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Sample records for human epo increase

  1. Does recombinant human Epo increase exercise capacity by means other than augmenting oxygen transport?

    DEFF Research Database (Denmark)

    Lundby, C; Robach, P; Boushel, R

    2008-01-01

    This study was performed to test the hypothesis that administration of recombinant human erythropoietin (rHuEpo) in humans increases maximal oxygen consumption by augmenting the maximal oxygen carrying capacity of blood. Systemic and leg oxygen delivery and oxygen uptake were studied during...... before rHuEpo treatment). Blood buffer capacity remained unaffected by rHuEpo treatment and hemodilution. The augmented hematocrit did not compromise peak cardiac output. In summary, in healthy humans, rHuEpo increases maximal oxygen consumption due to augmented systemic and muscular peak oxygen delivery....

  2. Epo receptors are not detectable in primary human tumor tissue samples.

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    Steve Elliott

    Full Text Available Erythropoietin (Epo is a cytokine that binds and activates an Epo receptor (EpoR expressed on the surface of erythroid progenitor cells to promote erythropoiesis. While early studies suggested EpoR transcripts were expressed exclusively in the erythroid compartment, low-level EpoR transcripts were detected in nonhematopoietic tissues and tumor cell lines using sensitive RT-PCR methods. However due to the widespread use of nonspecific anti-EpoR antibodies there are conflicting data on EpoR protein expression. In tumor cell lines and normal human tissues examined with a specific and sensitive monoclonal antibody to human EpoR (A82, little/no EpoR protein was detected and it was not functional. In contrast, EpoR protein was reportedly detectable in a breast tumor cell line (MCF-7 and breast cancer tissues with an anti-EpoR polyclonal antibody (M-20, and functional responses to rHuEpo were reported with MCF-7 cells. In another study, a functional response was reported with the lung tumor cell line (NCI-H838 at physiological levels of rHuEpo. However, the specificity of M-20 is in question and the absence of appropriate negative controls raise questions about possible false-positive effects. Here we show that with A82, no EpoR protein was detectable in normal human and matching cancer tissues from breast, lung, colon, ovary and skin with little/no EpoR in MCF-7 and most other breast and lung tumor cell lines. We show further that M-20 provides false positive staining with tissues and it binds to a non-EpoR protein that migrates at the same size as EpoR with MCF-7 lysates. EpoR protein was detectable with NCI-H838 cells, but no rHuEpo-induced phosphorylation of AKT, STAT3, pS6RP or STAT5 was observed suggesting the EpoR was not functional. Taken together these results raise questions about the hypothesis that most tumors express high levels of functional EpoR protein.

  3. Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Kim, Yu-Sok; Krogh-Madsen, Rikke

    2012-01-01

    Administration of erythropoietin (EPO) has been linked to cerebrovascular events. EPO reduces vascular conductance, possibly because of the increase in hematocrit. Whether EPO in itself affects the vasculature remains unknown; here it was evaluated in healthy males by determining systemic...... and cerebrovascular variables following acute (30,000 IU/d for 3 d; n=8) and chronic (5000 IU/week for 13 wk; n=8) administration of EPO, while the responsiveness of the vasculature was challenged during cycling exercise, with and without hypoxia. Prolonged administration of EPO increased hematocrit from 42.5 ± 3...

  4. EPO Receptor Gain-of-Function Causes Hereditary Polycythemia, Alters CD34+ Cell Differentiation and Increases Circulating Endothelial Precursors

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    Perrotta, Silverio; Cucciolla, Valeria; Ferraro, Marcella; Ronzoni, Luisa; Tramontano, Annunziata; Rossi, Francesca; Scudieri, Anna Chiara; Borriello, Adriana; Roberti, Domenico; Nobili, Bruno; Cappellini, Maria Domenica; Oliva, Adriana; Amendola, Giovanni; Migliaccio, Anna Rita; Mancuso, Patrizia; Martin-Padura, Ines; Bertolini, Francesco; Yoon, Donghoon; Prchal, Josef T.; Della Ragione, Fulvio

    2010-01-01

    Background Gain-of-function of erythropoietin receptor (EPOR) mutations represent the major cause of primary hereditary polycythemia. EPOR is also found in non-erythroid tissues, although its physiological role is still undefined. Methodology/Principal Findings We describe a family with polycythemia due to a heterozygous mutation of the EPOR gene that causes a G→T change at nucleotide 1251 of exon 8. The novel EPOR G1251T mutation results in the replacement of a glutamate residue by a stop codon at amino acid 393. Differently from polycythemia vera, EPOR G1251T CD34+ cells proliferate and differentiate towards the erythroid phenotype in the presence of minimal amounts of EPO. Moreover, the affected individuals show a 20-fold increase of circulating endothelial precursors. The analysis of erythroid precursor membranes demonstrates a heretofore undescribed accumulation of the truncated EPOR, probably due to the absence of residues involved in the EPO-dependent receptor internalization and degradation. Mutated receptor expression in EPOR-negative cells results in EPOR and Stat5 phosphorylation. Moreover, patient erythroid precursors present an increased activation of EPOR and its effectors, including Stat5 and Erk1/2 pathway. Conclusions/Significance Our data provide an unanticipated mechanism for autosomal dominant inherited polycythemia due to a heterozygous EPOR mutation and suggest a regulatory role of EPO/EPOR pathway in human circulating endothelial precursors homeostasis. PMID:20700488

  5. Huh-7 cell line as an alternative cultural model for the production of human like erythropoietin (EPO

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    Kausar Humera

    2011-11-01

    Full Text Available Abstract Background and Aims Erythropoietin (EPO is a glycoprotein hormone which is required to regulate the production of red blood cells. Deficiency of EPO is known to cause anemia in chronically infected renal patients and they require regular blood transfusion. Availability of recombinant EPO has eliminated the need for blood transfusion and now it is extensively used for the treatment of anemia. Glycosylation of erythropoietin is essential for its secretion, stability, protein conformation and biological activity. However, maintenance of human like glycosylation pattern during manufacturing of EPO is a major challenge in biotechnology. Currently, Chinese hamster ovary (CHO cell line is used for the commercial production of erythropoietin but this cell line does not maintain glycosylation resembling human system. With the trend to eliminate non-human constituent from biopharmaceutical products, as a preliminary approach, we have investigated the potential of human hepatoma cell line (Huh-7 to produce recombinant EPO. Materials and methods Initially, the secretory signal and Kozak sequences was added before the EPO mature protein sequence using overlap extension PCR technique. PCR-amplified cDNA fragments of EPO was inserted into mammalian expression vector under the control of the cytomegalovirus (CMV promoter and transiently expressed in CHO and Huh-7 cell lines. After RT-PCR analysis, ELISA and Western blotting was performed to verify the immunochemical properties of secreted EPO. Results Addition of secretory signal and Kozak sequence facilitated the extra-cellular secretion and enhanced the expression of EPO protein. Significant expression (P Conclusion Huh-7 cell line has a great potential to produce glycosylated EPO, suggesting the use of this cell line to produce glycoproteins of the therapeutic importance resembling to the natural human system.

  6. Increasing the use of evaluation data collection in an EPO program

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    Taber, J. J.; Bohon, W.; Bravo, T. K.; Dordevic, M.; Dorr, P. M.; Hubenthal, M.; Johnson, J. A.; Sumy, D.; Welti, R.; Davis, H. B.

    2017-12-01

    Over the past two years, the Incorporated Research Institutions for Seismology Education and Public Outreach (EPO) program has sought to increase the evaluation rigor of its programs and products. Specifically we sought to make evaluation an integral part of our work; enabling staff to demonstrate why we do the activities we do, enhancing the impact or our products/programs, and empowering staff to make evidence-based claims. The Collaborative Impact Analysis Method (Davis and Scalice, 2015) was selected as it allowed us to combine staff's knowledge of programs, audiences and content with the expertise of an outside evaluation expert, through consultations and a qualitative rubric assessing the initial state of each product/program's evaluation. Staff then developed action plans to make improvements to the programs over time. A key part of the initial action plans has been the collection and analysis of new evaluation data. The most frequently used tools were surveys as they were relatively straightforward to implement and analyze, and could be adapted for different situations. Examples include: brand awareness, value of booth interactions, assessing community interest in a data app, and user surveys of social media and specific web pages. Other evaluation activities included beta testing of new software, and interviews with students and faculty involved in summer field experiences. The surveys have allowed us to document increased impact in some areas, to improve the usability of products and activities, and to provide baseline impact data. The direct involvement of staff in the process has helped staff appreciate the value of evaluation, but there are also challenges to this approach. Since many of the surveys are developed and conducted by EPO staff, rather than being primarily handled by the evaluator, the process takes considerably more staff time to implement. We are still determining how to best manage and present the data and analysis; our current approach

  7. Neuroprotective effect of a new variant of Epo nonhematopoietic against oxidative stress

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    C. Castillo

    2018-04-01

    Full Text Available Human erythropoietin is mainly recognized for its hematopoietic function; however, by binding to its receptor (EpoR, it can activate different signaling pathways as STAT, PI3K, MAPK and RAS to increase cellular differentiation or provide neuroprotective effects, among others. A recombinant human erythropoietin variant with low glycosylation and without hematopoietic effect (EpoL was purified from skimmed goat milk. Recombinant human erythropoietin (Epo was obtained from CHO cell line and used as control to compare EpoL effects. Neuroprotection studies were performed in PC12 cells and rat hippocampal slices. Cells were pretreated during 1 h with EpoL or Epo and exposed to oxidative agents (H2O2 or FCCP; cell viability was assayed at the end of the experiment by the MTT method. Hippocampal slices were exposed to 15 min of oxygen and glucose deprivation (OGD and the neuroprotective drugs EpoL or Epo were incubated for 2 h post-OGD in re-oxygenated medium. Cell cultures stressed with oxidative agents, and pretreated with EpoL, showed neuroprotective effects of 30% at a concentration 10 times lower than that of Epo. Moreover, similar differences were observed in OGD ex vivo assays. Neuroprotection elicited by EpoL was lost when an antibody against EpoR was present, indicating that its effect is EpoR-dependent. In conclusion, our results suggest that EpoL has a more potent neuroprotective profile than Epo against oxidative stress, mediated by activation of EpoR, thus EpoL represents an important target to develop a potential biopharmaceutical to treat different central nervous system pathologies related to oxidative stress such as stroke or neurodegenerative diseases. Keywords: Erythropoietin, Erythropoietin receptor, Neuroprotection, Oxidative stress

  8. PI3 kinase is important for Ras, MEK and Erk activation of Epo-stimulated human erythroid progenitors

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    Schmidt Enrico K

    2004-05-01

    Full Text Available Abstract Background Erythropoietin is a multifunctional cytokine which regulates the number of erythrocytes circulating in mammalian blood. This is crucial in order to maintain an appropriate oxygen supply throughout the body. Stimulation of primary human erythroid progenitors (PEPs with erythropoietin (Epo leads to the activation of the mitogenic kinases (MEKs and Erks. How this is accomplished mechanistically remained unclear. Results Biochemical studies with human cord blood-derived PEPs now show that Ras and the class Ib enzyme of the phosphatidylinositol-3 kinase (PI3K family, PI3K gamma, are activated in response to minimal Epo concentrations. Surprisingly, three structurally different PI3K inhibitors block Ras, MEK and Erk activation in PEPs by Epo. Furthermore, Erk activation in PEPs is insensitive to the inhibition of Raf kinases but suppressed upon PKC inhibition. In contrast, Erk activation induced by stem cell factor, which activates c-Kit in the same cells, is sensitive to Raf inhibition and insensitive to PI3K and PKC inhibitors. Conclusions These unexpected findings contrast with previous results in human primary cells using Epo at supraphysiological concentrations and open new doors to eventually understanding how low Epo concentrations mediate the moderate proliferation of erythroid progenitors under homeostatic blood oxygen levels. They indicate that the basal activation of MEKs and Erks in PEPs by minimal concentrations of Epo does not occur through the classical cascade Shc/Grb2/Sos/Ras/Raf/MEK/Erk. Instead, MEKs and Erks are signal mediators of PI3K, probably the recently described PI3K gamma, through a Raf-independent signaling pathway which requires PKC activity. It is likely that higher concentrations of Epo that are induced by hypoxia, for example, following blood loss, lead to additional mitogenic signals which greatly accelerate erythroid progenitor proliferation.

  9. Validation of whole-blood transcriptome signature during microdose recombinant human erythropoietin (rHuEpo) administration.

    Science.gov (United States)

    Wang, Guan; Durussel, Jérôme; Shurlock, Jonathan; Mooses, Martin; Fuku, Noriyuki; Bruinvels, Georgie; Pedlar, Charles; Burden, Richard; Murray, Andrew; Yee, Brendan; Keenan, Anne; McClure, John D; Sottas, Pierre-Edouard; Pitsiladis, Yannis P

    2017-11-14

    Recombinant human erythropoietin (rHuEpo) can improve human performance and is therefore frequently abused by athletes. As a result, the World Anti-Doping Agency (WADA) introduced the Athlete Biological Passport (ABP) as an indirect method to detect blood doping. Despite this progress, challenges remain to detect blood manipulations such as the use of microdoses of rHuEpo. Forty-five whole-blood transcriptional markers of rHuEpo previously derived from a high-dose rHuEpo administration trial were used to assess whether microdoses of rHuEpo could be detected in 14 trained subjects and whether these markers may be confounded by exercise (n = 14 trained subjects) and altitude training (n = 21 elite runners and n = 4 elite rowers, respectively). Differential gene expression analysis was carried out following normalisation and significance declared following application of a 5% false discovery rate (FDR) and a 1.5 fold-change. Adaptive model analysis was also applied to incorporate these markers for the detection of rHuEpo. ALAS2, BCL2L1, DCAF12, EPB42, GMPR, SELENBP1, SLC4A1, TMOD1 and TRIM58 were differentially expressed during and throughout the post phase of microdose rHuEpo administration. The CD247 and TRIM58 genes were significantly up- and down-regulated, respectively, immediately following exercise when compared with the baseline both before and after rHuEpo/placebo. No significant gene expression changes were found 30 min after exercise in either rHuEpo or placebo groups. ALAS2, BCL2L1, DCAF12, SLC4A1, TMOD1 and TRIM58 tended to be significantly expressed in the elite runners ten days after arriving at altitude and one week after returning from altitude (FDR > 0.059, fold-change varying from 1.39 to 1.63). Following application of the adaptive model, 15 genes showed a high sensitivity (≥ 93%) and specificity (≥ 71%), with BCL2L1 and CSDA having the highest sensitivity (93%) and specificity (93%). Current results provide further evidence that

  10. The use of /sup 125/I recombinant DNA/sub 125/ derived human erythropoietin (R-HuEPO) as a replacement for /sup 125/I human urinary epo as tracer antigen in a radioimmunoassay for human epo

    International Nuclear Information System (INIS)

    Cotes, P.M.; Tam, R.C.; GainesDas, R.E.

    1987-01-01

    This paper represents evidence that in a radioimmunoassay for human erythropoietin, recombinant DNA derived human erythropoietin can replace highly purified human urinary erythropoietin in the preparation of radioiodinated tracer antigen

  11. EPO-independent functional EPO receptor in breast cancer enhances estrogen receptor activity and promotes cell proliferation

    International Nuclear Information System (INIS)

    Reinbothe, Susann; Larsson, Anna-Maria; Vaapil, Marica; Wigerup, Caroline; Sun, Jianmin; Jögi, Annika; Neumann, Drorit; Rönnstrand, Lars; Påhlman, Sven

    2014-01-01

    Highlights: • New anti-human EPOR antibody confirms full-length EPOR expression in breast cancer cells. • Proliferation of breast cancer cells is not affected by rhEPO treatment in vitro. • EPOR knockdown impairs proliferation of ERa positive breast cancer cells. • EPOR knockdown reduces AKT phosphorylation and ERa activity. - Abstract: The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα + ) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity further supports a mechanism by which EPOR affects proliferation via ERα-mediated mechanisms. We show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation by an EPO-independent mechanism in ERα expressing breast cancer cells

  12. EPO-independent functional EPO receptor in breast cancer enhances estrogen receptor activity and promotes cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Reinbothe, Susann; Larsson, Anna-Maria; Vaapil, Marica; Wigerup, Caroline [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Sun, Jianmin [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); Jögi, Annika [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Neumann, Drorit [Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Rönnstrand, Lars [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); Påhlman, Sven, E-mail: sven.pahlman@med.lu.se [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel)

    2014-02-28

    Highlights: • New anti-human EPOR antibody confirms full-length EPOR expression in breast cancer cells. • Proliferation of breast cancer cells is not affected by rhEPO treatment in vitro. • EPOR knockdown impairs proliferation of ERa positive breast cancer cells. • EPOR knockdown reduces AKT phosphorylation and ERa activity. - Abstract: The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα{sup +}) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity further supports a mechanism by which EPOR affects proliferation via ERα-mediated mechanisms. We show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation by an EPO-independent mechanism in ERα expressing breast cancer cells.

  13. Comparison between two treatment protocols with recombinant Human Erythropoietin (rHuEpo in the treatment of late anemia in neonates with Rh-Isoimmunization

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    A.A. Zuppa

    2012-08-01

    Full Text Available Objectve. The Rh-hemolytic disease can lead to a late anemia by hemolytic and hyporigenerative mechanism. We compared the effectiveness of rHuEPO in two care protocols that differ for doses of rHuEPO administrated and for timing of administration. Methods. A cohort of 14 neonates was investigated. The neonates were treated with two different protocols. Protocol A: a dose of 200 U/kg/day of rHuEpo administered subcutaneously starting from the end of the second week of life; Protocol B: a dose of 400 U/kg/day of rHuEpo administered subcutaneously starting from the end of the first week of life. Results. The hematocrit values in the protocol A group decreased during treatment (32,5% vs 25,2%, whereas the hematocrit value in protocol B group remained almost stable (38,7% vs 42,8%. The mean numbers of platelets remained stable in both groups while neutrophils increased in protocol A group and decreased in protocol B (p<0,05. Reticulocyte count increased during treatment in both groups, although only in protocol B group it was statistically significative (p<0,05. Conclusions. Our results suggest a similar efficacy between the two treatment protocols. Increasing doses of rHuEPO do not seem enhancing their effectiveness and the incidence of side effects.

  14. The Use of Soluble Transferrin Receptor in the Detection of rHuEPO abuse in Sports

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    Donovan McGrowder

    2010-01-01

    Full Text Available Erythropoietin (EPO increases the number of circulating erythrocytes and muscle oxygenation. The recombinant forms of EPO have indiscriminately been used by athletes, mainly in endurance sports to increase their erythrocytes concentration, thus generating a better delivery of oxygen to the muscle tissue. The administration of recombinant human erythropoietin (rHuEPO except for therapeutic use was prohibited by the International Olympic Committee (IOC and its unauthorized use considered as doping. In the last few years, a number of studies using parameters indicative of accelerated erythropoiesis have investigated a number of indirect methods for the detection of rHuEPO abuse. No single indirect marker has been found that can satisfactorily demonstrated rHuEPO misuse. Soluble transferrin receptor (sTfR is a new marker of iron status and erythropoietic activity. It has been included in multivariable blood testing models for the detection of performance enhancing EPO abuse in sports. Indirect markers of altered erythropoiesis give reliable evidence of current or discontinued rHuEPO usage. This review describes the physical, biological and pharmacokinetic properties of endogenous EPO and its recombinant form. It also discusses the available strategies for the detection of rHuEPO abuse in sports, involving the use of sTfR concentration directly or in mathematical multivariate models.

  15. Characterization of a hypoxia-response element in the Epo locus of the pufferfish, Takifugu rubripes.

    Science.gov (United States)

    Kulkarni, Rashmi P; Tohari, Sumanty; Ho, Adrian; Brenner, Sydney; Venkatesh, Byrappa

    2010-06-01

    Animals respond to hypoxia by increasing synthesis of the glycoprotein hormone erythropoietin (Epo) which in turn stimulates the production of red blood cells. The gene encoding Epo has been recently cloned in teleost fishes such as the pufferfish Takifugu rubripes (fugu) and zebrafish (Danio rerio). It has been shown that the transcription levels of Epo in teleost fishes increase in response to anemia or hypoxia in a manner similar to its human ortholog. However, the cis-regulatory element(s) mediating the hypoxia response of Epo gene in fishes has not been identified. In the present study, using the human hepatoma cell line (Hep3B), we have identified and characterized a hypoxia response element (HRE) in the fugu Epo locus. The sequence of the fugu HRE (ACGTGCTG) is identical to that of the HRE in the human EPO locus. However, unlike the HRE in the mammalian Epo locus, which is located in the 3' region of the gene, the fugu HRE is located in the 5' flanking region and on the opposite strand of DNA. This HRE is conserved in other teleosts such as Tetraodon and zebrafish in a similar location. A 365-bp fragment containing the fugu HRE was able to drive GFP expression in the liver of transgenic zebrafish. However, we could not ascertain if the expression of transgene is induced by hypoxia in vivo due to the low and variable levels of GFP expression in transgenic zebrafish. Our investigations also revealed that the Epo locus has experienced extensive rearrangements during vertebrate evolution. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. The EPOS ICT Architecture

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    Jeffery, Keith; Harrison, Matt; Bailo, Daniele

    2016-04-01

    The EPOS-PP Project 2010-2014 proposed an architecture and demonstrated feasibility with a prototype. Requirements based on use cases were collected and an inventory of assets (e.g. datasets, software, users, computing resources, equipment/detectors, laboratory services) (RIDE) was developed. The architecture evolved through three stages of refinement with much consultation both with the EPOS community representing EPOS users and participants in geoscience and with the overall ICT community especially those working on research such as the RDA (Research Data Alliance) community. The architecture consists of a central ICS (Integrated Core Services) consisting of a portal and catalog, the latter providing to end-users a 'map' of all EPOS resources (datasets, software, users, computing, equipment/detectors etc.). ICS is extended to ICS-d (distributed ICS) for certain services (such as visualisation software services or Cloud computing resources) and CES (Computational Earth Science) for specific simulation or analytical processing. ICS also communicates with TCS (Thematic Core Services) which represent European-wide portals to national and local assets, resources and services in the various specific domains (e.g. seismology, volcanology, geodesy) of EPOS. The EPOS-IP project 2015-2019 started October 2015. Two work-packages cover the ICT aspects; WP6 involves interaction with the TCS while WP7 concentrates on ICS including interoperation with ICS-d and CES offerings: in short the ICT architecture. Based on the experience and results of EPOS-PP the ICT team held a pre-meeting in July 2015 and set out a project plan. The first major activity involved requirements (re-)collection with use cases and also updating the inventory of assets held by the various TCS in EPOS. The RIDE database of assets is currently being converted to CERIF (Common European Research Information Format - an EU Recommendation to Member States) to provide the basis for the EPOS-IP ICS Catalog. In

  17. rhEPO Enhances Cellular Anti-oxidant Capacity to Protect Long-Term Cultured Aging Primary Nerve Cells.

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    Wang, Huqing; Fan, Jiaxin; Chen, Mengyi; Yao, Qingling; Gao, Zhen; Zhang, Guilian; Wu, Haiqin; Yu, Xiaorui

    2017-08-01

    Erythropoietin (EPO) may protect the nervous system of animals against aging damage, making it a potential anti-aging drug for the nervous system. However, experimental evidence from natural aging nerve cell models is lacking, and the efficacy of EPO and underlying mechanism of this effect warrant further study. Thus, the present study used long-term cultured primary nerve cells to successfully mimic the natural aging process of nerve cells. Starting on the 11th day of culture, cells were treated with different concentrations of recombinant human erythropoietin (rhEPO). Using double immunofluorescence labeling, we found that rhEPO significantly improved the morphology of long-term cultured primary nerve cells and increased the total number of long-term cultured primary cells. However, rhEPO did not improve the ratio of nerve cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure nerve cell activity and showed that rhEPO significantly improved the activity of long-term cultured primary nerve cells. Moreover, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double immunofluorescence labeling flow cytometry revealed that rhEPO reduced the apoptotic rate of long-term cultured primary nerve cells. Senescence-associated β-galactosidase (SA-β-gal) immunohistochemistry staining showed that rhEPO significantly reduced the aging rate of long-term cultured primary nerve cells. Immunochemistry revealed that rhEPO enhanced intracellular superoxide dismutase (SOD) activity and glutathione (GSH) abundance and reduced the intracellular malondialdehyde (MDA) level. In addition, this effect depended on the dose, was maximized at a dose of 100 U/ml and was more pronounced than that of vitamin E. In summary, this study finds that rhEPO protects long-term cultured primary nerve cells from aging in a dose-dependent manner. The mechanism of this effect may be associated with the enhancement of the intracellular anti

  18. Detection of recombinant EPO in blood and urine samples with EPO WGA MAIIA, IEF and SAR-PAGE after microdose injections.

    Science.gov (United States)

    Dehnes, Yvette; Shalina, Alexandra; Myrvold, Linda

    2013-01-01

    The misuse of microdoses of performance enhancing drugs like erythropoietin (EPO) constitutes a major challenge in doping analysis. When injected intravenously, the half-life of recombinant human EPO (rhEPO) like epoetin alfa, beta, and zeta is only a few hours and hence, the window for direct detection of rhEPO in urine is small. In order to investigate the detection window for rhEPO directly in blood and urine with a combined affinity chromatography and lateral flow immunoassay (EPO WGA MAIIA), we recruited nine healthy people who each received six intravenously injected microdoses (7.5 IU/kg) of NeoRecormon (epoetin beta) over a period of three weeks. Blood and urine samples were collected in the days following the injections and analyzed with EPO WGA MAIIA as well as the current validated methods for rhEPO; isoelectric focusing (IEF) and sarcosyl polyacrylamide gel electrophoresis (SAR-PAGE). For samples collected 18 h after a microdose, the sensitivity of the EPO WGA MAIIA assay was 100% in plasma and 87.5% in urine samples at the respective 98% specificity threshold levels. In comparison, the sensitivity in plasma and urine was 75% and 100%, respectively, with IEF, and 87.5% in plasma and 100% in urine when analyzed with SAR-PAGE. We conclude that EPO WGA MAIIA is a sensitive assay for the detection of rhEPO, with the potential of being a fast, supplemental screening assay for use in doping analysis.

  19. Detection of EPO gene doping in blood.

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    Neuberger, Elmo W I; Jurkiewicz, Magdalena; Moser, Dirk A; Simon, Perikles

    2012-11-01

    Gene doping--or the abuse of gene therapy--will continue to threaten the sports world. History has shown that progress in medical research is likely to be abused in order to enhance human performance. In this review, we critically discuss the progress and the risks associated with the field of erythropoietin (EPO) gene therapy and its applicability to EPO gene doping. We present typical vector systems that are employed in ex vivo and in vivo gene therapy trials. Due to associated risks, gene doping is not a feasible alternative to conventional EPO or blood doping at this time. Nevertheless, it is well described that about half of the elite athlete population is in principle willing to risk its health to gain a competitive advantage. This includes the use of technologies that lack safety approval. Sophisticated detection approaches are a prerequisite for prevention of unapproved and uncontrolled use of gene therapy technology. In this review, we present current detection approaches for EPO gene doping, with a focus on blood-based direct and indirect approaches. Gene doping is detectable in principle, and recent DNA-based detection strategies enable long-term detection of transgenic DNA (tDNA) following in vivo gene transfer. Copyright © 2012 John Wiley & Sons, Ltd.

  20. Prolonged administration of recombinant human erythropoietin increases submaximal performance more than maximal aerobic capacity

    DEFF Research Database (Denmark)

    Thomsen, J J; Rentsch, R L; Robach, P

    2007-01-01

    HuEpo treatment VO2max increased (Ptime-to-exhaustion (80% VO2max) was increased by 54.0 and 54.3% (Ptime point...... week 11), TTE was decreased by 26.8% as compared to pre rHuEpo administration. In conclusion, in healthy non-athlete subjects rHuEpo administration prolongs submaximal exercise performance by about 54% independently of the approximately 12% increase in VO2max....

  1. Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic Gonadotropin β Subunit to the N-Terminal and C-Terminal Coding Sequence

    Directory of Open Access Journals (Sweden)

    Fuad Fares

    2011-01-01

    Full Text Available A new analog of EPO was designed by fusing one and two CTPs to the N-terminal and C-terminal ends of EPO (EPO-(CTP3, respectively. This analog was expressed and secreted efficiently in CHO cells. The in vitro test shows that the activity of EPO-(CTP3 in TFI-1 cell proliferation assay is similar to that of EPO-WT and commercial rHEPO. However, in vivo studies indicated that treatment once a week with EPO-(CTP3 (15 μg/kg dramatically increased (~8 folds haematocrit as it was compared to rHuEPO. Moreover, it was found that EPO-(CTP3 is more effective than rHuEPO and Aranesp in increasing reticulocyte number in mice blood. The detected circulatory half-lives of rHuEPO, Aranesp, and EPO-(CTP3 following IV injection of 20 IU were 4.4, 10.8, and 13.1 h, respectively. These data established the rational for using this chimera as a long-acting EPO analog in clinics. The therapeutic efficacy of EPO-CTP analog needs to be established in higher animals and in human clinical trials.

  2. Generation of a transplantable erythropoietin-producer derived from human mesenchymal stem cells.

    Science.gov (United States)

    Yokoo, Takashi; Fukui, Akira; Matsumoto, Kei; Ohashi, Toya; Sado, Yoshikazu; Suzuki, Hideaki; Kawamura, Tetsuya; Okabe, Masataka; Hosoya, Tatsuo; Kobayashi, Eiji

    2008-06-15

    Differentiation of autologous stem cells into functional transplantable tissue for organ regeneration is a promising regenerative therapeutic approach for cancer, diabetes, and many human diseases. Yet to be established, however, is differentiation into tissue capable of producing erythropoietin (EPO), which has a critical function in anemia. We report a novel EPO-producing organ-like structure (organoid) derived from human mesenchymal stem cells. Using our previously established relay culture system, a human mesenchymal stem cell-derived, human EPO-competent organoid was established in rat omentum. The organoid-derived levels of human EPO increased in response to anemia induced by rapid blood withdrawal. In addition, the presence of an organoid in rats suppressed for native (rat) EPO production enhanced recovery from anemia when compared with control animals lacking the organoid. Together these results confirmed the generation of a stem cell-derived organoid that is capable of producing EPO and sensitive to physiological regulation.

  3. EPOS Data and Service Provision

    Science.gov (United States)

    Bailo, Daniele; Jeffery, Keith G.; Atakan, Kuvvet; Harrison, Matt

    2017-04-01

    EPOS is now in IP (implementation phase) after a successful PP (preparatory phase). EPOS consists of essentially two components, one ICS (Integrated Core Services) representing the integrating ICT (Information and Communication Technology) and many TCS (Thematic Core Services) representing the scientific domains. The architecture developed, demonstrated and agreed within the project during the PP is now being developed utilising co-design with the TCS teams and agile, spiral methods within the ICS team. The 'heart' of EPOS is the metadata catalog. This provides for the ICS a digital representation of the TCS assets (services, data, software, equipment, expertise…) thus facilitating access, interoperation and (re-)use. A major part of the work has been interactions with the TCS. The original intention to harvest information from the TCS required (and still requires) discussions to understand fully the TCS organisational structures linked with rights, security and privacy; their (meta)data syntax (structure) and semantics (meaning); their workflows and methods of working and the services offered. To complicate matters further the TCS are each at varying stages of development and the ICS design has to accommodate pre-existing, developing and expected future standards for metadata, data, software and processes. Through information documents, questionnaires and interviews/meetings the EPOS ICS team has collected DDSS (Data, Data Products, Software and Services) information from the TCS. The ICS team developed a simplified metadata model for presentation to the TCS and the ICS team will perform the mapping and conversion from this model to the internal detailed technical metadata model using (CERIF: a EU recommendation to Member States maintained, developed and promoted by euroCRIS www.eurocris.org ). At the time of writing the final modifications of the EPOS metadata model are being made, and the mappings to CERIF designed, prior to the main phase of (meta

  4. Amateur Astronomers: Secret Agents of EPO

    Science.gov (United States)

    Berendsen, M.; White, V.; Devore, E.; Reynolds, M.

    2008-06-01

    Amateur astronomers prime the public to be more interested, receptive, and excited about space science, missions, and programs. Through recent research and targeted programs, amateur astronomy outreach is being increasingly recognized by professional astronomers, educators, and other amateurs as a valued and important service. The Night Sky Network program, administered by the ASP, is the first nationwide research-based program specifically targeted to support outreach by amateur astronomers. This Network of trained and informed amateur astronomers can provide a stimulating introduction to your EPO programs as Network members share the night sky with families, students, and youth groups.

  5. NASA Astrophysics EPO Resources For Engaging Girls in Science

    Science.gov (United States)

    Sharma, M.; Mendoza, D.; Smith, D.; Hasan, H.

    2011-09-01

    A new collaboration among the NASA Science Mission Directorate (SMD) Astrophysics EPO community is to engage girls in science who do not self-select as being interested in science, through the library setting. The collaboration seeks to (i) improve how girls view themselves as someone who knows about, uses, and sometimes contributes to science, and (ii) increase the capacity of EPO practitioners and librarians (both school and public) to engage girls in science. As part of this collaboration, we are collating the research on audience needs and best practices, and SMD EPO resources, activities and projects that focus on or can be recast toward engaging girls in science. This ASP article highlights several available resources and individual projects, such as: (i) Afterschool Universe, an out-of-school hands-on astronomy curriculum targeted at middle school students and an approved Great Science for Girls curriculum; (ii) Big Explosions and Strong Gravity, a Girl Scout patch-earning event for middle school aged girls to learn astronomy through hands-on activities and interaction with actual astronomers; and (iii) the JWST-NIRCAM Train the Trainer workshops and activities for Girl Scouts of USA leaders; etc. The NASA Astrophysics EPO community welcomes the broader EPO community to discuss with us how best to engage non-science-attentive girls in science, technology, engineering, and mathematics (STEM), and to explore further collaborations on this theme.

  6. Chronic preclinical safety evaluation of EPO-018B, a pegylated peptidic erythropoiesis-stimulating agent in monkeys and rats

    International Nuclear Information System (INIS)

    Gong, Xue-Lian; Gu, Xiao-Lei; Chen, Yong-Chun; Zhu, Hai; Xia, Zhen-Na; Li, Jian-Zhong; Lu, Guo-Cai

    2016-01-01

    EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is mainly designed for treatment of anemia caused by chronic renal failure and chemotherapy against cancer. It overcomes the deficiencies of currently approved ESA, including the frequent administration of temperature-sensitive recombinant protein and anti-EPO antibody-mediated pure red cell aplasia (PRCA). This study was designed to evaluate the potential chronic toxicity of EPO-018B. Subcutaneous administration doses were designed as 0, 0.2, 1 and 10 mg/kg for six months for 160 rats (20/gender/group) and 0, 0.3, 3 and 20 mg/kg for nine months for 32 monkeys (4/gender/group) once every three weeks. The vehicles received the same volume of physiological saline injection. All animals survived to the scheduled necropsies after six weeks (for rats) and fourteen weeks (for monkeys) recovery period, except for the two high-dose female rats and two high-dose male monkeys, which were considered related to the increased RBCs, chronic blood hyperviscosity and chronic cardiac injury. EPO-018B is supposed to be subcutaneously injected once every month and the intended human therapeutic dose is 0.025 mg/kg. The study findings at 0.2 mg/kg for rats and 0.3 mg/kg for monkeys were considered to be the study NOAEL (the no observed adverse effect level), which were more than ten times the intended human therapeutic dose. Higher doses caused adverse effects related to the liver toxicity, cardiotoxicity, appearance of neutralizing antibodies of EPO-018B and the decrease of serum glucose and cholesterol. Most treatment-induced effects were reversible or revealed ongoing recovery upon the discontinuation of treatment. The sequelae occurred in rats and monkeys were considered secondary to exaggerated pharmacology and would less likely occur in the intended patient population. As to the differences between human beings and animals, the safety of EPO-018B need to be further confirmed in the future clinical

  7. Chronic preclinical safety evaluation of EPO-018B, a pegylated peptidic erythropoiesis-stimulating agent in monkeys and rats

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Xue-Lian; Gu, Xiao-Lei [Department of Hygiene and Toxicology, Second Military Medical University, Shanghai 200433 (China); Chen, Yong-Chun [Department of Hygiene and Toxicology, Second Military Medical University, Shanghai 200433 (China); Department of Pharmacy, No.422 Hospital, Zhanjiang 524005 (China); Zhu, Hai; Xia, Zhen-Na [Department of Hygiene and Toxicology, Second Military Medical University, Shanghai 200433 (China); Li, Jian-Zhong, E-mail: lijianzhong1234@hotmail.com [Department of Biochemical Pharmacy, Second Military Medical University, Shanghai 200433 (China); Lu, Guo-Cai, E-mail: newdrug@smmu.edu.cn [Department of Hygiene and Toxicology, Second Military Medical University, Shanghai 200433 (China)

    2016-09-15

    EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is mainly designed for treatment of anemia caused by chronic renal failure and chemotherapy against cancer. It overcomes the deficiencies of currently approved ESA, including the frequent administration of temperature-sensitive recombinant protein and anti-EPO antibody-mediated pure red cell aplasia (PRCA). This study was designed to evaluate the potential chronic toxicity of EPO-018B. Subcutaneous administration doses were designed as 0, 0.2, 1 and 10 mg/kg for six months for 160 rats (20/gender/group) and 0, 0.3, 3 and 20 mg/kg for nine months for 32 monkeys (4/gender/group) once every three weeks. The vehicles received the same volume of physiological saline injection. All animals survived to the scheduled necropsies after six weeks (for rats) and fourteen weeks (for monkeys) recovery period, except for the two high-dose female rats and two high-dose male monkeys, which were considered related to the increased RBCs, chronic blood hyperviscosity and chronic cardiac injury. EPO-018B is supposed to be subcutaneously injected once every month and the intended human therapeutic dose is 0.025 mg/kg. The study findings at 0.2 mg/kg for rats and 0.3 mg/kg for monkeys were considered to be the study NOAEL (the no observed adverse effect level), which were more than ten times the intended human therapeutic dose. Higher doses caused adverse effects related to the liver toxicity, cardiotoxicity, appearance of neutralizing antibodies of EPO-018B and the decrease of serum glucose and cholesterol. Most treatment-induced effects were reversible or revealed ongoing recovery upon the discontinuation of treatment. The sequelae occurred in rats and monkeys were considered secondary to exaggerated pharmacology and would less likely occur in the intended patient population. As to the differences between human beings and animals, the safety of EPO-018B need to be further confirmed in the future clinical

  8. Skin regeneration with conical and hair follicle structure of deep second-degree scalding injuries via combined expression of the EPO receptor and beta common receptor by local subcutaneous injection of nanosized rhEPO

    Directory of Open Access Journals (Sweden)

    Ebert S

    2012-03-01

    Full Text Available Augustinus Bader1, Sabine Ebert1, Shibashish Giri1, Mathias Kremer2, Shuhua Liu2, Andreas Nerlich5, Christina I Günter³, Dagmar U Smith4, Hans-Günther Machens2,31Department of Applied Stem Cell Biology and Cell Techniques, Centre for Biotechnology and Biomedicine, University of Leipzig, Leipzieg, 2Department of Plastic and Hand Surgery, University of Lübeck, Lübeck, 3Department of Plastic and Hand Surgery, Technische Universität München, Munich, 4Münchner Studienzentrum, Technische Universität München, Munich, 5Institute of Pathology, Klinikum München-Bogenhausen, Munich, GermanyBackground: Acceleration of skin regeneration is still an unsolved problem in the clinical treatment of patients suffering from deep burns and scalds. Although erythropoietin (EPO has a protective role in a wide range of organs and cells during ischemia and after trauma, it has been recently discovered that EPO is not tissue-protective in the common β subunit receptor (βCR knockout mouse. The protective capacity of EPO in tissue is mediated via a heteroreceptor complex comprising both the erythropoietin receptor (EPOR and βCR. However, proof of coexpression of these heterogenic receptors in regenerating skin after burns is still lacking.Methods: To understand the role of nanosized recombinant human erythropoietin (rhEPO in wound healing, we investigated the effects of subcutaneous injections of EPO on skin regeneration after deep second-degree scalding injuries. Our aim was to determine if joint expression of EPOR and βCR is a prerequisite for the tissue-protective effect of rhEPO. The efficiency in wound regeneration in a skin scalding injury mouse model was examined. A deep second-degree dermal scald injury was produced on the backs of 20 female Balb/c mice which were subsequently randomized to four experimental groups, two of which received daily subcutaneous injections of rhEPO. At days 7 and 14, the mice were sacrificed and the effects of rhEPO were

  9. The EPOS e-Infrastructure

    Science.gov (United States)

    Jeffery, Keith; Bailo, Daniele

    2014-05-01

    The European Plate Observing System (EPOS) is integrating geoscientific information concerning earth movements in Europe. We are approaching the end of the PP (Preparatory Project) phase and in October 2014 expect to continue with the full project within ESFRI (European Strategic Framework for Research Infrastructures). The key aspects of EPOS concern providing services to allow homogeneous access by end-users over heterogeneous data, software, facilities, equipment and services. The e-infrastructure of EPOS is the heart of the project since it integrates the work on organisational, legal, economic and scientific aspects. Following the creation of an inventory of relevant organisations, persons, facilities, equipment, services, datasets and software (RIDE) the scale of integration required became apparent. The EPOS e-infrastructure architecture has been developed systematically based on recorded primary (user) requirements and secondary (interoperation with other systems) requirements through Strawman, Woodman and Ironman phases with the specification - and developed confirmatory prototypes - becoming more precise and progressively moving from paper to implemented system. The EPOS architecture is based on global core services (Integrated Core Services - ICS) which access thematic nodes (domain-specific European-wide collections, called thematic Core Services - TCS), national nodes and specific institutional nodes. The key aspect is the metadata catalog. In one dimension this is described in 3 levels: (1) discovery metadata using well-known and commonly used standards such as DC (Dublin Core) to enable users (via an intelligent user interface) to search for objects within the EPOS environment relevant to their needs; (2) contextual metadata providing the context of the object described in the catalog to enable a user or the system to determine the relevance of the discovered object(s) to their requirement - the context includes projects, funding, organisations

  10. Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice.

    Science.gov (United States)

    Hitomi, Hirofumi; Kasahara, Tomoko; Katagiri, Naoko; Hoshina, Azusa; Mae, Shin-Ichi; Kotaka, Maki; Toyohara, Takafumi; Rahman, Asadur; Nakano, Daisuke; Niwa, Akira; Saito, Megumu K; Nakahata, Tatsutoshi; Nishiyama, Akira; Osafune, Kenji

    2017-09-27

    The production of erythropoietin (EPO) by the kidneys, a principal hormone for the hematopoietic system, is reduced in patients with chronic kidney disease (CKD), eventually resulting in severe anemia. Although recombinant human EPO treatment improves anemia in patients with CKD, returning to full red blood cell production without fluctuations does not always occur. We established a method to generate EPO-producing cells from human induced pluripotent stem cells (hiPSCs) by modifying previously reported hepatic differentiation protocols. These cells showed increased EPO expression and secretion in response to low oxygen conditions, prolyl hydroxylase domain-containing enzyme inhibitors, and insulin-like growth factor 1. The EPO protein secreted from hiPSC-derived EPO-producing (hiPSC-EPO) cells induced the erythropoietic differentiation of human umbilical cord blood progenitor cells in vitro. Furthermore, transplantation of hiPSC-EPO cells into mice with CKD induced by adenine treatment improved renal anemia. Thus, hiPSC-EPO cells may be a useful tool for clarifying the mechanisms of EPO production and may be useful as a therapeutic strategy for treating renal anemia. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  11. The EPOS Implementation Phase: building thematic and integrated services for solid Earth sciences

    Science.gov (United States)

    Cocco, Massimo; Epos Consortium, the

    2015-04-01

    The European Plate Observing System (EPOS) has a scientific vision and approach aimed at creating a pan-European infrastructure for Earth sciences to support a safe and sustainable society. To follow this vision, the EPOS mission is integrating a suite of diverse and advanced Research Infrastructures (RIs) in Europe relying on new e-science opportunities to monitor and understand the dynamic and complex Earth system. To this goal, the EPOS Preparatory Phase has designed a long-term plan to facilitate integrated use of data and products as well as access to facilities from mainly distributed existing and new research infrastructures for solid Earth Science. EPOS will enable innovative multidisciplinary research for a better understanding of the Earth's physical processes that control earthquakes, volcanic eruptions, ground instability and tsunami as well as the processes driving tectonics and Earth surface dynamics. Through integration of data, models and facilities EPOS will allow the Earth Science community to make a step change in developing new concepts and tools for key answers to scientific and socio-economic questions concerning geo-hazards and geo-resources as well as Earth sciences applications to the environment and to human welfare. Since its conception EPOS has been built as "a single, Pan-European, sustainable and distributed infrastructure". EPOS is, indeed, the sole infrastructure for solid Earth Science in ESFRI and its pan-European dimension is demonstrated by the participation of 23 countries in its preparatory phase. EPOS is presently moving into its implementation phase further extending its pan-European dimension. The EPOS Implementation Phase project (EPOS IP) builds on the achievements of the successful EPOS preparatory phase project. The EPOS IP objectives are synergetic and coherent with the establishment of the new legal subject (the EPOS-ERIC in Italy). EPOS coordinates the existing and new solid Earth RIs within Europe and builds the

  12. Cytoprotective effect of recombinant human erythropoietin produced in transgenic tobacco plants.

    Directory of Open Access Journals (Sweden)

    Farooqahmed S Kittur

    Full Text Available Asialo-erythropoietin, a desialylated form of human erythropoietin (EPO lacking hematopoietic activity, is receiving increased attention because of its broader protective effects in preclinical models of tissue injury. However, attempts to translate its protective effects into clinical practice is hampered by unavailability of suitable expression system and its costly and limit production from expensive mammalian cell-made EPO (rhuEPO(M by enzymatic desialylation. In the current study, we took advantage of a plant-based expression system lacking sialylating capacity but possessing an ability to synthesize complex N-glycans to produce cytoprotective recombinant human asialo-rhuEPO. Transgenic tobacco plants expressing asialo-rhuEPO were generated by stably co-expressing human EPO and β1,4-galactosyltransferase (GalT genes under the control of double CaMV 35S and glyceraldehyde-3-phosphate gene (GapC promoters, respectively. Plant-produced asialo-rhuEPO (asialo-rhuEPO(P was purified by immunoaffinity chromatography. Detailed N-glycan analysis using NSI-FTMS and MS/MS revealed that asialo-rhuEPO(P bears paucimannosidic, high mannose-type and complex N-glycans. In vitro cytoprotection assays showed that the asialo-rhuEPO(P (20 U/ml provides 2-fold better cytoprotection (44% to neuronal-like mouse neuroblastoma cells from staurosporine-induced cell death than rhuEPO(M (21%. The cytoprotective effect of the asialo-rhuEPO(P was found to be mediated by receptor-initiated phosphorylation of Janus kinase 2 (JAK2 and suppression of caspase 3 activation. Altogether, these findings demonstrate that plants are a suitable host for producing cytoprotective rhuEPO derivative. In addition, the general advantages of plant-based expression system can be exploited to address the cost and scalability issues related to its production.

  13. Building thematic and integrated services for solid Earth sciences: the EPOS integrated approach

    Science.gov (United States)

    Cocco, Massimo; Consortium, Epos

    2016-04-01

    EPOS has been designed with the vision of creating a pan-European infrastructure for solid Earth science to support a safe and sustainable society. In accordance with this scientific vision, the EPOS mission is to integrate the diverse and advanced European Research Infrastructures for solid Earth science relying on new e-science opportunities to monitor and unravel the dynamic and complex Earth System. EPOS will enable innovative multidisciplinary research for a better understanding of the Earth's physical and chemical processes that control earthquakes, volcanic eruptions, ground instability and tsunami as well as the processes driving tectonics and Earth's surface dynamics. To accomplish its mission, EPOS is engaging different stakeholders, not limited to scientists, to allow the Earth sciences to open new horizons in our understanding of the planet. EPOS also aims at contributing to prepare society for geo-hazards and to responsibly manage the exploitation of geo-resources. Through integration of data, models and facilities, EPOS will allow the Earth science community to make a step change in developing new concepts and tools for key answers to scientific and socio-economic questions concerning geo-hazards and geo-resources as well as Earth sciences applications to the environment and human welfare. A long-term integration plan is necessary to accomplish the EPOS mission. EPOS is presently in its implementation phase further extending its pan-European dimension. The EPOS Implementation Phase builds on the achievements of the successful EPOS Preparatory Phase project and consists of two key activities: the legal establishment of the EPOS-ERIC and the EPOS IP project. The EPOS implementation phase will last from 2015 to 2019. Key objectives of the project are: implementing Thematic Core Services (TCS), the domain-specific service hubs for coordinating and harmonizing national resources/plans with the European dimension of EPOS; building the Integrated Core

  14. Ethics issues in scientific data and service provision: evidence and challenges for the European Plate Observing System (EPOS)

    Science.gov (United States)

    Cocco, Massimo; Freda, Carmela; Haslinger, Florian; Consortium, Epos

    2016-04-01

    monitor planet Earth is rapidly evolving through the development of new sensor technology and we can deliver this information with increasing rapidity, integrate it, provide solutions to scientific challenges and furnish essential information for decision makers. EPOS is aware that the research promoted by its data and service provision can have a profound influence on the environment, human health and wellbeing, economic development, national security, and other facets of human societies. For these reasons EPOS must address Ethics issues associated with the exploitation of its achievements involving security issues, use and misuse of data, environmental protection and risk communication. The EPOS community feels the obligation to adopt a responsible conduct, both within the scientific community and in the broader society, exploring the implications of open provisioning of data and services, up to imposing justified constraints. This requires that contributing to the DDSS provision cannot be simply limited to activities fostering the capacity (i.e., ability) to access scientific products, but must promote the creation of capabilities (i.e., conscious use of data) and the functioning (i.e., activities constitutive of a scientist's being) to access and use scientific products in an ethically consistent way. We will present and discuss Ethics issues envisaged in EPOS, focusing on the most relevant for its implementation phase: protection of personal data, misuse of data, communication, and societal impact.

  15. Erythropoietin augments the cytokine response to acute endotoxin-induced inflammation in humans

    DEFF Research Database (Denmark)

    Hojman, Pernille; Taudorf, Sarah; Lundby, Carsten

    2009-01-01

    in a human in vivo model of acute systemic low-grade inflammation, we measured circulating inflammatory mediators after intravenous administration of Escherichia coli endotoxin (LPS) bolus injection (0.1 ng/kg of body weight) in young healthy male subjects. The subjects were divided into three groups...... receiving either (1) LPS alone, (2) EPO alone (15,000 IE of rHuEPO) or (3) EPO and LPS. Endotoxin administration alone induced a 3-, 12- and 5-fold increase in plasma concentrations of TNF-alpha, IL-6 and IL-10, respectively, 3h after LPS challenge. When EPO was given prior to a bolus injection...... with endotoxin, the levels of TNF-alpha and IL-6 were enhanced by 5- and 40-fold, respectively, whereas the endotoxin-induced increase in IL-10 response was not influenced by EPO. In contrast to our hypothesis, we find that EPO augments the acute inflammatory effect....

  16. EPOS Thematic Core Service Anthropogenic Hazards: Implementation Plan

    Science.gov (United States)

    Orlecka-Sikora, Beata; Lasocki, Stanislaw; Grasso, Jean Robert; Schmittbuhl, Jean; Styles, Peter; Kwiatek, Grzegorz; Sterzel, Mariusz; Garcia, Alexander

    2015-04-01

    EPOS Thematic Core Service ANTHROPOGENIC HAZARDS (TCS AH) aims to integrate distributed research infrastructures (RI) to facilitate and stimulate research on anthropogenic hazards (AH) especially those associated with the exploration and exploitation of geo-resources. The innovative element is the uniqueness of the integrated RI which comprises two main deliverables: (1) Exceptional datasets, called "episodes", which comprehensively describe a geophysical process; induced or triggered by human technological activity, posing hazard for populations, infrastructure and the environment, (2) Problem-oriented, bespoke services uniquely designed for the discrimination and analysis of correlations between technology, geophysical response and resulting hazard. These objectives will be achieved through the Science-Industry Synergy (SIS) built by EPOS WG10, ensuring bi-directional information exchange, including unique and previously unavailable data furnished by industrial partners. The Episodes and services to be integrated have been selected using strict criteria during the EPOS PP. The data are related to a wide spectrum of inducing technologies, with seismic/aseismic deformation and production history as a minimum data set requirement and the quality of software services is confirmed and referenced in literature. Implementation of TCS AH is planned for four years and requires five major activities: (1) Strategic Activities and Governance: will define and establish the governance structure to ensure the long-term sustainability of these research infrastructures for data provision through EPOS. (2) Coordination and Interaction with the Community: will establish robust communication channels within the whole TCS AH community while supporting global EPOS communication strategy. (3) Interoperability with EPOS Integrated Core Service (ICS) and Testing Activities: will coordinate and ensure interoperability between the RIs and the ICS. Within this modality a functional e

  17. Building Thematic and Integrated Services for European Solid Earth Sciences: the EPOS Integrated Approach

    Science.gov (United States)

    Harrison, M.; Cocco, M.

    2017-12-01

    EPOS (European Plate Observing System) has been designed with the vision of creating a pan-European infrastructure for solid Earth science to support a safe and sustainable society. In accordance with this scientific vision, the EPOS mission is to integrate the diverse and advanced European Research Infrastructures for solid Earth science relying on new e-science opportunities to monitor and unravel the dynamic and complex Earth System. EPOS will enable innovative multidisciplinary research for a better understanding of the Earth's physical and chemical processes that control earthquakes, volcanic eruptions, ground instability and tsunami as well as the processes driving tectonics and Earth's surface dynamics. To accomplish its mission, EPOS is engaging different stakeholders, to allow the Earth sciences to open new horizons in our understanding of the planet. EPOS also aims at contributing to prepare society for geo-hazards and to responsibly manage the exploitation of geo-resources. Through integration of data, models and facilities, EPOS will allow the Earth science community to make a step change in developing new concepts and tools for key answers to scientific and socio-economic questions concerning geo-hazards and geo-resources as well as Earth sciences applications to the environment and human welfare. The research infrastructures (RIs) that EPOS is coordinating include: i) distributed geophysical observing systems (seismological and geodetic networks); ii) local observatories (including geomagnetic, near-fault and volcano observatories); iii) analytical and experimental laboratories; iv) integrated satellite data and geological information services; v) new services for natural and anthropogenic hazards; vi) access to geo-energy test beds. Here we present the activities planned for the implementation phase focusing on the TCS, the ICS and on their interoperability. We will discuss the data, data-products, software and services (DDSS) presently under

  18. The feed-back regulation of erythropoietin production in healthy humans

    International Nuclear Information System (INIS)

    Klausen, T.

    1998-01-01

    The proposed oxygen-dependent feed-back loop regulation of EPO (erythropoietin) production is mainly supported by data from studies in animals and cell cultures. The feed-back loop and its dependence on oxygen was therefore challenged by studies in healthy humans: Exposure of humans to different levels of acute and continued altitude hypobaria provided evidence for an oxygen dependence of the EPO response. This response is consistent with the proposed feed-back loop regulation of EPO production; Exposure to continued altitude hypobaria demonstrated that the decline in human EPO production is initiated before an EPO-induced erythopoiesis is detectable, and that this decline is related to a concomitant decrease in the haemoglobin-oxygen affinity. Contrary to the feed-back loop, this time-relation indicate that the feed-back regulation of EPO production during continued hypobaric hypoxia is exerted primarily through a decrease in the haemoglobin-oxygen affinity, rather than by the effects of an EPO-stimulated erythropoiesis; Increased circulating levels of the proinflammatory cytokine IL-6 was found in healthy humans during four days of altitude exposure as compared with sea level. The other proinflammatory cytokines IL-1 beta, and TNF alpha remained unchanged, and the increased serum IL-6 did not induce production of c-reactive protein; Comparable circadian variations in human EPO production were shown in sedentary subjects, athletes, and healthy but hypoxaemic subjects. Human EPO production could not be triggered by one hour of high-intensity exercise, whereas longitudinal changes in exercise showed a trend of relation between human EPO production, serum concentration of free testosterone, and indices of body composition. These results have demonstrated and endogenous, probably hormonal, and oxygen-independent regulation of human EPO production, which is at variance with the oxygen dependent feed-back loop regulation of EPO production. Conclusively, the present

  19. Antibody-based enzyme-linked lectin assay (ABELLA) for the sialylated recombinant human erythropoietin present in culture supernatant.

    Science.gov (United States)

    Kim, Hyoung Jin; Lee, Seung Jae; Kim, Hong-Jin

    2008-11-04

    The terminal sialic acid of human erythropoietin (hEPO) is essential for in vivo activity. The current resorcinol and HPLC methods for analyzing alpha2,3-linked sialic acid require more than a microgram of purified rhEPO, and purification takes a great deal of time and labor. In this study, we assessed the use of an antibody-based enzyme-linked lectin assay (ABELLA) for analyzing non-purified recombinant hEPO (rhEPO). The major problem of this method was the high background due to terminal sialylation of components of the assay (antibody and bovine serum albumin) other than rhEPO. To solve this problem, we used a monoclonal antibody (Mab 287) to capture the rhEPO, and oxidized the bovine serum albumin used for blocking with meta-periodate. The sialic acid content of non-purified rhEPO measured by ABELLA was similar to that obtained by the resorcinol method on purified rhEPO. ABELLA has advantages such as adaptability and need for minimal amounts of rhEPO (40 ng/ml). Our observations suggest that ABELLA should reduce the time and labor needed to improve culture conditions so as to increase protein sialylation, and also facilitate the study of sialylation mechanisms.

  20. Tumor biology of non-metastatic stages of clear cell renal cell carcinoma; overexpression of stearoyl desaturase-1, EPO/EPO-R system and hypoxia-related proteins.

    Science.gov (United States)

    Stoyanoff, Tania Romina; Rodríguez, Juan Pablo; Todaro, Juan Santiago; Espada, Joaquín Diego; Colavita, Juan Pablo Melana; Brandan, Nora Cristina; Torres, Adriana Mónica; Aguirre, María Victoria

    2016-10-01

    Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinomas. There is great interest to know the molecular basis of the tumor biology of ccRCC that might contribute to a better understanding of the aggressive biological behavior of this cancer and to identify early biomarkers of disease. This study describes the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (hypoxia-inducible factor (HIF)-1α, erythropoietin (EPO), vascular endothelial growth factor (VEGF)), their receptors (EPO-R, VEGFR-2), and stearoyl desaturase-1 (SCD-1) in early stages of ccRCC. Tissue samples were obtained at the Urology Unit of the J.R. Vidal Hospital (Corrientes, Argentina), from patients who underwent radical nephrectomy for renal cancer between 2011 and 2014. Four experimental groups according to pathological stage and nuclear grade were organized: T1G1 (n = 6), T2G1 (n = 4), T1G2 (n = 7), and T2G2 (n = 7). The expression of HIF-1α, EPO, EPO-R, VEGF, VEGFR-2, Bcl-x L , and SCD-1 were evaluated by immunohistochemistry, Western blotting, and/or RT-PCR. Apoptosis was assessed by the TUNEL in situ assay, and tumor proliferation was determined by Ki-67 immunohistochemistry. Data revealed that HIF-1α, EPO, EPO-R, VEGF, and VEGF-R2 were overexpressed in most samples. The T1G1 group showed the highest EPO levels, approximately 200 % compared with distal renal tissue. Bcl-x L overexpression was concomitant with the enhancement of proliferative indexes. SCD-1 expression increased with the tumor size and nuclear grade. Moreover, the direct correlations observed between SCD-1/HIF-1α and SCD-1/Ki-67 increments suggest a link among these molecules, which would determine tumor progression in early stages of ccRCC. Our results demonstrate the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (HIF-1α, EPO, VEGF), their

  1. FIN-EPOS - Finnish national initiative of the European Plate Observing System: Bringing Finnish solid Earth infrastructures into EPOS

    Science.gov (United States)

    Vuorinen, Tommi; Korja, Annakaisa

    2017-04-01

    FIN-EPOS consortium is a joint community of Finnish national research institutes tasked with operating and maintaining solid-earth geophysical and geological observatories and laboratories in Finland. These national research infrastructures (NRIs) seek to join EPOS research infrastructure (EPOS RI) and further pursue Finland's participation as a founding member in EPOS ERIC (European Research Infrastructure Consortium). Current partners of FIN-EPOS are the University of Helsinki (UH), the University of and Oulu (UO), Finnish Geospatial Research Institute (FGI) of the National Land Survey (NLS), Finnish Meteorological Institute (FMI), Geological Survey of Finland (GTK), CSC - IT Center for Science and MIKES Metrology at VTT Technical Research Centre of Finland Ltd. The consortium is hosted by the Institute of Seismology, UH (ISUH). The primary purpose of the consortium is to act as a coordinating body between various NRIs and the EPOS RI. FIN-EPOS engages in planning and development of the national EPOS RI and will provide support in EPOS implementation phase (IP) for the partner NRIs. FIN-EPOS also promotes the awareness of EPOS in Finland and is open to new partner NRIs that would benefit from participating in EPOS. The consortium additionally seeks to advance solid Earth science education, technologies and innovations in Finland and is actively engaging in Nordic co-operation and collaboration of solid Earth RIs. The main short term objective of FIN-EPOS is to make Finnish geoscientific data provided by NRIs interoperable with the Thematic Core Services (TCS) in the EPOS IP. Consortium partners commit into applying and following metadata and data format standards provided by EPOS. FIN-EPOS will also provide a national Finnish language web portal where users are identified and their user rights for EPOS resources are defined.

  2. Analysis of human reticulocyte genes reveals altered erythropoiesis: potential use to detect recombinant human erythropoietin doping.

    Science.gov (United States)

    Varlet-Marie, Emmanuelle; Audran, Michel; Lejeune, Mireille; Bonafoux, Béatrice; Sicart, Marie-Therese; Marti, Jacques; Piquemal, David; Commes, Thérèse

    2004-08-01

    Enhancement of oxygen delivery to tissues is associated with improved sporting performance. One way of enhancing oxygen delivery is to take recombinant human erythropoietin (rHuEpo), which is an unethical and potentially dangerous practice. However, detection of the use of rHuEpo remains difficult in situations such as: i) several days after the end of treatment ii) when a treatment with low doses is conducted iii) if the rHuEpo effect is increased by other substances. In an attempt to detect rHuEpo abuse, we selected erythroid gene markers from a SAGE library and analyzed the effects of rHuEpo administration on expression of the HBB, FTL and OAZ genes. Ten athletes were assigned to the rHuEpo or placebo group. The rHuEpo group received subcutaneous injections of rHuEpo (50 UI/kg three times a week, 4 weeks; 20 UI/kg three times a week, 2 weeks). HBB, FTL and OAZ gene profiles were monitored by real time-polymerase chain reaction (PCR) quantification during and for 3 weeks after drug administration. The global analysis of these targeted genes detected in whole blood samples showed a characteristic profile of subjects misusing rHuEpo with a increase above the threshold levels. The individual analysis of OAZ mRNA seemed indicative of rHuEpo treatment. The performance-enhancing effect of rHuEpo treatment is greater than the duration of hematologic changes associated with rHuEpo misuse. Although direct electrophoretic methods to detect rHuEpo have been developed, recombinant isoforms of rHuEpo are not detectable some days after the last subcutaneous injection. To overcome these limitations indirect OFF models have been developed. Our data suggest that, in the near future, it will be possible to consolidate results achievable with the OFF models by analyzing selected erythroid gene markers as a supplement to indirect methods.

  3. EPOS Seismology services and their users

    Science.gov (United States)

    Haslinger, Florian; Dupont, Aurelien; Michelini, Alberto; Rietbrock, Andreas; Sleeman, Reinoud; Wiemer, Stefan; Basili, Roberto; Bossu, Rémy; Cakti, Eser; Cotton, Fabrice; Crawford, Wayne; Crowley, Helen; Danciu, Laurentiu; Diaz, Jordi; Garth, Tom; Locati, Mario; Luzi, Lucia; Pitilakis, Kyriazis; Roumelioti, Zafeiria; Strollo, Angelo

    2017-04-01

    The construction of seismological community services for the European Plate Observing System Research Infrastructure (EPOS) is by now well under way. A significant number of services are already operational, largely based on those existing at established institutions or collaborations like ORFEUS, EMSC, AHEAD and EFEHR, and more are being added to be ready for internal validation by late 2017. In this presentation we focus on a number of issues related to the interaction of the community of users with the services provided by the seismological part of the EPOS research infrastructure. How users interact with a service (and how satisfied they are with this interaction) is viewed as one important component of the validation of a service within EPOS, and certainly is key to the uptake of a service and from that also it's attributed value. Within EPOS Seismology, the following aspects of user interaction have already surfaced: - user identification (and potential tracking) versus ease-of-access and openness Requesting users to identify themselves when accessing a service provides various advantages to providers and users (e.g. quantifying & qualifying the service use, customization of services and interfaces, handling access rights and quotas), but may impact the ease of access and also shy away users who don't wish to be identified for whatever reason. - service availability versus cost There is a clear and prominent connection between the availability of a service, both regarding uptime and capacity, and its operational cost (IT systems and personnel), and it is often not clear where to draw the line (and based on which considerations). In connection to that, how to best utilize third-party IT infrastructures (either commercial or public), and what the long-term cost implications of that might be, is equally open. - licensing and attribution The issue of intellectual property and associated licensing policies for data, products and services is only recently gaining

  4. Worldwide nanotechnology development: a comparative study of USPTO, EPO, and JPO patents (1976-2004)

    International Nuclear Information System (INIS)

    Li Xin; Lin Yiling; Chen Hsinchun; Roco, Mihail C.

    2007-01-01

    To assess worldwide development of nanotechnology, this paper compares the numbers and contents of nanotechnology patents in the United States Patent and Trademark Office (USPTO), European Patent Office (EPO), and Japan Patent Office (JPO). It uses the patent databases as indicators of nanotechnology trends via bibliographic analysis, content map analysis, and citation network analysis on nanotechnology patents per country, institution, and technology field. The numbers of nanotechnology patents published in USPTO and EPO have continued to increase quasi-exponentially since 1980, while those published in JPO stabilized after 1993. Institutions and individuals located in the same region as a repository's patent office have a higher contribution to the nanotechnology patent publication in that repository ('home advantage' effect). The USPTO and EPO databases had similar high-productivity contributing countries and technology fields with large number of patents, but quite different high-impact countries and technology fields after the average number of received cites. Bibliographic analysis on USPTO and EPO patents shows that researchers in the United States and Japan published larger numbers of patents than other countries, and that their patents were more frequently cited by other patents. Nanotechnology patents covered physics research topics in all three repositories. In addition, USPTO showed the broadest representation in coverage in biomedical and electronics areas. The analysis of citations by technology field indicates that USPTO had a clear pattern of knowledge diffusion from highly cited fields to less cited fields, while EPO showed knowledge exchange mainly occurred among highly cited fields

  5. Enhancement of bioavailability by formulating rhEPO ionic complex with lysine into PEG-PLA micelle

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yanan; Sun, Fengying; Wang, Dan; Zhang, Renyu [Jilin University, College of Life Science (China); Dou, Changlin; Liu, Wanhui; Sun, Kaoxiang, E-mail: sunkx@ytu.edu.cn [Yantai University, School of Pharmacy (China); Li, Youxin, E-mail: liyouxin@jlu.edu.cn [Jilin University, College of Life Science (China)

    2013-10-15

    A composite micelle of ionic complex encapsulated into poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA) di-block copolymeric micelles was used for protein drug delivery to improve its pharmacokinetic performance. In this study, recombinant human erythropoietin (rhEPO, as a model protein) was formulated with lysine into composite micelles at a diameter of 71.5 nm with narrow polydispersity indices (PDIs < 0.3). Only a trace amount of protein was in aggregate form. The zeta potential of the spherical micelles was ranging from -0.54 to 1.39 mv, and encapsulation efficiency is high (80 %). The stability of rhEPO was improved significantly in composite micelles in vitro. Pharmacokinetic studies in rats showed significant, enhanced plasma retention of the composite micelles in comparison with native rhEPO. Areas under curve (AUCs) of the rhEPO released from the composite micelles were 4.5- and 2.3-folds higher than those of the native rhEPO and rhEPO-loaded PEG-PLA micelle, respectively. In addition, the composite micelles exhibited good biocompatibility using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay with human embryonic kidney (HEK293T) cells. All these features are preferable for utilizing the composite micelles as a novel protein delivery system.

  6. Enhancement of bioavailability by formulating rhEPO ionic complex with lysine into PEG-PLA micelle

    Science.gov (United States)

    Shi, Yanan; Sun, Fengying; Wang, Dan; Zhang, Renyu; Dou, Changlin; Liu, Wanhui; Sun, Kaoxiang; Li, Youxin

    2013-10-01

    A composite micelle of ionic complex encapsulated into poly(ethylene glycol)-poly( d, l-lactide) (PEG-PLA) di-block copolymeric micelles was used for protein drug delivery to improve its pharmacokinetic performance. In this study, recombinant human erythropoietin (rhEPO, as a model protein) was formulated with lysine into composite micelles at a diameter of 71.5 nm with narrow polydispersity indices (PDIs protein was in aggregate form. The zeta potential of the spherical micelles was ranging from -0.54 to 1.39 mv, and encapsulation efficiency is high (80 %). The stability of rhEPO was improved significantly in composite micelles in vitro. Pharmacokinetic studies in rats showed significant, enhanced plasma retention of the composite micelles in comparison with native rhEPO. Areas under curve (AUCs) of the rhEPO released from the composite micelles were 4.5- and 2.3-folds higher than those of the native rhEPO and rhEPO-loaded PEG-PLA micelle, respectively. In addition, the composite micelles exhibited good biocompatibility using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay with human embryonic kidney (HEK293T) cells. All these features are preferable for utilizing the composite micelles as a novel protein delivery system.

  7. EPOS-Seismology: building the Thematic Core Service for Seismology during the EPOS Implementation Phase

    Science.gov (United States)

    Haslinger, Florian; EPOS Seismology Consortium, the

    2015-04-01

    After the successful completion of the EPOS Preparatory Phase, the community of European Research Infrastructures in Seismology is now moving ahead with the build-up of the Thematic Core Service (TCS) for Seismology in EPOS, EPOS-Seismology. Seismology is a domain where European-level infrastructures have been developed since decades, often supported by large-scale EU projects. Today these infrastructures provide services to access earthquake waveforms (ORFEUS), parameters (EMSC) and hazard data and products (EFEHR). The existing organizations constitute the backbone of infrastructures that also in future will continue to manage and host the services of the TCS EPOS-Seismology. While the governance and internal structure of these organizations will remain active, and continue to provide direct interaction with the community, EPOS-Seismology will provide the integration of these within EPOS. The main challenge in the build-up of the TCS EPOS-Seismology is to improve and extend these existing services, producing a single framework which is technically, organizationally and financially integrated with the EPOS architecture, and to further engage various kinds of end users (e.g. scientists, engineers, public managers, citizen scientists). On the technical side the focus lies on four major tasks: - the construction of the next generation software architecture for the European Integrated (waveform) Data Archive EIDA, developing advanced metadata and station information services, fully integrate strong motion waveforms and derived parametric engineering-domain data, and advancing the integration of mobile (temporary) networks and OBS deployments in EIDA; - the further development and expansion of services to access seismological products of scientific interest as provided by the community by implementing a common collection and development (IT) platform, improvements in the earthquake information services e.g. by introducing more robust quality indicators and diversifying

  8. The European Plate Observing System (EPOS) Services for Solid Earth Science

    Science.gov (United States)

    Cocco, Massimo; Atakan, Kuvvet; Pedersen, Helle; Consortium, Epos

    2016-04-01

    The European Plate Observing System (EPOS) aims to create a pan-European infrastructure for solid Earth science to support a safe and sustainable society. The main vision of the European Plate Observing System (EPOS) is to address the three basic challenges in Earth Sciences: (i) unravelling the Earth's deformational processes which are part of the Earth system evolution in time, (ii) understanding the geo-hazards and their implications to society, and (iii) contributing to the safe and sustainable use of geo-resources. The mission of EPOS is to monitor and understand the dynamic and complex Earth system by relying on new e-science opportunities and integrating diverse and advanced Research Infrastructures in Europe for solid Earth Science. EPOS will enable innovative multidisciplinary research for a better understanding of the Earth's physical and chemical processes that control earthquakes, volcanic eruptions, ground instability and tsunami as well as the processes driving tectonics and Earth's surface dynamics. EPOS will improve our ability to better manage the use of the subsurface of the Earth. Through integration of data, models and facilities EPOS will allow the Earth Science community to make a step change in developing new concepts and tools for key answers to scientific and socio-economic questions concerning geo-hazards and geo-resources as well as Earth sciences applications to the environment and to human welfare. EPOS has now started its Implementation Phase (EPOS-IP). One of the main challenges during the implementation phase is the integration of multidisciplinary data into a single e-infrastructure. Multidisciplinary data are organized and governed by the Thematic Core Services (TCS) and are driven by various scientific communities encompassing a wide spectrum of Earth science disciplines. These include Data, Data-products, Services and Software (DDSS), from seismology, near fault observatories, geodetic observations, volcano observations

  9. SIMBOL RAMA DAN EPOS RAMAYANA BAGI RAJA DAN MASYARAKAT JAWA

    Directory of Open Access Journals (Sweden)

    Wachid Eko Purwanto

    2015-06-01

    Full Text Available Epos Ramayana merupakan epos kuno yang ditulis dalam tujuh kanda terdiri atas 24.000 sloka. Di Jawa epos Ramayana pertama kali muncul secara lengkap dalam bentuk relief di Candi Lara Jonggrang yang dibangun sekitar tahun 782 hingga 872 M. Epos tua yang hidup di masyarakat Jawa ini pastilah mempunyai ajaran. Tokoh Rama sebagai tokoh utama merupakan simbol paling utama dalam epos ini. Berkait dengan simbol ajaran, tokoh Rama dalam epos Ramayana Jawa mempunyai fungsi bagi Raja Jawa dan masyarakat Jawa. Bagi raja simbol tokoh Rama memiliki tiga fungsi utama. Pertama sebagai fungsi spiritual. Kedua adalah fungsi legitimasi kekuasaan. Ketiga adalah fungsi pencitraan. Adapun bagi masyarakat Jawa, simbol tokoh Rama memiliki dua fungsi utama. Pertama adalah fungsi spiritual. Kedua adalah fungsi filosofis.

  10. Epo's Chronicles: A Weekly Webcomic That Teaches Space Science

    Science.gov (United States)

    Cominsky, Lynn R.; Prasad, K.; Simonnet, A.; John, K.; McLin, K.; Hill, L.

    2009-01-01

    Sonoma State University Education and Public Outreach presents Epo's Chronicles: a weekly web comic about Epo, a sentient spaceship/observatory and its humanoid companion, Alkina. Follow the adventures of Epo and Alkina as they explore the Universe and try to discover their origins. The comic employs a fictional story line incorporating both recent and classic scientific discoveries from NASA missions while educating the young and the young at heart in a creative and engaging way. Each weekly "eposode” is translated into French, Italian and Spanish, and is accompanied by supporting information including glossary entries, multi-media clips, and links to additional resources. Visit Epo's Chronicles at: http://eposchronicles.com

  11. Lessons learned from IRIS EPO program evaluations

    Science.gov (United States)

    Taber, J.; Hubenthal, M.

    2012-12-01

    Evaluating the overall impact of EPO programs that include activities ranging from formal education through broad public outreach, is a complex issue. The impact of education activities targeted at narrowly defined audiences is generally easier to quantify than the national impact of outreach activities conducted by a relatively small program. For educational activities, our approach has been to leverage the best-practices identified through research and to continuously assess the individual elements internally with the intention of making improvements based on the data generated and the existing research. By constructing our elements on the best practices identified by the research community we feel that internal formative evaluation is a valid means to determine if an activity is effective, particularly when the results are compared to similar programs. For example, effective practices of professional development are well documented in the literature. As a result, this allows us to shape our programs and our evaluations to monitor elements that have been identified as key by the educational research community. Further, such actions allow us to avoid allocating significant resources with the intention of pinning down direct causal relationships between our programs and consumers, when similar interventions (conducted by others) have already shown such relationships. Ongoing review by an EPO advisory committee also provides regular oversight of program impact. While we find internal and external formative evaluation extremely useful in shaping the program and documenting its impact, we also recognize the value of a summative evaluation process. For example, an external summative evaluation of the IRIS EPO program was conducted in 2009, followed by an external panel review, as part of the regular review of IRIS programs. We found that the most valuable part of the external evaluation was our preparation, including clarifying the goals of each of the elements of the

  12. Recombinant human erythropoietin therapy in critically ill Jehovah's Witnesses.

    Science.gov (United States)

    Ball, Amanda M; Winstead, P Shane

    2008-11-01

    Blood transfusions and blood products are often given as a life-saving measure in patients with critical illness. However, some patients, such as Jehovah's Witnesses, may refuse their administration due to religious beliefs. Jehovah's Witnesses accept most available medical treatments, but not blood transfusions or blood products due to their religion's interpretation of several passages from the Bible. Since recombinant human erythropoietin (rHuEPO) became available, several cases have been reported in which rHuEPO was successfully administered to critically ill Jehovah's Witnesses. Administration of rHuEPO in combination with other blood conservation techniques has been shown to increase hemoglobin levels and survival in patients who experienced trauma, burns, general surgery, or gastrointestinal hemorrhage. We performed a literature search of the MEDLINE and International Pharmaceutical Abstracts databases of rHuEPO therapy in the Jehovah's Witness population. Fourteen cases were identified in which rHuEPO was administered to Jehovah's Witnesses who required the drug for critical care resuscitation as an alternative to blood products. In each clinical situation, rHuEPO enhanced erythropoiesis; however, time to the start of treatment, dosages, route of administration, and treatment duration varied widely. Supplementation with adjunctive agents, such as iron, folic acid, and vitamin B12, was also beneficial. Use of rHuEPO in Jehovah's Witnesses may provide an alternative to blood transfusions or blood products. Other alternatives, such as hemoglobin-based oxygen carriers and perfluorocarbons, are also being explored.

  13. An Intranasal Formulation of Erythropoietin (Neuro-EPO) Prevents Memory Deficits and Amyloid Toxicity in the APPSwe Transgenic Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Rodríguez Cruz, Yamila; Strehaiano, Manon; Rodríguez Obaya, Teresita; García Rodríguez, Julío César; Maurice, Tangui

    2017-01-01

    Erythropoietin (EPO) is a cytokine known to have effective cytoprotective action in the brain, particularly in ischemic, traumatic, inflammatory, and neurodegenerative conditions. We previously reported the neuroprotective effect of a low sialic form of EPO, Neuro-EPO, applied intranasally in rodent models of stroke or cerebellar ataxia and in a non-transgenic mouse model of Alzheimer's disease (AD). Here we analyzed the protective effect of Neuro-EPO in APPSwe mice, a reference transgenic mouse model of AD. Mice were administered 3 times a day, 3 days in the week with Neuro-EPO (125, 250 μg/kg) intranasally, between 12 and 14 months of age. Motor responses, general activity, and memory responses were analyzed during and after treatment. The deficits in spontaneous alternation, place learning in the water-maze, and novel object recognition observed in APPSwe mice were alleviated by the low dose of Neuro-EPO. Oxidative stress, neuroinflammation, trophic factor levels, and a synaptic marker were analyzed in the hippocampus or cortex of the animals. The increases in lipid peroxidation or in GFAP and Iba-1 contents in APPSwe mice were significantly reduced after Neuro-EPO. Activation of intrinsic and extrinsic apoptotic pathways was analyzed. The increases in Bax/Bcl-2 ratio, TNFα, or Fas ligand levels observed in APPSwe mice were reduced by Neuro-EPO. Finally, immunohistochemical and ELISA analyses of Aβ1-42 levels in the APPSwe mouse cortex and hippocampus showed a marked reduction in Aβ deposits and in soluble and insoluble Aβ1-42 forms. This study therefore confirmed the neuroprotective activity of EPO, particularly for an intranasally deliverable formulation, devoid of erythropoietic side effects, in a transgenic mouse model of AD. Neuro-EPO alleviated memory alterations, oxidative stress, neuroinflammation, apoptosis induction, and amyloid load in 14-month-old APPSwe mice.

  14. Some Empirical Notes on the Epo Epidemic in Professional Cycling

    Science.gov (United States)

    Lodewijkx, Hein F. M.; Brouwer, Bram

    2011-01-01

    The 1990-2010 period in professional cycling is labeled by some as the epo epidemic. Surprisingly, performance enhancement by epo and blood doping is not that clear-cut for endurance athletes, leading to the question whether doping indeed strongly influenced cyclists' performances from the 1990s onwards. We examined the records (1947-2008) of the…

  15. Epothilone B induces extrinsic pathway of apoptosis in human SKOV-3 ovarian cancer cells.

    Science.gov (United States)

    Rogalska, Aneta; Gajek, Arkadiusz; Marczak, Agnieszka

    2014-06-01

    The molecular mechanisms underlying epothilone B (EpoB) induced apoptosis were investigated in SKOV-3 human ovarian cancer cells. The aim of this research was to compare EpoB's, which belongs to the new class of anticancer drugs, with paclitaxel's (PTX) ability to induce apoptosis. The mode of cell death was assessed colorimetrically, fluorimetrically and by immunoblot analyses through measuring DNA fragmentation, the level of intracellular calcium, the level of cytochrome c, TRAIL, the cleavage of poly(ADP-ribose) polymerase (PARP) and the activation of caspase-9, -8 and -3. EpoB leads to an increase of the cytosolic level of cytochrome c after 4 h of cell treatment. After 24 and 48 h of cell treatment the level of intracellular calcium also increased by about 21% and 24% respectively. Moreover, EpoB, similarly to PTX, promoted the expression of TRAIL in lymphocytes, although high TRAIL expression on tumor cells was detected only after adding EpoB to SKOV-3 cells. EpoB mediates caspases-8 and -3 activation, which is independent of the reduction in the amount of caspase-9. Epitope-specific monoclonal and polyclonal antibodies revealed characteristic apoptotic changes that included cleavage of the 116 kDa PARP polypeptide to 25 kDa fragments. The results of our study show that EpoB induces mainly the extrinsic pathway. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Does Legalized Prostitution Increase Human Trafficking?

    OpenAIRE

    Seo-Young Cho; Axel Dreher; Eric Neumayer

    2011-01-01

    This paper investigates the impact of legalized prostitution on human trafficking inflows. According to economic theory, there are two opposing effects of unknown magnitude. The scale effect of legalized prostitution leads to an expansion of the prostitution market, increasing human trafficking, while the substitution effect reduces demand for trafficked women as legal prostitutes are favored over trafficked ones. Our empirical analysis for a cross-section of up to 150 countries shows that th...

  17. Full-automatic measurement of the ELSA working point with 'EPOS'

    International Nuclear Information System (INIS)

    Goetz, T.

    1990-11-01

    Two years ago the Bonn Electron Stretcher Accelerator ELSA came into operation. Although the control system proved to be a valuable tool for operating the machine, there did not exist any high level application software dealing with beam diagnostics, orbit measurement and closed orbit correction. To cover these main fields of machine physics, a new program 'EPOS' was implemented on top of the existing control system. EPOS integrates data aquisition, beam diagnostics, digitial signal processing and automation of measurement and control in one interactive environment. The system is equipped with a new, easy to use programming language for machine physics and data analysis. EPOS is based on X-windows and can generate high quality diagrams and printouts for all kinds of measured or simulated data. The design and implementation of EPOS is sketched in this document. Its functionality is demonstrated by performing automatic measurements of the ELSA tune with high precision. By using a special method for error correction, the obtained precision can be increased by approximately two orders of magnitude, compared to standard Fourier analysis techniques. The resulting tune values for standard ELSA operating modes are discussed in detail. (orig.) [de

  18. Desert Research and Technology Studies (DRATS) 2010 Education and Public Outreach (EPO)

    Science.gov (United States)

    Paul, Heather L.

    2013-10-01

    The Exploration Systems Mission Directorate, Directorate Integration Office conducts analog field test activities, such as Desert Research and Technology Studies (DRATS), to validate exploration system architecture concepts and conduct technology demonstrations. Education and Public Outreach (EPO) activities have been a part of DRATS missions in the past to engage students, educators, and the general public in analog activities. However, in 2010, for the first time, EPO was elevated as a principal task for the mission and metrics were collected for all EPO activities. EPO activities were planned well in advance of the mission, with emphasis on creating a multitude of activities to attract students of all ages. Web-based and social media interaction between August 31 and September 14, 2010 resulted in 62,260 DRATS Flickr views; 10,906 views of DRATS videos on YouTube; 1,483 new DRATS Twitter followers; and a 111% increase in DRATS Facebook fan interactions. Over 7,000 outreach participants were directly involved in the DRATS 2010 analog mission via student visitations at both the integrated dry-runs prior to the field mission and during the field mission; by participating in live, interactive webcasts and virtual events; and online voting to determine a traverse site as part of the NASA initiative for Participatory Exploration (PE).

  19. How bio-questionable are the different recombinant human erythropoietin copy products in Thailand?

    Science.gov (United States)

    Halim, Liem Andhyk; Brinks, Vera; Jiskoot, Wim; Romeijn, Stefan; Praditpornsilpa, Kearkiat; Assawamakin, Anunchai; Schellekens, Huub

    2014-05-01

    The high prevalence of pure red cell aplasia in Thailand has been associated with the sharp increase in number of recombinant human erythropoietin (rhEPO) copy products, based on a classical generic regulatory pathway, which have entered the market. This study aims to assess the quality of rhEPO copy products being used in Thailand. Twelve rhEPO copy products were purchased from pharmacies in Thailand, shipped under controlled cold chain conditions to the Netherlands and characterized using (1) high performance size-exclusion chromatography, (2) asymmetrical flow field-flow fractionation, (3) sodium dodecyl sulfate polyacrylamide gel electrophoresis in combination with (4) Western blotting and additionally tested for (5) host cell protein impurities as well as (6) endotoxin contamination. Some of the tested rhEPO copy products showed high aggregate levels and contained a substantial amount of protein fragments. Also, one of rhEPO copy products had a high endotoxin level, exceeding the FDA limit. Our observations show that some of the tested copy products on the Thai market differ significantly from the originator rhEPO product, Epogen®. This comparison study supports a link between the quality attributes of copy rhEPO products and their immunogenicity.

  20. Romanian contribution to research infrastructure database for EPOS

    Science.gov (United States)

    Ionescu, Constantin; Craiu, Andreea; Tataru, Dragos; Balan, Stefan; Muntean, Alexandra; Nastase, Eduard; Oaie, Gheorghe; Asimopolos, Laurentiu; Panaiotu, Cristian

    2014-05-01

    European Plate Observation System - EPOS is a long-term plan to facilitate integrated use of data, models and facilities from mainly distributed existing, but also new, research infrastructures for solid Earth Science. In EPOS Preparatory Phase were integrated the national Research Infrastructures at pan European level in order to create the EPOS distributed research infrastructures, structure in which, at the present time, Romania participates by means of the earth science research infrastructures of the national interest declared on the National Roadmap. The mission of EPOS is to build an efficient and comprehensive multidisciplinary research platform for solid Earth Sciences in Europe and to allow the scientific community to study the same phenomena from different points of view, in different time periods and spatial scales (laboratory and field experiments). At national scale, research and monitoring infrastructures have gathered a vast amount of geological and geophysical data, which have been used by research networks to underpin our understanding of the Earth. EPOS promotes the creation of comprehensive national and regional consortia, as well as the organization of collective actions. To serve the EPOS goals, in Romania a group of National Research Institutes, together with their infrastructures, gathered in an EPOS National Consortium, as follows: 1. National Institute for Earth Physics - Seismic, strong motion, GPS and Geomagnetic network and Experimental Laboratory; 2. National Institute of Marine Geology and Geoecology - Marine Research infrastructure and Euxinus integrated regional Black Sea observation and early-warning system; 3. Geological Institute of Romania - Surlari National Geomagnetic Observatory and National lithoteque (the latter as part of the National Museum of Geology) 4. University of Bucharest - Paleomagnetic Laboratory After national dissemination of EPOS initiative other Research Institutes and companies from the potential

  1. The Satellite Data Thematic Core Service within the EPOS Research Infrastructure

    Science.gov (United States)

    Manunta, Michele; Casu, Francesco; Zinno, Ivana; De Luca, Claudio; Buonanno, Sabatino; Zeni, Giovanni; Wright, Tim; Hooper, Andy; Diament, Michel; Ostanciaux, Emilie; Mandea, Mioara; Walter, Thomas; Maccaferri, Francesco; Fernandez, Josè; Stramondo, Salvatore; Bignami, Christian; Bally, Philippe; Pinto, Salvatore; Marin, Alessandro; Cuomo, Antonio

    2017-04-01

    EPOS, the European Plate Observing System, is a long-term plan to facilitate the integrated use of data, data products, software and services, available from distributed Research Infrastructures (RI), for solid Earth science in Europe. Indeed, EPOS integrates a large number of existing European RIs belonging to several fields of the Earth science, from seismology to geodesy, near fault and volcanic observatories as well as anthropogenic hazards. The EPOS vision is that the integration of the existing national and trans-national research infrastructures will increase access and use of the multidisciplinary data recorded by the solid Earth monitoring networks, acquired in laboratory experiments and/or produced by computational simulations. The establishment of EPOS will foster the interoperability of products and services in the Earth science field to a worldwide community of users. Accordingly, the EPOS aim is to integrate the diverse and advanced European Research Infrastructures for solid Earth science, and build on new e-science opportunities to monitor and understand the dynamic and complex solid-Earth System. One of the EPOS Thematic Core Services (TCS), referred to as Satellite Data, aims at developing, implementing and deploying advanced satellite data products and services, mainly based on Copernicus data (namely Sentinel acquisitions), for the Earth science community. This work intends to present the technological enhancements, fostered by EPOS, to deploy effective satellite services in a harmonized and integrated way. In particular, the Satellite Data TCS will deploy five services, EPOSAR, GDM, COMET, 3D-Def and MOD, which are mainly based on the exploitation of SAR data acquired by the Sentinel-1 constellation and designed to provide information on Earth surface displacements. In particular, the planned services will provide both advanced DInSAR products (deformation maps, velocity maps, deformation time series) and value-added measurements (source model

  2. EMSODEV and EPOS-IP: key findings for effective management of EU research infrastructure projects

    Science.gov (United States)

    Materia, Paola; Bozzoli, Sabrina; Beranzoli, Laura; Cocco, Massimo; Favali, Paolo; Freda, Carmela; Sangianantoni, Agata

    2017-04-01

    EMSO (European Multidisciplinary Seafloor and water-column Observatory, http://www.emso-eu.org) and EPOS (European Plate Observing System, https://www.epos-ip.org) are pan-European Research Infrastructures (RIs) in the ESFRI 2016 Roadmap. EMSO has recently become an ERIC (European Research Infrastructure Consortium), whilst EPOS application is in progress. Both ERICs will be hosted in Italy and the "Representing Entity" is INGV. EMSO consists of oceanic environment observation systems spanning from the Arctic through the Atlantic and Mediterranean, to the Black Sea for long-term, high-resolution, real-time monitoring of natural and man-induced processes such as hazards, climate, and marine ecosystems changes to study their evolution and interconnections. EPOS aims at creating a pan-European infrastructure for solid Earth science to support a safe and sustainable society. EPOS will enable innovative multidisciplinary research for a better understanding of Earth's physical and chemical processes controlling earthquakes, volcanic eruptions, ground instability, tsunami, and all those processes driving tectonics and Earth's surface dynamics. Following the conclusion of their Preparatory Phases the two RIs are now in their Implementation Phase still supported by the EC through the EMSODEV and EPOS-IP projects, both run by dedicated Project Management Offices at INGV with sound experience in EU projects. EMSODEV (H2020 project, 2015-2018) involves 11 partners and 9 associate partners and aims at improving the harmonization among the EMSO ERIC observation systems through the realization of EMSO Generic Instrument Modules (EGIMs), and a Data Management Platform (DMP) to implement interoperability and standardization. The DMP will provide access to data from all EMSO nodes, providing a unified, homogeneous, infrastructure-scale and user-oriented platform integrated with the increased measurement capabilities and functions provided by the EGIMs. EPOS IP (H2020 project, 2015

  3. Increased red cell 2,3-diphosphoglycerate levels in haemodialysis patients treated with erythropoietin.

    Science.gov (United States)

    Horina, J H; Schwaberger, G; Brussee, H; Sauseng-Fellegger, G; Holzer, H; Krejs, G J

    1993-01-01

    The efficacy of recombinant human erythropoietin (rHuEpo) for the treatment of renal anaemia is well established. To assess the effect of rHuEpo treatment on physical performance we evaluated physical working capacity, oxygen uptake and red cell 2,3-diphosphoglycerate (DPG) values at rest and during and after exercise on a bicycle spiroergometer in eight chronically haemodialysed patients. Follow-up examination was carried out after a mean of 14 weeks (range 9-19 weeks), when mean haemoglobin had increased from 7.8 to a stable value of 13.0 g/dl in response to rHuEpo treatment (P level without rHuEpo treatment than after correction of anaemia. Therefore rHuEpo treatment results both in better oxygen transport capacity and reduced intraerythrocytic oxygen affinity, which is followed by improved oxygen delivery to tissues per unit of haemoglobin. These effects may explain the improvement of exercise capacity observed in dialysis patients after rHuEpo treatment.

  4. Thalidomide increases human keratinocyte migration and proliferation.

    Science.gov (United States)

    Nasca, M R; O'Toole, E A; Palicharla, P; West, D P; Woodley, D T

    1999-11-01

    Thalidomide is reported to have therapeutic utility in the treatment of pyoderma gangrenosum, Behçet's disease, aphthous ulcers, and skin wounds. We investigated the effect of thalidomide on human keratinocyte proliferation and migration, two early and critical events in the re-epithelialization of skin wounds. Thalidomide at concentrations less than 1 microM did not affect keratinocyte viability. Using a thymidine incorporation assay, we found that thalidomide, at therapeutic concentrations, induced more than a 2. 5-fold increase in the proliferative potential of the cells. Keratinocyte migration was assessed by two independent motility assays: a colloidal gold assay and an in vitro scratch assay. At optimal concentrations, thalidomide increased keratinocyte migration on a collagen matrix more than 2-fold in the colloidal gold assay and more than 3-fold in the scratch assay over control. Although pro-migratory, thalidomide did not alter the level of metalloproteinase-9 secreted into culture medium. Thalidomide did, however, induce a 2-4-fold increase in keratinocyte-derived interleukin-8, a pro-migratory cellular autocrine factor. Human keratinocyte migration and proliferation are essential for re-epithelialization of skin wounds. Interleukin-8 increases human keratinocyte migration and proliferation and is chemotactic for keratinocytes. Therefore, thalidomide may modulate keratinocyte proliferation and motility by a chemokine-dependent pathway.

  5. Multi-omic profiling of EPO-producing CHO cell panel reveals metabolic adaptation to heterologous protein production

    DEFF Research Database (Denmark)

    Ley, Daniel; Kazemi Seresht, Ali; Engmark, Mikael

    The Chinese hamster ovary (CHO) cell line is the predominant mammalian cell factory for production of therapeutic glycoproteins. In this work, we aimed to study bottlenecks in the secretory pathway associated with the production of human erythropoietin (EPO) in CHO cells. In connection to this, we...... discovered indications of metabolic adaptation of the amino acid catabolism in favor of heterologous protein production. We established a panel of stably EPO expressing CHO-K1 clones spanning a 25-fold productivity range and characterized the clones in batch and chemostat cultures. For this, we employed...... a multi-omic physiological characterization including metabolic foot printing of amino acids, metabolite fingerprinting of glycolytic intermediates, NAD(P)H-/NAD(P)+ and adenosine nucleotide phosphates. We used qPCR, qRT-PCR, western blots and Affymetrix CHO microarrays to assess EPO gene copy numbers...

  6. The Doppler paradigm and the APEX-EPOS-ORANGE quandary

    International Nuclear Information System (INIS)

    Griffin, J.J.

    1995-01-01

    The experimental detection of the sharp lines of the (e + e - ) Puzzle is viewed as a struggle against Doppler broadening. Gedanken experiments which are realistic in zeroth order of detail are analyzed to show that the ORANGE and EPOS/I geometries select narrower slices of a Doppler broadened line than spherically inclusive (APEX and EPOS/II -like) apparati. Roughly speaking, the latter require event-by-event Doppler reconstruction simply to regain an even footing with the former. This suggests that APEX' or EPOS/II's coincident pair distributions must be statistically superior to those of EPOS/I or ORANGE in order to support a comparable inference about sharp structure. Under such circumstances, independent alternative data is invaluable. Therefore, a corroboration of Sakai's 330.1 keV ( + or e - bombardments of U and Th targets could prove crucial

  7. EUDAT and EPOS moving towards the efficient management of scientific data sets

    Science.gov (United States)

    Fiameni, Giuseppe; Bailo, Daniele; Cacciari, Claudio

    2016-04-01

    This abstract presents the collaboration between the European Collaborative Data Infrastructure (EUDAT) and the pan-European infrastructure for solid Earth science (EPOS) which draws on the management of scientific data sets through a reciprocal support agreement. EUDAT is a Consortium of European Data Centers and Scientific Communities whose focus is the development and realisation of the Collaborative Data Infrastructure (CDI), a common model for managing data spanning all European research data centres and data repositories and providing an interoperable layer of common data services. The EUDAT Service Suite is a set of a) implementations of the CDI model and b) standards, developed and offered by members of the EUDAT Consortium. These EUDAT Services include a baseline of CDI-compliant interface and API services - a "CDI Gateway" - plus a number of web-based GUIs and command-line client tools. On the other hand,the EPOS initiative aims at creating a pan-European infrastructure for the solid Earth science to support a safe and sustainable society. In accordance with this scientific vision, the mission of EPOS is to integrate the diverse and advanced European Research Infrastructures for solid Earth Science relying on new e-science opportunities to monitor and unravel the dynamic and complex Earth System. EPOS will enable innovative multidisciplinary research for a better understanding of the Earth's physical and chemical processes that control earthquakes, volcanic eruptions, ground instability and tsunami as well as the processes driving tectonics and Earth's surface dynamics. Through the integration of data, models and facilities EPOS will allow the Earth Science community to make a step change in developing new concepts and tools for key answers to scientific and socio-economic questions concerning geo-hazards and geo-resources as well as Earth sciences applications to the environment and to human welfare. To achieve this integration challenge and the

  8. THE EFFECTS OF IL-1 AND IL-4 ON THE EPO-INDEPENDENT ERYTHROID PROGENITOR IN POLYCYTHEMIA-VERA

    NARCIS (Netherlands)

    DEWOLF, JTM; HENDRIKS, DW; ESSELINK, MT; HALIE, MR; VELLENGA, E

    1994-01-01

    Human recombinant interleukin-1 (IL-1) was studied for its effects on the erythroid progenitors from normal subjects and from patients with polycythaemia vera (PV). No supportive effect of IL-1 was noticed on the normal, erythropoietin (Epo) dependent, erythroid burst-forming unit (BFU-E) using

  9. Similarity increases altruistic punishment in humans.

    Science.gov (United States)

    Mussweiler, Thomas; Ockenfels, Axel

    2013-11-26

    Humans are attracted to similar others. As a consequence, social networks are homogeneous in sociodemographic, intrapersonal, and other characteristics--a principle called homophily. Despite abundant evidence showing the importance of interpersonal similarity and homophily for human relationships, their behavioral correlates and cognitive foundations are poorly understood. Here, we show that perceived similarity substantially increases altruistic punishment, a key mechanism underlying human cooperation. We induced (dis)similarity perception by manipulating basic cognitive mechanisms in an economic cooperation game that included a punishment phase. We found that similarity-focused participants were more willing to punish others' uncooperative behavior. This influence of similarity is not explained by group identity, which has the opposite effect on altruistic punishment. Our findings demonstrate that pure similarity promotes reciprocity in ways known to encourage cooperation. At the same time, the increased willingness to punish norm violations among similarity-focused participants provides a rationale for why similar people are more likely to build stable social relationships. Finally, our findings show that altruistic punishment is differentially involved in encouraging cooperation under pure similarity vs. in-group conditions.

  10. Exposure to Hedione Increases Reciprocity in Humans

    Directory of Open Access Journals (Sweden)

    Sebastian Berger

    2017-05-01

    Full Text Available Cooperation among unrelated humans is frequently regarded as a defining feature in the evolutionary success of our species. Whereas, much research has addressed the strategic and cognitive mechanisms that underlie cooperation, investigations into chemosensory processes have received very limited research attention. To bridge that gap, we build on recent research that has identified the chemically synthesized odorant Hedione (HED as a ligand for the putative human pheromone receptor (VN1R1 expressed in the olfactory mucosa, and hypothesize that exposure to HED may increase reciprocity. Applying behavioral economics paradigms, the present research shows that exposure to the ligand causes differentiated behavioral effects in reciprocal punishments (Study 1 as well as rewards (Study 2, two types of behaviors that are frequently regarded as essential for the development and maintenance of cooperation.

  11. Exposure to Hedione Increases Reciprocity in Humans

    Science.gov (United States)

    Berger, Sebastian; Hatt, Hanns; Ockenfels, Axel

    2017-01-01

    Cooperation among unrelated humans is frequently regarded as a defining feature in the evolutionary success of our species. Whereas, much research has addressed the strategic and cognitive mechanisms that underlie cooperation, investigations into chemosensory processes have received very limited research attention. To bridge that gap, we build on recent research that has identified the chemically synthesized odorant Hedione (HED) as a ligand for the putative human pheromone receptor (VN1R1) expressed in the olfactory mucosa, and hypothesize that exposure to HED may increase reciprocity. Applying behavioral economics paradigms, the present research shows that exposure to the ligand causes differentiated behavioral effects in reciprocal punishments (Study 1) as well as rewards (Study 2), two types of behaviors that are frequently regarded as essential for the development and maintenance of cooperation. PMID:28512400

  12. Therapeutic implications of recombinant human erythropoietin in ...

    African Journals Online (AJOL)

    AJB SERVER

    2006-12-29

    Dec 29, 2006 ... quence of both, RHUEPO has achieved the highest annual sales ... analysis of the US Medicare database (Ma et al., 1999) ... blood transfusions and improves quality of life (Eschbach, ... Large doses of EPO results increase in blood pressure .... human erythropoietin was obtained from human genomic.

  13. Exercise increases circulating GDF15 in humans

    Directory of Open Access Journals (Sweden)

    Maximilian Kleinert

    2018-03-01

    Full Text Available Objective: The growth differentiation factor 15 (GDF15 is a stress-sensitive circulating factor that regulates systemic energy balance. Since exercise is a transient physiological stress that has pleiotropic effects on whole-body energy metabolism, we herein explored the effect of exercise on a circulating GDF15 levels and b GDF15 release from skeletal muscle in humans. Methods: Seven healthy males either rested or exercised at 67% of their VO2max for 1 h and blood was sampled from the femoral artery and femoral vein before, during, and after exercise. Plasma GDF15 concentrations were determined in these samples. Results: Plasma GDF15 levels increased 34% with exercise (p < 0.001 and further increased to 64% above resting values at 120 min (p < 0.001 after the cessation of exercise. There was no difference between the arterial and venous GDF15 concentration before, during, and after exercise. During a resting control trial, GDF15 levels measured in the same subjects were unaltered. Conclusions: Vigorous submaximal exercise increases circulating GDF15 levels in humans, but skeletal muscle tissue does not appear to be the source. Keywords: Skeletal muscle, Growth differentiation factor 15, Recovery, Physical activity

  14. Biologically active, magnICON®-expressed EPO-Fc from stably transformed Nicotiana benthamiana plants presenting tetra-antennary N-glycan structures.

    Science.gov (United States)

    Nagels, Bieke; Van Damme, Els J M; Callewaert, Nico; Zabeau, Lennart; Tavernier, Jan; Delanghe, Joris R; Boets, Annemie; Castilho, Alexandra; Weterings, Koen

    2012-08-31

    In the past two decades plants have emerged as a valuable alternative for the production of pharmaceutical proteins. Since N-glycosylation influences functionality and stability of therapeutic proteins, the plant N-glycosylation pathway should be humanized. Here, we report the transient magnICON(®) expression of the erythropoietin fusion protein (EPO-Fc) in Nicotiana benthamiana plants that produce multi-antennary N-glycans without the plant-specific β1,2-xylose and α1,3-fucose residues in a stable manner (Nagels et al., 2011). The EPO-Fc fusion protein consists of EPO with a C-terminal-linked IgG-Fc domain and is used for pulmonary delivery of recombinant EPO to patients (Bitonti et al., 2004). Plant expressed EPO-Fc was quantified using a paramagnetic-particle chemiluminescent immunoassay and shown to be active in vitro via receptor binding experiments in HEK293T cells. Mass spectrometry-based N-glycan analysis confirmed the presence of multi-antennary N-glycans on plant-expressed EPO-Fc. The described research is the next step towards the development of a production platform for pharmaceutical proteins in plants. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. The EPOS Legal and Governance Framework : tailoring the infrastructure to fit the needs of the EPOS services

    Science.gov (United States)

    Kohler, Elisabeth; Pedersen, Helle; Kontkanen, Pirjo; Korja, Annakaisa; Lauterjung, Jörn; Haslinger, Florian; Sangianantoni, Agata; Bartolini, Alessandro; Consortium, Epos

    2016-04-01

    One of the most important issues regarding a pan-European distributed large scale research infrastructure is the setting up of its legal and governance structure as this will shape the very operation of the undertaking, i.e. the decision-making process, the allocation of tasks and resources as well as the relationship between the different bodies. Ensuring long-term operational services requires a robust, coherent and transparent legal and governance framework across all of the EPOS TCS (Thematic Core Services) and ICS (Integrated Core Services) that is well aligned to the EPOS global architecture. The chosen model for the EPOS legal entity is the ERIC (European Research Infrastructure Consortium). While the statutory seat of EPOS-ERIC will be in Rome, Italy, most of the services will be hosted in other countries. Specific agreements between EPOS-ERIC and the legal bodies hosting EPOS services will be implemented to allow proper coordination of activities. The objective is to avoid multiple agreements and, where possible, to standardize them in order to reach a harmonized situation across all services. For the governance careful attention will be paid to the decision-making process, the type of decisions and the voting rights, the definition of responsibilities, rights and duties, the reporting mechanisms, as well as other issues like who within a TCS represents the service to the 'outside' world or who advices the TCS on which subjects. Data policy is another crucial issue as EPOS aims to provide interdisciplinary services to researchers interested in geoscience, including access to data, metadata, data products, software and IT tools. EPOS also provides access to computational resources for visualization and processing. Beyond the general principles of Open Access and Open Source the following questions have to be addressed: scope and nature of data that will be accepted; intellectual property rights in data and terms under which data will be shared; openness and

  16. EPOS Thematic Core Service Anthropogenic Hazards for SHEER project: maintain, process and manage your project research data

    Science.gov (United States)

    Orlecka-Sikora, Beata; Lasocki, Stanislaw; Staszek, Monika; Olszewska, Dorota; Urban, Pawel; Jaroslawski, Janusz; Cielesta, Szymon; Mirek, Janusz; Wiszniowski, Jan; Picozzi, Matteo; Solaro, Giuseppe; Pringle, Jamie; Toon, Sam; Cesca, Simone; Kuehn, Daniela; Ruigrok, Elmer; Gunning, Andrew; Isherwood, Catherine

    2017-04-01

    The main objective of the "Shale gas exploration and exploitation induced risks - SHEER" project (Horizon 2020, call LCE 16-2014) is to develop a probabilistic methodology to assess and mitigate the short- and the long-term environmental risks associated with the exploration and exploitation of shale gas. To this end, the SHEER project makes use of a large amount of heterogeneous data of various types. This data, from different disciplines of science e.g. geophysical, geochemical, geological, technological, etc., must be homogenized, harmonized and made accessible exclusively for all project participants. This requires to develop an over-arching structure for high-level multidisciplinary data integration. The bespoke solution is provided by Thematic Core Service Anthropogenic Hazards (TCS AH) developed in the framework of European Plate Observing System Program (https://tcs.ah-epos.eu/, infrastructural projects IS-EPOS, POIG.02.03.00-14-090/13-00 and EPOS IP, H2020-INFRADEV-1-2015-1). TCS AH provides virtual access to a comprehensive, wide-scale and high quality research infrastructure in the field of induced seismicity and other anthropogenic hazards evoked by exploration and exploitation of geo-resources. TCS AH is designed as a functional e-research environment to ensure a researcher the maximum possible freedom for experimentation by providing a virtual laboratory flexible to create own workspace for processing streams. A data-management process promotes the use of research infrastructure in novel ways providing an access to (i) data gathered in the so-called "episodes", comprehensively describing a geophysical process, induced or triggered by human technological activity, which under certain circumstances can become hazardous for people, infrastructure and the environment, (ii) problem-oriented, specific services, with the particular attention devoted to methods analyzing correlations between technology, geophysical response and resulting hazards, (iii) the

  17. Exercise increases circulating GDF15 in humans

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Clemmensen, Christoffer; Sjøberg, Kim Anker

    2018-01-01

    OBJECTIVE: The growth differentiation factor 15 (GDF15) is a stress-sensitive circulating factor that regulates systemic energy balance. Since exercise is a transient physiological stress that has pleiotropic effects on whole-body energy metabolism, we herein explored the effect of exercise on a......) circulating GDF15 levels and b) GDF15 release from skeletal muscle in humans. METHODS: Seven healthy males either rested or exercised at 67% of their VO2max for 1 h and blood was sampled from the femoral artery and femoral vein before, during, and after exercise. Plasma GDF15 concentrations were determined...... in these samples. RESULTS: Plasma GDF15 levels increased 34% with exercise (p exercise. There was no difference between the arterial and venous GDF15 concentration before, during, and after exercise. During...

  18. The SDO Education and Outreach (E/PO) Program: Changing Perceptions One Program at a Time

    Science.gov (United States)

    Drobnes, E.; Littleton, A.; Pesnell, W. D.; Buhr, S.; Beck, K.; Durscher, R.; Hill, S.; McCaffrey, M.; McKenzie, D. E.; Myers, D.; hide

    2011-01-01

    The Solar Dynamics Observatory (SDO) Education and Public Outreach (E/PO) program began as a series of discrete efforts implemented by each of the instrument teams and has evolved into a well-rounded program with a full suite of national and international programs. The SDO E/PO team has put forth much effort in the past few years to increase our cohesiveness by adopting common goals and increasing the amount of overlap between our programs. In this paper, we outline the context and overall philosophy for our combined programs, present a brief overview of all SDO E/PO programs along with more detailed highlight of a few key programs, followed by a review of our results up to date. Concluding is a summary of the successes, failures, and lessons learned that future missions can use as a guide, while further incorporating their own content to enhance the public's knowledge and appreciation of NASA?s science and technology as well as its benefit to society.

  19. EPOS data and service provision to scientists and other stakeholders

    Science.gov (United States)

    Cocco, Massimo; EPOS Team

    2017-04-01

    EPOS brings together European nations and combines solid Earth science infrastructures and their associated data and services together with the scientific expertise into one integrated delivery system for solid Earth science. By improving and facilitating the integration, access, use, and re-use of solid Earth science data, data products, services and facilities EPOS is developing a holistic, sustainable, multidisciplinary research platform to provide coordinated access to harmonized and quality controlled data from diverse Earth science disciplines, together with tools for their use in analysis and modelling. EPOS has been designed with the vision of creating a single distributed pan-European infrastructure for solid Earth science to support a safe and sustainable society. In accordance with this scientific vision, the EPOS mission is to integrate the diverse and advanced European Research Infrastructures for solid Earth relying on new e-science opportunities to monitor and unravel the dynamic and complex Earth System. EPOS is presently in its implementation phase, which consists of the EPOS IP project and the legal establishment of EPOS-ERIC. The EPOS Implementation Phase builds on the achievements of the successful EPOS Preparatory Phase project. The EPOS implementation phase will last from 2015 to 2019. The key objectives of the project are: implementing Thematic Core Services (TCS), the domain-specific service hubs for coordinating and harmonizing national resources/plans with the European dimension of EPOS; building the Integrated Core Services (ICS) to provide a novel research platform to different stakeholders; designing the access to distributed computational resources (ICS-D); ensuring sustainability and governance of TCS and EPOS-ERIC. Here we present the activities planned for the implementation phase focusing on the TCS, the ICS and on their interoperability. We will present and discuss the data and service provision focusing on the data, data

  20. Hyperthyroidism increases brown fat metabolism in humans.

    Science.gov (United States)

    Lahesmaa, Minna; Orava, Janne; Schalin-Jäntti, Camilla; Soinio, Minna; Hannukainen, Jarna C; Noponen, Tommi; Kirjavainen, Anna; Iida, Hidehiro; Kudomi, Nobuyuki; Enerbäck, Sven; Virtanen, Kirsi A; Nuutila, Pirjo

    2014-01-01

    Thyroid hormones are important regulators of brown adipose tissue (BAT) development and function. In rodents, BAT metabolism is up-regulated by thyroid hormones. The purpose of this article was to investigate the impact of hyperthyroidism on BAT metabolism in humans. This was a follow-up study using positron emission tomography imaging. Glucose uptake (GU) and perfusion of BAT, white adipose tissue, skeletal muscle, and thyroid gland were measured using [18F]2-fluoro-2-deoxy-D-glucose and [15O]H2O and positron emission tomography in 10 patients with overt hyperthyroidism and in 8 healthy participants. Five of the hyperthyroid patients were restudied after restoration of euthyroidism. Supraclavicular BAT was quantified with magnetic resonance imaging or computed tomography and energy expenditure (EE) with indirect calorimetry. Compared with healthy participants, hyperthyroid participants had 3-fold higher BAT GU (2.7±2.3 vs 0.9±0.1 μmol/100 g/min, P=.0013), 90% higher skeletal muscle GU (Phyperthyroidism, serum free T4 and free T3 were strongly associated with EE and lipid oxidation rates (Pmetabolism (PHyperthyroidism had no effect on BAT perfusion, whereas it stimulated skeletal muscle perfusion (P=.04). Thyroid gland GU did not differ between hyperthyroid and euthyroid study subjects. Hyperthyroidism increases GU in BAT independently of BAT perfusion. Hyperthyroid patients are characterized by increased skeletal muscle metabolism and lipid oxidation rates.

  1. Recombinant human erythropoietin stimulates angiogenesis and wound healing in the genetically diabetic mouse.

    Science.gov (United States)

    Galeano, Mariarosaria; Altavilla, Domenica; Cucinotta, Domenico; Russo, Giuseppina T; Calò, Margherita; Bitto, Alessandra; Marini, Herbert; Marini, Rolando; Adamo, Elena B; Seminara, Paolo; Minutoli, Letteria; Torre, Valerio; Squadrito, Francesco

    2004-09-01

    The effects of recombinant human erythropoietin (rHuEPO) in diabetes-related healing defects were investigated by using an incisional skin-wound model produced on the back of female diabetic C57BL/KsJ-m(+/+)Lept(db) mice (db(+)/db(+)) and their normoglycemic littermates (db(+/+)m). Animals were treated with rHuEPO (400 units/kg in 100 microl s.c.) or its vehicle alone (100 microl). Mice were killed on different days (3, 6, and 12 days after skin injury) for measurement of vascular endothelial growth factor (VEGF) mRNA expression and protein synthesis, for monitoring angiogenesis by CD31 expression, and for evaluating histological changes. Furthermore, we evaluated wound-breaking strength at day 12. At day 6, rHuEPO injection in diabetic mice resulted in an increase in VEGF mRNA expression (vehicle = 0.33 +/- 0.1 relative amount of mRNA; rHuEPO = 0.9 +/- 0.09 relative amount of mRNA; P < 0.05) and protein wound content (vehicle = 23 +/- 5 pg/wound; rHuEPO = 92 +/- 12 pg/wound; P < 0.05) and caused a marked increase in CD31 gene expression (vehicle = 0.18 +/- 0.05 relative amount of mRNA; rHuEPO = 0.98 +/- 0.21 relative amount of mRNA; P < 0.05) and protein synthesis. Furthermore, rHuEPO injection improved the impaired wound healing and, at day 12, increased the wound-breaking strength in diabetic mice (vehicle = 12 +/- 2 g/mm; rHuEPO 21 +/- 5 g/mm; P < 0.05). Erythropoietin may have a potential application in diabetes-related wound disorders.

  2. Partnerships: The Key to Sustainability and Reach for E/PO

    Science.gov (United States)

    Eisenhamer, Bonnie; McCallister, D.; Ryer, H.

    2013-06-01

    The Space Telescope Science Institute (STScI) is the home institution for the E/PO activities of the Hubble and future James Webb space telescopes. Over time, STScI’s Office of Public Outreach has established the infrastructure needed for an E/PO program that reaches various audiences at the local, regional, and national levels. Partnerships are a critical element of this infrastructure, and sustainability of our E/PO program is ensured through our ongoing partnerships with organizations and institutions with staying power and reach. We have learned from past efforts that strategic partnerships can foster innovation, support diversity initiatives, and increase impact in a cost-effective way while providing target audiences with greater access to NASA SMD science and resources. Partnerships are utilized to field-test educational products and programs, disseminate materials and initiatives, and support professional development activities. Partners are selected based upon specific criteria such as potential for reach, the percentage of underrepresented educators and students served, complementary program goals, and willingness to collect and share evaluation data and results with us. This poster will highlight examples and benefits of strategic partnerships over time.

  3. E-research platform of EPOS Thematic Core Service "ANTHROPOGENIC HAZARDS"

    Science.gov (United States)

    Orlecka-Sikora, Beata; Lasocki, Stanisław; Grasso, Jean Robert; Schmittbuhl, Jean; Kwiatek, Grzegorz; Garcia, Alexander; Cassidy, Nigel; Sterzel, Mariusz; Szepieniec, Tomasz; Dineva, Savka; Biggare, Pascal; Saccorotti, Gilberto; Sileny, Jan; Fischer, Tomas

    2016-04-01

    EPOS Thematic Core Service ANTHROPOGENIC HAZARDS (TCS AH) aims to create new research opportunities in the field of anthropogenic hazards evoked by exploitation of georesources. TCS AH, based on the prototype built in the framework of the IS-EPOS project (https://tcs.ah-epos.eu/), financed from Polish structural funds (POIG.02.03.00-14-090/13-00), is being further developed within EPOS IP project (H2020-INFRADEV-1-2015-1, INFRADEV-3-2015). TCS AH is designed as a functional e-research environment to ensure a researcher the maximum possible freedom for in silico experimentation by providing a virtual laboratory in which researcher will be able to create own workspace with own processing streams. The unique integrated RI is: (i) data gathered in the so- called "episodes", comprehensively describing a geophysical process, induced or triggered by human technological activity, which under certain circumstances can become hazardous for people, infrastructure and the environment and (ii) problem-oriented, specific high-level services, with the particular attention devoted to methods analyzing correlations between technology, geophysical response and resulting hazard. Services to be implemented are grouped within six blocks: (1) Basic services for data integration and handling; (2) Services for physical models of stress/strain changes over time and space as driven by geo-resource production; (3) Services for analysing geophysical signals; (4) Services to extract the relation between technological operations and observed induced seismic/deformation; (5) Services to quantitative probabilistic assessments of anthropogenic seismic hazard - statistical properties of anthropogenic seismic series and their dependence on time-varying anthropogenesis; ground motion prediction equations; stationary and time-dependent probabilistic seismic hazard estimates, related to time-changeable technological factors inducing the seismic process; (6) Simulator for Multi

  4. Therapy of an incomplete spinal cord injury by intrathecal injection of EPO and subcutaneous injection of EPO, vitamin C and G-CSF.

    Science.gov (United States)

    Bader, Augustinus; Reinhardt, Martin; Beuthe, Achim; Röhl, Klaus; Giri, Shibashish

    2017-01-01

    Spinal cord injury is a rare disease with an incidence about 40 cases per million population in the USA. The most common reasons are traffic accidents, falls, violence and sports. A 53-year-old male patient presented with an incomplete tetraparesis as a result of a spinal cord injury after the accident. It was not possible to treat him with steroids because he was out of the therapeutic time period of 8 hours when he presented to the hospital. The main problem of spinal cord injuries is the secondary injury caused by inflammation and swelling of the spinal cord. To avoid this, the patient was experimentally treated with erythropoietin (EPO) intrathecal and EPO, granulocyte-colony-stimulating factor and vitamin C subcutaneous after his initial spinal cord relief surgery. These drugs might be able to relieve this secondary reaction but were never applied for this indication in human before. This study shows that it could be a promising treatment for spinal cord injuries with potential therapeutic benefits.

  5. Improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in PEG–PLA micelle

    Directory of Open Access Journals (Sweden)

    Shi YN

    2012-12-01

    Full Text Available Yanan Shi,1,2,* Wan Huang,1,* Rongcai Liang,1–3 Kaoxiang Sun,2,3 Fangxi Zhang,2,3 Wanhui Liu,2,3 Youxin Li1–31College of Life Science, Jilin University, Changchun, China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Luye Pharmaceutical Co, Ltd, Yantai, China; 3School of Pharmacy, Yantai University, Yantai, China*These authors contributed equally to this workAbstract: To improve the pharmacokinetics and stability of recombinant human erythropoietin (rhEPO, rhEPO was successfully formulated into poly(ethylene glycol–poly(d,l-lactide (PEG–PLA di-block copolymeric micelles at diameters ranging from 60 to 200 nm with narrow polydispersity indices (PDIs; PDI < 0.3 and trace amount of protein aggregation. The zeta potential of the spherical micelles was in the range of −3.78 to 4.65 mV and the highest encapsulation efficiency of rhEPO in the PEG–PLA micelles was about 80%. In vitro release profiles indicated that the stability of rhEPO in the micelles was improved significantly and only a trace amount of aggregate was found. Pharmacokinetic studies in rats showed highly enhanced plasma retention time of the rhEPO-loaded PEG-PLA micelles in comparison with the native rhEPO group. Increased hemoglobin concentrations were also found in the rat study. Native polyacrylamide gel electrophoresis results demonstrated that rhEPO was successfully encapsulated into the micelles, which was stable in phosphate buffered saline with different pHs and concentrations of NaCl. Therefore, PEG–PLA micelles can be a potential protein drug delivery system.Keywords: rhEPO, PEG–PLA micelle, in vitro, pharmacokinetics, pharmacodynamics

  6. Ethical implication of providing scientific data and services to diverse stakeholders: the case of the EPOS research infrastructure

    Science.gov (United States)

    Freda, Carmela; Atakan, Kuvvet; Cocco, Massimo

    2017-04-01

    EPOS, the European Plate Observing System, is an ESFRI infrastructure serving the needs of the solid Earth science community as a whole. EPOS promotes the use of multidisciplinary solid Earth data to improve the understanding of physical and chemical processes controlling earthquakes, volcanic eruptions, tsunamis as well as those driving tectonics and surface dynamics. The EPOS mission is to create a single, sustainable, and distributed infrastructure that integrates the diverse European research infrastructures for solid Earth science under a common framework with the final goal of delivering a suite of domain-specific and multidisciplinary data, products, and services in one single and integrated platform. Addressing ethics issues is a relevant challenge for any initiative, program or project dealing with scientific data and products provision, access to services for scientific purposes and communication with different stakeholders, including industry and society at large. In examining the role of EPOS on openly and freely delivering scientific data and products to diverse stakeholders including but not limited to scientists, we are looking at ethical issues associated with the use and re-use of these data and products possibly leading to a malevolent use and/or misuse of the data with implications on, for example, national security, environmental protection and risk communication. Moreover, EPOS is aware that the research promoted by the use of data delivered through its platform can have a profound influence on the environment, human health and wellbeing, economic development, and other facets of societies. We know there is nothing intrinsically bad about openly and freely delivering scientific data, as it serves as a tool for leveraging researches leading to solutions for a responsible management of Earth's resources and mitigation of natural hazards. However, we must evaluate the effects of such a data provision and feel the obligation to adopt a responsible

  7. The Demonstrator for the European Plate Observing System (EPOS)

    Science.gov (United States)

    Hoffmann, T. L.; Euteneuer, F.; Ulbricht, D.; Lauterjung, J.; Bailo, D.; Jeffery, K. G.

    2014-12-01

    An important outcome of the 4-year Preparatory Phase of the ESFRI project European Plate Observing System (EPOS) was the development and first implementation of the EPOS Demonstrator by the project's ICT Working Group 7. The Demonstrator implements the vertical integration of the three-layer architectural scheme for EPOS, connecting the Integrated Core Services (ICS), Thematic Core Services (TCS) and the National Research Infrastructures (NRI). The demonstrator provides a single GUI with central key discovery and query functionalities, based on already existing services by the seismic, geologic and geodetic communities. More specifically the seismic services of the Demonstrator utilize webservices and APIs for data and discovery of raw seismic data (FDSN webservices by the EIDA Network), events (Geoportal by EMSC) and analytical data products (e.g., hazard maps by EFEHR via OGC WMS). For geologic services, the EPOS Demonstrator accesses OneGeology Europe which serves the community with geologic maps and point information via OGC webservices. The Demonstrator also provides access to raw geodetic data via a newly developed universal tool called GSAC. The Demonstrator itself resembles the future Integrated Core Service (ICS) and provides direct access to the end user. Its core functionality lies in a metadata catalogue, which serves as the central information hub and stores information about all RIs, related persons, projects, financial background and technical access information. The database schema of the catalogue is based on CERIF, which has been slightly adapted. Currently, the portal provides basic query functions as well as cross domain search. [www.epos.cineca.it

  8. 2017 Solar Eclipse in Hopkinsville, KY: E/PO Feedback from Two Venues

    Science.gov (United States)

    Dowling, Timothy E.; Consolmagno, Guy

    2017-10-01

    Hopkinsville, Kentucky was the largest town in the region of maximum totality for the 21 August 2017 Solar Eclipse, and transformed itself into “Eclipseville” with extensive media attention. Here we give 2 on-the-ground reports on education and public outreach (E/PO) activities from Hopkinsville. One of us (TD) partnered with the Kentucky Division of Emergency Management (KYEM) and was in the Hopkinsville VIP area, and the other (GC) led a series of E/PO events at the Hopkinsville Church of Ss. Peter & Paul, which were nationally advertised in diocesan newspapers. In addition, both of us were interviewed extensively by local and national media before the event. Pre-event planning by KYEM extended for over a year, and culminated in a 6-hour, 12 July 2017 Tabletop Exercise (TTX) run by FEMA. This face-to-face workshop drew over 250 participants, including Kentucky’s Lt. Governor, health and public safety officials at the state-level and from the 21 Kentucky counties in the path of totality, mayors and convention-bureau officials from the affected KY towns, the KY National Guard, the U.S. Depts. of Health and Human Services, Homeland Security, and Transportation, the National Weather Service, the U.S. Coast Guard for riverboat traffic, the U.S. Forest Service, the American Red Cross, representatives from ATT, Verizon and Sprint, and representatives from local universities—it was the largest TTX in Kentucky’s history. Here, we report on E/PO feedback we assembled from the VIP and parochial sites, including the most frequently asked questions, which types of answers seemed to be most effective, and how actual events compared with the large-crowd preparations and planning.

  9. [The effect of hypoxia preconditioning no binding activity of HIF-1 on the HRE with EPO in the hippocampus of mice].

    Science.gov (United States)

    Shao, Guo; Zhou, Wei-Hua; Gao, Cui-Ying; Zhang, Ran; Lu, Guo-Wei

    2007-02-01

    To observe change of binding activity of HIF-1 with erythropoietin (EPO) hypoxia response element (HRE) in the hippocampus of mice preconditioned to hypoxia and explore relationship between the changes and the preconditioning. The hippocampus was removed from mice exposed to hypoxia for 0 run (control group), 1 run (H1 group) and 4 runs(H4 group). Electrophoretic mobility shift assays (EMSA), chromatin immunoprecipitation (ChIP)and real time PCR were used to detect the change of activity of HIF-1 on HRE of EPO. Both in vitro and in vivo binding tests showed that the HIF-1 DNA-binding activities were increased in group H1 and markedly increased in group H4. The increase of HIF-1 and HRE of EPO binding activities is thought be involved in hypoxic preconditioning.

  10. Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

    2017-05-01

    Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 in a lipid emulsion and dietary cholesterol with cholesterol-d 5 and sitostanol-d 4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE, P <0.0001) and low-density lipoprotein cholesterol 19.8±1.9% ( P =0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% ( P <0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% ( P <0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% ( P =0.0096). Fecal bile acids were unchanged. Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758. © 2017 American Heart Association, Inc.

  11. European Plate Observing System - Norway (EPOS-N): A National Consortium for the Norwegian Implementation of EPOS

    Science.gov (United States)

    Atakan, Kuvvet; Tellefsen, Karen

    2017-04-01

    The European Plate Observing System (EPOS) aims to create a pan-European infrastructure for solid Earth science to support a safe and sustainable society. The main vision of the European Plate Observing System (EPOS) is to address the three basic challenges in Earth Science: (i) unravelling the Earth's deformational processes which are part of the Earth system evolution in time, (ii) understanding geo-hazards and their implications to society, and (iii) contributing to the safe and sustainable use of geo-resources. The mission of EPOS-Norway is therefore in line with the European vision of EPOS, i.e. monitor and understand the dynamic and complex Earth system by relying on new e-science opportunities and integrating diverse and advanced Research Infrastructures for solid Earth science. The EPOS-Norway project started in January 2016 with a national consortium consisting of six institutions. These are: University of Bergen (Coordinator), NORSAR, National Mapping Authority, Geological Survey of Norway, Christian Michelsen Research and University of Oslo. EPOS-N will during the next five years focus on the implementation of three main components. These are: (i) Developing a Norwegian e-Infrastructure to integrate the Norwegian Solid Earth data from the seismological and geodetic networks, as well as the data from the geological and geophysical data repositories, (ii) Improving the monitoring capacity in the Arctic, including Northern Norway and the Arctic islands, and (iii) Establishing a national Solid Earth Science Forum providing a constant feedback mechanism for improved integration of multidisciplinary data, as well as training of young scientists for future utilization of all available solid Earth observational data through a single e-infrastructure. Currently, a list of data, data products, software and services (DDSS) is being prepared. These elements will be integrated in the EPOS-N data/web-portal, which will allow users to browse, select and download

  12. The EPOS Vision for the Open Science Cloud

    Science.gov (United States)

    Jeffery, Keith; Harrison, Matt; Cocco, Massimo

    2016-04-01

    Cloud computing offers dynamic elastic scalability for data processing on demand. For much research activity, demand for computing is uneven over time and so CLOUD computing offers both cost-effectiveness and capacity advantages. However, as reported repeatedly by the EC Cloud Expert Group, there are barriers to the uptake of Cloud Computing: (1) security and privacy; (2) interoperability (avoidance of lock-in); (3) lack of appropriate systems development environments for application programmers to characterise their applications to allow CLOUD middleware to optimize their deployment and execution. From CERN, the Helix-Nebula group has proposed the architecture for the European Open Science Cloud. They are discussing with other e-Infrastructure groups such as EGI (GRIDs), EUDAT (data curation), AARC (network authentication and authorisation) and also with the EIROFORUM group of 'international treaty' RIs (Research Infrastructures) and the ESFRI (European Strategic Forum for Research Infrastructures) RIs including EPOS. Many of these RIs are either e-RIs (electronic-RIs) or have an e-RI interface for access and use. The EPOS architecture is centred on a portal: ICS (Integrated Core Services). The architectural design already allows for access to e-RIs (which may include any or all of data, software, users and resources such as computers or instruments). Those within any one domain (subject area) of EPOS are considered within the TCS (Thematic Core Services). Those outside, or available across multiple domains of EPOS, are ICS-d (Integrated Core Services-Distributed) since the intention is that they will be used by any or all of the TCS via the ICS. Another such service type is CES (Computational Earth Science); effectively an ICS-d specializing in high performance computation, analytics, simulation or visualization offered by a TCS for others to use. Already discussions are underway between EPOS and EGI, EUDAT, AARC and Helix-Nebula for those offerings to be

  13. A Conjugated Aptamer-Gold Nanoparticle Fluorescent Probe for Highly Sensitive Detection of rHuEPO

    Directory of Open Access Journals (Sweden)

    Zhaoyang Zhang

    2011-11-01

    Full Text Available We present here a novel conjugated aptamer-gold nanoparticle (Apt-AuNPs fluorescent probe and its application for specific detection of recombinant human erythropoietin-α (rHuEPO-α. In this nanobiosensor, 12 nm AuNPs function as both a nano-scaffold and a nano-quencher (fluorescent energy acceptor, on the surface of which the complementary sequences are linked (as cODN-AuNPs and pre-hybridized with carboxymethylfluorescein (FAM-labeled anti-rHuEPO-α aptamers. Upon target protein binding, the aptamers can be released from the AuNP surface and the fluorescence signal is restored. Key variables such as the length of linker, the hybridization site and length have been designed and optimized. Full performance evaluation including sensitivity, linear range and interference substances are also described. This nanobiosensor provides a promising approach for a simple and direct quantification of rHuEPO-α concentrations as low as 0.92 nM within a few hours.

  14. Setting the stage for the EPOS ERIC: Integration of the legal, governance and financial framework

    Science.gov (United States)

    Atakan, Kuvvet; Bazin, Pierre-Louis; Bozzoli, Sabrina; Freda, Carmela; Giardini, Domenico; Hoffmann, Thomas; Kohler, Elisabeth; Kontkanen, Pirjo; Lauterjung, Jörn; Pedersen, Helle; Saleh, Kauzar; Sangianantoni, Agata

    2017-04-01

    EPOS - the European Plate Observing System - is the ESFRI infrastructure serving the need of the solid Earth science community at large. The EPOS mission is to create a single sustainable, and distributed infrastructure that integrates the diverse European Research Infrastructures for solid Earth science under a common framework. Thematic Core Services (TCS) and Integrated Core Services (Central Hub, ICS-C and Distributed, ICS-D) are key elements, together with NRIs (National Research Infrastructures), in the EPOS architecture. Following the preparatory phase, EPOS has initiated formal steps to adopt an ERIC legal framework (European Research Infrastructure Consortium). The statutory seat of EPOS will be in Rome, Italy, while the ICS-C will be jointly operated by France, UK and Denmark. The TCS planned so far cover: seismology, near-fault observatories, GNSS data and products, volcano observations, satellite data, geomagnetic observations, anthropogenic hazards, geological information modelling, multiscale laboratories and geo-energy test beds for low carbon energy. In the ERIC process, EPOS and all its services must achieve sustainability from a legal, governance, financial, and technical point of view, as well as full harmonization with national infrastructure roadmaps. As EPOS is a distributed infrastructure, the TCSs have to be linked to the future EPOS ERIC from legal and governance perspectives. For this purpose the TCSs have started to organize themselves as consortia and negotiate agreements to define the roles of the different actors in the consortium as well as their commitment to contribute to the EPOS activities. The link to the EPOS ERIC shall be made by service agreements of dedicated Service Providers. A common EPOS data policy has also been developed, based on the general principles of Open Access and paying careful attention to licensing issues, quality control, and intellectual property rights, which shall apply to the data, data products

  15. The European Plate Observing System (EPOS): Integrating Thematic Services for Solid Earth Science

    Science.gov (United States)

    Atakan, Kuvvet; Bailo, Daniele; Consortium, Epos

    2016-04-01

    The mission of EPOS is to monitor and understand the dynamic and complex Earth system by relying on new e-science opportunities and integrating diverse and advanced Research Infrastructures in Europe for solid Earth Science. EPOS will enable innovative multidisciplinary research for a better understanding of the Earth's physical and chemical processes that control earthquakes, volcanic eruptions, ground instability and tsunami as well as the processes driving tectonics and Earth's surface dynamics. Through integration of data, models and facilities EPOS will allow the Earth Science community to make a step change in developing new concepts and tools for key answers to scientific and socio-economic questions concerning geo-hazards and geo-resources as well as Earth sciences applications to the environment and to human welfare. EPOS, during its Implementation Phase (EPOS-IP), will integrate multidisciplinary data into a single e-infrastructure. Multidisciplinary data are organized and governed by the Thematic Core Services (TCS) and are driven by various scientific communities encompassing a wide spectrum of Earth science disciplines. These include Data, Data-products, Services and Software (DDSS), from seismology, near fault observatories, geodetic observations, volcano observations, satellite observations, geomagnetic observations, as well as data from various anthropogenic hazard episodes, geological information and modelling. In addition, transnational access to multi-scale laboratories and geo-energy test-beds for low-carbon energy will be provided. TCS DDSS will be integrated into Integrated Core Services (ICS), a platform that will ensure their interoperability and access to these services by the scientific community as well as other users within the society. This requires dedicated tasks for interactions with the various TCS-WPs, as well as the various distributed ICS (ICS-Ds), such as High Performance Computing (HPC) facilities, large scale data storage

  16. EPOS Thematic Core Service ANTHROPOGENIC HAZARDS (TCS AH) - development of e-research platform

    Science.gov (United States)

    Orlecka-Sikora, Beata

    2017-04-01

    TCS AH is based on IS-EPOS Platform. The Platform facilitates research on anthropogenic hazards and is available online, free of charge https://tcs.ah-epos.eu/. The Platform is a final product of the IS-EPOS project, founded by the national programme - POIG - which was implemented in 2013-2015 (POIG.02.03.00-14-090/13-00). The platform is a result of a joint work of scientific community and industrial partners. Currently, the development of TCS AH is carried under EPOS IP project (H2020-INFRADEV-1-2015-1, INFRADEV-3-2015). Platform is an open virtual access point for researchers and Ph. D. students interested in anthropogenic seismicity and related hazards. This environment is designed to ensure a researcher the maximum possible liberty for experimentation by providing a virtual laboratory, in which the researcher can design own processing streams and process the data integrated on the platform. TCS AH integrates: data and specific high-level services. Data gathered in the so-called "episodes", comprehensively describing a geophysical process, induced or triggered by human technological activity, which, under certain circumstances can become hazardous for people, infrastructure and the environment. 7 sets of seismic, geological and technological data were made available on the Platform. The data come from Poland, Germany, UK and Vietnam, and refer to underground mining, reservoir impoundment, shale gas exploitation and geothermal energy production. The next at least 19 new episodes related to conventional hydrocarbon extraction, reservoir treatment, underground mining and geothermal energy production are being integrated within the framework of EPOS IP project. The heterogeneous multi-disciplinary data (seismic, displacement, geomechanical data, production data etc.) are transformed to unified structures to form integrated and validated datasets. To deal with this various data the problem-oriented services were designed and implemented. The particular attention

  17. Erythropoietin Receptor in Human Tumor Cells: Expression and Aspects Regarding Functionality

    NARCIS (Netherlands)

    T.A. Knoch (Tobias); G. Westphal; E. Niederberger; C. Blum; Y. Wollman; W. Rebel; J. Debus; E. Friedrich

    2001-01-01

    textabstractRecombinant human erythropoietin (Epo)and granu l o cy t e - c o l o ny - s t i mulating factor (G-CSF) are used to stimulate hematopoiesis in patients with malignant dise a s e s . These cytokines transduce their biological signal via the Epo receptor (EpoR) and G-CSF receptor (G-CSF-R)

  18. Working with NASA's OSS E/PO Support Network

    Science.gov (United States)

    Miner, E. D.; Lowes, L. L.

    2001-11-01

    With greater and greater emphasis on the inclusion of a public engagement component in all government-supported research funding, many members of the DPS are finding it difficult to find sufficient time and funding to develop a wide-reaching and effective E/PO program. NASA's Office of Space Science, over the last five years, has built a Support Network to assist its funded scientists to establish partnerships with local and/or national science formal or informal education organizations, who are anxious to connect with and use the expertise of space scientists. The OSS Support Network consists of four theme-based 'Forums,' including the Solar System Exploration (SSE) Forum, specifically designed for working with planetary scientists, and seven regional 'Brokers-Facilitators' who are more familiar with partnership and other potential avenues for involvement by scientists. The services provided by the Support Network are free to both the scientists and their potential partners and is not limited to NASA-funded scientists. In addition to its assistance to space scientists, the Support Network is involved in a number of other overarching efforts, including support of a Solar System Ambassador Program, a Solar System Educator Program, Space Place (web and e-mail science products for libraries and small planetariums and museums), an on-line Space Science Resource Directory, annual reports of Space Science E/PO activity, identifying and filling in 'holes' and 'over-populations' in a solar system E/PO product matrix of grade level versus product versus content, research on product effectiveness, and scientific and educational evaluation of space science products. Forum and Broker-Facilitator contact information is available at http://spacescience.nasa.gov/education/resources/ecosystem/index.htm. Handouts with additional information will be available at the meeting.

  19. Multiscale Laboratory Infrastructure and Services to users: Plans within EPOS

    Science.gov (United States)

    Spiers, Chris; Willingshofer, Ernst; Drury, Martyn; Funiciello, Francesca; Rosenau, Matthias; Scarlato, Piergiorgio; Sagnotti, Leonardo; EPOS WG6, Corrado Cimarelli

    2015-04-01

    The participant countries in EPOS embody a wide range of world-class laboratory infrastructures ranging from high temperature and pressure experimental facilities, to electron microscopy, micro-beam analysis, analogue modeling and paleomagnetic laboratories. Most data produced by the various laboratory centres and networks are presently available only in limited "final form" in publications. Many data remain inaccessible and/or poorly preserved. However, the data produced at the participating laboratories are crucial to serving society's need for geo-resources exploration and for protection against geo-hazards. Indeed, to model resource formation and system behaviour during exploitation, we need an understanding from the molecular to the continental scale, based on experimental data. This contribution will describe the plans that the laboratories community in Europe is making, in the context of EPOS. The main objectives are: • To collect and harmonize available and emerging laboratory data on the properties and processes controlling rock system behaviour at multiple scales, in order to generate products accessible and interoperable through services for supporting research activities. • To co-ordinate the development, integration and trans-national usage of the major solid Earth Science laboratory centres and specialist networks. The length scales encompassed by the infrastructures included range from the nano- and micrometer levels (electron microscopy and micro-beam analysis) to the scale of experiments on centimetre sized samples, and to analogue model experiments simulating the reservoir scale, the basin scale and the plate scale. • To provide products and services supporting research into Geo-resources and Geo-storage, Geo-hazards and Earth System Evolution. If the EPOS Implementation Phase proposal presently under construction is successful, then a range of services and transnational activities will be put in place to realize these objectives.

  20. EPOS1 - a multiparameter measuring system to earthquake prediction research

    Energy Technology Data Exchange (ETDEWEB)

    Streil, T.; Oeser, V. [SARAD GmbH, Dresden (Germany); Heinicke, J.; Koch, U.; Wiegand, J.

    1998-12-31

    The approach to earthquake prediction by geophysical, geochemical and hydrological measurements is a long and winding road. Nevertheless, the results show a progress in that field (e.g. Kobe). This progress is also a result of a new generation of measuring equipment. SARAD has developed a versatile measuring system (EPOS1) based on experiences and recent results from different research groups. It is able to record selected parameters suitable to earthquake prediction research. A micro-computer system handles data exchange, data management and control. It is connected to a modular sensor system. Sensor modules can be selected according to the actual needs at the measuring site. (author)

  1. A Planetary Geophysicist Does EPO: Lessons Learned Along the Way

    Science.gov (United States)

    Kiefer, W. S.

    2011-12-01

    My "day job" is numerical modeling of the interiors of the terrestrial planets, but I have also done EPO projects for the last 17 years while at the Lunar and Planetary Institute. These range from single, hour long talks in classrooms or astronomy clubs, to week-long summer workshops for teachers and librarians, and even semester-long programs, along with a number of curriculum development projects. EPO projects are a great way to help develop both the next generation of scientists and, more importantly, of scientifically literate citizens and taxpayers. Here are a few lessons learned along the way in the school of hard knocks. (1) An engaging delivery style is even more important in EPO presentations than it is in college lectures or conference presentations. Emphasize a few key concepts rather than numerous facts, and keep the jargon out. Good analogies can go a long way towards explaining a concept to any age group. I teach the role of size in planetary cooling by first asking students how long it takes to cook food of various sizes (a hamburger, roast beef, turkey). (2) If you will be working with a group of students for more than one class period, classroom friendly activities strengthen the learning process. Such activities do not need to be elaborate - when teaching about the Moon, I sometimes assign students to take their parents outside at night and show them how to find lava flows on the Moon. Teachers usually need to have classroom activities that are aligned to state or national teaching standards. Fortunately, many effective, standards-aligned activities already exist, so you don't need to reinvent the wheel. For a useful listing of planetary science and astronomy activities, see the LPI website www.lpi.usra.edu/education/resources/ (3) Although EPO work can be personally rewarding, it is not always well rewarded in a professional context, and it can be difficult to find the time and financial resources to sustain major projects. We sometimes use a

  2. A Database of EPO-Patenting Firms in Denmark

    DEFF Research Database (Denmark)

    Nielsen, Anders Østergaard

    1998-01-01

    The first section gives a brief introduction of the basic stages to be observed by the patent applicant from idea to the patent is granted. Section two presents three examples of how patents are registered in the online patent database INPADOC. Section three accounts for the initial analysis...... of the existing patent stock issued to firms with domicile in Denmark. Sections four and five report the basic characteristics of the EPO-patent sample and the procedures for linking the patent statistics to accounting data at the firm level, and finally they present the basic properties of the resulting database...

  3. Exercise aggravates cardiovascular risks and mortality in rats with disrupted nitric oxide pathway and treated with recombinant human erythropoietin.

    Science.gov (United States)

    Meziri, Fayçal; Binda, Delphine; Touati, Sabeur; Pellegrin, Maxime; Berthelot, Alain; Touyz, Rhian M; Laurant, Pascal

    2011-08-01

    Chronic administration of recombinant human erythropoietin (rHuEPO) can generate serious cardiovascular side effects such as arterial hypertension (HTA) in clinical and sport fields. It is hypothesized that nitric oxide (NO) can protect from noxious cardiovascular effects induced by chronic administration of rHuEPO. On this base, we studied the cardiovascular effects of chronic administration of rHuEPO in exercise-trained rats treated with an inhibitor of NO synthesis (L-NAME). Rats were treated or not with rHuEPO and/or L-NAME during 6 weeks. During the same period, rats were subjected to treadmill exercise. The blood pressure was measured weekly. Endothelial function of isolated aorta and small mesenteric arteries were studied and the morphology of the latter was investigated. L-NAME induced hypertension (197 ± 6 mmHg, at the end of the protocol). Exercise prevented the rise in blood pressure induced by L-NAME (170 ± 5 mmHg). However, exercise-trained rats treated with both rHuEPO and L-NAME developed severe hypertension (228 ± 9 mmHg). Furthermore, in these exercise-trained rats treated with rHuEPO/L-NAME, the acetylcholine-induced relaxation was markedly impaired in isolated aorta (60% of maximal relaxation) and small mesenteric arteries (53%). L-NAME hypertension induced an internal remodeling of small mesenteric arteries that was not modified by exercise, rHuEPO or both. Vascular ET-1 production was not increased in rHuEPO/L-NAME/training hypertensive rats. Furthermore, we observed that rHuEPO/L-NAME/training hypertensive rats died during the exercise or the recovery period (mortality 51%). Our findings suggest that the use of rHuEPO in sport, in order to improve physical performance, represents a high and fatal risk factor, especially with pre-existing cardiovascular risk.

  4. Circulation of progenitor cells after intensive chemotherapy followed by combination G-CSF and EPO in breast carcinoma

    International Nuclear Information System (INIS)

    Filip, S.; Vanasek, J.; Blaha, M.; Vavrova, J.

    1997-01-01

    Hematologic effects of granulocyte colony-stimulating factor (G-CSF) and erythropoietic (EPO) combination after priming intensive chemotherapy in the treatment of female breast carcinoma are presented. In a previous group treated with G-CSF alone, 36% of patients became anemic and to be transfused for correction of their anemia. To the present study consecutive patients with different stages of breast carcinoma were admitted. All were given priming intensive chemotherapy (epirubicin 150 m/m 2 and cyclophosphamide 1300 mg/m 2 ) followed by subcutaneous application of G-CSF at a dose of 5 μg/kg/day and EPO 250 IU/kg/day. In cases where leucocyte counts dropped below 1 x 10 9 /dm 3 and hemoglobin level fell to 85 g/dm 3 administration of growth factors was started. The therapy was stopped when normal leukocyte count reached 4 x 10 9 /dm 3 for G-CSF and hemoglobin level rose to 115 g/dm 3 for EPO. Our results show significant difference between MNC/Tl (min.), CD34 + cells/μl (min.), CFU-GM/ml (min.), BFU-E/ml (min) and MNC/μl (max.), CD34 + cells/μl (max.), CFU-GM/ml (max.), BFU-E/ml (ml) p + cells/μl, 23.4-fold for CFU-GM/ml and 28.7-fold increase for BFU-E/ml. Side effects were minimal, no infectious complications occurred, body temperature did not rise over 3 grad C and no corrections of anemia were needed. It is concluded that the administration of G-CSF plus EPO combination following intensive chemotherapy reduces hematologic toxicity and induces large amount of hemopoietic progenitors suitable for autologous transplantation in women with breast carcinoma. (author)

  5. Tools for Scientist Engagement in E/PO: NASA SMD Community Workspace and Online Resources

    Science.gov (United States)

    Dalton, H.; Shipp, S. S.; Grier, J.; Gross, N. A.; Buxner, S.; Bartolone, L.; Peticolas, L. M.; Woroner, M.; Schwerin, T. G.

    2014-12-01

    The Science Mission Directorate (SMD) Science Education and Public Outreach (E/PO) Forums are here to help you get involved in E/PO! The Forums have been developing several online resources to support scientists who are - or who are interested in becoming - involved in E/PO. These include NASA Wavelength, EarthSpace, and the SMD E/PO online community workspace. NASA Wavelength is the one-stop shop of all peer-reviewed NASA education resources to find materials you - or your audiences - can use. Browse by audience (pre-K through 12, higher education, and informal education) or topic, or choose to search for something specific by keyword and audience. http://nasawavelength.org. EarthSpace, an online clearinghouse of Earth and space materials for use in the higher education classroom, is driven by a powerful search engine that allows you to browse the collection of resources by science topic, audience, type of material or key terms. All materials are peer-reviewed before posting, and because all submissions receive a digital object identifier (doi), submitted materials can be listed as publications. http://www.lpi.usra.edu/earthspace. The SMD E/PO online community workspace contains many resources for scientists. These include one-page guides on how to get involved, tips on how to make the most of your time spent on E/PO, and sample activities, as well as news on funding, policy, and what's happening in the E/PO community. The workspace also provides scientists and the public pathways to find opportunities for participation in E/PO, to learn about SMD E/PO projects and their impacts, to connect with SMD E/PO practitioners, and to explore resources to improve professional E/PO practice, including literature reviews, information about the Next Generation Science Standards, and best practices in evaluation and engaging diverse audiences. http://smdepo.org.

  6. Human erythropoietin response to hypocapnic hypoxia, normocapnic hypoxia, and hypocapnic normoxia

    DEFF Research Database (Denmark)

    Klausen, T; Christensen, H; Hansen, J M

    1996-01-01

    This study investigated the human erythropoietin (EPO) response to short-term hypocapnic hypoxia, its relationship to a normoxic or hypoxic increase of the haemoglobin oxygen affinity, and its suppression by the addition of CO2 to the hypoxic gas. On separate days, eight healthy male subjects were...

  7. Increasing Organizational Effectiveness through Better Human Resource Planning and Development

    Science.gov (United States)

    Schein, Edgar H.

    1977-01-01

    Discusses the increasing importance of human resource planning and development for organizational effectiveness, and examines how the major components of a human resource planning and development system should be coordinated for maximum effectiveness. Available from Alfred P. Sloan School of Management, Massachusetts Institute of Technology,…

  8. Automated Patent Searching in the EPO: From Online Searching to Document Delivery.

    Science.gov (United States)

    Nuyts, Annemie; Jonckheere, Charles

    The European Patent Office (EPO) has recently implemented the last part of its ambitious automation project aimed at creating an automated search environment for approximately 1200 EPO patent search examiners. The examiners now have at their disposal an integrated set of tools offering a full range of functionalities from online searching, via…

  9. A possible human counterpart of the principle of increasing entropy

    International Nuclear Information System (INIS)

    Liang, Y.; An, K.N.; Yang, G.; Huang, J.P.

    2014-01-01

    It is well-known that the principle of increasing entropy holds for isolated natural systems that contain non-adaptive molecules. Here we present, for the first time, an experimental evidence for a possible human counterpart of the principle in an isolated social system that involves adaptive humans. Our work shows that the human counterpart is valid even though interactions among humans in social systems are distinctly different from those among molecules in natural systems. Thus, it becomes possible to understand social systems from this natural principle, at least to some extent.

  10. Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds.

    Science.gov (United States)

    Galeano, Mariarosaria; Altavilla, Domenica; Bitto, Alessandra; Minutoli, Letteria; Calò, Margherita; Lo Cascio, Patrizia; Polito, Francesca; Giugliano, Giovanni; Squadrito, Giovanni; Mioni, Chiara; Giuliani, Daniela; Venuti, Francesco S; Squadrito, Francesco

    2006-04-01

    Erythropoietin interacts with vascular endothelial growth factor (VEGF) and stimulates endothelial cell mitosis and motility; thus it may be of importance in the complex phenomenon of wound healing. The purpose of this study was to investigate the effect of recombinant human erythropoietin (rHuEPO) on experimental burn wounds. Randomized experiment. Research laboratory. C57BL/6 male mice weighing 25-30 g. Mice were immersed in 80 degrees C water for 10 secs to achieve a deep-dermal second degree burn. Animals were randomized to receive either rHuEPO (400 units/kg/day for 14 days in 100 microL subcutaneously) or its vehicle alone (100 microl/day distilled water for 14 days subcutaneously). On day 14 the animals were killed. Burn areas were used for histologic examination, evaluation of neoangiogenesis by immunohistochemistry, and expression (Western blot) of the specific endothelial marker CD31 as well as quantification of microvessel density, measurement of VEGF wound content (enzyme-linked immunosorbent assay), expression (Western blot) of endothelial and inducible nitric oxide synthases, and determination of wound nitric oxide (NO) products. rHuEPO increased burn wound reepithelialization and reduced the time to final wound closure. These effects were completely abated by a passive immunization with specific antibodies against erythropoietin. rHuEPO improved healing of burn wound through increased epithelial proliferation, maturation of the extracellular matrix, and angiogenesis. The hematopoietic factor augmented neoangiogenesis as suggested by the marked increase in microvessel density and by the robust expression of the specific endothelial marker CD31. Furthermore, rHuEPO enhanced the wound content of VEGF caused a marked expression of endothelial and inducible nitric oxide synthases and increased wound content of nitric oxide products. Our study suggests that rHuEPO may be an effective therapeutic approach to improve clinical outcomes after thermal injury.

  11. Erythropoietin over-expression protects against diet-induced obesity in mice through increased fat oxidation in muscles.

    Directory of Open Access Journals (Sweden)

    Pernille Hojman

    Full Text Available Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo.At 12 weeks, EPO expression resulted in a 23% weight reduction (P<0.01 in EPO transfected obese mice; thus the mice weighed 21.9+/-0.8 g (control, normal diet, 21.9+/-1.4 g (EPO, normal diet, 35.3+/-3.3 g (control, high-fat diet and 28.8+/-2.6 g (EPO, high-fat diet. Correspondingly, DXA scanning revealed that this was due to a 28% reduction in adipose tissue mass.The decrease in adipose tissue mass was accompanied by a complete normalisation of fasting insulin levels and glucose tolerance in the high-fat fed mice. EPO expression also induced a 14% increase in muscle volume and a 25% increase in vascularisation of the EPO transfected muscle. Muscle force and stamina were not affected by EPO expression. PCR array analysis revealed that genes involved in lipid metabolism, thermogenesis and inflammation were increased in muscles in response to EPO expression, while genes involved in glucose metabolism were down-regulated. In addition, muscular fat oxidation was increased 1.8-fold in both the EPO transfected and contralateral muscles.In conclusion, we have shown that EPO when expressed in supra-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles.

  12. Progress of the intense positron beam project EPOS

    International Nuclear Information System (INIS)

    Krause-Rehberg, R.; Brauer, G.; Jungmann, M.; Krille, A.; Rogov, A.; Noack, K.

    2008-01-01

    EPOS (the ELBE POsitron Source) is a running project to build an intense, bunched positron beam for materials research. It makes use of the bunched electron beam of the ELBE radiation source (Electron Linac with high Brilliance and low Emittance) at the Research Centre Dresden-Rossendorf (40 MeV, 1 mA). ELBE has unique timing properties, the bunch length is <5 ps and the repetition time is 77 ns. In contrast to other Linacs made for Free Electron Lasers (e.g., TTF at DESY, Hamburg), ELBE can be operated in full cw-mode, i.e., with an uninterrupted sequence of bunches. The article continues an earlier publication. It concentrates on details of the timing system and describes issues of radiation protection

  13. Bioenergetics of the calf muscle in Friedreich ataxia patients measured by 31P-MRS before and after treatment with recombinant human erythropoietin.

    Directory of Open Access Journals (Sweden)

    Wolfgang Nachbauer

    Full Text Available Friedreich ataxia (FRDA is caused by a GAA repeat expansion in the FXN gene leading to reduced expression of the mitochondrial protein frataxin. Recombinant human erythropoietin (rhuEPO is suggested to increase frataxin levels, alter mitochondrial function and improve clinical scores in FRDA patients. Aim of the present pilot study was to investigate mitochondrial metabolism of skeletal muscle tissue in FRDA patients and examine effects of rhuEPO administration by phosphorus 31 magnetic resonance spectroscopy (31P MRS. Seven genetically confirmed FRDA patients underwent 31P MRS of the calf muscles using a rest-exercise-recovery protocol before and after receiving 3000 IU of rhuEPO for eight weeks. FRDA patients showed more rapid phosphocreatine (PCr depletion and increased accumulation of inorganic phosphate (Pi during incremental exercise as compared to controls. After maximal exhaustive exercise prolonged regeneration of PCR and slowed decline in Pi can be seen in FRDA. PCr regeneration as hallmark of mitochondrial ATP production revealed correlation to activity of complex II/III of the respiratory chain and to demographic values. PCr and Pi kinetics were not influenced by rhuEPO administration. Our results confirm mitochondrial dysfunction and exercise intolerance due to impaired oxidative phosphorylation in skeletal muscle tissue of FRDA patients. MRS did not show improved mitochondrial bioenergetics after eight weeks of rhuEPO exposition in skeletal muscle tissue of FRDA patients.EU Clinical Trials Register2008-000040-13.

  14. Current status of the EPOS WG4 - GNSS and Other Geodetic Data

    Science.gov (United States)

    Fernandes, Rui; Bastos, Luisa; Bruyninx, Carine; D'Agostino, Nicola; Dousa, Jan; Ganas, Athanassios; Lidberg, Martin; Nocquet, Jean-Mathieu

    2014-05-01

    WG4 - "EPOS Geodetic Data and Other Geodetic Data" is the Working Group of the EPOS project in charge of defining and preparing the integration of the existing Pan-European Geodetic Infrastructures that will support European Geosciences, which is the ultimate goal of the EPOS project. The WG4 is formed by representatives of the participating EPOS countries (23) but it is also open to the entire geodetic community. In fact, WG4 also already includes members from countries that formally are not integrating EPOS in this first step. The geodetic component of EPOS (WG4) is dealing essentially with Research Infrastructures focused on continuous operating GNSS (cGNSS) in the current phase. The option of concentrating the efforts on the presently most generalized geodetic tool supporting research on Solid Earth was decided in order to optimize the existing resources. Nevertheless, WG4 will continue to pursue the development of tools and methodologies that permit the access of the EPOS community to other geodetic information (e.g., gravimetry). Furthermore, although the focus is on Solid Earth applications, other research and technical applications (e.g., reference frames, meteorology, space weather) can also benefit from the efforts of WG4 EPOS towards the optimization of the geodetic resources in Europe. We will present and discuss the plans for the implementation of the thematic and core services (TCS) for geodetic data within EPOS and the related business plan. We will focus on strategies towards the implementation of the best solutions that will permit to the end-users, and in particular geo-scientists, to access the geodetic data, derived solutions, and associated metadata using transparent and uniform processes. Five pillars have been defined proposed for the TCS: Dissemination, Preservation, Monitoring, and Analysis of geodetic data plus the Support and Governance Infrastructure. Current proposals and remaining open questions will be discussed.

  15. Multiple distinct stimuli increase measured nucleosome occupancy around human promoters.

    Directory of Open Access Journals (Sweden)

    Chuong D Pham

    Full Text Available Nucleosomes can block access to transcription factors. Thus the precise localization of nucleosomes relative to transcription start sites and other factor binding sites is expected to be a critical component of transcriptional regulation. Recently developed microarray approaches have allowed the rapid mapping of nucleosome positions over hundreds of kilobases (kb of human genomic DNA, although these approaches have not yet been widely used to measure chromatin changes associated with changes in transcription. Here, we use custom tiling microarrays to reveal changes in nucleosome positions and abundance that occur when hormone-bound glucocorticoid receptor (GR binds to sites near target gene promoters in human osteosarcoma cells. The most striking change is an increase in measured nucleosome occupancy at sites spanning ∼1 kb upstream and downstream of transcription start sites, which occurs one hour after addition of hormone, but is lost at 4 hours. Unexpectedly, this increase was seen both on GR-regulated and GR-non-regulated genes. In addition, the human SWI/SNF chromatin remodeling factor (a GR co-activator was found to be important for increased occupancy upon hormone treatment and also for low nucleosome occupancy without hormone. Most surprisingly, similar increases in nucleosome occupancy were also seen on both regulated and non-regulated promoters during differentiation of human myeloid leukemia cells and upon activation of human CD4+ T-cells. These results indicate that dramatic changes in chromatin structure over ∼2 kb of human promoters may occur genomewide and in response to a variety of stimuli, and suggest novel models for transcriptional regulation.

  16. Integrating Near Fault Observatories (NFO) for EPOS Implementation Phase

    Science.gov (United States)

    Chiaraluce, Lauro

    2015-04-01

    Following the European Plate Observing System (EPOS) project vision aimed at creating a pan-European infrastructure for Earth sciences to support science for a more sustainable society, we are working on the integration of Near-Fault Observatories (NFOs). NFOs are state of the art research infrastructures consisting of advanced networks of multi-parametric sensors continuously monitoring the chemical and physical processes related to the common underlying earth instabilities governing active faults evolution and the genesis of earthquakes. Such a methodological approach, currently applicable only at the local scale (areas of tens to few hundreds of kilometres), is based on extremely dense networks and less common instruments deserving an extraordinary work on data quality control and multi-parameter data description. These networks in fact usually complement regional seismic and geodetic networks (typically with station spacing of 50-100km) with high-density distributions of seismic, geodetic, geochemical and geophysical sensors located typically within 10-20 km of active faults where large earthquakes are expected in the future. In the initial phase of EPOS-IP, seven NFO nodes will be linked: the Alto Tiberina and Irpinia Observatories in Italy, the Corinth Observatory in Greece, the South-Iceland Seismic Zone, the Valais Observatory in Switzerland, Marmara Sea GEO Supersite in Turkey (EU MARSite) and the Vrancea Observatory in Romania. Our work is aimed at establishing standards and integration within this first core group of NFOs while other NFOs are expected to be installed in the next years adopting the standards established and developed within the EPOS Thematic Core Services (TCS). The goal of our group is to build upon the initial development supported by these few key national observatories coordinated under previous EU projects (NERA and REAKT), inclusive and harmonised TCS supporting the installation over the next decade of tens of near

  17. Human disc degeneration is associated with increased MMP 7 expression.

    Science.gov (United States)

    Le Maitre, C L; Freemont, A J; Hoyland, J A

    2006-01-01

    During intervertebral disc (IVD) degeneration, normal matrix synthesis decreases and degradation of disc matrix increases. A number of proteases that are increased during disc degeneration are thought to be involved in its pathogenesis. Matrix metalloproteinase 7 (MMP 7) (Matrilysin, PUMP-1) is known to cleave the major matrix molecules found within the IVD, i.e., the proteoglycan aggrecan and collagen type II. To date, however, it is not known how its expression changes with degeneration or its exact location. We investigated the localization of MMP 7 in human, histologically graded, nondegenerate, degenerated and prolapsed discs to ascertain whether MMP 7 is up-regulated during disc degeneration. Samples of human IVD tissue were fixed in neutral buffered formalin, embedded in paraffin, and sections stained with hematoxylin and eosin to score the degree of morphological degeneration. Immunohistochemistry was performed to localize MMP 7 in 41 human IVDs with varying degrees of degeneration. We found that the chondrocyte-like cells of the nucleus pulposus and inner annulus fibrosus were MMP 7 immunopositive; little immunopositivity was observed in the outer annulus. Nondegenerate discs showed few immunopositive cells. A significant increase in the proportion of MMP 7 immunopositive cells was seen in the nucleus pulposus of discs classified as showing intermediate levels of degeneration and a further increase was seen in discs with severe degeneration. Prolapsed discs showed more MMP 7 immunopositive cells compared to nondegenerated discs, but fewer than those seen in cases of severe degeneration.

  18. Erythropoietin over-expression protects against diet-induced obesity in mice through increased fat oxidation in muscles.

    Science.gov (United States)

    Hojman, Pernille; Brolin, Camilla; Gissel, Hanne; Brandt, Claus; Zerahn, Bo; Pedersen, Bente Klarlund; Gehl, Julie

    2009-06-12

    Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo.At 12 weeks, EPO expression resulted in a 23% weight reduction (Pincrease in muscle volume and a 25% increase in vascularisation of the EPO transfected muscle. Muscle force and stamina were not affected by EPO expression. PCR array analysis revealed that genes involved in lipid metabolism, thermogenesis and inflammation were increased in muscles in response to EPO expression, while genes involved in glucose metabolism were down-regulated. In addition, muscular fat oxidation was increased 1.8-fold in both the EPO transfected and contralateral muscles.In conclusion, we have shown that EPO when expressed in supra-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles.

  19. Sky Fest: A Model of Successful Scientist Participation in E/PO

    Science.gov (United States)

    Dalton, H.; Shipp, S. S.; Shaner, A. J.; LaConte, K.; Shupla, C. B.

    2014-12-01

    Participation in outreach events is an easy way for scientists to get involved with E/PO and reach many people with minimal time commitment. At the Lunar and Planetary Institute (LPI) in Houston, Texas, the E/PO team holds Sky Fest outreach events several times a year. These events each have a science content theme and include several activities for children and their parents, night sky viewing through telescopes, and scientist presentations. LPI scientists have the opportunity to participate in Sky Fest events either by helping lead an activity or by giving the scientist presentation (a short lecture and/or demonstration). Scientists are involved in at least one preparation meeting before the event. This allows them to ask questions, understand what activity they will be leading, and learn the key points that they should be sharing with the public, as well as techniques for effectively teaching members of the public about the event topic. During the event, each activity is run by one E/PO specialist and one scientist, enabling the scientist to learn about effective E/PO practices from the E/PO specialist and the E/PO specialist to get more science information about the event topic. E/PO specialists working together with scientists at stations provides a more complete, richer experience for event participants. Surveys of event participants have shown that interacting one-on-one with scientists is often one of their favorite parts of the events. Interviews with scientists indicated that they enjoyed Sky Fest because there was very little time involved on their parts outside of the actual event; the activities were created and/or chosen by the E/PO professionals, and setup for the events was completed before they arrived. They also enjoyed presenting their topic to people without a background in science, and who would not have otherwise sought out the information that was presented.

  20. Reducing consistency in human realism increases the uncanny valley effect; increasing category uncertainty does not.

    Science.gov (United States)

    MacDorman, Karl F; Chattopadhyay, Debaleena

    2016-01-01

    Human replicas may elicit unintended cold, eerie feelings in viewers, an effect known as the uncanny valley. Masahiro Mori, who proposed the effect in 1970, attributed it to inconsistencies in the replica's realism with some of its features perceived as human and others as nonhuman. This study aims to determine whether reducing realism consistency in visual features increases the uncanny valley effect. In three rounds of experiments, 548 participants categorized and rated humans, animals, and objects that varied from computer animated to real. Two sets of features were manipulated to reduce realism consistency. (For humans, the sets were eyes-eyelashes-mouth and skin-nose-eyebrows.) Reducing realism consistency caused humans and animals, but not objects, to appear eerier and colder. However, the predictions of a competing theory, proposed by Ernst Jentsch in 1906, were not supported: The most ambiguous representations-those eliciting the greatest category uncertainty-were neither the eeriest nor the coldest. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Human lactoferrin increases Helicobacter pylori internalisation into AGS cells.

    Science.gov (United States)

    Coray, Dorien S; Heinemann, Jack A; Tyrer, Peter C; Keenan, Jacqueline I

    2012-05-01

    Helicobacter pylori has high global infection rates and can cause other undesirable clinical manifestations such as duodenal ulcer (DU) and gastric cancer (GC). Frequencies of re-infection after therapeutic clearance and rates of DU versus GC vary geographically and differ markedly between developed and developing countries, which suggests additional factors may be involved. The possibility that, in vivo, lactoferrin (Lf) may play a subtle role in modulating micronutrient availability or bacterial internalisation with implications for disease etiology is considered. Lf is an iron binding protein produced in mammals that has antimicrobial and immunomodulatory properties. Some bacteria that regularly colonise mammalian hosts have adapted to living in high Lf environments and we investigated if this included the gastric pathogen H. pylori. We found that H. pylori was able to use iron from fully iron-saturated human Lf (hLf) whereas partially iron-saturated hLf (apo) did not increase H. pylori growth. Instead, apo-hLf increased adherence to and internalisation of bacteria into cultured epithelial cells. By increasing internalisation, we speculate that apo-human lactoferrin may contribute to H. pylori's ability to persistence in the human stomach, an observation that potentially has implications for the risk of H. pylori-associated disease.

  2. Examination of the e{sup +} and e{sup +}e{sup -} pair emission from heavy ion collisions at the EPoS II spectrometer; Untersuchung der e{sup +}- und e{sup +}e{sup -}-Paaremission aus Schwerionenkollisionen mit dem EPoS II Spektrometer

    Energy Technology Data Exchange (ETDEWEB)

    Baumann, J.

    1996-12-01

    In the course of examination of the positron and positron-electron pair emission from heavy ion collisions at the Coulomb barrier, the research groups EPOS I and ORANGE have found a number of line structures in the measured positron energy and cumulative pair energy spectra which up to present could not be fully explained, as theoretical interpretations so far remain inconsistent in some respects. For clarification, further measurements have been made at the completely new designed EPoS II spectrometer. Reproducibility of the lines is possible at a high level of statistical significance. (orig./CB) [Deutsch] Bei Untersuchungen der Positron- und Positron- Elektron- Paaremissionaus Schwerionenkollisionen an der Coulombbarriere wurde von den Gruppen EPOS I und ORANGE eine Reihe von Linienstrukturen in den gemessenen Positronenenergie- und Paarsummenenergiespektren beobachtet, fuer die bislang keine in allen Punkten konsistente, theoretische Erklaerunggefunden werden konnte. Um ihre Ursachen zu klaeren, wurden mit dem voellig neu aufgebauten EPoS II Spektrometer weitere Messreihen durgefuehrt. Die Reproduzierbarkeit der Linien ist auf einem hohen statistischen Signifikanzniveau moeglich.

  3. Brain and skin do not contribute to the systemic rise in erythropoietin during acute hypoxia in humans

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Nordsborg, Nikolai; Taudorf, Sarah

    2012-01-01

    these findings apply to humans remains unknown. We exposed healthy young subjects to hypoxia (equivalent to 3800 m) and measured EPO in arterial and jugular venous plasma and in cerebrospinal fluid. To examine the role of the skin for EPO production during hypoxia, subjects were exposed to 8 h of hypobaric......Erythropoietin (EPO) preserves arterial oxygen content by controlling red blood cell and plasma volumes. Synthesis of EPO was long thought to relate inversely to renal oxygenation, but in knockout mice, brain and skin have been identified as essential for the acute hypoxic EPO response. Whether...

  4. A Novel EPO Receptor Agonist Improves Glucose Tolerance via Glucose Uptake in Skeletal Muscle in a Mouse Model of Diabetes

    Directory of Open Access Journals (Sweden)

    Michael S. Scully

    2011-01-01

    Full Text Available Patients treated with recombinant human Epo demonstrate an improvement in insulin sensitivity. We aimed to investigate whether CNTO 530, a novel Epo receptor agonist, could affect glucose tolerance and insulin sensitivity. A single administration of CNTO 530 significantly and dose-dependently reduced the area under the curve in a glucose tolerance test in diet-induced obese and diabetic mice after 14, 21, and 28 days. HOMA analysis suggested an improvement in insulin sensitivity, and this effect was confirmed by a hyperinsulinemic-euglycemic clamp. Uptake of 14C-2-deoxy-D-glucose indicated that animals dosed with CNTO 530 transported more glucose into skeletal muscle and heart relative to control animals. In conclusion, CNTO530 has a profound effect on glucose tolerance in insulin-resistant rodents likely because of improving peripheral insulin sensitivity. This effect was observed with epoetin-α and darbepoetin-α, suggesting this is a class effect, but the effect with these compounds relative to CNTO530 was decreased in duration and magnitude.

  5. Enhancement of gene expression under hypoxic conditions using fragments of the human vascular endothelial growth factor and the erythropoietin genes

    International Nuclear Information System (INIS)

    Shibata, Toru; Akiyama, Nobutake; Noda, Makoto; Sasai, Keisuke; Hiraoka, Masahiro

    1998-01-01

    Purpose: Selective gene expression in response to tumor hypoxia may provide new avenues, not only for radiotherapy and chemotherapy, but also for gene therapy. In this study, we have assessed the extent of hypoxia responsiveness of various DNA constructs by the luciferase assay to help design vectors suitable for cancer therapy. Materials and Methods: Reporter plasmids were constructed with fragments of the human vascular endothelial growth factor (VEGF) and the erythropoietin (Epo) genes encompassing the putative hypoxia-responsive elements (HRE) and the pGL3 promoter vector. Test plasmids and the control pRL-CMV plasmid were cotransfected into tumor cells by the calcium phosphate method. After 6 h hypoxic treatment, the reporter assay was performed. Results: The construct pGL3/VEGF containing the 385 bp fragment of the 5' flanking region in human VEGF gene showed significant increases in luciferase activity in response to hypoxia. The hypoxic/aerobic ratios were about 3-4, and 8-12 for murine and human tumor cells, respectively. Despite the very high degree of conservation among the HREs of mammalian VEGF genes, murine cells showed lower responsiveness than human cells. We next tested the construct pGL3/Epo containing the 150 bp fragment of the 3' flanking region in the Epo gene. Luciferase activity of pGL3/Epo was increased with hypoxia only in human cell lines. The insertion of 5 copies of the 35-bp fragments derived from the VEGF HREs and 32 bp of the E1b minimal promoter resulted in maximal enhancement of hypoxia responsiveness. Conclusions: The constructs with VEGF or Epo fragments containing HRE may be useful for inducing specific gene expression in hypoxic cells. Especially, the application of multiple copies of the HREs and an E1b minimal promoter appears to have the advantage of great improvement in hypoxia responsiveness

  6. Pet ownership increases human risk of encountering ticks.

    Science.gov (United States)

    Jones, E H; Hinckley, A F; Hook, S A; Meek, J I; Backenson, B; Kugeler, K J; Feldman, K A

    2018-02-01

    We examined whether pet ownership increased the risk for tick encounters and tickborne disease among residents of three Lyme disease-endemic states as a nested cohort within a randomized controlled trial. Information about pet ownership, use of tick control for pets, property characteristics, tick encounters and human tickborne disease were captured through surveys, and associations were assessed using univariate and multivariable analyses. Pet-owning households had 1.83 times the risk (95% CI = 1.53, 2.20) of finding ticks crawling on and 1.49 times the risk (95% CI = 1.20, 1.84) of finding ticks attached to household members compared to households without pets. This large evaluation of pet ownership, human tick encounters and tickborne diseases shows that pet owners, whether of cats or dogs, are at increased risk of encountering ticks and suggests that pet owners are at an increased risk of developing tickborne disease. Pet owners should be made aware of this risk and be reminded to conduct daily tick checks of all household members, including the pets, and to consult their veterinarian regarding effective tick control products. © 2017 Blackwell Verlag GmbH.

  7. Compensations for increased rotational inertia during human cutting turns.

    Science.gov (United States)

    Qiao, Mu; Brown, Brian; Jindrich, Devin L

    2014-02-01

    Locomotion in a complex environment is often not steady state, but unsteady locomotion (stability and maneuverability) is not well understood. We investigated the strategies used by humans to perform sidestep cutting turns when running. Previous studies have argued that because humans have small yaw rotational moments of inertia relative to body mass, deceleratory forces in the initial velocity direction that occur during the turning step, or 'braking' forces, could function to prevent body over-rotation during turns. We tested this hypothesis by increasing body rotational inertia and testing whether braking forces during stance decreased. We recorded ground reaction force and body kinematics from seven participants performing 45 deg sidestep cutting turns and straight running at five levels of body rotational inertia, with increases up to fourfold. Contrary to our prediction, braking forces remained consistent at different rotational inertias, facilitated by anticipatory changes to body rotational speed. Increasing inertia revealed that the opposing effects of several turning parameters, including rotation due to symmetrical anterior-posterior forces, result in a system that can compensate for fourfold changes in rotational inertia with less than 50% changes to rotational velocity. These results suggest that in submaximal effort turning, legged systems may be robust to changes in morphological parameters, and that compensations can involve relatively minor adjustments between steps to change initial stance conditions.

  8. Ozone exposure increases respiratory epithelial permeability in humans

    International Nuclear Information System (INIS)

    Kehrl, H.R.; Vincent, L.M.; Kowalsky, R.J.; Horstman, D.H.; O'Neil, J.J.; McCartney, W.H.; Bromberg, P.A.

    1987-01-01

    Ozone is a respiratory irritant that has been shown to cause an increase in the permeability of the respiratory epithelium in animals. We used inhaled aerosolized /sup 99m/Tc-labeled diethylene triamine pentacetic acid (/sup 99m/Tc-DTPA) to investigate whether human respiratory epithelial permeability is similarly affected by exposure to ozone. In a randomized, crossover double-blinded study, 8 healthy, nonsmoking young men were exposed for 2 h to purified air and 0.4 ppm ozone while performing intermittent high intensity treadmill exercise (minute ventilation = 66.8 L/min). SRaw and FVC were measured before and at the end of exposures. Seventy-five minutes after the exposures, the pulmonary clearance of /sup 99m/Tc-DTPA was measured by sequential posterior lung imaging with a computer-assisted gamma camera. Ozone exposure caused respiratory symptoms in all 8 subjects and was associated with a 14 +/- 2.8% (mean +/- SEM) decrement in FVC (p less than 0.001) and a 71 +/- 22% increase in SRaw (p = 0.04). Compared with the air exposure day, 7 of the 8 subjects showed increased /sup 99m/Tc-DTPA clearance after the ozone exposure, with the mean value increasing from 0.59 +/- 0.08 to 1.75 +/- 0.43%/min (p = 0.03). These data show that ozone exposure sufficient to produce decrements in the pulmonary function of human subjects also causes an increase in /sup 99m/Tc-DTPA clearance

  9. EPOS-GNSS - Improving the infrastructure for GNSS data and products in Europe

    Science.gov (United States)

    Fernandes, Rui; Bos, Machiel; Bruyninx, Carine; Crocker, Paul; Dousa, Jan; Socquet, Anne; Walpersdorf, Andrea; Avallone, Antonio; Ganas, Athanassios; Gunnar, Benedikt; Ionescu, Constantin; Kenyeres, Ambrus; Ozener, Haluk; Vergnolle, Mathilde; Lidberg, Martin; Liwosz, Tomek; Soehne, Wolfgang

    2017-04-01

    EPOS-IP WP10 - "GNSS Data & Products" is the Working Package 10 of the European Plate Observing System - Implementation Phase project in charge of implementing services for the geo-sciences community to access existing Pan-European Geodetic Infrastructures. WP10 is currently formed by representatives of participating European institutions but in the operational phase contributions will be solicited from the entire geodetic community. In fact, WP10 also includes members from other institutions/countries that formally are not participating in the EPOS-IP but will be key players in the future services to be provided by EPOS. Additionally, several partners are also key partners at EUREF, which is also actively collaborating with EPOS. The geodetic component of EPOS is dealing essentially with implementing an e-infrastructure to store and disseminate the continuous GNSS data from existing Research Infrastructures. Present efforts are on developing geodetic tools to support Solid Earth research by optimizing the existing resources. However, other research and technical applications (e.g., reference frames, meteorology, space weather) can also benefit in the future from the optimization of the geodetic resources in Europe. We present and discuss the status of the implementation of the thematic and core services (TCS) for GNSS data within EPOS and the related business plan. We explain the tools and web-services being developed towards the implementation of the best solutions that will permit to the end-users, and in particular geo-scientists, to access the geodetic data, derived solutions, and associated metadata using a transparent and standardized processes. We also detail the different DDSS (Data, Data-Products, Services, Software) that will be made available for the Operational Phase of EPOS, which will start to be tested and made available during 2017 and 2018.

  10. Dopamine receptor activation increases HIV entry into primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Peter J Gaskill

    Full Text Available Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers.

  11. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

    Science.gov (United States)

    Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

    2014-01-01

    Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

  12. Endurance exercise training increases peripheral vascular response in human fingers.

    Science.gov (United States)

    Katayama, K; Shimoda, M; Maeda, J; Takemiya, T

    1998-10-01

    The purpose of this study was to clarify whether peripheral vascular response to alteration of transmural pressure is changed by endurance exercise training. The healthy male subjects (training group; n = 6) performed endurance exercise training that consisted of cycle ergometer exercise 5 d.week-1 and 30 min.d-1 for a period of 8 weeks. Changes in the peripheral vascular response to alteration of transmural pressure in the human finger were measured by a differential digital photoplethysmogram (DeltaDPG) and blood pressure during passive movement of the arm to different vertical hand positions relative to heart level. Following 8 weeks of endurance training, percent changes in DeltaDPG from heart level in the training group increased significantly (mean +/- SD, -48.1 +/- 7. 3 to -58.7 +/- 9.3% at the lowered position, 46.1 +/- 13.4 to 84.6 +/- 8.8% at the elevated position, ppressure, also significantly changed in the training group over the 8 weeks (5.6 +/- 1.3 to 2.7 +/- 1.6 mV. V-1.s-1.mmHg-1 at the lowered position, 30.0 +/- 12.4 to 54.4 +/- 18. 9 mV.V-1.s-1.mmHg-1 at the elevated position ). Maximal oxygen uptake (V.O2 max) was significantly increased in the training group. On the other hand, the control group (n = 6) showed no significant changes in all parameters for 8 weeks. Therefore these results suggest that endurance exercise training induces an increase in peripheral vascular response to alteration of transmural pressure in the human finger.

  13. Vitamin K3-2,3-epoxide induction of apoptosis with activation of ROS-dependent ERK and JNK protein phosphorylation in human glioma cells.

    Science.gov (United States)

    Wu, Jender; Chien, Chih-Chiang; Yang, Liang-Yo; Huang, Guan-Cheng; Cheng, Min-Chi; Lin, Che-Tong; Shen, Shing-Chuan; Chen, Yen-Chou

    2011-08-15

    2-Methyl-1,4-naphthoquinone (menadione or vitamin K3; EPO) and K3-2,3-epoxide (EPO1), but not vitamin K3-3-OH (EPO2), exhibited cytotoxicity that caused DNA fragmentation and chromatin condensation in U87 and C6 cells. EPO1 showed more-potent cytotoxicity than EPO, and the IC(50) values of EPO and EPO1 in U87 cells were 37.5 and 15.7μM, respectively. Activation of caspase 3 enzyme activity with cleavage of caspase 3 protein was detected in EPO1-treated U87 and C6 cells, and the addition of the caspase 3 peptidyl inhibitor, DEVD-FMK, reduced the cytotoxic effect of EPO1. An increase in the intracellular ROS level by EPO1 was observed in the DCHF-DA analysis, and EPO1-induced apoptosis and caspase 3 protein cleavage were prevented by adding the antioxidant, N-acetyl-cysteine (NAC), with decreased ROS production elicited by EPO1. Activation of ERK and JNK, but not p38, via phosphorylation induction was identified in EPO1- but not EPO- or EPO2-treated U87 and C6 cells, and this was blocked by adding NAC. However, the ERK inhibitor, PD98059, and the JNK inhibitor, SP600125, showed no effect on EPO1-induced cytotoxicity in either cell type. Our findings demonstrate that 2,3-epoxide substitution significantly potentiates the apoptotic effect of vitamin K3 via stimulating ROS production, which may be useful in the chemotherapy of glioblastoma cells. Copyright © 2011. Published by Elsevier Ireland Ltd.

  14. Oxidative stress induces the decline of brain EPO expression in aging rats.

    Science.gov (United States)

    Li, Xu; Chen, Yubao; Shao, Siying; Tang, Qing; Chen, Weihai; Chen, Yi; Xu, Xiaoyu

    2016-10-01

    Brain Erythropoietin (EPO), an important neurotrophic factor and neuroprotective factor, was found to be associated with aging. Studies found EPO expression was significantly decreased in the hippocampus of aging rat compared with that of the youth. But mechanisms of the decline of the brain EPO during aging remain unclear. The present study utilized a d-galactose (d-gal)-induced aging model in which the inducement of aging was mainly oxidative injury, to explore underlying mechanisms for the decline of brain EPO in aging rats. d-gal-induced aging rats (2months) were simulated by subcutaneously injecting with d-gal at doses of 50mg·kg(-1), 150mg·kg(-1) and 250mg·kg(-1) daily for 8weeks while the control group received vehicle only. These groups were all compared with the aging rats (24months) which had received no other treatment. The cognitive impairment was assessed using Morris water maze (MWM) in the prepared models, and the amount of β-galactosidase, the lipid peroxidation product malondialdehyde (MDA) level and the superoxide dismutase (SOD) activity in the hippocampus was examined by assay kits. The levels of EPO, EPOR, p-JAK2 and hypoxia-inducible factor-2α (HIF-2α) in the hippocampus were detected by western blot. Additionally, the correlation coefficient between EPO/EPOR expression and MDA level was analyzed. The MWM test showed that compared to control group, the escape latency was significantly extended and the times of crossing the platform was decreased at the doses of 150mg·kg(-1) and 250mg·kg(-1) (paging rats, the expressions of EPO, EPOR, p-JAK2, and HIF-2αin the brain of d-gal-treated rats were significantly decreased (paging could result in the decline of EPO in the hippocampus and oxidative stress might be the main reason for the decline of brain EPO in aging rats, involved with the decrease of HIF-2α stability. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. SGLT2 Protein Expression Is Increased in Human Diabetic Nephropathy

    Science.gov (United States)

    Wang, Xiaoxin X.; Levi, Jonathan; Luo, Yuhuan; Myakala, Komuraiah; Herman-Edelstein, Michal; Qiu, Liru; Wang, Dong; Peng, Yingqiong; Grenz, Almut; Lucia, Scott; Dobrinskikh, Evgenia; D'Agati, Vivette D.; Koepsell, Hermann; Kopp, Jeffrey B.; Rosenberg, Avi Z.; Levi, Moshe

    2017-01-01

    There is very limited human renal sodium gradient-dependent glucose transporter protein (SGLT2) mRNA and protein expression data reported in the literature. The first aim of this study was to determine SGLT2 mRNA and protein levels in human and animal models of diabetic nephropathy. We have found that the expression of SGLT2 mRNA and protein is increased in renal biopsies from human subjects with diabetic nephropathy. This is in contrast to db-db mice that had no changes in renal SGLT2 protein expression. Furthermore, the effect of SGLT2 inhibition on renal lipid content and inflammation is not known. The second aim of this study was to determine the potential mechanisms of beneficial effects of SGLT2 inhibition in the progression of diabetic renal disease. We treated db/db mice with a selective SGLT2 inhibitor JNJ 39933673. We found that SGLT2 inhibition caused marked decreases in systolic blood pressure, kidney weight/body weight ratio, urinary albumin, and urinary thiobarbituric acid-reacting substances. SGLT2 inhibition prevented renal lipid accumulation via inhibition of carbohydrate-responsive element-binding protein-β, pyruvate kinase L, SCD-1, and DGAT1, key transcriptional factors and enzymes that mediate fatty acid and triglyceride synthesis. SGLT2 inhibition also prevented inflammation via inhibition of CD68 macrophage accumulation and expression of p65, TLR4, MCP-1, and osteopontin. These effects were associated with reduced mesangial expansion, accumulation of the extracellular matrix proteins fibronectin and type IV collagen, and loss of podocyte markers WT1 and synaptopodin, as determined by immunofluorescence microscopy. In summary, our study showed that SGLT2 inhibition modulates renal lipid metabolism and inflammation and prevents the development of nephropathy in db/db mice. PMID:28196866

  16. Studies on cationic UV curing of epoxidised palm oil (EPO) for surface coatings

    International Nuclear Information System (INIS)

    Mek Zah Salleh; Mohd Hilmi Mahmood; Wan Rosli Wan Daud; Kumar, R.N.

    2000-01-01

    Epoxidised palm oil (EPO) resin can be cured by ultraviolet (UV) radiation either by radical, cationic or hybrid system. Cationic curing system has been chosen in this study due to the fact that epoxy groups present in EPO can be utilised directly to form crosslinking. Curing was done by means of a 20 cm wide UV IST machine with the conditions of 7.5 A current and 4 m/min conveyor speed. Sulphonium and ferrocenium salts were used as cationic photoinitiator. A formulations study was performed on the selected grades of EPO with other materials. These include types and concentration of photoinitiator, monomers, concentration of EPO and post-cure. The properties of the cured film such as pendulum hardness, percentage of gel content and tensile strength were determined. It was found that triarylsulphonium hexafluorophosphate has a very low solubility in EPO. Addition of vinyl ether monomer to the formulation did not enhance pendulum hardness and gel content of the cured films. It is also found that the post cure temperature has no significant effect on the cured film

  17. Silicon effects on formation of EPO oxide coatings on aluminum alloys

    International Nuclear Information System (INIS)

    Wang, L.; Nie, X.

    2006-01-01

    Electrolytic plasma processes (EPP) can be used for cleaning, metal-coating, carburizing, nitriding, and oxidizing. Electrolytic plasma oxidizing (EPO) is an advanced technique to deposit thick and hard ceramic coatings on a number of aluminum alloys. However, the EPO treatment on Al-Si alloys with a high Si content has rarely been reported. In this research, an investigation was conducted to clarify the effects of silicon contents on the EPO coating formation, morphology, and composition. Cast hypereutectic 390 alloys (∼ 17% Si) and hypoeutectic 319 alloys (∼ 7% Si) were chosen as substrates. The coating morphology, composition, and microstructure of the EPO coatings on those substrates were investigated using scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) analysis and X-ray diffraction (XRD). A stylus roughness tester was used for surface roughness measurement. It was found that the EPO process had four stages where each stage was corresponding to various coating surface morphology, composition, and phase structures, characterised by different coating growth mechanisms

  18. Selective attention increases choice certainty in human decision making.

    Science.gov (United States)

    Zizlsperger, Leopold; Sauvigny, Thomas; Haarmeier, Thomas

    2012-01-01

    Choice certainty is a probabilistic estimate of past performance and expected outcome. In perceptual decisions the degree of confidence correlates closely with choice accuracy and reaction times, suggesting an intimate relationship to objective performance. Here we show that spatial and feature-based attention increase human subjects' certainty more than accuracy in visual motion discrimination tasks. Our findings demonstrate for the first time a dissociation of choice accuracy and certainty with a significantly stronger influence of voluntary top-down attention on subjective performance measures than on objective performance. These results reveal a so far unknown mechanism of the selection process implemented by attention and suggest a unique biological valence of choice certainty beyond a faithful reflection of the decision process.

  19. Therapy with recombinant human erythropoietin in patients with myelodysplastic syndromes.

    Science.gov (United States)

    Stone, R M; Bernstein, S H; Demetri, G; Facklam, D P; Arthur, K; Andersen, J; Aster, J C; Kufe, D

    1994-10-01

    We conducted a Phase I-II trial of recombinant human erythropoietin-beta (rhEPO) in patients with myelodysplastic syndrome (MDS). Patients with anemia and pathologically confirmed MDS were eligible for the study. Treatment consisted of rhEPO by subcutaneous injection thrice weekly for 6 weeks at one of three dose levels (100 U/kg (three patients), 200 U/kg (three patients) and 400 U/kg (14 patients)). Ferrous sulfate (325 mg po tid) was also administered if the transferrin saturation was below 30% (two patients). Patients were monitored with weekly CBC, white cell differential, and reticulocyte counts. Bone marrow examinations were performed at the conclusion of the treatment period and after a 2 week washout period. Patients who responded to therapy were continued on rhEPO at the same dose for 6 additional months. Response criteria included: 50% reduction in transfusion requirements compared with the 6 week pre-study period; doubling of reticulocyte count that was maintained on two determinations at least 1 week apart; or an increase in hemoglobin by at least 1.2 gm/dl without transfusions. Pre-treatment factors potentially predictive of response were analyzed by univariate analysis and in a multivariate fashion by classification and regression trees. Seven of the twenty patients sustained an untransfused rise in serum hemoglobin > or = 1.2 gm/dl. Four of the sixteen patients (including three of seven patients experiencing a rise in serum hemoglobin) who were transfusion-dependent prior to the study achieved a reduction or elimination of their transfusion requirements. Five of thirteen patients who received rhEPO during the extension phase had a continued response. A low baseline erythropoietin level (< 50 mU/ml) was the best predictor of hemoglobin response when controlling for other variables. rhEPO has a role in the treatment of certain patients with MDS, particularly in those whose endogenous serum erythropoietin levels are not markedly elevated.

  20. Designing, Supporting, and Sustaining an Online Community of Practice: NASA EPO Workspace as an Ongoing Exploration of the Value of Community

    Science.gov (United States)

    Davey, B.; Davis, H. B.

    2015-12-01

    Increasingly, geographically diverse organizations, like NASA's Science Mission Directorate Education and Public Outreach personnel (SMD EPO), are looking for ways to facilitate group interactions in meaningful ways while limiting costs. Towards this end, of particular interest, and showing great potential are communities of practice. Communities of practice represent relationships in real-time between and among people sharing a common practice. They facilitate the sharing of information, building collective knowledge, and growing of the principles of practice. In 2010-11, SMD EPO established a website to support EPO professionals, facilitate headquarters reporting, and foster a community of practice. The purpose of this evaluation is to examine the design and use of the workspace and the value created for both individual community members and SMD EPO, the sponsoring organization. The online workspace was launched in 2010-11 for the members of NASA's SMDEPO community. The online workspace was designed to help facilitate the efficient sharing of information, be a central repository for resources, help facilitate and support knowledge creation, and ultimately lead to the development of an online community of practice. This study examines the role of the online workspace component of a community in the work of a community of practice. Much has been studied revealing the importance of communities of practice to organizations, project success, and knowledge management and some of these same successes hold true for virtual communities of practice. Additionally, we look at the outcomes of housting the online community for these past years in respect to knowledge building and personal and organizational value, the affects on professional dvelopment opportunities, how community members have benefited, and how the workspace has evolved to better serve the community.

  1. Erythropoetin receptor expression in the human diabetic retina

    Directory of Open Access Journals (Sweden)

    Tsang Stephen H

    2009-11-01

    Full Text Available Abstract Background Recent evidence suggests erythropoietin (EPO and the erythropoietin receptor (EPOR may play a direct role in the pathogenesis of diabetic retinopathy. Better characterization of the EPO-EPOR signaling system in the ischemic retina may offer a new therapeutic modality for ischemic ophthalmic diseases. This study was performed to identify EPOR mRNA expression in the human diabetic eye. Findings EPOR antisense RNA probes were validated on human pancreas tissue. In the normal eye, EPOR was expressed in the retinal ganglion cell layer. Minimal expression was observed in the inner and outer nuclear layer. Under conditions of diabetic retinopathy, EPOR expression shifted to photoreceptor cells. Increased expression was also observed in the peripheral retina. Conclusion EPOR expression may be a biomarker or contribute to disease mechanisms in diabetic retinopathy.

  2. Mass spectrometric analysis of EPO IEF-PAGE interfering substances in nitrile examination gloves.

    Science.gov (United States)

    Reichel, Christian

    2012-10-01

    Direct detection of doping with recombinant erythropoietins (rhEPO) is accomplished by isoelectric focusing (IEF) or sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis (PAGE). In a recent publication, Lasne et al. (Electrophoresis 2011, 32, 1444) showed that improper use of nitrile examination gloves during sample collection, sample preparation, and IEF-PAGE may lead to distorted or absent EPO IEF-profiles. In order to clarify which substances are responsible for this observation, a mass spectrometric study on water extractable compounds found in nitrile gloves was performed. Several substance classes were shown to be present, among them polyethylene glycols (PEG), anionic and nonionic surfactants, as well as alcohol ethoxylates and plasticizers. It could be demonstrated that alkylbenzenesulfonates, the main category of detectable anionic detergents, and among them sodium dodecylbenzenesulfonate (SDBS) and its homologs, are the prime reason for the interference of nitrile gloves with EPO IEF-PAGE. Copyright © 2012 John Wiley & Sons, Ltd.

  3. EPOS-IP WP10: services and data provision for the GNSS community

    Science.gov (United States)

    Fernandes, Rui

    2016-04-01

    The EPOS-IP WP10 - "GNSS Data & Products" is the Working Package of the EPOS-IP project in charge of implementing the necessary services in order that the geo-sciences community can access the existing Pan-European Geodetic Infrastructures. The WP10 is formed by representatives of the participating institutions (10) but it is also open to the entire geodetic community. In fact, WP10 also includes members from other institutions/countries that formally are not participating in the EPOS-IP. During the EPOS-IP project, the geodetic component of EPOS (WP10) is dealing essentially with Research Infrastructures focused on continuous operating GNSS (cGNSS). The option of concentrating the efforts on the presently most generalized geodetic tool supporting research on Solid Earth was decided in order to optimize the existing resources. Furthermore, although the focus is on Solid Earth applications, other research and technical applications (e.g., reference frames, meteorology, space weather) can also benefit from the efforts of WP10 towards the optimization of the geodetic resources in Europe. We will present and discuss the plans for the implementation of the thematic and core services (TCS) for GNSS data within EPOS and the related business plan. We will focus on strategies towards the implementation of the best solutions that will permit to the end-users, and in particular geo-scientists, to access the geodetic data, derived solutions, and associated metadata using transparent and uniform processes. The collaboration with EUREF is also an essential component of the implementation plan.

  4. Calorie restriction increases muscle mitochondrial biogenesis in healthy humans.

    Directory of Open Access Journals (Sweden)

    Anthony E Civitarese

    2007-03-01

    Full Text Available Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood.The current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8 +/- 1.0 y, overweight (body mass index, 27.8 +/- 0.7 kg/m(2 individuals randomized into one of three groups for a 6-mo intervention: Control, 100% of energy requirements; CR, 25% caloric restriction; and CREX, caloric restriction with exercise (CREX, 12.5% CR + 12.5% increased energy expenditure (EE. In the controls, 24-h EE was unchanged, but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass (CR, -135 +/- 42 kcal/d, p = 0.002 and CREX, -117 +/- 52 kcal/d, p = 0.008. Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p < 0.05. In parallel, mitochondrial DNA content increased by 35% +/- 5% in the CR group (p = 0.005 and 21% +/- 4% in the CREX group (p < 0.004, with no change in the control group (2% +/- 2%. However, the activity of key mitochondrial enzymes of the TCA (tricarboxylic acid cycle (citrate synthase, beta-oxidation (beta-hydroxyacyl-CoA dehydrogenase, and electron transport chain (cytochrome C oxidase II was unchanged. DNA damage was reduced from baseline in the CR (-0.56 +/- 0.11 arbitrary units, p = 0.003 and CREX (-0.45 +/- 0.12 arbitrary units, p = 0.011, but not in the controls. In primary cultures of human myotubes, a nitric oxide donor (mimicking eNOS signaling induced mitochondrial biogenesis but failed to induce SIRT1 protein expression, suggesting that additional factors may regulate SIRT1 content during CR.The observed increase in

  5. Fractalkine is expressed in the human ovary and increases progesterone biosynthesis in human luteinised granulosa cells

    Directory of Open Access Journals (Sweden)

    Yan Jie

    2011-06-01

    Full Text Available Abstract Background Recent evidence from rodent ovaries has demonstrated expression of fractalkine and the existence of fractalkine receptor, and showed that there is a significant increase in steroidogenesis in response to fractalkine, yet the role of fractalkine and CX3CR1 in the human ovary is still unknown. This study aimed to determine the expression levels of fractalkine and CX3CR1 in the human ovary and to investigate their roles in sexual hormone biosynthesis by human luteinising granulosa cells. This is the first detailed report of fractalkine and CX3CR1 expression and function in the human ovary. Methods Fractalkine and CX3CR1 expression levels were measured by immunohistochemistry using ovarian tissue from pathological specimens from five individuals. Granulosa cells were obtained from patients during IVF treatment. They were cultured and treated with increasing doses of hCG with or without fractalkine. Media were collected to detect estradiol and progesterone by chemiluminescence. StAR, 3-βHSD and CYP11A expression were determined in granulosa cells treated with or without fractalkine by real-time RT-PCR. Results Fractalkine and CX3CR1 were expressed in the human ovary and in luteinising granulosa cells. However, fractalkine expression was stronger in luteinising granulosa cells. Treatment with fractalkine augmented hCG stimulation of progesterone production in a dose-dependent manner with concomitant increases in transcript levels for key steroidogenic enzymes (StAR, 3-βHSD and CYP11A but had no effect on estradiol biosynthesis(P Conclusions Fractalkine and CX3CR1 were found to express in human ovary and luteinising granulosa cells. Fractalkine can increase the biosynthesis of progesterone in a dose-dependent manner by enhancing transcript levels of key steroidogenic enzymes.

  6. Increased Plasma Levels of Heme Oxygenase-1 in Human Brucellosis.

    Science.gov (United States)

    Chen, Zhe; Zhang, Yu-Xue; Fu, Dong-Wei; Gao, Qing-Feng; Ge, Feng-Xia; Liu, Wei-Hua

    2016-08-01

    Brucellosis is associated with inflammation and the oxidative stress response. Heme oxygenase-1 (HO-1) is a cytoprotective stress-responsive enzyme that has anti-inflammatory and anti-oxidant effects. Nevertheless, the role of HO-1 in human brucellosis has not yet been studied. The aim of this study was to examine the plasma levels of HO-1 in patients with brucellosis and to evaluate the ability of plasma HO-1 levels as an auxiliary diagnosis, a severity predictor, and a monitor for brucellosis treatments. A total of 75 patients with brucellosis were divided into the acute, subacute, chronic active, and chronic stable groups. An additional 20 volunteers were included as the healthy control group. The plasma HO-1 levels and other laboratory parameters were measured in all groups. Furthermore, the plasma levels of HO-1 in the acute group were compared before and after treatment. The plasma HO-1 levels were considerably increased in the acute (4.97 ± 3.55), subacute (4.98 ± 3.23), and chronic active groups (4.43 ± 3.00) with brucellosis compared to the healthy control group (1.03 ± 0.63) (p brucellosis (r = 0.707, p brucellosis status and may be used as a supplementary plasma marker for diagnosing brucellosis and monitoring its treatment.

  7. Engaging Scientists in Meaningful E/PO: How the NASA SMD E/PO Community Addresses the Needs of the Higher Ed Community

    Science.gov (United States)

    Manning, James; Meinke, Bonnie K.; Schultz, Gregory R.; Smith, Denise A.; Lawton, Brandon L.; Gurton, Suzanne; NASA Astrophysics E/PO Community

    2015-01-01

    The NASA Astrophysics Science Education and Public Outreach Forum (SEPOF) coordinates the work of NASA Science Mission Directorate (SMD) Astrophysics EPO projects and their teams to bring cutting-edge discoveries of NASA missions to the introductory astronomy college classroom. The Astrophysics Forum assists scientist and educator involvement in SMD E/PO (uniquely poised to foster collaboration between scientists with content expertise and educators with pedagogy expertise) and makes SMD E/PO resources and expertise accessible to the science and education communities. We present three new opportunities for college instructors to bring the latest NASA discoveries in Astrophysics into their classrooms.To address the expressed needs of the higher education community, the Astrophysics Forum collaborated with the Astrophysics E/PO community, researchers, and Astronomy 101 instructors to place individual science discoveries and learning resources into context for higher education audiences. Among these resources are two Resource Guides on the topics of cosmology and exoplanets, each including a variety of accessible sources.The Astrophysics Forum also coordinates the development of the Astro 101 slide set series--5 to 7-slide presentations on new discoveries from NASA Astrophysics missions relevant to topics in introductory astronomy courses. These sets enable Astronomy 101 instructors to include new discoveries not yet in their textbooks into the broader context of the course: http://www.astrosociety.org/education/astronomy-resource-guides/.The Astrophysics Forum also coordinated the development of 12 monthly Universe Discovery Guides, each featuring a theme and a representative object well-placed for viewing, with an accompanying interpretive story, strategies for conveying the topics, and supporting NASA-approved education activities and background information from a spectrum of NASA missions and programs: http://nightsky.jpl.nasa.gov/news-display.cfm?News_ID=611

  8. Effects of recombinant human erythropoietin injections on physical self in endurance athletes.

    Science.gov (United States)

    Ninot, Grégory; Connes, Philippe; Caillaud, Corrine

    2006-04-01

    This study examined the time course of mean self-esteem and physical self scores in three groups: male endurance athletes treated with recombinant human erythropoietin (rHuEPO group, n = 6), a placebo group (n = 5) injected with a sodium chloride solution and a control group who did not receive any injection (n = 6). Each participant completed the Physical Self Inventory twice a day (between 07.00 and 09.00 h and between 19.00 and 21.00 h). Using a 10 cm visual analog scale, the participants assessed global self-esteem, physical self-worth and the sub-domains of physical condition, sport competence, attractive body and physical strength (Fox & Corbin, 1989). This was conducted over three consecutive periods: in the 2 weeks before the course of injections, during the 6 weeks of injections and for 4 weeks after the injections. Aerobic capacity was assessed before and after 4 weeks of treatment. The results showed a significant increase in aerobic physical fitness in the rHuEPO group and a significant increase in perceived physical condition and physical strength scores at the end of treatment. The main psychological result was that endurance athletes were highly sensitive to the effects of rHuEPO on physical fitness. The perception of increased physical condition may lead to a stronger commitment to training. The rHuEPO injections presented a dangerous hedonic effect linked to endurance training. These results confirm the need to tackle rHuEPO abuse at any time during the training season.

  9. Increasing transmission of antibiotic resistance from animals to humans

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller; Frimodt-Møller, Niels

    2011-01-01

    The importance of the animal reservoir for emergence of antimicrobial resistance in bacteria in humans is difficult to estimate. In this article we give our estimate of the importance and also highlight on which points we have become wiser during recent years. We conclude that it still is the human...... usage of antibiotics which contributes most to resistance observed in humans, but also that the contribution from animals is large and larger than estimated just a few years ago. This indicates the need to implement restriction on antimicrobial usage for both humans and animals....

  10. Increasing transmission of antibiotic resistance from animals to humans

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller; Frimodt-Møller, Niels

    2011-01-01

    usage of antibiotics which contributes most to resistance observed in humans, but also that the contribution from animals is large and larger than estimated just a few years ago. This indicates the need to implement restriction on antimicrobial usage for both humans and animals.......The importance of the animal reservoir for emergence of antimicrobial resistance in bacteria in humans is difficult to estimate. In this article we give our estimate of the importance and also highlight on which points we have become wiser during recent years. We conclude that it still is the human...

  11. Healing human myocardial infarction associated with increased chymase immunoreactivity

    NARCIS (Netherlands)

    Daemen, M. J.; Urata, H.

    1997-01-01

    We studied the immunoreactivity of the chymase protein in normal human myocardium and in human myocardial infarctions at various postinfarction times using immuno-histochemistry. In noninfarcted hearts chymase was mainly present in cardiomyocytes and endothelial cells. At 6 h after infarction the

  12. An integrative 'omics' solution to the detection of recombinant human erythropoietin and blood doping.

    Science.gov (United States)

    Pitsiladis, Yannis P; Durussel, Jérôme; Rabin, Olivier

    2014-05-01

    Administration of recombinant human erythropoietin (rHumanEPO) improves sporting performance and hence is frequently subject to abuse by athletes, although rHumanEPO is prohibited by the WADA. Approaches to detect rHumanEPO doping have improved significantly in recent years but remain imperfect. A new transcriptomic-based longitudinal screening approach is being developed that has the potential to improve the analytical performance of current detection methods. In particular, studies are being funded by WADA to identify a 'molecular signature' of rHumanEPO doping and preliminary results are promising. In the first systematic study to be conducted, the expression of hundreds of genes were found to be altered by rHumanEPO with numerous gene transcripts being differentially expressed after the first injection and further transcripts profoundly upregulated during and subsequently downregulated up to 4 weeks postadministration of the drug; with the same transcriptomic pattern observed in all participants. The identification of a blood 'molecular signature' of rHumanEPO administration is the strongest evidence to date that gene biomarkers have the potential to substantially improve the analytical performance of current antidoping methods such as the Athlete Biological Passport for rHumanEPO detection. Given the early promise of transcriptomics, research using an 'omics'-based approach involving genomics, transcriptomics, proteomics and metabolomics should be intensified in order to achieve improved detection of rHumanEPO and other doping substances and methods difficult to detect such a recombinant human growth hormone and blood transfusions.

  13. Human Adenovirus 36 Infection Increased the Risk of Obesity

    Science.gov (United States)

    Xu, Mei-Yan; Cao, Bing; Wang, Dong-Fang; Guo, Jing-Hui; Chen, Kai-Li; Shi, Mai; Yin, Jian; Lu, Qing-Bin

    2015-01-01

    Abstract Human adenovirus 36 (HAdV-36), as the key pathogen, was supposed and discussed to be associated with obesity. We searched the references on the association between HAdV-36 infection and obesity with the different epidemiological methods, to explore the relationship with a larger sample size by meta-analysis and compare the differences of epidemiological methods and population subsets by the subgroup analyses. We conducted literature search on the association between HAdV-36 infections and obesity in English or Chinese published up to July 1, 2015. The primary outcome was the HAdV-36 infection rate in the obese and lean groups; the secondary outcomes were the BMI level and BMI z-score in the HAdV-36 positive and negative groups. The pooled odds ratio (OR) was calculated for the primary outcome; the standardized mean differences (SMDs) were calculated for the secondary and third outcomes. Prediction interval (PI) was graphically presented in the forest plot of the random effect meta-analyses. Metaregression analysis and subgroup analysis were performed. Finally 24 references with 10,191 study subjects were included in the meta-analysis. The obesity subjects were more likely to be infected with HAdV-36 compared to the lean controls (OR = 2.00; 95%CI: 1.46, 2.74; PI: 0.59, 6.76; P infection for obesity were 1.77 (95%CI: 1.19, 2.63; PI: 0.44, 7.03; P = 0.005) and 2.26 (95%CI: 1.67, 3.07; PI: 1.45, 3.54; P SMD of BMI was 0.28 (95% CI: 0.08, 0.47; PI: −0.53, 1.08; P = 0.006) in the HAdV-36 positive subjects with a high heterogeneity (I2 = 86.5%; P infection was higher than those without HAdV-36 infection (SMD = 0.19; 95%CI: −0.31, 0.70; PI: −2.10, 2.49), which had no significantly statistical difference (P = 0.453). HAdV-36 infection increased the risk of obesity. HAdV-36 also increased the risk of weight gain in adults, which was not observed in children. PMID:26705235

  14. Studies on cationic UV curing of cycloaliphatic diepoxide - epoxidised palm oil (EPO) for surface coatings

    International Nuclear Information System (INIS)

    Mek Zah Salleh; Mohd Hilmi Mahmood; Wan Rosli Wan Daud; Kumar, R.N.

    1999-01-01

    In recent years, there are growing trends in using vegetables oil as raw materials in resin production. Development of new products from palm oil derivatives such as epoxidised palm oil (EPO) is of particular interest to this country. The compatibility of EPO with cycloaliphatic diepoxide allows the development of a wide range of radiation curable formulations by cationic photoinitiators. Curing was done by means of a 20 cm wide IST UV, machine with the conditions of 7.5A current and 4 m/min conveyor speed. Sulphonium and ferrocenium salts were used as the cationic photoinitiators. A study was formulated to compromise the investigation of various effects on the cured film properties. These effects include; types and concentration of photoinitiators, formulating ratios, reactive diluents, photosensitizers and postcuring conditions. The effects on the gel fraction, pendulum hardness, tensile strength and elongation at break were investigated. The results showed that 30% of EPO was the maximum value that can be used in the formulation. It was also found that triarylsulphonium hexafluorophosphate has a very low solubility in EPO

  15. In vivo evaluation of EPO-secreting cells immobilized in different alginate-PLL microcapsules.

    Science.gov (United States)

    Ponce, S; Orive, G; Hernández, R M; Gascón, A R; Canals, J M; Muñoz, M T; Pedraz, J L

    2006-11-01

    Alginates are the most employed biomaterials for cell encapsulation due to their abundance, easy gelling properties and apparent biocompatibility. However, as natural polymers different impurities including endotoxins, proteins and polyphenols can be found in their composition. Several purification protocols as well as different batteries of assays to prove the biocompatibility of the alginates in vitro have been recently developed. However, little is known about how the use of alginates with different purity grade may affect the host immune response after their implantation in vivo. The present paper investigates the long-term functionality and biocompatibility of murine erythropoietin (EPO) secreting C2C12 cells entrapped in microcapsules elaborated with alginates with different properties (purity, composition and viscosity). Results showed that independently of the alginate type employed, the animals presented elevated hematocrit levels until day 130, remaining at values between 70-87%. However, histological analysis of the explanted devices showed higher overgrowth around non-biomedical grade alginate microcapsules which could be directly related with higher impurity content of this type of alginate. Although EPO delivery may be limited by the formation of a fibrotic layer around non-biomedical grade alginate microcapsules, the high EPO secretion of the encapsulated cells together with the pharmacodynamic behaviour and the angiogenic and immune-modulatory properties of EPO result in no direct correlation between the biocompatibility of the alginate and the therapeutic response obtained.

  16. Therapeutic levels of erythropoietin (EPO) achieved after gene electrotransfer to skin in mice

    DEFF Research Database (Denmark)

    Gothelf, A; Hojman, P; Gehl, Julie

    2010-01-01

    Gene electrotransfer refers to gene transfection by electroporation and is an effective non-viral method for delivering naked DNA into cells and tissues. This study presents data from gene electrotransfer with erythropoietin (EPO) to mouse skin. Nine-week-old female NMRI mice received one, two...

  17. Therapy-resistant anaemia in congenital nephrotic syndrome of the Finnish type--implication of EPO, transferrin and transcobalamin losses.

    Science.gov (United States)

    Toubiana, Julie; Schlageter, Marie-Hélène; Aoun, Bilal; Dunand, Olivier; Vitkevic, Renata; Bensman, Albert; Ulinski, Tim

    2009-04-01

    Congenital nephrotic syndrome of the Finnish type (CNF) is due to NPHS1 mutation and is responsible for a variety of urinary protein losses. We report the case of a 4-month-old girl with a particularly severe form (proteinuria approximately 150 g/l) of CNF. She developed severe non-regenerative anaemia requiring bi-monthly blood transfusions despite daily EPO (600 UI/kg) and iron supplementation. Epoetin pharmacokinetics revealed a urinary loss of 27% of the given dose within the first 24 h after IV injection. However, plasma levels remained increased after 24 h (228 UI/l). Plasma transferrin and transcobalamin levels were undetectable. Atransferrinaemia and atranscobalaminaemia seem to be responsible for disturbed erythropoiesis.

  18. Early Erythropoietin Administration does not Increase the Risk of Retinopathy in Preterm Infants

    Directory of Open Access Journals (Sweden)

    Hsin-Hsu Chou

    2017-02-01

    Conclusion: EPO administration did not significantly increase the risk of ROP of any stage reported or Stage ≥3. Further clinical trials investigating the impact of EPO on ROP in premature infants should include all confounding factors to clarify this important issue.

  19. Yeast Biodiversity in Vineyard Environments Is Increased by Human Intervention.

    Directory of Open Access Journals (Sweden)

    João Drumonde-Neves

    Full Text Available One hundred and five grape samples were collected during two consecutive years from 33 locations on seven oceanic islands of the Azores Archipelago. Grape samples were obtained from vineyards that were either abandoned or under regular cultivation involving common viticultural interventions, to evaluate the impact of regular human intervention on grape yeast biota diversity in vineyards. A total of 3150 yeast isolates were obtained and 23 yeast species were identified. The predominant species were Hanseniaspora uvarum, Pichia terricola, Starmerella bacillaris and Issatchenkia hanoiensis. The species Barnettozyma californica, Candida azymoides and Pichia cecembensis were reported in grapes or wine-associated environments for the first time. A higher biodiversity was found in active vineyards where regular human intervention takes place (Shannon index: 1.89 and 1.53 in the first and second years, respectively when compared to the abandoned ones (Shannon index: 0.76 and 0.31. This finding goes against the assumptions that human intervention can destroy biodiversity and lead to homogeneity in the environment. Biodiversity indices were considerably lower in the year with the heaviest rainfall. This study is the first to report on the grape yeast communities from several abandoned vineyards that have undergone no human intervention.

  20. Seasonal differences in human responses to increasing temperatures

    DEFF Research Database (Denmark)

    Kitazawa, Sachie; Andersen, Rune Korsholm; Wargocki, Pawel

    2014-01-01

    to be sleepier. Heart rate slightly increased during exposure, and SpO2 and ETCO2 began to decrease while core temperature started to increase. Performance of Tsai-partington test and addition test improved during exposures due to learning though lesser in winter. Results show negative effects of the temperature......Experiments were conducted in late summer and winter with 80 young and elderly Danish subjects exposed for 3.5 hours in a climate chamber to the temperature increasing from 24°C to 35.2°C at a rate of 3.7K/h. Psychological and physiological measurements were performed during exposure and subjects...... assessed comfort and acute health symptoms. Thermal sensation increased with increasing chamber temperature and did not differ during late summer and winter exposures. Skin temperature increased with increasing temperature and was slightly but significantly higher in the late summer in the first half...

  1. Exercise increases human skeletal muscle insulin sensitivity via coordinated increases in microvascular perfusion and molecular signaling

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Frøsig, Christian; Kjøbsted, Rasmus

    2017-01-01

    and increased similarly in both legs during the clamp and L-NMMA had no effect on these insulin-stimulated signaling pathways. Therefore, acute exercise increases insulin sensitivity of muscle by a coordinated increase in insulin-stimulated microvascular perfusion and molecular signaling at the level of TBC1D4...... and glycogen synthase in muscle. This secures improved glucose delivery on the one hand and increased ability to take up and dispose of the delivered glucose on the other hand....

  2. The use of vertical and horizontal surface displacements at EPOS GNSS stations in Greenland to study ice sheet mass balance

    DEFF Research Database (Denmark)

    Khan, Shfaqat Abbas

    2014-01-01

    The European Plate Observing System (EPOS) includes e.g. seismic and geodetic permanent national monitoring networks on a European scale. The main purpose is to create data platforms for monitoring and study geophysics processes like earthquakes, volcanoes, surface dynamics and tectonics. Here we...... present data from arctic GNSS stations included in the EPOS network. The arctic EPOS GNSS network consists of 16 continuous GPS stations spread across Greenland. This network is able to map the velocity fields associated with, plate motion, postglacial rebound and improve our understanding of tectonic...

  3. Therapeutic superiority and safety of combined hydroxyurea with recombinant human erythropoietin over hydroxyurea in young β-thalassemia intermedia patients.

    Science.gov (United States)

    Elalfy, Mohsen S; Adly, Amira A M; Ismail, Eman A; Elhenawy, Yasmine I; Elghamry, Islam R

    2013-12-01

    To assess the efficacy and safety of combined hydroxyurea (HU) and recombinant human erythropoietin (rHuEPO) in β-thalassemia intermedia (TI) patients compared with single HU therapy. An interventional prospective randomized study registered in the ClinicalTrials.gov (NCT01624038) was performed on 80 TI patients (≤ 18 yr) divided into group A (40 patients received combined HU and rHuEPO) and group B (40 patients received single HU therapy). Baseline serum EPO levels were measured, and both groups were followed up for a mean period of 1 yr with regular assessment of transfusion requirements, blood pressure, ferritin, liver and renal functions, hemoglobin, and HbF. Quality of life (QoL) was assessed at the start and end of the study. Transfusion frequency and index were significantly decreased, while QoL was increased in group A compared with group B where 85% of patients showed improvement on combined therapy compared with 50% of patients on HU. Hemoglobin and HbF were significantly increased in both TI groups; however, this was more evident in group A than in group B. Also, 37.5% of patients in group A became transfusion-independent compared with 15% in group B. EPO levels were negatively related to increments of hemoglobin and HbF. Splenectomized patients and those with initial HbF% >40% had the best response to combined therapy. No serious adverse events necessitating discontinuation of therapy in both groups. HU was effective in management of TI; however, combination with rHuEPO gave a superior therapeutic effect resulting in the best clinical and hematological responses without adverse events. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Engaging Scientists in Meaningful E/PO: How the NASA SMD E/PO Community Addresses Informal Educators' Preferences for PD and Materials

    Science.gov (United States)

    Bartolone, Lindsay; Nelson, Andi; Smith, Denise A.; NASA SMD Astrophysics E/PO Community

    2015-01-01

    The NASA Astrophysics Science Education and Public Outreach Forum (SEPOF) coordinates the work of NASA Science Mission Directorate (SMD) Astrophysics EPO projects. These teams work together to capitalize on the cutting-edge discoveries of NASA Astrophysics missions to support educators in Science, Technology, Engineering, and Math (STEM) and to enable youth to engage in doing STEM inside and outside of school. The Astrophysics Forum assists scientists and educators with becoming involved in SMD E/PO, which is uniquely poised to foster collaboration between scientists with content expertise and educators with pedagogy expertise, and makes SMD E/PO resources and expertise accessible to the science and education communities. Informal educators participated in a recent nationally-distributed survey from the NASA SMD SEPOF Informal Education Working Group. The results show the preferences of staff from museums, parks, public libraries, community/afterschool centers, and others with regard to professional development and material resources. The results of the survey will be presented during this session.In addition, we present opportunities for the astronomy community to participate in collaborations supporting the NASA SMD efforts in K-12 Formal Education, Informal Science Education, and Outreach. These efforts focus on enhancing instruction, as well as youth and public engagement, in STEM via use of research-based best practices, collaborations with libraries, partnerships with local and national organizations, and remote engagement of audiences. The Forums' efforts for the Formal, Informal Science Education and Outreach communities include a literature review, appraisal of informal educators' needs, coordination of audience-based NASA resources and opportunities, professional development, plus support with the Next Generation Science Standards. Learn how to join in our collaborative efforts to support the K-12 Formal Education community and to reach the informal

  5. Minimal doses of a sequence-optimized transgene mediate high-level and long-term EPO expression in vivo: challenging CpG-free gene design.

    Science.gov (United States)

    Kosovac, D; Wild, J; Ludwig, C; Meissner, S; Bauer, A P; Wagner, R

    2011-02-01

    Advanced gene delivery techniques can be combined with rational gene design to further improve the efficiency of plasmid DNA (pDNA)-mediated transgene expression in vivo. Herein, we analyzed the influence of intragenic sequence modifications on transgene expression in vitro and in vivo using murine erythropoietin (mEPO) as a transgene model. A single electro-gene transfer of an RNA- and codon-optimized mEPOopt gene into skeletal muscle resulted in a 3- to 4-fold increase of mEPO production sustained for >1 year and triggered a significant increase in hematocrit and hemoglobin without causing adverse effects. mEPO expression and hematologic levels were significantly lower when using comparable amounts of the wild type (mEPOwt) gene and only marginal effects were induced by mEPOΔCpG lacking intragenic CpG dinucleotides, even at high pDNA amounts. Corresponding with these observations, in vitro analysis of transfected cells revealed a 2- to 3-fold increased (mEPOopt) and 50% decreased (mEPOΔCpG) erythropoietin expression compared with mEPOwt, respectively. RNA analyses demonstrated that the specific design of the transgene sequence influenced expression levels by modulating transcriptional activity and nuclear plus cytoplasmic RNA amounts rather than translation. In sum, whereas CpG depletion negatively interferes with efficient expression in postmitotic tissues, mEPOopt doses <0.5 μg were sufficient to trigger optimal long-term hematologic effects encouraging the use of sequence-optimized transgenes to further reduce effective pDNA amounts.

  6. Dynamic ligand modulation of EPO receptor pools, and dysregulation by polycythemia-associated EPOR alleles.

    Directory of Open Access Journals (Sweden)

    Seema Singh

    Full Text Available Erythropoietin (EPO and its cell surface receptor (EPOR are essential for erythropoiesis; can modulate non-erythroid target tissues; and have been reported to affect the progression of certain cancers. Basic studies of EPOR expression and trafficking, however, have been hindered by low-level EPOR occurrence, and the limited specificity of anti-EPOR antibodies. Consequently, these aspects of EPOR biology are not well defined, nor are actions of polycythemia- associated mutated EPOR alleles. Using novel rabbit monoclonal antibodies to intracellular, PY- activated and extracellular EPOR domains, the following properties of the endogenous hEPOR in erythroid progenitors first are unambiguously defined. 1 High- Mr EPOR forms become obviously expressed only when EPO is limited. 2 EPOR-68K plus -70K species sequentially accumulate, and EPOR-70K comprises an apparent cell surface EPOR population. 3 Brefeldin A, N-glycanase and associated analyses point to EPOR-68K as a core-glycosylated intracellular EPOR pool (of modest size. 4 In contrast to recent reports, EPOR inward trafficking is shown (in UT7epo cells, and primary proerythroblasts to be sharply ligand-dependent. Beyond this, when C-terminal truncated hEPOR-T mutant alleles as harbored by polycythemia patients are co-expressed with the wild-type EPOR in EPO-dependent erythroid progenitors, several specific events become altered. First, EPOR-T alleles are persistently activated upon EPO- challenge, yet are also subject to apparent turn-over (to low-Mr EPOR products. Furthermore, during exponential cell growth EPOR-T species become both over-represented, and hyper-activated. Interestingly, EPOR-T expression also results in an EPO dose-dependent loss of endogenous wild-type EPOR's (and, therefore, a squelching of EPOR C-terminal- mediated negative feedback effects. New knowledge concerning regulated EPOR expression and trafficking therefore is provided, together with new insight into mechanisms via

  7. EPOS IP - Data, Data Products, Services and Software (DDSS Master Table)

    Science.gov (United States)

    Michalek, Jan; Atakan, Kuvvet

    2017-04-01

    The "European Plate Observing System - Implementation Phase" (EPOS IP, 2014-2019) project is about building a pan-European infrastructure for accessing solid Earth science data. This ambitious plan started in 2002 already with a Conception Phase and continued by an EPOS PP (Preparatory Phase, 2010-2014) where about 20 partners joined the project. The current EPOS IP project includes 47 partners plus 6 associate partners from 25 countries from all over Europe and several international organizations (ORFEUS, EMSC, EUREF). However, the community contributing to the EPOS integration plan is larger than the official partnership of EPOS IP project, because more countries are represented by the international organizations and because within each country there are several research institutions involved. The list of Data, Data Products, Services and Software (DDSS) provided by individual institutions, consortia or organizations which will become part of the EPOS system are currently collected in document called DDSS Master Table. There are 10 work packages (WP8-WP17) creating the Thematic Core Services (TCS) always grouped by a specific topic: Seismology, Near Fault Observatories, GNSS Data and Products, Volcano Observations, Satellite Data, Geomagnetic Observations, Anthropogenic Hazards, Geological Information and Modelling, Multi-scale laboratories and Geo-Energy Test Beds for Low Carbon Energy. Each of this group declared a list of DDSS elements which are about to be implemented. Currently there are about 455 DDSS elements in the DDSS Master Table. These DDSS elements are of different maturity and about 122 are declared by TCS groups to be ready for implementation which means that the data are well described with metadata, following the standards specific for their domain and, in the best case, with some services allowing their access already. The DDSS elements differ by its complexity as well. The DDSS Master Table serves as an overview of the DDSS elements and

  8. Dynamic Ligand Modulation of EPO Receptor Pools, and Dysregulation by Polycythemia-Associated EPOR Alleles

    Science.gov (United States)

    Singh, Seema; Verma, Rakesh; Pradeep, Anamika; Leu, Karen; Mortensen, R. Bruce; Young, Peter R.; Oyasu, Miho; Schatz, Peter J.; Green, Jennifer M.; Wojchowski, Don M.

    2012-01-01

    Erythropoietin (EPO) and its cell surface receptor (EPOR) are essential for erythropoiesis; can modulate non-erythroid target tissues; and have been reported to affect the progression of certain cancers. Basic studies of EPOR expression and trafficking, however, have been hindered by low-level EPOR occurrence, and the limited specificity of anti-EPOR antibodies. Consequently, these aspects of EPOR biology are not well defined, nor are actions of polycythemia- associated mutated EPOR alleles. Using novel rabbit monoclonal antibodies to intracellular, PY- activated and extracellular EPOR domains, the following properties of the endogenous hEPOR in erythroid progenitors first are unambiguously defined. 1) High- Mr EPOR forms become obviously expressed only when EPO is limited. 2) EPOR-68K plus -70K species sequentially accumulate, and EPOR-70K comprises an apparent cell surface EPOR population. 3) Brefeldin A, N-glycanase and associated analyses point to EPOR-68K as a core-glycosylated intracellular EPOR pool (of modest size). 4) In contrast to recent reports, EPOR inward trafficking is shown (in UT7epo cells, and primary proerythroblasts) to be sharply ligand-dependent. Beyond this, when C-terminal truncated hEPOR-T mutant alleles as harbored by polycythemia patients are co-expressed with the wild-type EPOR in EPO-dependent erythroid progenitors, several specific events become altered. First, EPOR-T alleles are persistently activated upon EPO- challenge, yet are also subject to apparent turn-over (to low-Mr EPOR products). Furthermore, during exponential cell growth EPOR-T species become both over-represented, and hyper-activated. Interestingly, EPOR-T expression also results in an EPO dose-dependent loss of endogenous wild-type EPOR's (and, therefore, a squelching of EPOR C-terminal- mediated negative feedback effects). New knowledge concerning regulated EPOR expression and trafficking therefore is provided, together with new insight into mechanisms via which

  9. EPO for the NASA SDO Extreme Ultraviolet Variability Experiment (EVE) Learning Suite for Educators

    Science.gov (United States)

    Kellagher, Emily; Scherrer, D. K.

    2013-07-01

    EVE Education and Public Outreach (EPO) promotes an understanding of the process of science and concepts within solar science and sun-earth connections. EVE EPO also features working scientists, current research and career awareness. One of the highlights for of this years projects is the digitization of solar lessons and the collaboration with the other instrument teams to develop new resources for students and educators. Digital lesson suite: EVE EPO has taken the best solar lessons and reworked then to make then more engaging, to reflect SDO data and made them SMARTboard compatible. We are creating a website that Students and teachers can access these lesson and use them online or download them. Project team collaboration: The SDO instruments (EVE, AIA and HMI) teams have created a comic book series for upper elementary and middle school students with the SDO mascot Camilla. These comics may be printed or read on mobile devices. Many teachers are looking for resources to use with their students via the Ipad so our collaboration helps supply teachers with a great resource that teachers about solar concepts and helps dispel solar misconceptions.Abstract (2,250 Maximum Characters): EVE Education and Public Outreach (EPO) promotes an understanding of the process of science and concepts within solar science and sun-earth connections. EVE EPO also features working scientists, current research and career awareness. One of the highlights for of this years projects is the digitization of solar lessons and the collaboration with the other instrument teams to develop new resources for students and educators. Digital lesson suite: EVE EPO has taken the best solar lessons and reworked then to make then more engaging, to reflect SDO data and made them SMARTboard compatible. We are creating a website that Students and teachers can access these lesson and use them online or download them. Project team collaboration: The SDO instruments (EVE, AIA and HMI) teams have created a

  10. Human preference and acceptance of increased air velocity to offset warm sensation at increased room temperatures

    DEFF Research Database (Denmark)

    Cattarin, Giulio; Simone, Angela; Olesen, Bjarne W.

    . The present climatic chamber study examined energy performance and achievable thermal comfort of traditional and bladeless desk fans. Different effects of mechanical and simulated-natural airflow patterns were also investigated. 32 Scandinavians, performing office activities and wearing light clothes , were......Previous studies have demonstrated that in summertime increased air velocities can compensate for higher room temperatures to achieve comfortable conditions. In order to increase air movement, windows opening, ceiling or desk fans can be used at the expense of relatively low energy consumption...... exposed to a increased air movement generated by a personal desk fan. The subjects could continuously regulate the fans under three fixed environmental conditions (operative temperatures equal to 26 °C, 28 °C, or 30 °C, and same absolute humidity 12.2 g/m3). The experimental study showed that increased...

  11. Human preference and acceptance of increased air velocity to offset warm sensation at increased room temperatures

    OpenAIRE

    Cattarin, Giulio; Simone, Angela; Olesen, Bjarne W.

    2012-01-01

    Previous studies have demonstrated that in summertime increased air velocities can compensate for higher room temperatures to achieve comfortable conditions. In order to increase air movement, windows opening, ceiling or desk fans can be used at the expense of relatively low energy consumption. The present climatic chamber study examined energy performance and achievable thermal comfort of traditional and bladeless desk fans. Different effects of mechanical and simulated-natural airflow patte...

  12. Increased intrinsic mitochondrial function in humans with mitochondrial haplogroup H

    DEFF Research Database (Denmark)

    Larsen, Steen; Díez-Sánchez, Carmen; Rabøl, Rasmus

    2014-01-01

    and determined their mitochondrial haplogroup, mitochondrial oxidative phosphorylation capacity (OXPHOS), mitochondrial content (citrate synthase (CS)) and VO2max. Intrinsic mitochondrial function is calculated as mitochondrial OXPHOS capacity divided by mitochondrial content (CS). Haplogroup H showed a 30......% higher intrinsic mitochondrial function compared with the other haplo group U. There was no relationship between haplogroups and VO2max. In skeletal muscle from men with mitochondrial haplogroup H, an increased intrinsic mitochondrial function is present....

  13. Risks of increased UV-B radiation for humans

    International Nuclear Information System (INIS)

    Przybilla, B.; Eberlein-Koenig, B.; Bergner, T.

    1994-01-01

    If not compensated in any way, depletion of the stratospheric ozone layer leads to an increase of UV-B radiation at the earth's surface, especially towards the short-wave range, which is biologically the more active. The most concerning effect here is that of UV-B induced skin reactions, in particular malignant skintumors (malignant melanoma, spinocellular carcinoma, basalioma), whose incidence is expected to increase in future. As some photoreactions can be inhibited or enhanced also by radiation outside their action spectrum, it is possible for changes in solar spectral radiation flux density to influence photo-induced reactions that are driven at wavelengths outside the UV-B range. The authors have performed studies for developing methods of quantifying individual UV sensitivity. In vitro studies have shown that UV-A dependent photoreactions can be partly inhibited by UV-B. A number of drugs, as well as sulphites, which are used as preservatives amongst other things, have been shown to have phototoxic properties that may be relevant to photocarcinogenesis. Irradiation tests on cell cultures for different UV-B ranges have shown that irradiation at shorter wavelengths leads to a stronger release of proinflammatory cytokines that ar longer wavelengths with the same dose. Altogether it can be said that despite compelling theoretical evidence it is not easily possible to predict the actual consequences of an increase in particular of short-wave UV-B radiation at the earth's surface. The assumed effects must be examined individually by appropriate methods. (orig.) [de

  14. Significant increase of Echinococcus multilocularis prevalencein foxes, but no increased predicted risk for humans

    NARCIS (Netherlands)

    Maas, M.; Dam-Deisz, W.D.C.; Roon, van A.M.; Takumi, K.; Giessen, van der J.W.B.

    2014-01-01

    The emergence of the zoonotic tapeworm Echinococcus multilocularis, causative agent ofalveolar echinococcosis (AE), poses a public health risk. A previously designed risk mapmodel predicted a spread of E. multilocularis and increasing numbers of alveolar echinococ-cosis patients in the province of

  15. Training Young Astronomers in EPO: An Update on the AAS Astronomy Ambassadors Program

    Science.gov (United States)

    Fraknoi, A.; Fienberg, R. T.; Gurton, S.; Schmitt, A. H.; Schatz, D.; Prather, E. E.

    2014-07-01

    The American Astronomical Society, with organizations active in EPO, has launched professional-development workshops and a community of practice to help improve early-career astronomers' ability to communicate effectively. Called “Astronomy Ambassadors,” the program provides mentoring and training for participants, from advanced undergraduates to beginning faculty. By learning to implement effective EPO strategies, Ambassadors become better teachers, meeting presenters, and representatives of our science to the public and government. Because young astronomers are a more diverse group than those who now do most outreach, they help the astronomy community present a more multicultural and gender-balanced face to the public, enabling underserved groups to see themselves as scientists. Ambassadors are given a library of outreach activities and materials, including many developed by cooperating organizations such as the ASP, plus some that have been created by Andrew Fraknoi specifically for this program.

  16. Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution.

    Directory of Open Access Journals (Sweden)

    Niels Jacob Aachmann-Andersen

    Full Text Available The membrane-assisted isoform immunoassay (MAIIA quantitates erythropoietin (EPO isoforms as percentages of migrated isoforms (PMI. We evaluated the effect of recombinant human EPO (rhEPO on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross-over study. 16 healthy subjects received either low-dose Epoetin beta (5000 IU on days 1, 3, 5, 7, 9, 11 and 13; high-dose Epoetin beta (30.000 IU on days 1, 2 and 3 and placebo on days 5, 7, 9, 11 and 13; or placebo on all days. PMI on days 4, 11 and 25 was determined by interaction of N-acetyl glucosamine with the glycosylation dependent desorption of EPO isoforms. At day 25, plasma-EPO in both rhEPO groups had returned to values not different from the placebo group. PMI with placebo, reflecting the endogenous EPO isoforms, averaged 82.5 (10.3 % (mean (SD. High-dose Epoetin beta decreased PMI on days 4 and 11 to 31.0 (4.2% (p<0.00001 and 45.2 (7.3% (p<0.00001. Low-dose Epoetin beta decreased PMI on days 4 and 11 to 46.0 (12.8% (p<0.00001 and 46.1 (10.4% (p<0.00001. In both rhEPO groups, PMI on day 25 was still decreased (high-dose Epoetin beta: 72.9 (19.4% (p=0.029; low-dose Epoetin beta: 73.1 (17.8% (p=0.039. In conclusion, Epoetin beta leaves a footprint in the plasma-EPO isoform pattern. MAIIA can detect changes in EPO isoform distribution up til at least three weeks after administration of Epoetin beta even though the total EPO concentration has returned to normal.

  17. Nurturing The STEM Pipeline: Graduate Student Leadership In NIRCam's Ongoing E/PO Mission For JWST

    Science.gov (United States)

    Schlingman, Wayne M.; Stock, N.; Teske, J.; Tyler, K.; Biller, B.; Donley, J.; Hedden, A.; Knierman, K.; Young, P.

    2011-01-01

    The Astronomy Camp for Girl Scout Leaders is an education and public outreach (E/PO) program offered by the science team of the Near-InfraRed Camera (NIRCam) for NASA's 6.5-meter James Webb Space Telescope (JWST). Since 2003, astronomy graduate students have helped design and lead biannual "Train the Trainer” workshops for adults from the Girl Scouts of the USA (GSUSA), engaging these trainers in the process of scientific inquiry and equipping them to host astronomy-related activities at the troop level. These workshops have helped revise the national GSUSA badge curriculum and directly benefitted thousands of young girls of all ages, not only in general science and math education but also in specific astronomical and technological concepts relating to JWST. To date, nine graduate students have become members of NIRCam's E/PO team. They have developed curriculum and activities used to teach concepts in stellar nucleosynthesis, lookback time, galaxy classification, etc. They have also contributed to the overall strategic approach and helped lead more general activities in basic astronomy (night sky, phases of the Moon, the scale of the Solar System and beyond, stars, galaxies, telescopes, etc.) as well as JWST-specific research areas in extrasolar planetary systems and cosmology, to pave the way for girls and women to understand the first images from JWST. The resulting experience has empowered these students to propose and to develop their own E/PO programs after graduation as postdocs and young faculty. They also continue as part of NIRCam's growing worldwide network of 160 trainers teaching young women essential STEM-related concepts using astronomy, the night sky environment, applied math, engineering, and critical thinking. NIRCam and its E/PO program are funded by NASA under contract NAS5-02105.

  18. Progranulin is increased in human and murine lipodystrophy.

    Science.gov (United States)

    Miehle, Konstanze; Ebert, Thomas; Kralisch, Susan; Hoffmann, Annett; Kratzsch, Jürgen; Schlögl, Haiko; Stumvoll, Michael; Fasshauer, Mathias

    2016-10-01

    Lipodystrophies (LD) are genetic or acquired disorders sharing the symptom of partial or complete adipose tissue deficiency and a dysregulation of adipokines including leptin and adiponectin. Progranulin, an adipokine with proinflammatory and insulin resistance-inducing characteristics, has not been investigated in LD so far. Circulating progranulin was determined in LD patients (N=37) and in age-, gender-, and body mass index-matched healthy control subjects (N=37). Additionally, we investigated progranulin expression in an LD mouse model as compared to wild-type mice. Moreover, we elucidated circulating progranulin before and during metreleptin supplementation in 10 patients with LD. Median [interquartile range] circulating progranulin was increased in patients with LD (82.9 [25.9] μg/l) as compared to controls (73.6 [22.8] μg/l) (p=0.005). C-reactive protein (CRP) remained an independent and positive predictor of progranulin in multivariate analysis. Progranulin mRNA was significantly upregulated in all adipose tissue depots, i.e. visceral, subcutaneous, and brown adipose tissue, and in muscle of LD animals versus wild-type mice. Progranulin levels did not significantly change during metreleptin supplementation. Progranulin serum concentration is increased in patients with LD, and shows an independent and positive correlation with CRP. Different adipose tissue depots and muscle might be potential origins of elevated progranulin. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Humanizing machines: Anthropomorphization of slot machines increases gambling.

    Science.gov (United States)

    Riva, Paolo; Sacchi, Simona; Brambilla, Marco

    2015-12-01

    Do people gamble more on slot machines if they think that they are playing against humanlike minds rather than mathematical algorithms? Research has shown that people have a strong cognitive tendency to imbue humanlike mental states to nonhuman entities (i.e., anthropomorphism). The present research tested whether anthropomorphizing slot machines would increase gambling. Four studies manipulated slot machine anthropomorphization and found that exposing people to an anthropomorphized description of a slot machine increased gambling behavior and reduced gambling outcomes. Such findings emerged using tasks that focused on gambling behavior (Studies 1 to 3) as well as in experimental paradigms that included gambling outcomes (Studies 2 to 4). We found that gambling outcomes decrease because participants primed with the anthropomorphic slot machine gambled more (Study 4). Furthermore, we found that high-arousal positive emotions (e.g., feeling excited) played a role in the effect of anthropomorphism on gambling behavior (Studies 3 and 4). Our research indicates that the psychological process of gambling-machine anthropomorphism can be advantageous for the gaming industry; however, this may come at great expense for gamblers' (and their families') economic resources and psychological well-being. (c) 2015 APA, all rights reserved).

  20. Correlation of EPO resistance with oxidative stress response and inflammatory response in patients with maintenance hemodialysis

    Directory of Open Access Journals (Sweden)

    Xiao-Hui Yan

    2017-08-01

    Full Text Available Objective: To study the correlation of erythropoietin (EPO resistance with oxidative stress response and inflammatory response in patients with maintenance hemodialysis. Methods: A total of 184 patients with end-stage renal disease who received maintenance hemodialysis in Shaanxi Provincial People’s Hospital between March 2015 and October 2016 were selected as dialysis group, 102 volunteers who received physical examination in Shaanxi Provincial People’s Hospital during the same period were selected as control group, the EPO resistance index was assessed, the median was calculated, and serum oxidative stress and inflammatory response indexes were detected. Results: Serum T-AOC, SOD and CAT levels in dialysis group were significantly lower than those in control group while MDA, AOPP, IFN-γ, HMGB-1, ICAM-1, IL-4 and IL-10 levels were significantly higher than those in control group; serum T-AOC, SOD and CAT levels in patients with high ERI were significantly lower than those in patients with low ERI while MDA, AOPP, IFN-γ, HMGB-1, ICAM-1, IL-4 and IL-10 levels were significantly higher than those in patients with low ERI. Conclusion: The degree of EPO resistance in patients with maintenance hemodialysis is closely related to the activation of oxidative stress response and inflammatory response.

  1. Epo Is Relevant Neither for Microvascular Formation Nor for the New Formation and Maintenance of Mice Skeletal Muscle Fibres in Both Normoxia and Hypoxia

    Directory of Open Access Journals (Sweden)

    Luciana Hagström

    2010-01-01

    Full Text Available Erythropoietin (Epo and vascular growth factor (VEGF are known to be involved in the regulation of cellular activity when oxygen transport is reduced as in anaemia or hypoxic conditions. Because it has been suggested that Epo could play a role in skeletal muscle development, regeneration, and angiogenesis, we aimed to assess Epo deficiency in both normoxia and hypoxia by using an Epo-deficient transgenic mouse model (Epo-TAgh. Histoimmunology, ELISA and real time RT-PCR did not show any muscle fiber atrophy or accumulation of active HIF-1 but an improvement of microvessel network and an upregulation of VEGFR2 mRNA in Epo-deficient gastrocnemius compared with Wild-Type one. In hypoxia, both models exhibit an upregulation of VEGF120 and VEGFR2 mRNA but no accumulation of Epo protein. EpoR mRNA is not up-regulated in both Epo-deficient and hypoxic gastrocnemius. These results suggest that muscle deconditioning observed in patients suffering from renal failure is not due to Epo deficiency.

  2. Altered behavior in spotted hyenas associated with increased human activity

    Science.gov (United States)

    Boydston, Erin E.; Kapheim, Karen M.; Watts, Heather E.; Szykman, Micaela; Holekamp, Kay E.

    2003-01-01

    To investigate how anthropogenic activity might affect large carnivores, we studied the behaviour of spotted hyenas (Crocuta crocuta) during two time periods. From 1996 to 1998, we documented the ecological correlates of space utilization patterns exhibited by adult female hyenas defending a territory at the edge of a wildlife reserve in Kenya. Hyenas preferred areas near dense vegetation but appeared to avoid areas containing the greatest abundance of prey, perhaps because these were also the areas of most intensive livestock grazing. We then compared hyena behaviour observed in 1996–98 with that observed several years earlier and found many differences. Female hyenas in 1996–98 were found farther from dens, but closer to dense vegetation and to the edges of their territory, than in 1988–90. Recent females also had larger home ranges, travelled farther between consecutive sightings, and were more nocturnal than in 1988–90. Finally, hyenas occurred in smaller groups in 1996–98 than in 1988–90. We also found several changes in hyena demography between periods. We next attempted to explain differences observed between time periods by testing predictions of hypotheses invoking prey abundance, climate, interactions with lions, tourism and livestock grazing. Our data were consistent with the hypothesis that increased reliance on the reserve for livestock grazing was responsible for observed changes. That behavioural changes were not associated with decreased hyena population density suggests the behavioural plasticity typical of this species may protect it from extinction.

  3. Communities of Practice Transition Online - Lessons learned from NASA's EPO Online Workspace

    Science.gov (United States)

    Davey, B.

    2012-12-01

    The Earth Forum Education and Public Outreach (EP/O) community has long interacted to better their practice as a community as well as individually. Working together to share knowledge and grow, they function as a community of practice. In 2009, NASA designed and implemented an online workspace in hopes of promoting the communities continued interactions. This study examines the role of an online workspace component of a community in the work of a community of practice. Much has been studied revealing the importance of communities of practice to organizations, project success, and knowledge management and some of these same successes hold true for virtual communities of practice. Study participants were 75 Education and Public Outreach community members of NASA's Science Mission Directorate Earth Forum. In this mixed methods study, online workspace metrics were used to track participation and a survey completed by 21 members was used to quantify participation. For a more detailed analysis, 15 community members (five highly active users, five average users, and five infrequent users) selected based on survey responses, were interviewed. Finally, survey data was gathered from seven online facilitators to understand their role in the community. Data collected from these 21 community members and five facilitating members suggest that highly active users (logging into the workspace daily), were more likely to have transformative experiences, co-create knowledge, feel ownership of community knowledge, have extended opportunities for community exchange, and find new forms of evaluation. Average users shared some similar characteristics with both the highly active members and infrequent users, representing a group in transition as they become more engaged and active in the online workspace. Inactive users viewed the workspace as having little value, being difficult to navigate, being mainly for gaining basic information about events and community news, and as another demand

  4. Proteasome inhibitors activate autophagy involving inhibition of PI3K-Akt-mTOR pathway as an anti-oxidation defense in human RPE cells.

    Directory of Open Access Journals (Sweden)

    Bingrong Tang

    Full Text Available The two major intracellular protein degradation systems, the ubiquitin-proteasome system (UPS and autophagy, work collaboratively in many biological processes including development, apoptosis, aging, and countering oxidative injuries. We report here that, in human retinal pigment epithelial cells (RPE, ARPE-19 cells, proteasome inhibitors, clasto-lactacystinβ-lactone (LA or epoxomicin (Epo, at non-lethal doses, increased the protein levels of autophagy-specific genes Atg5 and Atg7 and enhanced the conversion of microtubule-associated protein light chain (LC3 from LC3-I to its lipidative form, LC3-II, which was enhanced by co-addition of the saturated concentration of Bafilomycin A1 (Baf. Detection of co-localization for LC3 staining and labeled-lysosome further confirmed autophagic flux induced by LA or Epo. LA or Epo reduced the phosphorylation of the protein kinase B (Akt, a downstream target of phosphatidylinositol-3-kinases (PI3K, and mammalian target of rapamycin (mTOR in ARPE-19 cells; by contrast, the induced changes of autophagy substrate, p62, showed biphasic pattern. The autophagy inhibitor, Baf, attenuated the reduction in oxidative injury conferred by treatment with low doses of LA and Epo in ARPE-19 cells exposed to menadione (VK3 or 4-hydroxynonenal (4-HNE. Knockdown of Atg7 with siRNA in ARPE-19 cells reduced the protective effects of LA or Epo against VK3. Overall, our results suggest that treatment with low levels of proteasome inhibitors confers resistance to oxidative injury by a pathway involving inhibition of the PI3K-Akt-mTOR pathway and activation of autophagy.

  5. Erythropoietin over-expression protects against diet-induced obesity in mice through increased fat oxidation in muscles

    DEFF Research Database (Denmark)

    Hojman, Pernille; Brolin, Camilla; Gissel, Hanne

    2009-01-01

    patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo.At 12 weeks, EPO expression resulted in a 23% weight reduction (Pobese mice; thus the mice weighed 21.9+/-0.8 g (control, normal diet,) 21.9+/-1.4 g (EPO, normal diet), 35.......3+/-3.3 g (control, high-fat diet) and 28.8+/-2.6 g (EPO, high-fat diet). Correspondingly, DXA scanning revealed that this was due to a 28% reduction in adipose tissue mass.The decrease in adipose tissue mass was accompanied by a complete normalisation of fasting insulin levels and glucose tolerance......-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles....

  6. Get Involved in Education and Public Outreach! The Science Mission Directorate Science E/PO Forums Are Here to Help

    Science.gov (United States)

    Shipp, S. S.; Buxner, S.; Schwerin, T. G.; Hsu, B. C.; Peticolas, L. M.; Smith, D.; Meinke, B. K.

    2013-12-01

    NASA's Science Mission Directorate (SMD) Education and Public Outreach (E/PO) Forums help to engage, extend, support, and coordinate the efforts of the community of E/PO professionals and scientists involved in Earth and space science education activities. This work is undertaken to maximize the effectiveness and efficiency of the overall national NASA science education and outreach effort made up of individual efforts run by these education professionals. This includes facilitating scientist engagement in education and outreach. The Forums have been developing toolkits and pathways to support planetary, Earth, astrophysics, and heliophysics scientists who are - or who are interested in becoming - involved in E/PO. These tools include: 1) Pathways to learn about SMD and E/PO community announcements and opportunities, share news about E/PO programs, let the E/PO community know you are interested in becoming involved, and discover education programs needing scientist input and/or support. These pathways include weekly e-news, the SMD E/PO online community workspace, monthly community calls, conferences and meetings of opportunity. 2) Portals to help you find out what education resources already exist, obtain resources to share with students of all levels - from K-12 to graduate students, - and disseminate your materials. These include E/PO samplers and toolkits (sampling of resources selected for scientists who work with students, teachers, and the public), the one-stop shop of reviewed resources from the NASA Earth and space science education portfolio NASAWavelength.org, and the online clearinghouse of Earth and space science higher education materials EarthSpace (http://www.lpi.usra.edu/earthspace). 3) Connections to education specialists who can help you design and implement meaningful E/PO programs - small to large. Education specialists can help you understand what research says about how people learn and effective practices for achieving your goals, place your

  7. Marked increase in leptospirosis infections in humans and dogs in the Netherlands, 2014

    NARCIS (Netherlands)

    Pijnacker, Roan; Goris, M.G.; Wierik, te M.J.; Broens, E.M.; Giessen, van der J.W.; Rosa, de M.; Wagenaar, J.A.; Hartskeerl, R.A.; Notermans, D.W.; Maassen, K.; Schimmer, B.

    2016-01-01

    In the Netherlands, 97 human leptospirosis cases were notified in 2014. This represents a 4.6-fold increase in autochthonous cases (n = 60) compared with the annual average between 2010 and 2013. Most cases had symptom onset between June and November. This marked increase in humans coincided with

  8. Marked increase in leptospirosis infections in humans and dogs in the Netherlands, 2014

    NARCIS (Netherlands)

    Pijnacker, Roan; Goris, Marga G. A.; te Wierik, Margreet J. M.; Broens, Els M.; van der Giessen, Joke W. B.; de Rosa, Mauro; Wagenaar, Jaap A.; Hartskeerl, Rudy A.; Notermans, Daan W.; Maassen, Kitty; Schimmer, Barbara

    2016-01-01

    In the Netherlands, 97 human leptospirosis cases were notified in 2014. This represents a 4.6-fold increase in autochthonous cases (n = 60) compared with the annual average between 2010 and 2013. Most cases had symptom onset between June and November. This marked increase in humans coincided with an

  9. Increased cross-bridge recruitment contributes to transient increase in force generation beyond maximal capacity in human myocardium.

    Science.gov (United States)

    Milani-Nejad, Nima; Chung, Jae-Hoon; Canan, Benjamin D; Fedorov, Vadim V; Whitson, Bryan A; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L

    2018-01-01

    Cross-bridge attachment allows force generation to occur, and rate of tension redevelopment (k tr ) is a commonly used index of cross-bridge cycling rate. Tension overshoots have been observed briefly after a slack-restretch k tr maneuver in various species of animal models and humans. In this study, we set out to determine the properties of these overshoots and their possible underlying mechanism. Utilizing human cardiac trabeculae, we have found that tension overshoots are temperature-dependent and that they do not occur at resting states. In addition, we have found that myosin cross-bridge cycle is vital to these overshoots as inhibition of the cycle results in the blunting of the overshoots and the magnitude of the overshoots are dependent on the level of myofilament activation. Lastly, we show that the number of cross-bridges transiently increase during tension overshoots. These findings lead us to conclude that tension overshoots are likely due to a transient enhancement of the recruitment of myosin heads into the cross-bridge cycling, regulated by the myocardium, and with potential physiological significance in determining cardiac output. We show that isolated human myocardium is capable of transiently increasing its maximal force generation capability by increasing cross-bridge recruitment following slack-restretch maneuver. This process can potentially have important implications and significance in cardiac contraction in vivo. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. EPOS-An intense positron beam project at the ELBE radiation source in Rossendorf

    International Nuclear Information System (INIS)

    Krause-Rehberg, R.; Sachert, S.; Brauer, G.; Rogov, A.; Noack, K.

    2006-01-01

    EPOS, the acronym of ELBE Positron Source, describes a running project to build an intense pulsed beam of mono-energetic positrons (0.2-40 keV) for materials research. Positrons will be created via pair production at a tungsten target using the pulsed 40 MeV electron beam of the superconducting linac electron linac with high brilliance and low emittance (ELBE) at Forschungszentrum Rossendorf (near Dresden, Germany). The chosen design of the system under construction is described and results of calculations simulating the interaction of the electron beam with the target are presented, and positron beam formation and transportation is also discussed

  11. Agrochemicals increase risk of human schistosomiasis by supporting higher densities of intermediate hosts.

    Science.gov (United States)

    Halstead, Neal T; Hoover, Christopher M; Arakala, Arathi; Civitello, David J; De Leo, Giulio A; Gambhir, Manoj; Johnson, Steve A; Jouanard, Nicolas; Loerns, Kristin A; McMahon, Taegan A; Ndione, Raphael A; Nguyen, Karena; Raffel, Thomas R; Remais, Justin V; Riveau, Gilles; Sokolow, Susanne H; Rohr, Jason R

    2018-02-26

    Schistosomiasis is a snail-borne parasitic disease that ranks among the most important water-based diseases of humans in developing countries. Increased prevalence and spread of human schistosomiasis to non-endemic areas has been consistently linked with water resource management related to agricultural expansion. However, the role of agrochemical pollution in human schistosome transmission remains unexplored, despite strong evidence of agrochemicals increasing snail-borne diseases of wildlife and a projected 2- to 5-fold increase in global agrochemical use by 2050. Using a field mesocosm experiment, we show that environmentally relevant concentrations of fertilizer, a herbicide, and an insecticide, individually and as mixtures, increase densities of schistosome-infected snails by increasing the algae snails eat and decreasing densities of snail predators. Epidemiological models indicate that these agrochemical effects can increase transmission of schistosomes. Identifying agricultural practices or agrochemicals that minimize disease risk will be critical to meeting growing food demands while improving human wellbeing.

  12. Applying e-procurement system in the healthcare: the EPOS paradigm

    Science.gov (United States)

    Ketikidis, Panayiotis H.; Kontogeorgis, Apostolos; Stalidis, George; Kaggelides, Kostis

    2010-03-01

    One of the goals of procurement is to establish a competitive price, while e-procurement utilises electronic commerce to identify potential sources of supply, to purchase goods and services, to exchange contractual information and to interact with suppliers. Extensive academic work has been extensively devoted to e-procurement in diverse industries. However, applying e-procurement in the healthcare sector remains unexplored. It lacks an efficient e-procurement mechanism that will enable hospitals and healthcare suppliers to electronically exchange contractual information, aided by the technologies of optimisation and business rules. The development and deployment of e-procurement requires a major effort in the coordination of complex interorganisational business process. This article presents an e-procurement optimised system (EPOS) for the healthcare marketplace, a complete methodological approach for deploying and operating such system, as piloted in public and private hospitals in three European countries (Greece, Spain and Belgium) and suppliers of healthcare items in the fourth country (Italy). The efficient e-procurement mechanism that EPOS suggests enables hospitals and pharmaceutical and medical equipment suppliers to electronically exchange contractual information.

  13. Enduring Power of Attorney (EPoA – comparison between Austrian and German Law

    Directory of Open Access Journals (Sweden)

    Michael Ganner

    2015-04-01

    Full Text Available ENGLISH: With the establishment of the United Nations Convention on the Rights of Persons with Disabilities (CRPD the treatment of people with disabilities is changing from a protective perspective to a rights - based approach. The Enduring Power of Attorney (EPoA is an important instrument, which helps with the implementation of the CRPD into national law. As an instrument of self - determined substituted decision - making it is recognised as the best practice model to safeguard the autonomy of people suffering the deprivations of age and other disabilities. This article touches briefly on general supported and substituted decision - making instruments and then goes on to examine the differences and similarities, advantages and disadvantages b e- tween Austrian and German laws concerning EPoAs. DEUTSCH: Mit der Umsetzung der UN-Behindertenrechtskonvention findet ein Paradigmenwechsel und Umdenken im Umgang mit Personen mit Behinderungen statt. Der Primat der Fürsorge weicht einem liberalen, auf Menschenrechten basierenden Ansatz. In diesem Kontext ist die Vorsorgevollmacht ein effektives Mittel, das die Implementation der UN-Behindertenrechtskonvention in nationales Recht vorantreibt und die Selbstbestimmung und Eigenständigkeit altersbedingt eingeschränkter Menschen und von Menschen mit Behinderungen gewährleistet. Dieser Artikel beschäftigt sich einleitend mit allgemeinen Rechtsinstrumenten der (unterstützten Entscheidungsfindung bei nicht selbst entscheidungsfähigen Personen und analysiert in weiterer Folge Gemeinsamkeiten und Unterschiede sowie Vor- und Nachteile der Vorsorgevollmacht nach österreichischem und deutschem Recht.

  14. Engaging Scientists in Meaningful E/PO: NASA Science4Girls and Their Families

    Science.gov (United States)

    Meinke, B. K.; Smith, D. A.; Bleacher, L.; Hauck, K.; Soeffing, C.

    2014-12-01

    The NASA Science Mission Directorate (SMD) Science Education and Public Outreach Forums coordinate the participation of SMD education and public outreach (EPO) programs in Women's History Month through the NASA Science4Girls and Their Families initiative. The initiative partners NASA science education programs with public libraries to provide NASA-themed hands-on education activities for girls and their families. These NASA science education programs are mission- and grant-based E/PO programs are uniquely poised to foster collaboration between scientists with content expertise and educators with pedagogy expertise. As such, the initiative engages girls in all four NASA science discipline areas (Astrophysics, Earth Science, Planetary Science, and Heliophysics), which enables audiences to experience the full range of NASA science topics and the different career skills each requires. The events focus on engaging underserved and underrepresented audiences in Science, Technology, Engineering, and Mathematics (STEM) via use of research-based best practices, collaborations with libraries, partnerships with local and national organizations, and remote engagement of audiences.

  15. The human milk project: a quality improvement initiative to increase human milk consumption in very low birth weight infants.

    Science.gov (United States)

    Ward, Laura; Auer, Christine; Smith, Carrie; Schoettker, Pamela J; Pruett, Raymond; Shah, Nilesh Y; Kotagal, Uma R

    2012-08-01

    Human milk has well-established health benefits for preterm infants. We conducted a multidisciplinary quality improvement effort aimed at providing at least 500 mL of human milk/kg in the first 14 days of life to very low birth weight (VLBW) (milk program, and twice-daily physician evaluation of infants' ability to tolerate feedings. The number of infants receiving at least 500 mL of human milk/kg in their first 14 days of life increased from 50% to 80% within 11 months of implementation, and this increase has been sustained for 4 years. Infants who met the feeding goal because they received donor milk increased each year. Since September 2007, infants have received, on average, 1,111 mL of human milk/kg. Approximately 4% of infants did not receive any human milk. Respiratory instability was the most frequent physiological reason given by clinicians for not initiating or advancing feedings in the first 14 days of life. Our quality improvement initiative resulted in a higher consumption of human milk in VLBW infants in the first 14 days of life. Other clinicians can use these described quality improvement methods and techniques to improve their VLBW babies' consumption of human milk.

  16. The Solar Dynamics Observatory (SDO) Education and Outreach (E/PO) Program: Changing Perceptions One Program at a Time

    Science.gov (United States)

    Drobnes, Emilie; Littleton, A.; Pesnell, William D.; Beck, K.; Buhr, S.; Durscher, R.; Hill, S.; McCaffrey, M.; McKenzie, D. E.; Myers, D.; hide

    2013-01-01

    We outline the context and overall philosophy for the combined Solar Dynamics Observatory (SDO) Education and Public Outreach (E/PO) program, present a brief overview of all SDO E/PO programs along with more detailed highlights of a few key programs, followed by a review of our results to date, conclude a summary of the successes, failures, and lessons learned, which future missions can use as a guide, while incorporating their own content to enhance the public's knowledge and appreciation of science and technology as well as its benefit to society.

  17. Women in EPOS: the role of women in a large pan-European Research Infrastructure for Solid Earth sciences

    Science.gov (United States)

    Calignano, Elisa; Freda, Carmela; Baracchi, Laura

    2017-04-01

    Women are outnumbered by men in geosciences senior research positions, but what is the situation if we consider large pan-European Research Infrastructures? With this contribution we want to show an analysis of the role of women in the implementation of the European Plate Observing System (EPOS): a planned research infrastructure for European Solid Earth sciences, integrating national and transnational research infrastructures to enable innovative multidisciplinary research. EPOS involves 256 national research infrastructures, 47 partners (universities and research institutes) from 25 European countries and 4 international organizations. The EPOS integrated platform demands significant coordination between diverse solid Earth disciplinary communities, national research infrastructures and the policies and initiatives they drive, geoscientists and information technologists. The EPOS architecture takes into account governance, legal, financial and technical issues and is designed so that the enterprise works as a single, but distributed, sustainable research infrastructure. A solid management structure is vital for the successful implementation and sustainability of EPOS. The internal organization relies on community-specific Working Packages (WPs), Transversal WPs in charge of the overall EPOS integration and implementation, several governing, executive and advisory bodies, a Project Management Office (PMO) and the Project Coordinator. Driven by the timely debate on gender balance and commitment of the European Commission to promote gender equality in research and innovation, we decided to conduct a mapping exercise on a project that crosses European national borders and that brings together diverse geoscience disciplines under one management structure. We present an analysis of women representation in decision-making positions in each EPOS Working Package (WP Leader, proxy, legal, financial and IT contact persons), in the Boards and Councils and in the PMO

  18. Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution

    DEFF Research Database (Denmark)

    Aachmann-Andersen, Niels Jacob; Just Christensen, Søren; Lisbjerg, Kristian

    2014-01-01

    The membrane-assisted isoform immunoassay (MAIIA) quantitates erythropoietin (EPO) isoforms as percentages of migrated isoforms (PMI). We evaluated the effect of recombinant human EPO (rhEPO) on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross......-over study. 16 healthy subjects received either low-dose Epoetin beta (5000 IU on days 1, 3, 5, 7, 9, 11 and 13); high-dose Epoetin beta (30.000 IU on days 1, 2 and 3 and placebo on days 5, 7, 9, 11 and 13); or placebo on all days. PMI on days 4, 11 and 25 was determined by interaction of N......-acetyl glucosamine with the glycosylation dependent desorption of EPO isoforms. At day 25, plasma-EPO in both rhEPO groups had returned to values not different from the placebo group. PMI with placebo, reflecting the endogenous EPO isoforms, averaged 82.5 (10.3) % (mean (SD)). High-dose Epoetin beta decreased PMI...

  19. Contributions of the German Research Center for Geosciences (GFZ) to the EPOS (European Plate Observing System) Implementation Phase 2015-18

    Science.gov (United States)

    Hoffmann, T. L.; Lauterjung, J.

    2017-12-01

    The European Plate Observing System project is currently approaching the end of year two of its four-year Implementation Phase 2015-18 (EPOS-IP). Under the Horizon 2020 Programme INFRADEV-3, the EPOS cyberinfrastructure is being established as an ERIC (European Research Infrastructure Consortium) and encompasses the implementation of both the EPOS Integrated Core Services (ICS) for solid Earth Science and a multitude of EPOS Thematic Core Services (TCS). During year two, a basic set of ICS and TCS services was developed and implemented, so that in October 2017 the validation phase (year 3) of EPOS is ready to be launched. Up to now, various TCS-Elements have integrated different Service Providers (SD) that are delivering Data, Data Products, Services and Software (DDSS) to their specific scientific community. As one of the 29 awardees of the EC grant, the German Research Center for Geosciences (GFZ) plays an important role in the implementation of EPOS and its Thematic and Integrated Core Services. The presented poster will give an overview of GFZ's participation in the work of nine technical EPOS Work Packages (WP7 ICS Development, WP8 Seismology, WP11 Volcano Observations, WP12 Satellite Data, WP13 Geomagnetic Observations, WP14 Anthropogenic Hazards, WP15 Geological Information and Modelling, WP16 Multi-Scale Laboratories and WP17 Geo Energy Test Beds) as well as in four administrative EPOS Work Packages (WP2 Communication, WP3 Harmonization, WP4 Legal & Governance, and WP5 Financial).

  20. Brain mitochondrial function in a murine model of cerebral malaria and the therapeutic effects of rhEPO

    DEFF Research Database (Denmark)

    Karlsson, Michael; Hempel, Casper; Sjövall, Fredrik

    2013-01-01

    and no connection between disease severity and mitochondrial respiratory function. Treatment with rhEPO similarly had no effect on respiratory function. Thus cerebral metabolic dysfunction in CM does not seem to be directly linked to altered mitochondrial respiratory capacity as analyzed in brain homogenates ex...

  1. How to Do More with Less: Handling an Increased Workload While Maintaining Human Capital Level

    National Research Council Canada - National Science Library

    Doerr, Jr., James C; Glazman, Emily

    2008-01-01

    ...) and local situation with regard to "human capital." The DoD is particularly concerned with the issue of maintaining its knowledge base in the face of large numbers of workers retiring and with an ever-increasing and increasingly complex workload...

  2. Faster Increases in Human Life Expectancy Could Lead to Slower Population Aging

    Science.gov (United States)

    2015-01-01

    Counterintuitively, faster increases in human life expectancy could lead to slower population aging. The conventional view that faster increases in human life expectancy would lead to faster population aging is based on the assumption that people become old at a fixed chronological age. A preferable alternative is to base measures of aging on people’s time left to death, because this is more closely related to the characteristics that are associated with old age. Using this alternative interpretation, we show that faster increases in life expectancy would lead to slower population aging. Among other things, this finding affects the assessment of the speed at which countries will age. PMID:25876033

  3. Microwave Energy Increases Fatty Acid Methyl Ester Yield in Human Whole Blood Due to Increased Sphingomyelin Transesterification.

    Science.gov (United States)

    Metherel, Adam H; Aristizabal Henao, Juan J; Ciobanu, Flaviu; Taha, Ameer Y; Stark, Ken D

    2015-09-01

    Dried blood spots (DBS) by fingertip prick collection for fatty acid profiling are becoming increasingly popular due to ease of collection, minimal invasiveness and its amenability to high-throughput analyses. Herein, we assess a microwave-assisted direct transesterification method for the production of fatty acid methyl esters (FAME) from DBS. Technical replicates of human whole blood were collected and 25-μL aliquots were applied to chromatography strips prior to analysis by a standard 3-h transesterification method or microwave-assisted direct transesterification method under various power (variable vs constant), time (1-5 min) and reagent (1-10% H2SO4 in methanol) conditions. In addition, a standard method was compared to a 5-min, 30-W power microwave in 1% H2SO4 method for FAME yield from whole blood sphingomyelin, and sphingomyelin standards alone and spiked in whole blood. Microwave-assisted direct transesterification yielded no significant differences in both quantitative (nmol/100 µL) and qualitative (mol%) fatty acid assessments after as little as 1.5- and 1-min reaction times, respectively, using the variable power method and 5% H2SO4 in methanol. However, 30-W power for 5 min increased total FAME yield of the technical replicates by 14%. This increase appears largely due to higher sphingomyelin-derived FAME yield of up to 109 and 399% compared to the standard method when determined from whole blood or pure standards, respectively. In conclusion, microwave-assisted direct transesterification of DBS achieved in as little as 1-min, and 5-min reaction times increase total fatty acids primarily by significantly improving sphingomyelin-derived fatty acid yield.

  4. EPOS Multi-Scale Laboratory platform: a long-term reference tool for experimental Earth Sciences

    Science.gov (United States)

    Trippanera, Daniele; Tesei, Telemaco; Funiciello, Francesca; Sagnotti, Leonardo; Scarlato, Piergiorgio; Rosenau, Matthias; Elger, Kirsten; Ulbricht, Damian; Lange, Otto; Calignano, Elisa; Spiers, Chris; Drury, Martin; Willingshofer, Ernst; Winkler, Aldo

    2017-04-01

    With continuous progress on scientific research, a large amount of datasets has been and will be produced. The data access and sharing along with their storage and homogenization within a unique and coherent framework is a new challenge for the whole scientific community. This is particularly emphasized for geo-scientific laboratories, encompassing the most diverse Earth Science disciplines and typology of data. To this aim the "Multiscale Laboratories" Work Package (WP16), operating in the framework of the European Plate Observing System (EPOS), is developing a virtual platform of geo-scientific data and services for the worldwide community of laboratories. This long-term project aims at merging the top class multidisciplinary laboratories in Geoscience into a coherent and collaborative network, facilitating the standardization of virtual access to data, data products and software. This will help our community to evolve beyond the stage in which most of data produced by the different laboratories are available only within the related scholarly publications (often as print-version only) or they remain unpublished and inaccessible on local devices. The EPOS multi-scale laboratory platform will provide the possibility to easily share and discover data by means of open access, DOI-referenced, online data publication including long-term storage, managing and curation services and to set up a cohesive community of laboratories. The WP16 is starting with three pilot cases laboratories: (1) rock physics, (2) palaeomagnetic, and (3) analogue modelling. As a proof of concept, first analogue modelling datasets have been published via GFZ Data Services (http://doidb.wdc-terra.org/search/public/ui?&sort=updated+desc&q=epos). The datasets include rock analogue material properties (e.g. friction data, rheology data, SEM imagery), as well as supplementary figures, images and movies from experiments on tectonic processes. A metadata catalogue tailored to the specific communities

  5. Near Fault Observatories (NFO) services and integration plan for European Plate Observing System (EPOS) Implementation Phase

    Science.gov (United States)

    Chiaraluce, Lauro

    2016-04-01

    Coherently with the EPOS vision aimed at creating a pan-European infrastructure for Earth Sciences supporting research for a more sustainable society, we are working on the integration of NFOs and services implementation facilitating their data and products discovery and usage. NFOs are National Research Infrastructures (NRI) consisting of advanced networks of multi-parametric sensors continuously monitoring the chemical and physical processes related to the common underlying Earth instabilities governing active faults evolution and the genesis of earthquakes. These infrastructures will enable advancements in understanding of earthquakes generation processes and associated ground shaking due to their high-quality near-source multidisciplinary data. In EPOS-IP seven NFOs are going to be linked: 1) the Altotiberina and 2) Irpinia Observatories in Italy, 3) Corinth in Greece, 4) South-Iceland Seismic Zone, 5) Valais in Switzerland, 6) Marmara Sea (GEO Supersite) in Turkey and 7) Vrancea in Romania. EPOS-IP aims to implement integrated services from a technical, legal, governance and financial point of view. Accordingly, our first effort within this first core group of NFOs will be establishing legal governance for such a young community to ensure a long-term sustainability of the envisaged services including the full adoption of the EPOS data policy. The establishment of a Board including representatives of each NFO formally appointed by the Institutions supporting the NRI is a basic requirement to provide and validate a stable governance mechanism supporting the initiatives finalised to the services provision. Extremely dense networks and less common instruments deserve an extraordinary work on data quality control and description. We will work on linking all the NFOs in a single distributed network of observatories with instrumental and monitoring standards based on common protocols for observation, analysis, and data access and distributed channels. We will rely on

  6. What We Need: The 2012 NASA EPO Forum Survey on Two-Year College STEM Teaching

    Science.gov (United States)

    Low, R.; CoBabe-Ammann, E.; Schultz, G.

    2014-07-01

    A survey of community college STEM faculty, administered by the NASA SMD Higher Education Working Group (HEWG), was administered in fall 2012 in an effort to document the demographic make-up and views of community college faculty who teach NASA science-related STEM courses in astronomy, physics, Earth science, and engineering. Nearly half of respondents reported that less than 10% of students in their classroom are “STEMward bound” and indicated the need for STEM resources that can relate science course content and be relevant to the daily life of their students. A number of respondents also noted a new or renewed emphasis on outreach activities within the community served by their institution as part of their job description. The survey suggests specific directions and ways that the NASA SMD EPO forum can support two-year college stakeholders.

  7. The Invisible Universe Online for Teachers - A SOFIA and SIRTF EPO Project

    Science.gov (United States)

    Gauthier, A.; Bennett, M.; Buxner, S.; Devore, E.; Keller, J.; Slater, T.; Thaller, M.; Conceptual Astronomy; Physics Education Research CAPER Team

    2003-12-01

    The SOFIA and SIRTF EPO Programs have partnered with the Conceptual Astronomy and Physics Education Research (CAPER) Team in designing, evaluating, and facilitating an online program for K-12 teachers to experience multiwavelength astronomy. An aggressive approach to online course design and delivery has resulted in a highly successful learning experience for teacher-participants. Important aspects of the Invisible Universe Online will eventually be used as a part of SOFIA's Airborne Ambassadors Program for pre-flight training of educators. The Invisible Universe Online is delivered via WebCT through the Montana State University National Teacher Enhancement Network (http://btc.montana.edu/). Currently in its fourth semester, the course has served 115 K-12 teachers. This distance learning online class presents our search for astronomical origins and provides an enhanced understanding of how astronomers use all energies of light to unfold the secrets of the universe. We cover the long chain of events from the birth of the universe through the formation of galaxies, stars, and planets by focusing on the scientific questions, technological challenges, and space missions pursuing this search for origins. Through textbook and internet readings, inquiry exploration with interactive java applets, and asynchronous discussions, we help our students achieve the following course goals: develop scientific background knowledge of astronomical objects and phenomena at multiple wavelengths; understand contemporary scientific research questions related to how galaxies formed in the early universe and how stars and planetary systems form and evolve; describe strategies and technologies for using non-visible wavelengths of EM radiation to study various phenomena; and integrate related issues of astronomical science and technology into K-12 classrooms. This course is being developed, evaluated, and offered through the support of SOFIA and SIRTF EPO Programs, two NASA infrared missions

  8. Engaging Scientists in Meaningful E/PO: The Universe Discovery Guides

    Science.gov (United States)

    Meinke, B. K.; Lawton, B.; Gurton, S.; Smith, D. A.; Manning, J. G.

    2014-12-01

    For the 2009 International Year of Astronomy, the then-existing NASA Origins Forum collaborated with the Astronomical Society of the Pacific (ASP) to create a series of monthly "Discovery Guides" for informal educator and amateur astronomer use in educating the public about featured sky objects and associated NASA science themes. Today's NASA Astrophysics Science Education and Public Outreach Forum (SEPOF), one of a new generation of forums coordinating the work of NASA Science Mission Directorate (SMD) EPO efforts—in collaboration with the ASP and NASA SMD missions and programs--has adapted the Discovery Guides into "evergreen" educational resources suitable for a variety of audiences. The Guides focus on "deep sky" objects and astrophysics themes (stars and stellar evolution, galaxies and the universe, and exoplanets), showcasing EPO resources from more than 30 NASA astrophysics missions and programs in a coordinated and cohesive "big picture" approach across the electromagnetic spectrum, grounded in best practices to best serve the needs of the target audiences. Each monthly guide features a theme and a representative object well-placed for viewing, with an accompanying interpretive story, finding charts, strategies for conveying the topics, and complementary supporting NASA-approved education activities and background information from a spectrum of NASA missions and programs. The Universe Discovery Guides are downloadable from the NASA Night Sky Network web site at nightsky.jpl.nasa.gov. We will share the Forum-led Collaborative's experience in developing the guides, how they place individual science discoveries and learning resources into context for audiences, and how the Guides can be readily used in scientist public outreach efforts, in college and university introductory astronomy classes, and in other engagements between scientists, students and the public.

  9. EPOS-WP16: A Platform for European Multi-scale Laboratories

    Science.gov (United States)

    Spiers, Chris; Drury, Martyn; Kan-Parker, Mirjam; Lange, Otto; Willingshofer, Ernst; Funiciello, Francesca; Rosenau, Matthias; Scarlato, Piergiorgio; Sagnotti, Leonardo; W16 Participants

    2016-04-01

    The participant countries in EPOS embody a wide range of world-class laboratory infrastructures ranging from high temperature and pressure experimental facilities, to electron microscopy, micro-beam analysis, analogue modeling and paleomagnetic laboratories. Most data produced by the various laboratory centres and networks are presently available only in limited "final form" in publications. As such many data remain inaccessible and/or poorly preserved. However, the data produced at the participating laboratories are crucial to serving society's need for geo-resources exploration and for protection against geo-hazards. Indeed, to model resource formation and system behaviour during exploitation, we need an understanding from the molecular to the continental scale, based on experimental data. This contribution will describe the work plans that the laboratories community in Europe is making, in the context of EPOS. The main objectives are: - To collect and harmonize available and emerging laboratory data on the properties and processes controlling rock system behaviour at multiple scales, in order to generate products accessible and interoperable through services for supporting research activities. - To co-ordinate the development, integration and trans-national usage of the major solid Earth Science laboratory centres and specialist networks. The length scales encompassed by the infrastructures included range from the nano- and micrometer levels (electron microscopy and micro-beam analysis) to the scale of experiments on centimetre sized samples, and to analogue model experiments simulating the reservoir scale, the basin scale and the plate scale. - To provide products and services supporting research into Geo-resources and Geo-storage, Geo-hazards and Earth System Evolution.

  10. Increasing Human Neural Stem Cell Transplantation Dose Alters Oligodendroglial and Neuronal Differentiation after Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Katja M. Piltti

    2017-06-01

    Full Text Available Multipotent human central nervous system-derived neural stem cells transplanted at doses ranging from 10,000 (low to 500,000 (very high cells differentiated predominantly into the oligodendroglial lineage. However, while the number of engrafted cells increased linearly in relationship to increasing dose, the proportion of oligodendrocytic cells declined. Increasing dose resulted in a plateau of engraftment, enhanced neuronal differentiation, and increased distal migration caudal to the transplantation sites. Dose had no effect on terminal sensory recovery or open-field locomotor scores. However, total human cell number and decreased oligodendroglial proportion were correlated with hindlimb girdle coupling errors. Conversely, greater oligodendroglial proportion was correlated with increased Ab step pattern, decreased swing speed, and increased paw intensity, consistent with improved recovery. These data suggest that transplant dose, and/or target niche parameters can regulate donor cell engraftment, differentiation/maturation, and lineage-specific migration profiles.

  11. Erythropoietin receptor in human skeletal muscle and the effects of acute and long-term injections with recombinant human erythropoietin on the skeletal muscle

    DEFF Research Database (Denmark)

    Lundby, Carsten; Hellsten, Ylva; Jensen, Mie B. F.

    2008-01-01

    The presence and potential physiological role of the erythropoietin receptor (Epo-R) were examined in human skeletal muscle. In this study we demonstrate that Epo-R is present in the endothelium, smooth muscle cells, and in fractions of the sarcolemma of skeletal muscle fibers. To study...... the potential effects of Epo in human skeletal muscle, two separate studies were conducted: one to study the acute effects of a single Epo injection on skeletal muscle gene expression and plasma hormones and another to study the effects of long-term (14 wk) Epo treatment on skeletal muscle structure. Subjects...... was studied in subjects (n = 8) who received long-term Epo administration, and muscle biopsies were obtained before and after. Epo treatment did not alter mean fiber area (0.84 +/- 0.2 vs. 0.72 +/- 0.3 mm(2)), capillaries per fiber (4.3 +/- 0.5 vs. 4.4 +/- 1.3), or number of proliferating endothelial cells...

  12. Increasing Awareness of Insider Information Security Threats in Human Resource Department

    OpenAIRE

    Burcin Cetin Karabat; Cagatay Karabat

    2012-01-01

    An insider threat for companies is defined as a threat caused by malicious user who is an employee company. In recent years, there are number of work on insider threats in information security technologies. These works shows that companies should increasingly and seriously should take into account these threats. Human factors in companies constitute one of the weakest links in information security technology and its products used in human resource (HR) management departments. In the literatur...

  13. Polycythemia in transgenic mice expressing the human erythropoietin gene

    International Nuclear Information System (INIS)

    Semenza, G.L.; Traystman, M.D.; Gearhart, J.D.; Antonarakis, S.E.

    1989-01-01

    Erythropoietin is a glycoprotein hormone that regulates mammalian erythropoiesis. To study the expression of the human erythropoietin gene, EPO, 4 kilobases of DNA encompassing the gene with 0.4 kilobase of 5' flanking sequence and 0.7 kilobase of 3' flanking sequence was microinjected into fertilized mouse eggs. Transgenic mice were generated that are polycythemic, with increased erythrocytic indices in peripheral blood, increased numbers of erythroid precursors in hematopoietic tissue, and increased serum erythropoietin levels. Transgenic homozygotes show a greater degree of polycythemia than do heterozygotes as well as striking extramedullary erythropoiesis. Human erythropoietin RNA was found not only in fetal liver, adult liver, and kidney but also in all other transgenic tissues analyzed. Anemia induced increased human erythropoietin RNA levels in liver but not kidney. These transgenic mice represent a unique model of polycythemia due to increased erythropoietin levels

  14. Erythropoietin enhances hippocampal response during memory retrieval in humans

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla; O'Sullivan, Ursula; Harmer, Catherine J

    2007-01-01

    Although erythropoietin (Epo) is best known for its effects on erythropoiesis, recent evidence suggests that it also has neurotrophic and neuroprotective properties in animal models of hippocampal function. Such an action in humans would make it an intriguing novel compound for the treatment....... This is consistent with upregulation of hippocampal BDNF and neurotrophic actions found in animals and highlights Epo as a promising candidate for treatment of psychiatric disorders....

  15. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa

    DEFF Research Database (Denmark)

    Blomberg Jensen, Martin; Bjerrum, Poul J; Jessen, Torben E

    2011-01-01

    BACKGROUND The vitamin D receptor (VDR) is expressed in human spermatozoa, and VDR-knockout mice and vitamin D (VD) deficiency in rodents results in impaired fertility, low sperm counts and a low number of motile spermatozoa. We investigated the role of activated VD (1,25(OH)(2)D(3)) in human...... spermatozoa and whether VD serum levels are associated with semen quality. METHODS Cross-sectional association study of semen quality and VD serum level in 300 men from the general population, and in vitro studies on spermatozoa from 40 men to investigate the effects of VD on intracellular calcium, sperm......M). 1,25(OH)(2)D(3) increased intracellular calcium concentration in human spermatozoa through VDR-mediated calcium release from an intracellular calcium storage, increased sperm motility and induced the acrosome reaction in vitro. CONCLUSIONS 1,25(OH)(2)D(3) increased intracellular calcium...

  16. Defining an EPOR- regulated transcriptome for primary progenitors, including Tnfr-sf13c as a novel mediator of EPO- dependent erythroblast formation.

    Directory of Open Access Journals (Sweden)

    Seema Singh

    Full Text Available Certain concepts concerning EPO/EPOR action modes have been challenged by in vivo studies: Bcl-x levels are elevated in maturing erythroblasts, but not in their progenitors; truncated EPOR alleles that lack a major p85/PI3K recruitment site nonetheless promote polycythemia; and Erk1 disruption unexpectedly bolsters erythropoiesis. To discover novel EPO/EPOR action routes, global transcriptome analyses presently are applied to interrogate EPO/EPOR effects on primary bone marrow-derived CFUe-like progenitors. Overall, 160 EPO/EPOR target transcripts were significantly modulated 2-to 21.8-fold. A unique set of EPO-regulated survival factors included Lyl1, Gas5, Pim3, Pim1, Bim, Trib3 and Serpina 3g. EPO/EPOR-modulated cell cycle mediators included Cdc25a, Btg3, Cyclin-d2, p27-kip1, Cyclin-g2 and CyclinB1-IP-1. EPO regulation of signal transduction factors was also interestingly complex. For example, not only Socs3 plus Socs2 but also Spred2, Spred1 and Eaf1 were EPO-induced as negative-feedback components. Socs2, plus five additional targets, further proved to comprise new EPOR/Jak2/Stat5 response genes (which are important for erythropoiesis during anemia. Among receptors, an atypical TNF-receptor Tnfr-sf13c was up-modulated >5-fold by EPO. Functionally, Tnfr-sf13c ligation proved to both promote proerythroblast survival, and substantially enhance erythroblast formation. The EPOR therefore engages a sophisticated set of transcriptome response circuits, with Tnfr-sf13c deployed as one novel positive regulator of proerythroblast formation.

  17. Denying humanness to others: a newly discovered mechanism by which violent video games increase aggressive behavior.

    Science.gov (United States)

    Greitemeyer, Tobias; McLatchie, Neil

    2011-05-01

    Past research has provided abundant evidence that playing violent video games increases aggressive behavior. So far, these effects have been explained mainly as the result of priming existing knowledge structures. The research reported here examined the role of denying humanness to other people in accounting for the effect that playing a violent video game has on aggressive behavior. In two experiments, we found that playing violent video games increased dehumanization, which in turn evoked aggressive behavior. Thus, it appears that video-game-induced aggressive behavior is triggered when victimizers perceive the victim to be less human.

  18. Observation on the changes of serum erythropoietin (EPO) and ferritin (SF) levels after preserved red cells (PRC) transfusion in patients with iron deficiency anemia (IDA)

    International Nuclear Information System (INIS)

    Li Keqin; Lv Haijun; Li Xinghua

    2008-01-01

    Objective: To study the changes of serum EPO and SF levels after preserved red cells transfusion in patients with IDA. Methods: Serum EPO and SF levels were detected with RIA both before and after transfusing preserved red cells in 35 patients with IDA as well as in 30 controls. Results: Before transfusion serum EPO levels in the patients were significantly higher than those in the controls (P 0.05). Conclusion: Transfusing preserved red cells is an effective treatment and has important role in clinical application. (authors)

  19. Social Traces of Generic Humans Increase the Value of Everyday Objects.

    Science.gov (United States)

    Job, Veronika; Nikitin, Jana; Zhang, Sophia X; Carr, Priyanka B; Walton, Gregory M

    2017-06-01

    Past research finds that people behave as though the particular qualities of specific, strongly valenced individuals "rub off" on objects. People thus value a sweater worn by George Clooney but are disgusted by one worn by Hitler. We hypothesized that social traces of generic humans can also adhere to objects, increasing their value. Experiments 1 and 2 found that simply marking that consumer products (mugs, giftwrap) were made by generic strangers (e.g., "by people using machines" vs. "by machines run by people") increased their perceived value. Experiment 3 demonstrated that this effect was mediated by thoughts about attention the object received from other people, which, in turn, led people to see the object as possessing more positive social qualities (e.g., friendly), increasing valuation. The results suggest that generic humans are perceived positively, possessing warm social qualities, and these can "rub off" and adhere to everyday objects increasing their value.

  20. Elevated endogenous erythropoietin concentrations are associated with increased risk of brain damage in extremely preterm neonates.

    Directory of Open Access Journals (Sweden)

    Steven J Korzeniewski

    Full Text Available We sought to determine, in very preterm infants, whether elevated perinatal erythropoietin (EPO concentrations are associated with increased risks of indicators of brain damage, and whether this risk differs by the co-occurrence or absence of intermittent or sustained systemic inflammation (ISSI.Protein concentrations were measured in blood collected from 786 infants born before the 28th week of gestation. EPO was measured on postnatal day 14, and 25 inflammation-related proteins were measured weekly during the first 2 postnatal weeks. We defined ISSI as a concentration in the top quartile of each of 25 inflammation-related proteins on two separate days a week apart. Hypererythropoietinemia (hyperEPO was defined as the highest quartile for gestational age on postnatal day 14. Using logistic regression and multinomial logistic regression models, we compared risks of brain damage among neonates with hyperEPO only, ISSI only, and hyperEPO+ISSI, to those who had neither hyperEPO nor ISSI, adjusting for gestational age.Newborns with hyperEPO, regardless of ISSI, were more than twice as likely as those without to have very low (< 55 Mental (OR 2.3; 95% CI 1.5-3.5 and/or Psychomotor (OR 2.4; 95% CI 1.6-3.7 Development Indices (MDI, PDI, and microcephaly at age two years (OR 2.4; 95%CI 1.5-3.8. Newborns with both hyperEPO and ISSI had significantly increased risks of ventriculomegaly, hemiparetic cerebral palsy, microcephaly, and MDI and PDI < 55 (ORs ranged from 2.2-6.3, but not hypoechoic lesions or other forms of cerebral palsy, relative to newborns with neither hyperEPO nor ISSI.hyperEPO, regardless of ISSI, is associated with elevated risks of very low MDI and PDI, and microcephaly, but not with any form of cerebral palsy. Children with both hyperEPO and ISSI are at higher risk than others of very low MDI and PDI, ventriculomegaly, hemiparetic cerebral palsy, and microcephaly.

  1. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HU Hua; YAO Hong-tian; ZHANG Wei-ping; ZHANG LEI; DING Wei; ZHANG Shi-hong; CHEN Zhong; WEI Er-qing

    2005-01-01

    Objective: To characterize the expression of aquaporin-4 (AQP4), one of the aquaporins (AQPs), in human brain specimens from patients with traumatic brain injury or brain tumors. Methods: Nineteen human brain specimens were obtained from the patients with traumatic brain injury, brain tumors, benign meningioma or early stage hemorrhagic stroke. MRI or CT imaging was used to assess brain edema. Hematoxylin and eosin staining were used to evaluate cell damage. Immunohistochemistry was used to detect the AQP4 expression. Results: AQP4 expression was increased from 15h to at least 8 d after injury. AQP4immunoreactivity was strong around astrocytomas, ganglioglioma and metastatic adenocarcinoma. However, AQP4 immunoreactivity was only found in the centers of astrocytomas and ganglioglioma, but not in metastatic adenocarcinoma derived from lung.Conclusion: AQP4 expression increases in human brains after traumatic brain injury, within brain-derived tumors, and around brain tumors.

  2. Obesity and Low-Grade Inflammation Increase Plasma Follistatin-Like 3 in Humans

    DEFF Research Database (Denmark)

    Brandt, Claus; Pedersen, Maria; Rinnov, Anders

    2014-01-01

    , plasma leptin, fasting insulin, and HOMA B and negatively with HOMA S. Furthermore plasma fstl3 correlated positively with plasma TNF-α and IL-6 levels. Infusion of LPS and TNF-α, but not IL-6 and insulin, increased plasma fstl3 in humans. CONCLUSION: Plasma fstl3 is increased in obese subjects......BACKGROUND: Rodent models suggest that follistatin-like 3 (fstl3) is associated with diabetes and obesity. In humans, plasma fstl3 is reduced with gestational diabetes. In vitro, TNF-α induces fstl3 secretion, which suggests a link to inflammation. OBJECTIVE: To elucidate the association between...... plasma fstl3 and obesity, insulin resistance, and low-grade inflammation in humans. STUDY DESIGN: Plasma fstl3 levels were determined in a cross-sectional study including three groups: patients with type 2 diabetes, impaired glucose tolerance, and healthy controls. In addition, lipopolysaccharide (LPS...

  3. Conservation threats due to human-caused increases in fire frequency in Mediterranean-climate ecosystems.

    Science.gov (United States)

    Syphard, Alexandra D; Radeloff, Volker C; Hawbaker, Todd J; Stewart, Susan I

    2009-06-01

    Periodic wildfire is an important natural process in Mediterranean-climate ecosystems, but increasing fire recurrence threatens the fragile ecology of these regions. Because most fires are human-caused, we investigated how human population patterns affect fire frequency. Prior research in California suggests the relationship between population density and fire frequency is not linear. There are few human ignitions in areas with low population density, so fire frequency is low. As population density increases, human ignitions and fire frequency also increase, but beyond a density threshold, the relationship becomes negative as fuels become sparser and fire suppression resources are concentrated. We tested whether this hypothesis also applies to the other Mediterranean-climate ecosystems of the world. We used global satellite databases of population, fire activity, and land cover to evaluate the spatial relationship between humans and fire in the world's five Mediterranean-climate ecosystems. Both the mean and median population densities were consistently and substantially higher in areas with than without fire, but fire again peaked at intermediate population densities, which suggests that the spatial relationship is complex and nonlinear. Some land-cover types burned more frequently than expected, but no systematic differences were observed across the five regions. The consistent association between higher population densities and fire suggests that regardless of differences between land-cover types, natural fire regimes, or overall population, the presence of people in Mediterranean-climate regions strongly affects the frequency of fires; thus, population growth in areas now sparsely settled presents a conservation concern. Considering the sensitivity of plant species to repeated burning and the global conservation significance of Mediterranean-climate ecosystems, conservation planning needs to consider the human influence on fire frequency. Fine-scale spatial

  4. On the Increasing Fragility of Human Teeth with Age: ADeep-Ultraviolet Resonance Raman Study

    Energy Technology Data Exchange (ETDEWEB)

    Ager III, J.W.; Nalla, R.K.; Balooch, G.; Kim, G.; Pugach, M.; Habelitz, S.; Marshall, G.W.; Kinney, J.H.; Ritchie, R.O.

    2006-07-14

    Ultraviolet resonance Raman spectroscopy (UVRRS) using 244nm excitation was used to investigate the impact of aging on humandentin. The intensity of a spectroscopic feature from the peptide bondsin the collagen increases with tissue age, similar to a finding reportedpreviously for human cortical bone.

  5. Trastuzumab Induces an Immediate, Transient Volume Increase in Humans: A Randomised Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Joannes A.A. Reijers

    2015-08-01

    Interpretation: Single dose administration of trastuzumab in humans is associated with an immediate, transient extracellular volume increase, either as a primary or secondary (compensatory response, which can be detected easily using routine clinical assessments. Echocardiographic changes, both short and long term, could not be found after single dose administration to drug-naive patients.

  6. Declining human population but increasing residential development around protected areas in Puerto Rico

    Science.gov (United States)

    J. Castro-Prieto; S. Martinuzzi; V.C. Radeloff; D.P. Helmers; M. Quiñones; W.A. Gould

    2017-01-01

    Increasing residential development around protected areas is a major threat for protected areas worldwide, and human population growth is often the most important cause. However, population is decreasing in many regions as a result of socio-economic changes, and it is unclear how residential development around protected areas is affected in these situations. We...

  7. Human-accelerated weathering increases salinization, major ions, and alkalinization in fresh water across land use

    Science.gov (United States)

    Human land use increases transport of dissolved inorganic carbon and major ions in watersheds due to the combination of easily weathered materials in watersheds and anthropogenic inputs. Here, we show that dissolved inorganic carbon (DIC), alkalinity, and major ions are significa...

  8. Natural form of noncytolytic flexible human Fc as a long-acting carrier of agonistic ligand, erythropoietin.

    Directory of Open Access Journals (Sweden)

    Se Jin Im

    Full Text Available Human IgG1 Fc has been widely used as a bioconjugate, but exhibits shortcomings, such as antibody- and complement-mediated cytotoxicity as well as decreased bioactivity, when applied to agonistic proteins. Here, we constructed a nonimmunogenic, noncytolytic and flexible hybrid Fc (hyFc consisting of IgD and IgG4, and tested its function using erythropoietin (EPO conjugate, EPO-hyFc. Despite low amino acid homology (20.5% between IgD Fc and IgG4 Fc, EPO-hyFc retained "Y-shaped" structure and repeated intravenous administrations of EPO-hyFc into monkeys did not generate EPO-hyFc-specific antibody responses. Furthermore, EPO-hyFc could not bind to FcγR I and C1q in contrast to EPO-IgG1 Fc. In addition, EPO-hyFc exhibited better in vitro bioactivity and in vivo bioactivity in rats than EPO-IgG1 Fc, presumably due to the high flexibility of IgD. Moreover, the mean serum half-life of EPO-hyFc(H, a high sialic acid content form of EPO-hyFc, was approximately 2-fold longer than that of the heavily glycosylated EPO, darbepoetin alfa, in rats. More importantly, subcutaneous injection of EPO-hyFc(H not only induced a significantly greater elevation of serum hemoglobin levels than darbepoetin alfa in both normal rats and cisplatin-induced anemic rats, but also displayed a delayed time to maximal serum level and twice final area-under-the-curve (AUC(last. Taken together, hyFc might be a more attractive Fc conjugate for agonistic proteins/peptides than IgG1 Fc due to its capability to elongate their half-lives without inducing host effector functions and hindering bioactivity of fused molecules. Additionally, a head-to-head comparison demonstrated that hyFc-fusion strategy more effectively improved the in vivo bioactivity of EPO than the hyperglycosylation approach.

  9. Natural form of noncytolytic flexible human Fc as a long-acting carrier of agonistic ligand, erythropoietin.

    Science.gov (United States)

    Im, Se Jin; Yang, Sang In; Yang, Se Hwan; Choi, Dong Hoon; Choi, So Young; Kim, Hea Sook; Jang, Do Soo; Jin, Kyeong Sik; Chung, Yo-Kyung; Kim, Seung-Hee; Paik, Sang Hoon; Park, Yoo Chang; Chung, Moon Koo; Kim, Yong Bum; Han, Kang-Hyun; Choi, Kwan Yong; Sung, Young Chul

    2011-01-01

    Human IgG1 Fc has been widely used as a bioconjugate, but exhibits shortcomings, such as antibody- and complement-mediated cytotoxicity as well as decreased bioactivity, when applied to agonistic proteins. Here, we constructed a nonimmunogenic, noncytolytic and flexible hybrid Fc (hyFc) consisting of IgD and IgG4, and tested its function using erythropoietin (EPO) conjugate, EPO-hyFc. Despite low amino acid homology (20.5%) between IgD Fc and IgG4 Fc, EPO-hyFc retained "Y-shaped" structure and repeated intravenous administrations of EPO-hyFc into monkeys did not generate EPO-hyFc-specific antibody responses. Furthermore, EPO-hyFc could not bind to FcγR I and C1q in contrast to EPO-IgG1 Fc. In addition, EPO-hyFc exhibited better in vitro bioactivity and in vivo bioactivity in rats than EPO-IgG1 Fc, presumably due to the high flexibility of IgD. Moreover, the mean serum half-life of EPO-hyFc(H), a high sialic acid content form of EPO-hyFc, was approximately 2-fold longer than that of the heavily glycosylated EPO, darbepoetin alfa, in rats. More importantly, subcutaneous injection of EPO-hyFc(H) not only induced a significantly greater elevation of serum hemoglobin levels than darbepoetin alfa in both normal rats and cisplatin-induced anemic rats, but also displayed a delayed time to maximal serum level and twice final area-under-the-curve (AUC(last)). Taken together, hyFc might be a more attractive Fc conjugate for agonistic proteins/peptides than IgG1 Fc due to its capability to elongate their half-lives without inducing host effector functions and hindering bioactivity of fused molecules. Additionally, a head-to-head comparison demonstrated that hyFc-fusion strategy more effectively improved the in vivo bioactivity of EPO than the hyperglycosylation approach.

  10. EPOS-WP16: A coherent and collaborative network of Solid Earth Multi-scale laboratories

    Science.gov (United States)

    Calignano, Elisa; Rosenau, Matthias; Lange, Otto; Spiers, Chris; Willingshofer, Ernst; Drury, Martyn; van Kan-Parker, Mirjam; Elger, Kirsten; Ulbricht, Damian; Funiciello, Francesca; Trippanera, Daniele; Sagnotti, Leonardo; Scarlato, Piergiorgio; Tesei, Telemaco; Winkler, Aldo

    2017-04-01

    Laboratory facilities are an integral part of Earth Science research. The diversity of methods employed in such infrastructures reflects the multi-scale nature of the Earth system and is essential for the understanding of its evolution, for the assessment of geo-hazards and for the sustainable exploitation of geo-resources. In the frame of EPOS (European Plate Observing System), the Working Package 16 represents a developing community of European Geoscience Multi-scale laboratories. The participant and collaborating institutions (Utrecht University, GFZ, RomaTre University, INGV, NERC, CSIC-ICTJA, CNRS, LMU, C4G-UBI, ETH, CNR*) embody several types of laboratory infrastructures, engaged in different fields of interest of Earth Science: from high temperature and pressure experimental facilities, to electron microscopy, micro-beam analysis, analogue tectonic and geodynamic modelling and paleomagnetic laboratories. The length scales encompassed by these infrastructures range from the nano- and micrometre levels (electron microscopy and micro-beam analysis) to the scale of experiments on centimetres-sized samples, and to analogue model experiments simulating the reservoir scale, the basin scale and the plate scale. The aim of WP16 is to provide two services by the year 2019: first, providing virtual access to data from laboratories (data service) and, second, providing physical access to laboratories (transnational access, TNA). Regarding the development of a data service, the current status is such that most data produced by the various laboratory centres and networks are available only in limited "final form" in publications, many data remain inaccessible and/or poorly preserved. Within EPOS the TCS Multi-scale laboratories is collecting and harmonizing available and emerging laboratory data on the properties and process controlling rock system behaviour at all relevant scales, in order to generate products accessible and interoperable through services for supporting

  11. Human epithelial cells increase their rigidity with ageing in vitro: direct measurements

    International Nuclear Information System (INIS)

    Berdyyeva, Tamara K; Woodworth, Craig D; Sokolov, Igor

    2005-01-01

    The decrease in elasticity of epithelial tissues with ageing contributes to many human diseases. This change was previously attributed to increased crosslinking of extracellular matrix proteins. Here we show that individual human epithelial cells also become significantly more rigid during ageing in vitro. Using atomic force microscopy (AFM), we found that the Young's modulus of viable cells was consistently increased two- to four-fold in older versus younger cells. Direct visualization of the cytoskeleton using a novel method involving the AFM suggested that increased rigidity of ageing cells was due to a higher density of cytoskeletal fibres. Our results identify a unique mechanism that might contribute to the age-related loss of elasticity in epithelial tissues

  12. No increased sperm DNA fragmentation index in semen containing human papillomavirus or herpesvirus

    DEFF Research Database (Denmark)

    Kaspersen, Maja Døvling; Bungum, Mona; Fedder, Jens

    2013-01-01

    It remains unknown whether human papillomaviruses (HPVs) or human herpesviruses (HHVs) in semen affect sperm DNA integrity. We investigated whether the presence of these viruses in semen was associated with an elevated sperm DNA fragmentation index. Semen from 76 sperm donors was examined by a PCR......-based hybridization array that identifies all HHVs and 35 of the most common HPVs. Sperm DNA integrity was determined by the sperm chromatin structure assay. HPVs or HHVs, or both, were found in 57% of semen samples; however, sperm DNA fragmentation index was not increased in semen containing these viruses....

  13. Climate Discovery: Integrating Research With Exhibit, Public Tours, K-12, and Web-based EPO Resources

    Science.gov (United States)

    Foster, S. Q.; Carbone, L.; Gardiner, L.; Johnson, R.; Russell, R.; Advisory Committee, S.; Ammann, C.; Lu, G.; Richmond, A.; Maute, A.; Haller, D.; Conery, C.; Bintner, G.

    2005-12-01

    The Climate Discovery Exhibit at the National Center for Atmospheric Research (NCAR) Mesa Lab provides an exciting conceptual outline for the integration of several EPO activities with other well-established NCAR educational resources and programs. The exhibit is organized into four topic areas intended to build understanding among NCAR's 80,000 annual visitors, including 10,000 school children, about Earth system processes and scientific methods contributing to a growing body of knowledge about climate and global change. These topics include: 'Sun-Earth Connections,' 'Climate Now,' 'Climate Past,' and 'Climate Future.' Exhibit text, graphics, film and electronic media, and interactives are developed and updated through collaborations between NCAR's climate research scientists and staff in the Office of Education and Outreach (EO) at the University Corporation for Atmospheric Research (UCAR). With funding from NCAR, paleoclimatologists have contributed data and ideas for a new exhibit Teachers' Guide unit about 'Climate Past.' This collection of middle-school level, standards-aligned lessons are intended to help students gain understanding about how scientists use proxy data and direct observations to describe past climates. Two NASA EPO's have funded the development of 'Sun-Earth Connection' lessons, visual media, and tips for scientists and teachers. Integrated with related content and activities from the NASA-funded Windows to the Universe web site, these products have been adapted to form a second unit in the Climate Discovery Teachers' Guide about the Sun's influence on Earth's climate. Other lesson plans, previously developed by on-going efforts of EO staff and NSF's previously-funded Project Learn program are providing content for a third Teachers' Guide unit on 'Climate Now' - the dynamic atmospheric and geological processes that regulate Earth's climate. EO has plans to collaborate with NCAR climatologists and computer modelers in the next year to develop

  14. Engaging Scientists in Meaningful E/PO: How the NASA SMD E/PO Community Addresses the needs of Underrepresented Audiences through NASA Science4Girls and Their Families

    Science.gov (United States)

    Meinke, Bonnie K.; Smith, Denise A.; Bleacher, Lora; Hauck, Karin; Soeffing, Cassie; NASA SMD E/PO Community

    2015-01-01

    The NASA Astrophysics Science Education and Public Outreach Forum (SEPOF) coordinates the work of individual NASA Science Mission Directorate (SMD) Astrophysics EPO projects and their teams to bring the NASA science education resources and expertise to libraries nationwide. The Astrophysics Forum assists scientists and educators with becoming involved in SMD E/PO (which is uniquely poised to foster collaboration between scientists with content expertise and educators with pedagogy expertise) and makes SMD E/PO resources and expertise accessible to the science and education communities. The NASA Science4Girls and Their Families initiative partners NASA science education programs with public libraries to provide NASA-themed hands-on education activities for girls and their families. As such, the initiative engages girls in all four NASA science discipline areas (Astrophysics, Earth Science, Planetary Science, and Heliophysics), which enables audiences to experience the full range of NASA science topics and the different career skills each requires. The events focus on engaging this particular underserved and underrepresented audience in Science, Technology, Engineering, and Mathematics (STEM) via use of research-based best practices, collaborations with libraries, partnerships with local and national organizations, and remote engagement of audiences.

  15. Effect of increased HoxB4 on human megakaryocytic development

    International Nuclear Information System (INIS)

    Zhong, Yiming; Sullenbarger, Brent; Lasky, Larry C.

    2010-01-01

    Research highlights: → HoxB4 overexpression in human TF1 cells increased the expression of CD61 and CD41a. → HoxB4 fusion protein enhanced megakaryocytic development of CD34 + cord blood cells. → Ectopic HoxB4 increased Tpo receptor expression and decreased c-Myb expression. → HoxB4 RNA silencing increased c-Myb expression and decreased Fli-1 expression. -- Abstract: In order to produce clinically useful quantities of platelets ex vivo we may need to firstly enhance early self-renewal of hematopoietic stem cells (HSCs) and/or megakaryocyte (Mk) progenitors. The homeodomain transcription factor HoxB4 has been shown to be an important regulator of stem cell renewal and hematopoiesis; however, its effect on megakaryopoiesis is unclear. In this study, we investigated the effect of HoxB4 overexpression or RNA silencing on megakaryocytic development in the human TF1 progenitor cell line; we then used recombinant tPTD-HoxB4 fusion protein to study the effect of exogenous HoxB4 on megakaryocytic development of human CD34 positively-selected cord blood cells. We found that ectopic HoxB4 in TF1 cells increased the antigen expression of CD61and CD41a, increased the gene expression of thrombopoietin receptor (TpoR), Scl-1, Cyclin D1, Fog-1 and Fli-1 while it decreased c-Myb expression. HoxB4 RNA silencing in TF1 cells decreased the expression of CD61 and CD41a and decreased Fli-1 expression while it increased the expression of c-Myb. Recombinant tPTD-HoxB4 fusion protein increased the percentages and absolute numbers of CD41a and CD61 positive cells during megakaryocytic differentiation of CD34 positively-selected cord blood cells and increased the numbers of colony-forming unit-megakaryocyte (CFU-Mk). Adding tPTD-HoxB4 fusion protein increased the gene expression of TpoR, Cyclin D1, Fog-1 and Fli-1 while it inhibited c-Myb expression. Our data suggest that increased HoxB4 enhanced early megakaryocytic development in human TF1 cells and CD34 positively-selected cord

  16. Effect of increased HoxB4 on human megakaryocytic development

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Yiming [Department of Pathology, The Ohio State University, Columbus, OH (United States); Program in Molecular, Cellular, and Developmental Biology, The Ohio State University, Columbus, OH (United States); Sullenbarger, Brent [Department of Pathology, The Ohio State University, Columbus, OH (United States); Lasky, Larry C., E-mail: Lasky.4@osu.edu [Department of Pathology, The Ohio State University, Columbus, OH (United States); Program in Molecular, Cellular, and Developmental Biology, The Ohio State University, Columbus, OH (United States)

    2010-07-30

    Research highlights: {yields} HoxB4 overexpression in human TF1 cells increased the expression of CD61 and CD41a. {yields} HoxB4 fusion protein enhanced megakaryocytic development of CD34{sup +} cord blood cells. {yields} Ectopic HoxB4 increased Tpo receptor expression and decreased c-Myb expression. {yields} HoxB4 RNA silencing increased c-Myb expression and decreased Fli-1 expression. -- Abstract: In order to produce clinically useful quantities of platelets ex vivo we may need to firstly enhance early self-renewal of hematopoietic stem cells (HSCs) and/or megakaryocyte (Mk) progenitors. The homeodomain transcription factor HoxB4 has been shown to be an important regulator of stem cell renewal and hematopoiesis; however, its effect on megakaryopoiesis is unclear. In this study, we investigated the effect of HoxB4 overexpression or RNA silencing on megakaryocytic development in the human TF1 progenitor cell line; we then used recombinant tPTD-HoxB4 fusion protein to study the effect of exogenous HoxB4 on megakaryocytic development of human CD34 positively-selected cord blood cells. We found that ectopic HoxB4 in TF1 cells increased the antigen expression of CD61and CD41a, increased the gene expression of thrombopoietin receptor (TpoR), Scl-1, Cyclin D1, Fog-1 and Fli-1 while it decreased c-Myb expression. HoxB4 RNA silencing in TF1 cells decreased the expression of CD61 and CD41a and decreased Fli-1 expression while it increased the expression of c-Myb. Recombinant tPTD-HoxB4 fusion protein increased the percentages and absolute numbers of CD41a and CD61 positive cells during megakaryocytic differentiation of CD34 positively-selected cord blood cells and increased the numbers of colony-forming unit-megakaryocyte (CFU-Mk). Adding tPTD-HoxB4 fusion protein increased the gene expression of TpoR, Cyclin D1, Fog-1 and Fli-1 while it inhibited c-Myb expression. Our data suggest that increased HoxB4 enhanced early megakaryocytic development in human TF1 cells and CD34

  17. Haemoglobin mass and running time trial performance after recombinant human erythropoietin administration in trained men.

    Directory of Open Access Journals (Sweden)

    Jérôme Durussel

    Full Text Available UNLABELLED: Recombinant human erythropoietin (rHuEpo increases haemoglobin mass (Hb(mass and maximal oxygen uptake (v O(2 max. PURPOSE: This study defined the time course of changes in Hb(mass, v O(2 max as well as running time trial performance following 4 weeks of rHuEpo administration to determine whether the laboratory observations would translate into actual improvements in running performance in the field. METHODS: 19 trained men received rHuEpo injections of 50 IU•kg(-1 body mass every two days for 4 weeks. Hb(mass was determined weekly using the optimized carbon monoxide rebreathing method until 4 weeks after administration. v O(2 max and 3,000 m time trial performance were measured pre, post administration and at the end of the study. RESULTS: Relative to baseline, running performance significantly improved by ∼6% after administration (10:30±1:07 min:sec vs. 11:08±1:15 min:sec, p<0.001 and remained significantly enhanced by ∼3% 4 weeks after administration (10:46±1:13 min:sec, p<0.001, while v O(2 max was also significantly increased post administration (60.7±5.8 mL•min(-1•kg(-1 vs. 56.0±6.2 mL•min(-1•kg(-1, p<0.001 and remained significantly increased 4 weeks after rHuEpo (58.0±5.6 mL•min(-1•kg(-1, p = 0.021. Hb(mass was significantly increased at the end of administration compared to baseline (15.2±1.5 g•kg(-1 vs. 12.7±1.2 g•kg(-1, p<0.001. The rate of decrease in Hb(mass toward baseline values post rHuEpo was similar to that of the increase during administration (-0.53 g•kg(-1•wk(-1, 95% confidence interval (CI (-0.68, -0.38 vs. 0.54 g•kg(-1•wk(-1, CI (0.46, 0.63 but Hb(mass was still significantly elevated 4 weeks after administration compared to baseline (13.7±1.1 g•kg(-1, p<0.001. CONCLUSION: Running performance was improved following 4 weeks of rHuEpo and remained elevated 4 weeks after administration compared to baseline. These field performance effects coincided with rHuEpo

  18. Staurosporine Increases Lentiviral Vector Transduction Efficiency of Human Hematopoietic Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Gretchen Lewis

    2018-06-01

    Full Text Available Lentiviral vector (LVV-mediated transduction of human CD34+ hematopoietic stem and progenitor cells (HSPCs holds tremendous promise for the treatment of monogenic hematological diseases. This approach requires the generation of a sufficient proportion of gene-modified cells. We identified staurosporine, a serine/threonine kinase inhibitor, as a small molecule that could be added to the transduction process to increase the proportion of genetically modified HSPCs by overcoming a LVV entry barrier. Staurosporine increased vector copy number (VCN approximately 2-fold when added to mobilized peripheral blood (mPB CD34+ cells prior to transduction. Limited staurosporine treatment did not affect viability of cells post-transduction, and there was no difference in in vitro colony formation compared to vehicle-treated cells. Xenotransplantation studies identified a statistically significant increase in VCN in engrafted human cells in mouse bone marrow at 4 months post-transplantation compared to vehicle-treated cells. Prostaglandin E2 (PGE2 is known to increase transduction efficiency of HSPCs through a different mechanism. Combining staurosporine and PGE2 resulted in further enhancement of transduction efficiency, particularly in short-term HSPCs. The combinatorial use of small molecules, such as staurosporine and PGE2, to enhance LVV transduction of human CD34+ cells is a promising method to improve transduction efficiency and subsequent potential therapeutic benefit of gene therapy drug products. Keywords: lentiviral, HSPC, transduction

  19. Electronic cigarette liquid increases inflammation and virus infection in primary human airway epithelial cells.

    Science.gov (United States)

    Wu, Qun; Jiang, Di; Minor, Maisha; Chu, Hong Wei

    2014-01-01

    The use of electronic cigarettes (e-cigarettes) is rapidly increasing in the United States, especially among young people since e-cigarettes have been perceived as a safer alternative to conventional tobacco cigarettes. However, the scientific evidence regarding the human health effects of e-cigarettes on the lung is extremely limited. The major goal of our current study is to determine if e-cigarette use alters human young subject airway epithelial functions such as inflammatory response and innate immune defense against respiratory viral (i.e., human rhinovirus, HRV) infection. We examined the effects of e-cigarette liquid (e-liquid) on pro-inflammatory cytokine (e.g., IL-6) production, HRV infection and host defense molecules (e.g., short palate, lung, and nasal epithelium clone 1, SPLUNC1) in primary human airway epithelial cells from young healthy non-smokers. Additionally, we examined the role of SPLUNC1 in lung defense against HRV infection using a SPLUNC1 knockout mouse model. We found that nicotine-free e-liquid promoted IL-6 production and HRV infection. Addition of nicotine into e-liquid further amplified the effects of nicotine-free e-liquid. Moreover, SPLUNC1 deficiency in mice significantly increased lung HRV loads. E-liquid inhibited SPLUNC1 expression in primary human airway epithelial cells. These findings strongly suggest the deleterious health effects of e-cigarettes in the airways of young people. Our data will guide future studies to evaluate the impact of e-cigarettes on lung health in human populations, and help inform the public about potential health risks of e-cigarettes.

  20. Electronic cigarette liquid increases inflammation and virus infection in primary human airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Qun Wu

    Full Text Available The use of electronic cigarettes (e-cigarettes is rapidly increasing in the United States, especially among young people since e-cigarettes have been perceived as a safer alternative to conventional tobacco cigarettes. However, the scientific evidence regarding the human health effects of e-cigarettes on the lung is extremely limited. The major goal of our current study is to determine if e-cigarette use alters human young subject airway epithelial functions such as inflammatory response and innate immune defense against respiratory viral (i.e., human rhinovirus, HRV infection.We examined the effects of e-cigarette liquid (e-liquid on pro-inflammatory cytokine (e.g., IL-6 production, HRV infection and host defense molecules (e.g., short palate, lung, and nasal epithelium clone 1, SPLUNC1 in primary human airway epithelial cells from young healthy non-smokers. Additionally, we examined the role of SPLUNC1 in lung defense against HRV infection using a SPLUNC1 knockout mouse model. We found that nicotine-free e-liquid promoted IL-6 production and HRV infection. Addition of nicotine into e-liquid further amplified the effects of nicotine-free e-liquid. Moreover, SPLUNC1 deficiency in mice significantly increased lung HRV loads. E-liquid inhibited SPLUNC1 expression in primary human airway epithelial cells. These findings strongly suggest the deleterious health effects of e-cigarettes in the airways of young people. Our data will guide future studies to evaluate the impact of e-cigarettes on lung health in human populations, and help inform the public about potential health risks of e-cigarettes.

  1. Development and evaluation of gastroretentive raft forming systems incorporating curcumin-Eudragit® EPO solid dispersions for gastric ulcer treatment.

    Science.gov (United States)

    Kerdsakundee, Nattha; Mahattanadul, Sirima; Wiwattanapatapee, Ruedeekorn

    2015-08-01

    Novel raft forming systems incorporating curcumin-Eudragit® EPO solid dispersions were developed to prolong the gastric residence time and provide for a controlled release therapy of curcumin to treat gastric ulcers. The solid dispersions of curcumin with Eudragit® EPO were prepared by the solvent evaporation method at various ratios to improve the solubility and the dissolution of curcumin. The optimum weight ratio of 1:5 for curcumin to Eudragit® EPO was used to incorporate into the raft forming systems. The raft forming formulations were composed of curcumin-Eudragit® EPO solid dispersions, sodium alginate as a gelling polymer and calcium carbonate for generating divalent Ca(2+) ions and carbon dioxide to form a floating raft. All formulations formed a gelled raft in 1min and sustained buoyancy on the 0.1N hydrochloric acid (pH 1.2) surface with a 60-85% release of curcumin within 8h. The curative effect on the acetic acid-induced chronic gastric ulcer in rats was determined. The curcumin raft forming formulations at 40mg/kg once daily showed a superior curative effect on the gastric ulcer in terms of the ulcer index and healing index than the standard antisecretory agent: lansoprazole (1mg/kg, twice daily) and a curcumin suspension (40mg/kg, twice daily). These studies demonstrated that the new raft forming systems containing curcumin solid dispersions are promising carriers for a stomach-specific delivery of poorly soluble lipophilic compounds. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Practicing IEF-PAGE of EPO: the impact of detergents and sample application methods on analytical performance in doping control.

    Science.gov (United States)

    Reichel, Christian

    2010-01-01

    Electrophoretic techniques, namely isoelectric focusing polyacrylamide gel electrophoresis (IEF-PAGE) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) are key techniques used for confirming the doping-related abuse of recombinant erythropoietins and analogs. IEF-PAGE is performed on horizontal slab-gels with samples applied to the surface of the gel. Different sample application techniques can be employed, but application pieces and applicator strips are most frequently used. However, defective application pieces cause lane streaking during IEF of erythropoietin (EPO), which is especially pronounced in the acidic region of the gel. The effect is due to an incompatibility of the substance used for enhancing the wettability of the cellulose-based commercial product and is batch-dependent. A detailed mass spectrometric study was performed, which revealed that defective sample application pieces (bought between 2007 and 2010) contained a complex mixture of alcohol ethoxylates, alcohol ethoxysulfates, and alkyl sulfates (e.g. SDS). Anionic detergents, like the sulfates contained in these application pieces, are in general incompatible with IEF. Alternative application techniques proved partly useful. While homemade pieces made of blotting paper are a good alternative, the usage of applicator strips or shims is hampered by the risk of leaking wells, which lead to laterally diffused samples. Casting IEF-gels with wells appears to be the best solution, since sustained release of retained proteins from the application pieces can be avoided. Edge effects do not occur if wells are correctly filled with the samples. The evaluation of EPO-profiles with defects is prohibited by the technical document on EPO-analytics (TD2009EPO) of the World Anti-Doping Agency (WADA). Copyright © 2010 John Wiley & Sons, Ltd.

  3. In vitro expression of erythropoietin by transfected human mesenchymal stromal cells.

    Science.gov (United States)

    Mok, P-L; Cheong, S-K; Leong, C-F; Othman, A

    2008-01-01

    Mesenchymal stromal cells (MSC) are pluripotent progenitor cells that can be found in human bone marrow (BM). These cells have low immunogenicity and could suppress alloreactive T-cell responses. In the current study, MSC were tested for their capacity to carry and deliver the erythropoietin (EPO) gene in vitro. Expanded BM MSC was transfected with EPO-encoded plasmid pMCV1.2 and EPO-encoded MIDGE (minimalistic immunologically defined gene expression) vector by electroporation. The expressed EPO was used to induce hematopoietic stem cells (HSC) into erythroid colonies. The results showed that the MIDGE vector was more effective and stable than the plasmid (pMCV1.2) in delivering EPO gene into MSC. The supernatants containing EPO obtained from the transfected cell culture were able to induce the differentiation of HSC into erythroid colonies. MSC hold promise as a cell factory for the production of biologic molecules, and MIDGE vector is more effective and stable than the plasmid in nucleofection involving the EPO gene.

  4. Human population growth offsets climate-driven increase in woody vegetation in sub-Saharan Africa

    DEFF Research Database (Denmark)

    Brandt, Martin Stefan; Rasmussen, Kjeld; Peñuelas, Josep

    2017-01-01

    The rapidly growing human population in sub-Saharan Africa generates increasing demand for agricultural land and forest products, which presumably leads to deforestation. Conversely, a greening of African drylands has been reported, but this has been difficult to associate with changes in woody...... an increase in woody cover largely in drylands, and 11% had a decrease (2,150,000 km2), mostly in humid zones. Increases in woody cover were associated with low population growth, and were driven by increases in CO2 in the humid zones and by increases in precipitation in drylands, whereas decreases in woody...... cover were associated with high population growth. The spatially distinct pattern of these opposing trends reflects, first, the natural response of vegetation to precipitation and atmospheric CO2, and second, deforestation in humid areas, minor in size but important for ecosystem services...

  5. Exposure to ozone modulates human airway protease/antiprotease balance contributing to increased influenza A infection.

    Directory of Open Access Journals (Sweden)

    Matthew J Kesic

    Full Text Available Exposure to oxidant air pollution is associated with increased respiratory morbidities and susceptibility to infections. Ozone is a commonly encountered oxidant air pollutant, yet its effects on influenza infections in humans are not known. The greater Mexico City area was the primary site for the spring 2009 influenza A H1N1 pandemic, which also coincided with high levels of environmental ozone. Proteolytic cleavage of the viral membrane protein hemagglutinin (HA is essential for influenza virus infectivity. Recent studies suggest that HA cleavage might be cell-associated and facilitated by the type II transmembrane serine proteases (TTSPs human airway trypsin-like protease (HAT and transmembrane protease, serine 2 (TMPRSS2, whose activities are regulated by antiproteases, such as secretory leukocyte protease inhibitor (SLPI. Based on these observations, we sought to determine how acute exposure to ozone may modulate cellular protease/antiprotease expression and function, and to define their roles in a viral infection. We utilized our in vitro model of differentiated human nasal epithelial cells (NECs to determine the effects of ozone on influenza cleavage, entry, and replication. We show that ozone exposure disrupts the protease/antiprotease balance within the airway liquid. We also determined that functional forms of HAT, TMPRSS2, and SLPI are secreted from human airway epithelium, and acute exposure to ozone inversely alters their expression levels. We also show that addition of antioxidants significantly reduces virus replication through the induction of SLPI. In addition, we determined that ozone-induced cleavage of the viral HA protein is not cell-associated and that secreted endogenous proteases are sufficient to activate HA leading to a significant increase in viral replication. Our data indicate that pre-exposure to ozone disrupts the protease/antiprotease balance found in the human airway, leading to increased influenza susceptibility.

  6. Still Human: A Call for Increased Focus on Ethical Standards in Cadaver Research.

    Science.gov (United States)

    Bach, Michelle C

    2016-12-01

    Research on human cadavers is an important mechanism of scientific progress and comprises a large industry in the United States. However, despite its importance and influence, there is little ethical or regulatory oversight of cadaver-based research. This lack of transparency raises important ethical questions. Thus, this paper serves as a call for ethicists and regulators to pay increased attention to cadaver research. I argue that cadaver research ought to be considered a subset of human subjects research and held accountable to higher ethical standards. After describing current practices, I argue that oversight of cadaver research as a form of human subjects research is appropriate because cadaver research is similar to other types of human research, participants in cadaver research incur risks of harm, and a current lack of oversight has allowed the cadaver industry to entice research participation through ethically questionable practices. This paper urges greater dialogue among human subjects research ethicists and regulators about what constitutes appropriate protections for participants in cadaver research.

  7. Simulating the evolution of the human family: cooperative breeding increases in harsh environments.

    Science.gov (United States)

    Smaldino, Paul E; Newson, Lesley; Schank, Jeffrey C; Richerson, Peter J

    2013-01-01

    Verbal and mathematical models that consider the costs and benefits of behavioral strategies have been useful in explaining animal behavior and are often used as the basis of evolutionary explanations of human behavior. In most cases, however, these models do not account for the effects that group structure and cultural traditions within a human population have on the costs and benefits of its members' decisions. Nor do they consider the likelihood that cultural as well as genetic traits will be subject to natural selection. In this paper, we present an agent-based model that incorporates some key aspects of human social structure and life history. We investigate the evolution of a population under conditions of different environmental harshness and in which selection can occur at the level of the group as well as the level of the individual. We focus on the evolution of a socially learned characteristic related to individuals' willingness to contribute to raising the offspring of others within their family group. We find that environmental harshness increases the frequency of individuals who make such contributions. However, under the conditions we stipulate, we also find that environmental variability can allow groups to survive with lower frequencies of helpers. The model presented here is inevitably a simplified representation of a human population, but it provides a basis for future modeling work toward evolutionary explanations of human behavior that consider the influence of both genetic and cultural transmission of behavior.

  8. Simulating the evolution of the human family: cooperative breeding increases in harsh environments.

    Directory of Open Access Journals (Sweden)

    Paul E Smaldino

    Full Text Available Verbal and mathematical models that consider the costs and benefits of behavioral strategies have been useful in explaining animal behavior and are often used as the basis of evolutionary explanations of human behavior. In most cases, however, these models do not account for the effects that group structure and cultural traditions within a human population have on the costs and benefits of its members' decisions. Nor do they consider the likelihood that cultural as well as genetic traits will be subject to natural selection. In this paper, we present an agent-based model that incorporates some key aspects of human social structure and life history. We investigate the evolution of a population under conditions of different environmental harshness and in which selection can occur at the level of the group as well as the level of the individual. We focus on the evolution of a socially learned characteristic related to individuals' willingness to contribute to raising the offspring of others within their family group. We find that environmental harshness increases the frequency of individuals who make such contributions. However, under the conditions we stipulate, we also find that environmental variability can allow groups to survive with lower frequencies of helpers. The model presented here is inevitably a simplified representation of a human population, but it provides a basis for future modeling work toward evolutionary explanations of human behavior that consider the influence of both genetic and cultural transmission of behavior.

  9. The F309S mutation increases factor VIII secretion in human cell line

    Directory of Open Access Journals (Sweden)

    Daianne Maciely Carvalho Fantacini

    2016-06-01

    Full Text Available ABSTRACT OBJECTIVES: The capacity of a human cell line to secrete recombinant factor VIII with a F309S point mutation was investigated, as was the effect of the addition of chemical chaperones (betaine and sodium-4-phenylbutyrate on the secretion of factor VIII. METHODS: This work used a vector with a F309S mutation in the A1 domain to investigate FVIII production in the HEK 293 human cell line. Factor VIII activity was measured by chromogenic assay. Furthermore, the effects of chemical drugs on the culture were evaluated. RESULTS: The addition of the F309S mutation to a previously described FVIII variant increased FVIII secretion by 4.5 fold. Moreover, the addition of betaine or sodium-4-phenylbutyrate increased the secretion rate of FVIIIΔB proteins in HEK 293 cells, but the same effect was not seen for FVIIIΔB-F309S indicating that all the recombinant protein produced had been efficiently secreted. CONCLUSION: Bioengineering factor VIII expressed in human cells may lead to an efficient production of recombinant factor VIII and contribute toward low-cost coagulation factor replacement therapy for hemophilia A. FVIII-F309S produced in human cells can be effective in vivo.

  10. Antibody directed against human YKL-40 increases tumor volume in a human melanoma xenograft model in scid mice

    DEFF Research Database (Denmark)

    Salamon, Johannes; Hoffmann, Tatjana; Elies, Eva

    2014-01-01

    were treated with intraperitoneal injections of anti-YKL-40, isoptype control or PBS. Non-YKL-40 expressing human pancreatic carcinoma cell line PaCa 5061 served as additional control. MR imaging was used for evaluation of tumor growth. Two days after the first injections of anti-YKL-40, tumor volume...... had increased significantly compared with controls, whereas no effects were observed for control tumors from PaCa 5061 cells lacking YKL-40 expression. After 18 days, mean tumor size of the mice receiving repeated anti-YKL-40 injections was 1.82 g, >4 times higher than mean tumor size of the controls...

  11. Epidermal growth factor increases LRF/Pokemon expression in human prostate cancer cells.

    Science.gov (United States)

    Aggarwal, Himanshu; Aggarwal, Anshu; Agrawal, Devendra K

    2011-10-01

    Leukemia/lymphoma related factor/POK erythroid myeloid ontogenic factor (LRF/Pokemon) is a member of the POK family of proteins that promotes oncogenesis in several forms of cancer. Recently, we found higher LRF expression in human breast and prostate carcinomas compared to the corresponding normal tissues. The aim of this study was to examine the regulation of LRF expression in human prostate cells. Epidermal growth factor (EGF) and its receptors mediate several tumorigenic cascades that regulate cell differentiation, proliferation, migration and survival of prostate cancer cells. There was significantly higher level of LRF expression in the nucleus of LNCaP and PC-3 cells than RWPE-1 cells. A significant increase in LRF expression was observed with increasing doses of EGF in more aggressive and androgen-sensitive prostate cancer cells suggesting that EGF signaling pathway is critical in upregulating the expression of LRF/Pokemon to promote oncogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Federal STEM Policy and Politics and Their Impact on Astronomy EPO: Reflections and Provocations

    Science.gov (United States)

    Schultz, G.; Storksdieck, M.; Canright, S.

    2015-11-01

    The federal government invests more than $3 billion each year across its various units in supporting STEM education and outreach. Efforts in recent years to understand and better coordinate these investments have resulted in considerable pushback, particularly those efforts that aimed at consolidation and elimination of programs deemed ineffective or duplicative. While initial plans to streamline federal STEM education were defeated, many agencies nonetheless saw cuts and elimination, and a high-level effort to coordinate STEM education at the cross-agency level is now gaining steam (CoSTEM: Committee on Science, Technology, Engineering, and Mathematics Education). What do all of these developments mean for education and public outreach in astronomy and related fields? How should this community operate within the opportunities and threats that CoSTEM might pose? Former director of the National Academy of Science's Board on Science Education, and now director of the Center for Research on Lifelong STEM Learning, Martin Storksdieck, reflected on past and recent developments from the perspective of a close observer, and from the perspective of someone who has been involved in astronomy education research and evaluation for nearly 20 years. Shelley Canright, Senior Advisor for Education Integration at the NASA Office of Education, shared her insights and perspectives with respect to CoSTEM and EPO, in particular from co-chairing the Federal Coordination in Science, Technology, Engineering, and Mathematics Education (FC-STEM) group.

  13. Overview of the Education and Public Outreach (EPO) program of the Caltech Tectonics Observatory

    Science.gov (United States)

    Kovalenko, L.; Jain, K.; Maloney, J.

    2009-12-01

    The Caltech Tectonics Observatory (TO) is an interdisciplinary center, focused on geological processes occurring at the boundaries of Earth's tectonic plates (http://www.tectonics.caltech.edu). Over the past year, the TO has made a major effort to develop an Education and Public Outreach (EPO) program. Our goals are to (1) stimulate the interest of students and the general public in Earth Sciences, particularly in the study of tectonic processes, (2) inform and educate the general public about science in the context of TO discoveries and advancements, and (3) provide opportunities for graduate students, postdocs, and faculty to do outreach in the local K-12 schools. We have hosted local high school students and teachers to provide them with research experience (as part of Caltech’s “Summer Research Connection”); participated in teacher training workshops (organized by the local school district); hosted tours for local elementary school students; and brought hands-on activities into local elementary and middle school classrooms, science clubs, and science nights. We have also led local school students and teachers on geology field trips through nearby parks. In addition, we have developed education modules for undergraduate classes (as part of MARGINS program), and have written educational web articles on TO research (http://www.tectonics.caltech.edu/outreach). The presentation will give an overview of these activities and their impact on our educational program.

  14. Increasing the Efficiency of Education Systems by Improving Human Resource Management

    Directory of Open Access Journals (Sweden)

    George Bucata

    2016-06-01

    Full Text Available In today's economies, investment in education and in the training employees are at least as important as investments in heritage. We live increasingly longer in an economy based on information, technology and production, in which methods are changed rapidly and constantly. Human capital formation should be approached at least as good as physical capital formation and the reform in education should strive to treat the former obviously.

  15. Toward an Understanding of Beaver Management as Human and Beaver Densities Increase

    OpenAIRE

    Siemer, William F.; Jonker, Sandra A.; Decker, Daniel J.; Organ, John F.

    2013-01-01

    Estimates of beaver (Castor canadensis) density play an important role in wildlife managers’ decisions about beaver population management, because managers anticipate higher incidence of problem complaints when a beaver population increases. To manage the impacts of beavers in an urbanizing landscape, managers need better information on changes in stakeholder beliefs and attitudes as beaver and human densities reach high levels. We conducted additional analysis of data collected in 2002 throu...

  16. Overexpression of human sperm protein 17 increases migration and decreases the chemosensitivity of human epithelial ovarian cancer cells

    International Nuclear Information System (INIS)

    Li, Fang-qiu; Han, Yan-ling; Liu, Qun; Wu, Bo; Huang, Wen-bin; Zeng, Su-yun

    2009-01-01

    Most deaths from ovarian cancer are due to metastases that are resistant to conventional therapies. But the factors that regulate the metastatic process and chemoresistance of ovarian cancer are poorly understood. In the current study, we investigated the aberrant expression of human sperm protein 17 (HSp17) in human epithelial ovarian cancer cells and tried to analyze its influences on the cell behaviors like migration and chemoresistance. Immunohistochemistry and immunocytochemistry were used to identify HSp17 in paraffin embedded ovarian malignant tumor specimens and peritoneal metastatic malignant cells. Then we examined the effect of HSp17 overexpression on the proliferation, migration, and chemoresistance of ovarian cancer cells to carboplatin and cisplatin in a human ovarian carcinoma cell line, HO8910. We found that HSp17 was aberrantly expressed in 43% (30/70) of the patients with primary epithelial ovarian carcinomas, and in all of the metastatic cancer cells of ascites from 8 patients. The Sp17 expression was also detected in the metastatic lesions the same as in ovarian lesions. None of the 7 non-epithelial tumors primarily developed in the ovaries was immunopositive for HSp17. Overexpression of HSp17 increased the migration but decreased the chemosensitivity of ovarian carcinoma cells to carboplatin and cisplatin. HSp17 is aberrantly expressed in a significant proportion of epithelial ovarian carcinomas. Our results strongly suggest that HSp17 plays a role in metastatic disease and resistance of epithelial ovarian carcinoma to chemotherapy

  17. Human erythropoietin response to hypocapnic hypoxia, normocapnic hypoxia, and hypocapnic normoxia

    DEFF Research Database (Denmark)

    Klausen, T; Christensen, H; Hansen, J M

    1996-01-01

    exposed to 2 h each of hypocapnic hypoxia, normocapnic hypoxia, hypocapnic normoxia, and normal breathing of room air (control experiment). During the control experiment, serum-EPO showed significant variations (ANOVA P = 0.047) with a 15% increase in mean values. The serum-EPO measured in the other...... (10% Co2 with 10% O2) to the hypoxic gas mixture. This elicited an increased ventilation, unaltered arterial pH and haemoglobin oxygen affinity, a lower degree of hypoxia than during hypocapnic hypoxia, and no significant changes in serum-EPO (ANOVA P > 0.05). Hypocapnic normoxia, produced...

  18. Products of neutrophils and eosinophils increase the responsiveness of human isolated bronchial tissue.

    Science.gov (United States)

    Hallahan, A R; Armour, C L; Black, J L

    1990-05-01

    This study examines the possibility that products of neutrophils and eosinophils could increase the responsiveness of human isolated bronchial tissue. Neutrophils and eosinophils were isolated from the peripheral blood of healthy volunteers. The cells were incubated with 1 microM calcium ionophore A23187 for 10-15 min then centrifuged, the supernatant collected and stored at -70 degrees C. Human bronchial rings (2-3 mm diameter, 3-4 mm long) were prepared from specimens resected at thoracotomy. The tissues were suspended in organ baths under a 1 g load and changes in tension measured isometrically. Stable contractions to bolus doses of histamine (0.1-10 microM) or to electrical field stimulation (40-100 V, 4-16 Hz, 1 ms for 20 s) were established. Supernatant from 106 neutrophils or 105 eosinophils was then added and tissue responsiveness reassessed. Neutrophil supernatant increased tissue responsiveness to histamine and electrical field stimulation by 54 +/- 17% (n = 5, p less than 0.05) and 18 +/- 7% (n = 6, p less than 0.05), respectively. Eosinophil supernatant increased the histamine response by 60 +/- 23% (n = 8, p less than 0.05) while tissue responsiveness to electrical field stimulation was unchanged (n = 3). Thus, as neutrophils and eosinophils can change the responsiveness of human bronchus in vitro it is possible that they do this in vivo and may not simply be temporally related to the development of bronchial hyperresponsiveness.

  19. Increased expression of beta 2-microglobulin and histocompatibility antigens on human lymphoid cells induced by interferon

    DEFF Research Database (Denmark)

    Hokland, M; Heron, I; Berg, K

    1982-01-01

    Normal human peripheral blood lymphocytes were incubated in the presence of different concentrations of interferon for various incubation periods. Subsequently, the amount of beta 2-Microglobulin and HLA-A, B and C surface antigens was estimated by means of quantitative immunofluorescence (flow...... cytofluorometry) and by a radioimmunoassay for beta 2-Microglobulin. It was found that the amounts of these MHC antigens increased in a dose and time-dependent way after interferon treatment. Furthermore, the influence of different temperatures on this IFN-induced increase in beta 2-Microglobulin was gradually...

  20. Human θ burst stimulation enhances subsequent motor learning and increases performance variability.

    Science.gov (United States)

    Teo, James T H; Swayne, Orlando B C; Cheeran, Binith; Greenwood, Richard J; Rothwell, John C

    2011-07-01

    Intermittent theta burst stimulation (iTBS) transiently increases motor cortex excitability in healthy humans by a process thought to involve synaptic long-term potentiation (LTP), and this is enhanced by nicotine. Acquisition of a ballistic motor task is likewise accompanied by increased excitability and presumed intracortical LTP. Here, we test how iTBS and nicotine influences subsequent motor learning. Ten healthy subjects participated in a double-blinded placebo-controlled trial testing the effects of iTBS and nicotine. iTBS alone increased the rate of learning but this increase was blocked by nicotine. We then investigated factors other than synaptic strengthening that may play a role. Behavioral analysis and modeling suggested that iTBS increased performance variability, which correlated with learning outcome. A control experiment confirmed the increase in motor output variability by showing that iTBS increased the dispersion of involuntary transcranial magnetic stimulation-evoked thumb movements. We suggest that in addition to the effect on synaptic plasticity, iTBS may have facilitated performance by increasing motor output variability; nicotine negated this effect on variability perhaps via increasing the signal-to-noise ratio in cerebral cortex.

  1. Sugars increase non-heme iron bioavailability in human epithelial intestinal and liver cells.

    Directory of Open Access Journals (Sweden)

    Tatiana Christides

    Full Text Available Previous studies have suggested that sugars enhance iron bioavailability, possibly through either chelation or altering the oxidation state of the metal, however, results have been inconclusive. Sugar intake in the last 20 years has increased dramatically, and iron status disorders are significant public health problems worldwide; therefore understanding the nutritional implications of iron-sugar interactions is particularly relevant. In this study we measured the effects of sugars on non-heme iron bioavailability in human intestinal Caco-2 cells and HepG2 hepatoma cells using ferritin formation as a surrogate marker for iron uptake. The effect of sugars on iron oxidation state was examined by measuring ferrous iron formation in different sugar-iron solutions with a ferrozine-based assay. Fructose significantly increased iron-induced ferritin formation in both Caco-2 and HepG2 cells. In addition, high-fructose corn syrup (HFCS-55 increased Caco-2 cell iron-induced ferritin; these effects were negated by the addition of either tannic acid or phytic acid. Fructose combined with FeCl3 increased ferrozine-chelatable ferrous iron levels by approximately 300%. In conclusion, fructose increases iron bioavailability in human intestinal Caco-2 and HepG2 cells. Given the large amount of simple and rapidly digestible sugars in the modern diet their effects on iron bioavailability may have important patho-physiological consequences. Further studies are warranted to characterize these interactions.

  2. Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle Cells

    Directory of Open Access Journals (Sweden)

    Nataša Nikolić

    2012-01-01

    Full Text Available We investigated the effects of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α overexpression on the oxidative capacity of human skeletal muscle cells ex vivo. PGC-1α overexpression increased the oxidation rate of palmitic acid and mRNA expression of genes regulating lipid metabolism, mitochondrial biogenesis, and function in human myotubes. Basal and insulin-stimulated deoxyglucose uptake were decreased, possibly due to upregulation of PDK4 mRNA. Expression of fast fiber-type gene marker (MHCIIa was decreased. Compared to skeletal muscle in vivo, PGC-1α overexpression increased expression of several genes, which were downregulated during the process of cell isolation and culturing. In conclusion, PGC-1α overexpression increased oxidative capacity of cultured myotubes by improving lipid metabolism, increasing expression of genes involved in regulation of mitochondrial function and biogenesis, and decreasing expression of MHCIIa. These results suggest that therapies aimed at increasing PGC-1α expression may have utility in treatment of obesity and obesity-related diseases.

  3. Effect of increases in lung volume on clearance of aerosolized solute from human lungs

    Energy Technology Data Exchange (ETDEWEB)

    Marks, J.D.; Luce, J.M.; Lazar, N.M.; Wu, J.N.; Lipavsky, A.; Murray, J.F.

    1985-10-01

    To study the effect of increases in lung volume on solute uptake, we measured clearance of /sup 99m/Tc-diethylenetriaminepentaacetic acid (Tc-DTPA) at different lung volumes in 19 healthy humans. Seven subjects inhaled aerosols (1 micron activity median aerodynamic diam) at ambient pressure; clearance and functional residual capacity (FRC) were measured at ambient pressure (control) and at increased lung volume produced by positive pressure (12 cmH2O continuous positive airway pressure (CPAP)) or negative pressure (voluntary breathing). Six different subjects inhaled aerosol at ambient pressure; clearance and FRC were measured at ambient pressure and CPAP of 6, 12, and 18 cmH2O pressure. Six additional subjects inhaled aerosol at ambient pressure or at CPAP of 12 cmH2O; clearance and FRC were determined at CPAP of 12 cmH2O. According to the results, Tc-DTPA clearance from human lungs is accelerated exponentially by increases in lung volume, this effect occurs whether lung volume is increased by positive or negative pressure breathing, and the effect is the same whether lung volume is increased during or after aerosol administration. The effect of lung volume must be recognized when interpreting the results of this method.

  4. Effect of increases in lung volume on clearance of aerosolized solute from human lungs

    International Nuclear Information System (INIS)

    Marks, J.D.; Luce, J.M.; Lazar, N.M.; Wu, J.N.; Lipavsky, A.; Murray, J.F.

    1985-01-01

    To study the effect of increases in lung volume on solute uptake, we measured clearance of /sup 99m/Tc-diethylenetriaminepentaacetic acid (Tc-DTPA) at different lung volumes in 19 healthy humans. Seven subjects inhaled aerosols (1 micron activity median aerodynamic diam) at ambient pressure; clearance and functional residual capacity (FRC) were measured at ambient pressure (control) and at increased lung volume produced by positive pressure [12 cmH 2 O continuous positive airway pressure (CPAP)] or negative pressure (voluntary breathing). Six different subjects inhaled aerosol at ambient pressure; clearance and FRC were measured at ambient pressure and CPAP of 6, 12, and 18 cmH 2 O pressure. Six additional subjects inhaled aerosol at ambient pressure or at CPAP of 12 cmH 2 O; clearance and FRC were determined at CPAP of 12 cmH 2 O. According to the results, Tc-DTPA clearance from human lungs is accelerated exponentially by increases in lung volume, this effect occurs whether lung volume is increased by positive or negative pressure breathing, and the effect is the same whether lung volume is increased during or after aerosol administration. The effect of lung volume must be recognized when interpreting the results of this method

  5. Ultraviolet Radiation Increases the Toxicity of Pyrene, 1-Aminopyrene and 1-Hydroxypyrene to Human Keratinocytes

    Directory of Open Access Journals (Sweden)

    Huey-Min Hwang

    2005-04-01

    Full Text Available Over the past several years, a great deal of interest has been focused on the harmful effects of ultraviolet (UV radiation to human skin. UV light has been implicated in aging, sunburn and skin cancer. Few studies, however, have been done to determine the effects that UV light, in conjunction with other environmental contaminants, may have on human skin. Polycyclic Aromatic Hydrocarbons (PAHs are a class of compounds that have been reported to be toxic, mutagenic and carcinogenic to many eukaryotic organisms. UV light is also known to increase the toxicity of PAHs through photo-activation and photo-modification. The purpose of this study was to assess the effects of UV-A irradiated pyrene (Pyr, 1-aminopyrene (1-AP and 1-hydroxypyrene (1-HP on human keratinocytes, the skin primary site of UV irradiated PAH exposure. Our findings indicate that simultaneous treatment of human keratinocyte cell line, HaCaT, with 1.0μg/ml pyrene, 1-AP or 1-HP and 3.9 J/cm2/min UV-A light resulted in significant inhibition of cell proliferation. Approximately 100% of the cells died in the case of UV-A irradiated 1-AP and 1-HP. In the case of UV-A irradiated pyrene, more than 70% of the cells died, indicating that UV-A is able to transform these PAHs into more harmful intermediates.

  6. Humans and great apes share increased neocortical neuropeptide Y innervation compared to other haplorhine primates

    Directory of Open Access Journals (Sweden)

    Mary Ann eRaghanti

    2014-02-01

    Full Text Available Neuropeptide Y (NPY plays a role in a variety of basic physiological functions and has also been implicated in regulating cognition, including learning and memory. A decrease in neocortical NPY has been reported for Alzheimer’s disease, schizophrenia, bipolar disorder, and depression, potentially contributing to associated cognitive deficits. The goal of the present analysis was to examine variation in neocortical NPY-immunoreactive axon and varicosity density among haplorhine primates (monkeys, apes, and humans. Stereologic methods were used to measure the ratios of NPY-expressing axon length density to total neuron density (ALv/Nv and NPY-immunoreactive varicosity density to neuron density (Vv/Nv, as well as the mean varicosity spacing in neocortical areas 10, 24, 44, and 22 (Tpt of humans, African great apes, New World monkeys, and Old World monkeys. Humans and great apes showed increased cortical NPY innervation relative to monkey species for ALv/Nv and Vv/Nv. Furthermore, humans and great apes displayed a conserved pattern of varicosity spacing across cortical areas and layers, with no differences between cortical layers or among cortical areas. These phylogenetic differences may be related to shared life history variables and may reflect specific cognitive abilities.

  7. Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer

    International Nuclear Information System (INIS)

    Yu, Wei; Chai, Hongyan; Li, Ying; Zhao, Haixia; Xie, Xianfei; Zheng, Hao; Wang, Chenlong; Wang, Xue; Yang, Guifang; Cai, Xiaojun; Falck, John R.; Yang, Jing

    2012-01-01

    Cytochrome P450 (CYP) 4Z1, a novel CYP4 family member, is over-expressed in human mammary carcinoma and associated with high-grade tumors and poor prognosis. However, the precise role of CYP4Z1 in tumor progression is unknown. Here, we demonstrate that CYP4Z1 overexpression promotes tumor angiogenesis and growth in breast cancer. Stable expression of CYP4Z1 in T47D and BT-474 human breast cancer cells significantly increased mRNA expression and production of vascular endothelial growth factor (VEGF)-A, and decreased mRNA levels and secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), without affecting cell proliferation and anchorage-independent cell growth in vitro. Notably, the conditioned medium from CYP4Z1-expressing cells enhanced proliferation, migration and tube formation of human umbilical vein endothelial cells, and promoted angiogenesis in the zebrafish embryo and chorioallantoic membrane of the chick embryo. In addition, there were lower levels of myristic acid and lauric acid, and higher contents of 20-hydroxyeicosatetraenoic acid (20-HETE) in CYP4Z1-expressing T47D cells compared with vector control. CYP4Z1 overexpression significantly increased tumor weight and microvessel density by 2.6-fold and 1.9-fold in human tumor xenograft models, respectively. Moreover, CYP4Z1 transfection increased the phosphorylation of ERK1/2 and PI3K/Akt, while PI3K or ERK inhibitors and siRNA silencing reversed CYP4Z1-mediated changes in VEGF-A and TIMP-2 expression. Conversely, HET0016, an inhibitor of the CYP4 family, potently inhibited the tumor-induced angiogenesis with associated changes in the intracellular levels of myristic acid, lauric acid and 20-HETE. Collectively, these data suggest that increased CYP4Z1 expression promotes tumor angiogenesis and growth in breast cancer partly via PI3K/Akt and ERK1/2 activation. -- Highlights: ► CYP4Z1 overexpression promotes human breast cancer growth and angiogenesis. ► The pro-angiogenic effects of CYP4Z1 have

  8. Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Wei [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Li, Ying; Zhao, Haixia; Xie, Xianfei; Zheng, Hao; Wang, Chenlong; Wang, Xue [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yang, Guifang [Department of Pathology, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Cai, Xiaojun [Department of Ophthalmology, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Falck, John R. [Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 (United States); Yang, Jing, E-mail: yangjingliu@yahoo.com.cn [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2012-10-01

    Cytochrome P450 (CYP) 4Z1, a novel CYP4 family member, is over-expressed in human mammary carcinoma and associated with high-grade tumors and poor prognosis. However, the precise role of CYP4Z1 in tumor progression is unknown. Here, we demonstrate that CYP4Z1 overexpression promotes tumor angiogenesis and growth in breast cancer. Stable expression of CYP4Z1 in T47D and BT-474 human breast cancer cells significantly increased mRNA expression and production of vascular endothelial growth factor (VEGF)-A, and decreased mRNA levels and secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), without affecting cell proliferation and anchorage-independent cell growth in vitro. Notably, the conditioned medium from CYP4Z1-expressing cells enhanced proliferation, migration and tube formation of human umbilical vein endothelial cells, and promoted angiogenesis in the zebrafish embryo and chorioallantoic membrane of the chick embryo. In addition, there were lower levels of myristic acid and lauric acid, and higher contents of 20-hydroxyeicosatetraenoic acid (20-HETE) in CYP4Z1-expressing T47D cells compared with vector control. CYP4Z1 overexpression significantly increased tumor weight and microvessel density by 2.6-fold and 1.9-fold in human tumor xenograft models, respectively. Moreover, CYP4Z1 transfection increased the phosphorylation of ERK1/2 and PI3K/Akt, while PI3K or ERK inhibitors and siRNA silencing reversed CYP4Z1-mediated changes in VEGF-A and TIMP-2 expression. Conversely, HET0016, an inhibitor of the CYP4 family, potently inhibited the tumor-induced angiogenesis with associated changes in the intracellular levels of myristic acid, lauric acid and 20-HETE. Collectively, these data suggest that increased CYP4Z1 expression promotes tumor angiogenesis and growth in breast cancer partly via PI3K/Akt and ERK1/2 activation. -- Highlights: ► CYP4Z1 overexpression promotes human breast cancer growth and angiogenesis. ► The pro-angiogenic effects of CYP4Z1 have

  9. Nav1.7 expression is increased in painful human dental pulp

    Directory of Open Access Journals (Sweden)

    Levinson S Rock

    2008-04-01

    Full Text Available Abstract Background Animal studies and a few human studies have shown a change in sodium channel (NaCh expression after inflammatory lesions, and this change is implicated in the generation of pain states. We are using the extracted human tooth as a model system to study peripheral pain mechanisms and here examine the expression of the Nav1.7 NaCh isoform in normal and painful samples. Pulpal sections were labeled with antibodies against: 1 Nav1.7, N52 and PGP9.5, and 2 Nav1.7, caspr (a paranodal protein used to identify nodes of Ranvier, and myelin basic protein (MBP, and a z-series of optically-sectioned images were obtained with the confocal microscope. Nav1.7-immunofluorescence was quantified in N52/PGP9.5-identified nerve fibers with NIH ImageJ software, while Nav1.7 expression in myelinated fibers at caspr-identified nodal sites was evaluated and further characterized as either typical or atypical as based on caspr-relationships. Results Results show a significant increase in nerve area with Nav1.7 expression within coronal and radicular fiber bundles and increased expression at typical and atypical caspr-identified nodal sites in painful samples. Painful samples also showed an augmentation of Nav1.7 within localized areas that lacked MBP, including those associated with atypical caspr-identified sites, thus identifying NaCh remodeling within demyelinating axons as the basis for a possible pulpal pain mechanism. Conclusion This study identifies the increased axonal expression and augmentation of Nav1.7 at intact and remodeling/demyelinating nodes within the painful human dental pulp where these changes may contribute to constant, increased evoked and spontaneous pain responses that characterize the pain associated with toothache.

  10. Oxidized low density lipoprotein increases RANKL level in human vascular cells. Involvement of oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Mazière, Cécile, E-mail: maziere.cecile@chu-amiens.fr [Biochemistry Laboratory, South Hospital University, René Laennec Avenue, Amiens 80000 (France); Salle, Valéry [Internal Medicine, North Hospital University, Place Victor Pauchet, Amiens 80000 (France); INSERM U1088 (EA 4292), SFR CAP-Santé (FED 4231), University of Picardie – Jules Verne (France); Gomila, Cathy; Mazière, Jean-Claude [Biochemistry Laboratory, South Hospital University, René Laennec Avenue, Amiens 80000 (France)

    2013-10-18

    Highlights: •Oxidized LDL enhances RANKL level in human smooth muscle cells. •The effect of OxLDL is mediated by the transcription factor NFAT. •UVA, H{sub 2}O{sub 2} and buthionine sulfoximine also increase RANKL level. •All these effects are observed in human fibroblasts and endothelial cells. -- Abstract: Receptor Activator of NFκB Ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) have been shown to play a role not only in bone remodeling but also in inflammation, arterial calcification and atherosclerotic plaque rupture. In human smooth muscle cells, Cu{sup 2+}-oxidized LDL (CuLDL) 10–50 μg/ml increased reactive oxygen species (ROS) and RANKL level in a dose-dependent manner, whereas OPG level was not affected. The lipid extract of CuLDL reproduced the effects of the whole particle. Vivit, an inhibitor of the transcription factor NFAT, reduced the CuLDL-induced increase in RANKL, whereas PKA and NFκB inhibitors were ineffective. LDL oxidized by myeloperoxidase (MPO-LDL), or other pro-oxidant conditions such as ultraviolet A (UVA) irradiation, incubation with H{sub 2}O{sub 2} or with buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis{sub ,} also induced an oxidative stress and enhanced RANKL level. The increase in RANKL in pro-oxidant conditions was also observed in fibroblasts and endothelial cells. Since RANKL is involved in myocardial inflammation, vascular calcification and plaque rupture, this study highlights a new mechanism whereby OxLDL might, by generation of an oxidative stress, exert a deleterious effect on different cell types of the arterial wall.

  11. Transient p53 suppression increases reprogramming of human fibroblasts without affecting apoptosis and DNA damage

    DEFF Research Database (Denmark)

    Rasmussen, Mikkel Aabech; Holst, Bjørn; Tümer, Zeynep

    2014-01-01

    The discovery of human-induced pluripotent stem cells (iPSCs) has sparked great interest in the potential treatment of patients with their own in vitro differentiated cells. Recently, knockout of the Tumor Protein 53 (p53) gene was reported to facilitate reprogramming but unfortunately also led...... to genomic instability. Here, we report that transient suppression of p53 during nonintegrative reprogramming of human fibroblasts leads to a significant increase in expression of pluripotency markers and overall number of iPSC colonies, due to downstream suppression of p21, without affecting apoptosis...... and DNA damage. Stable iPSC lines generated with or without p53 suppression showed comparable expression of pluripotency markers and methylation patterns, displayed normal karyotypes, contained between 0 and 5 genomic copy number variations and produced functional neurons in vitro. In conclusion...

  12. Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

    Science.gov (United States)

    Hals, I. K.; Rokstad, A. M.; Strand, B. L.; Oberholzer, J.; Grill, V.

    2013-01-01

    Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death in the early posttransplantation period. Here we tested susceptibility of alginate microencapsulated human islets to experimental hypoxia (0.1–0.3% O2 for 8 h, followed by reoxygenation) on viability and functional parameters. Hypoxia reduced viability as measured by MTT by 33.8 ± 3.5% in encapsulated and 42.9 ± 5.2% in nonencapsulated islets (P microencapsulation of human islets does not increase susceptibility to acute hypoxia. This is a positive finding in relation to potential use of encapsulation for islet transplantation. PMID:24364039

  13. Indomethacin increases the formation of lipoxygenase products in calcium ionophore stimulated human neutrophils.

    Science.gov (United States)

    Docherty, J C; Wilson, T W

    1987-10-29

    Arachidonic acid metabolism in human neutrophils stimulated in vitro with the calcium ionophore A23187 was studied using combined HPLC and radioimmunoassays. Indomethacin (0.1 and 1.0 microM) caused a 300% increase in LTB4 formation in neutrophils stimulated with A23187. 5-, 12- and 15-HETE levels were also increased. In the presence of exogenous arachidonic acid 1.0 microM Indomethacin caused a 37% increase in LTB4 formation. Acetyl Salicylic Acid and Ibuprofen had no effect on the formation of lipoxygenase metabolites. The effect of indomethacin on LTB4 formation does not appear to be due to a simple redirection of substrate arachidonic acid from the cyclooxygenase to the lipoxygenase pathways.

  14. The Increase of the Functional Entropy of the Human Brain with Age

    Science.gov (United States)

    Yao, Y.; Lu, W. L.; Xu, B.; Li, C. B.; Lin, C. P.; Waxman, D.; Feng, J. F.

    2013-01-01

    We use entropy to characterize intrinsic ageing properties of the human brain. Analysis of fMRI data from a large dataset of individuals, using resting state BOLD signals, demonstrated that a functional entropy associated with brain activity increases with age. During an average lifespan, the entropy, which was calculated from a population of individuals, increased by approximately 0.1 bits, due to correlations in BOLD activity becoming more widely distributed. We attribute this to the number of excitatory neurons and the excitatory conductance decreasing with age. Incorporating these properties into a computational model leads to quantitatively similar results to the fMRI data. Our dataset involved males and females and we found significant differences between them. The entropy of males at birth was lower than that of females. However, the entropies of the two sexes increase at different rates, and intersect at approximately 50 years; after this age, males have a larger entropy. PMID:24103922

  15. Patterns of Snow Leopard Site Use in an Increasingly Human-Dominated Landscape.

    Directory of Open Access Journals (Sweden)

    Justine Shanti Alexander

    Full Text Available Human population growth and concomitant increases in demand for natural resources pose threats to many wildlife populations. The landscapes used by the endangered snow leopard (Panthera uncia and their prey is increasingly subject to major changes in land use. We aimed to assess the influence of 1 key human activities, as indicated by the presence of mining and livestock herding, and 2 the presence of a key prey species, the blue sheep (Pseudois nayaur, on probability of snow leopard site use across the landscape. In Gansu Province, China, we conducted sign surveys in 49 grid cells, each of 16 km2 in size, within a larger area of 3392 km2. We analysed the data using likelihood-based habitat occupancy models that explicitly account for imperfect detection and spatial auto-correlation between survey transect segments. The model-averaged estimate of snow leopard occupancy was high [0.75 (SE 0.10], but only marginally higher than the naïve estimate (0.67. Snow leopard segment-level probability of detection, given occupancy on a 500 m spatial replicate, was also high [0.68 (SE 0.08]. Prey presence was the main determinant of snow leopard site use, while human disturbances, in the form of mining and herding, had low predictive power. These findings suggest that snow leopards continue to use areas very close to such disturbances, as long as there is sufficient prey. Improved knowledge about the effect of human activity on large carnivores, which require large areas and intact prey populations, is urgently needed for conservation planning at the local and global levels. We highlight a number of methodological considerations that should guide the design of such research.

  16. Human Traumatic Brain Injury Results in Oligodendrocyte Death and Increases the Number of Oligodendrocyte Progenitor Cells.

    Science.gov (United States)

    Flygt, Johanna; Gumucio, Astrid; Ingelsson, Martin; Skoglund, Karin; Holm, Jonatan; Alafuzoff, Irina; Marklund, Niklas

    2016-06-01

    Oligodendrocyte (OL) death may contribute to white matter pathology, a common cause of network dysfunction and persistent cognitive problems in patients with traumatic brain injury (TBI). Oligodendrocyte progenitor cells (OPCs) persist throughout the adult CNS and may replace dead OLs. OL death and OPCs were analyzed by immunohistochemistry of human brain tissue samples, surgically removed due to life-threatening contusions and/or focal brain swelling at 60.6 ± 75 hours (range 4-192 hours) postinjury in 10 severe TBI patients (age 51.7 ± 18.5 years). Control brain tissue was obtained postmortem from 5 age-matched patients without CNS disorders. TUNEL and CC1 co-labeling was used to analyze apoptotic OLs, which were increased in injured brain tissue (p The OPC markers Olig2, A2B5, NG2, and PDGFR-α were used. In contrast to the number of single-labeled Olig2, A2B5, NG2, and PDGFR-α-positive cells, numbers of Olig2 and A2B5 co-labeled cells were increased in TBI samples (p human TBI results in OL death and increases in OPCs postinjury, which may influence white matter function following TBI. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

  17. Increasing cognitive load attenuates right arm swing in healthy human walking

    Science.gov (United States)

    Killeen, Tim; Easthope, Christopher S.; Filli, Linard; Lőrincz, Lilla; Schrafl-Altermatt, Miriam; Brugger, Peter; Linnebank, Michael; Curt, Armin; Zörner, Björn; Bolliger, Marc

    2017-01-01

    Human arm swing looks and feels highly automated, yet it is increasingly apparent that higher centres, including the cortex, are involved in many aspects of locomotor control. The addition of a cognitive task increases arm swing asymmetry during walking, but the characteristics and mechanism of this asymmetry are unclear. We hypothesized that this effect is lateralized and a Stroop word-colour naming task-primarily involving left hemisphere structures-would reduce right arm swing only. We recorded gait in 83 healthy subjects aged 18-80 walking normally on a treadmill and while performing a congruent and incongruent Stroop task. The primary measure of arm swing asymmetry-an index based on both three-dimensional wrist trajectories in which positive values indicate proportionally smaller movements on the right-increased significantly under dual-task conditions in those aged 40-59 and further still in the over-60s, driven by reduced right arm flexion. Right arm swing attenuation appears to be the norm in humans performing a locomotor-cognitive dual-task, confirming a prominent role of the brain in locomotor behaviour. Women under 60 are surprisingly resistant to this effect, revealing unexpected gender differences atop the hierarchical chain of locomotor control.

  18. Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

    Directory of Open Access Journals (Sweden)

    I. K. Hals

    2013-01-01

    Full Text Available Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death in the early posttransplantation period. Here we tested susceptibility of alginate microencapsulated human islets to experimental hypoxia (0.1–0.3% O2 for 8 h, followed by reoxygenation on viability and functional parameters. Hypoxia reduced viability as measured by MTT by 33.8±3.5% in encapsulated and 42.9±5.2% in nonencapsulated islets (P<0.2. Nonencapsulated islets released 37.7% (median more HMGB1 compared to encapsulated islets after hypoxic culture conditions (P<0.001. Glucose-induced insulin release was marginally affected by hypoxia. Basal oxygen consumption was equally reduced in encapsulated and nonencapsulated islets, by 22.0±6.1% versus 24.8±5.7%. Among 27 tested cytokines/chemokines, hypoxia increased the secretion of IL-6 and IL-8/CXCL8 in both groups of islets, whereas an increase of MCP-1/CCL2 was seen only with nonencapsulated islets. Conclusion. Alginate microencapsulation of human islets does not increase susceptibility to acute hypoxia. This is a positive finding in relation to potential use of encapsulation for islet transplantation.

  19. Hydrogen peroxide production is not primarily increased in human myotubes established from type 2 diabetic subjects.

    Science.gov (United States)

    Minet, A D; Gaster, M

    2011-09-01

    Increased oxidative stress and mitochondrial dysfunction have been implicated in the development of insulin resistance in type 2 diabetes. To date, it is unknown whether increased mitochondrial reactive oxygen species (ROS) production in skeletal muscle from patients with type 2 diabetes is primarily increased or a secondary adaptation to environmental, lifestyle, and hormonal factors. This study investigates whether ROS production is primarily increased in isolated diabetic myotubes. Mitochondrial membrane potential, hydrogen peroxide (H(2)O(2)), superoxide, and mitochondrial mass were determined in human myotubes precultured under normophysiological conditions. Furthermore, the corresponding ATP synthesis was measured in isolated mitochondria. Muscle biopsies were taken from 10 lean subjects, 10 obese subjects, and 10 subjects with type 2 diabetes; satellite cells were isolated, cultured, and differentiated to myotubes. Mitochondrial mass, membrane potential/mitochondrial mass, and superoxide-production/mitochondrial mass were not different between groups. In contrast, H(2)O(2) production/mitochondrial mass and ATP production were significantly reduced in diabetic myotubes compared to lean controls (P production is not primarily increased in diabetic myotubes but rather is reduced. Moreover, the comparable ATP/H(2)O(2) ratios indicate that the reduced ROS production in diabetic myotubes parallels the reduced ATP production because ROS production in diabetic myotubes must be considered to be in a proportion comparable to lean. Thus, the increased ROS production seen in skeletal muscle of type 2 diabetic patients is an adaptation to the in vivo conditions.

  20. Viral infection of human lung macrophages increases PDL1 expression via IFNβ.

    Directory of Open Access Journals (Sweden)

    Karl J Staples

    Full Text Available Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophages in response to viral infection. Ex-vivo viral infection models using influenza and RSV were established in human lung explants, isolated lung macrophages and monocyte-derived macrophages (MDM and analysed by flow cytometry and RT-PCR. Incubation of lung explants, lung macrophages and MDM with X31 resulted in mean cellular infection rates of 18%, 18% and 29% respectively. Viral infection significantly increased cell surface expression of PDL1 on explant macrophages, lung macrophages and MDM but not explant epithelial cells. Infected MDM induced IFNγ release from autologous CD8+ T cells, an effect enhanced by PDL1 blockade. We observed increases in PDL1 mRNA and IFNβ mRNA and protein release by MDM in response to influenza infection. Knockdown of IFNβ by siRNA, resulted in a 37.5% reduction in IFNβ gene expression in response to infection, and a significant decrease in PDL1 mRNA. Furthermore, when MDM were incubated with IFNβ, this cytokine caused increased expression of PDL1 mRNA. These data indicate that human macrophage PDL1 expression modulates CD8+ cell IFNγ release in response to virus and that this expression is regulated by autologous IFNβ production.

  1. Developing an Education and Public Outreach (EPO) program for Caltech's Tectonics Observatory

    Science.gov (United States)

    Kovalenko, L.; Jain, K.; Maloney, J.

    2012-12-01

    The Caltech Tectonics Observatory (TO) is an interdisciplinary center, focused on geological processes occurring at the boundaries of Earth's tectonic plates (http://www.tectonics.caltech.edu). Over the past four years, the TO has made a major effort to develop an Education and Public Outreach (EPO) program. Our goals are to (1) inspire students to learn Earth Sciences, particularly tectonic processes, (2) inform and educate the general public about science in the context of TO discoveries, and (3) provide opportunities for graduate students, postdocs, and faculty to do outreach in the local K-12 schools and community colleges. Our work toward these goals includes hosting local high school teachers and students each summer for six weeks of research experience (as part of Caltech's "Summer Research Connection"); organizing and hosting an NAGT conference aimed at Geoscience teachers at community colleges; participating in teacher training workshops (organized by the local school district); hosting tours for K-12 students from local schools as well as from China; and bringing hands-on activities into local elementary, middle, and high school classrooms. We also lead local school students and teachers on geology field trips through nearby canyons; develop education modules for undergraduate classes (as part of MARGINS program); write educational web articles on TO research (http://www.tectonics.caltech.edu/outreach/highlights/), and regularly give presentations to the general public. This year, we started providing content expertise for the development of video games to teach Earth Science, being created by GameDesk Institute. And we have just formed a scientist/educator partnership with a 6th grade teacher, to help in the school district's pilot program to incorporate new national science standards (NSTA's Next Generation Science Standards, current draft), as well as use Project-Based Learning. This presentation gives an overview of these activities.

  2. The AIA Solar Learning Center: Taking Inquiry-based EPO Online

    Science.gov (United States)

    Wills-Davey, Meredith; Attrill, G. D. R.; Engell, A.

    2009-05-01

    The observations of the Atmospheric Imaging Assembly aboard the Solar Dynamics Observatory (SDO-AIA) are expected to be groundbreaking within the field of heliophysics. To properly promote and explain the data produced by AIA, it is important that an innovative EPO effort be put forth. This has led to the development of "The AIA Solar Learning Center” (SLC), an inquiry-based educational website geared towards teaching about AIA and the Sun in general. The goal of the SLC is to provide K-12 students, teachers, parents, and homeschoolers with information and education about the Sun, primarily through hands-on activity modules that explain different aspects of our nearest star and the methods of observing it. While each module ultimately aims to impart information about the Sun or some related physical process, the activities also range across a host of different disciplines, including geology, chemistry, history, music, and art. In order to make the content applicable and accessible, activities are tailored to multiple difficulty levels, catering to different age groups. There is also a strong push towards facilitating teachers; activities are designed to fulfill specific teaching standards, and a host of additional teaching material is provided, including lesson plans and powerpoint presentations. Ultimately, the SLC aims to make science and the Sun inviting and accessible. The "Meet the Scientists” page will provide pictures and personal bios of participating scientists. Students will have the opportunity to interactively ask solar-related questions. There is even a host of lighter fare, such as a solar music playlist and links to relevant Facebook pages.

  3. GLP-1 increases microvascular recruitment but not glucose uptake in human and rat skeletal muscle

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Holst, Jens Juul; Rattigan, Stephen

    2014-01-01

    The insulinotropic gut hormone, glucagon-like-peptide-1 (GLP-1) has been proposed to have effects on vascular function and glucose disposal. However, whether GLP-1 is able to increase microvascular recruitment (MVR) in humans has not been investigated. GLP-1 was infused in the femoral artery...... in overnight fasted healthy young men. Microvascular recruitment was measured with real time contrast-enhanced ultrasound and leg glucose uptake by the leg balance technique with and without inhibition of the insulinotropic response of GLP-1 by co-infusion of octreotide. As a positive control, MVR and leg...

  4. Growing population and ecosystem change increase human schistosomiasis around Lake Malaŵi.

    Science.gov (United States)

    Van Bocxlaer, Bert; Albrecht, Christian; Stauffer, Jay R

    2014-05-01

    Multiple anthropogenic environmental stressors with reinforcing effects to the deterioration of ecosystem stability can obscure links between ecosystem change and the prevalence of infectious diseases. Incomplete understanding may lead to ineffective public health and disease control strategies, as appears to be the case with increased urogenital schistosomiasis in humans around Lake Malaŵi over recent decades. Sedimentation and eutrophication help explain historical changes in intermediate host range and parasite transmission. Hence, control strategies should account for abiotic changes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Antioxidant and antigenotoxic role of recombinant human erythropoeitin against alkylating agents: cisplatin and mitomycin C in cultured Vero cells.

    Science.gov (United States)

    Rjiba-Touati, Karima; Ayed-Boussema, Imen; Soualeh, Nidhal; Achour, Abdellatif; Bacha, Hassen; Abid, Salwa

    2013-08-01

    Cisplatin (CDDP) and mitomycin C (MMC), two alkylating agents used against various solid tumours, are a common source of acute kidney injury. Thus, strategies for minimizing CDDP and MMC toxicity are of a clinical interest. In this study, we aimed to investigate the protective role of recombinant human erythropoietin (rhEPO) against oxidative stress and genotoxicity induced by CDDP and MMC in cultured Vero cells. Three types of treatments were performed: (i) cells were treated with rhEPO 24 h before exposure to CDDP/MMC (pre-treatment), (ii) cells were treated with rhEPO and CDDP/MMC simultaneously (co-treatment), (iii) cells were treated with rhEPO 24 h after exposure to CDDP/MMC (post-treatment). Our results showed that rhEPO decreased the reactive oxygen species levels, the malondialdehyde levels and ameliorated glutathione (reduced and oxidized glutathione) modulation induced by CDDP and MMC in cultured Vero cells. Furthermore, rhEPO administration prevented alkylating agents-induced DNA damage accessed by comet test. Altogether, our results suggested a protective role of rhEPO, against CDDP- and MMC-induced oxidative stress and genotoxicity, especially in pre-treatment condition.

  6. Exercise increases TBC1D1 phosphorylation in human skeletal muscle

    Science.gov (United States)

    Jessen, Niels; An, Ding; Lihn, Aina S.; Nygren, Jonas; Hirshman, Michael F.; Thorell, Anders

    2011-01-01

    Exercise and weight loss are cornerstones in the treatment and prevention of type 2 diabetes, and both interventions function to increase insulin sensitivity and glucose uptake into skeletal muscle. Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1. Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation. In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood. In this study, we determined the effects of dietary intervention and a single bout of exercise on TBC1D1 and AS160 site-specific phosphorylation in human skeletal muscle. Ten obese (BMI 33.4 ± 2.4, M-value 4.3 ± 0.5) subjects were studied at baseline and after a 2-wk dietary intervention. Muscle biopsies were obtained from the subjects in the resting (basal) state and immediately following a 30-min exercise bout (70% V̇o2 max). Muscle lysates were analyzed for AMPK activity and Akt phosphorylation and for TBC1D1 and AS160 phosphorylation on known or putative AMPK and Akt sites as follows: AS160 Ser711 (AMPK), TBC1D1 Ser231 (AMPK), TBC1D1 Ser660 (AMPK), TBC1D1 Ser700 (AMPK), and TBC1D1 Thr590 (Akt). The diet intervention that consisted of a major shift in the macronutrient composition resulted in a 4.2 ± 0.4 kg weight loss (P < 0.001) and a significant increase in insulin sensitivity (M value 5.6 ± 0.6), but surprisingly, there was no effect on expression or phosphorylation of any of the muscle-signaling proteins. Exercise increased muscle AMPKα2 activity but did not increase Akt phosphorylation. Exercise increased phosphorylation on AS160 Ser711, TBC1D1 Ser231, and TBC1D1 Ser660 but had no effect on TBC1D1 Ser700. Exercise did not increase TBC1D1 Thr590 phosphorylation or TBC1D1/AS160 PAS

  7. Human and Autologous Adipose-derived Stromal Cells Increase Flap Survival in Rats Independently of Host Immune Response

    DEFF Research Database (Denmark)

    Toyserkani, Navid Mohamadpour; Jensen, Charlotte Harken; Andersen, Ditte Caroline

    2018-01-01

    evaluated after 7 days. RESULTS: The mean survival rates for SVF treatment regardless of human or autologous origin were significantly increased as compared with the control group. Adipose stem/stromal cell and SVF lysate injection did not increase flap survival. Vessel density was increased for human...... injections lead to increased vessel density, but it did not necessarily lead to increased flap survival. Further research should elaborate which molecular events make SVF treatment more efficacious than ASC....

  8. Stimulation of GPR30 increases release of EMMPRIN-containing microvesicles in human uterine epithelial cells.

    Science.gov (United States)

    Burnett, Lindsey A; Light, Mallory M; Mehrotra, Pavni; Nowak, Romana A

    2012-12-01

    Uterine remodeling is highly dependent on the glycosylated transmembrane protein extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN). Previous studies indicate estradiol can increase EMMPRIN expression in uterine cells and promote subsequent induction of MMP production. The aim of this study was to investigate the role of G protein-coupled receptor 30 (GPR30) stimulation on EMMPRIN microvesicle release in the human uterine epithelial cell line hTERT-EEC (EECs). We examined EMMPRIN release by human EECs in response to GPR30 stimulation by microvesicle isolation, Western blot, and immunocytochemistry. We employed a pharmacological approach using the GPR30-selective agonist G1 and the antagonist G15 to determine the receptor specificity of this response. We demonstrated GPR30 expression in EECs and release of EMMPRIN in microvesicles in response to stimulation of GPR30. G1, estradiol, and cholera toxin stimulated EMMPRIN release in microvesicles as detected by Western blot and immunocytochemistry, indicating that stimulation of GPR30 can induce EMMPRIN microvesicle release. These data indicate that EMMPRIN release in microvesicles can be mediated by stimulation of GPR30 in human EECs, suggesting that inappropriate stimulation or expression of this receptor may be significant in uterine pathology.

  9. Increased infectivity of anchorless mouse scrapie prions in transgenic mice overexpressing human prion protein.

    Science.gov (United States)

    Race, Brent; Phillips, Katie; Meade-White, Kimberly; Striebel, James; Chesebro, Bruce

    2015-06-01

    mice expressing only anchorless PrP were more infectious than prions produced in mice expressing anchored PrP. Thus, the lack of the GPI anchor on prions reduced the effect of the mouse-human species barrier. Our results suggest that prion diseases that produce higher levels of anchorless PrP may pose an increased risk for cross-species infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Increased p21ras activity in human fibroblasts transduced with survivin enhances cell proliferation

    International Nuclear Information System (INIS)

    Temme, Achim; Diestelkoetter-Bachert, Petra; Schmitz, Marc; Morgenroth, Agnieszka; Weigle, Bernd; Rieger, Michael A.; Kiessling, Andrea; Rieber, E. Peter

    2005-01-01

    Survivin is critically involved in mitosis and when overexpressed enhances the activity of the Aurora B kinase, a serine-threonine kinase belonging to the family of oncogenic Aurora/IpI1p-related kinases. Both proteins interact with Ras GTPase-activating protein suggesting an impact on the Ras pathway. This study aimed at defining the role of survivin in proliferation and potential transformation of cells. When survivin was overexpressed in normal human lung fibroblasts, the characteristic track lanes of fibroblasts were disturbed and the rate of cell proliferation was increased. An enhanced level of p21 ras mRNA and protein expression and concomitant rise in levels of activated p21 ras were observed. Despite increased proliferation cell survival remained dependent on serum and cells were not able to form colonies in soft agar assays. These data suggest that overexpression of survivin increases cell growth but, despite the increase in active p21 ras , is not sufficient to transform primary cells. Yet, in addition to its anti-apoptotic function it might contribute to the accelerated growth of tumour cells by increasing p21 ras activity

  11. Human population growth offsets climate-driven increase in woody vegetation in sub-Saharan Africa.

    Science.gov (United States)

    Brandt, Martin; Rasmussen, Kjeld; Peñuelas, Josep; Tian, Feng; Schurgers, Guy; Verger, Aleixandre; Mertz, Ole; Palmer, John R B; Fensholt, Rasmus

    2017-03-06

    The rapidly growing human population in sub-Saharan Africa generates increasing demand for agricultural land and forest products, which presumably leads to deforestation. Conversely, a greening of African drylands has been reported, but this has been difficult to associate with changes in woody vegetation. There is thus an incomplete understanding of how woody vegetation responds to socio-economic and environmental change. Here we used a passive microwave Earth observation data set to document two different trends in land area with woody cover for 1992-2011: 36% of the land area (6,870,000 km 2 ) had an increase in woody cover largely in drylands, and 11% had a decrease (2,150,000 km 2 ), mostly in humid zones. Increases in woody cover were associated with low population growth, and were driven by increases in CO 2 in the humid zones and by increases in precipitation in drylands, whereas decreases in woody cover were associated with high population growth. The spatially distinct pattern of these opposing trends reflects, first, the natural response of vegetation to precipitation and atmospheric CO 2 , and second, deforestation in humid areas, minor in size but important for ecosystem services, such as biodiversity and carbon stocks. This nuanced picture of changes in woody cover challenges widely held views of a general and ongoing reduction of the woody vegetation in Africa.

  12. Increased levels of unscheduled DNA synthesis in UV-irradiated human fibroblasts pretreated with sodium butyrate

    International Nuclear Information System (INIS)

    Williams, J.I.; Friedberg, E.C.

    1982-01-01

    Pretreatment of growing normal and xeroderma pigmentosum (XP) human fibroblasts with sodium butyrate at concentrations of 5-20 mM results in increased levels of DNA repair synthesis measured by autoradiography after exposure of the cells to 254 nm UV radiation in the fluence range 0-25 J/m 2 . The phenomenon manifests as an increased extent and an increased initial rate of unscheduled DNA synthesis (UDS). This experimental result is not due to an artifact of autoradiography related to cell size. Xeroderma pigmentosum cells from complementation groups A, C, D and E and XP variant cells all exhibit increases in the levels of UV-induced UDS in response to sodium butyrate proportional to those observed with normal cells. These UDS increases associated with butyrate pretreatment correlate with demonstrable changes in intracellular thymidine pool size and suggest that sodium butyrate enhances uptake of exogenous radiolabeled thymidine during UV-induced repair synthesis by reducing endogenous levels of thymidine. (author)

  13. Interleukin-17A increases leptin production in human bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Noh, Minsoo

    2012-03-01

    Lineage commitment of human bone marrow mesenchymal stem cells (hBM-MSCs) to adipocytes or osteoblasts has been suggested as a model system to study the relationship between type II diabetes and abnormal bone metabolism. Leptin and IL-17A inhibit adipogenesis whereas they promote osteogenesis in MSCs. Due to pathophysiologic roles of IL-17A in human metabolic diseases and bone metabolism, it was evaluated whether IL-17A-dependent inverse regulation on adipogenesis and osteogenesis was related to endogenous leptin production in hBM-MSCs. In the analysis of adiponectin and leptin secretion profiles of hBM-MSCs in response to various combinations of differentiation inducing factors, it was found that dexamethasone, a common molecule used for both adipogenesis and osteogenesis, increased leptin production in hBM-MSCs. Importantly, the level of leptin production during osteogenesis in hBM-MSCs was higher than that during adipogenesis, implicating a significant leptin production in extra-adipose tissues. IL-17A increased leptin production in hBM-MSCs and also under the condition of osteogenesis. In spite of direct inhibition on adipogenesis, IL-17A up-regulated leptin production in hBM-MSC-derived adipocytes. Anti-leptin antibody treatment partially antagonized the IL-17A dependent inhibition of adipogenesis in hBM-MSCs, suggesting a role of leptin in mediating the inverse regulation of IL-17A on osteogenesis and adipogenesis in hBM-MSCs. Therefore, the IL-17A-induced leptin production may provide a key clue to understand a molecular mechanism on the lineage commitment of hBM-MSCs into adipocytes or osteoblasts. In addition, leptin production in extra-adipose tissues like MSCs and osteoblasts should be considered in future studies on leptin-associated human diseases. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Increase in density and accumulation of serotonin by human aging platelets

    International Nuclear Information System (INIS)

    Mezzano, D.; Aranda, E.; Rodriguez, S.; Foradori, A.; Lira, P.

    1984-01-01

    51 Cr-labeled autologous platelets were infused into splenectomized subjects and the specific radioactivities of high-density (HD) and low-density (LD) platelet subpopulations were determined sequentially in postinfusion samples. These findings confirm previous observations in eusplenic individuals and support the hypothesis that human LD platelets are, on the average, younger than HD platelets. LD platelets contain 33.8 +/- 13.5 ng serotonin (5HT)/10(8) platelets and HD platelets 76.8 +/- 9.5 ng 5HT/10(8) platelets. Sequential measurements of 5HT in PRP platelets were performed during the recovery phase of thrombocytopenia following splenectomy in patients with idiopathic thrombocytopenic purpura (ITP), a condition associated with aging of platelets in circulation. Presplenectomy platelet 5HT was 17.7 ng/10(8) platelets and on days 1, 6, and 12 after surgery it increased to 18.1, 37.8, and 61.0 ng/10(8) platelets. When three healthy volunteers were given aspirin (500 mg/day) for up to 15 days, no significant change in the 5HT content of circulating platelets was observed. The observation that human HD platelets, enriched with older cells, contain more 5HT than LD platelets taken together with the parallel increase in platelet 5HT and age during the recovery from thrombocytopenia in ITP patients and the lack of effect of aspirin on platelet 5HT content, provides initial evidence that human platelets accumulate 5HT during their life-span in circulation

  15. Safflower oil consumption does not increase plasma conjugated linoleic acid concentrations in humans.

    Science.gov (United States)

    Herbel, B K; McGuire, M K; McGuire, M A; Shultz, T D

    1998-02-01

    Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of linoleic acid (LA) with conjugated double bonds. CLA has anticarcinogenic properties and has been identified in human tissues, dairy products, meats, and certain vegetable oils. A variety of animal products are good sources of CLA, but plant oils contain much less. However, plant oils are a rich source of LA, which may be isomerized to CLA by intestinal microorganisms in humans. To investigate the effect of triacylglycerol-esterified LA consumption on plasma concentrations of esterified CLA in total lipids, a dietary intervention (6 wk) was conducted with six men and six women. During the intervention period a salad dressing containing 21 g safflower oil providing 16 g LA/d was added to the subjects' daily diets. Three-day diet records and fasting blood were obtained initially and during dietary and postdietary intervention periods. Although LA intake increased significantly during the dietary intervention, plasma CLA concentrations were not affected. Plasma total cholesterol and LDL-cholesterol concentrations were significantly lower after addition of safflower oil to the diet. In summary, consumption of triacylglycerol-esterified LA in safflower oil did not increase plasma concentrations of esterified CLA in total lipids.

  16. Protease-activated receptor 2 agonist increases cell proliferation and invasion of human pancreatic cancer cells

    Science.gov (United States)

    XIE, LIQUN; DUAN, ZEXING; LIU, CAIJU; ZHENG, YANMIN; ZHOU, JING

    2015-01-01

    The aim of this study was to determine the expression of protease-activated receptor 2 (PAR-2) in the human pancreatic cancer cell line SW1990, and to evaluate its effect on cell proliferation and invasion. The expression of PAR-2 protein and mRNA in SW1990 cells was determined by immunocytochemistry and reverse transcription polymerase chain reaction (PCR), respectively. MTT and cell invasion and migration assays, as well as semi-quantitative PCR and zymography analysis, were additionally performed. PAR-2 mRNA was significantly upregulated in the cells treated with trypsin or the PAR-2 activating peptide Ser-Leu-Ile-Gly-Lys-Val (SLIGKV) (P0.05). Trypsin and SLIGKV significantly promoted SW1990 cell proliferation in a dose- and time-dependent manner (P<0.05). Compared with the control group, trypsin and SLIGKV significantly increased the mRNA expression (P<0.01) and gelatinolytic activity (P<0.01) of matrix metalloproteinase (MMP)-2. In conclusion, PAR-2 is expressed in SW1990 cells. PAR-2 activation may promote the invasion and migration of human pancreatic cancer cells by increasing MMP-2 expression. PMID:25452809

  17. SATB2 expression increased anchorage-independent growth and cell migration in human bronchial epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Feng; Jordan, Ashley; Kluz, Thomas [Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States); Shen, Steven [Center for Health Informatics and Bioinformatics, New York University Langone Medical Center, New York, NY 10016 (United States); Sun, Hong; Cartularo, Laura A. [Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States); Costa, Max, E-mail: Max.Costa@nyumc.org [Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States)

    2016-02-15

    The special AT-rich sequence-binding protein 2 (SATB2) is a protein that binds to the nuclear matrix attachment region of the cell and regulates gene expression by altering chromatin structure. In our previous study, we reported that SATB2 gene expression was induced in human bronchial epithelial BEAS-2B cells transformed by arsenic, chromium, nickel and vanadium. In this study, we show that ectopic expression of SATB2 in the normal human bronchial epithelial cell-line BEAS-2B increased anchorage-independent growth and cell migration, meanwhile, shRNA-mediated knockdown of SATB2 significantly decreased anchorage-independent growth in Ni transformed BEAS-2B cells. RNA sequencing analyses of SATB2 regulated genes revealed the enrichment of those involved in cytoskeleton, cell adhesion and cell-movement pathways. Our evidence supports the hypothesis that SATB2 plays an important role in BEAS-2B cell transformation. - Highlights: • We performed SATB2 overexpression in the BEAS-2B cell line. • We performed SATB2 knockdown in a Ni transformed BEAS-2B cell line. • SATB2 induced anchorage-independent growth and increased cell migration. • SATB2 knockdown significantly decreased anchorage-independent growth. • We identified alterations in gene involved in cytoskeleton, cell adhesion.

  18. SATB2 expression increased anchorage-independent growth and cell migration in human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Wu, Feng; Jordan, Ashley; Kluz, Thomas; Shen, Steven; Sun, Hong; Cartularo, Laura A.; Costa, Max

    2016-01-01

    The special AT-rich sequence-binding protein 2 (SATB2) is a protein that binds to the nuclear matrix attachment region of the cell and regulates gene expression by altering chromatin structure. In our previous study, we reported that SATB2 gene expression was induced in human bronchial epithelial BEAS-2B cells transformed by arsenic, chromium, nickel and vanadium. In this study, we show that ectopic expression of SATB2 in the normal human bronchial epithelial cell-line BEAS-2B increased anchorage-independent growth and cell migration, meanwhile, shRNA-mediated knockdown of SATB2 significantly decreased anchorage-independent growth in Ni transformed BEAS-2B cells. RNA sequencing analyses of SATB2 regulated genes revealed the enrichment of those involved in cytoskeleton, cell adhesion and cell-movement pathways. Our evidence supports the hypothesis that SATB2 plays an important role in BEAS-2B cell transformation. - Highlights: • We performed SATB2 overexpression in the BEAS-2B cell line. • We performed SATB2 knockdown in a Ni transformed BEAS-2B cell line. • SATB2 induced anchorage-independent growth and increased cell migration. • SATB2 knockdown significantly decreased anchorage-independent growth. • We identified alterations in gene involved in cytoskeleton, cell adhesion.

  19. Effects of prolonged recombinant human erythropoietin administration on muscle membrane transport systems and metabolic marker enzymes

    DEFF Research Database (Denmark)

    Juel, C; Thomsen, J J; Rentsch, R L

    2007-01-01

    on the expression of muscle membrane transport proteins. Likewise, improvements in performance may involve upregulation of metabolic enzymes. Since Epo is known to augment performance we tested the effect of rHuEpo on some marker enzymes that are related to aerobic capacity. For these purposes eight subjects...... performance by approximately 54%. Membrane transport systems and carbonic anhydrases involved in pH regulation remained unchanged. Of the Na(+), K(+)-pump isoforms only the density of the alpha2 subunit was decreased (by 22%) after treatment. The marker enzymes cytochrom c and hexokinase remained unchanged......Adaptations to chronic hypoxia involve changes in membrane transport proteins. The underlying mechanism of this response may be related to concomitant occurring changes in erythropoietin (Epo) levels. We therefore tested the direct effects of recombinant human erythropoietin (rHuEpo) treatment...

  20. The role of renal function loss on circadian misalignment of cytokines EPO, IGF-1, IL-6 and TNF-alfa in chronic renal disease.

    Science.gov (United States)

    van der Putten, Karien; Koch, Birgit; van Someren, Eus; Wielders, Jos; Ter Wee, Piet; Nagtegaal, Elsbeth; Gaillard, Carlo

    2011-01-01

    Chronic inflammation plays a pivotal role in the development of renal disease. Circadian sleep-wake rhythm is disturbed in renal disease. Awareness of other disturbed rhythms, such as inflammation processes, can affect the treatment of patients with renal disease. Knowledge of possibly related circadian misalignment of the cytokines erythropoietin (EPO), Insulin Growth Factor-1 (IGF-1) and interleukins (IL) however is limited. We therefore performed an observational study. The objective of this study was to characterize levels of EPO, IGF-1 and inflammation markers IL-6 and TNF-α, related to renal function. The study population consisted of patients with various degrees of renal function, admitted to our hospital. During 24 hours, blood of 28 subjects with various degrees of renal function was collected every 2 hours. The patients were stable, not acutely ill and they were waiting for a procedure, such as elective surgery. Circadian parameters of EPO, IGF-1, IL-6 and TNF-α were measured in serum and were correlated with glomerular filtration rate (GFR) and Hb, using Pearson correlations. Although diurnal variations in EPO level were found in 15 out of 28 patients, the curves did not show a consistent phase. The presence of an EPO rhythm was not related to GFR. No diurnal rhythm could be detected for IGF-1, IL-6 and TNF-α. Mean levels of IGF-1 were correlated inversely to mean levels of EPO (p=0.03). When divided based on GFR and Hb subjects with GFR 10-30 ml/min and lower Hb had the highest IGF-1 levels (p=0.02). A relationship between Il-6, TNF-α and EPO or GFR was not found. The existence of a circadian (mis)alignment of EPO, IGF-1, IL-6 and TNF-α was not found. The association between high IGF-1 and low Hb suggests that EPO and IGF-1 have an alternating role, dependent on GFR, in stimulating erythropoiesis. These results could have consequences for the treatment of anemia.

  1. Aberrant phenotypes of transgenic mice expressing dimeric human erythropoietin

    Directory of Open Access Journals (Sweden)

    Yun Seong-Jo

    2012-01-01

    Full Text Available Abstract Background Dimeric human erythropoietin (dHuEPO peptides are reported to exhibit significantly higher biological activity than the monomeric form of recombinant EPO. The objective of this study was to produce transgenic (tg mice expressing dHuEPO and to investigate the characteristics of these mice. Methods A dHuEPO-expressing vector under the control of the goat beta-casein promoter, which produced a dimer of human EPO molecules linked by a 2-amino acid peptide linker (Asp-Ile, was constructed and injected into 1-cell fertilized embryos by microinjection. Mice were screened using genomic DNA samples obtained from tail biopsies. Blood samples were obtained by heart puncture using heparinized tubes, and hematologic parameters were assessed. Using the microarray analysis tool, we analyzed differences in gene expression in the spleens of tg and control mice. Results A high rate of spontaneous abortion or death of the offspring was observed in the recipients of dHuEPO embryos. We obtained 3 founder lines (#4, #11, and #47 of tg mice expressing the dHuEPO gene. However, only one founder line showed stable germline integration and transmission, subsequently establishing the only transgenic line (#11. We obtained 2 F1 mice and 3 F2 mice from line #11. The dHuEPO protein could not be obtained because of repeated spontaneous abortions in the tg mice. Tg mice exhibited symptoms such as short lifespan and abnormal blood composition. The red blood cell count, white blood cell count, and hematocrit levels in the tg mice were remarkably higher than those in the control mice. The spleens of the tg mice (F1 and F2 females were 11- and -21-fold larger than those of the control mice. Microarray analysis revealed 2,672 spleen-derived candidate genes; more genes were downregulated than upregulated (849/764. Reverse transcriptase-polymerase chain reaction (RT-PCR and quantitative real-time PCR (qRT-PCR were used for validating the results of the microarray

  2. Comparison of neuroprotective effects of erythropoietin (EPO) and carbamylerythropoietin (CEPO) against ischemia-like oxygen-glucose deprivation (OGD) and NMDA excitotoxicity in mouse hippocampal slice cultures

    DEFF Research Database (Denmark)

    Montero, Maria; Rom Poulsen, Frantz; Noraberg, Jens

    2007-01-01

    of hematopoietic bioactivity, is the chemically modified, EPO-derivative carbamylerythropoietin (CEPO). For comparison of the neuroprotective effects of CEPO and EPO, we subjected organotypic hippocampal slice cultures to oxygen-glucose deprivation (OGD) or N-methyl-d-aspartate (NMDA) excitotoxicity. Hippocampal...... slice cultures were pretreated for 24 h with 100 IU/ml EPO (=26 nM) or 26 nM CEPO before OGD or NMDA lesioning. Exposure to EPO and CEPO continued during OGD and for the next 24 h until histology, as well as during the 24 h exposure to NMDA. Neuronal cell death was quantified by cellular uptake...... of propidium iodide (PI), recorded before the start of OGD and NMDA exposure and 24 h after. In cultures exposed to OGD or NMDA, CEPO reduced PI uptake by 49+/-3 or 35+/-8%, respectively, compared to lesion-only controls. EPO reduced PI uptake by 33+/-5 and 15+/-8%, respectively, in the OGD and NMDA exposed...

  3. Calcimimetic R-568 and its enantiomer S-568 increase nitric oxide release in human endothelial cells.

    Directory of Open Access Journals (Sweden)

    Mario Bonomini

    Full Text Available Calcimimetics, such as R-568, are thought to activate G protein-linked Ca(2+-sensing receptor (CaSR by allosterically increasing the affinity of the receptor for Ca(2+ allowing for efficient control of uremic hyperparathyroidism. Several recent studies suggest they possess additional vascular actions. Although it has been postulated that calcimimetics may have a direct effect on CaSR in the blood vessels, further studies are needed to elucidate their vascular CaSR-dependent versus CaSR-independent effects.Focusing on human umbilical vein endothelial cells (HUVECs, we studied the CaSR expression and distribution by Immunofluorescence and Western Blot analysis. CaSR function was evaluated by measuring the potential effect of calcimimetic R-568 and its enantiomer S-568 upon the modulation of intracellular Ca(2+ levels (using a single cell approach and FURA-2AM, in the presence or absence of Calhex-231, a negative modulator of CaSR. To address their potential vascular functions, we also evaluated R- and S-568-stimulated enzymatic release of Nitric Oxide (NO by DAF-2DA, by Nitric Oxide Synthase (NOS radiometric assay (both in HUVECs and in Human Aortic Endothelial Cells and by measuring eNOS-ser1177 phosphorylation levels (Immunoblotting. We show that, although the CaSR protein was expressed in HUVECs, it was mainly distributed in cytoplasm while the functional CaSR dimers, usually localized on the plasma membrane, were absent. In addition, regardless of the presence or absence of Calhex-231, both R- and S-568 significantly increased intracellular Ca(2+ levels by mobilization of Ca(2+ from intracellular stores, which in turn augmented NO release by a time- and Ca(2+-dependent increase in eNOS-ser1177 phosphorylation levels.Taken together, these data indicate that in human endothelium there is no stereoselectivity in the responses to calcimimetics and that CaSR is probably not involved in the action of R- and S-568. This suggests an additional

  4. Increasing trunk flexion transforms human leg function into that of birds despite different leg morphology.

    Science.gov (United States)

    Aminiaghdam, Soran; Rode, Christian; Müller, Roy; Blickhan, Reinhard

    2017-02-01

    Pronograde trunk orientation in small birds causes prominent intra-limb asymmetries in the leg function. As yet, it is not clear whether these asymmetries induced by the trunk reflect general constraints on the leg function regardless of the specific leg architecture or size of the species. To address this, we instructed 12 human volunteers to walk at a self-selected velocity with four postures: regular erect, or with 30 deg, 50 deg and maximal trunk flexion. In addition, we simulated the axial leg force (along the line connecting hip and centre of pressure) using two simple models: spring and damper in series, and parallel spring and damper. As trunk flexion increases, lower limb joints become more flexed during stance. Similar to birds, the associated posterior shift of the hip relative to the centre of mass leads to a shorter leg at toe-off than at touchdown, and to a flatter angle of attack and a steeper leg angle at toe-off. Furthermore, walking with maximal trunk flexion induces right-skewed vertical and horizontal ground reaction force profiles comparable to those in birds. Interestingly, the spring and damper in series model provides a superior prediction of the axial leg force across trunk-flexed gaits compared with the parallel spring and damper model; in regular erect gait, the damper does not substantially improve the reproduction of the human axial leg force. In conclusion, mimicking the pronograde locomotion of birds by bending the trunk forward in humans causes a leg function similar to that of birds despite the different morphology of the segmented legs. © 2017. Published by The Company of Biologists Ltd.

  5. Decreased Polyunsaturated Fatty Acid Content Contributes to Increased Survival in Human Colon Cancer

    Directory of Open Access Journals (Sweden)

    Manuela Oraldi

    2009-01-01

    Full Text Available Among diet components, some fatty acids are known to affect several stages of colon carcinogenesis, whereas others are probably helpful in preventing tumors. In light of this, our aim was to determine the composition of fatty acids and the possible correlation with apoptosis in human colon carcinoma specimens at different Duke's stages and to evaluate the effect of enriching human colon cancer cell line with the possible reduced fatty acid(s. Specimens of carcinoma were compared with the corresponding non-neoplastic mucosa: a significant decrease of arachidonic acid, PPARα, Bad, and Bax and a significant increase of COX-2, Bcl-2, and pBad were found. The importance of arachidonic acid in apoptosis was demonstrated by enriching a Caco-2 cell line with this fatty acid. It induced apoptosis in a dose- and time-dependent manner via induction of PPARα that, in turn, decreased COX-2. In conclusion, the reduced content of arachidonic acid is likely related to carcinogenic process decreasing the susceptibility of cancer cells to apoptosis.

  6. Cigarette Smoke-Exposed Candida albicans Increased Chitin Production and Modulated Human Fibroblast Cell Responses

    Directory of Open Access Journals (Sweden)

    Humidah Alanazi

    2014-01-01

    Full Text Available The predisposition of cigarette smokers for development of respiratory and oral bacterial infections is well documented. Cigarette smoke can also contribute to yeast infection. The aim of this study was to investigate the effect of cigarette smoke condensate (CSC on C. albicans transition, chitin content, and response to environmental stress and to examine the interaction between CSC-pretreated C. albicans and normal human gingival fibroblasts. Following exposure to CSC, C. albicans transition from blastospore to hyphal form increased. CSC-pretreated yeast cells became significantly (P<0.01 sensitive to oxidation but significantly (P<0.01 resistant to both osmotic and heat stress. CSC-pretreated C. albicans expressed high levels of chitin, with 2- to 8-fold recorded under hyphal conditions. CSC-pretreated C. albicans adhered better to the gingival fibroblasts, proliferated almost three times more and adapted into hyphae, while the gingival fibroblasts recorded a significantly (P<0.01 slow growth rate but a significantly higher level of IL-1β when in contact with CSC-pretreated C. albicans. CSC was thus able to modulate both C. albicans transition through the cell wall chitin content and the interaction between C. albicans and normal human gingival fibroblasts. These findings may be relevant to fungal infections in the oral cavity in smokers.

  7. TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts.

    Science.gov (United States)

    Bernstein, Diana L; Le Lay, John E; Ruano, Elena G; Kaestner, Klaus H

    2015-05-01

    Current strategies to alter disease-associated epigenetic modifications target ubiquitously expressed epigenetic regulators. This approach does not allow specific genes to be controlled in specific cell types; therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. Here, we have developed a method for directing DNA methylation to specific gene loci by conjugating catalytic domains of DNA methyltransferases (DNMTs) to engineered transcription activator-like effectors (TALEs). We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. Further, we determined that minimizing direct nucleotide sequence repeats within the TALE moiety permits efficient lentivirus transduction, allowing easy targeting of primary cell types. Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A expression and increased replication of primary human fibroblasts, as intended. Moreover, overexpression of p16 in these cells reversed the proliferative phenotype, demonstrating the specificity of our epigenetic targeting. Together, our results demonstrate that TALE-DNMTs can selectively target specific genes and suggest that this strategy has potential application for the development of locus-specific epigenetic therapeutics.

  8. SadA-Expressing Staphylococci in the Human Gut Show Increased Cell Adherence and Internalization.

    Science.gov (United States)

    Luqman, Arif; Nega, Mulugeta; Nguyen, Minh-Thu; Ebner, Patrick; Götz, Friedrich

    2018-01-09

    A subgroup of biogenic amines, the so-called trace amines (TAs), are produced by mammals and bacteria and can act as neuromodulators. In the genus Staphylococcus, certain species are capable of producing TAs through the activity of staphylococcal aromatic amino acid decarboxylase (SadA). SadA decarboxylates aromatic amino acids to produce TAs, as well as dihydroxy phenylalanine and 5-hydroxytryptophan to thus produce the neurotransmitters dopamine and serotonin. SadA-expressing staphylococci were prevalent in the gut of most probands, where they are part of the human intestinal microflora. Furthermore, sadA-expressing staphylococci showed increased adherence to HT-29 cells and 2- to 3-fold increased internalization. Internalization and adherence was also increased in a sadA mutant in the presence of tryptamine. The α2-adrenergic receptor is required for enhanced adherence and internalization. Thus, staphylococci in the gut might contribute to gut activity and intestinal colonization. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. SadA-Expressing Staphylococci in the Human Gut Show Increased Cell Adherence and Internalization

    Directory of Open Access Journals (Sweden)

    Arif Luqman

    2018-01-01

    Full Text Available Summary: A subgroup of biogenic amines, the so-called trace amines (TAs, are produced by mammals and bacteria and can act as neuromodulators. In the genus Staphylococcus, certain species are capable of producing TAs through the activity of staphylococcal aromatic amino acid decarboxylase (SadA. SadA decarboxylates aromatic amino acids to produce TAs, as well as dihydroxy phenylalanine and 5-hydroxytryptophan to thus produce the neurotransmitters dopamine and serotonin. SadA-expressing staphylococci were prevalent in the gut of most probands, where they are part of the human intestinal microflora. Furthermore, sadA-expressing staphylococci showed increased adherence to HT-29 cells and 2- to 3-fold increased internalization. Internalization and adherence was also increased in a sadA mutant in the presence of tryptamine. The α2-adrenergic receptor is required for enhanced adherence and internalization. Thus, staphylococci in the gut might contribute to gut activity and intestinal colonization. : Luqman et al. examine the sadA gene and argue that it contributes to TAs. They found that neuromodulator-producing staphylococci were present in the gut of most probands. The produced neuromodulators enhanced the adherence and internalization of staphylococci to cells in culture. Keywords: adherence, aromatic amino acid decarboxylase, gut microbiota, internalization, neuromodulator, neurotransmitter, staphylococcus

  10. A Ketone Ester Drink Increases Postexercise Muscle Glycogen Synthesis in Humans.

    Science.gov (United States)

    Holdsworth, David A; Cox, Peter J; Kirk, Tom; Stradling, Huw; Impey, Samuel G; Clarke, Kieran

    2017-09-01

    Physical endurance can be limited by muscle glycogen stores, in that glycogen depletion markedly reduces external work. During carbohydrate restriction, the liver synthesizes the ketone bodies, D-β-hydroxybutyrate, and acetoacetate from fatty acids. In animals and in the presence of glucose, D-β-hydroxybutyrate promotes insulin secretion and increases glycogen synthesis. Here we determined whether a dietary ketone ester, combined with plentiful glucose, can increase postexercise glycogen synthesis in human skeletal muscle. After an interval-based glycogen depletion exercise protocol, 12 well-trained male athletes completed a randomized, three-arm, blinded crossover recovery study that consisted of consumption of either a taste-matched, zero-calorie control or a ketone monoester drink, followed by a 10-mM glucose clamp or saline infusion for 2 h. The three postexercise conditions were control drink then saline infusion, control drink then hyperglycemic clamp, or ketone ester drink then hyperglycemic clamp. Skeletal muscle glycogen content was determined in muscle biopsies of vastus lateralis taken before and after the 2-h clamps. The ketone ester drink increased blood D-β-hydroxybutyrate concentrations to a maximum of 5.3 versus 0.7 mM for the control drink (P glycogen was 50% higher (246 vs 164 mmol glycosyl units per kilogram dry weight, P glycogen synthesis.

  11. Adoption of the B2SAFE EUDAT replication service by the EPOS community

    Science.gov (United States)

    Cacciari, Claudio; Fares, Massimo; Fiameni, Giuseppe; Michelini, Alberto; Danecek, Peter; Wittenburg, Peter

    2014-05-01

    B2SAFE is the EUDAT service for moving and replicating data between sites and storage systems for different purposes. The goal of B2SAFE is to keep the data from a repository safe by replicating it across different geographical and administrative zones according to a set of well-defined policies. It is also a way to store large volumes of data permanently at those sites which are providing powerful on-demand data analysis facilities. In particular, B2SAFE operates on the domain of registered data where data objects are referable via persistent identifiers (PIDs). B2SAFE is more than just copying data because the PIDs must be carefully managed when data objects are moved or replicated. The EUDAT B2SAFE Service offers functionality to replicate datasets across different data centres in a safe and efficient way while maintaining all information required to easily find and query information about the replica locations. The information about the replica locations and other important information is stored in PID records, each managed in separate administrative domains. The B2SAFE Service is implemented as an iRODS module providing a set of iRODS rules or policies to interface with the EPIC handle API and uses the iRODS middleware to replicate datasets from a source data (or community) centre to a destination data centre. The definition of the dataset(s) to replicate is flexible and up to the communities using the B2SAFE service. While the B2SAFE is internally using the EPIC handle API, communities have the choice to use any PID system they prefer to assign PIDs to their digital objects. A reference to one or more EUDAT B2SAFE PIDs is returned by the B2SAFE service when a dataset is replicated. The presentation will introduce the problem space of B2SAFE, presents the achievements that have been made during the last year for enabling communities to make use of the B2SAFE service, demonstrates a EPOS use cases, outlines the commonalities and differences between the policies

  12. Insulin increases phosphorylation of mitochondrial proteins in human skeletal muscle in vivo

    DEFF Research Database (Denmark)

    Zhao, Xiaolu; Bak, Steffen; Pedersen, Andreas James Thestrup

    2014-01-01

    , we investigated the effect of insulin on the phosphorylation of mitochondrial proteins in human skeletal muscle in vivo. Using a combination of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC−MS/MS, we compared the phosphoproteomes of isolated mitochondria from skeletal muscle samples...... obtained from healthy individuals before and after 4 h of insulin infusion. In total, we identified 207 phosphorylation sites in 95 mitochondrial proteins. Of these phosphorylation sites, 45% were identified in both basal and insulin-stimulated samples. Insulin caused a 2-fold increase in the number...... of different mitochondrial phosphopeptides (87 ± 7 vs 40 ± 7, p = 0.015) and phosphoproteins (46 ± 2 vs 26 ± 3, p = 0.005) identified in each mitochondrial preparation. Almost half of the mitochondrial phosphorylation sites (n = 94) were exclusively identified in the insulin-stimulated state and included...

  13. Linking an agency strategic review to increase knowledge management: San Francisco County Human Service Agency.

    Science.gov (United States)

    Harrison, Lindsay

    2012-01-01

    Led by the agency director, the agency engaged in a Strategic Review, based on a comprehensive assessment of agency performance that identified strategies to improve organizational effectiveness through increased data-informed practice and knowledge management. The Strategic Review gathered information on staff perceptions, perceptions of external stakeholders, changing citywide and neighborhood demographics, policy mandates, and budget and workload issues. The need for the review was based upon multiple, substantial changes not addressed in the 2000 Strategic Plan, including the 2004 merger of the Department of Human Services and the Department of Aging and Adult Services, changes among the executive management team, transitions among key political entities, new policy mandates and changing budget allocations. This case study describes the Strategic Review process and content, summarizing key challenges and lessons related to addressing workload demands, fostering positive staff attitudes, balancing internal and external information needs, and integrating data use and planning processes across the agency. Copyright © Taylor & Francis Group, LLC

  14. The evidence for increased L1 activity in the site of human adult brain neurogenesis.

    Directory of Open Access Journals (Sweden)

    Alexey A Kurnosov

    Full Text Available Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus-the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory.

  15. Repeated static contractions increase mitochondrial vulnerability toward oxidative stress in human skeletal muscle

    DEFF Research Database (Denmark)

    Sahlin, Kent; Nielsen, Jens Steen; Mogensen, Martin

    2006-01-01

    Repeated static contractions (RSC) induce large fluctuations in tissue oxygen tension and increase the generation of reactive oxygen species (ROS). This study investigated the effect of RSC on muscle contractility, mitochondrial respiratory function, and in vitro sarcoplasmic reticulum (SR) Ca(2......+) kinetics in human muscle. Ten male subjects performed five bouts of static knee extension with 10-min rest in between. Each bout of RSC (target torque 66% of maximal voluntary contraction torque) was maintained to fatigue. Muscle biopsies were taken preexercise and 0.3 and 24 h postexercise from vastus...... lateralis. Mitochondria were isolated and respiratory function measured after incubation with H(2)O(2) (HPX) or control medium (Con). Mitochondrial function was not affected by RSC during Con. However, RSC exacerbated mitochondrial dysfunction during HPX, resulting in decreased respiratory control index...

  16. Inhibition of autophagy induced by proteasome inhibition increases cell death in human SHG-44 glioma cells.

    Science.gov (United States)

    Ge, Peng-Fei; Zhang, Ji-Zhou; Wang, Xiao-Fei; Meng, Fan-Kai; Li, Wen-Chen; Luan, Yong-Xin; Ling, Feng; Luo, Yi-Nan

    2009-07-01

    The ubiquitin-proteasome system (UPS) and lysosome-dependent macroautophagy (autophagy) are two major intracellular pathways for protein degradation. Recent studies suggest that proteasome inhibitors may reduce tumor growth and activate autophagy. Due to the dual roles of autophagy in tumor cell survival and death, the effect of autophagy on the destiny of glioma cells remains unclear. In this study, we sought to investigate whether inhibition of the proteasome can induce autophagy and the effects of autophagy on the fate of human SHG-44 glioma cells. The proteasome inhibitor MG-132 was used to induce autophagy in SHG-44 glioma cells, and the effect of autophagy on the survival of SHG-44 glioma cells was investigated using an autophagy inhibitor 3-MA. Cell viability was measured by MTT assay. Apoptosis and cell cycle were detected by flow cytometry. The expression of autophagy related proteins was determined by Western blot. MG-132 inhibited cell proliferation, induced cell death and cell cycle arrest at G(2)/M phase, and activated autophagy in SHG-44 glioma cells. The expression of autophagy-related Beclin-1 and LC3-I was significantly up-regulated and part of LC3-I was converted into LC3-II. However, when SHG-44 glioma cells were co-treated with MG-132 and 3-MA, the cells became less viable, but cell death and cell numbers at G(2)/M phase increased. Moreover, the accumulation of acidic vesicular organelles was decreased, the expression of Beclin-1 and LC3 was significantly down-regulated and the conversion of LC3-II from LC3-I was also inhibited. Inhibition of the proteasome can induce autophagy in human SHG-44 glioma cells, and inhibition of autophagy increases cell death. This discovery may shed new light on the effect of autophagy on modulating the fate of SHG-44 glioma cells.Acta Pharmacologica Sinica (2009) 30: 1046-1052; doi: 10.1038/aps.2009.71.

  17. Inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer

    Institute of Scientific and Technical Information of China (English)

    Zhao Li; Ma Yongjie; Gu Feng; Fu Li

    2014-01-01

    Background Paclitaxel (PAC) is the first-line chemotherapy drug for most breast cancer patients,but clinical studies showed that some breast cancer patients were insensitive to PAC,which led to chemotherapy failure.It was reported that Notch1 signaling participated in drug resistance of breast cancer.Here,we show whether Notch1 expression is related to PAC sensitivity of breast cancer.Methods We employed Notch1 siRNA and Notch1 inhibitor,N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT),to down regulate Notch1 expression in human breast cancer cells MDA-MB-231,and detected the inhibition effect by Western blotting and reverse trans cription-polymerase chain reaction,respectively.After 24 hours exposure to different concentration of PAC (0,1,5,10,15,20,and 25 μg/ml),the viability of the control group and experimental group cells was tested by MTT.We also examined the expression of Notch1 in PAC sensitive and nonsensitive breast cancer patients,respectively by immunohistochemistry (IHC).The PAC sensitivity of breast cancer patients were identified by collagen gel droplet embedded culture-drug sensitivity test (CD-DST).Results Down regulation of Notch1 expression by Notch1siRNA interference or Notch1 inhibitor increased the PAC sensitivity in MDA-MB-231 cells (P <0.05).Also,the expression of Notch1 in PAC sensitive patients was much lower than that of PAC non-sensitive patients (P <0.01).Conclusion Notch1 expression has an effect on PAC sensitivity in breast cancer patients,and the inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer.

  18. A sustained increase in plasma NEFA upregulates the Toll-like receptor network in human muscle.

    Science.gov (United States)

    Hussey, Sophie E; Lum, Helen; Alvarez, Andrea; Cipriani, Yolanda; Garduño-Garcia, Jesús; Anaya, Luis; Dube, John; Musi, Nicolas

    2014-03-01

    Insulin-sensitive tissues (muscle, liver) of individuals with obesity and type 2 diabetes mellitus are in a state of low-grade inflammation, characterised by increased Toll-like receptor (TLR) expression and TLR-driven signalling. However, the cause of this mild inflammatory state is unclear. We tested the hypothesis that a prolonged mild increase in plasma NEFA will increase TLR expression and TLR-driven signalling (nuclear factor κB [NFκB] and mitogen-activated kinase [MAPK]) and impair insulin action in muscle of lean healthy individuals. Twelve lean, normal-glucose-tolerant participants were randomised to receive a 48 h infusion (30 ml/h) of saline or Intralipid followed by a euglycaemic-hyperinsulinaemic clamp. Vastus lateralis muscle biopsies were performed before and during the clamp. Lipid infusion impaired insulin-stimulated IRS-1 tyrosine phosphorylation and reduced peripheral insulin sensitivity (p < 0.01). The elevation in circulating NEFA increased expression of TLR3, TLR4 and TLR5, and several MAPK (MAPK8, MAP4K4, MAP2K3) and inhibitor of κB kinase-NFκB (CHUK [IKKA], c-REL [REL] and p65 [RELA, NFKB3, p65]) signalling genes (p < 0.05). The lipid infusion also increased extracellular signal-regulated kinase (ERK) phosphorylation (p < 0.05) and tended to reduce the content of inhibitor of kappa Bα (p = 0.09). The muscle content of most diacylglycerol, ceramide and acylcarnitine species was unaffected. In summary, insulin resistance induced by prolonged low-dose lipid infusion occurs together with increased TLR-driven inflammatory signalling and impaired insulin-stimulated IRS-1 tyrosine phosphorylation. A sustained, mild elevation in plasma NEFA is sufficient to increase TLR expression and TLR-driven signalling (NFκB and MAPK) in lean individuals. The activation of this pathway by NEFA may be involved in the pathogenesis of insulin resistance in humans. ClinicalTrials.gov NCT01740817.

  19. Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

    Science.gov (United States)

    Stampfer, Martha R; Garbe, James C

    2015-02-24

    Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

  20. Analysis of Human Resource Competency as Effort to Increase SMEs Economic Sector Productivity with Gender as Differentiating Variable

    OpenAIRE

    Wibawa, Dian Prihardini

    2018-01-01

    Competence is a very important factor in increasing work productivity. A qualified workforce will have a positive impact on improving business productivity. Thus, the level of corporate profitability also increased. Human resource improvement strategy is an excellent strategy apart from other factors such as technology improves. Increased strategy through human resource competence can be done with the improvement of ability, attitude, knowledge, and expertise. The purpose of this research is ...

  1. Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, J.C. [Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou (China); Zheng, G.F. [Department of Vascular Surgery, The People' s Hospital of Ganzhou, Ganzhou (China); Wu, L.; Ou Yang, L.Y.; Li, W.X. [Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou (China)

    2014-08-08

    Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs) expressing human basic fibroblast growth factor (hbFGF). After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC), MSCs expressing hbFGF (hbFGF-MSC), MSC controls, and phosphate-buffered saline (PBS) controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF) expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001); however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008) and microvessel density (P<0.001). Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.

  2. Recruitment of single human low-threshold motor units with increasing loads at different muscle lengths.

    Science.gov (United States)

    McNulty, P A; Cresswell, A G

    2004-06-01

    We investigated the recruitment behaviour of low threshold motor units in flexor digitorum superficialis by altering two biomechanical constraints: the load against which the muscle worked and the initial muscle length. The load was increased using isotonic (low load), loaded dynamic (intermediate load) and isometric (high load) contractions in two studies. The initial muscle position reflected resting muscle length in series A, and a longer length with digit III fully extended in series B. Intramuscular EMG was recorded from 48 single motor units in 10 experiments on five healthy subjects, 21 units in series A and 27 in series B, while subjects performed ramp up, hold and ramp down contractions. Increasing the load on the muscle decreased the force, displacement and firing rate of single motor units at recruitment at shorter muscle lengths (Precruitment pattern was observed between loaded dynamic and isotonic contractions, but not between isometric and loaded dynamic contractions. Thus, the recruitment properties of single motor units in human flexor digitorum superficialis are sensitive to changes in both imposed external loads and the initial length of the muscle.

  3. EGFR inhibitor C225 increases the radiosensitivity of human lung squamous cancer cells

    Directory of Open Access Journals (Sweden)

    Yang Ruijie

    2010-10-01

    Full Text Available Abstract Background The purpose of the present study is to investigate the direct biological effects of the epidermal growth factor receptor (EGFR inhibitor C225 on the radiosensitivity of human lung squamous cancer cell-H520. H520 cells were treated with different dosage of 60Co γ ray irradiation (1.953 Gy/min in the presence or absence of C225. The cellular proliferation, colony forming capacity, apoptosis, the cell cycle distribution as well as caspase-3 were analyzed in vitro. Results We found that C225 treatment significantly increased radiosensitivity of H-520 cells to irradiation, and led to cell cycle arrest in G1 phase, whereas 60Co γ ray irradiation mainly caused G2 phase arrest. H-520 cells thus displayed both the G1 and G2 phase arrest upon treatment with C225 in combination with 60Co γ ray irradiation. Moreover, C225 treatment significantly increased the apoptosis percentage of H-520 cells (13.91% ± 1.88% compared with the control group (5.75% ± 0.64%, P Conclusion In this regard, C225 treatment may make H-520 cells more sensitive to irradiation through the enhancement of caspase-3 mediated tumor cell apoptosis and cell cycle arrest.

  4. Diquafosol Tetrasodium Increases the Concentration of Mucin-like Substances in Tears of Healthy Human Subjects.

    Science.gov (United States)

    Shigeyasu, Chika; Hirano, Shinichiro; Akune, Yoko; Yamada, Masakazu

    2015-09-01

    This study was undertaken to determine the effect of topical application of diquafosol tetrasodium on proteins and mucin-like substances from tears of clinically healthy subjects. Tears were collected from both the eyes of 10 healthy volunteers. Diquafosol tetrasodium solution (3%) was applied once to the right eye and 0.9% sodium chloride solution (saline) once to the left eye. Tear samples were collected by Schirmer test strips before application and 5, 15, 30 and 60 min after application. Sialic acid, a marker of mucin-like substances, and major tear proteins including secretory IgA, lactoferrin, lipocalin-1, and lysozyme were measured by high performance liquid chromatography. Levels of total protein, sIgA and lysozyme were transiently decreased in both groups but returned to baseline levels within 15 min after application. The concentration of lactoferrin and lipocalin-1 did not change significantly in both groups. Sialic acid in tears was significantly decreased 5 min after saline application, but significantly increased 5 min after diquafosol application. No significant difference in sialic acid was seen after 15 min in both groups. Topical application of saline and diquafosol resulted in transient decrease of tear proteins possibly due to wash out or dilution effects. In contrast, diquafosol application significantly increased sialic acid, although the effect was transient. This suggests diquafosol stimulates the secretion of mucins from ocular tissues of healthy human subjects.

  5. Camphor induces cold and warm sensations with increases in skin and muscle blood flow in human.

    Science.gov (United States)

    Kotaka, Tomohiko; Kimura, Shoji; Kashiwayanagi, Makoto; Iwamoto, Jun

    2014-01-01

    Application of camphor to the skin has been empirically thought to improve blood circulation. However, camphor's effects on blood circulation to the skin and on thermal sensation have not been well elucidated. In this study, we examined its effects on the quality of sensation as well as on skin and muscle blood flow in human. Nine adults (average age 37±9.4 years) participated in the study. Petroleum jelly containing 5%, 10%, 20% camphor, or 2% menthol was separately applied to the skin on the medial side of one forearm of each subject. Just after the application, camphor at each concentration induced a cold sensation in a dose-dependent manner. Within 10 min, each subject reported that the cold sensation had faded, after which it was replaced by a warm sensation. As reported previously, a cold sensation was induced by application of 2% menthol, but the subjects did not adapt to that sensation. In addition, menthol did not induce a warm sensation at all. Application of menthol has been shown to increase blood flow in the skin. Finally, we measured blood flow in skin and muscle after the application of camphor or menthol. Application of camphor or menthol separately induced increases in local blood flow in the skin and muscle. The present results indicate that camphor induces both cold and warm sensations and improves blood circulation.

  6. The public's belief in climate change and its human cause are increasing over time.

    Science.gov (United States)

    Milfont, Taciano L; Wilson, Marc S; Sibley, Chris G

    2017-01-01

    Polls examining public opinion on the subject of climate change are now commonplace, and one-off public opinion polls provide a snapshot of citizen's opinions that can inform policy and communication strategies. However, cross-sectional polls do not track opinions over time, thus making it impossible to ascertain whether key climate change beliefs held by the same group of individuals are changing or not. Here we examine the extent to which individual's level of agreement with two key beliefs ("climate change is real" and "climate change is caused by humans") remain stable or increase/decrease over a six-year period in New Zealand using latent growth curve modelling (n = 10,436). Data were drawn from the New Zealand Attitudes and Values Study, a probabilistic national panel study, and indicated that levels of agreement to both beliefs have steadily increased over the 2009-2015 period. Given that climate change beliefs and concerns are key predictors of climate change action, our findings suggest that a combination of targeted endeavors, as well as serendipitous events, may successfully convey the emergency of the issue.

  7. Working to Increase Vaccination for Human Papillomavirus: A Survey of Wisconsin Stakeholders, 2015.

    Science.gov (United States)

    Mroz, Sarah; Zhang, Xiao; Williams, Mercedes; Conlon, Amy; LoConte, Noelle K

    2017-09-28

    Infection with human papillomavirus (HPV) is common and can progress to various types of cancer. HPV infection can be prevented through vaccination; however, vaccination rates among adolescents are low. The objective of this study was to assess efforts among Wisconsin stakeholders in HPV vaccination and organizational capacity for future collaborative work. We conducted a cross-sectional online survey of 277 stakeholders in HPV vaccination activities, from April 30, 2015, through June 30, 2015. Stakeholders were public health professionals, health care providers, educators, quality improvement professionals, researchers, and advocates identified as engaged in HPV vaccination work. Of the 277 invited stakeholders, 117 (42%) responded to the survey. Findings showed that most current HPV vaccination activities targeted 3 groups: adolescents and parents, clinical and health professionals, and communities and health systems. The main activities directed at these groups were providing printed educational materials, professional education, and media campaigns to raise awareness. Common barriers reported were lack of understanding about the link between HPV and cancer, requests to delay vaccination, difficulty completing the 3-dose vaccine series, and reluctance to discuss sexuality. HPV vaccination rates are far below those of other vaccinations administered to adolescents in Wisconsin. Our study showed that various local efforts were being made to increase HPV vaccination uptake; however, many barriers exist to initiation and completion of the vaccine series. Future interventions should address barriers and employ evidence-based strategies for increasing HPV vaccination rates.

  8. Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

    Directory of Open Access Journals (Sweden)

    J.C. Zhang

    2014-10-01

    Full Text Available Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs expressing human basic fibroblast growth factor (hbFGF. After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC, MSCs expressing hbFGF (hbFGF-MSC, MSC controls, and phosphate-buffered saline (PBS controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001; however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008 and microvessel density (P<0.001. Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.

  9. Increased Expression of microRNA-17 Predicts Poor Prognosis in Human Glioma

    Directory of Open Access Journals (Sweden)

    Shengkui Lu

    2012-01-01

    Full Text Available Aim. To investigate the clinical significance of microRNA-17 (miR-17 expression in human gliomas. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR analysis was used to characterize the expression patterns of miR-17 in 108 glioma and 20 normal brain tissues. The associations of miR-17 expression with clinicopathological factors and prognosis of glioma patients were also statistically analyzed. Results. Compared with normal brain tissues, miR-17 expression was significantly higher in glioma tissues (P<0.001. In addition, the increased expression of miR-17 in glioma was significantly associated with advanced pathological grade (P=0.006 and low Karnofsky performance score (KPS, P=0.01. Moreover, Kaplan-Meier survival and Cox regression analyses showed that miR-17 overexpression (P=0.008 and advanced pathological grade (P=0.02 were independent factors predicting poor prognosis for gliomas. Furthermore, subgroup analyses showed that miR-17 expression was significantly associated with poor overall survival in glioma patients with high pathological grades (for grade III~IV: P<0.001. Conclusions. Our data offer the convinced evidence that the increased expression of miR-17 may have potential value for predicting poor prognosis in glioma patients with high pathological grades, indicating that miR-17 may contribute to glioma progression and be a candidate therapeutic target for this disease.

  10. Prebiotics increase heme iron bioavailability and do not affect non-heme iron bioavailability in humans.

    Science.gov (United States)

    Weinborn, Valerie; Valenzuela, Carolina; Olivares, Manuel; Arredondo, Miguel; Weill, Ricardo; Pizarro, Fernando

    2017-05-24

    The aim of this study was to establish the effect of a prebiotic mix on heme and non-heme iron (Fe) bioavailability in humans. To this purpose, twenty-four healthy women were randomized into one of two study groups. One group ate one yogurt per day for 12 days with a prebiotic mix (prebiotic group) and the other group received the same yogurt but without the prebiotic mix (control group). Before and after the intake period, the subjects participated in Fe absorption studies. These studies used 55 Fe and 59 Fe radioactive isotopes as markers of heme Fe and non-heme Fe, respectively, and Fe absorption was measured by the incorporation of radioactive Fe into erythrocytes. The results showed that there were no significant differences in heme and non-heme Fe bioavailability in the control group. Heme Fe bioavailability of the prebiotic group increased significantly by 56% post-prebiotic intake. There were no significant differences in non-heme Fe bioavailability in this group. We concluded that daily consumption of a prebiotic mix increases heme Fe bioavailability and does not affect non-heme iron bioavailability.

  11. The Serengeti food web : Empirical quantification and analysis of topological changes under increasing human impact

    NARCIS (Netherlands)

    de Visser, Sara N.; Freymann, Bernd P.; Olff, Han

    P>1. To address effects of land use and human overexploitation on wildlife populations, it is essential to better understand how human activities have changed species composition, diversity and functioning. Theoretical studies modelled how network properties change under human-induced, non-random

  12. Adaptive increase in D3 dopamine receptors in the brain reward circuits of human cocaine fatalities.

    Science.gov (United States)

    Staley, J K; Mash, D C

    1996-10-01

    The mesolimbic dopaminergic system plays a primary role in mediating the euphoric and rewarding effects of most abused drugs. Chronic cocaine use is associated with an increase in dopamine neurotransmission resulting from the blockade of dopamine uptake and is mediated by the activation of dopamine receptors. Recent studies have suggested that the D3 receptor subtype plays a pivotal role in the reinforcing effects of cocaine. The D3 receptor-preferring agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) is a reinforcer in rhesus monkeys trained to self-administer cocaine, but not in cocainenaive monkeys. In vitro autoradiographic localization of [3H]-(+)-7-OH-DPAT binding in the human brain demonstrated that D3 receptors were prevalent and highly localized over the ventromedial sectors of the striatum. Pharmacological characterization of [3H]-(+)-7-OH-DPAT binding to the human nucleus accumbens demonstrated a rank order of potency similar to that observed for binding to the cloned D3 receptor expressed in transfected cell lines. Region-of-interest analysis of [3H]-(+)-7-OH-DPAT binding to the D3 receptor demonstrated a one- to threefold elevation in the number of binding sites over particular sectors of the striatum and substantia nigra in cocaine overdose victims as compared with age-matched and drug-free control subjects. The elevated number of [3H]-(+)-7-OH-DPAT binding sites demonstrates that adaptive changes in the D3 receptor in the reward circuitry of the brain are associated with chronic cocaine abuse. These results suggest that the D3 receptor may be a useful target for drug development of anticocaine medications.

  13. Lung Beractant Increases Free Cytosolic Levels of Ca2+ in Human Lung Fibroblasts.

    Directory of Open Access Journals (Sweden)

    Alejandro Guzmán-Silva

    Full Text Available Beractant, a natural surfactant, induces an antifibrogenic phenotype and apoptosis in normal human lung fibroblasts (NHLF. As intracellular Ca2+ signalling has been related to programmed cell death, we aimed to assess the effect of beractant on intracellular Ca2+ concentration ([Ca2+]i in NHLF in vitro. Cultured NHLF were loaded with Fura-2 AM (3 μM and Ca2+ signals were recorded by microfluorimetric techniques. Beractant causes a concentration-dependent increase in [Ca2+]i with a EC50 of 0.82 μg/ml. The application of beractant, at a concentration of 500 μg/ml, which has been shown to exert an apoptotic effect in human fibroblasts, elicited different patterns of Ca2+ signals in NHLF: a a single Ca2+ spike which could be followed by b Ca2+ oscillations, c a sustained Ca2+ plateau or d a sustained plateau overlapped by Ca2+ oscillations. The amplitude and pattern of Ca2+ transients evoked by beractant were dependent on the resting [Ca2+]i. Pharmacological manipulation revealed that beractant activates a Ca2+ signal through Ca2+ release from intracellular stores mediated by phospholipase Cβ (PLCβ, Ca2+ release from inositol 1,4,5-trisphosphate receptors (IP3Rs and Ca2+ influx via a store-operated pathway. Moreover, beractant-induced Ca2+ release was abolished by preventing membrane depolarization upon removal of extracellular Na+ and Ca2+. Finally, the inhibition of store-operated channels prevented beractant-induced NHLF apoptosis and downregulation of α1(I procollagen expression. Therefore, beractant utilizes SOCE to exert its pro-apoptotic and antifibrinogenic effect on NHLF.

  14. Increased endothelial apoptotic cell density in human diabetic erectile tissue--comparison with clinical data.

    Science.gov (United States)

    Costa, Carla; Soares, Raquel; Castela, Angela; Adães, Sara; Hastert, Véronique; Vendeira, Pedro; Virag, Ronald

    2009-03-01

    Erectile dysfunction (ED) is a common complication of diabetes. Endothelial cell (EC) dysfunction is one of the main mechanisms of diabetic ED. However, loss of EC integrity has never been assessed in human diabetic corpus cavernosum. To identify and quantify apoptotic cells in human diabetic and normal erectile tissue and to compare these results with each patient's clinical data and erection status. Eighteen cavernosal samples were collected, 13 from diabetics with ED and 5 from nondiabetic individuals. Cavernosal structure and cell proliferation status were evaluated by immunohistochemistry. Tissue integrity was assessed by terminal transferase dUTP nick end labeling assay, an index of apoptotic cell density (ACD) established and compared with each patient age, type of diabetes, arterial risk factors number, arterial/veno-occlusive disease, response to intracavernous vasoactive injections (ICI), and penile nitric oxide release test (PNORT). Establish an index of ACD and correlate those results with patient clinical data. Nondiabetic samples presented few scattered cells in apoptosis and an ACD of 7.15 +/- 0.44 (mean apoptotic cells/tissue area mm(2) +/- standard error). The diabetic group showed an increased ACD of 23.82 +/- 1.53, and apoptotic cells were located specifically at vascular sites. Rehabilitation of these endothelial lesions seemed impaired, as no evidence of EC proliferation was observed. Furthermore, higher ACD in diabetic individuals correlated to poor response to PNORT and to ICI. We provided evidence for the first time that loss of cavernosal EC integrity is a crucial event involved in diabetic ED. Furthermore, we were able to establish a threshold between ACD values and cavernosal tissue functionality, as assessed by PNORT and vasoactive ICI.

  15. Hyperglycosylated human chorionic gonadotropin does not increase progesterone production by luteinized granulosa cells.

    Science.gov (United States)

    Crochet, John R; Shah, Anish A; Schomberg, David W; Price, Thomas M

    2012-09-01

    Trophoblast-derived human chorionic gonadotropin (hCG) promotes corpus luteum progesterone (P4) production, and wide ranges of serum P4 levels are noted in various pregnancy outcomes, despite similar hCG concentrations. There are five unique biologically active hCG variants in human pregnancy urine, and previous studies of P4 production in response to hCG have used only preparations containing all isoforms. Understanding exactly which hCG variant is primarily responsible for stimulating corpus luteum steroidogenesis may have great clinical and diagnostic implications, including in the setting of ectopic pregnancy. Our objective was to delineate the role of the standard and hyperglycosylated (H)-hCG isoforms in stimulating P4 production by luteinized granulosa cells. Cell culture, ELISA, and fluorometric-based protein assays were done at Duke University Medical Center. Patients were anonymous oocyte donors. Cultured luteinized granulosa cells were treated with 0.25, 0.5, and 1.0 ng/ml total hCG, which contains all isoforms, purified standard hCG (37.1 kDa), and purified H-hCG (42.8 kDa). P4 produced per total cellular protein (nanograms per microgram) was measured via ELISA and fluorometric protein determination kits. Both total hCG (P = 0.0003) and purified standard hCG (P production. Purified H-hCG did not change the P4 produced per total cellular protein response (P value not significant). Standard hCG stimulated P4 production by cultured granulosa cells and likely supports corpus luteum function via interactions with the LH/hCG receptor. In contrast, H-hCG did not increase P4 production, which indicates a nonsteroidogenic role for this protein during early gestation.

  16. Illicit stimulant use in humans is associated with a long-term increase in tremor.

    Directory of Open Access Journals (Sweden)

    Stanley C Flavel

    Full Text Available Use of illicit stimulants such as methamphetamine, cocaine, and ecstasy is a significant health problem. The United Nations Office on Drugs and Crime estimates that 14-57 million people use stimulants each year. Chronic use of illicit stimulants can cause neurotoxicity in animals and humans but the long-term functional consequences are not well understood. Stimulant users self-report problems with tremor whilst abstinent. Thus, the aim of the current study was to investigate the long-term effect of stimulant use on human tremor during rest and movement. We hypothesized that individuals with a history of stimulant use would exhibit abnormally large tremor during rest and movement. Tremor was assessed in abstinent ecstasy users (n = 9; 22 ± 3 yrs and abstinent users of amphetamine-like drugs (n = 7; 33 ± 9 yrs and in two control groups: non-drug users (n = 23; 27 ± 8 yrs and cannabis users (n = 12; 24 ± 7 yrs. Tremor was measured with an accelerometer attached to the index finger at rest (30 s and during flexion and extension of the index finger (30 s. Acceleration traces were analyzed with fast-Fourier transform. During movement, tremor amplitude was significantly greater in ecstasy users than in non-drug users (frequency range 3.9-13.3 Hz; P<0.05, but was unaffected in cannabis users or users of amphetamine-like drugs. The peak frequency of tremor did not significantly differ between groups nor did resting tremor. In conclusion, abstinent ecstasy users exhibit an abnormally large tremor during movement. Further work is required to determine if the abnormality translates to increased risk of movement disorders in this population.

  17. Diversity loss with persistent human disturbance increases vulnerability to ecosystem collapse.

    Science.gov (United States)

    MacDougall, A S; McCann, K S; Gellner, G; Turkington, R

    2013-02-07

    Long-term and persistent human disturbances have simultaneously altered the stability and diversity of ecological systems, with disturbances directly reducing functional attributes such as invasion resistance, while eliminating the buffering effects of high species diversity. Theory predicts that this combination of environmental change and diversity loss increases the risk of abrupt and potentially irreversible ecosystem collapse, but long-term empirical evidence from natural systems is lacking. Here we demonstrate this relationship in a degraded but species-rich pyrogenic grassland in which the combined effects of fire suppression, invasion and trophic collapse have created a species-poor grassland that is highly productive, resilient to yearly climatic fluctuations, and resistant to invasion, but vulnerable to rapid collapse after the re-introduction of fire. We initially show how human disturbance has created a negative relationship between diversity and function, contrary to theoretical predictions. Fire prevention since the mid-nineteenth century is associated with the loss of plant species but it has stabilized high-yield annual production and invasion resistance, comparable to a managed high-yield low-diversity agricultural system. In managing for fire suppression, however, a hidden vulnerability to sudden environmental change emerges that is explained by the elimination of the buffering effects of high species diversity. With the re-introduction of fire, grasslands only persist in areas with remnant concentrations of native species, in which a range of rare and mostly functionally redundant plants proliferate after burning and prevent extensive invasion including a rapid conversion towards woodland. This research shows how biodiversity can be crucial for ecosystem stability despite appearing functionally insignificant beforehand, a relationship probably applicable to many ecosystems given the globally prevalent combination of intensive long-term land

  18. A sulfur amino acid-free meal increases plasma lipids in humans.

    Science.gov (United States)

    Park, Youngja; Le, Ngoc-Anh; Yu, Tianwei; Strobel, Fred; Gletsu-Miller, Nana; Accardi, Carolyn J; Lee, Kichun S; Wu, Shaoxiong; Ziegler, Thomas R; Jones, Dean P

    2011-08-01

    The content of sulfur amino acid (SAA) in a meal affects postprandial plasma cysteine concentrations and the redox potential of cysteine/cystine. Because such changes can affect enzyme, transporter, and receptor activities, meal content of SAA could have unrecognized effects on metabolism during the postprandial period. This pilot study used proton NMR ((1)H-NMR) spectroscopy of human plasma to test the hypothesis that dietary SAA content changes macronutrient metabolism. Healthy participants (18-36 y, 5 males and 3 females) were equilibrated for 3 d to adequate SAA, fed chemically defined meals without SAA for 5 d (depletion), and then fed isoenergetic, isonitrogenous meals containing 56 mg·kg(-1)·d(-1) SAA for 4.5 d (repletion). On the first and last day of consuming the chemically defined meals, a morning meal containing 60% of the daily food intake was given and plasma samples were collected over an 8-h postprandial time course for characterization of metabolic changes by (1)H-NMR spectroscopy. SAA-free food increased peak intensity in the plasma (1)H-NMR spectra in the postprandial period. Orthogonal signal correction/partial least squares-discriminant analysis showed changes in signals associated with lipids, some amino acids, and lactate, with notable increases in plasma lipid signals (TG, unsaturated lipid, cholesterol). Conventional lipid analyses confirmed higher plasma TG and showed an increase in plasma concentration of the lipoprotein lipase inhibitor, apoC-III. The results show that plasma (1)H-NMR spectra can provide useful macronutrient profiling following a meal challenge protocol and that a single meal with imbalanced SAA content alters postprandial lipid metabolism.

  19. Saturation in Phosphene Size with Increasing Current Levels Delivered to Human Visual Cortex.

    Science.gov (United States)

    Bosking, William H; Sun, Ping; Ozker, Muge; Pei, Xiaomei; Foster, Brett L; Beauchamp, Michael S; Yoshor, Daniel

    2017-07-26

    Electrically stimulating early visual cortex results in a visual percept known as a phosphene. Although phosphenes can be evoked by a wide range of electrode sizes and current amplitudes, they are invariably described as small. To better understand this observation, we electrically stimulated 93 electrodes implanted in the visual cortex of 13 human subjects who reported phosphene size while stimulation current was varied. Phosphene size increased as the stimulation current was initially raised above threshold, but then rapidly reached saturation. Phosphene size also depended on the location of the stimulated site, with size increasing with distance from the foveal representation. We developed a model relating phosphene size to the amount of activated cortex and its location within the retinotopic map. First, a sigmoidal curve was used to predict the amount of activated cortex at a given current. Second, the amount of active cortex was converted to degrees of visual angle by multiplying by the inverse cortical magnification factor for that retinotopic location. This simple model accurately predicted phosphene size for a broad range of stimulation currents and cortical locations. The unexpected saturation in phosphene sizes suggests that the functional architecture of cerebral cortex may impose fundamental restrictions on the spread of artificially evoked activity and this may be an important consideration in the design of cortical prosthetic devices. SIGNIFICANCE STATEMENT Understanding the neural basis for phosphenes, the visual percepts created by electrical stimulation of visual cortex, is fundamental to the development of a visual cortical prosthetic. Our experiments in human subjects implanted with electrodes over visual cortex show that it is the activity of a large population of cells spread out across several millimeters of tissue that supports the perception of a phosphene. In addition, we describe an important feature of the production of phosphenes by

  20. Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

    Directory of Open Access Journals (Sweden)

    Ding F

    2014-09-01

    Full Text Available Fengan Ding,1 Yiping Li,1 Jing Liu,1 Lei Liu,1 Wenmin Yu,1 Zhi Wang,1 Haifeng Ni,2 Bicheng Liu,2 Pingsheng Chen1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Institute of Nephrology, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China Background: Gold nanoparticles (GNPs can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells.Results: Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM to human renal proximal tubular cells (HK-2 by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the

  1. Leukemic transformation of normal murine erythroid progenitors: v- and c-ErbB act through signaling pathways activated by the EpoR and c-Kit in stress erythropoiesis

    NARCIS (Netherlands)

    von Lindern, M.; Deiner, E. M.; Dolznig, H.; Parren-van Amelsvoort, M.; Hayman, M. J.; Mullner, E. W.; Beug, H.

    2001-01-01

    Primary erythroid progenitors can be expanded by the synergistic action of erythropoietin (Epo), stem cell factor (SCF) and glucocorticoids. While Epo is required for erythropoiesis in general, glucocorticoids and SCF mainly contribute to stress erythropoiesis in hypoxic mice. This ability of normal

  2. Increased dopamine D1 receptor binding in the human mesocortical system following central cholinergic activation

    International Nuclear Information System (INIS)

    Fedi, M.; Berkovic, S.F.; Tochon-Danguy, H.J.; Reutens, D.C.

    2002-01-01

    Full text: The interaction between the cholinergic and dopaminergic system has been implicated in many pathological processes including, Alzheimer's disease, schizophrenia and drug addiction. Little is known about the control of dopamine (DA) release following central cholinergic activation in humans, but experimental studies suggest that endogenously released Acetylcholine (ACh) achieved by the administration of cholinesterase inhibitors, can increase dopamine efflux in different regions of the brain. This leads to the activation of different types of post-synaptic dopaminergic receptors which belong to the family of G-protein coupled receptors (GPCRs). A common paradigm of the GPCRs desensitization is that agonist-induced receptor signaling is rapidly attenuated by receptor internalisation. Several experiments have shown that the activation of Dl receptors in acute conditions leads, within minutes, to translocation of the receptor from the surface of the neurons to the endosomal compartment in the cytoplasm and increased receptor turnover. To assess changes in Dl receptor density following an intravenous infusion of the selective cholinesterase inhibitor physostigmine salicylate (PHY), we studied eleven normal subjects (10 male and 1 female, mean age 36.1 and 61617; 9.9) using [11C]-SCH23390 and PET The binding potential (BP) for SCH23390 was significantly (p 0.05). There was no statistically significant difference between baseline and physostigmine Kl ratio (p>0.05) suggesting that BP changes observed were not secondary to regional blood flow changes or to an order effect of the scans. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  3. Increased complement C1q level marks active disease in human tuberculosis.

    Directory of Open Access Journals (Sweden)

    Yi Cai

    Full Text Available BACKGROUND: Complement functions as an important host defense system and complement C5 and C7 have been implicated in immunopathology of tuberculosis. However, little is known about the role of other complement components in tuberculosis. METHODS: Complement gene expression in peripheral blood mononuclear cells of tuberculosis patients and controls were determined using whole genome transcriptional microarray assays. The mRNA and protein levels of three C1q components, C1qA, C1qB, and C1qC, were further validated by qRT-PCR and enzyme-linked immunosorbent assay, respectively. The percentages of C1q expression in CD14 positive cells were determined by flow cytometry. Finally, C1qC protein level was quantified in the pleural fluid of tuberculosis and non-tuberculosis pleurisy. RESULTS: C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α. CONCLUSIONS: C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy.

  4. Increased expression of argininosuccinate synthetase protein predicts poor prognosis in human gastric cancer

    Science.gov (United States)

    SHAN, YAN-SHEN; HSU, HUI-PING; LAI, MING-DERG; YEN, MENG-CHI; LUO, YI-PEY; CHEN, YI-LING

    2015-01-01

    Aberrant expression of argininosuccinate synthetase (ASS1, also known as ASS) has been found in cancer cells and is involved in the carcinogenesis of gastric cancer. The aim of the present study was to investigate the level of ASS expression in human gastric cancer and to determine the possible correlations between ASS expression and clinicopathological findings. Immunohistochemistry was performed on paraffin-embedded tissues to determine whether ASS was expressed in 11 of 11 specimens from patients with gastric cancer. The protein was localized primarily to the cytoplasm of cancer cells and normal epithelium. In the Oncomine cancer microarray database, expression of the ASS gene was significantly increased in gastric cancer tissues. To investigate the clinicopathological and prognostic roles of ASS expression, we performed western blot analysis of 35 matched specimens of gastric adenocarcinomas and normal tissue obtained from patients treated at the National Cheng Kung University Hospital. The ratio of relative ASS expression (expressed as the ASS/β-actin ratio) in tumor tissues to that in normal tissues was correlated with large tumor size (P=0.007) and with the tumor, node, metastasis (TNM) stage of the American Joint Committee on Cancer staging system (P=0.031). Patients whose cancer had increased the relative expression of ASS were positive for perineural invasion and had poor recurrence-free survival. In summary, ASS expression in gastric cancer was associated with a poor prognosis. Further study of mechanisms to silence the ASS gene or decrease the enzymatic activity of ASS protein has the potential to provide new treatments for patients with gastric cancer. PMID:25333458

  5. Pragmatic trial of an intervention to increase human papillomavirus vaccination in safety-net clinics

    Directory of Open Access Journals (Sweden)

    Maureen Sanderson

    2017-02-01

    Full Text Available Abstract Background Human papillomavirus (HPV infection has been causally linked to six cancers, and many disproportionately affect minorties. This study reports on the development and effectiveness of an intervention aimed at increasing HPV vaccine uptake among African American and Hispanic pediatric patients in safety-net clinics. Methods Formative research, community engagement, and theory guided development of the intervention. A clustered, non-randomized controlled pragmatic trial was conducted in four clinics providing healthcare for the underserved in Tennessee, U.S., with two intervention sites and two usual care sites. Patients aged 9-18 years (N = 408 and their mothers (N = 305 enrolled, with children clustered within families. The intervention consisted of two provider/staff training sessions and provision of patient education materials, consisting of a video/flyer promoting HPV vaccine. Medical records were reviewed before/after the initial visit and after 12 months. Results At the initial visit, provision of patient education materials and provider recommendation were higher at intervention sites versus usual care sites, and receipt of HPV vaccine was higher at intervention sites (45.4% versus 32.9% but not significantly after adjusting for patient’s age and mother’s education. Provider recommendation, but not education materials, increased the likelihood of vaccine receipt at the initial visit, although over one-third of intervention mothers cited the flyer/video as motivating vaccination. Completion of the 3-dose series at follow-up was lower in the intervention arm. Conclusions Future interventions should combine patient education, intensive provider/staff education, and patient reminders. Research should compare patient education focusing on HPV vaccine only versus all adolescent vaccines. Trial registration Retrospectively registered with ClinicalTrials.gov NCT02808832 , 9/12/16

  6. Eccentric rehabilitation exercise increases peritendinous type I collagen synthesis in humans with Achilles tendinosis.

    Science.gov (United States)

    Langberg, H; Ellingsgaard, H; Madsen, T; Jansson, J; Magnusson, S P; Aagaard, P; Kjaer, M

    2007-02-01

    It has been shown that 12 weeks of eccentric heavy resistance training can reduce pain in runners suffering from chronic Achilles tendinosis, but the mechanism behind the effectiveness of this treatment is unknown. The present study investigates the local effect of an eccentric training regime on elite soccer players suffering from chronic Achilles tendinosis on the turnover of the peritendinous connective tissue. Twelve elite male soccer players, of whom six suffered from unilateral tendinosis and six were healthy controls, participated in this study. All participants performed 12 weeks of heavy-resistance eccentric training apart from their regular training and soccer activity. Before and after the training period the tissue concentration of indicators of collagen turnover was measured by the use of the microdialysis technique. After training, collagen synthesis was increased in the initially injured tendon (n=6; carboxyterminal propeptide of type I collagen (PICP): pre 3.9+/-2.5 microg/L to post 19.7+/-5.4 microg/L, Ptendons in response to training (n=6; PICP: pre 8.3+/-5.2 microg/L to post 11.5+/-5.0 microg/L, P>0.05). Collagen degradation, measured as carboxyterminal telopeptide region of type I collagen (ICTP), was not affected by training neither in the injured nor in the healthy tendons. The clinical effect of the 12 weeks of eccentric training was determined by using a standardized loading procedure of the Achilles tendons showing a decrease in pain in all the chronic injured tendons (VAS before 44+/-9, after 13+/-9; Peccentric training regime. The present study demonstrates that chronically injured Achilles tendons respond to 12 weeks of eccentric training by increasing collagen synthesis rate. In contrast, the collagen metabolism in healthy control tendons seems not to be affected by eccentric training. These findings could indicate a relation between collagen metabolism and recovery from injury in human tendons.

  7. Epoetin Delta Reduces Oxidative Stress in Primary Human Renal Tubular Cells

    Directory of Open Access Journals (Sweden)

    Annelies De Beuf

    2010-01-01

    Full Text Available Erythropoietin (EPO exerts (renal tissue protective effects. Since it is unclear whether this is a direct effect of EPO on the kidney or not, we investigated whether EPO is able to protect human renal tubular epithelial cells (hTECs from oxidative stress and if so which pathways are involved. EPO (epoetin delta could protect hTECs against oxidative stress by a dose-dependent inhibition of reactive oxygen species formation. This protective effect is possibly related to the membranous expression of the EPO receptor (EPOR since our data point to the membranous EPOR expression as a prerequisite for this protective effect. Oxidative stress reduction went along with the upregulation of renoprotective genes. Whilst three of these, heme oxygenase-1 (HO-1, aquaporin-1 (AQP-1, and B-cell CLL/lymphoma 2 (Bcl-2 have already been associated with EPO-induced renoprotection, this study for the first time suggests carboxypeptidase M (CPM, dipeptidyl peptidase IV (DPPIV, and cytoglobin (Cygb to play a role in this process.

  8. 2-Nonenal newly found in human body odor tends to increase with aging.

    Science.gov (United States)

    Haze, S; Gozu, Y; Nakamura, S; Kohno, Y; Sawano, K; Ohta, H; Yamazaki, K

    2001-04-01

    Human body odor consists of various kinds of odor components. Here, we have investigated the changes in body odor associated with aging. The body odor of subjects between the ages of 26 and 75 was analyzed by headspace gas chromatography/mass spectrometry. 2-Nonenal, an unsaturated aldehyde with an unpleasant greasy and grassy odor, was detected only in older subjects (40 y or older). Furthermore, analysis of skin surface lipids revealed that omega7 unsaturated fatty acids and lipid peroxides also increased with aging and that there were positive correlations between the amount of 2-nonenal in body odor and the amount of omega7 unsaturated fatty acids or lipid peroxides in skin surface lipids. 2-Nonenal was generated only when omega7 unsaturated fatty acids were degraded by degradation tests in which some main components of skin surface lipids were oxidatively decomposed using lipid peroxides as initiator of an oxidative chain reaction. The results indicate that 2-nonenal is generated by the oxidative degradation of omega7 unsaturated fatty acids, and suggest that 2-nonenal may be involved in the age-related change of body odor.

  9. Significance of Increasing n-3 PUFA Content in Pork on Human Health.

    Science.gov (United States)

    Ma, Xianyong; Jiang, Zongyong; Lai, Chaoqiang

    2016-01-01

    Evidence for the health-promoting effects of food rich in n-3 polyunsaturated fatty acids (n-3 PUFA) is reviewed. Pork is an important meat source for humans. According to a report by the US Department of Agriculture ( http://www.ers.usda.gov/topics ), the pork consumption worldwide in 2011 was about 79.3 million tons, much higher than that of beef (48.2 million tons). Pork also contains high levels of unsaturated fatty acids relative to ruminant meats (Enser, M., Hallett, K., Hewett, B., Fursey, G. A. J. and Wood, J. D. (1996) . Fatty acid content and composition of English beef, lamb, and pork at retail. Meat Sci. 44:443-458). The available literature indicates that the levels of eicosatetraenoic and docosahexaenoic in pork may be increased by fish-derived or linseed products, the extent of which being dependent on the nature of the supplementation. Transgenic pigs and plants show promise with high content of n-3 PUFA and low ratio of n-6/n-3 fatty acids in their tissues. The approaches mentioned for decreasing n-6/n-3 ratios have both advantages and disadvantages. Selected articles are critically reviewed and summarized.

  10. Increasing trend of wearables and multimodal interface for human activity monitoring: A review.

    Science.gov (United States)

    Kumari, Preeti; Mathew, Lini; Syal, Poonam

    2017-04-15

    Activity recognition technology is one of the most important technologies for life-logging and for the care of elderly persons. Elderly people prefer to live in their own houses, within their own locality. If, they are capable to do so, several benefits can follow in terms of society and economy. However, living alone may have high risks. Wearable sensors have been developed to overcome these risks and these sensors are supposed to be ready for medical uses. It can help in monitoring the wellness of elderly persons living alone by unobtrusively monitoring their daily activities. The study aims to review the increasing trends of wearable devices and need of multimodal recognition for continuous or discontinuous monitoring of human activity, biological signals such as Electroencephalogram (EEG), Electrooculogram (EOG), Electromyogram (EMG), Electrocardiogram (ECG) and parameters along with other symptoms. This can provide necessary assistance in times of ominous need, which is crucial for the advancement of disease-diagnosis and treatment. Shared control architecture with multimodal interface can be used for application in more complex environment where more number of commands is to be used to control with better results in terms of controlling. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Increase of {sup 210}Po levels in human semen fluid after mussel ingestion

    Energy Technology Data Exchange (ETDEWEB)

    Kelecom, Alphonse, E-mail: lararapls@hotmail.co [Laboratory of Radiobiology and Radiometry-LARARA-PLS, Universidade Federal Fluminense, P.O.Box 100.436, 24001-970 Niteroi, RJ (Brazil); Programs in Environmental Science and Marine Biology, Universidade Federal Fluminense, Niteroi, RJ (Brazil); Gouvea, Rita de Cassia dos Santos [Laboratory of Radiobiology and Radiometry-LARARA-PLS, Universidade Federal Fluminense, P.O.Box 100.436, 24001-970 Niteroi, RJ (Brazil)

    2011-05-15

    Polonium-210 ({sup 210}Po) radioactive concentrations were determined in human semen fluid of vasectomized non-smoker volunteers. The {sup 210}Po levels ranged from 0.10 to 0.39 mBq g{sup -1} (mean: 0.23 {+-} 0.08 mBq g{sup -1}). This value decreased to 0.10 {+-} 0.02 mBq g{sup -1} (range from 0.07 to 0.13 mBq g{sup -1}) after two weeks of a controlled diet, excluding fish and seafood. Then, volunteers ate during a single meal 200 g of the cooked mussel Perna perna L., and {sup 210}Po levels were determined again, during ten days, in semen fluid samples collected every morning. Volunteers continued with the controlled diet and maintained sexual abstinence through the period of the experiment. A 300% increase of {sup 210}Po level was observed the day following mussel consumption, with a later reduction, such that the level returned to near baseline by day 4.

  12. Analysis and Comparison of Shading Strategies to Increase Human Thermal Comfort in Urban Areas

    Directory of Open Access Journals (Sweden)

    Ivan Lee

    2018-03-01

    Full Text Available With the expected increase in warmer conditions caused by climate change, heat-related illnesses are becoming a more pressing issue. One way that humans can protect themselves from this is to seek shade. The design of urban spaces can provide individuals with a variety of ways to obtain this shade. The objective of this study was to perform a detailed evaluation and comparison of three shading strategies that could be used in an urban environment: shade from a building, from a tree, and from an umbrella. This was done through using field measurements to calculate the impact of each strategy on a thermal comfort index (Comfort Formula (COMFA in two urban settings during sunny days of the summer of 2013 and 2014 in London, Canada. Building shade was found to be the most effective cooling strategy, followed by the tree strategy and the umbrella strategy. As expected, the main determinant of this ranking was a strategy’s ability to block incoming shortwave radiation. Further analysis indicated that changes in the convective loss of energy and in longwave radiation absorption had a smaller impact that caused variations in the strategy effectiveness between settings. This suggests that under non-sunny days, these rankings could change.

  13. Assessing the sensitivity of human skin hyperspectral responses to increasing anemia severity levels

    Science.gov (United States)

    Baranoski, Gladimir V. G.; Dey, Ankita; Chen, Tenn F.

    2015-09-01

    Anemia is a prevalent medical condition that seriously affects millions of people all over the world. In many regions, not only its initial detection but also its monitoring are hindered by limited access to laboratory facilities. This situation has motivated the development of a wide range of optical devices and procedures to assist physicians in these tasks. Although noticeable progress has been achieved in this area, the search for reliable, low-cost, and risk-free solutions still continues, and the strengthening of the knowledge base about this disorder and its effects is essential for the success of these initiatives. We contribute to these efforts by closely examining the sensitivity of human skin hyperspectral responses (within and outside the visible region of the light spectrum) to reduced hemoglobin concentrations associated with increasing anemia severity levels. This investigation, which involves skin specimens with distinct biophysical and morphological characteristics, is supported by controlled in silico experiments performed using a predictive light transport model and measured data reported in the biomedical literature. We also propose a noninvasive procedure to be employed in the monitoring of this condition at the point-of-care.

  14. Online Citizen Science with Clickworkers & MRO HiRISE E/PO

    Science.gov (United States)

    Gulick, V. C.; Deardorff, G.; Kanefsky, B.; HiRISE Science Team

    2010-12-01

    The High-Resolution Imaging Science Experiment’s E/PO has fielded several online citizen science projects. Our efforts are guided by HiRISE E/PO’s philosophy of providing innovative opportunities for students and the public to participate in the scientific discovery process. HiRISE Clickworkers, a follow-on to the original Clickworkers crater identification and size diameter marking website, provides an opportunity for the public to identify & mark over a dozen landform feature types in HiRISE images, including dunes, gullies, patterned ground, wind streaks, boulders, craters, layering, volcanoes, etc. In HiRISE Clickworkers, the contributor views several sample images showing variations of different landforms, and simply marks all the landform types they could spot while looking at a small portion of a HiRISE image. Contributors then submit their work & once validated by comparison to the output of other participants, results are then added to geologic feature databases. Scientists & others will eventually be able to query these databases for locations of particular geologic features in the HiRISE images. Participants can also mark other features that they find intriguing for the HiRISE camera to target. The original Clickworkers website pilot study ran from November 2000 until September 2001 (Kanefsky et al., 2001, LPSC XXXII). It was among the first online Citizen Science efforts for planetary science. In its pilot study, we endeavored to answer two questions: 1) Was the public willing & able to help science, & 2) Can the public produce scientifically useful results? Since its inception over 3,500,000 craters have been identified, & over 350,000 of these craters have been classified. Over 2 million of these craters were marked on Viking Orbiter image mosaics, nearly 800,000 craters were marked on Mars Orbiter Camera (MOC) images. Note that these are not counts of distinct craters. For example, each crater in the Viking orbiter images was counted by about 50

  15. Planting local seed for growth to nationwide E/PO efforts

    Science.gov (United States)

    Fox, N.; Beisser, K.; Mendez, F.; Cockrell, D.; Wilhide, B.

    The Johns Hopkins University Applied Physics Laboratory (JHU/APL) is the home to hundreds of scientists and engineers, all involved in research, design and implementation of space missions. Many of these people actively seek out ways to raise awareness and interest in the local community by visiting schools, giving public lectures and supporting events held at the laboratory. During the past few years, APL has begun to foster a number of firm partnerships with organizations to further these community opportunities and provide a test bed for both formal and informal education activities through the Space Department E/PO office One of our ongoing partnerships is with the Maryland Science Center in Baltimore. A continual challenge faced by museums is how to stay current and allow visitors to experience the immediacy and excitement of scientific discovery. To help meet these challenges, the Maryland Science Center houses "SpaceLink", the Nation's first space, science and astronomy update center. Part media center, part discovery room, and part newsroom, the exhibit is a multi-purpose Professional Development Site for educators and a "classroom of the future" for K 12 students. APL scientists and- engineers regularly support SpaceLink's flexible programming, including scientist in residence, monthly credited seminars for educators (Teachers' Thursdays), a menu of Classroom Programs on request, Distance Learning Teacher Presentations, and special Live Events to highlight mission milestones and space-related anniversaries. This allows the guest scientists and engineers to interact directly with the public. These events also compliment the APL exhibits housed at the Science Center. JHU/APL offers an exciting environment for the study of applications in space by hosting the annual Maryland Summer Center for Space Science sponsored by the Maryland State Department of Education. Rising 6t h and 7t h grade students learn to harness the power of technology and keep pace with

  16. Increased levels of IgG antibodies against human HSP60 in patients with spondyloarthritis

    DEFF Research Database (Denmark)

    Hjelholt, Astrid; Carlsen, Thomas Gelsing; Deleuran, Bent Winding

    2013-01-01

    Introduction: Spondyloarthritis (SpA) comprises a heterogeneous group of inflammatory diseases, with strong association to human leukocyte antigen (HLA)-B27. SpA is suggested triggered by bacterial infection, and bacterial heat shock protein (HSP) seems to be a strong T cell antigen. Since...... against human HSP60, but not antibodies against bacterial HSP60, were elevated in the SpA group compared with the control group. Association between IgG3 antibodies against human HSP60 and BASMI was shown in HLA-B27+ patients. Only weak correlation between antibodies against bacterial and human HSP60...... was seen, and there was no indication of cross-reaction. Conclusion: These results suggest that antibodies against human HSP60 is associated with SpA, however, the theory that antibodies against human HSP60 is a specific part of the aetiology, through cross-reaction to bacterial HSP60, cannot be supported...

  17. Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation.

    Science.gov (United States)

    Emelyanova, Larisa; Ashary, Zain; Cosic, Milanka; Negmadjanov, Ulugbek; Ross, Gracious; Rizvi, Farhan; Olet, Susan; Kress, David; Sra, Jasbir; Tajik, A Jamil; Holmuhamedov, Ekhson L; Shi, Yang; Jahangir, Arshad

    2016-07-01

    Mitochondria are critical for maintaining normal cardiac function, and a deficit in mitochondrial energetics can lead to the development of the substrate that promotes atrial fibrillation (AF) and its progression. However, the link between mitochondrial dysfunction and AF in humans is still not fully defined. The aim of this study was to elucidate differences in the functional activity of mitochondrial oxidative phosphorylation (OXPHOS) complexes and oxidative stress in right atrial tissue from patients without (non-AF) and with AF (AF) who were undergoing open-heart surgery and were not significantly different for age, sex, major comorbidities, and medications. The overall functional activity of the electron transport chain (ETC), NADH:O2 oxidoreductase activity, was reduced by 30% in atrial tissue from AF compared with non-AF patients. This was predominantly due to a selective reduction in complex I (0.06 ± 0.007 vs. 0.09 ± 0.006 nmol·min(-1)·citrate synthase activity(-1), P = 0.02) and II (0.11 ± 0.012 vs. 0.16 ± 0.012 nmol·min(-1)·citrate synthase activity(-1), P = 0.003) functional activity in AF patients. Conversely, complex V activity was significantly increased in AF patients (0.21 ± 0.027 vs. 0.12 ± 0.01 nmol·min(-1)·citrate synthase activity(-1), P = 0.005). In addition, AF patients exhibited a higher oxidative stress with increased production of mitochondrial superoxide (73 ± 17 vs. 11 ± 2 arbitrary units, P = 0.03) and 4-hydroxynonenal level (77.64 ± 30.2 vs. 9.83 ± 2.83 ng·mg(-1) protein, P = 0.048). Our findings suggest that AF is associated with selective downregulation of ETC activity and increased oxidative stress that can contribute to the progression of the substrate for AF. Copyright © 2016 the American Physiological Society.

  18. Overexpression of 15-lipoxygenase-1 in PC-3 human prostate cancer cells increases tumorigenesis.

    Science.gov (United States)

    Kelavkar, U P; Nixon, J B; Cohen, C; Dillehay, D; Eling, T E; Badr, K F

    2001-11-01

    The effect of overexpression of 15-lipoxygenase-1 (15-LO-1) was studied in the human prostate cancer cell line, PC-3. Stable PC-3 cell lines were generated by transfection with 15-LO-1-sense (15-LOS), 15-LO-1-antisense (15-LOAS) or vector (Zeo) and selection with Zeocin. After characterization by RT-PCR, western and HPLC, a PC3-15LOS clone was selected that possessed 10-fold 15-LO-1 enzyme activity compared with parental PC-3 cells. The PC3-15LOAS clone displayed little or no 15-LO-1 activity. These PC-3 cell lines were characterized for properties of tumorigenesis. The proliferation rates of the cell lines were as follows: PC3-15LOS > PC-3 = PC3-Zeo > PC3-15LOAS. Addition of a specific 15-LO-1 inhibitor, PD146176, caused a dose-dependent inhibition of proliferation in vitro. Overexpression of 15-LO-1 also caused [(3)H]thymidine incorporation to increase by 4.0-fold (P < 0.01). Compared with parental and PC-3-Zeo cells, PC3-15LOS enhanced whereas PC3-15LOAS reduced the ability of PC-3 cells to grow in an anchorage-independent manner, as assessed by colony formation in soft agar. These data suggested a pro-tumorigenic role for 15-LO-1 in PC-3 cells in vitro. Therefore, to clarify the role of 15-LO-1 in vivo, the effect of 15-LO-1 expression on the growth of tumors in nude mice was investigated. The PC-3 cell lines were inoculated subcutaneously into athymic nude mice. The frequency of tumor formation was increased and the sizes of the tumors formed were much larger in the PC3-15LOS compared with PC3-15LOAS, parental PC-3 and PC-3-Zeo cells. Immunohistochemistry for 15-LO-1 confirmed expression throughout the duration of the experiment. The expression of factor VIII, an angiogenesis marker, in tumor sections was increased in tumors derived from PC3-15LOS cells and decreased in those from PC3-15LOAS cells compared with tumors from parental or Zeo cells. These data further supported the evaluation by ELISA of vascular endothelial growth factor (VEGF) secretion by PC-3

  19. Erythropoietin Action in Stress Response, Tissue Maintenance and Metabolism

    Directory of Open Access Journals (Sweden)

    Yuanyuan Zhang

    2014-06-01

    Full Text Available Erythropoietin (EPO regulation of red blood cell production and its induction at reduced oxygen tension provides for the important erythropoietic response to ischemic stress. The cloning and production of recombinant human EPO has led to its clinical use in patients with anemia for two and half decades and has facilitated studies of EPO action. Reports of animal and cell models of ischemic stress in vitro and injury suggest potential EPO benefit beyond red blood cell production including vascular endothelial response to increase nitric oxide production, which facilitates oxygen delivery to brain, heart and other non-hematopoietic tissues. This review discusses these and other reports of EPO action beyond red blood cell production, including EPO response affecting metabolism and obesity in animal models. Observations of EPO activity in cell and animal model systems, including mice with tissue specific deletion of EPO receptor (EpoR, suggest the potential for EPO response in metabolism and disease.

  20. Optimising land use and consumption of livestock products in the human diet with an increasing human population in the Netherlands

    NARCIS (Netherlands)

    Kernebeek, van H.R.J.; Oosting, S.J.; Ittersum, van M.K.; Boer, de I.J.M.

    2014-01-01

    Land use related to food production is generally quantified using product-based life cycle assessments. We, however, quantified land use of diet scenarios with a land use optimization model. Energy and protein requirement of human populations, varying from 15 to 30 mil-lion people, were met with the

  1. The influence of periodic increases of human activity on crepuscular and nocturnal mammals: Testing the weekend effect.

    Science.gov (United States)

    Nix, Joshua H; Howell, Ryan G; Hall, Lucas K; McMillan, Brock R

    2018-01-01

    Human recreation can negatively affect wildlife, particularly on weekends when human activity is highest (i.e., the weekend effect). Much of what we understand about the weekend effect is based on research conducted on diurnal species, which have greater temporal overlap with humans. Because nocturnal species generally avoid times when humans are active, they are likely less affected by anthropogenic activity on weekends. Our objective was to test the weekend effect in relation to the degree of nocturnality of mammals in a recreational area. We predicted that as nocturnality increased, the effect of human activity would decrease. To address our objective, we placed 50 remote cameras along the Diamond Fork River in Utah from January to June 2015. We found that three out of the four focal species supported our predictions. Mule deer (crepuscular) reduced activity throughout our entire study area during weekends and avoided campgrounds. Beavers and mountain lions (both nocturnal) did not negatively respond to increased human activity. Raccoons (nocturnal) reduced activity during weekends, but only within campground areas. Our findings indicate that as the temporal overlap increases between wildlife and humans, so does the influence that humans have on wildlife. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Do Colleges and Universities Increase Their Region's Human Capital? Staff Report No. 401

    Science.gov (United States)

    Abel, Jaison R.; Deitz, Richard

    2009-01-01

    We investigate whether the degree production and research and development (R&D) activities of colleges and universities are related to the amount and types of human capital present in the metropolitan areas where the institutions are located. We find that degree production has only a small positive relationship with local stocks of human capital,…

  3. Human mast cell neutral proteases generate modified LDL particles with increased proteoglycan binding.

    Science.gov (United States)

    Maaninka, Katariina; Nguyen, Su Duy; Mäyränpää, Mikko I; Plihtari, Riia; Rajamäki, Kristiina; Lindsberg, Perttu J; Kovanen, Petri T; Öörni, Katariina

    2018-04-13

    Subendothelial interaction of LDL with extracellular matrix drives atherogenesis. This interaction can be strengthened by proteolytic modification of LDL. Mast cells (MCs) are present in atherosclerotic lesions, and upon activation, they degranulate and release a variety of neutral proteases. Here we studied the ability of MC proteases to cleave apoB-100 of LDL and affect the binding of LDL to proteoglycans. Mature human MCs were differentiated from human peripheral blood-derived CD34 + progenitors in vitro and activated with calcium ionophore to generate MC-conditioned medium. LDL was incubated in the MC-conditioned medium or with individual MC proteases, and the binding of native and modified LDL to isolated human aortic proteoglycans or to human atherosclerotic plaques ex vivo was determined. MC proteases in atherosclerotic human coronary artery lesions were detected by immunofluorescence and qPCR. Activated human MCs released the neutral proteases tryptase, chymase, carboxypeptidase A3, cathepsin G, and granzyme B. Of these, cathepsin G degraded most efficiently apoB-100, induced LDL fusion, and enhanced binding of LDL to isolated human aortic proteoglycans and human atherosclerotic lesions ex vivo. Double immunofluoresence staining of human atherosclerotic coronary arteries for tryptase and cathepsin G indicated that lesional MCs contain cathepsin G. In the lesions, expression of cathepsin G correlated with the expression of tryptase and chymase, but not with that of neutrophil proteinase 3. The present study suggests that cathepsin G in human atherosclerotic lesions is largely derived from MCs and that activated MCs may contribute to atherogenesis by enhancing LDL retention. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Trace metals in Antarctica related to climate change and increasing human impact.

    Science.gov (United States)

    Bargagli, R

    2000-01-01

    Metals are natural constituents of the abiotic and biotic components of all ecosystems, and under natural conditions they are cycled within and between the geochemical spheres--the atmosphere, lithosphere, hydrosphere, and biosphere--at quite steady fluxes. In the second half of the twentieth century, the huge increase in energy and mineral consumption determined anthropogenic emissions of several metals exceeding those from natural sources, e.g., volcanoes and windborne soil particles. In the Northern Hemisphere, the biogeochemical cycles of Pb, Cd, Zn, Cu, and other metals were significantly altered, even in Arctic regions. On the contrary, available data on trace metal concentrations in abiotic matrices from continental Antarctica, summarized in this review, suggest that the biogeochemical cycle of Pb is probably the only one that has been significantly altered by anthropogenic emissions in Antarctica and elsewhere in the Southern Hemisphere, especially in the period 1950-1975. Environmental contamination by other metals from anthropogenic sources in Antarctica itself can generally only be detected in snow samples taken within a range of a few kilometers or several hundred meters from scientific stations. Local metal pollution from human activities in Antarctica may compromise studies aimed at assessing the biogeochemical cycle of trace elements and the effects of global climate change. Thus, this review focuses on concentrations of metals in atmospheric particulate, snow, surface soils, and freshwater from the Antarctic continent and surface sediments and seawater from the Southern Ocean, which can plausibly be regarded as global background values of trace elements. These baselines are also necessary in view of the construction of new stations, the expansion of existing facilities to support research, and the growth of tourism and fisheries. Despite difficulties in making comparisons with data from other remote areas of the world, concentrations of trace metals

  5. Increased storage and secretion of phosphatidylcholines by senescent human peritoneal mesothelial cells.

    Science.gov (United States)

    Bartosova, Maria; Rudolf, Andras; Pichl, Sebastian; Schmidt, Kathrin; Okun, Jürgen G; Straub, Beate K; Rutkowski, Rafael; Witowski, Janusz; Schmitt, Claus P

    2016-08-01

    Human peritoneal mesothelial cells (HPMC) secrete phosphatidylcholines (PC) which form a lipid bilayer lining the peritoneum. They prevent frictions and adhesions and act as a barrier to the transport of water-soluble solutes while permitting water flux. PC may play an essential role in peritoneal integrity and function, the role of PD induced HPMC senescence on PC homeostasis, however, is unknown. HPMC cell lines were isolated from four non-uremic patients. Expression of the three PC synthesis genes (rt-PCR), and cellular storage and secretion of PC (ESI-mass-spectrometry) were analyzed in young and senescent HPMC (>Hayflick-limit). Senescent cells displayed significantly altered morphology; flow cytometry demonstrated extensive staining for senescence-associated beta galactosidase. Nine different PC were detected in HPMC with palmitoyl-myristoyl phosphatidylcholine (PMPC) being most abundant. In senescent HPMC mRNA expression of the three key PC synthesis genes was 1.5-, 2.4- and 6-fold increased as compared to young HPMC, with the latter, phosphatidylcholine cytidylyltransferase, being rate limiting. Intracellular storage of the nine PC was 75-450 % higher in senescent vs. young HPMC, PC secretion rates were 100-300 % higher. Intracellular PC concentrations were not correlated with the PC secretion rates. Electron microscopy demonstrated lamellar bodies, the primary storage site of PC, in senescent but not in young cells. Senescent HPMC store and secrete substantially more PC than young cells. Our findings indicate a novel protective mechanism, which should counteract peritoneal damage induced by chronic exposure to PD fluids.

  6. Increasing our Understanding of Human Cognition Through the Study of Fragile X Syndrome

    Science.gov (United States)

    Denise, Cook; Erin, Nuro; Keith, K. Murai

    2014-01-01

    Fragile X Syndrome (FXS) is considered the most common form of inherited intellectual disability. It is caused by reductions in the expression level or function of a single protein, the Fragile X Mental Retardation Protein (FMRP), a translational regulator which binds to approximately 4% of brain messenger RNAs. Accumulating evidence suggests that FXS is a complex disorder of cognition, involving interactions between genetic and environmental influences, leading to difficulties in acquiring key life skills including motor skills, language, and proper social behaviors. Since many FXS patients also present with one or more features of autism spectrum disorders (ASDs), insights gained from studying the monogenic basis of FXS could pave the way to a greater understanding of underlying features of multigenic ASDs. Here we present an overview of the FXS and FMRP field with the goal of demonstrating how loss of a single protein involved in translational control affects multiple stages of brain development and leads to debilitating consequences on human cognition. We also focus on studies which have rescued or improved FXS symptoms in mice using genetic or therapeutic approaches to reduce protein expression. We end with a brief description of how deficits in translational control are implicated in FXS and certain cases of ASDs, with many recent studies demonstrating that ASDs are likely caused by increases or decreases in the levels of certain key synaptic proteins. The study of FXS and its underlying single genetic cause offers an invaluable opportunity to study how a single gene influences brain development and behavior. © 2013 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 74: 147–177, 2014 PMID:23723176

  7. Human Adenovirus 36 Infection Increased the Risk of Obesity: A Meta-Analysis Update.

    Science.gov (United States)

    Xu, Mei-Yan; Cao, Bing; Wang, Dong-Fang; Guo, Jing-Hui; Chen, Kai-Li; Shi, Mai; Yin, Jian; Lu, Qing-Bin

    2015-12-01

    Human adenovirus 36 (HAdV-36), as the key pathogen, was supposed and discussed to be associated with obesity. We searched the references on the association between HAdV-36 infection and obesity with the different epidemiological methods, to explore the relationship with a larger sample size by meta-analysis and compare the differences of epidemiological methods and population subsets by the subgroup analyses.We conducted literature search on the association between HAdV-36 infections and obesity in English or Chinese published up to July 1, 2015. The primary outcome was the HAdV-36 infection rate in the obese and lean groups; the secondary outcomes were the BMI level and BMI z-score in the HAdV-36 positive and negative groups. The pooled odds ratio (OR) was calculated for the primary outcome; the standardized mean differences (SMDs) were calculated for the secondary and third outcomes. Prediction interval (PI) was graphically presented in the forest plot of the random effect meta-analyses. Metaregression analysis and subgroup analysis were performed.Finally 24 references with 10,191 study subjects were included in the meta-analysis. The obesity subjects were more likely to be infected with HAdV-36 compared to the lean controls (OR = 2.00; 95%CI: 1.46, 2.74; PI: 0.59, 6.76; P infection for obesity were 1.77 (95%CI: 1.19, 2.63; PI: 0.44, 7.03; P = 0.005) and 2.26 (95%CI: 1.67, 3.07; PI: 1.45, 3.54; P SMD of BMI was 0.28 (95% CI: 0.08, 0.47; PI: -0.53, 1.08; P = 0.006) in the HAdV-36 positive subjects with a high heterogeneity (I = 86.5%; P infection was higher than those without HAdV-36 infection (SMD = 0.19; 95%CI: -0.31, 0.70; PI: -2.10, 2.49), which had no significantly statistical difference (P = 0.453).HAdV-36 infection increased the risk of obesity. HAdV-36 also increased the risk of weight gain in adults, which was not observed in children.

  8. Clinical significance of measurement of plasma relevant cytokines (GM-CSF, IL-2, TPO, EPO) levels in patients with aplastic anemia

    International Nuclear Information System (INIS)

    Yu Tintin

    2006-01-01

    Objective: To investigate the role of relevant cytokines in the development and pathogenesis of aplastic anemia. Methods: Plasma GM-CSF, IL-2, TPO (with RIA) and EPO (with CLIA) contents were measured in 100 patients (acute 43, chronic 57) with aplastic anemia and 50 controls. Complete blood count was also performed in all these subjects. Results: The peripheral RBC, WBC, platelet counts and GM-CSF contents were significantly lower in the patients with aplastic anemia than those in the controls (P<0.05), while the IL-2, EPO and TPO contents were significantly higher in the patients (P<0.05). GM-CSF contents were positively correlated with the WBC numbers. EPO contents were negatively correlated with the RBC counts and TPO contents were correlated (negatively) with the platelet counts. Conclusion: There was correlationship between each blood elements (WBC, RBC, platelet) and its corresponding cytokine (GS-CSF, EPO, TPO respectively). IL-2 contents were not correlated with WBC counts. (authors)

  9. Effect of mild hypothermia combined with VitC and EPO therapy on target organ damage in children with neonatal asphyxia

    Directory of Open Access Journals (Sweden)

    Shu-Yun Wang

    2017-10-01

    Full Text Available Objective: To study the effect of mild hypothermia combined with vitamin C (VitC and erythropoietin (EPO therapy on target organ damage in children with neonatal asphyxia. Methods: Children with neonatal asphyxia who were treated in Taihe County People’s Hospital between April 2014 and February 2017 were selected and randomly divided into two groups, mild hypothermia group received mild hypothermia combined VitC and EPO therapy, and control group received VitC and EPO therapy. Serum levels of of target organ damage markers, oxidative stress indexes and apoptosis indexes were measured before treatment as well as 3 d and 7 d after treatment. Results: 3 d and 7 d after treatment, serum NSE, H-FABP, cTnI, CysC, MDA, Caspase-3, PDCD5, sFas and sFasL levels of both groups of children were significantly lower than those before treatment while TAS, SOD, GSH and Bcl-2 levels were significantly higher than those before treatment, and serum NSE, H-FABP, cTnI, CysC, MDA, Caspase-3, PDCD5, sFas and sFasL levels of mild hypothermia group were significantly lower than those of control group while TAS, SOD, GSH and Bcl-2 levels were significantly higher than those of control group. Conclusion: Mild hypothermia combined with VitC and EPO therapy can reduce the target organ damage of children with neonatal asphyxia by inhibiting oxidative stress and apoptosis.

  10. The EPOS-CC Score: An Integration of Independent, Tumor- and Patient-Associated Risk Factors to Predict 5-years Overall Survival Following Colorectal Cancer Surgery.

    Science.gov (United States)

    Haga, Yoshio; Ikejiri, Koji; Wada, Yasuo; Ikenaga, Masakazu; Koike, Shoichiro; Nakamura, Seiji; Koseki, Masato

    2015-06-01

    Surgical audit is an essential task for the estimation of postoperative outcome and comparison of quality of care. Previous studies on surgical audits focused on short-term outcomes, such as postoperative mortality. We propose a surgical audit evaluating long-term outcome following colorectal cancer surgery. The predictive model for this audit is designated as 'Estimation of Postoperative Overall Survival for Colorectal Cancer (EPOS-CC)'. Thirty-one tumor-related and physiological variables were prospectively collected in 889 patients undergoing elective resection for colorectal cancer between April 2005 and April 2007 in 16 Japanese hospitals. Postoperative overall survival was assessed over a 5-years period. The EPOS-CC score was established by selecting significant variables in a uni- and multivariate analysis and allocating a risk-adjusted multiplication factor to each variable using Cox regression analysis. For validation, the EPOS-CC score was compared to the predictive power of UICC stage. Inter-hospital variability of the observed-to-estimated 5-years survival was assessed to estimate quality of care. Among the 889 patients, 804 (90%) completed the 5-years follow-up. Univariate analysis displayed a significant correlation with 5-years survival for 14 physiological and nine tumor-related variables (p model for the prediction of survival. Risk-adjusted multiplication factors between 1.5 (distant metastasis) and 0.16 (serum sodium level) were accorded to the different variables. The predictive power of EPOS-CC was superior to the one of UICC stage; area under the curve 0.87, 95% CI 0.85-0.90 for EPOS-CC, and 0.80, 0.76-0.83 for UICC stage, p < 0.001. Quality of care did not differ between hospitals. The EPOS-CC score including the independent variables age, performance status, serum sodium level, TNM stage, and lymphatic invasion is superior to the UICC stage in the prediction of 5-years overall survival. This higher accuracy might be explained by the

  11. Actovegin, a non-prohibited drug increases oxidative capacity in human skeletal muscle

    DEFF Research Database (Denmark)

    Søndergård, Stine D; Dela, Flemming; Helge, Jørn W

    2016-01-01

    Actovegin, a deproteinized haemodialysate of calf blood, is suggested to have ergogenic properties, but this potential effect has never been investigated in human skeletal muscle. To investigate this purported ergogenic effect, we measured the mitochondrial respiratory capacity in permeabilized h...

  12. Increased Susceptibility of Humanized NSG Mice to Panton-Valentine Leukocidin and Staphylococcus aureus Skin Infection.

    Directory of Open Access Journals (Sweden)

    Ching Wen Tseng

    Full Text Available Staphylococcus aureus is a leading cause of skin and soft-tissue infections worldwide. Mice are the most commonly used animals for modeling human staphylococcal infections. However a supra-physiologic S. aureus inoculum is required to establish gross murine skin pathology. Moreover, many staphylococcal factors, including Panton-Valentine leukocidin (PVL elaborated by community-associated methicillin-resistant S. aureus (CA-MRSA, exhibit selective human tropism and cannot be adequately studied in mice. To overcome these deficiencies, we investigated S. aureus infection in non-obese diabetic (NOD/severe combined immune deficiency (SCID/IL2rγnull (NSG mice engrafted with human CD34+ umbilical cord blood cells. These "humanized" NSG mice require one to two log lower inoculum to induce consistent skin lesions compared with control mice, and exhibit larger cutaneous lesions upon infection with PVL+ versus isogenic PVL- S. aureus. Neutrophils appear important for PVL pathology as adoptive transfer of human neutrophils alone to NSG mice was sufficient to induce dermonecrosis following challenge with PVL+ S. aureus but not PVL- S. aureus. PMX53, a human C5aR inhibitor, blocked PVL-induced cellular cytotoxicity in vitro and reduced the size difference of lesions induced by the PVL+ and PVL- S. aureus, but PMX53 also reduced recruitment of neutrophils and exacerbated the infection. Overall, our findings establish humanized mice as an important translational tool for the study of S. aureus infection and provide strong evidence that PVL is a human virulence factor.

  13. Sustainable access to data, products, services and software from the European seismological Research Infrastructures: the EPOS TCS Seismology

    Science.gov (United States)

    Haslinger, Florian; Dupont, Aurelien; Michelini, Alberto; Rietbrock, Andreas; Sleeman, Reinoud; Wiemer, Stefan; Basili, Roberto; Bossu, Rémy; Cakti, Eser; Cotton, Fabrice; Crawford, Wayne; Diaz, Jordi; Garth, Tom; Locati, Mario; Luzi, Lucia; Pinho, Rui; Pitilakis, Kyriazis; Strollo, Angelo

    2016-04-01

    Easy, efficient and comprehensive access to data, data products, scientific services and scientific software is a key ingredient in enabling research at the frontiers of science. Organizing this access across the European Research Infrastructures in the field of seismology, so that it best serves user needs, takes advantage of state-of-the-art ICT solutions, provides cross-domain interoperability, and is organizationally and financially sustainable in the long term, is the core challenge of the implementation phase of the Thematic Core Service (TCS) Seismology within the EPOS-IP project. Building upon the existing European-level infrastructures ORFEUS for seismological waveforms, EMSC for seismological products, and EFEHR for seismological hazard and risk information, and implementing a pilot Computational Earth Science service starting from the results of the VERCE project, the work within the EPOS-IP project focuses on improving and extending the existing services, aligning them with global developments, to at the end produce a well coordinated framework that is technically, organizationally, and financially integrated with the EPOS architecture. This framework needs to respect the roles and responsibilities of the underlying national research infrastructures that are the data owners and main providers of data and products, and allow for active input and feedback from the (scientific) user community. At the same time, it needs to remain flexible enough to cope with unavoidable challenges in the availability of resources and dynamics of contributors. The technical work during the next years is organized in four areas: - constructing the next generation software architecture for the European Integrated (waveform) Data Archive EIDA, developing advanced metadata and station information services, fully integrate strong motion waveforms and derived parametric engineering-domain data, and advancing the integration of mobile (temporary) networks and OBS deployments in

  14. Our Place in Space: Exploring the Earth-Moon System and Beyond with NASA's CINDI E/PO Program

    Science.gov (United States)

    Urquhart, M. L.; Hairston, M. R.

    2010-12-01

    Where does space begin? How far is the Moon? How far is Mars? How does our dynamic star, the Sun, affect its family of planets? All of these questions relate to exploration of our Solar System, and are also part of the Education/Public Outreach (E/PO) Program for NASA’s CINDI project, a space weather mission of opportunity. The Coupled Ion Neutral Dynamics Investigation has been flying aboard the US Air Force Communication/Navigation Outage Forecast System (C/NOFS) satellite in the upper atmosphere of the Earth since April 2008. The Earth’s ionosphere, the part of the atmosphere CINDI studies, is also in space. The CINDI E/PO program uses this fact in lessons designed to help students in middle schools and introductory astronomy classes develop a sense of their place in space. In the activity "How High is Space?" students’ start by building an 8-page scale model of the Earth’s atmosphere with 100 km/page. The peak of Mount Everest, commercial airplanes, and the tops of thunderheads all appear at the bottom of the first page of the model, with astronaut altitude -where space begins- at the top of the same sheet of paper. In "Where Would CINDI Be?" the idea of scale is further developed by modeling the Earth-Moon system to scale first in size, then in distance, using half of standard containers of play dough. With a lowest altitude of about 400 km, similar to that of the International Space Station and orbiting Space Shuttle, CINDI is close to the Earth when compared with the nearly thousand times greater distance to the Moon. Comparing and combining the atmosphere and Earth-Moon system models help reinforce ideas of scale and build student understanding of how far away the Moon actually is. These scale models have also been adapted for use in Family Science Nights, and to include the planet Mars. In this presentation, we will show how we use CINDI’s scale modeling activities and others from our broader space sciences E/PO program in formal and informal

  15. Enhanced hepatocarcinogenesis in mouse models and human hepatocellular carcinoma by coordinate KLF6 depletion and increased messenger RNA splicing

    NARCIS (Netherlands)

    Vetter, Diana; Cohen-Naftaly, Michal; Villanueva, Augusto; Lee, Youngmin A.; Kocabayoglu, Peri; Hannivoort, Rebekka; Narla, Goutham; M. Llovet, Josep; Thung, Swan N.; Friedman, Scott L.

    2012-01-01

    KLF6-SV1 (SV1), the major splice variant of KLF6, antagonizes the KLF6 tumor suppressor by an unknown mechanism. Decreased KLF6 expression in human hepatocellular carcinoma (HCC) correlates with increased mortality, but the contribution of increased SV1 is unknown. We sought to define the impact of

  16. Nonalcoholic fatty liver disease (NAFLD)--is it a new marker of hyporesponsiveness to recombinant human erythropoietin in patients that are on chronic hemodialysis?

    Science.gov (United States)

    Orlic, L; Mikolasevic, I; Lukenda, V; Racki, S; Stimac, D; Milic, S

    2014-12-01

    Anemia is a major consequence of chronic kidney disease (CKD) that develops early in the course of illness and affects most patients who exhibit some degree of reduced renal function. Erythropoietin (EPO) deficiency is considered the most important cause of anemia in CKD. Renal anemia has serious clinical consequence. In addition to reducing patient physical capacity and quality of life, anemia induces adaptive cardiovascular mechanisms that increase the risk of cardiovascular disease and death. Thus, treatment of anemia in CKD is very important. While EPO is effective in correcting anemia in most cases, up to 10% of patients however, have an inadequate response to therapy. The two most common and important reasons why patients become relatively unresponsive to EPO therapy are the development of true iron deficiency and the onset of an inflammatory state that impairs the response to EPO. Indeed, the role of inflammation and pro-inflammatory cytokines in resistance to EPO therapy is gaining increasing recognition. On the other hand, the main organ for C-reactive protein (CRP) synthesis is the liver and it is well known that the synthesis of an acute-phase proteins by the liver is up regulated by inflammation. The main consequence of nonalcoholic fatty liver disease (NAFLD) is sub-chronic liver inflammation that leads and contributes to dyslipidemia, inflammation, enhanced oxidative stress and endothelial dysfunction. Considering the recent data about high prevalence of NAFLD in CKD patients, probably due to shared metabolic risk factors, we hypothesized that end-stage renal disease (ESRD) patients with NAFLD will need a much higher dose of EPO to achieve the target hemoglobin levels in comparison with ESRD patients without NAFLD. The possible underlying mechanism is sub-chronic liver inflammation in NAFLD patients that leads and contributes to poor response to EPO. Therefore, we believe that NAFLD could be a new clinical marker of poor response to EPO therapy in

  17. Measurement of the capability of DNA synthesis of human fetal liver cells by the assay of 3H-TdR incorporation

    International Nuclear Information System (INIS)

    Wang Tao; Ma Xiangrui; Wang Hongyun; Cao Xia

    1987-01-01

    The fetal liver is one of the major sites of hematopoiesis during gestation. Under erythropoietin (EPO) stimulation, in erythroid precusor cells of fetal liver, proliferation and differentiation occurred and function of metabolism was enhanced. The technique of 3 H-TdR incorporation was used to measure the function of fetal liver cellular DNA synthesis. As EPO concentration at the range of approximately 20 ∼ 100 mU/ml, the counts of 3 H-TdR incorporation into fetal liver cells increased. As the concentration of EPO increased, however, its incorporation counts are lower than that in bone marrow of either the fetal or the adult. It suggested that precusors of erythrocyte of fetal liver has differentiated to later phases with the progressive accumulation of mature cells, therefore, both proliferation and function of metabolism are more or less decreased respectively. Under EPO stimulation, however, precusor of erythroid of fetal liver can greatly increase potential effects on DNA synthesis

  18. Human umbilical cord mesenchymal stem cells increase interleukin-9 production of CD4+ T cells

    OpenAIRE

    Yang, Zhou Xin; Chi, Ying; Ji, Yue Ru; Wang, You Wei; Zhang, Jing; Luo, Wei Feng; Li, Li Na; Hu, Cai Dong; Zhuo, Guang Sheng; Wang, Li Fang; Han, Zhi-Bo; Han, Zhong Chao

    2017-01-01

    Mesenchymal stem cells (MSC) are able to differentiate into cells of multiple lineage, and additionally act to modulate the immune response. Interleukin (IL)-9 is primarily produced by cluster of differentiation (CD)4+ T cells to regulate the immune response. The present study aimed to investigate the effect of human umbilical cord derived-MSC (UC-MSC) on IL-9 production of human CD4+ T cells. It was demonstrated that the addition of UC-MSC to the culture of CD4+ T cells significantly enhance...

  19. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HuaHu; Wei-PingZhang; LeiZhang; ZhongChen; Er-QingWei

    2004-01-01

    Aquaporin-4 (AQP4) is one of the aquaporins (AQPs), a water channel family. In the brain, AQP4 is expressed in astroeyte foot processes, and plays an important role in water homeostasis and in the formation of brain edema. In our study, AQP4 expression in human brain specimens from patients with traumatic brain injury or different brain tumors was detected

  20. Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

    NARCIS (Netherlands)

    Geuken, Erwin; Visser, Dorien; Kuipers, Folkert; Blokzijl, Hans; Leuvenink, Henri G. D.; de Jong, Koert P.; Peeters, Paul M. J. G.; Jansen, Peter L. M.; Slooff, Maarten J. H.; Gouw, Annette S. H.; Porte, Robert J.

    2004-01-01

    BACKGROUND/AIMS: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. METHODS: In 28 liver transplant recipients, bile samples were collected daily

  1. Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

    NARCIS (Netherlands)

    Geuken, E; Visser, D; Kuipers, F; Blokzijl, H; Leuvenink, HGD; de Jong, KP; Peeters, PMJG; Jansen, PLM; Slooff, MJH; Gouw, ASH; Porte, RJ

    2004-01-01

    Background/Aims: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. Methods: In 28 liver transplant recipients, bile samples were collected daily

  2. Acute maternal rehydration increases the urine production rate in the near-term human fetus

    NARCIS (Netherlands)

    Haak, MC; Aarnoudse, JG; Oosterhof, H.

    OBJECTIVE: We sought to investigate the effect of a decrease of maternal plasma osmolality produced by hypotonic rehydration on the fetal urine production rate in normal near-term human fetuses. STUDY DESIGN: Twenty-one healthy pregnant women attending the clinic for antenatal care were studied

  3. Opportunities for Increasing Human Papillomavirus Vaccine Provision in School Health Centers

    Science.gov (United States)

    Moss, Jennifer L.; Feld, Ashley L.; O'Malley, Brittany; Entzel, Pamela; Smith, Jennifer S.; Gilkey, Melissa B.; Brewer, Noel T.

    2014-01-01

    Background: Uptake of human papillomavirus (HPV) vaccine remains low among adolescents in the United States. We sought to assess barriers to HPV vaccine provision in school health centers to inform subsequent interventions. Methods: We conducted structured interviews in the fall of 2010 with staff from all 33 school health centers in North…

  4. Human Papillomavirus Vaccine Increases High-Risk Sexual Behaviors: A Myth or Valid Concern

    Science.gov (United States)

    Ratanasiripong, Nop T.

    2014-01-01

    In 2006, the first human pappilomavirus (HPV) vaccine was approved for females aged 9 to 26. However, the national HPV vaccination rate among young women has been low. Public concerns were raised in regard to the fact that HPV vaccination might encourage unsafe sex. This cross-sectional study examined the differences in sexual practices between…

  5. Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration

    NARCIS (Netherlands)

    Dumont, G J H; Sweep, F C G J; van der Steen, R; Hermsen, R; Donders, A R T; Touw, D J; van Gerven, J M A; Buitelaar, J K; Verkes, R J

    2009-01-01

    MDMA (3,4-methylenedioxymethamphetamine or "ecstasy") is a recreationally used drug with remarkable and characteristic prosocial effects. In spite of abundant attention in the scientific literature, the mechanism of its prosocial effects has not been elucidated in humans. Recently, research in

  6. Human Protein C produces anticoagulation and increased fibrinolytic activity in the cat

    International Nuclear Information System (INIS)

    Burdick, M.D.; Schaub, R.G.

    1986-01-01

    The effect of activated human Protein C (PCa) infusion on the coagulation and fibrinolytic systems of the Nembutal anesthetized cat was assessed. Human Protein C was activated by incubation with thrombin or by passage over a column of thrombin immobilized on CNBr Sepharose 4B. Cats were given bolus i.v. injections of either vehicle or PCa in a dose range of 3-16 μg/mL of calculated whole body volume. Citrated blood samples (9:1) were taken from a femoral vein prior to and at 5, 10, 20, 30, 60, 120, and 180 min. after PCa. Activated partial thromboplastin time (APTT), thrombin time (TT) euglobulin clot lysis (ECLT) and I-125 fibrin release (FR) was measured. Vehicle treated cats had no change in any parameter. PCa produced a dose and time dependent prolongation of APTT while TT was unchanged. Anticoagulation was evident immediately after PCa infusion and began to normalize within 20 min. Fibrinolytic activity measured by ECLT and FR was also stimulated by PCa but was not evident until 40-60 minutes after PCa injection. The results show that human PCa induces anticoagulation effects in the cat similar to other species. However, stimulation of fibrinolysis requires a longer period of time before expression. This delay of fibrinolytic stimulation should be considered when assessing the effects of human Protein C in other species

  7. Tumour necrosis factor blockade increases lymphangiogenesis in murine and human arthritic joints

    NARCIS (Netherlands)

    Polzer, K.; Baeten, D.; Soleiman, A.; Distler, J.; Gerlag, D. M.; Tak, P. P.; Schett, G.; Zwerina, J.

    2008-01-01

    OBJECTIVE: To investigate the presence and regulation of lymphatic vessels in inflamed joints of mice with experimental arthritis as well as patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: Lymphatic vessels and blood vessels were assessed in synovial tissue of human

  8. N-glycosylation increases the circulatory half-life of human growth hormone

    DEFF Research Database (Denmark)

    Flintegaard, Thomas V; Thygesen, Peter; Rahbek-Nielsen, Henrik

    2010-01-01

    Therapeutic use of recombinant GH typically involves daily sc injections. We examined the possibilities for prolonging the in vivo circulation of GH by introducing N-glycans. Human GH variants with a single potential N-glycosylation site (N-X-S/T) introduced by site-directed mutagenesis were expr...

  9. Recombinant human erythropoietin alpha improves the efficacy of radiotherapy of a human tumor xenograft, affecting tumor cells and microvessels

    International Nuclear Information System (INIS)

    Loevey, J.; Bereczky, B.; Gilly, R.; Kenessey, I.; Raso, E.; Simon, E.; Timar, J.; Dobos, J.; Vago, A.; Kasler, M.; Doeme, B.; Tovari, J.

    2008-01-01

    Background and purpose: tumor-induced anemia often occurs in cancer patients, and is corrected by recombinant human erythropoietins (rHuEPOs). Recent studies indicated that, besides erythroid progenitor cells, tumor and endothelial cells express erythropoietin receptor (EPOR) as well; therefore, rHuEPO may affect their functions. Here, the effect of rHuEPOα on irradiation in EPOR-positive human squamous cell carcinoma xenograft was tested. Material and methods: A431 tumor-bearing SCID mice were treated from the tumor implantation with rHuEPOα at human-equivalent dose. Xenografts were irradiated (5 Gy) on day 14, and the final tumor mass was measured on day 22. The systemic effects of rHuEPOα on the hemoglobin level, on tumor-associated blood vessels and on hypoxia-inducible factor-(HIF-)1α expression of the tumor xenografts were monitored. The proliferation, apoptosis and clonogenic capacity of A431 cancer cells treated with rHuEPOα and irradiation were also tested in vitro. Results: in vitro, rHuEPOα treatment alone did not modify the proliferation of EPOR-positive A431 tumor cells but enhanced the effect of irradiation on proliferation, apoptosis and clonogenic capacity. In vivo, rHuEPOα administration compensated the tumor-induced anemia in SCID mice and decreased tumoral HIF-1α expression but had no effect on tumor growth. At the same time rHuEPOα treatment significantly increased the efficacy of radiotherapy in vivo (tumor weight of 23.9 ± 4.7 mg and 34.9 ± 4.6 mg, respectively), mediated by increased tumoral blood vessel destruction. Conclusion: rHuEPOα treatment may modulate the efficacy of cancer radiotherapy not only by reducing systemic hypoxia and tumoral HIF-1α expression, but also by destroying tumoral vessels. (orig.)

  10. Epoetin Alpha and Epoetin Zeta: A Comparative Study on Stimulation of Angiogenesis and Wound Repair in an Experimental Model of Burn Injury.

    Science.gov (United States)

    Irrera, Natasha; Bitto, Alessandra; Pizzino, Gabriele; Vaccaro, Mario; Squadrito, Francesco; Galeano, Mariarosaria; Stagno d'Alcontres, Francesco; Stagno d'Alcontres, Ferdinando; Buemi, Michele; Minutoli, Letteria; Colonna, Michele Rosario; Altavilla, Domenica

    2015-01-01

    Deep second-degree burns are characterized by delayed formation of granulation tissue and impaired angiogenesis. Erythropoietin (EPO) is able to stimulate angiogenesis and mitosis, activating vascularization and cell cycle. The aim of our study was to investigate whether two biosimilar recombinant human erythropoietins, EPO-α and EPO-Z, may promote these processes in an experimental model of burn injury. A total of 84 mice were used and a scald burn was produced on the back after shaving, in 80°C water for 10 seconds. Mice were then randomized to receive EPO-α (400 units/kg/day/sc) or EPO-Z (400 units/kg/day/sc) or their vehicle (100 μL/day/sc 0.9% NaCl solution). After 12 days, both EPO-α and EPO-Z increased VEGF protein expression. EPO-α caused an increased cyclin D1/CDK6 and cyclin E/CDK2 expression compared with vehicle and EPO-Z (p<0.001). Our study showed that EPO-α and EPO-Z accelerated wound closure and angiogenesis; however EPO-α resulted more effectively in achieving complete skin regeneration. Our data suggest that EPO-α and EPO-Z are not biosimilars for the wound healing effects. The higher efficacy of EPO-α might be likely due to its different conformational structure leading to a more efficient cell proliferation and skin remodelling.

  11. Human amniotic epithelial cell feeder layers maintain human iPS cell pluripotency via inhibited endogenous microRNA-145 and increased Sox2 expression

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Te, E-mail: liute79@yahoo.com [School of Environmental Science and Engineering, Donghua University, Shanghai 201620 (China); Shanghai Geriatric Institute of Chinese Medicine, Shanghai 200031 (China); Cheng, Weiwei [International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University, Shanghai 200030 (China); Huang, Yongyi [Laboratoire PROTEE, Batiment R, Universite du Sud Toulon-Var, 83957 LA GARDE Cedex (France); Huang, Qin; Jiang, Lizhen [Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Guo, Lihe, E-mail: liute79@yahoo.com [Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)

    2012-02-15

    Currently, human induced pluripotent stem (iPS) cells were generated from patient or disease-specific sources and share the same key properties as embryonic stem cells. This makes them attractive for personalized medicine, drug screens or cellular therapy. Long-term cultivation and maintenance of normal iPS cells in an undifferentiated self-renewing state are a major challenge. Our previous studies have shown that human amniotic epithelial cells (HuAECs) could provide a good source of feeder cells for mouse and human embryonic stem cells, or spermatogonial stem cells, but the mechanism for this is unknown. Here, we examined the effect of endogenous microRNA-145 regulation on Sox2 expression in human iPS cells by HuAECs feeder cells regulation, and in turn on human iPS cells pluripotency. We found that human IPS cells transfected with a microRNA-145 mutant expressed Sox2 at high levels, allowing iPS to maintain a high level of AP activity in long-term culture and form teratomas in SCID mice. Expression of stem cell markers was increased in iPS transfected with the microRNA-145 mutant, compared with iPS was transfected with microRNA-145. Besides, the expression of Drosha proteins of the microRNA-processor complex, required for the generation of precursor pre-miRNA, was significantly increased in human iPS cells cultured on MEF but not on HuAECs. Taken together, these results suggest that endogenous Sox2 expression may be regulated by microRNA-145 in human iPS cells with HuAECs feeder cells, and Sox2 is a crucial component required for maintenance of them in an undifferentiated, proliferative state capable of self-renewal. Highlights: Black-Right-Pointing-Pointer microRNA-145 inhibits Sox2 expression in human iPS cells. Black-Right-Pointing-Pointer microRNA-145 suppresses the self-renewal and pluripotency of human iPS cells. Black-Right-Pointing-Pointer HuAECs regulate expression of microRNA-145 and Sox2 in human iPS cells. Black-Right-Pointing-Pointer HuAECs feeder

  12. Human amniotic epithelial cell feeder layers maintain human iPS cell pluripotency via inhibited endogenous microRNA-145 and increased Sox2 expression

    International Nuclear Information System (INIS)

    Liu, Te; Cheng, Weiwei; Huang, Yongyi; Huang, Qin; Jiang, Lizhen; Guo, Lihe

    2012-01-01

    Currently, human induced pluripotent stem (iPS) cells were generated from patient or disease-specific sources and share the same key properties as embryonic stem cells. This makes them attractive for personalized medicine, drug screens or cellular therapy. Long-term cultivation and maintenance of normal iPS cells in an undifferentiated self-renewing state are a major challenge. Our previous studies have shown that human amniotic epithelial cells (HuAECs) could provide a good source of feeder cells for mouse and human embryonic stem cells, or spermatogonial stem cells, but the mechanism for this is unknown. Here, we examined the effect of endogenous microRNA-145 regulation on Sox2 expression in human iPS cells by HuAECs feeder cells regulation, and in turn on human iPS cells pluripotency. We found that human IPS cells transfected with a microRNA-145 mutant expressed Sox2 at high levels, allowing iPS to maintain a high level of AP activity in long-term culture and form teratomas in SCID mice. Expression of stem cell markers was increased in iPS transfected with the microRNA-145 mutant, compared with iPS was transfected with microRNA-145. Besides, the expression of Drosha proteins of the microRNA-processor complex, required for the generation of precursor pre-miRNA, was significantly increased in human iPS cells cultured on MEF but not on HuAECs. Taken together, these results suggest that endogenous Sox2 expression may be regulated by microRNA-145 in human iPS cells with HuAECs feeder cells, and Sox2 is a crucial component required for maintenance of them in an undifferentiated, proliferative state capable of self-renewal. Highlights: ► microRNA-145 inhibits Sox2 expression in human iPS cells. ► microRNA-145 suppresses the self-renewal and pluripotency of human iPS cells. ► HuAECs regulate expression of microRNA-145 and Sox2 in human iPS cells. ► HuAECs feeder layers maintain human iPS cells pluripotency. ► HuAECs negatively regulates the synthesis of

  13. Exercise-induced increase in glucose transport, GLUT-4, and VAMP-2 in plasma membrane from human muscle

    DEFF Research Database (Denmark)

    Kristiansen, S; Hargreaves, Mark; Richter, Erik

    1996-01-01

    contractions may induce trafficking of GLUT-4-containing vesicles via a mechanism similar to neurotransmitter release. Our results demonstrate for the first time exercise-induced translocation of GLUT-4 and VAMP-2 to the plasma membrane of human muscle and increased sarcolemmal glucose transport.......A major effect of muscle contractions is an increase in sarcolemmal glucose transport. We have used a recently developed technique to produce sarcolemmal giant vesicles from human muscle biopsy samples obtained before and after exercise. Six men exercised for 10 min at 50% maximal O2 uptake (Vo2max...

  14. Using the mouse to model human disease: increasing validity and reproducibility

    Directory of Open Access Journals (Sweden)

    Monica J. Justice

    2016-02-01

    Full Text Available Experiments that use the mouse as a model for disease have recently come under scrutiny because of the repeated failure of data, particularly derived from preclinical studies, to be replicated or translated to humans. The usefulness of mouse models has been questioned because of irreproducibility and poor recapitulation of human conditions. Newer studies, however, point to bias in reporting results and improper data analysis as key factors that limit reproducibility and validity of preclinical mouse research. Inaccurate and incomplete descriptions of experimental conditions also contribute. Here, we provide guidance on best practice in mouse experimentation, focusing on appropriate selection and validation of the model, sources of variation and their influence on phenotypic outcomes, minimum requirements for control sets, and the importance of rigorous statistics. Our goal is to raise the standards in mouse disease modeling to enhance reproducibility, reliability and clinical translation of findings.

  15. Increase of Universality in Human Brain during Mental Imagery from Visual Perception

    OpenAIRE

    Bhattacharya, Joydeep

    2009-01-01

    BACKGROUND: Different complex systems behave in a similar way near their critical points of phase transitions which leads to an emergence of a universal scaling behaviour. Universality indirectly implies a long-range correlation between constituent subsystems. As the distributed correlated processing is a hallmark of higher complex cognition, I investigated a measure of universality in human brain during perception and mental imagery of complex real-life visual object like visual art. METHODO...

  16. A Sulfur Amino Acid–Free Meal Increases Plasma Lipids in Humans123

    OpenAIRE

    Park, Youngja; Le, Ngoc-Anh; Yu, Tianwei; Strobel, Fred; Gletsu-Miller, Nana; Accardi, Carolyn J.; Lee, Kichun S.; Wu, Shaoxiong; Ziegler, Thomas R.; Jones, Dean P.

    2011-01-01

    The content of sulfur amino acid (SAA) in a meal affects postprandial plasma cysteine concentrations and the redox potential of cysteine/cystine. Because such changes can affect enzyme, transporter, and receptor activities, meal content of SAA could have unrecognized effects on metabolism during the postprandial period. This pilot study used proton NMR (1H-NMR) spectroscopy of human plasma to test the hypothesis that dietary SAA content changes macronutrient metabolism. Healthy participants (...

  17. Increasing Hematopoietic Stem Cell Yield to Develop Mice with Human Immune Systems

    Directory of Open Access Journals (Sweden)

    Juan-Carlos Biancotti

    2013-01-01

    Full Text Available Hematopoietic stem cells (HSCs are unique in their capacity to give rise to all mature cells of the immune system. For years, HSC transplantation has been used for treatment of genetic and neoplastic diseases of the hematopoietic and immune systems. The sourcing of HSCs from human umbilical cord blood has salient advantages over isolation from mobilized peripheral blood. However, poor sample yield has prompted development of methodologies to expand HSCs ex vivo. Cytokines, trophic factors, and small molecules have been variously used to promote survival and proliferation of HSCs in culture, whilst strategies to lower the concentration of inhibitors in the culture media have recently been applied to promote HSC expansion. In this paper, we outline strategies to expand HSCs in vitro, and to improve engraftment and reconstitution of human immune systems in immunocompromised mice. To the extent that these “humanized” mice are representative of the endogenous human immune system, they will be invaluable tools for both basic science and translational medicine.

  18. Hydrogen peroxide production is not primarily increased in human myotubes established from type 2 diabetic subjects

    DEFF Research Database (Denmark)

    Minet, A D; Gaster, M

    2011-01-01

    Increased oxidative stress and mitochondrial dysfunction have been implicated in the development of insulin resistance in type 2 diabetes. To date, it is unknown whether increased mitochondrial reactive oxygen species (ROS) production in skeletal muscle from patients with type 2 diabetes is prima......Increased oxidative stress and mitochondrial dysfunction have been implicated in the development of insulin resistance in type 2 diabetes. To date, it is unknown whether increased mitochondrial reactive oxygen species (ROS) production in skeletal muscle from patients with type 2 diabetes...

  19. High Glucose-Induced Oxidative Stress Increases the Copy Number of Mitochondrial DNA in Human Mesangial Cells

    Directory of Open Access Journals (Sweden)

    Ghada Al-Kafaji

    2013-01-01

    Full Text Available Oxidative damage to mitochondrial DNA (mtDNA has been linked to the pathogenicity of diabetic nephropathy. We tested the hypothesis that mtDNA copy number may be increased in human mesangial cells in response to high glucose-induced reactive oxygen species (ROS to compensate for damaged mtDNA. The effect of manganese superoxide dismutase mimetic (MnTBAP on glucose-induced mtDNA copy number was also examined. The copy number of mtDNA was determined by real-time PCR in human mesangial cells cultured in 5 mM glucose, 25 mM glucose, and mannitol (osmotic control, as well as in cells cultured in 25 mM glucose in the presence and absence of 200 μM MnTBAP. Intracellular ROS was assessed by confocal microscopy and flow cytometry in human mesangial cells. The copy number of mtDNA was significantly increased when human mesangial cells were incubated with 25 mM glucose compared to 5 mM glucose and mannitol. In addition, 25 mM glucose rapidly generated ROS in the cells, which was not detected in 5 mM glucose. Furthermore, mtDNA copy number was significantly decreased and maintained to normal following treatment of cells with 25 mM glucose and MnTBAP compared to 25 mM glucose alone. Inclusion of MnTBAP during 25 mM glucose incubation inhibited mitochondrial superoxide in human mesangial cells. Increased mtDNA copy number in human mesangial cells by high glucose could contribute to increased mitochondrial superoxide, and prevention of mtDNA copy number could have potential in retarding the development of diabetic nephropathy.

  20. Study of temperature increase and optic depth penetration in photo irradiated human tissues

    International Nuclear Information System (INIS)

    Stolik, Suren; Delgado, Jose A.; Perez, Arllene M.; Anasagasti, Lorenzo

    2009-01-01

    Optical radiation is widely applied in the treatment and diagnosis of different pathologies. If the power density of the incident light is sufficiently high to induce a significant temperature rise in the irradiated tissue, then it is also needed the knowledge of the thermal properties of the tissue for a complete understanding of the therapeutic effects. The thermal penetration depth of several human tissues has been measured applying the diffusion approximation of the radiative transfer equation for the distribution of optical radiation. The method, the experimental setup and the results are presented and discussed. (Author)

  1. Modern Virtual Reality. And the effects of affecting human senses to increase immersion

    OpenAIRE

    Ekros, Matthias

    2015-01-01

    Modern virtual reality is an ever growing subject in today’s society. I delved deeper into some key moments in the development of modern virtual reality. Oculus Rift has shown incredible potential. Some developments even seek to envelope the human senses in virtual reality as well.   With several different approaches to the same solution there are many ways that the experience can affect the overall immersion of a consumer into the product.  The tests I performed were primarily focused around...

  2. Increased protein expression of LHCG receptor and 17a-hydroxylase/17,20-lyase in human polycystic ovaries

    NARCIS (Netherlands)

    Comim, F.V.; Teerds, K.J.; Hardy, K.; Franks, S.

    2013-01-01

    STUDY QUESTION Does the expression of LHCG receptor (LHCGR) protein and key enzymes in the androgen biosynthetic pathway differ in normal human versus polycystic ovarian tissue? SUMMARY ANSWER LHCGR and 17a-hydroxylase/17-20-lyase (CYP17A1) protein levels are increased in polycystic ovaries (PCOs).

  3. Increased energy expenditure and glucose oxidation during acute nontraumatic skin pain in humans.

    Science.gov (United States)

    Holland-Fischer, Peter; Greisen, Jacob; Grøfte, Thorbjørn; Jensen, Troels S; Hansen, Peter O; Vilstrup, Hendrik

    2009-04-01

    Tissue injury is accompanied by pain and results in increased energy expenditure, which may promote catabolism. The extent to which pain contributes to this sequence of events is not known. In a cross-over design, 10 healthy volunteers were examined on three occasions; first, during self-controlled nontraumatic electrical painful stimulus to the abdominal skin, maintaining an intensity of 8 on the visual analogue scale (0-10). Next, the electrical stimulus was reproduced during local analgesia and, finally, there was a control session without stimulus. Indirect calorimetry and blood and urine sampling was done in order to calculate energy expenditure and substrate utilization. During pain stimulus, energy expenditure increased acutely and reversibly by 62% (95% confidence interval, 43-83), which was abolished by local analgesia. Energy expenditure paralleled both heart rate and blood catecholamine levels. The energy expenditure increase was fuelled by all energy sources, with the largest increase in glucose utilization. The pain-related increase in energy expenditure was possibly mediated by adrenergic activity and was probably to a large extent due to increased muscle tone. These effects may be enhanced by cortical events related to the pain. The increase in glucose consumption favours catabolism. Our findings emphasize the clinical importance of pain management.

  4. Glycopyrrolate abolishes the exercise-induced increase in cerebral perfusion in humans

    DEFF Research Database (Denmark)

    Seifert, Thomas; Fisher, James P; Young, Colin N

    2010-01-01

    Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow (CBF) regulation, but whether a cholinergic receptor mechanism is involved in the exercise-induced increase in cerebral perfusion or affects cerebral metabolism remains unknown. We evaluated CBF and cerebral......(mean) during ergometer cycling (n = 8). Separate, randomized and counterbalanced trials were performed in control (no drug) conditions and following muscarinic cholinergic receptor blockade by glycopyrrolate. Glycopyrrolate increased resting heart rate from approximately 60 to approximately 110 beats min(-1...... abolished by glycopyrrolate (P important for the exercise-induced increase in cerebral perfusion without affecting the cerebral metabolic rate for oxygen....

  5. Unnatural amino acids increase activity and specificity of synthetic substrates for human and malarial cathepsin C.

    Science.gov (United States)

    Poreba, Marcin; Mihelic, Marko; Krai, Priscilla; Rajkovic, Jelena; Krezel, Artur; Pawelczak, Malgorzata; Klemba, Michael; Turk, Dusan; Turk, Boris; Latajka, Rafal; Drag, Marcin

    2014-04-01

    Mammalian cathepsin C is primarily responsible for the removal of N-terminal dipeptides and activation of several serine proteases in inflammatory or immune cells, while its malarial parasite ortholog dipeptidyl aminopeptidase 1 plays a crucial role in catabolizing the hemoglobin of its host erythrocyte. In this report, we describe the systematic substrate specificity analysis of three cathepsin C orthologs from Homo sapiens (human), Bos taurus (bovine) and Plasmodium falciparum (malaria parasite). Here, we present a new approach with a tailored fluorogenic substrate library designed and synthesized to probe the S1 and S2 pocket preferences of these enzymes with both natural and a broad range of unnatural amino acids. Our approach identified very efficiently hydrolyzed substrates containing unnatural amino acids, which resulted in the design of significantly better substrates than those previously known. Additionally, in this study significant differences in terms of the structures of optimal substrates for human and malarial orthologs are important from the therapeutic point of view. These data can be also used for the design of specific inhibitors or activity-based probes.

  6. Human umbilical cord mesenchymal stem cells increase interleukin-9 production of CD4+ T cells

    Science.gov (United States)

    Yang, Zhou Xin; Chi, Ying; Ji, Yue Ru; Wang, You Wei; Zhang, Jing; Luo, Wei Feng; Li, Li Na; Hu, Cai Dong; Zhuo, Guang Sheng; Wang, Li Fang; Han, Zhi-Bo; Han, Zhong Chao

    2017-01-01

    Mesenchymal stem cells (MSC) are able to differentiate into cells of multiple lineage, and additionally act to modulate the immune response. Interleukin (IL)-9 is primarily produced by cluster of differentiation (CD)4+ T cells to regulate the immune response. The present study aimed to investigate the effect of human umbilical cord derived-MSC (UC-MSC) on IL-9 production of human CD4+ T cells. It was demonstrated that the addition of UC-MSC to the culture of CD4+ T cells significantly enhanced IL-9 production by CD4+ T cells. Transwell experiments suggested that UC-MSC promotion of IL-9 production by CD4+ T cells was dependent on cell-cell contact. Upregulated expression of CD106 was observed in UC-MSC co-cultured with CD4+ T cells, and the addition of a blocking antibody of CD106 significantly impaired the ability of UC-MSC to promote IL-9 production by CD4+ T cells. Therefore, the results of the present study demonstrated that UC-MSC promoted the generation of IL-9 producing cells, which may be mediated, in part by CD106. The findings may act to expand understanding and knowledge of the immune modulatory role of UC-MSC. PMID:29042945

  7. Sufentanil does not increase cerebral blood flow in healthy human volunteers

    International Nuclear Information System (INIS)

    Mayer, N.; Weinstabl, C.; Podreka, I.; Spiss, C.K.

    1990-01-01

    The effect of sufentanil on human cerebral blood flow (CBF) was studied in seven unpremedicated, healthy volunteers 31 +/- 3.5 yr of age (mean +/- SD) and either sex. CBF (ml.100 g-1.min-1) was measured noninvasively with the 133Xe clearance technique and a scintillation camera before and after sufentanil 0.5 micrograms/kg administered intravenously. This technique provides values for global blood flow and for gray and white matter blood flow, and from 13 preselected regions in one hemisphere. After the administration of sufentanil, the volunteers were stimulated verbally in order to prevent their loss of consciousness and hypercarbia. Heart rate (HR), arterial pressure, oxyhemoglobin saturation, and end-tidal CO2 ETCO2 were recorded during the measurements. Neither global CBF (46.1 +/- 1.6 control and 43 +/- 1.9 after sufentanil, mean +/- SEM) nor gray (76.5 +/- 3.2 and 70.9 +/- 6.1) or white (22.7 +/- 1.5 and 24.2 +/- 1.6) matter blood flow changed significantly after sufentanil administration. As well, no significant differences in HR (72 +/- 4 control and 79 +/- 4 beats per min after sufentanil) and ETCO2 (39.8 +/- 1.4 and 41.1 +/- 1.1 mmHg) were observed. It is concluded that sufentanil has no significant effect on CBF in healthy human volunteers

  8. Increased bioactive lipids content in human subcutaneous and epicardial fat tissue correlates with insulin resistance.

    Science.gov (United States)

    Błachnio-Zabielska, Agnieszka U; Baranowski, Marcin; Hirnle, Tomasz; Zabielski, Piotr; Lewczuk, Anna; Dmitruk, Iwona; Górski, Jan

    2012-12-01

    Obesity is a risk factor for metabolic diseases. Intramuscular lipid accumulation of ceramides, diacylglycerols, and long chain acyl-CoA is responsible for the induction of insulin resistance. These lipids are probably implicated in obesity-associated insulin resistance not only in skeletal muscle but also in fat tissue. Only few data are available about ceramide content in human subcutaneous adipose tissue. However, there are no data on DAG and LCACoA content in adipose tissue. The aim of our study was to measure the lipids content in human SAT and epicardial adipose tissue we sought to determine the bioactive lipids content by LC/MS/MS in fat tissue from lean non-diabetic, obese non-diabetic, and obese diabetic subjects and test whether the lipids correlate with HOMA-IR. We found, that total content of measured lipids was markedly higher in OND and OD subjects in both types of fat tissue (for all p lipids content is greater in subcutaneous and epicardial fat tissue and the particular lipids content positively correlates with HOMA-IR.

  9. Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans

    Science.gov (United States)

    RATIONALE: Air pollution has been associated with increased prevalence of type 2 diabetes; however, the mechanisms remain unknown. We have shown that acute ozone exposure in rats induces release of stress hormones, hyperglycemia, leptinemia, and gluoose intolerance that are assoc...

  10. Glycopyrrolate abolishes the exercise-induced increase in cerebral perfusion in humans

    DEFF Research Database (Denmark)

    Seifert, Thomas; Fisher, James P; Young, Colin N

    2010-01-01

    (mean) during ergometer cycling (n = 8). Separate, randomized and counterbalanced trials were performed in control (no drug) conditions and following muscarinic cholinergic receptor blockade by glycopyrrolate. Glycopyrrolate increased resting heart rate from approximately 60 to approximately 110 beats min(-1...

  11. The "Volcano Observations" Thematic Core Service of the European Plate Observing System (EPOS): status of the implementation.

    Science.gov (United States)

    Puglisi, Giuseppe

    2017-04-01

    The European volcanological community contributes to implementation of European Plate Observing System (EPOS) by making operational an integrated platform to guarantee a seamless access to the data provided by the European Solid Earth communities. To achieve this objective, the Volcano Observations Work Package (WP11) will implement a Thematic Core Services (TCS) which is planned to give access to the data and services provided by the European Volcano Observatories (VO) and some Volcanological Research Institutions (VRI; as university departments, laboratories, etc.); both types are considered as national research infrastructures (RI) over which to build the TCS. Currently, the networks on European volcanoes consist of thousands of stations or sites where volcanological parameters are continuously or periodically measured. These sites are equipped with instruments for geophysical (seismic, geodetic, gravimetric, electromagnetic), geochemical (volcanic plumes, fumaroles, groundwater, rivers, soils), environmental observations (e.g. meteorological and air quality parameters), as well as various prototypal monitoring systems (e.g. Doppler radars, ground based SAR). In Europe also operate laboratories for sample analysis (rocks, gases, isotopes, etc.), and almost continuous analysis of space-borne data (SAR, thermal imagery, SO2 and ash), as well as high-performance computing centres. All these RIs provide high-quality information (observations) on the current status of European volcanoes and the geodynamic background of the surrounding areas. The implementation of the Volcano Observations TCS is addressing technical and management issues, both considering the current heterogeneous state of the art of the volcanological research infrastructures in Europe. Indeed, the frame of the VO and VRI is now too fragmented to be considered as a unique distributed infrastructure, thus the main effort planned in the frame of the EPOS-IP is focused to create services aimed at

  12. Diagnosis and characterization of mania: Quantifying increased energy and activity in the human behavioral pattern monitor

    OpenAIRE

    Perry, William; McIlwain, Meghan; Kloezeman, Karen; Henry, Brook L.; Minassian, Arpi

    2016-01-01

    Increased energy or activity is now an essential feature of the mania of Bipolar Disorder (BD) according to DSM-5. This study examined whether objective measures of increased energy can differentiate manic BD individuals and provide greater diagnostic accuracy compared to rating scales, extending the work of previous studies with smaller samples. We also tested the relationship between objective measures of energy and rating scales. 50 hospitalized manic BD patients were compared to healthy s...

  13. Erythropoietin treatment enhances muscle mitochondrial capacity in humans

    DEFF Research Database (Denmark)

    Plenge, Ulla; Belhage, Bo; Guadalupe-Grau, Amelia

    2012-01-01

    in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis...

  14. Haemostatic aspects of recombinant human erythropoietin in colorectal surgery

    DEFF Research Database (Denmark)

    Poulsen, K A; Qvist, N; Winther, K

    1998-01-01

    OBJECTIVE: To find out whether recombinant human erythropoietin (r-HuEPO) given perioperatively has any effect on haemostatic activity in patients undergoing elective colorectal resection. DESIGN: A placebo-controlled double-blind study. SETTING: Odense university hospital, Denmark. SUBJECTS: 24...

  15. Extracellular Histones Increase Tissue Factor Activity and Enhance Thrombin Generation by Human Blood Monocytes.

    Science.gov (United States)

    Gould, Travis J; Lysov, Zakhar; Swystun, Laura L; Dwivedi, Dhruva J; Zarychanski, Ryan; Fox-Robichaud, Alison E; Liaw, Patricia C

    2016-12-01

    Sepsis is characterized by systemic activation of inflammatory and coagulation pathways in response to infection. Recently, it was demonstrated that histones released into the circulation by dying/activated cells may contribute to sepsis pathology. Although the ability of extracellular histones to modulate the procoagulant activities of several cell types has been investigated, the influence of histones on the hemostatic functions of circulating monocytes is unknown. To address this, we investigated the ability of histones to modulate the procoagulant potential of THP-1 cells and peripheral blood monocytes, and examined the effects of plasmas obtained from septic patients to induce a procoagulant phenotype on monocytic cells. Tissue factor (TF) activity assays were performed on histone-treated THP-1 cells and blood monocytes. Exposure of monocytic cells to histones resulted in increases in TF activity, TF antigen, and phosphatidylserine exposure. Histones modulate the procoagulant activity via engagement of Toll-like receptors 2 and 4, and this effect was abrogated with inhibitory antibodies. Increased TF activity of histone-treated cells corresponded to enhanced thrombin generation in plasma determined by calibrated automated thrombography. Finally, TF activity was increased on monocytes exposed to plasma from septic patients, an effect that was attenuated in plasma from patients receiving unfractionated heparin (UFH). Our studies suggest that increased levels of extracellular histones found in sepsis contribute to dysregulated coagulation by increasing TF activity of monocytes. These procoagulant effects can be partially ameliorated in sepsis patients receiving UFH, thereby identifying extracellular histones as a potential therapeutic target for sepsis treatment.

  16. Glucagon-like peptide 1 (GLP-1) suppresses ghrelin levels in humans via increased insulin secretion

    DEFF Research Database (Denmark)

    Hagemann, Dirk; Holst, Jens Juul; Gethmann, Arnica

    2007-01-01

    INTRODUCTION: Ghrelin is an orexigenic peptide predominantly secreted by the stomach. Ghrelin plasma levels rise before meal ingestion and sharply decline afterwards, but the mechanisms controlling ghrelin secretion are largely unknown. Since meal ingestion also elicits the secretion...... of the incretin hormone glucagon-like peptide 1 (GLP-1), we examined whether exogenous GLP-1 administration reduces ghrelin secretion in humans. PATIENTS AND METHODS: 14 healthy male volunteers were given intravenous infusions of GLP-1(1.2 pmol x kg(-1) min(-1)) or placebo over 390 min. After 30 min, a solid test...... meal was served. Venous blood was drawn frequently for the determination of glucose, insulin, C-peptide, GLP-1 and ghrelin. RESULTS: During the infusion of exogenous GLP-1 and placebo, GLP-1 plasma concentrations reached steady-state levels of 139+/-15 pmol/l and 12+/-2 pmol/l, respectively (p

  17. Increased dermal mast cell prevalence and susceptibility to development of basal cell carcinoma in humans

    DEFF Research Database (Denmark)

    Grimbaldeston, Michele A; Skov, Lone; Finlay-Jones, John J

    2002-01-01

    eliminate them. Studies in a range of inbred mouse strains as well as mast cell-depleted mice reconstituted with mast cell precursors support a functional link between histamine-staining dermal mast cells and the extent of susceptibility to UVB-induced systemic immunomodulation. Humans, like mouse strains......, display variations in dermal mast cell prevalence. In a study of Danish and South Australian BCC patients and control subjects, one 4-mm punch biopsy of non-sun-exposed buttock skin was sampled from each participant. This skin site was investigated to avoid any changes in mast cell prevalence caused...... by sun exposure. Two sections (4 microm) per biopsy were immunohistochemically stained for detection of histamine-containing dermal mast cells. Computer-generated image analysis evaluated dermal mast cell prevalence in both sections by quantifying the total number of mast cells according to the total...

  18. A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Sung Kook [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Chung, Sooyoung [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Kim, Hee-Dae [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Lee, Ju Hyung [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Jang, Jaebong [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Kim, Jeongah; Kim, Doyeon [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Son, Gi Hoon [Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Oh, Young J. [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Suh, Young-Ger [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Lee, Cheol Soon [Gachon Clinical Trials Center, Gachon University, Incheon, 417-842 (Korea, Republic of); and others

    2015-11-13

    Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

  19. A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

    International Nuclear Information System (INIS)

    Chun, Sung Kook; Chung, Sooyoung; Kim, Hee-Dae; Lee, Ju Hyung; Jang, Jaebong; Kim, Jeongah; Kim, Doyeon; Son, Gi Hoon; Oh, Young J.; Suh, Young-Ger; Lee, Cheol Soon

    2015-01-01

    Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

  20. The contribution of human agricultural activities to increasing evapotranspiration is significantly greater than climate change effect over Heihe agricultural region.

    Science.gov (United States)

    Zou, Minzhong; Niu, Jun; Kang, Shaozhong; Li, Xiaolin; Lu, Hongna

    2017-08-18

    Evapotranspiration (ET) is a major component linking the water, energy, and carbon cycles. Understanding changes in ET and the relative contribution rates of human activity and of climate change at the basin scale is important for sound water resources management. In this study, changes in ET in the Heihe agricultural region in northwest China during 1984-2014 were examined using remotely-sensed ET data with the Soil and Water Assessment Tool (SWAT). Correlation analysis identified the dominant factors that influence change in ET per unit area and those that influence change in total ET. Factor analysis identified the relative contribution rates of the dominant factors in each case. The results show that human activity, which includes factors for agronomy and irrigation, and climate change, including factors for precipitation and relative humidity, both contribute to increases in ET per unit area at rates of 60.93% and 28.01%, respectively. Human activity, including the same factors, and climate change, including factors for relative humidity and wind speed, contribute to increases in total ET at rates of 53.86% and 35.68%, respectively. Overall, in the Heihe agricultural region, the contribution of human agricultural activities to increased ET was significantly greater than that of climate change.

  1. Omalizumab Increases the Intrinsic Sensitivity of Human Basophils to IgE-Mediated Stimulation

    Science.gov (United States)

    MacGlashan, Donald; Saini, Sarbjit S.

    2013-01-01

    Background Treatment of allergic patients with omalizumab results in a paradoxical increase in their basophil histamine release response, ex vivo, to crosslinking anti-IgE antibody. It is not known whether this change in response is associated with an increase in intrinsic cellular sensitivity, which would be a paradoxical response. Objective To determine if the increase in response to anti-IgE Ab is a reflection of an increased cellular sensitivity, expressed as molecules of antigen-specific IgE per basophil required to produce a 50% of maximal response. Methods Patients were treated with omalizumab or placebo agent for 12 weeks (NCT01003301 at ClinicalTrials.gov) and the metric of basophil sensitivity was assessed at 4 time points, baseline, 6–8 weeks, 12 weeks (after which treatment stopped) and 24 weeks (12 weeks after the end of treatment). Results As observed previously, treatment with omalizumab resulted in a marked increase in the maximal histamine release induced by crosslinking anti-IgE Ab. This change was accompanied by a marked shift in intrinsic basophil sensitivity, ranging from 2.5 to 125 fold, with an average of 6 fold at the midpoint of the treatment to 12 fold after 12 weeks. The magnitude of the increase in cellular sensitivity was inversely related to the starting sensitivity or the starting maximum histamine release. The increased cellular sensitivity also occurred when using LTC4 secretion as a metric of the basophil response. 12 weeks after the end of treatment, cellular sensitivity was found to shift towards the baseline level although the return to baseline was not yet complete at this time point. Conclusions Treatment with omalizumab results in a markedly increased sensitivity of basophils to IgE-mediated stimulation, in terms of the number of IgE molecules required to produce a given response. These results provide a better quantitative sense of the phenotypic change that occurs in basophils during omalizumab treatment which has

  2. Self-Sampling for Human Papillomavirus Testing among Non-Attenders Increases Attendance to the Norwegian Cervical Cancer Screening Programme

    DEFF Research Database (Denmark)

    Enerly, Espen; Bonde, Jesper; Schee, Kristina

    2016-01-01

    Increasing attendance to screening offers the best potential for improving the effectiveness of well-established cervical cancer screening programs. Self-sampling at home for human papillomavirus (HPV) testing as an alternative to a clinical sampling can be a useful policy to increase attendance....... To determine whether self-sampling improves screening attendance for women who do not regularly attend the Norwegian Cervical Cancer Screening Programme (NCCSP), 800 women aged 25-69 years in the Oslo area who were due to receive a 2nd reminder to attend regular screening were randomly selected and invited...... alternative for increasing cervical cancer screening coverage in Norway....

  3. A propos de la formule homérique « enenipen epos t’ephat’ ek t’onomazen »

    Directory of Open Access Journals (Sweden)

    Rossella Saetta-Cottone

    2006-05-01

    Full Text Available Cet article propose une analyse des huit occurrences de la formule homérique epos t’ephat’ ek t’onomazen qui sont précédées, dans le premier hémistiche de l’hexamètre, par le verbe enenipein, dans le but de mettre en lumière la signification particulière qu’y recouvre le verbe onomazein  « apostropher par des mots injurieux ».This article aims to analyze the eight cases of the homeric formula epos t’ephat’ ek t’onomazen they are preceeded, within the first hemistich of the hexametre, by the verb enenipein, so as to clarify the particular meaning that recovers here the verb onomazein « to shout at with injurious words ».

  4. Impact of Increased Corn Production on Ground Water Quality and Human Health

    Science.gov (United States)

    In this study, we use a complex coupled modeling system to assess the impacts of increased corn production on groundwater. In particular, we show how the models provide new information on the drivers of contamination in groundwater, and then relate pollutant concentration change...

  5. Increase in vagal activity during hypotensive lower-body negative pressure in humans

    DEFF Research Database (Denmark)

    Sander-Jensen, K; Mehlsen, J; Stadeager, C

    1988-01-01

    Progressive central hypovolemia is characterized by a normotensive, tachycardic stage followed by a reversible, hypotensive stage with slowing of the heart rate (HR). We investigated circulatory changes and arterial hormone concentrations in response to lower-body negative pressure (LBNP) in six...... volunteers before and after atropine administration. LBNP of 55 mmHg initially resulted in an increase in HR from 55 +/- 4 to 90 +/- 5 beats/min and decreases in mean arterial pressure (MAP) from 94 +/- 4 to 81 +/- 5 mmHg, in central venous pressure from 7 +/- 1 to -3 +/- 1 mmHg, and in cardiac output from 6.......1 +/- 0.5 to 3.7 +/- 0.11/min. Concomitantly, epinephrine and norepinephrine levels increased. After 8.2 +/- 2.3 min of LBNP, the MAP had decreased to 41 +/- 7 mmHg and HR had decreased to 57 +/- 3 beats/min. Vasopressin increased from 1.2 +/- 0.3 to 137 +/- 45 pg/ml and renin activity increased from 1...

  6. Increased Bile Acid Synthesis and Impaired Bile Acid Transport in Human Obesity

    OpenAIRE

    Haeusler, Rebecca A.; Camastra, Stefania; Nannipieri, Monica; Astiarraga, Brenno; Castro-Perez, Jose; Xie, Dan; Wang, Liangsu; Chakravarthy, Manu; Ferrannini, Ele

    2015-01-01

    We measured plasma bile acids, markers of bile acid synthesis, and expression of bile acid transporters in obese and nonobese subjects. We found that obesity was associated with increased bile acid synthesis and 12-hydroxylation, blunted response of plasma bile acids to insulin infusion or a mixed meal, and decreased expression of liver bile acid transporters.

  7. Increase in oxidative stress levels following welding fume inhalation: a controlled human exposure study.

    Science.gov (United States)

    Graczyk, Halshka; Lewinski, Nastassja; Zhao, Jiayuan; Sauvain, Jean-Jacques; Suarez, Guillaume; Wild, Pascal; Danuser, Brigitta; Riediker, Michael

    2016-06-10

    Tungsten inert gas (TIG) welding represents one of the most widely used metal joining processes in industry. It has been shown to generate a large majority of particles at the nanoscale and to have low mass emission rates when compared to other types of welding. Despite evidence that TIG fume particles may produce reactive oxygen species (ROS), limited data is available for the time course changes of particle-associated oxidative stress in exposed TIG welders. Twenty non-smoking male welding apprentices were exposed to TIG welding fumes for 60 min under controlled, well-ventilated settings. Exhaled breathe condensate (EBC), blood and urine were collected before exposure, immediately after exposure, 1 h and 3 h post exposure. Volunteers participated in a control day to account for oxidative stress fluctuations due to circadian rhythm. Biological liquids were assessed for total reducing capacity, hydrogen peroxide (H2O2), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations at each time point. A linear mixed model was used to assess within day and between day differences. Significant increases in the measured biomarkers were found at 3 h post exposure. At 3 h post exposure, we found a 24 % increase in plasma-H2O2 concentrations ([95%CI: 4 % to 46 %], p = 0.01); a 91 % increase in urinary-H2O2 ([2 % to 258 %], p = 0.04); a 14 % increase in plasma-8-OHdG ([0 % to 31 %], p = 0.049); and a 45 % increase in urinary-8-OHdG ([3 % to 105 %], p = 0.03). Doubling particle number concentration (PNC) exposure was associated with a 22 % increase of plasma-8-OHdG at 3 h post exposure (p = 0.01). A 60-min exposure to TIG welding fume in a controlled, well-ventilated setting induced acute oxidative stress at 3 h post exposure in healthy, non-smoking apprentice welders not chronically exposed to welding fumes. As mass concentration of TIG welding fume particles is very low when compared to other types of welding, it is

  8. Exposure to dim artificial light at night increases REM sleep and awakenings in humans.

    Science.gov (United States)

    Cho, Chul-Hyun; Lee, Heon-Jeong; Yoon, Ho-Kyoung; Kang, Seung-Gul; Bok, Ki-Nam; Jung, Ki-Young; Kim, Leen; Lee, Eun-Il

    2016-01-01

    Exposure to artificial light at night (ALAN) has become increasing common, especially in developed countries. We investigated the effect of dALAN exposure during sleep in healthy young male subjects. A total of 30 healthy young male volunteers from 21 to 29 years old were recruited for the study. They were randomly divided into two groups depending on light intensity (Group A: 5 lux and Group B: 10 lux). After a quality control process, 23 healthy subjects were included in the study (Group A: 11 subjects, Group B: 12 subjects). Subjects underwent an NPSG session with no light (Night 1) followed by an NPSG session randomly assigned to two different dim light conditions (5 or 10 lux, dom λ: 501.4 nm) for a whole night (Night 2). We found significant sleep structural differences between Nights 1 and 2, but no difference between Groups A and B. Exposure to dALAN during sleep was significantly associated with increased wake time after sleep onset (WASO; F = 7.273, p = 0.014), increased Stage N1 (F = 4.524, p = 0.045), decreased Stage N2 (F = 9.49, p = 0.006), increased Stage R (F = 6.698, p = 0.017) and non-significantly decreased REM density (F = 4.102, p = 0.056). We found that dALAN during sleep affects sleep structure. Exposure to dALAN during sleep increases the frequency of arousals, amount of shallow sleep and amount of REM sleep. This suggests adverse effects of dALAN during sleep on sleep quality and suggests the need to avoid exposure to dALAN during sleep.

  9. Desert RATS 2011: Near-Earth Asteroid Human Exploration Operations

    Science.gov (United States)

    Abercromby, Andrew; Gernhardt, Michael L.; Chappel, Steve

    2012-01-01

    The Desert Research and Technology Studies (D-RATS) 2011 field test involved the planning and execution of a series of exploration scenarios under operational conditions similar to those that would be expected during a human exploration mission to a near-Earth asteroid (NEA). The focus was on understanding the operations tempo during simulated NEA exploration and the implications of communications latency and limited data bandwidth. Anchoring technologies and sampling techniques were not evaluated due to the immaturity of those technologies and the inability to meaningfully test them at D-RATS. Reduced gravity analogs and simulations are being used to fully evaluate Multi-Mission Space Exploration Vehicle (MMSEV) and extravehicular (EVA) operations and interactions in near-weightlessness at a NEA as part of NASA s integrated analogs program. Hypotheses were tested by planning and performing a series of 1-day simulated exploration excursions comparing test conditions all of which involved a single Deep Space Habitat (DSH) and either zero, one, or two MMSEVs; three or four crewmembers; one of two different communications bandwidths; and a 100-second roundtrip communications latency between the field site and Houston. Excursions were executed at the Black Point Lava Flow test site with a Mission Control Center and Science Support Room at Johnson Space Center (JSC) being operated with 100-second roundtrip communication latency to the field. Crews were composed of astronauts and professional field geologists and teams of Mission Operations, Science, and Education & Public Outreach (EPO) experts also supported the mission simulations each day. Data were collected separately from the Crew, Mission Operations, Science, and EPO teams to assess the test conditions from multiple perspectives. For the operations tested, data indicates practically significant benefits may be realized by including at least one MMSEV and by including 4 versus 3 crewmembers in the NEA exploration

  10. Caffeine increases the velocity of rapid eye movements in unfatigued humans.

    Science.gov (United States)

    Connell, Charlotte J W; Thompson, Benjamin; Turuwhenua, Jason; Hess, Robert F; Gant, Nicholas

    2017-08-01

    Caffeine is a widely used dietary stimulant that can reverse the effects of fatigue on cognitive, motor and oculomotor function. However, few studies have examined the effect of caffeine on the oculomotor system when homeostasis has not been disrupted by physical fatigue. This study examined the influence of a moderate dose of caffeine on oculomotor control and visual perception in participants who were not fatigued. Within a placebo-controlled crossover design, 13 healthy adults ingested caffeine (5 mg·kg -1 body mass) and were tested over 3 h. Eye movements, including saccades, smooth pursuit and optokinetic nystagmus, were measured using infrared oculography. Caffeine was associated with higher peak saccade velocities (472 ± 60° s -1 ) compared to placebo (455 ± 62° s -1 ). Quick phases of optokinetic nystagmus were also significantly faster with caffeine, whereas pursuit eye movements were unchanged. Non-oculomotor perceptual tasks (global motion and global orientation processing) were unaffected by caffeine. These results show that oculomotor control is modulated by a moderate dose of caffeine in unfatigued humans. These effects are detectable in the kinematics of rapid eye movements, whereas pursuit eye movements and visual perception are unaffected. Oculomotor functions may be sensitive to changes in central catecholamines mediated via caffeine's action as an adenosine antagonist, even when participants are not fatigued.

  11. Increased proinflammatory responses from asthmatic human airway smooth muscle cells in response to rhinovirus infection

    Directory of Open Access Journals (Sweden)

    King Nicholas JC

    2006-05-01

    Full Text Available Abstract Background Exacerbations of asthma are associated with viral respiratory tract infections, of which rhinoviruses (RV are the predominant virus type. Airway smooth muscle is important in asthma pathogenesis, however little is known about the potential interaction of RV and human airway smooth muscle cells (HASM. We hypothesised that rhinovirus induction of inflammatory cytokine release from airway smooth muscle is augmented and differentially regulated in asthmatic compared to normal HASM cells. Methods HASM cells, isolated from either asthmatic or non-asthmatic subjects, were infected with rhinovirus. Cytokine production was assayed by ELISA, ICAM-1 cell surface expression was assessed by FACS, and the transcription regulation of IL-6 was measured by luciferase activity. Results RV-induced IL-6 release was significantly greater in HASM cells derived from asthmatic subjects compared to non-asthmatic subjects. This response was RV specific, as 5% serum- induced IL-6 release was not different in the two cell types. Whilst serum stimulated IL-8 production in cells from both subject groups, RV induced IL-8 production in only asthmatic derived HASM cells. The transcriptional induction of IL-6 was differentially regulated via C/EBP in the asthmatic and NF-κB + AP-1 in the non-asthmatic HASM cells. Conclusion This study demonstrates augmentation and differential transcriptional regulation of RV specific innate immune response in HASM cells derived from asthmatic and non-asthmatics, and may give valuable insight into the mechanisms of RV-induced asthma exacerbations.

  12. Cystoisosporiasis-related human acalculous cholecystitis: the need for increased awareness

    Directory of Open Access Journals (Sweden)

    Mahmoud Agholi

    2016-11-01

    Full Text Available Cholecystitis is one of the common surgical indications affecting human beings in many countries. A variety of infectious agents can be associated with acute or chronic acalculous cholecystitis, especially in HIV/AIDS patients. In this investigation, the authors aim to describe two cases of histologically and molecularly documented cystoisosporiasis (syn. isosporiasis as the cause of chronic acalculous cholecystitis in two immunodeficient patients. During microscopic examinations of more than 2500 diarrheic patients’ samples, 11 cases of cystoisosporiasis-related recurrent persistent/chronic diarrhea were detected. A review of the medical records of Cystoisospora belli (syn. Isospora belli-positive patients showed that two of them, i.e. a patient with prolonged corticosteroid therapy and an AIDS patient, several months prior to fecal examinations had undergone cholecystectomy due to acalculous cholecystitis. The study was continued by a review of the histopathological investigation of the recuts prepared from the excised gallbladder tissue sections and stained with hematoxylin and eosin in order to detect a possible specific clinical correlation with cystoisosporiasis. Light microscopic examination revealed the presence of various developmental stages of a coccidial parasite, namely Cystoisospora belli , in both patients’ gallbladder tissue sections. To the best of our knowledge, C. bellii -associated cholecystitis has not been previously reported in a patient with prolonged corticosteroid therapy.

  13. Lesion-induced increase in survival and migration of human neural progenitor cells releasing GDNF

    Science.gov (United States)

    Behrstock, Soshana; Ebert, Allison D.; Klein, Sandra; Schmitt, Melanie; Moore, Jeannette M.; Svendsen, Clive N.

    2009-01-01

    The use of human neural progenitor cells (hNPC) has been proposed to provide neuronal replacement or astrocytes delivering growth factors for brain disorders such as Parkinson’s and Huntington’s disease. Success in such studies likely requires migration from the site of transplantation and integration into host tissue in the face of ongoing damage. In the current study, hNPC modified to release glial cell line derived neurotrophic factor (hNPCGDNF) were transplanted into either intact or lesioned animals. GDNF release itself had no effect on the survival, migration or differentiation of the cells. The most robust migration and survival was found using a direct lesion of striatum (Huntington’s model) with indirect lesions of the dopamine system (Parkinson’s model) or intact animals showing successively less migration and survival. No lesion affected differentiation patterns. We conclude that the type of brain injury dictates migration and integration of hNPC which has important consequences when considering transplantation of these cells as a therapy for neurodegenerative diseases. PMID:19044202

  14. Functional ADA polymorphism increases sleep depth and reduces vigilant attention in humans.

    Science.gov (United States)

    Bachmann, Valérie; Klaus, Federica; Bodenmann, Sereina; Schäfer, Nikolaus; Brugger, Peter; Huber, Susanne; Berger, Wolfgang; Landolt, Hans-Peter

    2012-04-01

    Homeostatically regulated slow-wave oscillations in non-rapid eye movement (REM) sleep may reflect synaptic changes across the sleep-wake continuum and the restorative function of sleep. The nonsynonymous c.22G>A polymorphism (rs73598374) of adenosine deaminase (ADA) reduces the conversion of adenosine to inosine and predicts baseline differences in sleep slow-wave oscillations. We hypothesized that this polymorphism affects cognitive functions, and investigated whether it modulates electroencephalogram (EEG), behavioral, subjective, and biochemical responses to sleep deprivation. Attention, learning, memory, and executive functioning were quantified in healthy adults. Right-handed carriers of the variant allele (G/A genotype, n = 29) performed worse on the d2 attention task than G/G homozygotes (n = 191). To test whether this difference reflects elevated homeostatic sleep pressure, sleep and sleep EEG before and after sleep deprivation were studied in 2 prospectively matched groups of G/A and G/G genotype subjects. Deep sleep and EEG 0.75- to 1.5-Hz oscillations in non-REM sleep were significantly higher in G/A than in G/G genotype. Moreover, attention and vigor were reduced, whereas waking EEG alpha activity (8.5-12 Hz), sleepiness, fatigue, and α-amylase in saliva were enhanced. These convergent data demonstrate that genetic reduction of ADA activity elevates sleep pressure and plays a key role in sleep and waking quality in humans.

  15. Traditional Acupuncture Triggers a Local Increase in Adenosine in Human Subjects

    OpenAIRE

    Takano, Takahiro; Chen, Xiaolin; Luo, Fang; Fujita, Takumi; Ren, Zeguang; Goldman, Nanna; Zhao, Yuanli; Markman, John D.; Nedergaard, Maiken

    2012-01-01

    Acupuncture is a form of Eastern medicine that has been practiced for centuries. Despite its long history and worldwide application, the biological mechanisms of acupuncture in relieving pain have been poorly defined. Recent studies in mice, however, demonstrate that acupuncture triggers increases in interstitial adenosine, which reduces the severity of chronic pain through adenosine A1 receptors, suggesting that adenosine-mediated antinociception contributes to the clinical benefits of acupu...

  16. Noradrenaline increases the expression and release of Hsp72 by human neutrophils.

    Science.gov (United States)

    Giraldo, E; Multhoff, G; Ortega, E

    2010-05-01

    The blood concentration of extracellular 72kDa heat shock protein (eHsp72) increases under conditions of stress, including intense exercise. However, the signal(s), source(s), and secretory pathways in its release into the bloodstream have yet to be clarified. The aim of the present study was to evaluate the role of noradrenaline (NA) as a stress signal on the expression and release of Hsp72 by circulating neutrophils (as a source), all within a context of the immunophysiological regulation during exercise-induced stress in sedentary and healthy young (21-26years) women. The expression of Hsp72 on the surface of isolated neutrophils was determined by flow cytometry, and its release by cultured isolated neutrophils was determined by ELISA. Incubation with cmHsp70-FITC showed that neutrophils express Hsp72 on their surface under basal conditions. In addition, cultured isolated neutrophils (37 degrees C and 5% CO(2)) also released Hsp72 under basal conditions, with this release increasing from 10min to 24h in the absence of cell damage. NA at 10(-9)-10(-5)M doubled the percentage of neutrophils expressing Hsp72 after 60min and 24h incubation. NA also stimulated (by about 20%) the release of Hsp72 after 10min of incubation. (1) Hsp72 is expressed on the surface of isolated neutrophils under basal conditions, and this expression is augmented by NA. (2) Isolated neutrophils can also release Hsp72 under cultured basal conditions in the absence of cell death, and NA can increase this release. These results may contribute to confirming the hypothesis that NA can act as a "stress signal" for the increased eHsp72 in the context of exercise stress, with a role for neutrophils as a source for the expression and, to a lesser degree, the release of Hsp72 after activation by NA. Copyright 2010 Elsevier Inc. All rights reserved.

  17. The role of oxygen-increased respirator in humans ascending to high altitude

    Directory of Open Access Journals (Sweden)

    Shen Guanghao

    2012-08-01

    Full Text Available Abstract Background Acute mountain sickness (AMS is common for people who live in low altitude areas ascending to the high altitude. Many instruments have been developed to treat mild cases of AMS. However, long-lasting and portable anti-hypoxia equipment for individual is not yet available. Methods Oxygen-increased respirator (OIR has been designed to reduce the risk of acute mountain sickness in acute exposure to low air pressure. It can increase the density of oxygen by increasing total atmospheric pressure in a mask. Male subjects were screened, and eighty-eight were qualified to perform the experiments. The subjects were divided into 5 groups and were involved in some of the tests at 4 different altitudes (Group 1, 2: 3700 m; Group 3,4,5: 4000 m, 4700 m, 5380 m with and without OIR. These tests include heart rate, saturation of peripheral oxygen (SpO2, malondialdehyde (MDA, superoxide dismutase (SOD, blood lactate (BLA and PWC (physical work capacity -170. Results The results showed that higher SpO2, lower heart rate (except during exercise and better recovery of heart rate were observed from all the subjects ’with OIR’ compared with ’without OIR’ (P Conclusions We suggested that OIR may play a useful role in protecting people ascending to high altitude before acclimatization.

  18. Virtual water maze learning in human increases functional connectivity between posterior hippocampus and dorsal caudate.

    Science.gov (United States)

    Woolley, Daniel G; Mantini, Dante; Coxon, James P; D'Hooge, Rudi; Swinnen, Stephan P; Wenderoth, Nicole

    2015-04-01

    Recent work has demonstrated that functional connectivity between remote brain regions can be modulated by task learning or the performance of an already well-learned task. Here, we investigated the extent to which initial learning and stable performance of a spatial navigation task modulates functional connectivity between subregions of hippocampus and striatum. Subjects actively navigated through a virtual water maze environment and used visual cues to learn the position of a fixed spatial location. Resting-state functional magnetic resonance imaging scans were collected before and after virtual water maze navigation in two scan sessions conducted 1 week apart, with a behavior-only training session in between. There was a large significant reduction in the time taken to intercept the target location during scan session 1 and a small significant reduction during the behavior-only training session. No further reduction was observed during scan session 2. This indicates that scan session 1 represented initial learning and scan session 2 represented stable performance. We observed an increase in functional connectivity between left posterior hippocampus and left dorsal caudate that was specific to scan session 1. Importantly, the magnitude of the increase in functional connectivity was correlated with offline gains in task performance. Our findings suggest cooperative interaction occurs between posterior hippocampus and dorsal caudate during awake rest following the initial phase of spatial navigation learning. Furthermore, we speculate that the increase in functional connectivity observed during awake rest after initial learning might reflect consolidation-related processing. © 2014 Wiley Periodicals, Inc.

  19. APE/Ref-1 is increased in nuclear fractions of human thyroid hyperfunctioning nodules.

    Science.gov (United States)

    Russo, D; Celano, M; Bulotta, S; Bruno, R; Arturi, F; Giannasio, P; Filetti, S; Damante, G; Tell, G

    2002-08-30

    Apurinic/apyrimidinic endonuclease APE/Ref-1 is a multifunctional protein provided with DNA repair, transcription-factor regulation and anti-apoptotic activities. We have previously reported that, in thyroid cells, TSH regulates both the synthesis and nuclear translocation of APE/Ref-1. We have also shown that nuclear levels of this protein are reduced both in thyroid carcinoma tissues and cell lines. In the present study, APE/Ref-1 expression and cellular localization were analysed by Western blot in hyperfunctioning thyroid nodules from patients with toxic adenoma and/or toxic multinodular goiter. The total content of APE/Ref-1 protein was increased in the majority of the hyperfunctioning tissues with respect to normal adjacent tissue. There was also an increase in the nuclear levels of APE/Ref-1, suggesting enhanced cytoplasm-to-nucleus translocation of the protein in addition to its increased rate of synthesis. These results demonstrate that the phenomenon of nuclear translocation of APE/Ref-1 hypothesized on the basis of cell culture experiments does actually occur in vivo. Together with previous observations in thyroid carcinomas and tumoral cell lines, our findings suggest a two-stage model of APE/Ref-1 behaviour during malignant thyrocyte transformation: an early stage characterized by simple hyperplasia and upregulation of APE/Ref-1 in the nuclear compartment of the cell and a later stage in which nuclear levels of the protein drop to below-normal levels as the cell becomes progressively undifferentiated.

  20. Characterization of innate lymphoid cells in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis.

    Science.gov (United States)

    Villanova, Federica; Flutter, Barry; Tosi, Isabella; Grys, Katarzyna; Sreeneebus, Hemawtee; Perera, Gayathri K; Chapman, Anna; Smith, Catherine H; Di Meglio, Paola; Nestle, Frank O

    2014-04-01

    Innate lymphoid cells (ILCs) are increasingly appreciated as key regulators of tissue immunity. However, their role in human tissue homeostasis and disease remains to be fully elucidated. Here we characterize the ILCs in human skin from healthy individuals and from the inflammatory skin disease psoriasis. We show that a substantial proportion of IL-17A and IL-22 producing cells in the skin and blood of normal individuals and psoriasis patients are CD3-negative innate lymphocytes. Deep immunophenotyping of human ILC subsets showed a statistically significant increase in the frequency of circulating NKp44+ ILC3 in the blood of psoriasis patients compared with healthy individuals or atopic dermatitis patients. More than 50% of circulating NKp44+ ILC3 expressed cutaneous lymphocyte-associated antigen, indicating their potential for skin homing. Analysis of skin tissue revealed a significantly increased frequency of total ILCs in the skin compared with blood. Moreover, the frequency of NKp44+ ILC3 was significantly increased in non-lesional psoriatic skin compared with normal skin. A detailed time course of a psoriasis patient treated with anti-tumor necrosis factor showed a close association between therapeutic response, decrease in inflammatory skin lesions, and decrease of circulating NKp44+ ILC3. Overall, data from this initial observational study suggest a potential role for NKp44+ ILC3 in psoriasis pathogenesis.

  1. Characterization of innate lymphoid cells (ILC) in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis

    Science.gov (United States)

    Tosi, Isabella; Grys, Katarzyna; Sreeneebus, Hemawtee; Perera, Gayathri K; Chapman, Anna; Smith, Catherine H; Di Meglio, Paola; Nestle, Frank O

    2013-01-01

    Innate lymphoid cells (ILC) are increasingly appreciated as key regulators of tissue immunity. However, their role in human tissue homeostasis and disease remains to be fully elucidated. Here we characterise the ILC in human skin from healthy individuals and from the inflammatory skin disease psoriasis. We show that a substantial proportion of IL-17A and IL-22 producing cells in skin and blood of normal individuals and psoriasis patients are CD3 negative innate lymphocytes. Deep immunophenotyping of human ILC subsets showed a statistically significant increase in the frequency of circulating NKp44+ ILC3 in blood of psoriasis patients compared to healthy individuals or atopic dermatitis patients. More than 50% of circulating NKp44+ ILC3 expressed cutaneous lymphocyte-associated antigen indicating their potential for skin homing. Analysis of skin tissue revealed a significantly increased frequency of total ILC in skin compared to blood. Moreover the frequency of NKp44+ ILC3 was significantly increased in non-lesional psoriatic skin compared to normal skin. A detailed time course of a psoriasis patient treated with anti-TNF showed a close association between therapeutic response, decrease in inflammatory skin lesions, and decrease of circulating NKp44+ ILC3. Overall, data from this initial observational study suggest a potential role for NKp44+ ILC3 in psoriasis pathogenesis. PMID:24352038

  2. The alpha hemolisina of Escherichia Coli induces increases in the calcium citoplasmico of neutrofilos and monocytes human beings

    International Nuclear Information System (INIS)

    Garcia, J.

    2000-01-01

    Escherichia coli alpha hemolysin (AH) and the calcium ionophores ionomycin and 4 Br A23187 caused increases in cell fluorescence, indicative of elevations in cytoplasmic calcium, in fura 2-loaded human polymorphonuclear leukocytes(PMN) and monocytes (MN). The increase in fluorescence caused by AH was dose dependent. Quelation of extracellular calcium with EGTA prevented fluorescence increases in PMN exposed to 2 HU50/ml AH, but did not prevent a small increase in 4 μM, ionomycin-treated PMN, indicating that ionomycin treatment under conditions of calcium quelation can mobilize calcium from internal stores, and that entry of external calcium accounts for most of the increases in cell fluorescence in cells treated with both AH and calcium ionophores. AH, as well as calcium ionophores and the chemotactic peptide FMLP caused rease of myeloperoxidase (MPO) from PMM suggesting that increments in intracellular calcium cause degramulation with release of granule contents (Author) [es

  3. Heat and exercise acclimation increases intracellular levels of Hsp72 and inhibits exercise-induced increase in intracellular and plasma Hsp72 in humans.

    Science.gov (United States)

    Magalhães, Flávio de Castro; Amorim, Fabiano Trigueiro; Passos, Renata L Freitas; Fonseca, Michele Atalla; Oliveira, Kenya Paula Moreira; Lima, Milene Rodrigues Malheiros; Guimarães, Juliana Bohen; Ferreira-Júnior, João Batista; Martini, Angelo R P; Lima, Nilo R V; Soares, Danusa Dias; Oliveira, Edilamar Menezes; Rodrigues, Luiz Oswaldo Carneiro

    2010-11-01

    In order to verify the effects of heat and exercise acclimation (HA) on resting and exercise-induced expression of plasma and leukocyte heat shock protein 72 (Hsp72) in humans, nine healthy young male volunteers (25.0 ± 0.7 years; 80.5 ± 2.0 kg; 180 ± 2 cm, mean ± SE) exercised for 60 min in a hot, dry environment (40 ± 0°C and 45 ± 0% relative humidity) for 11 days. The protocol consisted of running on a treadmill using a controlled hyperthermia technique in which the work rate was adjusted to elevate the rectal temperature by 1°C in 30 min and maintain it elevated for another 30 min. Before and after the HA, the volunteers performed a heat stress test (HST) at 50% of their individual maximal power output for 90 min in the same environment. Blood was drawn before (REST), immediately after (POST) and 1 h after (1 h POST) HST, and plasma and leukocytes were separated and stored. Subjects showed expected adaptations to HA: reduced exercise rectal and mean skin temperatures and heart rate, and augmented sweat rate and exercise tolerance. In HST1, plasma Hsp72 increased from REST to POST and then returned to resting values 1 h POST (REST: 1.11 ± 0.07, POST: 1.48 ± 0.10, 1 h POST: 1.22 ± 0.11 ng mL(-1); p  0.05). HA increased resting levels of intracellular Hsp72 (HST1: 1 ± 0.02 and HST2: 4.2 ± 1.2 density units, p  0.05). Regression analysis showed that the lower the pre-exercise expression of intracellular Hsp72, the higher the exercise-induced increase (R = -0.85, p < 0.05). In conclusion, HA increased resting leukocyte Hsp72 levels and inhibited exercise-induced expression. This intracellular adaptation probably induces thermotolerance. In addition, the non-increase in plasma Hsp72 after HA may be related to lower stress at the cellular level in the acclimated individuals.

  4. Procrastination in the pigeon: Can conditioned reinforcement increase the likelihood of human procrastination?

    Science.gov (United States)

    Zentall, Thomas R; Case, Jacob P; Andrews, Danielle M

    2017-11-29

    Procrastination is the tendency to put off initiation or completion of a task. Although people are typically known to procrastinate, recent research suggests that they sometimes "pre-crastinate" by initiating a task sooner than they need to (Rosenbaum et al. in Psychological Science, 25(7), 1487-1496, 2014). A similar finding of precrastination was reported by Wasserman and Brzykcy (Psychonomic Bulletin & Review, 22, 1130-1134, 2015) with pigeons using a somewhat different procedure. In the present experiment, we used a procedure with pigeons that was more similar to the procedure used by Rosenbaum et al. Pigeons were given a choice between two sequences of events (concurrent chains). Choice of the procrastination chain resulted in color A, which 15-s later would change to color B and 5-s later resulted in reinforcement. Choice of the precrastination chain resulted in color C, which 5-s later would change to color D and 15-s later resulted in reinforcement. Thus, both chains led to reinforcement after 20 s. Results indicated that the pigeons procrastinated. That is, they preferred the 15-5 chain over the 5-15 chain. The results are consistent with Fantino's (Journal of the Experimental Analysis of Behavior, 12, 723-730, 1969) delay reduction theory, which posits that stimuli that signal a reduction in the delay to reinforcement, such as the 5-s stimulus that occurred immediately prior to reinforcement, serve as strong conditioned reinforcers and should be preferred. In support of this theory, the pigeons pecked most at the 5-s stimulus that led immediately to reinforcement, indicating that it had become a strong conditioned reinforcer. The results suggest that delay reduction theory, a theory that emphasizes the attraction to stimuli that predict reinforcement with a short delay, also may contribute to human procrastination behavior because when task completion comes just before the deadline, it may become a stronger conditioned reinforcer than if task completion

  5. Student artistry sparks eclipse excitement on Maui: NSO/DKIST EPO for the 2016 Partial Solar Eclipse

    Science.gov (United States)

    Schad, Thomas A.; Penn, Matthew J.; Armstrong, James

    2016-05-01

    Local creativity and artistry is a powerful resource that enhances education programs and helps us generate excitement for science within our communities. In celebration of the 2016 Solar Eclipse, the National Solar Observatory (NSO) and its Daniel K Inouye Solar Telescope (DKIST) project were pleased to engage with students across Maui County, Hawai`i, via the 2016 Maui Eclipse Art Contest. With the help of the Maui Economic Development Board and the University of Hawai'is Institute for Astronomy, we solicited art entries from all K-12 schools in Maui County approximately 6 months prior to the eclipse. Along with divisional prizes, a grand prize was selected by a panel of local judges, which was subsequently printed on 25,000 solar eclipse viewing glasses and distributed to all Maui students. We found that the impact of a locally-sourced glasses design cannot be understated. Overall, the success of this program relied upon reaching out to individual teachers, supplying educational flyers to all schools, and visiting classrooms. On the day of the eclipse, all of the art entries were prominently displayed during a community eclipse viewing event at Kalama Beach Park in Kihei, HI, that was co-hosted by NSO and the Maui Science Center. This eclipse art contest was integral to making local connections to help promote science education on Maui, and we suggest that it could be adapted to the solar community's EPO activities for the upcoming 2017 Great American Solar Eclipse.

  6. Gemfibrozil, a lipid-lowering drug, increases myelin genes in human oligodendrocytes via peroxisome proliferator-activated receptor-β.

    Science.gov (United States)

    Jana, Malabendu; Mondal, Susanta; Gonzalez, Frank J; Pahan, Kalipada

    2012-10-05

    An increase in CNS remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis. Earlier studies have shown that gemfibrozil, a lipid-lowering drug, has anti-inflammatory properties. The current study identified another novel property of gemfibrozil in stimulating the expression of myelin-specific genes (myelin basic protein, myelin oligodendrocyte glycoprotein, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, and proteolipid protein (PLP)) in primary human oligodendrocytes, mixed glial cells, and spinal cord organotypic cultures. Although gemfibrozil is a known activator of peroxisome proliferator-activated receptor-α (PPAR-α), we were unable to detect PPAR-α in either gemfibrozil-treated or untreated human oligodendrocytes, and gemfibrozil increased the expression of myelin genes in oligodendrocytes isolated from both wild type and PPAR-α(-/-) mice. On the other hand, gemfibrozil markedly increased the expression of PPAR-β but not PPAR-γ. Consistently, antisense knockdown of PPAR-β, but not PPAR-γ, abrogated the stimulatory effect of gemfibrozil on myelin genes in human oligodendrocytes. Gemfibrozil also did not up-regulate myelin genes in oligodendroglia isolated from PPAR-β(-/-) mice. Chromatin immunoprecipitation analysis showed that gemfibrozil induced the recruitment of PPAR-β to the promoter of PLP and myelin oligodendrocyte glycoprotein genes in human oligodendrocytes. Furthermore, gemfibrozil treatment also led to the recruitment of PPAR-β to the PLP promoter in vivo in the spinal cord of experimental autoimmune encephalomyelitis mice and suppression of experimental autoimmune encephalomyelitis symptoms in PLP-T cell receptor transgenic mice. These results suggest that gemfibrozil stimulates the expression of myelin genes via PPAR-β and that gemfibrozil, a prescribed drug for humans, may find further therapeutic use in demyelinating diseases.

  7. Gemfibrozil, a Lipid-lowering Drug, Increases Myelin Genes in Human Oligodendrocytes via Peroxisome Proliferator-activated Receptor-β*

    Science.gov (United States)

    Jana, Malabendu; Mondal, Susanta; Gonzalez, Frank J.; Pahan, Kalipada

    2012-01-01

    An increase in CNS remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis. Earlier studies have shown that gemfibrozil, a lipid-lowering drug, has anti-inflammatory properties. The current study identified another novel property of gemfibrozil in stimulating the expression of myelin-specific genes (myelin basic protein, myelin oligodendrocyte glycoprotein, 2′,3′-cyclic-nucleotide 3′-phosphodiesterase, and proteolipid protein (PLP)) in primary human oligodendrocytes, mixed glial cells, and spinal cord organotypic cultures. Although gemfibrozil is a known activator of peroxisome proliferator-activated receptor-α (PPAR-α), we were unable to detect PPAR-α in either gemfibrozil-treated or untreated human oligodendrocytes, and gemfibrozil increased the expression of myelin genes in oligodendrocytes isolated from both wild type and PPAR-α(−/−) mice. On the other hand, gemfibrozil markedly increased the expression of PPAR-β but not PPAR-γ. Consistently, antisense knockdown of PPAR-β, but not PPAR-γ, abrogated the stimulatory effect of gemfibrozil on myelin genes in human oligodendrocytes. Gemfibrozil also did not up-regulate myelin genes in oligodendroglia isolated from PPAR-β(−/−) mice. Chromatin immunoprecipitation analysis showed that gemfibrozil induced the recruitment of PPAR-β to the promoter of PLP and myelin oligodendrocyte glycoprotein genes in human oligodendrocytes. Furthermore, gemfibrozil treatment also led to the recruitment of PPAR-β to the PLP promoter in vivo in the spinal cord of experimental autoimmune encephalomyelitis mice and suppression of experimental autoimmune encephalomyelitis symptoms in PLP-T cell receptor transgenic mice. These results suggest that gemfibrozil stimulates the expression of myelin genes via PPAR-β and that gemfibrozil, a prescribed drug for humans, may find further therapeutic use in demyelinating diseases. PMID:22879602

  8. Sulfur mustard primes human neutrophils for increased degranulation and stimulates cytokine release via TRPM2/p38 MAPK signaling

    Energy Technology Data Exchange (ETDEWEB)

    Ham, Hwa-Yong [Department of Pharmacology, Infectious Diseases Medical Research Center, College of Medicine, Hallym University, Chuncheon (Korea, Republic of); Hong, Chang-Won, E-mail: chyj7983@hallym.ac.kr [Department of Chemical and Biological Warfare Research, The Armed Forces Medical Research Institute, Daejeon (Korea, Republic of); Lee, Si-Nae [Department of Pharmacology, Infectious Diseases Medical Research Center, College of Medicine, Hallym University, Chuncheon (Korea, Republic of); Kwon, Min-Soo [Department of Pharmacology, School of Medicine, CHA University, Seongnam (Korea, Republic of); Kim, Yeon-Ja [Department of Pharmacology, Infectious Diseases Medical Research Center, College of Medicine, Hallym University, Chuncheon (Korea, Republic of); Song, Dong-Keun, E-mail: dksong@hallym.ac.kr [Department of Pharmacology, Infectious Diseases Medical Research Center, College of Medicine, Hallym University, Chuncheon (Korea, Republic of)

    2012-01-01

    Sulfur mustard (2,2′-bis-chloroethyl-sulfide; SM) has been a military threat since the World War I. The emerging threat of bioterrorism makes SM a major threat not only to military but also to civilian world. SM injury elicits an inflammatory response characterized by infiltration of neutrophils. Although SM was reported to prime neutrophils, the mechanism has not been identified yet. In the present study, we investigated the mechanism of SM-induced priming in human neutrophils. SM increased [Ca{sup 2+}]{sub i} in human neutrophils in a concentration-dependent fashion. Transient receptor potential melastatin (TRPM) 2 inhibitors (clotrimazole, econazole and flufenamic acid) and silencing of TRPM2 by shRNA attenuated SM-induced [Ca{sup 2+}]{sub i} increase. SM primed degranulation of azurophil and specific granules in response to activation by fMLP as previously reported. SB203580, an inhibitor of p38 MAPK, inhibited SM-induced priming. Neither PD98057, an ERK inhibitor, nor SP600215, a JNK inhibitor, inhibited SM-induced priming. In addition, SM enhanced phosphorylation of NF-kB p65 and release of TNF-α, interleukin (IL)-6 and IL-8. SB203580 inhibited SM-induced NF-kB phosphorylation and cytokine release. These results suggest the involvement of TRPM2/p38 MAPK pathway in SM-induced priming and cytokines release in neutrophils. -- Highlights: ► SM increased [Ca{sup 2+}]{sub i} in human neutrophils through TPRM2-mediated calcium influx. ► SM primed degranulation of azurophil and specific granules. ► SM enhanced p38 MAPK and NF-κB p65 phosphorylation in human neutrophils. ► SM enhanced release of TNF-α, interleukin (IL)-6 and IL-8 from human neutrophils. ► SB203580 inhibited SM-induced priming, NF-κB p65 phosphorylation and cytokine release.

  9. Amiodarone increases the accumulation of DEA in a human alveolar epithelium-derived cell line.

    Science.gov (United States)

    Seki, Satoru; Itagaki, Shirou; Kobayashi, Masaki; Hirano, Takeshi; Iseki, Ken

    2008-07-01

    Amiodarone (AMD)-induced pulmonary toxicity (AIPT) is the most life-threatening side-effect of AMD treatment. N-Monodesethylamiodarone (DEA), an active metabolite of AMD, also exhibits cytotoxicity and tends to accumulate in the lung more intensively than AMD. In this study, we characterized the mechanism of DEA accumulation using A549 cells as a model of the alveolar epithelium. Typical ATP-depletion compounds caused an approximately 30% increase in the accumulation of DEA in A549 cells, although these effects were less than those in Caco-2 cells. Triiodothyronine (T(3)), which exhibited an inhibitory effect on DEA efflux in Caco-2 cells, did not affect the accumulation of DEA in A549 cells. On the other hand, 100 microM AMD caused an approximately 200% increase in DEA content in A549 cells, although AMD accumulation was not affected by 100 microM DEA. Since the reducing effect of AMD on cellular ATP levels and that of FCCP were similar, the mechanism by which DEA accumulation is increased by AMD might be different from the ATP-dependent DEA efflux mechanism. The decrease in cell viability by DEA in the presence of AMD (IC(50) value of DEA for A549 cell viability: 25.4+/-2.4 microM) was more pronounced than that by DEA alone (IC(50) value: 11.5+/-3.0 microM). This further DEA accumulation by AMD might be a factor responsible for the greater accumulation of DEA than that of AMD in the lung in long-term AMD-treated patients.

  10. Increasing blood flow to exercising muscle attenuates systemic cardiovascular responses during dynamic exercise in humans.

    Science.gov (United States)

    Ichinose, Masashi; Ichinose-Kuwahara, Tomoko; Kondo, Narihiko; Nishiyasu, Takeshi

    2015-11-15

    Reducing blood flow to working muscles during dynamic exercise causes metabolites to accumulate within the active muscles and evokes systemic pressor responses. Whether a similar cardiovascular response is elicited with normal blood flow to exercising muscles during dynamic exercise remains unknown, however. To address that issue, we tested whether cardiovascular responses are affected by increases in blood flow to active muscles. Thirteen healthy subjects performed dynamic plantarflexion exercise for 12 min at 20%, 40%, and 60% of peak workload (EX20, EX40, and EX60) with their lower thigh enclosed in a negative pressure box. Under control conditions, the box pressure was the same as the ambient air pressure. Under negative pressure conditions, beginning 3 min after the start of the exercise, the box pressure was decreased by 20, 45, and then 70 mmHg in stepwise fashion with 3-min step durations. During EX20, the negative pressure had no effect on blood flow or the cardiovascular responses measured. However, application of negative pressure increased blood flow to the exercising leg during EX40 and EX60. This increase in blood flow had no significant effect on systemic cardiovascular responses during EX40, but it markedly attenuated the pressor responses otherwise seen during EX60. These results demonstrate that during mild exercise, normal blood flow to exercising muscle is not a factor eliciting cardiovascular responses, whereas it elicits an important pressor effect during moderate exercise. This suggests blood flow to exercising muscle is a major determinant of cardiovascular responses during dynamic exercise at higher than moderate intensity. Copyright © 2015 the American Physiological Society.

  11. Transient increase in phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol trisphosphate during activation of human neutrophils

    International Nuclear Information System (INIS)

    Traynor-Kaplan, A.E.; Thompson, B.L.; Harris, A.L.; Taylor, P.; Omann, G.M.; Sklar, L.A.

    1989-01-01

    We recently showed that phosphatidylinositol trisphosphate (PIP3) was present in a unique lipid fraction generated in neutrophils during activation. Here, we demonstrate that the band containing this fraction isolated from thin layer chromatography consists primarily of PIP3 and that only small amounts of radiolabeled PIP3 exist prior to activation. In addition, high performance liquid chromatography of deacylated phospholipids from stimulated cells reveals an increase in a fraction eluting ahead of glycerophosphoinositol 4,5-P2. After removal of the glycerol we found that it coeluted with inositol 1,3,4-P3 when resubjected to high performance liquid chromatography. Thus, we have detected a second, novel form of phosphatidylinositol bisphosphate in activated neutrophils, PI-(3,4)P2. The elevation of PIP3 through the formyl peptide receptor is blocked by pretreatment with pertussis toxin, implicating mediation of the increase in PIP3 by a guanosine triphosphate-binding (G) protein. The rise in PIP3 is not secondary to calcium elevation. Buffering the rise in intracellular calcium did not diminish the increase in PIP3. The elevation of PIP3 appears to occur during activation with physiological agonists, its level varying with the degree of activation. Leukotriene B4, which elicits many of the same responses as stimulation of the formyl peptide receptor but with minimal oxidant production, stimulates a much attenuated rise in PIP3. Isoproterenol, which inhibits oxidant production also reduces the rise in PIP3. Hence formation of PI(3,4)P2 and PIP3 (presumed to be PI(3,4,5)P3) correlates closely with the early events of neutrophil activation

  12. Increased p38-MAPK is responsible for chemotherapy resistance in human gastric cancer cells

    International Nuclear Information System (INIS)

    Guo, Xianling; Zhang, Baihe; Wu, Mengchao; Wei, Lixin; Ma, Nannan; Wang, Jin; Song, Jianrui; Bu, Xinxin; Cheng, Yue; Sun, Kai; Xiong, Haiyan; Jiang, Guocheng

    2008-01-01

    Chemoresistance is one of the main obstacles to successful cancer therapy and is frequently associated with Multidrug resistance (MDR). Many different mechanisms have been suggested to explain the development of an MDR phenotype in cancer cells. One of the most studied mechanisms is the overexpression of P-glycoprotein (P-gp), which is a product of the MDR1 gene. Tumor cells often acquire the drug-resistance phenotype due to upregulation of the MDR1 gene. Overexpression of MDR1 gene has often been reported in primary gastric adenocarcinoma. This study investigated the role of p38-MAPK signal pathway in vincristine-resistant SGC7901/VCR cells. P-gp and MDR1 RNA were detected by Western blot analysis and RT-PCR amplification. Mitgen-activated protein kinases and function of P-gp were demonstrated by Western blot and FACS Aria cytometer analysis. Ap-1 activity and cell apoptosis were detected by Dual-Luciferase Reporter Assay and annexin V-PI dual staining. The vincristine-resistant SGC7901/VCR cells with increased expression of the multidrug-resistance 1 (MDR1) gene were resistant to P-gp-related drug and P-gp-unrelated drugs. Constitutive increases of phosphorylated p38-MAPK and AP-1 activities were also found in the drug-resistant cells. Inhibition of p38-MAPK by SB202190 reduced activator protein-1 (AP-1) activity and MDR1 expression levels and increased the sensitivity of SGC7901/VCR cells to chemotherapy. Activation of the p38-MAPK pathway might be responsible for the modulation of P-glycoprotein-mediated and P-glycoprotein-unmediated multidrug resistance in the SGC7901/VCR cell line

  13. Nanoparticle pollution and associated increasing potential risks on environment and human health: a case study of China.

    Science.gov (United States)

    Gao, Yang; Yang, Tiantian; Jin, Jin

    2015-12-01

    The aims of this study are (1) to discuss the mechanism of nanoparticle lifecycle and estimate the impacts of its associated pollution on environment and human health; and (2) to provide recommendation to policy makers on how to leverage nanopollution and human health along with the rapid development of economics in China. Manufactured nanoparticles (MNPs) could either directly or indirectly impair human health and the environment. Exposures to MNP include many ways, such as via inhalation, ingestion, direct contact, or the use of consumer products over the lifecycle of the product. In China, the number of people exposed to MNP has been increasing year by year. To better provide medical care to people exposed to MNP, the Chinese government has established many disease control and prevention centers over China. However, the existing facilities and resources for controlling MNP are still not enough considering the number of people impacted by MNP and the number of ordinary workers in the MNP related industry applying for their occupational identification through the Center for Disease Control and Prevention. China should assess the apparent risk environment and human health being exposed to MNP and develop action plans to reduce the possibility of direct contacts between human beings and the emerging nanomaterials. In addition, we suggest more comprehensive studies on the MNP behavior and the development of quantitative approaches to measure MNP transport, and persistence should be carried out.

  14. Increased expression of protease-activated receptor 4 and Trefoil factor 2 in human colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Guoyu Yu

    Full Text Available Protease-activated receptor 4 (PAR4, a member of G-protein coupled receptors family, was recently reported to exhibit decreased expression in gastric cancer and esophageal squamous cancer, yet increased expression during the progression of prostate cancer. Trefoil factor 2 (TFF2, a small peptide constitutively expressed in the gastric mucosa, plays a protective role in restitution of gastric mucosa. Altered TFF2 expression was also related to the development of gastrointestinal cancer. TFF2 has been verified to promote cell migration via PAR4, but the roles of PAR4 and TFF2 in the progress of colorectal cancer are still unknown. In this study, the expression level of PAR4 and TFF2 in colorectal cancer tissues was measured using real-time PCR (n = 38, western blotting (n=38 and tissue microarrays (n = 66. The mRNA and protein expression levels of PAR4 and TFF2 were remarkably increased in colorectal cancer compared with matched noncancerous tissues, especially in positive lymph node and poorly differentiated cancers. The colorectal carcinoma cell LoVo showed an increased response to TFF2 as assessed by cell invasion upon PAR4 expression. However, after intervention of PAR4 expression, PAR4 positive colorectal carcinoma cell HT-29 was less responsive to TFF2 in cell invasion. Genomic bisulfite sequencing showed the hypomethylation of PAR4 promoter in colorectal cancer tissues and the hypermethylation in the normal mucosa that suggested the low methylation of promoter was correlated to the increased PAR4 expression. Taken together, the results demonstrated that the up-regulated expression of PAR4 and TFF2 frequently occurs in colorectal cancer tissues, and that overexpression of PAR4 may be resulted from promoter hypomethylation. While TFF2 promotes invasion activity of LoVo cells overexpressing PAR4, and this effect was significantly decreased when PAR4 was knockdowned in HT-29 cells. Our findings will be helpful in further investigations into the

  15. Dioxin increases the interaction between aryl hydrocarbon receptor and estrogen receptor alpha at human promoters

    DEFF Research Database (Denmark)

    Ahmed, Shaaima; Valen, Eivind; Sandelin, Albin Gustav

    2009-01-01

    genes with little knowledge of what was occurring at other genomic regions. In this study, we showed using chromatin immunoprecipitation followed by hybridization to promoter focused microarrays (ChIP-chip) that 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment significantly increased the overlap of genomic...... , suggesting that AHR was the important factor determining the recruitment of ER to these regions. RNA interference-mediated knockdown of AHR confirmed its requirement for the recruitment of ER to some, but not all, of the shared regions. Our findings demonstrate not only that dioxin induces the recruitment...

  16. Reduction of dietary saturated fatty acids correlates with increased plasma lecithin cholesterol acyltransferase activity in humans.

    Science.gov (United States)

    Bérard, A M; Dabadie, H; Palos-Pinto, A; Dumon, M-F; Darmon, M

    2004-06-01

    Increas