to differentiate along the myeloid lineage, e.g., into dendritic cells (DC). This is a concern for utilization of monocyte-derived DC for vaccination of patients with melanoma or other cancers exhibiting accumulation of CD14+ MDSC. When producing DC according to standard operating procedures of two currently ongoing clinical trials, we found that MDSC co-purified with monocytes isolated by elutriation. MDSC frequencies did not affect yield or viability of the produced DC, but induced a dose-dependent decrease in DC maturation, ability to take up antigen, migrate and induce T-cell IFNγ production. Changes in DC characteristics were most notable when 'pathological' frequencies of >50% CD14+HLA-DR- cells were present in the starting culture. The impaired DC quality could not be explained by altered cytokine production or increased oxidative stress in the cultures. Tracking of HLA-DR- cells throughout the culture period revealed that the observed changes were partially due to the impaired maturation and functionality of the originally HLA-DR- population, but also to their negative effects on HLA-DR+ cells. In conclusion, MDSC could be induced to differentiate into DC but, due to the impairment of overall DC vaccine quality when >50% HLA-DR- cells were present in the starting culture, their removal could be advisable.

  9. No evidence that genetic variation in the myeloid-derived suppressor cell pathway influences ovarian cancer survival

    DEFF Research Database (Denmark)

    Sucheston-Campbell, Lara E; Cannioto, Rikki; Clay, Alyssa I;

    2016-01-01

    BACKGROUND: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immune suppressive/pro-tumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be one prominent mechanism contributing to immunologic...

  10. Circulating myeloid-derived suppressor cells in patients with pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Xiao-Dong Xu; Jun Hu; Min Wang; Feng Peng; Rui Tian; Xing-Jun Guo; Yu Xie; Ren-Yi Qin

    2016-01-01

    BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopula-tions are increased in patients with pancreatic cancer. The present study was to investigate a specific subset of MDSCs in patients with pancreatic cancer and the mechanism of MDSCs increase in these patients. METHODS: Myeloid cells from whole blood were collected from 37 patients with pancreatic cancer, 17 with cholangiocarcinoma, and 47 healthy controls. Four pancreatic cancer cell lines were co-culturedwithnormalperipheralbloodmononuclearcells(PBMCs) to test the effect of tumor cells on the conversion of PBMCs to MDSCs. Levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and arginase activity in the plasma of cancer patients were analyzed by enzyme-linked immunosorbent assay. RESULTS: CD14+/CD11b+/HLA-DR- MDSCs were increased in patients with pancreatic or bile duct cancer compared with those in healthy controls, and this increase was correlated with clinical cancer stage. Pancreatic cancer cell lines induced PBMCs to MDSCs in a dose-dependent manner. GM-CSF and arginase activity levels were significantly increased in the se-rum of patients with pancreatic cancer. CONCLUSIONS: MDSCsweretumorrelated:tumorcellsinduced PBMCs to MDSCs in a dose-dependent manner and circulating CD14+/CD11b+/HLA-DR- MDSCs in pancreatic cancer patients were positively correlated with tumor burden. MDSCs might be useful markers for pancreatic cancer detection and progression.

  11. Clinical Perspectives on Targeting of Myeloid Derived Suppressor Cells in the Treatment of Cancer

    Directory of Open Access Journals (Sweden)

    Yana George Najjar

    2013-03-01

    Full Text Available Tumors escape immune recognition by several mechanisms, and induction of myeloid derived suppressor cells (MDSC is thought to play a major role in tumor mediated immune evasion. MDSC arise from myeloid progenitor cells that do not differentiate into mature dendritic cells, granulocytes or macrophages, and are characterized by the ability to suppress T cell and natural killer (NK cell function. They are increased in patients with cancer including renal cell carcinoma (RCC, and their levels have been shown to correlate with prognosis and overall survival. Multiple methods of inhibiting MDSCs are currently under investigation. These can broadly be categorized into methods that a promote differentiation of MDSC into mature, non-suppressive cells (all trans retinoic acid, vitamin D, b decrease MDSC levels (sunitinib, gemcitabine, 5-FU, CDDO-Me, or c functionally inhibit MDSC (PDE-5 inhibitors, COX-2 inhibitors. Recently, several pre-clinical tumor models of combination therapy involving sunitinib plus vaccines and/or adoptive therapy have shown promise in MDSC inhibition and improved outcomes in the tumor bearing host. Current clinical trials are underway in RCC patients to assess not only the impact on clinical outcome, but how this combination can enhance anti-tumor immunity and reduce immune suppression. Decreasing immune suppression by MDSC in the cancer host may improve outcomes and prolong survival in this patient population.

  12. Exosomes released by granulocytic myeloid-derived suppressor cells attenuate DSS-induced colitis in mice.

    Science.gov (United States)

    Wang, Yungang; Tian, Jie; Tang, Xinyi; Rui, Ke; Tian, Xinyu; Ma, Jie; Ma, Bin; Xu, Huaxi; Lu, Liwei; Wang, Shengjun

    2016-03-29

    Myeloid-derived suppressor cells (MDSC) have been described in inflammatory bowel disease (IBD), but their role in the disease remains controversial. We sought to define the effect of granulocytic MDSC-derived exosomes (G-MDSC exo) in dextran sulphate sodium (DSS)-induced murine colitis. G-MDSC exo-treated mice showed greater resistance to colitis, as reflected by lower disease activity index, decreased inflammatory cell infiltration damage. There was a decrease in the proportion of Th1 cells and an increase in the proportion of regulatory T cells (Tregs) in mesenteric lymph nodes (MLNs) from G-MDSC exo-treated colitis mice. Moreover, lower serum levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α were detected in G-MDSC exo-treated colitis mice. Interestingly, inhibition of arginase (Arg)-1 activity in G-MDSC exo partially abrogated the spontaneous improvement of colitis. In addition, G-MDSC exo could suppress CD4+ T cell proliferation and IFN-γ secretion in vitro and inhibit the delayed-type hypersensitivity (DTH) response, and these abilities were associated with Arg-1 activity. Moreover, G-MDSC exo promoted the expansion of Tregs in vitro. Taken together, these results suggest that G-MDSC exo attenuate DSS-induced colitis through inhibiting Th1 cells proliferation and promoting Tregs expansion.

  13. Myeloid-derived suppressor cells are elevated in patients with psoriasis and produce various molecules

    Science.gov (United States)

    Ilkovitch, Dan; Ferris, Laura K.

    2016-01-01

    Psoriasis is a debilitating chronic inflammatory disease. In addition to the characteristic effects on the skin, chronic inflammation associated with the disease is recognized to contribute to cardiovascular, hepatic and renal comorbidities. Immature myeloid regulatory cells, known as myeloid-derived suppressor cells (MDSCs), have been demonstrated to accumulate in various diseases and chronic inflammatory states, including inflammatory bowel disease and various types of cancer. The results of the present study, obtained using flow cytometry and cell culture analysis of peripheral blood mononuclear cells from psoriasis and healthy patients, revealed that MDSC levels are significantly increased in the blood of patients with psoriasis compared with healthy controls. Furthermore, these cells are capable of producing various molecules, including matrix metalloproteinase-9 and-1, interleukin-8, growth-related oncogene, and monocyte chemoattractant protein 1. These molecules may recruit additional immune cells involved in the pathogenesis of the disease, and contribute to the chronic inflammatory state in these patients. Therefore, MDSCs, which have various immune regulatory functions, may contribute to the pathogenesis of psoriasis as a systemic inflammatory disease. PMID:27574042

  14. Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells

    Science.gov (United States)

    Pallett, Laura J.; Gill, Upkar S.; Quaglia, Alberto; Sinclair, Linda V.; Jover-Cobos, Maria; Schurich, Anna; Singh, Kasha P.; Thomas, Niclas; Das, Abhishek; Chen, Antony; Fusai, Giuseppe; Bertoletti, Antonio; Cantrell, Doreen A.; Kennedy, Patrick T.; Davies, Nathan A.; Haniffa, Muzlifah; Maini, Mala K.

    2015-01-01

    Infection with hepatitis B virus (HBV) results in disparate degrees of tissue injury: it can replicate without pathological consequences or trigger immune-mediated necroinflammatory liver damage. We investigated the potential for myeloid-derived suppressor cells (MDSC) to suppress T cell-mediated immunopathology in this setting. Granulocytic MDSC (gMDSC) expanded transiently in acute resolving HBV, decreasing before peak hepatic injury. In persistent infection, arginase-expressing gMDSC (and circulating arginase) increased most in phases characterized by HBV replication without immunopathology, whilst L-arginine decreased. gMDSC expressed liver-homing chemokine receptors and accumulated in the liver, their expansion being supported by hepatic stellate cells. We provide in vitro and ex vivo evidence that gMDSC potently inhibited T cells in a partially arginase-dependent manner. L-arginine-deprived T cells upregulated system-L amino acid transporters to increase uptake of essential nutrients and attempt metabolic reprogramming. These data demonstrate the capacity of expanded arginase-expressing gMDSC to regulate liver immunopathology in HBV infection. PMID:25962123

  15. Gene expression profiling of human fibrocytic myeloid-derived suppressor cells (f-MDSCs

    Directory of Open Access Journals (Sweden)

    Emilia Maria Cristina Mazza

    2014-12-01

    Full Text Available Myeloid-derived suppressor cells (MDSCs have been shown to control self-reactive and anti-graft effector T-cells in autoimmunity and transplantation, but their therapeutic use is limited by their scarce availability in the peripheral blood of tumor-free donors. We isolated and characterized a novel population of myeloid suppressor cells, named fibrocytic MDSC (f-MDSC, which are differentiated from umbilical cord blood (UCB precursors (Zoso et al., 2014. This MDSC subset promotes regulatory T-cell expansion and induces normoglycemia in a xenogeneic model of type 1 diabetes. Here we describe in details the experimental design and the bioinformatics analyses of the gene expression dataset used to investigate the molecular mechanisms at the base of MDSC tolerogenic and suppressive properties. We also provide an R code to easily access the data and perform the quality controls and basic analyses relevant to this dataset. Raw and pre-processed data are available at Gene Expression Omnibus under accession GSE52376.

  16. Curdlan blocks the immune suppression by myeloid-derived suppressor cells and reduces tumor burden.

    Science.gov (United States)

    Rui, Ke; Tian, Jie; Tang, Xinyi; Ma, Jie; Xu, Ping; Tian, Xinyu; Wang, Yungang; Xu, Huaxi; Lu, Liwei; Wang, Shengjun

    2016-08-01

    Tumor-elicited immunosuppression is one of the essential mechanisms for tumor evasion of immune surveillance. It is widely thought to be one of the main reasons for the failure of tumor immunotherapy. Myeloid-derived suppressor cells (MDSCs) comprise a heterogeneous population of cells that play an important role in tumor-induced immunosuppression. These cells expand in tumor-bearing individuals and suppress T cell responses via various mechanisms. Curdlan, the linear (1 → 3)-β-glucan from Agrobacterium, has been applied in the food industry and other sectors. The anti-tumor property of curdlan has been recognized for a long time although the underlying mechanism still needs to be explored. In this study, we investigated the effect of curdlan on MDSCs and found that curdlan could promote MDSCs to differentiate into a more mature state and then significantly reduce the suppressive function of MDSCs, decrease the MDSCs in vivo and down-regulate the suppression in tumor-bearing mice, thus leading to enhanced anti-tumor immune responses. We, therefore, increase the understanding of further mechanisms by which curdlan achieves anti-tumor effects. PMID:26832917

  17. CCL2 Promotes Colorectal Carcinogenesis by Enhancing Polymorphonuclear Myeloid-Derived Suppressor Cell Population and Function

    Directory of Open Access Journals (Sweden)

    Eunyoung Chun

    2015-07-01

    Full Text Available Our study reveals a non-canonical role for CCL2 in modulating non-macrophage, myeloid-derived suppressor cells (MDSCs and shaping a tumor-permissive microenvironment during colon cancer development. We found that intratumoral CCL2 levels increased in patients with colitis-associated colorectal cancer (CRC, adenocarcinomas, and adenomas. Deletion of CCL2 blocked progression from dysplasia to adenocarcinoma and reduced the number of colonic MDSCs in a spontaneous mouse model of colitis-associated CRC. In a transplantable mouse model of adenocarcinoma and an APC-driven adenoma model, CCL2 fostered MDSC accumulation in evolving colonic tumors and enhanced polymorphonuclear (PMN-MDSC immunosuppressive features. Mechanistically, CCL2 regulated T cell suppression of PMN-MDSCs in a STAT3-mediated manner. Furthermore, CCL2 neutralization decreased tumor numbers and MDSC accumulation and function. Collectively, our experiments support that perturbing CCL2 and targeting MDSCs may afford therapeutic opportunities for colon cancer interception and prevention.

  18. Pathogenic Fungi Regulate Immunity by Inducing Neutrophilic Myeloid-Derived Suppressor Cells

    Science.gov (United States)

    Rieber, Nikolaus; Singh, Anurag; Öz, Hasan; Carevic, Melanie; Bouzani, Maria; Amich, Jorge; Ost, Michael; Ye, Zhiyong; Ballbach, Marlene; Schäfer, Iris; Mezger, Markus; Klimosch, Sascha N.; Weber, Alexander N.R.; Handgretinger, Rupert; Krappmann, Sven; Liese, Johannes; Engeholm, Maik; Schüle, Rebecca; Salih, Helmut Rainer; Marodi, Laszlo; Speckmann, Carsten; Grimbacher, Bodo; Ruland, Jürgen; Brown, Gordon D.; Beilhack, Andreas; Loeffler, Juergen; Hartl, Dominik

    2015-01-01

    Summary Despite continuous contact with fungi, immunocompetent individuals rarely develop pro-inflammatory antifungal immune responses. The underlying tolerogenic mechanisms are incompletely understood. Using both mouse models and human patients, we show that infection with the human pathogenic fungi Aspergillus fumigatus and Candida albicans induces a distinct subset of neutrophilic myeloid-derived suppressor cells (MDSCs), which functionally suppress T and NK cell responses. Mechanistically, pathogenic fungi induce neutrophilic MDSCs through the pattern recognition receptor Dectin-1 and its downstream adaptor protein CARD9. Fungal MDSC induction is further dependent on pathways downstream of Dectin-1 signaling, notably reactive oxygen species (ROS) generation as well as caspase-8 activity and interleukin-1 (IL-1) production. Additionally, exogenous IL-1β induces MDSCs to comparable levels observed during C. albicans infection. Adoptive transfer and survival experiments show that MDSCs are protective during invasive C. albicans infection, but not A. fumigatus infection. These studies define an innate immune mechanism by which pathogenic fungi regulate host defense. PMID:25771792

  19. Pathogenic fungi regulate immunity by inducing neutrophilic myeloid-derived suppressor cells.

    Science.gov (United States)

    Rieber, Nikolaus; Singh, Anurag; Öz, Hasan; Carevic, Melanie; Bouzani, Maria; Amich, Jorge; Ost, Michael; Ye, Zhiyong; Ballbach, Marlene; Schäfer, Iris; Mezger, Markus; Klimosch, Sascha N; Weber, Alexander N R; Handgretinger, Rupert; Krappmann, Sven; Liese, Johannes; Engeholm, Maik; Schüle, Rebecca; Salih, Helmut Rainer; Marodi, Laszlo; Speckmann, Carsten; Grimbacher, Bodo; Ruland, Jürgen; Brown, Gordon D; Beilhack, Andreas; Loeffler, Juergen; Hartl, Dominik

    2015-04-01

    Despite continuous contact with fungi, immunocompetent individuals rarely develop pro-inflammatory antifungal immune responses. The underlying tolerogenic mechanisms are incompletely understood. Using both mouse models and human patients, we show that infection with the human pathogenic fungi Aspergillus fumigatus and Candida albicans induces a distinct subset of neutrophilic myeloid-derived suppressor cells (MDSCs), which functionally suppress T and NK cell responses. Mechanistically, pathogenic fungi induce neutrophilic MDSCs through the pattern recognition receptor Dectin-1 and its downstream adaptor protein CARD9. Fungal MDSC induction is further dependent on pathways downstream of Dectin-1 signaling, notably reactive oxygen species (ROS) generation as well as caspase-8 activity and interleukin-1 (IL-1) production. Additionally, exogenous IL-1β induces MDSCs to comparable levels observed during C. albicans infection. Adoptive transfer and survival experiments show that MDSCs are protective during invasive C. albicans infection, but not A. fumigatus infection. These studies define an innate immune mechanism by which pathogenic fungi regulate host defense. PMID:25771792

  20. miR-34a expands myeloid-derived suppressor cells via apoptosis inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Anfei, E-mail: huang_anfei@163.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Zhang, Haitao, E-mail: zhanghtjp@126.com [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215021, Jiangsu Province (China); Chen, Si, E-mail: chensisdyxb@126.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Xia, Fei, E-mail: xiafei87@gmail.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Yang, Yi, E-mail: 602744364@qq.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Dong, Fulu, E-mail: adiok0903@126.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Sun, Di, E-mail: dongfl@suda.edu.cn [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Xiong, Sidong, E-mail: sdxiong@suda.edu.cn [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Zhang, Jinping, E-mail: j_pzhang@suda.edu.cn [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China)

    2014-08-15

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population and show significant expansion under pathological conditions. microRNA plays important roles in many biological processes, whether microRNAs have a function in the expansion of MDSCs is still not very clear. In this study, miR-34a overexpression can induce the expansion of MDSCs in bone marrow chimera and transgenic mice model. The experimental results suggest that miR-34a inhibited the apoptosis of MDSCs but did not affect the proliferation of MDSCs. The distinct mRNA microarray profiles of MDSCs of wild type and miR-34a over-expressing MDSCs combined with the target prediction of miR-34a suggest that miR-34a may target genes such as p2rx7, Tia1, and plekhf1 to inhibit the apoptosis of MDSCs. Taken together, miR-34a contributes to the expansion of MDSCs by inhibiting the apoptosis of MDSCs. - Highlights: • Over-expression of miR-34a increases the number of MDSCs. • miR-34a inhibits the apoptosis of MDSCs, but does not affects their proliferation. • miR-34a may inhibit the apoptosis of MDSCs via targeting the p2rx7, Tia1 and plekhf1.

  1. Novel role for tumor-induced expansion of myeloid-derived cells in cancer cachexia.

    Science.gov (United States)

    Cuenca, Alex G; Cuenca, Angela L; Winfield, Robert D; Joiner, Dallas N; Gentile, Lori; Delano, Matthew J; Kelly-Scumpia, Kindra M; Scumpia, Philip O; Matheny, Michael K; Scarpace, Philip J; Vila, Lizette; Efron, Philip A; LaFace, Drake M; Moldawer, Lyle L

    2014-06-15

    Cancer progression is associated with inflammation, increased metabolic demand, infection, cachexia, and eventually death. Myeloid-derived suppressor cells (MDSCs) commonly expand during cancer and are associated with adaptive immune suppression and inflammatory metabolite production. We propose that cancer-induced cachexia is driven at least in part by the expansion of MDSCs. MDSC expansion in 4T1 mammary carcinoma-bearing hosts is associated with induction of a hepatic acute-phase protein response and altered host energy and fat metabolism, and eventually reduced survival to polymicrobial sepsis and endotoxemia. Similar results are also seen in mice bearing a Lewis lung carcinoma and a C26 colon adenocarcinoma. However, a similar cachexia response is not seen with equivalent growth of the 66C4 subclone of 4T1, in which MDSC expansion does not occur. Importantly, reducing MDSC numbers in 4T1-bearing animals can ameliorate some of these late responses and reduce susceptibility to inflammation-induced organ injury and death. In addition, administering MDSCs from both tumor- and nontumor-bearing mice can produce an acute-phase response. Thus, we propose a previously undescribed mechanism for the development of cancer cachexia, whereby progressive MDSC expansion contributes to changes in host protein and energy metabolism and reduced resistance to infection.

  2. miR-34a expands myeloid-derived suppressor cells via apoptosis inhibition

    International Nuclear Information System (INIS)

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population and show significant expansion under pathological conditions. microRNA plays important roles in many biological processes, whether microRNAs have a function in the expansion of MDSCs is still not very clear. In this study, miR-34a overexpression can induce the expansion of MDSCs in bone marrow chimera and transgenic mice model. The experimental results suggest that miR-34a inhibited the apoptosis of MDSCs but did not affect the proliferation of MDSCs. The distinct mRNA microarray profiles of MDSCs of wild type and miR-34a over-expressing MDSCs combined with the target prediction of miR-34a suggest that miR-34a may target genes such as p2rx7, Tia1, and plekhf1 to inhibit the apoptosis of MDSCs. Taken together, miR-34a contributes to the expansion of MDSCs by inhibiting the apoptosis of MDSCs. - Highlights: • Over-expression of miR-34a increases the number of MDSCs. • miR-34a inhibits the apoptosis of MDSCs, but does not affects their proliferation. • miR-34a may inhibit the apoptosis of MDSCs via targeting the p2rx7, Tia1 and plekhf1

  3. Emerging roles of myeloid derived suppressor cells in hepatic inflammation and fibrosis

    Institute of Scientific and Technical Information of China (English)

    Linda; Hammerich; Frank; Tacke

    2015-01-01

    Myeloid derived suppressor cells(MDSC) are a heterogeneous population of immune cells that are potent suppressors of immune responses. MDSC emerge in various compartments in the body, such as blood, bonemarrow or spleen, especially in conditions of cancer, infections or inflammation. MDSC usually express CD11 b, CD33, and low levels of human leukocyte antigen-DR in humans or CD11 b and Gr1(Ly6C/G) in mice, and they can be further divided into granulocytic or monocytic MDSC. The liver is an important organ for MDSC induction and accumulation in hepatic as well as extrahepatic diseases. Different hepatic cells, especially hepatic stellate cells, as well as liver-derived soluble factors, including hepatocyte growth factor and acute phase proteins(SAA, KC), can promote the differentiation of MDSC from myeloid cells. Importantly, hepatic myeloid cells like neutrophils, monocytes and macrophages fulfill essential roles in acute and chronic liver diseases. Recent data from patients with liver diseases and animal models linked MDSC to the pathogenesis of hepatic inflammation, fibrosis and hepatocellular carcinoma(HCC). In settings of acute hepatitis, MDSC can limit immunogenic T cell responses and subsequent tissue injury. In patients with chronic hepatitis C, MDSC increase and may favor viral persistence. Animal models of chronic liver injury, however, have not yet conclusively clarified the involvement of MDSC for hepatic fibrosis. In human HCC and mouse models of liver cancer, MDSC are induced in the tumor environment and suppress anti-tumoral immune responses. Thus, the liver is a primary site of MDSC in vivo, and modulating MDSC functionality might represent a promising novel therapeutic target for liver diseases.

  4. Emerging roles of myeloid derived suppressor cells in hepatic inflammation and fibrosis.

    Science.gov (United States)

    Hammerich, Linda; Tacke, Frank

    2015-08-15

    Myeloid derived suppressor cells (MDSC) are a heterogeneous population of immune cells that are potent suppressors of immune responses. MDSC emerge in various compartments in the body, such as blood, bone marrow or spleen, especially in conditions of cancer, infections or inflammation. MDSC usually express CD11b, CD33, and low levels of human leukocyte antigen-DR in humans or CD11b and Gr1 (Ly6C/G) in mice, and they can be further divided into granulocytic or monocytic MDSC. The liver is an important organ for MDSC induction and accumulation in hepatic as well as extrahepatic diseases. Different hepatic cells, especially hepatic stellate cells, as well as liver-derived soluble factors, including hepatocyte growth factor and acute phase proteins (SAA, KC), can promote the differentiation of MDSC from myeloid cells. Importantly, hepatic myeloid cells like neutrophils, monocytes and macrophages fulfill essential roles in acute and chronic liver diseases. Recent data from patients with liver diseases and animal models linked MDSC to the pathogenesis of hepatic inflammation, fibrosis and hepatocellular carcinoma (HCC). In settings of acute hepatitis, MDSC can limit immunogenic T cell responses and subsequent tissue injury. In patients with chronic hepatitis C, MDSC increase and may favor viral persistence. Animal models of chronic liver injury, however, have not yet conclusively clarified the involvement of MDSC for hepatic fibrosis. In human HCC and mouse models of liver cancer, MDSC are induced in the tumor environment and suppress anti-tumoral immune responses. Thus, the liver is a primary site of MDSC in vivo, and modulating MDSC functionality might represent a promising novel therapeutic target for liver diseases. PMID:26301117

  5. Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Maruyama, Akira; Shime, Hiroaki, E-mail: shime@med.hokudai.ac.jp; Takeda, Yohei; Azuma, Masahiro; Matsumoto, Misako; Seya, Tsukasa, E-mail: seya-tu@pop.med.hokudai.ac.jp

    2015-02-13

    Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that exhibit potent immunosuppressive activity. They are increased in tumor-bearing hosts and contribute to tumor development. Toll-like receptors (TLRs) on MDSCs may modulate the tumor-supporting properties of MDSCs through pattern-recognition. Pam2 lipopeptides represented by Pam2CSK4 serve as a TLR2 agonist to exert anti-tumor function by dendritic cell (DC)-priming that leads to NK cell activation and cytotoxic T cell proliferation. On the other hand, TLR2 enhances tumor cell progression/invasion by activating tumor-infiltrating macrophages. How MDSCs respond to TLR2 agonists has not yet been determined. In this study, we found intravenous administration of Pam2CSK4 systemically up-regulated the frequency of MDSCs in EG7 tumor-bearing mice. The frequency of tumor-infiltrating MDSCs was accordingly increased in response to Pam2CSK4. MDSCs were not increased by Pam2CSK4 stimuli in TLR2 knockout (KO) mice. Adoptive transfer experiments using CFSE-labeled MDSCs revealed that the TLR2-positive MDSCs survived long in tumor-bearing mice in response to Pam2CSK4 treatment. Since the increased MDSC population sustained immune-suppressive properties, our study suggests that Pam2CSK4-triggered TLR2 activation enhances the MDSC potential and suppress antitumor immune response in tumor microenvironment. - Highlights: • Pam2CSK4 administration induces systemic accumulation of CD11b{sup +}Gr1{sup +} MDSCs. • TLR2 is essential for Pam2CSK4-induced accumulation of CD11b{sup +}Gr1{sup +} MDSCs. • Pam2CSK4 supports survival of CD11b{sup +}Gr1{sup +} MDSCs in vivo.

  6. Histone deacetylase 11: A novel epigenetic regulator of myeloid derived suppressor cell expansion and function.

    Science.gov (United States)

    Sahakian, Eva; Powers, John J; Chen, Jie; Deng, Susan L; Cheng, Fengdong; Distler, Allison; Woods, David M; Rock-Klotz, Jennifer; Sodre, Andressa L; Youn, Je-In; Woan, Karrune V; Villagra, Alejandro; Gabrilovich, Dmitry; Sotomayor, Eduardo M; Pinilla-Ibarz, Javier

    2015-02-01

    Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of cells capable of suppressing anti-tumor T cell function in the tumor microenvironment, represent an imposing obstacle in the development of cancer immunotherapeutics. Thus, identifying elements essential to the development and perpetuation of these cells will undoubtedly improve our ability to circumvent their suppressive impact. HDAC11 has emerged as a key regulator of IL-10 gene expression in myeloid cells, suggesting that this may represent an important targetable axis through which to dampen MDSC formation. Using a murine transgenic reporter model system where eGFP expression is controlled by the HDAC11 promoter (Tg-HDAC11-eGFP), we provide evidence that HDAC11 appears to function as a negative regulator of MDSC expansion/function in vivo. MDSCs isolated from EL4 tumor-bearing Tg-HDAC11-eGFP display high expression of eGFP, indicative of HDAC11 transcriptional activation at steady state. In striking contrast, immature myeloid cells in tumor-bearing mice display a diminished eGFP expression, implying that the transition of IMC to MDSC's require a decrease in the expression of HDAC11, where we postulate that it acts as a gate-keeper of myeloid differentiation. Indeed, tumor-bearing HDAC11-knockout mice (HDAC11-KO) demonstrate a more suppressive MDSC population as compared to wild-type (WT) tumor-bearing control. Notably, the HDAC11-KO tumor-bearing mice exhibit enhanced tumor growth kinetics when compare to the WT control mice. Thus, through a better understanding of this previously unknown role of HDAC11 in MDSC expansion and function, rational development of targeted epigenetic modifiers may allow us to thwart a powerful barrier to efficacious immunotherapies.

  7. Myeloid derived suppressor cells in multiple myeloma: preclinical research and translational opportunities

    Directory of Open Access Journals (Sweden)

    Cirino eBotta

    2014-12-01

    Full Text Available Immunosuppressive cells have been reported to play an important role in tumor progression mainly because of their capability to promote immune-escape, angiogenesis and metastasis. Among them, myeloid derived suppressor cells (MDSCs have been recently identified as immature myeloid cells, induced by tumor-associated inflammation, able to impair both innate and adaptive immunity. While murine MDSCs are usually identified by the expression of CD11b and Gr-1, human MDSCs represent a more heterogeneous population characterized by the expression of CD33 and CD11b, low or no HLA-DR and variable CD14 and CD15. In particular, the last two may alternatively identify monocyte-like or granulocyte-like MDSC subsets with different immunosuppressive properties. Recently, a substantial increase of MDSCs has been found in peripheral blood and bone marrow (BM of multiple myeloma (MM patients with a role in disease progression and/or drug resistance. Preclinical models recapitulating the complexity of the MM-related BM microenvironment (BMM are major tools for the study of the interactions between MM cells and cells of the BMM (including MDSCs and for the development of new agents targeting MM-associated immune suppressive cells.This review will focus on current strategies for human MDSCs generation and investigation of their immunosuppressive function in vitro and in vivo, taking into account the relevant relationship occurring within the MM-BMM. We will then provide trends in MDSC-associated research and suggest potential application for the treatment of MM.

  8. Histone deacetylase 11: A novel epigenetic regulator of myeloid derived suppressor cell expansion and function.

    Science.gov (United States)

    Sahakian, Eva; Powers, John J; Chen, Jie; Deng, Susan L; Cheng, Fengdong; Distler, Allison; Woods, David M; Rock-Klotz, Jennifer; Sodre, Andressa L; Youn, Je-In; Woan, Karrune V; Villagra, Alejandro; Gabrilovich, Dmitry; Sotomayor, Eduardo M; Pinilla-Ibarz, Javier

    2015-02-01

    Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of cells capable of suppressing anti-tumor T cell function in the tumor microenvironment, represent an imposing obstacle in the development of cancer immunotherapeutics. Thus, identifying elements essential to the development and perpetuation of these cells will undoubtedly improve our ability to circumvent their suppressive impact. HDAC11 has emerged as a key regulator of IL-10 gene expression in myeloid cells, suggesting that this may represent an important targetable axis through which to dampen MDSC formation. Using a murine transgenic reporter model system where eGFP expression is controlled by the HDAC11 promoter (Tg-HDAC11-eGFP), we provide evidence that HDAC11 appears to function as a negative regulator of MDSC expansion/function in vivo. MDSCs isolated from EL4 tumor-bearing Tg-HDAC11-eGFP display high expression of eGFP, indicative of HDAC11 transcriptional activation at steady state. In striking contrast, immature myeloid cells in tumor-bearing mice display a diminished eGFP expression, implying that the transition of IMC to MDSC's require a decrease in the expression of HDAC11, where we postulate that it acts as a gate-keeper of myeloid differentiation. Indeed, tumor-bearing HDAC11-knockout mice (HDAC11-KO) demonstrate a more suppressive MDSC population as compared to wild-type (WT) tumor-bearing control. Notably, the HDAC11-KO tumor-bearing mice exhibit enhanced tumor growth kinetics when compare to the WT control mice. Thus, through a better understanding of this previously unknown role of HDAC11 in MDSC expansion and function, rational development of targeted epigenetic modifiers may allow us to thwart a powerful barrier to efficacious immunotherapies. PMID:25155994

  9. Therapeutic targeting of myeloid-derived suppressor cells involves a novel mechanism mediated by clusterin.

    Science.gov (United States)

    Zhou, Junmin; Donatelli, Sarah S; Gilvary, Danielle L; Tejera, Melba M; Eksioglu, Erika A; Chen, Xianghong; Coppola, Domenico; Wei, Sheng; Djeu, Julie Y

    2016-01-01

    Myeloid-derived suppressor cells (MDSCs) constitute a key checkpoint that impedes tumor immunity against cancer. Chemotherapeutic intervention of MDSCs has gained ground as a strategy for cancer therapy but its mechanism remains obscure.We report here a unique mechanism by which monocytic (M)-MDSCs are spared, allowing them to polarize towards M1 macrophages for reactivation of immunity against breast cancer. We first demonstrated that curcumin, like docetaxel (DTX), can selectively target CD11b(+)Ly6G(+)Ly6C(low) granulocytic (G)-MDSCs, sparing CD11b(+)Ly6G(-)Ly6C(high) M-MDSCs, with reduced tumor burden in 4T1-Neu tumor-bearing mice. Curcumin treatment polarized surviving M-MDSCs toward CCR7(+) Dectin-1(-)M1 cells, accompanied by IFN-γ production and cytolytic function in T cells. Selective M-MDSC chemoresistence to curcumin and DTX was mediated by secretory/cytoplasmic clusterin (sCLU). sCLU functions by trapping Bax from mitochondrial translocation, preventing the apoptotic cascade. Importantly, sCLU was only found in M-MDSCs but not in G-MDSCs. Knockdown of sCLU in M-MDSCs and RAW264.7 macrophages was found to reverse their natural chemoresistance. Clinically, breast cancer patients possess sCLU expression only in mature CD68(+) macrophages but not in immature CD33(+) immunosuppressive myeloid cells infiltrating the tumors. We thus made the seminal discovery that sCLU expression in M-MDSCs accounts for positive immunomodulation by chemotherapeutic agents. PMID:27405665

  10. Therapeutic targeting of myeloid-derived suppressor cells involves a novel mechanism mediated by clusterin

    Science.gov (United States)

    Zhou, Junmin; Donatelli, Sarah S.; Gilvary, Danielle L.; Tejera, Melba M.; Eksioglu, Erika A.; Chen, Xianghong; Coppola, Domenico; Wei, Sheng; Djeu, Julie Y.

    2016-01-01

    Myeloid-derived suppressor cells (MDSCs) constitute a key checkpoint that impedes tumor immunity against cancer. Chemotherapeutic intervention of MDSCs has gained ground as a strategy for cancer therapy but its mechanism remains obscure.We report here a unique mechanism by which monocytic (M)-MDSCs are spared, allowing them to polarize towards M1 macrophages for reactivation of immunity against breast cancer. We first demonstrated that curcumin, like docetaxel (DTX), can selectively target CD11b+Ly6G+Ly6Clow granulocytic (G)-MDSCs, sparing CD11b+Ly6G−Ly6Chigh M-MDSCs, with reduced tumor burden in 4T1-Neu tumor-bearing mice. Curcumin treatment polarized surviving M-MDSCs toward CCR7+ Dectin-1−M1 cells, accompanied by IFN-γ production and cytolytic function in T cells. Selective M-MDSC chemoresistence to curcumin and DTX was mediated by secretory/cytoplasmic clusterin (sCLU). sCLU functions by trapping Bax from mitochondrial translocation, preventing the apoptotic cascade. Importantly, sCLU was only found in M-MDSCs but not in G-MDSCs. Knockdown of sCLU in M-MDSCs and RAW264.7 macrophages was found to reverse their natural chemoresistance. Clinically, breast cancer patients possess sCLU expression only in mature CD68+ macrophages but not in immature CD33+ immunosuppressive myeloid cells infiltrating the tumors. We thus made the seminal discovery that sCLU expression in M-MDSCs accounts for positive immunomodulation by chemotherapeutic agents. PMID:27405665

  11. Myeloid-derived suppressor cells as intruders and targets: clinical implications in cancer therapy.

    Science.gov (United States)

    Baniyash, Michal

    2016-07-01

    Chronic inflammation, typical of various diseases including cancer, is a "silent bomb within the body," leading to complications that are only evident in most cases upon their appearance, when disease is already deteriorated. Chronic inflammation is associated with accumulation of myeloid-derived suppressor cells (MDSCs), which lead to immunosuppression. MDSCs have numerous harmful effects as they support tumor initiation, tumor growth and spreading, which in turn, perpetuate the inflammatory and suppressive conditions, thus preventing anticancer responses. As the concept of the immune system combating many types of tumors was revived in recent years, immunotherapy has dramatically changed the view of cancer treatment, and numerous novel therapies have been developed and approved by the FDA. However, cumulative clinical data point at very limited success rates. It is most likely that the developing chronic inflammation and MDSC-induced immunosuppression interfere with responses to such treatments and hence are major obstacles in achieving higher response rates to immune-based therapies. Moreover, chemotherapies were shown to have adverse immunoregulatory effects, enhancing or decreasing MDSC levels and activity, thus affecting treatment success. Therefore, therapeutic manipulations of chronic inflammation and MDSCs during cancer development are likely to enhance efficacy of immune- and chemo-based treatments, switching chronic pro-cancer inflammatory environments to an anticancerous milieu. Based on the functional relevance of immune networking in tumors, it is critical to merge monitoring immune system biomarkers into the traditional patient's categorization and treatment regimens. This will provide new tools for clinical practice, allowing appropriate management of cancer patients toward a better-personalized medicine. PMID:27225641

  12. Identification of myeloid derived suppressor cells in the peripheral blood of tumor bearing dogs

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    Sherger Matthew

    2012-10-01

    Full Text Available Abstract Background Myeloid derived suppressor cells (MDSCs are a recently described population of immune cells that significantly contribute to the immunosuppression seen in cancer patients. MDSCs are one of the most important factors that limit the efficacy of cancer immunotherapy (e.g. cancer vaccines and MDSC levels are increased in cancer in multiple species. Identifying and targeting MDSCs is actively being investigated in the field of human oncology and is increasingly being investigated in veterinary oncology. The treatment of canine cancer not only benefits dogs, but is being used for translational studies evaluating and modifcying candidate therapies for use in humans. Thus, it is necessary to understand the immune alterations seen in canine cancer patients which, to date, have been relatively limited. This study investigates the use of commercially available canine antibodies to detect an immunosuppressive (CD11blow/CADO48low cell population that is increased in the peripheral blood of tumor-bearing dogs. Results Commercially available canine antibodies CD11b and CADO48A were used to evaluate white blood cells from the peripheral blood cells of forty healthy control dogs and forty untreated, tumor-bearing dogs. Tumor-bearing dogs had a statistically significant increase in CD11blow/CADO48Alow cells (7.9% as compared to the control dogs (3.6%. Additionally, sorted CD11blow/CADO48Alow generated in vitro suppressed the proliferation of canine lymphocytes. Conclusions The purpose of this study was aimed at identifying potential canine specific markers for identifying MDSCs in the peripheral blood circulation of dogs. This study demonstrates an increase in a unique CD11blow/CADO48Alow cell population in tumor-bearing dogs. This immunophenotype is consistent with described phenotypes of MDSCs in other species (i.e. mice and utilizes commercially available canine-specific antibodies. Importantly, CD11blow/CADO48Alow from a tumor environment

  13. Targeting myeloid-derived suppressor cells augments antitumor activity against lung cancer

    Directory of Open Access Journals (Sweden)

    Srivastava MK

    2012-10-01

    Full Text Available Minu K Srivastava,1,2 Li Zhu,1,2 Marni Harris-White,2 Min Huang,1–3 Maie St John,1,3 Jay M Lee,1,3 Ravi Salgia,4 Robert B Cameron,1,3,5 Robert Strieter,6 Steven Dubinett,1–3 Sherven Sharma1–31Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA, Los Angeles, CA, 2Molecular Gene Medicine Laboratory, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, 3Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, 4Department of Medicine, University of Chicago, Chicago, IL, 5Department of Surgery, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, 6Department of Medicine, University of Virginia, Charlottesville, VA, USAAbstract: Lung cancer evades host immune surveillance by dysregulating inflammation. Tumors and their surrounding stromata produce growth factors, cytokines, and chemokines that recruit, expand, and/or activate myeloid-derived suppressor cells (MDSCs. MDSCs regulate immune responses and are frequently found in malignancy. In this review the authors discuss tumor-MDSC interactions that suppress host antitumor activities and the authors' recent findings regarding MDSC depletion that led to improved therapeutic vaccination responses against lung cancer. Despite the identification of a repertoire of tumor antigens, hurdles persist for immune-based anticancer therapies. It is likely that combined therapies that address the multiple immune deficits in cancer patients will be required for effective therapy. MDSCs play a major role in the suppression of T-cell activation and they sustain tumor growth, proliferation, and metastases. Regulation of MDSC recruitment, differentiation or expansion, and inhibition of the MDSC suppressive function with pharmacologic agents will be useful in the control of cancer growth and progression. Pharmacologic agents that regulate MDSCs may be more effective when combined with

  14. T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid-derived suppressor cells.

    Science.gov (United States)

    Azzaoui, Imane; Uhel, Fabrice; Rossille, Delphine; Pangault, Celine; Dulong, Joelle; Le Priol, Jerome; Lamy, Thierry; Houot, Roch; Le Gouill, Steven; Cartron, Guillaume; Godmer, Pascal; Bouabdallah, Krimo; Milpied, Noel; Damaj, Gandhi; Tarte, Karin; Fest, Thierry; Roussel, Mikael

    2016-08-25

    In diffuse large B-cell lymphoma (DLBCL), the number of circulating monocytes and neutrophils represents an independent prognostic factor. These cell subsets include monocytic and granulocytic myeloid-derived suppressor cells (M- and G-MDSCs) defined by their ability to suppress T-cell responses. MDSCs are a heterogeneous population described in inflammatory and infectious diseases and in numerous tumors including multiple myeloma, chronic lymphocytic leukemia, and DLBCL. However, their mechanisms of action remain unclear. We broadly assessed the presence and mechanisms of suppression of MDSC subsets in DLBCL. First, a myeloid suppressive signature was identified by gene expression profiling in DLBCL peripheral blood. Accordingly, we identified, in a cohort of 66 DLBCL patients, an increase in circulating G-MDSC (Lin(neg)HLA-DR(neg)CD33(pos)CD11b(pos)) and M-MDSC (CD14(pos)HLA-DR(low)) counts. Interestingly, only M-MDSC number was correlated with the International Prognostic Index, event-free survival, and number of circulating Tregs. Furthermore, T-cell proliferation was restored after monocyte depletion. Myeloid-dependent T-cell suppression was attributed to a release of interleukin-10 and S100A12 and increased PD-L1 expression. In summary, we identified expanded MDSC subsets in DLBCL, as well as new mechanisms of immunosuppression in DLBCL. PMID:27338100

  15. Activated hepatic stellate cells promote liver cancer by induction of myeloid-derived suppressor cells through cyclooxygenase-2

    Science.gov (United States)

    Xu, Jianfeng; Li, Jie; Hong, Zaifa; Yin, Zhenyu; Wang, Xiaomin

    2016-01-01

    Hepatic stellate cells (HSCs) are critical mediators of immunosuppression and the pathogenesis of hepatocellular carcinoma (HCC). Our previous work indicates that HSCs promote HCC progression by enhancing immunosuppressive cell populations including myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). MDSCs are induced by inflammatory cytokines (e.g., prostaglandins) and are important in immune suppression. However, how HSCs mediate expansion of MDSCs is uncertain. Thus, we studied activated HSCs that could induce MDSCs from bone marrow cells and noted that HSC-induced MDSCs up-regulated immunosuppressive activity via iNOS, Arg-1, and IL-4Rα. After treating cells with a COX-2 inhibitor or an EP4 antagonist, we established that HSC-induced MDSC accumulation was mediated by the COX2-PGE2-EP4 signaling. Furthermore, in vivo animal studies confirmed that inhibition of HSC-derived PGE2 could inhibit HSC-induced MDSC accumulation and HCC growth. Thus, our data show that HSCs are required for MDSC accumulation mediated by the COX2-PGE2-EP4 pathway, and these data are the first to link HSC and MDSC subsets in HCC immune microenvironment and provide a rationale for targeting PGE2 signaling for HCC therapy. PMID:26758420

  16. Myeloid-Derived Suppressor Cells in Psoriasis Are an Expanded Population Exhibiting Diverse T-Cell-Suppressor Mechanisms.

    Science.gov (United States)

    Cao, Lauren Y; Chung, Jin-Sung; Teshima, Takahiro; Feigenbaum, Lawrence; Cruz, Ponciano D; Jacobe, Heidi T; Chong, Benjamin F; Ariizumi, Kiyoshi

    2016-09-01

    Psoriasis vulgaris is an inflammatory skin disease caused by hyperactivated T cells regulated by positive and negative mechanisms; although the former have been much studied, the latter have not. We studied the regulatory mechanism mediated by myeloid-derived suppressor cells (MDSCs) and showed that MDSCs expanded in melanoma patients express dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand, a critical mediator of T-cell suppressor function. We examined expansion of DC-HIL(+) MDSCs in psoriasis and characterized their functional properties. Frequency of DC-HIL(+) monocytic MDSCs (CD14(+)HLA-DR(no/low)) in blood and skin was markedly increased in psoriatic patients versus healthy control subjects, but there was no statistically significant relationship with disease severity (based on Psoriasis Area and Severity Index score). Blood DC-HIL(+) MDSC levels in untreated patients were significantly higher than in treated patients. Compared with melanoma-derived MDSCs, psoriatic MDSCs exhibited significantly reduced suppressor function and were less dependent on DC-HIL, but they were capable of inhibiting proliferation and IFN-γ and IL-17 responses of autologous T cells. Psoriatic MDSCs were functionally diverse among patients in their ability to suppress allogeneic T cells and in the use of either IL-17/arginase I or IFN-γ/inducible nitric oxide synthase axis as suppressor mechanisms. Thus, DC-HIL(+) MDSCs are expanded in psoriasis patients, and their mechanistic heterogeneity and relative functional deficiency may contribute to the development of psoriasis. PMID:27236103

  17. Cancer Stem Cell-Secreted Macrophage Migration Inhibitory Factor Stimulates Myeloid Derived Suppressor Cell Function and Facilitates Glioblastoma Immune Evasion.

    Science.gov (United States)

    Otvos, Balint; Silver, Daniel J; Mulkearns-Hubert, Erin E; Alvarado, Alvaro G; Turaga, Soumya M; Sorensen, Mia D; Rayman, Patricia; Flavahan, William A; Hale, James S; Stoltz, Kevin; Sinyuk, Maksim; Wu, Qiulian; Jarrar, Awad; Kim, Sung-Hak; Fox, Paul L; Nakano, Ichiro; Rich, Jeremy N; Ransohoff, Richard M; Finke, James; Kristensen, Bjarne W; Vogelbaum, Michael A; Lathia, Justin D

    2016-08-01

    Shifting the balance away from tumor-mediated immune suppression toward tumor immune rejection is the conceptual foundation for a variety of immunotherapy efforts currently being tested. These efforts largely focus on activating antitumor immune responses but are confounded by multiple immune cell populations, including myeloid-derived suppressor cells (MDSCs), which serve to suppress immune system function. We have identified immune-suppressive MDSCs in the brains of GBM patients and found that they were in close proximity to self-renewing cancer stem cells (CSCs). MDSCs were selectively depleted using 5-flurouracil (5-FU) in a low-dose administration paradigm, which resulted in prolonged survival in a syngeneic mouse model of glioma. In coculture studies, patient-derived CSCs but not nonstem tumor cells selectively drove MDSC-mediated immune suppression. A cytokine screen revealed that CSCs secreted multiple factors that promoted this activity, including macrophage migration inhibitory factor (MIF), which was produced at high levels by CSCs. Addition of MIF increased production of the immune-suppressive enzyme arginase-1 in MDSCs in a CXCR2-dependent manner, whereas blocking MIF reduced arginase-1 production. Similarly to 5-FU, targeting tumor-derived MIF conferred a survival advantage to tumor-bearing animals and increased the cytotoxic T cell response within the tumor. Importantly, tumor cell proliferation, survival, and self-renewal were not impacted by MIF reduction, demonstrating that MIF is primarily an indirect promoter of GBM progression, working to suppress immune rejection by activating and protecting immune suppressive MDSCs within the GBM tumor microenvironment. Stem Cells 2016;34:2026-2039. PMID:27145382

  18. Myeloid-derived suppressor cells contribute to systemic lupus erythaematosus by regulating differentiation of Th17 cells and Tregs.

    Science.gov (United States)

    Ji, Jianjian; Xu, Jingjing; Zhao, Shuli; Liu, Fei; Qi, Jingjing; Song, Yuxian; Ren, Jing; Wang, Tingting; Dou, Huan; Hou, Yayi

    2016-08-01

    Although major advancements have made in investigating the aetiology of SLE (systemic lupus erythaematosus), the role of MDSCs (myeloid-derived suppressor cells) in SLE progression remains confused. Recently, some studies have revealed that MDSCs play an important role in lupus mice. However, the proportion and function of MDSCs in lupus mice and SLE patients are still poorly understood. In the present study, we investigated the proportion and function of MDSCs using different stages of MRL/lpr lupus mice and specimens from SLE patients with different activity. Results showed that splenic granulocytic (G-)MDSCs were significantly expanded by increasing the expression of CCR1 (CC chemokine receptor 1) in diseased MRL/lpr lupus mice and in high-disease-activity SLE patients. However, the proportion of monocytic (M-)MDSCs remains similar in MRL/lpr lupus mice and SLE patients. G-MDSCs produce high levels of ROS (reactive oxygen species) through increasing gp91(phox) expression, and activated TLR2 (Toll-like receptor 2) and AIM2 (absent in melanoma 2) inflammasome in M-MDSCs lead to IL-1β (interleukin 1β) expression in diseased MRL/lpr mice and high-disease-activity SLE patients. Previous study has revealed that MDSCs could alter the plasticity of Th17 (T helper 17) cells and Tregs (regulatory T-cells) via ROS and IL-1β. Co-culture experiments showed that G-MDSCs impaired Treg differentiation via ROS and M-MDSCs promoted Th17 cell polarization by IL-1β in vitro Furthermore, adoptive transfer or antibody depletion of MDSCs in MRL/lpr mice confirmed that MDSCs influenced the imbalance of Tregs and Th17 cells in vivo Our results indicate that MDSCs with the capacity to regulate Th17 cell/Treg balance may be a critical pathogenic factor in SLE. PMID:27231253

  19. Diminished immune response to vaccinations in obesity: role of myeloid-derived suppressor and other myeloid cells.

    Science.gov (United States)

    Chen, Shiyi; Akbar, Sheikh Mohammad Fazle; Miyake, Teruki; Abe, Masanori; Al-Mahtab, Mamun; Furukawa, Shinya; Bunzo, Matsuura; Hiasa, Yoichi; Onji, Morikazu

    2015-01-01

    Obesity is a chronic inflammatory condition associated with an increased production of cytokines and exacerbated immune response. However, obese subjects are susceptible to infections and respond poorly to vaccines. This study evaluated the immune responses of obese mice and the underlying mechanisms by exploring the roles of myeloid cells. Diet-induced obese (DIO) mice were prepared from C57BL/6J mice fed a high-calorie and high-fat diet for 12 weeks. Humoral and cellular immune responses of DIO mice to a hepatitis B vaccine containing the hepatitis B surface antigen (HBsAg) were assessed in sera and via a lymphoproliferative assay, respectively. The effects of CD11b(+)GR1(+) myeloid-derived suppressor cells (MDSC) and CD11b(+)GR1(-) non-MDSC on T cell proliferation and cytokine production were compared via a cell culture system. The production of cytokines, expression of activation and exhaustion markers, and proportions of apoptotic T cells were estimated with flow cytometry. Increased T and B lymphocyte proliferation and higher interferon-γ and tumor necrosis factor-α levels were detected in spleen cells and liver non-parenchymal cell cultures of DIO mice compared to controls (pproduction, decrease in T cell activation, and increase in T cell exhaustion and apoptosis (p<0.05). MDSC play an important role in mediating impaired antigen-specific immunity. PMID:25660173

  20. The bone marrow microenvironment enhances multiple myeloma progression by exosome-mediated activation of myeloid-derived suppressor cells.

    Science.gov (United States)

    Wang, Jinheng; De Veirman, Kim; De Beule, Nathan; Maes, Ken; De Bruyne, Elke; Van Valckenborgh, Els; Vanderkerken, Karin; Menu, Eline

    2015-12-22

    Exosomes, extracellular nanovesicles secreted by various cell types, modulate the bone marrow (BM) microenvironment by regulating angiogenesis, cytokine release, immune response, inflammation, and metastasis. Interactions between bone marrow stromal cells (BMSCs) and multiple myeloma (MM) cells play crucial roles in MM development. We previously reported that BMSC-derived exosomes directly promote MM cell growth, whereas the other possible mechanisms for supporting MM progression by these exosomes are still not clear. Here, we investigated the effect of BMSC-derived exosomes on the MM BM cells with specific emphasis on myeloid-derived suppressor cells (MDSCs). BMSC-derived exosomes were able to be taken up by MM MDSCs and induced their expansion in vitro. Moreover, these exosomes directly induced the survival of MDSCs through activating STAT3 and STAT1 pathways and increasing the anti-apoptotic proteins Bcl-xL and Mcl-1. Inhibition of these pathways blocked the enhancement of MDSC survival. Furthermore, these exosomes increased the nitric oxide release from MM MDSCs and enhanced their suppressive activity on T cells. Taken together, our results demonstrate that BMSC-derived exosomes activate MDSCs in the BM through STAT3 and STAT1 pathways, leading to increased immunosuppression which favors MM progression.

  1. PcpA Promotes Higher Levels of Infection and Modulates Recruitment of Myeloid-Derived Suppressor Cells during Pneumococcal Pneumonia.

    Science.gov (United States)

    Walker, Melissa M; Novak, Lea; Widener, Rebecca; Grubbs, James Aaron; King, Janice; Hale, Joanetha Y; Ochs, Martina M; Myers, Lisa E; Briles, David E; Deshane, Jessy

    2016-03-01

    We used two different infection models to investigate the kinetics of the PcpA-dependent pneumococcal disease in mice. In a bacteremic pneumonia model, we observed a PcpA-dependent increase in bacterial burden in the lungs, blood, liver, bronchoalveolar lavage, and spleens of mice at 24 h postinfection. This PcpA-dependent effect on bacterial burden appeared earlier (within 12 h) in the focal pneumonia model, which lacks bacteremia or sepsis. Histological changes show that the ability of pneumococci to make PcpA was associated with unresolved inflammation in both models of infection. Using our bacteremic pneumonia model we further investigated the effects of PcpA on recruitment of innate immune regulatory cells. The presence of PcpA was associated with increased IL-6 levels, suppressed production of TRAIL, and reduced infiltration of polymorphonuclear cells. The ability of pneumococci to make PcpA negatively modulated both the infiltration and apoptosis of macrophages and the recruitment of myeloid-derived suppressor-like cells. The latter have been shown to facilitate the clearance and control of bacterial pneumonia. Taken together, the ability to make PcpA was strongly associated with increased bacterial burden, inflammation, and negative regulation of innate immune cell recruitment to the lung tissue during bacteremic pneumonia. PMID:26829988

  2. Low dose gemcitabine-loaded lipid nanocapsules target monocytic myeloid-derived suppressor cells and potentiate cancer immunotherapy.

    Science.gov (United States)

    Sasso, Maria Stella; Lollo, Giovanna; Pitorre, Marion; Solito, Samantha; Pinton, Laura; Valpione, Sara; Bastiat, Guillaume; Mandruzzato, Susanna; Bronte, Vincenzo; Marigo, Ilaria; Benoit, Jean-Pierre

    2016-07-01

    Tumor-induced expansion of myeloid-derived suppressor cells (MDSCs) is known to impair the efficacy of cancer immunotherapy. Among pharmacological approaches for MDSC modulation, chemotherapy with selected drugs has a considerable interest due to the possibility of a rapid translation to the clinic. However, such approach is poorly selective and may be associated with dose-dependent toxicities. In the present study, we showed that lipid nanocapsules (LNCs) loaded with a lauroyl-modified form of gemcitabine (GemC12) efficiently target the monocytic (M-) MDSC subset. Subcutaneous administration of GemC12-loaded LNCs reduced the percentage of spleen and tumor-infiltrating M-MDSCs in lymphoma and melanoma-bearing mice, with enhanced efficacy when compared to free gemcitabine. Consistently, fluorochrome-labeled LNCs were preferentially uptaken by monocytic cells rather than by other immune cells, in both tumor-bearing mice and human blood samples from healthy donors and melanoma patients. Very low dose administration of GemC12-loaded LNCs attenuated tumor-associated immunosuppression and increased the efficacy of adoptive T cell therapy. Overall, our results show that GemC12-LNCs have monocyte-targeting properties that can be useful for immunomodulatory purposes, and unveil new possibilities for the exploitation of nanoparticulate drug formulations in cancer immunotherapy.

  3. Mast cell histamine promotes the immunoregulatory activity of myeloid-derived suppressor cells.

    Science.gov (United States)

    Martin, Rebecca K; Saleem, Sheinei J; Folgosa, Lauren; Zellner, Hannah B; Damle, Sheela R; Nguyen, Giang-Kim T; Ryan, John J; Bear, Harry D; Irani, Anne-Marie; Conrad, Daniel H

    2014-07-01

    It has been shown recently that MCs are required for differential regulation of the immune response by granulocytic versus monocytic MDSCs. Granulocytic MDSCs promoted parasite clearance, whereas monocytic MDSCs enhanced tumor progression; both activities were abrogated in MC-deficient mice. Herein, we demonstrate that the lack of MCs also influences MDSC trafficking. Preferential trafficking to the liver was not seen in MC-deficient mice. In addition, evidence that the MC mediator histamine was important in MDSC trafficking and activation is also shown. MDSCs express HR1-3. Blockade of these receptors by HR1 or HR2 antagonists reversed the histamine enhancement of MDSC survival and proliferation observed in cell culture. In addition, histamine differentially influenced Arg1 and iNOS gene expression in MDSCs and greatly enhanced IL-4 and IL-13 message, especially in granulocytic MDSCs. Evidence that histamine influenced activity seen in vitro translated to in vivo when HR1 and HR2 antagonists blocked the effect of MDSCs on parasite expulsion and tumor metastasis. All of these data support the MDSC-mediated promotion of Th2 immunity, leading to the suggestion that allergic-prone individuals would have elevated MDSC levels. This was directly demonstrated by looking at the relative MDSC levels in allergic versus control patients. Monocytic MDSCs trended higher, whereas granulocytic MDSCs were increased significantly in allergic patients. Taken together, our studies indicate that MCs and MC-released histamine are critical for MDSC-mediated immune regulation, and this interaction should be taken into consideration for therapeutic interventions that target MDSCs.

  4. Myeloid-derived suppressor cells contribute to bone erosion in collagen-induced arthritis by differentiating to osteoclasts.

    Science.gov (United States)

    Zhang, Hui; Huang, Yuefang; Wang, Shuang; Fu, Rong; Guo, Chaohuan; Wang, Hongyue; Zhao, Jijun; Gaskin, Felicia; Chen, Jingxian; Yang, Niansheng; Fu, Shu Man

    2015-12-01

    Bone erosion is a sign of severe rheumatoid arthritis and osteoclasts play a major role in the bone resorption. Recently, myeloid-derived suppressor cells (MDSC) has been reported to be increased in collagen-induced arthritis (CIA). The number of circulating MDSCs is shown to correlate with rheumatoid arthritis. These findings suggest that MDSCs are precursor cells involved in bone erosion. In this study, MDSCs isolated from mice with CIA stimulated with M-CSF and RANKL in vitro expressed osteoclast markers and acquired osteoclast bone resorption function. MDSCs sorted from CIA mice were transferred into the tibia of normal DBA/1J mice and bones were subjected to histological and Micro CT analyses. The transferred CIA-MDSCs were shown to differentiate into TRAP(+) osteoclasts that were capable of bone resorption in vivo. MDSCs isolated from normal mice had more potent suppressor activity and much less capability to differentiate to osteoclast. Additional experiments showed that NF-κB inhibitor Bay 11-7082 or IκB inhibitor peptide blocked the differentiation of MDSCs to osteoclast and bone resorption. IL-1Ra also blocked this differentiation. In contrast, the addition of IL-1α further enhanced osteoclast differentiation and bone resorption. These results suggest that MDSCs are a source of osteoclast precursors and inflammatory cytokines such as IL-1, contributing significantly to erosive changes seen in rheumatoid arthritis and related disorders.

  5. Influence of different fluid resuscitation techniques on the number of myeloid-derived suppressor cells in rats.

    Science.gov (United States)

    Wang, Z J; Wang, H X; Li, L; Wang, L; Dou, H H

    2016-04-28

    We investigated the influence of different fluid resuscitation techniques on the number of myeloid-derived suppressor cells (MDSCs) in rats. Seventy-two healthy Sprague-Dawley rats were randomly divided into groups that received sham operation (Sham group), hypertonic saline (HRS group), lactated ringer's solution (LRS group), or crystalloid solution (LCRS group). Six rats from each group were sacrificed by cervical dislocation at 12, 24, and 48 h after resuscitation. The spleens were harvested under sterile conditions and spleen cell suspension was prepared. The number of MDSCs was detected using flow cytometry. The number of MDSCs in the Sham group did not differ significantly among the different time points. Compared with the Sham group, the number of MDSCs after the use of the different fluid resuscitation techniques increased to varying extents and the differences among the groups were significant. The number of MDSCs in the HRS group was much lower than that of the LRS and LCRS groups at both 24 and 48 h (P number of MDSCs in the HRS group was significantly lower than that of the LRS group (P < 0.05). The differences between the HRS and LCRS groups were not statistically significant. Shortly after hemorrhagic shock resuscitation, the immune function of rats was suppressed to a varying extent and was gradually restored over time. Resuscitation with HRS alleviated the immunosuppression at the early stage after shock.

  6. Osteoclasts in multiple myeloma are derived from Gr-1+CD11b+myeloid-derived suppressor cells.

    Directory of Open Access Journals (Sweden)

    Junling Zhuang

    Full Text Available Osteoclasts play a key role in the development of cancer-associated osteolytic lesions. The number and activity of osteoclasts are often enhanced by tumors. However, the origin of osteoclasts is unknown. Myeloid-derived suppressor cells (MDSCs are one of the pre-metastatic niche components that are induced to expand by tumor cells. Here we show that the MDSCs can differentiate into mature and functional osteoclasts in vitro and in vivo. Inoculation of 5TGM1-GFP myeloma cells into C57BL6/KaLwRij mice led to a significant expansion of MDSCs in blood, spleen, and bone marrow over time. When grown in osteoclastogenic media in vitro, MDSCs from tumor-challenged mice displayed 14 times greater potential to differentiate into mature and functional osteoclasts than those from non-tumor controls. Importantly, MDSCs from tumor-challenged LacZ transgenic mice differentiated into LacZ+osteoclasts in vivo. Furthermore, a significant increase in tumor burden and bone loss accompanied by increased number of osteoclasts was observed in mice co-inoculated with tumor-challenged MDSCs and 5TGM1 cells compared to the control animals received 5TGM1 cells alone. Finally, treatment of MDSCs from myeloma-challenged mice with Zoledronic acid (ZA, a potent inhibitor of bone resorption, inhibited the number of osteoclasts formed in MDSC cultures and the expansion of MDSCs and bone lesions in mice. Collectively, these data provide in vitro and in vivo evidence that tumor-induced MDSCs exacerbate cancer-associated bone destruction by directly serving as osteoclast precursors.

  7. Toward harmonized phenotyping of human myeloid-derived suppressor cells by flow cytometry: results from an interim study.

    Science.gov (United States)

    Mandruzzato, Susanna; Brandau, Sven; Britten, Cedrik M; Bronte, Vincenzo; Damuzzo, Vera; Gouttefangeas, Cécile; Maurer, Dominik; Ottensmeier, Christian; van der Burg, Sjoerd H; Welters, Marij J P; Walter, Steffen

    2016-02-01

    There is an increasing interest for monitoring circulating myeloid-derived suppressor cells (MDSCs) in cancer patients, but there are also divergences in their phenotypic definition. To overcome this obstacle, the Cancer Immunoguiding Program under the umbrella of the Association of Cancer Immunotherapy is coordinating a proficiency panel program that aims at harmonizing MDSC phenotyping. After a consultation period, a two-stage approach was designed to harmonize MDSC phenotype. In the first step, an international consortium of 23 laboratories immunophenotyped 10 putative MDSC subsets on pretested, peripheral blood mononuclear cells of healthy donors to assess the level of concordance and define robust marker combinations for the identification of circulating MDSCs. At this stage, no mandatory requirements to standardize reagents or protocols were introduced. Data analysis revealed a small intra-laboratory, but very high inter-laboratory variance for all MDSC subsets, especially for the granulocytic subsets. In particular, the use of a dead-cell marker altered significantly the reported percentage of granulocytic MDSCs, confirming that these cells are especially sensitive to cryopreservation and/or thawing. Importantly, the gating strategy was heterogeneous and associated with high inter-center variance. Overall, our results document the high variability in MDSC phenotyping in the multicenter setting if no harmonization/standardization measures are applied. Although the observed variability depended on a number of identified parameters, the main parameter associated with variation was the gating strategy. Based on these findings, we propose further efforts to harmonize marker combinations and gating parameters to identify strategies for a robust enumeration of MDSC subsets.

  8. Protein tyrosine phosphatase 1B deficiency ameliorates murine experimental colitis via the expansion of myeloid-derived suppressor cells.

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B is a key molecule in modulating low-degree inflammatory conditions such as diabetes. The role of PTP1B in other chronic inflammations, however, remains unknown. Here, we report that PTP1B deficiency ameliorates Dextran Sulfate Sodium (DSS-induced murine experimental colitis via expanding CD11b(+Gr-1(+ myeloid-derived suppressor cells (MDSCs. Employing DSS-induced murine experimental colitis as inflammatory animal model, we found that, compared with wild-type littermates, PTP1B-null mice demonstrated greater resistance to DSS-induced colitis, as reflected by slower weight-loss, greater survival rates and decreased PMN and macrophage infiltration into the colon. The evidence collectively also demonstrated that the resistance of PTP1B-null mice to DSS-induced colitis is based on the expansion of MDSCs. First, PTP1B-null mice exhibited a greater frequency of MDSCs in the bone marrow (BM, peripheral blood and spleen when compared with wild-type littermates. Second, PTP1B levels in BM leukocytes were significantly decreased after cells were induced into MDSCs by IL-6 and GM-CSF, and the MDSC induction occurred more rapidly in PTP1B-null mice than in wild-type littermates, suggesting PTP1B as a negative regulator of MDSCs. Third, the adoptive transfer of MDSCs into mice with DSS-colitis significantly attenuated colitis, which accompanies with a decreased serum IL-17 level. Finally, PTP1B deficiency increased the frequency of MDSCs from BM cells likely through enhancing the activities of signal transducer and activator of transcription 3 (STAT3 and Janus kinase 2 (JAK2. In conclusion, our study provides the first evidences that PTP1B deficiency ameliorates murine experimental colitis via expanding MDSCs.

  9. Suppression of proteoglycan-induced autoimmune arthritis by myeloid-derived suppressor cells generated in vitro from murine bone marrow.

    Directory of Open Access Journals (Sweden)

    Júlia Kurkó

    Full Text Available Myeloid-derived suppressor cells (MDSCs are innate immune cells capable of suppressing T-cell responses. We previously reported the presence of MDSCs with a granulocytic phenotype in the synovial fluid (SF of mice with proteoglycan (PG-induced arthritis (PGIA, a T cell-dependent autoimmune model of rheumatoid arthritis (RA. However, the limited amount of SF-MDSCs precluded investigations into their therapeutic potential. The goals of this study were to develop an in vitro method for generating MDSCs similar to those found in SF and to reveal the therapeutic effect of such cells in PGIA.Murine bone marrow (BM cells were cultured for 3 days in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF, interleukin-6 (IL-6, and granulocyte colony-stimulating factor (G-CSF. The phenotype of cultured cells was analyzed using flow cytometry, microscopy, and biochemical methods. The suppressor activity of BM-MDSCs was tested upon co-culture with activated T cells. To investigate the therapeutic potential of BM-MDSCs, the cells were injected into SCID mice at the early stage of adoptively transferred PGIA, and their effects on the clinical course of arthritis and PG-specific immune responses were determined.BM cells cultured in the presence of GM-CSF, IL-6, and G-CSF became enriched in MDSC-like cells that showed greater phenotypic heterogeneity than MDSCs present in SF. BM-MDSCs profoundly inhibited both antigen-specific and polyclonal T-cell proliferation primarily via production of nitric oxide. Injection of BM-MDSCs into mice with PGIA ameliorated arthritis and reduced PG-specific T-cell responses and serum antibody levels.Our in vitro enrichment strategy provides a SF-like, but controlled microenvironment for converting BM myeloid precursors into MDSCs that potently suppress both T-cell responses and the progression of arthritis in a mouse model of RA. Our results also suggest that enrichment of BM in MDSCs could improve the

  10. Cysteine cathepsin activity suppresses osteoclastogenesis of myeloid-derived suppressor cells in breast cancer

    NARCIS (Netherlands)

    Edgington-Mitchell, L.E.; Rautela, J.; Duivenvoorden, H.M.; Jayatilleke, K.M.; Linden, W.A. van der; Verdoes, M.; Bogyo, M.; Parker, B.S.

    2015-01-01

    Cysteine cathepsin proteases contribute to many normal cellular functions, and their aberrant activity within various cell types can contribute to many diseases, including breast cancer. It is now well accepted that cathepsin proteases have numerous cell-specific functions within the tumor microenvi

  11. C-reactive protein exacerbates renal ischemia-reperfusion injury: are myeloid-derived suppressor cells to blame?

    Science.gov (United States)

    Pegues, Melissa A; McWilliams, Ian L; Szalai, Alexander J

    2016-07-01

    Myeloid-derived suppressor cells (MDSCs) are a CD11b(+)Gr1(+) population in mice that can be separated into granulocytic (g-MDSC) and monocytic (m-MDSC) subtypes based on their expression of Ly6G and Ly6C. Both MDSC subtypes are potent suppressors of T cell immunity, and their contribution has been investigated in a plethora of diseases including renal cancer, renal transplant, and chronic kidney disease. Whether MDSCs contribute to the pathogenesis of acute kidney injury (AKI) remains unknown. Herein, using human C-reactive protein (CRP) transgenic (CRPtg) and CRP-deficient mice (CRP(-/-)) subjected to bilateral renal ischemia-reperfusion injury (IRI), we confirm our earlier finding that CRP exacerbates renal IRI and show for the first time that this effect is accompanied in CRPtg mice by a shift in the balance of kidney-infiltrating MDSCs toward a suppressive Ly6G(+)Ly6C(low) g-MDSC subtype. In CRPtg mice, direct depletion of g-MDSCs (using an anti-Gr1 monoclonal antibody) reduced the albuminuria caused by renal IRI, confirming they play a deleterious role. Remarkably, treatment of CRPtg mice with an antisense oligonucleotide that specifically blocks the human CRP acute-phase response also led to a reduction in renal g-MDSC numbers and improved albuminuria after renal IRI. Our study in CRPtg mice provides new evidence that MDSCs participate in the pathogenesis of renal IRI and shows that their pharmacological depletion is beneficial. If ongoing investigations confirm that CRP is an endogenous regulator of MDSCs in CRPtg mice, and if this action is recapitulated in humans, then targeting CRP or/and MDSCs might offer a new approach for the treatment of AKI. PMID:27053688

  12. Immunosuppressive activity enhances central carbon metabolism and bioenergetics in myeloid-derived suppressor cells in vitro models

    Directory of Open Access Journals (Sweden)

    Hammami Ines

    2012-07-01

    Full Text Available Abstract Background The tumor microenvironment contains a vast array of pro- and anti-inflammatory cytokines that alter myelopoiesis and lead to the maturation of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs. Incubating bone marrow (BM precursors with a combination of granulocyte-macrophage colony-stimulating factor (GM-CSF and interleukin-6 (IL-6 generated a tumor-infiltrating MDSC-like population that impaired anti-tumor specific T-cell functions. This in vitro experimental approach was used to simulate MDSC maturation, and the cellular metabolic response was then monitored. A complementary experimental model that inhibited L-arginine (L-Arg metabolizing enzymes in MSC-1 cells, an immortalized cell line derived from primary MDSCs, was used to study the metabolic events related to immunosuppression. Results Exposure of BM cells to GM-CSF and IL-6 activated, within 24 h, L-Arg metabolizing enzymes which are responsible for the MDSCs immunosuppressive potential. This was accompanied by an increased uptake of L-glutamine (L-Gln and glucose, the latter being metabolized by anaerobic glycolysis. The up-regulation of nutrient uptake lead to the accumulation of TCA cycle intermediates and lactate as well as the endogenous synthesis of L-Arg and the production of energy-rich nucleotides. Moreover, inhibition of L-Arg metabolism in MSC-1 cells down-regulated central carbon metabolism activity, including glycolysis, glutaminolysis and TCA cycle activity, and led to a deterioration of cell bioenergetic status. The simultaneous increase of cell specific concentrations of ATP and a decrease in ATP-to-ADP ratio in BM-derived MDSCs suggested cells were metabolically active during maturation. Moreover, AMP-activated protein kinase (AMPK was activated during MDSC maturation in GM-CSF and IL-6–treated cultures, as revealed by the continuous increase of AMP-to-ATP ratios and the phosphorylation of AMPK. Likewise, AMPK activity was

  13. Correlation between frequencies of blood monocytic myeloid-derived suppressor cells, regulatory T cells and negative prognostic markers in patients with castration-resistant metastatic prostate cancer

    DEFF Research Database (Denmark)

    Idorn, Manja; Køllgaard, Tania; Kongsted, Per;

    2014-01-01

    function of immune suppressive cell subsets in the peripheral blood of 41 patients with prostate cancer (PC) and 36 healthy donors (HD) showed a significant increase in circulating CD14(+) HLA-DR(low/neg) monocytic MDSC (M-MDSC) and Tregs in patients with PC compared to HD. Furthermore, M-MDSC frequencies......Myeloid-derived suppressor cells (MDSC) are believed to play a role in immune suppression and subsequent failure of T cells to mount an efficient anti-tumor response, by employing both direct T-cell inhibition as well as induction of regulatory T cells (Tregs). Investigating the frequency and...... correlated positively with Treg levels. In vitro proliferation assay with autologous T cells confirmed M-MDSC-mediated T-cell suppression, and intracellular staining of immune suppressive enzyme iNOS revealed a higher expression in M-MDSC from patients with PC. Increased frequencies of M-MDSC correlated with...

  14. Prognostic Significance of Monocytes and Monocytic Myeloid-Derived Suppressor Cells in Diffuse Large B-Cell Lymphoma Treated with R-CHOP

    Directory of Open Access Journals (Sweden)

    Chongyang Wu

    2016-07-01

    Full Text Available Background/Aims: To evaluate the prognostic significance of monocytes and monocytic myeloid-derived suppressor cells (M-MDSCs for patients with diffuse large B-cell lymphoma (DLBCL under R-CHOP chemotherapy. Methods: Flow cytometry (FCM was applied to measure M-MDSCs (CD14+ HLA-DRlow/− M-MDSCs. Results: Analysis of 144 patients with DLBCL under R-CHOP treatment showed that the 5-year overall survival rate was 61.09% (95% CI: 43.72%-72.56% and the average survival time of patients with monocytes (% ≥ 8% was shorter than those with monocytes (% 2 (P = 0.0397, meanwhile, there was no significant difference in survival of patients with monocytes (% ≥ 8% compared to patients with monocytes (% Conclusion: Our results indicated that monocytes (% and M-MDSCs combined with R-IPI may be a simple and efficient immunological index to evaluate prognosis.

  15. 髓源性抑制细胞——肿瘤免疫治疗的新靶点%Myeloid-derived suppressor cells:a new target of cancer immunotherapy

    Institute of Scientific and Technical Information of China (English)

    武丽华; 王东亮

    2012-01-01

    Myeloid - derived suppressor eells(MDSCs)are a heterogeneous population of myeloid derived cells Which were amplified in pathological status,which is characterized as negatively regulating the anti -tumor immune response with the result of promoting tnmorigenesis and cancer development. It is a promising strategy to enhance the effect of cancer immimothcrapy through blocking the immimosupprcssivc pathway of MDSCs.%髓源性抑制细胞(Myeloid-derived suppressor cells,MDSCs)是在病理情况下扩增的一种髓源性抑制细胞群,其特点是能负向调节机体的抗肿瘤免疫反应从而促进肿瘤的发生和发展.通过阻断MDSCs的免疫抑制通路来提高肿瘤免疫治疗的效果,是一个颇有前景的治疗策略.

  16. Hepatitis C virus-induced myeloid-derived suppressor cells regulate T-cell differentiation and function via the signal transducer and activator of transcription 3 pathway.

    Science.gov (United States)

    Ren, Jun P; Zhao, Juan; Dai, Jun; Griffin, Jeddidiah W D; Wang, Ling; Wu, Xiao Y; Morrison, Zheng D; Li, Guang Y; El Gazzar, Mohamed; Ning, Shun B; Moorman, Jonathan P; Yao, Zhi Q

    2016-08-01

    T cells play a pivotal role in controlling viral infection; however, the precise mechanisms responsible for regulating T-cell differentiation and function during infections are incompletely understood. In this study, we demonstrated an expansion of myeloid-derived suppressor cells (MDSCs), in particular the monocytic MDSCs (M-MDSCs; CD14(+) CD33(+) CD11b(+) HLA-DR(-/low) ), in patients with chronic hepatitis C virus (HCV) infection. Notably, HCV-induced M-MDSCs express high levels of phosphorylated signal transducer and activator of transcription 3 (pSTAT3) and interleukin-10 (IL-10) compared with healthy subjects. Blocking STAT3 signalling reduced HCV-mediated M-MDSC expansion and decreased IL-10 expression. Importantly, we observed a significant increase in the numbers of CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells following incubation of healthy peripheral blood mononuclear cells (PBMCs) with MDSCs derived from HCV-infected patients or treated with HCV core protein. In addition, depletion of MDSCs from PBMCs led to a significant reduction of Foxp3(+) Treg cells developed during chronic HCV infection. Moreover, depletion of MDSCs from PBMCs significantly increased interferon-γ production by CD4(+) T effector (Teff) cells derived from HCV patients. These results suggest that HCV-induced MDSCs promote Treg cell development and inhibit Teff cell function, suggesting a novel mechanism for T-cell regulation and a new strategy for immunotherapy against human viral diseases. PMID:27149428

  17. Treatment of tumors with vitamin E suppresses myeloid derived suppressor cells and enhances CD8+ T cell-mediated antitumor effects.

    Directory of Open Access Journals (Sweden)

    Tae Heung Kang

    Full Text Available Vitamin E has been shown to have strong anticarcinogenic properties, including antioxidant characteristics, making it an ideal candidate for use in combination with immunotherapies that modify the tumor microenvironment. The tumor microenvironment contains immunosuppressive components, which can be diminished, and immunogenic components, which can be augmented by immunotherapies in order to generate a productive immune response. In the current study, we employ the α-tocopherol succinate isomer of vitamin E to reduce immunosuppression by myeloid derived suppressor cells (MDSCs as well as adoptive transfer of antigen-specific CD8+ T cells to generate potent antitumor effects against the HPV16 E7-expressing TC-1 tumor model. We show that vitamin E alone induces necrosis of TC-1 cells and elicits antitumor effects in TC-1 tumor-bearing mice. We further demonstrate that vitamin E reverses the suppression of T cell activation by MDSCs and that this effect is mediated in part by a nitric oxide-dependent mechanism. Additionally, treatment with vitamin E reduces the percentage of MDSCs in tumor loci, and induces a higher percentage of T cells, following T cell adoptive transfer. Finally, we demonstrate that treatment with vitamin E followed by E7-specific T cell adoptive transfer experience elicits potent antitumor effects in tumor-bearing mice. Our data provide additional evidence that vitamin E has anticancer properties and that it has promise for use as an adjuvant in combination with a variety of cancer therapies.

  18. Protection against HPV-16-Associated Tumors Requires the Activation of CD8+ Effector Memory T Cells and the Control of Myeloid-Derived Suppressor Cells.

    Science.gov (United States)

    Diniz, Mariana O; Sales, Natiely S; Silva, Jamile R; Ferreira, Luís Carlos S

    2016-08-01

    Active anticancer immunotherapeutic approaches have been shown to induce cellular or humoral immune responses in patients, but, thus far, the observed outcomes did not ensure their recommendation for clinical use. The induction of tumor-specific CD8(+) T cells, although required for the clearance of most solid tumors, was shown to be insufficient for the development of a successful immunotherapeutic approach. The suppressive immune environment triggered by tumors, including the expansion of myeloid-derived suppressor cells (MDSC), is detrimental to the development of antitumor immune responses and precludes the generation of more promising clinical outcomes. In this work, we characterized the CD8(+) T-cell population specifically involved in the control of tumor growth and the role of MDSCs after administration of an antitumor therapeutic DNA vaccine targeting human papillomavirus type 16 (HPV-16)-associated tumors. Activation of cytotoxic high-avidity CD8(+) T cells with an effector memory phenotype was found in mice grafted with tumor cells expressing the HPV-16 oncoproteins. In addition, MDSC antibody depletion further enhanced the immunotherapeutic effects of the vaccine, resulting in the complete eradication of tumor cells. Collectively, the current results indicate that the simultaneous control of MDSCs and activation of high-avidity tumor-specific effector memory CD8(+) T cells are key features for tumor protection by immunotherapeutic approaches and deserve further testing under clinical conditions. Mol Cancer Ther; 15(8); 1920-30. ©2016 AACR. PMID:27222537

  19. Contact-dependent depletion of hydrogen peroxide by catalase is a novel mechanism of myeloid-derived suppressor cell induction operating in human hepatic stellate cells.

    Science.gov (United States)

    Resheq, Yazid J; Li, Ka-Kit; Ward, Stephen T; Wilhelm, Annika; Garg, Abhilok; Curbishley, Stuart M; Blahova, Miroslava; Zimmermann, Henning W; Jitschin, Regina; Mougiakakos, Dimitrios; Mackensen, Andreas; Weston, Chris J; Adams, David H

    2015-03-15

    Myeloid-derived suppressor cells (MDSC) represent a unique cell population with distinct immunosuppressive properties that have been demonstrated to shape the outcome of malignant diseases. Recently, human hepatic stellate cells (HSC) have been reported to induce monocytic-MDSC from mature CD14(+) monocytes in a contact-dependent manner. We now report a novel and unexpected mechanism by which CD14(+)HLADR(low/-) suppressive cells are induced by catalase-mediated depletion of hydrogen peroxide (H2O2). Incubation of CD14(+) monocytes with catalase led to a significant induction of functional MDSC compared with media alone, and H2O2 levels inversely correlated with MDSC frequency (r = -0.6555, p Catalase was detected in primary HSC and a stromal cell line, and addition of the competitive catalase inhibitor hydroxylamine resulted in a dose-dependent impairment of MDSC induction and concomitant increase of H2O2 levels. The NADPH-oxidase subunit gp91 was significantly increased in catalase-induced MDSC as determined by quantitative PCR outlining the importance of oxidative burst for the induction of MDSC. These findings represent a so far unrecognized link between immunosuppression by MDSC and metabolism. Moreover, this mechanism potentially explains how stromal cells can induce a favorable immunological microenvironment in the context of tissue oxidative stress such as occurs during cancer therapy.

  20. DNA demethylating agent 5-azacytidine inhibits myeloid-derived suppressor cells induced by tumor growth and cyclophosphamide treatment

    OpenAIRE

    Mikyšková, R; Indrová, M. (Marie); Vlková, V. (Veronika); Bieblová, J. (Jana); Šímová, J; Paračková, Z. (Zuzana); Pajtasz-Piasecka, E.; Rossowska, J.; Reiniš, M

    2014-01-01

    MDSCs represent one of the key players mediating immunosuppression. These cells accumulate in the TME, lymphoid organs, and blood during tumor growth. Their mobilization was also reported after CY therapy. DNMTi 5AC has been intensively studied as an antitumor agent. In this study, we examined, using two different murine tumor models, the modulatory effects of 5AC on TU-MDSCs and CY-MDSCs tumor growth and CY therapy. Indeed, the percentage of MDSCs in the TME and spleens of 5AC-treated mice b...

  1. 6-Thioguanine-loaded polymeric micelles deplete myeloid-derived suppressor cells and enhance the efficacy of T cell immunotherapy in tumor-bearing mice.

    Science.gov (United States)

    Jeanbart, Laura; Kourtis, Iraklis C; van der Vlies, André J; Swartz, Melody A; Hubbell, Jeffrey A

    2015-08-01

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that suppress effector T cell responses and can reduce the efficacy of cancer immunotherapies. We previously showed that ultra-small polymer nanoparticles efficiently drain to the lymphatics after intradermal injection and target antigen-presenting cells, including Ly6c(hi) Ly6g(-) monocytic MDSCs (Mo-MDSCs), in skin-draining lymph nodes (LNs) and spleen. Here, we developed ultra-small polymer micelles loaded with 6-thioguanine (MC-TG), a cytotoxic drug used in the treatment of myelogenous leukemia, with the aim of killing Mo-MDSCs in tumor-bearing mice and thus enhancing T cell-mediated anti-tumor responses. We found that 2 days post-injection in tumor-bearing mice (B16-F10 melanoma or E.G7-OVA thymoma), MC-TG depleted Mo-MDSCs in the spleen, Ly6c(lo) Ly6g(+) granulocytic MDSCs (G-MDSCs) in the draining LNs, and Gr1(int) Mo-MDSCs in the tumor. In both tumor models, MC-TG decreased the numbers of circulating Mo- and G-MDSCs, as well as of Ly6c(hi) macrophages, for up to 7 days following a single administration. MDSC depletion was dose dependent and more effective with MC-TG than with equal doses of free TG. Finally, we tested whether this MDSC-depleting strategy might enhance cancer immunotherapies in the B16-F10 melanoma model. We found that MC-TG significantly improved the efficacy of adoptively transferred, OVA-specific CD8(+) T cells in melanoma cells expressing OVA. These findings highlight the capacity of MC-TG in depleting MDSCs in the tumor microenvironment and show promise in promoting anti-tumor immunity when used in combination with T cell immunotherapies. PMID:25982370

  2. Myeloid derived suppressor cells (MDSCs are increased and exert immunosuppressive activity together with polymorphonuclear leukocytes (PMNs in chronic myeloid leukemia patients.

    Directory of Open Access Journals (Sweden)

    Cesarina Giallongo

    Full Text Available Tumor immune tolerance can derive from the recruitment of suppressor cell population, including myeloid derived suppressor cells (MDSCs, able to inhibit T cells activity. We identified a significantly expanded MDSCs population in chronic myeloid leukemia (CML patients at diagnosis that decreased to normal levels after imatinib therapy. In addition, expression of arginase 1 (Arg1 that depletes microenvironment of arginine, an essential aminoacid for T cell function, resulted in an increase in patients at diagnosis. Purified CML CD11b+CD33+CD14-HLADR- cells markedly suppressed normal donor T cell proliferation in vitro. Comparing CML Gr-MDSCs to autologous polymorphonuclear leukocytes (PMNs we observed a higher Arg1 expression and activity in PMNs, together with an inhibitory effect on T cells in vitro. Our data indicate that CML cells create an immuno-tolerant environment associated to MDSCs expansion with immunosuppressive capacity mediated by Arg1. In addition, we demonstrated for the first time also an immunosuppressive activity of CML PMNs, suggesting a strong potential immune escape mechanism created by CML cells, which control the anti-tumor reactive T cells. MDSCs should be monitored in imatinib discontinuation trials to understand their importance in relapsing patients.

  3. Differential induction of Ly6G and Ly6C positive myeloid derived suppressor cells in chronic kidney and liver inflammation and fibrosis.

    Directory of Open Access Journals (Sweden)

    Bastian Höchst

    Full Text Available CD11b+Gr1+ myeloid derived suppressor cells (MDSC are known to be very potent suppressors of T cell immunity and can be further stratified into granulocytic MDSC and monocytic MDSC in mice based on expression of Ly6G or Ly6C, respectively. Here, using these markers and functional assays, we aimed to identify whether MDSC are induced during chronic inflammation leading to fibrosis in both kidney and liver and whether additional markers could more specifically identify these MDSC subsets. In an adenine-induced model of kidney inflammation/fibrosis suppressive Ly6Gpos MDSC were induced. The suppressive function within the Ly6G+ MDSC population was exclusively present in IFNγRβ expressing cells. In contrast, in chronic inflammation in the liver induced by bile duct ligation, suppressive capacity was exclusively present in the Ly6Cpos MDSC subset. Gene expression analyses confirmed the differential origins and regulation of those MDSC subsets. Additionally, depletion of MDSC in either kidney or liver fibrosis enhanced fibrosis markers, indicating a protective role for MDSC in organ fibrosis. Thus, our data demonstrate that during liver inflammation and kidney fibrosis MDSC with similar function arise bearing a distinct marker profile and arising from different cell populations.

  4. Resistance to Streptozotocin-Induced Autoimmune Diabetes in Absence of Complement C3: Myeloid-Derived Suppressor Cells Play a Role.

    Directory of Open Access Journals (Sweden)

    Xiaogang Gao

    Full Text Available The contribution of complement to the development of autoimmune diabetes has been proposed recently. The underlying mechanisms, however, remain poorly understood. We hypothesize that myeloid-derived suppressor cells (MDSC, which act as regulators in autoimmunity, play a role in resistance to diabetes in absence of complement C3. Indeed, MDSC number was increased significantly in STZ-treated C3-/- mice. These cells highly expressed arginase I and inducible nitric oxide synthase (iNOS. Importantly, depletion of MDSC led to the occurrence of overt diabetes in C3-/- mice after STZ. Furthermore, C3-/- MDSC actively suppressed diabetogenic T cell proliferation and prevented/delayed the development of diabetes in arginase and/or iNOS-dependent manner. Both Tregs and transforming growth factor-β (TGF-β are crucial for MDSC induction in STZ-treated C3-/- mice as depletion of Tregs or blocking TGF-β bioactivity dramatically decreased MDSC number. These findings indicate that MDSC are implicated in resistance to STZ-induced diabetes in the absence of complement C3, which may be helpful for understanding of mechanisms underlying preventive effects of complement deficiency on autoimmune diseases.

  5. DNA demethylating agent 5-azacytidine inhibits myeloid-derived suppressor cells induced by tumor growth and cyclophosphamide treatment.

    Science.gov (United States)

    Mikysková, Romana; Indrová, Marie; Vlková, Veronika; Bieblová, Jana; Símová, Jana; Paracková, Zuzana; Pajtasz-Piasecka, Elzbieta; Rossowska, Joanna; Reinis, Milan

    2014-01-01

    MDSCs represent one of the key players mediating immunosuppression. These cells accumulate in the TME, lymphoid organs, and blood during tumor growth. Their mobilization was also reported after CY therapy. DNMTi 5AC has been intensively studied as an antitumor agent. In this study, we examined, using two different murine tumor models, the modulatory effects of 5AC on TU-MDSCs and CY-MDSCs tumor growth and CY therapy. Indeed, the percentage of MDSCs in the TME and spleens of 5AC-treated mice bearing TRAMP-C2 or TC-1/A9 tumors was found decreased. The changes in the MDSC percentage were accompanied by a decrease in the Arg-1 gene expression, both in the TME and spleens. CY treatment of the tumors resulted in additional MDSC accumulation in the TME and spleens. This accumulation was subsequently inhibited by 5AC treatment. A combination of CY with 5AC led to the highest tumor growth inhibition. Furthermore, in vitro cultivation of spleen MDSCs in the presence of 5AC reduced the percentage of MDSCs. This reduction was associated with an increased percentage of CD11c(+) and CD86(+)/MHCII(+) cells. The observed modulatory effect on MDSCs correlated with a reduction of the Arg-1 gene expression, VEGF production, and loss of suppressive capacity. Similar, albeit weaker effects were observed when MDSCs from the spleens of tumor-bearing animals were cultivated with 5AC. Our findings indicate that beside the direct antitumor effect, 5AC can reduce the percentage of MDSCs accumulating in the TME and spleens during tumor growth and CY chemotherapy, which can be beneficial for the outcome of cancer therapy. PMID:24389335

  6. Identification of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the peripheral blood of Hodgkin and non-Hodgkin lymphoma patients

    Science.gov (United States)

    Marini, Olivia; Spina, Cecilia; Mimiola, Elda; Cassaro, Adriana; Malerba, Giovanni; Todeschini, Giuseppe; Perbellini, Omar; Scupoli, Maria; Carli, Giuseppe; Facchinelli, Davide; Cassatella, Marco; Scapini, Patrizia; Tecchio, Cristina

    2016-01-01

    Human granulocytic myeloid-derived suppressor cells (G-MDSCs) have been described as low-density immunosuppressive CD66b+CD33dimHLA-DR-granulocytes that co-purify with mononuclear cells after density gradient centrifugation of blood from cancer patients. The role of G-MDSCs in Hodgkin (HL) and non-Hodgkin lymphoma (NHL) remains unclear. The percentage and immunophenotype of CD66b+CD33dimHLA-DR-cells were analyzed in PBMCs from HL and B-cell NHL patients (n = 124) and healthy donors (n = 48). The immunosuppressive functions of these cells were tested in vitro. Correlations between CD66b+CD33dimHLA-DR-cells and patient clinicopathological features and outcome, were evaluated. CD66b+CD33dimHLA-DR-cells were increased in PBMCs from HL and B-cell NHL patients as compared to healthy donors: 2.18 (0.02–70.92) vs 0.42 (0.04–2.97), p expression as compared to conventionally isolated (normal-density) autologous or healthy donor neutrophils. The in vitro depletion of CD66b+ cells from patient PBMCs restored the proliferation of autologous T cells. Higher frequencies of CD66b+CD33dimHLA-DR− G-MDSCs correlated significantly with unfavorable prognostic index scores and a shorter freedom from disease progression. PBMCs from HL and B-cell NHL patients contain a population of CD66b+CD33dimHLA-DR− G-MDSCs, mostly composed of activated low-density neutrophils with immunosuppressive properties. These findings disclose a previously unknown G-MDSC-mediated mechanism of immune-escape in lymphomas, therefore anticipating possible targets for therapeutic interventions. PMID:27050283

  7. Myeloid-derived suppressor cells have a central role in attenuated Listeria monocytogenes-based immunotherapy against metastatic breast cancer in young and old mice

    Science.gov (United States)

    Chandra, D; Jahangir, A; Quispe-Tintaya, W; Einstein, M H; Gravekamp, C

    2013-01-01

    Background: Myeloid-derived suppressor cells (MDSCs) are present in large numbers in blood of mice and humans with cancer, and they strongly inhibit T-cell and natural killer (NK) cell responses, at young and old age. We found that a highly attenuated bacterium Listeria monocytogenes (Listeriaat)-infected MDSC and altered the immune-suppressing function of MDSC. Methods: Young (3 months) and old (18 months) BALB/cByJ mice with metastatic breast cancer (4T1 model) were immunised with Listeriaat semi-therapeutically (once before and twice after tumour development), and analysed for growth of metastases and primary tumour, in relation to MDSC-, CD8 T-cell and NK cell responses. Results: We found that Listeriaat-infected MDSC, which delivered Listeriaat predominantly to the microenvironment of metastases and primary tumours, where they spread from MDSC into tumour cells (infected tumour cells will ultimately become a target for Listeria-activated immune cells). Immunotherapy with Listeriaat significantly reduced the population of MDSC in blood and primary tumours, and converted a remaining subpopulation of MDSC into an immune-stimulating phenotype producing IL-12, in correlation with significantly improved T-cell and NK cell responses to Listeriaat at both ages. This was accompanied with a dramatic reduction in the number of metastases and tumour growth at young and old age. Conclusions: Although preclinical studies show that immunotherapy is less effective at old than at young age, our study demonstrates that Listeriaat-based immunotherapy can be equally effective against metastatic breast cancer at both young and old age by targeting MDSC. PMID:23640395

  8. Myeloid-derived suppressor cell function is reduced by Withaferin A, a potent and abundant component of Withania somnifera root extract.

    Science.gov (United States)

    Sinha, Pratima; Ostrand-Rosenberg, Suzanne

    2013-11-01

    Myeloid cells play a crucial role in tumor progression. The most common tumor-infiltrating myeloid cells are myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAMs). These cells promote tumor growth by their inherent immune suppressive activity which is enhanced by their cross-talk. The root extract of the plant Withania somnifera (Ashwagandha) (WRE) has been reported to reduce tumor growth. HPLC analysis identified Withaferin A (WA) as the most abundant constituent of WRE and led us to determine whether the anti-tumor effects of WRE and WA involve modulating MDSC and TAM activity. A prominent effect of MDSC is their production of IL-10 which increases upon cross-talk with macrophages, thus polarizing immunity to a pro-tumor type 2 phenotype. In vitro treatment with WA decreased MDSC production of IL-10 and prevented additional MDSC production of IL-10 generated by MDSC-macrophage cross-talk. Macrophage secretion of IL-6 and TNFα, cytokines that increase MDSC accumulation and function, was also reduced by in vitro treatment with WA. Much of the T-cell suppressive activity of MDSC is due to MDSC production of reactive oxygen species (ROS), and WA significantly reduced MDSC production of ROS through a STAT3-dependent mechanism. In vivo treatment of tumor-bearing mice with WA decreased tumor weight, reduced the quantity of granulocytic MDSC, and reduced the ability of MDSC to suppress antigen-driven activation of CD4+ and CD8+ T cells. Thus, adjunctive treatment with WA reduced myeloid cell-mediated immune suppression, polarized immunity toward a tumor-rejecting type 1 phenotype, and may facilitate the development of anti-tumor immunity.

  9. ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells.

    Directory of Open Access Journals (Sweden)

    David Gallego-Ortega

    2015-12-01

    Full Text Available During pregnancy, the ETS transcription factor ELF5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. In breast cancer, ELF5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. In the mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT model of luminal breast cancer, induction of ELF5 levels increased leukocyte infiltration, angiogenesis, and blood vessel permeability in primary tumors and greatly increased the size and number of lung metastasis. Myeloid-derived suppressor cells, a group of immature neutrophils recently identified as mediators of vasculogenesis and metastasis, were recruited to the tumor in response to ELF5. Depletion of these cells using specific Ly6G antibodies prevented ELF5 from driving vasculogenesis and metastasis. Expression signatures in luminal A breast cancers indicated that increased myeloid cell invasion and inflammation were correlated with ELF5 expression, and increased ELF5 immunohistochemical staining predicted much shorter metastasis-free and overall survival of luminal A patients, defining a group who experienced unexpectedly early disease progression. Thus, in the MMTV-PyMT mouse mammary model, increased ELF5 levels drive metastasis by co-opting the innate immune system. As ELF5 has been previously implicated in the development of antiestrogen resistance, this finding implicates ELF5 as a defining factor in the acquisition of the key aspects of the lethal phenotype in luminal A breast cancer.

  10. ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells.

    Science.gov (United States)

    Gallego-Ortega, David; Ledger, Anita; Roden, Daniel L; Law, Andrew M K; Magenau, Astrid; Kikhtyak, Zoya; Cho, Christina; Allerdice, Stephanie L; Lee, Heather J; Valdes-Mora, Fatima; Herrmann, David; Salomon, Robert; Young, Adelaide I J; Lee, Brian Y; Sergio, C Marcelo; Kaplan, Warren; Piggin, Catherine; Conway, James R W; Rabinovich, Brian; Millar, Ewan K A; Oakes, Samantha R; Chtanova, Tatyana; Swarbrick, Alexander; Naylor, Matthew J; O'Toole, Sandra; Green, Andrew R; Timpson, Paul; Gee, Julia M W; Ellis, Ian O; Clark, Susan J; Ormandy, Christopher J

    2015-12-01

    During pregnancy, the ETS transcription factor ELF5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. In breast cancer, ELF5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. In the mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT) model of luminal breast cancer, induction of ELF5 levels increased leukocyte infiltration, angiogenesis, and blood vessel permeability in primary tumors and greatly increased the size and number of lung metastasis. Myeloid-derived suppressor cells, a group of immature neutrophils recently identified as mediators of vasculogenesis and metastasis, were recruited to the tumor in response to ELF5. Depletion of these cells using specific Ly6G antibodies prevented ELF5 from driving vasculogenesis and metastasis. Expression signatures in luminal A breast cancers indicated that increased myeloid cell invasion and inflammation were correlated with ELF5 expression, and increased ELF5 immunohistochemical staining predicted much shorter metastasis-free and overall survival of luminal A patients, defining a group who experienced unexpectedly early disease progression. Thus, in the MMTV-PyMT mouse mammary model, increased ELF5 levels drive metastasis by co-opting the innate immune system. As ELF5 has been previously implicated in the development of antiestrogen resistance, this finding implicates ELF5 as a defining factor in the acquisition of the key aspects of the lethal phenotype in luminal A breast cancer. PMID:26717410

  11. Reductions in Myeloid-Derived Suppressor Cells and Lung Metastases using AZD4547 Treatment of a Metastatic Murine Breast Tumor Model

    Directory of Open Access Journals (Sweden)

    Li Liu

    2014-03-01

    Full Text Available Background: AZD4547, a small-molecule inhibitor targeting the tyrosine kinase of Fibroblast Growth Factor Receptors (FGFRs, is currently under phase II clinical study for human subjects having breast cancer, while the underlying mechanism remains elusive. The aim of this study is to explore the potential mechanism by which AZD4547 inhibits breast tumor lung metastases at the level of the tumor microenvironment. Methods: First, through in vitro experiments, we investigated the efficacy of the FGFRs inhibitor AZD4547 on 4T1 tumor cells for their proliferation, apoptosis, migration, and invasion. Second, by in vivo animal experiments, we evaluated the effects of AZD4547 on tumor growth and lung metastases in 4T1 tumor-bearing mice. Finally, we examined the impact of AZD4547 on the infiltration of myeloid-derived suppressor cells (MDSCs in lung, spleens, peripheral blood and tumor. Results: Through this study we found that AZD4547 could efficiently suppress tumor 4T1 cells through restraining their proliferation, blocking migration and invasion, and inducing apoptosis in vitro. In animal model we also demonstrated that AZD4547 was able to inhibit tumor growth and lung metastases, consistent with the decreased MDSCs accumulation in the tumor and lung tissues, respectively. Moreover, the reduced number of MDSCs in peripheral blood and spleens were also observed in the AZD4547-treated mice. Importantly, through the AZD4547 treatment, the CD4+ and CD8+ T-cells were significantly increased in tumor and spleens. Conclusion: Our studies showed that AZD4547 can inhibit breast cancer cell proliferation, induce its apoptosis and block migration and invasion in vitro and suppress tumor growth and lung metastases by modulating the tumor immunologic microenvironment in vivo.

  12. Analysis of Monocytic and Granulocytic Myeloid-Derived Suppressor Cells Subsets in Patients with Hepatitis C Virus Infection and Their Clinical Significance

    Directory of Open Access Journals (Sweden)

    Gang Ning

    2015-01-01

    Full Text Available Myeloid-derived suppressor cells (MDSCs have been shown to inhibit T-cell responses in many diseases, but, in hepatitis C virus (HCV infected patients, MDSCs are still poorly studied. In this assay, we investigated the phenotype and frequency of two new populations of MDSCs denoted as monocytic and granulocytic MDSCs (M-MDSCs and G-MDSCs in HCV infected patients and analyzed their clinical significance in these patients respectively. We found that the frequency of CD14+HLA-DR-/low cells (M-MDSCs from HCV infected patients (mean ± SE, 3.134% ± 0.340% was significantly increased when compared to healthy controls (mean ± SE, 1.764% ± 0.461% (Z = −2.438, P = 0.015, while there was no statistical difference between the frequency of HLA-DR-/lowCD33+CD11b+CD15+ (G-MDSCs of HCV infected patients and healthy donors (0.201% ± 0.038% versus 0.096% ± 0.026%, P > 0.05, which suggested that HCV infection could cause the proliferation of M-MDSCs instead of G-MDSCs. Besides, we found that the frequency of M-MDSCs in HCV infected patients had certain relevance with age (r = 0.358, P = 0.003; patients older than 40 years old group (mean ± SE, 3.673% ± 0.456% had a significantly higher frequency of M-MDSCs than that of age less than 40 years old group (mean ± SE, 2.363% ± 0.482% (Z = −2.685, P = 0.007. The frequency of M-MDSCs, however, had no correlation with HCV RNA loads, aspartate aminotransferase (AST, alanine aminotransferase (ALT, and the level of liver inflammation degree.

  13. A novel role of hematopoietic CCL5 in promoting triple-negative mammary tumor progression by regulating generation of myeloid-derived suppressor cells

    Institute of Scientific and Technical Information of China (English)

    Yan Zhang; Dandan Lv; Ha-Jeong Kim; Robert A Kurt; Wen Bu; Yi Li; Xiaojing Ma

    2013-01-01

    CCL5 is a member of the CC chemokine family expressed in a wide array of immune and non-immune cells in response to stress signals.CCL5 expression correlates with advanced human breast cancer.However,its functional significance and mode of action have not been established.Here,we show that CCL5-deficient mice are resistant to highly aggressive,triple-negative mammary tumor growth.Hematopoietic CCL5 is dominant in this phenotype.The absence of hematopoietic CCL5 causes aberrant generation of CD11b+/Gr-1+,myeloid-derived suppressor cells (MDSCs) in the bone marrow in response to tumor growth by accumulating Ly6Chi and Ly6G+ MDSCs with impaired capacity to suppress cytotoxicity of CD8+ T cells.These properties of CCL5 are observed in both orthotopic and spontaneous mammary tumors.Antibody-mediated systemic blockade of CCL5 inhibits tumor progression and enhances the efficacy of therapeutic vaccination against non-immunogenic tumors.CCL5 also helps maintain the immunosuppressive capacity of human MDSCs.Our study uncovers a novel,chemokine-independent activity of the hematopoietically derived CCL5 that promotes mammary tumor progression via generating MDSCs in the bone marrow in cooperation with tumor-derived colony-stimulating factors.The study sheds considerable light on the interplay between the hematopoietic compartment and tumor niche.Because of the apparent dispensable nature of this molecule in normal physiology,CCL5 may represent an excellent therapeutic target in immunotherapy for breast cancer as well as a broad range of solid tumors that have significant amounts of MDSC infiltration.

  14. Increased level of both CD4+FOXP3+ regulatory T cells and CD14+HLA-DR⁻/low myeloid-derived suppressor cells and decreased level of dendritic cells in patients with multiple myeloma

    DEFF Research Database (Denmark)

    Brimnes, M K; Vangsted, Annette Juul; Knudsen, L M;

    2010-01-01

    immune status in patients with MM seems crucial prior to active immune therapy. We evaluated the proportion of both, DC, Treg cells and myeloid-derived suppressor cells (MDSC) in peripheral blood from patients with MM at diagnosis and in remission as well as patients with monoclonal gammopathy of......+FOXP3+ Treg cells was increased in patients at diagnosis and not in patients in remission or with MGUS. Also, Treg cells from patients with MM were functionally intact as they were able to inhibit proliferation of both CD4 and CD8 T cells. Finally, we observed an increase in the proportion of CD14+HLA......-DR¿/low MDSC in patients with MM at diagnosis, illustrating that this cell fraction is also distorted in patients with MM. Taken together, our results illustrate that, both mDC, pDC, Treg cells and MDSC are affected in patients with MM underlining the fact that the immune system is dysregulated as a...

  15. 髓系衍生抑制性细胞与感染性疾病的关系%Research progress on myeloid-derived suppressor cells in infective diseases

    Institute of Scientific and Technical Information of China (English)

    吴丹霄; 夏大静

    2008-01-01

    Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of myeloid cells composed of immature dendritic cells, macrophages, granulocytes and other myeloid cells at early stages of differentiation. Infection and other diseases can induce the MDSC's accumulation in lymphoid organs and pathological site and, eventually, their acti-vation. These cells which have suppressive function can negatively regulate the immune system through several ways. Recent findings on the M DSC's phenotype, properties, recruiting and activating factors, mechanisms of immunoregulation and relations to infection diseases are summarized in the review.%髓系衍生抑制性细胞(MDSC)是一群具有高度异质性的髓系细胞群体,包括未成熟DC、巨噬细胞、粒细胞和其他早期分化阶段的髓系细胞等.在感染等疾病状态下,机体内环境产生募集和活化MDSC的因素,导致大量MDSC在淋巴器官及病变局部聚集并活化,随后通过多条途径下调机体的免疫应答,发挥免疫抑制的功能.此文就MDSC的性质、募集和活化的因素、免疫调节机制及其与感染性疾病的关系进行综述.

  16. Research progress on myeloid-derived suppressor cells in rheumatoid arthritis%髓源性抑制细胞在类风湿关节炎中的研究进展

    Institute of Scientific and Technical Information of China (English)

    李东仕; 郑若婷; 林素娟; 陈式仪; 陈慎仁

    2015-01-01

    Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of cells that expand during tumor, chronic infection, marrow transplantation and other pathological conditions, and are responsible for regulating immune responses. The earliest researches about MDSCs focused on oncology field. In recent years, the researches about MDSCs in aotuimmune diseases is increasing. In this review, the origin, subsets and mechanisms of MDSCs, as well as the relationship between MDSCs and rheumatoid arthritis were discussed.%髓源性抑制细胞(MDSCs)是一群免疫异质性细胞,通常在肿瘤、慢性炎症和骨髓移植等病理状态下出现扩增,在机体免疫系统中起调节作用。对 MDSCs 的研究早期集中在肿瘤方面,近年来对自身免疫性疾病研究逐渐增多。本文综述 MDSCs 的来源、不同分型功能、作用机制及与类风湿关节炎关系的相关研究。

  17. Recipient myeloid-derived immunomodulatory cells induce PD-1 ligand-dependent donor CD4+Foxp3+ regulatory T cell proliferation and donor-recipient immune tolerance after murine nonmyeloablative bone marrow transplantation.

    Science.gov (United States)

    van der Merwe, Marie; Abdelsamed, Hossam A; Seth, Aman; Ong, Taren; Vogel, Peter; Pillai, Asha B

    2013-12-01

    We showed previously that nonmyeloablative total lymphoid irradiation/rabbit anti-thymocyte serum (TLI/ATS) conditioning facilitates potent donor-recipient immune tolerance following bone marrow transplantation (BMT) across MHC barriers via recipient invariant NKT (iNKT) cell-derived IL-4-dependent expansion of donor Foxp3(+) naturally occurring regulatory T cells (nTregs). In this study, we report a more specific mechanism. Wild-type (WT) BALB/c (H-2(d)) hosts were administered TLI/ATS and BMT from WT or STAT6(-/-) C57BL/6 (H-2(b)) donors. Following STAT6(-/-) BMT, donor nTregs demonstrated no loss of proliferation in vivo, indicating that an IL-4-responsive population in the recipient, rather than the donor, drives donor nTreg proliferation. In graft-versus-host disease (GVHD) target organs, three recipient CD11b(+) cell subsets (Gr-1(high)CD11c(-), Gr-1(int)CD11c(-), and Gr-1(low)CD11c(+)) were enriched early after TLI/ATS + BMT versus total body irradiation/ATS + BMT. Gr-1(low)CD11c(+) cells induced potent H-2K(b+)CD4(+)Foxp3(+) nTreg proliferation in vitro in 72-h MLRs. Gr-1(low)CD11c(+) cells were reduced significantly in STAT6(-/-) and iNKT cell-deficient Jα18(-/-) BALB/c recipients after TLI/ATS + BMT. Depletion of CD11b(+) cells resulted in severe acute GVHD, and adoptive transfer of WT Gr-1(low)CD11c(+) cells to Jα18(-/-) BALB/c recipients of TLI/ATS + BMT restored day-6 donor Foxp3(+) nTreg proliferation and protection from CD8 effector T cell-mediated GVHD. Blockade of programmed death ligand 1 and 2, but not CD40, TGF-β signaling, arginase 1, or iNOS, inhibited nTreg proliferation in cocultures of recipient-derived Gr-1(low)CD11c(+) cells with donor nTregs. Through iNKT-dependent Th2 polarization, myeloid-derived immunomodulatory dendritic cells are expanded after nonmyeloablative TLI/ATS conditioning and allogeneic BMT, induce PD-1 ligand-dependent donor nTreg proliferation, and maintain potent graft-versus-host immune tolerance.

  18. Polysaccharide Agaricus blazei Murill stimulates myeloid derived suppressor cell differentiation from M2 to M1 type, which mediates inhibition of tumour immune-evasion via the Toll-like receptor 2 pathway.

    Science.gov (United States)

    Liu, Yi; Zhang, Lingyun; Zhu, Xiangxiang; Wang, Yuehua; Liu, WenWei; Gong, Wei

    2015-11-01

    Gr-1(+) CD11b(+) myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing animals and play a critical negative role during tumor immunotherapy. Strategies for inhibition of MDSCs are expected to improve cancer immunotherapy. Polysaccharide Agaricus blazei Murill (pAbM) has been found to have anti-cancer activity, but the underlying mechanism of this is poorly understood. Here, pAbM directly activated the purified MDSCs through inducing the expression of interleukin-6 (IL-6), IL-12, tumour necrosis factor and inducible nitric oxide synthase (iNOS), CD86, MHC II, and pSTAT1 of it, and only affected natural killer and T cells in the presence of Gr-1(+) CD11b(+) monocytic MDSCs. On further analysis, we demonstrated that pAbM could selectively block the Toll-like receptor 2 (TLR2) signal of Gr-1(+) CD11b(+) MDSCs and increased their M1-type macrophage characteristics, such as producing IL-12, lowering expression of Arginase 1 and increasing expression of iNOS. Extensive study showed that Gr-1(+) CD11b(+) MDSCs by pAbM treatment had less ability to convert the CD4(+) CD25(-) cells into CD4(+) CD25(+) phenotype. Moreover, result from selective depletion of specific cell populations in xenograft mice model suggested that the anti-tumour effect of pAbM was dependent on Gr-1(+ ) CD11b(+) monocytes, nether CD8(+) T cells nor CD4(+) T cells. In addition to, pAbM did not inhibit tumour growth in TLR2(-/-) mice. All together, these results suggested that pAbM, a natural product commonly used for cancer treatment, was a specific TLR2 agonist and had potent anti-tumour effects through the opposite of the suppressive function of Gr-1(+) CD11b(+) MDSCs. PMID:26194418

  19. Polysaccharide Agaricus blazei Murill stimulates myeloid derived suppressor cell differentiation from M2 to M1 type, which mediates inhibition of tumour immune-evasion via the Toll-like receptor 2 pathway.

    Science.gov (United States)

    Liu, Yi; Zhang, Lingyun; Zhu, Xiangxiang; Wang, Yuehua; Liu, WenWei; Gong, Wei

    2015-11-01

    Gr-1(+) CD11b(+) myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing animals and play a critical negative role during tumor immunotherapy. Strategies for inhibition of MDSCs are expected to improve cancer immunotherapy. Polysaccharide Agaricus blazei Murill (pAbM) has been found to have anti-cancer activity, but the underlying mechanism of this is poorly understood. Here, pAbM directly activated the purified MDSCs through inducing the expression of interleukin-6 (IL-6), IL-12, tumour necrosis factor and inducible nitric oxide synthase (iNOS), CD86, MHC II, and pSTAT1 of it, and only affected natural killer and T cells in the presence of Gr-1(+) CD11b(+) monocytic MDSCs. On further analysis, we demonstrated that pAbM could selectively block the Toll-like receptor 2 (TLR2) signal of Gr-1(+) CD11b(+) MDSCs and increased their M1-type macrophage characteristics, such as producing IL-12, lowering expression of Arginase 1 and increasing expression of iNOS. Extensive study showed that Gr-1(+) CD11b(+) MDSCs by pAbM treatment had less ability to convert the CD4(+) CD25(-) cells into CD4(+) CD25(+) phenotype. Moreover, result from selective depletion of specific cell populations in xenograft mice model suggested that the anti-tumour effect of pAbM was dependent on Gr-1(+ ) CD11b(+) monocytes, nether CD8(+) T cells nor CD4(+) T cells. In addition to, pAbM did not inhibit tumour growth in TLR2(-/-) mice. All together, these results suggested that pAbM, a natural product commonly used for cancer treatment, was a specific TLR2 agonist and had potent anti-tumour effects through the opposite of the suppressive function of Gr-1(+) CD11b(+) MDSCs.

  20. 靶向髓系抑制性细胞抗肿瘤治疗策略研究进展%Research progress on cancer therapy targeted at myeloid derived suppressor cells

    Institute of Scientific and Technical Information of China (English)

    刘鑫; 李杰

    2010-01-01

    髓系抑制性细胞(MDSC)来源于骨髓祖细胞和未成熟的髓细胞(IMC),在荷瘤小鼠及肿瘤患者的骨髓、脾脏、外周血大量扩增,并募集到肿瘤组织.MDSC高表达精氨酸酶1(ARG1)、一氧化氮合酶(iNOS)、活性氧族(ROS)、过氧亚硝酸盐等介质,通过细胞接触依赖或非依赖方式诱导效应T细胞失能,或诱导调节性T细胞(Treg)等机制,抑制机体的抗肿瘤免疫功能.因此,靶向MDSC抗肿瘤策略成为研究热点,也取得了一定进展,现就当前靶向MDSC抗肿瘤免疫治疗策略及相关机制的研究进展做一简要介绍,为从事该领域的研究者提供参考.%Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of cells of myeloid origin that comprises myeloid progenitor cells and immature macrophages, which expand in tumorbearing mice and patients' bone marrow, spleen and peripheral blood and recruit to the tumor site. MDSC express high levels of arginase 1 (ARG1), inducible-nitric oxide syntheses (iNOS), reactive oxygen species (ROS) and peroxynitrite. They could suppress T-cell functions by cell contact or not, and induce regulatory T cells (Treg), all of the above are its weapons to defend individuals' immune system. Anti-tumor strategies targeted at MDSC develop rapidly now. In this review, we briefly introduce the strategies that targeted at MDSC and their mechanisms.

  1. ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells

    OpenAIRE

    Gallego-Ortega, David; Ledger, Anita; Roden, Daniel L.; Law, Andrew M. K.; Magenau, Astrid; Kikhtyak, Zoya; Cho, Christina; Allerdice, Stephanie L.; Lee, Heather J.; Valdes-Mora, Fatima; Herrmann, David; Salomon, Robert; Young, Adelaide I. J.; Lee, Brian Y.; Sergio, C Marcelo

    2015-01-01

    During pregnancy, the ETS transcription factor ELF5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. In breast cancer, ELF5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. In the mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT) model of luminal breast cancer, induction of ELF5 levels increased leukocyte infiltration, angi...

  2. ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells.

    OpenAIRE

    David Gallego-Ortega; Anita Ledger; Roden, Daniel L.; Law, Andrew M. K.; Astrid Magenau; Zoya Kikhtyak; Christina Cho; Allerdice, Stephanie L.; Lee, Heather J.; Fatima Valdes-Mora; David Herrmann; Robert Salomon; Young, Adelaide I. J.; Lee, Brian Y.; C Marcelo Sergio

    2015-01-01

    During pregnancy, the ETS transcription factor ELF5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. In breast cancer, ELF5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. In the mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT) model of luminal breast cancer, induction of ELF5 levels increased leukocyte infiltration, angi...

  3. Piperlongumine attenuates collagen-induced arthritis via expansion of myeloid-derived suppressor cells and inhibition of the activation of fibroblast-like synoviocytes.

    Science.gov (United States)

    Sun, Jian; Xu, Ping; Du, Xueping; Zhang, Qinggang; Zhu, Yuchang

    2015-04-01

    Piperlonguminine (PL), a key compound from the Piper longum fruit, is known to exhibit anti‑tumor and anti‑inflammatory activities. However, little is known about its effects on collagen‑induced arthritis (CIA). Fibroblast‑like synoviocytes (FLS) have a pivotal role in the development of rheumatoid arthritis (RA). Myeloid‑derived suppressor cells (MDSCs) are able to suppress T cell responses and have important roles in the regulation of autoimmune arthritis. The current study investigated whether PL alters the progression of RA. It was determined that PL reduces the arthritis score and histopathologic lesions in a mouse model of CIA. PL also reduces the expression levels of serum anti‑collagen II antibodies (anti‑CⅡ), tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑1β, IL‑23 and IL‑17 in CIA mice. In draining lymph nodes (DLNs), MDSCs were significantly expanded, however, the number of Th17 cells was markedly decreased by PL treatment. Additionally, PL reduced secretion of IL‑1β, IL‑23 and IL‑17 by TNF‑α‑stimulated human RA FLS. PL significantly inhibited the migration and invasion of TNF‑α‑stimulated human RA FLS. These results indicate that PL may be a candidate therapeutic agent for the treatment of RA, via the expansion of MDSCs and the inhibition of the Th17 response and activation of FLS. PMID:25435301

  4. Relationship between myeloid-derived suppressor cells and related immune cells in the process of tumor progression%髓源性抑制细胞在肿瘤进展过程中与相关免疫细胞的作用

    Institute of Scientific and Technical Information of China (English)

    林生力; 牛伟新

    2013-01-01

    Myeloid-derived suppressor cells are a heterogeneous population of early myeloid progenitors,immature granulocytes,macrophages,and dendritic cells at different stages of differentiation.These cells have the capacity to suppress both the innate immunity response mediated by the cytotoxic natural killer cells and natural killer T cells,and the adaptive immune response mediated by CD4+ and CD8+ T cells.In addition,myeloid-derived suppressor cells have close links with macrophages,dendritic cells,regulate T cells and so on,and also play an important role in the process of tumor progression.%髓源性抑制细胞是一群异质性细胞的统称,包括各种分化状态的骨髓祖细胞、未成熟粒细胞、巨噬细胞和树突细胞等.髓源性抑制细胞可以抑制肿瘤毒性自然杀伤细胞和自然杀伤T细胞介导的固有免疫,以及CD4+CD8+T细胞介导的适应性免疫,并与巨噬细胞、树突细胞、调节性T细胞等有着密切联系,在肿瘤的发生、发展过程中起着重要的作用.

  5. Δ9-Tetrahydrocannabinol-mediated epigenetic modifications elicit myeloid-derived suppressor cell activation via STAT3/S100A8.

    Science.gov (United States)

    Sido, Jessica Margaret; Yang, Xiaoming; Nagarkatti, Prakash S; Nagarkatti, Mitzi

    2015-04-01

    MDSCs are potent immunosuppressive cells that are induced during inflammatory responses, as well as by cancers, to evade the anti-tumor immunity. We recently demonstrated that marijuana cannabinoids are potent inducers of MDSCs. In the current study, we investigated the epigenetic mechanisms through which THC, an exogenous cannabinoid, induces MDSCs and compared such MDSCs with the naïve MDSCs found in BM of BL6 (WT) mice. Administration of THC into WT mice caused increased methylation at the promoter region of DNMT3a and DNMT3b in THC-induced MDSCs, which correlated with reduced expression of DNMT3a and DNMT3b. Furthermore, promoter region methylation was decreased at Arg1 and STAT3 in THC-induced MDSCs, and consequently, such MDSCs expressed higher levels of Arg1 and STAT3. In addition, THC-induced MDSCs secreted elevated levels of S100A8, a calcium-binding protein associated with accumulation of MDSCs in cancer models. Neutralization of S100A8 by use of anti-S100A8 (8H150) in vivo reduced the ability of THC to trigger MDSCs. Interestingly, the elevated S100A8 expression also promoted the suppressive function of MDSCs. Together, the current study demonstrates that THC mediates epigenetic changes to promote MDSC differentiation and function and that S100A8 plays a critical role in this process. PMID:25713087

  6. Distinct microRNA expression profile and targeted biological pathways in functional myeloid-derived suppressor cells induced by Δ9-tetrahydrocannabinol in vivo: regulation of CCAAT/enhancer-binding protein α by microRNA-690.

    Science.gov (United States)

    Hegde, Venkatesh L; Tomar, Sunil; Jackson, Austin; Rao, Roshni; Yang, Xiaoming; Singh, Udai P; Singh, Narendra P; Nagarkatti, Prakash S; Nagarkatti, Mitzi

    2013-12-27

    Δ(9)-Tetrahydrocannabinol (THC), the major bioactive component of marijuana, has been shown to induce functional myeloid-derived suppressor cells (MDSCs) in vivo. Here, we studied the involvement of microRNA (miRNA) in this process. CD11b(+)Gr-1(+) MDSCs were purified from peritoneal exudates of mice administered with THC and used for genome-wide miRNA profiling. Expression of CD31 and Ki-67 confirmed that the THC-MDSCs were immature and proliferating. THC-induced MDSCs exhibited distinct miRNA expression signature relative to various myeloid cells and BM precursors. We identified 13 differentially expressed (>2-fold) miRNA in THC-MDSCs relative to control BM precursors. In silico target prediction for these miRNA and pathway analysis using multiple bioinformatics tools revealed significant overrepresentation of Gene Ontology clusters within hematopoiesis, myeloid cell differentiation, and regulation categories. Insulin-like growth factor 1 signaling involved in cell growth and proliferation, and myeloid differentiation pathways were among the most significantly enriched canonical pathways. Among the differentially expressed, miRNA-690 was highly overexpressed in THC-MDSCs (∼16-fold). Transcription factor CCAAT/enhancer-binding protein α (C/EBPα) was identified as a potential functional target of miR-690. Supporting this, C/EBPα expression was attenuated in THC-MDSCs as compared with BM precursors and exhibited an inverse relation with miR-690. miR-690 knockdown using peptide nucleic acid-antagomiR was able to unblock and significantly increase C/EBPα expression establishing the functional link. Further, CD11b(+)Ly6G(+)Ly6C(+) and CD11b(+)Ly6G(-)Ly6C(+) purified subtypes showed high levels of miR-690 with attenuated C/EBPα expression. Moreover, EL-4 tumor-elicited MDSCs showed increased miR-690 expression. In conclusion, miRNA are significantly altered during the generation of functional MDSC from BM. Select miRNA such as miR-690 targeting genes involved in

  7. 脓毒症时髓源性抑制细胞亚群及其比值的变化%Variation of subsets of myeloid derived suppressor cells and their ratio in septic mice

    Institute of Scientific and Technical Information of China (English)

    王慧; 赵擎宇; 黄朝峰; 赵梅; 徐小谢

    2016-01-01

    Objective To investigate the dynamic variation of subsets of myeloid derived suppressor cells (MDSC) and their ratio in septic mice, and to discuss their role in the development of sepsis. Methods Male C57BL/6 mice were randomly divided into sepsis model group and sham group according to random number table. Polymicrobial sepsis was induced by using cecal ligation and puncture (CLP), while mice in sham group only underwent laparotomy and laparorrhaphy without CLP. Thirty mice in each group were used to observe living condition, and the 20-day survival rate was compared between the two groups. In addition, subsets of MDSC in peripheral blood, spleen and bone marrow were analyzed with flow cytometry for other 60 mice (12 mice at each time point, as 0, 3, 7, 12 and 20 days). Spleens were harvested at 7 days for weighing, and single cell suspension of spleen tissue was prepared for splenocyte counting. Histopathologic changes in spleen tissue and liver tissue were observed under light microscope after hematoxylin and eosin (HE) stain. Results ① No mice died in sham group within 20 days after the operation. On the other hand, 10 mice in model group died within 20 days, and the difference in survival rate between the two groups was statistically significant (100.0% vs. 66.7%, χ2 = 11.861, P = 0.001). ② The spleens in model group showed obvious enlargement and significantly outweighed as compared with those in sham group (mg: 413.33±41.63 vs. 111.67±17.56, t = 11.564, P = 0.000), and the total count of splenocytes was significantly higher than that in sham group (×109/L: 21.20±2.43 vs. 1.87±0.06, t = 13.578, P = 0.005). ③ Pathological sections with HE staining showed that the liver tissue and spleen tissue remained normal in sham group. In model group, the hepatic tissue showed acute inflammatory reaction, including tissue disruption, capillary congestion, infiltration of neutrophils, marked edema of hepatocytes and focal hepatocellular necrosis. Abnormalities

  8. Correlations of the infiltration of myeloid-derived suppressor cells with IL-6 expression and prognosis in patients with breast cancer%乳腺癌髓系来源抑制细胞浸润与IL-6表达水平及患者预后的相关性研究

    Institute of Scientific and Technical Information of China (English)

    陈洁英; 蒋蒙蒙; 于文文; 魏枫; 任秀宝; 于津浦

    2016-01-01

    目的:探讨乳腺癌髓系来源抑制细胞(myeloid-derived suppressor cells,MDSCs)浸润与肿瘤组织原位白介素-6(interleukin-6,IL-6)表达及患者预后的相关性。方法:收集天津医科大学肿瘤医院2012年10月至2014年10月间经手术切除的113例女性乳腺癌石蜡组织切片、上海芯超生物科技有限公司提供的2001年1月至2004年8月经手术切除的女性乳腺癌患者组织芯片140例,免疫组织化学方法检测肿瘤源性IL-6表达水平和MDSCs浸润情况,分析MDSCs的浸润与IL-6表达的相关性,以及MDSCs浸润与临床病理指标及预后的相关性。结果:MDSCs浸润与肿瘤大小、淋巴结受累、病理分期、组织分级和患者预后相关,MDSCs浸润数与IL-6表达水平相关。结论:乳腺癌细胞分泌的IL-6可能是肿瘤局部MDSCs浸润与募集的原因之一,乳腺癌MDSCs浸润可作为患者预后不良的预测因素。%Objective:To investigate the correlation of the infiltration of myeloid-derived suppressor cells (MDSC) with interleukin-6 (IL-6) expression and prognosis in patients with breast cancer. Methods:Tumor tissue slices were obtained from patients with breast can-cer who underwent surgery. The expression of IL-6 and the number of MDSCs were detected through immunohistochemistry analysis. The correlation of MDSC infiltration with IL-6 expression and prognosis in patients with breast cancer was also analyzed. Results:MD-SC infiltration was correlated with the infiltration of lymph nodes, tumor volume, tumor stage, histology grade, and overall survival of the patients. MDSC infiltration was also significantly correlated with IL-6 expression. Conclusion:IL-6 secreted by breast cancer cells may induce local infiltration and aggregation of MDSCs. Increased number of MDSCs could be the negative prognostic factor of pa-tients with breast cancer.

  9. Inhibition of lipopolysaccharide-induced myeloid-derived suppressor cells in the proliferation of spleen T lymphocytes%脂多糖诱导的CD11b+Gr-1+髓源抑制性细胞对小鼠脾脏T细胞增殖的抑制作用

    Institute of Scientific and Technical Information of China (English)

    郑燕妮; 于化鹏; 陈新; 邓火金; 樊慧珍; 龚雨新; 刘俊芳

    2012-01-01

    Objective To explore the effects of lipopolysaccharide (LPS)-induced myeloid-derived suppressor cells (MDSCs) on the proliferation of spleen T lymphocytes.Methods BALB/c mice were randomly divided into two groups:LPS group and normal control group.They were injected intraperitoneally with LPS and normal saline solution respectively.MDSCs were separated with CD11b immunomagnetic beads from the spleen extract of mice. The morphological characteristics of MDCSs were observed by Wright-Giemsa staining and the characteristic molecules on cell surface identified by flow cytometry.And the effects of MDSCs on the in vitro proliferation of T cells were determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT).Results The proportion of MDSCs in the spleen of the LPS group was much more than that of the normal control group ( 27.4% ± 6.6% vs 5.1% ± 3.8% ; t =5.06,P =0.007 ).CD11b + Gr-1 +MDSCs could be separated by CD11b immunomagnetic beads from the spleen of mice injected with LPS at a high purity of 84.0% +4.2%.MTT method showed that the proliferation of T cells decreased significantly after a co-cultivation with CD11 b+ M DSCs versus the control group.And it was positively correlated with the number of M DSCs ( F =46.26,P =0.000 ).Conclusions A high purity of LPS-induced myeloid-derived suppressor cells may be separated with CD11 h immunomagnetic beads.And it has dose-dependent inhibitory effects on the proliferation of the spleen T lymphocytes.%目的 观察脂多糖诱导的CD11b+Gr-1+髓源抑制性细胞(MDSCs)对小鼠脾脏T细胞增殖的影响,探讨其在免疫调控可能发挥的作用.方法 10只6~8周龄BALB/c小鼠随机数字表法随机分为脂多糖组和对照组各5只,分别予脂多糖或生理盐水腹腔注射;采用CD11b磁珠从脾脏组织中分选MDSCs,通过瑞氏-姬姆萨染色观察细胞形态,并用流式细胞术检测细胞表面特征分子表达情况;四唑盐(MTT)比色法测定与MDSCs在体外共培养

  10. 小鼠原位肝癌移植模型中髓系来源抑制性细胞的表达%The expression of myeloid-derived suppressor cells in an orthotopic transplantation liver tumor model in mice

    Institute of Scientific and Technical Information of China (English)

    赵文秀; 张正奇; 许雅苹; 尹震宇; 王效民

    2013-01-01

    目的 观察小鼠原位肝癌移植模型中髓系来源抑制性细胞(MDSCs)的表达.方法 将10只BALB/c小鼠随机分为两组:正常组和荷瘤组,后组是将H22肝癌细胞注射到肝左外叶,制作小鼠原位肝癌移植模型.10d后处死小鼠.流式细胞术检测两组小鼠外周血、骨髓、脾脏及肝脏组织中MDSCs的表达.结果 荷瘤组小鼠外周血、骨髓和脾脏中的MDSCs比例为[(47.73±6.00)、(71.90±4.30)、(11.21±1.19)%],均明显高于正常组小鼠[(18.33±2.31)、(59.03±4.50)、(5.82±0.58)%];正常小鼠肝组织中MDSCs占肝内白细胞6.5%,荷瘤小鼠肝癌组织、癌旁组织中MDSCs占肝内白细胞分别为43.8%和12.8%.结论 在小鼠原位肝癌移植模型中,MDSCs表达明显上调,为研究MDSCs在肝癌发生发展中的作用提供了良好的动物模型.%Objective To investigate the expression of myeloid-derived suppressor cells (MDSCs)in an orthotopic transplantation liver tumour model in BALB/c mice.Methods Ten healthy BALB/c mice were randomly divided into two groups (n =5 each):normal group and tumor-bearing group.The murine hepatic cancer cell line H22 cells were transplanted into the left liver lobe of mice to establish an orthotopic transplantation liver tumor model.The mice were sacrificed at 10th day.The expression of MDSCs in peripheral blood,bone marrow,spleen and liver was analyzed by flow cytometry.Results The presence of CD11b+ Gr-1 + MDSCs was significantly increased in the peripheral blood,bone marrow,and spleen of tumor-bearing mice [(47.73 ±.6.00),(71.90 ±4.30),(11.21 ± 1.19)%] as compared with normal mice [(18.33 ±2.31),(59.03 ±4.50),(5.82 ±0.58)%].The percentage of CD11b+ Gr-1 + MDSCs of intrahepatic leukocytes in normal mice was 6.5%.However,the percentage of MDSCs of intrahepatic leukocytes in tumor and paracancerous tissue was up to 43.8% and 12.8% respectively.Conclusion MDSCs were elevated in an orthotopic transplantation tumor mouse model

  11. Identification and significance of myeloid-derived suppressor cells in peripheral blood of breast cancer patients%乳腺癌患者外周血中髓样抑制细胞的鉴定及其临床意义

    Institute of Scientific and Technical Information of China (English)

    王长青; 赵丹丹; 李慧; 魏刚; 徐贵颖; 王佳铭; 卞隽; 马牧松; 王巍; 许多; 周子君

    2016-01-01

    目的:分析乳腺癌患者外周血中髓样抑制细胞( MDSCs)水平,鉴定乳腺癌特异性MDSCs 的生物学特征并评估其临床意义。方法抽取乳腺癌患者(84例)、乳腺良性肿瘤患者(37例)和健康体检者(21例)静脉血2 ml,其中乳腺癌患者采血时间为新辅助治疗前后或手术治疗前后。采用流式细胞术,通过抗 CD11b、CD33、CD14和 HLA-DR 等荧光抗体鉴定受检者外周血中 MDSCs 的表面标志,并分析 MDSCs 水平与乳腺癌患者临床病理特征的关系。采用体外分离和细胞增殖实验检测 MDSCs 对 T 细胞功能的影响。结果乳腺癌患者外周血中存在 MDSCs,其特征性细胞表面标志为CD11b+CD33+CD14-,CD11b+CD33+CD14-细胞在组织形态上属于单个核细胞。体外实验显示, CD11b+CD33+CD14-细胞能抑制 T 细胞增殖。乳腺癌组、乳腺良性肿瘤组和健康体检组患者外周血中 MDSCs 水平分别为(15.93±3.17)%、(8.92±4.42)%和(5.02±2.75)%,乳腺癌组患者外周血中MDSCs 水平显著高于乳腺良性肿瘤组和健康体检组,差异有统计学意义(P<0.001)。乳腺癌患者外周血中 MDSCs 水平与手术治疗有关,而与患者年龄、肿瘤分期、淋巴结转移、雌激素受体、孕激素受体表达无关。早期乳腺癌患者手术前后的 MDSCs 水平分别为(15.37±2.49)%和(7.83±3.78)%,差异有统计学意义(P<0.001)。结论乳腺癌患者外周血中存在具有疾病特征性的 MDSCs。 CD11b+CD33+CD14-MDSCs 与乳腺癌的发生和发展有关,可以作为一种新的生物标志物用于辅助诊断乳腺癌,并预测乳腺癌的转归。%Objective To investigate the presence, biological features, and clinical significance of myeloid-derived suppressor cells (MDSCs) in breast cancer patients.Methods Eighty-four cases of breast cancer, 37 cases of benign breast

  12. 老年小鼠CD11b+GR-1+髓源性抑制细胞免疫功能特点及机制研究%Study on characteristics and immune mechanisms of CD11b+GR-1+ myeloid-derived suppressor cells in elderly mice

    Institute of Scientific and Technical Information of China (English)

    陈思文; 王翎; 苏楠; 张光波; 刘红梅; 潘旭东; 李洁

    2015-01-01

    目的 以健康青年小鼠为对照,探讨健康老年小鼠CD11b+ GR 1+髓源性抑制细胞(MDSCs)免疫功能特点及机制. 方法 随机选取健康C57BL/6青年鼠(1~2月龄)和老年鼠(>18月龄)各20只,采用免疫磁珠分选法获得足量健康青年鼠、老年鼠脾脏CD11b+ GR-1+ MDSCs,运用溴脱氧尿嘧啶核苷-酶联免疫吸附实验(BrdU Elisa)测定青年鼠、老年鼠CD11b+ GR-1+ MDSCs对T细胞增殖的影响.通过Transwcll小室共培养实验及实时荧光定量PCR法检测青年鼠、老年鼠CD11b+ GR 1+ MDSCs免疫抑制功能的差异. 结果 与青年鼠比较,老年鼠MDSCs能明显抑制T细胞增殖(t=8.67,P<0.001),而这一作用可被Transwell明显逆转(t=6.93,P<0.001);与青年鼠比较,老年鼠MDSCs的精氨酸酶-1、诱导型一氧化氮合成酶、活性氧、白介素-10、白介素-13和转化生长因子-β基因表达量明显增高(t值分别为9.04、4.86、7.04、6.92、4.51、5.46,P<0.05或P<0.01). 结论 健康老年小鼠CD11b+ GR-1+ MDSCs可通过细胞-细胞间接触抑制和分泌免疫抑制性介质两种途径显著抑制T细胞增殖.%Objective To study characteristics and immune mechanisms of CD11b+ GR-1-myeloid-derived suppressor cells (CD11b+ GR 1+ MDSCs) in elderly mice,as compared with those of healthy young mice.Methods Totally 20 healthy C57BL/6 young mice (aged 1-2 months) and 20 elderly mice (aged over 18 months) were randomly chosen and splenetic CD11b+ GR-1+ MDSCs were sorted with the MDSCs Isolation Kit.In vitro assays,the effects of young and elderly CD1 1b+ GR 1+ MDSCs on the proliferation of T cells were determined by Brdu Elisa.Transwell co-culture and real-timePCR were used to identify the mechanisms of different immune suppressive functions of CD11b+GR 1+ MDSCs sorted from young mice and elderly mice.Results Compared with young MDSCs,elderly MDSCs could evidently suppress the proliferation of T cells (t=8.67,P<0.001),and this function could be reversed by trans

  13. Advances in Stem Cell Mobilization

    OpenAIRE

    Hopman, Rusudan K.; DiPersio, John F.

    2014-01-01

    Use of granulocyte colony stimulating factor (G-CSF)–mobilized peripheral blood hematopoietic progenitor cells (HPC) has largely replaced bone marrow (BM) as a source of stem cells for both autologous and allogeneic cell transplantation. With G-CSF alone, up to 35% of patients are unable to mobilize sufficient numbers of CD34 cells/kg to ensure successful and consistent multi-lineage engraftment and sustained hematopoietic recovery. To this end, research is ongoing to identify new agents or c...

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

    Science.gov (United States)

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

    2016-01-01

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

  15. Plerixafor for autologous CD34+ cell mobilization

    Directory of Open Access Journals (Sweden)

    Huda Salman

    2011-02-01

    Full Text Available Huda Salman, Hillard M LazarusDivision of Hematology-Oncology, Blood and Marrow Transplant Program, University Hospitals Case Medical Center, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USAAbstract: High-dose chemotherapy and autologous transplantation of hematopoietic cells is a crucial treatment option for hematologic malignancy patients. Current mobilization regimes often do not provide adequate numbers of CD34+ cells. The chemokine receptor CXCR4 and ligand SDF-1 are integrally involved in homing and mobilization of hematopoietic progenitor cells. Disruption of the CXCR4/SDF-1 axis by the CXCR4 antagonist, plerixafor, has been demonstrated in Phase II and Phase III trials to improve mobilization when used in conjunction with granulocyte colony-stimulating factor (G-CSF. This approach is safe with few adverse events and produces significantly greater numbers of CD34+ cells when compared to G-CSF alone. New plerixafor initiatives include use in volunteer donors for allogeneic hematopoietic cell transplant and in other disease targets.Keywords: plerixafor, autologous hematopoietic cell transplant, CD34, lymphoma, myeloma, granulocyte colony-stimulating factor (G-CSF

  16. Diabetes Impairs Stem Cell and Proangiogenic Cell Mobilization in Humans

    OpenAIRE

    Fadini, Gian Paolo; Albiero, Mattia; Vigili de Kreutzenberg, Saula; Boscaro, Elisa; Cappellari, Roberta; Marescotti, Mariacristina; Poncina, Nicol; Agostini, Carlo; Avogaro, Angelo

    2013-01-01

    OBJECTIVE Diabetes mellitus (DM) increases cardiovascular risk, at least in part, through shortage of vascular regenerative cells derived from the bone marrow (BM). In experimental models, DM causes morphological and functional BM alterations, but information on BM function in human DM is missing. Herein, we sought to assay mobilization of stem and proangiogenic cells in subjects with and without DM. RESEARCH DESIGN AND METHODS In a prospective trial (NCT01102699), we tested BM responsiveness...

  17. Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function

    NARCIS (Netherlands)

    Sander, L.E.; Sackett, S.D.; Dierssen, U.; Beraza, N.; Linke, R.; Müller, M.R.; Blander, J.M.; Tacke, F.; Trautwein, C.

    2010-01-01

    Acute-phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and antiinflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined. Us

  18. Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function

    OpenAIRE

    Sander, L.E.; Sackett, S.D.; Dierssen, U.; Beraza, N.; Linke, R.; Müller, M.R.; Blander, J.M.; Tacke, F; Trautwein, C

    2010-01-01

    Acute-phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and antiinflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined. Using a mouse model of polymicrobial sepsis, we show that abrogation of APP production by hepatocyte-specific gp130 deletion, the signaling receptor shared by IL-6 family cytokines, strongly increase...

  19. Fuel cell technology for prototype logistic fuel cell mobile systems

    Energy Technology Data Exchange (ETDEWEB)

    Sederquist, R.A.; Garow, J.

    1995-08-01

    Under the aegis of the Advanced Research Project Agency`s family of programs to develop advanced technology for dual use applications, International Fuel Cells Corporation (IFC) is conducting a 39 month program to develop an innovative system concept for DoD Mobile Electric Power (MEP) applications. The concept is to integrate two technologies, the phosphoric acid fuel cell (PAFC) with an auto-thermal reformer (ATR), into an efficient fuel cell power plant of nominally 100-kilowatt rating which operates on logistic fuels (JP-8). The ATR fuel processor is the key to meeting requirements for MEP (including weight, volume, reliability, maintainability, efficiency, and especially operation on logistic fuels); most of the effort is devoted to ATR development. An integrated demonstration test unit culminates the program and displays the benefits of the fuel cell system, relative to the standard 100-kilowatt MEP diesel engine generator set. A successful test provides the basis for proceeding toward deployment. This paper describes the results of the first twelve months of activity during which specific program aims have remained firm.

  20. Precise Location Acquisition of Mobility Data Using Cell ID

    Directory of Open Access Journals (Sweden)

    Shafqat Ali Shad

    2012-05-01

    Full Text Available Cellular network data has become a hot source of study for extraction of user-mobility and spatio-temporal trends. Location binding in mobility data can be done through different methods like GPS, service provider assisted faux-GPS and Cell Global Identity (CGI. Among these Cell Global Identity is most inexpensive method and readily available solution for mobility extraction; however exact spatial extraction is somehow a problem in it. This paper presents the spatial extraction technique of mobile phone user raw data which carries the information like location information, proximity location and activity of subjects. This work mainly focuses on the data pre-processing methodology and technique to interpret the low level mobility data into high level mobility information using the designed clustering methodology and publically available Cell-IDs databases. Work proposed the semi- supervised strategy to derive the missing locations thorough the usage of semantic tag information and removal of spatial outliers for precise mobility profile building.

  1. Molecular mobility of scaffolds' biopolymers influences cell growth.

    Science.gov (United States)

    Podlipec, Rok; Gorgieva, Selestina; Jurašin, Darija; Urbančič, Iztok; Kokol, Vanja; Strancar, Janez

    2014-09-24

    Understanding biocompatibility of materials and scaffolds is one of the main challenges in the field of tissue engineering and regeneration. The complex nature of cell-biomaterial interaction requires extensive preclinical functionality testing by studying specific cell responses to different biomaterial properties, from morphology and mechanics to surface characteristics at the molecular level. Despite constant improvements, a more general picture of biocompatibility is still lacking and tailormade scaffolds are not yet available. The scope of our study was thus the investigation of the correlation of fibroblast cell growth on different gelatin scaffolds with their morphological, mechanical as well as surface molecular properties. The latter were thoroughly investigated via polymer molecular mobility studied by site-directed spin labeling and electron paramagnetic resonance spectroscopy (EPR) for the first time. Anisotropy of the rotational motion of the gelatin side chain mobility was identified as the most correlated quantity with cell growth in the first days after adhesion, while weaker correlations were found with scaffold viscoelasticity and no correlations with scaffold morphology. Namely, the scaffolds with highly mobile or unrestricted polymers identified with the cell growth being five times less efficient (N(cells) = 60 ± 25 mm(-2)) as compared to cell growth on the scaffolds with considerable part of polymers with the restricted rotational motion (N(cells) = 290 ± 25 mm(-2)). This suggests that molecular mobility of scaffold components could play an important role in cell response to medical devices, reflecting a new aspect of the biocompatibility concept.

  2. Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Ursula; M; Gehling; Marc; Willems; Kathleen; Schlagner; Ralf; A; Benndorf; Maura; Dandri; Jrg; Petersen; Martina; Sterneck; Joerg-Matthias; Pollok; Dieter; K; Hossfeld; Xavier; Rogiers

    2010-01-01

    AIM:To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells. METHODS:Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry.Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1(SDF-1) were measured using an enzyme linked immunosorbent assay.RESULTS:Progenitor cells with a CD133 + /CD45 + CD14 + phenotype we...

  3. Stress analysis for wall structure in mobile hot cell design

    Energy Technology Data Exchange (ETDEWEB)

    Bahrin, Muhammad Hannan, E-mail: hannan@nuclearmalaysia.gov.my; Rahman, Anwar Abdul, E-mail: anwar@nuclearmalaysia.gov.my; Hamzah, Mohd Arif, E-mail: arif@nuclearmalaysia.gov.my; Mamat, Mohd Rizal; Azman, Azraf; Hasan, Hasni [Prototype and Plant Development Centre, Technical Services Division, Malaysian Nuclear Agency (Malaysia)

    2016-01-22

    Malaysian Nuclear Agency is developing a Mobile Hot Cell (MHC) in order to handle and manage Spent High Activity Radioactive Sources (SHARS) such as teletherapy heads and irradiators. At present, there are only two units of MHC in the world, in South Africa and China. Malaysian Mobile Hot cell is developed by Malaysian Nuclear Agency with the assistance of IAEA expert, based on the design of South Africa and China, but with improved features. Stress analysis has been performed on the design in order to fulfil the safety requirement in operation of MHC. This paper discusses the loading analysis effect from the sand to the MHC wall structure.

  4. Mapping eGFP Oligomer Mobility in Living Cell Nuclei

    OpenAIRE

    Nicolas Dross; Corentin Spriet; Monika Zwerger; Gabriele Müller; Waldemar Waldeck; Jörg Langowski

    2009-01-01

    Movement of particles in cell nuclei can be affected by viscosity, directed flows, active transport, or the presence of obstacles such as the chromatin network. Here we investigate whether the mobility of small fluorescent proteins is affected by the chromatin density. Diffusion of inert fluorescent proteins was studied in living cell nuclei using fluorescence correlation spectroscopy (FCS) with a two-color confocal scanning detection system. We first present experiments exposing FCS-specific...

  5. Mobilization of stem and progenitor cells in cardiovascular diseases

    OpenAIRE

    Wojakowski, W; Landmesser, U.; Bachowski, R; Jadczyk, T; M. Tendera

    2012-01-01

    Circulating bone marrow (BM)-derived stem and progenitor cells (SPCs) participate in turnover of vascular endothelium and myocardial repair after acute coronary syndromes. Acute myocardial infarction (MI) produces a generalized inflammatory reaction, including mobilization of SPCs, increased local production of chemoattractants in the ischemic myocardium, as well as neural and humoral signals activating the SPC egress from the BM. Several types of circulating BM cells were identified in the p...

  6. Mapping eGFP Oligomer Mobility in Living Cell Nuclei

    Science.gov (United States)

    Zwerger, Monika; Müller, Gabriele; Waldeck, Waldemar; Langowski, Jörg

    2009-01-01

    Movement of particles in cell nuclei can be affected by viscosity, directed flows, active transport, or the presence of obstacles such as the chromatin network. Here we investigate whether the mobility of small fluorescent proteins is affected by the chromatin density. Diffusion of inert fluorescent proteins was studied in living cell nuclei using fluorescence correlation spectroscopy (FCS) with a two-color confocal scanning detection system. We first present experiments exposing FCS-specific artifacts encountered in live cell studies as well as strategies to prevent them, in particular those arising from the choice of the fluorophore used for calibration of the focal volume, as well as temperature and acquisition conditions used for fluorescence fluctuation measurements. After defining the best acquisition conditions, we show for various human cell lines that the mobility of GFP varies significantly within the cell nucleus, but does not correlate with chromatin density. The intranuclear diffusional mobility strongly depends on protein size: in a series of GFP-oligomers, used as free inert fluorescent tracers, the diffusion coefficient decreased from the monomer to the tetramer much more than expected for molecules free in aqueous solution. Still, the entire intranuclear chromatin network is freely accessible for small proteins up to the size of eGFP-tetramers, regardless of the chromatin density or cell line. Even the densest chromatin regions do not exclude free eGFP-monomers or multimers. PMID:19347038

  7. Mapping eGFP oligomer mobility in living cell nuclei.

    Directory of Open Access Journals (Sweden)

    Nicolas Dross

    Full Text Available Movement of particles in cell nuclei can be affected by viscosity, directed flows, active transport, or the presence of obstacles such as the chromatin network. Here we investigate whether the mobility of small fluorescent proteins is affected by the chromatin density. Diffusion of inert fluorescent proteins was studied in living cell nuclei using fluorescence correlation spectroscopy (FCS with a two-color confocal scanning detection system. We first present experiments exposing FCS-specific artifacts encountered in live cell studies as well as strategies to prevent them, in particular those arising from the choice of the fluorophore used for calibration of the focal volume, as well as temperature and acquisition conditions used for fluorescence fluctuation measurements. After defining the best acquisition conditions, we show for various human cell lines that the mobility of GFP varies significantly within the cell nucleus, but does not correlate with chromatin density. The intranuclear diffusional mobility strongly depends on protein size: in a series of GFP-oligomers, used as free inert fluorescent tracers, the diffusion coefficient decreased from the monomer to the tetramer much more than expected for molecules free in aqueous solution. Still, the entire intranuclear chromatin network is freely accessible for small proteins up to the size of eGFP-tetramers, regardless of the chromatin density or cell line. Even the densest chromatin regions do not exclude free eGFP-monomers or multimers.

  8. Effects of non-thermal mobile phone radiation on breast adenocarcinoma cells

    OpenAIRE

    Zen Fourie; Dariusz Leszczynski; Sumari Marais; Carin Huyser; Annie M. Joubert; Barend A. Stander

    2011-01-01

    Mobile phone usage currently exceeds landline communication in Africa. The extent of this usage has raised concerns about the long-term health effects of the ongoing use of mobile phones. To assess the physiological effects of radiation from mobile phones in vitro, MCF-7 breast adenocarcinoma cells were exposed to 2W/kg non-thermal 900-MHz mobile phone radiation. The effects investigated were those on metabolic activity, cell morphology, cell cycle progression, phosphatid...

  9. Mobilities

    DEFF Research Database (Denmark)

    simple movements of people, goods, and information from A to B. The ‘mobilities turn’ has made it its hallmark to explore the ‘more than’ effects of a world increasingly on the move. This new title in the Routledge Series ‘Critical Concepts in Built Environment’ creates a state-of-the-art reference work...... to social networks, personal identities, and our relationship to the built environment. The omnipresence of mobilities within everyday life, high politics, technology, and tourism (to mention but a few) all point to a key insight harnessed by the ‘mobilities turn’. Namely that mobilities is much more than...... will cover diverse topics such as theories, concepts, methods, and approaches as well as it will explore various modes of mobilities and the relationship to everyday life practices. The selection also covers the ‘politics of mobilities’ from local urban planning schemes to geopolitical issues of refugees...

  10. Polymer mobility in cell walls of cucumber hypocotyls

    Science.gov (United States)

    Fenwick, K. M.; Apperley, D. C.; Cosgrove, D. J.; Jarvis, M. C.

    1999-01-01

    Cell walls were prepared from the growing region of cucumber (Cucumis sativus) hypocotyls and examined by solid-state 13C NMR spectroscopy, in both enzymically active and inactivated states. The rigidity of individual polymer segments within the hydrated cell walls was assessed from the proton magnetic relaxation parameter, T2, and from the kinetics of cross-polarisation from 1H to 13C. The microfibrils, including most of the xyloglucan in the cell wall, as well as cellulose, behaved as very rigid solids. A minor xyloglucan fraction, which may correspond to cross-links between microfibrils, shared a lower level of rigidity with some of the pectic galacturonan. Other pectins, including most of the galactan side-chain residues of rhamnogalacturonan I, were much more mobile and behaved in a manner intermediate between the solid and liquid states. The only difference observed between the enzymically active and inactive cell walls, was the loss of a highly mobile, methyl-esterified galacturonan fraction, as the result of pectinesterase activity.

  11. A conceptual model of public medical service system based-on cell phone mobile platform

    Science.gov (United States)

    Fu, Hongjiao; Zhao, Yue

    In recent years, cell phones have played an increasingly important role in rapidly-developing global telecommunication services. At present, mobile business develops very fast. However, the development in other mobile service fields, such as public service, mobile medical service, etc, is still in its infant stage. Drawing on the experience of the 'doctor workstation project' which is cooperated by Renmin University of China and Norway Fredskorps Corporation, this paper discusses the research and implementation of the Doctor Workstation System based on cell phone mobile platform. From the practice of the Doctor Workstation System, the paper advances a conceptual model of public medical service system based-on cell phone mobile platform.

  12. Pharmacological inhibition of EGFR signaling enhances G-CSF-induced hematopoietic stem cell mobilization.

    Science.gov (United States)

    Ryan, Marnie A; Nattamai, Kalpana J; Xing, Ellen; Schleimer, David; Daria, Deidre; Sengupta, Amitava; Köhler, Anja; Liu, Wei; Gunzer, Matthias; Jansen, Michael; Ratner, Nancy; Le Cras, Timothy D; Waterstrat, Amanda; Van Zant, Gary; Cancelas, Jose A; Zheng, Yi; Geiger, Hartmut

    2010-10-01

    Mobilization of hematopoietic stem and progenitor cells (HSPCs) from bone marrow into peripheral blood by the cytokine granulocyte colony-stimulating factor (G-CSF) has become the preferred source of HSPCs for stem cell transplants. However, G-CSF fails to mobilize sufficient numbers of stem cells in up to 10% of donors, precluding autologous transplantation in those donors or substantially delaying transplant recovery time. Consequently, new regimens are needed to increase the number of stem cells in peripheral blood upon mobilization. Using a forward genetic approach in mice, we mapped the gene encoding the epidermal growth factor receptor (Egfr) to a genetic region modifying G-CSF-mediated HSPC mobilization. Amounts of EGFR in HSPCs inversely correlated with the cells' ability to be mobilized by G-CSF, implying a negative role for EGFR signaling in mobilization. In combination with G-CSF treatment, genetic reduction of EGFR activity in HSPCs (in waved-2 mutant mice) or treatment with the EGFR inhibitor erlotinib increased mobilization. Increased mobilization due to suppression of EGFR activity correlated with reduced activity of cell division control protein-42 (Cdc42), and genetic Cdc42 deficiency in vivo also enhanced G-CSF-induced mobilization. Our findings reveal a previously unknown signaling pathway regulating stem cell mobilization and provide a new pharmacological approach for improving HSPC mobilization and thereby transplantation outcomes. PMID:20871610

  13. Bone marrow stem cell mobilization in stroke: a ‘bonehead’ may be good after all!

    OpenAIRE

    Borlongan, CV

    2011-01-01

    Mobilizing bone cells to the head, astutely referred to as ‘bonehead’ therapeutic approach, represents a major discipline of regenerative medicine. The last decade has witnessed mounting evidence supporting the capacity of bone marrow (BM)-derived cells to mobilize from BM to peripheral blood (PB), eventually finding their way to the injured brain. This homing action is exemplified in BM stem cell mobilization following ischemic brain injury. Here, I review accumulating laboratory studies imp...

  14. Integrating cell phones and mobile technologies into public health practice: a social marketing perspective.

    Science.gov (United States)

    Lefebvre, Craig

    2009-10-01

    Mobile communications are being used for many purposes, from instant messaging (IM), mobile or microblogging (Twitter), social networking sites (Facebook, MySpace), e-mail to basic voicemail. A brief background on cell phone and mobile technology use in public health is reviewed. The focus of the article is framing the use of mobile technologies in public health from a social marketer's perspective--using the 4 Ps marketing mix as a guide. PMID:19809002

  15. CXCL17 expression by tumor cells recruits CD11b+Gr1 high F4/80- cells and promotes tumor progression.

    Directory of Open Access Journals (Sweden)

    Aya Matsui

    Full Text Available BACKGROUND: Chemokines are involved in multiple aspects of pathogenesis and cellular trafficking in tumorigenesis. In this study, we report that the latest member of the C-X-C-type chemokines, CXCL17 (DMC/VCC-1, recruits immature myeloid-derived cells and enhances early tumor progression. METHODOLOGY/PRINCIPAL FINDINGS: CXCL17 was preferentially expressed in some aggressive types of gastrointestinal, breast, and lung cancer cells. CXCL17 expression did not impart NIH3T3 cells with oncogenic potential in vitro, but CXCL17-expressing NIH3T3 cells could form vasculature-rich tumors in immunodeficient mice. Our data showed that CXCL17-expressing tumor cells increased immature CD11b(+Gr1(+ myeloid-derived cells at tumor sites in mice and promoted CD31(+ tumor angiogenesis. Extensive chemotactic assays proved that CXCL17-responding cells were CD11b(+Gr1(highF4/80(- cells (≈ 90% with a neutrophil-like morphology in vitro. Although CXCL17 expression could not increase the number of CD11b(+Gr1(+ cells in tumor-burdened SCID mice or promote metastases of low metastatic colon cancer cells, the existence of CXCL17-responding myeloid-derived cells caused a striking enhancement of xenograft tumor formation. CONCLUSIONS/SIGNIFICANCE: These results suggest that aberrant expression of CXCL17 in tumor cells recruits immature myeloid-derived cells and promotes tumor progression through angiogenesis.

  16. Electrophoretic mobilities of cultured human embryonic kidney cells in various buffers

    Science.gov (United States)

    1985-01-01

    Data on the electrophoretic mobility distributions of cells in the new D-1 buffer and the interlaboratory standardization of urokinase assay methods are presented. A table of cell strains and recent data on cell dispersal methods are also included. It was decided that glycerol in A-1 electrophoretic mobility data on cultured human embryonic kidney cells subjected to electrophoresis in this buffer. The buffer composition is presented.

  17. Recovery Act: Advanced Direct Methanol Fuel Cell for Mobile Computing

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, James H. [University of North Florida; Cox, Philip [University of North Florida; Harrington, William J [University of North Florida; Campbell, Joseph L [University of North Florida

    2013-09-03

    ABSTRACT Project Title: Recovery Act: Advanced Direct Methanol Fuel Cell for Mobile Computing PROJECT OBJECTIVE The objective of the project was to advance portable fuel cell system technology towards the commercial targets of power density, energy density and lifetime. These targets were laid out in the DOE’s R&D roadmap to develop an advanced direct methanol fuel cell power supply that meets commercial entry requirements. Such a power supply will enable mobile computers to operate non-stop, unplugged from the wall power outlet, by using the high energy density of methanol fuel contained in a replaceable fuel cartridge. Specifically this project focused on balance-of-plant component integration and miniaturization, as well as extensive component, subassembly and integrated system durability and validation testing. This design has resulted in a pre-production power supply design and a prototype that meet the rigorous demands of consumer electronic applications. PROJECT TASKS The proposed work plan was designed to meet the project objectives, which corresponded directly with the objectives outlined in the Funding Opportunity Announcement: To engineer the fuel cell balance-of-plant and packaging to meet the needs of consumer electronic systems, specifically at power levels required for mobile computing. UNF used existing balance-of-plant component technologies developed under its current US Army CERDEC project, as well as a previous DOE project completed by PolyFuel, to further refine them to both miniaturize and integrate their functionality to increase the system power density and energy density. Benefits of UNF’s novel passive water recycling MEA (membrane electrode assembly) and the simplified system architecture it enabled formed the foundation of the design approach. The package design was hardened to address orientation independence, shock, vibration, and environmental requirements. Fuel cartridge and fuel subsystems were improved to ensure effective fuel

  18. Recovery Act: Advanced Direct Methanol Fuel Cell for Mobile Computing

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, James H. [University of North Florida; Cox, Philip [University of North Florida; Harrington, William J [University of North Florida; Campbell, Joseph L [University of North Florida

    2013-09-03

    ABSTRACT Project Title: Recovery Act: Advanced Direct Methanol Fuel Cell for Mobile Computing PROJECT OBJECTIVE The objective of the project was to advance portable fuel cell system technology towards the commercial targets of power density, energy density and lifetime. These targets were laid out in the DOE’s R&D roadmap to develop an advanced direct methanol fuel cell power supply that meets commercial entry requirements. Such a power supply will enable mobile computers to operate non-stop, unplugged from the wall power outlet, by using the high energy density of methanol fuel contained in a replaceable fuel cartridge. Specifically this project focused on balance-of-plant component integration and miniaturization, as well as extensive component, subassembly and integrated system durability and validation testing. This design has resulted in a pre-production power supply design and a prototype that meet the rigorous demands of consumer electronic applications. PROJECT TASKS The proposed work plan was designed to meet the project objectives, which corresponded directly with the objectives outlined in the Funding Opportunity Announcement: To engineer the fuel cell balance-of-plant and packaging to meet the needs of consumer electronic systems, specifically at power levels required for mobile computing. UNF used existing balance-of-plant component technologies developed under its current US Army CERDEC project, as well as a previous DOE project completed by PolyFuel, to further refine them to both miniaturize and integrate their functionality to increase the system power density and energy density. Benefits of UNF’s novel passive water recycling MEA (membrane electrode assembly) and the simplified system architecture it enabled formed the foundation of the design approach. The package design was hardened to address orientation independence, shock, vibration, and environmental requirements. Fuel cartridge and fuel subsystems were improved to ensure effective fuel

  19. Mobile Cell Selection In 4G Long Term Evolution-Advanced (LTE-A Networks

    Directory of Open Access Journals (Sweden)

    Murtadha Ali Nsaif Shukur

    2016-08-01

    Full Text Available With the high demands for broadband mobile wireless communications and the emergence of new wireless multimedia applications constitute the motivation to the development of broadband wireless access technologies in recent years. The Long Term Evolution/System Architecture Evolution (LTE/SAE system has been specified by the Third Generation Partnership Project (3GPP on the way towards fourth-generation (4G mobile to ensure 3GPP keeping the dominance of the cellular communication technologies. Through the design and optimization of new radio access techniques and a further evolution of the LTE-A systems, Cell selection is the process of determining the cell(s that provide service to each mobile station. By study the potential benefits of global cell selection versus the current local mobile SNR-based decision protocol. In particular, and present the new possibility available in OFDMA & SC-FDMA based systems, such as IEEE 802.16m and LTEAdvanced, of satisfying the minimal demand of a mobile station simultaneously by more than one base station. After formalized the problems as an optimization problem; it's present how the mobile unit establishes this connection with the strongest cell station in vicinity. To do this, the mobile unit has to overcome the challenges of estimating the channel to communicate with the cell site and frequency synchronization. Also, multiple mobile units communicate to the same receiver and from various distances. Hence, it is up to the mobile to synchronize itself appropriately to the base stations. LTE-A uses two signals, the Primary Synchronization Signal and the Secondary Synchronization Signal sequentially to determine which of the available cell sites, a mobile would lock in to it. While inter-cell interference (ICI one of problems for the downlink and uplink of multi-cell systems (in general and OFDMA& SC-FDMA networks (in particular.

  20. DI-3-butylphthalide-enhanced hematopoietic stem cell transplantation and endogenous stem cell mobilization for the treatment of cerebral infarcts

    Institute of Scientific and Technical Information of China (English)

    Baoquan Lu; Xiaoming Shang; Yongqiu Li; Hongying Ma; Chunqin Liu; Jianmin Li; Yingqi Zhang; Shaoxin Yao

    2011-01-01

    Exogenous stem cell transplantation and endogenous stem cell mobilization are both effective for the treatment of acute cerebral infarction. The compound dl-3-butylphthalide is known to improve microcirculation and help brain cells at the infarct loci. This experiment aimed to investigate the effects of dl-3-butylphthalide intervention based on the transplantation of hematopoietic stem cells and mobilization of endogenous stem cells in a rat model of cerebral infarction, following middle cerebral artery occlusion. Results showed that neurological function was greatly improved and infarct volume was reduced in rats with cerebral infarction. Data also showed that dl-3-butylphthalide can promote hematopoietic stem cells to transform into vascular endothelial cells and neuronal-like cells, and also enhance the therapeutic effect on cerebral infarction by hematopoietic stem cell transplantation and endogenous stem cell mobilization.

  1. Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice

    Institute of Scientific and Technical Information of China (English)

    TIAN Bei; LI Xiao-xin; SHEN Li; ZHAO Min; YU Wen-zhen

    2010-01-01

    Background Hematopoietic stem cells (HSCs) can be used to deliver functionally active angiostatic molecules to the retinal vasculature by targeting active astrocytes and may be useful in targeting pre-angiogenic retinal lesions. We sought to determine whether HSC mobilization can ameliorate early diabetic retinopathy in mice.Methods Mice were devided into four groups: normal mice control group, normal mice HSC-mobilized group, diabetic mice control group and diabetic mice HSC mobilized group. Murine stem cell growth factor (murine SCF) and recombined human granulocyte colony stimulating factor (rhG-csf) were administered to the mice with diabetes and without diabetes for continuous 5 days to induce autologous HSCs mobilization, and subcutaneous injection of physiological saline was used as control. Immunohistochemical double staining was conducted with anti-mouse rat CD31 monoclonal antibody and anti-BrdU rat antibody.Results Marked HSCs clearly increased after SCF plus G-csf-mobilization. Non-mobilized diabetic mice showed more HSCs than normal mice (P=0.032), and peripheral blood significantly increased in both diabetic and normal mice (P=0.000).Diabetic mice showed more CD31 positive capillary vessels (P=0.000) and accelerated endothelial cell regeneration. Only diabetic HSC-mobilized mice expressed both BrdU and CD31 antigens in the endothelial cells of new capillaries.Conclusion Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice.

  2. Balancing High-Load Scenarios with Next Cell Predictions and Mobility Pattern Recognition

    OpenAIRE

    Michaelis, Stefan

    2012-01-01

    Knowing where a mobile user will be next can deliver a tremendous increase in network performance under high load, as this knowledge enables pro-active load balancing. To derive this information, sequences of traversed cells are fed into pattern detection algorithms. After the training phase the learned model predicts each user’s next cell. Even for complex scenarios, the prediction accuracy can exceed 90%. Predictions are used to rearrange mobile connections in a simulat...

  3. Role of Endogenous Bone Marrow Stem Cells Mobilization in Repair of Damaged Inner Ear in Rats

    OpenAIRE

    Elbana, Ahmed M.; Abdel-Salam, Seddik; Ghada M. Morad; Ahmed A. Omran

    2015-01-01

    Background and Objectives The utilization of the stem cells is widely used in the last few years in different fields of medicine, either by external transplantation or endogenous mobilization, most of these studies still experimental on animals; few were tried on human as in the spinal cord injury or myocardial infarction. As regard its use in the inner ear, stem cell transplantation was examined in many previous studies, while the mobilization idea is a new method to be experimented in inner...

  4. Regulatory Systems in Bone Marrow for Hematopoietic Stem/Progenitor Cells Mobilization and Homing

    Directory of Open Access Journals (Sweden)

    P. Alvarez

    2013-01-01

    Full Text Available Regulation of hematopoietic stem cell release, migration, and homing from the bone marrow (BM and of the mobilization pathway involves a complex interaction among adhesion molecules, cytokines, proteolytic enzymes, stromal cells, and hematopoietic cells. The identification of new mechanisms that regulate the trafficking of hematopoietic stem/progenitor cells (HSPCs cells has important implications, not only for hematopoietic transplantation but also for cell therapies in regenerative medicine for patients with acute myocardial infarction, spinal cord injury, and stroke, among others. This paper reviews the regulation mechanisms underlying the homing and mobilization of BM hematopoietic stem/progenitor cells, investigating the following issues: (a the role of different factors, such as stromal cell derived factor-1 (SDF-1, granulocyte colony-stimulating factor (G-CSF, and vascular cell adhesion molecule-1 (VCAM-1, among other ligands; (b the stem cell count in peripheral blood and BM and influential factors; (c the therapeutic utilization of this phenomenon in lesions in different tissues, examining the agents involved in HSPCs mobilization, such as the different forms of G-CSF, plerixafor, and natalizumab; and (d the effects of this mobilization on BM-derived stem/progenitor cells in clinical trials of patients with different diseases.

  5. Human progenitor cells rapidly mobilized by AMD3100 repopulate NOD/SCID mice with increased frequency in comparison to cells from the same donor mobilized by granulocyte colony stimulating factor

    DEFF Research Database (Denmark)

    Hess, David A; Bonde, Jesper; Craft, Timothy P;

    2007-01-01

    ) or purified CD34(+) cells was compared at limiting dilution into NOD/SCID mice. Human AMD3100-mobilized MNC possessed enhanced repopulating frequency in comparison to G-CSF-mobilized MNC from paired donors, and purified CD34(+) progenitors were at least as efficient as the G-CSF mobilized cells. The...... frequencies of NOD/SCID repopulating cells (SRC) were 1 SRC in 8.7 x 10(6) AMD3100-mobilized MNC compared to 1 SRC in 29.0 x 10(6) G-CSF-mobilized MNC, and 1 SRC in 1.2 x 10(5) AMD3100-mobilized CD34(+) cells compared to 1 SRC in 1.8 x 10(5) G-CSF-mobilized CD34(+) cells. Hematopoietic differentiation of...

  6. Plerixafor for autologous stem-cell mobilization and transplantation for patients in Ontario

    Science.gov (United States)

    Kouroukis, C.T.; Varela, N.P.; Bredeson, C.; Kuruvilla, J.; Xenocostas, A.

    2016-01-01

    Background High-dose chemotherapy with autologous stem-cell transplantation (asct) is an accepted part of standard therapy for patients with hematologic malignancies. Usually, stem-cell mobilization uses granulocyte colony–stimulating factor (g-csf); however, some patients are not able to be mobilized with chemotherapy and g-csf, and such patients could be at higher risk of failing mobilization. Plerixafor is a novel mobilization agent that is absorbed quickly after subcutaneous injection and, at the recommended dose of 0.24 mg/kg, provides a sustained increase in circulating CD34+ cells for 10–18 hours. The main purpose of the present report was to evaluate the most current evidence on the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct for patients in Ontario so as to make recommendations for clinical practice and to assist Cancer Care Ontario in decision-making with respect to this intervention. Methods The medline and embase databases were systematically searched for evidence from January 1996 to March 2015, and the best available evidence was used to draft recommendations relevant to the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct. Final approval of this practice guideline report was obtained from both the Stem Cell Transplant Steering Committee and the Report Approval Panel of the Program in Evidence-Based Care. Recommendations These recommendations apply to adult patients considered for asct: ■ Adding plerixafor to g-csf is an option for initial mobilization in patients with non-Hodgkin lymphoma or multiple myeloma who are eligible for asct when chemotherapy cannot be used and only g-csf mobilization is available.■ For patients with a low peripheral blood CD34+ cell count (for example, <10/μL) at the time of anticipated stem-cell harvesting, or with an inadequate first-day apheresis collection, it is recommended that plerixafor be added to the

  7. Proteomics analysis of human endothelial cells after shortterm exposure to mobile phone radiation

    International Nuclear Information System (INIS)

    Mobile phones have been a part of our everyday life in the developed world since the late 1990s. This has raised concerns over the potential health risks of mobile phone use. Biological and health effects potentially caused by mobile phone radiation have been extensively studied and several biological and medical endpoints have been examined. So far, results have not been conclusive on the potential effects of mobile phone radiation. Mobile phones generate a modulated radio frequency electromagnetic field (RF-EMF), which is a form of non-ionizing radiation. This means that mobile phone radiation does not have enough energy to ionize atoms and it cannot break chemical bonds directly (e.g., in DNA strands). There could, however, be other mechanisms by which mobile phone radiation may affect cellular and physiological functions. Whether these mechanisms exist is unknown. In this thesis, large-scale screening techniques, such as proteomics, were applied to examine changes on the proteome level after exposure to mobile phone radiation. Proteomics techniques allow the screening of several hundreds, and even thousands, of proteins simultaneously, and are thus more efficient than single endpoint techniques. Four different types of human endothelial cells (two cell lines, two types of primary cells) were exposed to two types of mobile phone radiation (900 and 1800 MHz GSM). The proteome of these cells was examined immediately after short-term exposure using two-dimensional gel electrophoresis (2DE). Two protein detection/analysis techniques were used: silver staining for the cell line samples and difference gel electrophoresis (DIGE) for the primary cells. 2DE-DIGE technology is currently a state-of-the-art technique in 2DE studies. Several changes were found in the proteome of the human endothelial cell line EA.hy926 after exposure to 900 MHz GSM mobile phone radiation. In addition, the proteome of a variant of the same cell line, the EA.hy926v1, was affected after 900 MHz

  8. Modification of T cell responses by stem cell mobilization requires direct signaling of the T cell by G-CSF and IL-10

    DEFF Research Database (Denmark)

    MacDonald, Kelli P.A.; Le Texier, Laetitia; Zhang, Ping;

    2014-01-01

    The majority of allogeneic stem cell transplants are currently undertaken using G-CSF mobilized peripheral blood stem cells. G-CSF has diverse biological effects on a broad range of cells and IL-10 is a key regulator of many of these effects. Using mixed radiation chimeras in which......, stem cell mobilization with the CXCR4 antagonist AMD3100 did not alter the donor T cell's ability to induce acute GVHD. These studies provide an explanation for the effects of G-CSF on T cell function and demonstrate that IL-10 is required to license regulatory function but T cell production of IL-10...... is not itself required for the attenuation GVHD. Although administration of CXCR4 antagonists is an efficient means of stem cell mobilization, this fails to evoke the immunomodulatory effects seen during G-CSF mobilization. These data provide a compelling rationale for considering the immunological benefits...

  9. Effects of non-thermal mobile phone radiation on breast adenocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Zen Fourie

    2011-09-01

    Full Text Available Mobile phone usage currently exceeds landline communication in Africa. The extent of this usage has raised concerns about the long-term health effects of the ongoing use of mobile phones. To assess the physiological effects of radiation from mobile phones in vitro, MCF-7 breast adenocarcinoma cells were exposed to 2W/kg non-thermal 900-MHz mobile phone radiation. The effects investigated were those on metabolic activity, cell morphology, cell cycle progression, phosphatidylserine (PS externalisation and the generation of reactive oxygen species and nitrogen species. Statistically insignificant increases in mitochondrial dehydrogenase activity were observed in irradiated cells when compared to controls. Fluorescent detection of F-actin demonstrated an increase in F-actin stress fibre formation in irradiated MCF-7 cells. Cell cycle progression revealed no statistically significant variation. A small increase in early and late apoptotic events in irradiated MCF-7 cells was observed. No statistically significant changes were observed in reactive oxygen and reactive nitrogen species generation. In addition, quantitative and qualitative analyses of cell cycle activity and nuclear and cytosolic changes, respectively, revealed no significant changes. In conclusion, exposure to 1 h of 900-MHz irradiation induced an increase in PS externalisation and an increase in the formation of F-actin stress fibres in MCF-7 cells. Data obtained from this study, and their correlation with other studies, provides intriguing links between radio frequency radiation and cellular events and warrant further investigation.

  10. Using technology to promote mobile learning: engaging students with cell phones in the classroom.

    Science.gov (United States)

    Robb, Meigan; Shellenbarger, Teresa

    2012-01-01

    Advancements in cell phone technology have impacted every aspect of society. Individuals have instant access to social networks, Web sites, and applications. Faculty need to consider using these mobile devices to enrich the classroom. The authors discuss how they successfully designed and incorporated cell phone learning activities into their classrooms. Teaching-learning strategies using cell phone technology and recommendations for overcoming challenges associated with cell phone use in the classroom are discussed. PMID:23086071

  11. Using technology to promote mobile learning: engaging students with cell phones in the classroom.

    Science.gov (United States)

    Robb, Meigan; Shellenbarger, Teresa

    2012-01-01

    Advancements in cell phone technology have impacted every aspect of society. Individuals have instant access to social networks, Web sites, and applications. Faculty need to consider using these mobile devices to enrich the classroom. The authors discuss how they successfully designed and incorporated cell phone learning activities into their classrooms. Teaching-learning strategies using cell phone technology and recommendations for overcoming challenges associated with cell phone use in the classroom are discussed.

  12. G-CSF: From granulopoietic stimulant to bone marrow stem cell mobilizing agent.

    Science.gov (United States)

    Bendall, Linda J; Bradstock, Kenneth F

    2014-08-01

    G-CSF was among the first cytokines to be identified and rapidly transitioned into clinical medicine. Initially used to promote the production of neutrophils in patients with chemotherapy-induced neutropenia it helped to revolutionize the delivery of cancer therapy. Its ability to mobilize hematopoietic stem cells from the bone marrow into the blood was subsequently exploited, changing the face of hematopoietic stem cell transplantation. Today the knowledge gained in unraveling the mechanisms of stem cell mobilization by G-CSF is being explored as a means to increase chemosensitivity in hematological malignancies. This review provides a brief history of G-CSF and then focuses on recent advances in our understanding of G-CSF-induced stem cell mobilization and the potential clinical application of this knowledge in chemo-sensitization. PMID:25131807

  13. Autophagy is required for stem cell mobilization by G-CSF

    DEFF Research Database (Denmark)

    Leveque-El Mouttie, Lucie; Vu, Therese; Lineburg, Katie E.;

    2015-01-01

    Granulocyte colony-stimulating factor (G-CSF) is widely used clinically to prevent neutropenia after cytotoxic chemotherapy and to mobilize hematopoietic stem cells (HSCs) for transplantation. Autophagy, a process of cytoplasmic component recycling, maintains cellular homeostasis and protects...... the cell during periods of metabolic stress or nutrient deprivation. We have observed that G-CSF activates autophagy in neutrophils and HSCs from both mouse and human donors. Furthermore, G-CSF-induced neutrophil and HSC mobilization is impaired in the absence of autophagy. In contrast, autophagy...... is dispensable for direct HSC mobilization in response to the CXCR4 antagonist AMD3100. Altogether, these data demonstrate an important role for G-CSF in invoking autophagy within hematopoietic and myeloid cells and suggest that this pathway is critical for ensuring cell survival in response to clinically...

  14. Measurement of myeloid cell immune suppressive activity.

    Science.gov (United States)

    Dolcetti, Luigi; Peranzoni, Elisa; Bronte, Vincenzo

    2010-11-01

    This unit presents simple methods to assess the immunosuppressive properties of immunoregulatory cells of myeloid origin, such as myeloid-derived suppressor cells (MDSCs), both in vitro and in vivo. These methods are general and could be adapted to test the impact of different suppressive populations on T cell activation, proliferation, and cytotoxic activity; moreover they could be useful to assess the influence exerted on immune suppressive pathways by genetic modifications, chemical inhibitors, and drugs.

  15. Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Peter E Westerweel

    Full Text Available BACKGROUND: Circulating Endothelial Progenitor Cell (EPC levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment. METHODS: Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+Flk-1(+ EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+ hematopoietic progenitor cells (HPC and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. RESULTS: In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. CONCLUSION: EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

  16. Low-mobility solar cells: a device physics primer with application to amorphous silicon

    Energy Technology Data Exchange (ETDEWEB)

    Schiff, E.A. [Syracuse University, New York (United States). Department of Physics

    2003-07-01

    The properties of pin solar cells based on photogeneration of charge carriers into low-mobility materials were calculated for two models. Ideal p- and n-type electrode layers were assumed in both cases. The first, elementary case involves only band mobilities and direct electron-hole recombination. An analytical approximation indicates that the power in thick cells rises as the 1/4 power of the lower band mobility, which reflects the buildup of space-charge under illumination. The approximation agrees well with computer simulation. The second model includes exponential bandtail trapping, which is commonly invoked to account for very low hole drift mobilities in amorphous silicon and other amorphous semiconductors. The two models have similar qualitative behavior. Predictions for the solar conversion efficiency of amorphous silicon-based cells that are limited by valence bandtail trapping are presented. The predictions account adequately for the efficiencies of present a-Si : H cells in their 'as-prepared' state (without light-soaking), and indicate the improvement that may be expected if hole drift mobilities (and valence bandtail widths) can be improved. (author)

  17. Mobility-lifetime product and interface property in amorphous silicon solar cells

    Science.gov (United States)

    Okamoto, H.; Kida, H.; Nonomura, S.; Fukumoto, K.; Hamakawa, Y.

    1983-06-01

    A technique for evaluating the mobility-lifetime product of electrons and holes for amorphous Si solar cells is reported and used to assay the variation of the products with impurity doping, temperature, and prolonged light exposure. The product was examined as a significant indicator of solar cell performance and durability. The a-Si:H cells examined were prepared by an rf technique, and the spectral response of the photocurrent was examined in monochromatic light. The maximum products were observed when small amounts of boron atoms were used as the dopant. The hole lifetime dominated the photoconductivity in undoped and phosphorus doped cells, while the electron lifetime was dominant in boron doped cells. The mobility-lifetime product controlled the effective surface recombination factor. The method was concluded useful for optimizing the material, structure, and manufacturing processes for producing higher performance, reproducible, and stable a-Si:H pin solar cells.

  18. Impaired Endothelial Progenitor Cell Mobilization and Dysfunctional Bone Marrow Stroma in Diabetes Mellitus

    Science.gov (United States)

    Rafii, Shahin; Jaspers, Janneke E.; White, Ian A.; Hooper, Andrea T.; Doevendans, Pieter A.; Verhaar, Marianne C.

    2013-01-01

    Background Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired –at least partly– due to dysfunction of the bone marrow stromal compartment. Methods Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1+Flk-1+ EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34+ hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell–endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. Results In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. Conclusion EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients. PMID:23555959

  19. Electron and Hole Drift Mobility Measurements on Methylammonium Lead Iodide Perovskite Solar Cells

    Energy Technology Data Exchange (ETDEWEB)

    Maynard, Brian; Long, Qi; Schiff, Eric A.; Yang, Mengjin; Zhu, Kai; Kottokkaran, Ranjith; Abbas, Hisham; Dalal, Vikram L.

    2016-04-25

    We report nanosecond domain time-of-flight measurements of electron and hole photocarriers in methylammonium lead iodide perovskite solar cells. The mobilities ranged from 0.06 to 1.4 cm2/Vs at room temperature, but there is little systematic difference between the two carriers. We also find that the drift mobilities are dispersive (time-dependent). The dispersion parameters are in the range of 0.4-0.7, and they imply that terahertz domain mobilities will be much larger than nanosecond domain mobilities. The temperature-dependences of the dispersion parameters are consistent with confinement of electron and hole transport to fractal-like spatial networks within nanoseconds of their photogeneration.

  20. Electron and hole drift mobility measurements on methylammonium lead iodide perovskite solar cells

    Science.gov (United States)

    Maynard, Brian; Long, Qi; Schiff, Eric A.; Yang, Mengjin; Zhu, Kai; Kottokkaran, Ranjith; Abbas, Hisham; Dalal, Vikram L.

    2016-04-01

    We report nanosecond domain time-of-flight measurements of electron and hole photocarriers in methylammonium lead iodide perovskite solar cells. The mobilities ranged from 0.06 to 1.4 cm2/Vs at room temperature, but there is little systematic difference between the two carriers. We also find that the drift mobilities are dispersive (time-dependent). The dispersion parameters are in the range of 0.4-0.7, and they imply that terahertz domain mobilities will be much larger than nanosecond domain mobilities. The temperature-dependences of the dispersion parameters are consistent with confinement of electron and hole transport to fractal-like spatial networks within nanoseconds of their photogeneration.

  1. Mobilization of bone marrow-derived progenitor cells in acute coronary syndromes.

    Directory of Open Access Journals (Sweden)

    Wojciech Wojakowski

    2005-12-01

    Full Text Available Two hypotheses explain the role of adult progenitor cells in myocardial regeneration. Stem cell plasticity which involves mobilization of stem cells from the bone marrow and other niches, homing to the area of tissue injury and transdifferentiation into functional cardiomyocytes. Alternative hypothesis is based on the observations that bone marrow harbors a heterogenous population of cells positive for CXCR4 - receptor for chemokine SDF-1. This population of non-hematopoietic cells expresses genes specific for early muscle, myocardial and endothelial progenitor cells (EPC. These tissue-committed stem cells circulate in the peripheral blood at low numbers and can be mobilized by hematopoietic cytokines in the setting of myocardial ischemia. Endothelial precursors capable of transforming into mature, functional endothelial cells are present in the pool of peripheral mononuclear cells in circulation. Their number significantly increases in acute myocardial infarction (AMI with subsequent decrease after 1 month, as well as in patients with unstable angina in comparison to stable coronary heart disease (CHD. There are numerous physiological and pathological stimuli which influence the number of circulating EPC such as regular physical activity, medications (statins, PPAR-gamma agonists, estrogens, as well as numerous inflammatory and hematopoietic cytokines. Mobilization of stem cells in AMI involves not only the endothelial progenitors but also hematopoietic, non-hematopoietic stem cells and most probably the mesenchymal cells. In healthy subjects and patients with stable CHD, small number of circulating CD34+, CXCR4+, CD117+, c-met+ and CD34/CD117+ stem cells can be detected. In patients with AMI, a significant increase in CD34+/CXCR4+, CD117+, c-met+ and CD34/CD117+ stem cell number the in peripheral blood was demonstrated with parallel increase in mRNA expression for early cardiac, muscle and endothelial markers in peripheral blood mononuclear

  2. Exposure to 3G mobile phone signals does not affect the biological features of brain tumor cells

    OpenAIRE

    Liu, Yu-xiao; Li, Guo-Qing; Fu, Xiang-ping; Xue, Jing-hui; Ji, Shou-Ping; Zhang, Zhi-Wen; Zhang, Yi; Li, An-ming

    2015-01-01

    Background The increase in mobile phone use has generated concerns about possible risks to human health, especially the development of brain tumors. Whether tumor patients should continue to use mobile telephones has remained unclear because of a paucity of information. Herein, we investigated whether electromagnetic fields from mobile phones could alter the biological features of human tumor cells and act as a tumor-promoting agent. Methods Human glioblastoma cell lines, U251-MG and U87-MG, ...

  3. Cell cycle-dependent mobility of Cdc45 determined in vivo by fluorescence correlation spectroscopy.

    Directory of Open Access Journals (Sweden)

    Ronan Broderick

    Full Text Available Eukaryotic DNA replication is a dynamic process requiring the co-operation of specific replication proteins. We measured the mobility of eGFP-Cdc45 by Fluorescence Correlation Spectroscopy (FCS in vivo in asynchronous cells and in cells synchronized at the G1/S transition and during S phase. Our data show that eGFP-Cdc45 mobility is faster in G1/S transition compared to S phase suggesting that Cdc45 is part of larger protein complex formed in S phase. Furthermore, the size of complexes containing Cdc45 was estimated in asynchronous, G1/S and S phase-synchronized cells using gel filtration chromatography; these findings complemented the in vivo FCS data. Analysis of the mobility of eGFP-Cdc45 and the size of complexes containing Cdc45 and eGFP-Cdc45 after UVC-mediated DNA damage revealed no significant changes in diffusion rates and complex sizes using FCS and gel filtration chromatography analyses. This suggests that after UV-damage, Cdc45 is still present in a large multi-protein complex and that its mobility within living cells is consistently similar following UVC-mediated DNA damage.

  4. Augmentation of cutaneous wound healing by pharmacologic mobilization of endogenous bone marrow stem cells.

    Science.gov (United States)

    Tolar, Jakub; McGrath, John A

    2014-09-01

    Novel therapeutic tools to accelerate wound healing would have a major impact on the overall burden of skin disease. Lin et al. demonstrate in mice that endogenous bone marrow stem cell mobilization, produced by a pharmacologic combination of AMD3100 and tacrolimus, leads to faster and better-quality wound healing, findings that have exciting potential for clinical translation. PMID:25120149

  5. Fuel cells in mobile applications; Die Brennstoffzelle im mobilen Einsatz

    Energy Technology Data Exchange (ETDEWEB)

    Friedrich, J.K.H. [Daimler Benz AG, Stuttgart (Germany)

    1996-06-01

    The contribution presents the new electric vehicle developed by Daimler Benz AG, NECAR II (New Electric Car), which is fuelled by fuel cells. The future prospects of this technology are discussed. (MM) [Deutsch] Berichtet wird kurz ueber das von Daimler Benz AG vorgestellte Brennstoffzellen-Elektrofahrzeug NECAR II - New Electric Car - sowie ueber die Zukunftsaussichten dieses Antriebs. (MM) (MM)

  6. Addition of plerixafor for CD34+ cell mobilization in six healthy stem cell donors ensured satisfactory grafts for transplantation

    DEFF Research Database (Denmark)

    Hauge, Anne Werner; Haastrup, Eva Kannik; Sengeløv, Henrik;

    2014-01-01

    In allogeneic hematopoietic stem cell (HSC) transplantation, collection of a sufficient number of HSCs at a fixed time point is crucial. For HSC mobilization into the peripheral blood, the standard regimen, that is, granulocyte-colony-stimulating factor (G-CSF), may be inadequate. Use of plerixafor...... as adjuvant to G-CSF is so far off-label in healthy donors....

  7. Mobilities Mobilities

    Directory of Open Access Journals (Sweden)

    César Pompeyo

    2011-12-01

    Full Text Available Urry, John (2007 Mobilities.Oxford: Polity Press.Urry, John (2007 Mobilities.Oxford: Polity Press.John Urry (1946-, profesor en la Universidad de Lancaster, es un sociólogo de sobra conocido y altamente reputado en el panorama internacional de las ciencias sociales. Su dilatada carrera, aparentemente dispersa y diversificada, ha seguido senderos bastante bien definidos dejando tras de sí un catálogo extenso de obras sociológicas de primer nivel. Sus primeros trabajos se centraban en el campo de la teoría social y la filosofía de las ciencias sociales o de la sociología del poder [...

  8. Cell-wall hemicelluloses as mobile carbon stores in plants

    OpenAIRE

    Schädel, Christina

    2009-01-01

    Hemicelluloses are the second most abundant polysaccharide in nature after cellulose. So far, the chemical heterogeneity of cell-wall hemicelluloses and the relatively large sample-volume required in existing methods represent major obstacles for large-scale, cross-species analyses of this important plant compounds. Here, we apply a new micro-extraction method to analyse hemicelluloses and the ratio of ‘cellulose and lignin’ to hemicelluloses in different tissues of 28 plant species comprisin...

  9. Mobilization of regulatory T cells in response to carotid injury does not influence subsequent neointima formation.

    Directory of Open Access Journals (Sweden)

    Amit Saxena

    Full Text Available AIM: T cells have been attributed an important role in modulating repair responses following vascular injury. The aim of this study was to investigate the role of different T cell subsets in this context. METHODS AND RESULTS: A non-obstructive collar was introduced to inflict carotid artery injury in mice and subsequent activation of immune cells in draining lymph nodes and spleen were studied by flow cytometry. Carotid artery injury of wild type mice was associated with mobilization of both Th1 type CD4(+IFNγ(+ and regulatory CD4(+CD25(+FoxP3(+ T cells in draining lymph nodes. Studies using FoxP3-green fluorescent protein (GFP transgenic C57/Bl6 mice demonstrated scattered presence of regulatory T cells in the adventitial tissue of injured arteries as well as a massive emigration of regulatory T cells from the spleen in response to carotid injury. However, deletion of antigen presentation to CD4+ T cells (H2(0 mice, as well as deletion of regulatory T cells (through treatment with blocking anti-CD25 antibodies, did not affect neointima formation. Also deletion of antigen presentation to CD8(+ T cells (Tap1(0 mice was without effect on carotid collar-induced neointima formation. CONCLUSION: The results demonstrate that carotid artery injury is associated with mobilization of regulatory T cells. Depletion of regulatory T cells does not, however, influence the subsequent repair processes leading to the formation of a neointima. The results also demonstrate that lack of CD8(+ T cells does not influence neointima formation in presence of functional CD4(+ T cells and B cells.

  10. Tbo-Filgrastim versus Filgrastim during Mobilization and Neutrophil Engraftment for Autologous Stem Cell Transplantation.

    Science.gov (United States)

    Elayan, Mohammed M; Horowitz, Justin G; Magraner, Jose M; Shaughnessy, Paul J; Bachier, Carlos

    2015-11-01

    There are limited data available supporting the use of the recombinant granulocyte colony-stimulating factor (G-CSF), tbo-filgrastim, rather than traditionally used filgrastim to mobilize peripheral blood stem cells (PBSC) or to accelerate engraftment after autologous stem cell transplantation (ASCT). We sought to compare the efficacy and cost of tbo-filgrastim to filgrastim in these settings. Patients diagnosed with lymphoma or plasma cell disorders undergoing G-CSF mobilization, with or without plerixafor, were included in this retrospective analysis. The primary outcome was total collected CD34(+) cells/kg. Secondary mobilization endpoints included peripheral CD34(+) cells/μL on days 4 and 5 of mobilization, adjunctive use of plerixafor, CD34(+) cells/kg collected on day 5, number of collection days and volumes processed, number of collections reaching 5 million CD34(+) cells/kg, and percent reaching target collection goal in 1 day. Secondary engraftment endpoints included time to neutrophil and platelet engraftment, number of blood product transfusions required before engraftment, events of febrile neutropenia, and length of stay. A total of 185 patients were included in the final analysis. Patients receiving filgrastim (n = 86) collected a median of 5.56 × 10(6) CD34(+) cells/kg, compared with a median of 5.85 × 10(6) CD34(+) cells/kg in the tbo-filgrastim group (n = 99; P = .58). There were no statistically significant differences in all secondary endpoints with the exception of apheresis volumes processed (tbo-filgrastim, 17.0 liters versus filgrastim, 19.7 liters; P units versus filgrastim, 1.4 units; P = .04). In conclusion, tbo-filgrastim demonstrated similar CD34(+) yield compared with filgrastim in mobilization and post-transplantation settings, with no clinically meaningful differences in secondary efficacy and safety endpoints. Furthermore, tbo-filgrastim utilization was associated with cost savings of approximately $1406 per patient

  11. Encapsulating Mobile Proton Carriers into Structural Defects in Coordination Polymer Crystals: High Anhydrous Proton Conduction and Fuel Cell Application.

    Science.gov (United States)

    Inukai, Munehiro; Horike, Satoshi; Itakura, Tomoya; Shinozaki, Ryota; Ogiwara, Naoki; Umeyama, Daiki; Nagarkar, Sanjog; Nishiyama, Yusuke; Malon, Michal; Hayashi, Akari; Ohhara, Takashi; Kiyanagi, Ryoji; Kitagawa, Susumu

    2016-07-13

    We describe the encapsulation of mobile proton carriers into defect sites in nonporous coordination polymers (CPs). The proton carriers were encapsulated with high mobility and provided high proton conductivity at 150 °C under anhydrous conditions. The high proton conductivity and nonporous nature of the CP allowed its application as an electrolyte in a fuel cell. The defects and mobile proton carriers were investigated using solid-state NMR, XAFS, XRD, and ICP-AES/EA. On the basis of these analyses, we concluded that the defect sites provide space for mobile uncoordinated H3PO4, H2PO4(-), and H2O. These mobile carriers play a key role in expanding the proton-hopping path and promoting the mobility of protons in the coordination framework, leading to high proton conductivity and fuel cell power generation. PMID:27324658

  12. Encapsulating Mobile Proton Carriers into Structural Defects in Coordination Polymer Crystals: High Anhydrous Proton Conduction and Fuel Cell Application.

    Science.gov (United States)

    Inukai, Munehiro; Horike, Satoshi; Itakura, Tomoya; Shinozaki, Ryota; Ogiwara, Naoki; Umeyama, Daiki; Nagarkar, Sanjog; Nishiyama, Yusuke; Malon, Michal; Hayashi, Akari; Ohhara, Takashi; Kiyanagi, Ryoji; Kitagawa, Susumu

    2016-07-13

    We describe the encapsulation of mobile proton carriers into defect sites in nonporous coordination polymers (CPs). The proton carriers were encapsulated with high mobility and provided high proton conductivity at 150 °C under anhydrous conditions. The high proton conductivity and nonporous nature of the CP allowed its application as an electrolyte in a fuel cell. The defects and mobile proton carriers were investigated using solid-state NMR, XAFS, XRD, and ICP-AES/EA. On the basis of these analyses, we concluded that the defect sites provide space for mobile uncoordinated H3PO4, H2PO4(-), and H2O. These mobile carriers play a key role in expanding the proton-hopping path and promoting the mobility of protons in the coordination framework, leading to high proton conductivity and fuel cell power generation.

  13. Conditions for charge transport without recombination in low mobility organic solar cells and photodiodes (Presentation Recording)

    Science.gov (United States)

    Stolterfoht, Martin; Armin, Ardalan; Philippa, Bronson; White, Ronald D.; Burn, Paul L.; Meredith, Paul; Juška, Gytis; Pivrikas, Almantas

    2015-10-01

    Organic semiconductors typically possess low charge carrier mobilities and Langevin-type recombination dynamics, which both negatively impact the performance of organic solar cells and photodetectors. Charge transport in organic solar cells is usually characterized by the mobility-lifetime product. Using newly developed transient and steady state photocurrent measurement techniques we show that the onset of efficiency limiting photocarrier recombination is determined by the charge that can be stored on the electrodes of the device. It is shown that significant photocarrier recombination can be avoided when the total charge inside the device, defined by the trapped, doping-induced and mobile charge carriers, is less than the electrode charge. Based upon this physics we propose the mobility-recombination coefficient product as an alternative and more convenient figure of merit to minimize the recombination losses. We validate the results in 3 different organic semiconductor-based light harvesting systems with very different charge transport properties. The findings allow the determination of the charge collection efficiency in fully operational devices. In turn, knowing the conditions under which non-geminate recombination is eliminated enables one to quantify the generation efficiency of free charge carriers. The results are relevant to a wide range of light harvesting systems, particularly those based upon disordered semiconductors, and require a rethink of the critical parameters for charge transport.

  14. Mobile phone

    International Nuclear Information System (INIS)

    Almost the entire Norwegian population has cell phone. The usefulness of the cell phone is great, but can use a mobile phone to health or discomfort? How can exposure be reduced? NRPA follows research and provides advice on mobile phone use. (AG)

  15. The Change of Mobility and Deformability of Red Cell Membrane in the Patients with Cerebral Infarction

    Institute of Scientific and Technical Information of China (English)

    Wang Hongyu

    2000-01-01

    To study the blood cell hemoyheology,the mobility and deformability of red cell membrane,the activity and assembly of platelets ,the content of cholesterol crvstals and thrombus in circulation in cerebral infarction patientrs. Observing the cell hemorheologi cal condition of the red clee, platelet,cholesterol cryitals, and active thrombus in active blood analysis with Bradford's microscope(15,000 times). The study indicates that in the ceredral infarction patients,the red cell appeared rowleax and its deformbility was poor and its membrane mobility reduvde(P<0.05). In this group blood viscosity was higher, the platelet assembling rate rose and the thrombus in circulation increases more signifi cantly than the nomal group (P<0.01). The change of membrane mobility,the rsising of platelet assemble rate, the in creasing of plasma viscosity and flowing embolism are the important pathological basis of cerebral infarction. It may provide important material and practical meaning for precluding,diagnosing,curing and prognosising ischmia cerebralvas cular diseases.

  16. Endogenous bone marrow stem cell mobilization in rats: Its potential role in homing and repair of damaged inner ear

    OpenAIRE

    Elbana, Ahmed M.; Seddik Abdel-Salam; Ghada M. Morad; Mohamed Ibrahim; Ahmed A. Omran

    2015-01-01

    The stem cells are widely used in the last few years in different fields of medicine, either by external transplantation or endogenous mobilization, most of these studies are still experimental on animals; few were tried on humans as in the spinal cord injury or myocardial infarction. As regards its use in the inner ear, stem cell transplantation was examined in many previous studies, while the mobilization idea is a new method to be experimented in inner ear hair cell regeneration. The ai...

  17. Chinese preparation Xuesaitong promotes the mobilization of bone marrow mesenchymal stem cells in rats with cerebral infarction

    OpenAIRE

    Bao-xia Zhang; Jin-sheng Zhang; Mei-mei Du; Xiao-ya Wang; Wei Li

    2016-01-01

    After cerebral ischemia, bone marrow mesenchymal stem cells are mobilized and travel from the bone marrow through peripheral circulation to the focal point of ischemia to initiate tissue regeneration. However, the number of bone marrow mesenchymal stem cells mobilized into peripheral circulation is not enough to exert therapeutic effects, and the method by which blood circulation is promoted to remove blood stasis influences stem cell homing. The main ingredient of Xuesaitong capsules is Pana...

  18. Proliferation and telomere length in acutely mobilized blood mononuclear cells in HIV infected patients

    DEFF Research Database (Denmark)

    Søndergaard, S R; Essen, M V; Schjerling, P;

    2002-01-01

    The aim of the study was to investigate the mobilization of T cells in response to a stressful challenge (adrenalin stimulation), and to access T cells resided in the peripheral lymphoid organs in HIV infected patients. Seventeen patients and eight HIV seronegative controls received an adrenalin...... infusion for 1 h. Blood was sampled before, during and 1 h after adrenalin infusion. Proliferation and mean telomere restriction fragment length (telomeres) of blood mononuclear cells (BMNC) and purified CD8+ and CD4+ cells were investigated at all time points. In patients, the proliferation to pokeweed...... mitogens (PWM) was lower and decreased more during adrenalin infusion. After adrenalin infusion the proliferation to PWM was restored only in the controls. In all subjects telomeres in CD4+ cells declined during adrenalin infusion. Additionally, the patients had shortened telomeres in their CD8+ cells...

  19. Proton NMR visible mobile lipid signals in sensitive and multidrug-resistant K562 cells are modulated by rafts

    Directory of Open Access Journals (Sweden)

    Leray Geneviève

    2005-02-01

    Full Text Available Abstract Background Most cancer cells are characterized by mobile lipids visible on proton NMR (1H-NMR, these being comprised mainly of methyl and methylene signals from lipid acyl chains. Erythroleukemia K562 cells show narrow signals at 1.3 and 0.9 ppm, corresponding to mobile lipids (methylene and methyl, respectively, which are reduced when K562 cells are multidrug resistant (MDR. While the significance of the mobile lipids is unknown, their subcellular localization is still a matter of debate and may lie in the membrane or the cytoplasm. In this study, we investigate the role of cholesterol in the generation of mobile lipid signals. Results The proportion of esterified cholesterol was found to be higher in K562-sensitive cells than in resistant cells, while the total cholesterol content was identical in both cell lines. Cholesterol extraction in the K562 wild type (K562wt cell line and its MDR counterpart (K562adr, using methyl-β-cyclodextrin, was accompanied by a rise of mobile lipids in K562wt cells only. The absence of caveolae was checked by searching for the caveolin-1 protein in K562wt and K562adr cells. However, cholesterol was enriched in another membrane microdomain designated as "detergent-insoluble glycosphingomyelin complexes" or rafts. These microdomains were studied after extraction with triton X-100, a mild non-ionic detergent, revealing mobile lipid signals preserved only in the K562wt spectra. Moreover, following perturbation/disruption of these microdomains using sphingomyelinase, mobile lipids increased only in K562wt cells. Conclusion These results suggest that cholesterol and sphingomyelin are involved in mobile lipid generation via microdomains of detergent-insoluble glycosphingomyelin complexes such as rafts. Increasing our knowledge of membrane microdomains in sensitive and resistant cell lines may open up new possibilities in resistance reversion.

  20. Restricted mobility of specific functional groups reduces anti-cancer drug activity in healthy cells

    Science.gov (United States)

    Martins, Murillo L.; Ignazzi, Rosanna; Eckert, Juergen; Watts, Benjamin; Kaneno, Ramon; Zambuzzi, Willian F.; Daemen, Luke; Saeki, Margarida J.; Bordallo, Heloisa N.

    2016-03-01

    The most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti-cancer drug into a biocompatible matrix. In-vitro assays indicate that this bio-nanocomposite is able to interact and cause morphological changes in cancer cells. Meanwhile, no alterations were observed in monocytes and fibroblasts, indicating that this system might carry the drug in living organisms with reduced clearance rate and toxicity. X-rays and neutrons were used to investigate the carrier structure, as well as to assess the drug mobility within the bio-nanocomposite. From these unique data we show that partial mobility restriction of active groups of the drug molecule suggests why this carrier design is potentially safer to healthy cells.

  1. Optimization of a Cell Counting Algorithm for Mobile Point-of-Care Testing Platforms

    Directory of Open Access Journals (Sweden)

    DaeHan Ahn

    2014-08-01

    Full Text Available In a point-of-care (POC setting, it is critically important to reliably count the number of specific cells in a blood sample. Software-based cell counting, which is far faster than manual counting, while much cheaper than hardware-based counting, has emerged as an attractive solution potentially applicable to mobile POC testing. However, the existing software-based algorithm based on the normalized cross-correlation (NCC method is too time- and, thus, energy-consuming to be deployed for battery-powered mobile POC testing platforms. In this paper, we identify inefficiencies in the NCC-based algorithm and propose two synergistic optimization techniques that can considerably reduce the runtime and, thus, energy consumption of the original algorithm with negligible impact on counting accuracy. We demonstrate that an AndroidTM smart phone running the optimized algorithm consumes 11.5× less runtime than the original algorithm.

  2. Transplantation of mobilized peripheral blood mononuclear cells for peripheral arterial occlusive disease of the lower extremity

    Institute of Scientific and Technical Information of China (English)

    Xiaofeng YANG; Yanxiang WU; Hongmei WANG; Yifeng XU; Bo XU; Xin LU; Yibin ZANG; Fa WANG; Yue ZHANG

    2006-01-01

    Objectives To assess the clinical efficacy, safety, and feasibility of autologous transplantation of mobilized peripheral blood mononuclear cells (PBMNCs) for patients with peripheral arterial occlusive disease (PAOD) of the lower extremity. Methods A total of 152 patients with PAOD of the lower extremity were enrolled into this non-controlled observational study from November 2003 to March 2006. All patients received subcutaneous injections of recombinant human granulocyte colony-stimulating factor (G-CSF, 450600 μg/day) for 5 days in order to mobilize stem/progenitor cells; their PBMNCs were collected and transplanted by multiple intramuscular injections into ischemic limbs. Patients were followed up for at least 12 weeks. Results At 12 weeks, primarymanifestations,including lower limb pain and coldness, were significantly improved in 137 (90.1%) of the patients; limb ulcers improved or healed in 46 (86.8%) of the 53 patients, while 25 of the 48 (47.9%) patients with limb gangrene remained steady or improved. Ankle-brachial index (ABI) improved in 33 (22%) of the cases, and TcPO2 increased in 45 (30%) of the cases. Angiography before treatment, and at 12 weeks after treatment, was performed in 10 of the patients and showed formation of new collateral vessels. No severe adverse effects or complications specifically related to cell transplantation were observed. Conclusion Autologous transplantation of G-CSF-mobilized PBMNCs might be a safe and effective treatment for lower limb ischemic disorder.(J Geriatr Cardiol 2006; 3:178-80.)

  3. Impact of parathyroid hormone on bone marrow-derived stem cell mobilization and migration

    Institute of Scientific and Technical Information of China (English)

    Bruno; C; Huber; Ulrich; Grabmaier; Stefan; Brunner

    2014-01-01

    Parathyroid hormone(PTH) is well-known as the principal regulator of calcium homeostasis in the human body and controls bone metabolism via actions on the survival and activation of osteoblasts. The intermittent administration of PTH has been shown to stimulate bone production in mice and men and therefore PTH administration has been recently approved for the treatment of osteoporosis. Besides to its physiological role in bone remodelling PTH has been demonstrated to influence and expand the bone marrow stem cell niche where hematopoietic stem cells, capable of both self-renewal and differentiation, reside. Moreover, intermittent PTH treatment is capable to induce mobilization of progenitor cells from the bone marrow into the bloodstream. This novel function of PTH on modulating the activity of the stem cell niche in the bone marrow as well as on mobilization and regeneration of bone marrow-derived stem cells offers new therapeutic options in bone marrow and stem cell transplantation as well as in the field of ischemic disorders.

  4. Impact of parathyroid hormone on bone marrow-derived stem cell mobilization and migration.

    Science.gov (United States)

    Huber, Bruno C; Grabmaier, Ulrich; Brunner, Stefan

    2014-11-26

    Parathyroid hormone (PTH) is well-known as the principal regulator of calcium homeostasis in the human body and controls bone metabolism via actions on the survival and activation of osteoblasts. The intermittent administration of PTH has been shown to stimulate bone production in mice and men and therefore PTH administration has been recently approved for the treatment of osteoporosis. Besides to its physiological role in bone remodelling PTH has been demonstrated to influence and expand the bone marrow stem cell niche where hematopoietic stem cells, capable of both self-renewal and differentiation, reside. Moreover, intermittent PTH treatment is capable to induce mobilization of progenitor cells from the bone marrow into the bloodstream. This novel function of PTH on modulating the activity of the stem cell niche in the bone marrow as well as on mobilization and regeneration of bone marrow-derived stem cells offers new therapeutic options in bone marrow and stem cell transplantation as well as in the field of ischemic disorders. PMID:25426261

  5. HIC-5: A Mobile Molecular Scaffold Regulating the Anchorage Dependence of Cell Growth

    Directory of Open Access Journals (Sweden)

    Motoko Shibanuma

    2012-01-01

    Full Text Available HIC-5 is a multidomain LIM protein homologous to paxillin that serves as a molecular scaffold at focal adhesions and in the nucleus. It forms mobile molecular units with LIM-only proteins, PINCH, and CRP2 and translocates in and out of the nucleus via a nuclear export signal (NES. Of note, NES of HIC-5 is distinctive in its sensitivity to the cellular redox state. Recently, the mobile units of HIC-5 have been suggested to be involved in the regulation of the anchorage dependence of cell growth. On loss of adhesion, an increase in reactive oxygen species in the cells modifies NES and stops shuttling, which leads to cell-cycle control. More specifically, the system circumvents nuclear localization of cyclin D1 and transactivates p21Cip1 in detached cells, thereby avoiding anchorage-independent cell growth. Thus, the HIC-5-LIM only protein complex has emerged as a fail-safe system for regulating the anchorage dependence of cell growth.

  6. Down-Regulated MAC30 Expression Inhibits Proliferation and Mobility of Human Gastric Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xiao-Yan Xu

    2014-05-01

    Full Text Available Background: Gastric cancer is one of the most common cancers in the world. MAC30/Transmembrane protein 97 (TMEM97 is aberrantly up-regulated in many human carcinoma cells. However, the function of MAC30 in gastric carcinoma cells is not studied. Material and Methods: To investigate the function of MAC30 in gastric carcinoma, we used RNA silencing technology to knock down the expression of MAC30 in gastric cancer cells BGC-823 and AGS. Real-time quantitative PCR and Western blot were used to analyze the mRNA level and the related protein expression. The localization of MAC30 and lamellipodia was observed by immunofluorescence. The biological phenotypes of gastric cells were examined by cell proliferation assay, cell cycle analysis, apoptosis assay, cell migration and invasion assay. Results: We found that down-regulation of MAC30 expression efficiently inhibited the proliferation of gastric cancer cells. Furthermore, the mobility of gastric cancer cells was also inhibited by down-regulation of MAC30. Moreover, we found that MAC30 knockdown inhibited AKT phosphorylation and reduced the expression of cyclinB1 and WAVE2. Conclusion: To our knowledge, this is the first report investigating the effect of MAC30 on growth, cell cycle, migration, and invasion in gastric carcinoma cells via suppressing AKT signaling pathway. MAC30 may be a potential therapeutic target for treatment of gastric carcinoma.

  7. Mobilization of CD133+ progenitor cells in patients with acute cerebral infarction.

    Directory of Open Access Journals (Sweden)

    Dominik Sepp

    Full Text Available Progenitor cells (PCs contribute to the endogenous repair mechanism after ischemic events. Interleukin-8 (IL-8 as part of the acute inflammatory reaction may enhance PC mobilization. Also, statins are supposed to alter number and function of circulating PCs. We aimed to investigate PC mobilization after acute ischemic stroke as well as its association with inflammatory markers and statin therapy. Sixty-five patients with ischemic stroke were enrolled in the study. The number of CD133+ PCs was analyzed by flow cytometry. Blood samples were drawn within 24 hours after symptom onset and after 5 days. The number of CD133+ PCs increased significantly within 5 days (p<0.001. We found no correlation between CD133+ PCs and the serum levels of IL-8, IL-6, or C-reactive protein (CRP. Multivariate analysis revealed that preexisting statin therapy correlated independently with the increase of CD133+ PCs (p=0.001. This study showed a mobilization of CD133+ PCs in patients with acute cerebral infarction within 5 days after symptom onset. The early systemic inflammatory response did not seem to be a decisive factor in the mobilization of PCs. Preexisting statin therapy was associated with the increase in CD133+ PCs, suggesting a potentially beneficial effect of statin therapy in patients with stroke.

  8. The cell and the corridor: imprisonment as waiting, and waiting as mobile

    OpenAIRE

    Armstrong, Sarah

    2015-01-01

    Imprisonment is the exemplary symbol of waiting, of being stuck in a space and for a time not of our choosing. This concept of waiting is perfectly represented by the image of the prison cell. In this paper, I contrast the cell with the less familiar imagery of the corridor, a space of prison that evokes and involves mobility. Through this juxtaposition, I aim to show that prisons are as much places of movement as stillness with associated implications for penal power and purpose. I argue tha...

  9. Serpina1 is a potent inhibitor of IL-8-induced hematopoietic stem cell mobilization

    DEFF Research Database (Denmark)

    van Pel, M.; van Os, R.; Velders, G.A.;

    2006-01-01

    Here, we report that cytokine-induced (granulocyte colony-stimulating factor and IL-8) hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) mobilization is completely inhibited after low-dose (0.5 Gy) total-body irradiation (TBI). Because neutrophil granular proteases......-dose TBI, both Serpina1 mRNA and protein concentrations were increased in BM extracts, compared with extracts that were obtained from controls. The inhibitory activity in BM extracts of irradiated mice was reversed by addition of an Ab directed against Serpina1. To further study a possible in vivo role...

  10. Avemar and Echinacea extracts enhance mobilization and homing of CD34+ stem cells in rats with acute myocardial infarction

    OpenAIRE

    Abdelmonem, Maha; Kassem, Samar H.; Gabr, Hala; Shaheen, Amira A.; Aboushousha, Tarek

    2015-01-01

    Introduction Activation of endogenous stem cell mobilization can contribute to myocardial regeneration after ischemic injury. This study aimed to evaluate the possible role of Avemar or Echinacea extracts in inducing mobilization and homing of CD34+ stem cells in relation to the inflammatory and hematopoietic cytokines in rats suffering from acute myocardial infarction (AMI). Methods AMI was developed by two consecutive subcutaneous injections of isoprenaline (85 mg/kg). AMI rats were either ...

  11. Effect of cholesterol liposomes on calcium mobilization in muscle cells from the rabbit sphincter of Oddi

    Institute of Scientific and Technical Information of China (English)

    Xin-Jiang Wang; Jing-Guo Wei; Chun-Mei Wang; Yao-Cheng Wang; Qiu-Zhen Wu; Jia-Kuan Xu; Xiang-Xin Yang

    2002-01-01

    AIM: To analyze the influence of cholesterol liposomes onthe Ca2 + mobilization of cultured muscle cells in the rabbitsphincter of Oddi.METHODS: New Zealand rabbit was sacrificed and thesphincter of Oddi (SO) segement wes obtained aseptically.The SO segment was cut into pieces and cultured in DMEMsolution. Then the smooth muscle cells were subcultured,and the 4th-7th passage cells were used for furtherinvestigation. The intracellular Ca2 + increase was measuredunder confocal microscope after the addition of 20mmol@ L- 1KCl, 10-7 mol @ L-1 acetylcholine and 10-7 mol @ L-1cholecystokinin, and different antagonists were added toanalyze the Ca2+ mobilization pathway. After the cells wereincubated with 1g@ L-1 cholesterol liposome (CL) (rnoarratio wes ~ 2: 1 ), the intracellular Ca2+ increase wasmeasured again to determine the effect of CL on cellularCa2+ mobilization.RESULTS: The resting cellular calcium concentration ofcultured SO cell was 108 ± nmol @ L-1 21 nmol @ L-1. Theintracellular Ca2 + increases induced by 20rmmol@ L- 1 KCl, 10-7mol@ L- 1 ACh and 10-7 mol@ L- 1 CCK were 183% ± 56%, 161%± 52% and 130% ± 43%, respectively. When theextracellular Ca2+ was eliminated by 2mmol@ L-1 EGTA and5μrnol@L-1 verapamil, the intracellular Ca2+ increasesinduced by KCl, ACh and CCK were 20% ± 14%, 82% ± 21%and 104% ± 23%, respectively. After the preincubation withheparin, the Ca2+ increases were 62% ± 23% and 23% ± 19%induced by ACh and CCK, as for preincubation withprocaine they were 72% ± 28% and 85% ± 37% induced byACh and CCK, respectively. Pretreatment with CL for 18h,the resting cellular Ca2 + concentration elevated to 152nmol@L-1 ± 26nmol@ L-1, however, the cellular Ca2+ increasepercentages in response to these agonists were 67% ± 32%,56% ± 33% and 34% ± 15%.CONCLUSION: KCl elicites the SO cellular Ca2+ increasedepends on influx of extracellular Ca2+ , ACh evoked the SOcelllular Ca2+ increase is through the mobilization ofintracellular Ca2+ pool and

  12. Long-Term Outcome after Autologous Stem Cell Transplantation with Adequate Peripheral Blood Stem Cell Mobilization Using Plerixafor and G-CSF in Poor Mobilizer Lymphoma and Myeloma Patients

    Directory of Open Access Journals (Sweden)

    Jan S. Moreb

    2011-01-01

    Full Text Available Poor peripheral blood stem cell (PBSC mobilization predicts worse outcome for myeloma and lymphoma patients post autologous stem cell transplant (ASCT. We hypothesize that PBSC harvest using plerixafor and G-CSF in poor mobilizers may improve long-term outcome. We retrospectively analyzed the data on patients who had second PBSC mobilization using plerixafor and G-CSF as a rescue. Nine lymphoma and 8 multiple myeloma (MM patients received the drug. A control group of 25 MM and lymphoma patients who were good mobilizers with G-CSF only was used for comparison. Sixteen of the 17 poor mobilizers proceeded to ASCT, and one MM patient had tandem transplants. Length of hospital stay, infection incidence, granulocyte engraftment, and long-term hematopoietic recovery were not significantly different between the two groups. In conclusion, all poor mobilizers were able to obtain adequate stem cells transplant dose and had similar transplant course and long-term outcome to that of the control good mobilizers group.

  13. Prevention of diabetic microangiopathy by prophylactic transplant of mobilized peripheral blood mononuclear cells

    Institute of Scientific and Technical Information of China (English)

    Bin ZHOU; Xiao-cang CAO; Zhi-hong FANG; Cui-lin ZHENG; Zhi-bo HAN; He REN; Man-chiu POON; Zhong-chao HAN

    2007-01-01

    Aim: To investigate whether the prophylactic local delivery of mobilized periph-eral blood mononuclear cells (M-PBMNC) could prevent peripheral microangio-pathy in diabetic nude mice. Methods: Diabetic nude mice were induced with intraperitoneal injections of streptozotocin. With the time course of diabetes, we detected the capillary and arteriole density of mice adductor muscles by immuno-histopathy. In situ apoptosis was detected by using TdT-mediated dUTP nick end labeling (TUNEL) methods. M-PBMNC were labeled and locally delivered to the adductor muscles. Mononuclear cells were also isolated and cultured in vitro for the detection and counting of endothelial progenitor cells(EPC). Results: Rarefication of capillaries and arterioles, enhanced apoptosis in adductor muscles,and reduced circulating EPC in diabetic nude mice. Prophylactic local delivery of M-PBMNC halted the progression of microvascular rarefaction in hind-limb skel-etal muscles by inhibiting apoptosis. We detected the survival, migration and incorporation of transplanted M-PBMNC into the murine vasculature in vivo. In addition, more EPC were available from M-PBMNC than non-mobilized cells.Conclusion: These results suggested that the prophylactic local delivery of M-PBMNC may represent a novel approach for the treatment of microvascular complications in diabetics.

  14. Methods to study differences in cell mobility during skin wound healing in vitro.

    Science.gov (United States)

    Monsuur, Hanneke N; Boink, Mireille A; Weijers, Ester M; Roffel, Sanne; Breetveld, Melanie; Gefen, Amit; van den Broek, Lenie J; Gibbs, Susan

    2016-05-24

    Wound healing events which occur in humans are difficult to study in animals due to differences in skin physiology. Furthermore there are increasing restrictions in Europe for using animals for testing the therapeutic properties of new compounds. Therefore, in line with the 3Rs (reduction, refinement and replacement of test animals), a number of human in vitro models of different levels of complexity have been developed to investigate cell mobility during wound healing. Keratinocyte, melanocyte, fibroblast and endothelial cell mobility are described, since these are the residential cells which are responsible for restoring the main structural features of the skin. A monolayer scratch assay is used to study random fibroblast and endothelial cell migration in response to EGF and bFGF respectively and a chemotactic assay is used to study directional fibroblast migration towards CCL5. In order to study endothelial sprouting in response to bFGF or VEGF, which involves continuous degradation and resynthesis of a 3D matrix, a fibrin gel is used. Human physiologically relevant tissue-engineered skin models are used to investigate expansion of the stratified, differentiated epidermis (keratinocytes and melanocytes) over a fibroblast populated dermis and also to study migration and distribution of fibroblasts into the dermis. Together these skin models provide a platform for testing the mode of action of novel compounds for enhanced and scar free wound healing. PMID:26903411

  15. Ion mobility mass spectrometry of peptide, protein, and protein complex ions using a radio-frequency confining drift cell.

    Science.gov (United States)

    Allen, Samuel J; Giles, Kevin; Gilbert, Tony; Bush, Matthew F

    2016-02-01

    Ion mobility mass spectrometry experiments enable the characterization of mass, assembly, and shape of biological molecules and assemblies. Here, a new radio-frequency confining drift cell is characterized and used to measure the mobilities of peptide, protein, and protein complex ions. The new drift cell replaced the traveling-wave ion mobility cell in a Waters Synapt G2 HDMS. Methods for operating the drift cell and determining collision cross section values using this experimental set up are presented within the context of the original instrument control software. Collision cross sections for 349 cations and anions are reported, 155 of which are for ions that have not been characterized previously using ion mobility. The values for the remaining ions are similar to those determined using a previous radio-frequency confining drift cell and drift tubes without radial confinement. Using this device under 2 Torr of helium gas and an optimized drift voltage, denatured and native-like ions exhibited average apparent resolving powers of 14.2 and 16.5, respectively. For ions with high mobility, which are also low in mass, the apparent resolving power is limited by contributions from ion gating. In contrast, the arrival-time distributions of low-mobility, native-like ions are not well explained using only contributions from ion gating and diffusion. For those species, the widths of arrival-time distributions are most consistent with the presence of multiple structures in the gas phase. PMID:26739109

  16. Ion mobility mass spectrometry of peptide, protein, and protein complex ions using a radio-frequency confining drift cell.

    Science.gov (United States)

    Allen, Samuel J; Giles, Kevin; Gilbert, Tony; Bush, Matthew F

    2016-02-01

    Ion mobility mass spectrometry experiments enable the characterization of mass, assembly, and shape of biological molecules and assemblies. Here, a new radio-frequency confining drift cell is characterized and used to measure the mobilities of peptide, protein, and protein complex ions. The new drift cell replaced the traveling-wave ion mobility cell in a Waters Synapt G2 HDMS. Methods for operating the drift cell and determining collision cross section values using this experimental set up are presented within the context of the original instrument control software. Collision cross sections for 349 cations and anions are reported, 155 of which are for ions that have not been characterized previously using ion mobility. The values for the remaining ions are similar to those determined using a previous radio-frequency confining drift cell and drift tubes without radial confinement. Using this device under 2 Torr of helium gas and an optimized drift voltage, denatured and native-like ions exhibited average apparent resolving powers of 14.2 and 16.5, respectively. For ions with high mobility, which are also low in mass, the apparent resolving power is limited by contributions from ion gating. In contrast, the arrival-time distributions of low-mobility, native-like ions are not well explained using only contributions from ion gating and diffusion. For those species, the widths of arrival-time distributions are most consistent with the presence of multiple structures in the gas phase.

  17. Mobile-to-mobile wireless channels

    CERN Document Server

    Zajic, Alenka

    2013-01-01

    Present-day mobile communications systems can be classified as fixed-to-mobile because they allow mobility on only one end (e.g. the mobile phone to a fixed mobile operator's cell tower). In answer to the consumer demand for better coverage and quality of service, emerging mobile-to-mobile (M-to-M) communications systems allow mobile users or vehicles to directly communicate with each other. This practical book provides a detailed introduction to state-of-the-art M-to-M wireless propagation. Moreover, the book offers professionals guidance for rapid implementation of these communications syste

  18. Analytical Investigation and Improvement of Performance of a Proton Exchange Membrane (Pem Fuel Cell in Mobile Applications

    Directory of Open Access Journals (Sweden)

    Khazaee I.

    2015-05-01

    Full Text Available In this study, the performance of a proton exchange membrane fuel cell in mobile applications is investigated analytically. At present the main use and advantages of fuel cells impact particularly strongly on mobile applications such as vehicles, mobile computers and mobile telephones. Some external parameters such as the cell temperature (Tcell , operating pressure of gases (P and air stoichiometry (λair affect the performance and voltage losses in the PEM fuel cell. Because of the existence of many theoretical, empirical and semi-empirical models of the PEM fuel cell, it is necessary to compare the accuracy of these models. But theoretical models that are obtained from thermodynamic and electrochemical approach, are very exact but complex, so it would be easier to use the empirical and smi-empirical models in order to forecast the fuel cell system performance in many applications such as mobile applications. The main purpose of this study is to obtain the semi-empirical relation of a PEM fuel cell with the least voltage losses. Also, the results are compared with the existing experimental results in the literature and a good agreement is seen.

  19. Internal Ca2+ mobilization and secretion in bovine adrenal chromaffin cells

    DEFF Research Database (Denmark)

    Cheek, T R; Thastrup, Ole

    1989-01-01

    Since secretion from intact bovine adrenal chromaffin cells in response to depolarization by nicotine is triggered by a rise in the concentration of intracellular Ca2+ ([Ca2+]i) to about 200-300 nM above basal, it has been assumed that the failure of the inositol 1,4,5-trisphosphate (InsP3......+ store. The role of this Ca2+ store in secretion from bovine adrenal chromaffin cells is therefore unclear. In order to investigate in more detail the role of the InsP3-sensitive Ca2+ store in secretion from these cells, we have used a combination of an InsP3-mobilizing muscarinic agonist...

  20. Amlodipine Ameliorates Ischemia-Induced Neovascularization in Diabetic Rats through Endothelial Progenitor Cell Mobilization.

    Science.gov (United States)

    Sun, Jiayin; Xie, Jun; Kang, Lina; Ferro, Albert; Dong, Li; Xu, Biao

    2016-01-01

    Objectives. We investigated whether amlodipine could improve angiogenic responses in a diabetic rat model of acute myocardial infarction (AMI) through improving bone marrow endothelial progenitor cell (EPC) mobilization, in the same way as angiotensin converting enzyme inhibitors. Methods. After induction of AMI by coronary artery ligation, diabetic rats were randomly assigned to receive perindopril (2 mgkg(-1) day(-1)), amlodipine (2.5 mgkg(-1) day(-1)), or vehicle by gavage (n = 20 per group). Circulating EPC counts before ligation and on days 1, 3, 5, 7, 14, and 28 after AMI were measured in each group. Microvessel density, cardiac function, and cardiac remodeling were assessed 4 weeks after treatment. The signaling pathway related to EPC mobilization was also measured. Results. Circulating EPC count in amlodipine- and perindopril-treated rats peaked at day 7, to an obvious higher level than the control group peak which was reached earlier (at day 5). Rats treated with amlodipine showed improved postischemia neovascularization and cardiac function, together with reduced cardiac remodeling, decreased interstitial fibrosis, and cardiomyocyte apoptosis. Amlodipine treatment also increased cardiac SDF-1/CXCR4 expression and gave rise to activation of VEGF/Akt/eNOS signaling in bone marrow. Conclusions. Amlodipine promotes neovascularization by improving EPC mobilization from bone marrow in diabetic rats after AMI, and activation of VEGF/Akt/eNOS signaling may in part contribute to this. PMID:27243031

  1. Amlodipine Ameliorates Ischemia-Induced Neovascularization in Diabetic Rats through Endothelial Progenitor Cell Mobilization

    Directory of Open Access Journals (Sweden)

    Jiayin Sun

    2016-01-01

    Full Text Available Objectives. We investigated whether amlodipine could improve angiogenic responses in a diabetic rat model of acute myocardial infarction (AMI through improving bone marrow endothelial progenitor cell (EPC mobilization, in the same way as angiotensin converting enzyme inhibitors. Methods. After induction of AMI by coronary artery ligation, diabetic rats were randomly assigned to receive perindopril (2 mgkg−1 day−1, amlodipine (2.5 mgkg−1 day−1, or vehicle by gavage (n=20 per group. Circulating EPC counts before ligation and on days 1, 3, 5, 7, 14, and 28 after AMI were measured in each group. Microvessel density, cardiac function, and cardiac remodeling were assessed 4 weeks after treatment. The signaling pathway related to EPC mobilization was also measured. Results. Circulating EPC count in amlodipine- and perindopril-treated rats peaked at day 7, to an obvious higher level than the control group peak which was reached earlier (at day 5. Rats treated with amlodipine showed improved postischemia neovascularization and cardiac function, together with reduced cardiac remodeling, decreased interstitial fibrosis, and cardiomyocyte apoptosis. Amlodipine treatment also increased cardiac SDF-1/CXCR4 expression and gave rise to activation of VEGF/Akt/eNOS signaling in bone marrow. Conclusions. Amlodipine promotes neovascularization by improving EPC mobilization from bone marrow in diabetic rats after AMI, and activation of VEGF/Akt/eNOS signaling may in part contribute to this.

  2. Connectivity in Later Life: The Declining Age Divide in Mobile Cell Phone Ownership

    OpenAIRE

    Chris Gilleard; Ian Jones; Paul Higgs

    2015-01-01

    In recent decades changes in social connectivity have become key features in the changing contexts of later life. Communities of propinquity no longer seem to be as determining of social relationships as they once were. Mobile cell phone technology and the Internet have redefined what it means to ‘keep in touch’. Some authors have argued that these new forms of connectivity have created a ‘digital divide’ between those who have become active adopters of these technologies and those wh...

  3. A fuel cell energy storage system concept for the Space Station Freedom Extravehicular Mobility Unit

    Science.gov (United States)

    Adlhart, Otto J.; Rosso, Matthew J., Jr.; Marmolejo, Jose

    1989-01-01

    An update is given on work to design and build a Fuel Cell Energy Storage System (FCESS) bench-tested unit for the Space Station Freedom Extravehicular Mobility Unit (EMU). Fueled by oxygen and hydride-stored hydrogen, the FCESS is being considered as an alternative to the EMU zinc-silver oxide battery. Superior cycle life and quick recharge are the main attributes of FCESS. The design and performance of a nonventing, 28 V, 34 Ahr system with 7 amp rating are discussed.

  4. The smart IV stand design through human tracking mobile robot system by CDS cell

    Science.gov (United States)

    Jo, Seong-Hyeon; Choe, Jong-Hun; Seo, Suk-Hyun; Kim, Won-Hoe; Lee, Hong-Kyu; Park, Se-Ho

    2015-03-01

    Vision-based recognition of the object as a general interface gives us high cost and complicated problem. This research suggests human tracking system by Arduino, and Laser-CdS cell system track wire that pass laser line. In this paper, we review existing literature on application systems of recognition which involves many interdisciplinary studies. We conclude that our method can only reduce cost, but is easy way to trace people's location with the use of wire. Furthermore, we apply several recognition systems including CdS-based mobile robot that is applied IV stand used at the hospital effectively.

  5. Evaluation of the Interference of the Microwave Radiation Emitted from GSM Mobile Phones on the Performance of Cell Counters

    Directory of Open Access Journals (Sweden)

    Bahaedini ,N.

    2009-01-01

    Full Text Available Background and Objectives: Incidents related to electromagneticinterference with medical devices have been reported over the past decades.It has also been indicated that the microwave radiation emitted from mobilephones interferes with the operation of medical devices; therefore, this studyaimed at testing the interference by GSM mobile phones with cell counters.Material and Methods: We did this experimental Study on thirty-twoheparinized blood samples of 32 healthy individuals Selected randomly. TheCell Counting was Carried out in the presence of Electro magnetic fieldproduced by three Cell phones with different levels of SAR (Low,intermediate and High and without being in electromagnetic field.Statistical tests were used to analyze the data (p<0.05.Results: Microwave radiation emitted from cell phones, regardless of theirSAR, interferes with the proper operation of cell Counter. This interferenceleads to false Counting.Conclusion: As mobile phones emit microwave radiation in an isotropicmanner, keeping mobile phones at a safe distance, 15cm, from medicalequipments will be necessary. These observations confirm the need for somerestrictions of mobile phone use in hospitals and medical laboratories.Key words: Interference, Cell Counters, Mobile Phone, MicrowaveRadiation

  6. Membrane Protein Mobility and Orientation Preserved in Supported Bilayers Created Directly from Cell Plasma Membrane Blebs.

    Science.gov (United States)

    Richards, Mark J; Hsia, Chih-Yun; Singh, Rohit R; Haider, Huma; Kumpf, Julia; Kawate, Toshimitsu; Daniel, Susan

    2016-03-29

    Membrane protein interactions with lipids are crucial for their native biological behavior, yet traditional characterization methods are often carried out on purified protein in the absence of lipids. We present a simple method to transfer membrane proteins expressed in mammalian cells to an assay-friendly, cushioned, supported lipid bilayer platform using cell blebs as an intermediate. Cell blebs, expressing either GPI-linked yellow fluorescent proteins or neon-green fused transmembrane P2X2 receptors, were induced to rupture on glass surfaces using PEGylated lipid vesicles, which resulted in planar supported membranes with over 50% mobility for multipass transmembrane proteins and over 90% for GPI-linked proteins. Fluorescent proteins were tracked, and their diffusion in supported bilayers characterized, using single molecule tracking and moment scaling spectrum (MSS) analysis. Diffusion was characterized for individual proteins as either free or confined, revealing details of the local lipid membrane heterogeneity surrounding the protein. A particularly useful result of our bilayer formation process is the protein orientation in the supported planar bilayer. For both the GPI-linked and transmembrane proteins used here, an enzymatic assay revealed that protein orientation in the planar bilayer results in the extracellular domains facing toward the bulk, and that the dominant mode of bleb rupture is via the "parachute" mechanism. Mobility, orientation, and preservation of the native lipid environment of the proteins using cell blebs offers advantages over proteoliposome reconstitution or disrupted cell membrane preparations, which necessarily result in significant scrambling of protein orientation and typically immobilized membrane proteins in SLBs. The bleb-based bilayer platform presented here is an important step toward integrating membrane proteomic studies on chip, especially for future studies aimed at understanding fundamental effects of lipid interactions

  7. Eosinophils Modulate CD4+ T Cell Responses via High Mobility Group Box-1 in the Pathogenesis of Asthma

    OpenAIRE

    Shim, Eun-Jin; Chun, Eunyoung; Lee, Hyun-Seung; Bang, Bo-Ram; Cho, Sang-Heon; Min, Kyung-Up; Park, Heung-Woo

    2014-01-01

    Eosinophils have been reported to modulate T cell responses. Previously, we reported that high-mobility group box 1 protein (HMGB1) played a key role in the pathogenesis of asthma. This study was conducted to test our hypothesis that eosinophils could modulate T cell responses via HMGB1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation. We performed in vitro experiments using eosinophils, dendritic cells (DCs), and CD4+ T cells obtained from a murine model of ast...

  8. VEGFR2-Mediated Vascular Dilation as a Mechanism of VEGF-Induced Anemia and Bone Marrow Cell Mobilization

    Directory of Open Access Journals (Sweden)

    Sharon Lim

    2014-10-01

    Full Text Available Molecular mechanisms underlying tumor VEGF-induced host anemia and bone marrow cell (BMC mobilization remain unknown. Here, we report that tumor VEGF markedly induced sinusoidal vasculature dilation in bone marrow (BM and BMC mobilization to tumors and peripheral tissues in mouse and human tumor models. Unexpectedly, anti-VEGFR2, but not anti-VEGFR1, treatment completely blocked VEGF-induced anemia and BMC mobilization. Genetic deletion of Vegfr2 in endothelial cells markedly ablated VEGF-stimulated BMC mobilization. Conversely, deletion of the tyrosine kinase domain from Vegfr1 gene (Vegfr1TK−/− did not affect VEGF-induced BMC mobilization. Analysis of VEGFR1+/VEGFR2+ populations in peripheral blood and BM showed no significant ratio difference between VEGF- and control tumor-bearing animals. These findings demonstrate that vascular dilation through the VEGFR2 signaling is the mechanism underlying VEGF-induced BM mobilization and anemia. Thus, our data provide mechanistic insights on VEGF-induced BMC mobilization in tumors and have therapeutic implications by targeting VEGFR2 for cancer therapy.

  9. Mobilization of endothelial precursor cells: systemic vascular response to musculoskeletal trauma.

    LENUS (Irish Health Repository)

    Laing, A J

    2012-02-03

    Postnatal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells (EPC) migrate, differentiate, and incorporate into the nacent endothelium contributing to physiological and pathological neovascularization, has stimulated much interest. Its contribution to tumor nonvascularization, wound healing, and revascularization associated with skeletal and cardiac muscles ischaemia is established. We evaluated the mobilization of EPCs in response to musculoskeletal trauma. Blood from patients (n = 15) following AO type 42a1 closed diaphyseal tibial fractures was analyzed for CD34 and AC133 cell surface marker expression. Immunomagnetically enriched CD34+ mononuclear cell (MNC(CD34+)) populations were cultured and examined for phenotypic and functional vascular endothelial differentiation. Circulating MNC(CD34+) levels increased sevenfold by day 3 postinjury. Circulating MNC(AC133+) increased 2.5-fold. Enriched MNC(CD34+) populations from day 3 samples in culture exhibited cell cluster formation with sprouting spindles. These cells bound UEA-1 and incorporated fluorescent DiI-Ac-LDL intracellularily. Our findings suggest a systemic provascular response is initiated in response to musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of fracture healing.

  10. Mobilization of hematopoietic progenitor cells from allogeneic healthy donors using a new biosimilar G-CSF (Zarzio®).

    Science.gov (United States)

    Antelo, María Luisa; Zabalza, Amaya; Sánchez Antón, María Piva; Zalba, Saioa; Aznar, Mariví; Mansilla, Cristina; Ramírez, Natalia; Olavarría, Eduardo

    2016-02-01

    Peripheral blood progenitor cells (PBPCs) have become the major source of hematopoietic progenitor cells for allogeneic transplantation. In February 2008, Zarzio® was approved by the European Medicine Agency for PBPCs mobilization, but this authorization was not based in trials analyzing safety and efficacy for PBPCs mobilization. Since August 2011, Zarzio® has been used at our institution for PBPCs mobilization. In total 36 healthy family donors underwent PBPCs mobilization, 18 with Neupogen® and 18 with Zarzio®. Donor characteristics were equivalent between groups, and no severe adverse effects were registered in the Zarzio® group. The number of CD34 cells collected/Kg recipient body weight was 6.7 × 10(6) (3.8-11.1) in the Zarzio® group versus 8.4 × 10(6) (5.6-16.6) in the Neupogen® group (P = 0.04). We collected the minimal target cell dose (2 × 10(6) /kg) in all donors from each group and no significant differences were found in the collection of the optimal cell dose (5 × 10(6) /kg) between groups, although 3/18 (16.6%) donors that received Zarzio® failed to mobilize the optimal cell dose compared with 0% in the Neupogen® group. A total of 35 patients proceeded to transplantation (17 in the Zarzio® and 18 in the Neupogen® groups, respectively). Platelet and neutrophil median time to engraftment was comparable between the two groups. Our retrospective study supports the conclusion that Zarzio® mobilization of PBPCs in healthy donors is safe but perhaps not as effective as the reference Neupogen. However, more prospective trials are required to definitively asses the safety and efficacy of G-CSF biosimilars for PBPCs mobilization in healthy donors. PMID:26011178

  11. Stem Cell Mobilization with G-CSF versus Cyclophosphamide plus G-CSF in Mexican Children

    Directory of Open Access Journals (Sweden)

    José Eugenio Vázquez Meraz

    2016-01-01

    Full Text Available Fifty-six aphaereses were performed in 23 pediatric patients with malignant hematological and solid tumors, following three different protocols for PBPC mobilization and distributed as follows: A: seventeen mobilized with 4 g/m2 of cyclophosphamide (CFA and 10 μg/kg/day of granulocyte colony stimulating factor (G-CSF, B: nineteen with CFA + G-CSF, and C: twenty only with G-CSF when the WBC count exceeded 10 × 109/L. The average number of MNC/kg body weight (BW/aphaeresis was 0.4 × 108 (0.1–1.4, 2.25 × 108 (0.56–6.28, and 1.02 × 108 (0.34–2.5 whereas the average number of CD34+ cells/kg BW/aphaeresis was 0.18 × 106/kg (0.09–0.34, 1.04 × 106 (0.19–9.3, and 0.59 × 106 (0.17–0.87 and the count of CFU/kg BW/aphaeresis was 1.11 × 105 (0.31–2.12, 1.16 × 105 (0.64–2.97, and 1.12 × 105 (0.3–6.63 in groups A, B, and C, respectively. The collection was better in group B versus group A (p=0.007 and p=0.05, resp. and in group C versus group A (p=0.08 and p=0.05, resp.. The collection of PBPCs was more effective in the group mobilized with CFM + G-CSF when the WBC exceeded 10 × 103/μL in terms of MNC and CD34+ cells and there was no toxicity of the chemotherapy.

  12. Infection Mobilizes Hematopoietic Stem Cells through Cooperative NOD-like Receptor and Toll-like Receptor Signaling

    OpenAIRE

    Burberry, Aaron; Zeng, Melody Y.; Ding, Lei; Wicks, Ian; Inohara, Naohiro; Morrison, Sean J; Núñez, Gabriel

    2014-01-01

    Adult hematopoietic stem cells (HSCs) are maintained in specialized niches within the bone marrow under steady-state conditions and mobilized for extramedullary hematopoiesis during periods of stress such as bacterial infections. However, the underlying mechanisms are unclear. We show that systemic infection of mice with Escherichia coli, commonly associated with bacteremia in humans, mobilizes functional HSCs to the spleen. Accumulation of splenic HSCs (CD150+CD48-Lin−/lowScal1+cKit+) was di...

  13. Controlled method of reducing electrophoretic mobility of macromolecules, particles, or cells

    Science.gov (United States)

    Vanalstine, James M. (Inventor)

    1992-01-01

    A method of reducing electrophoretic mobility of macromolecules, particles, cells, and other substances is provided which comprises interacting in a conventional electrophoretic separating procedure, the substances with a polymer-linked affinity compound comprised of a hydrophilic neutral polymer such as polyethylene glycol bound to a second component such as a hydrophobic compound, an immunocompound such as an antibody or antibody active fragment, or a ligand such as a hormone, drug, antigen, or a hapten. The reduction of electrophoretic mobility achieved is directly proportional to the concentration of the polymer-linked affinity compound employed, and such reduction can comprise up to 100 percent for particular particles and cells. The present invention is advantageous in that electrophoretic separation can now be achieved for substances whose native surface charge structure had prevented them from being separated by normal electrophoretic means. Depending on the affinity component utilized, separation can be achieved on the basis of the specific/irreversible, specific/reversible, semi-specific/reversible, relatively nonspecific/reversible, or relatively nonspecific/irreversible ligand-substance interactions.

  14. Species-specific cell mobility of bacteria-feeding myxamoebae in plasmodial slime molds.

    Science.gov (United States)

    Hoppe, Thomas; Kutschera, Ulrich

    2015-01-01

    On decaying wood or litter in forests, plasmodial slime molds (myxomycetes) represent a large fraction of eukaryotic protists that feed on bacteria. In his seminal book Experimental Physiology of Plants (1865), Julius Sachs referred to the multinucleate plasmodium of myxomycetes, which were considered at that time as primitive plants (or fungi). Today it is well established that myxomycetes are members of the Amoebozoa (Protista). In this study we compare the mobility of myxamoebae of 3 European species, Lycogala epidendrum (order Liceales), Tubulifera arachnoidea, and Trichia decipiens (order Trichiales). Using agar plates, on which 3 separate bacterial species were cultivated as prey organisms (Methylobacterium mesophilicum, Escherichia coli, Agrobacterium tumefaciens), we document large differences in cell motility between the myxomycetes investigated. In addition, we show that the 3 species of myxamoebae can be distinguished based on their average cell size. These data shed light on the mode of co-occurrence via differential substrate utilization in these members of the Amoebozoa. PMID:26357877

  15. Potentiation of NMDA receptor-dependent cell responses by extracellular high mobility group box 1 protein.

    Directory of Open Access Journals (Sweden)

    Marco Pedrazzi

    Full Text Available BACKGROUND: Extracellular high mobility group box 1 (HMGB1 protein can operate in a synergistic fashion with different signal molecules promoting an increase of cell Ca(2+ influx. However, the mechanisms responsible for this effect of HMGB1 are still unknown. PRINCIPAL FINDINGS: Here we demonstrate that, at concentrations of agonist per se ineffective, HMGB1 potentiates the activation of the ionotropic glutamate N-methyl-D-aspartate receptor (NMDAR in isolated hippocampal nerve terminals and in a neuroblastoma cell line. This effect was abolished by the NMDA channel blocker MK-801. The HMGB1-facilitated NMDAR opening was followed by activation of the Ca(2+-dependent enzymes calpain and nitric oxide synthase in neuroblastoma cells, resulting in an increased production of NO, a consequent enhanced cell motility, and onset of morphological differentiation. We have also identified NMDAR as the mediator of HMGB1-stimulated murine erythroleukemia cell differentiation, induced by hexamethylenebisacetamide. The potentiation of NMDAR activation involved a peptide of HMGB1 located in the B box at the amino acids 130-139. This HMGB1 fragment did not overlap with binding sites for other cell surface receptors of HMGB1, such as the advanced glycation end products or the Toll-like receptor 4. Moreover, in a competition assay, the HMGB1((130-139 peptide displaced the NMDAR/HMGB1 interaction, suggesting that it comprised the molecular and functional site of HMGB1 regulating the NMDA receptor complex. CONCLUSION: We propose that the multifunctional cytokine-like molecule HMGB1 released by activated, stressed, and damaged or necrotic cells can facilitate NMDAR-mediated cell responses, both in the central nervous system and in peripheral tissues, independently of other known cell surface receptors for HMGB1.

  16. Embodied Germ Cell at Work: Building an Expansive Concept of Physical Mobility in Home Care

    Science.gov (United States)

    Engestrom, Yrjo; Nummijoki, Jaana; Sannino, Annalisa

    2012-01-01

    This article presents a process of collective formation of a new concept of mobility between home care workers and their elderly clients, who are at risk of losing physical mobility and functional capacity. A new tool called mobility agreement was introduced to facilitate the inclusion of regular mobility exercises in home care visits and in the…

  17. Condensin II subunit dCAP-D3 restricts retrotransposon mobilization in Drosophila somatic cells.

    Directory of Open Access Journals (Sweden)

    Andrew T Schuster

    2013-10-01

    Full Text Available Retrotransposon sequences are positioned throughout the genome of almost every eukaryote that has been sequenced. As mobilization of these elements can have detrimental effects on the transcriptional regulation and stability of an organism's genome, most organisms have evolved mechanisms to repress their movement. Here, we identify a novel role for the Drosophila melanogaster Condensin II subunit, dCAP-D3 in preventing the mobilization of retrotransposons located in somatic cell euchromatin. dCAP-D3 regulates transcription of euchromatic gene clusters which contain or are proximal to retrotransposon sequence. ChIP experiments demonstrate that dCAP-D3 binds to these loci and is important for maintaining a repressed chromatin structure within the boundaries of the retrotransposon and for repressing retrotransposon transcription. We show that dCAP-D3 prevents accumulation of double stranded DNA breaks within retrotransposon sequence, and decreased dCAP-D3 levels leads to a precise loss of retrotransposon sequence at some dCAP-D3 regulated gene clusters and a gain of sequence elsewhere in the genome. Homologous chromosomes exhibit high levels of pairing in Drosophila somatic cells, and our FISH analyses demonstrate that retrotransposon-containing euchromatic loci are regions which are actually less paired than euchromatic regions devoid of retrotransposon sequences. Decreased dCAP-D3 expression increases pairing of homologous retrotransposon-containing loci in tissue culture cells. We propose that the combined effects of dCAP-D3 deficiency on double strand break levels, chromatin structure, transcription and pairing at retrotransposon-containing loci may lead to 1 higher levels of homologous recombination between repeats flanking retrotransposons in dCAP-D3 deficient cells and 2 increased retrotransposition. These findings identify a novel role for the anti-pairing activities of dCAP-D3/Condensin II and uncover a new way in which dCAP-D3/Condensin

  18. Measuring the complete cross-cell carrier mobility distributions in bulk heterojunction solar cells

    Science.gov (United States)

    Seifter, Jason; Sun, Yanming; Choi, Hyosung; Lee, Byoung Hoon; Heeger, Alan

    2015-03-01

    Carbon nanotube-enabled, vertical, organic field effect transistors (CN-VFETs) based on the small molecule dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT) have demonstrated high current, low-power operation suitable for driving active matix organic light emitting diode (AMOLED) displays. This performance is achieved without the need for costly high-resolution patterning, despite the low mobility of the organic semiconductor, by employing sub-micron channel widths, defined in the vertical devices by the thickness of the semiconducting layer. Replacing the thermally evaporated small molecule semiconductor with a solution-processed polymer would possibly further simplify the fabrication process and reduce manufacturing cost. Here we investigate several polymer systems as wide bandgap semiconducting channel layers for potentially air stable and transparent CN-VFETs. The field effect mobility and optical transparency of the polymer layers are determined, and the performance and air stability of CN-VFET devices are measured. A. S. gratefully acknowledges support from the National Science Foundation under DMR-1156737.

  19. Stem cell mobilization by granulocyte colony-stimulating factor for myocardial recovery after acute myocardial infarction: a meta-analysis

    DEFF Research Database (Denmark)

    Zohlnhofer, D.; Dibra, A.; Koppara, T.;

    2008-01-01

    OBJECTIVES: The objective of this meta-analysis was to evaluate the effect of stem cell mobilization by granulocyte colony-stimulating factor (G-CSF) on myocardial regeneration on the basis of a synthesis of the data generated by randomized, controlled clinical trials of G-CSF after acute...... myocardial infarction (AMI). BACKGROUND: Experimental studies and early-phase clinical trials suggest that stem cell mobilization by G-CSF may have a positive impact on cardiac regeneration after AMI. The role of G-CSF in patients with AMI remains unclear considering the inconsistent results of several...... independently identified studies and abstracted data on sample size, baseline characteristics, and outcomes of interest. Eligible studies were randomized trials with stem cell mobilization by G-CSF after reperfused AMI that reported data regarding the change in left ventricular ejection fraction (LVEF...

  20. Prostate stromal cells express the progesterone receptor to control cancer cell mobility.

    Directory of Open Access Journals (Sweden)

    Yue Yu

    Full Text Available BACKGROUND: Reciprocal interactions between epithelium and stroma play vital roles for prostate cancer development and progression. Enhanced secretions of cytokines and growth factors by cancer associated fibroblasts in prostate tumors create a favorable microenvironment for cancer cells to grow and metastasize. Our previous work showed that the progesterone receptor (PR was expressed specifically in prostate stromal fibroblasts and smooth muscle cells. However, the expression levels of PR and its impact to tumor microenvironment in prostate tumors are poorly understood. METHODS: Immunohistochemistry assays are applied to human prostate tissue biopsies. Cell migration, invasion and proliferation assays are performed using human prostate cells. Real-time PCR and ELISA are applied to measure gene expression at molecular levels. RESULTS: Immunohistochemistry assays showed that PR protein levels were decreased in cancer associated stroma when compared with paired normal prostate stroma. Using in vitro prostate stromal cell models, we showed that conditioned media collected from PR positive stromal cells inhibited prostate cancer cell migration and invasion, but had minor suppressive impacts on cancer cell proliferation. PR suppressed the secretion of stromal derived factor-1 (SDF-1 and interlukin-6 (IL-6 by stromal cells independent to PR ligands. Blocking PR expression by siRNA or supplementation of exogenous SDF-1 or IL-6 to conditioned media from PR positive stromal cells counteracted the inhibitory effects of PR to cancer cell migration and invasion. CONCLUSIONS: Decreased expression of the PR in cancer associated stroma may contribute to the elevated SDF-1 and IL-6 levels in prostate tumors and enhance prostate tumor progression.

  1. Mobile cell-phones (M-phones in telemicroscopy: increasing connectivity of isolated laboratories

    Directory of Open Access Journals (Sweden)

    Missoni Eduardo

    2009-06-01

    Full Text Available Abstract Background The development of modern information telecommunication (ITC technology and its use in telemedicine plays an increasingly important role in facilitating access to some diagnostic services even to people living in the most remote areas. However, physical and economical constraints in the access to broad band data-transmission network, still represent a considerable obstacle to the transmission of images for the purpose of tele-pathology. Methods Indifferently using m-phones of different brands, and a variety of microscopic preparations, images were taken without the use of any adaptor simply approaching the lens of the mobile cell phone camera to the ocular of common optical microscopes, and subsequently sent via Multimedia Messaging Services (MMS to distant reference centres for tele-diagnosis. Access to MMS service was reviewed with specific reference to the African information communication technology (ICT market. Results Images of any pathologic preparation could be captured and sent over the mobile phone with an MMS, without being limited by appropriate access to the internet for transmission (i.e. access to broad-band services. The quality of the image was not influenced by the brand or model of the mobile-phone used, but only by its digital resolution, with any resolution above 0.8 megapixel resulting in images sufficient for diagnosis. Access to MMS services is increasingly reaching remote disadvantaged areas. Current penetration of the service in Africa was mapped appearing already available in almost every country, with penetration index varying from 1.5% to 92.2%. Conclusion The use of otherwise already widely available technologies, without any need for adaptors or otherwise additional technology, could significantly increase opportunities and quality diagnostics while lowering costs and considerably increasing connectivity between most isolated laboratories and distant reference center.

  2. VEGF 165 Gene Therapy for Patients with Refractory Angina: Mobilization of Endothelial Progenitor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Clarissa G. [Instituto de Cardiologia/Fundação Universitária de Cardiologia - Programa de Pós Graduação em Ciências da Saúde: Cardiologia, Porto Alegre, RS (Brazil); Duke University Medical Center, Durham, North Carolina (United States); Plentz, Rodrigo D.M. [Instituto de Cardiologia/Fundação Universitária de Cardiologia - Programa de Pós Graduação em Ciências da Saúde: Cardiologia, Porto Alegre, RS (Brazil); Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Dipp, Thiago [Instituto de Cardiologia/Fundação Universitária de Cardiologia - Programa de Pós Graduação em Ciências da Saúde: Cardiologia, Porto Alegre, RS (Brazil); Salles, Felipe B. [Instituto de Cardiologia/Fundação Universitária de Cardiologia - Programa de Pós Graduação em Ciências da Saúde: Cardiologia, Porto Alegre, RS (Brazil); Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Giusti, Imarilde I.; Sant' Anna, Roberto T.; Eibel, Bruna; Nesralla, Ivo A.; Markoski, Melissa [Instituto de Cardiologia/Fundação Universitária de Cardiologia - Programa de Pós Graduação em Ciências da Saúde: Cardiologia, Porto Alegre, RS (Brazil); Beyer, Nance N. [Instituto de Cardiologia/Fundação Universitária de Cardiologia - Programa de Pós Graduação em Ciências da Saúde: Cardiologia, Porto Alegre, RS (Brazil); Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Kalil, Renato A. K., E-mail: kalil.pesquisa@gmail.com [Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil)

    2013-08-15

    Vascular endothelial growth factor (VEGF) induces mobilization of endothelial progenitor cells (EPCs) with the capacity for proliferation and differentiation into mature endothelial cells, thus contributing to the angiogenic process. We sought to assess the behavior of EPCs in patients with ischemic heart disease and refractory angina who received an intramyocardial injections of 2000 µg of VEGF 165 as the sole therapy. The study was a subanalysis of a clinical trial. Patients with advanced ischemic heart disease and refractory angina were assessed for eligibility. Inclusion criteria were as follows: signs and symptoms of angina and/or heart failure despite maximum medical treatment and a myocardial ischemic area of at least 5% as assessed by single-photon emission computed tomography (SPECT). Exclusion criteria were as follows: age > 65 years, left ventricular ejection fraction < 25%, and a diagnosis of cancer. Patients whose EPC levels were assessed were included. The intervention was 2000 µg of VEGF 165 plasmid injected into the ischemic myocardium. The frequency of CD34+/KDR+ cells was analyzed by flow cytometry before and 3, 9, and 27 days after the intervention. A total of 9 patients were included, 8 males, mean age 59.4 years, mean left ventricular ejection fraction of 59.3% and predominant class III angina. The number of EPCs on day 3 was significantly higher than that at baseline (p = 0.03); however, that on days 9{sup th} and 27{sup th} was comparable to that at baseline. We identified a transient mobilization of EPCs, which peaked on the 3th day after VEGF 165 gene therapy in patients with refractory angina and returned to near baseline levels on 9{sup th} and 27{sup th}days.

  3. VEGF 165 Gene Therapy for Patients with Refractory Angina: Mobilization of Endothelial Progenitor Cells

    International Nuclear Information System (INIS)

    Vascular endothelial growth factor (VEGF) induces mobilization of endothelial progenitor cells (EPCs) with the capacity for proliferation and differentiation into mature endothelial cells, thus contributing to the angiogenic process. We sought to assess the behavior of EPCs in patients with ischemic heart disease and refractory angina who received an intramyocardial injections of 2000 µg of VEGF 165 as the sole therapy. The study was a subanalysis of a clinical trial. Patients with advanced ischemic heart disease and refractory angina were assessed for eligibility. Inclusion criteria were as follows: signs and symptoms of angina and/or heart failure despite maximum medical treatment and a myocardial ischemic area of at least 5% as assessed by single-photon emission computed tomography (SPECT). Exclusion criteria were as follows: age > 65 years, left ventricular ejection fraction < 25%, and a diagnosis of cancer. Patients whose EPC levels were assessed were included. The intervention was 2000 µg of VEGF 165 plasmid injected into the ischemic myocardium. The frequency of CD34+/KDR+ cells was analyzed by flow cytometry before and 3, 9, and 27 days after the intervention. A total of 9 patients were included, 8 males, mean age 59.4 years, mean left ventricular ejection fraction of 59.3% and predominant class III angina. The number of EPCs on day 3 was significantly higher than that at baseline (p = 0.03); however, that on days 9th and 27th was comparable to that at baseline. We identified a transient mobilization of EPCs, which peaked on the 3th day after VEGF 165 gene therapy in patients with refractory angina and returned to near baseline levels on 9th and 27thdays

  4. Salidroside Reduces Cell Mobility via NF-κB and MAPK Signaling in LPS-Induced BV2 Microglial Cells

    Directory of Open Access Journals (Sweden)

    Haixia Hu

    2014-01-01

    Full Text Available The unregulated activation of microglia following stroke results in the production of toxic factors that propagate secondary neuronal injury. Salidroside has been shown to exhibit protective effects against neuronal death induced by different insults. However, the molecular mechanisms responsible for the anti-inflammatory activity of salidroside have not been elucidated clearly in microglia. In the present study, we investigated the molecular mechanism underlying inhibiting LPS-stimulated BV2 microglial cell mobility of salidroside. The protective effect of salidroside was investigated in microglial BV2 cell, subjected to stretch injury. Moreover, transwell migration assay demonstrated that salidroside significantly reduced cell motility. Our results also indicated that salidroside suppressed LPS-induced chemokines production in a dose-dependent manner, without causing cytotoxicity in BV2 microglial cells. Moreover, salidroside suppressed LPS-induced activation of nuclear factor kappa B (NF-κB by blocking degradation of IκBα and phosphorylation of MAPK (p38, JNK, ERK1/2, which resulted in inhibition of chemokine expression. These results suggest that salidroside possesses a potent suppressive effect on cell migration of BV2 microglia and this compound may offer substantial therapeutic potential for treatment of ischemic strokes that are accompanied by microglial activation.

  5. Mobile Applications in Cell Biology Present New Approaches for Cell Modelling

    Science.gov (United States)

    de Oliveira, Mayara Lustosa; Galembeck, Eduardo

    2016-01-01

    Cell biology apps were surveyed in order to identify whether there are new approaches for modelling cells allowed by the new technologies implemented in tablets and smartphones. A total of 97 apps were identified in 3 stores surveyed (Apple, Google Play and Amazon), they are presented as: education 48.4%, games 26.8% and medicine 15.4%. The apps…

  6. Commercializing Light-Duty Plug-In/Plug-Out Hydrogen-Fuel-Cell Vehicles: "Mobile Electricity" Technologies, Early California Household Markets, and Innovation Management

    OpenAIRE

    Williams, Brett D.

    2010-01-01

    Starting from the premise that new consumer value must drive hydrogen-fuel-cell-vehicle (H2FCV) commercialization, a group of opportunities collectively called “Mobile Electricity” is characterized. Mobile Electricity (Me-) redefines H2FCVs as innovative products able to import and export electricity across the traditional vehicle boundary. Such vehicles could provide home recharging and mobile power, for example for tools, mobile activities, emergencies, and electric-grid-support services. T...

  7. MURINE MOBILIZED PERIPHERAL BLOOD STEM CELLS HAVE A LOWER CAPACITY THAN BONE MARROW TO INDUCE MIXED CHIMERISM AND TOLERANCE

    OpenAIRE

    Koporc, Zvonimir; Pilat, Nina; Nierlich, Patrick; Blaha, Peter; Bigenzahn, Sinda; Pree, Ines; Selzer, Edgar; Sykes, Megan; Muehlbacher, Ferdinand; Wekerle, Thomas

    2008-01-01

    Allogeneic bone marrow transplantation (BMT) under costimulation blockade allows induction of mixed chimerism and tolerance without global T cell depletion. The mildest such protocols without recipient cytoreduction, however, require clinically impracticable bone marrow (BM) doses. The successful use of mobilized peripheral blood stem cells (PBSC) instead of BM in such regimens would provide a substantial advance, allowing transplantation of higher doses of hematopoietic donor cells. We thus ...

  8. Safrole-induced Ca2+ mobilization and cytotoxicity in human PC3 prostate cancer cells.

    Science.gov (United States)

    Chang, H C; Cheng, H H; Huang, C J; Chen, W C; Chen, I S; Liu, S I; Hsu, S S; Chang, H T; Wang, J K; Lu, Y C; Chou, C T; Jan, C R

    2006-01-01

    The effect of the carcinogen safrole on intracellular Ca2+ mobilization and on viability of human PC3 prostate cancer cells was examined. Cytosolic free Ca2+ levels ([Ca2+]i) were measured by using fura-2 as a probe. Safrole at concentrations above 10 microM increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 350 microM. The Ca2+ signal was reduced by more than half after removing extracellular Ca2+ but was unaffected by nifedipine, nicardipine, nimodipine, diltiazem, or verapamil. In Ca2+-free medium, after treatment with 650 microM safrole, 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) failed to release Ca2+. Neither inhibition of phospholipase C with U73122 nor modulation of protein kinase C activity affected safrole-induced Ca2+ release. Overnight incubation with 0.65-65 microM safrole did not affect cell viability, but incubation with 325-625 microM safrole decreased viability. Collectively, the data suggest that in PC3 cells, safrole induced a [Ca2+]i increase by causing Ca2+ release from the endoplasmic reticulum in a phospholipase C- and protein kinase C-independent fashion, and by inducing Ca2+ influx. Safrole can decrease cell viability in a concentration-dependent manner.

  9. Effect of high mobility group box-1 protein on immune cells and its regulatory mechanism

    Institute of Scientific and Technical Information of China (English)

    Ying-yi LUAN; Feng-huaYAO; Qing-hong ZHANG; Xiao-mei ZHU; Ning DONG; Yong-ming YAO

    2012-01-01

    High mobility group box-1 protein (HMGB1),which is a nuclear protein,participates in chromatin architecture and transcriptional regulation.When released from cells,HMGB1 also plays a well-established role as a pro-inflammatory mediator during innate immune responses to injury.In the initial stage of injury,there is a release of large quantities of early pro-inflammatory mediators to initiate or perpetuate immune responses against pathogens,but this pro-inflammatory period is transient,and it is followed by a prolonged period of immune suppression.At present,several lines of evidences have suggested that HMGB1 is a late cytokine provoking delayed endotoxin morbidity,which may enhance the production of early proinflammatory mediators,and it can contribute potently to the activation of different immune cells and play a role in the development of host cell-mediated immunity.The biology of HMGB1 has been extensively studied as a pro-inflammatory cytokine of systemic inflammation,however,this review will attempt to provide a summary of the effects of HMGB1 on different immune cells and its regulatory mechanism in acute insults.

  10. Inhibition of Gli1 mobilizes endogenous neural stem cells for remyelination

    Science.gov (United States)

    Samanta, Jayshree; Grund, Ethan M.; Silva, Hernandez M.; Lafaille, Juan J.; Fishell, Gord; Salzer, James L.

    2016-01-01

    Summary Enhancing repair of myelin is an important, but still elusive therapeutic goal in many neurological disorders1. In Multiple Sclerosis (MS), an inflammatory demyelinating disease, endogenous remyelination does occur but is frequently insufficient to restore function. Both parenchymal oligodendrocyte progenitor cells (OPCs) and endogenous adult neural stem cells (NSCs) resident within the subventricular zone (SVZ) are known sources of remyelinating cells2. Here, we characterize the contribution to remyelination of a subset of adult NSCs, identified by their expression of Gli1, a transcriptional effector of the Sonic Hedgehog (Shh) pathway. We show that these cells are recruited from the SVZ to populate demyelinated lesions in the forebrain but never enter healthy, white matter tracts. Unexpectedly, recruitment of this pool of NSCs, and their differentiation into oligodendrocytes, is significantly enhanced by genetic or pharmacological inhibition of Gli1. Importantly, complete inhibition of canonical hedgehog signaling was ineffective indicating that Gli1’s role in both augmenting hedgehog signaling and retarding myelination is specialized. Indeed, inhibition of Gli1 improves the functional outcome in a relapsing/remitting model of experimental autoimmune encephalomyelitis (RR-EAE) and is neuroprotective. Thus, endogenous NSCs can be mobilized for the repair of demyelinated lesions by inhibiting Gli1, identifying a new therapeutic avenue for the treatment of demyelinating disorders. PMID:26416758

  11. Anabolic Properties of High Mobility Group Box Protein-1 in Human Periodontal Ligament Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Michael Wolf

    2014-01-01

    Full Text Available High mobility group box protein-1 (HMGB1 is mainly recognized as a chemoattractant for macrophages in the initial phase of host response to pathogenic stimuli. However, recent findings provide evidence for anabolic properties in terms of enhanced proliferation, migration, and support of wound healing capacity of mesenchymal cells suggesting a dual role of the cytokine in the regulation of immune response and subsequent regenerative processes. Here, we examined potential anabolic effects of HMGB1 on human periodontal ligament (PDL cells in the regulation of periodontal remodelling, for example, during orthodontic tooth movement. Preconfluent human PDL cells (hPDL were exposed to HMGB1 protein and the influence on proliferation, migration, osteogenic differentiation, and biomineralization was determined by MTS assay, real time PCR, immunofluorescence cytochemistry, ELISA, and von Kossa staining. HMGB1 protein increased hPDL cell proliferation, migration, osteoblastic marker gene expression, and protein production as well as mineralized nodule formation significantly. The present findings support the dual character of HMGB1 with anabolic therapeutic potential that might support the reestablishment of the structural and functional integrity of the periodontium following periodontal trauma such as orthodontic tooth movement.

  12. The more, the less: age and chemotherapy load are predictive of poor stem cell mobilization in patients with hematologic malignancies

    Institute of Scientific and Technical Information of China (English)

    YANG Shen-miao; CHEN Huan; CHEN Yu-hong; ZHU Hong-hu; ZHAO Ting; LIU Kai-yan

    2012-01-01

    Background Intensive treatment such as autologous peripheral blood stem cell (PBSC) transplantation is an important therapeutic strategy in many hematologic malignancies.A number of factors have been reported to impact PBSC mobilization,but the predictive factors varied from one study to another.This retrospective study assessed our current mobilization and collection protocols,and explored the factors predictive of PBSC mobilization in patients with hematologic malignancies.Methods Data of 64 consecutive patients with hematologic malignancies (multiple myeloma,n=22; acute leukemia,n=27; lymphoma,n=15) who underwent PBSC mobilization for over 1 year were analyzed.Four patients with response to treatment of near complete remission or better were administered granulocyte colony-stimulating factor (G-CSF) to mobilize PBSCs.Sixty patients received G-CSF followed by chemotherapy mobilizing regimens.Poor mobilization (PM) was defined as when ≤2.0×106 CD34+ cells/kg body weight were collected within three leukapheresis procedures.Results The incidence of PM at the first mobilization attempt was 19% (12/64).The PM group was older than the non-PM group (median age,51 vs.40 years; P=0.013).In univariate analysis,there were no significant differences in gender,diagnosis,and body weight between the PM and non-PM groups.A combination of chemotherapy and G-CSF was more effective than G-CSF alone as a mobilizing regimen (P=0.019).Grade Ⅲ or Ⅳ hematopoietic toxicity of chemotherapy had no significant effect on the mobilization efficacy.Supportive care and the incidence of febrile neutropenia were not significantly different between the two groups.In multivariate analysis,age (odds ratio (OR),9.536;P=-0.002) and number of previous chemotherapy courses (OR 3.132; P=0.024) were two independent negative predictive factors for CD34+ cell yield.PM patients could be managed well by remobilization.Conclusion Older age and a heavy load of previous chemotherapy are the negative

  13. Myeloid Cells' Evasion of Melanoma Immunity

    Science.gov (United States)

    Wang, Jun; Chen, Lieping

    2015-01-01

    An immune-suppressive role of myeloid-derived suppressor cells (MDSCs) in melanoma has long been speculated, whereas molecular mechanisms underlying this role are not well understood. Here, Chung and colleagues show that dendritic cell-associated, heparan sulfate proteoglycans-dependent integrin ligand (DC-HIL), a cell surface immune-modulatory molecule, is highly expressed on tumor-associated MDSCs. Genetic ablation or antibody blockade of DC-HIL delays the growth of transplantable B16 melanoma in syngeneic mice, which is accompanied by enhanced antitumor T-cell activities. These findings support a role for DC-HIL in immune evasion within the melanoma microenvironment. PMID:25318429

  14. Propranolol Restricts the Mobility of Single EGF-Receptors on the Cell Surface before Their Internalization

    Science.gov (United States)

    Otero, Carolina; Linke, Max; Sanchez, Paula; González, Alfonso; Schaap, Iwan A. T.

    2013-01-01

    The epidermal growth factor receptor is involved in morphogenesis, proliferation and cell migration. Its up-regulation during tumorigenesis makes this receptor an interesting therapeutic target. In the absence of the ligand, the inhibition of phosphatidic acid phosphohydrolase activity by propranolol treatment leads to internalization of empty/inactive receptors. The molecular events involved in this endocytosis remain unknown. Here, we quantified the effects of propranolol on the mobility of single quantum-dot labelled receptors before the actual internalization took place. The single receptors showed a clear stop-and-go motion; their diffusive tracks were continuously interrupted by sub-second stalling events, presumably caused by transient clustering. In the presence of propranolol we found that: i) the diffusion rate reduced by 22 %, which indicates an increase in drag of the receptor. Atomic force microscopy measurements did not show an increase of the effective membrane tension, such that clustering of the receptor remains the likely mechanism for its reduced mobility. ii) The receptor got frequently stalled for longer periods of multiple seconds, which may signal the first step of the internalization process. PMID:24349439

  15. Silencing of high mobility group A1 enhances gemcitabine chemosensitivity of lung adenocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    CAO Yuan-dong; DENG Yu-xia; GE Xiao-lin; HUANG Pei-lin; SUN Xin-chen; MA Jun; JIN Zhi-liang; CHENG Hong-yan; XU Rui-zhi; LI Fan; QIN Shu-kui

    2011-01-01

    Background The high mobility group A1 (HMGA1) proteins are architectural transcription factors found to be overexpressed in lung adenocarcinoma. Lentivirus-mediated RNA interference (RNAi) technology is a powerful tool for silencing endogenous or exogenous genes in human cancer cells. Our preliminary study shows that gemcitabine inhibits growth of the human lung cancer cell line SPCA-1 and induces apoptosis,and this effect might link with down-regulation of HMGA1 expression. This study aimed to investigate the chemosensitivity change of the lung adenocarcinoma cells SPCA-1 after HMGA1 inhibition by lentivirus-mediated RNAi.Methods We studied a highly malignant lung adenocarcinoma cell line (SPCA-1 cells). Lentiviral short-hairpin RNA (shHMGA1) expression vectors targeting HMGA1 were used for generation of lentiviral particles. After being transfected into the lung adenocarcinoma cell line SPCA-1,the expression of HMGA1 was determined by retrotranscriptase polymerase chain reaction (RT-PCR) and Western blotting. The effect of gemcitabine on proliferation of positive and negative cells was observed by methyl thiazolyl tetrazolium (MTT) assay and clonogenic survival assay. Apoptosis was observed by flow cytometery. Chemosensitivity to gemcitabine was determined by IC50 analysis. Caspase activity was quantitated by a caspase colorimetric protease assay kit.Results HMGA1-siRNA silenced its target mRNA specifically and effectively in SPCA-1 cells. The apoptotic rates of the scramble control group were (7.43±0.21)%,(11.00±0.20)%,and (14.93±0.31)%,and the apoptotic rates in the silenced group were (9.53±0.42)%,(16.67±0.45)%,and (25.40±0.79)% under exposure to 0.05,0.5 and 5.0 μg/ml of gemcitabine (P <0.05). The IC5o of the silenced group was (0.309±0.003) μg/ml which was significantly lower than in the scramble control group,(0.653±0.003) μg/ml (P <0.05). It reduced cancer cell proliferation and increased apoptotic cell death after being treated with

  16. Effect of staurosporine on the mobility and invasiveness of lung adenocarcinoma A549 cells: an in vitro study

    International Nuclear Information System (INIS)

    Lung cancer is one of the most malignant tumors, representing a significant threat to human health. Lung cancer patients often exhibit tumor cell invasion and metastasis before diagnosis which often render current treatments ineffective. Here, we investigated the effect of staurosporine, a potent protein kinase C (PKC) inhibitor on the mobility and invasiveness of human lung adenocarcinoma A549 cells. All experiments were conducted using human lung adenocarcinoma A549 cells that were either untreated or treated with 1 nmol/L, 10 nmol/L, or 100 nmol/L staurosporine. Electron microscopy analyses were performed to study ultrastructural differences between untreated A549 cells and A549 cells treated with staurosporine. The effect of staurosporine on the mobility and invasiveness of A549 was tested using Transwell chambers. Western blot analyses were performed to study the effect of staurosporine on the levels of PKC-α, integrin β1, E-cadherin, and LnR. Changes in MMP-9 and uPA levels were identified by fluorescence microscopy. We demonstrated that treatment of A549 cells with staurosporine caused alterations in the cell shape and morphology. Untreated cells were primarily short spindle- and triangle-shaped in contrast to staurosporine treated cells which were retracted and round-shaped. The latter showed signs of apoptosis, including vacuole fragmentation, chromatin degeneration, and a decrease in the number of microvilli at the surface of the cells. The A549 cell adhesion, mobility, and invasiveness significantly decreased with higher staurosporine concentrations. E-cadherin, integrin β1, and LnR levels changed by a factor of 1.5, 0.74, and 0.73, respectively compared to untreated cells. In addition, the levels of MMP-9 and uPA decreased in cells treated with staurosporine. In summary, this study demonstrates that staurosporine inhibits cell adhesion, mobility, and invasion of A549 cells. The staurosporine-mediated inhibition of PKC-α, induction of E

  17. Impact of the intermixed phase and the channel network on the carrier mobility of nanostructured solar cells.

    Science.gov (United States)

    Woellner, Cristiano F; Freire, José A

    2016-02-28

    We analyzed the impact of the complex channel network of donor and acceptor domains in nanostructured solar cells on the mobility of the charge carriers moving by thermally activated hopping. Particular attention was given to the so called intermixed phase, or interface roughness, that has recently been shown to promote an increase in the cell efficiency. The domains were obtained from a Monte Carlo simulation of a two-species lattice gas. We generated domain morphologies with controllable channel size and interface roughness. The field and density dependence of the carrier hopping mobility in different morphologies was obtained by solving a master equation. Our results show that the mobility decreases with roughness and increases with typical channel sizes. The deleterious effect of the roughness on the mobility is quite dramatic at low carrier densities and high fields. The complex channel network is shown to be directly responsible for two potentially harmful effects to the cell performance: a remarkable decrease of the mobility with increasing field and the accumulation of charge at the domains interface, which leads to recombination losses.

  18. Mobile Commerce

    OpenAIRE

    Maria Cristina Enache

    2016-01-01

    Mobile commerce, or m-commerce, refers to the use of wireless digital devices to enable transactions on the Web. Described more fully in Chapter 3, m-commerce involves the use of wireless networks to connect cell phones, handheld devices such Blackberries, and personal computers to the Web. Once connected, mobile consumers can conduct transactions, including stock trades, in-store price comparisons, banking, travel reservations, and more.

  19. Green heterogeneous small-cell networks: Toward reducing the CO2 emissions of mobile communications industry using uplink power adaptation

    KAUST Repository

    Shakir, Muhammad Zeeshan

    2013-06-01

    Heterogeneous small cell networks, or Het- SNets, are considered as a standard part of future mobile networks in which multiple lowpower low-cost user deployed base stations complement the existing macrocell infrastructure. This article proposes an energy-efficient deployment of the cells where the small cell base stations are arranged around the edge of the reference macrocell, and the deployment is referred to as cell-on-edge (COE) deployment. The proposed deployment ensures an increase in the network spectral and energy efficiency by facilitating cell edge mobile users with small cells. Moreover, COE deployment guarantees reduction of the carbon footprint of mobile operations by employing adaptive uplink power control. In order to calibrate the reduction in CO2 emissions, this article quantifies the ecological and associated economical impacts of energy savings in the proposed deployment. Simulation results quantify the improvements in CO2 emissions and spectral and energy gains of the proposed COE deployment compared to macro-only networks and typical small cell deployment strategies where small cells are randomly deployed within a given macrocell. © 2013 IEEE.

  20. Protective effects of transplanted and mobilized bone marrow stem cells on mice with severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Hui-Fei Cui; Zeng-Liang Bai

    2003-01-01

    AIM: To evaluate the protective effects of transplanted and mobilized bone marrow stem cells (BMSCs) on mice with severe acute pancreatitis (SAP) and to probe into their possible mechanisms.METHODS: A mouse model of SAP induced by intraparitoneal injections of L-arginine was employed in the present study.Two hundred female Balb/c mice weighing 18-22 g were randomly assigned into 4 groups. Group A was the stem cell mobilized group treated by injection of granulocytecolony stimulating factor (G-CSF) into mice for 4 days at a dose of 40 μg@kg-1@d-1 before induction of SAP. Group B was the group of BMSCs transplantation, in which the mice were given the isolated BMSCs via the tail vein 4 days prior to induction of SAP. Group C served as the model control and only SAP was induced. The mice without induction of SAP in group D acted as the normal control. At the time of animal sacrifice at 24, 48 and 72 h after induction of SAP, blood samples were obtained and prepared to detect serum amylase, while the abdominal viscera were examined both grossly and microscopically for the observation of pathological changes.RESULTS: The mortality of mice in the model control, groups A and B was 34%, 8% and 10% respectively within 72 h after induction of SAP. The serum level of amylase in the model control was significantly increased at all time points after induction of SAP as compared with that of the normal control (P<0.05-0.01). When the mice were pretreated with BMSCs' transplantation or G-CSF injection, their serum level of amylase was significantly reduced at 48 h and 72 h after induction of SAP in comparison with that of the model control (P<0.05-0.01). In accordance with these observations,both gross and microscopic examinations revealed that the pathological changes of SAP in mice pretreated with BMSCs transplantation or G-CSF injection were considerably attenuated as compared with those in the model control at all observed time points.CONCLUSION: Both transplanted

  1. M-Learning, Mobile Experimentation and Telepresence with Cell Phones and PDAs

    Directory of Open Access Journals (Sweden)

    Andreas Bischoff

    2009-01-01

    Full Text Available Mobile devices such as notebooks and PDAs are very interesting tools for web-based teaching and distant teaching today. We have adapted Web-based remote laboratory environments to mobile devices like PDAs and smartphones to remotely control a Pioneer 3 AT mobile robot.

  2. Mobilized progenitor cells as a bridging therapy for radiation casualties: a brief review of tocopherol succinate-based approaches.

    Science.gov (United States)

    Singh, Vijay K; Singh, Pankaj K; Wise, Stephen Y; Seed, Thomas M

    2011-07-01

    Nuclear detonation through either military or terrorist action would most likely lead to a mass-casualty scenario involving victims with varying degrees of exposure to ionizing radiation. As a result of radiation injury to the hematopoietic system, victims would suffer from a lack of red blood cells that deliver oxygen, immune cells that detect and eliminate infectious agents, and blood platelets that promote blood clot formation. In part, these symptoms are generally referred to as acute radiation syndrome (ARS). While some victims of moderate to high levels of radiation will be beyond saving, most will have received enough radiation to injure but not kill their bone marrow cells completely. Such people will recover from their injuries but face a 30-60day period during which they cannot fully fight infections and are prone to uncontrolled bleeding and anemia. To keep them alive until their hematopoietic system recovers, they must receive supportive care. Recently, using experimental animal models of ARS, transfusion of myeloid progenitor cells have been tried as a bridging therapy for radiation-exposed animals. Such cells have been shown to be effective in protecting animals exposed to lethal doses of radiation. These myeloid progenitors (along with of other hematopoietic progenitor cell types) can be mobilized out of the bone marrow into the blood for the reconstitution of hematopoiesis. This review discusses various approaches to the mobilization of progenitors using different mobilizing agents, and their utility as a bridging therapy for radiation casualties. We suggest that α-tocopherol succinate (TS) is an optimal mobilizing agent for progenitors. The extent of progenitor mobilization TS elicits in experimental mice is comparable to clinically used drugs such as recombinant granulocyte-colony stimulating factor rhG-CSF/Neupogen® and the bicyclam AMD3100 (plerixafor/Mozobil); therefore, we propose that TS be considered for further translational development

  3. Chinese preparation Xuesaitong promotes the mobilization of bone marrow mesenchymal stem cells in rats with cerebral infarction.

    Science.gov (United States)

    Zhang, Jin-Sheng; Zhang, Bao-Xia; Du, Mei-Mei; Wang, Xiao-Ya; Li, Wei

    2016-02-01

    After cerebral ischemia, bone marrow mesenchymal stem cells are mobilized and travel from the bone marrow through peripheral circulation to the focal point of ischemia to initiate tissue regeneration. However, the number of bone marrow mesenchymal stem cells mobilized into peripheral circulation is not enough to exert therapeutic effects, and the method by which blood circulation is promoted to remove blood stasis influences stem cell homing. The main ingredient of Xuesaitong capsules is Panax notoginseng saponins, and Xuesaitong is one of the main drugs used for promoting blood circulation and removing blood stasis. We established rat models of cerebral infarction by occlusion of the middle cerebral artery and then intragastrically administered Xuesaitong capsules (20, 40 and 60 mg/kg per day) for 28 successive days. Enzyme-linked immunosorbent assay showed that in rats with cerebral infarction, middle- and high-dose Xuesaitong significantly increased the level of stem cell factors and the number of CD117-positive cells in plasma and bone marrow and significantly decreased the number of CD54- and CD106-positive cells in plasma and bone marrow. The effect of low-dose Xuesaitong on these factors was not obvious. These findings demonstrate that middle- and high-dose Xuesaitong and hence Panax notoginseng saponins promote and increase the level and mobilization of bone marrow mesenchymal stem cells in peripheral blood. PMID:27073383

  4. Hematopoietic Progenitor Cell Mobilization with Ifosfamide, Carboplatin, and Etoposide Chemotherapy versus Plerixafor-Based Strategies in Patients with Hodgkin and Non-Hodgkin Lymphoma.

    Science.gov (United States)

    Dhakal, Binod; Veltri, Lauren Westfall; Fenske, Timothy S; Eastwood, Daniel; Craig, Michael D; Cumpston, Aaron; Shillingburg, Alexandra; Esselman, Jean; Watkins, Kathy; Pasquini, Marcelo C; D'Souza, Anita; Hari, Parameswaran; Kanate, Abraham Sebastian; Hamadani, Mehdi

    2016-10-01

    Studies comparing the efficacy and safety of chemo-mobilization with ifosfamide, carboplatin, and etoposide (ICE) ± rituximab with plerixafor-based approaches in lymphoma patients have not been performed. We analyzed hematopoietic progenitor cell mobilization outcomes in lymphoma patients undergoing chemo-mobilization with ICE (n = 35) compared with either routine plerixafor (n = 30) or "just in time" (JIT) plerixafor-based mobilization (n = 33). Chemo-mobilization provided a significantly higher total CD34(+) cell yield (median collection, 5.35 × 10(6) cells/kg for ICE versus 3.15 × 10(6) cells/kg for routine plerixafor and 3.6 × 10(6) cells/kg for JIT plerixafor, P JIT plerixafor, P = .20). There was no significant difference in the 3 groups in terms of total number of apheresis sessions performed (median, 2 in each group; P = .78). There were no mobilization failures (inability to collect at least 2 × 10(6) cells/kg) in the chemo-mobilization group, whereas 5 patients (16.7%) in the routine plerixafor and 3 patients (9.1%) in JIT group had mobilization failure (P = .04). Mean time to neutrophil engraftment was faster in the chemo-mobilization group, 10.3 days (±1.2) compared with 12.1 days (±3.6) in the routine plerixafor group and 11.6 days (±3.0) in the JIT group (P JIT group (P JIT, P < .001). Our data suggests that chemo-mobilization with ICE provides a higher total CD34(+) cell yield, lower rates of mobilization failure, faster engraftment, and lower cost compared to plerixafor-based approaches with comparable toxicity profile between the groups, except for higher transfusion requirements with chemo-mobilization.

  5. A unified algorithm for mobility load balancing in 3GPP LTE multi-cell networks

    Institute of Scientific and Technical Information of China (English)

    WANG Hao; LIU Nan; LI ZhiHang; WU Ping; PAN ZhiWen; YOU XiaoHu

    2013-01-01

    3GPP long term evolution (LTE) is a promising candidate for the next-generation wireless network, which is expected to achieve high spectrum efficiency by using advanced physical layer techniques and flat network structures. However, the LTE network still faces the problem of load imbalance as in GSM/WCDMA networks, and this may cause significant deterioration of system performance. To deal with this problem, mobility load balancing (MLB) has been proposed as an important use case in 3GPP self-organizing network (SON), in which the serving cell of a user can be selected to achieve load balancing rather than act as the cell with the maximum received power. Furthermore, the LTE network aims to serve users with different quality-of-service (QoS) requirements, and the network-wide objective function for load balancing is distinct for different kinds of users. Thus, in this paper, a unified algorithm is proposed for MLB in the LTE network. The load balancing problem is first formulated as an optimization problem with the optimizing variables being cell-user connections. Then the complexity and overhead of the optimal solution is analyzed and a practical and distributed algorithm is given. After that, the proposed algorithm is evaluated for users with different kinds of QoS requirements, i.e., guaranteed bit rate (GBR) users with the objective function of load balance index and non-GBR (nGBR) users with the objective function of total utility, respectively. Simulation results show that the proposed algorithm leads to significantly balanced load distribution for GBR users to decrease the new call blocking rate, and for nGBR users to improve the cell-edge throughput at the cost of only slight deterioration of total throughput.

  6. Evaluation of a Mobile Hot Cell Technology for Processing Idaho National Laboratory Remote-Handled Wastes

    Energy Technology Data Exchange (ETDEWEB)

    B.J. Orchard; L.A. Harvego; R.P. Miklos; F. Yapuncich; L. Care

    2009-03-01

    The Idaho National Laboratory (INL) currently does not have the necessary capabilities to process all remote-handled wastes resulting from the Laboratory’s nuclear-related missions. Over the years, various U.S. Department of Energy (DOE)-sponsored programs undertaken at the INL have produced radioactive wastes and other materials that are categorized as remote-handled (contact radiological dose rate > 200 mR/hr). These materials include Spent Nuclear Fuel (SNF), transuranic (TRU) waste, waste requiring geological disposal, low-level waste (LLW), mixed waste (both radioactive and hazardous per the Resource Conservation and Recovery Act [RCRA]), and activated and/or radioactively-contaminated reactor components. The waste consists primarily of uranium, plutonium, other TRU isotopes, and shorter-lived isotopes such as cesium and cobalt with radiological dose rates up to 20,000 R/hr. The hazardous constituents in the waste consist primarily of reactive metals (i.e., sodium and sodium-potassium alloy [NaK]), which are reactive and ignitable per RCRA, making the waste difficult to handle and treat. A smaller portion of the waste is contaminated with other hazardous components (i.e., RCRA toxicity characteristic metals). Several analyses of alternatives to provide the required remote-handling and treatment capability to manage INL’s remote-handled waste have been conducted over the years and have included various options ranging from modification of existing hot cells to construction of new hot cells. Previous analyses have identified a mobile processing unit as an alternative for providing the required remote-handled waste processing capability; however, it was summarily dismissed as being a potentially viable alternative based on limitations of a specific design considered. In 2008 INL solicited expressions of interest from Vendors who could provide existing, demonstrated technology that could be applied to the retrieval, sorting, treatment (as required), and

  7. Staging Mobilities / Designing Mobilities

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    2015-01-01

    as people are ‘staging themselves’ (from below). Staging mobilities is a dynamic process between ‘being staged’ (for example, being stopped at traffic lights) and the ‘mobile staging’ of interacting individuals (negotiating a passage on the pavement). Staging mobilities is about the fact that mobility...

  8. Infection mobilizes hematopoietic stem cells through cooperative NOD-like receptor and Toll-like receptor signaling.

    Science.gov (United States)

    Burberry, Aaron; Zeng, Melody Y; Ding, Lei; Wicks, Ian; Inohara, Naohiro; Morrison, Sean J; Núñez, Gabriel

    2014-06-11

    Adult hematopoietic stem cells (HSCs) are maintained in specialized niches within the bone marrow under steady-state conditions and mobilize for extramedullary hematopoiesis during periods of stress such as bacterial infections. However, the underlying mechanisms are unclear. We show that systemic infection of mice with Escherichia coli, commonly associated with bacteremia in humans, mobilizes functional HSCs to the spleen. Accumulation of splenic HSCs (CD150+CD48-Lin(-/low)Sca1+cKit+) was diminished in TLR4-deficient and RIPK2-deficient mice, implicating TLRs and cytosolic NOD1/NOD2 signaling in the process. Accordingly, dual stimulation of NOD1 and TLR4 in radio-resistant cells alone was sufficient to mobilize HSCs, while TLR4 expression on HSCs was dispensable. Mechanistically, TLR4 and NOD1 synergistically induced granulocyte colony-stimulating factor (G-CSF), which was required for extramedullary HSC accumulation. Mobilized HSCs and progenitor cells gave rise to neutrophils and monocytes and contributed to limiting secondary infection. PMID:24882704

  9. Nickel Mobilizes Intracellular Zinc to Induce Metallothionein in Human Airway Epithelial Cells

    Science.gov (United States)

    Nemec, Antonia A.; Leikauf, George D.; Pitt, Bruce R.; Wasserloos, Karla J.; Barchowsky, Aaron

    2009-01-01

    We recently reported that induction of metallothionein (MT) was critical in limiting nickel (Ni)-induced lung injury in intact mice. Nonetheless, the mechanism by which Ni induces MT expression is unclear. We hypothesized that the ability of Ni to mobilize zinc (Zn) may contribute to such regulation and therefore, we examined the mechanism for Ni-induced MT2A expression in human airway epithelial (BEAS-2B) cells. Ni induced MT2A transcript levels and protein expression by 4 hours. Ni also increased the activity of a metal response element (MRE) promoter luciferase reporter construct, suggesting that Ni induces MRE binding of the metal transcription factor (MTF-1). Exposure to Ni resulted in the nuclear translocation of MTF-1, and Ni failed to induce MT in mouse embryonic fibroblasts lacking MTF-1. As Zn is the only metal known to directly bind MTF-1, we then showed that Ni increased a labile pool of intracellular Zn in cells as revealed by fluorescence-activated cell sorter using the Zn-sensitive fluorophore, FluoZin-3. Ni-induced increases in MT2A mRNA and MRE-luciferase activity were sensitive to the Zn chelator, TPEN, supporting an important role for Zn in mediating the effect of Ni. Although neither the source of labile Zn nor the mechanism by which Ni liberates labile Zn was apparent, it was noteworthy that Ni increased intracellular reactive oxygen species (ROS). Although both N-acetyl cysteine (NAC) and ascorbic acid (AA) decreased Ni-induced increases in ROS, only NAC prevented Ni-induced increases in MT2A mRNA, suggesting a special role for interactions of Ni, thiols, and Zn release. PMID:19097988

  10. Erythropoietic Potential of CD34+ Hematopoietic Stem Cells from Human Cord Blood and G-CSF-Mobilized Peripheral Blood

    Directory of Open Access Journals (Sweden)

    Honglian Jin

    2014-01-01

    Full Text Available Red blood cell (RBC supply for transfusion has been severely constrained by the limited availability of donor blood and the emergence of infection and contamination issues. Alternatively, hematopoietic stem cells (HSCs from human organs have been increasingly considered as safe and effective blood source. Several methods have been studied to obtain mature RBCs from CD34+ hematopoietic stem cells via in vitro culture. Among them, human cord blood (CB and granulocyte colony-stimulating factor-mobilized adult peripheral blood (mPB are common adult stem cells used for allogeneic transplantation. Our present study focuses on comparing CB- and mPB-derived stem cells in differentiation from CD34+ cells into mature RBCs. By using CD34+ cells from cord blood and G-CSF mobilized peripheral blood, we showed in vitro RBC generation of artificial red blood cells. Our results demonstrate that CB- and mPB-derived CD34+ hematopoietic stem cells have similar characteristics when cultured under the same conditions, but differ considerably with respect to expression levels of various genes and hemoglobin development. This study is the first to compare the characteristics of CB- and mPB-derived erythrocytes. The results support the idea that CB and mPB, despite some similarities, possess different erythropoietic potentials in in vitro culture systems.

  11. Molecular deregulation induced by silencing of the high mobility group protein A2 gene in retinoblastoma cells

    OpenAIRE

    Venkatesan, Nalini; Krishnakumar, Subramanian; Deepa, Perinkulam Ravi; Deepa, Murali; Khetan, Vikas; Reddy, M. Ashwin

    2012-01-01

    Aim To explore the molecular mechanisms deregulated by high mobility group protein A2 (HMGA2) gene silencing in retinoblastoma (RB) cells. Methods Synthetic anti-HMGA2 short interfering RNA (siRNA) was used to silence the HMGA2 gene in cultured Y79 RB cells that were subjected to whole genome microarray analysis. The expression of differentially regulated key genes was confirmed with quantitative reverse-transcriptase polymerase chain reaction (qRT–PCR) in post-silenced RB cell lines (Y79 and...

  12. High electron mobility ZnO film for high-performance inverted polymer solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Peiwen; Chen, Shan-Ci; Zheng, Qingdong; Huang, Feng, E-mail: fhuang@fjirsm.ac.cn; Ding, Kai [Key Laboratory of Optoelectronic Materials Chemistry and Physics, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou Fujian, 350002 (China)

    2015-04-20

    High-quality ZnO films (ZnO-MS) are prepared via magnetron sputtering deposition with a high mobility of about 2 cm{sup 2}/(V·s) and are used as electron transport layer for inverted polymer solar cells (PSCs) with polymer poly[4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b:4,5-b′] dithiophene-co-3-fluorothieno[3,4-b]thiophene-2-carboxylate]:[6,6]-phenyl C71-butyric acid methyl ester as the active layer. A significant improvement of J{sub SC}, about 20% enhancement in contrast to the devices built on sol-gel derived ZnO film (ZnO-Sol), is found in the ZnO-MS based device. High performance ZnO-MS based PSCs exhibit power conversion efficiency (PCE) up to 8.55%, which is much better than the device based on ZnO-Sol (PCE = 7.78%). Further research on cathode materials is promising to achieve higher performance.

  13. Gliadin peptides induce tissue transglutaminase activation and ER-stress through Ca2+ mobilization in Caco-2 cells.

    Directory of Open Access Journals (Sweden)

    Ivana Caputo

    Full Text Available BACKGROUND: Celiac disease (CD is an intestinal inflammatory condition that develops in genetically susceptible individuals after exposure to dietary wheat gliadin. The role of post-translational modifications of gliadin catalyzed by tissue transglutaminase (tTG seems to play a crucial role in CD. However, it remains to be established how and where tTG is activated in vivo. We have investigated whether gliadin peptides modulate intracellular Ca(2+ homeostasis and tTG activity. METHODS/PRINCIPAL FINDINGS: We studied Ca(2+ homeostasis in Caco-2 cells by single cell microfluorimetry. Under our conditions, A-gliadin peptides 31-43 and 57-68 rapidly mobilized Ca(2+ from intracellular stores. Specifically, peptide 31-43 mobilized Ca(2+ from the endoplasmic reticulum (ER and mitochondria, whereas peptide 57-68 mobilized Ca(2+ only from mitochondria. We also found that gliadin peptide-induced Ca(2+ mobilization activates the enzymatic function of intracellular tTG as revealed by in situ tTG activity using the tTG substrate pentylamine-biotin. Moreover, we demonstrate that peptide 31-43, but not peptide 57-68, induces an increase of tTG expression. Finally, we monitored the expression of glucose-regulated protein-78 and of CCAAT/enhancer binding protein-homologous protein, which are two biochemical markers of ER-stress, by real-time RT-PCR and western blot. We found that chronic administration of peptide 31-43, but not of peptide 57-68, induces the expression of both genes. CONCLUSIONS: By inducing Ca(2+ mobilization from the ER, peptide 31-43 could promote an ER-stress pathway that may be relevant in CD pathogenesis. Furthermore, peptides 31-43 and 57-68, by activating intracellular tTG, could alter inflammatory key regulators, and induce deamidation of immunogenic peptides and gliadin-tTG crosslinking in enterocytes and specialized antigen-presenting cells.

  14. Mobility performance of LTE co-channel deployment of macro and pico cells

    DEFF Research Database (Denmark)

    Barbera, Simone; Michaelsen, Per Henrik; Säily, Mikko;

    2012-01-01

    This paper aims at analyzing the mobility performance in heterogeneous 3GPP (3rd Generation Partnership Project) Long Term Evolution (LTE) networks. The main objective is to analyze the behavior of LTE macro/pico co-channel networks with different mobility parameters, such as the “Time-To- Trigger...

  15. Dendritic cell-based vaccines in the setting of peripheral blood stem cell transplantation: CD34+ cell-depleted mobilized peripheral blood can serve as a source of potent dendritic cells.

    Science.gov (United States)

    Choi, D; Perrin, M; Hoffmann, S; Chang, A E; Ratanatharathorn, V; Uberti, J; McDonagh, K T; Mulé, J J

    1998-11-01

    We are investigating the use of tumor-pulsed dendritic cell (DC)-based vaccines in the treatment of patients with advanced cancer. In the current study, we evaluated the feasibility of obtaining both CD34+ hematopoietic stem/ progenitor cells (HSCs) and functional DCs from the same leukapheresis collection in adequate numbers for both peripheral blood stem cell transplantation (PBSCT) and immunization purposes, respectively. Leukapheresis collections of mobilized peripheral blood mononuclear cells (PBMCs) were obtained from normal donors receiving granulocyte colony-stimulating factor (G-CSF) (for allogeneic PBSCT) and from intermediate grade non-Hodgkin's lymphoma or multiple myeloma patients receiving cyclophosphamide plus G-CSF (for autologous PBSCT). High enrichment of CD34+ HSCs was obtained using an immunomagnetic bead cell separation device. After separation, the negative fraction of mobilized PBMCs from normal donors and cancer patients contained undetectable levels of CD34+ HSCs by flow cytometry. This fraction of cells was then subjected to plastic adherence, and the adherent cells were cultured for 7 days in GM-CSF (100 ng/ml) and interleukin 4 (50 ng/ml) followed by an additional 7 days in GM-CSF, interleukin 4, and tumor necrosis factor alpha (10 ng/ml) to generate DCs. Harvested DCs represented yields of 4.1+/-1.4 and 5.8+/-5.4% of the initial cells plated from the CD34+ cell-depleted mobilized PBMCs of normal donors and cancer patients, respectively, and displayed a high level expression of CD80, CD86, HLA-DR, and CD11c but not CD14. This phenotypic profile was similar to that of DCs derived from non-CD34+ cell-depleted mobilized PBMCs. DCs generated from CD34+ cell-depleted mobilized PBMCs elicited potent antitetanus as well as primary allogeneic T-cell proliferative responses in vitro, which were equivalent to DCs derived from non-CD34+ cell-depleted mobilized PBMCs. Collectively, these results demonstrate the feasibility of obtaining both DCs and

  16. Bone Marrow Plasma Cell Assessment before Peripheral Blood Stem Cell Mobilization in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Sung-Eun Lee

    2014-01-01

    Full Text Available The current definition of complete response (CR in multiple myeloma (MM includes negative serum and urine immunofixation (IFE tests and <5% bone marrow plasma cells (BMPCs. However, many studies of the prognostic impact of pretransplant response have not included BMPCs. We evaluated the prognostic impact of BMPC assessment before peripheral blood stem cell (PBSC mobilization on subsequent transplant outcomes. BMPCs were assessed by CD138, kappa, and lambda immunostaining in 106 patients. After a median followup of 24.5 months, patients with <5% BMPCs had a significantly better progression-free survival (PFS compared to those with ≥5% BMPCs (P=0.005. Patients with <5% BMPCs + serologic CR showed superior PFS compared to those with <5% BMPCs + serologic non-CR (P=0.050 or ≥5% BMPCs + serologic non-CR (P=0.001. Interestingly, the prognostic impact of BMPCs was more apparent for patients who did not achieve a serologic CR (P=0.042 compared to those with a serologic CR (P=0.647. We concluded that IFE negativity and <5% BMPCs before PBSC mobilization were important factors to predict PFS in patients with MM undergoing ASCT. Particularly, a significant impact of <5% BMPCs was observed in patients who did not achieve IFE negativity.

  17. Micromorph thin-film silicon solar cells with transparent high-mobility hydrogenated indium oxide front electrodes

    OpenAIRE

    Battaglia, Corsin; Erni, Lukas; Boccard, Mathieu; Barraud, Loris; Escarré, Jordi; SöDerströM, Karin; Bugnon, Grégory; Billet, Adrian; Ding, Laura; Despeisse, Matthieu; Haug, Franz-Josef; De Wolf, Stefaan; Ballif, Christophe

    2011-01-01

    We investigate the performance of hydrogenated indium oxide as a transparent front electrode for micromorph thin-film silicon solar cells on glass. Light trapping is achieved by replicating the morphology of state-of-the-art zinc oxide electrodes, known for their outstanding light trapping properties, via ultraviolet nanoimprint lithography. As a result of the high electron mobility and excellent near-infrared transparency of hydrogenated indium oxide, the short-circuit current density of the...

  18. Negative-pressure wound therapy induces endothelial progenitor cell mobilization in diabetic patients with foot infection or skin defects

    OpenAIRE

    Seo, Sang Gyo; Yeo, Ji Hyun; Kim, Ji Hye; Kim, Ji-Beom; Cho, Tae-Joon; Lee, Dong Yeon

    2013-01-01

    Non healing chronic wounds are difficult to treat in patients with diabetes and can result in severe medical problems for these patients and for society. Negative-pressure wound therapy (NPWT) has been adopted to treat intractable chronic wounds and has been reported to be effective. However, the mechanisms underlying the effects of this treatment have not been elucidated. To assess the vasculogenic effect of NPWT, we evaluated the systemic mobilization of endothelial progenitor cells (EPCs) ...

  19. Evaluating the extent of LINE-1 mobility following exposure to heavy metals in HepG2 cells.

    Science.gov (United States)

    Karimi, Abbas; Madjd, Zahra; Habibi, Laleh; Akrami, Seyed Mohammad

    2014-07-01

    The long interspersed elements-1 (LINE1 or L1 retrotransposon) constitute 17% of the human genome and retain mobility properties within the genome. At present, 80-100 human L1 elements are thought to be active in the genome. The mobilization of these active elements may be influenced upon exposure to the heavy metals. In the present study, we evaluated the association of aluminum, lead, and copper exposure with L1 retrotransposition in human hepatocellular carcinoma (HepG2) cell line. An in vitro retrotransposition assay using an enhanced green fluorescent protein (EGFP)-tagged L1RP cassette was established to track EGFP shining as the mark of retrotransposition. Following determination of noncytotoxic concentrations of these metals, pL1RP-EGFP-transfected HepG2 cells were subjected to long-term treatment. Flow cytometry analysis of cells treated with various concentrations of these metals along with quantitative real-time PCR was used to quantify L1 retrotransposition frequencies. Aluminum significantly increased L1 retrotransposition frequency, while no significant association was found concerning lead exposure and L1 retrotransposition. Copper treatment downregulated L1 retrotransposition as a result of EGFP-tagged L1RP expression. Our findings suggest that aluminum might have the potential to cause genomic instability by the enhancement of L1 mobilization. Thus, the risk of induced L1 retrotransposition should be considered during drug safety evaluation and risk assessments of exposure to toxic environmental agents. Further studies are needed for a more robust assay to evaluate any associations between long-term lead exposure and L1 mobility in cell culture assay.

  20. Analysis of chromosomal aberrations, micronuclei and hematological disorders among workers of wireless communication instruments and cell phone (Mobile) users

    International Nuclear Information System (INIS)

    This study was carried out to investigate the hazardous effect of electromagnetic radiation (EMR) such as chromosomal aberration, disturbed micronucleus formation and hematological disorders that may detected among workers of wireless communication instruments and mobile phone users. Seven individuals ( 3 males and 4 females) of a central workers in the microwave unit of the wireless station and 7 users of Mobil phone (4 males and 3 females ) were volunteered to give blood samples. Chromosomes and micronucleus were prepared for cytogenetic analysis as well as blood film for differential count. The results obtained in the microwave group indicated that, the total summation of all types of aberrations (chromosomes and chromatid aberrations) had a frequency of 6. 14% for the exposed group, whereas, the frequency in the control group amounted to 1.57%. In Mobil phone users, the total summation of all types of aberrations(chromosome and chromatid aberrations) had a frequency of 4.43% for the exposed group and 1.71% for the control group. The incidence of the total number of micronuclei in the exposed microwave group was increased 4.3 folds as compared with those of the control group The incidence of the total number of micronuclei in the exposed mobile phone group was increased 2 fold as compared with those in the control group. On the other hand, normal ranges of total white blood cells counts were determined for mobile phone users but abnormalities in the differential counts of the different types of the white blood cells such as neutropenia, eosinophilia and lymphocytosis were observed in the individuals number 1,2,3,7 in microwave group

  1. Best Signal Quality in Cellular Networks: Asymptotic Properties and Applications to Mobility Management in Small Cell Networks

    Directory of Open Access Journals (Sweden)

    Baccelli François

    2010-01-01

    Full Text Available The quickly increasing data traffic and the user demand for a full coverage of mobile services anywhere and anytime are leading mobile networking into a future of small cell networks. However, due to the high-density and randomness of small cell networks, there are several technical challenges. In this paper, we investigate two critical issues: best signal quality and mobility management. Under the assumptions that base stations are uniformly distributed in a ring-shaped region and that shadowings are lognormal, independent, and identically distributed, we prove that when the number of sites in the ring tends to infinity, then (i the maximum signal strength received at the center of the ring tends in distribution to a Gumbel distribution when properly renormalized, and (ii it is asymptotically independent of the interference. Using these properties, we derive the distribution of the best signal quality. Furthermore, an optimized random cell scanning scheme is proposed, based on the evaluation of the optimal number of sites to be scanned for maximizing the user data throughput.

  2. Hematopoietic Stem Cell Mobilization and Homing after Transplantation: The Role of MMP-2, MMP-9, and MT1-MMP

    Directory of Open Access Journals (Sweden)

    Neeta Shirvaikar

    2012-01-01

    Full Text Available Hematopoietic stem/progenitor cells (HSPCs are used in clinical transplantation to restore hematopoietic function. Here we review the role of the soluble matrix metalloproteinases MMP-2 and MMP-9, and membrane type (MT1-MMP in modulating processes critical to successful transplantation of HSPC, such as mobilization and homing. Growth factors and cytokines which are employed as mobilizing agents upregulate MMP-2 and MMP-9. Recently we demonstrated that MT1-MMP enhances HSPC migration across reconstituted basement membrane, activates proMMP-2, and contributes to a highly proteolytic bone marrow microenvironment that facilitates egress of HSPC. On the other hand, we reported that molecules secreted during HSPC mobilization and collection, such as hyaluronic acid and thrombin, increase MT1-MMP expression in cord blood HSPC and enhance (prime their homing-related responses. We suggest that modulation of MMP-2, MMP-9, and MT1-MMP expression has potential for development of new therapies for more efficient mobilization, homing, and engraftment of HSPC, which could lead to improved transplantation outcomes.

  3. Mobile Therapy: Case Study Evaluations of a Cell Phone Application for Emotional Self-Awareness

    OpenAIRE

    Morris, Margaret E; Kathawala, Qusai; Leen, Todd K.; Gorenstein, Ethan E.; Guilak, Farzin; Labhard, Michael; DeLeeuw, William

    2010-01-01

    Background Emotional awareness and self-regulation are important skills for improving mental health and reducing the risk of cardiovascular disease. Cognitive behavioral therapy can teach these skills but is not widely available. Objective This exploratory study examined the potential of mobile phone technologies to broaden access to cognitive behavioral therapy techniques and to provide in-the-moment support. Methods We developed a mobile phone application with touch screen scales for mood r...

  4. Dynamic tracking and mobility analysis of single GLUT4 storage vesicle in live 3T3-L1 cells

    Institute of Scientific and Technical Information of China (English)

    Chen Hong LI; Li BAI; Dong Dong LI; Sheng XIA; Tao XU

    2004-01-01

    Glucose transporter 4 (GLUT4) is responsible for insulin-stimulated glucose transporting into the insulin-sensitive fat and muscle cells. The dynamics of GLUT4 storage vesicles (GSVs) remains to be explored and it is unclear how GSVs are arranged based on their mobility. We examined this issue in 3T3-L1 cells via investigating the three-dimensional mobility of single GSV labeled with EGFP-fused GLUT4. A thin layer of cytosol right adjacent to the plasma membrane was illuminated and successively imaged at 5 Hz under a total internal reflection fluorescence microscope with a penetration depth of 136 nm. Employing single particle tracking, the three-dimensional subpixel displacement of single GSV was tracked at a spatial precision of 22 nm. Both the mean square displacement and the diffusion coefficient were calculated for each vesicle. Tracking results revealed that vesicles moved as if restricted within a cage that has a mean radius of 160 nm, suggesting the presence of some intracellular tethering matrix. By constructing the histogram of the diffusion coefficients of GSVs, we observed a smooth distribution instead of the existence of distinct groups. The result indicates that GSVs are dynamically retained in a continuous and wide range of mobility rather than into separate classes.

  5. Hematopoietic Progenitor Cell Mobilization with “Just-in-Time” Plerixafor Approach is a Cost Effective Alternative to Routine Plerixafor Use

    Science.gov (United States)

    Veltri, Lauren; Cumpston, Aaron; Shillingburg, Alexandra; Wen, Sijin; Luo, Jin; Leadmon, Sonia; Watkins, Kathy; Craig, Michael; Hamadani, Mehdi; Kanate, Abraham S.

    2015-01-01

    Hematopoietic progenitor cell (HPC) mobilization with granulocyte-colony stimulating factor (G-CSF) and plerixafor results in superior CD34+ cell yield, when compared to mobilization with G-CSF alone in patients with myeloma and lymphoma. However, plerixafor-based approaches are associated with high costs. To circumvent this, several institutions use a so-called “just-in-time” plerixafor (JIT-P) approach, where plerixafor is only administered to patients likely to fail mobilization with G-CSF alone. Whether such a JIT-P approach is cost effective has not been confirmed to date. We present here, results of 136 patients with myeloma or lymphoma who underwent mobilization with two different approaches of plerixafor utilization. Between Jan 2010-Oct 2012 (n=76) patients uniformly received mobilization with G-CSF and plerixafor (routine G+P cohort). To reduce mobilization costs, between Nov 2012-Jun 2014 (n=60) patients were mobilized with JIT-P where plerixafor was only administered to patients likely to fail mobilization with G-CSF alone. Patients in routine G+P group had a higher median peak peripheral blood CD34+ cell count (62 vs. 29 cells/μL, pJIT-P group 40% (n=24) completed adequate HPC collection without plerixafor. There was no difference in mobilization failure rates. The mean number of plerixafor doses utilized in JIT-P was lower (1.3 vs. 2.1, p=0.0002). The mean estimated cost in the routine G+P group was higher than that in the JIT-P group (USD 27,513 vs. USD 23,597, p=0.01). Our analysis demonstrates that mobilization with a JIT-P approach is a safe, effective and cost efficient strategy for HPC collection. PMID:26475754

  6. Cell Selection Game for Densely-Deployed Sensor and Mobile Devices In 5G Networks Integrating Heterogeneous Cells and the Internet of Things.

    Science.gov (United States)

    Wang, Lusheng; Wang, Yamei; Ding, Zhizhong; Wang, Xiumin

    2015-09-18

    With the rapid development of wireless networking technologies, the Internet of Things and heterogeneous cellular networks (HCNs) tend to be integrated to form a promising wireless network paradigm for 5G. Hyper-dense sensor and mobile devices will be deployed under the coverage of heterogeneous cells, so that each of them could freely select any available cell covering it and compete for resource with others selecting the same cell, forming a cell selection (CS) game between these devices. Since different types of cells usually share the same portion of the spectrum, devices selecting overlapped cells can experience severe inter-cell interference (ICI). In this article, we study the CS game among a large amount of densely-deployed sensor and mobile devices for their uplink transmissions in a two-tier HCN. ICI is embedded with the traditional congestion game (TCG), forming a congestion game with ICI (CGI) and a congestion game with capacity (CGC). For the three games above, we theoretically find the circular boundaries between the devices selecting the macrocell and those selecting the picocells, indicated by the pure strategy Nash equilibria (PSNE). Meanwhile, through a number of simulations with different picocell radii and different path loss exponents, the collapse of the PSNE impacted by severe ICI (i.e., a large number of picocell devices change their CS preferences to the macrocell) is profoundly revealed, and the collapse points are identified.

  7. Trophic Effects and Regenerative Potential of Mobilized Mesenchymal Stem Cells From Bone Marrow and Adipose Tissue as Alternative Cell Sources for Pulp/Dentin Regeneration.

    Science.gov (United States)

    Murakami, Masashi; Hayashi, Yuki; Iohara, Koichiro; Osako, Yohei; Hirose, Yujiro; Nakashima, Misako

    2015-01-01

    Dental pulp stem cell (DPSC) subsets mobilized by granulocyte-colony-stimulating factor (G-CSF) are safe and efficacious for complete pulp regeneration. The supply of autologous pulp tissue, however, is very limited in the aged. Therefore, alternative sources of mesenchymal stem/progenitor cells (MSCs) are needed for the cell therapy. In this study, DPSCs, bone marrow (BM), and adipose tissue (AD)-derived stem cells of the same individual dog were isolated using G-CSF-induced mobilization (MDPSCs, MBMSCs, and MADSCs). The positive rates of CXCR4 and G-CSFR in MDPSCs were similar to MADSCs and were significantly higher than those in MBMSCs. Trophic effects of MDPSCs on angiogenesis, neurite extension, migration, and antiapoptosis were higher than those of MBMSCs and MADSCs. Pulp-like loose connective tissues were regenerated in all three MSC transplantations. Significantly higher volume of regenerated pulp and higher density of vascularization and innervation were observed in response to MDPSCs compared to MBMSC and MADSC transplantation. Collagenous matrix containing dentin sialophosphoprotein (DSPP)-positive odontoblast-like cells was the highest in MBMSCs and significantly higher in MADSCs compared to MDPSCs. MBMSCs and MADSCs, therefore, have potential for pulp regeneration, although the volume of regenerated pulp tissue, angiogenesis, and reinnervation, were less. Thus, in conclusion, an alternative cell source for dental pulp/dentin regeneration are stem cells from BM and AD tissue.

  8. Cell Selection Game for Densely-Deployed Sensor and Mobile Devices In 5G Networks Integrating Heterogeneous Cells and the Internet of Things.

    Science.gov (United States)

    Wang, Lusheng; Wang, Yamei; Ding, Zhizhong; Wang, Xiumin

    2015-01-01

    With the rapid development of wireless networking technologies, the Internet of Things and heterogeneous cellular networks (HCNs) tend to be integrated to form a promising wireless network paradigm for 5G. Hyper-dense sensor and mobile devices will be deployed under the coverage of heterogeneous cells, so that each of them could freely select any available cell covering it and compete for resource with others selecting the same cell, forming a cell selection (CS) game between these devices. Since different types of cells usually share the same portion of the spectrum, devices selecting overlapped cells can experience severe inter-cell interference (ICI). In this article, we study the CS game among a large amount of densely-deployed sensor and mobile devices for their uplink transmissions in a two-tier HCN. ICI is embedded with the traditional congestion game (TCG), forming a congestion game with ICI (CGI) and a congestion game with capacity (CGC). For the three games above, we theoretically find the circular boundaries between the devices selecting the macrocell and those selecting the picocells, indicated by the pure strategy Nash equilibria (PSNE). Meanwhile, through a number of simulations with different picocell radii and different path loss exponents, the collapse of the PSNE impacted by severe ICI (i.e., a large number of picocell devices change their CS preferences to the macrocell) is profoundly revealed, and the collapse points are identified. PMID:26393617

  9. Cell Selection Game for Densely-Deployed Sensor and Mobile Devices In 5G Networks Integrating Heterogeneous Cells and the Internet of Things

    Directory of Open Access Journals (Sweden)

    Lusheng Wang

    2015-09-01

    Full Text Available With the rapid development of wireless networking technologies, the Internet of Things and heterogeneous cellular networks (HCNs tend to be integrated to form a promising wireless network paradigm for 5G. Hyper-dense sensor and mobile devices will be deployed under the coverage of heterogeneous cells, so that each of them could freely select any available cell covering it and compete for resource with others selecting the same cell, forming a cell selection (CS game between these devices. Since different types of cells usually share the same portion of the spectrum, devices selecting overlapped cells can experience severe inter-cell interference (ICI. In this article, we study the CS game among a large amount of densely-deployed sensor and mobile devices for their uplink transmissions in a two-tier HCN. ICI is embedded with the traditional congestion game (TCG, forming a congestion game with ICI (CGI and a congestion game with capacity (CGC. For the three games above, we theoretically find the circular boundaries between the devices selecting the macrocell and those selecting the picocells, indicated by the pure strategy Nash equilibria (PSNE. Meanwhile, through a number of simulations with different picocell radii and different path loss exponents, the collapse of the PSNE impacted by severe ICI (i.e., a large number of picocell devices change their CS preferences to the macrocell is profoundly revealed, and the collapse points are identified.

  10. Restricted mobility of specific functional groups reduces anti-cancer drug activity in healthy cells

    DEFF Research Database (Denmark)

    Longo Martins, Murillo; Ignazzi, Rosanna; Eckert, Juergen;

    2016-01-01

    The most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti...... with reduced clearance rate and toxicity. X-rays and neutrons were used to investigate the carrier structure, as well as to assess the drug mobility within the bio-nanocomposite. From these unique data we show that partial mobility restriction of active groups of the drug molecule suggests why this carrier...

  11. SDN-controlled topology-reconfigurable optical mobile fronthaul architecture for bidirectional CoMP and low latency inter-cell D2D in the 5G mobile era.

    Science.gov (United States)

    Cvijetic, Neda; Tanaka, Akihiro; Kanonakis, Konstantinos; Wang, Ting

    2014-08-25

    We demonstrate the first SDN-controlled optical topology-reconfigurable mobile fronthaul (MFH) architecture for bidirectional coordinated multipoint (CoMP) and low latency inter-cell device-to-device (D2D) connectivity in the 5G mobile networking era. SDN-based OpenFlow control is used to dynamically instantiate the CoMP and inter-cell D2D features as match/action combinations in control plane flow tables of software-defined optical and electrical switching elements. Dynamic re-configurability is thereby introduced into the optical MFH topology, while maintaining back-compatibility with legacy fiber deployments. 10 Gb/s peak rates with <7 μs back-to-back transmission latency and 29.6 dB total power budget are experimentally demonstrated, confirming the attractiveness of the new approach for optical MFH of future 5G mobile systems. PMID:25321284

  12. Creating mobile traffic grids based on geospatial data and using cell assignment probabilities

    NARCIS (Netherlands)

    Phillipson, F.; Erdbrink, R.T.A.

    2015-01-01

    Mobile operators’ investments depend largely on the costs of the radio network. The efficiency of building and maintaining the radio network is determined largely by the quality of the radio planning process. The planning tool, the propagation predictions and the spatial traffic input together are t

  13. The effect of morphology upon mobility : Implications for bulk heterojunction solar cells with nonuniform blend morphology

    NARCIS (Netherlands)

    Groves, C.; Koster, L. J. A.; Greenham, N. C.

    2009-01-01

    We use a Monte Carlo model to predict the effect of composition, domain size, and energetic disorder upon the mobility of carriers in an organic donor-acceptor blend. These simulations show that, for the changes in local morphology expected within the thickness of a typical bulk heterojunction photo

  14. Micro-scale spatial expansion of microbial cells and mobile genetic elements

    DEFF Research Database (Denmark)

    Smets, Barth F.; Kreft, Jan-Ulrich; Or, Dani;

    Microbes can actively explore their local spatial environment when sufficiently hydrated pathways are present - mobile gene elements can also travel in local environments when cellular density is sufficient. In this presentation, I will present our efforts at predicting the dynamics of these two ...

  15. Melatonin and N-acetyl-serotonin cross the red blood cell membrane and evoke calcium mobilization in malarial parasites

    Directory of Open Access Journals (Sweden)

    Hotta C.T.

    2003-01-01

    Full Text Available The duration of the intraerythrocytic cycle of Plasmodium is a key factor in the pathogenicity of this parasite. The simultaneous attack of the host red blood cells by the parasites depends on the synchronicity of their development. Unraveling the signals at the basis of this synchronicity represents a challenging biological question and may be very important to develop alternative strategies for therapeutic approaches. Recently, we reported that the synchrony of Plasmodium is modulated by melatonin, a host hormone that is synthesized only during the dark phases. Here we report that N-acetyl-serotonin, a melatonin precursor, also releases Ca2+ from isolated P. chabaudi parasites at micro- and nanomolar concentrations and that the release is blocked by 250 mM luzindole, an antagonist of melatonin receptors, and 20 mM U73122, a phospholipase C inhibitor. On the basis of confocal microscopy, we also report the ability of 0.1 µM melatonin and 0.1 µM N-acetyl-serotonin to cross the red blood cell membrane and to mobilize intracellular calcium in parasites previously loaded with the fluorescent calcium indicator Fluo-3 AM. The present data represent a step forward into the understanding of the signal transduction process in the host-parasite relationship by supporting the idea that the host hormone melatonin and N-acetyl-serotonin generate IP3 and therefore mobilize intracellular Ca2+ in Plasmodium inside red blood cells.

  16. Cyclic AMP suppresses interleukin-5 synthesis by human helper T cells via the downregulation of the calcium mobilization pathway

    OpenAIRE

    Kaminuma, Osamu; Mori, Akio; Ogawa, Koji; Kikkawa, Hideo; Nakata, Aya; Ikezawa, Katsuo; Okudaira, Hirokazu

    1999-01-01

    To delineate the mechanism by which cyclic AMP (cAMP) suppresses interleukin (IL)-5 synthesis, the effects of prostaglandin (PG) E2, forskolin, dibutyryl (db)-cAMP and the Ca2+ ionophore, ionomycin on cytokine synthesis, proliferation and CD25 expression of human T cells were investigated. Further studies were performed by measurement of the intracellular concentrations of cyclic AMP ([cAMP]i) and Ca2+ ([Ca2+]i) and by electrophoretic mobility shift analysis (EMSA).PGE2, forskolin and db-cAMP...

  17. Effects of surface treatments on high mobility ITiO coated glass substrates for dye sensitized solar cells and their tandem solar cell applications

    Energy Technology Data Exchange (ETDEWEB)

    Bowers, J.W.; Upadhyaya, H.M. [Centre for Renewable Energy Systems Technology, Department of Electronic and Electrical Engineering, Loughborough University, Leicestershire LE11 3TU (United Kingdom); Nakada, T. [Department of Electrical Engineering and Electronics, Aoyama Gakuin University, Setagaya-ku, Tokyo 157-8572 (Japan); Tiwari, A.N. [Laboratory for Thin Films and Photovoltaics, EMPA (Swiss Federal Laboratories for Material Testing and Research), Ueberlandstrasse 129, CH-8600 Duebendorf (Switzerland)

    2010-04-15

    Dye sensitized solar cells (DSCs) have the potential to be used as a top device in a tandem solar cell structure with a bottom Cu(In,Ga)Se{sub 2} (CIGS) cell. Optical losses, however, within the fluorine doped tin oxide (FTO) conducting electrode used with DSCs limit the light available for the bottom cell for photocurrent generation, and therefore the whole device. High mobility transparent conducting oxides have the potential to reduce these optical losses, since the transmission in the near infrared of these substrates is high compared to standard conducting oxides. Attempts have in the past been made to use these conducting oxide substrates as the electrodes in DSCs; however delamination of the deposited TiO{sub 2} layer and an increase in sheet resistance of the high mobility material have caused problems. Here we present alternative surface treatments to ensure that delamination is significantly reduced, as well as a method to recover lost conductivity of heated indium oxide films, which result in transparent cells of over 7% efficiency, which is close to that reached on standard FTO substrates. (author)

  18. Cost and clinical analysis of autologous hematopoietic stem cell mobilization with G-CSF and plerixafor compared to G-CSF and cyclophosphamide.

    Science.gov (United States)

    Shaughnessy, Paul; Islas-Ohlmayer, Miguel; Murphy, Julie; Hougham, Maureen; MacPherson, Jill; Winkler, Kurt; Silva, Matthew; Steinberg, Michael; Matous, Jeffrey; Selvey, Sheryl; Maris, Michael; McSweeney, Peter A

    2011-05-01

    Plerixafor plus granulocyte-colony stimulating factor (G-CSF) has been shown to mobilize more CD34(+) cells than G-CSF alone for autologous hematopoietic stem cell transplantation (HSCT). However, many centers use chemotherapy followed by G-CSF to mobilize CD34(+) cells prior to HSCT. We performed a retrospective study of patients who participated in the expanded access program (EAP) of plerixafor and G-CSF for initial mobilization of CD34(+) cells, and compared outcomes to matched historic controls mobilized with cyclophosphamide 3-5 g/m(2) and G-CSF at 2 centers that participated in the EAP Control patients were matched for age, sex, disease, disease stage, and number of prior therapies. Mobilization costs were defined to be the costs of medical procedures, resource utilization, and medications. Median national CMS reimbursement rates were used to establish the costs of procedures, hospitalization, provider visits, apheresis, CD34(+) cell processing and cryopreservation. Average sale price was used for G-CSF, plerixafor, cyclophosphamide, MESNA, antiemetics, and antimicrobials. A total of 33 patients from the EAP and 33 matched controls were studied. Two patients in the control group were hospitalized for neutropenic fever during the mobilization period. Apheresis started on the scheduled day in 33 (100%) study patients and in 29 (88%) control patients (P = 0.04). Sixteen (48%) control patients required weekend apheresis. There was no difference in number of CD34(+) cells collected between the groups, and all patients proceeded to HSCT with no difference in engraftment outcomes. Median total cost of mobilization was not different between the plerixafor/G-CSF and control groups ($14,224 versus $18,824; P = .45). In conclusion, plerixafor/G-CSF and cyclophosphamide/G-CSF for upfront mobilization of CD34(-) cells resulted in similar numbers of cells collected, costs of mobilization, and clinical outcomes. Additionally, plerixafor/G-CSF mobilization resulted in more

  19. The Consequence of Immune Suppressive Cells in the Use of Therapeutic Cancer Vaccines and Their Importance in Immune Monitoring

    Directory of Open Access Journals (Sweden)

    Matteo Vergati

    2011-01-01

    Full Text Available Evaluating the number, phenotypic characteristics, and function of immunosuppressive cells in the tumor microenvironment and peripheral blood could elucidate the antitumor immune response and provide information to evaluate the efficacy of cancer vaccines. Further studies are needed to evaluate the correlation between changes in immunosuppressive cells and clinical outcomes of patients in cancer vaccine clinical trials. This paper focuses on the role of T-regulatory cells, myeloid-derived suppressor cells, and tumor-associated macrophages in cancer and cancer immunotherapy and their role in immune monitoring.

  20. Downregulation of high mobility group box 1 modulates telomere homeostasis and increases the radiosensitivity of human breast cancer cells.

    Science.gov (United States)

    Ke, Shaobo; Zhou, Fuxiang; Yang, Hui; Wei, Yuehua; Gong, Jun; Mei, Zijie; Wu, Lin; Yu, Haijun; Zhou, Yunfeng

    2015-03-01

    The functions of the high mobility group box 1 (HMGB1) in tumor cells include replenishing telomeric DNA and maintaining cell immortality. There is a negative correlation between human telomerase reverse transcriptase (hTERT) and radiosensitivity in tumor cells. Our aim was to elucidate the relationship among HMGB1, telomere homeostasis and radiosensitivity in MCF-7 cells. In this study, we established stably transfected control (MCF-7-NC) and HMGB1 knockdown (MCF-7-shHMGB1) cell lines. The expression of HMGB1 mRNA and the relative telomere length were examined by real-time PCR. Radiosensitivity was detected by clonogenic assay. The protein expressions were determined by western blot analysis. The telomerase activity was detected by PCR-ELISA. Proliferation ability was examined by CCK-8 assay. Cell cycle and apoptosis were examined by flow cytometry. DNA damage foci were detected by immunofluorescence. ShRNA-mediated downregulation of HMGB1 expression increased the radiosensitivity of MCF-7 cells, and reduced the accumulation of hTERT and cyclin D1. Moreover, knockdown of HMGB1 in MCF-7 cells inhibited telomerase activity and cell proliferation, while increasing the extent of apoptosis. Downregulation of HMGB1 modulated telomere homeostasis by changing the level of telomere-binding proteins, such as TPP1 (PTOP), TRF1 and TRF2. This downregulation also inhibited the ATM and ATR signaling pathways. The current data demonstrate that knockdown of HMGB1 breaks telomere homeostasis, enhances radiosensitivity, and suppresses the repair of DNA damage in human breast cancer cells. These results suggested that HMGB1 might be a potential radiotherapy target in human breast cancer. PMID:25501936

  1. Analytical modeling and performance evaluation of cell selection algorithms for mobile networks with backhaul capacity constraints

    OpenAIRE

    Olmos Bonafé, Juan José; Ferrús Ferré, Ramón Antonio; Galeana Zapién, Hiram

    2013-01-01

    Wireless communications technologies play an essential role to support the Public Protection and Disaster Relief (PPDR) operational needs. The current Private/Professional Mobile Radio (PMR) technologies used for PPDR communications offer a rich set of voice-centric services but have very limited data transmission capabilities, which are unable to handle the increasing PPDR community demand for a wider range of data-centric services. Though some efforts have been devoted to upgrade PMR techno...

  2. MHC I Expression Regulates Co-clustering and Mobility of Interleukin-2 and -15 Receptors in T Cells.

    Science.gov (United States)

    Mocsár, Gábor; Volkó, Julianna; Rönnlund, Daniel; Widengren, Jerker; Nagy, Péter; Szöllősi, János; Tóth, Katalin; Goldman, Carolyn K; Damjanovich, Sándor; Waldmann, Thomas A; Bodnár, Andrea; Vámosi, György

    2016-07-12

    MHC glycoproteins form supramolecular clusters with interleukin-2 and -15 receptors in lipid rafts of T cells. The role of highly expressed MHC I in maintaining these clusters is unknown. We knocked down MHC I in FT7.10 human T cells, and studied protein clustering at two hierarchic levels: molecular aggregations and mobility by Förster resonance energy transfer and fluorescence correlation spectroscopy; and segregation into larger domains or superclusters by superresolution stimulated emission depletion microscopy. Fluorescence correlation spectroscopy-based molecular brightness analysis revealed that the studied molecules diffused as tight aggregates of several proteins of a kind. Knockdown reduced the number of MHC I containing molecular aggregates and their average MHC I content, and decreased the heteroassociation of MHC I with IL-2Rα/IL-15Rα. The mobility of not only MHC I but also that of IL-2Rα/IL-15Rα increased, corroborating the general size decrease of tight aggregates. A multifaceted analysis of stimulated emission depletion images revealed that the diameter of MHC I superclusters diminished from 400-600 to 200-300 nm, whereas those of IL-2Rα/IL-15Rα hardly changed. MHC I and IL-2Rα/IL-15Rα colocalized with GM1 ganglioside-rich lipid rafts, but MHC I clusters retracted to smaller subsets of GM1- and IL-2Rα/IL-15Rα-rich areas upon knockdown. Our results prove that changes in expression level may significantly alter the organization and mobility of interacting membrane proteins. PMID:27410738

  3. Ifosfamide, Cisplatin or Carboplatin, and Etoposide (ICE)-based Chemotherapy for Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Lymphomas

    Institute of Scientific and Technical Information of China (English)

    Ping Zhou; Peng Liu; Sheng-Yu Zhou; Xiao-Hui He; Xiao-Hong Han; Yan Qin; Sheng Yang

    2015-01-01

    Background:High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a promising approach for lymphomas.This study aimed to evaluate the effect of ifosfamide,cisplatin or carboplatin,and etoposide (ICE)-based regimen as a mobilization regimen on relapsed,refractory,or high-risk aggressive lymphoma.Methods:From June 2001 to May 2013,patients with lymphomas who mobilized by ICE-based regimen for ASCT were analyzed in this retrospective study.The results of the autologous peripheral blood stem cells collection,toxicity,engraftment after ICE-based mobilization regimen were analyzed in this study.Furthermore,risk factors for overall survival (OS) and progression free survival (PFS) were evaluated by univariate analysis.Results:The stem cells were mobilized using ICE-based regimen plus rituximab or ICE-based regimen alone in 12 patients and 54 patients,respectively.The results of stem cell mobilization were excellent.Ninety-seven percentages of the patients had the stem cell collection of at least 2.0 × 106 CD34+ cells/kg and 68% had at least 5 × 106 CD34+ cells/kg.Fifty-eight percentage of the patients experienced Grade 4 neutropenia,20% developed febrile neutropenia,and only 12% had Grade 4 thrombocytopenia.At a median follow-up of 63.8 months,the 5-year PFS and OS were 64.4% and 75.3%,respectively.Conclusion:ICE is a powerful regimen for stem cell mobilization in patients with lymphomas.

  4. Frozen cord blood hematopoietic stem cells differentiate into higher numbers of functional natural killer cells in vitro than mobilized hematopoietic stem cells or freshly isolated cord blood hematopoietic stem cells.

    Science.gov (United States)

    Luevano, Martha; Domogala, Anna; Blundell, Michael; Jackson, Nicola; Pedroza-Pacheco, Isabela; Derniame, Sophie; Escobedo-Cousin, Michelle; Querol, Sergio; Thrasher, Adrian; Madrigal, Alejandro; Saudemont, Aurore

    2014-01-01

    Adoptive natural killer (NK) cell therapy relies on the acquisition of large numbers of NK cells that are cytotoxic but not exhausted. NK cell differentiation from hematopoietic stem cells (HSC) has become an alluring option for NK cell therapy, with umbilical cord blood (UCB) and mobilized peripheral blood (PBCD34(+)) being the most accessible HSC sources as collection procedures are less invasive. In this study we compared the capacity of frozen or freshly isolated UCB hematopoietic stem cells (CBCD34(+)) and frozen PBCD34(+) to generate NK cells in vitro. By modifying a previously published protocol, we showed that frozen CBCD34(+) cultures generated higher NK cell numbers without loss of function compared to fresh CBCD34(+) cultures. NK cells generated from CBCD34(+) and PBCD34(+) expressed low levels of killer-cell immunoglobulin-like receptors but high levels of activating receptors and of the myeloid marker CD33. However, blocking studies showed that CD33 expression did not impact on the functions of the generated cells. CBCD34(+)-NK cells exhibited increased capacity to secrete IFN-γ and kill K562 in vitro and in vivo as compared to PBCD34(+)-NK cells. Moreover, K562 killing by the generated NK cells could be further enhanced by IL-12 stimulation. Our data indicate that the use of frozen CBCD34(+) for the production of NK cells in vitro results in higher cell numbers than PBCD34(+), without jeopardizing their functionality, rendering them suitable for NK cell immunotherapy. The results presented here provide an optimal strategy to generate NK cells in vitro for immunotherapy that exhibit enhanced effector function when compared to alternate sources of HSC.

  5. Frozen cord blood hematopoietic stem cells differentiate into higher numbers of functional natural killer cells in vitro than mobilized hematopoietic stem cells or freshly isolated cord blood hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Martha Luevano

    Full Text Available Adoptive natural killer (NK cell therapy relies on the acquisition of large numbers of NK cells that are cytotoxic but not exhausted. NK cell differentiation from hematopoietic stem cells (HSC has become an alluring option for NK cell therapy, with umbilical cord blood (UCB and mobilized peripheral blood (PBCD34(+ being the most accessible HSC sources as collection procedures are less invasive. In this study we compared the capacity of frozen or freshly isolated UCB hematopoietic stem cells (CBCD34(+ and frozen PBCD34(+ to generate NK cells in vitro. By modifying a previously published protocol, we showed that frozen CBCD34(+ cultures generated higher NK cell numbers without loss of function compared to fresh CBCD34(+ cultures. NK cells generated from CBCD34(+ and PBCD34(+ expressed low levels of killer-cell immunoglobulin-like receptors but high levels of activating receptors and of the myeloid marker CD33. However, blocking studies showed that CD33 expression did not impact on the functions of the generated cells. CBCD34(+-NK cells exhibited increased capacity to secrete IFN-γ and kill K562 in vitro and in vivo as compared to PBCD34(+-NK cells. Moreover, K562 killing by the generated NK cells could be further enhanced by IL-12 stimulation. Our data indicate that the use of frozen CBCD34(+ for the production of NK cells in vitro results in higher cell numbers than PBCD34(+, without jeopardizing their functionality, rendering them suitable for NK cell immunotherapy. The results presented here provide an optimal strategy to generate NK cells in vitro for immunotherapy that exhibit enhanced effector function when compared to alternate sources of HSC.

  6. Computer and cell phone access for individuals with mobility impairments: an overview and case studies.

    Science.gov (United States)

    Burgstahler, Sheryl; Comden, Dan; Lee, Sang-Mook; Arnold, Anthony; Brown, Kayla

    2011-01-01

    Computers, telephones, and assistive technology hold promise for increasing the independence, productivity, and participation of individuals with disabilities in academic, employment, recreation, and other activities. However, to reach this goal, technology must be accessible to, available to, and usable by everyone. The authors of this article share computer and telephone access challenges faced by individuals with neurological and other impairments, assistive technology solutions, issues that impact product adoption and use, needs for new technologies, and recommendations for practitioners and researchers. They highlight the stories of three individuals with neurological/mobility impairments, the technology they have found useful to them, and their recommendations for future product development. PMID:21558625

  7. Lateral Mobility and Nanoscale Spatial Arrangement of Chemokine-activated α4β1 Integrins on T Cells*

    Science.gov (United States)

    Sosa-Costa, Alberto; Isern de Val, Sol; Sevilla-Movilla, Silvia; Teixidó, Joaquin

    2016-01-01

    Chemokine stimulation of integrin α4β1-dependent T lymphocyte adhesion is a key step during lymphocyte trafficking. A central question regarding α4β1 function is how its lateral mobility and organization influence its affinity and avidity following cell stimulation with chemokines and/or ligands. Using single particle tracking and superresolution imaging approaches, we explored the lateral mobility and spatial arrangement of individual α4β1integrins on T cells exposed to different activating stimuli. We show that CXCL12 stimulation leads to rapid and transient α4β1activation, measured by induction of the activation epitope recognized by the HUTS-21 anti-β1antibody and by increased talin-β1 association. CXCL12-dependent α4β1 activation directly correlated with restricted lateral diffusion and integrin immobilization. Moreover, co-stimulation by CXCL12 together with soluble VCAM-1 potentiated integrin immobilization with a 5-fold increase in immobile integrins compared with unstimulated conditions. Our data indicate that docking by talin of the chemokine-activated α4β1 to the actin cytoskeleton favors integrin immobilization, which likely facilitates ligand interaction and increased adhesiveness. Superresolution imaging showed that the nanoscale organization of high-affinity α4β1 remains unaffected following chemokine and/or ligand addition. Instead, newly activated α4β1 integrins organize on the cell membrane as independent units without joining pre-established integrin sites to contribute to cluster formation. Altogether, our results provide a rationale to understand how the spatiotemporal organization of activated α4β1 integrins regulates T lymphocyte adhesion. PMID:27481944

  8. Mobile Learning Using Mobile Phones

    Science.gov (United States)

    Vicente, Paula

    2013-01-01

    The participation in mobile learning programs is conditioned by having/using mobile communication technology. Those who do not have or use such technology cannot participate in mobile learning programs. This study evaluates who are the most likely participants of mobile learning programs by examining the demographic profile and mobile phone usage…

  9. Expanding the List of Dysregulated Immunosuppressive Cells in Psoriasis.

    Science.gov (United States)

    Soler, David C; McCormick, Thomas S

    2016-09-01

    Traditionally, myeloid-derived suppressor cells (MDSC) have been studied in regard to their increased numbers of circulating cells in cancer patients. Recent research efforts have also increased awareness of MDSC in non-malignant inflammatory diseases, including asthma, inflammatory bowel disease, and arthritis. Psoriasis can now be added to the growing list of inflammatory disorders with an MDSC component. Cao et al. report increased numbers of monocytic myeloid-derived suppressor cells (Mo-MDSC) in psoriasis patients and examine the implication of dysregulated Mo-MDSC function. Cao et al. describe psoriatic Mo-MDSC that produce increased IL-23, IL-1b, and CCL4 cytokines compared to Mo-MDSC from healthy controls. These results complement previous research demonstrating psoriatic Mo-MDSC are unable to suppress autologous and heterologous CD8 T-cell proliferations, display decreased expression levels of PD-1 as well as PD-L1, and fail to produce effective immuno-competent regulatory T cells (Tregs). Cao et al. also identify the unique expression of the surface protein DC-HIL on psoriatic Mo-MDSC. The expanded population of DC-HIL(+) Mo-MDSC in psoriasis patients, however, display inferior suppressive capabilities compared to DC-HIL(+) Mo-MDSC found in melanoma patients, suggesting contextual signaling as a potential contributing factor to Mo-MDSC function. PMID:27542294

  10. Effect of cellular mobility on immune response

    Science.gov (United States)

    Pandey, R. B.; Mannion, R.; Ruskin, H. J.

    2000-08-01

    Mobility of cell types in our HIV immune response model is subject to an intrinsic mobility and an explicit directed mobility, which is governed by Pmob. We investigate how restricting the explicit mobility, while maintaining the innate mobility of a viral-infected cell, affects the model's results. We find that increasing the explicit mobility of the immune system cells leads to viral dominance for certain levels of viral mutation. We conclude that increasing immune system cellular mobility indirectly increases the virus’ inherent mobility.

  11. Molecular crosstalk between cancer cells and tumor microenvironment components suggests potential targets for new therapeutic approaches in mobile tongue cancer

    International Nuclear Information System (INIS)

    We characterized tumor microenvironment (TME) components of mobile tongue (MT) cancer patients in terms of overall inflammatory infiltrate, focusing on the protumorigenic/anti-inflammatory phenotypes and on cancer-associated fibroblasts (CAFs) in order to determine their interrelations and associations with clinical outcomes. In addition, by culturing tongue carcinoma cells (HSC-3) on a three-dimensional myoma organotypic model that mimics TME, we attempted to investigate the possible existence of a molecular crosstalk between cancer cells and TME components. Analysis of 64 cases of MT cancer patients revealed that the overall density of the inflammatory infiltrate was inversely correlated to the density of CAFs (P = 0.01), but that the cumulative density of the protumorigenic/anti-inflammatory phenotypes, including regulatory T cells (Tregs, Foxp3+), tumor-associated macrophages (TAM2, CD163+), and potentially Tregs-inducing immune cells (CD80+), was directly correlated with the density of CAFs (P = 0.01). The hazard ratio (HR) for recurrence in a TME rich in CD163+ Foxp3+ CD80+ was 2.9 (95% CI 1.03–8.6, P = 0.043 compared with low in CD163+ Foxp3+ CD80+). The HR for recurrence in a TME rich in CAFs was 4.1 (95% confidence interval [CI] 1.3–12.8, P = 0.012 compared with low in CAFs). In vitro studies showed cancer-derived exosomes, epithelial–mesenchymal transition process, fibroblast-to-CAF-like cell transdifferentiation, and reciprocal interrelations between different cytokines suggesting the presence of molecular crosstalk between cancer cells and TME components. Collectively, these results highlighted the emerging need of new therapies targeting this crosstalk between the cancer cells and TME components in MT cancer

  12. Commercializing Light-Duty Plug-In/Plug-Out Hydrogen-Fuel-Cell Vehicles:“Mobile Electricity†Technologies, Early California Household Markets, and Innovation Management

    OpenAIRE

    Williams, Brett D.

    2007-01-01

    Starting from the premise that new consumer value must drive hydrogen-fuel-cell-vehicle (H2FCV) commercialization, a group of opportunities collectively called “Mobile Electricity†is characterized. Mobile Electricity (Me-) redefines H2FCVs as innovative products able to import and export electricity across the traditional vehicle boundary. Such vehicles could provide home recharging and mobile power, for example for tools, mobile activities, emergencies, and electric-grid-support services...

  13. Increased protein synthesis by cells exposed to a 1,800-MHz radio-frequency mobile phone electromagnetic field, detected by proteome profiling

    OpenAIRE

    Gerner, Christopher; Haudek, Verena; Schandl, Ulla; Bayer, Editha; Gundacker, Nina; Hutter, Hans Peter; Mosgoeller, Wilhelm

    2010-01-01

    Purpose To investigate whether or not low intensity radio frequency electromagnetic field exposure (RF-EME) associated with mobile phone use can affect human cells, we used a sensitive proteome analysis method to study changes in protein synthesis in cultured human cells. Methods Four different cell kinds were exposed to 2 W/kg specific absorption rate in medium containing 35S-methionine/cysteine, and autoradiography of 2D gel spots was used to measure the increased synthesis of individual pr...

  14. Stroma-contact prevents loss of hematopoietic stem cell quality during ex vivo expansion of CD34+ mobilized peripheral blood stem cells.

    Science.gov (United States)

    Breems, D A; Blokland, E A; Siebel, K E; Mayen, A E; Engels, L J; Ploemacher, R E

    1998-01-01

    Stroma-supported long-term cultures (LTC) allow estimation of stem cell quality by simultaneous enumeration of hematopoietic stem cell (HSC) frequencies in a graft using the cobblestone area forming cell (CAFC) assay, and the ability of the graft to generate progenitors in flask LTC (LTC-CFC). We have recently observed that the number and quality of mobilized peripheral blood stem cells (PBSC) was low in patients having received multiple rounds of chemotherapy. Moreover, grafts with low numbers of HSC and poor HSC quality had a high probability to cause graft failure upon their autologous infusion. Because ex vivo culture of stem cells has been suggested to present an attractive tool to improve hematological recovery or reduce graft size, we have studied the possibility that such propagation may affect stem cell quality. In order to do so, we have assessed the recovery of different stem cell subsets in CD34+ PBSC after a 7-day serum-free liquid culture using CAFC and LTC-CFC assays. A numerical expansion of stem cell subsets was observed in the presence of interleukin-3 (IL-3), stem cell factor, and IL-6, while stroma-contact, stromal soluble factors, or combined addition of FLT3-ligand and thrombopoietin improved this parameter. In contrast, ex vivo culture severely reduced the ability of the graft to produce progenitors in LTC while stromal soluble factors partly abrogated this quality loss. The best conservation of graft quality was observed when the PBSC were cultured in stroma-contact. These data suggest that ex vivo propagation of PBSC may allow numerical expansion of various stem cell subsets, however, at the expense of their quality. In addition, cytokine-driven PBSC cultures require stroma for optimal maintenance of graft quality. PMID:9414274

  15. A molecular smart surface for spatio-temporal studies of cell mobility.

    Directory of Open Access Journals (Sweden)

    Eun-ju Lee

    Full Text Available Active migration in both healthy and malignant cells requires the integration of information derived from soluble signaling molecules with positional information gained from interactions with the extracellular matrix and with other cells. How a cell responds and moves involves complex signaling cascades that guide the directional functions of the cytoskeleton as well as the synthesis and release of proteases that facilitate movement through tissues. The biochemical events of the signaling cascades occur in a spatially and temporally coordinated manner then dynamically shape the cytoskeleton in specific subcellular regions. Therefore, cell migration and invasion involve a precise but constantly changing subcellular nano-architecture. A multidisciplinary effort that combines new surface chemistry and cell biological tools is required to understand the reorganization of cytoskeleton triggered by complex signaling during migration. Here we generate a class of model substrates that modulate the dynamic environment for a variety of cell adhesion and migration experiments. In particular, we use these dynamic substrates to probe in real-time how the interplay between the population of cells, the initial pattern geometry, ligand density, ligand affinity and integrin composition affects cell migration and growth. Whole genome microarray analysis indicates that several classes of genes ranging from signal transduction to cytoskeletal reorganization are differentially regulated depending on the nature of the surface conditions.

  16. A molecular smart surface for spatio-temporal studies of cell mobility.

    Science.gov (United States)

    Lee, Eun-ju; Luo, Wei; Chan, Eugene W L; Yousaf, Muhammad N

    2015-01-01

    Active migration in both healthy and malignant cells requires the integration of information derived from soluble signaling molecules with positional information gained from interactions with the extracellular matrix and with other cells. How a cell responds and moves involves complex signaling cascades that guide the directional functions of the cytoskeleton as well as the synthesis and release of proteases that facilitate movement through tissues. The biochemical events of the signaling cascades occur in a spatially and temporally coordinated manner then dynamically shape the cytoskeleton in specific subcellular regions. Therefore, cell migration and invasion involve a precise but constantly changing subcellular nano-architecture. A multidisciplinary effort that combines new surface chemistry and cell biological tools is required to understand the reorganization of cytoskeleton triggered by complex signaling during migration. Here we generate a class of model substrates that modulate the dynamic environment for a variety of cell adhesion and migration experiments. In particular, we use these dynamic substrates to probe in real-time how the interplay between the population of cells, the initial pattern geometry, ligand density, ligand affinity and integrin composition affects cell migration and growth. Whole genome microarray analysis indicates that several classes of genes ranging from signal transduction to cytoskeletal reorganization are differentially regulated depending on the nature of the surface conditions. PMID:26030281

  17. Rare myeloid sarcoma/acute myeloid leukemia with adrenal mass after allogeneic mobilization peripheral blood stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Ya-Fei Wang; Qian Li; Wen-Gui Xu; Jian-Yu Xiao; Qing-Song Pang; Qing Yang; Yi-Zuo Zhang

    2013-01-01

    Myeloid sarcoma (MS) is a rare hematological neoplasm that develops either de novo or concurrently with acute myeloid leukemia (AML). This neoplasm can also be an initial manifestation of relapse in a previously treated AML that is in remission. A 44-year-old male patient was diagnosed with testis MS in a local hospital in August 2010. Atfer one month, bone marrow biopsy and aspiration conifrmed the diagnosis of AML. Allogeneic mobilization peripheral blood stem cell transplantation was performed, with the sister of the patient as donor, after complete remission (CR) was achieved by chemotherapy. Five months after treatment, an adrenal mass was detected by positron emission tomography-computed tomography (PET-CT). Radiotherapy was performed for the localized mass after a multidisciplinary team (MDT) discussion. hTe patient is still alive as of May 2013, with no evidence of recurrent MS or leukemia.

  18. Rare myeloid sarcoma/acute myeloid leukemia with adrenal mass after allogeneic mobilization peripheral blood stem cell transplantation

    International Nuclear Information System (INIS)

    Myeloid sarcoma (MS) is a rare hematological neoplasm that develops either de novo or concurrently with acute myeloid leukemia (AML). This neoplasm can also be an initial manifestation of relapse in a previously treated AML that is in remission. A 44-year-old male patient was diagnosed with testis MS in a local hospital in August 2010. After one month, bone marrow biopsy and aspiration confirmed the diagnosis of AML. Allogeneic mobilization peripheral blood stem cell transplantation was performed, with the sister of the patient as donor, after complete remission (CR) was achieved by chemotherapy. Five months after treatment, an adrenal mass was detected by positron emission tomography-computed tomography (PET-CT). Radiotherapy was performed for the localized mass after a multidisciplinary team (MDT) discussion. The patient is still alive as of May 2013, with no evidence of recurrent MS or leukemia

  19. A high-throughput three-dimensional cell migration assay for toxicity screening with mobile device-based macroscopic image analysis

    Science.gov (United States)

    Timm, David M.; Chen, Jianbo; Sing, David; Gage, Jacob A.; Haisler, William L.; Neeley, Shane K.; Raphael, Robert M.; Dehghani, Mehdi; Rosenblatt, Kevin P.; Killian, T. C.; Tseng, Hubert; Souza, Glauco R.

    2013-10-01

    There is a growing demand for in vitro assays for toxicity screening in three-dimensional (3D) environments. In this study, 3D cell culture using magnetic levitation was used to create an assay in which cells were patterned into 3D rings that close over time. The rate of closure was determined from time-lapse images taken with a mobile device and related to drug concentration. Rings of human embryonic kidney cells (HEK293) and tracheal smooth muscle cells (SMCs) were tested with ibuprofen and sodium dodecyl sulfate (SDS). Ring closure correlated with the viability and migration of cells in two dimensions (2D). Images taken using a mobile device were similar in analysis to images taken with a microscope. Ring closure may serve as a promising label-free and quantitative assay for high-throughput in vivo toxicity in 3D cultures.

  20. Electron mobility and injection dynamics in mesoporous ZnO, SnO₂, and TiO₂ films used in dye-sensitized solar cells.

    Science.gov (United States)

    Tiwana, Priti; Docampo, Pablo; Johnston, Michael B; Snaith, Henry J; Herz, Laura M

    2011-06-28

    High-performance dye-sensitized solar cells are usually fabricated using nanostructured TiO(2) as a thin-film electron-collecting material. However, alternative metal-oxides are currently being explored that may offer advantages through ease of processing, higher electron mobility, or interface band energetics. We present here a comparative study of electron mobility and injection dynamics in thin films of TiO(2), ZnO, and SnO(2) nanoparticles sensitized with Z907 ruthenium dye. Using time-resolved terahertz photoconductivity measurements, we show that, for ZnO and SnO(2) nanoporous films, electron injection from the sensitizer has substantial slow components lasting over tens to hundreds of picoseconds, while for TiO(2), the process is predominantly concluded within a few picoseconds. These results correlate well with the overall electron injection efficiencies we determine from photovoltaic cells fabricated from identical nanoporous films, suggesting that such slow components limit the overall photocurrent generated by the solar cell. We conclude that these injection dynamics are not substantially influenced by bulk energy level offsets but rather by the local environment of the dye-nanoparticle interface that is governed by dye binding modes and densities of states available for injection, both of which may vary from site to site. In addition, we have extracted the electron mobility in the three nanoporous metal-oxide films at early time after excitation from terahertz conductivity measurements and compared these with the time-averaged, long-range mobility determined for devices based on identical films. Comparison with established values for single-crystal Hall mobilities of the three materials shows that, while electron mobility values for nanoporous TiO(2) films are approaching theoretical maximum values, both early time, short distance and interparticle electron mobility in nanoporous ZnO or SnO(2) films offer considerable scope for improvement.

  1. Stem and Progenitor Cell Expansion in Co-culture of Mobilized CD34 + Cells and Osteopetrotic Mouse Stroma

    Institute of Scientific and Technical Information of China (English)

    Na LI; Shahin Rafii; JF Stoltz; Malcolm A.S. Moore; Pierre Feugier; Deog-Yeon JO; Jae Hung Shieh; Karen L. MacKenzie; JF Lesesve; V Latger-Cannard; D Bensoussan; Ronald G Crystal

    2005-01-01

    @@ 1 Introduction Culture systems capable of expanding and/or maintaining hematopoietic stem cells will not only facilitate our understanding of stem cell biology, but also broaden clinical applications. Among various in vitro hematopoietic culture systems, co-cultures of marrow or CD34+ cells with an adherent stromal layer that can produce cytokines and extracellular matrix components most effectively supports long-term hematopoiesis ( LTC ), mimicking the bone marrow micro-environment.

  2. Dissociation of Ca sup 2+ entry and Ca sup 2+ mobilization responses to angiotensin II in bovine adrenal chromaffin cells

    Energy Technology Data Exchange (ETDEWEB)

    Stauderman, K.A.; Pruss, R.M. (Merrell Dow Research Institute, Cincinnati, OH (USA))

    1989-11-05

    In fura-2-loaded bovine adrenal chromaffin cells, 0.5 microM angiotensin II (AII) stimulated a 185 +/- 19 nM increase of intracellular-free calcium (( Ca2+)i) approximately 3 s after addition. The time from the onset of the response until achieving 50% recovery (t 1/2) was 67 +/- 10 s. Concomitantly, AII stimulated both the release of 45Ca2+ from prelabeled cells, and a 4-5-fold increase of (3H)inositol 1,4,5-trisphosphate (( 3H)Ins(1,4,5)P3) levels. In the presence of 50 microM LaCl3, or when extracellular-free Ca2+ (( Ca2+)o) was less than 100 nM, AII still rapidly increased (Ca2+)i by 95-135 nM, but the t 1/2 for recovery was then only 23-27 s. In medium with 1 mM MnCl2 present, AII also stimulated a small amount of Mn2+ influx, as judged by quenching of the fura-2 signal. When (Ca2+)o was normal (1.1 mM) or low (less than 60 nM), 1-2 microM ionomycin caused (Ca2+)i to increase 204 +/- 26 nM, while also releasing 45-55% of bound 45Ca2+. With low (Ca2+)o, ionomycin pretreatment abolished both the (Ca2+)i increase and 45Ca2+ release stimulated by AII. However, after ionomycin pretreatment in normal medium, AII produced a La3+-inhibitable increase of (Ca2+)i (103 +/- 13 nM) with a t 1/2 of 89 +/- 8 s, but no 45Ca2+ release. No pretreatment condition altered AII-induced formation of (3H)Ins(1,4,5)P3. We conclude that AII increased (Ca2+)i via rapid and transient Ca2+ mobilization from Ins(1,4,5)P3- and ionomycin-sensitive stores, accompanied (and/or followed) by Ca2+ entry through a La3+-inhibitable divalent cation pathway. Furthermore, the ability of AII to activate Ca2+ entry in the absence of Ca2+ mobilization (i.e. after ionomycin pretreatment) suggests a receptor-linked stimulus other than Ca2+ mobilization initiates Ca2+ entry.

  3. SUMOylation regulates the nuclear mobility of CREB binding protein and its association with nuclear bodies in live cells

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, Colm M.; Kindle, Karin B.; Collins, Hilary M. [Gene Regulation Group, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom); Heery, David M., E-mail: david.heery@nottingham.ac.uk [Gene Regulation Group, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom)

    2010-01-01

    The lysine acetyltransferase CREB binding protein (CBP) is required for chromatin modification and transcription at many gene promoters. In fixed cells, a large proportion of CBP colocalises to PML or nuclear bodies. Using live cell imaging, we show here that YFP-tagged CBP expressed in HEK293 cells undergoes gradual accumulation in nuclear bodies, some of which are mobile and migrate towards the nuclear envelope. Deletion of a short lysine-rich domain that contains the major SUMO acceptor sites of CBP abrogated its ability to be SUMO modified, and prevented its association with endogenous SUMO-1/PML speckles in vivo. This SUMO-defective CBP showed enhanced ability to co-activate AML1-mediated transcription. Deletion mapping revealed that the SUMO-modified region was not sufficient for targeting CBP to PML bodies, as C-terminally truncated mutants containing this domain showed a strong reduction in accumulation at PML bodies. Fluorescence recovery after photo-bleaching (FRAP) experiments revealed that YFP-CBP{Delta}998-1087 had a retarded recovery time in the nucleus, as compared to YFP-CBP. These results indicate that SUMOylation regulates CBP function by influencing its shuttling between nuclear bodies and chromatin microenvironments.

  4. Mobilization of Intracellular Copper by Gossypol and Apogossypolone Leads to Reactive Oxygen Species-Mediated Cell Death: Putative Anticancer Mechanism

    Directory of Open Access Journals (Sweden)

    Haseeb Zubair

    2016-06-01

    Full Text Available There is compelling evidence that serum, tissue and intracellular levels of copper are elevated in all types of cancer. Copper has been suggested as an important co-factor for angiogenesis. It is also a major metal ion present inside the nucleus, bound to DNA bases, particularly guanine. We have earlier proposed that the interaction of phenolic-antioxidants with intracellular copper leads to the generation of reactive oxygen species (ROS that ultimately serve as DNA cleaving agents. To further validate our hypothesis we show here that the antioxidant gossypol and its semi-synthetic derivative apogossypolone induce copper-mediated apoptosis in breast MDA-MB-231, prostate PC3 and pancreatic BxPC-3 cancer cells, through the generation of ROS. MCF10A breast epithelial cells refractory to the cytotoxic property of these compounds become sensitized to treatment against gossypol, as well as apogossypolone, when pre-incubated with copper. Our present results confirm our earlier findings and strengthen our hypothesis that plant-derived antioxidants mobilize intracellular copper instigating ROS-mediated cellular DNA breakage. As cancer cells exist under significant oxidative stress, this increase in ROS-stress to cytotoxic levels could be a successful anticancer approach.

  5. Micromorph thin-film silicon solar cells with transparent high-mobility hydrogenated indium oxide front electrodes

    Science.gov (United States)

    Battaglia, Corsin; Erni, Lukas; Boccard, Mathieu; Barraud, Loris; Escarré, Jordi; Söderström, Karin; Bugnon, Grégory; Billet, Adrian; Ding, Laura; Despeisse, Matthieu; Haug, Franz-Josef; Wolf, Stefaan De; Ballif, Christophe

    2011-06-01

    We investigate the performance of hydrogenated indium oxide as a transparent front electrode for micromorph thin-film silicon solar cells on glass. Light trapping is achieved by replicating the morphology of state-of-the-art zinc oxide electrodes, known for their outstanding light trapping properties, via ultraviolet nanoimprint lithography. As a result of the high electron mobility and excellent near-infrared transparency of hydrogenated indium oxide, the short-circuit current density of the cells is improved with respect to indium tin oxide and zinc oxide electrodes. We assess the potential for further current gains by identifying remaining sources of parasitic absorption and evaluate the light trapping capacity of each electrode. We further present a method, based on nonabsorbing insulating silicon nitride electrodes, allowing one to directly relate the optical reflectance to the external quantum efficiency. Our method provides a useful experimental tool to evaluate the light trapping potential of novel photonic nanostructures by a simple optical reflectance measurement, avoiding complications with electrical cell performance.

  6. Dose-Modified Ifosfamide, Epirubicin, and Etoposide is a Safe and Effective Salvage Therapy with High Peripheral Blood Stem Cell Mobilization Capacity for Poorly Mobilized Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma Patients.

    Science.gov (United States)

    Fukunaga, Akiko; Hyuga, Mizuki; Iwasaki, Makoto; Nakae, Yoshiki; Kishimoto, Wataru; Maesako, Yoshitomo; Arima, Nobuyoshi

    2016-01-01

    A dose modified ifosfamide, epirubicin, and etoposide (IVE) regimen was prospectively assessed for its efficacy in mobilizing peripheral blood stem cells for autologous transplantation. Two patients with Hodgkin's lymphoma and two with non-Hodgkin's lymphoma who were undergoing stem cell therapy were studied. All patients had a history of multiple treatments with insufficient stem cell mobilization. The dose modified IVE regimen consisted of ifosfamide 3 g/m(2) intravenously (IV) administered on days 1-2 in combination with epirubicin 50 mg/m(2) IV on day 1 and etoposide 200 mg/m(2) (100 mg/m(2) in two patients with complete remission) IV on days 1-3. The ifosfamide dosage was reduced to two-thirds of the original protocol. A substantial high yield of CD34(+) cells was achieved when patients were treated with a dose-modified IVE regimen, compared with that during the previous regimen (two with the ifosfamide, carboplatin, and etoposide [ICE] regimen, one with high-dose cyclophosphamide and one with the original IVE regimen). Two patients who had refractory and residual disease received a 200 mg/m(2) dose of etoposide, which resulted in tumor reduction (one patient with complete remission and one with further reduction in tumor size). After the IVE regimen, all four patients had a sufficient yield of CD34(+) cells in total, which was available for stem cell transplantation. Hematological and non-hematological toxicities were comparable in all regimens. This single-center prospective study demonstrated that the dose-modified IVE regimen can be used as a safe treatment with high mobilizing efficacy in heavily pretreated lymphoma patients. PMID:27334858

  7. Batroxobin mobilizes circulating endothelial progenitor cells in patients with deep vein thrombosis.

    Science.gov (United States)

    Lei Zhang; Shi Hong Lu; Li Li; Tao, Yu-Guo; Yong Ling Wan; Senga, Hirobumi; Renchi Yang; Zhong Chao Han

    2011-02-01

    Batroxobin, a thrombin-like enzyme from Bothrops atrox moojeni venom, is associated with the reduction of fibrinogen levels in plasma and the enhancement of anticoagulation and fibrinolysis. In this study, 15 patients with deep vein thrombosis (DVT) achieved successful limb salvage after the administration of batroxobin. We found that the levels of CD34+, CD31+, CD34+/CD31+, and vascular endothelial cadherin (VE-cadherin+) cells had increased in the peripheral blood of patients at 7 days and 14 days after treatment. At 0 day, 7 days, and 14 days, the percentages of CD34+ cells, which are assumed to be hematopoietic stem cells, are 0.39% ± 0.43%, 0.71% ± 0.50%, and 1.11% ± 0.66%, respectively. The levels of CD34+ cells at 14 days are significantly higher than the levels on the first day (P = .004). The levels of CD31+ cells and VE-cadherin+ cells, which represent mature endothelial cells, at 7 days (34.15% ± 11.32%, P = .013; 1.25% ± 1.39%, P = .014) and 14 days (35.21% ± 7.66%, P = .071; 1.85% ± 2.60%, P = .117) were slightly elevated compared with those at 0 day (27.55% ± 8.65%; 0.25 ± 0.39%). The double positive of CD34 and CD31 cells are assumed to be endothelial progenitor cells (EPCs). The levels of CD34+/CD31+ cells at 7 days (0.69% ± 0.50%, P = .001) and 14 days (1.07% ± 0.66%, P = .006) are significantly higher than that on the initial day (0.28% ± 0.30%). The number of CD34+/CD31+ cells significantly increased, indicating that in addition to its role in anticoagulation and fibrinolysis, treatment with batroxobin might simultaneously activate circulating EPCs that might promote the recanalization of the damaged vessel wall. PMID:19825915

  8. Mobile Lexicography

    DEFF Research Database (Denmark)

    Køhler Simonsen, Henrik

    2015-01-01

    Mobile phones are ubiquitous and have completely transformed the way we live, work, learn and conduct our everyday activities. Mobile phones have also changed the way users access lexicographic data. In fact, it can be argued that mobile phones and lexicography are not yet compatible. Modern users...... are already mobile – but lexicography is not yet fully ready for the mobile challenge, mobile users and mobile user situations. The article is based on empirical data from two surveys comprising 10 medical doctors, who were asked to look up five medical substances with the medical dictionary app Medicin...... lexicography....

  9. Acute Stress-Induced Changes in Follicular Dermal Papilla Cells and Mobilization of Mast Cells: Implications for Hair Growth

    Science.gov (United States)

    Shin, Hyoseung; Choi, Soon-Jin; Cho, A-Ri; Kim, Dong Young; Kim, Kyu Han

    2016-01-01

    Background Stress is a known cause of hair loss in many species. Objective In this study, we investigated the role of acute stress on hair growth using a rat model. Methods Rats were immobilized for 24 hours and blood samples, and skin biopsies were taken. The effect of stress-serum on the in vitro proliferation of rat and human dermal papilla cells (hDPCs), as well as serum cortisol and corticotropin-releasing hormone levels, were measured. Mast cell staining was performed on the biopsied tissue. In addition, Western blot and quantitative real time polymerase chain reaction were used to assess mast cell tryptase and cytokine expression, respectively in rat skin biopsies. Results Stress-serum treatment reduced significantly the number of viable hDPCs and arrested the cell cycle in the G1 phase, compared to serum from unrestrained rats (phair growth via cortisol release in addition to substance P-mast cell pathway.

  10. Heat shock factor 1 contributes to ischemia-induced angiogenesis by regulating the mobilization and recruitment of bone marrow stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Masayuki Kubo

    Full Text Available Bone marrow (BM-derived stem/progenitor cells play an important role in ischemia-induced angiogenesis in cardiovascular diseases. Heat shock factor 1 (HSF1 is known to be induced in response to hypoxia and ischemia. We examined whether HSF1 contributes to ischemia-induced angiogenesis through the mobilization and recruitment of BM-derived stem/progenitor cells using HSF1-knockout (KO mice. After the induction of ischemia, blood flow and microvessel density in the ischemic hindlimb were significantly lower in the HSF1-KO mice than in the wild-type (WT mice. The mobilization of BM-derived Sca-1- and c-kit-positive cells in peripheral blood after ischemia was significantly lower in the HSF1-KO mice than in the WT mice. BM stem/progenitor cells from HSF1-KO mice showed a significant decrease in their recruitment to ischemic tissue and in migration, adhesion, and survival when compared with WT mice. Blood flow recovery in the ischemic hindlimb significantly decreased in WT mice receiving BM reconstitution with donor cells from HSF1-KO mice. Conversely, blood flow recovery in the ischemic hindlimb significantly increased in HSF1-KO mice receiving BM reconstitution with donor cells from WT mice. These findings suggest that HSF1 contributes to ischemia-induced angiogenesis by regulating the mobilization and recruitment of BM-derived stem/progenitor cells.

  11. Immunomodulation Induced by Stem Cell Mobilization and Harvesting in Healthy Donors: Increased Systemic Osteopontin Levels after Treatment with Granulocyte Colony-Stimulating Factor

    Science.gov (United States)

    Melve, Guro Kristin; Ersvaer, Elisabeth; Akkök, Çiğdem Akalın; Ahmed, Aymen Bushra; Kristoffersen, Einar K.; Hervig, Tor; Bruserud, Øystein

    2016-01-01

    Peripheral blood stem cells from healthy donors mobilized by granulocyte colony-stimulating factor (G-CSF) and harvested by leukapheresis are commonly used for allogeneic stem cell transplantation. The frequency of severe graft versus host disease is similar for patients receiving peripheral blood and bone marrow allografts, even though the blood grafts contain more T cells, indicating mobilization-related immunoregulatory effects. The regulatory phosphoprotein osteopontin was quantified in plasma samples from healthy donors before G-CSF treatment, after four days of treatment immediately before and after leukapheresis, and 18–24 h after apheresis. Myeloma patients received chemotherapy, combined with G-CSF, for stem cell mobilization and plasma samples were prepared immediately before, immediately after, and 18–24 h after leukapheresis. G-CSF treatment of healthy stem cell donors increased plasma osteopontin levels, and a further increase was seen immediately after leukapheresis. The pre-apheresis levels were also increased in myeloma patients compared to healthy individuals. Finally, in vivo G-CSF exposure did not alter T cell expression of osteopontin ligand CD44, and in vitro osteopontin exposure induced only small increases in anti-CD3- and anti-CD28-stimulated T cell proliferation. G-CSF treatment, followed by leukapheresis, can increase systemic osteopontin levels, and this effect may contribute to the immunomodulatory effects of G-CSF treatment. PMID:27447610

  12. Research Resource: Androgen Receptor Activity Is Regulated Through the Mobilization of Cell Surface Receptor Networks.

    Science.gov (United States)

    Hsiao, Jordy J; Ng, Brandon H; Smits, Melinda M; Martinez, Harryl D; Jasavala, Rohini J; Hinkson, Izumi V; Fermin, Damian; Eng, Jimmy K; Nesvizhskii, Alexey I; Wright, Michael E

    2015-08-01

    The aberrant expression of androgen receptor (AR)-dependent transcriptional programs is a defining pathology of the development and progression of prostate cancers. Transcriptional cofactors that bind AR are critical determinants of prostate tumorigenesis. To gain a deeper understanding of the proteins linked to AR-dependent gene transcription, we performed a DNA-affinity chromatography-based proteomic screen designed to identify proteins involved in AR-mediated gene transcription in prostate tumor cells. Functional experiments validated the coregulator roles of known AR-binding proteins in AR-mediated transcription in prostate tumor cells. More importantly, novel coregulatory functions were detected in components of well-established cell surface receptor-dependent signal transduction pathways. Further experimentation demonstrated that components of the TNF, TGF-β, IL receptor, and epidermal growth factor signaling pathways modulated AR-dependent gene transcription and androgen-dependent proliferation in prostate tumor cells. Collectively, our proteomic dataset demonstrates that the cell surface receptor- and AR-dependent pathways are highly integrated, and provides a molecular framework for understanding how disparate signal-transduction pathways can influence AR-dependent transcriptional programs linked to the development and progression of human prostate cancers.

  13. Chimeric Allografts Induced by Short-Term Treatment With Stem Cell Mobilizing Agents Result in Long-Term Kidney Transplant Survival Without Immunosuppression: II, Study in Miniature Swine.

    Science.gov (United States)

    Cameron, A M; Wesson, R N; Ahmadi, A R; Singer, A L; Hu, X; Okabayashi, T; Wang, Y; Shigoka, M; Fu, Y; Gao, W; Raccusen, L C; Montgomery, R A; Williams, G M; Sun, Z

    2016-07-01

    Transplantation is now lifesaving therapy for patients with end-stage organ failure but requires lifelong immunosuppression with resultant morbidity. Current immunosuppressive strategies inhibit T cell activation and prevent donor-recipient engagement. Therefore, it is not surprising that few host cells are demonstrated in donor grafts. However, our recent small animal studies found large numbers of recipient stem cells present after transplantation and pharmacological mobilization, resulting in a chimeric, repopulated organ. We now confirm these findings in a well-characterized large animal preclinical model. Here, we show that AMD3100 and FK506 mobilization of endogenous stem cells immediately post kidney transplantation combined with repeat therapy at 1, 2, and 3 months led to drug-free long-term survival in maximally immunologically mismatched swine. Three long-term recipients have stable chimeric transplants, preserved antidonor skin graft responses, and normal serum creatinine levels despite withdrawal of all medication for 3 years. PMID:26748958

  14. Mobilization of endothelial progenitor cells after endovascular interventions in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Marina Sergeevna Michurova

    2014-12-01

    Full Text Available AimTo investigate the mobilisation of endothelial progenitor cells (EPC in patients with type 2 diabetes mellitus (T2DM after endovascular interventions for coronary and peripheral arteries.Materials and MethodsThe levels of EPC in peripheral blood were determined by flow cytometry in 42 patients prior to endovascular intervention and 2–4 days after surgery. EPC were defined as CD34+ VEGFR2+ CD45- and CD34+ CD133+CD45- cells. Twenty-three patients with T2DM were included in group 1, and 19 patients without metabolic disorders were included in group 2.ResultsThe levels of EPC in the peripheral blood of patients with T2DM before and after endovascular interventions were not significantly different. In the subgroup of patients without TDM2, the levels of CD34+VEGFR2 +CD45- cells increased after surgery to 55,5% (p <0,01, and the levels of CD34 + CD133 + CD45- cells increased to 27,7% (p <0,05. After endovascular intervention for the subgroup of patients with T2DM and with the levels of HbA1c ≤7,5%, the levels of CD34+VEGFR2+CD45- cells increased to 46,6% (p=0,01, and the levels of CD34+CD133+CD45- cells increased to 40,3 % (p=0,006 compared with the subgroup of patients with T2DM and with HbA1c levels of ≥7,5%.ConclusionThe patients with T2DM displayed alterations in EPC mobilisation after endovascular interventions. In addition, the EPC level changes were dependent on glycaemic control. Thus, in the subgroup of patients with T2DM and with good glycaemic control (HbA1c ≤7,5%, the EPC levels were significantly higher after endovascular interventions.

  15. Cooperation between lateral ligand mobility and accessibility for receptor recognition in selectin-induced cell rolling

    NARCIS (Netherlands)

    Bakowsky, U; Schumacher, G; Gege, C; Schmidt, RR; Rothe, U; Bendas, G

    2002-01-01

    Selectin-induced leukocyte rolling along the endothelial surface is an essential step in the immune response. Several in vitro studies showed that this cell rolling is a highly regulated adhesion phenomenon, controlled by the kinetics and forces of selectin-ligand interactions. In the flow chamber s

  16. [Establishment of stable subline of K562 cells overexpressing high mobility group B1 protein].

    Science.gov (United States)

    Yan, Fan-Zhi; Yan, Jin-Song; Zhao, Jia; Li, Wei-Ping; Chen, Xue-Yu; Yang, Yan; Rao, Shu-Mei; Jin, Jing

    2011-02-01

    This study was aimed to establish a stable subline of K562 cells (K562-HMGB1) overexpressing HMGB1 protein and K562-HMGB1 sublines served as control, so as to provide a basis for exploring the role of hmgb1 gene in occurrence and development of leukemia and their mechanism. Protein-coding gene of hmgb1 was amplified by PCR with cDNA as template, which was synthesized by reverse transcription from total RNA extracted from U937 cells. The PCR-amplified hmgb1 gene was ligated into PMD18-T vector (PMD18-T-HMGB1 vector), and then transformed into E. coli strain DH5α. DH5α containing PMD18-T-HMGB1 vector were grown on LB agar plate supplemented with 100 µg/ml ampicillin overnight. The single ampicillin-selected DH5α clone was picked for culturing overnight and then harvested for plasmid extraction. The extracted plasmid was characterized to contain hmgb1 gene digested with the desired restriction enzymes of KpnI/XhoI. The correctness of hmgb1 sequence was confirmed with DNA sequencing. The insert of hmgb1 gene contained in PMD18-T-HMGB1 vector was cut out with restriction enzymes of KpnI/XhoI and then ligated into eukaryotic expression vector pcDNA3.1 to form pcDNA3.1-HMGB1 vector. 10µg of pcDNA3.1-HMGB1 or pcDNA3.1 plasmid was separately electroporated into K562 cells. At 48 hours after electroporation the cells were cultured with G418 at a final concentration of 800 µg/ml for over 2 weeks. Finally stably transfected sublines of K562 cells containing hmgb1 gene (K562-HMGB1), and of K562 containing pcDNA3.1 vector (K562-pcDNA3.1) served as a control, were obtained. The transcriptional or translational expression of hmgb1 gene was detected with RT-PCR or Western blot, respectively, to testify transfected efficiency and validity of stable subline of K562-HMGB1. The results indicated that the eukaryotic expression vector pcDNA3.1-HMGB1 plasmid was successfully constructed and was electroporated into K562 cells. The transcriptional or translational expression of hmgb1

  17. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells

    International Nuclear Information System (INIS)

    Highlights: • HMGB1 translocated from nucleus to cytoplasm during dental pulp inflammation. • HMGB1and its receptor RAGE were up-regulated in hDPCs under LPS stimulation. • HMGB1 enhanced hDPCs migration and induces cytoskeleton reorganization. • HMGB1 may play a critical role in dental pulp repair during inflamed state. - Abstract: High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration

  18. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xufang, E-mail: xufang.zhang@student.qut.edu.au [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059 (Australia); Jiang, Hongwei, E-mail: jianghw@163.com [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Gong, Qimei, E-mail: gongqmei@gmail.com [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Fan, Chen, E-mail: c3.fan@student.qut.edu.au [Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059 (Australia); Huang, Yihua, E-mail: enu0701@163.com [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Ling, Junqi, E-mail: lingjq@mail.sysu.edu.cn [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China)

    2014-08-08

    Highlights: • HMGB1 translocated from nucleus to cytoplasm during dental pulp inflammation. • HMGB1and its receptor RAGE were up-regulated in hDPCs under LPS stimulation. • HMGB1 enhanced hDPCs migration and induces cytoskeleton reorganization. • HMGB1 may play a critical role in dental pulp repair during inflamed state. - Abstract: High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration.

  19. Cross-talk between Bone Marrow and Tissue Injury : Novel Regenerative Therapy for Severely Damaged Tissues by Mobilizing Bone Marrow Mesenchymal Stem Cells in Vivo

    OpenAIRE

    Tamai, Katsuto; Kaneda, Yasufumi

    2013-01-01

    group box 1 (HMGB1), which mobilizes a sub-population of non-hematopoietic cells from bone marrow into the circulation to repair skin and restore Col 7 expression. These bone marrow-derived epithelial stem/progenitor cells are derived from a lineage-negative, platelet-derived growth factor alpha-positive mesenchymal stem cell pool in bone marrow, which represents less than 0.3% of the total bone marrow cell population. In addition, systemic administration of HMGB1 to wounded wild-type mice le...

  20. Bordetella adenylate cyclase toxin mobilizes its beta2 integrin receptor into lipid rafts to accomplish translocation across target cell membrane in two steps.

    Directory of Open Access Journals (Sweden)

    Ladislav Bumba

    2010-05-01

    Full Text Available Bordetella adenylate cyclase toxin (CyaA binds the alpha(Mbeta(2 integrin (CD11b/CD18, Mac-1, or CR3 of myeloid phagocytes and delivers into their cytosol an adenylate cyclase (AC enzyme that converts ATP into the key signaling molecule cAMP. We show that penetration of the AC domain across cell membrane proceeds in two steps. It starts by membrane insertion of a toxin 'translocation intermediate', which can be 'locked' in the membrane by the 3D1 antibody blocking AC domain translocation. Insertion of the 'intermediate' permeabilizes cells for influx of extracellular calcium ions and thus activates calpain-mediated cleavage of the talin tether. Recruitment of the integrin-CyaA complex into lipid rafts follows and the cholesterol-rich lipid environment promotes translocation of the AC domain across cell membrane. AC translocation into cells was inhibited upon raft disruption by cholesterol depletion, or when CyaA mobilization into rafts was blocked by inhibition of talin processing. Furthermore, CyaA mutants unable to mobilize calcium into cells failed to relocate into lipid rafts, and failed to translocate the AC domain across cell membrane, unless rescued by Ca(2+ influx promoted in trans by ionomycin or another CyaA protein. Hence, by mobilizing calcium ions into phagocytes, the 'translocation intermediate' promotes toxin piggybacking on integrin into lipid rafts and enables AC enzyme delivery into host cytosol.

  1. Intra-articular Injected synovial stem cells differentiate into meniscal cells directly and promote meniscal regeneration without mobilization to distant organs in rat massive meniscal defect.

    Science.gov (United States)

    Horie, Masafumi; Sekiya, Ichiro; Muneta, Takeshi; Ichinose, Shizuko; Matsumoto, Kenji; Saito, Hirohisa; Murakami, Takashi; Kobayashi, Eiji

    2009-04-01

    Osteoarthritis in the knees, which can be caused by meniscal defect, constitutes an increasingly common medical problem. Repair for massive meniscal defect remains a challenge owing to a lack of cell kinetics for the menisci precursors in knee joint. The synovium plays pivotal roles during the natural course of meniscal healing and contains mesenchymal stem cells (MSCs) with high chondrogenic potential. Here, we investigated whether intra-articular injected synovium-MSCs enhanced meniscal regeneration in rat massive meniscal defect. To track the injected cells, we developed transgenic rats expressing dual luciferase (Luc) and LacZ. The cells derived from synovium of the rats demonstrated colony-forming ability and multipotentiality, both characteristics of MSCs. Hierarchical clustering analysis revealed that gene expression of meniscal cells was closer to that of synovium-MSCs than to that of bone marrow-MSCs. Two to 8 weeks after five million Luc/LacZ+ synovium-MSCs were injected into massive meniscectomized knee of wild-type rat, macroscopically, the menisci regenerated much better than it did in the control group. After 12 weeks, the regenerated menisci were LacZ positive, produced type 2 collagen, and showed meniscal features by transmission electron microscopy. In in-vivo luminescence analysis, photons increased in the meniscus-resected knee over a 3-day period, then decreased without detection in all other organs. LacZ gene derived from MSCs could not be detected in other organs except in synovium by real-time PCR. Synovium-MSCs injected into the massive meniscectomized knee adhered to the lesion, differentiated into meniscal cells directly, and promoted meniscal regeneration without mobilization to distant organs.

  2. DESIGN OF LOW EPI AND HIGH THROUGHPUT CORDIC CELL TO IMPROVE THE PERFORMANCE OF MOBILE ROBOT

    Directory of Open Access Journals (Sweden)

    P. VELRAJKUMAR

    2014-04-01

    Full Text Available This paper mainly focuses on pass logic based design, which gives an low Energy Per Instruction (EPI and high throughput COrdinate Rotation Digital Computer (CORDIC cell for application of robotic exploration. The basic components of CORDIC cell namely register, multiplexer and proposed adder is designed using pass transistor logic (PTL design. The proposed adder is implemented in bit-parallel iterative CORDIC circuit whereas designed using DSCH2 VLSI CAD tool and their layouts are generated by Microwind 3 VLSI CAD tool. The propagation delay, area and power dissipation are calculated from the simulated results for proposed adder based CORDIC cell. The EPI, throughput and effect of temperature are calculated from generated layout. The output parameter of generated layout is analysed using BSIM4 advanced analyzer. The simulated result of the proposed adder based CORDIC circuit is compared with other adder based CORDIC circuits. From the analysis of these simulated results, it was found that the proposed adder based CORDIC circuit dissipates low power, gives faster response, low EPI and high throughput.

  3. G-CSF therapy with mobilization of bone marrow stem cells for myocardial recovery after acute myocardial infarction - a relevant treatment?

    DEFF Research Database (Denmark)

    Ripa, R.S.; Kastrup, J.

    2008-01-01

    -CSF treatment. Current controversies in interpretation of the results include 1) importance of direct cardiac effect of G-CSF vs indirect through bone marrow stem and progenitor cell mobilization, 2) importance of timing of G-CSF therapy, 3) importance of G-CSF dose, and 4) importance of cell types mobilized...... from the bone-marrow. Cell-based therapies to improve cardiac function remain promising and further experimental and clinical studies are warranted to determine the future role of G-CSF Udgivelsesdato: 2008/6......This review of adjunctive therapy with subcutaneous granulocyte-colony stimulating factor (G-CSF) to patients with acute myocardial infarction (AMI) focus on the cardioprotective effects and potential mechanisms of G-CSF and discuss the therapeutic potential of G-CSF. All clinical trials published...

  4. Mobility Divides

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    Contemporary mobilities are cultural and social manifestations, and the mobile practices in the everyday life of billions of humans are re-configuring senses of place, self, other and relationships to the built environment. The way ‘mobile situations’ are staged in designed and built environments...... are increasingly becoming ‘second nature’ but also expressions of power, exclusion, and difference. In this talk I will be applying a perspective of ‘mobile situationism’ illustrating how mobile everyday life practices are staged ‘from above’ in planning and policy frameworks, design codes and architectural...... designs, but also how the situated and embodied mobile everyday life practices are staged ‘from below’ in concrete acts of choice concerning modes of mobilities, ways of moving and interacting. The ‘staging mobilites’ framework opens up to an understanding of the meaning of ‘mobilities design...

  5. Mobile payment

    CERN Document Server

    Lerner, Thomas

    2013-01-01

    Paying with mobile devices such as mobile phones or smart phones will expand worldwide in the coming years. This development provides opportunities for various industries (banking, telecommunications, credit card business, manufacturers, suppliers, retail) and for consumers.

  6. Direct Methanol Fuel Cell Power Supply For All-Day True Wireless Mobile Computing

    Energy Technology Data Exchange (ETDEWEB)

    Brian Wells

    2008-11-30

    PolyFuel has developed state-of-the-art portable fuel cell technology for the portable computing market. A novel approach to passive water recycling within the MEA has led to significant system simplification and size reduction. Miniature stack technology with very high area utilization and minimalist seals has been developed. A highly integrated balance of plant with very low parasitic losses has been constructed around the new stack design. Demonstration prototype systems integrated with laptop computers have been shown in recent months to leading OEM computer manufacturers. PolyFuel intends to provide this technology to its customers as a reference design as a means of accelerating the commercialization of portable fuel cell technology. The primary goal of the project was to match the energy density of a commercial lithium ion battery for laptop computers. PolyFuel made large strides against this goal and has now demonstrated 270 Wh/liter compared with lithium ion energy densities of 300 Wh/liter. Further, more incremental, improvements in energy density are envisioned with an additional 20-30% gains possible in each of the next two years given further research and development.

  7. Mobile marketing

    OpenAIRE

    KLEČKOVÁ, Zuzana

    2013-01-01

    The main aim of this thesis was to provide a comprehensive overview of the mobile marketing and analyze selected campaigns of Czech mobile marketing in comparison to world successful campaigns. The research contained studying of available literature about the theme to gain general knowledge about the issue. The theoretical part of the thesis contains predominantly various definitions of mobile marketing and its tools, advantages of these tools and some information about Mobile Marketing Assoc...

  8. Mobile robots

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe, W.J.; Marquina, N.

    1986-01-01

    This book presents papers given at a conference on mobile robots. Topics the conference included are the following: mobility systems for robotic vehicles; detection and control of mobile robot motion by real-time computer vision, obstacle avoidance algorithms for an autonomous land vehicle; hierarchical processor and matched filters for range image processing; asynchronous distributed control system for a mobile robot, and, planning in a hierarchical nested autonomous control system.

  9. Hybridization and control of a mobile direct methanol fuel cell system; Hybridisierung und Regelung eines mobilen Direktmethanol-Brennstoffzellen-Systems

    Energy Technology Data Exchange (ETDEWEB)

    Wilhelm, Joerg Christoph

    2010-07-01

    Direct methanol fuel cells (DMFCs) are characterized by the fact that they directly convert the chemical energy of the liquid fuel methanol into electrical energy. Methanol has a high energy density and can be stored relatively easily. Due to these advantages, direct methanol fuel cell systems are suitable, for example, as a battery replacement for light-traction applications in the kW class. Since refuelling is much faster than recharging a battery, almost interruption-free operation is possible. The aim of this thesis is therefore to develop a direct methanol fuel cell system for light-traction applications. The systems technology development and characterization of a mobile direct methanol fuel cell system is initially examined in general and then applied to the example of a horizontal order picker, a type of forklift truck. A hybridization and control concept is developed for this type of truck. The procedure is structured into the theoretical characterization of the application, the development of theoretical concepts and a concluding systems analysis using data from the test stand and simulations. The characteristic driving cycle of the application results from the characterization. The concept development is based on key data such as maximum peak power during acceleration and braking as well as average power. The two-stage theoretical development of a hybridization concept is based on a pure fuel cell vehicle. A systems analysis of all possible concepts with respect to the criteria of fuel cell power, total system efficiency and dynamic fuel cell loading eventually leads to the preferred concept of indirect coupling. A cascade controller with map control, the control concept developed for this purpose, keeps the energy storage unit at a constant state of charge and provides for the fuel cell aging protection as well as aging detection. The driving cycle, operational states of the vehicle and the efficiencies of the individual components play a decisive role

  10. Mobile Lexicography

    DEFF Research Database (Denmark)

    Køhler Simonsen, Henrik

    2014-01-01

    Users are already mobile, but the question is to which extent knowledge-based dictionary apps are designed for the mobile user situation. The objective of this article is to analyse the characteristics of the mobile user situation and to look further into the stationary user situation and the mob...

  11. Staging Mobilities

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    and lived as people are “staging themselves” (from below). Staging mobilities is a dynamic process between “being staged” (for example, being stopped at traffic lights) and the “mobile staging” of interacting individuals (negotiating a passage on the pavement). Staging Mobilities is about the fact...

  12. Daratumumab depletes CD38+ immune-regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma

    DEFF Research Database (Denmark)

    Krejcik, Jakub; Casneuf, Tineke; Nijhof, Inger S;

    2016-01-01

    Daratumumab targets CD38-expressing myeloma cells through a variety of immune-mediated mechanisms (complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis) and direct apoptosis with cross-linking. These mechanisms may also...... target non-plasma cells that express CD38, which prompted evaluation of daratumumab's effects on CD38-positive immune subpopulations. Peripheral blood (PB) and bone marrow (BM) from patients with relapsed/refractory myeloma from two daratumumab monotherapy studies were analyzed before and during therapy...... and at relapse. Regulatory B cells (Bregs) and myeloid-derived suppressor cells (MDSCs), previously shown to express CD38, were evaluated for immunosuppressive activity and daratumumab sensitivity in the myeloma setting. A novel subpopulation of regulatory T cells (Tregs) expressing CD38 was identified...

  13. A Gaijin-like miniature inverted repeat transposable element is mobilized in rice during cell differentiation

    Directory of Open Access Journals (Sweden)

    Dong Hai-Tao

    2012-04-01

    Full Text Available Abstract Background Miniature inverted repeat transposable element (MITE is one type of transposable element (TE, which is largely found in eukaryotic genomes and involved in a wide variety of biological events. However, only few MITEs were proved to be currently active and their physiological function remains largely unknown. Results We found that the amplicon discrepancy of a gene locus LOC_Os01g0420 in different rice cultivar genomes was resulted from the existence of a member of Gaijin-like MITEs (mGing. This result indicated that mGing transposition was occurred at this gene locus. By using a modified transposon display (TD analysis, the active transpositions of mGing were detected in rice Jiahua No. 1 genome under three conditions: in seedlings germinated from the seeds received a high dose γ-ray irradiation, in plantlets regenerated from anther-derived calli and from scutellum-derived calli, and were confirmed by PCR validation and sequencing. Sequence analysis revealed that single nucleotide polymorphisms (SNPs or short additional DNA sequences at transposition sites post mGing transposition. It suggested that sequence modification was possibly taken place during mGing transposition. Furthermore, cell re-differentiation experiment showed that active transpositions of both mGing and mPing (another well studied MITE were identified only in regenerated plantlets. Conclusions It is for the first time that mGing active transposition was demonstrated under γ-ray irradiation or in cell re-differentiation process in rice. This newly identified active MITE will provide a foundation for further analysis of the roles of MITEs in biological process.

  14. Morphological aspects of starch and cell wall material mobilization in developing lupine cotyledons and the effect of kinetin on these processes

    Directory of Open Access Journals (Sweden)

    Fortunat Młodzianowski

    2015-05-01

    Full Text Available In the cotyledons of dry lupine seeds the presence of starch was not demonstrated. Its formation during seed imbibition in darkness is accompanied by a reduction in the thickness of cell walls containing hemicelluloses. It is believed that the products of hemicellulose hydrolysis, particullarily in isolated cotyledons, arę the main source of materials for the synthesis of starch, In the process of cell wall decomposition the invaginations of plasmalemma appear to be involved. Kinetin enhance the hydrolysis of cell walls and the mobilization of starch in isolated cotyledons.

  15. Mobile Probes in Mobile Learning

    DEFF Research Database (Denmark)

    Ørngreen, Rikke; Blomhøj, Ulla; Duvaa, Uffe

    as an agent for acquiring empirical data (as the situation in hitherto mobile probe settings) but was also the technological medium for which data should say something about (mobile learning). Consequently, not only the content of the data but also the ways in which data was delivered and handled, provided......In this paper experiences from using mobile probes in educational design of a mobile learning application is presented. The probing process stems from the cultural probe method, and was influenced by qualitative interview and inquiry approaches. In the project, the mobile phone was not only acting...... a valuable dimension for investigating mobile use. The data was collected at the same time as design activities took place and the collective data was analysed based on user experience goals and cognitive processes from interaction design and mobile learning. The mobile probe increased the knowledge base...

  16. Isolation of highly suppressive CD25+FoxP3+ T regulatory cells from G-CSF-mobilized donors with retention of cytotoxic anti-viral CTLs: application for multi-functional immunotherapy post stem cell transplantation.

    Science.gov (United States)

    Samuel, Edward R; Beloki, Lorea; Newton, Katy; Mackinnon, Stephen; Lowdell, Mark W

    2014-01-01

    Previous studies have demonstrated the effective control of cytomegalovirus (CMV) infections post haematopoietic stem cell transplant through the adoptive transfer of donor derived CMV-specific T cells (CMV-T). Strategies for manufacturing CMV immunotherapies has involved a second leukapheresis or blood draw from the donor, which in the unrelated donor setting is not always possible. We have investigated the feasibility of using an aliquot of the original G-CSF-mobilized graft as a starting material for manufacture of CMV-T and examined the activation marker CD25 as a targeted approach for identification and isolation following CMVpp65 peptide stimulation. CD25+ cells isolated from G-CSF-mobilized apheresis revealed a significant increase in the proportion of FoxP3 expression when compared with conventional non-mobilized CD25+ cells and showed a superior suppressive capacity in a T cell proliferation assay, demonstrating the emergence of a population of Tregs not present in non-mobilized apheresis collections. The expansion of CD25+ CMV-T in short-term culture resulted in a mixed population of CD4+ and CD8+ T cells with CMV-specificity that secreted cytotoxic effector molecules and lysed CMVpp65 peptide-loaded phytohaemagglutinin-stimulated blasts. Furthermore CD25 expanded cells retained their suppressive capacity but did not maintain FoxP3 expression or secrete IL-10. In summary our data indicates that CD25 enrichment post CMV stimulation in G-CSF-mobilized PBMCs results in the simultaneous generation of both a functional population of anti-viral T cells and Tregs thus illustrating a potential single therapeutic strategy for the treatment of both GvHD and CMV reactivation following allogeneic haematopoietic stem cell transplantation. The use of G-CSF-mobilized cells as a starting material for cell therapy manufacture represents a feasible approach to alleviating the many problems incurred with successive donations and procurement of cells from unrelated donors

  17. Profibus protocol extensions for enabling inter-cell mobility in bridge-based hybrid wired/wireless networks

    OpenAIRE

    Ferreira, Luis; Tovar, Eduardo; Alves, Mário

    2003-01-01

    Future industrial control/multimedia applications will increasingly impose or benefit from wireless and mobile communications. Therefore, there is an enormous eagerness for extending currently available industrial communications networks with wireless and mobility capabilities. The RFieldbus European project is just one example, where a PROFIBUS-based hybrid (wired/wireless) architecture was specified and implemented. In the RFieldbus architecture, interoperability between wire...

  18. Lysophosphatidic acid induced nuclear translocation of nuclear factor-κB in Panc-1 cells by mobilizing cytosolic free calcium

    Institute of Scientific and Technical Information of China (English)

    Yoshiyuki Arita; Tetsuhide Ito; Takamasa Pond; Ken Kawabe; Terumasa Hisano; Ryoichi Takayanagi

    2008-01-01

    AIM: To clarify whether Lysophosphatidic acid (LPA) activates the nuclear translocation of nuclear factor-κB (NF-κB) in pancreatic cancer.METHODS: Panc-1, a human pancreatic cancer cell line, was used throughout the study. The expression of LPA receptors was confirmed by reverse-transcript polymerase chain reaction (RT-PCR). Cytosolic free calcium was measured by fluorescent calcium indicator fura-2, and the localization of NF-κB was visualized by immunofluorescent method with or without various agents, which effect cell signaling.RESULTS: Panc-1 expressed LPA receptors, LPAA1,LPA2 and LPA3. LPA caused the elevation of cytosolic free calcium dose-dependently. LPA also caused the nuclear translocation of NF-κB. Cytosolic free calcium was attenuated by pertussis toxin (PTX) and U73122,an inhibitor of phospholipase C. The translocation of NF-κB was similarly attenuated by PTX and U73122,but phorbol ester, an activator of protein kinase C,alone did not translocate NF-κB. Furthermore, the transtocation of NF-κB was completely blocked by Ca2+ chelator BAPTA-AM. Thapsigargin, an endoplasmic-reticulum Ca2+-ATPase pump inhibitor, also promoted the translocation of NF-κB. Staurosporine, a protein kinase C inhibitor, attenuated translocation of NF-κB induced by LPA.CONCLUSlON: These findings suggest that protein kinase C is activated endogenously in Panc-1, and protein kinase C is essential for activating NF-κB with cytosolic calcium and that LPA induces the nuclear translocation of NF-κB in Panc-1 by mobilizing cytosolic free calcium.

  19. Hydrogen from methanol for fuel cells in mobile systems: development of a compact reformer

    Science.gov (United States)

    Höhlein, B.; Boe, M.; Bøgild-Hansen, J.; Bröckerhoff, P.; Colsman, G.; Emonts, B.; Menzer, R.; Riedel, E.

    On-board generation of hydrogen from methanol with a reformer in connection with the use of a proton-exchange membrane fuel cell (PEMFC) is an attractive option for a passenger car drive. Special considerations are required to obtain low weight and volume. Furthermore, the PEMFC of today cannot tolerate more than 10 ppm of carbon monoxide in the fuel. Therefore a gas conditioning step is needed after the methanol reformer. Our main research activities focus on the conceptual design of a drive system for a passenger car with methanol reformer and PEMFC: engineering studies with regard to different aspects of this design including reformer, catalytic burner, gas conditioning, balances of the fuel cycles and basic design of a compact methanol reformer. The work described here was carried out within the framework of a JOULE II project of the European Union (1993-1995). Extensive experimental studies have been carried out at the Forschungszentrum Jülich GmbH (KFA) in Germany and at Haldor Topsøe A/S in Denmark.

  20. Mobilities Design

    DEFF Research Database (Denmark)

    Jensen, Ole B.; Lanng, Ditte Bendix

    Contemporary society is marked and defined by the ways in which mobile goods, bodies, vehicles, objects, and data are organized, moved and staged. On the background of the ‘mobilities turn’ (e.g. Cresswell 2006, Urry 2007) this book articulates a new and emerging research field, namely that of ‘m...... enter into a fruitful relationship with mobilities research, offering a relational and mobile design thinking and a valuable base for a reflective design practice around the ubiquitous structures, spaces and systems of mobilities....... that of ‘mobilities design’. The book revolves around the following research question: How are design decisions and interventions staging mobilities? It builds upon the Staging Mobilities model (Jensen 2013) in an explorative inquiry into the problems and potentials of the design of mobilities. The exchange value...... between mobilities and design research is twofold. To mobilities research this means getting closer to the ‘material’, and to engage in the creative, explorative and experimental approaches of the design world which offer new potentials for innovative research. Design research, on the other hand, might...

  1. Mobile Semiotics - signs and mobilities

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    a potential for mobilities studies if the awareness of seeing the environment as a semiotic layer and system can be sensitized to the insights of the ‘mobilities turn’. Empirically the paper tentatively explores the usefulness of a mobile semiotics approach to cases such as street signage, airport design...

  2. Mobile Phone on Campus

    Institute of Scientific and Technical Information of China (English)

    周成

    2005-01-01

    Communication revolution has brought a great convenience to modem society and people. Especially, the occurrence of mobile phone, in away, has changed the world where we live. Maybe the mobile phone was a luxury for only a decade ago. Now, it is no exaggeration4 to say that the difference between the parts and the present is as vast as that between earth and heaven. With no exception6, campus students also fall into the category called “cell-phone school”.

  3. 手机用于词汇学习研究述评%A Review of Mobile Language Vocabulary Learning with Cell Phone

    Institute of Scientific and Technical Information of China (English)

    林梅

    2014-01-01

    介绍了近年来国外手机用于词汇学习的实证研究的主要成果,总结出手机词汇学习的有效性及其优缺点,并分析了此领域内有待思考的问题及未来研究的趋势。%Studies investigating using cell phones for learning vocabulary have started to appear in the literature. This paper reviews mobile language vocabulary learning with cell phone abroad and illustrates the effectiveness of vocabulary learning via mobile phone ,the advantages and disadvantages of these researches. However, there are still issues that must be considered and remained further investigation.

  4. Mobilities Design

    DEFF Research Database (Denmark)

    Jensen, Ole B.; Lanng, Ditte Bendix; Wind, Simon

    2016-01-01

    In this paper, we identify the nexus between design (architecture, urban design, service design, etc.) and mobilities as a new and emerging research field. In this paper, we apply a “situational mobilities” perspective and take point of departure in the pragmatist question: “What design decisions...... and interventions affords this particular mobile situation?” The paper presents the contours of an emerging research agenda within mobilities research. The advent of “mobilities design” as an emerging research field points towards a critical interest in the material as well as practical consequences of contemporary......-making. The paper proposes that increased understanding of the material affordances facilitated through design provides important insight to planning and policymaking that at times might be in risk of becoming too detached from the everyday life of the mobile subject within contemporary mobilities landscapes....

  5. Mobility Work

    DEFF Research Database (Denmark)

    Bardram, Jakob Eyvind; Bossen, Claus

    2005-01-01

    We posit the concept of Mobility Work to describe efforts of moving about people and things as part of accomplishing tasks. Mobility work can be seen as a spatial parallel to the concept of articulation work proposed by the sociologist Anselm Strauss. Articulation work describes efforts...... of coordination necessary in cooperative work, but focuses, we argue, mainly on the temporal aspects of cooperative work. As a supplement, the concept of mobility work focuses on the spatial aspects of cooperative work. Whereas actors seek to diminish the amount of articulation work needed in collaboration...... by constructing Standard Operation Procedures (SOPs), actors minimise mobility work by constructing Standard Operation Configurations (SOCs). We apply the concept of mobility work to the ethnography of hospital work, and argue that mobility arises because of the need to get access to people, places, knowledge and...

  6. Mobile Clouds

    DEFF Research Database (Denmark)

    Fitzek, Frank; Katz, Marcos

    A mobile cloud is a cooperative arrangement of dynamically connected communication nodes sharing opportunistic resources. In this book, authors provide a comprehensive and motivating overview of this rapidly emerging technology. The book explores how distributed resources can be shared by mobile...... users in very different ways and for various purposes. The book provides many stimulating examples of resource-sharing applications. Enabling technologies for mobile clouds are also discussed, highlighting the key role of network coding. Mobile clouds have the potential to enhance communications...... performance, improve utilization of resources and create flexible platforms to share resources in very novel ways. Energy efficient aspects of mobile clouds are discussed in detail, showing how being cooperative can bring mobile users significant energy saving. The book presents and discusses multiple...

  7. Do all β-blockers attenuate the excess hematopoietic progenitor cell mobilization from the bone marrow following trauma/hemorrhagic shock?

    Science.gov (United States)

    Pasupuleti, Latha V.; Cook, Kristin M.; Sifri, Ziad C.; Alzate, Walter D.; Livingston, David H.; Mohr, Alicia M.

    2016-01-01

    BACKGROUND Severe injury results in increased mobilization of hematopoietic progenitor cells (HPC) from the bone marrow (BM) to sites of injury, which may contribute to persistent BM dysfunction after trauma. Norepinephrine is a known inducer of HPC mobilization, and nonselective β-blockade with propranolol has been shown to decrease mobilization after trauma and hemorrhagic shock (HS). This study will determine the role of selective β-adrenergic receptor blockade in HPC mobilization in a combined model of lung contusion (LC) and HS. METHODS Male Sprague-Dawley rats were subjected to LC, followed by 45 minutes of HS. Animals were then randomized to receive atenolol (LCHS + β1B), butoxamine (LCHS + β2B), or SR59230A (LCHS + β3B) immediately after resuscitation and daily for 6 days. Control groups were composed of naive animals. BM cellularity, %HPCs in peripheral blood, and plasma granulocyte-colony stimulating factor levels were assessed at 3 hours and 7 days. Systemic plasma-mediated effects were evaluated in vitro by assessment of BM HPC growth. Injured lung tissue was graded histologically by a blinded reader. RESULTS The use of β2B or β3B following LCHS restored BM cellularity and significantly decreased HPC mobilization. In contrast, β1B had no effect on HPC mobilization. Only β3B significantly reduced plasma G-CSF levels. When evaluating the plasma systemic effects, both β2B and β3B significantly improved BM HPC growth as compared with LCHS alone. The use of β2 and β3 blockade did not affect lung injury scores. CONCLUSION Both β2 and β3 blockade can prevent excess HPC mobilization and BM dysfunction when given after trauma and HS, and the effects seem to be mediated systemically, without adverse effects on subsequent healing. Only treatment with β3 blockade reduced plasma G-CSF levels, suggesting different mechanisms for adrenergic-induced G-CSF release and mobilization of HPCs. This study adds to the evidence that therapeutic strategies that

  8. Tuning superior solar cell performance of carrier mobility and absorption in perovskite CH3NH3GeCl3: A density functional calculations

    Science.gov (United States)

    Zhao, Yu-Qing; Wu, Li-Juan; Liu, Biao; Wang, Ling-Zhi; He, Peng-Bin; Cai, Meng-Qiu

    2016-05-01

    The solar cell based on hybrid organic-inorganic halide perovskite has received considerable attention. One of the most important issues in the pursuit of further developments in this area is to obtain both a high carrier mobility and an excellent ability of light adsorption. In this paper, we investigate the electronic structure and electronic effective masses of the new non-toxic material CH3NH3GeCl3 by first-principle calculations. The results show that the absorption efficiency of CH3NH3GeCl3 is more superior to that of CH3NH3PbI3 in short wavelength region. We trace this result to the ferroelectricity caused by the more serious octahedral GeCl6- distortion. We also discover a new relationship between the carrier effective masses anisotropy and the anisotropy of electronic density of states along three principal directions. Moreover, while applied the isotropic compressive pressure, the absorption efficiency and carrier mobility of CH3NH3GeCl3 in orthorhombic phase are improved greatly due to changes of electronic structure. We speculate that these are general results of tuning of the carrier mobility by controlling the band gap and the electronic occupation along different directions, to obtain both a high carrier mobility and an excellent ability of light adsorption.

  9. Mobile phones and mobile communication

    DEFF Research Database (Denmark)

    Ling, Richard; Donner, Jonathan

    With staggering swiftness, the mobile phone has become a fixture of daily life in almost every society on earth. In 2007, the world had over 3 billion mobile subscriptions. Prosperous nations boast of having more subscriptions than people. In the developing world, hundreds of millions of people who...... researchers in the field, this volume presents an overview of the mobile telephone as a social and cultural phenomenon. Research is summarized and made accessible though detailed descriptions of ten mobile users from around the world. These illustrate popular debates, as well as deeper social forces at work...... could never afford a landline telephone now have a mobile number of their own. With a mobile in our hand many of us feel safer, more productive, and more connected to loved ones, but perhaps also more distracted and less involved with things happening immediately around us. Written by two leading...

  10. Hybridization and control of a mobile direct methanol fuel cell system; Hybridisierung und Regelung eines mobilen Direktmethanol-Brennstoffzellen-Systems

    Energy Technology Data Exchange (ETDEWEB)

    Wilhelm, Joerg Christoph

    2010-07-01

    Direct methanol fuel cells (DMFCs) are characterized by the fact that they directly convert the chemical energy of the liquid fuel methanol into electrical energy. Methanol has a high energy density and can be stored relatively easily. Due to these advantages, direct methanol fuel cell systems are suitable, for example, as a battery replacement for light-traction applications in the kW class. Since refuelling is much faster than recharging a battery, almost interruption-free operation is possible. The aim of this thesis is therefore to develop a direct methanol fuel cell system for light-traction applications. The systems technology development and characterization of a mobile direct methanol fuel cell system is initially examined in general and then applied to the example of a horizontal order picker, a type of forklift truck. A hybridization and control concept is developed for this type of truck. The procedure is structured into the theoretical characterization of the application, the development of theoretical concepts and a concluding systems analysis using data from the test stand and simulations. The characteristic driving cycle of the application results from the characterization. The concept development is based on key data such as maximum peak power during acceleration and braking as well as average power. The two-stage theoretical development of a hybridization concept is based on a pure fuel cell vehicle. A systems analysis of all possible concepts with respect to the criteria of fuel cell power, total system efficiency and dynamic fuel cell loading eventually leads to the preferred concept of indirect coupling. A cascade controller with map control, the control concept developed for this purpose, keeps the energy storage unit at a constant state of charge and provides for the fuel cell aging protection as well as aging detection. The driving cycle, operational states of the vehicle and the efficiencies of the individual components play a decisive role

  11. Actin filaments at the leading edge of cancer cells are characterized by a high mobile fraction and turnover regulation by profilin I.

    Directory of Open Access Journals (Sweden)

    Gisela Lorente

    Full Text Available Cellular motility is the basis for cancer cell invasion and metastasis. In the case of breast cancer, the most common type of cancer among women, metastasis represents the most devastating stage of the disease. The central role of cellular motility in cancer development emphasizes the importance of understanding the specific mechanisms involved in this process. In this context, tumor development and metastasis would be the consequence of a loss or defect of the mechanisms that control cytoskeletal remodeling. Profilin I belongs to a family of small actin binding proteins that are thought to assist in actin filament elongation at the leading edge of migrating cells. Traditionally, Profilin I has been considered to be an essential control element for actin polymerization and cell migration. Expression of Profilin I is down-regulated in breast and various other cancer cells. In MDA-MB-231 cells, a breast cancer cell line, further inhibition of Profilin I expression promotes hypermotility and metastatic spread, a finding that contrasts with the proposed role of Profilin in enhancing polymerization. In this report, we have taken advantage of the fluorescence recovery after photobleaching (FRAP of GFP-actin to quantify and compare actin dynamics at the leading edge level in both cancer and non-cancer cell models. Our results suggest that (i a high level of actin dynamics (i.e., a large mobile fraction of actin filaments and a fast turnover is a common characteristic of some cancer cells; (ii actin polymerization shows a high degree of independence from the presence of extracellular growth factors; and (iii our results also corroborate the role of Profilin I in regulating actin polymerization, as raising the intracellular levels of Profilin I decreased the mobile fraction ratio of actin filaments and slowed their polymerization rate; furthermore, increased Profilin levels also led to reduced individual cell velocity and directionality.

  12. Osteoclasts Are Required for Hematopoietic Stem and Progenitor Cell Mobilization but Not for Stress Erythropoiesis in Plasmodium chabaudi adami Murine Malaria

    Directory of Open Access Journals (Sweden)

    Hugo Roméro

    2016-01-01

    Full Text Available The anemia and inflammation concurrent with blood stage malaria trigger stress haematopoiesis and erythropoiesis. The activity of osteoclasts seems required for the mobilization of hematopoietic stem and progenitor cells (HSPC from the bone marrow to the periphery. Knowing that BALB/c mice with acute Plasmodium chabaudi adami malaria have profound alterations in bone remodelling cells, we evaluated the extent to which osteoclasts influence their hematopoietic response to infection. For this, mice were treated with osteoclast inhibiting hormone calcitonin prior to parasite inoculation, and infection as well as hematological parameters was studied. In agreement with osteoclast-dependent HSPC mobilization, administration of calcitonin led to milder splenomegaly, reduced numbers of HSPC in the spleen, and their retention in the bone marrow. Although C-terminal telopeptide (CTX levels, indicative of bone resorption, were lower in calcitonin-treated infected mice, they remained comparable in naive and control infected mice. Calcitonin-treated infected mice conveniently responded to anemia but generated less numbers of splenic macrophages and suffered from exacerbated infection; interestingly, calcitonin also decreased the number of macrophages generated in vitro. Globally, our results indicate that although osteoclast-dependent HSC mobilization from bone marrow to spleen is triggered in murine blood stage malaria, this activity is not essential for stress erythropoiesis.

  13. Mobile Semiotics

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    2013-01-01

    is a ‘mobile sense making’ where signs and materially situated meanings connect to the moving human body and thus create particular challenges and complexities of making sense of the world. The chapter includes notions of mobility systems and socio-technical networks in order to show how a ‘semiotic layer’ may...

  14. Designing Mobilities

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    Within the so-called ‘mobilities turn’ (Adey 2010; Cresswell 2006; Urry 2007) much research has taken place during the last decade bringing mobilities into the centre of sociological analysis. However, the materiality and spatiality of artefacts, infrastructures, and sites hosting mobilities...... are often still not engaged with in a sufficiently manner. Often social sciences keep distance to the physical and material as if the social was still to be understood as a realm separate of technology, architecture, and design (for a critique of this see; Latour 2005 and Urry 2000). This paper takes point...... of departure in the sociological perspective termed ‘Staging Mobilities’ (Jensen 2013a) and utilizes this as an analytical frame for exploring cases of mobility design. The paper put focus on how the material shape, design and architectures of technologies, spaces and sites influence mobilities practices...

  15. Mobility Challenges

    DEFF Research Database (Denmark)

    Jensen, Ole B.; Lassen, Claus

    2011-01-01

    This article takes point of departure in the challenges to understand the importance of contemporary mobility. The approach advocated is a cross-disciplinary one drawing on sociology, geography, urban planning and design, and cultural studies. As such the perspective is to be seen as a part...... of the so-called ‘mobility turn’ within social science. The perspective is illustrative for the research efforts at the Centre for Mobility and Urban Studies (C-MUS), Aalborg University. The article presents the contours of a theoretical perspective meeting the challenges to research into contemporary urban...... mobilities. In particular the article discusses 1) the physical city, its infrastructures and technological hardware/software, 2) policies and planning strategies for urban mobility and 3) the lived everyday life in the city and the region....

  16. Pretransplant mobilization with granulocyte colony-stimulating factor improves B-cell reconstitution by lentiviral vector gene therapy in SCID-X1 mice.

    Science.gov (United States)

    Huston, Marshall W; Riegman, Adriaan R A; Yadak, Rana; van Helsdingen, Yvette; de Boer, Helen; van Til, Niek P; Wagemaker, Gerard

    2014-10-01

    Hematopoietic stem cell (HSC) gene therapy is a demonstrated effective treatment for X-linked severe combined immunodeficiency (SCID-X1), but B-cell reconstitution and function has been deficient in many of the gene therapy treated patients. Cytoreductive preconditioning is known to improve HSC engraftment, but in general it is not considered for SCID-X1 since the poor health of most of these patients at diagnosis and the risk of toxicity preclude the conditioning used in standard bone marrow stem cell transplantation. We hypothesized that mobilization of HSC by granulocyte colony-stimulating factor (G-CSF) should create temporary space in bone marrow niches to improve engraftment and thereby B-cell reconstitution. In the present pilot study supplementing our earlier preclinical evaluation (Huston et al., 2011), Il2rg(-/-) mice pretreated with G-CSF were transplanted with wild-type lineage negative (Lin(-)) cells or Il2rg(-/-) Lin(-) cells transduced with therapeutic IL2RG lentiviral vectors. Mice were monitored for reconstitution of lymphocyte populations, level of donor cell chimerism, and antibody responses as compared to 2 Gy total body irradiation (TBI), previously found effective in promoting B-cell reconstitution. The results demonstrate that G-CSF promotes B-cell reconstitution similar to low-dose TBI and provides proof of principle for an alternative approach to improve efficacy of gene therapy in SCID patients without adverse effects associated with cytoreductive conditioning. PMID:25222508

  17. Radix Ilicis Pubescentis total flavonoids combined with mobilization of bone marrow stem cells to protect against cerebral ischemia/reperfusion injury.

    Science.gov (United States)

    Miao, Ming-San; Guo, Lin; Li, Rui-Qi; Ma, Xiao

    2016-02-01

    Previous studies have shown that Radix Ilicis Pubescentis total flavonoids have a neuroprotective effect, but it remains unclear whether Radix Ilicis Pubescentis total flavonoids have a synergistic effect with the recombinant human granulocyte colony stimulating factor-mobilized bone marrow stem cell transplantation on cerebral ischemia/reperfusion injury. Rat ischemia models were administered 0.3, 0.15 and 0.075 g/kg Radix Ilicis Pubescentis total flavonoids from 3 days before modeling to 2 days after injury. Results showed that Radix Ilicis Pubescentis total flavonoids could reduce pathological injury in rats with cerebral ischemia/reperfusion injury. The number of Nissl bodies increased, Bax protein expression decreased, Bcl-2 protein expression increased and the number of CD34-positive cells increased. Therefore, Radix Ilicis Pubescentis total flavonoids can improve the bone marrow stem cell mobilization effect, enhance the anti-apoptotic ability of nerve cells, and have a neuroprotective effect on cerebral ischemia/reperfusion injury in rats. PMID:27073381

  18. Negative association of donor age with CD34+ cell dose in mixture allografts of G-CSF-primed bone marrow and G-CSF-mobilized peripheral blood harvests

    Institute of Scientific and Technical Information of China (English)

    Li Yan; Chang Yingjun; Xu Lanping; Zhang Xiaohui; Huang Xiaojun

    2014-01-01

    Background The effects of donor characteristics on CD34+ cell dose remain controversial.Recently,we developed a novel haploidentical transplant protocol,in which mixture allografts of granulocyte colony-stimulating factor (G-CSF)-primed bone marrow (G-BM) and G-CSF-mobilized peripheral blood (G-PB) were used.The aim of this study was to investigate the effects of donor characteristics on CD34+ cell dose in mixture allografts of G-BM and G-PB.Methods A total of 162 healthy adult donors,who underwent bone marrow harvest and peripheral blood collection between January 2009 and November 2010 in Peking University People's Hospital,were prospectively investigated.G-CSF was administered subcutaneously at a dose of 5 μg/kg once a day for 5-6 consecutive days.Bone marrow and peripheral blood stem cells were harvested on the fourth day and fifth day,respectively.A final total CD34+ cell dose less than 2× 106 cells/kg recipient body weight was considered a poor mobilization.Results Of the 162 donors,31 (19.1%) did not attain this threshold.The obtained median CD34+ cell doses in bone marrow,peripheral blood,and mixture allografts were 0.83×106/kg,2.40×106/kg,and 3.47×106/kg,respectively.Multiple regression analysis showed that donor age had a significant negative effect on CD34+ cell dose in either G-BM,or G-PB,or mixture allografts of G-BM and G-PB.And a 1-year increase in age was associated with a 5.6% decrease in the odds of achieving mobilization cutoff.No significant correlation was found for donor gender,body mass index (BMI),and weight.Conclusion Donor age is the only factor among the four parameters,including age,gender,weight,and BMI,that influence CD34+ cell dose in mixture allografts of G-BM and G-PB,and younger donors should be chosen to obtain sufficient CD34+ cells for transplantation.

  19. Sustainable Mobility

    DEFF Research Database (Denmark)

    Kjærulff, Aslak Aamot

    This paper combines strands of mobilities theory and planning theory, and develops a qualitative approach to look across emerging planning practices. By actively following 8 Danish urban and transport planners, over the course of 2 years, we learn how their practices have changed, inspired...... by mobility management, a concept aiming to reduce carbon emissions from transportation in western societies. The article focuses on how municipal planners formulate the role of mobility management activities organized around private companies, and how their practices are connected to wider ideas on planning....

  20. Accentual mobility

    DEFF Research Database (Denmark)

    Olander, Thomas Kristoffer

    slaviske mobile accentparadigmer i høj grad stemmer overens med hinanden, er det sandsynligt at accentmobiliteten i de to sproggrupper går tilbage til et fælles udgangspunkt. Formålet med afhandlingen er at bestemme den urindoeuropæiske baggrund for de baltoslaviske mobile accentparadigmer. I de...... paradigmatiske accent i urbaltoslavisk på grundlag af materiale fra de tre baltiske sprog og urslavisk. I kapitel IV foretages af en undersøgelse af den foreslåede accentlov ud fra en sammenligning af de rekonstruerede urindoeuropæiske endelser og de tilsvarende former i de urbaltoslaviske mobile...

  1. Subversive Mobilities

    DEFF Research Database (Denmark)

    Thelle, Mikkel

    2013-01-01

    The article approaches mobility through a cultural history of urban conflict. Using a case of “The Copenhagen Trouble,“ a series of riots in the Danish capital around 1900, a space of subversive mobilities is delineated. These turn-of-the-century riots points to a new pattern of mobile gathering......, the swarm; to a new aspect of public action, the staging; and to new ways of configuring public space. These different components indicate an urban assemblage of subversion, and a new characterization of the “throwntogetherness“ of the modern public....

  2. Going Mobile?

    DEFF Research Database (Denmark)

    Tallon, Loic; Froes, Isabel Cristina G.

    2011-01-01

    If the future is mobile, how is the museum community developing within that future? What are the challenges museums face within it? In which directions should we be seeking to evolve our collective knowledge share? It was to gain observations on questions such as these that the 2011 Museums & Mob...... & Mobile survey was developed: 660 museum professionals responded. In this paper the authors highlight nine survey observations that they believe are important to the museum community’s increased understanding of and continued progress within mobile interpretation....

  3. A large mobility of hydrophilic molecules at the outmost layer controls the protein adsorption and adhering behavior with the actin fiber orientation of human umbilical vein endothelial cells (HUVEC).

    Science.gov (United States)

    Kakinoki, Sachiro; Seo, Ji-Hun; Inoue, Yuuki; Ishihara, Kazuhiko; Yui, Nobuhiko; Yamaoka, Tetsuji

    2013-01-01

    Adhesion behaviors of human umbilical vein endothelial cells (HUVECs) are interestingly affected by the mobility of hydrophilic chains on the material surfaces. Surfaces with different molecular mobilities were prepared using ABA-type block copolymers consisting polyrotaxane (PRX) or poly(ethylene glycol) (PEG) central block (A block), and amphiphilic anchoring B blocks of poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB). Two different molecular mobilities of the PRX chains were designed by using normal α-cyclodextrin (α-CD) or α-CD whose hydroxyl groups were converted to methoxy groups in a given ratio to improve its molecular mobility (PRX-PMB and OMe-PRX-PMB). The surface mobility of these materials was assessed as the mobility factor (Mf), which is measured by quartz crystal microbalance with dissipation monitoring system. HUVECs adhered on OMe-PRX-PMB surface much more than PRX-PMB and PMB-block-PEG-block-PMB (PEG-PMB) surfaces. These different HUVEC adhesions were correlated with the density of cell-binding site of adsorbed fibronectin. In addition, the alignment of the actin cytoskeleton of adhered HUVECs was strongly suppressed on the PEG-PMB, PRX-PMB, and OMe-PRX-PMB in response to the increased Mf value. Remarkably, the HUVECs adhered on the OMe-PRX-PMB surface with much less actin organization. We concluded that not only the cell adhesion but also the cellular function are regulated by the molecular mobility of the outmost material surfaces. PMID:23796033

  4. 77 FR 22331 - Submission for OMB Review; Comment Request; Solar Cell: A Mobile UV Manager for Smart Phones...

    Science.gov (United States)

    2012-04-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND... Mobile UV Manager for Smart Phones Phase II (NCI) Summary: Under the provisions of Section 3507(a)(1)(D... of Health (NIH), has submitted to the Office of Management and Budget (OMB) a request to review...

  5. Evaluation of Pulsed-FRAP and Conventional-FRAP for Determination of Protein Mobility in Prokaryotic Cells

    NARCIS (Netherlands)

    Mika, Jacek T.; Krasnikov, Viktor; Bogaart, Geert van den; Haan, Foppe de; Poolman, Bert

    2011-01-01

    Background: Macromolecule mobility is often quantified with Fluorescence Recovery After Photobleaching (FRAP). Throughout literature a wide range of diffusion coefficients for GFP in the cytoplasm of Escherichia coli (3 to 14 mu m(2)/s) is reported using FRAP-based approaches. In this study, we have

  6. Restricted Mobilities

    DEFF Research Database (Denmark)

    Nielsen, Mette; Lassen, Claus

    2012-01-01

    and stratification mechanisms. In conclusion the article therefore suggests that future urban research and planning also needs a mobile understanding of spaces in the cities and how different mobility systems play an important role to sustain the exclusiveness that often characterises the private/public spaces...... in the article is that the many mobility systems enable specialization of places that are targeted at a special section of the population. This means that various forms of motilities not only create new opportunities for urban life but it is also one of the most critical components of production of new exclusion......Privatisation of public spaces in the contemporary city has increased during the last decades but only few studies have approached this field from a mobility perspective. Therefore the article seeks to rectify this by exploring two Australian examples of private spaces in the city; gated...

  7. Mobile museology

    DEFF Research Database (Denmark)

    Baggesen, Rikke Haller

    posts from the research project blog with three research articles: ‘Museum metamorphosis à la mode’, proposing a fashion perspective on ongoing museum developments; ‘Augmenting the agora: media and civic engagement in museums’, questioning the idea of social media holding a vital potential......Drawing together perspectives from museology, digital culture studies and fashion theory, this thesis considers changes in and challenges for current - day museums as related to ‘mobile museology’. This concept is developed for and elucidated in the thesis to describe an orientation towards...... the fashionable, the ephemeral, and towards an (ideal) state of change and changeability. This orientation is characterised with the triplet concepts of mobile, mobility, and mobilisation, as related to mobile media and movability; to ‘trans - museal’ mediation; and to the mobilisation of collections, audiences...

  8. The efficacy of prophylactic outpatient antibiotics for the prevention of neutropenic fever associated with high-dose etoposide (VP-16) for stem cell mobilization.

    Science.gov (United States)

    Avery, R K; Pohlman, B L; Mossad, S B; Goormastic, M; Longworth, D L; Kalaycio, M E; Sobecks, R M; Andresen, S W; Kuczkowski, E; Bernhard, L; Ostendorf, H; Wise, K; Bolwell, B J

    2002-09-01

    High-dose etoposide (2 g/m(2)) plus G-CSF is a very effective regimen for peripheral blood progenitor cell (PBPC) mobilization. Unfortunately, neutropenia is common. The infectious complications associated with high-dose etoposide have not been previously described. After noting a high incidence of hospitalizations for neutropenic fever, we began a vigorous prophylactic antibiotic regimen for patients receiving high-dose etoposide plus G-CSF, attempting to reduce infectious complications. Ninety-eight patients underwent etoposide mobilization between December 1997 and June 2000. Three chronological patient groups received: (1) no specific antibiotic prophylaxis (n = 44); (2) vancomycin i.v., cefepime i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27); and (3) vancomycin i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27). The patients not receiving antibiotic prophylaxis had a 68% incidence of hospitalization for neutropenic fever. In the patients receiving prophylaxis, the incidence was reduced to 26% and 15% respectively, for an overall incidence of 20% (P < 0.001 for comparison between prophylaxed and unprophylaxed groups). We conclude that etoposide mobilization is associated with a significant incidence of neutropenic fever, which can be substantially reduced by a vigorous antimicrobial prophylactic program. PMID:12209353

  9. Simvastatin mobilizes bone marrow stromal cells migrating to injured areas and promotes functional recovery after spinal cord injury in the rat.

    Science.gov (United States)

    Han, Xiaoguang; Yang, Ning; Cui, Yueyi; Xu, Yingsheng; Dang, Gengting; Song, Chunli

    2012-07-19

    This study investigated the therapeutic effects of simvastatin administered by subarachnoid injection after spinal cord injury (SCI) in rats; explored the underlying mechanism from the perspective of mobilization, migration and homing of bone marrow stromal cells (BMSCs) to the injured area induced by simvastatin. Green fluorescence protein labeled-bone marrow stromal cells (GFP-BMSCs) were transplanted into rats through the tail vein for stem cell tracing. Twenty-four hours after transplantation, spinal cord injury (SCI) was produced using weight-drop method (10g 4cm) at the T10 level. Simvastatin (5mg/kg) or vehicle was administered by subarachnoid injection at lumbar level 4 after SCI. Locomotor functional recovery was assessed in the 4 weeks following surgery using the open-field test and inclined-plane test. At the end of the study, MRI was used to evaluate the reparation of the injured spinal cord. Animals were then euthanized, histological evaluation was used to measure lesion cavity volumes. Immunofluorescence for GFP and cell lineage markers (NeuN and GFAP) was used to evaluate simvastatin-mediated mobilization and differentiation of transplanted BMSCs. Western blot and immunohistochemistry were used to assess the expression of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). Simvastatin-treated animals showed significantly better locomotor recovery, less signal abnormality in MRI and a smaller cavity volume compared to the control group. Immunofluorescence revealed that simvastatin increased the number of GFP-positive cells in the injured spinal cord, and the number of cells double positive for GFP/NeuN or GFP/GFAP was larger in the simvastatin treated group than the control group. Western blot and immunohistochemistry showed higher expression of BDNF and VEGF in the simvastatin treated group than the control group. In conclusion, simvastatin can help to repair spinal cord injury in rat, where the underlying

  10. Glutamate receptor activation in cultured cerebellar granule cells increases cytosolic free Ca2+ by mobilization of cellular Ca2+ and activation of Ca2+ influx

    DEFF Research Database (Denmark)

    Bouchelouche, P; Belhage, B; Frandsen, A;

    1989-01-01

    The Ca2+ sensitive fluorescent probe, fura-2 has been used to monitor cytosolic free calcium levels in mature primary cultures of cerebellar granule cells during exposure to L-glutamate and other excitatory amino acids: quisqualate (QA) kainate (KA) and N-methyl-D-aspartate (NMDA). Glutamate...... at micromolar concentrations produced a prompt and dose-related increase in the intracellular concentration of free Ca2+, ([Ca2+]i), whereas QA, KA and NMDA had no effect. This increase was also seen in the absence of extracellular Ca2+, suggesting that L-glutamate promotes mobilization of Ca2+ from...

  11. 自体干细胞移植治疗糖尿病足的干细胞动员和采集%Stem cell mobilization and collection for autologous peripheral blood stem cells transplantation in diabetic foot treatment

    Institute of Scientific and Technical Information of China (English)

    李华; 陈旭艳; 周斌; 冯亮华; 肖萍萍; 吴完婷

    2011-01-01

    背景:在自体干细胞移植治疗下肢缺血性疾病的干细胞动员期间,国内外大多数研究组均常规应用5~10 μg/(kg?d)的粒细胞集落刺激因子动员,5 d后采集干细胞进行移植,这是否为最佳的动员时间和采集时机未见相关报道.目的:分析探讨自体干细胞移植最佳动员方案及采集时机,提高该方法的安全性.方法:对备行干细胞移植的18例糖尿病足患者分别采用粒细胞集落刺激因子5,10 μg/(kg?d)进行造血干细胞动员,分析粒细胞集落刺激因子动员天数、剂量与外周血白细胞、单个核细胞、CD34+细胞数的关系,并检测干细胞动员前后、采集前后患者凝血指标、血小板计数的变化,观察患者动员及采集过程的不良反应.结果与结论:随着动员天数的增加,白细胞和单个核细胞、CD34+细胞数也随之增加,干细胞获得的效率与粒细胞集落刺激因子的剂量、动员时间有关,外周血中CD34+总数与单个核细胞总数呈正相关.患者的凝血指标在动员和采集前后无显著变化.血小板计数在动员前后无变化,但在采集后有显著下降;18例患者中仅有1例在粒细胞集落刺激因子动员中发生轻度骨头酸痛,1例出现发热,其他患者均无不良反应发生.提示,糖尿病足患者干细胞采集的最佳时机不能单凭动员天数和外周血白细胞数决定,而是由外周血单个核细胞数和CD34+的数量来决定.且干细胞动员和采集对患者的不良反应小,安全性高.%BACKGROUND: Autologous stem cell transplantation in the treatment of lower limb ischemia has been developed extensively in domestic and overseas and achieved better clinical curative effect. 5-10 μg/(kg · D) of granulocyte colony-stimulating factor (G-CSF) mobilization is often used, and stem cells are harvested after 5 days for transplantation. Whether the above-mentioned is the optimal mobilization scheme and harvesting opportunity is not reported

  12. Etoposide, Filgrastim, and Plerixafor in Improving Stem Cell Mobilization in Treating Patients With Non-Hodgkin Lymphoma

    Science.gov (United States)

    2016-09-15

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  13. Polydatin (PD) inhibits IgE-mediated passive cutaneous anaphylaxis in mice by stabilizing mast cells through modulating Ca{sup 2+} mobilization

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Meichun [Department of Pathophysiology, School of Medicine, Shenzhen University, Shenzhen 518060 (China); Department of Physiology, Hubei University of Medicine, Shiyan (China); Li, Jianjie [State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, Shenzhen 518060 (China); Lv, Jingzhang [Shenzhen Entry-Exit Inspection and Quarantine Bureau, Shenzhen 518045 (China); Mo, Xucheng; Yang, Chengbin [State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, Shenzhen 518060 (China); Chen, Xiangdong [Department of Pathophysiology, School of Medicine, Shenzhen University, Shenzhen 518060 (China); Liu, Zhigang [State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, Shenzhen 518060 (China); Liu, Jie, E-mail: ljljz@yahoo.com [Department of Pathophysiology, School of Medicine, Shenzhen University, Shenzhen 518060 (China)

    2012-11-01

    Mast cells play a key role in the pathogenesis of asthma and are a promising target for therapeutic intervention in asthma. This study investigated the effects of polydatin (PD), a resveratrol glucoside, on mast cell degranulation upon cross-linking of the high-affinity IgE receptors (FcεRI), as well as the anti-allergic activity of PD in vivo. Herein, we demonstrated that PD treatment for 30 min suppressed FcεRI-mediated mast cell degranulation in a dose-dependent manner. Concomitantly, PD significantly decreased FcεRI-mediated Ca{sup 2+} increase in mast cells. The suppressive effects of PD on FcεRI-mediated Ca{sup 2+} increase were largely inhibited by using LaCl{sub 3} to block the Ca{sup 2+} release-activated Ca{sup 2+} channels (CRACs). Furthermore, PD significantly inhibited Ca{sup 2+} entry through CRACs evoked by thapsigargin (TG). Knocking down protein expression of Orai1, the pore-forming subunit of CRACs, significantly decreased PD suppression of FcεRI-induced intracellular Ca{sup 2+} influx and mast cell degranulation. In a mouse model of mast cell-dependent passive cutaneous anaphylaxis (PCA), in vivo PD administration suppressed mast cell degranulation and inhibited anaphylaxis. Taken together, our data indicate that PD stabilizes mast cells by suppressing FcεRI-induced Ca{sup 2+} mobilization mainly through inhibiting Ca{sup 2+} entry via CRACs, thus exerting a protective effect against PCA. -- Highlights: ► Polydatin can prevent the pathogenesis of passive cutaneous anaphylaxis in mice. ► Polydatin stabilizes mast cells by decreasing FcεRI-mediated degranulation. ► Polydatin suppresses Ca{sup 2+} entry through CRAC channels in mast cells.

  14. Characterization of arabinoxylan/cellulose nanocrystals gels to investigate fluorescent probes mobility in bioinspired models of plant secondary cell wall.

    Science.gov (United States)

    Paës, Gabriel; Chabbert, Brigitte

    2012-01-01

    Biomass from lignocellulose (LC) is a highly complex network of cellulose, hemicellulose, and lignin, which is considered to be a sustainable source of fuels, chemicals and materials. To achieve an environmental friendly and efficient LC upgrading, a better understanding of the LC architecture is necessary. We have devised some LC bioinspired model systems, based on arabinoxylan gels, in which mobility of dextrans and BSA grafted with FITC has been studied by FRAP. Our results indicate that the probes diffusion is more influenced by their hydrodynamic radius than by the gel mesh size. The addition of some cellulose nanocrystals (CNCs) decreases polymer chain mobility and has low effect on the probes diffusion, suggesting that the gels are better organized in the presence of CNCs, as shown by rheological measurements and scanning electronic microscopy observations. This demonstrates that the FRAP analysis can be a powerful tool to screen the architecture of LC model systems.

  15. High mobility group box-1 protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Lu-WenWang; Hui Chen; Zuo-Jiong Gong

    2010-01-01

    BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMGB1) protein is involved in the process of endotoxemia. Regulatory T (Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection. However, the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients, and whether HMGB1 affects the immune activity of Treg cells are poorly known at present, and so were explored in this study. METHODS: The levels of HMGB1 expression were detected by ELISA, real-time RT-PCR, and Western blotting, and the percentage of CD4+CD25+CD127low Treg cells among CD4+cells was detected by flow cytometry in liver failure patients with chronic HBV infection, CHB patients, and healthy controls. Then, CD4+CD25+CD127low Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals. The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response. The levels of forkhead box P3 (Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting. RESULTS: A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CD4+ cells were found in liver failure patients than in CHB patients (82.6±20.1 μg/L vs. 34.2±13.7 μg/L; 4.55±1.34% vs. 9.52± 3.89%, respectively). The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose- or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro. CONCLUSIONS: The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with chronic HBV infection

  16. Ca2+-mobilizing actions of platelet-derived growth factor differ from those of bombesin and vasopressin in Swiss 3T3 mouse cells

    International Nuclear Information System (INIS)

    Addition of the mitogenic peptides bombesin and vasopressin to quiescent Swiss 3T3 mouse cells increased the cytosolic Ca2+ concentration without any measurable delay. In contrast, there was a significant lag period (16 +/- 1.2 s) before platelet-derived growth factor (PDGF) increased cytosolic Ca2+ concentration. This lag was not diminished at high concentrations of either porcine or human PDGF. Similar results were obtained in 3T3 cells loaded with quin-2 or fura-2. The differences in the effects of bombesin, vasopressin, and PDGF on Ca2+ movements were also substantiated by measurements of 45Ca2+ efflux and of cellular 45Ca2+ content. Activation of protein kinase C by phorbol esters inhibited Ca2+ mobilization induced by either bombesin or vasopressin. In contrast, phorbol esters had no effect on PDGF-induced cytosolic Ca2+ concentration increase or acceleration of 45Ca2+ efflux. Finally, bombesin and vasopressin caused a rapid increase in the production of inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate, whereas PDGF, even at a saturating concentration, exerted only a small effect. These results indicate that the signal transduction pathway activated by PDGF that lead to Ca2+ mobilization can be distinguished form those utilized by bombesin and vasopressin

  17. Notch-RBP-J signaling regulates the mobilization and function of endothelial progenitor cells by dynamic modulation of CXCR4 expression in mice.

    Directory of Open Access Journals (Sweden)

    Lin Wang

    Full Text Available Bone marrow (BM-derived endothelial progenitor cells (EPC have therapeutic potentials in promoting tissue regeneration, but how these cells are modulated in vivo has been elusive. Here, we report that RBP-J, the critical transcription factor mediating Notch signaling, modulates EPC through CXCR4. In a mouse partial hepatectomy (PHx model, RBP-J deficient EPC showed attenuated capacities of homing and facilitating liver regeneration. In resting mice, the conditional deletion of RBP-J led to a decrease of BM EPC, with a concomitant increase of EPC in the peripheral blood. This was accompanied by a down-regulation of CXCR4 on EPC in BM, although CXCR4 expression on EPC in the circulation was up-regulated in the absence of RBP-J. PHx in RBP-J deficient mice induced stronger EPC mobilization. In vitro, RBP-J deficient EPC showed lowered capacities of adhering, migrating, and forming vessel-like structures in three-dimensional cultures. Over-expression of CXCR4 could at least rescue the defects in vessel formation by the RBP-J deficient EPC. These data suggested that the RBP-J-mediated Notch signaling regulated EPC mobilization and function, at least partially through dynamic modulation of CXCR4 expression. Our findings not only provide new insights into the regulation of EPC, but also have implications for clinical therapies using EPC in diseases.

  18. Are mobile phones harmful?

    DEFF Research Database (Denmark)

    Blettner, M; Berg, Gabriele

    2000-01-01

    effect, genetic and carcinogenic effects and cancer related investigations. Mobile phones transmit and receive waves of frequencies mainly at 800-1800 MHz. Findings on the thermal effect of acute exposure to radiofrequency fields were consistent, resulting in an increase of cellular, tissue or body......There is increasing public interest in health risks of mobile phone use. Although there is a vast body of material on the biological effects of radiofrequency fields, current risk assessment is still limited. The article describes several hypotheses and results of biological effects such as thermal...... in cells. Implications of these experimental results on public health concerns are yet unclear. Few epidemiological studies are available on the use of mobile phones or on the radiofrequency exposure and the development of cancer. Most of these studies have no or little quantitative exposure data...

  19. Influence of Blend Ratio and Processing Additive on Free Carrier Yield and Mobility in PTB7:PC71BM Photovoltaic Solar Cells

    Science.gov (United States)

    2016-01-01

    Charge separation and extraction dynamics were investigated in high-performance bulk heterojunction solar cells made from the polymer PTB7 and the soluble fullerene PC71BM on a broad time scale from subpicosecond to microseconds using ultrafast optical probing of carrier drift and the integral-mode photocurrent measurements. We show that the short circuit current is determined by the separation of charge pairs into free carriers, which is strongly influenced by blend composition. This separation is found to be efficient in fullerene-rich blends where a high electron mobility of >0.1 cm2 V–1 s–1 is observed in the first 10 ps after excitation. Morphology optimization using the solvent additive 1,8-diiodooctane (DIO) doubles the charge pair separation efficiency and the short-circuit current. Carrier extraction at low internal electric field is slightly faster from the cells prepared with DIO, which can reduce recombination losses and enhance a fill factor. PMID:27293495

  20. Mobile medical image retrieval

    Science.gov (United States)

    Duc, Samuel; Depeursinge, Adrien; Eggel, Ivan; Müller, Henning

    2011-03-01

    Images are an integral part of medical practice for diagnosis, treatment planning and teaching. Image retrieval has gained in importance mainly as a research domain over the past 20 years. Both textual and visual retrieval of images are essential. In the process of mobile devices becoming reliable and having a functionality equaling that of formerly desktop clients, mobile computing has gained ground and many applications have been explored. This creates a new field of mobile information search & access and in this context images can play an important role as they often allow understanding complex scenarios much quicker and easier than free text. Mobile information retrieval in general has skyrocketed over the past year with many new applications and tools being developed and all sorts of interfaces being adapted to mobile clients. This article describes constraints of an information retrieval system including visual and textual information retrieval from the medical literature of BioMedCentral and of the RSNA journals Radiology and Radiographics. Solutions for mobile data access with an example on an iPhone in a web-based environment are presented as iPhones are frequently used and the operating system is bound to become the most frequent smartphone operating system in 2011. A web-based scenario was chosen to allow for a use by other smart phone platforms such as Android as well. Constraints of small screens and navigation with touch screens are taken into account in the development of the application. A hybrid choice had to be taken to allow for taking pictures with the cell phone camera and upload them for visual similarity search as most producers of smart phones block this functionality to web applications. Mobile information access and in particular access to images can be surprisingly efficient and effective on smaller screens. Images can be read on screen much faster and relevance of documents can be identified quickly through the use of images contained in

  1. Mobile Usability

    DEFF Research Database (Denmark)

    Aryana, Bijan; Clemmensen, Torkil

    2013-01-01

    In this article, a country specific comparative mobile usability study is presented, using Iran and Turkey as the two chosen emerging/emergent nation exemplars of smartphone usage and adoption. In a focus group study, three mobile applications were selected by first-time users of smartphones...... personal contacts. The results and analysis establish the existence of country specific issues and concerns, as well as reveal generic usability issues. The article concludes that the source of these issues is most likely due to a combination of certain contextual features endemic to both Iran and Turkey...

  2. High mobility group box associated with cell proliferation appears to play an important role in hepatocellular carcinogenesis in rats and humans

    International Nuclear Information System (INIS)

    To identify genes important in hepatocellular carcinogenesis, especially processes involved in malignant transformation, we focused on differences in gene expression between adenomas and carcinomas by DNA microarray. Eighty-one genes for which expression was specific in carcinomas were analyzed using Ingenuity Pathway Analysis software and Gene Ontology, and found to be associated with TP53 and regulators of cell proliferation. In the genes associated with TP53, we selected high mobility group box (HMGB) for detailed analysis. Immunohistochemistry revealed expression of HMGBs in carcinomas to be significantly higher than in other lesions among both human and rat liver, and a positive correlation between HMGBs and TP53 was detected in rat carcinomas. Knock-down of HMGB 2 expression in a rat hepatocellular carcinoma cell line by RNAi resulted in inhibition of cell growth, although no effects on invasion were evident in vitro. These results suggest that acquisition of malignant potential in the liver requires specific signaling pathways related to high cell proliferation associated with TP53. In particular, HMGBs appear to have an important role for progression and cell proliferation associated with loss of TP53 function in rat and in human hepatocarcinogenesis

  3. Effect of Mobile Phone-Induced Electromagnetic Field on Brain Hemodynamics and Human Stem Cell Functioning: Possible Mechanistic Link to Cancer Risk and Early Diagnostic Value of Electronphotonic Imaging.

    Science.gov (United States)

    Bhargav, Hemant; Srinivasan, T M; Varambally, S; Gangadhar, B N; Koka, Prasad

    2015-01-01

    The mobile phones (MP) are low power radio devices which work on electromagnetic fields (EMFs), in the frequency range of 900-1800 MHz. Exposure to MPEMFs may affect brain physiology and lead to various health hazards including brain tumors. Earlier studies with positron emission tomography (PET) have found alterations in cerebral blood flow (CBF) after acute exposure to MPEMFs. It is widely accepted that DNA double-strand breaks (DSBs) and their misrepair in stem cells are critical events in the multistage origination of various leukemia and tumors, including brain tumors such as gliomas. Both significant misbalance in DSB repair and severe stress response have been triggered by MPEMFs and EMFs from cell towers. It has been shown that stem cells are most sensitive to microwave exposure and react to more frequencies than do differentiated cells. This may be important for cancer risk assessment and indicates that stem cells are the most relevant cellular model for validating safe mobile communication signals. Recently developed technology for recording the human bio-electromagnetic (BEM) field using Electron photonic Imaging (EPI) or Gas Discharge Visualisation (GDV) technique provides useful information about the human BEM. Studies have recorded acute effects of Mobile Phone Electromagnetic Fields (MPEMFs) using EPI and found quantifiable effects on human BEM field. Present manuscript reviews evidences of altered brain physiology and stem cell functioning due to mobile phone/cell tower radiations, its association with increased cancer risk and explores early diagnostic value of EPI imaging in detecting EMF induced changes on human BEM.

  4. Estradiol attenuates EGF-induced rapid uPAR mobilization and cell migration via the G-protein-coupled receptor 30 in ovarian cancer cells

    DEFF Research Database (Denmark)

    Henic, Emir; Noskova, Vera; Høyer-Hansen, Gunilla;

    2009-01-01

    mobilization of uPAR from detergent-resistant domains such as lipid rafts. Estradiol influenced neither the amount of uPAR mRNA nor the rate of uPAR degradation or solubilization. The nuclear ER antagonists ICI 182780 and tamoxifen, which are GPR30 agonists, as well as the specifically constructed GPR30...

  5. Activated platelet supernatant can augment the angiogenic potential of human peripheral blood stem cells mobilized from bone marrow by G-CSF.

    Science.gov (United States)

    Kang, Jeehoon; Hur, Jin; Kang, Jin-A; Yun, Ji-Yeon; Choi, Jae-Il; Ko, Seung Bum; Lee, Choon-Soo; Lee, Jaewon; Han, Jung-Kyu; Kim, Hyun Kyung; Kim, Hyo-Soo

    2014-10-01

    Platelets not only play a role in hemostasis, but they also promote angiogenesis and tissue recovery by releasing various cytokines and making an angiogenic milieu. Here, we examined autologous 'activated platelet supernatant (APS)' as a priming agent for stem cells; thereby enhance their pro-angiogenic potential and efficacy of stem cell-based therapy for ischemic diseases. The mobilized peripheral blood stem cells ((mob)PBSCs) were isolated from healthy volunteers after subcutaneous injection of granulocyte-colony stimulating factor. APS was collected separately from the platelet rich plasma after activation by thrombin. (mob)PBSCs were primed for 6h before analysis. Compared to naive platelet supernatants, APS had a higher level of various cytokines, such as IL8, IL17, PDGF and VEGF. APS-priming for 6h induced (mob)PBSCs to express key angiogenic factors, surface markers (i.e. CD34, CD31, and CXCR4) and integrins (integrins α5, β1 and β2). Also (mob)PBSCs were polarized toward CD14(++)/CD16(+) pro-angiogenic monocytes. The priming effect was reproduced by an in vitro reconstruction of APS. Through this phenotype, APS-priming increased cell-cell adhesion and cell-extracellular matrix adhesion. The culture supernatant of APS-primed (mob)PBSCs contained high levels of IL8, IL10, IL17 and TNFα, and augmented proliferation and capillary network formation of human umbilical vein endothelial cells. In vivo transplantation of APS-primed (mob)PBSCs into athymic mice ischemic hindlimbs and Matrigel plugs elicited vessel differentiation and tissue repair. In safety analysis, platelet activity increased after mixing with (mob)PBSCs regardless of priming, which was normalized by aspirin treatment. Collectively, our data identify that APS-priming can enhance the angiogenic potential of (mob)PBSCs, which can be used as an adjunctive strategy to improve the efficacy of cell therapy for ischemic diseases. PMID:25016235

  6. Mobile Misfortune

    DEFF Research Database (Denmark)

    Vigh, Henrik Erdman

    2015-01-01

    of the mobility it enables. This article, thus, looks at the motives and manners in which young men in Bissau become caught up in transnational flows of cocaine. It shows how motion is emotively anchored and affectively bound: tied to and directed toward a feeling of worth and realisation of being, and how...

  7. Designing Mobilities

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    How is the width of the pavement shaping the urban experience? How is the material design of transport infrastructure and mobile technology affording social interaction in everyday life spaces? How do people inhabit these spaces with their bodies and in accordance to social and cultural norms...

  8. Mobil nationalisme

    DEFF Research Database (Denmark)

    Koefoed, Lasse Martin

    2006-01-01

    , varer, mennesker og kapital men derimod en integreret del af disse tendenser. Gennem begrebet mobil nationalisme argumenteres der for en analytisk optik, hvor nationalisme forstås som en proces hvorigennem skiftende relationer og bevægelser mellem forskellige socio-rumlige skalaer som kroppen...

  9. Mobile Phone

    Institute of Scientific and Technical Information of China (English)

    籍万杰

    2004-01-01

    Your mobile phone rings.and instead of usual electronic signals,it's playing your favorite music.A friend sends your favorite song to cheer you up.One day,a record company might forward new records and music videos to your phone.

  10. Effect of mobilization of bone marrow stem cells by granulocyte colony stimulating factor on clinical symptoms, left ventricular perfusion and function in patients with severe chronic ischemic heart disease

    DEFF Research Database (Denmark)

    Wang, Yongzhong; Tägil, Kristina; Ripa, Rasmus S.;

    2005-01-01

    OBJECTIVES: A phase I safety and efficacy study with granulocyte colony stimulating factor (G-CSF) mobilization of bone marrow stem cells to induce vasculogenesis in patients with severe ischemic heart disease (IHD) was conducted. DESIGN, PATIENTS AND RESULTS: 29 patients with IHD participated...... with echocardiography. CONCLUSIONS: Treatment by G-CSF improved symptoms but not signs of myocardial ischemia in patients with severe IHD. The effects seemed related to mobilization of stem cells. An adverse effect on ejection fraction could not be excluded...... in the study. Thirteen patients were treated with G-CSF for 6 days and 16 patients served as controls. G-CSF treatment was without any serious adverse events. Four patients were 'poor mobilizers' with a maximal increase in CD34+ cells to 5,000+/-700/mL blood (mean+/-S.D.) compared to 28,900+/-5,100/mL blood...

  11. Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-{kappa}B translocation and ROS production in synoviocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Fen; Yang, Shuang; Zhao, Dan; Zhu, Shuyan; Wang, Yuxiang [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China); Li, Junying, E-mail: jyli04@nankai.edu.cn [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China)

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer Moderate extracellular acidification regulates intracellular Ca{sup 2+} mobilization. Black-Right-Pointing-Pointer Moderate acidification activates NF-{kappa}B nuclear translocation in synoviocytes. Black-Right-Pointing-Pointer Moderate acidification depresses the ROS production induced by capsaicin. Black-Right-Pointing-Pointer Moderate acidification inhibits capsaicin-caused synoviocyte death. -- Abstract: We previously show the expression of transient receptor potential vanilloid 1 (TRPV1) in primary synoviocytes from collagen-induced arthritis (CIA) rats. Capsaicin and lowered extracellular pH from 7.4 to 5.5 induce cell death through TRPV1-mediated Ca{sup 2+} entry and reactive oxygen species (ROS) production. However, under the pathological condition in rheumatoid arthritis, the synovial fluid is acidified to a moderate level (about pH 6.8). In the present study, we examined the effects of pH 6.8 on the TRPV1-mediated cell death. Our finding is different or even opposite from what was observed at pH 5.5. We found that the moderate extracellular acidification (from pH 7.4 to 6.8) inhibited the capsaicin-induced Ca{sup 2+} entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca{sup 2+} release from intracellular stores. The nuclear translocation of NF-{kappa}B was found at pH 6.8, and this also depends on PLC activation. Moreover, the capsaicin-evoked massive ROS production and cell death were depressed at pH 6.8, both of which are dependent on the activation of PLC and NF-{kappa}B. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca{sup 2+} mobilization, activating NF-{kappa}B nuclear translocation and depressing ROS production.

  12. Gliadin-Specific T-Cells Mobilized in the Peripheral Blood of Coeliac Patients by Short Oral Gluten Challenge: Clinical Applications

    Directory of Open Access Journals (Sweden)

    Stefania Picascia

    2015-12-01

    Full Text Available Celiac disease (CD is a common lifelong food intolerance triggered by dietary gluten affecting 1% of the general population. Gliadin-specific T-cell lines and T-cell clones obtained from intestinal biopsies have provided great support in the investigation of immuno-pathogenesis of CD. In the early 2000 a new in vivo, less invasive, approach was established aimed to evaluate the adaptive gliadin-specific T-cell response in peripheral blood of celiac patients on a gluten free diet. In fact, it has been demonstrated that three days of ingestion of wheat-containing food induces the mobilization of memory T lymphocytes reactive against gliadin from gut-associated lymphoid tissue into peripheral blood of CD patients. Such antigen-specific T-cells releasing interferon-γ can be transiently detected by using the enzyme-linked immunospot (ELISPOT assays or by flow cytometry tetramer technology. This paper discusses the suitability of this in vivo tool to investigate the repertoire of gluten pathogenic peptides, to support CD diagnosis, and to assess the efficacy of novel therapeutic strategies. A systematic review of all potential applications of short oral gluten challenge is provided.

  13. Embedded LTPS flash cells with oxide-nitride-oxynitride stack structure for realization of multi-function mobile flat panel displays

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Sungwook; Kim, Jaehong; Son, Hyukjoo; Jang, Kyungsoo; Cho, Jaehyun; Kim, Kyunghae; Choi, Byoungdeog; Yi, Junsin [School of Information and Communication Engineering, Sungkyunkwan University, Suwon, 440-746 (Korea, Republic of)], E-mail: yi@yurim.skku.ac.kr

    2008-09-07

    In this paper, embedded flash (eFlash) cells were fabricated for realization of multi-functions, such as systems on panels (SOPs) and threshold voltage (V{sub TH}) stabilization of flat panel displays (FPDs). Fabrication was via low temperature polycrystalline silicon (LTPS) thin film transistor (TFT) technology and an oxide-nitride-oxynitride (ONOn) stack structure on glass. Poly-silicon (poly-Si) on glass, which was annealed via an excimer laser, has a very rough surface. To fabricate LTPS eFlash cells on glass with a very rough poly-Si surface, plasma-assisted oxynitridation was performed; nitrous oxide (N{sub 2}O) served as a reactive gas. LTPS eFlash cells have excellent TFT electrical properties, such as V{sub TH}, a high On/Off current ratio and a low sub-threshold swing (S). The results demonstrate that eFlash cells fabricated on glass with a rough silicon surface, via an ONOn stack structure, have switching characteristics suitable for data storage, such as a low operating voltage (<{+-}10 V) suitable for mobile FPDs, a threshold voltage window, {delta}V{sub TH}, which exceeds 2.3 V, between the programming and erasing (P/E) states, over a period of 10 years, and the capacity to retain the initial {delta}V{sub TH} over a period of 10{sup 5} P/E operations. (fast track communication)

  14. Characterization of anthocyanin based dye-sensitized organic solar cells (DSSC) and modifications based on bio-inspired ion mobility improvements

    Science.gov (United States)

    Mawyin, Jose Amador

    The worldwide electrical energy consumption will increase from currently 10 terawatts to 30 terawatts by 2050. To decrease the current atmospheric CO2 would require our civilization to develop a 20 terawatts non-greenhouse emitting (renewable) electrical power generation capability. Solar photovoltaic electric power generation is thought to be a major component of proposed renewable energy-based economy. One approach to less costly, easily manufactured solar cells is the Dye-sensitized solar cells (DSSC) introduced by Greatzel and others. This dissertation describes the work focused on improving the performance of DSSC type solar cells. In particular parameters affecting dye-sensitized solar cells (DSSC) based on anthocyanin pigments extracted from California blackberries (Rubus ursinus) and bio-inspired modifications were analyzed and solar cell designs optimized. Using off-the-shelf materials DSSC were constructed and tested using a custom made solar spectrum simulator and photoelectric property characterization. This equipment facilitated the taking of automated I-V curve plots and the experimental determination of parameters such as open circuit voltage (V OC), short circuit current (JSC), fill factor (FF), etc. This equipment was used to probe the effect of various modifications such as changes in the annealing time and composition of the of the electrode counter-electrode. Solar cell optimization schemes included novel schemes such as solar spectrum manipulation to increase the percentage of the solar spectrum capable of generating power in the DSSC. Solar manipulation included light scattering and photon upconversion. Techniques examined here focused on affordable materials such as silica nanoparticles embedded inside a TiO2 matrix. Such materials were examined for controlled scattering of visible light and optimize light trapping within the matrix as well as a means to achieve photon up-energy-conversion using the Raman effect in silica nano-particles (due

  15. Rapid Exercise-Induced Mobilization of Dendritic Cells Is Potentially Mediated by a Flt3L- and MMP-9-Dependent Process in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Nathalie Deckx

    2015-01-01

    Full Text Available In healthy individuals, one exercise bout induces a substantial increase in the number of circulating leukocytes, while their function is transiently suppressed. The effect of one exercise bout in multiple sclerosis (MS is less studied. Since recent evidence suggests a role of dendritic cells (DC in the pathogenesis of MS, we investigated the effect of one combined endurance/resistance exercise bout on the number and function of DC in MS patients and healthy controls. Our results show a rapid increase in the number of DC in response to physical exercise in both MS patients and controls. Further investigation revealed that in particular DC expressing the migratory molecules CCR5 and CD62L were increased upon acute physical activity. This may be mediated by Flt3L- and MMP-9-dependent mobilization of DC, as demonstrated by increased circulating levels of Flt3L and MMP-9 following one exercise bout. Circulating DC display reduced TLR responsiveness after acute exercise, as evidenced by a less pronounced upregulation of activation markers, HLA-DR and CD86, on plasmacytoid DC and conventional DC, respectively. Our results indicate mobilization of DC, which may be less prone to drive inflammatory processes, following exercise. This may present a negative feedback mechanism for exercise-induced tissue damage and inflammation.

  16. Emotional change-associated T cell mobilization at the early stage of a mouse model of multiple sclerosis

    OpenAIRE

    Giuseppa ePiras; Lorenza eRattazzi; Adam eMcDermott; Robert eDeacon; Fulvio eD'acquisto

    2013-01-01

    Autoimmune diseases like multiple sclerosis are known to be associated with debilitating emotional disorders that manifest long before the flaring of motor dysfunctions. Given the emerging role of T cells in controlling both emotions and autoimmunity, in this study we explored possible correlation between T cell activation and changes in emotional behavior in a mouse model of multiple sclerosis. Our results showed a significant increase in blood circulating T cells as soon as at day 4 post-im...

  17. Emotional Change-Associated T Cell Mobilization at the Early Stage of a Mouse Model of Multiple Sclerosis

    OpenAIRE

    Piras, Giuseppa; Rattazzi, Lorenza; McDermott, Adam; Deacon, Robert; D’Acquisto, Fulvio

    2013-01-01

    Autoimmune diseases like multiple sclerosis (MS) are known to be associated with debilitating emotional disorders that manifest long before the flaring of motor dysfunctions. Given the emerging role of T cells in controlling both emotions and autoimmunity, in this study we explored possible correlation between T cell activation and changes in emotional behavior in a mouse model of MS. Our results showed a significant increase in blood circulating T cells as soon as at day 4 post immunization....

  18. Amyloid Deposits in the Bone Marrow of Patients with AL Amyloidosis Do Not Impact Stem Cell Mobilization or Engraftment

    OpenAIRE

    Cowan, Andrew J.; Seldin, David C.; Skinner, Martha; Quillen, Karen; Doros, Gheorghe; Tan, Josenia; O'Hara, Carl; Finn, Kathleen T.; Sanchorawala, Vaishali

    2012-01-01

    Amyloid deposits are often found in the bone marrow in patients with AL amyloidosis; we sought to determine whether this affects stem cell collection or engraftment following high dose melphalan and autologous stem cell transplantation (HDM/SCT). Data on 361 patients with AL amyloidosis who had Congo red staining of the pre-treatment bone marrow biopsy and underwent HDM/SCT from July 1994 to December 2011 were reviewed. Data were analyzed for stem cell yield, number of days of stem cell colle...

  19. Polymer blend solar cells based on a high-mobility naphthalenediimide-based polymer acceptor: device physics, photophysics and morphology

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Jennifer R.; Albert-Seifried, Sebastian; Rao, Akshay; Massip, Sylvain; Friend, Richard H.; McNeill, Christopher R.; Sirringhaus, Henning [Department of Physics, Cavendish Laboratory, JJ Thomson Avenue, Cambridge CB3 0HE (United Kingdom); Watts, Benjamin [Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); Morgan, David J. [Cardiff Catalysis Institute, School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT (United Kingdom)

    2011-03-18

    A high electron mobility polymer, poly{l_brace}[N,N'-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene) (P(NDI2OD-T2)) is investigated for use as an electron acceptor in all-polymer blends. Despite the high bulk electron mobility, near-infrared absorption band and compatible energy levels, bulk heterojunction devices fabricated with poly(3-hexylthiophene) (P3HT) as the electron donor exhibit power conversion efficiencies of only 0.2%. In order to understand this disappointing photovoltaic performance, systematic investigations of the photophysics, device physics and morphology of this system are performed. Ultra-fast transient absorption spectroscopy reveals a two-stage decay process with an initial rapid loss of photoinduced polarons, followed by a second slower decay. This second slower decay is similar to what is observed for efficient P3HT:PCBM ([6,6]-phenyl C{sub 61}-butyric acid methyl ester) blends, however the initial fast decay that is absent in P3HT:PCBM blends suggests rapid, geminate recombination of charge pairs shortly after charge transfer. X-ray microscopy reveals coarse phase separation of P3HT:P(NDI2OD-T2) blends with domains of size 0.2 to 1 micrometer. P3HT photoluminescence, however, is still found to be efficiently quenched indicating intermixing within these mesoscale domains. This hierarchy of phase separation is consistent with the transient absorption, whereby localized confinement of charges on isolated chains in the matrix of the other polymer hinders the separation of interfacial electron-hole pairs. These results indicate that local, interfacial processes are the key factor determining the overall efficiency of this system and highlight the need for improved morphological control in order for the potential benefit of high-mobility electron accepting polymers to be realized. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  20. Intensive mobilities:

    DEFF Research Database (Denmark)

    Vannini, Phillip; Bissell, David; Jensen, Ole B.

    This paper explores the intensities of long distance commuting journeys as a way of exploring how bodily sensibilities are being changed by the mobilities that they undertake. The context of this paper is that many people are travelling further to work than ever before owing to a variety of factors...... with fieldwork conducted in Canada, Denmark and Australia to develop our understanding of the experiential politics of long distance workers. Rather than focusing on the extensive dimensions of mobilities that are implicated in patterns and trends, our paper turns to the intensive dimensions of this experience....... By exploring how experiences of long-distance workers become constituted by a range of different material forces enables us to more sensitively consider the practical, technical, and political implications of this increasingly prevalent yet underexplored regime of work....

  1. Regulatory T Cells in the Tumor Microenvironment and Cancer Progression: Role and Therapeutic Targeting

    Science.gov (United States)

    Chaudhary, Belal; Elkord, Eyad

    2016-01-01

    Recent years have seen significant efforts in understanding and modulating the immune response in cancer. In this context, immunosuppressive cells, including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), have come under intense investigation for their proposed roles in suppressing tumor-specific immune responses and establishing an immunosuppressive tumor microenvironment, thus enabling tumor immune evasion. Additionally, recent evidence indicates that Tregs comprise diverse and heterogeneous subsets; phenotypically and functionally distinct subsets of tumor-infiltrating Tregs could contribute differently to cancer prognosis and clinical outcomes. Understanding Treg biology in the setting of cancer, and specifically the tumor microenvironment, is important for designing effective cancer therapies. In this review, we critically examine the role of Tregs in the tumor microenvironment and in cancer progression focusing on human studies. We also discuss the impact of current therapeutic modalities on Treg biology and the therapeutic opportunities for targeting Tregs to enhance anti-tumor immune responses and clinical benefits. PMID:27509527

  2. Network Mobiles

    Directory of Open Access Journals (Sweden)

    Alhamali Masoud Alfrgani .Ali

    2015-07-01

    Full Text Available Mobile devices are becoming increasingly popular for delivering multimedia content, particularly by means of streaming. The main disadvantage of these devices is their limited battery life. Unfortunately, streaming of multimedia content causes the battery of the device to discharge very fast, often causing the battery to deplete before the streaming task finishes, resulting in user dissatisfaction. It is generally not possible to charge the device while on the go as electricity socket and charger are required. Therefore, to avoid this user dissatisfaction, it is necessary to find ways to prolong the battery lifetime and to support the completion of the multimedia streaming tasks. A typical architecture for mobile multimedia streaming is presented In this architecture, a wired server streams multimedia content over a wireless IP network to a number of client devices. These devices could be PDAs, smartphones or any other mobile device with 802.11 connectivity. In relation to possible power savings, the multimedia streaming process can be described as consisting of three stages: reception, decoding and playing. Other researchers have shown that energy savings can be made in each stage, for example by using pre-buffering in the reception stage, feedback control during decoding and backlight adjustment for playing. However, it is not a common practice to combine energy savings in the three stages in order to achieve the best

  3. The African Mobile Story

    DEFF Research Database (Denmark)

    This book identifies the factors that has enabled the growth of mobile telephony in Africa. The book covers the regulatory factors, the development and usage of mobile application, mobile security and sustainable power source for mobile networks......This book identifies the factors that has enabled the growth of mobile telephony in Africa. The book covers the regulatory factors, the development and usage of mobile application, mobile security and sustainable power source for mobile networks...

  4. Tissue plasminogen activator followed by antioxidant-loaded nanoparticle delivery promotes activation/mobilization of progenitor cells in infarcted rat brain.

    Science.gov (United States)

    Petro, Marianne; Jaffer, Hayder; Yang, Jun; Kabu, Shushi; Morris, Viola B; Labhasetwar, Vinod

    2016-03-01

    Inherent neuronal and circulating progenitor cells play important roles in facilitating neuronal and functional recovery post stroke. However, this endogenous repair process is rather limited, primarily due to unfavorable conditions in the infarcted brain involving reactive oxygen species (ROS)-mediated oxidative stress and inflammation following ischemia/reperfusion injury. We hypothesized that during reperfusion, effective delivery of antioxidants to ischemic brain would create an environment without such oxidative stress and inflammation, thus promoting activation and mobilization of progenitor cells in the infarcted brain. We administered recombinant human tissue-type plasminogen activator (tPA) via carotid artery at 3 h post stroke in a thromboembolic rat model, followed by sequential administration of the antioxidants catalase (CAT) and superoxide dismutase (SOD), encapsulated in biodegradable nanoparticles (nano-CAT/SOD). Brains were harvested at 48 h post stroke for immunohistochemical analysis. Ipsilateral brain slices from animals that had received tPA + nano-CAT/SOD showed a widespread distribution of glial fibrillary acidic protein-positive cells (with morphology resembling radial glia-like neural precursor cells) and nestin-positive cells (indicating the presence of immature neurons); such cells were considerably fewer in untreated animals or those treated with tPA alone. Brain sections from animals receiving tPA + nano-CAT/SOD also showed much greater numbers of SOX2- and nestin-positive progenitor cells migrating from subventricular zone of the lateral ventricle and entering the rostral migratory stream than in t-PA alone treated group or untreated control. Further, animals treated with tPA + nano-CAT/SOD showed far fewer caspase-positive cells and fewer neutrophils than did other groups, as well as an inhibition of hippocampal swelling. These results suggest that the antioxidants mitigated the inflammatory response, protected neuronal cells

  5. Bortezomib and Filgrastim in Promoting Stem Cell Mobilization in Patients With Non-Hodgkin Lymphoma or Multiple Myeloma Undergoing Stem Cell Transplant

    Science.gov (United States)

    2016-04-19

    Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular

  6. Emotional change-associated T cell mobilization at the early stage of a mouse model of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Giuseppa ePiras

    2013-11-01

    Full Text Available Autoimmune diseases like multiple sclerosis are known to be associated with debilitating emotional disorders that manifest long before the flaring of motor dysfunctions. Given the emerging role of T cells in controlling both emotions and autoimmunity, in this study we explored possible correlation between T cell activation and changes in emotional behavior in a mouse model of multiple sclerosis. Our results showed a significant increase in blood circulating T cells as soon as at day 4 post-immunization. This lymphocytosis remained stable with time and preceded the infiltration of T cell in the CNS. The kinetic of T cell entry in the blood matched the kinetic of changes in behavior measured using the open field test. Treatment with glatiramer acetate, a well-known immunomodulatory drug for multiple sclerosis, suppressed behavioral changes while retaining the T cells in the draining lymph nodes. Together these results provide evidence of a positive correlation between the emigration of T cells in circulation and changes in emotions during chronic inflammatory diseases. The validation of these findings in the clinic might help to better understand the cause of the emotional and psychological burden of patients suffering multiple sclerosis or other autoimmune diseases. Most importantly our study suggests novel therapeutic venues for the treatment of the emotional changes associated with autoimmunity.

  7. Commercializing light-duty plug-in/plug-out hydrogen-fuel-cell vehicles: "Mobile electricity" technologies, early California household markets, and innovation management

    Science.gov (United States)

    Williams, Brett David

    Starting from the premise that new consumer value must drive hydrogen-fuel-cell-vehicle (H2FCV) commercialization, a group of opportunities collectively called "Mobile Electricity" (Me-) is characterized. Me- redefines H2 FCVs as innovative products able to provide home recharging and mobile power, for example for tools, mobile activities, emergencies, and electric-grid-support services. To characterize such opportunities, this study first integrates and extends previous analyses of H2FCVs, plug-in hybrids, and vehicle-to-grid (V2G) power. It uses a new model to estimate zero-emission-power vs. zero-emission-driving tradeoffs, costs, and grid-support revenues for various electric-drive vehicle types and levels of infrastructure service. Next, the initial market potential for Me- enabled vehicles, such as H2FCVs and plug-in hybrids, is estimated by eliminating unlikely households from consideration for early adoption. 5.2 million of 33.9 million Californians in the 2000 Census live in households pre-adapted to Me-, 3.9 million if natural gas is required for home refueling. The possible sales base represented by this population is discussed. Several differences in demographic and other characteristics between the target market and the population as a whole are highlighted, and two issues related to the design of H2FCVs and their supporting infrastructure are discussed: vehicle range and home hydrogen refueling. These findings argue for continued investigation of this and similar target segments-which represent more efficient research populations for subsequent study by product designers and other decision-makers wishing to understand the early market dynamics facing Me- innovations. Next, Me-H2FCV commercialization issues are raised from the perspectives of innovation, product development, and strategic marketing. Starting with today's internalcombustion hybrids, this discussion suggests a way to move beyond the battery vs. fuel-cell zero-sum game and towards the

  8. Mobile Web Design for Dummies

    CERN Document Server

    Warner, Janine

    2010-01-01

    The perfect place to learn how to design Web sites for mobile devices!. With the popularity of Internet access via cell phones and other mobile devices, Web designers now have to consider as many as eight operating systems, several browsers, and a slew of new devices as they plan a new site, a new interface, or a new sub-site. This easy-to-follow friendly book guides you through this brave new world with a clear look at the fundamentals and offers practical techniques and tricks you may not have considered.: Explores all issues to consider in planning a mobile site; Covers the tools needed for

  9. Infection of the germ line by retroviral particles produced in the follicle cells: a possible mechanism for the mobilization of the gypsy retroelement of Drosophila.

    Science.gov (United States)

    Song, S U; Kurkulos, M; Boeke, J D; Corces, V G

    1997-07-01

    The gypsy retroelement of Drosophila moves at high frequency in the germ line of the progeny of females carrying a mutation in the flamenco (flam) gene. This high rate of de novo insertion correlates with elevated accumulation of full-length gypsy RNA in the ovaries of these females, as well as the presence of an env-specific RNA. We have prepared monoclonal antibodies against the gypsy Pol and Env products and found that these proteins are expressed in the ovaries of flam females and processed in the manner characteristic of vertebrate retroviruses. The Pol proteins are expressed in both follicle and nurse cells, but they do not accumulate at detectable levels in the oocyte. The Env proteins are expressed exclusively in the follicle cells starting at stage 9 of oogenesis, where they accumulate in the secretory apparatus of the endoplasmic reticulum. They then migrate to the inner side of the cytoplasmic membrane where they assemble into viral particles. These particles can be observed in the perivitelline space starting at stage 10 by immunoelectron microscopy using anti-Env antibodies. We propose a model to explain flamenco-mediated induction of gypsy mobilization that involves the synthesis of gypsy viral particles in the follicle cells, from where they leave and infect the oocyte, thus explaining gypsy insertion into the germ line of the subsequent generation. PMID:9226450

  10. HCMV infection of humanized mice after transplantation of G-CSF-mobilized peripheral blood stem cells from HCMV-seropositive donors.

    Science.gov (United States)

    Hakki, Morgan; Goldman, Devorah C; Streblow, Daniel N; Hamlin, Kimberly L; Krekylwich, Craig N; Fleming, William H; Nelson, Jay A

    2014-01-01

    Human cytomegalovirus (HCMV) infection, including primary infection resulting from transmission from a seropositive donor to a seronegative recipient (D(+)/R(-)), remains a significant problem in the setting of peripheral blood stem cell transplantation (PBSCT). The lack of a suitable animal model for studying HCMV transmission after PBSCT is a major barrier to understanding this process and, consequently, developing novel interventions to prevent HCMV infection. Our previous work demonstrated that human CD34(+) progenitor cell-engrafted NOD-scid IL2Rγc(null) (NSG) mice support latent HCMV infection after direct inoculation and reactivation after treatment with granulocyte colony-stimulating factor. To more accurately recapitulate HCMV infection in the D(+)/R(-) PBSCT setting, granulocyte colony-stimulating factor-mobilized peripheral blood stem cells from seropositive donors were used to engraft NSG mice. All recipient mice demonstrated evidence of HCMV infection in liver, spleen, and bone marrow. These findings validate the NSG mouse model for studying HCMV transmission during PBSCT.

  11. Pathological Mobilization and Activities of Dendritic Cells in Tumor-Bearing Hosts: Challenges and Opportunities for Immunotherapy of Cancer

    Science.gov (United States)

    Tesone, Amelia J.; Svoronos, Nikolaos; Allegrezza, Michael J.; Conejo-Garcia, Jose R.

    2013-01-01

    A common characteristic of solid tumors is the pathological recruitment of immunosuppressive myeloid cells, which in certain tumors includes dendritic cells (DCs). DCs are of particular interest in the field of cancer immunotherapy because they induce potent and highly specific anti-tumor immune responses, particularly in the early phase of tumorigenesis. However, as tumors progress, these cells can be transformed into regulatory cells that contribute to an immunosuppressive microenvironment favoring tumor growth. Therefore, controlling DC phenotype has the potential to elicit effective anti-tumor responses while simultaneously weakening the tumor’s ability to protect itself from immune attack. This review focuses on the dual nature of DCs in the tumor microenvironment, the regulation of DC phenotype, and the prospect of modifying DCs in situ as a novel immunotherapeutic approach. PMID:24339824

  12. Auto-regeneration of mice testicle seminiferous tubules due to malnutrition based on stem cells mobilization using honey

    Directory of Open Access Journals (Sweden)

    Erma Safitri

    2016-03-01

    Conclusions: Results of this study revealed a significantly different of C34 and CD45 expressions between groups, also an increase SSCs expression and testicle seminiferous tubules cells regeneration as well.

  13. Molecular purging of multiple myeloma cells by ex-vivo culture and retroviral transduction of mobilized-blood CD34+ cells

    OpenAIRE

    Corneo Gianmarco; Pogliani Enrico; Monari Marta; Vai Sergio; Voena Claudia; Dando Jonathan; Ficara Francesca; Cergnul Massimiliano; Birolo Roberto; Scaramuzza Samantha; Deola Sara; Peccatori Jacopo; Selleri Silvia; Bordignon Claudio; Roncarolo Maria

    2007-01-01

    Abstract Background Tumor cell contamination of the apheresis in multiple myeloma is likely to affect disease-free and overall survival after autografting. Objective To purge myeloma aphereses from tumor contaminants with a novel culture-based purging method. Methods We cultured myeloma-positive CD34+ PB samples in conditions that retained multipotency of hematopoietic stem cells, but were unfavourable to survival of plasma cells. Moreover, we exploited the resistance of myeloma plasma cells ...

  14. Molecular purging of multiple myeloma cells by ex-vivo culture and retroviral transduction of mobilized-blood CD34+ cells

    Directory of Open Access Journals (Sweden)

    Corneo Gianmarco

    2007-07-01

    Full Text Available Abstract Background Tumor cell contamination of the apheresis in multiple myeloma is likely to affect disease-free and overall survival after autografting. Objective To purge myeloma aphereses from tumor contaminants with a novel culture-based purging method. Methods We cultured myeloma-positive CD34+ PB samples in conditions that retained multipotency of hematopoietic stem cells, but were unfavourable to survival of plasma cells. Moreover, we exploited the resistance of myeloma plasma cells to retroviral transduction by targeting the hematopoietic CD34+ cell population with a retroviral vector carrying a selectable marker (the truncated form of the human receptor for nerve growth factor, ΔNGFR. We performed therefore a further myeloma purging step by selecting the transduced cells at the end of the culture. Results Overall recovery of CD34+ cells after culture was 128.5%; ΔNGFR transduction rate was 28.8% for CD34+ cells and 0% for CD138-selected primary myeloma cells, respectively. Recovery of CD34+ cells after ΔNGFR selection was 22.3%. By patient-specific Ig-gene rearrangements, we assessed a decrease of 0.7–1.4 logs in tumor load after the CD34+ cell selection, and up to 2.3 logs after culture and ΔNGFR selection. Conclusion We conclude that ex-vivo culture and retroviral-mediated transduction of myeloma leukaphereses provide an efficient tumor cell purging.

  15. Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy.

    Science.gov (United States)

    Chakravarthy, Harshini; Beli, Eleni; Navitskaya, Svetlana; O'Reilly, Sandra; Wang, Qi; Kady, Nermin; Huang, Chao; Grant, Maria B; Busik, Julia V

    2016-01-01

    Diabetic retinopathy is a sight-threatening complication of diabetes, affecting 65% of patients after 10 years of the disease. Diabetic metabolic insult leads to chronic low-grade inflammation, retinal endothelial cell loss and inadequate vascular repair. This is partly due to bone marrow (BM) pathology leading to increased activity of BM-derived pro-inflammatory monocytes and impaired function of BM-derived reparative circulating angiogenic cells (CACs). We propose that diabetes has a significant long-term effect on the nature and proportion of BM-derived cells that circulate in the blood, localize to the retina and home back to their BM niche. Using a streptozotocin mouse model of diabetic retinopathy with GFP BM-transplantation, we have demonstrated that BM-derived circulating pro-inflammatory monocytes are increased in diabetes while reparative CACs are trapped in the BM and spleen, with impaired release into circulation. Diabetes also alters activation of splenocytes and BM-derived dendritic cells in response to LPS stimulation. A majority of the BM-derived GFP cells that migrate to the retina express microglial markers, while others express endothelial, pericyte and Müller cell markers. Diabetes significantly increases infiltration of BM-derived microglia in an activated state, while reducing infiltration of BM-derived endothelial progenitor cells in the retina. Further, control CACs injected into the vitreous are very efficient at migrating back to their BM niche, whereas diabetic CACs have lost this ability, indicating that the in vivo homing efficiency of diabetic CACs is dramatically decreased. Moreover, diabetes causes a significant reduction in expression of specific integrins regulating CAC migration. Collectively, these findings indicate that BM pathology in diabetes could play a role in both increased pro-inflammatory state and inadequate vascular repair contributing to diabetic retinopathy.

  16. Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy.

    Directory of Open Access Journals (Sweden)

    Harshini Chakravarthy

    Full Text Available Diabetic retinopathy is a sight-threatening complication of diabetes, affecting 65% of patients after 10 years of the disease. Diabetic metabolic insult leads to chronic low-grade inflammation, retinal endothelial cell loss and inadequate vascular repair. This is partly due to bone marrow (BM pathology leading to increased activity of BM-derived pro-inflammatory monocytes and impaired function of BM-derived reparative circulating angiogenic cells (CACs. We propose that diabetes has a significant long-term effect on the nature and proportion of BM-derived cells that circulate in the blood, localize to the retina and home back to their BM niche. Using a streptozotocin mouse model of diabetic retinopathy with GFP BM-transplantation, we have demonstrated that BM-derived circulating pro-inflammatory monocytes are increased in diabetes while reparative CACs are trapped in the BM and spleen, with impaired release into circulation. Diabetes also alters activation of splenocytes and BM-derived dendritic cells in response to LPS stimulation. A majority of the BM-derived GFP cells that migrate to the retina express microglial markers, while others express endothelial, pericyte and Müller cell markers. Diabetes significantly increases infiltration of BM-derived microglia in an activated state, while reducing infiltration of BM-derived endothelial progenitor cells in the retina. Further, control CACs injected into the vitreous are very efficient at migrating back to their BM niche, whereas diabetic CACs have lost this ability, indicating that the in vivo homing efficiency of diabetic CACs is dramatically decreased. Moreover, diabetes causes a significant reduction in expression of specific integrins regulating CAC migration. Collectively, these findings indicate that BM pathology in diabetes could play a role in both increased pro-inflammatory state and inadequate vascular repair contributing to diabetic retinopathy.

  17. Robotique Mobile

    OpenAIRE

    Filliat, David

    2011-01-01

    1 Introduction I Les bases de la navigation 2 Les différents types de navigation 3 Les sources d'information 4 Matériels courants en robotique mobile II Navigation réactive 5 Navigation vers un but 6 Évitement d'obstacles 7 Apprentissage par renforcement III Navigation utilisant une carte 8 Localisation, Cartographie et Planification 9 Les représentations de l'environne 10 Localisation 11 Cartographie 12 Planification École d'ingénieur

  18. Modified TEM cell design exposure system for in vitro exposure of cultured human astrocytes to 900 MHz GSM mobile phone type signals

    International Nuclear Information System (INIS)

    Full text: A key to the rigour of any experiment seeking to investigate possible effects on living systems of the electromagnetic energy (EME) from mobile phones is to ensure that the exposures used are accurately known and reflect the actual exposures. To achieve well controlled and characterised radiofrequency (RF) exposures is not trivial, and has been a concern in many previous studies. At St Vincent's Hospital Centre for Immunology (CFI), an in vitro study is being performed of possible gene expression changes in cultured human astrocytes exposed to GSM mobile phone type signals. In order to provide rigorous RF dosimetry for the study, Telstra Research Laboratories (TRL) has developed a modified transverse electromagnetic (TEM) cell exposure system. This paper will describe salient aspects of the design and development of the system used at CFI. In the experimental design proposed by CFI, live human astrocyte cells are exposed in standard FalconTM 25 cm3 plastic culture flasks while incubated in a CO2 atmosphere at 37 deg C. The cells typically exist as a very thin monolayer (microns) adhered to the bottom of the flask under a layer of several millimetres of nutrient media. This particular arrangement presents a number of challenges for the design of an appropriate RF exposure system. Many RF exposure systems rely on measurements of average absorption within the target material to determine the specific absorption rate (SAR) in the sample. The actual SAR at any given point in the exposed volume may differ markedly from this average value, and typically varies quadratically with height (h) within the sample, where h is taken to be in the direction of the incident electric (E) field. This variance may be tolerable where the cells are distributed in solution throughout the volume, but this is not the case in this instance. Alternatively, keeping the sample very thin can reduce the variance. However, this limits the efficiency of the system, so that high input

  19. Optimum Mobility Performance with Mobile IP & SIP

    OpenAIRE

    B. Naresh Kumar; DR. R. V. KRISHNAIAH

    2013-01-01

    Mobility will place an efficient role in now days in the wireless communications. Mobile IP andSIP provide the mobility service to the handset users. The problems in Mobile IP and SIP s are triangular,handoff, Intra domain problems. These problems create signal lose and improper signalling to the user. Toovercome these we provide add of service to the Mobile IP and SIP with the integration of the two services.This service provides optimum performance of the system.

  20. Effects of ACE inhibition on endothelial progenitor cell mobilization and prognosis after acute myocardial infarction in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Jia-Yin Sun

    2013-05-01

    Full Text Available OBJECTIVE: We aimed to assess the chemotactic response of endothelial progenitor cells to angiotensin-converting enzyme inhibitors in T2DM patients after acute myocardial infarction, as well as the associated prognosis. METHODS: Sixty-eight T2DM patients with acute myocardial infarction were randomized to either receive or not receive daily oral perindopril 4 mg, and 36 non-diabetic patients with acute myocardial infarction were enrolled as controls. The numbers of circulating CD45−/low+CD34+CD133+KDR+ endothelial progenitor cells, as well as the stromal cell-derived factor-α and high-sensitivity C reactive protein levels, were measured before acute percutaneous coronary intervention and on days 1, 3, 5, 7, 14, and 28 after percutaneous coronary intervention. Patients were followed up for 6 months. Chinese Clinical Trial Registry: ChiCTR-TRC-12002599. RESULTS: T2DM patients had lower circulating endothelial progenitor cell counts, decreased plasma vascular endothelial growth factor and α levels, and higher plasma high-sensitivity C reactive protein levels compared with non-diabetic controls. After receiving perindopril, the number of circulating endothelial progenitor cells increased from day 3 to 7, as did the plasma levels of vascular endothelial growth factor and stromal cell-derived factor-α, compared with the levels in T2DM controls. Plasma high-sensitivity C reactive protein levels in the treated group decreased to the same levels as those in non-diabetic controls. Furthermore, compared with T2DM controls, the perindopril-treated T2DM patients had lower cardiovascular mortality and occurrence of heart failure symptoms (p<0.05 and better left ventricle function (p<0.01. CONCLUSIONS: The use of angiotensin-converting enzyme inhibitors represents a novel approach for improving cardiovascular repair after acute myocardial infarction in T2DM patients.

  1. Functional effects of TGF-β1 on mesenchymal stem cell mobilization in cockroach allergen-induced asthma.

    Science.gov (United States)

    Gao, Peisong; Zhou, Yufeng; Xian, Lingling; Li, Changjun; Xu, Ting; Plunkett, Beverly; Huang, Shau-Ku; Wan, Mei; Cao, Xu

    2014-05-15

    Mesenchymal stem cells (MSCs) have been suggested to participate in immune regulation and airway repair/remodeling. TGF-β1 is critical in the recruitment of stem/progenitor cells for tissue repair, remodeling, and cell differentiation. In this study, we sought to investigate the role of TGF-β1 in MSC migration in allergic asthma. We examined nestin expression (a marker for MSCs) and TGF-β1 signaling activation in airways in cockroach allergen extract (CRE)-induced mouse models. Compared with control mice, there were increased nestin(+) cells in airways and higher levels of active TGF-β1 in serum and p-Smad2/3 expression in lungs of CRE-treated mice. Increased activation of TGF-β1 signaling was also found in CRE-treated MSCs. We then assessed MSC migration induced by conditioned medium from CRE-challenged human epithelium in air/liquid interface culture in Transwell assays. MSC migration was stimulated by epithelial-conditioned medium, but was significantly inhibited by either TGF-β1-neutralizing Ab or TβR1 inhibitor. Intriguingly, increased migration of MSCs from blood and bone marrow to the airway was also observed after systemic injection of GFP(+) MSCs and from bone marrow of Nes-GFP mice following CRE challenge. Furthermore, TGF-β1-neutralizing Ab inhibited the CRE-induced MSC recruitment, but promoted airway inflammation. Finally, we investigated the role of MSCs in modulating CRE-induced T cell response and found that MSCs significantly inhibited CRE-induced inflammatory cytokine secretion (IL-4, IL-13, IL-17, and IFN-γ) by CD4(+) T cells. These results suggest that TGF-β1 may be a key promigratory factor in recruiting MSCs to the airways in mouse models of asthma. PMID:24711618

  2. IL-13-induced proliferation of airway epithelial cells: mediation by intracellular growth factor mobilization and ADAM17

    Directory of Open Access Journals (Sweden)

    Sandifer Tracy

    2007-07-01

    Full Text Available Abstract Background The pleiotrophic cytokine interleukin (IL-13 features prominently in allergic and inflammatory diseases. In allergic asthma, IL-13 is well established as an inducer of airway inflammation and tissue remodeling. We demonstrated previously that IL-13 induces release of transforming growth factor-α (TGFα from human bronchial epithelial cells, with proliferation of these cells mediated by the autocrine/paracrine action of this growth factor. TGFα exists as an integral membrane protein and requires proteolytic processing to its mature form, with a disintegrin and metalloproteinase (ADAM17 responsible for this processing in a variety of tissues. Methods In this study, normal human bronchial epithelial (NHBE cells grown in air/liquid interface (ALI culture were used to examine the mechanisms whereby IL-13 induces release of TGFα and cellular proliferation. Inhibitors and antisense RNA were used to examine the role of ADAM17 in these processes, while IL-13-induced changes in the intracellular expression of TGFα and ADAM17 were visualized by confocal microscopy. Results IL-13 was found to induce proliferation of NHBE cells, and release of TGFα, in an ADAM17-dependent manner; however, this IL-13-induced proliferation did not appear to result solely from ADAM17 activation. Rather, IL-13 induced a change in the location of TGFα expression from intracellular to apical regions of the NHBE cells. The apical region was also found to be a site of significant ADAM17 expression, even prior to IL-13 stimulation. Conclusion Results from this study indicate that ADAM17 mediates IL-13-induced proliferation and TGFα shedding in NHBE cells. Furthermore, they provide the first example wherein a cytokine (IL-13 induces a change in the intracellular expression pattern of a growth factor, apparently inducing redistribution of intracellular stores of TGFα to the apical region of NHBE cells where expression of ADAM17 is prominent. Thus, IL-13

  3. Mobile Transporter

    Science.gov (United States)

    2001-01-01

    The Space Shuttle Atlantis, STS-110 mission, deployed this railcar, called the Mobile Transporter, and an initial 43-foot section of track, the S0 (S-zero) truss, preparing the International Space Station (ISS) for future spacewalks. The first railroad in space, the Mobile Transporter will allow the Station's robotic arm to travel up and down the finished truss for future assembly and maintenance. The 27,000-pound S0 truss is the first of 9 segments that will make up the Station's external framework that will eventually stretch 356 feet (109 meters), or approximately the length of a football field. The completed truss structure will hold solar arrays and radiators to provide power and cooling for additional international research laboratories from Japan and Europe that will be attached to the Station. The Space Shuttle Orbiter Atlantis, STS-110 mission, was launched April 8, 2002 and returned to Earth April 19, 2002. STS-110's Extravehicular Activity (EVA) marked the first use of the Station's robotic arm to maneuver spacewalkers around the Station.

  4. Simulating hypoxia-induced acidic environment in cancer cells facilitates mobilization and redox-cycling of genomic copper by daidzein leading to pro-oxidant cell death: implications for the sensitization of resistant hypoxic cancer cells to therapeutic challenges.

    Science.gov (United States)

    Ullah, Mohammad F; Ahmad, Aamir; Bhat, Showket H; Khan, Husain Y; Zubair, Haseeb; Sarkar, Fazlul H; Hadi, Sheikh M

    2016-04-01

    This study was conducted to investigate the mechanism of action involved in the anti-cancer activity of daidzein and identification of cancer specific micro-environment as therapeutic target of this secondary metabolite derived from soy. Our data indicated that daidzein induces cellular DNA breakage, anti-proliferative effects and apoptosis in a concentration-dependent manner. We demonstrated that such a daidzein-induced anti-cancer action involves a copper-dependant pathway in which endogenous copper is mobilized by daidzein and redox-cycled to generate reactive oxygen species which act as an upstream signal leading to pro-oxidant cell death. Further in the context of hypoxia being a resistant factor against standard therapies and that an effect secondary to hypoxia is the intracellular acidification, we show that the anticancer activity of daidzein is modulated positively in acidic pH but copper-specific chelator is still able to inhibit daidzein activity. Moreover, an experimental setup of hypoxia mimic (cobalt chloride) revealed an enhanced sensitivity of cancer cells to the cytotoxic effects of daidzein which was neutralized in the presence of neocuproine. The findings support a paradigm shift from the conventional antioxidant property of dietary isoflavones to molecules capable of initiating a pro-oxidant signaling mediated by reactive oxygen species. Further, the clinical relevance of such an action mechanism in cancer chemoprevention is also proposed. This study identified endogenous copper as a molecular target and acidic pH as a modulating factor for the therapeutic activity of daidzein against cancer. The evidence presented highlights the potential of dietary agents as adjuvants to standard therapeutic regimens.

  5. Plerixafor and Filgrastim For Mobilization of Donor Peripheral Blood Stem Cells Before A Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

    Science.gov (United States)

    2011-07-25

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular

  6. 3-Dimensional ZnO/CdS nanocomposite with high mobility as an efficient electron transport layer for inverted polymer solar cells.

    Science.gov (United States)

    Wang, Yilin; Fu, Haiyan; Wang, Ying; Tan, Licheng; Chen, Lie; Chen, Yiwang

    2016-04-28

    The inclusions of solution-processed ZnO electron transport layers (ETLs) of inverted polymer solar cells can lead to various surface defects, which can act as interfacial recombination centers for photogenerated charges and thereby can lead to degradation of the device performance. Three-dimensional (3D) CdS with different morphologies, such as flower-like CdS (F-CdS), branched CdS (B-CdS), and spherical CdS (S-CdS), are synthesized to modify ZnO ETLs, by effectively removing the intragap states of the ZnO nanocrystal films by forming ZnO/F-CdS, ZnO/B-CdS, and ZnO/S-CdS composite ETLs, respectively. Moreover, ZnO/CdS possesses higher electron mobility and provides a larger interface between the ETL and active layer, which is beneficial for enhancing the power conversion efficiency (PCE) of the inverted organic solar cells. In particular, a device based on a ZnO/S-CdS ETL and thieno[3,4-b]-thiophene/benzodithiophene (PTB7):[6,6]-phenyl-C71-butyric acid methyl ester (PC71BM) active layer achieved a PCE of 8.0%, together with better long-term stability. PMID:27074904

  7. Legionella pneumophila infection induces programmed cell death, caspase activation, and release of high-mobility group box 1 protein in A549 alveolar epithelial cells: inhibition by methyl prednisolone

    Directory of Open Access Journals (Sweden)

    Koide Michio

    2008-05-01

    Full Text Available Abstract Background Legionella pneumophila pneumonia often exacerbates acute lung injury (ALI and acute respiratory distress syndrome (ARDS. Apoptosis of alveolar epithelial cells is considered to play an important role in the pathogenesis of ALI and ARDS. In this study, we investigated the precise mechanism by which A549 alveolar epithelial cells induced by L. pneumophila undergo apoptosis. We also studied the effect of methyl prednisolone on apoptosis in these cells. Methods Nuclear deoxyribonucleic acid (DNA fragmentation and caspase activation in L. pneumophila-infected A549 alveolar epithelial cells were assessed using the terminal deoxyribonucleotidyl transferase-mediated triphosphate (dUTP-biotin nick end labeling method (TUNEL method and colorimetric caspase activity assays. The virulent L. pneumophila strain AA100jm and the avirulent dotO mutant were used and compared in this study. In addition, we investigated whether methyl prednisolone has any influence on nuclear DNA fragmentation and caspase activation in A549 alveolar epithelial cells infected with L. pneumophila. Results The virulent strain of L. pneumophila grew within A549 alveolar epithelial cells and induced subsequent cell death in a dose-dependent manner. The avirulent strain dotO mutant showed no such effect. The virulent strains of L. pneumophila induced DNA fragmentation (shown by TUNEL staining and activation of caspases 3, 8, 9, and 1 in A549 cells, while the avirulent strain did not. High-mobility group box 1 (HMGB1 protein was released from A549 cells infected with virulent Legionella. Methyl prednisolone (53.4 μM did not influence the intracellular growth of L. pneumophila within alveolar epithelial cells, but affected DNA fragmentation and caspase activation of infected A549 cells. Conclusion Infection of A549 alveolar epithelial cells with L. pneumophila caused programmed cell death, activation of various caspases, and release of HMGB1. The dot/icm system, a

  8. Fibroblast Growth Factor 2 Regulates High Mobility Group A2 Expression in Human Bone Marrow-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Kalomoiris, Stefanos; Cicchetto, Andrew C; Lakatos, Kinga; Nolta, Jan A; Fierro, Fernando A

    2016-09-01

    Mesenchymal stem cells (MSCs) are an excellent source for numerous cellular therapies due to their simple isolation, low immunogenicity, multipotent differentiation potential and regenerative secretion profile. However, over-expanded MSCs show decreased therapeutic efficacy. This shortcoming may be circumvented by identifying methods that promote self-renewal of MSCs in culture. HMGA2 is a DNA-binding protein that regulates self-renewal in multiple types of stem cells through chromatin remodeling, but its impact on human bone marrow-derived MSCs is not known. Using an isolation method to obtain pure MSCs within 9 days in culture, we show that expression of HMGA2 quickly decreases during early expansion of MSCs, while let-7 microRNAs (which repress HMGA2) are simultaneously increased. Remarkably, we demonstrate that FGF-2, a growth factor commonly used to promote self-renewal in MSCs, rapidly induces HMGA2 expression in a time- and concentration-dependent manner. The signaling pathway involves FGF-2 receptor 1 (FGFR1) and ERK1/2, but acts independent from let-7. By silencing HMGA2 using shRNAs, we demonstrate that HMGA2 is necessary for MSC proliferation. However, we also show that over-expression of HMGA2 does not increase cell proliferation, but rather abrogates the mitogenic effect of FGF-2, possibly through inhibition of FGFR1. In addition, using different methods to assess in vitro differentiation, we show that modulation of HMGA2 inhibits adipogenesis, but does not affect osteogenesis of MSCs. Altogether, our results show that HMGA2 expression is associated with highly proliferating MSCs, is tightly regulated by FGF-2, and is involved in both proliferation and adipogenesis of MSCs. J. Cell. Biochem. 117: 2128-2137, 2016. © 2016 Wiley Periodicals, Inc. PMID:26888666

  9. High mobility group A1 protein expression reduces the sensitivity of colon and thyroid cancer cells to antineoplastic drugs

    OpenAIRE

    D’Angelo, Daniela; Mussnich, Paula; De Rosa, Roberta; Bianco, Roberto; Tortora, Giampaolo; Fusco, Alfredo

    2014-01-01

    Background Development of resistance to conventional drugs and novel biological agents often impair long-term chemotherapy. HMGA gene overexpression is often associated with antineoplastic drug resistance and reduced survival. Inhibition of HMGA expression in thyroid cancer cells reduces levels of ATM protein, the main cellular sensor of DNA damage, and enhances cellular sensitivity to DNA-damaging agents. HMGA1 overexpression promotes chemoresistance to gemcitabine in pancreatic adenocarcino...

  10. Mobile shearography

    Science.gov (United States)

    Kalms, Michael; Jueptner, Werner

    2005-04-01

    By reason of their sensitivity, accuracy and non-contact as well as non-destructive characteristics, modern optical methods such as digital speckle shearography have found an increasing interest for NDT applications on the factory floor. With new carbon filter technologies and other lightweight constructions in aircraft and automotive manufacturing, adapted examination designs and especially developed testing methods are necessary. Shearography as a coherent optical method has been widely accepted as an useful NDT tool. It is a robust interferometric method to determine locations with maximum stress on various material structures. However, limitations of this technique can be found in the bulky equipment components, the interpretation of the complex sherographic result images and at the work with non-cooperative surfaces (dark absorber, bright shining reflectors). We report a mobile shearography system that was especially designed for investigations at aircraft and automotive constructions.

  11. Role of Sulfhydryl Sites on Bacterial Cell Walls in the Biosorption, Mobility and Bioavailability of Mercury and Uranium

    Energy Technology Data Exchange (ETDEWEB)

    Myneni, Satish C.; Mishra, Bhoopesh; Fein, Jeremy

    2009-04-01

    The goal of this exploratory study is to provide a quantitative and mechanistic understanding of the impact of bacterial sulfhydryl groups on the bacterial uptake, speciation, methylation and bioavailability of Hg and redox changes of uranium. The relative concentration and reactivity of different functional groups present on bacterial surfaces will be determined, enabling quantitative predictions of the role of biosorption of Hg under the physicochemical conditions found at contaminated DOE sites.The hypotheses we propose to test in this investigation are as follows- 1) Sulfhydryl groups on bacterial cell surfaces modify Hg speciation and solubility, and play an important role, specifically in the sub-micromolar concentration ranges of metals in the natural and contaminated systems. 2) Sulfhydryl binding of Hg on bacterial surfaces significantly influences Hg transport into the cell and the methylation rates by the bacteria. 3) Sulfhydryls on cell membranes can interact with hexavalent uranium and convert to insoluble tetravalent species. 4) Bacterial sulfhydryl surface groups are inducible by the presence of metals during cell growth. Our studies focused on the first hypothesis, and we examined the nature of sulfhydryl sites on three representative bacterial species: Bacillus subtilis, a common gram-positive aerobic soil species; Shewanella oneidensis, a facultative gram-negative surface water species; and Geobacter sulfurreducens, an anaerobic iron-reducing gram-negative species that is capable of Hg methylation; and at a range of Hg concentration (and Hg:bacterial concentration ratio) in which these sites become important. A summary of our findings is as follows- Hg adsorbs more extensively to bacteria than other metals. Hg adsorption also varies strongly with pH and chloride concentration, with maximum adsorption occurring under circumneutral pH conditions for both Cl-bearing and Cl-free systems. Under these conditions, all bacterial species tested exhibit

  12. Mobile video with mobile IPv6

    CERN Document Server

    Minoli, Daniel

    2012-01-01

    Increased reliance on mobile devices and streaming of video content are two of the most recent changes that have led those in the video distribution industry to be concerned about the shifting or erosion of traditional advertising revenues. Infrastructure providers also need to position themselves to take advantage of these trends. Mobile Video with Mobile IPv6provides an overview of the current mobile landscape, then delves specifically into the capabilities and operational details of IPv6. The book also addresses 3G and 4G services, the application of Mobile IPv6 to streaming and other mobil

  13. The impact of cHS4 insulators on DNA transposon vector mobilization and silencing in retinal pigment epithelium cells.

    Directory of Open Access Journals (Sweden)

    Nynne Sharma

    Full Text Available DNA transposons have become important vectors for efficient non-viral integration of transgenes into genomic DNA. The Sleeping Beauty (SB, piggyBac (PB, and Tol2 transposable elements have distinct biological properties and currently represent the most promising transposon systems for animal transgenesis and gene therapy. A potential obstacle, however, for persistent function of integrating vectors is transcriptional repression of the element and its genetic cargo. In this study we analyze the insulating effect of the 1.2-kb 5'-HS4 chicken β-globin (cHS4 insulator element in the context of SB, PB, and Tol2 transposon vectors. By examining transgene expression from genomically inserted transposon vectors encoding a marker gene driven by a silencing-prone promoter, we detect variable levels of transcriptional silencing for the three transposon systems in retinal pigment epithelium cells. Notably, the PB system seems less vulnerable to silencing. Incorporation of cHS4 insulator sequences into the transposon vectors results in 2.2-fold and 1.5-fold increased transgene expression levels for insulated SB and PB vectors, respectively, but an improved persistency of expression was not obtained for insulated transgenes. Colony formation assays and quantitative excision assays unveil enhanced SB transposition efficiencies by the inclusion of the cHS4 element, resulting in a significant increase in the stable transfection rate for insulated SB transposon vectors in human cell lines. Our findings reveal a positive impact of cHS4 insulator inclusion for SB and PB vectors in terms of increased transgene expression levels and improved SB stable transfection rates, but also the lack of a long-term protective effect of the cHS4 insulator against progressive transgene silencing in retinal pigment epithelium cells.

  14. Development of a Low-Cost, Durable Membrane and Membrane Electrode Assemby for Stationary and Mobile Fuel Cell Applications

    Energy Technology Data Exchange (ETDEWEB)

    Foure, Michel; Gaboury, Scott; Goldbach, Jim; Mountz, David; Yi, Jung

    2008-01-31

    The development of low cost, durable membranes and membranes electrode assemblies (MEAs) remain a critical challenge for the successful introduction of fuel cells into mass markets. It was the goal of the team lead by Arkema, Inc. (formerly Atofina, Inc.) to address these shortages. Thus, this project addresses the following technical barriers from the Fuel Cells section of the Hydrogen Fuel Cells and Infrastructure Technologies Program Multi-Year Research, Development and Demonstration Plan: (A) Durability (B) Cost Arkema’s approach consisted in using blends of polyvinylidenefluoride (PVDF) and proprietary sulfonated polyelectrolytes. The strength and originality of Arkema’s approach lies in the decoupling of ion conductivity from the other requirements. Kynar® (Arkema trade name for PVDF) provides an exceptional combination of properties that make it ideally suited for a membrane matrix. In a first phase, Arkema demonstrated the feasibility of the concept with the M31 membrane generation. After MEA optimization, it was shown that the beginning-of-life (BOL) performance of M31 MEAs was essentially on a par with that of PFSA MEAs at 60ºC under fully humidified conditions. On the other hand, long-term durability studies showed a high decay rate of 45µV/h over a 2100 hr. test. Arkema then designed several families of polyelectrolyte candidates, which, in principle, could not undergo the same failure mechanisms. A new membrane candidate was developed: M41. It offered the same generally good mechanical, ex-situ conductivity and gas barrier properties as M31. In addition, ex-situ accelerated testing suggested a several orders of magnitude improvement in chemical stability. M41 based MEAs showed comparable BOL performance with that of PFSA (80ºC, 100% RH). M41 MEAs were further shown to be able to withstand several hours temperature excursions at 120ºC without apparent damage. Accelerated studies were carried out using the DOE and/or US Fuel Cell Council

  15. Angiotensin II rapidly increases phosphatidate-phosphoinositide synthesis and phosphoinositide hydrolysis and mobilizes intracellular calcium in cultured arterial muscle cells.

    OpenAIRE

    Smith, J B; Smith, L; Brown, E R; Barnes, D; Sabir, M A; Davis, J S; Farese, R V

    1984-01-01

    Smooth muscle cells were cultured from rat thoracic aorta and labeled to a stable specific activity with 45Ca2+, myo-[2-3H]inositol, or 32Pi. The efflux of 45Ca2+ was monitored over 10-sec intervals. Angiotensin II (AII) increased the amount of 45Ca2+ lost by 5-fold in the first 10-sec interval after the addition of AII and by 10-fold in the second 10-sec interval. AII-stimulated 45Ca2+ release was blocked by the angiotensin antagonist [1-sarcosine, 8-leucine]AII and by La3+. The removal of e...

  16. Mobile OS Comparative Study

    OpenAIRE

    Joseph, Jyothy; K, Shinto Kurian

    2013-01-01

    In the fast growing mobile revolutionary era, many operating systems are playing vital role in present market. This study is intending to identify the apt and secure mobile based on mobile operating systems capability and user requirements.

  17. Mobile Inquiry Based Learning

    NARCIS (Netherlands)

    Specht, Marcus

    2012-01-01

    Specht, M. (2012, 8 November). Mobile Inquiry Based Learning. Presentation given at the Workshop "Mobile inquiry-based learning" at the Mobile Learning Day 2012 at the Fernuniversität Hagen, Hagen, Germany.

  18. Micro Mobility Marketing

    DEFF Research Database (Denmark)

    Hosbond, Jens Henrik; Skov, Mikael B.

    2008-01-01

    Mobile marketing refers to marketing of services or goods using mobile technology and mobile marketing holds potentially great economical opportunities. Traditionally, mobile marketing has been viewed as mobility in the large taking place virtually anywhere, anytime. Further, research shows...... considerable number of studies on push-based SMS mobile marketing campaigns. This paper explores a related yet different form of mobile marketing namely micro mobility marketing. Micro mobility marketing denotes mobility in the small, meaning that promotion of goods takes place within a circumscribed location......, in our case a medium-sized retail supermarket. Two prototypes based on push and pull marketing strategies are implemented and evaluated. Taking outset in a synthesis of central issues in contemporary research on mobile marketing, we discuss their role in micro mobility marketing to point to similarities...

  19. Osteopathic manipulative therapy induces early plasma cytokine release and mobilization of a population of blood dendritic cells.

    Directory of Open Access Journals (Sweden)

    Stevan Walkowski

    Full Text Available It has been claimed that osteopathic manipulative treatment (OMT is able to enhance the immune response of individuals. In particular, it has been reported that OMT has the capability to increase antibody titers, enhance the efficacy of vaccination, and upregulate the numbers of circulating leukocytes. Recently, it has been shown in human patients suffering chronic low back pain, that OMT is able to modify the levels of cytokines such as IL-6 and TNF-α in blood upon repeated treatment. Further, experimental animal models show that lymphatic pump techniques can induce a transient increase of cytokines in the lymphatic circulation. Taking into account all these data, we decided to investigate in healthy individuals the capacity of OMT to induce a rapid modification of the levels of cytokines and leukocytes in circulation. Human volunteers were subjected to a mixture of lymphatic and thoracic OMT, and shortly after the levels of several cytokines were evaluated by protein array technology and ELISA multiplex analysis, while the profile and activation status of circulating leukocytes was extensively evaluated by multicolor flow cytometry. In addition, the levels of nitric oxide and C-reactive protein (CRP in plasma were determined. In this study, our results show that OMT was not able to induce a rapid modification in the levels of plasma nitrites or CRP or in the proportion or activation status of central memory, effector memory or naïve CD4 and CD8 T cells. A significant decrease in the proportion of a subpopulation of blood dendritic cells was detected in OMT patients. Significant differences were also detected in the levels of immune molecules such as IL-8, MCP-1, MIP-1α and most notably, G-CSF. Thus, OMT is able to induce a rapid change in the immunological profile of particular circulating cytokines and leukocytes.

  20. Osteopathic manipulative therapy induces early plasma cytokine release and mobilization of a population of blood dendritic cells.

    Science.gov (United States)

    Walkowski, Stevan; Singh, Manindra; Puertas, Juan; Pate, Michelle; Goodrum, Kenneth; Benencia, Fabian

    2014-01-01

    It has been claimed that osteopathic manipulative treatment (OMT) is able to enhance the immune response of individuals. In particular, it has been reported that OMT has the capability to increase antibody titers, enhance the efficacy of vaccination, and upregulate the numbers of circulating leukocytes. Recently, it has been shown in human patients suffering chronic low back pain, that OMT is able to modify the levels of cytokines such as IL-6 and TNF-α in blood upon repeated treatment. Further, experimental animal models show that lymphatic pump techniques can induce a transient increase of cytokines in the lymphatic circulation. Taking into account all these data, we decided to investigate in healthy individuals the capacity of OMT to induce a rapid modification of the levels of cytokines and leukocytes in circulation. Human volunteers were subjected to a mixture of lymphatic and thoracic OMT, and shortly after the levels of several cytokines were evaluated by protein array technology and ELISA multiplex analysis, while the profile and activation status of circulating leukocytes was extensively evaluated by multicolor flow cytometry. In addition, the levels of nitric oxide and C-reactive protein (CRP) in plasma were determined. In this study, our results show that OMT was not able to induce a rapid modification in the levels of plasma nitrites or CRP or in the proportion or activation status of central memory, effector memory or naïve CD4 and CD8 T cells. A significant decrease in the proportion of a subpopulation of blood dendritic cells was detected in OMT patients. Significant differences were also detected in the levels of immune molecules such as IL-8, MCP-1, MIP-1α and most notably, G-CSF. Thus, OMT is able to induce a rapid change in the immunological profile of particular circulating cytokines and leukocytes.

  1. Trends in Mobile Marketing

    OpenAIRE

    Chocholová, Petra

    2010-01-01

    The principal aim of this thesis is to assess the state of the mobile marketing as of the first quarter of 2011 and to discuss various scenarios of the future development. This thesis defines the terms "mobile marketing" and "mobile advertising" and identifies the main players in the industry. It explores the main categories of mobile advertising such as mobile messaging, in-content and mobile internet advertising. Later, it analyzes the latest trends in the industry and describes in detail t...

  2. Cooperating mobile robots

    Energy Technology Data Exchange (ETDEWEB)

    Harrington, John J.; Eskridge, Steven E.; Hurtado, John E.; Byrne, Raymond H.

    2004-02-03

    A miniature mobile robot provides a relatively inexpensive mobile robot. A mobile robot for searching an area provides a way for multiple mobile robots in cooperating teams. A robotic system with a team of mobile robots communicating information among each other provides a way to locate a source in cooperation. A mobile robot with a sensor, a communication system, and a processor, provides a way to execute a strategy for searching an area.

  3. Mobile Schools for a Mobile World

    Science.gov (United States)

    Booth, Susan

    2013-01-01

    Overwhelmingly, independent schools are embracing mobile devices--laptops, iPads or other tablets, and smartphones--to enhance teaching and learning. This article describes the results of the "NAIS 2012 Mobile Learning Survey." Among its findings were that 75 percent of NAIS-member schools currently use mobile learning devices in at…

  4. Enhanced Power Conversion Efficiency of P3HT : PC71BM Bulk Heterojunction Polymer Solar Cells by Doping a High-Mobility Small Organic Molecule

    Directory of Open Access Journals (Sweden)

    Hanyu Wang

    2015-01-01

    Full Text Available The effect of molecular doping with TIPS-pentacene on the photovoltaic performance of polymer solar cells (PSCs with a structure of ITO/ZnO/poly(3-hexylthiophene-2,5-diyl (P3HT : [6,6]-phenyl C71-butyric acid methyl ester (PC71BM : TIPS-pentacene/MoOx/Ag was systematically investigated by adjusting TIPS-pentacene doping ratios ranged from 0.3 to 1.2 wt%. The device with 0.6 wt% TIPS-pentacene exhibited the enhanced short-circuit current and fill factor by 1.23 mA/cm2 and 7.8%, respectively, resulting in a maximum power conversion efficiency of 4.13%, which is one-third higher than that of the undoped one. The photovoltaic performance improvement was mainly due to the balanced charge carrier mobility, enhanced crystallinity, and matched cascade energy level alignment in TIPS-pentacene doped active layer, resulting in the efficient charge separation, transport, and collection.

  5. Cilostazol Enhances Mobilization of Circulating Endothelial Progenitor Cells and Improves Endothelium-Dependent Function in Patients at High Risk of Cardiovascular Disease.

    Science.gov (United States)

    Chao, Ting-Hsing; Chen, I-Chih; Lee, Cheng-Han; Chen, Ju-Yi; Tsai, Wei-Chuan; Li, Yi-Heng; Tseng, Shih-Ya; Tsai, Liang-Miin; Tseng, Wei-Kung

    2016-08-01

    This is the first study to investigate the vasculoangiogenic effects of cilostazol on endothelial progenitor cells (EPCs) and flow-mediated dilatation (FMD) in patients at high risk of cardiovascular disease (CVD). This double-blind, placebo-controlled study included 71 patients (37 received 200 mg/d cilostazol and 34 received placebo for 12 weeks). Use of cilostazol, but not placebo, significantly increased circulating EPC (kinase insert domain receptor(+)CD34(+)) counts (percentage changes: 149.0% [67.9%-497.8%] vs 71.9% [-31.8% to 236.5%], P = .024) and improved triglyceride and high-density lipoprotein cholesterol levels (P = .002 and P = .003, respectively). Plasma levels of vascular endothelial growth factor (VEGF)-A165 and FMD significantly increased (72.5% [32.9%-120.4%] vs -5.8% [-46.0% to 57.6%], P = .001; 232.8% ± 83.1% vs -46.9% ± 21.5%, P = .003, respectively) in cilostazol-treated patients. Changes in the plasma triglyceride levels significantly inversely correlated with the changes in the VEGF-A165 levels and FMD. Cilostazol significantly enhanced the mobilization of EPCs and improved endothelium-dependent function by modifying some metabolic and angiogenic markers in patients at high risk of CVD. PMID:27401788

  6. Unrelated donor granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell transplantation after nonmyeloablative conditioning: the effect of postgrafting mycophenolate mofetil dosing.

    Science.gov (United States)

    Maris, Michael B; Sandmaier, Brenda M; Storer, Barry E; Maloney, David G; Shizuru, Judith A; Agura, Edward; Kliem, Constanze; Pulsipher, Michael; Maziarz, Richard T; McSweeney, Peter A; Wade, James; Langston, Amelia A; Chauncey, Thomas R; Bruno, Benedetto; Blume, Karl G; Storb, Rainer

    2006-04-01

    We previously reported results in 71 patients with advanced hematologic malignancies given HLA-matched unrelated granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC) grafts after fludarabine 90 mg/m(2), 2 Gy of total body irradiation, and postgrafting mycophenolate mofetil (MMF) 15 mg/kg twice daily and cyclosporine 6.25 mg/kg twice daily orally. Graft rejection was 15%; the cumulative probability of acute graft-versus-host disease (GVHD) was 52%. According to MMF pharmacokinetic studies, which showed a short half-life of its active metabolite, mycophenolic acid, we increased MMF dosing from 15 mg/kg twice daily to 15 mg/kg 3 times daily to increase immunosuppression and reduce the incidence of both graft rejection and acute GVHD. Among 103 patients so treated, graft rejection occurred in 5%, whereas acute GVHD remained at 53%. Outcomes were compared with results of previous G-PBMC recipients given MMF twice daily. Infection rates were slightly higher with MMF 3 times daily than with MMF twice daily. Nevertheless, 2-year nonrelapse mortality and overall and progression-free survivals were similar for MMF 3-times-daily and twice-daily patients (19%, 58%, and 49% versus 20%, 48%, and 37%, respectively). Nonmyeloablative conditioning with postgrafting cyclosporine and MMF given 3 times daily allowed 95% durable engraftment of unrelated donor G-PBMC grafts.

  7. Estimating the early household market for light-duty hydrogen-fuel-cell vehicles and other "Mobile Energy" innovations in California: A constraints analysis

    Science.gov (United States)

    Williams, Brett D.; Kurani, Kenneth S.

    Facing stiff competition from conventional and gasoline-hybrid vehicles, the commercialization prospects for hydrogen-fuel-cell vehicles (H 2FCVs) are uncertain. Starting from the premise that new consumer value must drive their adoption, early markets for H 2FCVs are explored in the context of a group of promising opportunities collectively called mobile energy (ME) innovation. An estimate of the initial market potential for ME-enabled vehicles is produced by applying various constraints that eliminate unlikely households from consideration for early adoption of H 2FCVs and other ME technologies (such as plug-in hybrids). Currently 5.2 million of 33.9 million Californians live in households pre-adapted to ME-enabled vehicles, 3.9 million if natural gas is required for home refueling. Several differences in demographic and other characteristics between the target market and the population as a whole are highlighted, and two issues related to the design of H 2FCVs and their supporting infrastructure are discussed: vehicle range and home hydrogen refueling. These findings argue for continued investigation of this and similar target segments-which represent more efficient research populations for subsequent study by product designers and other decision-makers wishing to understand the early market dynamics facing H 2FCVs and related ME innovations.

  8. The role of intracellular high-mobility group box 1 in the early activation of Kupffer cells and the development of Con A-induced acute liver failure.

    Science.gov (United States)

    Yang, Qiao; Liu, Yanning; Shi, Yu; Zheng, Min; He, Jiliang; Chen, Zhi

    2013-10-01

    Acute liver failure (ALF) is a highly complex syndrome characterized by devastating activation of early activation of Kupffer cells (KCs) has been implicated in the pathogenesis of ALF. However, the factors regulating KC early activation are virtually unexplored. The aim of present study was to determine the role of the intracellular high-mobility group box 1 (HMGB1) in modulating the early activation of KCs during ALF. The intravenous injection of Concanavalin A (Con A) was used to establish a mouse model of ALF. The dynamic pro-inflammatory properties and MHC II expression of KCs were measured by qRT-PCR and flow cytometry. HMGB1 expression in KCs was measured by qRT-PCR and Western blotting. The immunofluorescence was implemented to determine the relocation of HMGB1 in KCs, and the siRNA against HMGB1 was utilized to assess the impact of HMGB1 on KC pro-inflammatory properties. The peak of pro-inflammatory cytokines production and MHC II expression in KCs appeared at the early stage of ALF. The up-regulation of HMGB1 expression and the translocation of HMGB1 in KCs were in parallel with the early activation of KCs. The blockade of intracellular HMGB1 expression caused by siRNA significantly inhibited the production of KC-derived pro-inflammatory cytokines, and led to a down-regulation of MAP kinase activation in KCs. The self-derived HMGB1 is an "early alarmin" of KC activation during Con A-induced ALF. HMGB1 might be a potential target for cell-specific strategy in ALF.

  9. Extracellular Adenosine Diphosphate Ribose Mobilizes Intracellular Ca2+ via Purinergic-Dependent Ca2+ Pathways in Rat Pulmonary Artery Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Chun Huang

    2015-11-01

    Full Text Available Background/Aims: Adenosine diphosphate ribose (ADPR, a product of β-NAD+ metabolism generated by the multifunctional enzyme CD38, is recognized as a novel signaling molecule. The catalytic site of CD38 orients extracellularly or intracellularly, capable of generating ADPR outside and inside the cells. CD38-dependent pathways have been characterized in pulmonary artery smooth muscle cells (PASMCs; however the physiological function of extracellular ADPR is unclear. Methods: Ca2+ mobilizing and proliferative effects of extracellular ADPR were characterized and compared with the ATP-induced responses in rat PASMCs; and the expression of purinergic receptor (P2X and P2Y subtypes were examined in pulmonary arteries. Results: ADPR elicited concentration-dependent increase in [Ca2+]i with a fast transient and a sustained phase in PASMCs. The sustained phase was abolished by Ca2+ removal and inhibited by the non-selective cation channel blocker SKF-96365, but was unaffected by TRPM2 antagonists or nifedipine. The purinergic receptor (P2X antagonist pyridoxal-phosphate-6-azophenyl-2', 4'-disulfonate inhibited partially the transient and the sustained Ca2+ response, while the P2(XY inhibitor suramin and the phospholipase C inhibitor U73122 abolished the sustained Ca2+ influx. The P2Y1 antagonist MRS2179 had no effect on the response. By contrast, ATP and ADP activated Ca2+ response exhibited a high and a low affinity component, and the pharmacological profile of ATP-induced Ca2+ response was distinctive from that of ADPR. BrdU incorporation assay showed that ADPR caused significant inhibition whereas ATP caused slight stimulation of PASMC proliferation. RT-PCR analysis found that almost all P2X and P2Y subtypes are expressed in PAs. Conclusion: ADPR and ATP activate Ca2+ responses through different combinations of multiple purinergic receptor subtypes; and extracellular ADPR may exert an autocrine/paracrine action via purinergic receptors on PASMCs.

  10. 5-Azacytidine treatment sensitizes tumor cells to T-cell mediated cytotoxicity and modulates NK cells in patients with myeloid malignancies.

    Science.gov (United States)

    Gang, A O; Frøsig, T M; Brimnes, M K; Lyngaa, R; Treppendahl, M B; Grønbæk, K; Dufva, I H; Straten, P Thor; Hadrup, S R

    2014-01-01

    Treatment with the demethylating agent 5-Azacytidine leads to prolonged survival for patients with myelodysplastic syndrome, and the demethylation induces upregulation of cancer-testis antigens. Cancer-testis antigens are well-known targets for immune recognition in cancer, and the immune system may have a role in this treatment regimen. We show here that 5-Azacytidine treatment leads to increased T-cell recognition of tumor cells. T-cell responses against a large panel of cancer-testis antigens were detected before treatment, and these responses were further induced upon initiation of treatment. These characteristics point to an ideal combination of 5-Azacytidine and immune therapy to preferentially boost T-cell responses against cancer-testis antigens. To initiate such combination therapy, essential knowledge is required about the general immune modulatory effect of 5-Azacytidine. We therefore examined potential treatment effects on both immune stimulatory (CD8 and CD4 T cells and Natural Killer (NK) cells) and immune inhibitory cell subsets (myeloid-derived suppressor cells and regulatory T cells). We observed a minor decrease and modulation of NK cells, but for all other populations no effects could be detected. Together, these data support a strategy for combining 5-Azacytidine treatment with immune therapy for potential clinical benefit. PMID:24681961

  11. 5-Azacytidine treatment sensitizes tumor cells to T-cell mediated cytotoxicity and modulates NK cells in patients with myeloid malignancies

    Science.gov (United States)

    Gang, A O; Frøsig, T M; Brimnes, M K; Lyngaa, R; Treppendahl, M B; Grønbæk, K; Dufva, I H; Straten, P thor; Hadrup, S R

    2014-01-01

    Treatment with the demethylating agent 5-Azacytidine leads to prolonged survival for patients with myelodysplastic syndrome, and the demethylation induces upregulation of cancer-testis antigens. Cancer-testis antigens are well-known targets for immune recognition in cancer, and the immune system may have a role in this treatment regimen. We show here that 5-Azacytidine treatment leads to increased T-cell recognition of tumor cells. T-cell responses against a large panel of cancer-testis antigens were detected before treatment, and these responses were further induced upon initiation of treatment. These characteristics point to an ideal combination of 5-Azacytidine and immune therapy to preferentially boost T-cell responses against cancer-testis antigens. To initiate such combination therapy, essential knowledge is required about the general immune modulatory effect of 5-Azacytidine. We therefore examined potential treatment effects on both immune stimulatory (CD8 and CD4 T cells and Natural Killer (NK) cells) and immune inhibitory cell subsets (myeloid-derived suppressor cells and regulatory T cells). We observed a minor decrease and modulation of NK cells, but for all other populations no effects could be detected. Together, these data support a strategy for combining 5-Azacytidine treatment with immune therapy for potential clinical benefit. PMID:24681961

  12. Influence of the vocal cord mobility in salvage surgery after radiotherapy for early-stage squamous cell carcinoma of the glottic larynx.

    Science.gov (United States)

    Gorphe, Philippe; Blanchard, Pierre; Temam, Stephane; Janot, François

    2015-10-01

    Disease relapses occur in up to 40% of cases after radiotherapy (RT) for early-stage glottic laryngeal neoplasms, and the foremost remaining treatment option is salvage total laryngectomy (STL). Our objectives were to review the outcomes of patients treated with salvage surgery after RT for early-stage carcinoma of the glottic larynx and to assess prognostic factors. We retrospectively analyzed 43 patients who underwent surgery. Overall and disease-free survival rates among subgroups were calculated and compared, stratified by preoperative stage, vocal cord mobility and postoperative histopathologic data. Recurrences occurred 22.7 months after the end of RT. Surgery was STL in 33 cases (76.8%). The main prognostic factors associated with survival rates were initial vocal cord mobility, vocal cord mobility at the diagnosis of recurrence, and changes in mobility. Vocal cord mobility is an important clinical criterion in treatment decision making for early-stage glottis carcinoma and remains important during follow-up.

  13. Mobile Learning Devices. Essentials for Principals

    Science.gov (United States)

    Rogers, Kipp D.

    2011-01-01

    In "Mobile Learning Devices," the author helps educators confront and overcome their fears and doubts about using mobile learning devices (MLDs) such as cell phones, personal digital assistants, MP3 players, handheld games, digital audio players, and laptops in classrooms. School policies that ban such tools are outdated, the author suggests;…

  14. EFL College Students' Attitudes towards Mobile Learning

    Science.gov (United States)

    Dashti, Fatimah A.; Aldashti, Abdulmohsen A.

    2015-01-01

    Recently, cell phones have received much attention in the context of EFL/ESL learning. Mobile learning, in general, and distant learning, in particular, in educational contexts has been approached by educationalist all over the world (Hwang & Chang, 2011). Presently, countries pay ample attention to mobile learning in education. Despite the…

  15. Use of the heteroduplex mobility assay and cell sorting to select genome sequences of the CCR5 gene in HEK 293T cells edited by transcription activator-like effector nucleases

    Directory of Open Access Journals (Sweden)

    Arildo Nerys-Junior

    2014-01-01

    Full Text Available Engineered nucleases such as zinc finger nucleases (ZFN and transcription activator-like effector nucleases (TALEN are one of the most promising tools for modifying genomes. These site-specific enzymes cause double- strand breaks that allow gene disruption or gene insertion, thereby facilitating genetic manipulation. The major problem associated with this approach is the labor-intensive procedures required to screen and confirm the cellular modification by nucleases. In this work, we produced a TALEN that targets the human CCR5 gene and developed a heteroduplex mobility assay for HEK 293T cells to select positive colonies for sequencing. This approach provides a useful tool for the quick detection and easy assessment of nuclease activity.

  16. Evaluation of LINE-1 mobility in neuroblastoma cells by in vitro retrotransposition reporter assay: FACS analysis can detect only the tip of the iceberg of the inserted L1 elements

    Energy Technology Data Exchange (ETDEWEB)

    Del Re, Brunella, E-mail: brunella.delre@unibo.it [Department of Evolutionary Experimental Biology, University of Bologna, via Selmi 3, 40126 Bologna (Italy); Inter-departmental Center ' L. Galvani' , via Selmi 3, 40126 Bologna (Italy); Marcantonio, Pamela [Department of Evolutionary Experimental Biology, University of Bologna, via Selmi 3, 40126 Bologna (Italy); Capri, Miriam [Department of Experimental Pathology, University of Bologna, via S. Giacomo 8, 40126 Bologna (Italy); Inter-departmental Center ' L. Galvani' , via Selmi 3, 40126 Bologna (Italy); Giorgi, Gianfranco [Department of Evolutionary Experimental Biology, University of Bologna, via Selmi 3, 40126 Bologna (Italy); Inter-departmental Center ' L. Galvani' , via Selmi 3, 40126 Bologna (Italy)

    2010-12-10

    Long Interspersed Nuclear Elements (L1) are retroelements generally repressed in most differentiated somatic cells. Their activity has been observed in some undifferentiated and tumour cells and could be involved in tumour onset and progression. Growing evidences show that the L1 activation can occur in neuronal precursor cells during differentiation process. Neuroblastoma is a tumour originating from neuronal precursor cells, and, although the molecular basis of its progression is still poorly understood, the implication of L1 activation has not yet been investigated. In this study L1 mobility in neuroblastoma BE(2)C cells was assessed using the in vitro retrotransposition assay consisting in an episomal EGFP-tagged L1{sub RP} element, whose mobility can be evaluated by cytofluorimetric analysis (FACS) of EGFP expression. FACS results have shown a low retrotransposition activity. To detect L1{sub RP} integrated in transcriptionally repressed genomic sites, both a cell treatment with a stimulator of reporter gene promoter, and a quantitative Real-Time PCR analysis were performed. A retrotransposition activity ten and one thousand times that of FACS was found, respectively. These results point out that the real rate of L1 retrotransposition events in tumour cells might be considerably higher than that reported so far by evaluating only the reporter gene expression.

  17. Evaluation of LINE-1 mobility in neuroblastoma cells by in vitro retrotransposition reporter assay: FACS analysis can detect only the tip of the iceberg of the inserted L1 elements.

    Science.gov (United States)

    Del Re, Brunella; Marcantonio, Pamela; Capri, Miriam; Giorgi, Gianfranco

    2010-12-10

    Long Interspersed Nuclear Elements (L1) are retroelements generally repressed in most differentiated somatic cells. Their activity has been observed in some undifferentiated and tumour cells and could be involved in tumour onset and progression. Growing evidences show that the L1 activation can occur in neuronal precursor cells during differentiation process. Neuroblastoma is a tumour originating from neuronal precursor cells, and, although the molecular basis of its progression is still poorly understood, the implication of L1 activation has not yet been investigated. In this study L1 mobility in neuroblastoma BE(2)C cells was assessed using the in vitro retrotransposition assay consisting in an episomal EGFP-tagged L1(RP) element, whose mobility can be evaluated by cytofluorimetric analysis (FACS) of EGFP expression. FACS results have shown a low retrotransposition activity. To detect L1(RP) integrated in transcriptionally repressed genomic sites, both a cell treatment with a stimulator of reporter gene promoter, and a quantitative Real-Time PCR analysis were performed. A retrotransposition activity ten and one thousand times that of FACS was found, respectively. These results point out that the real rate of L1 retrotransposition events in tumour cells might be considerably higher than that reported so far by evaluating only the reporter gene expression.

  18. Cross platform Mobile Applications Development: Mobile Apps Mobility

    OpenAIRE

    Redda, Yonathan Aklilu

    2012-01-01

    In recent years, the mobile computing sector has been having quite a revolution.Mobile computing devices have shed loads of weight, gone slim, achieved mass popularityand a great market penetration. But one of the challenges that has been part ofmobile computing is technology and device fragmentation leaving application developersfor mobile phones bewildered. Platform developers, device manufacturers comewith so many features and functionalities that it has been dicult to provide developerswi...

  19. Further phenotypic characterization of the primitive lineage− CD34+CD38−CD90+CD45RA− hematopoietic stem cell/progenitor cell sub-population isolated from cord blood, mobilized peripheral blood and patients with chronic myelogenous leukemia

    International Nuclear Information System (INIS)

    The most primitive hematopoietic stem cell (HSC)/progenitor cell (PC) population reported to date is characterized as being Lin−CD34+CD38−CD90+CD45R. We have a long-standing interest in comparing the characteristics of hematopoietic progenitor cell populations enriched from normal subjects and patients with chronic myelogenous leukemia (CML). In order to investigate further purification of HSCs and for potential targetable differences between the very primitive normal and CML stem/PCs, we have phenotypically compared the normal and CML Lin−CD34+CD38−CD90+CD45RA− HSC/PC populations. The additional antigens analyzed were HLA-DR, the receptor tyrosine kinases c-kit and Tie2, the interleukin-3 cytokine receptor, CD33 and the activation antigen CD69, the latter of which was recently reported to be selectively elevated in cell lines expressing the Bcr-Abl tyrosine kinase. Notably, we found a strikingly low percentage of cells from the HSC/PC sub-population isolated from CML patients that were found to express the c-kit receptor (<1%) compared with the percentages of HSC/PCs expressing the c-kitR isolated from umbilical cord blood (50%) and mobilized peripheral blood (10%). Surprisingly, Tie2 receptor expression within the HSC/PC subset was extremely low from both normal and CML samples. Using in vivo transplantation studies, we provide evidence that HLA-DR, c-kitR, Tie2 and IL-3R may not be suitable markers for further partitioning of HSCs from the Lin−CD34+CD38−CD90+CD45RA− sub-population

  20. Evidence that a lipolytic enzyme--hematopoietic-specific phospholipase C-β2--promotes mobilization of hematopoietic stem cells by decreasing their lipid raft-mediated bone marrow retention and increasing the promobilizing effects of granulocytes.

    Science.gov (United States)

    Adamiak, M; Poniewierska-Baran, A; Borkowska, S; Schneider, G; Abdelbaset-Ismail, A; Suszynska, M; Abdel-Latif, A; Kucia, M; Ratajczak, J; Ratajczak, M Z

    2016-04-01

    Hematopoietic stem/progenitor cells (HSPCs) reside in the bone marrow (BM) microenvironment and are retained there by the interaction of membrane lipid raft-associated receptors, such as the α-chemokine receptor CXCR4 and the α4β1-integrin (VLA-4, very late antigen 4 receptor) receptor, with their respective specific ligands, stromal-derived factor 1 and vascular cell adhesion molecule 1, expressed in BM stem cell niches. The integrity of the lipid rafts containing these receptors is maintained by the glycolipid glycosylphosphatidylinositol anchor (GPI-A). It has been reported that a cleavage fragment of the fifth component of the activated complement cascade, C5a, has an important role in mobilizing HSPCs into the peripheral blood (PB) by (i) inducing degranulation of BM-residing granulocytes and (ii) promoting their egress from the BM into the PB so that they permeabilize the endothelial barrier for subsequent egress of HSPCs. We report here that hematopoietic cell-specific phospholipase C-β2 (PLC-β2) has a crucial role in pharmacological mobilization of HSPCs. On the one hand, when released during degranulation of granulocytes, it digests GPI-A, thereby disrupting membrane lipid rafts and impairing retention of HSPCs in BM niches. On the other hand, it is an intracellular enzyme required for degranulation of granulocytes and their egress from BM. In support of this dual role, we demonstrate that PLC-β2-knockout mice are poor mobilizers and provide, for the first time, evidence for the involvement of this lipolytic enzyme in the mobilization of HSPCs.

  1. Mobile Operating Systems

    OpenAIRE

    Vipin Kamboj; Hitesh Gupta

    2012-01-01

    Mobile phones are used by every people in today’s life. We use mobile phones without knowing the different factors that a mobile used including its technology, operating system, CPU ,RAM etc. Many types of operating system are used by different mobile. Every operating system has their advantage

  2. TYPOLOGIES OF MOBILE APPLICATIONS

    OpenAIRE

    Ion Ivan; Alin Zamfiroiu; Dragoş Palaghiţă3

    2013-01-01

    Mobile applications and their particularities are analyzed. Mobile application specific characteristics are defined. Types of applications are identified and analyzed. The paper established differences between mobile applications and mobile application categories. For each identified type the specific structures and development model are identified.

  3. Next generation mobile broadcasting

    CERN Document Server

    Gómez-Barquero, David

    2013-01-01

    Next Generation Mobile Broadcasting provides an overview of the past, present, and future of mobile multimedia broadcasting. The first part of the book-Mobile Broadcasting Worldwide-summarizes next-generation mobile broadcasting technologies currently available. This part covers the evolutions of the Japanese mobile broadcasting standard ISDB-T One-Seg, ISDB-Tmm and ISDB-TSB; the evolution of the South Korean T-DMB mobile broadcasting technology AT-DMB; the American mobile broadcasting standard ATSC-M/H; the Chinese broadcasting technologies DTMB and CMMB; second-generation digital terrestrial

  4. Mobile platform security

    CERN Document Server

    Asokan, N; Dmitrienko, Alexandra

    2013-01-01

    Recently, mobile security has garnered considerable interest in both the research community and industry due to the popularity of smartphones. The current smartphone platforms are open systems that allow application development, also for malicious parties. To protect the mobile device, its user, and other mobile ecosystem stakeholders such as network operators, application execution is controlled by a platform security architecture. This book explores how such mobile platform security architectures work. We present a generic model for mobile platform security architectures: the model illustrat

  5. Tenured Public Servant Mobility

    OpenAIRE

    Aline Pauron

    2003-01-01

    The mobility of tenured public servants is studied from three points of view: geographic mobility (defined by a change of regional study and planning area (ZEAT) or department within a ZEAT), socio-economic mobility (change of socio-economic group) and structural mobility (change of ministry or service within a ministry). Geographic mobility is the most frequent, concerning an average 4.2% of staff every year. Not including upgrading (from grade D to grade C and from primary school teacher to...

  6. MOBILE MARKETING FUTURE TRENDS

    OpenAIRE

    CĂTOIU, Iacob; GÂRDAN, Daniel Adrian; GÂRDAN, Doru Lucian

    2010-01-01

    The present article proposes an introspection into the field of a new marketing specialization – mobile marketing. The concept mainly refers to all marketing activities related to the new communication channel – Short Message Service, Multimedia Messaging Service, and internet access from mobile phone. The article provides, at the same time, a marketing perspective about future trends of mobile marketing and mobile media, and also a technical perspective related to the future mobile communica...

  7. ON MOBILE MESH NETWORKS

    OpenAIRE

    Namiot, Dmitry

    2015-01-01

    With the advances in mobile computing technologies and the growth of the Net, mobile mesh networks are going through a set of important evolutionary steps. In this paper, we survey architectural aspects of mobile mesh networks and their use cases and deployment models. Also, we survey challenging areas of mobile mesh networks and describe our vision of promising mobile services. This paper presents a basic introductory material for Masters of Open Information Technologies Lab, interested in m...

  8. MOBILE TELECOMMUNICATIONS SERVICES AND MOBILE HEALTH DEVICES

    OpenAIRE

    Gheorghe Meghisan; Georgeta-Madalina Meghisan

    2015-01-01

    The purpose of this research paper is to identify the potential of mobile health devices with a positive impact on the public health care system from Romania. More people monitoring their health situation with the help of mobile health applications could lead to less money spent by the public health sector with treating more advanced diseases. Approach/ methodology. The analysis of the Romanian mobile telecommunications market and health situation of the population from Romania was based on s...

  9. Mobile Notes: Mobile Devices in Creative Discussions

    OpenAIRE

    Bollen, Lars; Juarez, Guillermo; Hoppe, Ulrich

    2006-01-01

    The trendy notion of "mobile learning" has different connotations: On the one hand, it can be understood as "learning on the move" - often referred to as "learning any time anywhere". Of course this interpretation relies on specific kinds of technological enabling, but the definition aims at the general setting of learning activities. Particularly, it includes informal learning settings (cf. [1]). A second interpretation sees mobile learning somewhat more pragmatically as learning with mobile...

  10. Growth factor-induced mobilization of cardiac progenitor cells reduces the risk of arrhythmias, in a rat model of chronic myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Leonardo Bocchi

    Full Text Available Heart repair by stem cell treatment may involve life-threatening arrhythmias. Cardiac progenitor cells (CPCs appear best suited for reconstituting lost myocardium without posing arrhythmic risks, being commissioned towards cardiac phenotype. In this study we tested the hypothesis that mobilization of CPCs through locally delivered Hepatocyte Growth Factor and Insulin-Like Growth Factor-1 to heal chronic myocardial infarction (MI, lowers the proneness to arrhythmias. We used 133 adult male Wistar rats either with one-month old MI and treated with growth factors (GFs, n = 60 or vehicle (V, n = 55, or sham operated (n = 18. In selected groups of animals, prior to and two weeks after GF/V delivery, we evaluated stress-induced ventricular arrhythmias by telemetry-ECG, cardiac mechanics by echocardiography, and ventricular excitability, conduction velocity and refractoriness by epicardial multiple-lead recording. Invasive hemodynamic measurements were performed before sacrifice and eventually the hearts were subjected to anatomical, morphometric, immunohistochemical, and molecular biology analyses. When compared with untreated MI, GFs decreased stress-induced arrhythmias and concurrently prolonged the effective refractory period (ERP without affecting neither the duration of ventricular repolarization, as suggested by measurements of QTc interval and mRNA levels for K-channel α-subunits Kv4.2 and Kv4.3, nor the dispersion of refractoriness. Further, markers of cardiomyocyte reactive hypertrophy, including mRNA levels for K-channel α-subunit Kv1.4 and β-subunit KChIP2, interstitial fibrosis and negative structural remodeling were significantly reduced in peri-infarcted/remote ventricular myocardium. Finally, analyses of BrdU incorporation and distribution of connexin43 and N-cadherin indicated that cytokines generated new vessels and electromechanically-connected myocytes and abolished the correlation of infarct size with deterioration

  11. Mobility Charters and Manifestos

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    2010-01-01

    This paper explore a number of different cases of articulating notions of ‘correct’ mobility behavior and practice by looking into charters, manifestos and codes of mobility regulation. Within such discourses of ‘correct mobility’ more or less subtle expressions of power as well as normative...... and ethical positions on mobility prevail. Such ‘imagined correct mobility behavior’ are drawing on larger issues of societal change that need to be brought out in a critical analysis and discussion reflecting the attempts to control, design and orchestrate mobility patterns. The paper therefore argues within...... the ‘mobility turn’ that mobility is much more than movement from A to B. Seeing the cultural dimension as well as the underpinning power plays of normative mobility discourses opens up the reflection about imagined futures and imagined mobile subjects. Theoretically the paper bridges discourse studies...

  12. Investigation of the effects of distance from sources on apoptosis, oxidative stress and cytosolic calcium accumulation via TRPV1 channels induced by mobile phones and Wi-Fi in breast cancer cells.

    Science.gov (United States)

    Çiğ, Bilal; Nazıroğlu, Mustafa

    2015-10-01

    TRPV1 is a Ca2+ permeable channel and gated by noxious heat, oxidative stress and capsaicin (CAP). Some reports have indicated that non-ionized electromagnetic radiation (EMR)-induces heat and oxidative stress effects. We aimed to investigate the effects of distance from sources on calcium signaling, cytosolic ROS production, cell viability, apoptosis, plus caspase-3 and -9 values induced by mobile phones and Wi-Fi in breast cancer cells MCF-7 human breast cancer cell lines were divided into A, B, C and D groups as control, 900, 1800 and 2450 MHz groups, respectively. Cells in Group A were used as control and were kept in cell culture conditions without EMR exposure. Groups B, C and D were exposed to the EMR frequencies at different distances (0 cm, 1 cm, 5 cm, 10 cm, 20 cm and 25 cm) for 1h before CAP stimulation. The cytosolic ROS production, Ca2+ concentrations, apoptosis, caspase-3 and caspase-9 values were higher in groups B, C and D than in A group at 0 cm, 1 cm and 5 cm distances although cell viability (MTT) values were increased by the distances. There was no statistically significant difference in the values between control, 20 and 25 cm. Wi-Fi and mobile phone EMR placed within 10 cm of the cells induced excessive oxidative responses and apoptosis via TRPV1-induced cytosolic Ca2+ accumulation in the cancer cells. Using cell phones and Wi-Fi sources which are farther away than 10 cm may provide useful protection against oxidative stress, apoptosis and overload of intracellular Ca2+. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

  13. Mobile Portal Implementation Strategy

    DEFF Research Database (Denmark)

    Gao, Ping; Damsgaard, Jan

    2005-01-01

    Mobile portal plays an important role in mobile commerce market. Current literature focuses on static analysis on the value chain of mobile portals. This article provides a dynamic perspective on mobile portal strategy. Drawing upon network economics, we describe mobile portal implementation...... as a fourphase process. In different phase, a portal provider has various challenges to overcome and adopt diverse strategies, and correspondingly the regulator has different foci. The conceptual framework proposed in this article offers a basis for further analyses on the market dynamics of mobile commerce......, and can be generalized to studying other networked technologies...

  14. Head First Mobile Web

    CERN Document Server

    Gardner, Lyza; Grigsby, Jason

    2011-01-01

    Despite the huge number of mobile devices and apps in use today, your business still needs a website. You just need it to be mobile. Head First Mobile Web walks you through the process of making a conventional website work on a variety smartphones and tablets. Put your JavaScript, CSS media query, and HTML5 skills to work-then optimize your site to perform its best in the demanding mobile market. Along the way, you'll discover how to adapt your business strategy to target specific devices. Navigate the increasingly complex mobile landscapeTake both technical and strategic approaches to mobile

  15. Exploring the Mobility of Mobile Phone Users

    CERN Document Server

    Csáji, Balázs Cs; Traag, V A; Delvenne, Jean-Charles; Huens, Etienne; Van Dooren, Paul; Smoreda, Zbigniew; Blondel, Vincent D

    2013-01-01

    Mobile phone datasets allow for the analysis of human behavior on an unprecedented scale. The social network, temporal dynamics and mobile behavior of mobile phone users have often been analyzed independently from each other using mobile phone datasets. In this article, we explore the connections between various features of human behavior extracted from a large mobile phone dataset. Our observations are based on the analysis of communication data of 100000 anonymized and randomly chosen individuals in a dataset of communications in Portugal. We show that clustering and principal component analysis allow for a significant dimension reduction with limited loss of information. The most important features are related to geographical location. In particular, we observe that most people spend most of their time at only a few locations. With the help of clustering methods, we then robustly identify home and office locations and compare the results with official census data. Finally, we analyze the geographic spread ...

  16. Mobile Phones on Campus

    Institute of Scientific and Technical Information of China (English)

    朴春宝

    2007-01-01

    After entering the 21st century, more and more people have mobile phones in China. At the end of 2002, there were 20 million mobile phone users. By the year 2005 the number has reached up to 30 million.

  17. Making Everyday Mobility

    DEFF Research Database (Denmark)

    Wind, Simon

    Based upon a qualitative PhD study of 11 families everyday mobility, this paper inquiries into the everyday mobility of families with children in the Greater Copenhagen Area and the role mobility plays in contributing to coping in the families’ everyday life. Drawing on Mobilities theory (Jensen...... 2013; Urry 2007) and family theory (Holdsworth 2013; Morgan 2011), it is argued that family mobility is far from only an instrumental phenomenon, displacing family members back and forth between activities and doings, but also a type of family practice (Morgan, 2011) carrying social and emotional...... repercussions. Moreover, family mobility does not simply happen, rather the successful performance of everyday mobility is a creative process that requires labour, skill and knowledge (Vannini 2012). It is proposed that families cope with everyday life through the on-going making and performance of mobility...

  18. Ion mobility sensor system

    Science.gov (United States)

    Xu, Jun; Watson, David B.; Whitten, William B.

    2013-01-22

    An ion mobility sensor system including an ion mobility spectrometer and a differential mobility spectrometer coupled to the ion mobility spectrometer. The ion mobility spectrometer has a first chamber having first end and a second end extending along a first direction, and a first electrode system that generates a constant electric field parallel to the first direction. The differential mobility spectrometer includes a second chamber having a third end and a fourth end configured such that a fluid may flow in a second direction from the third end to the fourth end, and a second electrode system that generates an asymmetric electric field within an interior of the second chamber. Additionally, the ion mobility spectrometer and the differential mobility spectrometer form an interface region. Also, the first end and the third end are positioned facing one another so that the constant electric field enters the third end and overlaps the fluid flowing in the second direction.

  19. Tandem mobile robot system

    Science.gov (United States)

    Buttz, James H.; Shirey, David L.; Hayward, David R.

    2003-01-01

    A robotic vehicle system for terrain navigation mobility provides a way to climb stairs, cross crevices, and navigate across difficult terrain by coupling two or more mobile robots with a coupling device and controlling the robots cooperatively in tandem.

  20. Mobile Informal Learning

    NARCIS (Netherlands)

    Glahn, Christian; Börner, Dirk

    2010-01-01

    Glahn, C., & Börner, D. (2009). Mobile Informal Learning. Presented at Mobile Learning in Context Symposium at the Open University of the Netherlands. September, 11, 2009, Heerlen, The Netherlands: Open University of the Netherlands.

  1. Influence of microglia on retinal progenitor cell turnover and cell replacement.

    Science.gov (United States)

    Dick, A D

    2009-10-01

    Microglia within the retina are continually replaced from the bone marrow and are the resident myeloid-derived cells within the retina. Throughout life, microglial function is conditioned by the microenvironment affording immunomodulation to control inflammation as well as functioning to enable normal development and, during adulthood, maintain normal retinal function. In adulthood, recent evidence supports the concept that the retina continues to replace cells to maintain optimal function. Although in some cases after injury, degeneration, or inflammation there remains an inextricable decline in visual function inferring a deficit in cell replacement, the deficit could be explained by microglial cell activation influencing the ability of either retinal progenitor cells or recruited progenitor cells to integrate and differentiate appropriately. Myeloid cell response differs depending on insult: it is evident that during inflammation microglia and the infiltrating myeloid cell function are conditioned by the cytokine environment. Indeed, modulating myeloid cell function therapeutically suppresses disease in experimental models of autoimmunity, whereas in non-inflammatory models microglia have little or no effect on the course of degeneration. The extent of myeloid activation can help determine retinal progenitor cell turnover. Retinal progenitor cells may be isolated from adult human retina, which, albeit limited, display mitotic activity and can differentiate. Microglial activation secreting IL-6 limits progenitor cell turnover and the extent to which differentiation to post-mitotic retinal cells occurs. Such experimental data illustrate the need to develop methods to replenish normal retinal myeloid cell function facilitating integration, either by cell transplantation or by encouraging retinal progenitor cells to recover retinal function.

  2. Mobile Marketing in Japan

    OpenAIRE

    Noah H. N. Lynn; Paul D. Berger

    2014-01-01

    In this paper we describe the state of mobile marketing in Japan. We consider the various aspects of mobile marketing in Japan and what has led to the overwhelming adoption by Japanese youth, and to a degree Japanese society as a whole, of social media and associated activities. This growth of mobile marketing has dramatic, positive implications for marketing, in general, as well as for the sale of selected product classes. We also consider markers for suggesting what the future of mobile mar...

  3. Ion mobility spectrometry

    CERN Document Server

    Eiceman, GA

    2005-01-01

    Key Developments for Faster, More Precise Detection Capabilities Driven by the demand for the rapid and advanced detection of explosives, chemical and biological warfare agents, and narcotics, ion mobility spectrometry (IMS) undergone significant refinements in technology, computational capabilities, and understanding of the principles of gas phase ion chemistry and mobility. Beginning with a thorough discussion of the fundamental theories and physics of ion mobility, Ion Mobility Spectrometry, Second Edition describes the recent advances in instrumentation and newly

  4. Mobile internet protocol analysis

    OpenAIRE

    Brachfeld, Lawrence J.

    1999-01-01

    Mobile Internet Protocol (IP) is a proposed standard that builds on the current Internet Protocol by making the fact that a user is mobile transparent to applications and higher level protocols such as Transmission Control Protocol (TCP) and User Datagram Protocol (UDP). Mobile IP allows mobile computers to send and receive packets addressed with their home network IP address, regardless of the IP address of their current point of attachment on the Internet while maintaining any current conne...

  5. Staging interrail mobilities

    DEFF Research Database (Denmark)

    Jensen, Martin Trandberg; Gyimóthy, Szilvia; Jensen, Ole B.

    2016-01-01

    This article applies the multiscalar ‘staging mobilities’ framework from the emergent subfield of mobilities design to analyse an enduring European rail travel phenomenon, interrail. This discussion extends and contributes to tourism mobilities research. Second, the article enriches previous stud...... and seat reservations. To reach these aims, the research design intertwines multi-sited ethnography, netnography, survey and interviews. The conclusion offers theoretical reflections pertaining to the role of mobilities designs and methodical hybrids in tourism mobilities research....

  6. PSiS Mobile

    OpenAIRE

    Anacleto, Ricardo; Luz, Nuno; Figueiredo, Lino

    2010-01-01

    In this paper, we present a state of the art on applications of mobile devices to support decision of a tourist running on a trip. We focus on two types of applications, tourism recommendation and tourism guide, making a brief description of the main characteristics of each one of them. We also refer the main problems encountered on the development of applications for mobile devices, and present PSiS (Personalized Sightseeing Tours Recommendation System) Mobile, our proposal to a mobile recom...

  7. Mobile connections : curator's statement.

    OpenAIRE

    Hemment, Drew

    2004-01-01

    The Mobile Connections exhibition at the Futuresonic 2004 festival explored how mobile and locative media reconfigure social, cultural and information space. It looked beyond computing in its current form, towards the social and cultural possibilities opened by a new generation of networked, location-aware media. It sought an art of mobile communications: asking, are there any forms of expression that are intrinsic or unique to mobile and locative media?

  8. Fixed mobile convergence handbook

    CERN Document Server

    Ahson, Syed A

    2010-01-01

    From basic concepts to future directions, this handbook provides technical information on all aspects of fixed-mobile convergence (FMC). The book examines such topics as integrated management architecture, business trends and strategic implications for service providers, personal area networks, mobile controlled handover methods, SIP-based session mobility, and supervisory and notification aggregator service. Case studies are used to illustrate technical and systematic implementation of unified and rationalized internet access by fixed-mobile network convergence. The text examines the technolo

  9. Mobile Student Information System

    Science.gov (United States)

    Asif, Muhammad; Krogstie, John

    2011-01-01

    Purpose: A mobile student information system (MSIS) based on mobile computing and context-aware application concepts can provide more user-centric information services to students. The purpose of this paper is to describe a system for providing relevant information to students on a mobile platform. Design/methodology/approach: The research…

  10. Superintendent Vulnerability and Mobility.

    Science.gov (United States)

    Parker, Phyllis

    1996-01-01

    Examined Callahan's vulnerability thesis to determine its ability to explain the mobility of superintendents in Texas between 1985 and 1990. Questionnaire and interview data indicated that, at least in Texas where superintendent mobility reached 50% in that time period, vulnerability did not appear to account for much of superintendent mobility.…

  11. Expression of the B-cell receptor component CD79a on immature myeloid cells contributes to their tumor promoting effects.

    Directory of Open Access Journals (Sweden)

    Dror Luger

    Full Text Available The role of myeloid derived suppressor cells (MDSCs in promoting tumorigenesis is well-established, and significant effort is being made to further characterize surface markers on MDSCs both for better diagnosis and as potential targets for therapy. Here we show that the B cell receptor adaptor molecule CD79a is unexpectedly expressed on immature bone marrow myeloid cells, and is upregulated on MDSCs generated in multiple different mouse models of metastatic but not non-metastatic cancer. CD79a on MDSCs is upregulated and activated in response to soluble factors secreted by tumor cells. Activation of CD79a on mouse MDSCs, by crosslinking with a specific antibody, maintained their immature phenotype (CD11b+Gr1+, enhanced their migration, increased their suppressive effect on T cell proliferation, and increased secretion of pro-tumorigenic cytokines such as IL-6 and CCL22. Furthermore, crosslinking CD79a on myeloid cells activated signaling through Syk, BLNK, ERK and STAT3 phosphorylation. In vivo, CD79+ myeloid cells showed enhanced ability to promote primary tumor growth and metastasis. Finally we demonstrate that CD79a is upregulated on circulating myeloid cells from lung cancer patients, and that CD79a+ myeloid cells infiltrate human breast tumors. We propose that CD79a plays a functional role in the tumor promoting effects of myeloid cells, and may represent a novel target for cancer therapy.

  12. Myeloid derived hypoxia inducible factor 1-alpha is required for protection against pulmonary Aspergillus fumigatus infection.

    Directory of Open Access Journals (Sweden)

    Kelly M Shepardson

    2014-09-01

    Full Text Available Hypoxia inducible factor 1α (HIF1α is the mammalian transcriptional factor that controls metabolism, survival, and innate immunity in response to inflammation and low oxygen. Previous work established that generation of hypoxic microenvironments occurs within the lung during infection with the human fungal pathogen Aspergillus fumigatus. Here we demonstrate that A. fumigatus stabilizes HIF1α protein early after pulmonary challenge that is inhibited by treatment of mice with the steroid triamcinolone. Utilizing myeloid deficient HIF1α mice, we observed that HIF1α is required for survival and fungal clearance early following pulmonary challenge with A. fumigatus. Unlike previously reported research with bacterial pathogens, HIF1α deficient neutrophils and macrophages were surprisingly not defective in fungal conidial killing. The increase in susceptibility of the myeloid deficient HIF1α mice to A. fumigatus was in part due to decreased early production of the chemokine CXCL1 (KC and increased neutrophil apoptosis at the site of infection, resulting in decreased neutrophil numbers in the lung. Addition of recombinant CXCL1 restored neutrophil survival and numbers, murine survival, and fungal clearance. These results suggest that there are unique HIF1α mediated mechanisms employed by the host for protection and defense against fungal pathogen growth and invasion in the lung. Additionally, this work supports the strategy of exploring HIF1α as a therapeutic target in specific immunosuppressed populations with fungal infections.

  13. Myeloid derived hypoxia inducible factor 1-alpha is required for protection against pulmonary Aspergillus fumigatus infection.

    Science.gov (United States)

    Shepardson, Kelly M; Jhingran, Anupam; Caffrey, Alayna; Obar, Joshua J; Suratt, Benjamin T; Berwin, Brent L; Hohl, Tobias M; Cramer, Robert A

    2014-09-01

    Hypoxia inducible factor 1α (HIF1α) is the mammalian transcriptional factor that controls metabolism, survival, and innate immunity in response to inflammation and low oxygen. Previous work established that generation of hypoxic microenvironments occurs within the lung during infection with the human fungal pathogen Aspergillus fumigatus. Here we demonstrate that A. fumigatus stabilizes HIF1α protein early after pulmonary challenge that is inhibited by treatment of mice with the steroid triamcinolone. Utilizing myeloid deficient HIF1α mice, we observed that HIF1α is required for survival and fungal clearance early following pulmonary challenge with A. fumigatus. Unlike previously reported research with bacterial pathogens, HIF1α deficient neutrophils and macrophages were surprisingly not defective in fungal conidial killing. The increase in susceptibility of the myeloid deficient HIF1α mice to A. fumigatus was in part due to decreased early production of the chemokine CXCL1 (KC) and increased neutrophil apoptosis at the site of infection, resulting in decreased neutrophil numbers in the lung. Addition of recombinant CXCL1 restored neutrophil survival and numbers, murine survival, and fungal clearance. These results suggest that there are unique HIF1α mediated mechanisms employed by the host for protection and defense against fungal pathogen growth and invasion in the lung. Additionally, this work supports the strategy of exploring HIF1α as a therapeutic target in specific immunosuppressed populations with fungal infections.

  14. 外科手术联合自体骨髓干细胞动员治疗大鼠脑缺血%Surgical operation combined with autologous bone marrow stem cell mobilization to treat ischemic cerebrovascular diseases in rats

    Institute of Scientific and Technical Information of China (English)

    张圣旭; 步星耀; 程培训; 刘猛; 姜金豆; 李志营; 张峰

    2011-01-01

    BACKGROUND: Studies have shown that stem cell therapy can promote recovery of brain function, and stem cells combined with surgical intervention can be more effective in improving the prognosis.OBJECTIVE: To explore the effect and mechanism of surgical operation combined with autologous bone marrow stem cell mobilization in treatment of cerebral ischemia.METHODS: Male Sprague-Dawley rats were used to produce rat cerebral ischemia models using suture method and then divided into four groups. We used surgery, recombinant human granulocyte colony stimulating factor (rhG-CSF) and rhGM-CSF mobilization of autologous bone marrow stem cell therapy respectively.RESULTS AND CONCLUSION: In the surgery combined with autologous bone marrow stem cell mobilization group, the neurological deficit score, cerebral infarction area and the number of apoptosis were significantly lower than those in the control group, surgery group and bone marrow stem cell mobilization group (P < 0.01); Histopathology examination showed that BrdU, BDNF positive cells and angiogenesis were much more than those in the other three groups (P < 0.05). The surgery combined with autologous bone marrow stem cell mobilization can reduce the size of cerebral infarction, inhibit cell apoptosis, promote nerve regeneration and repair, and then improve brain function.%背景:研究表明干细胞治疗能够促进脑功能恢复,联合外科干预能更有效地改善预后.目的:分析外科手术联合自体骨髓干细胞动员治疗脑缺血的疗效和机制.方法:用线栓法制作SD大鼠脑缺血模型后随机分为4组:对照组不干预,其他3组分别行外科手术、重组人粒细胞集落刺激因子和粒/巨噬细胞集落刺激因子动员自体骨髓干细胞治疗或联合治疗.结果与结论:外科手术联合自体骨髓干细胞动员组大鼠的神经功能缺损评分、缺血坏死面积和细胞凋亡数明显低于对照组、外科手术组和自体骨髓干细胞动员组(P<0

  15. A comparative study of radiofrequency emission from roof top mobile phone base station antennas and tower mobile phone base antennas located at some selected cell sites in Accra, Ghana

    International Nuclear Information System (INIS)

    RF radiation exposure from antennas mounted on rooftop mobile phone base stations have become a serious issue in recent years due to the rapidly developing technologies in wireless telecommunication. The heightening numbers of base station and their closeness to the general public has led to possible health concerns as a result of exposure to RF radiations. The primary objective of this study was to assess the level of RF radiation emitted from roof top mobile phone base station antennas and compare the measured results with the guidelines set by International Commission on Non-ionization Radiation. The maximum and minimum average power density measured from the rooftop sites inside buildings were 2.46xI0-2 and 1.68x10-3 W/m2 respectively whereas that for outside buildings at the same rooftop site was also 7.44x 10-5 and 3.35x 10-3 W/m2 respectively. Public exposure quotient also ranged between 3.74x10-10 to 1.31x10-07 inside buildings whilst that for outside varied between 7.44x 10-10 to 1.65x 10-06. Occupational exposure quotient inside buildings varied between 1.66x 10-11 to 2.11 x 10-09 whereas that for outside ranged from 3.31x10-09 to 3.30x10-07 all at the rooftop site. The results obtained for a typical tower base station also indicated that the maximum and minimum average power density was 4.57x10-1 W/m2 and 7.13x10-3 W/m2 respectively. The public exposure quotient varied between 1.58x10-09 to 1.01x10-07 whilst that for occupational exposure quotient ranged between 3.17x10-10 to 2.03x10-08. The values of power densities levels inside buildings at rooftop sites are low compared to that of tower sites. This could be due to high attenuation caused by thick concrete walls and ceilings. The results obtained were found to be in compliance with ICNIRP and FCC guidance levels of 4.5 W/m2 and 6 W/m2 respectively. (au)

  16. Distributed mobility management - framework & analysis

    NARCIS (Netherland